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Biomedical subjects

Vishal Gupta

Publications and source records attributed to Vishal Gupta.

At least 19 recordsLinked to original sources
PubMed2006

Effects of static and cyclic loading in regulating extracellular matrix synthesis by cardiovascular cells.

Extracellular matrix (ECM) provides several structural and functional characteristics to tissues including cell support, mechanical integrity and biological signaling. In cardiovascular tissues, cells produce various ECM components such as collagen, elastin, proteoglycans, matrix metalloproteinases, growth factors and signaling molecules. The cardiovascular cells (cardiac fibroblasts, cardiomyocytes, endothelial cells, and vascular smooth muscle cells) sense the changes in mechanical strains applied to them, through cell-surface receptors such as integrins and ion channels, and adjust their expression and synthesis of ECM molecules in order to adapt their environment to these changes. ECM changes due to altered mechanics are evident in numerous pathological situations including hypertension, cardiac hypertrophy, myocardial infarction, myxomatous heart valve disease, and atherosclerosis. In hypertrophic conditions, for example, increased mechanical loading is involved with enhanced collagen synthesis, whereas in myxomatous and atherosclerotic conditions reduced mechanical strains are accompanied by an accumulation of proteoglycans. Therefore, investigating the effects of various strain patterns on cardiovascular cells can enhance our understanding of ECM regulation and pathologies. This review focuses on the in vitro modulation of the synthesis of various ECM molecules through static or cyclic stretching of cardiovascular cells.

Animals↗
PubMed2006

Quantifying influenza vaccine efficacy and antigenic distance.

We introduce a new measure of antigenic distance between influenza A vaccine and circulating strains. The measure correlates well with efficacies of the H3N2 influenza A component of the annual vaccine between 1971 and 2004, as do results of a theory of the immune response to influenza following vaccination. This new measure of antigenic distance is correlated with vaccine efficacy to a greater degree than are current state of the art phylogenetic sequence analyses or ferret antisera inhibition assays. We suggest that this new measure of antigenic distance be used in the design of the annual influenza vaccine and in the interpretation of vaccine efficacy monitoring.

Algorithms↗
PubMed2006

Primary chondrosarcoma of the breast.

Mammary sarcomas are uncommon tumours. Of these, pure chondrosarcoma without any other area of epithelial or mesenchymal differentiation feature is even rarer. This excludes tumours like malignant cystosarcoma phylloides and metaplastic carcinoma where malignant cartilaginous areas may be present. Further, primary chondrosarcoma arises from breast stroma and not from underlying bone or cartilage. Here is this case, a 46-year-old female was presented with a huge lump in her left breast. FNAC reported it to be a case of infiltrating duct carcinoma. Microscopically a well differentiated chondrosarcoma was identified. The case is presented because of its rarity.

Biopsy, Fine-Needle↗
PubMed2005

Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma.

PURPOSE: To evaluate pleurectomy/decortication (P/D) and adjuvant radiotherapy (RT) in the treatment of malignant pleural mesothelioma (MPM). METHODS AND MATERIALS: In a retrospective review, we included MPM patients treated with P/D and adjuvant RT at Memorial Sloan-Kettering Cancer Center from 1974 to 2003. When indicated, patients received intraoperative brachytherapy to residual tumor. RESULTS: All 123 patients received external beam RT (median dose, 42.5 Gy; range, 7.2-67.8 Gy) to the ipsilateral hemithorax postoperatively. Fifty-four patients underwent brachytherapy (matched peripheral dose, 160 Gy). The median and 2-year overall survival for all patients was 13.5 months (range, 1-199 months) and 23%, respectively. One-year actuarial local control for all patients was 42%. Multivariate analysis for overall survival revealed radiation dose <40 Gy (p = 0.001), nonepithelioid histology (p = 0.002), left-sided disease (p = 0.01), and the use of an implant (p = 0.02) to be unfavorable. Two patients (1.6%) died from Grade 5 toxicity within 1 month of treatment. CONCLUSIONS: Pleurectomy/decortication with adjuvant radiotherapy is not an effective treatment option for patients with MPM. Our results imply that residual disease cannot be eradicated with external RT with or without brachytherapy and that a more extensive surgery followed by external RT might be required to improve local control and overall survival.

Adult↗
PubMed2005

Tuberculous meningitis and HIV.

OBJECTIVE: To identify factors associated with HIV-infected status in children admitted with tuberculous meningitis (TBM), and to find out whether HIV co-infection affects in-hospital outcome. METHODS: This prospective hospital-based study was conducted from May 2000 to August 2003. All consecutive children, aged 1 month to 12 years of age, admitted with a diagnosis of TBM were enrolled. Relationship between 35 features viz., two demographic factors, nine clinical features, 13 neurological features, five laboratory (including cerebrospinal fluid) parameters, six radiological (including computed tomography scan brain) features, and the two outcomes (disabled survivor or death); with HIV-infected status was assessed. RESULTS: Of a total 123 TBM cases enrolled, eight (6.5%) were HIV-infected. There was no significant difference between the two groups, except that more children in the HIV-infected group had Hb < 8 gm/dl: both on bivariate analysis, (OR, 12.0; 95% CI, 2.6-55.9; P = 0.001) and on multivariate analysis (OR, 12.30; 95% CI, 1.9-79.6; P = 0.008). Outcome was similar in both the groups. CONCLUSION: Only presence of Hb < 8 gm/dl was associated with HIV-infected status. HIV co-infection did not affect the outcome.

Antitubercular Agents↗
PubMed2005

Prognostic clinical variables in childhood tuberculous meningitis: an experience from Mumbai, India.

BACKGROUND: In India, tuberculous meningitis (TBM) is still a major cause of neurological disabilities and death. AIM: To identify the clinical variables which predict the outcome in childhood TBM. SETTING: Tertiary teaching hospital. DESIGN: Prospective observational study. MATERIALS AND METHODS: Thirty-six clinical variables were analyzed in 123 consecutive children with TBM admitted between May 2000 and August 2003. The outcome was assessed in terms of survival or death. Survival meant that the patient was discharged from hospital having made a complete recovery, or with disability. RESULTS: Twenty-five (20%) children recovered completely, 70 (57%) survived with disability, and 28 (23%) died. Employing univariate analysis nine variables correlated with survival with disability outcome: presence of tonic motor posturing, cranial nerve palsy, focal neurological deficit, hypertonia, moderate to severe hydrocephalus, cerebral infarction on cranial CT, and requiring shunt surgery, and absence of extracranial tuberculosis and no antituberculous-related hepatotoxicity; two variables correlated with fatal outcome: presence of deep coma (Glasgow coma scale score P = 0.012, d.f. = 1, OR 0.12, 95% CI 0.02-0.62) correlated with survival with disability outcome, and presence of deep coma (P = 0.030, d.f. = 1, OR 0.35, 95% CI 0.14-0.90) with fatal outcome. CONCLUSION: In children with TBM, the presence of hypertonia at admission is an independent predictor of neurological sequelae in survivors, and deep coma is an independent predictor of mortality.

Child↗
PubMed2004

Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading.

This study was designed to identify the specific proteoglycans and glycosaminoglycans (GAGs) in the leaflets and chordae of the mitral valve and to interpret their presence in relation to the tensile and compressive loads borne by these tissues. Leaflets and chordae from normal human mitral valves (n = 31, obtained at autopsy) were weighed and selected portions digested using proteinase K, hyaluronidase, and chondroitinases. After fluorescent derivatization, fluorophore-assisted carbohydrate electrophoresis was used to separate and quantify the derivatized saccharides specific for each GAG type. In addition, the lengths of the chondroitin/dermatan sulfate chains were determined. Proteoglycans were identified by western blotting. The regions of the valve that experience tension, such as the chordae and the central portion of the anterior leaflet, contained less water, less hyaluronan, and mainly iduronate and 4-sulfated N-acetylgalactosamine with chain lengths of 50-70 disaccharides. These GAGs are likely associated with the small proteoglycans decorin and biglycan, which were found in abundance in the tensile regions. The valve regions that experience compression, such as the posterior leaflet and the free edge of the anterior leaflet, contained significantly more water, hyaluronan, and glucuronate and 6-sulfated N-acetylgalactosamine with chain lengths of 80-90 disaccharides. These GAGs are likely components of water-binding versican aggregates, which were abundant in the compressive loading regions. The relative amounts and distributions of these GAGs are therefore consistent with the tensile and compressive loads that these tissues bear. Finally, the concentrations of total GAGs and many different chondroitin/dermatan sulfate subclasses were significantly decreased with advancing age.

Acetylgalactosamine↗
PubMed2004

Novel germline mutations in breast cancer susceptibility genes BRCA1, BRCA2 and p53 gene in breast cancer patients from India.

Mutations in breast cancer susceptibility genes, BRCA1 and BRCA2 account for more than 80% of hereditary breast and ovarian cancers. p53 tumor suppressor gene that controls cellular growth and differentiation is also known to be mutated in more than 50% of human cancers including breast cancer. We have carried out a study on BRCA1 and BRCA2 along with p53 gene mutations in both sporadic as well as familial breast cancer patients from India where breast cancer is fast emerging as a major cancer among premenopausal urban women. We examined 124 untreated primary breast cancer patients comprising 100 sporadic and 24 familial cases including 56 age-matched healthy controls for the presence of BRCA1, BRCA2 and the p53 gene mutations using PCR-SSCP and direct nucleotide sequencing. Certain frequently mutated exons such as 2, 5, 11, 13 and 20 of BRCA1, exons 2, 9, 11 (for 6174delT), 18 and 20 of BRCA2 and 4-9 exons of p53 gene were analyzed in sporadic breast cancer while all 22 coding exons of BRCA1 including its flanking intronic regions along with above mentioned exons of BRCA2 and p53 gene were analyzed in familial breast cancer patients. We identified six patients (25%) with BRCA1 mutation of which three were found to be of novel type one in exon 16 (4956insG) and two in exon 7 (Lys110Thr) (Ser114Pro) out of 24 familial breast cancer patients studied from two different geographic regions/populations of India. Two sisters from a single family (12.5%) out of eight families from Goa with Portuguese colonial origin showed presence of founder Ashkenazi Jewish BRCA1 mutation (185delAG) along with (IVS7 561-34T>C; IVS18 5271 + 66G > A). While from New Delhi, four (25%) of 16 breast cancer families showed BRCA1 mutations; a frame shift protein truncating (4956insG), a transition nonsense (Gln1395Stop) and two amino acid substitutions (Lys110Thr) and (Ser114Pro). Only one (4%) p53 mutation (Val97Ile) in its exon 4 along with BRCA1 mutation (4956insG) could be detected. No major sequence variation in BRCA2 gene was observed except for G203A at 5' UTR of exon 2, a common population polymorphism in two Goan patients who also showed silent nucleotide change for amino acid serine at codon 1436 of BRCA1 gene. None of the 100 sporadic breast cancer patients revealed any protein truncating or deleterious BRCA1 or BRCA2 gene mutation. Interestingly, three (3%) p53 mutations in its exon 5 were detected in sporadic breast cancer patients. Although three novel BRCA1 mutations including a founder Ashkenazi Jewish BRCA1 mutation were recorded in Indian women with familial breast cancer, the overall prevalence of BRCA gene mutations in Indian women with a family history of breast cancer appears to be low.

Adult↗
PubMed2004

A prospective longterm study of primary chronic angle closure glaucoma.

PURPOSE: To prospectively evaluate the longterm outcome of therapy for chronic primary angle closure glaucoma (PACG) and to assess the efficacy of medical and surgical treatment in terms of intraocular pressure (IOP) and visual field stabilization. METHODS: Seventy consecutive patients with chronic PACG, whose IOP remained > 21 mmHg despite a patent iridotomy, had their IOP controlled by medications or trabeculectomy performed without antimetabolites. They were followed over a 6-year period. Best corrected visual acuity, IOP (mean of annual diurnal variation readings), cup : disc ratio and visual fields were recorded. A trabeculectomy was performed if the IOP was not adequately controlled on maximal tolerable medical therapy or if there was a progression of the glaucomatous defect. Data from one eye of each patient were analysed; if both eyes met the inclusion criteria, one was randomly selected for the analysis. The baseline parameters were compared with those at the end of 6 years. RESULTS: A total of 46 eyes (65%) were controlled medically throughout the 6-year follow-up period, while 24 eyes (35%) required surgery. The mean IOP was 25.4 +/- 4.9 mmHg at baseline and 15.6 +/- 4.6 mmHg at 6 years follow-up (p < 0.001). Stereoscopic evaluation of the cup : disc ratio did not show a significant change from a mean of 0.6 +/- 0.18 at baseline to a mean of 0.64 +/- 0.2 at 6 years (p = 0.12). Progression of visual field defects was seen in seven eyes (10%), which had statistically larger cup : disc ratios (p = 0.04) and more extensive visual field deficits at the initial assessment (p = 0.04), and which also maintained higher levels of IOP (p = 0.03) over the 6 years of follow-up. CONCLUSIONS: Stable visual fields and good longterm IOP control were seen in 90% of chronic primary angle closure glaucoma eyes on medical/surgical therapy over 6 years.

Aged↗
PubMed2004

Microbial keratitis following lamellar keratoplasty.

OBJECTIVE: To determine the predisposing factors, etiologic agents, and clinical and visual outcomes in infectious keratitis following lamellar keratoplasty (LK). METHODS: One hundred thirty-five eyes (135 patients) that had undergone LK were retrospectively analyzed for the occurrence of infectious keratitis following LK. The parameters evaluated were predisposing factors, seasonal variation, indications and type of LK, time interval between LK and infection, site and depth of infection, etiologic organisms, type of treatment, outcome in terms of graft status, secondary surgery, visual acuity, and the donor tissue profile. RESULTS: The incidence of infectious keratitis following LK was 11.11%. The most significant predisposing factor was persistent epithelial defect (3 eyes) and suture abscesses (3 eyes). Most cases occurred between May and August (9/15). Twelve cases developed infection within 2 weeks of surgery (80%). Seven cases (7/15) occurred with onlay grafts, 6 with inlay grafts, and 2 with large-diameter LK. Cultures of corneal scrapings were positive in 11 eyes (73.3%), and the most common isolated organism was coagulase-negative Staphylococcus (CNS). Only 2 eyes responded to medical therapy, and graft sloughing occurred in 9 cases. Six eyes underwent penetrating keratoplasty to either salvage the integrity of globe or for visual rehabilitation of cases where infection resulted in corneal opacity. CONCLUSIONS: Infections after LK may not be amenable to antimicrobial therapy and may necessitate the removal of the graft or a therapeutic penetrating keratoplasty.

Adult↗
PubMed2004

Treatment of pain symptoms in irritable bowel syndrome patients.

Irritable bowel syndrome represents a common gastrointestinal disorder that significantly impacts patients' lives. It is defined by Rome II criteria and characterized by abdominal pain and bloating associated with changes in bowel habit. Visceral hypersensitivity is currently considered a biological marker for the disease. Current therapeutic treatments include the use of fiber supplements, antidiarrheal agents, laxatives, antispasmodics, tricyclic antidepressants and serotonergic agents. Through a proper understanding of the diagnostic criteria, pathophysiology and treatment options, this disorder can be treated effectively in many patients.

Abdominal Pain↗
PubMed2004

Reduction of subacute stent thrombosis (SAT) using heparin-coated stents in a large-scale, real world registry.

PURPOSE: This study was designed to compare the rates of subacute stent thrombosis (SAT) among patients receiving heparin-coated stents to patients receiving bare-metal stents in real world, contemporary coronary interventions. BACKGROUND: Controlled trials with heparin-coated coronary stents have shown a trend toward decreased rates of SAT. METHODS AND RESULTS: The data in this study were collected from a single, large cardiac center over a period of 9 months. All patients who underwent coronary stent implantation during this 9-month period were included in the study (1,288 patients; 1,366 procedures; 2,231 stents). All patients were treated with aspirin and clopidogrel (or ticlopidine) after stenting. Primary thrombotic outcome was defined as angiographically documented SAT and/or sudden unexplained cardiac death (SCD) within 30 days of the procedure. Follow-up data (1,264/1,276 patients) were obtained in 99% of patients. A total of 337 patients received 543 heparin-coated stents (BX Velocity Hepacoat) and 939 patients received bare-metal stents (1,688 stents). SAT was seen in 25/1,024 procedures (2.44%) in the bare-metal stent group and 1/342 procedures (0.29%) in the heparin-coated stent group. Primary thrombotic outcomes (SAT or SCD) were observed in 31/1,024 procedures (3.03%) in the bare-metal stent cohort and in 2/342 procedures (0.58%) in the heparin-coated stent group. The vast majority (96%) of the patients who had SAT within 30 days had initial stent placement for an acute coronary syndrome (p<0.0001). CONCLUSION: This large, single-center registry demonstrates a significant reduction of SAT using heparin-coated stents compared to bare-metal stents in real world coronary interventions.

Angioplasty, Balloon, Coronary↗
PubMed2003

The carboxy-terminal, M3 motifs of PACT and TRBP have opposite effects on PKR activity.

PKR is an interferon(IFN)-induced, serine-threonine protein kinase, which plays a crucial role in IFN's antiviral and antiproliferative actions. The three known activators of PKR are dsRNA, heparin, and PACT. PACT activates PKR by direct protein-protein interaction in response to cellular stress. The human TAR (trans-activating region)-binding protein (TRBP), which is very homologous to PACT, also interacts with PKR, leading to an inhibition of PKR activity. Since these two highly homologous proteins have opposite effects on PKR, we examined if they interact with PKR differently by assaying their interaction with various point mutants of PKR. Our results indicate that TRBP and PACT interact with PKR through the same residues, and no differences were identified in these two interactions. Domain swap experiments between PACT and TRBP indicated that the inhibitory effects of TRBP on PKR activity are mediated through its carboxy-terminal residues, which contain TRBP's third dsRNA-binding motif.

Amino Acid Motifs↗
PubMed2003

PRK for epithelial ingrowth in buttonhole after LASIK.

PURPOSE: To evaluate the efficacy of photorefractive keratectomy (PRK) in progressive central epithelial ingrowth after buttonholes after laser in situ keratomileusis (LASIK). METHODS: Two eyes of two patients with progressive central epithelial ingrowth and fibrosis in flap buttonholes after LASIK underwent PRK 6 months following primary surgery. RESULTS: Epithelial ingrowth was treated successfully in both eyes. The uncorrected visual acuities were 20/20, and there was no evidence of recurrent epithelial ingrowth after 6 months. CONCLUSIONS: Photorefractive keratectomy is a useful modality in the treatment of central epithelial ingrowth in buttonholes following LASIK. As a single-step surgery, it offers both therapeutic and optical advantages by simultaneously clearing the corneal opacity and correcting the refractive error in selected cases.

Adult↗
PubMed2003

Racial differences in thoracic aorta atherosclerosis among ischemic stroke patients.

BACKGROUND AND PURPOSE: Atherosclerosis of the thoracic aorta is an independent risk factor for stroke. There is little information on the impact of race in the prevalence of thoracic aorta atherosclerotic plaques among ischemic stroke patients. This study was an attempt to objectively assess the prevalence, thickness, and burden of thoracic aorta atherosclerotic plaques in a large population of ischemic stroke patients and to compare the differences between American blacks and whites. METHODS: This is a retrospective study of clinical data and transesophageal echocardiography (TEE) of 1553 ischemic stroke patients (664 blacks, 889 whites) over a period of 4.5 years. Atherosclerotic plaque prevalence, thickness, morphology, and burden (sum of maximum thickness in ascending aorta [AA], aortic arch [AO], and descending aorta [DA]) were assessed with TEE. Charts were reviewed for clinical information. RESULTS: Age and sex were similar among blacks and whites. Analyses of clinical data found that blacks had significantly higher hypertension (odds ratio [OR], 2.61; P<0.0001) and diabetes mellitus (OR, 1.99; P<0.0001) and significantly lower coronary artery disease (OR, 0.75; P=0.017) and carotid artery disease (OR, 0.62; P=0.0008) compared with whites. TEE showed that whites had significantly greater plaque prevalence (AA: OR, 1.37; P=0.04; AO: OR, 1.26; P=0.03; DA: OR, 1.39; P=0.002) and plaque burden (blacks, 4.28 mm; whites, 4.97 mm; P=0.007). Whites also had a trend of increased complex plaques and plaques >4 mm thick in all regions of the thoracic aorta. CONCLUSIONS: Among ischemic stroke patients, blacks had a lower prevalence of extra cranial atherosclerotic disease even though they had significantly higher hypertension and diabetes mellitus compared with whites. This difference cannot be explained by the existing risk factors in ischemic stroke patients.

Adult↗