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Biomedical subjects

Tarun Sharma

Publications and source records attributed to Tarun Sharma.

At least 37 records · Page 2Linked to original sources

Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS 1): study design and research methodology.

PURPOSE: To describe the methodology of the Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS 1), an ongoing population-based study to estimate the prevalence of diabetes and diabetic retinopathy in urban Chennai, Tamil Nadu, South India, and also to elucidate the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy. METHODS: In this ongoing study, we anticipate recruiting a total of 5830 participants. Eligible patients, over the age of 40 years, are enumerated using the multistage random sampling method. Demographic data, socioeconomic status, physical activity, risk of sleep apnea, dietary habits, and anthropometric measurements are collected. A detailed medical and ocular history and a comprehensive eye examination, including stereo fundus photographs, are taken at the base hospital. Biochemical investigations (total serum cholesterol, high-density lipoproteins, serum triglycerides, hemoglobin, glycosylated hemoglobin HbA1c) and genetic studies of eligible subjects are conducted. A computerized database is created for the records. CONCLUSION: The study is expected to result in an estimate of the prevalence of diabetes and diabetic retinopathy and a better understanding of biochemical and genetic risk factors associated with diabetic retinopathy in an urban South Indian population. Worldwide, the prevalence of diabetes mellitus, in particular type II diabetes, is rising at an alarming rate. The World Health Organization (WHO) and International Diabetes Federation (IDF) have predicted that the number of cases of adult-onset diabetes would more than double by 2030 from the present level of 171 million to 366 million-an increase of 214%.1 In developed countries, this increase in diabetic population would be around 42% and in developing countries, particularly in India, it is even higher; i.e. 150%.1 In India, the prevalence of diabetes mellitus in the urban population is around 12.1%, as reported by the national urban diabetes study2 conducted in six major cities. Studies have shown the prevalence of diabetes to be higher among the high-income groups (25.5%) as compared to low-income groups (12.6%).3,4,5 The assessment of socioeconomic status was based on income,6, 7 education,2, 7 occupation2 or caste6-which are not representative of the actual socioeconomic status. In the present study, however, the sample was stratified on socioeconomic scoring. This scoring was calculated on the basis of several parameters such as the residence being rented or owned, the number of rooms in the house, the highest educational status, the highest salary, the highest occupation, material possessions (cycle, TV, audio, car, etc.) and house/land value. To the best of our knowledge, this kind of comprehensive socioeconomic scoring has not been done before for prevalence studies on diabetic retinopathy in the general population.

Anthropometry↗

Synthesis and evaluation of glycosidase inhibitory activity of octahydro-2H-pyrido[1,2-a]pyrimidine and octahydro-imidazo[1,2-a]pyridine bicyclic diazasugars.

An efficient chiron approach for the synthesis of bicyclic diazasugars 4a and 4b having both -CH(2)OH and -OH functionality at the same carbon atom (C-6) is reported. Thus, easily available alpha-D-xylo-pentodialdo-1,4-furanose 5, obtained from D-glucose, on aldol-crossed Cannizzaro reaction followed by hydrogenolysis afforded 7. The regio-selective beta- and alpha-sulfonylation of hydroxymethyl groups in 7 afforded 8a (beta-sulfonylation) and 11 (alpha-sulfonylation) in good yields. The cleavage of the 1,2-acetonide functionality, individually in 8a and 11, followed by reaction with ethylenediamine gave in situ formation of sugar aminals that undergo concomitant nucleophilic displacement of the sulfonyloxy group, by amino functionality, to give hitherto unknown bicyclic diazasugars 4a and 4b, respectively. The inhibitory potency of the earlier reported bicyclic diazasugars 3a,b and 4a,b was evaluated against alpha- and beta-glycosidases and they were found to be potent and specific against the beta-glycosidases with IC(50) and K(1) values in the micro molar range.

Aza Compounds↗

Major histocompatibility antigens and antigen-processing molecules in retinoblastoma.

BACKGROUND: Malignant transformation of cells is frequently associated with abnormalities in human leukocyte antigen (HLA) expression. These abnormalities may play a role in the clinical course of the disease, because HLAs mediate interactions of tumor cells with cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Retinoblastoma is the most common intraocular malignant tumor in childhood and is characterized by direct spread to the optic nerve and orbit as well as hematogeneous and lymphatic spread. Little is known about the role of HLA expression in the progression of this malignant disease. METHODS: HLA Class I antigen, beta2-microglobulin (beta2-m), HLA Class II antigens, and the antigen-processing molecules (APMs) of the HLA Class I pathway, including proteasomal subunits (low-molecular mass polypeptide 2 [LMP-2] and LMP-10), the transporter-associated protein (TAP-1) subunit, the binding protein tapasin, and the chaperone molecule calnexin, were studied in 30 archival retinoblastoma specimens by immunohistochemistry. Immunoanalysis was performed based on the International Histocompatibility Working Group Project Description. RESULTS: HLA Class I antigen, beta2-m, HLA Class II antigen, and APMs were positive in 12 tumors with no invasion and were decreased in 13 tumors with choroidal and optic nerve invasion. The difference in HLA and APM expression between the 2 groups was statistically significant (P < 0.001). CONCLUSIONS: Decreased expression of HLA was observed in aggressive tumors and in poorly differentiated tumors. The current findings support a role for both CTLs and NK cell-mediated control of tumor growth in the clinical course of retinoblastoma.

Biomarkers, Tumor↗

Visual outcome after discontinuation of corticosteroids in atypical severe central serous chorioretinopathy.

PURPOSE: To elucidate the effect of discontinuation of corticosteroids in patients with atypical severe central serous chorioretinopathy (CSC) on retinal reattachment, resolution of retinal pigment epithelium (RPE) leaks, and improvement in visual acuity (VA). DESIGN: Prospective, noncomparative, observational case series. PARTICIPANTS: Twenty-four eyes of 17 patients who were being treated with corticosteroids for atypical severe CSC. Of these 17 patients, 16 were treated inappropriately with corticosteroids for their ocular condition; presumably, these patients' conditions were misdiagnosed, and they were thought to have choroiditis, Harada's syndrome, or similar entities, and not central serous chorioretinopathy. INTERVENTION: Observation or laser photocoagulation. MAIN OUTCOME MEASURES: Reattachment of the retina, obliteration of RPE leaks on fundus fluorescein angiography, and improvement in Snellen VA. RESULTS: Discontinuation of corticosteroids resulted in reattachment of the retina in 21 eyes (87.5%), with median time to reattachment of 49 days (range, 32-400); only 3 eyes required laser photocoagulation. Fundus fluorescein angiography showed obliteration of RPE leaks at a median period of 75 days (range, 32-400) in the observed eyes; the median VA improved from 20/80 to 20/30. The mean follow-up was 16.5 months. CONCLUSIONS: Discontinuation of corticosteroids in atypical CSC helped in obliteration of RPE leaks and retinal reattachment in 87.5% of the eyes without laser treatment, and improvement in VA was observed.

Adult↗

Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in choroidal neovasularisation (CNVM) secondary to age related macular degeneration (AMD). MATERIAL AND METHODS: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed) secondary to AMD. RESULTS: Fifteen patients (53.57%) maintained their pre-treatment vision, 2 (7.14%) patients showed improvement of more than 2 lines and 11 (39.28%) patients showed deterioration of vision by >2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8%) on an average follow up of 15.32 +/- 3.31 months. CONCLUSION: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.

Aged↗

Trace elements iron, copper and zinc in vitreous of patients with various vitreoretinal diseases.

PURPOSE: To measure the concentrations of iron, copper and zinc in human vitreous and to interpret their levels with various vitreoretinal diseases like proliferative diabetic retinopathy, retinal detachment, intraocular foreign body, Eales' disease and macular hole. METHODS: Undiluted vitreous fluid collected during pars plana vitrectomy was used to measure trace elements using an atomic absorption spectrophotometer. RESULTS: The level of vitreous iron increased threefold in Eales' disease (1.85 +/- 0.36 pg/ml), 2.5-fold in proliferative diabetic retinopathy (1.534 +/- 0.17 pg/ml) and 2.3-fold in eyes with intraocular foreign body (1.341 +/- 0.25 pg/ml) when compared with macular hole (0.588 +/- 0.16 pg/ml). This was statistically significant (P < 0.05). Zinc was found to be low in Eales' disease (0.57 +/- 0.22 pg/ ml) when compared with other groups, though the difference was not statistically significant. CONCLUSION: The increased level of iron with decreased zinc content in Eales' disease confirms the earlier reported oxidative stress mechanism for the disease. In proliferative diabetic retinopathy and intraocular foreign body the level of iron increases. This is undesirable as iron can augment glycoxidation, which can lead to increased susceptibility to oxidative damage, in turn causing vitreous liquefaction, posterior vitreous detachment and ultimately retinal detachment and vision loss.

Adolescent↗

Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity.

The aim of this study was to investigate whether the mean around which arterial oxygen fluctuations take place was important in a unique animal model of oxygen-induced retinopathy. Retinopathy of prematurity (ROP) is associated with fluctuating arterial oxygen. A recent retrospective study suggested that management of high-risk preterm infants at lower oxygen saturations was associated with less severe ROP. Rat pups were raised in a variable oxygen environment around a high (24%), normal (21%) or low (17%) mean inspired oxygen for 14 d. Rat pups raised in the high (24%) mean variable oxygen environment had more retarded retinal vascular development than did rats raised in an environment that fluctuated around 21% mean oxygen. In contrast, rats raised in a lower mean (17%) but still variable oxygen environment had no discernible retinal differences from controls raised in constant room air. Rats raised in a relatively hypoxic but variable oxygen environment develop less severe retinal vascular abnormalities than those raised in variable oxygen around higher oxygen means.

Animals↗

N-hydroxyethyl-piperidine and -pyrrolidine homoazasugars: preparation and evaluation of glycosidase inhibitory activity.

An efficient and practical strategy for the synthesis of N-hydroxyethyl-1-deoxy-homonojirimycins 4 and 5 and N-hydroxyethyl-pyrrolidine homoazasugars 6 and 7 with full stereocontrol is being reported. The key step involved is the intermolecular Michael addition of benzylamine to D-glucose derived alpha,beta-unsaturated ester 8 followed by N-alkylation with ethyl bromoacetate. Reduction with LAH, acetylation, hydrogenation and protection with -Cbz group afforded compounds 14a and 14b. Removal of 1,2-acetonide functionality, hydrogenation and deacetylation afforded N-hydroxyethyl-D-gluco-1-deoxyhomonojirimycin (4) and N-hydroxyethyl-L-ido-1-deoxyhomonojirimycin (5), respectively. Compounds 14a and 14b on acetylation followed by removal of 1,2-acetonide functionality, sodium metaperiodate oxidation, hydrogenation and deacetylation gave 1,4,5-trideoxy-1,4-imino-N-hydroxyethyl-D-arabino-hexitol (6) and 1,4,5-trideoxy-1,4-imino-N-hydroxyethyl-L-xylo-hexitol (7), respectively. The glycosidase inhibition activity of compounds 4, 5, 6, 7, 16a and 16b was evaluated using sweet almond seed as a rich source of different glycosidases.

Aza Compounds↗

Intraocular cysticercosis: clinical characteristics and visual outcome after vitreoretinal surgery.

PURPOSE: To report the clinical characteristics of, discuss the surgical options for, and analyze the factors affecting the anatomic and visual outcome of intraocular cysticercosis. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Forty-five eyes of 44 Indian patients with posterior segment intraocular cysticercosis. METHODS: The charts of 45 eyes, in which intraocular cysticercosis was removed by vitreoretinal surgery (either transscleral or transvitreal), were reviewed. MAIN OUTCOME MEASURES: These included the postoperative retinal status and the best-corrected Snellen visual acuity. RESULTS: Intraocular cysticercosis was present in the vitreous cavity of 27 eyes (60%) and in the subretinal space of 18 eyes (40%). Anterior segment inflammation was seen in 13 eyes (28.8%) and vitreous inflammation in 38 eyes (84.4%). Retinal detachment was observed in 22 eyes (48.8%), with proliferative vitreoretinopathy in 13 eyes (59.09%). Subretinal cysts anterior to the equator (4 eyes) were removed transsclerally, whereas subretinal cysts posterior to the equator and intravitreal cysts (41 eyes) were removed transvitreally. The mean follow-up was 10.5 months. At the last follow-up, the retina was attached in 39 eyes (86.6%); visual acuity of >/=5/200 was achieved in 67.5%. CONCLUSIONS: Current vitreoretinal surgical techniques enable removal of intraocular cysticercosis in all cases, with reattachment of the retina in 86.6% and recovery of ambulatory vision in approximately 67% of cases.

Adolescent↗

Z-2 aldose reductase allele and diabetic retinopathy in India.

Genetic factors have been identified that regulate the severity and the rapidity of onset of retinopathy in diabetic patients. Polymorphisms in (CA)( n) present upstream of the promoter of the aldose reductase (ALR2 ) gene have been shown to be associated with retinopathy in different ethnic populations. We aimed to study the association between the (CA)( n) polymorphism and type 2 diabetic patients with and without retinopathy in the Asian Indian population. We screened 105 diabetic patients with retinopathy (DR) and 109 diabetic patients without retinopathy (DNR) for the (CA)( n) polymorphism and compared the results with those of an unrelated healthy control group (CT). We identified 13 alleles in our diabetic population. The Z-2 allele (136 bp) showed an association with the DR group (13.81%) with a significant p value (p = 0.029) when compared with the DNR group (7.34%). The Z-2 allele also showed a significant association with those DR patients who had proliferative retinopathy (PDR) and maculopathy (MAC) (p = 0.004). The Z-2 allele is, therefore, a high-risk allele for diabetic retinopathy in the Asian Indian patients.

Aldehyde Reductase↗

Scleral buckling: implant versus explant.

PURPOSE: To compare the implant and explant techniques of scleral buckling. METHODS: This prospective, randomized clinical study compared the two techniques of scleral buckling. Variables such as size and extent of the buckle, duration of the surgery, complications, and anatomical and visual outcome were studied. The height of the buckle as measured by ultrasonography was also studied. RESULTS: No significant difference was found between the two groups for total duration of the surgery, complications, anatomical results, visual outcome, and buckle height. For the 1- to 2-quadrant buckles, duration of the surgery up to initiation of subretinal fluid drainage was found to be significantly shorter for the explant group. Serial ultrasonography showed significant reduction in buckle height over 6 months in both groups to an equal degree. CONCLUSIONS: Scleral buckling seems to be equally effective whether performed as an implant or explant.

Adult↗

Endophthalmitis caused by Acinetobacter calcoaceticus. A profile.

PURPOSE: To report the clinical and microbiological profile of endophthalmitis caused by Acinetobacter calcoaceticus. METHODS: A retrospective study of case series of Acinetobacter calcoaceticus endophthalmitis. Outcome measures included ability to sterilise the eye, anatomical result (clear media and attached retina) and visual recovery (visual acuity > 6/60). RESULTS: Of the 20 cases studied, 10 were cases of postoperative endophthalmitis, 3 were posttraumatic, 6 were endogenous and one was bleb-related endophthalmitis. Specific features of interest observed were relative chronicity of presentation and absence of any obvious predisposing factor in endogenous endophthalmitis cases. All cases could be sterilised except one, which needed evisceration. Cases with postoperative endophthalmitis had better anatomical outcome (7/10 with attached retina and clear media) and visual outcome (4/10 regained vision > 6/18). Higher smear positivity was seen in vitreous samples (72.2%) compared to aqueous samples (37.5%). Culture positivity was higher from the vitreous cavity compared to aqueous. The organism was sensitive to ciprofloxacin in a high percentage (88.9%) of cases. CONCLUSIONS: Visual recovery in Acinetobacter calcoaceticus endophthalmitis is modest. Ciprofloxacin is the antibiotic of choice.

Acinetobacter Infections↗

Management of recurrent retinal detachment in silicone oil-filled eyes.

PURPOSE: To report causes of failure, management options, and outcomes after reoperations for recurrent retinal detachment in silicone oil-filled eyes. METHODS: One hundred eighteen silicone oil-filled eyes with recurrent retinal detachment were managed with revision of vitrectomy with membrane surgery with or without silicone oil removal, just scleral buckling, or both. Anatomical success was defined as complete reattachment of the retina, and functional success was defined as recovery of ambulatory visual acuity of >or=5/200 at the last follow-up (mean follow-up, 29.7 months). RESULTS: In 82.2% of the cases, proliferative vitreoretinopathy was responsible for recurrent retinal detachment in silicone oil-filled eyes. Reoperations without removal of the silicone oil were performed in 65.3% of the cases. Anatomical success occurred in 62.7% of the eyes, and functional success occurred in 52.5%. Silicone oil was removed in 59.5% of the eyes with retinal reattachment; the retina remained attached in 90.9% of the eyes. Predictors of poor anatomical success were presence of posterior diffuse proliferative vitreoretinopathy and combined posterior and anterior proliferative vitreoretinopathy (P <0.02). CONCLUSION: Reoperations for recurrent retinal detachment in silicone oil-filled eyes were successful in nearly two thirds of the cases, and over one half of the eyes recovered ambulatory vision.

Adolescent↗

Comparison of pH-adjusted bupivacaine with a mixture of non-pH-adjusted bupivacaine and lignocaine in primary vitreoretinal surgery.

PURPOSE: To compare the efficacy of alkalinized bupivacaine with that of a mixture of nonalkalinized bupivacaine and lignocaine for local anesthesia in primary vitreoretinal surgery. METHODS: Through a prospective, double-blind, randomized, controlled clinical trial, 540 consecutive patients undergoing primary vitreoretinal surgery received either alkalinized 0.5% bupivacaine (group B) or a mixture of nonalkalinized 0.5% bupivacaine and 2% lignocaine (group BL), both of which were administered with hyaluronidase, for periocular anesthetic block. The periocular block involved two injections in the extraconal space-one in the lower temporal quadrant and the other in the medial periconal space. The efficacy of the block was graded from 0 to 5 depending on the adequacy of anesthesia and akinesia and the need for local supplementation. RESULTS: Adequate anesthesia and akinesia (grade 5) were achieved in 72.2% of the patients in group B compared with 57.4% in group BL (P = 0.0003). Intraoperative supplementation was needed in 9.6% and 20.7% of the patients in groups B and BL, respectively (P = 0.0003). Postoperative analgesics were required in 7.4% of the patients in group B and in 15.2% of those in group BL (P = 0.004). CONCLUSION: Alkalinized 0.5% bupivacaine provides better quality of anesthesia than does the mixture of nonalkalinized 0.5% bupivacaine and 2% lignocaine for patients undergoing primary vitreoretinal surgery.

Alkalies↗

Retinal detachment in Marfan syndrome: clinical characteristics and surgical outcome.

PURPOSE: To describe the clinical characteristics of retinal detachments in patients with Marfan syndrome and report the surgical outcome of vitreoretinal surgery. METHODS: Records relating to 53 eyes of 45 patients with Marfan syndrome who underwent surgery for rhegmatogenous retinal detachment were reviewed. Of the 53 eyes, 24 (45.3%) underwent scleral buckling as the first procedure and 29 (54.7%) underwent vitrectomy surgery with scleral buckle as the first procedure. Main outcome measures included clinical characteristics of retinal detachment, reattachment rates, and functional improvement in vision. RESULTS: Characteristic findings included total retinal detachment in 40 (75.5%) eyes, atrophic holes in 24 (45.3%) eyes, more than four retinal breaks in 21 eyes (39.6%), preequatorial and postequatorial breaks in 20 (37.7%) eyes, giant retinal tears in six (11.3%) eyes, and proliferative vitreoretinopathy (posterior, anterior, or both) in nine (17%) eyes. In 30 (56.6%) eyes, retinal breaks were located only in the temporal half of the retina. Of the 24 eyes with myopia, 13 (54.2%) had a myopic correction greater than 7 diopters. At the median follow-up of 10.7 months, complete retinal reattachment was obtained in 87.6% and 86.2% of patients undergoing scleral buckling (including additional procedures such as vitrectomy) and vitrectomy surgery, respectively. In eyes with reattached retinas, a final visual acuity of 20/200 or better was obtained in 81% of the patients after scleral buckling and in 56% of the patients after vitrectomy surgery (P = 0.07). CONCLUSIONS: Retinal detachment in Marfan syndrome is complete in 75% of the eyes. More than half (56%) the eyes had a retinal break only in the temporal half of the retina, and 83% had at least a break in the temporal half of the retina. Currently available vitreoretinal surgical techniques result in successful reattachment of the retina in approximately 86% of the eyes.

Adolescent↗

Eales disease--an update.

Eales disease, first described by Henry Eales in 1880, remains an enigma. The disease, observed more commonly in the Indian subcontinent than in the rest of the world, occurs in young healthy adult males, initially presenting as retinal periphlebitis and later as retinal ischemia that may lead to vascular alterations and neovascularization. Recurrent vitreous hemorrhage with or without retinal detachment is the common sequelae. In recent years, immunological, molecular biological, and biochemical studies have indicated the role of human leukocyte antigen, retinal autoimmunity, mycobacterium tuberculosis genome, and free radical mediated damage in the etiopathogenesis of this disease. However, its etiology appears to be multifactorial. The management depends on the stage of the disease and consists of medical treatment with oral corticosteroids in the active inflammatory stage and laser photocoagulation in the advanced retinal ischemia and neovascularization stages. The results of vitreoretinal surgery have been found to be satisfactory in case of vitreous hemorrhage with or without retinal detachment.

Diagnosis, Differential↗

Association of Gly82Ser polymorphism in the RAGE gene with diabetic retinopathy in type II diabetic Asian Indian patients.

AIM/HYPOTHESIS: The binding of advanced glycation end products (AGE) to the receptor induces cellular oxidative stress and vascular dysfunction and this is implicated in the pathogenesis of diabetic retinopathy (DR). This study aims to investigate the frequency of Gly82Ser polymorphism in exon 3 of the receptor for AGE (RAGE) gene and its association with DR in Asian Indian patients who have type II diabetes. METHODS: 200 Asian Indian patients with at least 15-year duration of type II diabetes were identified. This group included (1) 100 patients with retinopathy (DR) and (2) 100 patients without retinopathy (DNR). Fifty unrelated healthy controls (CT) were also included in the study. Genotype frequencies of Gly82Ser polymorphism were studied by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism analysis using AluI enzyme. Later, the nucleotide change was confirmed by DNA sequencing. RESULTS: The frequency of the Ser82 allele was significantly higher, 18% in the DNR group compared to 7% in the DR group (P=.03). The same genotype was 2% in the CT group. CONCLUSION/INTERPRETATION: Our result suggests that Ser82 allele in the receptor for AGE gene is a low-risk allele for developing DR in Asian Indian patients who have type II diabetes.

Amino Acid Substitution↗