Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30General SciencesCOMMUNITY-ACQUIRED METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS
English0110Veni Emilda J. K.English Shrikala BaligaEnglish Shenoy M.English Gopalkrishna Bhat K.EnglishMethicillin resistant S.aureus (MRSA) has emerged as an important pathogen first in hospitals and then in the community. Community - acquired MRSA (CA-MRSA) has recently emerged as a significant pathogen, mainly causing skin and soft tissue infections in immunocompetent individuals residing in the community. It may also cause serious infections such as pneumonia. Person to person spread of CA-MRSAoccurs mainly due to overcrowding, skin to skin contact, compromised skin integrity, sharingcontaminated materials and poor hygiene. Possession of staphylococcal cassette chromosome mec type IV (SCCmec IV) encoding for mecA gene, susceptibility to non β-lactam antibiotics and a pvl gene encoding Panton-Valentine Leukocidin (PVL) primarily distinguish CA-MRSA from healthcare-associated MRSA. In addition to PVL, CA-MRSA produces many other virulence factors which play important role in its pathogenicity.
EnglishCommunity-acquired MRSA, Panton - Valentine Leukocidin, Staphylococcal cassette chromosome mec IVNTRODUCTION
Staphylococcus aureus continues to be an important pathogen due to its versatility of diseases caused, virulence factors and drug resistance. Methicillin resistant S. aureus (MRSA) emerged in the 1960s, making S. aureus resistant to many antibiotics.1 MRSA is a significant pathogen causing both health care-associated (HAMRSA) and community-acquired (CA-MRSA) infections. HA-MRSA has been a serious problem in hospitals and health care facilities worldwide including India.1,2 In the 1990s, MRSA, which was once confined to hospital setting was seen to affect immunocompetent people with no health care risk factors such as athletes and other sportsmen.3CAMRSA then gained importance as a serious threat following the death of 4 children in North Dakota and Minnesota with severe CA-MRSA infection.4 In the recent years, there have been increasing reports of CA-MRSA from various parts of the world. Initially, it was believed that CA-MRSA emerged fromHA-MRSA since clonal relation was seen among them.5However, with epidemiological and molecular profiling, it was observed that CAMRSA are different from HA-MRSA in terms of risk factors associated, drug susceptibility pattern, virulence factors and molecular properties.1 Comparison of CA-MRSA and HA-MRSA is shown in Table 1.6,7
DEFINITION
According to CDC, CA-MRSA is defined based on the following criteria.8 ? Diagnosis of MRSA in the outpatient setting or by positive culture within 48 hours of hospital admission. ? No history of MRSA infection or colonization. ? No following history in the previous year 1. Hospitalization/Admission to a nursing home, skilled nursing facility or hospice 2. Dialysis 3. Surgery ? No permanent indwelling catheters or medical devices that pass through the skin into the body. CA-MRSA is usually susceptible to trimethoprim / sulfamethoxazole, clindamycin and gentamicin, possess staphylococcal cassette chromosome mec(SCCmec) type IV and Panton-Valentine Leukocidin (PVL).9,10There is still a lot of confusion regarding the prevalence of MRSA in the community due to difficulty in differentiating HA-MRSA and CA-MRSA.5A person may have become a carrier of MRSA during a hospital stay or following exposure to healthcare facility and transmit the pathogen in the community when he enters it.11 Such infections can be rightly called as community-onset MRSA rather than CA-MRSA.12
Epidemiology
Patients infected with CA-MRSA and carriers are the most common sources of infection. Infections are commonly seen among children and young adults.13According to CDC, athletes and other sports participants, military recruits, children, Pacific islanders, Alaskan natives, Native Americans, men who have sex with men and prisoners are at increased risk of CA-MRSA infections.7 Factors associated with spread of CAMRSA are overcrowding, sharing of contaminated items and surfaces, skin to skin contact, cuts and abrasions on skin and improper maintenance of hygiene and personal cleanliness.14,15 MRSA carriage is a significant risk factor for subsequent development of skin and soft tissue infection (SSTI).15 High CA-MRSA carrier state is seen in people living in mud-thatch houses where there is overcrowding, lack of hygiene, space and ventilation.16 A single clone of CA-MRSA is present in few regions whereas many clones may be responsible for infections in other parts of the world.17The most common clone prevalent in North America is pulse-field type USA300 mostly causing SSTI, bacteraemia, necrotizing fasciitis and severe pneumonia.18-20 USA400 is the second most common clone predominant in Alaska causing SSTI and fulminant sepsis.21 Most common clones seen in Europe and Australia are ST80 MRSA IV and ST93 MRSA IV respectively.17 ST59 MRSA IV/V is seen in Taiwan. However, limited data is available from Asia.17 In spite of all the differences in definitions of CAMRSA and limited number of population based studies, high incidence of CA-MRSA has been reported.5Cynthia and colleagues observed a rise in prevalence of CA-MRSA from 17% in 1999 to 56% in 2003.22 Previous studies have shown a difference in the rate of CA-MRSA infections varying from 10.9% to 29%.11,23,24 In an international surveillance study conducted by Song et al., prevalence of CA-MRSA in Asian countries was 25.5% of which India accounted for 4.3%.25 The study also suggested that CA-MRSA with various genotypic characteristics have spread from community to hospitals and major endemic HA-MRSA strains have spread from hospital to community in some Asian countries.25
Virulence Factors
CA-MRSA is known to produce many virulence factors
1. Cell wall polymers
Cell wall polymers include peptidoglycan and teichoic acid which have been implicated in shock.26,27
2. Cell wall proteins
Adherence of CA-MRSA to host tissue is mediated by cell surface proteins called Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs).27 MSCRAMMs like clumping factor, fibronectin-binding proteins and protein A bind to host cell components like fibrinogen, fibronectin and Fc portion of Immunoglobulin G respectively.27 Other cell surface proteins include iron regulated proteins, polysaccharide intercellular adhesins and capsular polysaccharides.28MSCRAMMs are implicated in bone and joint infections and endovascular infections.27 One of the important MSCRAMMs in CA-MRSA, collagen adhesin protein is important in the pathogenesis of septic arthritis and osteomyelitis.29,30The microcapsule present in a few clinical isolates of CA-MRSA help in evading host defenses by its antiphagocytic activity and induce abscess formation.31A novel gene cluster bsa (bacteriocin of S.aureus) helps in invading an established microbial community and is implicated in quorum sensing and intercellular communication.27,32 CA-MRSA also have better tolerance to salt which may help colonization on skin
3. Enzymes
CA-MRSA has the ability to produce different enzymes like coagulase, staphylokinase, lipase, deoxyribonulease, protease and elastases which contribute to the pathogenesis of this organism.27 USA300 harbours a genomic island termed “arginine catabolic mobile element” (ACME) which encodes an arginine deaminase pathway.27 Arginine deaminase, a known virulence factor may further enhance the pathogenesis of CAMRSA
staphylococcal food poisoning, toxic shock syndrome (TSS) like illness and also epidemic furunculosis and necrotizing pneumonia.5,26 Superantigens SEB, SEC, SEA and SEH are produced by most of CA-MRSA isolates.5 SEB and SEC are implicated in non-menstrual TSS.28
5. Cytotoxins
Cytotoxins like α, β, γ, δ toxins and PVL are produced by CA-MRSA, which are hemolytic and toxic to leukocytes respectively.28
Panton-Valentine Leukocidin (PVL): Most CAMRSA carry pvl genes encoding for the PVL toxin, suggesting its role in virulence.33PVL is an extracellular bi-component toxin produced as two non-associated secreted proteins LukS-PV and LukF-PV.33 LukS-PV is dimerized with LukF-PV after connecting to the polymorphonuclear cell membrane forming a heptamer.5 PVL targets and induces leukocyte death by creating pores in the cell membrane releasing cytokines and intracellular proteases.1 PVL at low concentration causes apoptosis by forming pores in mitochondrial membrane.34 Horizontal transmission and clonal expansion of pvl genes leads to spread among CA-MRSA isolates.35 However studies reveal that PVL negative CAMRSA infections result in a worse outcome of SSTI when compared to PVL positive CAMRSA.36 Few β-lactam antibiotics enhance PVL production while antibiotics like clindamycin inhibit its production.37 α-toxin is a pore-forming toxin similar to PVL and causes dermonecrosis.5 It does not target neutrophils but lyses other cells like RBCs, macrophages, lymphocytes, platelets and fibroblasts.6,38
6. Epidermolytic / Exfoliative toxins CA-MRSA also produce exfoliative toxins such as exfoliative toxin A and B (eta and etb) that cause staphylococcal scalded skin syndrome and bullous impetigo.39
Molecular Properties
Hartman and colleagues described the mechanism of methicillin resistance attributed to PBP 2a – an altered penicillin binding protein with reduced affinity to methicillin.40 SCCmec, a mobile DNA element carries the mecA gene in a mec gene complex, which encodes PBP2a.41 It also carries direct repeat sequences, integration site sequence and chromosome cassette recombinase (ccr) gene in a ccr gene complex which integrates and excises SCCmec. 41 Eight SCCmec types have been identified – Type I to VIII depending on the class of mecA gene and the type of ccr gene complex.41 No drug resistant determinants other than mecA has been associated with types I, IV and V, while multiple drug resistance determinants are seen in types II and III.5 Due to the small size of SCCmec IV, it can be transferred horizontally to other species resulting in a higher degree of methicillin resistance amongCA-MRSA whereas SCCmec II and III, due to their large size, can be transferred vertically on selective antibiotic pressure as seen in HAMRSA.42Horizontal exchange of genes among Staphylococci has been further supported by identifying a few sequences of SCCmec IV identical in S.epidermidis.43 CA-MRSA that carry SCCmec IV also grow faster and reach high numbers in an infection.44 Theyare susceptible to a wide range of non β lactam antibiotics with susceptibility profile similar to that prevalent among methicillin susceptible S. aureus (MSSA).6,44 CA-MRSA associated with SCCmec IV cause SSTI (87.6%) and are recovered in high numbers in children than adults.45
Clinical Significance
Infections caused by CA-MRSA are similar to those caused by S. aureus except for a few that have arisen in epidemic proportions like SSTI and necrotizing pneumonia.6 Skin infections are the most common clinical manifestation seen with CA-MRSA. The appearance of red lesions is usually confused with spider bites and may be ignored by the clinicians.14 Such lesions have the tendency to develop necrotic areas.14 Furunculosis is the most common clinical presentation associated with CAMRSA.5However, in a previous study done in Mangalore, deep abscesses were seen in 83% of patients in comparison to 16.7% patients with superficial skin infections.46 Several cases of impetigo, bullous impetigo due to CA-MRSA have been described although 17-20% of S.aureus isolated from bullous impetigo in Japan were PVLnegative CA-MRSA.47,48 PVL producing CAMRSA is responsible for another major clinical presentation- necrotizing pneumonia leading to septic shock and respiratory distress syndrome with high mortality.49 CA-MRSA also causes necrotizing fasciitis, musculoskeletal infections and septic arthritis.50-52Toxins are also responsible for post antibiotic diarrhoea.53
Laboratory Diagnosis
CA-MRSA should be considered in the differential diagnosis of purulent SSTI.8Clinical specimens should be collected based on the site and type of infection and processed without delay. Gram stain of the specimen can give an immediate clue of staphylococcus infection. Further, culture of the specimen on blood agar is needed to isolate the organism. Once isolated, S.aureus is identified by standard procedures involving colony morphology, gram stain, catalase test and coagulase test.54 Clinical Laboratory Standards Institute (CLSI) recommends disk diffusion test using cefoxitin (30 µg) disc for identifying methicillin resistance as it is a better inducer of mecA gene.55Alternative methods include latex agglutination test for PBP2a and agar screen method using Mueller-Hinton agar with 6 µg/ml oxacillin and NaCl (4% w/v).56 Chromogenic media like ChromID MRSA, MRSASELECT can also be used for detection of methicillin resistance among isolates.57 PCR can be used for the detection of mecA gene that encodes for altered PBP.57 Further typing of CA-MRSA can be done using various methods like SCCmec typing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and S.aureus protein A (spa) typing.58 SCCmec typing is done using PCR for the detection of the class of mecA gene complex and the type of ccr gene complex.54
Treatment of CA-MRSA Infections
A new approach in empiric antibiotic therapy and management of staphylococcal infection is needed due to the emergence of MRSA in the community.5 For severe life-threatening infection and for infections among patients with associated risk factors,vancomycin should be used for empiric therapy.5 In low CA-MRSA prevalent regions,less severe infections and for patients with absence of healthcare risk factors, empirical therapy with first generation cephalosporin is adequate.5 Infections are generally not treated with fluoroquinolones as first line due to the risk of developing drug resistance.14 High resistance of MRSA to quinolones was reported in a previous study.59Clindamycin is one of the most common antibiotics used for empiric therapy of CA-MRSA infections, co-trimoxazole is preferred when inducible clindamycin resistance is detected.5 However, co-trimoxazole must be avoided in paediatric cases less than 8 years due to the reported contraindications.14 Non-antibiotic management of CA-MRSA infections have to be considered as drainage can manage many SSTI and must be considered as an adjunct to drug therapy.5 Simple skin infections caused by CA-MRSA can be treated with hot soaks, elevation, topical therapies, incision and drainage.6 Proper drainage and debridement can resolve cutaneous abscesses. Hospitalization and parenteral therapy may be necessary for more severe CAMRSA infections.5 Efforts should be made to collect appropriate specimens for culture and susceptibility testing in areas with high MRSA prevalence and / or in
Prevention
Basic principles for prevention of CA-MRSA infection as recommended by CDC include hand hygiene, avoiding sharing of personal hygiene items, covering draining wounds, early management of infections, environmental cleanliness and sterilization.14Patients should be isolated with implementation of contact precautions if confirmed positive for MRSA infection or colonization.5 Since nasal colonization is associated with recurrent pyoderma, nasal culture can be done for individuals at high risk.5Due to high mortality and morbidity associated with systemic invasive CAMRSA infections, it is better to screen and treat colonization with mupirocin among individuals with recurrent skin infections and their contacts.5 This however is not recommended for general population due to the possibility of the development of drug resistance.5
CONCLUSION
CA-MRSA has emerged in recent years as an important community acquired pathogen. To date, the true incidence of CA-MRSA infection is not known in many countries because most studies have characterized this organism in a relatively small group of patients over a short, fixed time interval. CA-MRSA differs from HA-MRSA in producing PVL, the type of infections caused and antibiotic resistance pattern. Normally, CA-MRSA is more susceptible to antibiotics such as tetracyclines, clindamycin, co-trimoxazole and gentamicin. It usually causes SSTIs, but can also cause severe deep seated infections such as necrotizing pneumonia. Early diagnosis and prompt treatment help in the management of the cases. In recent years, there have been reports of CA-MRSA causing hospital infections. Transmission of SCCmec IV via plasmids or bacteriophages could create bacteria that have antibiotic resistance of HA-MRSA and the virulence of CA-MRSA.
ACKNOWLEDGEMENT
The authors are thankful to Manipal University for providing continuous academic support. Authors are thankful to the Head of the Institution and Head of the Department of Microbiology, Kasturba Medical College, Mangalore (A constituent college of Manipal University) for their encouragement and support. The authors acknowledge the immense help received from the scholars whose article are cited and included in the references of this manuscript. The authors are also grateful to authors / editors / publishers of all these articles, journals and books from where the literature to this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=877http://ijcrr.com/article_html.php?did=877REFERENCES
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30General SciencesTHERMO-MAGNETIC CONVECTION OF AN OLDROYDIAN FLUID THROUGH A BRINKMAN POROUS MEDIUM
English1117Anand KumarEnglish Rajan SinghEnglishObjective: The objective in the present investigation is to study the effect of magnetic field on thermal convection of an Oldroydian viscoelastic fluid through a Brinkman porous medium. Methods: The normal mode method is used to obtain the dispersion relation. Conclusions: For the case of stationary convection, Oldroydian viscoelastic fluid behaves like an ordinary Newtonian fluid and medium permeability and medium porosity have destabilizing effects on the system whereas the magnetic field and Darcy-Brinkman number have stabilizing effects on the system. It is also found that the modes may be oscillatory and non-oscillatory and the principle of exchange of stabilities is valid under certain condition.
EnglishStability, Magnetic Field, Brinkman Porous Medium.INTRODUCTION
The problem of the onset of convection in a horizontal layer of Newtonian fluid heated from below under varying assumptions of hydrodynamics and hydromagnetics has been discussed in detail by Chandrasekhar (1981).A porous medium is defined as a material consisting of a solid matrix with an interconnected void.A comprehensive and detailed study of thermal convection through various porous mediums has been given by Nield andBejan (2006). Tissues can be treated as a porous medium as it is composed of dispersed cells separated by connective voids which allow for flow of nutrients, minerals, etc. There are several evidences, both theoretical and experimental, which suggest that the Darcy’s equation gives inadequate resultsof the hydrodynamic conditions particularly near the boundaries of a porous medium. The DarcyBrinkman equation, which takes into account the boundary effects, has been employed in recent years in biomedical hydrodynamic studies (Khaled and Vafai, 2003). An experimental demonstration by Toms and Strawbridge (1953) reveals that a dilute solution of methyl methacrylate in n-butyl acetate behaves in accordance with the theoretical model of Oldroyd fluid (1958).Sharma (1975) studied the stability of a layer of an electrically conducting Oldroyd fluid in the presence of a magnetic field and found that the magnetic field has a stabilizing influence.Sharma and Sunil (1994) considered the thermal instability of an Oldroydian viscoelastic fluid permeated with suspended particles in hydromagnetics in a porous medium and concluded that for the case of stationary convection, magnetic field has a stabilizing effect whereas medium permeability and suspended particles have destabilizing effects on the system. Kumar et al. (2013) investigated theoretically the influences of dust particles, variable gravity and magnetic field of an Oldroydian Viscoelastic fluid through a Brinkman Porous Medium. The purpose of the present study is to investigate the problem of the onset of stability of an Oldroydian viscoelastic fluid through a Brinkman porous medium in hydromagnetics.
RESEARCH METHODOLOGY
The following Research Methodology is adopted for the proposed Research paper: ? Identification of the problem
FORMULATION OF THE PROBLEM
Consider an infinite horizontal layer of an Oldroydian viscoelastic fluid bounded by the planes z=0 and z=d in a porous medium of porosity ? and medium permeability 1 k . The fluid layer is acted on by a uniform vertical magnetic field H (0, 0, H). The governing equations of motion and continuity for anOldroydian viscoelastic fluid are defined as:? Collection and study of related literature ? Mathematical formulation of the problem ? Stability analysis and use of normal mode method ? Interpretation of results ? Conclusion
Englishhttp://ijcrr.com/abstract.php?article_id=878http://ijcrr.com/article_html.php?did=878EFERENCES
1. Chandrasekhar, S.C. (1981). Hydrodynamic and Hydromagnetic Stability, Dover Publication, New York.
2. Khaled, A.R.A. and Vafai, K. (2003). The role of porous media in modeling flow and heat transfer in biological tissues. Int. J. Heat Mass Transfer, Vol.46, pp.4989-5003.
3. Kumar, K., Singh, V. and Sharma, S. (2013). Stability of an Oldroydian Viscoelastic Fluid Permeated with Suspended Particles through a Brinkman Porous Medium with variable gravity field in Hydromagnetics, American Journal of fluid Dynamics, Vol. 3, 3, pp. 58- 66. doi: 10.5923/j.ajfd.20130303.02
4. Nield, D.A. and Bejan, A. (2006). Convection in porous media. Springer, New-York.
5. Oldroyd J.G. (1958). Non-Newtonian effects in steady motion of some idealized elasticviscous liquids, Proc. Royal Soc. London, A 245, pp. 278-297.
6. Sharma R.C. (1975). Thermal instability in a viscoelastic fluid in hydromagnetics, Acta Phys. Hung., Vol. 38, pp. 293-298.
7. Sharma R.C. and Sunil. (1994). Thermal instability of Oldroydian viscoelastic fluid with suspended particles in hydromagnetics in porous medium, Polymer Plastics Technology and Engineering, Vol. 33, Issue 3, pp. 323- 339.
8. Toms B.A. and Strawbridge D.J. (1953). Elastic and viscous properties of dilute solutions of polymethyl methacrylate in organic liquids, Trans. Faraday Soc., Vol. 49, pp. 1225-1232.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN2014May12General SciencesVALIDATION OF NEWLY FORMULATED LAPORTEA ARISHTA BY USING DIFFERENT ANALYTICAL METHODS
English1829Deepa Deepa Deepa Deepa Deepa Deepa P.English SeenaEnglishPurposPurposPurposPurposPurposPurpose: Traditional medicines have nurtured the knowledge of natural remedies against diseases since ages. Growing awareness about harmful side effects of modern medicine has led to interest in Ayurveda. Method: Laporteainterrupta (L) Chew of family Urticaceae having common name Hawaii woodnettle is an herb having many traditional uses. physicochemical analysis of crude drug, Laporteainterrupta-leaves were performed,Laporteainterrupta leaves extracted in soxhlet apparatus using ethyl acetate, petroleum ether, chloroform, methanol and water for identification of constituents by qualitative phytochemical analysis (tests for protein, carbohydrates, phenols and tannins, flavanoids, saponins, glycosides, steroids, terpenoids and alkaloids) and quantitative phytochemical analysis (total phenol content and total flavanoid content). The collected leaves of Laporteainterrupta was used to prepare arishta. After preparing the arishta the organoleptic characteristics (color, odor, taste and appearance), the physicochemical analysis ( pH, acid value, alcohol content, total solid content, viscosity and refractive index), quantitative analysis (alcohol content by spectrophotometry by dichromate method, total reducing sugar, total phenol content and total flavanoid content), anti-oxidant activity determination ( Ferric Thiocyanate method, Thiobarbituric acid method and Total Antioxidant Activity by FRAP method) were performed. LCMS was performed for determining various constituents (Qualitative analysis) and standardization of formulation was done by using UV and HPLC. The above formulated LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical LAPORTEA ARISHTA was validated by using different analytical equipmentequipmentequipmentequipmentequipmentequipmentequipmentequipmentequipment’s as per ICH guidelines.guidelines.guidelines.guidelines.guidelines.guidelines.guidelines.guidelines.guidelines.guidelines.guidelines. Results: Results: All results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. results are coming between standard ranges. Conclusion: Conclusion: Conclusion: Laporteainterrupta (L) Chew of family Urticaceae found to have number of active constituents from LCMS reports, which may can take as a proof for its traditional uses. Laporteainterruptaleaves have been successfully formulated and determined its anti-oxidant activity and validated using HPLC.
EnglishArishta, Physicochemical analysis, organoleptic characteristicsINTRODUCTION
Herbal medicine (or "Herbalism") is the study and use of medicinal properties of plants. They have the ability to synthesize a wide variety of chemical compounds that are used to perform important biological functions, and to defend against attack from predators such as insects, fungi and herbivorous mammals. Ayurveda - The Natural Way of Treating Disease Ayurveda is a form of alternative medicine that uses different parts of herbs, plants and parts of animals to cure diseases and ailments. Arishta are medicinal preparations made by soaking the drugs in coarse powder form or in the form of decoction (Kashaya), in a solution of sugar or jaggery, as the case may be, for a specified period of time, during which it undergoes a process of fermentation generating alcohol, thus facilitating the extraction of the active principles contained in the drugs. Laportea interrupta (L) Chew of family Urticaceae having common name Hawaii woodnettle is an herb having many traditional uses like Allergies, Alopecia, Amenorrhea, Arthritis, Asthma, Bedwetting/incontinence, Female Hormones, Fibromyalgia, Libido, Longevity/tonics, Menorrhagia, Nutrition, Osteoporosis, PMS, Prostate, Rheumatoid arthritis. Flavanoids have been reported to exert wide range of biological activities like anti-inflammatory, antibacterial, antiviral, anti-allergic, cytotoxic antitumor, treatment of neurodegenerative diseases, vasodilatory action. Standardization is the development and implementation of concepts, doctrines, procedures and designs to achieve and maintain the required levels of compatibility, interchangeability or commonality in the operational, procedural, material, technical and administrative fields to attain interoperability. Validation is documenting that a process meets its pre-determined specifications and quality attributes the objective of validation of an analytical procedure is to demonstrate that it is suitable for its intended purpose. Typical validation characteristics which should be considered are accuracy, precision, repeatability, intermediate precision, specificity, detection limit, quantisation limit, linearity, range.
MATERIALS AND METHOD
Collection of plant material: The leaves of Laportea interrupta were collected and washed well then dried under shade and coarsely powdered. Physicochemical analysis of crude drug: Total ash value, Acid insoluble ash, Water insoluble ash, Sulphated ash, Moisture content. Extraction of plant material: The plant material was dried and coarsely powdered and then extracted in Soxhlet Apparatus using 250ml of ethyl acetate (70-80°c), 250ml of Petroleum Ether (60-80°c), 250ml of Chloroform (50.5-61.5°c ), 250ml of methanol (60-70°c) and 250ml of Distilled water (0.25%) by continuous hot percolation according to their polarity. (Harborne, J.B., 2007). Qualitative phytochemical analysis: The extracts were subjected to qualitative tests for identification of phytochemical constituents such as proteins ( Million’s test and Ninhydrin test), carbohydrates ( Fehling’s test, Benedict’s test, Molisch’s test and Iodine test), phenols and tannins (Ferric Chloride test and Lead Acetate test), flavanoids ( Shinoda test and Alkaline Reagent test), saponins, glycosides (Liebermann’s test, Salkowski’s test and Keller-Kilani), steroids, terpenoids, alkaloids ( Mayer’s test and Wagner’s test) present in it. (RNS Yadev et al. 2011) . Quantitative phytochemical analysis Total Phenol Content: The amount of phenol in the ethyl acetate extract was determined by Folinciocalteu reagent method with some modification and then absorbance were measured at 765nm. Total Flavanoid Content: The amount of phenol in the ethyl acetate extract was determined by Aluminium chloride colorimetric method with some modification and then absorbance were measured at 420nm.
Preparation of formulation: An earthen pot sufficiently large and strong is chosen. The proportion of the different ingredients are 32 seers of distilled water, boiled and added 1.25 seers dried plant leaf powder jaggery 12.5 seers, honey 6.25 seers and sugar 6.25 seers, mixed well to form a uniform solution and pour into it . Pot is buried in a pit made in the soil for 30 days. Physicocemical analysis of formulation: Determination of PH of formulation, Determination of acid value, Determination of alcohol content, Total solid content, Determination of viscosity of formulation, Determination of refractive index. Quantitative analysis of formulation Alcohol content by spectrophotometry (Dichromate Method): Alcohol was estimated by caputi et al (1968) and measured the absorbance at 620nm. Total reducing sugar: Total phenol content: The amount of phenol in the formulation was determined by Folin-ciocalteu reagent method with some modification and then absorbance were measured at 765nm and the results were determined from the standard curve and expressed in gallic acid equivalents (mg/g of extracted compound).. Total flavanoid content: The amount of phenol in the formulation was determined by Aluminium chloride colorimetric method with some modification and then absorbance were measured at 420nm and the results were determined from the standard curve and expressed in Quercetin equivalents (mg/g of extracted compound) Anti-oxidant activity determination of formulation: Ferric Thiocyanate (FTC) method, Thiobarbituric Acid (TBA) method, Total Antioxidant activity by FRAP method. Qualitative analysis of formulation by LCMS: Specifications of LCMS are LC Column: REVERSE PHASE C-18, Pump: SPD 10 AVP, Mobile Phase: 2% OPA IN WATER: METHANOL (50:50), Ionization Mode: ELECTRONIC SPRAY IONIZATION, Mode: BOTH POSITIVE, Injection Volume: 10 µL, Flow Rate: 2 ML/MIN, Column Temperature: 250°C, Column: PHENOMENEX RP 18, Column Dimension: 25CM 2.5 MM,LC Detection: 254NM,m/z range: 50- 1000,Soft Ware: CLASS V P INTEGRATED AND Library: METWIN 2.0. Standardisation of formulation using UV: Specifications of UV are Model: ELICO SL 164, Instrument: UV-Visible Double Beam Spectrophotometer, Wavelength Range: 190-999.9 nm, Accuracy: +/- 0.5nm, Repeatability: +/- 0.2nm, Resolution: 0.1nm, Bandwidth: 0.5-6.0 nm (Variable at an Interval of 0.1nm), Photometric range: -2.5 TO +2.5 Abs, Accuracy: +/- 0.005 Abs at 0.1Abs from 200-850nm, Repeatability: +/- 0.002 Abs at 1.0 Abs from 200-850nm, Stray light: less than 0.05% at 220-340nm,Base line correction: Automatic Base Line Correction, Scan speed: Slow, Medium and Fast, Data interval: Depend Upon Wavelength, Sample holder: 5 Position, Automatic positioning far 10mm and Sample Cuvette and Fixed position for Reference Cuvette, Source: Tungsten- Halogen lamp (310-999.9nm) and Deuterium lamb with Quartz window (190-340nm) and Detectors: Photomultiplier Tube (PMT).Validation experiments were performed to demonstrate linearity, precision, accuracy, robustness, ruggedness, LOD and LOQ as per ICH guidelines. Standardisation of formulation using HPLC: Specification of HPLC is Instrument: Schimadzu, LC Column: Reverse Phase C-18 Phenomenex C18, Pump: SPD 10 AVP, Mobilephase: Acetonitrile: Methanol (40:60), Injection volume: 10 µl, Flow Rate: 2.0 ml/min, Column Temperature: 25°C, Column: Phenomenex RP 18, Column Dimension: 5cm 1.5 cm,LC detection: 254nm and Soft Ware: Class V P Integrated.Validation experiments were performed to demonstrate system suitability, linearity, precision, accuracy study and robustness as per ICH guidelines.
CONCLUSION
Laportea interrupta (L) Chew of family Urticaceae found to have number of active constituents from LCMS reports, which may can take as a proof for its traditional uses. Laportea interrupta leaves have been successfully formulated and determined its anti-oxidant activity and validated using UV and HPL
Englishhttp://ijcrr.com/abstract.php?article_id=879http://ijcrr.com/article_html.php?did=8791. RNS Yadav , Munin Agarwala. Phytochemical Analysis of Some Medicinal Plants, Journal of Phytology .2011; 3(12):10-14.
2. N. Savithramma, M. Linga Rao and D. Suhrulatha. Screening of Medicinal Plants for Secondary Metabolites, leucoanthocyanins and emodins. Middle-East Journal of Scientific Research, 2011; 8 (3):579-584.
3. S.K Sharma, Compliance of Pharmacopoeial Quality Standards of Ayurvedic Medicine, July-sep 2009;30:221-224.
4. S.Sekar. Traditionally Fermented Biomedicines, Arishtas and Asavas from Ayurveda, Oct 2008;7(4): 548-556.
5. Richa Kushwahaet al, Standardization of Aswagandharishta Formulation by TLC Method, International Journal of Chem Tech Research.2011; 3: 1033-1036.
6. S.F.Sayyad, Preparation and Evaluation of Fermented Ayurvedic Formulation: Arjunarishta, Journal of Applied Pharmaceutical Science, 2012 ;2(5), 122-124.
7. Shitalgiramkaret al,Effect of Pre-Sterilization on Physicochemical Parameters and in Vitro Free Radicle Scavenging Potential of Saraswatarishta, Journal of Pharmacy Research, 2012, Vol 5(5), pp: 2657-2663.
8. Giuseppagattusoet al, Flavanoid Composition of Citrus Juices, 2007,Vol: 12, pp: 1641-1673.
9. Luis adriano.S.do nascimentoet al,Biflavones and Triterpenoids isolated Fromouratea castaneifolia (dc.)Engl. Ochnaceae, RevistaBrasileira de Farmacognosia, oct-dec 2009,Vol: 19(4), pp: 823-827..
10. Rezaeizadeh A, Determination of Antioxidant activity in Methanolic and Chloroformic extracts of Mamordica charantia, African Journal of Biotechnology, (2011); 10(24):4932-4940.
11. N.P. Damodaran, Standardisation of Ayurvedic Medicines-Dasamulam Kasayam, Anc Sci Life, 1989; 9(2): 54–60.
12. Kunle et al, Standardization of Herbal Medicines - A Review, International Journal of Biodiversity and Conservation, March 2012; 4(3): 101-112.
13. Ajay KR Meena , Standardisation of Ayurvedic Polyherbal Formulation-Pancasama Churna, International Journal of Pharmacognosy and Phytochemical Research,2010; 2(1): 11-14.
14. Maithani Jyoti , Preparation and Standardization of a Polyherbal Formulation, Journal of Advanced Scientific Research,2012;3(2): 84-85.
15. Pravin Het , Future Trends in Standardization of Herbal Drugs, Journal of Applied Pharmaceutical Science,2012;02 (06): 38-44.
16. Neeli Rose Ekka. Kamta Prasad Namdeo , Pradeep Kumar Samal ,Standardization Strategies for Herbal Drugs- An Overview, Research J. Pharm and Tech, 2008; 1(4):310-312
17. ManishaK.Gharate, Development and Validation of RP-HPLC Method for Determination of Marker in Polyherbal Marketed Kankasava Formulation, Scholars Research Library, 2011;3(5) : 28-33.
18. L. Haber , Validation of HPLC method, Biopharm, 1999; 12: 64-66.
19. Himanshu Kumar, Prashant Kumar Pandey, V. V. Doiphode, Sanjay Vir, K. K. Bhutani, M. S. Patole, Y. S. Shouche. HPLC Analysis And Standardisation Of Arjunarishta- An Ayurvedic Cardio Protective Formulation, Scientia Pharmaceutica. 2013; 53(1):11-17
20. N. Vador ,B. Vador, Rupali Hole. Simple Spectrophotometric Methods Of Standardizing Ayurvedic Formulation, Indian J Pharm Sci, 2012,74(2): 161–163.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN2014May12HealthcareAWARENESS AND KNOWLEDGE OF ATTENTION DEFICIT HYPERACTIVITY DISORDERS AMONG PRIMARY SCHOOL TEACHERS IN INDIA
English3036Anil ShettyEnglish B. Sanjeev RaiEnglishObjectives: The prevalence of Attention hyperactivity disorders (ADHD) in children ranges from 5-10% but has not received adequate attention in developing countries like India. There are also several misconceptions and stigmas associated with ADHD. Teachers could play a significant role in identifying children with ADHD. The purpose of this study is to assess the awareness and knowledge of ADHD in elementary school teachers and the variables influencing that knowledge. Material and Methods: 312 teachers were given a self- report questionnaire and socio-demographic information and their ability to identify signs and symptoms of ADHD based on DSM-IV-TR criteria were evaluated. Results: 268 teachers were aware of the term ADHD and their knowledge of ADHD ranged from poor to adequate.28 (9%) of teachers had prior training. Only 92 (29%) of the teachers had a good understanding of ADHD. Conclusion: The teachers had an inadequate knowledge about ADHD. Teaching experience and prior training had a positive bearing on knowledge. Majority of teachers queried felt that their knowledge was inadequate and were willing to be trained on features of ADHD.
EnglishAttention Deficit Hyperactivity Disorders, Teachers Knowledge, Behavioral Disorders.INTRODUCTION
Behavioral disorders in children such as Attention Deficit Hyperactivity Disorder (ADHD) are not considered a health priority in developing countries. Health resources and efforts are targeted at treating infectious and nutritional diseases. In developed countries however, behavioral disorders receive significant attention. Rising literacy levels and fast paced economic growth is gradually fuelling an increased awareness of ADHD in India. The incidence of ADHD according to various studies ranges from 5 to 10%. Prevalence estimates of ADHD show a wide degree of variance, 303 full test articles and 102 studies involving 171,756 subjects worldwide were reviewed and the pooled prevalence was 5.29%1 . A comprehensive meta-analysis of 86 studies in children and adolescents revealed that the incidence of ADHD ranges from 5.9-7.1%2 . Individual studies also have revealed similar figures, One thousand four hundred and twenty five children from eight schools selected by random sampling methods in Turkey were given a questionnaire that was completed by their teachers or parents, 8.1% were found to have ADHD3 . A similar study in Iran revealed a prevalence rate in of 9.7%4 .Studies conducted in developing countries indicate an even higher incidence. Indian studies5, 6, 7 have estimated an incidence of 11-12%. Children with ADHD and learning disorders were frequently branded as either ‘difficult’ or ‘dullards’ in the past. Coverage of these topics in the press, movies, television and online have generated some awareness among the public but many assumptions, myths and misconceptions of ADHD persist, especially in non- metropolitan cities. There is a social and educational stigma associated with ADHD and most parents have difficulty in accepting or coming to terms with a diagnosis of ADHD8 . In India it is logistically difficult for health personnel to screen millions of students and identify children with ADHD. The people best suited for this purpose and to guide both pupils and parents are elementary school teachers. The purpose of this study is to assess the knowledge of ADHD among teachers in India and to correlate their knowledge with variables such as teaching experience and prior training or exposure.
MATERIAL AND METHODS
A self - report questionnaire was given to teachers in 32 primary schools, informed consent was obtained. 312 school teachers were assessed on their knowledge of ADHD. Sociodemographic information such as gender, teaching experience and prior training was elicited. The teachers were asked about any prior suspicion of ADHD in the classroom and their response to those suspicions in terms of reporting it to a superior, parental counselling or referral to a doctor. The source of their knowledge and the factors influencing their perception of ADHD was assessed. The teachers were asked about the need for a workshop/module on ADHD and their willingness to attend it. The knowledge of ADHD among the teachers was assessed by their awareness about 11 diagnostic symptoms and signs for ADHD based on the Diagnostic and statistical manual (DSM-IV-TR) 9 criteria.
RESULTS
In our study, out of the 312 respondents only 5 were males and an overwhelming majority was females. Nearly half the teachers in the study were relatively inexperienced and had less than 5 years of experience. 52 teachers had a teaching career spanning more than 20 years, but the best performers were not the teachers with the most experience or the novices, but the teachers in between, the ones with an experience of 10-20 years of pedagogy. The teaching Experience of the teachers is shown on Figure I. Only 28 teachers had prior training on ADHD. Eighty four teachers had past occasions where they suspected a student of having ADHD and had informed a superior or had counselled a parent to consult a doctor. All the teachers who had prior training were among this group of 84 teachers. A majority, 270 teachers felt a training session on ADHD was needed for teachers, but ironically 104 or one third of the teachers did not wish to attend such sessions. This is displayed on Table I. Most of the teachers who had some understanding of ADHD derived their knowledge from books and colleagues; this is shown on Figure II. Table II shows the knowledge of symptoms and signs of ADHD. Most of the teachers were aware of the term ‘ADHD’. But even among those aware, more than 4 out of every 5 teachers felt that their knowledge was inadequate, 7 of the 11 criteria were identified correctly by more than 50% of teachers. Table III shows the variables influencing awareness, since women outnumbered men among the teachers by a massive margin, gender as a variable was not considered. The two variables considered were teaching experience and prior knowledge. Teaching experience had a positive influence on awareness but the teachers in the middle rungs of experience performed a shade better than the veterans. Prior training also had a significant positive bearing on knowledge. None of the teachers got all 11 criteria correct but 19
teachers were able to identify 10 criteria correctly. The teacher’s questionnaires were evaluated and the scores obtained were divided into 4 subsets- those who were not aware of the term ‘ADHD’, correct score of 1 to 4, 4 to 8, and above 8. Teachers who identified more than 8 criteria correctly were rated to have good knowledge and only 92 teacher’s qualified for this accolade.
DISCUSSION
Teachers are uniquely placed to identify ADHD in children; they interact with children on a regular basis for lengthy durations, and may not have the emotional baggage and biases parents sometimes harbor. They are more likely to view the signs dispassionately and encourage referral. Teachers are also more likely to have prior experience or awareness and information on ADHD. In a Romanian study One hundred and eighty nine kindergarten and elementary school teachers had their knowledge on ADHD tested across 3 domains- general information, symptoms and treatment. The teachers performed best on the symptoms and diagnosis aspect. Teaching experience and prior exposure had a positive effect on their performance10. The present study too showed similar findings, all the 28 teachers who had prior training performed significantly better than their other colleagues. Teachers with more teaching experience tended to do better. A study on specific learning disabilities recruited 34 teachers in Puducherry, a multiple choice questionnaire format with 50 questions was used to assess teacher’s knowledge, and each question had 5 choices. The mean total score for this sample was 14.50 ± 9 and total item score for the 50 items was 9.90 ± 4. The researchers concluded that validation of this new screening questionnaire was successful in an Indian setting11. Although teachers are highly suited to identify behavioral disorders in children, not many teachers are sufficiently equipped with the training and knowledge required. A self- report questionnaire was given to American and Canadian school teachers. The questionnaire consisted of 20 true/false questions. Many teachers believed that affected children could outgrow ADHD and that diet had a role in its management. Only 14% of teachers had been involved in diagnosis of ADHD12. One hundred and thirty two school teachers in San Juan were given a questionnaire with 29 true or false questions derived from DSM IV TR diagnostic criteria for ADHD, 72 % of the teachers had poor knowledge13. Many teachers have misconceptions and biases about ADHD, A descriptive cross sectional study was conducted among 202 school teachers in Sri Lanka, only a minority had adequate knowledge about ADHD. Eighty percent of school teachers believed that parents were to be blamed for the child’s ADHD. The majority believed that disturbances created by these children were deliberate and malicious14. Teachers sometimes can tend to overestimate ADHD in classrooms; they may pigeon hole difficult children as behaviorally different. Teachers in a study identified 23.97% of students as meeting the criteria for having ADHD. The study revealed that class size and culture influences teachers perception of what students have the disorder15 . Perception of ADHD in children may differ in parents and teachers. In a study in Kuala Lumpur, 410 children, 37 school teachers and 367 parents from seven schools reliability of reporting ADHD symptoms were studied and there was weak correlations existed between the different group of participants16. The sources of information and consequently shaping of perception may vary. In a study conducted in 196 elementary school teachers in Iran the main sources of knowledge were revealed to be television, radio, friends, relatives and newspapers17 . In the present study books were attributed as the main source of information by nearly half the respondents, colleagues followed by television and movies were the other sources.
The present study also revealed that while teachers were aware of some symptoms and signs of ADHD, they were ignorant of many other signs and symptoms, very few teachers had a high score. In a study knowledge and attitude of ADHD in undergraduate education students was compared with school teachers, and teachers had better knowledge18. In the present study only 9% of the teachers had prior training on some aspects of ADHD and their performance was significantly better than their peers, therefore training teachers could make a difference in creating awareness and identifying more ADHD affected children. A teachers training program was conducted for 49 teachers in Karachi and the knowledge of ADHD was conducted prior and after the training and subsequently another test was repeated after 6 months, the teacher’s knowledge improved after training and was significantly better even after six months19. The mode of training or information could also have a bearing, There is a vociferous debate about whether workshops or training modules are better than distributing self - study material. Sixty seven school teachers in a study were divided into two groups, workshop education and non- attendance. A pre- test and post- test were administered in both groups while the first group went through a 2 day workshop the second group studied a booklet on ADHD. The knowledge in both groups was similar after the post –test but the workshop was more effective in attitude change20. Two groups of teachers, those who taught at academic school (25 teachers) and those who taught at a special education school (21 teachers) were tested for their knowledge and attitude about ADHD. Knowledge was similar in both groups but the special education teachers had a more positive attitude towards ADHD21.Innovative ideas such as online course material or interactive web based sessions may be more practical and as effective. A study in Nova Scotia revealed that a web based medium is a useful tool for ADHD knowledge creation and to bring about a behavior and attitude change in school teachers22 .
CONCLUSION
This study reveals that knowledge about ADHD is poor among primary school teachers in India. While a majority was aware of the term ‘ADHD’, only a small minority had adequate knowledge. Only 1 in 10 teachers had received some training on ADHD, these teachers performed better than their peers in the study. Most teachers attributed their knowledge about ADHD to books and colleagues. Teaching experience and prior training was positively correlated with knowledge of ADHD. Training teachers on aspects of ADHD would be beneficial and most teachers expressed a willingness to attend training sessions.
ACKNOWLEDGEMENT
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Ethical Clearance: Obtained. Conflict of Interest: None.
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10. Ezster P. Teachers knowledge about different features of attention deficit/hyperactivity disorder. Studia Universitatis Babes-Bolyai - PsychologiaPaedagogia 2011;1:47-54.
11. Lingeswaran A. Assessing knowledge of primary school teachers on specific learning disabilities in two schools in India. J Educ Health Promot 2013;2:30.
12. Jerome L, Gordon M, Hustler P. A comparison of American and Canadian teachers' knowledge and attitudes towards Attention Deficit Hyperactivity Disorder (ADHD). Can J Psychiatry 1994;39:563-7.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareAN AUDIT OF APPROPRIATE USAGE OF BLOOD PRODUCTS IN BLOOD BANK IN A TERTIARY CARE HOSPITAL RAJKOT
English3740Ankita A. Katara English Amit H. AgravatEnglish Gauravia DhruvaEnglish Jagdish D. DalsaniaEnglish Rutvi G. DaveEnglishTransfusion of blood and blood products such as Whole Blood, Red Cell Concentrate, Platelet Concentrate, and Fresh Frozen Plasma play an important role in treating hospitalised patients. The irrational use of medical technology is a major factor in increased healthcare expenses. We have done a crossectional studyto estimate the appropriate usage of blood and blood products transfusions in P.D.U. Medical College and Hospital, Rajkot,Gujarat,(India). Methodology: We analysed 1050 blood and blood products requests for transfusion. A total of 1078 blood and blood products transfusions were evaluated in these patients. A review of the patients medical record was done on each request for blood and blood products for examplediagnosis, indication for transfusion, number of units requested and the speciality prescribing it. Overall prevalence of appropriate use of blood and blood products was assessed according to NACO (National AIDS Control Organization) guidelines. Results: A total of 1050 requests were received for blood and blood products transfusion from various departments .These patients received 1078 transfusions.Maximum number of blood transfusion requests were received from Obstetrics and Gynecology department. Maximumnumber of transfusions were done in Medicine department. Out of these total transfusions, Red Cell Concentrates were maximum. According to our study maximum inappropriate transfusions were of Red Cell Concentrates.Total prevalence of appropriate use of blood and blood products was 81%. Conclusion: There is a need for continuous auditabout the use of blood and blood products as therapy. This helps in reduction of prevalence of inappropriate use of blood products, thus thereby reduces the expenditure on health care.
Englishwhole blood, RCC (Red Cell Concentrate, PC(Platelet Concentrate), FFP(Fresh Frozen Plasma), Prevalenceof appropriate useINTRODUCTION
Blood transfusion has become a very important part of modern health care. If used correctly, it can save life and improve health.However, like other therapeutic interventions, it may result in various types of complications. In addition, it carries the riskof transmission of infections like HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), Syphilis etc. It is also expensive and uses a scarcehuman resource. Inappropriate use causes increase in health expenditure and also puts patients at higher risk in acquiring Transfusion Transmitted Infections.The risks associated with transfusion can only be decreased by collaboration between the blood transfusion service and clinicians in managing the blood components for transfusion, approach of both should be to provide an adequate supply of safe blood and blood products and the effective clinical use of blood and blood products There is no any absolute acceptable level for all patients exists. But the concept of transfusion is only indicated when HemoglobinEnglishhttp://ijcrr.com/abstract.php?article_id=881http://ijcrr.com/article_html.php?did=881REFERENCES
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcarePHOSPHORUS-31 MR SPECTROSCOPY OF THE HUMAN BRAIN : TECHNICAL ASPECTS AND BIOMEDICAL APPLICATIONS
English4157Celi S. AndradeEnglish Maria C. G. OtaduyEnglish Eun J. ParkEnglish Claudia C. LeiteEnglishPhosphorus-31 magnetic resonance spectroscopy (31P-MRS) is a non-invasive method that provides useful information about metabolism and phosphoenergetic status in both physiologic and pathologic conditions of the human brain. With the progressive advances in magnetic resonance imaging (MRI) technology, particularly with higher magnetic field strengths, 31P-MRS has been more easily implemented and more readily available in the past few years, which has increasingly extended its access and favored its use in different research fields. However, the current knowledge about this advanced neuroimaging modality is still scarce and fragmented in the literature. Hence, in order to contribute to future researches and to shorten the gap between neuroscientific studies and common clinical routines, we present a comprehensive review about the basic technical aspects and biomedical applications of 31P-MRS.v
English31P-MRS, MRI, phosphorus spectroscopy, magnetic resonance imaging, neurometabolism, energetics, phospholipids, pH, magnesium, cell membraneINTRODUCTION
Magnetic resonance spectroscopy (MRS) offers the unique ability to noninvasively measure, in vivo, the chemical composition of biological tissues. This method can be combined to the anatomic information provided by magnetic resonance imaging (MRI), giving functional data that can improve the understanding of the pathophysiological processes at a molecular level (1,2) . Most MRS studies have focused in the evaluation of proton (1H) signal, due to the intrinsic physical characteristics of this nucleus and because it is possible to perform the proton spectroscopic acquisition with the same coil used to obtain conventional magnetic resonance (MR) images. However, with the progressive technical improvements in recent years, such as the development of different MRS pulse sequences, improvement of data processing, as well as commercial availability of high and ultra-high magnetic field scanners, phosphorus-31 magnetic resonance spectroscopy (31P-MRS) has been more easily implemented (3-5) . Our purpose is to provide a comprehensive overview about the concepts, technical aspects and implementation of 31P-MRS. Thereafter, we summarize the metabolites identified and their roles in brain physiology and pathology. The aim of this review is not to be an exhaustive compendium, but rather to guide and familiarize researchers and students with the basic principles of 31P-MRS
TECHNICAL ASPECTS
The nucleus has an intrinsic magnetic spin that is resultant from the uneven number of protons or neutrons. When exposed to a strong magnetic field, there is an alignment of these spins in a parallel or antiparallel direction to the applied field. If a specific radiofrequency pulse is applied for few microseconds (with the Characteristic precession frequency for each nucleus studied), there is a misalignment of the total Magnetization vector. When the radiofrequency (RF) pulse ceases, there is a realignment of the magnetic field, which generates a small electric signal, known as free induction decay (FID). This signal is detected by a RF coil, and, by means of transformation from time domain to frequency domain through a mathematical equation (Fourier transform), the spectral graph is obtained (6,7) . The precession frequency of the nuclei can be calculated by the Larmor equation, and it is proportional to the intensity of the magnetic field and to the gyromagnetic constant, which is specific to each chemical element or isotope. The nuclei within the molecules, however, suffer from small shifts of the precession frequency due to the magnetic field generated by adjacent electrons, and this phenomenon is called chemical shift. Each molecule has then specific chemical shifts, measured in Hertz (Hz) or parts per million (ppm) (6) . The result of this process is not an anatomical image, but a spectral graph, in which each metabolite has its specific position corresponding to the variation of resonance frequency (chemical shift), expressed in ppm on the horizontal scale (X axis), while the amplitude of each metabolite is represented in the vertical axis (Y axis), which allows their relative quantification (2,7-11) . Albeit not fully explored, 31P-MRS provides unique and relevant information about the bioenergetics state, the composition of the cell membrane, intracellular pH and the concentration of magnesium (Mg 2+), which cannot be obtained with other conventional or spectroscopic techniques (12) . However, this method has not been implemented widespread because it is necessary that the MR equipment is prepared to work in the resonance frequency of the phosphorus-31 ( 31P) nucleus, and it is also required a dedicated brain coil (Fig. 1) to detect the specific signal (12,13) . Just like the 1H nucleus, the 31P nucleus also represents a nuclear spin number of ½, capable to produce an MRI signal (Table 1). However, because of the physical characteristics of 31P (for example, greater mass), its gyromagnetic ratio (that indicates the level of the interaction between the nucleus and the magnetic field of the MRI scanner) is approximately 2.5 times lower than for 1H. This results in a lower resonance frequency - 51.7 MHz as compared to 127.7 MHz in a field of 3.0 T - and in a much lower sensitivity, only 6.6% when compared to 1H signal (14,15) . These factors imply that to obtain a satisfactory 31P spectrum, comparable to 1H spectrum, it is necessary to repeat the same acquisition several times in order to increase the signal-to-noise ratio (SNR) of the spectrum, resulting in a much longer acquisition time (16) . It should also be noted that the concentration of 31P metabolites (1- 14 mM) is lower than that of the metabolites detected in the 1H-MRS, which makes it even more difficult to obtain a 31P spectrum with sufficient signal intensity (Table 2) (14, 17-21) . Due to the short transverse relaxation time (T2) of the 31P metabolites, the techniques most commonly used to obtain the 1H spectrum, like stimulated echo acquisition mode (STEAM) and point resolved spectroscopy (PRESS), which are based on the formation of an echo, are not recommended for the acquisition of the 31P spectrum. These techniques require a minimum TE around 8 to 20 ms, which would result in a large loss of signal due to the transverse relaxation times for most metabolites. For this reason, the most commonly used techniques are the image selected in vivo spectroscopy (ISIS) or the pulse acquire technique (direct acquisition of the FID signal immediately after the RF pulse), which allow to obtain the signal with a minimum TE around 300 ?s (22,23) . In the ISIS technique, the localization of a slice is made through the acquisition of two FIDs, one generated after the application of a 180º pulse selective for one dimension, and the other generated without the prior application of this pulse. The subtraction of these two signals corresponds to the signal of one single slice (onedimensional, 1D ISIS). For the localization of a volume (three-dimensional, 3D ISIS), it is necessary to acquire eight FIDs. The difference is only whether the selective180º pulse is applied or not in a determined direction, resulting in eight different combinations. In practice, instead of working with subsequent subtraction of the signals, they are acquired with alternating phases (phase cycling), and only the signal of interest is recorded (24,25) . On the other hand, the pulse acquire technique allows only the selection of one single slice, but not a volume, the reason why it is not suitable for the study of minute structures. However, when combined with twodimensional (2D) or three-dimensional (3D) acquisition of the spectrum (acquisition of multiple volumes of interest, or voxels), it can also be used for evaluation of smaller volumes. The metabolites present in the spectral curve as single, double, triple or multiple peaks. The factor that generates the division of a resonance signal in two or more peaks in the spectrum is the interaction known as J coupling between adjacent nuclei in the same molecule (4) . The J coupling effect can be reduced or completely canceled in the spectrum if, during the signal acquisition, the nucleus responsible for this effect is irradiated by a second RF channel. This technique, used to reduce the J coupling effect, is known as decoupling (26) . 31P-MRS in vivo presents two double peaks and one triple peak of the adenosine triphosphate molecule (ATP) (27) . However, in this case, the cause of the J coupling effect is the interaction of a 31P nucleus with another 31P nucleus, what precludes the reduction of this effect by decoupling in the frequency of 1H nucleus. However, it is observed that the interaction between 1H and 31P within the same molecules, or even with the adjacent water, is large enough to cause broadening of the peaks observed in the 31P spectrum. This effect is particularly important for the phosphodiester peak (Fig. 2), but may also have a lesser effect on the intensity of the other peaks (28,29-33) . Through previous irradiation of the 1H nucleus, it is possible to transfer some of the energy absorbed by 1H to 31P, and thus increase the basic signal from the 31P nuclei. This effect is known as nuclear Overhauser enhancement (nOe). The intensity of the basic signal can be increased depending on the relation between the gyromagnetic constants of the irradiated and the observed nucleus, on the relaxation times of the nuclei, and on the chosen irradiation method. The nOe effect can also be produced when it is used only a decoupling pulse (because the 1H spins absorb energy that can be transferred to the 31P spins), and thus it could become an extra factor of variability that may affect the reproducibility of the method (34-36) . Therefore, it is recommended that, whenever a decoupling technique is applied, the1H nuclei should be irradiated prior to the acquisition of 31P-MRS, in order to produce a larger and more controlled nOe effect (Fig. 2). The spectroscopic examinations benefit from the use of higher magnetic field strengths that increase the sensitivity of the study and the spectral resolution, with at least linear increases in SNR. On the other hand, there is also an increase in distortions of the field related to the effects of magnetic susceptibility, which can be minimized with a procedure known as "shimming", held in the preparation phase of the exam with the aim to increase the homogeneity of the magnetic field within the region of interest (37- 39) . In order to achieve a spatial resolution that allows assessment of multiple regions of the brain and still offers sufficient SNR, the ideal strategy is to acquire 3D volumes, with a non-selective and adiabatic radiofrequency pulse, where the spatial localization is done with application of phase encoding gradients(16,40-42) . Figure 3 shows the planning of a 31P-MRS acquired with a three-dimensional chemical shift imaging (3DCSI) sequence with a multivoxel matrix that had total exam duration of 36 minutes. However, despite the need for adjustments of multiple parameters and the technical challenges for the acquisition of 31P-MRS, there are also some advantages of this modality of spectroscopy. A convenience of the 31P-MRS, as compared to 1H-MRS, is that, because it does not present signals from the water molecules, it is not necessary to apply saturation methods (6) . Another convenience in favor of 31P-MRS is that it presents a large range of dispersion of the chemical shift, around 30 ppm (parts per million) or 2000 Hz (at 3.0 T) (43) . This contributes to a good spectral resolution, with a satisfactory differentiation between the different resonances in the spectrum and an easy identification of the various metabolites, explained in detail in the next section.
METABOLITES
The great interest in 31P-MRS relies on the role that the phosphorylated molecules play in brain biochemistry, energy metabolism, and composition of cell membranes. Three main types of information can be obtained with this examination. The first one is related to the energy pool itself, with the resonances of phosphocreatine (PCr), inorganic phosphate (Pi) and the three isotopomers of adenosine triphosphate (α-, β-, and γ- ATP). Second, the phospholipids, represented by phosphomonoesters (PME) and phosphodiesters (PDE), inform about the synthesis and degradation of the cell membrane, respectively. Finally, it is possible to obtain the value of intracellular pH and the concentration of magnesium (Mg2+ ) (11). Figure 4 shows a typical 31P spectrum of the brain with identification of the main metabolites. Adenosine Triphosphate and Phosphocreatine 31P-MRS is able to distinguish ATP isotopomers in the form of three distinct peaks, from left to right in the curve: a doublet γ-ATP, a doublet α-ATP and a triplet β-ATP(43) .The ATP is mainly synthesized in the mitochondria (Fig. 5) from the oxidative phosphorylation of ADP (adenosine diphosphate) catalyzed by the enzyme ATP-synthase, and to a lesser extent by mechanisms of glycolysis, besides the synthesis from the creatinekinase reaction (44-46) . The PCr peak is the most prominent of the 31P spectrum of the brain, resonates at zero ppm, and, therefore, it is the reference to the localization of the other metabolites. PCr is a high-energy molecule, very abundant in the neural tissues, serving as a buffer to maintain a constant level of ATP and to support the demand of energy through the reaction catalyzed by creatinekinase (47) , as illustrated in Figure 5. Membrane Phospholipids The phosphomonoesters (PME) represent the anabolic activity of cell membranes and their main constituents are the phosphoethanolamine (PE) and phosphocholine (PC), precursors of membrane synthesis. The phosphodiesters (PDE) indicate, in turn, the catabolism of cell membranes, and are constituted by their degradation products, the glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC). The PDE are products of the phospholipase enzyme activity and are converted into PME by the activity of the enzyme phosphodiesterase. The ratio PME / PDE is an indicator of the turnover of cell membranes, and it is representative of changes in the phospholipids double-layer (48,49) . The functioning and the plasticity of the brain are dramatically influenced by the physical and chemical properties of the neuronal membrane. This membrane is formed by a double layer of phospholipids, with immersed receptors, ion channels and other proteins involved in signal transduction and maintenance of cellular homeostasis (50) . The structure of the cell membrane determines its fluidity, as well as the number, density and affinity of receptors that modulate the signaling mechanisms. In addition, phospholipids serve as a substrate for the synthesis of intra and intercellular mediators, which indicates their relevance in the mechanisms of neurotransmission (51-54) .
Intracellular pH and Magnesium
The peak of inorganic phosphate (Pi) is localized between the PME and PDE peaks. It is directly involved in the synthesis of ATP (Fig. 5), and its chemical shift relative to PCr peak (δ1) is used to calculate the intracellular pH, according to the formula (55-58):
Modulation of pH in the human brain is a puzzling combination of countless osmotic and metabolic mechanisms that are primarily related to the transport and diffusion of ions, buffer systems, activity of carbonic anhydrase and energy consumption (59-63) . Free cytosolic Mg2+ (pMg) can be estimated by in vivo 31P-MRS from the β-ATP chemical shift (δβ), which in turn depends on the fraction of total ATP linked to Mg2+, according to the equation below (55,64):
Table 3 summarizes the main metabolites obtained with 31P-MRS, indicating their position in the spectral curve and their roles in brain metabolism.
BIOMEDICAL APPLICATIONS
31P-MRS has been used in metabolic evaluation of the heart (65,66), liver (67-69), skeletal muscle (70-72) , and brain (73-75) in humans and animal models. In the investigation of the human brain, in particular, this method has shown some peculiarities in the pattern of physiological distribution of the phosphate metabolites. It was identified higher levels of PCr and PCr/ATP in gray matter compared to the white matter (76,77) . Another study found significant differences in the values of PME and PDE, which were higher in white matter compared to gray matter (78) . On the other hand, it does not seem to exist significant differences in the levels of Pi, intracellular pH or the concentration of Mg2+ between the white and gray matters (18,76). Most authors assume that the tissue specificity (gray matter versus white matter) is more important than the topography of the tissue (for example, occipital lobe versus frontal lobe). There is also no evidence of variations between the cortical or deep gray matters (77-79) . Evidence from studies in animals and humans suggest that the mitochondria undergo progressive morphological and functional changes with aging (80-82). The most consistent findings of studies that evaluated the effects of aging on the quantification of metabolites with 31P-MRS were increased levels of PCr and decreased intracellular pH. These investigations have also reported a reduction in PME and an increase in PDE, probably reflecting reduced synthesis and increased degradation of cell membranes (83-87) . In a study of 34 healthy volunteers, there were no significant differences between males and females for any of the brain metabolites quantified with 31P-MRS (85) . Because human brain is highly dependent on energy production in comparison to other organs, it is not surprising that energetic abnormalities are related to various brain disorders. 31P-MRS has been used in the investigation of a variety of neurological disorders: multiple sclerosis (88,89) , cerebral ischemia (90-92), migraine (93-95), and various neurodegenerative disorders (96-100) . 31P-MRS was also used in various studies to determine the metabolic profile of brain tumors. The results demonstrated trends to alkalinization in different histologic types, such as meningiomas, pituitary adenomas and glial tumors (101-105) . However, it is in the field of neuropsychiatric research that 31P-MRS has played a greater role. Indeed, it is believed that the phospholipid membrane plays a major role in some deterministic hypotheses of these diseases (52, 106, 107) . Some studies have shown a variety of abnormalities, mainly related to the membrane phospholipids and to measurements of intracellular pH in various diseases, such as schizophrenia (48, 108, 109), attention-deficit/ hyperactivity disorder (110, 111) , depression (107, 112) , and bipolar disorder (113) . Most studies of 31P-MRS in epilepsy were directed to the evaluation of mesial temporal sclerosis (MTS) (114- 118) . Despite some controversial findings and methodological differences in previous studies, it is believed that 31P-MRS will become a potential tool to aid in the lateralization of the epileptogenic focus, in the monitoring of clinical treatments, in defining the extent of surgical resection, and to predict the postoperative result (118-121). Our group has recently demonstrated several abnormalities in patients with epilepsy secondary to cortical malformations detected with 31P-MRS at 3.0 T (122) .
CONCLUSIONS
In conclusion, phosphorus metabolites play an important role in brain metabolism. However, the exact mechanisms in which they are involved in different neurological disorders remain to be determined. In the future, 31P-MRS may be a useful diagnostic tool, and may also help in the follow-up of patients and on the decision-making process. New studies are needed to better evaluate this method, and to ultimately shorten the distances between neuroscience and routine clinical practices. We believe that a better understanding of the 31P-MRS methodology and its applications is critical in the development of upcoming researches.
ACKNOWLEDGEMENTS
We are very grateful to FAPESP (São Paulo Research Foundation, ClnAPCe project 05/56464- 9) and CNPq (National Council for Scientific and Technological Development) for funding and support. Dr. Celi Santos Andrade is a recipient of a post-doctoral grant from FAPESP (2012/00398- 1 and 2013/1552-9). Dr. Claudia Costa Leite is supported by CNPq (308267/008-7).
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareSURGICAL MANAGEMENT OF CHRONIC SUPPURATIVE OSTEOMYELITIS OF MANDIBLE IN AN ELDERLY PATIENT - A CASE REPORT
English5864Meena VoraEnglish Harshal SuryavanshiEnglish Hemant BaonerkarEnglish Chaitanya HawaldarEnglishOsteomyelitis is usually the inflammation of bone and its marrow contents. Osteomyelitis of jaw commonly occurs as a complication of dental sepsis, but it is also seen in various other situations. It is usually a polymicrobial infection. It has been associated with multiple systemic diseases including diabetes, autoimmune states, malignancies, malnutrition, and acquired immunodeficiency syndrome. Before confirmation of osteomyelitis, one should rule out tooth as source of infection. The medications linked to osteomyelitis are steroids, chemotherapeutic agents, and bisphosphonates. Different terminologies and classification systems are used, based on a variety of features such as clinical course, pathological–anatomical or radiological features, etiology, and pathogenesis. It may be classified as acute, subacute or chronic, depending on the clinical presentation. Osteomyelitis of jaw is still a fairly common disease in maxillofacial clinics despite the introduction of new antibiotics and the improvement of dental care. The disease may occur at any age, with most common site being mandible. This is a case of an adult patient with chronic suppurative osteomyelitis (CSO), who reported to our department with pain and swelling in molar region of the mandible on right side. Here we report a case with detailed clinical, radiographical and histopathological features with differential diagnosis and treatment.
EnglishOsteomyelitis of jaws , surgical treatment of osteomyelitis, decortication, sequestrectomyINTRODUCTION
Osteomyelitis is one of the oldest diseases known to human being.(1) The word “Osteomyelitis” originates from the ancient Greek words osteon (bone) and muelinos (marrow) and means infection of medullary portion of the bone.(2) Osteomyelitis is an acute or chronic inflammatory process that can involve cortical and trabecular aspects of bone or bone marrow. The condition was originally described by Rees in 1947.(3) Osteomyelitis of jaw mainly caused by untreated odontogenic infection. Long standing infection in jaw can leads to the Chronicsuppurative osteomyelitis (CSO). It is an inflammatory reaction of bone to infection which originates from either decayed tooth, fracture site, soft tissue wound or surgical site.(4) Incidence can be aggravated with various systemic diseases. Chronic suppurative osteomyelitis is more common in mandible because of thick cortical bone and limited blood supply.(5) clinical presentation of CSO are with pain, swelling, trismus, localized pus discharge,paresthesia, warmth, erythema and tenderness.(2) CSO usually requires both medical and surgical treatment. The aim of surgery is to eliminate all of the infected and necrotic bony tissue.
CASE REPORT
A male patient aged of 50 years was reported to our department of oral and maxillofacial surgery with chief complaint of pain and swelling in the lower right posterior region of jaw and face since past 2 months.(fig 1) He also gave the history of decreased sensory sensation over the same area. History also revealed that swelling was gradual in onset and slowly increased, but it was decreased after pus discharge. He also gave the history of extraction of lower right 1st molar 3 months back. Medical history was not contributory in this case. On extraoral clinical examination draining sinus was observed on right side of inferior border of mandible region. Cervical lymphadenopathy and regional paresthesia was also present.(fig 2) On intraoral clinical examination pus discharge was seen in extraction socket of right mandibular 1 st molar. There was mild appreciable swelling present on buccal aspect of right mandibular 2nd molar. This area was also slightly tender on palpation.(fig 2) Then patient was advised for radiological investigations. Onorthopantogram, multi locular radiolucency with ill defined borders was seen in right body of mandible, which gave presentation of typical “Moth eaten” appearance.(fig 3) Bone biopsy was also done under local anesthesia. It shows nonspecific inflammatory cell infiltration in bone. On the basis of case history, clinical and radiological finding, the provisional diagnosis as chronic suppurative osteomyelitis was made. Immediate treatment was started with empirical antibiotic (amoxicillin + potassium Clavulanic acid + metronidazole), than surgical treatment as sequestrectomy and decortication was planned. Surgery was planned under general anesthesia. Under proper surgical protocol , the pathology was exposed intra orally. Decortication was done with help of bone rongeurand rotary bone cutting instrument.(fig 4) At same time sequestrectomy and curettage was also done. Excised specimen was send to histopathology department.(fig 5) Extra orally the sinus tract was located and excised. Extra oral and intra oral suturing was done.(fig 6)Post operative antibiotic therapy was given for four weeks. Patient was well responded to both antibiotic and surgical treatment. After surgery healing over surgical area was uneventful. Histopathological report confirmed the final diagnosis as chronic suppurative osteomyelitis. Patient was kept under constant follow up. Clinically there was no sign of residual infection reported after 3 months.(fig 7)Orthopantogram was also taken after 3 months.(fig 8)
DISCUSSION
Osteomyelitis is unique jaw pathology with typical clinical and radiological presentation, but still it is challenging condition to diagnose and treat.Now a days it is less common condition due to improved nutrition, dental care and availability of newer antibiotics.Osteomyelitis may be defined as inflammatory condition of bone, that begins as an infection of medullary cavity and haversian system of the cortex and extends to involve the periosteum of affected bone.(6) It can be classify as acute, subacute, chronic, suppurative and non suppurative variant.(2)Odontogenic infection, traumatic injuries, radiations, these are main etiological factors of CSO.(4) The four primary factors which are responsible for deep bacterial invasion into the medullary cavity and cortical bone and hence establishment of the infection are number of pathogens, virulence of pathogens, local and systemic host immunity, local tissue perfusion. Pathological fracture and paresthesia are serious complications associated with osteomyelitis.(5) Our case report is typically demonstrate the features of CSO. The typical age of presentation is in the fifties to the sixties, with males more likely to be affected.(4) The commonest site is the posterior body of the mandible, because of poor blood supply and dense cortical bone.(2) Pain, fever, cheek swelling, pus discharge, exposed bone are common symptoms.(2) But progressive bone destruction and formation of sequestra are hallmark of osteomyelitis.(5) For understanding of accurate extent of bone destruction panoramic radiography, cone beam computed tomography and scintigraphy are preferred. In our case radiographic “moth eaten” appearance seen, And on histological study “inflammatory cells infiltrating in necrotic bone with loss of osteoblast” was reported which are typical presentation of CSO.(12)(6) The treatment of osteomyelitis is consider most difficult. Treatment of CSO includes antibiotic therapy, elimination of cause, incision and drainage, sequestrectomy, saucerisation, decortication, resection of jaw with reconstruction and hyperbaric oxygen.(7) Osteomyelitis is polymicrobial infection but Staphylococcus aureus and staphylococcus epidermidis are said to be primarily causative agent.(6)(8) Selecting antibiotics is based on identified bacteria from culture sensitivity test, but empirical antibiotics started as early as possible. Penicillin remain drug of choice for osteomyelitis,(2) but penicillinase resistant penicillin, clindamycin, cephalosporines are also used. Surgical management as an adjunct to medical treatment usually is necessary. The goal of surgical intervention is to disrupt the infectious foci and removal of necrotic bone or sequesra.(9) Treatment mainly involves decortication and sequestrectomy. Sequestrum is avascular, therefore poorly penetrated by antibiotics. Which leads to progression of bone destruction. Once the sequestrum has formed completely, it can be removed with a minimum of surgical trauma, which is known as sequestrectomy.(5)(6) Decortication refers to the removal of chronically infected cortex of bone. Which brings reflected buccalmucoperiostealflap closer to the medullary cavity , thus facilitate the healing process.(5)(6) Now a days medicinal and surgical treatment is combined with newer treatment such as hyperbaric oxygen (HBO) therapy, gentamycin/tobramycin beads, heaparin, streptokinase infusion, which leads to better result.(5)
CONCLUSION
We conclude our study and experience on following notes,
Early recognition of osteomyelitis and its treatment can reduce extensive loss ofbone, thereby preventing further spread of disease and possible loss of teeth. • If it is not treated can be resulting in discontinuity defect. • Associated Systemic disease should always be considered. • Culture sensitivity test plays vital role in selection of antibiotic therapy. • HBO (Hyperbaric oxygen) therapy provides better results in resistant osteomyelitis. • Risk of infection remaining in latent form should always be kept in mind.
ACKNOWLEDGEMENT
Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. We also would like to thank our senior professor Late Dr.M.D.Shringarpure (MDS - oral surgery & oral radiology) for his valuable guidance during treatment of this case.
Englishhttp://ijcrr.com/abstract.php?article_id=883http://ijcrr.com/article_html.php?did=883REFERENCES
1. Klenerman L.A history of osteomyelitis from the Journal of Bone and Joint Surgery.J Bone Joint Surg [Br] 2007;89-B:667-70.
2. Mallikarjun K, Kohli A, Arvind K, Vatsala V, Bhayya DP, Shyagali TR.Chronic Suppurative Osteomyelitis of the mandible- A Case Report.J. Int Oral Health 2011;Volume 3 Issue 2.
3. Singh M, Singh S, Jain J, Singh KT. Chronic suppurative osteomyelitis of maxilla mimicking actinimycotic osteomyelitis: A rare case report.Natl J Maxillofac Surg. 2010 Jul;1(2):153-6
4. Yeoh SC, MacMahon S, Schifter M.Chronic suppurative osteomyelitis of the mandible: case report.Aust Dent J. 2005 Sep;50(3):200-3
5. Mamatha NS,Shah AK, Singh M, Pavan VN.Chronic suppurative osteomyelitis in a six year old boy.Journal of Health Sciences and Research,2011 Aug; Volume 2, Number 2.
6. Topazian RG, Golgberg MH, Hupp JR. Oral and maxillofacial infections. 4th ed. USA: Saunders company press; 2002 .p. 214-42.
7. Nezafati S,Ghavimi MA, Yavari AS.Localized Osteomyelitis of the Mandible Secondary to Dental Treatment: Report of a Case.J Dent Res Dent Clin Dent Prospect 2009; 3(2):67- 69.
8. Gaetti-Jardim, E. Jr. Ciesielski, F, I, N, Possagno, R, Castro, A. L,Marqueti AC, Gaetti-Jardim.Chronic osteomyelitis of the maxilla and mandible: microbiological and clinical aspects. Int. J. Odontostomat., 4(2):197-202, 2010.
9. Arunkumar JS, Naik AS, Prasad KC, Santhosh SG.Role of Nasal Endoscopy in Chronic Osteomyelitis of Maxilla and Zygoma: A Case Report.Case Reports in Medicine;Volume 2011, Article ID 802964.
10. Yanamoto S, Kawasaki G, Yoshitomi I, Mizuno A.Diffuse chronic sclerosing osteomyelitis of the mandible with synovitis, acne, pustulosis, hyperostosis, and osteitis: report of a long-term follow-up case.J Oral Maxillofac Surg. 2010 Jan;68(1):212-7.
11. Ali K, Akram A, Akhtar MU.An unusual case of chronic suppurative osteomyelitis of the mandible.Arch Orofac Sci (2012), 7(1): 37-41.
12. Shafer WG, Hine MK, Levy BM, A textbook of Oral Pathology. 4th ed. Philadelphia: Saunders; 1993: p. 498.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareCONSUMER CONCERNS ABOUT THE USE OF ADDITIVES IN PROCESSED FOODS
English6572Ismail B.B.English Yusuf H.L.EnglishObjective: To determine the level of concerns of the respondents about the use of additives in processed foods and how it affects the way that they behave when purchasing processed foods containing additives. Method: A total of 50 respondents from the Medway area of Kent, United Kingdom, participated in the face to face interview which comprised 20 questions out of which six were used to determine the level of concern of the consumers about the use of additives in foods. Additional questions were asked on the respondents’ demographic status and purchasing pattern of processed foods. Result: The result indicated that themajority of the respondents are concerned about the use of additives in processed foods from the viewpoint of health. Specific concerns by the majority of the respondents include the use of salt, sugar, preservatives and colouring agents in foods which is viewed as something negative, and this outweighed any perceptions about the positive functions that additives can perform, including improving the safety and extending the shelf life of foods. Conclusion: Most concerns regarding the use of additives in processed foods were related to long term health effects which include development of allergies, hyperactivity, asthma, hay fever and cancer.
EnglishConsumer concerns, health effects, food additives, questionnaire surveyINTRODUCTION
In the 20th Century, food industries have gone through immense development through technological advancement accompanied by the increased use of additives in food processing (Diehl, 2002). Many people nowadays eat readyto-eat foods rather than preparing meals at home and for the maintenance of quality and shelf life of these foods, additives and preservatives are used, with salt and sugar being the most commonly used (Abdulmumeen et al.,2012). However, in recent times, despite the fact that additives have been used for many centuries, there have been increasing concerns amongst consumers about the use of additives, particularly artificial additives, in processed foods. Scientific studies have suggested that excessive intake of synthetic additives may result in adverse health conditions including hyperactivity, the development of an allergy and asthma (Wilson and Bahna, 2005; Randhawa and Bahna, 2009). Consumers are also doubtful about the effectiveness of various regulations on food additives established for the protection of their health (Tarnavölgyi, 2003; Shim et al., 2012). This has resulted in certain misconceptions and perceived adverse effects which may sometimes be false due to lack of scientific evidence. A survey conducted in 2007 by the Food Standards Agency (FSA) in the United Kingdom (UK) on Consumer Attitudes to Food Standards which aimed at determining the consumer attitudes, knowledge, and awareness with regards to food related issues indicated an increase in consumer safety concerns and more specifically regarding food additives/preservatives (Figure 1) with levels of concern about issues such as salt and sugar levels in foods higher than in earlier surveys. Salt was a major concern and mentioned by almost half of the UK respondents (50%), sugar (39%) and food additives (35%) (FSA, 2007).
Regarding issues related to foods (Figure 2), Food additives/preservatives had the highest percentage of consumer concern (8%) followed by poor, unhealthy diet/children’s diet (4%) and 3% for both use of pesticides/chemicals, price, packaging and food labelling
In 2012, the Biannual Public Attitudes Tracker survey conducted by the FSA (Figure 3) revealed similar results with the amount of salt in foods being the second highest food issue of concern (49%)) although food prices (63%) were the area of highest concern amongst respondents. The other main areas of concern related to food safety included the amount of sugar in food (42%) food additives in processed foods (28%) and food poisoning (32%).
MATERIALS AND METHODS
The aim of this study was to investigate the level of concern about the use of additives in processed foods. Data were collected using a questionnaire survey conducted through face to face interviews. The questionnaire consisted of 20 questions out of which six questionswere used to determine the concerns of the consumers. The respondents’ demographic information was also collected for building a profile of the respondents and when using the data to see whether these characteristics have affected their responses to questions. A total of 50 respondents mostly adults over the age of 18 participated in the face to face interview carried out in public places such as cafes, parks, kiosks and other public gathering centres in the Medway area of Kent, United Kingdom. The type of questions and their justification is presented in Table 1.
Analysis of data
The responses from the survey were calculated in percentage for each question and the results are presented in tables and figures and discussed.
RESULTS
Demographic data were collected for the respondents and their influence on responses was determined. Of the people who took part in the survey, 54% were male and 46% female. For the level of education, 24% have secondary level, 24% vocational training/college, 18% undergraduate and 24% postgraduate levels of education.
DISCUSSIONS
Safety concerns and perceptions about food additives
In order to determine the level of concern among the respondents about food additives in relation to other food issues, respondents were asked to select the type/basis of concern that they have about various issues on the basis of food safety, long term health effects, and food quality. The results presented in Table 2 show that the majority of the respondents (62%) were concerned about high levels of sugar/salt in foods followed by the use of additives/preservatives in foods (52%) on the basis of long term health effects. This indicates that most concerns about the use of additives in processed foods were based on their long term health effects. This agrees with the findings of the previous surveys conducted in 2007 and 2012 by the FSA on Consumer Attitudes to Food Standards which indicated that from the health point of view, salt was a major concern and mentioned by almost half of the UK respondents (50%), sugar (39%) and food additives (35%), With regards to food safety, pesticides residues in foods were cited as being a concern by the highest percentage of respondents (44%) and this may be attributed to the controversies and rising consumer concerns about pesticide residues in foods and its impact on the safety of foods (FSA 2007; FSA 2012). The food issue with the highest percentage of respondents saying that they were “not concerned” was GMOs and this may be attributed to the general unavailability of products containing GMOs on the UK market due to restrictions by various EU regulations which put in place stringent controls on the sale of GMOs in the EU.
Perceived health risks associated with the consumption of additives in processed foods
A list of health risks that have been linked to food additives in the press (Randhawa and Bahna 2009) was presented to the respondents and they were asked to select the one they were most concerned about. Figure 4 shows “developing an allergy” was selected by the largest proportion of the respondents (44%), followed by hyperactivity (24%). This was similar to the findings of a review by Randhawa and Bahna (2009) on hypersensitivity reactions to food additives and a survey by Wu et al. (2013) on identifying critical factors influencing the use of additives by food enterprises in China which indicated that consumer perceived health risks linked to the consumption of additives in food include hyperactivity, developing an allergy, asthma, hay fever as well as body reactions.“Other” health risks mentioned by 8% of the respondents included cancer and ill health. Dicks (2007) suggested that when consumers have real concerns, they fail to trust food regulators, producers and processors. Hence, this can serve as an obstacle that could influence their purchasing behaviour.
Additives used in processed foods that are of concern from the health point of view
A list of natural and artificial additives was presented to the respondents and they were asked to select those that they were concerned about from a health point of view. Respondents were allowed to choose more than one option. Table 3 shows that the majority of the respondents chose salt (70%) as the additive of concern from the health point of view. This was followed by sugar and colouring agents (52% each) and preservatives (50%). Salt is a major concern for the public despite its importance in foods due its link with hypertension, which leads to cardiovascular disease (He and MacGregor 2008). Consumers are also concerned about high sugar levels in food. Findings by Morengaet al. (2013) on dietary sugars and body weight suggested that despite the importance of sugar in foods, its prolonged consumption has been attributed to some adverse health conditions such as dental caries, cardiovascular disease, obesity, gout, some cancers, hyperactivity and fatty liver disease. From the list of artificial additives of the majority of the respondents, (52%) said that they were concerned about colouring agents. Many consumers have been concerned that colouring agents are used by processors as ways of hiding the inferior quality of foods and are disturbed by reports that some artificial colouring agents used in foods may be carcinogenic or cause allergic reactions (Dicks 2007).
Concern about the levels of salt in processed foods
Respondents were asked whether they were concerned about the levels of salt in processed foods and if they were aware of the recommended maximum daily intake in the UK. Interestingly, Table 4 shows that the vast majority of the respondents (96%) were concerned about the levels of salt in processed foods and 64% were aware that the recommended maximum daily intake is 6g. This can be attributed to public education reduction strategies and campaigns that have been implemented in the UK by the FSA. Surprisingly, despite concerns about high levels of salt in processed foods, most respondents (96% in Table 4) still reported that they consumed high salt foods such as snacks and pickled foods.
Main reasons for avoiding food additives
Respondents were asked about the main reasons that they had for avoiding food additives. Figure 5 shows that 46% said that they avoided additives because they are bad for their health and 36% said they are unnatural. This is linked to Question (1) about the basis of concern for the use of additives which indicated health risk as an important concern by the consumers regarding the use of additives in foods.
CONCLUSIONS
This questionnaire survey determined consumer concerns about the use of additives in processed foods and how it affects the way that they behave when purchasing processed foods containing additives. The basis of concern is also important for the Government and other stakeholders such as processors to understand, in order to maintain consumer confidence in their ability to protect their interests, and make sure that their safety had not been compromised. The result of the study indicated the rising concern about the use of additives in processed foods especially salt which is a major concern by the vast majority of the respondents (94%). The recommended daily intake of salt was correctly identified by a majority of respondents. Recent information campaigns produced by the FSA that informed consumers about the recommended maximum daily intake of salt may explain this. The results of the study indicated that most respondent’s concerns regarding the use of additives in processed foods were related to long term health effects. Additives have been linked with various health issues such as the development of allergies, hyperactivity, asthma, hay fever and cancer. A contradiction in the views of respondents was that despite their concern about potential health risks, everyone reported buying processed foods containing additives. Specific examples included crisps, chocolate bars and pickled vegetables; onions, gherkins and olives which contain significant levels of salt, sugar or other artificial additives. Provision of abalanced and science based information about food additives through consumer trusted sources describing the potential benefits and risks of food additives, and addressing the concerns of consumers, will likely reduce the level of concern about long term health effects.
ACKNOWLEDGEMENT
I wish to acknowledge the generous guidance and support of my MSc supervisor Dr. Richard Fuchs, Programme Leader for the MSc programme in Food safety and quality management, University of Greenwich, United Kingdom. Authors acknowledged the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=884http://ijcrr.com/article_html.php?did=884REFERENCES
1. AbdulmumeenHA, Risikat AN, Sururah AR Foods: its preservatives additives and applications. International Journal of Chemical and Biochemical Sciences2012; 1: 36-47.
2. Dicks EG. (2007) A model of consumers' perceptions of food additives and consequent Purchasing behaviour Available from: https://www.google.co.uk/search?q=A+model +of+consumers'+perceptions+of+food+additiv es+and+consequentpurchasing+behaviourand rls =com.microsoft:en-gband ie=UTF-8and oe=UTF- 8and startIndex=and startPage=1and gws_rd=crand ei= RQpwUubHGuLR0QW7zIDwCQ(accessed 24 October 2013).
3. Diehl JF. Some established facts and some new concepts in food toxicology. A review.ActaAlimentaria2002;31:355-369.
4. Food Standards Agency (2007) Consumer attitudes to food standards: Wave 8 UK Report Final. Available from: http://www.foodbase.org.uk//admintools/repor tdocuments/441-1-777_cas2007ukreport.pdf (accessed 6 July 2013).
5. Food Standards Agency (2012) Biannual Public Attitudes Tracker UK Report Final. Available from: http://www.food.gov.uk/multimedia/pdfs/bian nualpublicattitudestrack.pdf (accessed 24 September 2013).
6. He F, MacGregor GA. A comprehensive review on salt and health and current experience of world-wide salt reduction programmes. Journal of Human Hypertension 2008; 23:1-22.
7. Morenga LT, Mallard S, Mann J. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies. British Medical Journal 2013; 349:1-25.
8. Randhawa S, Bahna SL. Hypersensitivity reactions to food additives. Current Opinion in Allergy and Clinical Immunology 2009; 9: 278–283.
9. Shim S, Seo SH, Lee Y, Moon G, Kim M, Park J. Consumers’ knowledge and safety perceptions of food additives: Evaluation on the effectiveness of transmitting information on preservatives. Journal of Food Control 2012;22: 1054-1060.
10. Tarnavölgyi G. Analysis of consumers. Attitudes towards food additives using focus group survey. Agriculturae Conspectus Scientificus 2003; 68:193-196.
11. Wilson BG, Bahna S L. Adverse reactions to food additives. Annals of Allergy, Asthma and Immunology 2005; 95:499-507.
12. Wu L, Zhang Q, Shan L, Chen Z. Identifying critical factors influencing the use of additives by food enterprises in China. Journal of Food Control 2013; 31: 425-432.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareROLE OF INTRAMEDULLARY INTERLOCKING NAIL IN FRACTURE FEMUR AMONG ADULTS - A PROSPECTIVE STUDY IN A TERTIARY CARE HOSPITAL, ANDHRA PRADESH, INDIA
English7379V. Nageswara RaoEnglish Lavanya K.M.English C. Hanumantha RaoEnglishBackground: Fractures of the femur are among the most common fractures encountered in orthopaedic practice since this long bone along with tibia form the principle load bearing bone in the lower extremity.They also form the strongest bones of the body, however, they are frequently fractured due to multiple causes. With recent advances in biplanar imaging, there has been a renewed interest in closed intramedullary interlocking nailing. Hence an attempt has been made to study the role of intramedullary interlocking nail in fracture femur among adults. Aims and Objectives: To study the role of intramedullary interlocking nail in fracture femur among adults in a tertiary care hospital, Andhra Pradesh, India. Material and Methods: Study Design: Prospective study Study Area: Tertiary care hospital, Rajahmundry. Study Period: 18 months (July 2011 to Dec 2012) Study Tools: A Predesigned and Pretested questionnaire, Measuring tape, Stethoscope, X-ray Chest and Femur, Routine blood investigations, Urine routine, ECG Sample Size:102, Statistical Analysis: Analyzed using Microsoft Excel 2007 and Epi info version 3.5.2 Results: The age of presentation varied from 19-64 years with a Mean age of 37.39.The incidence was significantly higher in Males (42 males and 8 females), Right side (65.2%) involvement was more, RTA was the main cause of trauma. 84 (91.28%), Closed type 72 (78.24%) of injuries was more commonMajority of the cases were Oblique type 48 (52.16%).Most of the fractures occurred at middle third zone 36 (39.12%).Most common complication was Hip Pain, 16 (17.39%).Union was achieved in majority 76 (82.6%) of the cases, between 12-24 weeks.Mean union time was 16.6 weeks. Conclusions: Closed interlocking nail fixation is the procedure of choicefor femoral shaft fractures.
EnglishIntramedullary interlocking nail, Fracture femur, AdultsINTRODUCTION
Fractures of the femur are among the most common fractures encountered in orthopaedic practice since this long bone along with tibia form the principle load bearing bone in the lower extremity. They also form the strongest bones of the body, however, they are frequently fractured due to multiple causes. With recent advances in biplanar imaging, there has been a renewed interest in closed intramedullary interlocking nailing. Hence an attempt has been made to study the role of intramedullary interlocking nail in fracture femur among adults.
AIMS AND OBJECTIVES:
To study the role of intramedullary interlocking nail in fracture femur among adults in a tertiary care hospital, Andhra Pradesh, India.
MATERIAL AND METHODS
AProspective study of all cases with fracture femur admitted in a tertiary care hospital, Andhra Pradesh, during a period of 18 months (July 2011 to Dec 2012) was conducted. A total of 102 cases were admitted of which 10 patients did not consent for the study and hence the number came to 92. All patients with fracture shaft of femur above 18 years of age, all closed fractures and open fractures of type I, II, IIIA (Gustilo – Anderson) who consented for the study were included while pathological fractures, fractures within 5 cm distal to lesser trochanter and 5 cm proximal to knee joint, open fractures of type IIIB, IIIC (Gustilo – Anderson), ipsilateral fractures of femur and tibia and those who failed to consent were excluded from the study. A Predesigned and Pretested questionnaire containing questions about the detailed history with special reference to the mode of injury and severity of trauma was used. This was followed by physical examination including a comprehensive orthopaedic examination of the injured limb and other limbs. The involved extremity was examined for swelling, deformity, discoloration, skin integrity, neurological, motor and vascular compromise and signs or symptoms of compartment syndrome. Medical and General surgical evaluation was sought expeditiously for all high – energy accident victims to rule out polytrauma. Radiological examination of Femur with ipsilateral hip and knee joints both preoperatively and postoperatively were taken for evaluation.X-ray Chest, Routine blood investigations, Urine routine, ECG were all done and also medical and anaesthetist opinion were taken to explore fitness of the patients for surgery.The purpose of the study was explained in local language and a written informed consent was taken from the patients. They were free to withdraw from the study anytime they wished.
Management of diaphyseal fractures of femur
Our management followed the following fixedpattern for every patient Pre-Operative management include 1) Stabilization 2) Diagnosing other associated injuries 1) Stabilization of the patient a) Emergency care b) Immobilization of the affected limb c) Investigations a) Emergency care Special attention was given to cardiopulmonary status. Vital signs were monitored. The arterial status of the limb was under constant supervision in cases of the fracture distal 1/3rd of Femur. All the open injuries were thoroughly debrided in the operation theatre. b) Immobilization of the affected limb: Immobilization of the affected limb was done in Thomas splint, to prevent soft tissue damage, to decrease pain, and for easy mobilization of the patient. Skeletal traction was applied for open and comminuted fractures. c) Investigations: The following investigations were carried out routinely. i) Routine blood investigations ii) Urine routine iii) Special tests:ECG, Chest X-ray PA view (> 40 years) iv) Radiographs: 1. Anteroposterior and lateral views of the entire long bone including the joint proximal and distal to it. 2. The pelvis exposing both the hip joints: AP view. The interval between the injury and the definitive operation ranged from 2 days to 12 days (mean 7 days).
Nail used in the study
First generation intramedullary interlocking nail
It is a hollow tubular nail with a circular cross section. Proximal end is expanded to give additional strength for proximal screw fixation. It has position slots to lock the jig. Its 2mm wall thickness gives the nail certain flexibility on bending. Proximal end has got threads on the inner side that provides secure fixation of the threaded conical bolt for attachment of jig/extractor. Nail used for femur interlocking has a curvature to the average anatomic curvature of the femur. For locking there are 2 holes on either side, at the proximal and distal ends of the nail. Circular holes for static locking measure 5 mm. Nails in diameters of 9, 10 and 11mm with length from 340-440 mm with increments of 20 mm were used for femur interlocking. Locking screws are self tapping, 4.5mm available from 25-95mm in 5 mm increments. Follow up All the patients were followed up. With each follow up, clinical and radiological examinations were performed at 6 weeks,12 weeks,18 weeks, 24 weeks. Final assessment was done at the end of 6 months. Clinical examination included evaluation of complaints by the patients, assessment of the range of motion, assessment of the soft tissues, evaluation of the rotational alignment, leg length discrepancy and deformities, if any. Finally the functional implications were evaluated. Radiological examination was performed in two planes and assessed for callus formation. Varus / Valgus and Flexion / Extension deformities if any were assessed. ?Union? was defined as the appearance of bridging callus and trabeculations extending across the fracture site. ?Nonunion? was defined as no evidence of fracture union progression in 6 months of follow up. ?Delayed union? was defined as the appearance of the signs of fracture union, but the progress of union to consolidation is delayed than is otherwise expected.
FUNCTIONAL RESULTS
Functional results were graded based on the classification system for the results of treatment by
Thoresen B.O., et al., (1985)
1 The results were designated as excellent, good, fair or poor according to the alignment of the fracture, the range of motion of ipsilateral knee, and the shortening of femur, and the degree of pain or swelling.
RESULTS
Age – wise distribution of patients showed that Majority 44 (47.81%) of them were between 21 to 40 years, followed by 32 (34.78%) in 41 to 60 years and 8 (8.7%) each below 20 years and above 60 years. Mean age for fracture Femur was 37.39 years Sex distribution: Majority 80 (86.9%) of the patients in our study were males and 12 (13.1%) were females. Side incidence: showed right side predominance 60 (65.23%) with32 (34.77%) on left side. RTA was the main cause of trauma. 84 (91.28%) met with accident while 8 (8.72%) had fall from heightresulting in fracture femur Closed type 72 (78.24%) of injuries was more common than open type 20 (21.76%)
Pattern of fracture
Majority of the fractures were oblique type followed by transverse, spiral, comminuted and segmental types.
Anatomical location:
Majority36 (39.12%) of fractures were at the middle third zone followed by the junction of middle third and lower third 32 (34.78%) and the junction of upper third and middle third 24 (26%) Associated injuries with fracture shaft of femur: There were 12 (13%) cases with head injury, 8 (8.7%) cases with fracture clavicle, 4 (4.3%) case each with Colles fracture and fracture pelvis, associated with fracture shaft of femur amounting to a total of 28 (30.43%).
Complications
Most common complication was Hip Pain, 16 (17.39%) followed by Superficial Infection 8 (8.7%), Delayed Union 8 (8.7%) and Shortening 4 (4.34%) Superficial infections resolved by regular dressings and antibiotics
Weight bearing:
Patients were allowed to walk without bearing weight on the operated leg with the help of crutches/walker on an average between postoperative day 2 - day 5. Three patients with significant comminution were advised delayed weight bearing.Weightbearing without support was advocated when clinico-radiological signs of union was observed.In 85 (92.39%) patients full weight bearing was started between 12-14 weeks.
Secondary procedure
Eight (8.7%) patients of fracture femur who showed minimal radiological signs of union at the end of 6 weeks underwent dynamisation and union occurred at 25 to 26 weeks.
Range of motion
88 (95.65%) of the 92 patients had full range of motion at the knee at union.4 (4.35%) patients had flexion at knee around 900 -1000 . All patients had full range of hip motion at union.
Union Rates
In ourstudy of 92 cases, union was achieved in majority 76 (82.6%) of the cases, between 12-24 weeks. Only in 8 (8.7%) cases, union was achieved in 2cm in 2% of cases and malrotation>20 degrees in 2.3% of the patients. In series of Douglas and Wiss4 nonunion was seen in 2% of cases, angulation >10 degrees in 2.5% of the patients, external rotation deformity in 7% of patients. There were no instances of deep infection or osteomyelitis. In the series of George White et. al. nonunion was seen in 1.1% cases, 5.5% had a mild angulatory deformity, shortening >1cm seen in 3.1% of the pts. Final assessment was done at end of 6 months and functional results were graded based on the classification system for the results of treatment of fracture shaft of femur by Thoresen B.O., et al.1 .The results were designated as excellent, good, fair or poor according to the alignment of the fracture, the range of motion of ipsilateral knee, and the shortening of femur, and the degree of pain or swelling. In the current series of fracture femur, 78.24% have got excellent results, 17.39% good and 4.34% fair results. The series of Thoresenet al1 .had excellent results in 63.8%, good in 16.9%, fair in 14.8% and poor in 4.2%.
CONCLUSION
Fractures of the femur are the injuries sustained in high velocity trauma. Internal fixation is the mainstay of treatment. Conventional plating is associated with high risk of infection, malunion, non union, implant failure.Interlocking techniques lead to fewer complications of nonunion/malunion, lesser soft tissue dissection, earlier fracture healing and lesser chances of infection. Fractures in any zone from the Subtrochanteric to distal supracondylar part of the femur is accessible to nailing.Closed nailing results in less intraoperative blood loss, shorter operative time, earlier weight bearing and union and early return to work with reduced morbidity compared to the open techniques. Closed interlocking nail fixation is the procedure of choicefor femoral shaft fractures.
ACKNOWLEDGEMENT
Authors acknowledge all the study subjects who have extended their kind co-operation and support in this research. Authors also acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=885http://ijcrr.com/article_html.php?did=885REFERENCES
1. Thoresen BO, Acho A, Ekeland A, Stromsoe K, Folleras G, Haukebo A. Interlocking intramedullary nailing in femoral shaft fractures - A report of forty eight cases. J Bone and Joint Surg, 1985; 67 A (9): 1313- 1320.
2. Brumback RJ, Jr. Poka A, Lakatos R, Bathon GH, Burgess AR. Intramedullary nailing of femoral shaft fractures. J Bone and Joint Surg, (Am), 1988; 70:1441-1452.
3. Kenneth D Johnson et al., Comminuted femoral shaft fractures: treatment by roller traction, cerclage wires and an intramedullary, or an interlocking intramedullary nail. JBJS,1984: 66 A, No.8 : 1222-1235
4. Wiss DA, Fleming CH, Matta JM, Clark D. Comminuted and rotationally unstable fractures of the femur treated with an interlocking nail. ClinOrthop, 1986; 212: 35- 47.
5. Jack Wickstrom, Magrudes and Guy, ?Complications following intramedullary fixation of 324 fractured femurs?,Clin. Orthop and related research, 212:1986, 35-47
6. Lawrence B. Bone, Kenneth D. Johnson.: Treatment of tibial fractures by reaming and intramedullary nailing; Journal of Bone and Joint Surgery, 1986, 68A:877-886.
7. Kempf I, Grosse A, Beck G. Closed locked intramedullary nailing - Its application to comminuted fractures of the femur. J Bone and Joint Surg, 1985; 67(5): 709-720.
8. Winquist R.A., Hansen S.T., Clawson D.K.: Closed intramedullary nailing of femoral fractures. A report of five hundred and twenty cases. J Bone Joint Surg Am 1984; 66:529-539.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareROLE OF ANTIOXIDANTS IN PREVENTION OF CANCER : A REVIEW
English8088Mobeen KhanEnglish Asad IqubalEnglish Anuja JoshiEnglish Kratika AjaiEnglishThe realization that reactive oxygen species and oxidative stress play an important role in the etiology and progression of major human degenerative diseases has triggered enormous and worldwide interest in endogenous and exogenous antioxidants. Antioxidants are capable of stabilizing, or deactivating, free radicals before they attack cells. Antioxidants are absolutely critical for maintaining optimal cellular and systemic health and well-being. A biological antioxidant may be defined as “a substance present in low concentrations compared to an oxidizable substrate (eg., proteins, lipids, carbohydrates and nucleic acids) that significantly delays or inhibits oxidation of a substrate. Antioxidants may be considered as the scavengers of free radicals”. To protect the cells and organ systems of the body against reactive oxygen species, humans have evolved a highly sophisticated and complex antioxidant protection system.It involves a variety of components, both endogenous and exogenous in origin, that function interactively and synergistically to neutralize free radicals.
EnglishAntioxidants, Free Radicals, Oxidizable SubstrateINTRODUCTION
Even with improved living standard of modern life, many diseases still develop and the factors are likely to be as follows: imbalanced diet, overly consuming high levels of calories, absorbing few fibers, and the lack of vitamins and mineral substances. As a result, the patients of all kinds of chronic diseases are increasing by record numbers. Free radicals are atoms or molecules that contain one or more unpaired electrons. Many radicals are highly reactive and can function as reducing or oxidizing agents by donating electrons to or removing electrons from other molecules. Small amounts of free radicals are constantly being generated in all living organisms. Although free radicals are potentially harmful to cellular components, a substantial body of evidence supports a role for these highly reactive chemical molecules in fundamental cellular reactions and cell–cycle regulation. Nature has endowed each cell with adequate protective antioxidant mechanisms against any harmful effects of free radicals for eg., superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase, thioredoxin, thiols and disulfide bonding are buffering systems in every cell. Antioxidants are substances or agents that scavenge reactive oxygen metabolites, block their generation or enhance endogenous antioxidants capabilities [1]. Moureuand Dufraise (1921) introduced the term “antioxygen” to describe these compounds that act catalytically by retarding oxidation [2].
Free Radicals
Oxygen is a highly reactive atom that is capable of becoming part of potentially damaging molecules commonly called “free radicals.” A free radical can be defined as chemical species possessing unpaired electron [3].Free radicals are capable of
ttacking the healthy cells of the body, causing them tolose their structure and function. Reactive oxygen species (ROS) is a term which encompasses all highly reactive, oxygencontaining molecules, including free radicals. Types of ROSinclude the hydroxyl radical (OH- ), the superoxide anion radical (SO2- ), hydrogen peroxide (H2O2), singlet oxygen (O- ), nitric oxide radical (NO- ), hypochlorite radical (HOCl- ), and various lipid peroxides. All are capable of reacting with membrane lipids, nucleic acids, proteins and enzymes, and other small molecules, resulting in cellular damage [4].
VARIOUS ROS and CORRESPONDING NEUTRALIZING ANTIOXIDANTS
Free radicals Corresponding neutralizing antioxidants
Hydroxyl radical Vitamin C, Glutathione, Flavonoids, Lipoic Acid Superoxide radical Vitamin C, Glutathione, Flavonoids, SOD Hydrogen peroxidase vitamin C, Glutathione, Beta Carotene, Vitamin E, CoQ10, Flavonoids, Lipoic Acid Lipid peroxides Β- carotene, Vitamin E, ubiquinone, flavonoids, Glutathione peroxidas
ROS are generated by a number of pathways. Most of the oxidants produced by cells occur as [5] 1. A consequence of normal aerobic metabolism: approximately 90% of the oxygen utilized by the cell is consumed by the mitochondrial electron transport system. 2. Oxidative burst from phagocytes (white blood cells) as part of the mechanism by which bacteria and viruses are killed, and by which foreign proteins (antigens) are denatured. 3. Xenobiotic metabolism, i.e., detoxification of toxic substances. Consequently, things like vigorous exercise, which accelerates cellular metabolism; chronic inflammation, infections, and other illnesses; exposure to allergens and the presence of “leaky gut” syndrome; and exposure to drugs or toxins such as cigarette smoke, pollution, pesticides, and insecticides may all contribute to an increase in the body’s oxidant load[5].
Oxidative stress and disease
The body is normally in a steady state condition with free radicals being continuously generated andquenched. However, the accumulated longterm damage done by free radicals is implicated innumerous degenerative diseases. Evidence from many has heavily implicated oxidative stress in aspectrum of diseases and of states of body dysfunction, Oxidative stress has been shown variouslyas depressed levels of antioxidant substances (e.g., vitamin E, urate), low levels of enzymes whichform part of the antioxidant defence system, and increased levels of oxidation products (e.g.,malondialdehyde, DNA damage). A well-known example of an oxidation product apparently leading to disease is oxidized cholesterolin low-density lipoprotein (LDL). This is more atherogenic than native LDL, thereby implicatingoxidative stress in atherosclerosis and coronary heart disease (U-ID)[6]. The following is a partial list of the conditions considered to be associated with oxidative stress: in atherosclerosis and coronary heart disease (CHD) The following is a partial list of the conditions considered to be associated with oxidative stress; animpaired immune system and increased risk of infectious disease [7]; cancer [8]; diabetes (bothnoninsulin-dependent and insulin-dependent diabetes) [9,10]; autoimmune conditions includingrheumatoid [11] and ankylosing spondylitis [9]; various respiratory diseases [12]; eye disease,including cataracts [13] and retinal damage leading to age-related macular degeneration [14]; Alzheimer’s disease[15]; and schizophrenia [16].
How important are antioxidants?
The possible benefit of vitamin C and p-carotene has been studied in other conditions apart fromcancer and CHD. Epidemiological evidence suggests that vitamin C protects against cataracts [13] asthma [12] and a decline in pulmonary function [17]. As emphasized earlier such associationsmust be viewed cautiously. However, in the case of vitamin C and asthma, there is also somesupporting evidence from intervention studies [12]. Supplemental doses of p-carotene and ofvitamin C each help prevent oxidative damage of DNA [18, 19], while O-carotene also improvesimmune function [20]. Studying the relationship between antioxidant status and disease has proven to be a highlyprofitable line of research. It has expanded our knowledge concerning the etiology of numerousdiseases and the means by which they might be prevented. But it is essential to take a balancedperspective and avoid the danger of overenthusiasm for the potential of antioxidants. The importance of the association between oxidative stress and disease should not be exaggerated.Halliwell et al [21] pointed out that disease processes can give rise to oxidative stress (in addition tothe reverse). Halliwell [22] also noted that: “In most human diseases oxidative stress is a secondaryphenomenon, not the primary cause of the disease.” Likewise, Dusinska et al. [9] caution that therole of oxidative DNA damage in carcinogenesis has not been proven and that there are manyinconsistencies in therelationship. Red wine has significant antioxidant activity [23] but evidencefrom case-control and prospective studies indicate that it has a no greater protective associationwith CHD than any other type of alcoholic beverage [24]. Taking the evidence as a whole it is difficult to escape the lack of convincing evidence that placesoxidative stress at the center of any disease process or gives antioxidants a major role in theprevention of disease. While many studies have shown associations between intake of antioxidantsand disease risk, very few studies have provided evidence that antioxidants actually prevent anydisease. Conversely, there is strong evidence that fruits and vegetables prevent cancer, CHD andpossibly other diseases. We cannot at this time say how much of this, if any, is due to antioxidantsand how much to nutrients and phytochemicals.
Role of vitamins as antioxidants
Antioxidants namely Vitamin A, E, C, and lycopene as they are the mostcommonly used antioxidants in treatment of oral leukoplakia to assess the outcomemeasures such as clinical resolution, adverse effects, recurrence and malignanttransformation.
Vitamin A
Retinoids are promising chemopreventiveagents. They exert a beneficial effect onepithelial differentiation and can inhibitmalignant transformation and suppress tumorpromotion; hence more clinical trials are triedwith vitamin A and its analogues than otherantioxidants like lycopene, alpha-tocoferol andascorbic acid [25]. Fat soluble vitamin A mainly obtained from animal foods like meat, milk, egg yolk etc., and main function of vitamin A in retinal form is to maintain vision [26] and main tanance of epithelial integrity and is needed for proper haematological, immune and reproductive functions of the body. Theeffects of retinoids are mediated by retinoid acid receptors (RARs) and retinoid X receptors (RXRs). Three subtypes, designated as α, β and both RARsand RXRs, have been described. Recently, retinoids have been implicated in the induction of cell death in many tumor-derived culture cell systems in bothretinoid receptordependent and independent manners. The continued development of new synthetic drugs to up-regulate RA receptors and receptorindependent drugs would be valuable. It appears that exploiting the apoptotic potential of Oral Squamous Cell Carcinoma would lead to contemporarytherapies that might be less toxic to normal cells due to their physiologically controlled survival pathways. It is suggested that these newer therapies wouldalso be effective in treatment of epithelial dysplasia. Ideally, the root of cancer control lies in instituting chemoprevention. In addition to thechemotherapeutic and chemopreventive agents, a number of dietary components and micronutrients are emerging with considerable potential for theinduction of apoptosis. These agents include green tea constituents (EGCG and others), and a number of other phytochemicals, such as carotenoids(lycopene) and retinoids [27].
Vitamin E
Vitamin E exhibits antioxidant properties by acting as a lipid soluble free radical scavenger in cell membrane. Thus, vitamin E may be involving in both initiation and promotion stages. Among the other potentially anti-carcinogenic effect of vitamin e are its ability to inhibit the formation of the carcinogenic chemical nitrosamine from nitrites in some foods, and its ability to promote immune system function [28]. Tocoferol (AT) is the commonest and most active form of vitamin E. It is found in plant oil, margarine, and green leaves. Tocoferol is an effectiveantioxidant at high levels of oxygen, protecting cellular membranes from lipidic peroxidation. Main actions of AT includes;
in cancer cells Recent studies by BalwantRai et al (2008) [29] have proved that antioxidants such as Vitamin C and Vitamin E may be utilized in oral Lichenplanus patients to counteract free radical mediated cell disturbances.
Vitamin C Vitamin C (ascorbic acid) also act as antioxidant, and through its ability to scavenge free radicals, it may be protective effects on biopolymers such as DNA. Like vitamin E, vitamin c may be protective for both initiation and promotion of carcinogenesis. Also, like vitamin E, it is thought to prevent formation of nitrosamine (by converting nitrite to nitrous oxide) and to influence immune system function. Vitamin C has also been reported to affect liver enzymes responsible for detoxification and transformation of carcinogens [28]. L-ascorbic acid (L-AA), the so-called vitamin C, is found in citrus fruits such as kiwi, strawberries, papaya, and mango. It has been suggested that a dailyintake of at least 140mg/day is required for smokers because they usually present a reduction of the L-AA concentration in serum leukocytes. L-AA hasanti-oxidizing properties and reacts with superoxide produced as a result of the cells’ normal metabolic processes; this inactivation of superoxide inhibitsthe formation of nitrosamines during protein digestion and helps avoid damage to DNA and cellular proteins [30]. LAA apart from being antioxidant also hasfollowing actions:
Other antioxidants
Lycopene
The prominent carotenoid in serum is the antioxidant red pigment called lycopene. This is a fat-soluble red pigment found in some fruit and vegetables.The primary sources of lycopene include tomatoes, apricots, papaya and other yellow fruits. In particular, lycopene and other carotenoids rich foods alsoare inversely related to upper digestive tract neoplasms including oral cancer [27]. Lycopene has been hypothesized to prevent carcinogenesis andatherogenesis by protecting critical cellular biomolecules, including lipids, lipoproteins, proteins, and DNA. Lycopene has the uncommon feature of gettingbound to chemical species that react to oxygen, thus being the most efficient biological antioxidizing agent [31].
Green Tea
One of the richest sources for polyphenols is from the tea leaves of Camellia sinensis. The tea leaves contain approximately 40% polyphenols by dryweight. The majority of the tea consumed in the world is black tea (78%) while green tea consumption comprises 20%10. In vitro studies showed thatgreen tea causes reversible G1 arrest of the cell cycle by inhibition of Rb phosphorylation in oral leukoplakia [32]. EGCG alone or green tea polyphenolswere able to induce apoptosis in oral squamous carcinoma cells, while normal human epidermal keratinocytes survived [33]. EGCG or a mixture of greentea polyphenols (GTPP) induced TNF-a gene expression and TNF- α release from cells [34]. The evidence from these studies attests to the feasibility thatEGCG is a potential candidate for prevention of human oral cancer.
Carotene
β -carotene is a vitamin A precursor commonly found in dark green, orange or yellowish vegetables, such as spinach, carrots, sweet potato, mango,papaya, and oranges. Main actions of betacarotene include;
β -carotene is especially used for scavenging free radicals in areas of low oxygen concentration. A result from a recent study has demonstrated that onethird of patients (15 out of 46) that used 360 mg β carotene per week during 12 months presented a complete resolution of oral leukoplakia [35].
Natural sources of antioxidants
Fruits, Vegetables and Cancer
The purported close association between a state of oxidative stress and disease implies thatantioxidants will be protective against these same diseases. Particularly important in this regard isthe strong inverse relationship seen between intake of fruit and vegetables and the risk of cancer[36] with an overall risk reduction of between 30 and 50% [37]. If these impressive benefits are aresult of the intake of antioxidants, then the obvious protective substances may be vitamin C and thecarotenoids. Epidemiological data link vitamin C intake with reduced risk of several cancers, especially oral cavity, esophagus, stomach and, to a lesser extent, colon and lung [38,39]. Likewise, theepidemiological evidence clearly shows a strong inverse association between the intake of β- caroteneand the risk of several cancers, especially lung and stomach [40]. Some attention has beenpaid to other carotenoids. Epidemiological studies have reported that a-carotene has an inverseassociation with cancer of a similastrength to that seen for p-carotene [41]. Lycopene, a carotenoidpresent in tomatoes, has attracted much attention recently; it shows a strong inverse relationshipwith several types of cancer, especially prostate, lung and stomach [42]. A weaker association hasbeen described for lutein [41]. Each of these substances is an antioxidant. It must be stressed,however, that “association does not prove causation.” In reality, vitamin C and carotenoids may beacting merely as surrogate measures of fruit and vegetables and it is other components of thesefoods that prevent cancer. The crucial evidence - the gold standard - is a controlled clinical trial. Butthe results of three such trials provided no evidence of cancer prevention by supplements of β-carotene [43-47]. There is some evidence of protection against cancer by supplemental p-carotene based on early endpoints.One study reported significant reversal of leukoplakia, a precancerous oral lesion [48]. Similarly, another study observed partial regression of precancerous changes of the stomach [49]. Atrial on Filipino betel nut chewers reported a reduction in numbers of buccal mucosa cells withmicronuclei [50]. This indicates the prevention of precancerous changes of the oral cavity. Let us now address the question as to why trials using p-carotene failed to prevent cancerPossibilities that have been suggested include: the wrong carotenoid was given. or it was given atthe wrong dose, or for an insufficient duration, or at the wrong stage of carcinogenesis However,another very real possibility is that antioxidants are not the common denominator between fruit,vegetables and the prevention of cancer. Other factors that may offer a partial explanation are. 1. There is a strong inverse relationship between the intake of dietary fiber and colon cancer [51].There is also evidence suggestive of an inverse relationship between fiber and breast cancer [52].However, as vegetables (and, to a lesser extent, fruit) are a major source of fiber, part of thisassociation may represent confounding by associated substances. 2. Cruciferous vegetables - broccoli, cabbage, cauliflower, brussels sprouts, and others – containphytochemicals which induce the synthesis of detoxifying enzymes and may thereby beanticarcinogenic [53]. This helps explain the epidemiological evidence indicating a protectiverelationship between these vegetables and colon cancer [54].
CONCLUSION
An increasing public awareness ofantioxidants may prompt a patient’s request to betreated without surgery if a premalignant lesion isdiscovered. Reactive oxygen species likemalondialdehyde (MDA), nitroxide (NO), lipidperoxidation, and decreased activities ofantioxidants including glutathione (GSH),ascorbic acid (AA), glutathione peroxidise (GPx), glutathione reductase (GR), superoxidedismutase (SOD), and catalase associated with tobacco users and potentially malignantdisorders, produce both phenotypic andgenotypic alterations which may progress tocancer. Antioxidantsnutrients can play a significant role in theprevention of oral cancer.
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54. Graham S, Mettlin C. Diet and colon cancer. Am J Epidemiol 1979; 109: l-2
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN2014May12HealthcareORAL CANDIDIASIS - A SHORT REVIEW
English8992Nausheen MobeenEnglishOral candidiasis, a common opportunistic fungal infection of oral cavity, which may be a cause of discomfort in patient. It is caused by Candida species on mucous membranes of mouth. The majority of infection is due to Candida albicans. There are few factors that make oral tissue susceptible to Candida infection, they are saliva, xerostomia, night use of denture, tobacco, carbohydrate rich diets, and patients that receive radiotherapy and chemotherapy. It is also known as Oral thrush, oropharyngeal candidiasis. Maintance of oral hygiene and early diagnosis of this condition is very necessary.
EnglishOral Candidiasis, candida, fungal infectionhttp://ijcrr.com/abstract.php?article_id=887http://ijcrr.com/article_html.php?did=887Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN2014May12HealthcareCURRENT SCENARIO OF PHARMACOVIGILANCE AMONGST THE HEALTH CARE PROFESSIONALS WORKING IN A TEACHING HOSPITAL IN RAJASTHAN
English9398Neha SharmaEnglish Manjula BhargavaEnglish Ajitesh Kumar MishraEnglish Rahul Parakh Dhruva Sharma Dhirendra MahawarEnglishAim: The concept of Pharmacovigilance has been given to keep a watch on ADRs. The science and the activities which relate to the detection, assessment, understanding and the prevention of adverse effects or any other drug-related problems is referred to as Pharmacovigilance.Adverse drug reactions (ADRs) have a major impact on public health as they are associated with significant morbidity and mortality .Healthcare professionals are one of the important pillars of an efficient Pharmacovigilance system because of their contribution in the form of spontaneous reporting.The objective of this study is to assess the awareness of Pharmacovigilance amongst the health care professionals working in NIMS medical college and hospital, Jaipur, India. Methodology: An anonymous questionnaire based survey for health care professionals working in NIMS Hospital, Jaipur was conducted after getting approval from the Institutional Ethical Committee. A structured validated questionnaire consisting of thirteen questions was distributed amongst doctors and residents of all the departments during a single visit to the NIMS Hospital. Results: 150 questionnaires were distributed amongst the doctors of NIMS Hospital after brief description about the study out of which 96 forms were included for evaluation .Hence response rate was 64% (96/150). In our study 66.66 % respondents were males and 33.34% were females. We found that 96% respondents were having knowledge that Pharmacovigilance deals with ADRs and 41.5% respondents had knowledge about the phases of clinical trial and knew that Pharmacovigilance is done in Phase IVof clinical trial. To our surprise only 21% doctors were of the view that all the physicians, dentists, nurses, physiotherapists and even pharmacists can report ADR. Interestingly only 36% doctors were aware of the fact that events related to allopathic drugs, herbal medicines, vaccines and blood products can be reported but maximum doctors thought that only allopathic drug ADRs should be reported. Interestingly 87.5% responders were aware of the National Pharmacovigilance Centre in India but only 16.7% actually reported suspected ADRs to any ADR Reporting centre. Conclusion: To conclude poor knowledge of Pharmacovigilance and underreporting of ADRs in a developing country like India is a matter of great concern and needs prompt intervention.
EnglishADR, Pharmacovigilance, ReportingINTRODUCTION
World Health Organization (WHO) has defined anAdverse drug reaction (ADR) as any noxious, unintended, and undesired effect of a drug, which occurs at the doses which are used in humans for prophylaxis, diagnosis, or therapy. [1] The concept of Pharmacovigilance has been given to keep a watch on ADRs. The science and the activities which relate to the detection, assessment, understanding and the prevention of adverse effects or any other drug-related problems is referred to as Pharmacovigilance.[1][2] Adverse drug reactions (ADRs) have a major impact on public health as they are associated with significant morbidity and mortality. [3] Healthcare professionals are one of the important pillars of an efficient pharmacovigilance system because of their contribution in the form of spontaneous reporting. [4]Spontaneous reporting of ADRs is one method of Pharmacovigilance and which is undertaken through the Yellow Card Scheme (YCS) in UK.[5] The Uppsala Monitoring Centre (UMC, WHO), Sweden is maintaining the international database of ADR reports.[6] In India it is maintained by Central Drugs Standard Control Organization (CDSCO) with the Drug Controller General(India) [DCG(I)] as its head. Underreporting of ADRs is the major problem amongst doctors and needs serious rethinking. To improve this, the knowledge, attitude and practice of doctors towards Pharmacovigilance and the reporting system should be improved and awareness should be created. The objective of this study is to assess the awareness of Pharmacovigilance amongst the health care professionals, working in NIMS medical college and hospital, Jaipur, India.
MATERIALS AND METHODS
This study was an anonymous questionnaire based survey for health care professionals working in NIMS Hospital, Jaipur. The study was conducted after getting approval from the Institutional Ethical Committee. A structured validated questionnaire consisting of thirteen questions was distributed amongst doctors and residents of all the departments during a single visit to the NIMS Hospital , to each of them and they were asked to tick the option/s which they felt was/ were the best. All the doctors and residents in all the OPDs and wards of all the departments were contacted during this single visit. Consenting participants anonymously completed the questionnaire and were collected on the same day. Doctors were allowed to give suggestions regarding improvement of ADR Reporting. Questionnaire was based on previous study done on pharmacovigilance.[1][6] Survey was descriptive and after completion of data collection it was organized and compiled as percentages. The sum total of percentages was not always 100% because some questions contained multiple options to choose from.
STATISTICAL ANALYSIS:
The data was subjected to descriptive analysis using microsoft excel. Different parameters were given as percentile.
RESULTS
150 questionnaires were distributed amongst the doctors of NIMS Hospital after brief description about the study. The dully filled forms were collected on the same working day.Incompletely filled and forms which were not filled were excluded from the study. 96 forms were included for evaluation. In our study 66.66 % respondents were males and 33.34% were females as shown in figure:1.
Response rate was 64% (96/150) as 96 dully filled forms were collected back. Out of 96 responders, 40 were senior doctors and 56 were residents. We found that 96% respondents were having knowledge that Pharmacovigilance deals with ADRs. We found that 41.5% respondents had knowledge about the phases of clinical trial and knew that Pharmacovigilance is done in Phase IV of clinical trial. while 37.5% thought that pharmacovigilance is done in Phase I clinical trial. On the other hand 8.4% doctors were in favour of Phase II while 7.3% ticked on Phase III clinical trials.We found that knowledge of location of WHO Uppsala Monitoring centre( Sweden) was present amongst 68.8% doctors while rest were unaware of its location. To our surprise only 21% doctors were of the view that all the physicians, dentists, nurses, physiotherapists and even pharmacists can report ADR. Still maximum number of doctors thought that only physicians can send the ADR report. Interestingly only 36% doctors were aware of the fact that events related to allopathic drugs, herbal medicines, vaccines and blood products can be reported but maximum doctors thought that only allopathic drug ADRs should be reported.ADR reporting is generally done by most of the doctors only for allopathic drugs and vaccines. But it actually encompasses other products also like herbals, traditional medicines,and blood products, biological and medical devices .[6]Events which should be reported has been depicted in figure :2.
Interestingly 87.5% responders were aware of the National Pharmacovigilance Centre in India but only 16.7% actually reported suspected ADRs to any ADR Reporting centre. In our study attitude regarding ADR Reporting amongst respondents has been shown in the following table:1.
Majority of doctors were of the view that the doctors should be trained in ADR reporting (37.5%) and ADR reports should be kept confidential. 18.6% opined thatmore CMEs should be arranged on Pharmacovigilance while 8.4% felt need about tollfree number for ADR reporting. There should be an emphasis oninculcation of knowledge about Pharmacovigilance right from the second year when a medical student steps into the world of pharmacology.
DISCUSSION
Male preponderance was seen in our study which corresponds with the study done by Pankaj G et al 2011[6] . In contradiction to our study female preponderance was seen in study performed by Subish P et al 2011 in Nepal.[8] We got a response rate of 64% in our study. Our findings coincide with the findings of Khan S A et al 2013 (response rate was 62.9%). [7] while it was 67.9% in a study done in Nepal.[8] In contradiction to this very high response rate of 93.3% was present in a study done by Pimpalkhute SAetal 2012[3] Similarly in a Nigerian study response rate of 82.5% was observed.[9] We found that 96% respondents were having knowledge that Pharmacovigilance deals with ADRs. But in another Indian study 77% of the subjects knew the term ‘Pharmacovigilance.[1] In an Indian study by Chopra D et al nearly two third (66%) of the doctors knew the definition of ADR. [11] We found that 41.5% respondents had knowledge about the phases of clinical trial and knew that Pharmacovigilance is done in Phase IV of clinical trial. In a study done by Hardeep et al 2013 68.9% knew about Periodic Safety Update Report.[1] In our study, only 21% doctors were of the view that all the physicians, dentists, nurses, physiotherapists and even pharmacists can report ADR. Similarly in Nigeria 89.9% considered doctors, as the most qualified health professionals to report ADRs.[9] Interestingly in a study by Khan SA et al 2013 , major proportion (85.3%) of the doctors were aware that all ADRs should be reported.[7] Surprisingly in a study done by Chopra D et al 2011, only one tenth of the doctors (10%) knew ,what should be reported ? [11] In a study performed in China , 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers.[16] Interestingly 87.5% responders in our study were aware of the National Pharmacovigilance Centre in India but only 16.7% actually reported suspected ADRs to any ADR Reporting centre. But, only 59% subjects were aware of the existence of a National Pharmacovigilance Centre in India in a previous Indian study.[1] 73% respondents were aware of the existing programme in India in another study.[11] Santosh KCet al2013 concluded that there were 74.8% of healthcare professionals who had seen patient experiencing an ADR; however, only 20.1% had reported.[13] Similarly in a study performed in Tamil Nadu , 47.5% respondents had observed ADRs in their practice, and 37% had reported it to the national pharmacovigilance center.[14] In an Iranian study done amongst pharmacists, more than half of those responding felt that ADR reporting should be voluntary, while 26% felt it was a professional obligation. [15]
CONCLUSION
This study has given us an overall pattern of awareness of pharmacovigilance amongst doctors working in NIMS Hospital. Our study will help in promoting knowledge about Pharmacovigilanceamong clinicians. To conclude despite of shortcomings our study can offer a wealth of data on implementation of Pharmacovigilance.Poor knowledge of Pharmacovigilance and underreporting of ADRs in a developing country like India is a matter of great concern and needs prompt intervention.
CONFLICTS OF INTEREST
The authors declare that they have no competing interests. FUNDING:Not applicable.
ACKNOWLEDGEMENT
I would like to thank Dr. Manjula Bhargavaand all the doctors of NIMS Hospital who participated in this study. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=888http://ijcrr.com/article_html.php?did=8881. Hardeep, JagminderKaur Bajaj, Kumar Rakesh. A survey on the knowledge , attitude and practice of pharmacovigilance among health care professionals in a teaching hospital in North India.JClinDiagn Res. Jan 2013; 7(1): 97–99.
2. The World Health Organization. Safety of medicines: A guide to detecting and reporting adverse drug reactions. Geneva: 2002. WHO/EDM/QSM/2002 2.
3. Pimpalkhute SA, Jaiswal KM, SontakkeSD.Evaluation of awareness about pharmacovigilance and adverse drug reaction monitoring in resident doctors of a tertiary care teaching hospital. Indian J Med Sci. 2012 Mar-Apr;66(3-4):55-61.
4. Sanghavi DR, Dhande PP, Pandit VA. Perception of pharmacovigilance among doctors in a tertiary care hospital: influence of an interventional lecture. Int J Risk Saf Med. 2013;25(4):197-204.
5. Avery AJ, Anderson C, Bond CM. Evaluation of patient reporting of adverse drug reactions to the UK 'Yellow Card Scheme': literature review, descriptive and qualitative analyses, and questionnaire surveys.Health Technol Assess. 2011 May;15(20):1-234
6. Dr. PankajGupta,Dr. AadityaUdupa. Adverse Drug Reaction Reporting and Pharmacovigilance:Knowledge, Attitudes and Perceptions amongst Resident Doctors.J. Pharm. Sci. and Res. Vol.3(2), 2011,1064-1069
7. Khan SA, Goyal C, Chandel N. Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study. J Nat ScBiol Med 2013;4:191-6
8. SubishPalaian, Mohamed I. Ibrahim, Pranaya Mishra. Health professionals' knowledge, attitude and practices towards pharmacovigilance in Nepal. Pharm Pract (Granada). 2011 Oct-Dec; 9(4): 228–235.
9. Oshikoya KA, AwobusuyiJO.Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria. BMC ClinPharmacol. 2009 Aug 11;9:14.
10. Oreagba IA, Ogunleye OJ, OlayemiSOThe knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):30-5.
11. Chopra D, Wardhan N, Rehan HS. Knowledge, attitude and practices associated with adverse drug reaction reporting amongst doctors in a teaching hospital. Int J Risk Saf Med. 2011;23(4):227-32.
12. Desai CK, Iyer G, Panchal J. An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital. PerspectClin Res. 2011 Oct;2(4):129-36.
13. Santosh KC, Tragulpiankit P, Gorsanan S. Attitudes among healthcare professionals to the reporting of adverse drug reactions in Nepal. BMC PharmacolToxicol. 2013 Mar 8;14:16.
14. Ahmad A, Patel I, Balkrishnan R. An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction reporting: A pilot study. PerspectClin Res. 2013 Oct;4(4):204-10.
15. Vessal G, Mardani Z, Mollai M. Knowledge, attitudes, and perceptions of pharmacists to adverse drug reaction reporting in Iran. Pharm World Sci. 2009 Apr;31(2):183-7.
16. Li Q, Zhang SM, Chen HT. Study on the knowledge and attitude to adverse drug reactions reporting among healthcare professionals in Wuhan city. Zhonghua Liu Xing Bing XueZaZhi. 2004 Oct;25(10):894-7.
17. Sweis D, Wong IC. A survey on factors that could affect adverse drug reaction reporting according to hospital pharmacists in Great Britain. Drug Saf. 2000 Aug;23(2):165-72.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareST-SEGMENT RESOLUTION: A CRITERION OF SUCCESSFUL THROMBOLYSIS IN ACUTE MYOCARDIAL INFARCTION
English99108Nilay SutharEnglish Paltial PalatEnglish Shivkumar MasaraddiEnglish Manish PatelEnglish Dilip ModiEnglishBackground: Thrombosis of the coronary artery is the principal cause of myocardial infarction in the territory of the affected vessel. To limit the size of infract area and for the salvage of the jeopardized myocardium, restoration of patency of infarct related coronary artery is very important to reduce morbidity and mortality in these patients.1,2 The physician's ability to predict patency of the infarct related artery from clinical variables however is disappointing. The role of ST-segment resolution during an ST segment infarction has over the years, grown into not only an alternative way of approximating risk and chances of reperfusion in the absence of a coronary angiogram, but also a method challenging the traditional "gold standard" for predicting risk and reperfusion at the myocardial level. Thus, ST-segment resolution at 90 minutes is an excellent marker of successful myocardial reperfusion1 and a strong predictor of survival and preservation of left ventricular function.3-5 Aims and Objectives: We studied the relation between ST-segment resolution and various outcomes in cases of acute myocardial infarction at our institute.Our aim was to study ST-segment resolution as a marker and a simple bedside tool for predicting of successful myocardial reperfusion, 90 minutes after thrombolysis in STEMI (ST elevation myocardial infarction).We also studied and attempted to correlate ST-segment resolution at 90 minutes after thrombolysis as a predictor of recovery, in-hospital adverse events, morbidity and mortality in STEMI. Methods: The present study was conducted on 50 patients who had received thrombolytic therapy with streptokinase for ST Elevation AMI, in our ICCU. Detailed clinical history with specific emphasis on presenting complaint and associated coronary risk factors and management done were captured. Results: The study corroborates the evidence that the recanalization and the patency of the IRA (Infarct Related Artery) remained higher in the patients with complete resolution of ST-segment at 90 minutes group, than the patients with partial resolution and the no resolution groups. Conclusions: ST-segment resolution can be used as a simple non-invasive tool for the prediction of the patency of the IRA after thrombolysis.
EnglishSt-segment, resolution, Acute Myocardial Infarction, thrombolysis.INTRODUCTION
World Health Organization (WHO) has defined anAdverse drug reaction (ADR) as any noxious, unintended, and undesired effect of a drug, which occurs at the doses which are used in humans for prophylaxis, diagnosis, or therapy. [1] The concept of Pharmacovigilance has been given to keep a watch on ADRs. The science and the activities which relate to the detection, assessment, understanding and the prevention of adverse effects or any other drug-related problems is referred to as Pharmacovigilance.[1][2] Adverse drug reactions (ADRs) have a major impact on public health as they are associated with significant morbidity and mortality. [3] Healthcare professionals are one of the important pillars of an efficient pharmacovigilance system because of their contribution in the form of spontaneous reporting. [4]Spontaneous reporting of ADRs is one method of Pharmacovigilance and which is undertaken through the Yellow Card Scheme (YCS) in UK.[5] The Uppsala Monitoring Centre (UMC, WHO), Sweden is maintaining the international database of ADR reports.[6] In India it is maintained by Central Drugs Standard Control Organization (CDSCO) with the Drug Controller General(India) [DCG(I)] as its head. Underreporting of ADRs is the major problem amongst doctors and needs serious rethinking. To improve this, the knowledge, attitude and practice of doctors towards Pharmacovigilance and the reporting system should be improved and awareness should be created. The objective of this study is to assess the awareness of Pharmacovigilance amongst the health care professionals, working in NIMS medical college and hospital, Jaipur, India.
MATERIALS AND METHODS
This study was an anonymous questionnaire based survey for health care professionals working in NIMS Hospital, Jaipur. The study was conducted after getting approval from the Institutional Ethical Committee. A structured validated questionnaire consisting of thirteen questions was distributed amongst doctors and residents of all the departments during a single visit to the NIMS Hospital , to each of them and they were asked to tick the option/s which they felt was/ were the best. All the doctors and residents in all the OPDs and wards of all the departments were contacted during this single visit. Consenting participants anonymously completed the questionnaire and were collected on the same day. Doctors were allowed to give suggestions regarding improvement of ADR Reporting. Questionnaire was based on previous study done on pharmacovigilance.[1][6] Survey was descriptive and after completion of data collection it was organized and compiled as percentages. The sum total of percentages was not always 100% because some questions contained multiple options to choose from.
STATISTICAL ANALYSIS:
The data was subjected to descriptive analysis using microsoft excel. Different parameters were given as percentile.
RESULTS
150 questionnaires were distributed amongst the doctors of NIMS Hospital after brief description about the study. The dully filled forms were collected on the same working day.Incompletely filled and forms which were not filled were excluded from the study. 96 forms were included for evaluation. In our study 66.66 % respondents were males and 33.34% were females as shown in figure:1.
Response rate was 64% (96/150) as 96 dully filled forms were collected back. Out of 96 responders, 40 were senior doctors and 56 were residents. We found that 96% respondents were having knowledge that Pharmacovigilance deals with ADRs. We found that 41.5% respondents had knowledge about the phases of clinical trial and knew that Pharmacovigilance is done in Phase IV of clinical trial. while 37.5% thought that pharmacovigilance is done in Phase I clinical trial. On the other hand 8.4% doctors were in favour of Phase II while 7.3% ticked on Phase III clinical trials.We found that knowledge of location of WHO Uppsala Monitoring centre( Sweden) was present amongst 68.8% doctors while rest were unaware of its location. To our surprise only 21% doctors were of the view that all the physicians, dentists, nurses, physiotherapists and even pharmacists can report ADR. Still maximum number of doctors thought that only physicians can send the ADR report. Interestingly only 36% doctors were aware of the fact that events related to allopathic drugs, herbal medicines, vaccines and blood products can be reported but maximum doctors thought that only allopathic drug ADRs should be reported.ADR reporting is generally done by most of the doctors only for allopathic drugs and vaccines. But it actually encompasses other products also like herbals, traditional medicines,and blood products, biological and medical devices .[6]Events which should be reported has been depicted in figure :2.
Interestingly 87.5% responders were aware of the National Pharmacovigilance Centre in India but only 16.7% actually reported suspected ADRs to any ADR Reporting centre. In our study attitude regarding ADR Reporting amongst respondents has been shown in the followingtable:1.
Majority of doctors were of the view that the doctors should be trained in ADR reporting (37.5%) and ADR reports should be kept confidential. 18.6% opined thatmore CMEs should be arranged on Pharmacovigilance while 8.4% felt need about tollfree number for ADR reporting. There should be an emphasis oninculcation of knowledge about Pharmacovigilance right from the second year when a medical student steps into the world of pharmacology.
DISCUSSION
Male preponderance was seen in our study which corresponds with the study done by Pankaj G et al 2011[6] . In contradiction to our study female preponderance was seen in study performed by Subish P et al 2011 in Nepal.[8] We got a response rate of 64% in our study. Our findings coincide with the findings of Khan S A et al 2013 (response rate was 62.9%). [7] while it was 67.9% in a study done in Nepal.[8] In contradiction to this very high response rate of 93.3% was present in a study done by Pimpalkhute SAetal 2012[3] Similarly in a Nigerian study response rate of 82.5% was observed.[9] We found that 96% respondents were having knowledge that Pharmacovigilance deals with ADRs. But in another Indian study 77% of the subjects knew the term ‘Pharmacovigilance.[1] In an Indian study by Chopra D et al nearly two third (66%) of the doctors knew the definition of ADR. [11] We found that 41.5% respondents had knowledge about the phases of clinical trial and knew that Pharmacovigilance is done in Phase IV of clinical trial. In a study done by Hardeep et al 2013 68.9% knew about Periodic Safety Update Report.[1] In our study, only 21% doctors were of the view that all the physicians, dentists, nurses, physiotherapists and even pharmacists can report ADR. Similarly in Nigeria 89.9% considered doctors, as the most qualified health professionals to report ADRs.[9] Interestingly in a study by Khan SA et al 2013 , major proportion (85.3%) of the doctors were aware that all ADRs should be reported.[7] Surprisingly in a study done by Chopra D et al 2011, only one tenth of the doctors (10%) knew ,what should be reported ? [11] In a study performed in China , 61.7% of the doctors, 62.7% of the nurses and 61.1% of the administrators had ever encountered an ADR during their practices, but did not report to the national monitoring center or other centers.[16] Interestingly 87.5% responders in our study were aware of the National Pharmacovigilance Centre in India but only 16.7% actually reported suspected ADRs to any ADR Reporting centre. But, only 59% subjects were aware of the existence of a National Pharmacovigilance Centre in India in a previous Indian study.[1] 73% respondents were aware of the existing programme in India in another study.[11] Santosh KCet al2013 concluded that there were 74.8% of healthcare professionals who had seen patient experiencing an ADR; however, only 20.1% had reported.[13] Similarly in a study performed in Tamil Nadu , 47.5% respondents had observed ADRs in their practice, and 37% had reported it to the national pharmacovigilance center.[14] In an Iranian study done amongst pharmacists, more than half of those responding felt that ADR reporting should be voluntary, while 26% felt it was a professional obligation. [15]
CONCLUSION
This study has given us an overall pattern of awareness of pharmacovigilance amongst doctors working in NIMS Hospital. Our study will help in promoting knowledge about Pharmacovigilanceamong clinicians. To conclude despite of shortcomings our study can offer a wealth of data on implementation of Pharmacovigilance.Poor knowledge of Pharmacovigilance and underreporting of ADRs in a developing country like India is a matter of great concern and needs prompt intervention.
CONFLICTS OF INTEREST
The authors declare that they have no competing interests.
FUNDING:
Not applicable.
ACKNOWLEDGEMENT
I would like to thank Dr. Manjula Bhargavaand all the doctors of NIMS Hospital who participated in this study. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=889http://ijcrr.com/article_html.php?did=889REFERENCES
1. Hardeep, JagminderKaur Bajaj, Kumar Rakesh. A survey on the knowledge , attitude and practice of pharmacovigilance among health care professionals in a teaching hospital in North India.JClinDiagn Res. Jan 2013; 7(1): 97–99.
2. The World Health Organization. Safety of medicines: A guide to detecting and reporting adverse drug reactions. Geneva: 2002. WHO/EDM/QSM/2002 2.
3. Pimpalkhute SA, Jaiswal KM, SontakkeSD.Evaluation of awareness about pharmacovigilance and adverse drug reaction monitoring in resident doctors of a tertiary care teaching hospital. Indian J Med Sci. 2012 Mar-Apr;66(3-4):55-61.
4. Sanghavi DR, Dhande PP, Pandit VA. Perception of pharmacovigilance among doctors in a tertiary care hospital: influence of an interventional lecture. Int J Risk Saf Med. 2013;25(4):197-204.
5. Avery AJ, Anderson C, Bond CM. Evaluation of patient reporting of adverse drug reactions to the UK 'Yellow Card Scheme': literature review, descriptive and qualitative analyses, and questionnaire surveys.Health Technol Assess. 2011 May;15(20):1-234
6. Dr. PankajGupta,Dr. AadityaUdupa. Adverse Drug Reaction Reporting and Pharmacovigilance:Knowledge, Attitudes and Perceptions amongst Resident Doctors.J. Pharm. Sci. and Res. Vol.3(2), 2011,1064-1069
7. Khan SA, Goyal C, Chandel N. Knowledge, attitudes, and practice of doctors to adverse drug reaction reporting in a teaching hospital in India: An observational study. J Nat ScBiol Med 2013;4:191-6
8. SubishPalaian, Mohamed I. Ibrahim, Pranaya Mishra. Health professionals' knowledge, attitude and practices towards pharmacovigilance in Nepal. Pharm Pract (Granada). 2011 Oct-Dec; 9(4): 228–235.
9. Oshikoya KA, AwobusuyiJO.Perceptions of doctors to adverse drug reaction reporting in a teaching hospital in Lagos, Nigeria. BMC ClinPharmacol. 2009 Aug 11;9:14.
10. Oreagba IA, Ogunleye OJ, OlayemiSOThe knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria. Pharmacoepidemiol Drug Saf. 2011 Jan;20(1):30-5.
11. Chopra D, Wardhan N, Rehan HS. Knowledge, attitude and practices associated with adverse drug reaction reporting amongst doctors in a teaching hospital. Int J Risk Saf Med. 2011;23(4):227-32.
12. Desai CK, Iyer G, Panchal J. An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital. PerspectClin Res. 2011 Oct;2(4):129-36.
13. Santosh KC, Tragulpiankit P, Gorsanan S. Attitudes among healthcare professionals to the reporting of adverse drug reactions in Nepal. BMC PharmacolToxicol. 2013 Mar 8;14:16.
14. Ahmad A, Patel I, Balkrishnan R. An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction reporting: A pilot study. PerspectClin Res. 2013 Oct;4(4):204-10.
15. Vessal G, Mardani Z, Mollai M. Knowledge, attitudes, and perceptions of pharmacists to adverse drug reaction reporting in Iran. Pharm World Sci. 2009 Apr;31(2):183-7.
16. Li Q, Zhang SM, Chen HT. Study on the knowledge and attitude to adverse drug reactions reporting among healthcare professionals in Wuhan city. Zhonghua Liu Xing Bing XueZaZhi. 2004 Oct;25(10):894-7.
17. Sweis D, Wong IC. A survey on factors that could affect adverse drug reaction reporting according to hospital pharmacists in Great Britain. Drug Saf. 2000 Aug;23(2):165-72.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN2014May12HealthcareLONG TERM FUNCTIONAL OUTCOME OF FEMORAL DIAPHYSEAL FRACTURES TREATED WITH DYNAMIC COMPRESSION PLATE AND TITANIUM ELASTIC NAILING
English109114Pawan Kumar K. M.1English Chandrarashekar H. S.EnglishBackground: There are a wide variety of non surgical treatment and surgical options available such as spica casting, traction followed by casting, plate fixation and flexible intramedullary nails for femur diaphyseal fractures in children. There is no clear consensus as to the ideal treatment. Methods: We report our experience with a prospective comparative study involving 120 cases of femoral diaphyseal fractures treated with DCP and TENS with follow up of over a period of three years. Outcome was assessed with criteria of Flynn et al1. At the end of second and third year Harris hip score2 was applied to assess the functional outcome. Results: Out of the hundred and twenty cases 96 had middle / 3rd fractures. Mean age was 10.85± 2.26 years. Time taken for toe touch walking and union time for Group-I (DCP) and Group-II (TENS) were 7.85±2.23 &17.90±5.09 weeks and 3.97±1.68 & 13.00±1.37 weeks respectively. Nine cases in Group-I and 6 cases in Group-II had limb length discrepancy and there were 6 cases with coronal plane angulation in Group-II. Functional outcome was better in Group-II at the end of one year. But the functional outcome at the end of second and third year of both the groups was similar. Conclusion: Even though long term functional outcome of both procedures are similar, TENS has several statistically significant advantages over DCP in relation to patient morbidity. Hence a better choice of implant for pediatric femoral diaphyseal fractures.
EnglishFemur; Dynamic compression plating (DCP); Titanium elastic nailing (TENS).INTRODUCTION
Femoral shaft fracture is an incapacitating pediatric injury3 .There are a wide variety of non surgical treatment and surgical options available such as spica casting, traction followed by casting, plate fixation and flexible intramedullary nails with no clear consensus as to the preferred treatment4 . Internal fixation of paediatric shaft femur fracture by elastically stable intramedullary nail (ESIN) is gradually replacing conservative treatment5 . The material properties of titanium confer advantages for an implant used to stabilize pediatric femur fractures6 .Although good results have been reported with elastic intramedullary nails, plate fixation continues to be a viable alternative in surgical treatment of femoral shaft fractures7 . It is also considered that, compression plate fixation is a safe and effective treatment in children with both isolated femoral shaft fracture and those associated multiple injuries8 . The aim of this study was to identify the implant of choice for femoral diaphyseal fractures in paediatric age group with regard to immediate and long term functional outcomes.
MATERIAL AND METHODS The ethical clearance for the study was obtained from the Institutional Ethical Committee of our hospital on 21-07-2008 and Informed consent was taken from each of the parents/guardians of the patients in their own vernacular language. We conducted a prospective comparative study. Patients who presented to the out-patient department and casualty of the hospital with femoral diaphyseal fractures during August 2008 to August 2010 were considered for the study and each case was followed up for a period of three years from the date of enrollment. Closed femur diaphyseal fractures in the age group of 6-14 years were included in the study. Children aged < 6 years and > 14 years, children with open fractures and in whom metaphyseal extension was present were excluded from the study. DCP Procedure: Lateral approach for femur was used in all patients. After achieving the temporary anatomical stable reduction with k-wires, it was fixed with Dynamic Compression Plate. TENS Procedure: Nail diameter was determined by using the formula, Nail Diameter=Diameter of the medullary cavity at its narrowest part/2 - 0.59 . The nails were prebent to three times the diameter of the narrowest part of the medullary cavity to generate optimal resistance to malaligning forces10.The insertion points on femur were marked 2 to 3 cms proximal to the distal epiphyseal plate, determined under image intensifier. Nails of predetermined diameter were prebent and inserted to the medullary cavity with the help of a nail inserter. Postoperatively 2 days of intravenous third generation cephalosporin was given. Isometric quadriceps strengthening exercise, hip and knee joint mobilization exercises were advised on first post operative day. Toe touch walking was delayed till the appearance of callus radiologically. All the patients had regular follow ups at an interval of 4 weeks till six months and then, they were followed up once in every three months for one year and once in six months for next two years. There were no drop outs. The TENS outcome score suggested by Flynn et.al1 was applied to all the cases in the study after fracture union, irrespective of the mode of treatment. The outcome was graded as Excellent / Satisfactory / Poor. Then Harris hip score2 was applied the end of second and third year of follow up. RESULTS Femur shaft fractures were found to have high incidence in the age group of 12-14 years with Mean ± SD 10.85±2.26. Out of the 120 cases there were 93 (77.5%) males and 27 (22.5%) females. The most common mode of injury in our study was road traffic accident (RTA). In the study 96 cases (80%) had femur shaft fracture in the middle 3rd. There were 54 cases (45%), 51 cases (42.5%) and 15 cases (12.5%) of transverse, oblique and spiral fractures respectively. The time taken for the completion of procedure in group I was 95.60±8.47 minutes and in group II was 93.±9.04 minutes with a p value of 0.496. The amount of blood loss in group I was 96.5± 13.02 ml and in group II was 36.75± 8.77ml with a p value of Englishhttp://ijcrr.com/abstract.php?article_id=890http://ijcrr.com/article_html.php?did=890Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareCYTOLOGICAL EVALUATION OF THYROID LESIONS BY FINE NEEDLE ASPIRATION VERSUS NON-ASPIRATION CYTOLOGY TECHNIQUES- A COMPARATIVE STUDY
English115117Purushotham KrishnappaEnglish Sowmya RamakrishnappaEnglishAim: To compare the fine-needle non-aspiration cytology (FNNAC) with fine-needle aspiration cytology (FNAC) in providing the adequate samples for the evaluation of thyroid lesions. Materials and Methods: A total of 48 patients presenting with thyroid lesions at Standard Diagnostics Laboratory, Bangalore during period of Jan 2009 to October 2010, underwent both FNAC and FNNAC techniques. All the needle-sampling procedures were done by a single pathologist. The obtained samples were assessed for cytological evaluation based on sample adequacy, aspiration of blood, cellular features and possible diagnosis. Results: FNNAC produced less inadequate samples (20.9 %) than FNA (31.25%). Conclusion: The FNNAC is a better technique of sampling thyroid nodules and appears to produce more adequate specimen.
EnglishThyroid lesions, Fine Needle Aspiration Cytology, Non-aspirationINTRODUCTION
Femoral shaft fracture is an incapacitating pediatric injury3 .There are a wide variety of non surgical treatment and surgical options available such as spica casting, traction followed by casting, plate fixation and flexible intramedullary nails with no clear consensus as to the preferred treatment4 . Internal fixation of paediatric shaft femur fracture by elastically stable intramedullary nail (ESIN) is gradually replacing conservative treatment5 . The material properties of titanium confer advantages for an implant used to stabilize pediatric femur fractures6 .Although good results have been reported with elastic intramedullary nails, plate fixation continues to be a viable alternative in surgical treatment of femoral shaft fractures7 . It is also considered that, compression plate fixation is a safe and effective treatment in children with both isolated femoral shaft fracture and those associated multiple injuries8 . The aim of this study was to identify the implant of choice for femoral diaphyseal fractures in paediatric age group with regard to immediate and long term functional outcomes
MATERIAL AND METHODS
The ethical clearance for the study was obtained from the Institutional Ethical Committee of our hospital on 21-07-2008 and Informed consent was taken from each of the parents/guardians of the patients in their own vernacular language. We conducted a prospective comparative study. Patients who presented to the out-patient department and casualty of the hospital with femoral diaphyseal fractures during August 2008 to August 2010 were considered for the study and each case was followed up for a period of three years from the date of enrollment. Closed femur diaphyseal fractures in the age group of 6-14 years were included in the study. Children aged < 6 years and > 14 years, children with open fractures and in whom metaphyseal extension was present were excluded from the study. DCP Procedure: Lateral approach for femur was used in all patients. After achieving the temporary anatomical stable reduction with k-wires, it was fixed with Dynamic Compression Plate. TENS Procedure: Nail diameter was determined by using the formula, Nail Diameter=Diameter of the medullary cavity at its narrowest part/2 - 0.59 . The nails were prebent to three times the diameter of the narrowest part of the medullary cavity to generate optimal resistance to malaligning forces10.The insertion points on femur were marked 2 to 3 cms proximal to the distal epiphyseal plate, determined under image intensifier. Nails of predetermined diameter were prebent and inserted to the medullary cavity with the help of a nail inserter. Postoperatively 2 days of intravenous third generation cephalosporin was given. Isometric quadriceps strengthening exercise, hip and knee joint mobilization exercises were advised on first post operative day. Toe touch walking was delayed till the appearance of callus radiologically. All the patients had regular follow ups at an interval of 4 weeks till six months and then, they were followed up once in every three months for one year and once in six months for next two years. There were no drop outs. The TENS outcome score suggested by Flynn et.al1 was applied to all the cases in the study after fracture union, irrespective of the mode of treatment. The outcome was graded as Excellent / Satisfactory / Poor. Then Harris hip score2 was applied the end of second and third year of follow up.
RESULTS
Femur shaft fractures were found to have high incidence in the age group of 12-14 years with Mean ± SD 10.85±2.26. Out of the 120 cases there were 93 (77.5%) males and 27 (22.5%) females. The most common mode of injury in our study was road traffic accident (RTA). In the study 96 cases (80%) had femur shaft fracture in the middle 3rd. There were 54 cases (45%), 51 cases (42.5%) and 15 cases (12.5%) of transverse, oblique and spiral fractures respectively. The time taken for the completion of procedure in group I was 95.60±8.47 minutes and in group II was 93.±9.04 minutes with a p value of 0.496. The amount of blood loss in group I was 96.5± 13.02 ml and in group II was 36.75± 8.77ml with a p value of Englishhttp://ijcrr.com/abstract.php?article_id=891http://ijcrr.com/article_html.php?did=891REFERENCES
1. Flynn JM, Hresko T, Reynolds RA. Titanium elastic nails for pediatric femur fractures: A multicentric study of early results with analysis of complications. J Pediatr Orthop 2001; 21:4-8.
2. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969 Jun;51(4):737-55.
3. Flynn JM, Skaggs DL , Sponseller PD, Ganley Tj, Kay Rm, Leitch Kk. The operative management of pediatric fractures of the lower extremity. J Bone Joint Surg Am 2002; 84:2288-2300.
4. Clinscales CM, Peterson HA. Isolated closed diaphyseal fractures of the femur in children: Comparison of effectiveness and cost of several treatment methods. Orthopedics 1997; 20 (12) :1131-6.
5. Saikat Sarkar Ranadeb Bandyopadhyay Arindam Mukherjee Titanium elastic nail - complications in the treatment of paediatric diaphyseal fracture of femur .Open Orthop J. 2013; 7: 12–17
6. Roop Singh, SC Sharma , Magu NK , Amit Singla. Titanium elastic nailing in pediatric femoral diaphyseal fractures. Ind J Orthop 2006; 40(1) : 29-34.
7. Eren OT, Kucukkaya M, Kockesen C, Kabukcuoglu Y, Kuzgun U. Open reduction and plate fixation of femoral shaft fractures in children aged 4 to 10. J Pediatr Orthop 2003; 23(2):190-193.
8. Caird MS, Mueller KA, Puryear A, Farley FA. Compression plating of pediatric femoral shaft fractures. J Pediatr Orthop 2003; 23(4):448- 452.
9. Ligier JN, Metaizeau JP, Prevot J, Lascombes P. Elastic stable intramedullary nailing of femoral shaft fractures in children. J Bone Joint Surg Br 1988; 70: 74-77.
10. Titanium Elastic Nail- Surgical Techinique. Synthes (Original instruments and implants of the assosiation for the study of internal fixation-ASIF): 2- 24.
11. David AS, Theodore JG, John MF. Titanium elastic nailing of pediatric femur fractures. Oper Tech Orthop 2005; 15: 326-330.
12. Li Y, Hedequist DJ. Submuscular plating of pediatric femur fracture. J Am Acad Orthop Surg. 2012 Sep;20(9):596-603.
13. Fyodorov I, Sturm PF, Robertson WW. Compression-plate fixation of femoral shaft fractures in children aged 8 to 12 years. J Pediatr Orthop 1999; 19(5): 578-584.
14. Agus H, Kalenderer O, Erynilmaz G, Omeroglu H. Biological internal fixation of comminuted femur shaft fractures by bridge plating in children. J Pediatr Orthop 2003; 23(2): 184-189. 15. Sink EL, Hedequist D, Morgan SJ, Hresko T. Results and technique of unstable pediatric femoral fractures treated with submuscular bridge plating. J Pediatr Orthop 2006; 26(2): 177-181.
16. Carey TP, Galpin RD. Flexible intramedullary nail fixation of pediatric femoral fractures. Clin Orthop Relat Res 1996; 332: 110-118.
17. Saikia KC, Bhuyan SK, Bhattacharya TD, Saikia SP. Titanium elastic nailing in femoral diaphyseal fractures of children in 6-16 years of age. Ind J Orthop 2007; 41(4): 381-385.
18. Moroz LA, Launay F, Kocher MS, Newton PO, Frick SL, Sponseller PD, Flynn JM. Titanium elastic nailing of fractures of the femur in children. J Bone Joint Surg Br 2006; 88: 1361-1366.
19. Timothy W, Jon L, Andrew K. Compression plating for child and adolescent femur fractures. J Pediatr Orthop 1992; 12: 626-632.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareSTUDY OF JONE'S SPINAL INDEX AS AN INDICATOR OF NARROW LUMBAR SPINAL CANAL
English118123Rupali Sureshrao Shastrakar English Arun P. KasoteEnglishThe present study was carried out on 200 subjects with 100 asymptomatic control ( 50 male and 50 female) and 100 symptomatic cases( 50 male and 50 female). The symptomatic subjects were having complaints of low backache, sciatica and neurogenic claudication of more than 6 months duration. Their age group was between 30 -80 years. The aim of the study was to find out the Jone’s spinal index on plain radiographs of the lumbar spine in normal and symptomatic subjects and to compare them. It was found that the lower normal limit of the Jone’s spinal index was 1:2.21 which indicated a wider canal. The highest value observed in controls was 1:6.08. Jone’s Spinal Index, when positive is suggestive of narrowing of the lumbar spinal canal but when negative does not exclude the possibility of narrow spinal canal
EnglishRadiographs , Lumbar spine , Neurogenic claudication , SciaticaINTRODUCTION
Low back pain resulting from degenerative diseases of the lumbosacral spine is a major cause of morbidity, disability and lost productivity. A ubiquitous and potentially disabling cause of osteoarthritic pain of the lower back and legs is stenosis of the lumbar spinal canal (Alvarez J. A., Hardy R. H.,1998). Jones R. A. C. , Salford, Thomson J. L. G. (1968), Janjua M. Z., Muhammad F. (Oct 1989) stated that Jone’s spinal index is a useful parameter in narrow spinal canal. In this study dimensions of the lumbar spinal canal were measured and Jone’s spinal index (ratio of product of transverse diameter of the canal (A) and anteroposterior diameter of the canal (B) to the product of transverse diameter of the body (C) and anteroposterior diameter of body (D) that is, AB:CD) was determined in normal and symptomatic subjects presenting with symptoms supposed to be related to narrow spinal canal by simple investigation like plain radiograph of the lumbar spine.
MATERIAL AND METHODS
The present study was carried out in the department of Anatomy at Government Medical College, Nagpur. The symptomatic subjects for the study were the patients attending the Orthopedic OPD for different complaints suggestive of narrow spinal canal. Their X-rays were taken in the Radiology department with their informed consent. Overall plain radiographs (both anteroposterior and lateral view ) of 200 subjects were included in this study
Control
Inclusion criteria:
1. Normal healthy subjects, 50 male and 50 female without any complaints suggestive of back pathology.
2. Age range between 30-80 years
.Exclusion criteria:
Subjects with significant skeletal anomalies, other problems likely to influence growth and development and younger age group (less than 19 years) were excluded to avoid lowering of the mean as lumbar spinal canal is distinctly narrower in them. ( Hink V. C., Clark W. M., Hopkins C. E. May 1966). Cases
Cases Inclusion criteria:
Symptomatic subjects aged between 30-80 years with symptoms supposed to be related to narrow lumbar spinal canal that is, 1. Chronic low back pain (more than 6 months duration), 2. Sciatica (which is defined as low back pain with radiation to one or both legs may be associated with numbness and paraesthesia) 3. Neurogenic claudication (as described by Gelderen V.,1948) and Ehni G.(Nov 1969), is characterized by leg pain, leg achiness, numbness and tingling as well as cramping and weakness, symptoms worsens with walking and distance reduces progressively
Exclusion criteria :
Those with short (acute) duration of complaints , absent peripheral pulses and any history of trauma or lifting heavy weight were excluded . The radiographs of the control and cases were taken in lying down position with an anode film distance of 110 cm. centered on L3 vertebra. Xrays were taken in anteroposterior and lateral views. All measurements were made by Vernier Calipers and were recorded in millimeters . Keeping in view the aims of the study ,following observations were made on x-rays: ? Transverse diameter of the lumbar spinal canal (TC) was measured as the minimum distance between the medial surfaces of the pedicles of a given vertebra (interpedicular distance). ? Antero-posterior (AP) diameter of the lumbar spinal canal (B) in lateral radiographs from middle of the back of the vertebral body to the base of the opposing spinous process, which can be recognized by tracing forwards its inferior margin. ? Transverse diameter of the vertebral body (C) was measured as the minimum distance across the waist of the vertebral body, which is between its upper and lower border. ? AP diameter of the vertebral body (D) at the level of inferior margin of spinous process. ? Canal to body ratio calculated i.e. Jone’s Spinal Index(ratio of product of transverse diameter of the canal (A) and anteroposterior diameter of the canal (B)to the product of transverse diameter of the body (C) and anteroposterior diameter of body (D) that is, AB:CD (Jones and Thomson ,1968). From above measurements mean values and standard deviation were calculated for each vertebral level.By calculating this ratio, it is possible to determine whether this individual measurements are within normal limits for respective vertebral body size or not.
OBSERVATION AND RESULTS
It was observed that value of Jone’s spinal index (JI) range between 1:2.0 at L4 and 1:2.5 at L5 to 1:5.5 in both male and female subjects of control and cases. .In cases the highest value observed at L4 was 1:6.5 and at L5 one value was greater than 1:7. The number of cases with value of Jone’s spinal index (JI) more than 1:4.5 when compared with number of subjects in control group were found to be highly significant at each vertebral level. Other observations on plain x rays includes varying severity of spondylotic changes in most of the symptomatic subjects. Spondylolisthesis was noted in 3 cases of symptomatic subjects.
DISCUSSION
Jone’s Spinal Index is also called as canal to body ratio(C:B)which is calculated as the ratio of product of transverse diameter of the canal (A) and anteroposterior diameter of the canal (B)to the product of transverse diameter of the body (C) and anteroposterior diameter of body(D) that is, AB:CD.
Jones R. A. C. , Salford , Thomson J. L. G. (1968), stated that, most of the normal lumbar spinal canal lie in the range of 1:2 to 1:4.5. The former ratio indicate a large canal,and the latter ratio a small canal. Janjua M. Z. , Muhammad F.(Oct 1989) stated that the normal values of the canal to vertebral body ratio (Jone’s Spinal Index) varies between 1:2 to1:5.The ratio 1:2 indicates a wider canal whereas any ratio beyond 1:5 would be conclusive of stenosis. The findings in this study were consistent with the studies of the above mentioned authors. In the study group 45 cases (45%) were having Jone’s Spinal Index more than 1:4.5 at L4 and in 59 cases (59%) at L5, suggesting a small bony canal. When spinal index was more than 1:4.5 it was suggestive of the canal stenosis, but when it was less than that, did not rule out the possibility of canal stenosis. This is because most common causes of canal stenosis includes degenerative changes in soft tissues not visualized by plain radiographs. According to Eisenstein S.( May 1977) and Naylor A. (1979) Jone’s Spinal Index is an unreliable test for assessing spinal stenosis.
CONCLUSION
Jone’s Spinal Index, when positive is suggestive of narrowing of the lumbar spinal canal but when negative does not exclude the possibility of narrow spinal canal (as narrowing of the canal in majority of cases is due to degenerative soft tissue changes)consistent with Eisenstein S.( May 1977) and Naylor A. (1979) . There are no significant differences between values of Jone’s Spinal Index of male and female cases. An advantage of Jone’s Spinal Index is that there is no need for correction regarding patients position and geometric magnification factors. These variables cancel out when the diameters of the lumbar spinal canal were related to the size of the vertebral body. Plain radiographs, it is true do not indicate the cross sectional shape of the canal, nor do they demonstrate the degree of soft tissue thickening, but various parameters used in this study can be used as an inexpensive, easy screening methods for narrow spinal canal.
ACKNOWLEDGEMENTS
We are indebted to our revered teacher and guide Dr. A. P. Kasote, associate professor , department of anatomy, government medical college , Nagpur, for his priceless guidance. We are specially obliged and thankful to our parents, family. We are grateful to technical staff in radiology department. Last but not the least, we would like to thank the almighty, who gave us the opportunity and all patients without whom, the study would not have been possible.
Englishhttp://ijcrr.com/abstract.php?article_id=892http://ijcrr.com/article_html.php?did=892REFERENCES
1. Alvarez J. A., Hardy R. H .( 1998) : Lumbar Spine Stenosis : A CommonCause of Back and Leg Pain. Am fam physician. Vol 15 ,57 (8), pp 1825-34, 1839-40.
2. Ehni G. (Nov 1969): Significance of the small lumbar spinal canal : Cauda equine compression syndromes due to spondylosis. J. Neurosurgery Vol 31. pp 490-494.
3. Eisenstein S. ( May 1977):The morphometry and pathological anatomy of the lumbar spine in South African Negroes and Caucasoids with specific reference to spinal stenosis. J Bone Joint Surg. Vol 59 B.2, pp 173-180.
4. Gelderen V. (1948): Ein Orthotisches (Lordotisches) Kauda –syndrome.Acta Psychiatr. Neurol.Vol 23., pp 57-68 (Quoted by reference no.19).
5. Hink V. C., Clark W. M., Hopkins C. E. ( May 1966): Normal interpediculate distances (minimum and maximum) in children and adults. American Journal of Roentgenology. Vol 97, no 1., pp 141- 153.
6. Janjua M. Z., Muhammad F. (Oct1989): Measurement of the normal adult lumbar spinal canal. J Pak Med Assoc. Vol 39 (10)., pp 264-8.
7. Jones R. A. C., Salford, Thomson J. L. G.(1968): The narrow lumbar canal. J Bone Joint Surg. Vol, 50B 3., pp 595-605.
8. Naylor A;J Bone Joint Surg. Vol 61B. 1979, pp306-309.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareA STUDY OF VARIATION OF CIRCLE OF WILLIS IN ADULT HUMAN BRAINS IN NAGPUR REGION OF MAHARASHTRA, INDIA
English124130Saniya H. LadeEnglish Sonal TalokarEnglish Ashish RadkeEnglishObjective: The purpose of the study was to examine the variations in arteries contributing in the formation of Circle of Willis in adult human brains from Nagpur region of Maharashtra. Material and methods: The external diameters of posterior cerebral artery (PCA), posterior communicating artery (PCOM), internal carotid artery (ICA), anterior cerebral artery (ACA) and anterior communicating artery (ACOM) in 50 male and 50 female brains were measured with verniercaliper. Photographs were taken and results studied by applying t.test and z test. Results: In this study 99% circles were complete.One circle with absent right sided PCA was found.Hypoplasia was noted in about 37 to 39% circles for PCA, about 39% circles for PCOM, 20% circles for ICA, 44% circles for ACA and 44% circles for ACOM.6% ACOM showed duplication. Regarding gender differences, hypoplasia of vessels overall was found to be more common in females than males. Duplication of ACOM was another finding found in female circles only. Conclusion: In present study it appears that there do exist variation in arteries forming circle of willis. Some preponderance to some arteries is also found in this study. Again male and female comparison is also helpful as it has revealed some significant findings. Such knowledge of circle of willis is of utmost importance to surgeons before performing any surgery related to ICA and also important for physicians to lead to conclusions in stroke and infarct patients where MRI can be used to find out status of arteries.
EnglishCircle of Willis, Anterior Cerebral Artery, Anterior Communicating Artery, Posterior Cerebral Artery, Internal Carotid Artery, Posterior Communicating Artery.INTRODUCTION
Thomas Willis is considered as one of the greatest anatomist of all times. His name is associated with the Circle of Willis, an anastomotic circle at the base of the brain. His work also formed the foundation of basic neuroanatomical description and nomenclature and comparative neuroanatomy. Willis provided a complete description of this vascular pattern and indicated that he understood the probable function of the circle. (Cagatay Ûstun ) 1 . It is a circle that supplies blood to the brain and is also known as Willis Polygon. It comprises ofanterior cerebral artery, anterior communicating artery, posterior cerebral artery, internal carotid artery, posterior communicating artery.It is an anastomosis of basilar system and internal carotid system lying in the interpeduncular cistern. (Satheesha Nayak)2 The Circle of Willis has an important role in maintaining a stable and constant blood flow to the cerebral hemisphere especially old people who may have reduced brain blood supply. The most common reason for this is senile arterioscelosis. Researchers have found a close correlation between a low capacity circle and an increased risk of stroke.Collateral ability of circle of willis be best used when there is emergency which again depends on the size of lumen and caliber of its component vessels. (K Ranil D De Silva) 3 Abnormalities in diameter of vessels forming circle of willis is found by many workers .Two reports appear in literature that of Alpers, Berry andPaddison(1959) and that of Fetterman and Moran(1941) stating that an external diameter of 1mm and 0.5mm or less, respectively would be considered abnormal. (Sylvia Kamath) 4 Against this background present study is carried out with following aims and objectives: 1. To study the variations of vessels forming the circle of willis 2. To find out any preponderance of variation in any particular vessel in this region. 3. To find out differences in males and females if any. 4. To compare the frequencies of different variants with previous autopsy studies
MATERIAL AND METHODS
The present study was carried out in the department of anatomy from July 2009 to August 2011.It includes100 human brains (50 males and 50 females) irrespective of the cause of death. Brains were obtained from Forensic department of IGGMC, Nagpur and from the cadavers in the dissection hall of our college. Steps in studying the circle of willis: 1. Skull bones were carefully cut with hammer and chisel. Vault was removed and brain was taken out carefully after cutting the dura folds. 2. The removed brains were dipped in water and then washed under running water for 15 mins and now placed inverted over a clean surface to expose the base of brain; the water was soaked with tissue paper. 3. The circle of willis was observed at the base of brain. Measurements of arteries forming the cicle of willis were taken with vernier calipers graduated to measure upto 0.5mm, at two ifferent points and values were noted down on a preformed data sheet. 4. Finally, photographs were taken with digital cameras in order to avoid errors due to different angles of view, images were taken almost perpendicular to the plane of the circles. Arteries of 1mm and less diameter were considered abnormal, barring the communicating arteries, where 0.5 mm and less was considered abnormal. The measurements were then subject to stastisticalanalysis
Morphology of vessels forming Circle of Willis: Segments from the following corresponding regions were included in study by K Ranil D De Silva5 as right and left internal carotid arteries (ICA) close to their distal ends, precommunicating and postcommunicating part of the anterior cerebral arteries (a1), (a2) and the posterior cerebral arteries (p1), (p2) close to their origin, right and left posterior communicating arteries (PCOA) at their middle point and anterior communicating artery (ACOA) (with its variations if present) at its middle point. (K Ranil D De Silva)5 In this study following points were taken into consideration for measurement of the external diameter of arteries with the vernier calipers. A 1-PCA just before bifurcation on right side B 1- PCA after bifurcation on right side A 2- PCA just before bifurcation on left side B 2- PCA after bifurcation on left side C 1-PCOM near PCA right side D 1- PCOM near ICA right side C 2 - PCOM near PCA left side D 2- PCOM near ICA left side E 1-ICA before forming circle of willis on right side F 1- ICA after forming circle of willis on right side E 2- ICA before forming circle of willis on left side F 2- ICA after forming circle of willis on left side G 1-ACA at its origin on right sideH 1-ACA near ACOM on right side G 2- ACA at its origin on left side H 2-ACA near ACOM on left side Diameter of ACOM at its center point After the collection of data mean value of the measurements from the above two different points was taken out. Single value of right sided vessels was now ready for comparison with single value of left sided vessel.
Symmetrical circle: Circle which has the external diameters of vessels on right side exactly equal to that on left side is the symmetrical circle. (Prof.E.Fawcett 1905)6 . Circle with variation in external diameters of corresponding vessels are considered as asymmetrical circles. The arteries were measured and mean was taken.Normal measuring arteries, hypoplastic arteries and absent arteries were noted. Posterior cerebral artery: 63% of right sided arteries and 61% of left sided arteries were of normal measurement while 37% of right side and 39% of left sided arteries were hypoplastic. One artery on right side in a male brain was found to be absent. Posterior communicating artery: 64% arteries on right side and 61% arteries on left side were normal. Hypoplasia was observed in 36% on right side and 39% on left side. Internal carotid artery: 80% of arteries were normal on both side while only 20% showed hypoplasia. Anterior cerebral artery: 56% arteries on right side and 58% arteries on left were normal .44% and 42% arteries on right and left side respectively showed hypoplasia. One circle of a male brain showed stenosis. Anterior communicating artery: 56% arteries were normal while 44% were hypoplastic. Gender differences In posterior cerebral artery more percentage ofhypoplasia was seen in males (48%) than in females(42%). 2% of male brains show absent right sided artery.No aplasia was observed in female brains. There was a significant finding regarding hypoplasia of posterior communicating artery, internal carotid artery, anterior cerebral artery and anterior communicating artery. Frequency of hypoplasia was more in females than males. Posterior communicating artery: Frequency of vessels measuring >0.5mm is more in females both for right (74%) and left(62%) as compared to males where the values are 54% for right and 60% for left. Internal carotid artery: In females hypoplasia is more (32%) as compared to males (8%) on both right and left side. Anterior cerebral artery: In males right sided artery is larger than left side in 14% circles which is more than females where the value is 4%.viceversa is true where 9% of females show left sided artery larger than right .In males this value is only 2%. Frequency of hypoplasia is more in females with preponderance to right side (54%).Only 46% circles show hypoplasia on left side.Male circles show only 32% and 30% hypoplastic arteries on right and left side respectively. Anterior communicating artery:Frequency of hypoplasia is more common in females which is 62% than males which is 26%.Duplication is seen in 3% of female circle .In present study duplication is 0% in male circles.
P value is also significant for ACOM i.e 0.001209. Mean diameter of ACOM in males is larger than females.
DISCUSSION
The study reveals some unknown facts regarding vessels contributing in formation of CirleOf Willis in adult human brains in Nagpur region with preponderance to some arteries.Complete circles are more common with aplasia of any vessel being a rare finding. (Prof. E Fawcett)6 Aplasia of PCA on right side is noted in one male brain which is a significant finding with no literature coinciding with this finding. Frequency of hypoplasia in ICA is more as compared to previous findings. In present study it is 20%. It means that people in this region have more hypoplastic ICA as compared to other places when the previous literatures are reviewed. ACA again show higher percentage of hypoplasia (44%) which is too high to coincide with the previous studies. Abubakhr7 and Bertram8 revealed only 0.7% and 10% hypoplasticACA.Stenosis is noted on left side which is very significant finding in present study. Hypoplasia is a common finding in communicating vessels which is a finding in this study also.Range of hypoplasia is very wide from 0.2% to 86% as literature states.Bertram8 noted duplication as most common abnormality.In present study 6% of ACOM showed duplication which can be compared to the finding of Prof. Fawcett6 which is 7.2%. Symmetrical circles are more common in females than males. Mean diameter of anterior cerebral artery is significantly larger in males than in females. (pEnglishhttp://ijcrr.com/abstract.php?article_id=893http://ijcrr.com/article_html.php?did=893REFERENCES
1. CagatayÛstunDr. Thomas WillisÕ Famous Eponym: The Circle of Willis;Turk J Med Sci 34 (2004) 271-274.
2. SatheeshaNayak,Somayaji S N,Saumya K V ;Variant arteries at the base of the brain; International Journal of Anatomical Variation[2008]60-61.
3. K Ranil D De Silva, RukmalSilva, W.S.LGunasekera , R W Jayesekera; Prevalence of typical circle of willis and variation in anterior communicating artery :A study of a Sri Lankan population;Annals of Indian Academy of Neurology; July-Sept 2009;vol.12;issue 3;157- 161.
4. Sylvia Kamath;Observations on length and diameter of vessels forming the circle of willis;Journal of Anatomy(1981);133;3;419-423. 5
. K Ranil D De Silva ,Rukmal Silva , DhammikaAmaratunga , WSL Gunasekera and Rohan W Jayesekera.Types of the cerebral arterial circle (circle of Willis) in a Sri Lankan Population .BMC Neurology 2011, 11:5.
6. ProfessorE.Fawcett,Dr.J.V.Blachford;The circle of willis:An examination of 700 specimens; journal of anatomy and physiology; 1905;vol.XL ,pg.83.
7. Abubakr HM Alawad, Mustafa A Hussein , Mohamed A Hassan. Morphology and normal variations of the Cerebral Arterial Circle ?of Willis? in Khartoum Diagnostic Centre. Khartoum Medical Journal (2009) Vol. 02, No. 02, pp. 215 – 219.
8. BertramC.A.Windle-On arteries forming the circle of willis;journal of anatomy and physiology;1888 Jan;22[pt.2];289-293.
9. Paul S And Mishra S;Variation of the anterior cerebral artery in human cadavers:A dissection study;Journal of Anatomical society India 53[1]15-16[2004]
10. Sylvia Kamath;Observations on length and diameter of vessels forming the circle of willis;Journal of Anatomy(1981);133;3;419-423.
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareSERUM LEVELS OF ANTIOXIDANT TRACE ELEMENTS ZINC AND COPPER IN SENILE MATURE CATARACT
English131137Manoj B.English Shubha JayaramEnglishBackground: There is much evidence suggesting that nutrition and nutritional factors, especially the trace elements zinc and copper may play a role in the formation of human cataract, a disease that is on the increase due to the growing percentage of elderly persons in the world population. Objectives: The present study was done to estimate levels of antioxidant trace elements zinc and copper in the serum samples of senile mature cataract patients. Methods: This is a case control study carried out in the Department of Biochemistry, PES Institute of Medical Sciences & Research, Kuppam, Chittoor district, Andhra Pradesh. 30 senile mature cataract patients and 30 normal age and sex matched controls were selected for the study. Serum zinc and copper levels were measured in above groups. Results: Serum Zinc levels in senile mature cataract patients was 126.63+78.40 μg/dl and in controls 131.01 + 90.2 μg/dl. serum copper levels in senile mature cataract patients was 85.82 ± 48.1 μg/dl and in controls it was94.23 ± 52.4μg/dl. The zinc copper ratio was found to be 1.47 in senile mature cataract patients and 1.39 in controls. There was no significant difference in the zinc and copper levels between the two groups. Conclusions: The present study showed no significant alterations in the levels of zinc and copper in serum samples of senile mature cataract patients. Further studies are required involving a larger study group regarding the nutritional behavior, correlation of antioxidant enzymes with zinc and copper levels and the effect of smoking and alcohol consumption on the levels of zinc and copper in senile mature cataract patients.
EnglishZinc, Copper, Trace elements, Senile mature cataract.INTRODUCTION
In the recent years there has been a steady rise in the mean age of the global population. A rise in prevalence of senile cataract is one of the consequences of expanding elderly population. Cataract is the most common cause of blindness and visual disability worldwide. At the turn of the century, WHO and the International Agency for Prevention of Blindness launched the Vision 2020: the right to sight initiative(1).The most recent estimates from WHO reveal that 47.8% of global blindness is due to cataract and in South Asia region which includes India, 51% of blindness is due to cataract.(2) The causes of cataract, the world’s largest single cause of blindness are multi factorial. Cataract can include cases developmental in origin or secondary to trauma, systemic diseases, drugs and age related factors. Senile or age related cataract is responsible for more than 80% of all cataracts.(3) . Cataract being age related disorder; it is but natural that its incidence increases as longevity increases. For example, in the west, the incidence of cataract in people over 50 years is 15% while in developing countries it is about 40%.(4).The absolute number of cataract blind would increase from 7.75 million in 2001 to 8.25 million in 2020 due to a substantial increase in the population above 50 years in India over this period(5). There is much evidence suggesting that nutrition and nutritional factors especially trace elements zinc and copper may play a role in the formation of human cataract and also in causation and acceleration of cataract.(6) Recent studies have showed increased lipid peroxidation due to oxidative stress as an important causative factor for cataract. The lens is under constant oxidative stress from reactive species of oxygen. These species can damage the lens cellular membrane and macromolecule, as well as enzymes involved in energy production and membrane transport. With ageing, enzymatic and non enzymatic antioxidant capabilities change. The excessive free radical attack implicated in the development of cataract can be protected by dietary intake of micronutrients with antioxidant capabilities. . It appears possible that in cataract the oxidant antioxidant equilibrium is shifted towards oxidant stress and there might be an increased demand for antioxidant micronutrients (vitamins and trace metals) and enzymes concerned with meeting such oxidant stress. Zinc and Copper are important cofactors for antioxidant enzymes like super oxide dismutase, which is one of the most important antioxidant enzymes which combat against this increasing oxidative stress in senile cataract.(7) Senile cataracts were found to have low levels of Zinc and high levels of Copper(8). Plasma levels of Zinc and Copper are significantly low in cataract patients (9). Trace element analysis of diets consumed by Indians has revealed the inadequacy of copper and zinc as compared to recommend daily intakes. Thus copper and zinc deficiency might play an important contributory role in cataract risk. While some studies have shown normal serum zinc levels, other studies have shown a decreased serum zinc levels and there are very few studies regarding the status of these trace elements in senile cataract in a rural population. Hence the present study to estimate the serum levels of zinc and copper in senile mature cataract patients
OBJECTIVES
1. Estimation of serum levels of zinc and copper in senile mature cataract patients
2. Comparing the same with healthy normal controls.
MATERIALS AND METHODS
This study was conducted in Department of Biochemistry, PES Medical College and Department of Ophthalmology, PES Institute of Medical Sciences & Research, Kuppam, Chittoor district, Andhra Pradesh. The study was approved by the ethical committee of the institution. Total number of subjects taken up for the study was 60, out of these 30 cases, diagnosed as senile mature cataract patients were included as cases.30 normal,age and sex matched healthy subjects were considered as controls.This sample size was arrived at by keeping 5% significance and allowable error of 20%. The subjects for the study were divided into 2 groups namely: Group – I Cases with senile mature cataract. Group – II normal healthy controls
Sample collection
All the samples were collected from the Ophthalmology OPD. After obtaining informed consent, 5 ml of venous blood was collected from cubital vein taking aseptic precautions. The sample was centrifuged for 10 minutes at 3000 rpm and serum was separated. All the samples were analyzed on the same day of sample collection. The following biochemical parameters were assayed: 1. Serum zinc 2.Serum Copper 3. Blood glucose (FBS) All the biochemical parameters were assayed using chem well fully automated analyzer. Estimation of Blood Glucose levels were done to rule out diabetes mellitus .Blood glucose estimation was done by glucose oxidaseperoxidase method.Serum Zinc levels were estimated by nitro PAPS colorimetric method. Nitro-PAPS react with zinc in alkaline solution to form a purple colour complex, and theintensity of the complex formed is directly proportional to the amount of zinc present in the sample at 570 nm(10) . Serum Copper levels were estimated by Di-BrPAESA colorimetric method. 3, 5-Di-Br-PAESA combines with Copper to form a blue–violet complex, the absorbance is measured at 580 nm(11). Statistical methods: the results were tabulated, data was analysed , mean,standard deviation was calculated and the results were compared by using student t test using instat statistical software.
RESULTS
The study was carried out at PES Institute of Medical Sciences and Research, Kuppam, Chittoor (District), A.P. The salient findings in the present study are the study of zinc and copper in senile mature cataract patients. In the present study zinc and copper levels were analyzed in serum samples of subjects with senile mature cataract and the levels were compared with normal healthy individuals. In the current study 60 subjects wereselected out of this 30 are senile mature cataract cases and 30 normal healthy individuals. Samples were age and gender matched. More number of cases was found in age group 51 -60 years (40%). This has been shown in table no.1. The mean Serum Zinc value in senile mature cataract patients was126.63+78.40 µg/dl and in controls the mean value was 131.01+ 90.2 µg/dl. The difference between the mean values between the two groups was not statistically significant.(p=0.841). This has been shown in table no.2 The mean serum copper values in senile mature cataract patients was 85.82 ± 48.1 µg/dl and in controls it was 94.23 ± 52.4µg/dl. The means of cases and control values was not statistically significant. This has been shown in table no. 3. The zinc copper ratio was found to be 1.47 in senile mature cataract patients and 1.39 in controls .there was no significant difference between the zinc copper ratio between the two groups.
DISCUSSION
At the turn of the century, WHO and the International Agency for Prevention of Blindness launched the Vision 2020: the right to sight initiative. Since cataract is a major cause of avoidable blindness in the developing countries, the key to the success of the Global Vision 2020: the right to sight initiative is a special effort to tackle cataract blindness(5). It has been observed in most of the studies that the metabolism and status of micronutrients are altered in senile mature cataract patients(1). There is much evidence suggesting that nutrition and nutritional factors, especially the trace elements zinc and copper may play a role in the formation of human cataract, a disease that is on the increase due to the growing percentage of elderly persons in the world population(6).
Serum Zinc
There was no significant difference between zinc values of cases and controls in the present study. Karcioglu(12) in 1982 described the knowledge about zinc metabolism in the eye as fragmentary and quite confusing .This statement is still appropriate as there has been a good amount of controversy regarding the status of these trace elements in serum as well as in the tissue of the eye like aqueous humor and lens and their possible role in senile cataractogenesis. Akyol(13) on a study of cataract patients reported serum Zn concentration within the normal range (80-140 µg/dl) and no significant difference was found. Bhat(14) in a study in India showed that plasma levels of Zn and Cu were lower in patients compared to controls, but Mohan and his colleagues in a larger study were unable to demonstrate such an association(15). IssaNourmohammadi et al(16), have also shown lower serum zinc levels in cataractous patients compared to controls. Indranilchakraborthy et al, have also found a decreased serum zinc levels in cataract patients compared to controls(17). The present study is in concordance with that of Akyol et al(13)and mohan et al(15), who have also reported no significant changes between zinc levels of cataract patients and controls. A study by K. N. Sulochana, R. Punitham, and S. Ramakrishnan(18) has also shown no significant changes in zinc levels of cataract patients and controls. But it has shown significant difference in zinc levels between smokers with cataract and non smokers with cataract. This shows that zinc supplementation may be of help in such patients. Zinc being chiefly an intracellular metal is stored in various intracellular protein and enzymes, SOD (superoxide dismutase) being one of them. Although circulating zinc in plasma and serum often has been shown to indicate human zinc deficiency, it does not always accurately reflect the whole body zinc status. The diagnosis of zinc deficiency is difficult due to the lack of a single specific and sensitive biochemical index of zinc status. The most reliable method for diagnosing marginal zinc deficiency in humans is considered to be a positive response to zinc supplementation. An alternative approach is to use a combination of biochemical and functional tests to evaluate zinc status. Serum or plasma zinc on its own is neither sensitive nor specific. A number of comprehensive reviews have been published on the subject of assessing zinc status in the human population. This may be the reason for the inconclusive nature of serum zinc levels in the present study. There has been a few studies on estimation of zinc levels in cataractous lenses, which have shown increased zinc levels in cataractous lenses. In contrast, some studies have reported a significant decline in lens zinc concentration in the zincdeficient rats. This series of reports linking zinc to the lens suggests that the physiologic function of zinc in the lens should be explored as well as the impact of zinc deficiency on cataract development. Serum copper In the present study Mean Serum copper value in controls is 94.23+52.4 μg/dl where as the value in cataract patients is 85.8 ± 48.1 μg/dl . The difference between the means of patients and controls is not statistically significant. (p=0.60) Our study is concordant with that of Jacques et al(19) who studied serum Cu levels and increased risk of cataract but the association was not statistically significant. andakyol et al(13), and mohan et al(15) who have found the same results. A recent study by K.N.Sulochana et al(18) , has also shown no significant difference in blood copper levels and ceruloplasmin levels between cataract patients and controls. How everbhat et al(14), reported decreased levels of copper in serum samples of cataract patients compared to controls. Conflicting results have been reported in the literature regarding serum copper levels in cataract cases. Several epidemiological studies from various countries on elderly subjects showed lower Zn levels with values ranging from 18% lower levels to 40%. However, whether these concentration changes are the actual cause of cataract development or are the consequence of disease itself must be further studied. Therefore further assessment should be carried out on the safety and efficacy of Zn and Cu dietary supplementation in the treatment of senile cataract The present study has shown a zinc copper ratio of 1.47in cataract patients and 1.39 in control group. Nasiruddin. M et. al(20), using the data compiled from several studies has shown the normal zinc copper ratio to be 1.07 and have observed that the ratio remains normal in cataract cases, which is concordant with the present study. A slightly higher ratio in the present study may be due to smaller group size.
CONCLUSION
The present study has tried to estimate Antioxidant trace elements like zinc and copper in the serum samples of senile mature cataract patients and the comparative study of these parameters with controls . In conclusion no significant alterations of zinc and copper levels were found in the serum of senile mature cataract patients in the present study. Further studies are required involving a larger study group regarding the nutritional behaviour, correlation of antioxidant enzymes with zinc and copper levels and the effect of smoking and alcohol consumption on the levels of zinc and copper in senile mature cataract patients. A complete understanding of the role of zinc and copper at the molecular level is required to plan intervention studies to establish firm criteria for zinc and copper supplementation aimed at prevention of senile mature cataract.
ACKNOWLEDGEMENTS
The authors would like to acknowledge the support of all the patients who have taken part in the project. This study was conducted with support from the Indian Council of Medical Research (ICMR) as Short Term Studentship (ICMR-STS) program for Manoj B. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Englishhttp://ijcrr.com/abstract.php?article_id=894http://ijcrr.com/article_html.php?did=894REFERENCES
1. Foster A. Vision 2020: The Cataract Challenge. Community Eye Health 2000;13:17-21.
2. World Health Organization. Global initiative for the elimination of avoidable blindness: An informal consultation. WHO/PBL/97.61. Geneva: WHO; 1997.
3. Evans J, Minassian DC. Epidemiology of Age-related Cataract. J Comm Eye Hlth 1992;9:2-6.
4. Ohrloff C. Epidemiology of senile cataract. In Hockwin O, Sasaki K, Leske MC (eds). Risk factors for cataract development. Karger: Basel, 1989.pp1-5.
5. Murthy G, Gupta SK, John N, Vashist P. Current status of cataract blindness and Vision 2020: The right to sight initiative in India. Indian J Ophthalmol 2008;56:489-94
6. West Sk, Val Madrid CT. Epidemiology of risk factors for age related cataract. Survophthalmol 1995;39:323-34.
7. Minassian DC, Mehra V. 3.8 million blinded by cataract each year: Projections from the first epidemiological study of Incidence of Cataract Blindness in India. Br J ophthalmol 1990;74:341-3
8. Nath B, Srivastava SK, and Singh K. accumulation of copper and inhibition of lactate dehydrogenase activity in human senile cataractous lens. Indian J Exp Biology. 7:25-26,1969.
9. Bhat K. S. Nutritional Status of Thiamine, riboflavin and pyridoxine in cataract patients. Nutr Rep Int. 36:685-692,1987.
10. Makino T .A sensitive, direct colorimetric assay of serum zinc using nitro-PAPS and using micro well plates .Clinchem acta1991; 197:209-220.
11. Abe, Akita, S. Yamashita, and A. Noma. "Sensitive, direct colorimetric assay for copper in serum."Clinical chemistry 35.4 (1989): 552- 554.
12. Karcioglu ZA: Zinc in the eye. SurvOphthalmol 1982;27:114–122.
13. Akyol N, Deger D, Keha EE, Kilis S, et al. Aqueous humor and serum zinc and copper concentrations of patients with Glaucoma and Cataract. Br. J. ophthalmol.1988; 74:661-2.
14. Bhat K. S. plasma calcium and trace metals in human subjects with mature cataract. Nutr. Rev. Interanat. 1998:37:157-63.
15. Mohan M. Study design and data of WHONPCB blindness survey-1986-88. In Lim ASM (ed): World’s major Blinding conditions. Published by XXVI international congress.Opthalmol. Singapore, 1990, PP. 182187.
16. IssaNourmohammadi, Mansour Mirsamadi. Serum zinc and copper concentration in human age related cataract. MEJAA, Nov 2004, vol 1, issue 2 :10-14.
17. IndranilChakraborty, SanjoyKunti, MousumiBandyopadhyay, AnindyaDasgupt, Gopal Deb Chattopadhyay and SandipChakraborty. Evaluation of serum zinc level and plasma and activity in senile cataract patients under oxidative stress. Indian J. Clin.Biochem., 2007; 22: 109-13.
18. K.N.sulochana, R. Punitham, S. Ramakrishnan, Effect of cigarette smoking on cataract: Antioxidant enzymes and constituent minerals in the lens and blood of humans. Indian Journal of Pharmacology 2002; 34: 428-431.
19. Jacques PF, Hartz SC, Chylack LT Jr, et al. Nutritional status in persons with and without senile cataract: blood vitamins and minerals levels. Am J clinNutr. 48:152-158,1988.
20. Nasiruddin, M. "XXXV Annual Conference of the Indian Pharmacological Society, Gwalior, November 26-29, 2002, Abstracts of Research Papers (Part-Vi)." Indian Journal of Pharmacology 36.1 (2004): 54
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareESTIMATION OF GLYCATED ALBUMIN LEVELS IN VARIOUS THYROID DISORDERS
English138144Suresh Babu KondaveetiEnglish Bhanu Prakash G.English I. Anand ShakerEnglishBackground: Glycation is the linking of sugar molecule to various compounds such as glucose, lipid or protein. As albumin is one of major protein in our circulation, to which sugar has bonded to form Glycated albumin. Albumin is present not only in blood but also in major organs and body fluids and it serves to maintain cell shape and distribution of hormones. Objective: The present study was designed to compare the levels of GA in Various thyroid disorders group with Normal healthy control group. Materials and Methods:The present cross sectional study includes 200 cases, (n=50 in each group) newly diagnosed hyperthyroidism, hypothyroidism, subclinical hypothyroidism and normal controls between 30-55 years of both genders.serum samples obtained for the estimation of T3,T4,TSH and glycated albumin. Statistical analysis done by using SPSS, version16.0. One-way ANOVA was performed. All P-values which were ?0.05 were considered as stastically significant. Results: Glycated albumin values were found to be significantly correlated among the different groups (p=0.001). GA levels significantly increased in hypothyroidism, subclinical hypothyroidism and lowered in hyperthyroidism group compared to normal group. Significant correlation was found between T3, T4, TSH and GA levels. Conclusion: The present study showed increased levels of GA among experimental groups when compared with the normal control group. Hence It was concluded that estimation of serum GA will be useful as a noval parameterin thyroid disease cases.
EnglishGlycated albumin, Hypothyroidism, subclinical hypothyroidism, HyperthyroidismINTRODUCTION\
Thyroid gland is a body organ located in front of the neck. It has two lobes, one on each side of trachea. The thyroid gland takes iodine from blood and synthesizes two active hormones called triiodothyronine (T3) and thyroxine (T4) and these hormonal production regulated by TSH[1]. Thyroid hormones control the body’s cell metabolism. When thyroid hormones are released into the bloodstream, cells increase the rate at which they convert oxygen and nutrients into energy and heat for the body’s use [2]. Abnormalities of thyroid gland function are more common among individuals with developmental disabilities than in the general population, But overt hypothyroidism and subclinical hypothyroidisms are become relatively common now a days in general populationas well [3,4]. When thyroid gland is overactive and produces too much thyroid hormone an individual develops hyperthyroidism and Subclinical Hypothyroidism is defined as a condition in which serum TSH concentration above the statistically defined upper limit of the reference range, when the serum free T4 concentration is within its reference range [5,6]. Primary hypothyroidism and thyrotoxicosis are very common in adult female genders with prevalence rate 3.5per thousand and 0.8 per thousand respectively. There is increased T3 and T4 levels with decreased or normal TSH levels in case of thyrotoxicosis especially in developed countries[7]. Glycated albumin formed by non enzymaticglycation in which reducing sugars are covalently attached to amino acid residues especially serine, lysine residues of protein[8]. The reducing carbonyl group of glucose can react with the amine groups of human serum albumin (HSA) to form glycated albumin (GA) (Schiff-base) which results in a 162 Da molecular weight increase for each glucose-induced glycation on HSA. This is followed by the Schiff-base reorganized itself to the more stable aminomethyl ketone by the Amadori rearrangement [9] In hypothyroid patients the Glycated protein levels have been increased and in case of hypothyroid cases its levels were found to be decreased [10]. Compared to normal subjects the GA levels higher in primary hypothyroidism cases and lower in Grave’s disease. As thyroid hormone promotes albumin metabolism the mean concentration of albumin and total protein in serum were lower in hyperthyroid patients than the hypothyroid patients[11]. It has been proved from the previous studies that GA can be used to monitor short term glycemic controlthan glycated hemoglobin[12]. We therefore hypothesized that GA levels do not reflect accurately glycemia in hypothyroidism.
MATERIALS AND METHODS
The present cross-sectional study was conducted from December 2010 to January 2012 in MAPIMS&R hospitalMelmaruvathur, Tamil Nadu respectively. A total of 150 cases were selected (n=25 in each group) newly diagnosed hyperthyroidism, subclinical hypo thyroidism, hypothyroidism and normal control between the ages of 30-58 years of both sexes (M:F ratio 65:85) were selected for this cross sectional study from the outpatient department of endocrinology in MAPIMS&R and were compared with 50 (M: F 20:30) control subjects. After the full explanation of the study, written informed consent was obtained from each study subject. The study was approved by the Ethics committee of the institution prior (EC NoMAPIMS/RC/NOV/2010/24) the informed consent was obtained from all the subjects.Demographic and anthropometric details like age, weight, height, duration of disease, duration of treatment were recorded for all the study subjects. Family history of Thyroid disease and hypertension, smoking and alcohol consumption habits were obtained from the medical records of the study subjects.Patient on treatment for any disorder, lipid lowering drugs, diabetes, malignancy and pregnant women were excluded.Blood samples were collected for the biochemical estimations such as T3, T4, and TSH using Hitachi auto analyzer by Electro Chemiluminescence immune assay (ECLIA) method.Plasma glycated albumin (GA) levels were measured by an enzymatic method using albumin specific protease, ketoamine oxidase and albumin assay reagent on the Hitachi autoanalyser 912 (Lucica GA-L, Asahi Kasei Pharma Corp, Tokyo, Japan) [13,14] GA was hydrolyzed to amino acids by albumin specific protease and then oxidized by ketoamine oxidase to produce hydrogen peroxide, which was measured quantitatively. The GA value was calculated as the percentage of GA relative to total albumin, which was measured with bromocresol purple method. The measured values of GA was not influenced by the substances such as bilirubin F up to 14.6 mg/dl, bilirubin C up to 15.2 mg/dl, glucose up to 1000 mg/dl, ascorbic acid up to 100 mg/dl. The statistical analysis was done by using SPSS version 16.0. One Way ANOVA method was applied to observe association of microalbuminuriawith GA and duration ofdiabetes. P value < 0.0001 was considered as statistically significant.
RESULTS
The mean values of thyroid hormones among experimental group along with the normal group has shown in fig 1.GA values were much more elevated in hypothyroidism group compared to subclinical hypothyroidism group shown in figure 2 and the values were lower than the normal level in hyperthyroidism group and higher than normal in hypothyroidism group which is statistically significant.Figure3 shows the GA values and FPG levels of different groups which were below normal in case of hyperthyroidism and above normal in subclinical hypothyroidism which is stastically significant. GA values found to be significant among the groups (p=0.001). In hypothyroidism specificity and the sensitivity was found to be 100% and 98.4%and in hyperthyroidism it is 94.8% and 72%. Where as in Subclinical hypothyroidism it is around 95.5% and 78%. Compared to hypothyroidism group the albumin values in hyperthyroidism group found to be decreased which is statistically correlated negatively with hypothyroidism but no statistical significant correlation with total proteins. While comparing with the normal GA levels as 12-16 mg % the sensitivity, specificity, positive predictive value(PPV) of GA for hyperthyroidism, hypothyroidism, and subclinical hypothyroidism.fig 4 and fig 5 showing the serum MDA and protein carbonylation levels in the experimental groups which are elevated in hypothyroidism group as well as in subclinical hypothyroid group. At the same time serum antioxidants such as GSH levels decreased in respect to increase of oxidants in all the groups except normal group
DISCUSSION
Thyroid hormone exert profound effects in the regulation of glucose homeostasis, including modification of circulating insulin levels and other counter regulating hormones[15].thyroid disorders has got a major impact on glucose control. When thyroid dysfunction the glucose homeostatic balance is broken and it is mainly associatedwith increased hepatic gluconeogenesis whichis a characteristic of excess of thyroid hormones i.e Hyperthyroidism [16]. In hypothyroidism glucose homeostasis also get affected although it’s clinical impactless it’s because of less disposal of glucose [17]. At the same time insulin resistance has been reported in subclinical hypothyroidism with altered glucose levels [18]. As deficiency or over production of thyroid hormones plays major role in glucose homeostasis, so we tried to assess the glycated products such as glycated albumin levels in various thyroid disorders. In our study GA levels significantly correlated (p=0.001) when inter comparison was done among different groups and we found GA levels are above normal in case of hypothyroidism, subclinical hypothyroidism and lower the normal values in case of hyperthyroidism. The albumin values were found to be decreased in hyperthyroidism group compared to hypothyroidism which was statistically significant. The increased GA levels in hypothyroid patients along with non clinical hyperglycemia because of deterioration of protein metabolism which further decreases turnover of proteins and increase of half life of proteins. And the increase in glycation of proteins via auto oxidative glycation incase of increased oxidative stress[19]. There is marked increase in protein carbonylation, serum Malondialdehyde and decreased glutathione levels in hypothyroid cases explaining increased peroxidation of lipids might be a contributing factor for increased protein glycation[20] . Low grade inflammation and free radical formation causes increase in higher immunoglobulin production explains glycation of these immunoglobulins. Disturbance in glucose homeostasis with decreased glucose absorption and utilization leads to insulin resistance this further causes glycation of proteins. In case ofsubclinical hypothyroidism the GA levels were not that higher compared with hypothyroid group. The GA levels were lower in hyperthyroid in contrast to hypothyroid and subclinical hypothyroid groups but with higher plasma glucose levels[21,22,23]. Previous studies showed that there is increase in glycated HbA1c which corresponds to raise in glucose concentration but with the low levels of Glycated albumin which is very contradictive[24].
CONCLUSION
There are only studies reported about HbA1C levels in thyroid disorders so we tried to estimate glycated products such as GA other than HbA1C, and present study suggests an increase GA levels in all the thyroid disorders with which we conclude, that we can consider GA as a diagnostic criterion in thyroid disorders.
ACKNOWLEDGEMENT
The authors are thankful to the Management, MAPIMS&R and M.Sachithanandam, Vishnu Diagnostics Center, No. 1 Ennakara street, Kancheepuram 631501 Tamilnadu for providing the necessary facilities and permitting to carry out this research work. The authors are very much thankful to all the Physicians who had referred the cases to this Diagnostic Center. Authors also acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
Source of support: - Nil
Conflict of Interest: - None declared
Englishhttp://ijcrr.com/abstract.php?article_id=895http://ijcrr.com/article_html.php?did=895REFERENCES
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9. Day, J.F.; Thorpe, S.R.; Baynes, J.W. Nonenzymaticallyglucosylated albumin. In vitropreparation and isolation from normal human serum. J. Biol. Chem. 1979, 254, 595– 597.
10. CirilloR,Balzano S, Cossu E, BartelenaL,Solinas MP, Falcone M, Balestrieri A, Martino E. The effect of altered thyroid function on serum fructosamine concentrations. Clin Biochem.1988 Jun; 21(3):179-81.
11. Larsen P, Davies T. Hypothyroidism andthyroiditis. In Williams Textbook of Endocrionology. 10th ed. Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, Eds. Maryland Heights, Missouri, Saunders Elsevier, 2002, p. 423–455
12. Masaaki Inaba, SenjiOkunoet al. Glycated Albumin Is a Better Glycemic Indicator thanGlycated Hemoglobin Values in Hemodialysis Patients withDiabetes: Effect of Anemia and Erythropoietin Injection J Am SocNephrol 18: 896 –903, 2007. doi: 10.1681/ASN.2006070772
13. Kouzuma T, Usami T, Yamakoshi M, et al. An enzymatic method for the measurement of glycated albumin in biological samples. ClinChimActa 2004; 324: 61-71.
14. Kouzuma T. Study of glycated amino acid elimination for an improved enzymatic glycated albumin measurement method. ClinChimActa 2004; 346: 135-143
15. Raboudi N, Arem R, Jones RH et al. Fasting and postabsorptive hepaticglucose and insulin metabolism in hyperthyroidism. Am J Physiol1989;256:E159-66.
16. Weinstein SP, O’Boyle E, Fisher M, Haber RS. Regulation of GLUT2 glucose transporter expression in liver by thyroid hormone: evidencefor hormonal regulation of the hepatic glucose transport system.Endocrinology 1994:135:649-54.
17. R ochon C, Tauveron I, Dejax C et al. Response of glucose disposal to hyperinsulinemia in human hypothyroidism and hyperthyroidism. ClinSci2003;104:7-15.
18. Maratou E, Hadjidakis DJ, KolliasAet al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol2009;160:785-90.
19. Meller J, Zappel H, Conrad M, Roth C, Emrich D, Becker W. Diagnostic value Q of 123 iodine scintigraphy and perchlorate discharge test in the diagnosis of congenital hypothyroidism. ExpClinEndocrinol Diabetes. 1997;105:24-27.
20. Nanda N, Bobby Z, Hamide A. Oxidative stress and protein glycation in primary hypothyroidism.Male/female difference.ClinExp Med 2008;8:101-108.
21. Weijers RN, Slaats EH, Kruijswijk H, Fructos amine values in hyperthyroidism, hypothyroidism and gammopathy WeinKlinWochenschr 1990; 18 0:Suppl21-24.
22. Ford HC, Lim WC, Crooke MJ, HemoglobinA 1c and serum fructosamine levels in hyperthyroidism ClinChemActa 1987; 166:31 7-21.
23. Mohan Kumar, Bobby Z, Selvaraj N, Kumard as A, Chandra KonerB, Sen SK, Possible link between glycated hemoglobin and lipid peroxidation in hyperthyroidism ClinChemActa. 2004; 342:1 87-92.
24. Kim HB, Han KH, Lee BW, Kim H, Lee MH, Chung ES, HbA1c and serum fructosamine levels in hyperthyroidism J KorSocEndocrinol 1992; 7:46-51
Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareCURRENT TREATMENT PARADIGMS FOR RETINOBLASTOMA
English145155Shanti PandeyEnglish Kavita PandeyEnglish Vijay JoshiEnglish Swati GuptaEnglish KalpanaEnglishRetinoblastoma is a primary malignant neoplasm of the retina that arises from immature retinal cells
which affects infants and children and it is the most common primary tumor of the eye in children.
Retinoblastoma detected on time can lead the child to see and moreover can save his life.
Retinoblastoma in later stages can endanger life. It becomes essential to know most about this life
threating as well as sight threating condition. Let these children live and enjoy the color of life.
EnglishRetinoblastoma, chemotherapy, tumor, eyeINTRODUCTION
Retinoblastoma is a primary malignant neoplasm of the retina that arises from immature retinal cells which affects infants and children and it is the most common primary tumor of theeye in children.1 Out of newly diagnosed cases of retinoblastoma only 6% are familial while 94% are sporadic. Bilateral retinoblastoma are germline in all cases .Only 15% of unilateral retinoblastoma are caused by germline mutation, remaining 85% are sporadic. 2In 1971,Knudson proposed twohit hypothesis suggesting that in hereditary cases,germline mutations are present in all cells and somatic mutation occur only in retinal cells so they predisposed to nonocular carcinomas whereas in unilateral sporadic cases both hits occur during development of retina so no risk of secondary malignancy.3 In 1800s enucleation was the primary therapy to save life of the child. Then in early 1900s, external beam radiotherapy salvaged the life of child at the cost ofpoor vision and phthisis bulbi, secondary malignancy and orbital bone growth retardation. Refinements in radiotherapy including plaque beam therapy,laser therapy, thermotherapy, cryotherapy and latest being,periocular carboplatin injections has been done. In 1996, Kingston et al4 showed that ocular salvage rate improved to 90% if chemoreduction therapy is given prior to radiotherapyfor intraocular retinoblastoma. In a study on 158 eyes treated with vincristine, etoposide and carboplatin regimen given in six cycles ,allretinoblastoma,vitreous seeds and subretinal seeds initially regressed butatleast one vitreous seed recurrence was seen in 50% cases and at least one subretinal seed recurrence in 62% cases at 5 years follow up.5 Recent concept is of synergistic therapy (chemothermotherapy or chemocryotherapy) applying chemoreduction and focal tumor consolidation consecutively on tumor and seeds. Shields et al6 showed the recurrence in 18% cases treated with chemoreduction and thermotherapy compared with recurrences in 45% cases treated with chemotherapy alone in 7 year follow up in 457 patients of retinoblastoma. Studies showed similar effect on macular retinoblastoma.7 Various studies on high risk retinoblastomas showed that high dose chemotherapy in
Diagnosis of retinoblastoma
A thorough clinical evaluation with indirect ophthalmoscopy and ultrasonography B-scan, can establish the diagnosis of retinoblastoma.14 USG B-scan shows typical intra-lesional calcification of retinoblastoma. Computed tomography and magnetic resonance imaging are indicated when extraocular or intracranial spread of tumor is suspected.14Retcam is a wide angle fundus camerawhich helps in documenting retinoblastoma and monitoring of tumor regression on follow up.
Classification of retinoblastoma
The Reese Ellworth classification was introduced to prognosticate patients treated with methods other than enucleation mainly external beam radiotherapy.9 Group I a) solitary tumor, < 4 disc diameters in size, at or behind the equator b) multiple tumor, none > 4 disc diameters in size, at or behind the equator Group II a.) solitary tumor, 4–10 disc diameters in size, at or behind the equator b) multiple tumor, 4–10 disc diameters in size, behind the equator Group III a) any lesion anterior to the equator b) solitary tumor >10 disc diameters behind the equator Group IV a)multiple tumors, some >10 disk diameters b) any lesion extending anteriorly to the oraserrata Group V a)massive tumor involving more than half of retina b) vitreousseedings International retinoblastoma staging systemis based on collective information gathered by the clinical evaluation, imaging, systemic survey and histopathology.10 Stage 0: No enucleation(one or both eyes may have intraocular disease) Stage I: Eye enucleated, completely resected histologically Stage II: Eye enucleated with microscopic residual tumor Stage III: Regional extension a) Overt orbital disease b) Preauricular or cervical lymph node extension Stage IV: Metastatic disease a) Hematogenous metastasis 1. single lesion 2. multiple lesions b) CNS extension: 1. Prechiasmatic lesion 2. CNS mass 3. Leptomeningeal disease Management of retinoblastoma The management of retinoblastoma is a multidisciplinary approach, depends on the stage of the disease and it is highly individualized. There are several methods to manage intraocular retinoblastoma namely- focal methods like cryotherapy, laser photocoagulation, transpupillary thermotherapy and plaque brachytherapy; local methods like enucleation and external beam radiotherapy and systemic therapy like chemotherapy Chemotherapy Chemotherapy is currently the primary therapeutic option in most children with bilateral retinoblastoma11and in some children with unilateral disease when the affected eye is believed to be salvageable. Chemoreduction refers to a process involving reduction in tumor volume after chemotherapy.It is not effective alone but in adjunct with focal therapy it can avoid enucleation or external beam radiotherapy without significant toxicity.3,12,13 The most common chemotherapeutic regimen in use around the world today consists of a combination of carboplatin, etoposide or a related drug, and vincristine (CEV regimen) for 6 cycles. In some centers, cyclosporine is added to this regimen to reduce the multidrug resistance that occurs in many retinoblastomas.15 Several promising new drugs and alternative regimens are currently being evaluated.Thiotepaused in the treatment of ovarian and breast cancer, penetrates well intothe brain, and has been considered for HDC. The investigators observed considerable, but manageable, toxicity with high-dose thiotepa. A response of retinoblastoma to conventional dose thiotepa is documented in one case.16For all these reasons, Kremens et al 17 decided to include thiotepa into the HDC regimen for children with high-risk RB.Thus High Dose Chemotherapy withthiotepa, etoposideand carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma. Standard chemotherapy is given in 6 cycles; after first 2 cycles, local therapy in form of cryotherapy, thermotherapy or plaque radiation may be given to completely regressed tumors.18Chemoreduction therapy is most successful for tumors without intravitreal and subretinal seedings5,19Risk factors for recurrence of tumor ,subretinal seed and vitreous seed recurrence include5,19 a. Tumor with subretinal seeding at initial presentation b. Younger patients with large bulky tumor. In cases of recurrence ,external beam radiotherapy and/or enucleation is required. A study revealed that non-caucasian race, male sex and Rees Ellsworth group V had higher rate of tumor recurrence.19 Adverse effects of chemotherapy include myelosupression, febrile episodes ,neurotoxicities and non specific gastrointestinal toxicities Matsubara Het al20used high-dose chemotherapy (HDC) with autologous stem cell transplantation (SCT) in patients with metastatic retinoblastomawithout CNS involvement. Melphalan was a key drug, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Similarly Dunkel IJ et al21 suggested an intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma. They concluded that intensive multimodality therapy including highdose chemotherapy(carboplatin and thiotepa alone or with etoposide or topotecan) with autologous hematopoietic stem cell rescue was curative for the majority of patients with stage 4a metastatic retinoblastoma. The contribution of external beam radiation therapy is unclear. They also suggestedsimilar therapy for stage 4B retinoblastoma(central nervous system metastatic disease)22and concludedthatintensive multimodality therapy may be beneficial for such patients but longer follow-up is required to determine whether it has been curative. They also described a series of 13 patients with trilateral retinoblastoma treated with similar intensive chemotherapy, and concluded that intensive chemotherapy is potentially curative for some patients with trilateral retinoblastoma, especially those withlocalized (M-0) disease.23 Periocular Chemotherapy Periocular(subtenon) carboplatin injections are currently being evaluated as an adjunct to intravenous chemotherapy in management of Rees Ellsworth Group VB retinoblastoma with vitreous seeds. Honavar et al 24did study which showed that periocular chemotherapy can achieve 70% eye salvage in patients with retinoblastoma with diffuse vitreous seeds.
Enucleation
Enucleation still remains important therapeutic option for unilateral advanced intraocular retinoblastoma and some cases of bilateral faradvanced disease not amenable to any eyepreserving therapy.Primary enucleation remains treatment of choice for advanced intraocular retinoblastoma with neovascularisation of iris,secondary glaucoma, anterior chamber tumor invasion,tumors occupying >75% of vitreous volume,necrotic tumors with secondary orbital inflammation and tumors with hyphema or vitreous hemorrhage where tumor characteristics cannot be recognized especially when only one eye is involved.14
During enucleation10- 15mm long section of the optic nerve should be removed as the principal route of exit of tumor cells from the eye is along the optic nerve for which traction sutures applied over recti muscles and a 15 degree blunt tipped and angled tenotomy scissors or even straight scissors may be used. Pathological studies have shown enucleation to be curative if >5mm of optic nerve is sacrificed. 26 Necrotic tumor with aseptic orbital cellulitis and phthisis bulbi should be imaged before enucleation to rule out extraocular extension. Enucleation should be done when inflammation has subsided25 with brief course of preoperative oral and topical steroids.25Phthisis bulbi usually follows spontaneous tumor necrosis and an episode of aseptic orbital cellulitis. Enucleation in these cases is often complicated by intraoperative bleeding and excessive periorbital fibrosis.25 Insertion of an orbital implant at the time of enucleation appears to be appropriate except when there is a strong likelihood of residual tumor in the orbit which may require orbital radiation therapy. Biointegrated implants are avoided if adjunctive postoperative radiotherapy is necessary because implant vascularity is compromised by radiotherapy which increases risk of implant exposure25. Myoconjunctival technique and custom ocular prosthesis have optimized prosthetismotility.and static cosmesis. External Beam Radiation Therapy Now a days external beam radiation therapy is indicated when focal therapy or chemotherapy fails to control tumor or very rarely when chemotherapy is contraindicated14.It is also applicable to eyes containing one or more tumors that involve the optic disc and eyes that show diffuse intravitreal or subretinal seeding.Standard target doses of radiation to the eye and orbit are in the range of 40–50 Gy given in multiple fractions of 150–200 cGy over 4–5 weeks. External beam radiation therapy results in two main patterns of regression. In the first pattern (type I), the tumor regresses to an almost exclusively calcific, avascular residual mound. In the second pattern (type II), the tumor regresses without prominent calcification but with a gray-tan fish-flesh appearance. The dilated retinal vessels usually become markedly attenuated with both regression patterns. In type III regression, a combination of both regression patterns occurs. Major complications of external beam radiation therapy are stunting of orbital growth leading to cosmetic facial deformity28, dry eye, radiation cataract27, radiation retinopathy and optic neuropathy. Cataract typically begins as posterior subcapsular clouding and usually does not form for at least 6 months after radiation therapy and is often delayed for as much as 1–1.5 years after treatment. External beam radiation therapy also increases the risk of nonretinoblastoma malignancies in the field of treatment in survivors of germinal retinoblastoma29,30 by 30%compared to less than 6% chance in those who do not receive external beam radiotherapy. This effect also appears most pronounced in children irradiated before the age of 1 year.31
Plaque Radiation Therapy
In some children who have relatively large but localized retinoblastomas (less than 16mm in basal diameter and less than 8 mm in thickness), that does not involve optic disc or maculaeven in the presence of limited localized vitreous seeding, plaque radiation therapy may be employed successfully.32,33 Plaque radiation therapy entails surgical implantation of a radioactive device (eye plaque containing radioisotope iodine-125 and ruthenium106) of appropriate size and strength on the sclera overlying the intraocular tumor, leaving the plaque in place for a sufficient period of time (usually 2–5 days) to provide a predetermined radiation dose to the apex of the tumor, and subsequent surgical removal of the plaque. Currently it is performed as primary management only when chemotherapy is contraindicated. It is most usefull as secondary management in tumors which fail to respond to either chemotherapy or external beam radiotherapy or in cases of tumor recurrences. The advantages of plaque radiation therapy are focal delivery of radiation with minimal damage to surrounding normal structures, minimal periorbital tissue damage, absence of cosmetic deformity.
Laser photocoagulation
In photocoagulation, an argon green laser is employed using an indirect ophthalmoscope delivery system to delimit the tumor and coagulate the blood supply with two rows of overlapping laser burns.Laser photocoagulation is useful for small tumor 4mm in basal diameter and 2mm in thickness.14 Complications are transient serous retinal detachment, retinal vascular occlusion, retinal hole, retinal traction and preretinal fibrosis.Now with the advent of thermotherapy laser photocoagulation is less commonly used. Infact it is contraindicated when patient is on active chemoreduction protocol.14 Thermotherapy In transpupillary thermotherapy (TTT),34 an infrared laser beam (wavelength 810 nm) is directed at the retinal tumor using an operating microscope or indirect ophthalmoscope delivery systemto induce tissue necrosis.35by achieving a temperature of 40-60 degree celsius within the tumor with sparing of retinal vesselsuntil it appears homogeneously dull white.Large spot sizes (generally 2–3mm in diameter) are used if the pupil can be dilated widely. Infrared radiation can also be given by transscleral route with a diopexy probe. Thermotherapy is most appropriate for small intraretinal(4mm in basal diameter and 2mm in thickness)extramacular and extrapapillary tumors in eyes with clear optic media.35.It is not applicable to tumor associated with intravitreal or subretinal tumor seeds or retinal detachment.Common complications of thermotherapy are focal iris atrophy, focal paraxial lens opacity, retinal traction and serous retinal detachment. Major application of thermotherapy is as an adjunct to chemotherapy. The heat amplifies cytotoxic effects of platinum analogues. This synergistic combination with chemoreduction therapy is known as chemothermotherapy.
Cryotherapy
Trans-scleral cryotherapy is an obliterative focal treatment method that destroys targeted intraocular tissues by means of freezing36using an insulated retinal cryoprobeand indirect ophthalmoscopy.Double freeze-thaw method or triple freezethaw method may be applied according to the size of the tumor. This treatment is most applicable to small to medium size retinal tumors with minimal or no intravitreal or subretinal seeds or associated retinal detachment when the tumors are located in theequatorial or pre-equatorial region of the fundus.36Complications include serous retinal detachment, rhegmatogenous retinal detachment and retinal tear. Cryotherapy administered 2-3 hrs. before chemotherapy increase the delivery of chemodrugsacroos the blood retinal barrier and thus have synergistic effects.14
High risk retinoblastoma
High risk factors predictive of systemic metastasis include anterior chamber seedings, iris infiltration, ciliary body infiltration, massive choroidal infiltration, retrolaminar optic nerve invasion, invasion of optic nerve up to transaction, scleral infiltration and extrascleral extension.37 Current protocol is to administer standard dose chemotherapy including carboplatin, vincristine and etoposide in six cycles following enucleation in high risk charactersticpatients . Those cases with invasion of optic nerve transaction, sclera infiltration or extrascleral extension are treated with 12 cycles of HDC, orbital external beam radiotherapy, and/or enucleation8
Orbital retinoblastoma
Orbital retinoblastoma refers to orbital extension of retinoblastoma in the form of sclera infiltration, extrascleral extension or optic nerve invasion .When orbital extension is present at the time of diagnosis of tumor, it refers to primary orbital retinoblastoma. Orbital recurrence after uneventful enucleationfor intraocular retinoblastoma is referred to as secondary retinoblastoma. Sometimes inadvertent perforation, fine needle aspiration biopsy or intraocular surgery is done in cases of unsuspected retinoblastoma, orbital extension and systemic dissemination occurs. This orbital extension is called as accidental orbital retinoblastoma. Previously unrecognized orbital extension discovered macroscopically or microscopically at time of enucleation is referred as overt or microscopic overt retinoblastoma.38 Technetium -99 bone scan and PET- computed tomography can help in early detection of these subclinical metastasis.
Honavar etal developed a multimodality treatment protocol for management of orbital retinoblastoma which begins with 3 cycles of high dose chemotherapy followed by enucleation or orbital exentration, orbital external beam radiotherapy and finally extended 12 cycles of standard dose chemotherapy. Early results of this treatment protocol are encouraging.39 Some cases of retinoblastoma require intraocular surgery like cataract surgery for radiation cataract, sclera buckling or pars planavitrectomy for retinal detachment or vitreous hemorrhage. Specific guidelines for intraocular surgery after treatment of retinoblastoma have been described40
Metastatic retinoblastoma
Metastasis in retinoblastoma, which commonly spreads to orbital and regional lymph nodes, CNS, bones and bone marrow, usually develops within first year of diagnosis and the chances are very less after 5 years of diagnosis.Until recently the prognosis of metastatic disease was very poor. Various studies using high dose chemotherapy with autologous stem cell transplantation produced promising results in the cure of metastatic retinoblastoma especially those in bone and bone marrow20,21,22,23. Still CNS metastasis have grave prognosis and longer follow up is required to confirm the results of these studies.
Genetic counseling
It is an important aspect in management of retinoblastoma. In patients with positive family history,40% of the siblings would be at risk of developing retinoblastoma and 40% of the offsprings may develop retinoblastoma. In unilateral non familial retinoblastoma,1% of siblings and 8% of offsprings would be affected. In cases of bilateral nonfamilial retinoblastoma,6% of siblings and 40% of offsprings are at risk of developing retinoblastoma2 .Various studies on mutational analysis of RB1 gene have shown that by identifying specific mutations ,screening tests can be designed which help in computing specific ante natal risks.41
CONCLUSION
Retinoblastoma is a primary malignant neoplasm of the retina that arises from immature retinal cells which affects infants and children and it is the most common primary tumor of the eye in children. Retinoblastoma detected on time can lead the child to see and moreover can save his life. Retinoblastoma in later stages can endanger life. It becomes essential to know most about this life threating as well as sight threating condition. Let these children live and enjoy the color of life.
Englishhttp://ijcrr.com/abstract.php?article_id=896http://ijcrr.com/article_html.php?did=896REFERENCES
1. Donaldson SS, Egbert PR, Lee W. In: Pizzo PA, PoplackDG(eds). Principles and Practice of Pediatric Oncology.JBLippincott: Philadelphia, 1993, pp 683–696.
2. SheildsJA,Sheilds CL. Management and prognosis of retinoblastoma.In intraocular tumors. A text and atlas Philadelphia:WB Saunders 1992;337-392.
3. KnudsonAG:Mutation and cancer:Statistical study of retinoblastoma.ProcNatlAcadSci,USA 1971:68:820-823.
4. Kingston JE, Hungerford JL, Madreparla SA, Plowman PN. Results of combined radiotherapy and chemotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol 1996;114:1339-1343.
5. Shields CL, Honavar SG, Shields JA, Dimirci H, Medows AT, Naduvilath TJ. Factors predictive of recurrence of retinal tumors ,vitreous seed, and subretinal seeds following chemoreduction for retinoblastoma. Arch Ophthalmol 2002;120:460-464.
6. Shields CL, MashayekhiA ,Shelids JA, Cater J, Medows AT, Shields JA. Chemoreduction for retinoblastoma. Analysis of tumour control and risk of recurrence in 457 tumors.AM J Ophthalmol 2004;138:329-37.
7. Shields CL, MashayekhiA ,Shelil A, Ness S, Cater J, Medows AT, Shields JA.Macularretinoblastoma managed with chemoreduction. Analysis of tumor control with without thermotherapy in 68 tumors, Arch Ophthalmol 2005;123:765-73.
8. Honavar SG, Singh AD, Shields CL ,Medows AM, Dimirci H, Cater J, Shields JA . Postenucleation adjuvant therapy in high -risk retinoblastoma, Arch Ophthalmol 2002;120:923-931.
9. Ellsworth RM. The practical management of retinoblastoma. Trans Am OphthalmolSoc 1969:67:462-534.
10. Chantada G, Doz F, Antoneli CB ,et al A proposal for an international retinoblastoma staging system Pediatr Blood Cancer 2006:47;801-805.
11. Gombos D.S., Kelly A., Coen P.G., et al: Retinoblastoma treated with primary chemotherapy alone: the significance of tumor size, location, and age. Br J Ophthalmol 2002; 86:80-83.
12. Gallie BL, Budning A, Deboer G, Thiessen JJ, Koren G, Verjee Z, etal. Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy. Arch Ophtalmol 1996;114:1321-8.
13. Shields CL, De Potter P, Himelstein BP ,Shields JA , Medows AT, Maris JM. Chemoreduction in the initial management of intraocular retinoblastoma.ArchOphthalmol 1996;114:1330-8.
14. Murthy R, Honavar SG, Naik MN, Reddy VA. Retinoblastoma. In: Dutta LC, ed. Modern Ophthalmology. New Delhi, India ,Jaypee Brothers;2004:849-859.
15. Chan H.S., DeBoer G., Thiessen J.J., et al: Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation. Clin Cancer Res. 1996; 2:1499-1508.
16. Heidemann RL, Cole DE, Balis F et al. Phase I and pharmacoqkinetic evaluation of thiotepa in the cerebrospinal fluid andplasma of pediatric patients: evidence for dosedependent plasma clearance of thiotepa. Cancer Res 1989; 49: 736–741.
17. B Kremens, R Wieland, H Reinhard, D Neubert, JD Beck, T Klingebiel, N Bornfeldand W Havers.High-dose chemotherapy with autologous stem cell rescue in childrenwith retinoblastoma. Bone Marrow Transplantation (2003);31: 281–284.
18. Shields C.L., Mashayekhi A., Cater J., et al: Chemoreduction forretinlblastoma: analysis of tumor control and risks for recurrence in 457 tumors. Trans Am Ophthalmol Soc. 2004; 102:35-44.
19. Shields CL, Honavar SG, Meadows AT, Shields JA, Demirci H, Singh A, Friedman DL, Naduvilath TJ. Chemoreduction plus focal therapy for retinoblastoma:factors predictive of need for treatment with external beam radiotherapy or enucleation. AmJ Ophthalmol.2002;133:657-64.
20. Matsubara H, Makimoto A, Higa T, Kawamoto H, Sakiyama S, Hosono A, Takayama J, Takaue Y, Murayama S, Sumi M, Kaneko A, Ohira M. A multidisciplinary treatment strategy thatincludes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement.Bone Marrow Transplant. 2005 Apr;35(8):763-6.
21. Dunkel IJ, Khakoo Y, Kernan NA, Gershon T, Gilheeney S, Lyden DC, Wolden SL, Orjuela M, Gardner SL, Abramson DH. Intensive multimodality therapy for patients with stage 4a metastatic retinoblastoma Pediatr Blood Cancer. 2010 Jul 15;55(1):55-9.
22. Dunkel IJ, Chan HS, Jubran R, Chantada GL, Goldman S, Chintagumpala M, Khakoo Y, Abramson DH. High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma.Pediatr Blood Cancer. 2010 Jul 15;55(1):149-52.
23. Dunkel IJ, Jubran RF, Gururangan S, Chantada GL, Finlay JL, Goldman S, Khakoo Y, O'Brien JM, Orjuela M, Rodriguez-Galindo C, Souweidane MM, Abramson DH. Trilateralretinoblastoma: potentially curable with intensive chemotherapy. Pediatr Blood Cancer. 2010 Mar;54(3):384-7.
24. Honavar SG, Shome D, Reddy VAP. Periocular carboplatin in the management of advanced intraocular retinoblastoma. Proceedings of the XII International congress of ocular Oncology,Vancouver,Canada,2005.
25. Honavar SG, Singh AD. Management of advanced retinoblastoma.OphthalmolClin North Am.2005;18:65-73.
26. Khelfaoui F., Validire P., Auperin A., et al: Histopathologic risk factors in retinoblastoma. A retrospective study of 172 patients treated in a single institution. Cancer 1996; 77:1206-1213.
27. Brooks H.L., Meyer D., Shields J.A., et al: Removal of radiation-induced cataracts in patients treated for retinoblastoma. Arch Ophthalmol 1990; 108:1701-1708.
28. Egbert P.R., Donaldson S.S., Moazed K., et al: Visual results and ocular complications following radiotherapy for retinoblastoma. Arch Ophthalmol 1978; 96:1826-1830.
29. Roarty J.D., McLean I.W., Zimmerman L.E.: Incidence of second neoplasms in patients with bilateral retinoblastoma. Ophthalmology 1988; 95:1583-1587.
30. Mohney B.G., Robertson D.M., Schomberg P.J., Hodge D.O.: Second nonocular tumors in survivors of heritable retinoblastomaand prior radiation therapy. Am J Ophthalmol 1998; 126:269-277.
31. Abramson DH, Frank CM. Second nonocular tumors in survivors of bilateral retinoblastoma; a possible age effect on radiation-related risk. Ophthalmology.1998;105: 573-580.
32. Shields C.L., Shields J.A., De Potter P., et al: Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment. Ophthalmology 1993; 100:216-224.
33. Schueler A.O., Fluhs D., Anastassiou G., et al: Beta-ray brachytherapy with (106) Ru plaques for retinoblastoma. Int J RadiatOncolBiol Phys. 2006; 65:1212-1221.
34. Abramson D.H., Schefler A.C.: Transpupillary thermotherapy as initial treatment for small intraocular retinoblastoma: technique and predictors of success. Ophthalmology 2004; 111:984-991.
35. Shields CL, Santos MC, Diniz W et al. Thermotherapy for retinoblastoma.ArchOphthalmol 1999; 117:885-893.
36. Shields J.A., Parsons H., Shields C.L., et al: The role of cryotherapy in the management of retinoblastoma. Am J Ophthalmol 1989; 108:260-264.
37. Singh AD, Shields CL, Shields JA. Prognostic factors in retinoblastoma.JPediatrOphthalmolStrab 2000;37:134-41.
38. Shields CL, Honavar S, Shields JA, Demirci H, Meadows AT. Vitrectomy in eyes with unsuspected retinoblastoma. Ophthalmology. 2000;107: 2250-5.
39. Honavar SG, Shields CL, Shields JA, Demrici H, Naduvilath TJ. Intraocular surgery after treatment of retinoblastoma. Arch Ophthalmol.2001;119: 1613-21.
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Radiance Research AcademyInternational Journal of Current Research and Review2231-21960975-524169EnglishN-0001November30HealthcareBIOACTIVE COMPONENTS OF SPINACH AND THEIR EFFECT ON SOME PATHO PHYSIOLOGICAL CONDITIONS: A REVIEW
English156166Vaijayanthi KanaburEnglish R. P. Lalitha ReddyEnglishSpinach is a commonly consumed leafy vegetable packed with micronutrients and phytochemicals. It has functional ingredients such as lutein, betaine, flavonoids, neoxanthin, galactolipids. Each of these has its own physiological significance. Studies have indicated that regular consumption of spinach substantially lowers the risk of age related macular degeneration, one of the leading causes of irreversible blindness among adults. There is an inverse association between spinach consumption and cataract risk. Spinach leaf protein concentrate has a strong cholesterol lowering effect in rats. Age related changes on brain function can be delayed by long term consumption of spinach. It has high anti proliferative activity on cancer cells. However, people prone to oxalic acid stones are to reduce consumption of spinach. So quantityand frequency of spinach consumption can be increased.
Englishfunctional ingredients,antioxidant activity; age related macular degeneration; aging; cancerINTRODUCTION
Spinach (Spinaciaoleracea) is a commonly consumed green leafy vegetable.Although it is native to central and southwestern Asia, now it is produced andconsumed throughout the world. Green leafy vegetables such as spinach form animportant part of a balanced diet. Their micronutrient content, along with acombination of low calorie content, low glycemic index, dietary fiber make it anappealing healthy choice.The contribution of dark green leafy vegetables to total micro nutrient intake of 2-5 year old children in rural South Africa is quite significant. For children consumingdark green leafy vegetables, imifina (collective term for various dark green leavesthat are eaten as a vegetable) and Spinach contributed significantly to the dietaryintake of calcium (21 to 39%), iron (19-39%), vitamin A (42 to 68%) and riboflavin (9 to 22%). This contribution can be increased if these vegetables are consumed morefrequently and by a larger proportion of children1 .
COMPOSITION OF SPINACH
Spinach is a rich and affordable source of micronutrients and phytochemicals. Itcontains vitamin C (28.1 mg), vitamin K(482.9), folate (194 mcg), calcium (99 mg), iron (2.71mg), magnesium, manganese, zinc etc per 100g of edible portion2 . Xanthophyll is a class of carotenoids with oxygenated carotenes. Themolecular formula of xanthophyll is C40H56O2. They are typical yellow pigments ofleaves. Spinach contains a variety of xanthophylls. Rangaswamy L et al. (2005)3 have determined these by HPLC method. Table. 1 gives the xanthyphyll compositionof spinach. ? Bioactive Components Studies indicate that spinach is a source of bioactive components such as lutein, betaine, flavonoids, neoxanthins and galactolipids. Table 2 gives the quantity of each of these components. The general structure, physiological role and nutritional significance of each of these is discussed below. Lutein: It is one of the natural carotenoids synthesized only by plants. It has thefollowing structure (Fig 1). Lutein and zeaxanthin are the only carotenoids found in the retina. They are mainlypresent in the macula where they act as absorbers of blue light. By preventing asubstantial amount of blue light from reaching the underlying structures, they protectagainst oxidative damage induced by light. This oxidative damage is believed to playa role in the causation of age related macular degeneration (AMD). Betaine: Betaine is a chemical compound alternatively called trimethylglycine, glycine betaine, lycine, and oxyneurine. It is a zwitterionic quaternary ammoniumcompound. The chemical structure is shown below (Fig 2). Betaine performs the following physiological functions. (Stuart A.S. C. 2004).4 1. It is an osmolyte. So it protects the cells, proteins and enzymes fromenvironmental stress such as lack of water, unfavourable temperature, orsalinity 2. It is a source of methyl groups. Therefore it participates in methionine cycle inkidney and liver. 3. Betaine can reduce the serum homocysteine concentration in case of mild orsevere hyper homocystinuria Via Methionine cycle. 4. It may have a role in epigenetics and athletic performance. Deficiency of methyl groups results in hypomethylation which hasthe following consequences.Increase in plasma homocysteine concentration, decrease in s-denosyl methionine concentration, impaired hepatic fat metabolism resulting in fat accumulation (steatosis). This leads to dyslipedemia. Coronary, cerebral, hepatic and vascular diseases may result due to faulty liver metabolism.Spinach is one of the food items with high betaine content (600-645 mg/100g).5 : Betaine-aldehyde dehydrogenase was purified from spinachleaves and characterized by Keita A et al (1987).6 Flavonoids: They are a class of secondary plant metabolites widely distributed inplants. They function as plant pigments and are responsible for yellow / red / bluecolor. In vitro studies have shown that some of these flavonoids show antiallergic, anti-inflammatory, anti-oxidant, antimicrobial and anti-cancer activities. There is verylimited in vivo or clinical research to prove or disprove this claim. Rudolf Edenharder et al7 isolated 13 flavonoid compounds from spinach and some of these were foundto be potent antimutagens. Neoxanthin: It is a type of xanthophyll found in green leafy vegetables such asspinach (Table 1). It is an intermediate in the biosynthesis of plant hormone abscisicacid and is synthesized from violaxanthin. It has the following structure (fig 3). A study by Luca Dall'Osto et al (2007)8 has shown that neoxanthin acts as anantioxidant within the photosystem II super complex and neoxanthin protectsmembrane lipids from reactive oxygen species and superoxide anions. Eiichi Kotake-Nara et al (2001)9 have shown that neoxanthin can reduce the risk of prostatecancer and the details are discussed under spinach and cancer. Galactolipids: They are glycolipids with galactose as sugar group widely found inplant kingdom. They are present in cell membrane lipids.Monogalactosyldiacylglycerol (MGDG) and Diagalactosyldiacylglycerol (DGDG) arepresent in higher amounts in chloroplast membranes. They are believed to play arole in photosynthesis. The chemical structure of a common galactolipid is shownbelow (Fig 4). Wang R (2002)10 has estimated that spinach contains 3300-3880 (mg/kg) of MGDG (Monogalactosyldiacylglycerol ), a galactolipid. Lars P. Christensen (2009)11 hasreported that different studies have estimated MGDG (mg/kg) content of spinach onfresh weight basis as 546,850 and 3300-38, 800 and DGDG (mg/kg) content of spinach on fresh weight basis as 563. A study has shown that extraction of dry spinach leaves resulted in a glycolipid enriched fraction. This contained 3 types of glycolipids-MGDGs, DGDGs and sulphoquinovosyldiacyl glycerol at a high ratio. These play a role in DNA synthatase inhibitory activity, inhibition of cancer cell growth and antitumor activity (Mizushima et al 2005).1
Bioavailability of Nutrients
Bioavailability, defined as the proportion of an ingested trace element in food that isabsorbed and utilized for normal metabolic and physiological functions or storage (Jackson, 1997)13, is an important factor in deciding the nutritional status. The chemical form in which a nutrient is present in food, nutrient interactions within the food, the presence of anti nutritional factors and processing of food all influence the bioavailability of a nutrient. Spinach contains anti nutritional factors like oxalic acidwhich reduce the absorption of calcium and iron by forming insoluble complexes withthem. Oxalic acid may lead to oxalate stones in the urinary tract of some people.Therefore people who have oxalate stones in their urinary tract are advised toreduce eating vegetables like spinach. Dietary fiber may also interfere withabsorption of nutrients. Studies have shown that bioavailability of nutrients in spinach depends on the formin which it is consumed. β carotene present in raw spinach has less bioavailabilitycompared to cooked and pureed spinach (Cherry Rock et al (1998).13 The plasma βcarotene levels were three times higher after daily consumption of carrots andspinach for 4 weeks in processed form than when they were consumed in raw form.Bioavailability of β carotene is increased by the disruption of cell wall structure andloss of cellular integrity of spinach leaves (Jacqueline et al).14 The table 3 showsbioavailability of spinach in different forms. Bioavailability of lutein is higher than that of beta carotene.
Antioxidant Constituents:
Different antioxidant constituents present in a vegetable such as alpha tocopherol, beta carotene, vitamin C, selenium or phenolic compounds etc. contribute to the totalantioxidant capacity of a vegetable. Amin Ismail et al (2004) 15 have shown that thehigh antioxidant activity of spinach is due to high alpha tocopherol, beta caroteneand ferulic acid. The total antioxidant activity of spinach by different methods is given in Table 4. The active fractions from aqueous spinach extracts have been chemically identified (Margalit Bergman et al (2001).16 There are 4 hydrophobic fractions (glucuronic acidderivatives of flavonoids), 3 fractions of trans and cis isomers of p-coumaric acidderivatives and others are mesotartarate derivatives of p-coumaric acid. There is a variation in the flavonoid content among different genotypes of spinach (Mi Jin Cho et al (2008).17 18 flavonoids representing glucuronides and acylated diand triglycosides of methylated and methylene dioxide derivatives of 6 oxygenatedflavonols were identified (patuletin, spinacetin, spinatoside and jaceidin). There wasa 2.0 fold variation in the total flavonoids (1805- 3703 mg/Kg) and 1.7 fold variation in the total antioxidant capacity among genotypes. The correlation between antioxidantcapacity and total flavonoid content was found to be high (0.96). The medicinal effects may be enhanced in diseases such as cancer by usingantioxidant cocktails (RavitHait-Darshan et al 2009).18 There was a synergisticantioxidant activity between commercial antioxidants and natural antioxidant NAO ((NAO is a unique, powerful antioxidant isolated from spinach leaves). Thecommercial antioxidants used were 3 polyphenols- ferulic acid, caffeic acid and epigallocatechin-3-gallate (RGCG).
Effect of Spinach consumption on serum antioxidant status
Epidemiological studies have clearly established that fruit and vegetableconsumption is associated with better health. Antioxidants present in fruitsand vegetables are believed to be responsible for this. However the overall antioxidant status in humans as affected by fruit and vegetable consumption is not very clear. There was a 7-25% increase in serum antioxidant capacity during 4-h period afterthe consumption of spinach, strawberries, red wine or vitamin C (Cao G et al 1998).19 The absorption of phenolic compounds in these foods might have resultedin the increase in antioxidant capacity. Organic Spinach Organic farming does not use chemicals during food production, processing orstorage. So the pest pressure may put greater stress on the synthesis of a plant’schemical defense mechanism (Carl and Davis 2006).20 So, more secondary plantmetabolites are expected to be produced in organic plants. These secondary plantmetabolites, which are mostly antioxidants, may also benefit human health. Somestudies have shown that organic foods contain more antioxidants, although there isno conclusive evidence to prove or disprove this claim. The Environmental Working Group has reported that spinach is one of the dozenmost heavily pesticide-contaminated produce (EWGs 2011 Shoppers Guide to Pesticides in Produce)21 Permethrin, dimethoate, and DDT are common pesticidesfound on spinach. It will be interesting to know if these pesticides have any influenceon the nutritional composition or bioavailability of nutrients present in spinach. Ren et al (2001)22 have compared the antioxidant activity of five organicallycultivated and generally cultivated vegetables (welsh onion, quiang-gencal, spinach, chinese cabbage, green pepper). The results reveal that organically grown spinachhas 120% higher antioxidant activity compared to generally cultivated spinach. Atleast two flavonoid contents were more than double (significant at 95% level in t test) in organically grown welsh onion, quiang-gen-cal and spinach as revealed by LC/MS quantitative analysis compared to generally cultivated vegetables. A comparative study by Eunmi Koh et al (2012).23 has shown that the mean levels ofascorbic acid and flavonoids were significantly (PEnglishhttp://ijcrr.com/abstract.php?article_id=897http://ijcrr.com/article_html.php?did=897REFERENCES
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