Kumar V.,All India Institute of Medical Sciences
Retina | Year: 2017
PURPOSE:: To study the structural and functional outcomes of 25-gauge pars plana vitrectomy in giant retinal tear–associated retinal detachments. METHODS:: Seventeen eyes of 17 patients with giant retinal tear, who underwent 25-gauge pars plana vitrectomy over a period of 15 months at a tertiary eye care center by a single surgeon, were recruited in this retrospective interventional study. RESULTS:: Giant retinal tears were mostly traumatic (35.3%) or associated with myopia (35.3%) and occurred in young (mean age 25.7 years) males (94.1%). Most eyes had best-corrected visual acuity ≤20/1,200 (in 82.3%), foveal detachment (in 88.2%), and proliferative vitreoretinopathy ≤Grade B (in 82.3%). The giant retinal tear extent was more than 180° in 29.4% and the fellow eye was involved in 35.2% of eyes. All eyes underwent 25-gauge pars plana vitrectomy with encircling band in 41.1%, perfluorocarbon liquid use in 82.3%, and endotamponade with sulphur hexafluoride (23.6%) or silicone oil (76.4%). At mean follow-up of 10.2 months, reattachment rate was 88.2%. Only 35.2% of eyes achieved final visual acuity ≥20/80 with a cause of poor vision being cataract, secondary glaucoma, macular pucker, and corneal edema. CONCLUSION:: Twenty-five–gauge pars plana vitrectomy can achieve excellent attachment rates in eyes with giant retinal tear–associated retinal detachment. It can be as efficient as larger-gauge vitrectomy, at the same time retaining all advantages of smaller-gauge surgery. © 2017 by Ophthalmic Communications Society, Inc.
All India Institute of Medical Sciences and National Brain Research Center Nbrc | Date: 2014-07-03
The present invention demonstrates for the first time that FAT1 plays an important role in modulating PDCD4 expression, which in turn regulates AP-1 dependent transcription, controls processes crucial for migration and invasion in cancer cells, controls induction of a pro-inflammatory micro environment in cancer cells. The study illustrates a link between inflammation and cancer in cells or in a subject. This work highlights the importance of FAT1 in the induction of the cellular pathways of migration and invasion, proteolysis of the ECM and the expression of pro-inflammatory molecules leading to a favorable micro environment for tumor and cancer progression. The present invention also provides the use of FAT1 in regulating neoplastic phenotypes and genotypes including invasiveness and inflammatory micro environment of the cancer cells by acting as a novel apical regulator of a signaling pathway by affecting the AP1 transcriptional activity, affecting the property of both cell migration and invasion and at the same time affecting the expression of inflammatory modulators. The present invention also identifies a novel regulatory pathway for inflammatory mediators and inflammatory cellular responses via PDCD4 and AP1. The invention describes a pathway for the upregulation of inflammatory processes as such, and hence a means of regulating inflammatory pathologies in general.
National Brain Research Center and All India Institute of Medical Sciences | Date: 2014-05-10
The present invention relates to cell specific therapeutic modality by using a region of the PLAP Promoter. The invention further relates to specific expression of therapeutically PLAP useful sequences for specific transcriptional activation of this gene. The invention also relates to the PLAP region which may be used alone or in combination with other regions like enhancer sequences that augment cell or tumour specific gene expression.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 7.92M | Year: 2013
The trypanosomatid diseases, leishmaniasis, Human African trypanosomiasis (HAT) and Chagas disease (CD), continue to impart a heavy toll on human health. The treatments available are limited and threatened by drug resistance with few newdrugs in the pipeline. The KINDReD consortium integrates five leading academic laboratories in Europe (Portugal, United Kingdom, and Switzerland), the USA (California) and South America (Brazil) with high throughput screening (HTS) facilities equally distributed between all three major kinetoplastid parasites. Intracellular amastigote screening will be employed as the most relevant for Leishmania spp and T cruzi. Compound libraries (focused, diversity oriented or natural) will be screened in these systems, as well as compound series devised through target screening and in silico approaches. For carefully chosen protein targets, all three kinetoplastid parasite homologs will be screened against the closest human homolog to establish selectivity. Promising lead compounds will be optimised for efficacy and tolerability in cell-based and animal disease models. Toxicological markers will be evaluated in human cell lines prior to toxicity (acute,subacute,chronic) testing in lower then higher mammals. In parallel, and in line with the FDAs Critical Path Initiative, several check point controls will be built into the pipeline to flag, identify and allow early correction of potential toxicity/efficacy issues. These will include (i) a systems biology approach to identify drug target and off-target interactions via activity-based chemoproteomics (ii) uptake and metabolismas potential modulators of drug efficacy and/or resistance and (iii) the establishment of a firm set of rules for drug efficacy and safety in kinetoplastid chemotherapy. Our goal is to strengthen the drug development pipeline in order to achieve at least one new Phase I clinical candidate for each trypanosomatid disease at or shortly after the project completion date.
Sharma S.K.,All India Institute of Medical Sciences
The Cochrane database of systematic reviews | Year: 2013
Preventing active tuberculosis (TB) from developing in people with latent tuberculosis infection (LTBI) is important for global TB control. Isoniazid (INH) for six to nine months has 60% to 90% protective efficacy, but the treatment period is long, liver toxicity is a problem, and completion rates outside trials are only around 50%. Rifampicin or rifamycin-combination treatments are shorter and may result in higher and a 1998 trial in people without silicosis (two trials, 524 participants; high quality evidence). No difference was detected for treatment-limiting adverse events (two trials, 536 participants; low quality evidence), or hepatotoxicity (two trials, 536 participants; low quality evidence). Rifampicin plus pyrazinamide (two months) vs. INH (six months)Three small trials published in 1994, 2003, and 2005 compared these two regimens, and two reported a low occurrence of active TB, with no statistically significant differences between treatment regimens (two trials, 176 participants; very low quality evidence) though, apart from one child from the 1994 trial, these data on active TB were from the 2003 trial in adults with silicosis. Adherence with both regimens was low with no statistically significant differences (four trials, 700 participants; very low quality evidence). However, people receiving rifampicin plus pyrazinamide had more treatment-limiting adverse events (RR 3.61, 95% CI 1.82 to 7.19; two trials, 368 participants; high quality evidence), and hepatotoxicity (RR 4.59, 95% 2.14 to 9.85; three trials, 540 participants; moderate quality evidence). Weekly, directly-observed rifapentine plus INH (three months) vs. daily, self-administered INH (nine months)A large trial conducted from 2001 to 2008 among close contacts of TB in the USA, Canada, Brazil and Spain found directly observed weekly treatment to be non-inferior to nine months self-administered INH for the incidence of active TB (0.2% vs 0.4%, RR 0.44, 95% CI 0.18 to 1.07, one trial, 7731 participants; moderate quality evidence). The directly-observed, shorter regimen had higher treatment completion (82% vs 69%, RR 1.19, 95% CI 1.16 to 1.22, moderate quality evidence), and less hepatotoxicity (0.4% versus 2.4%; RR 0.16, 95% CI 0.10 to 0.27; high quality evidence), though treatment-limiting adverse events were more frequent (4.9% versus 3.7%; RR 1.32, 95% CI 1.07 to 1.64 moderate quality evidence) Trials to date of shortened prophylactic regimens using rifampicin alone have not demonstrated higher rates of active TB when compared to longer regimens with INH. Treatment completion is probably higher and adverse events may be fewer with shorter rifampicin regimens. Shortened regimens of rifampicin with INH may offer no advantage over longer INH regimens. Rifampicin combined with pyrazinamide is associated with more adverse events. A weekly regimen of rifapentine plus INH has higher completion rates, and less liver toxicity, though treatment discontinuation due to adverse events is probably more likely than with INH.
Udupi B.P.,All India Institute of Medical Sciences
Neurosurgery | Year: 2012
Among the percutaneous procedures for the treatment of trigeminal neuralgia, percutaneous anhydrous glycerol rhizolysis (PRGR) and radiofrequency (RF) ablation of trigeminal neuralgia have stood the test of time. A prospective study was conducted to compare PRGR and RF ablation techniques in patients with trigeminal neuralgia in terms of (1) efficacy of pain relief, (2) duration of pain relief and (3) side effects. All patients presenting to our pain clinic for the first time for the treatment of trigeminal neuralgia were enrolled to receive either PRGR or RF ablation; the treatment was chosen by the patient. Demographic data, magnetic resonance imaging scan, relevant medical disease, amount of anhydrous glycerol, lesion temperature, and total duration of RF were noted. The presence or absence of cerebrospinal fluid egress, immediate pain relief, duration of pain-free period, need for repeat injection or additional peripheral nerve block, and recurrence of pain were also noted. The degree of pain relief was recorded every 3 months. Any complications during the procedure and side effects were also recorded. Seventy-nine patients underwent either PRGR (n = 40) or RF thermocoagulation (n = 39). A total of 23 patients (58.9%) in the PRGR group and 33 patients (84.6%) in the RF group experienced excellent pain relief. The mean duration of excellent pain relief in the PRGR and RF groups was comparable. By the end of the study period, 39.1% patients in the PRGR group and 51.5% patients in the RF group experienced recurrence of pain. Both PRGR and RF techniques can achieve acceptable pain relief with minimal side effects.
Mouli V.P.,All India Institute of Medical Sciences
Gastroenterology | Year: 2013
Conservative treatment (intensive care, a combination of antimicrobial agents, and nutritional support, with or without drainage of the infected fluid) has recently been shown to be effective for patients with infected pancreatic necrosis (IPN), but the data from individual studies are not robust enough to recommend it as the standard of care. We performed a systematic review and meta-analysis of studies related to primary conservative management for IPN. We performed a literature search of MEDLINE/PubMed from January 1990 to March 2012 for studies of a priori protocols for primary conservative treatment, without necrosectomy, for consecutive patients with IPN. We analyzed data from 8 studies, comprising 324 patients with IPN who received primary conservative management. We then analyzed an additional 4 studies (comprising 157 patients) that reported the efficacy of percutaneous drainage in nonconsecutive patients with IPN. Outcome measures were the success of conservative management strategy, need for necrosectomy, and mortality. There was significant heterogeneity in results among the studies. Based on a random effects model, conservative management was successful for 64% of patients (95% confidence interval [CI], 51%-78%); mortality was 12% (95% CI, 6%-18%), and 26% of patients required necrosectomy or additional surgery for complications (95% CI, 15%-37%). A separate analysis of 4 studies that reported outcomes of nonconsecutive patients with IPN following percutaneous drainage had comparable results; 50% had successful outcomes (95% CI, 43%-58%), mortality was 18% (95% CI, 6%-30%), and 38% of patients required surgery (95% CI, 20%-56%). Conservative management without necrosectomy is a successful approach for 64% of patients with IPN. This approach has low mortality and prevents surgical necrosectomy. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
Mansoori N.,All India Institute of Medical Sciences
Neurobiology of aging | Year: 2012
Genetic risk factors play an important role in the pathogenesis of Alzheimer disease (AD) and vascular dementia (VaD). In this case-control study, we examined C677T and A1298C (rs1801133 and rs1801131) polymorphism in the methylenetetrahydrofolate reductase (MTHFR) genes and their correlation with plasma levels of homocysteine (Hcy) in AD and VaD cases and evaluated the gene-gene interaction (epistasis) with IL-6-174 G/C (rs1800795). CC genotype was associated with elevated levels of plasma homocysteine (p = 0.004) as compared with genotype AA of rs1801131. In AD, we observed a significant (p = 0.04) association with C alleles of rs1801131. Regression analysis revealed that the presence of both rs1801133 T and rs1800795 C alleles increased the odds of developing AD by 2.5 and VaD by 3.7-fold. While rs1800795 (CC or GC) genotypes alone increased the odds of developing VaD by 2.2-fold, the presence of CC genotype of rs1801131 nullified this effect. The findings support the hypothesis that multiple genes are involved to alter the odds of developing AD and VaD. Copyright Â© 2012 Elsevier Inc. All rights reserved.
Lakshmy R.,All India Institute of Medical Sciences
Reviews in Endocrine and Metabolic Disorders | Year: 2013
Development of metabolic syndrome is attributed to genes, dietary intake, physical activity and environmental factors. Fetal programming due to maternal nutrition is also an important factor especially in developing countries where intrauterine growth retardation followed by excess nutrition postnatally is causing mismatch predisposing individuals to development of metabolic syndrome and its components. Several epidemiological and animal studies have provided evidence for the link between intrauterine growth retardation and adult metabolic diseases. Deficiency of macronutrients, protein and carbohydrates, during pregnancy and gestation results in lower infant birth weight, a surrogate marker of fetal growth and subsequently insulin resistance, glucose intolerance, hypertension and adiposity in adulthood. The role of micronutrients is less extensively studied but however gaining attention with several recent studies focusing on this aspect. Several mechanisms have been proposed to explain the developmental origin of adult diseases important among them being alteration of hypothalamic pituitary axis, epigenetic regulation of gene expression and oxidative stress. All of these mechanisms may be acting at different time during gestation and contributing to development of metabolic syndrome in adulthood. © 2013 Springer Science+Business Media New York.
All India Institute of Medical Sciences | Date: 2014-06-09
The present invention pertains to the field of neurosurgery and describes new methods to reduce basilar invagination (BI) and atlanto-axial dislocation (AAD). The invention further discloses novel surgical instruments useful in reducing basilar invagination (BI) and atlanto-axial dislocation (AAD). The novel techniques disclosed include distraction, compression and extension reduction and dynamic distraction coupled with cable compression.