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Biomedical subjects

M Gupta

Publications and source records attributed to M Gupta.

At least 73 records · Page 4Linked to original sources
PubMed2001

Treatment refusal in the involuntarily hospitalized psychiatric population: Canadian policy and practice.

Policies governing coercive psychiatric interventions must be scrutinized to ensure they are not only beneficent but just. Within Canada, in seven of ten provinces, persons may be detained in hospital against their will for dangerousness due to mental disorder but, if capable of making treatment decisions, may refuse treatment for the very illness that led to detention. In examining this issue, the purpose of this paper is threefold. First, it will demonstrate that treatment refusal amongst involuntarily hospitalized psychiatric patients has arisen from a recent separation, in law, of hospitalization from treatment. Second, it will argue that legal provisions that allow the detention of psychiatric patients prior to assessment of their treatment decision-making capacity discriminate against the mentally ill and undermine health service delivery. Finally, this paper will propose that a more just policy would allow involuntary hospitalization of only those patients who are both incapable of making treatment decisions and harmful to themselves or others.

Canada↗
PubMed2001

Long-term results of the treatment of complete distal ureteral stenosis using a cutting balloon catheter device.

PURPOSE: We evaluated the long-term efficacy of endoscopic treatment of complete distal ureteral stenosis using a cutting balloon catheter. MATERIALS AND METHODS: We performed a total of 10 procedures in 9 patients with complete distal ureteral stenosis at or near the ureterovesical junction. Depending on presenting anatomy cases were treated with a retrograde only (6), antegrade only (1) or combined antegrade and retrograde (3) endoscopic technique. RESULTS: At a mean followup of 36 months (range 24 to 43) 9 of the 10 procedures (90%) were successful. Stenosis recurred in 1 of the 9 patients (10%) but a repeat procedure was successful. There were no intraoperative complications and no procedures required open surgical conversion. Although all patients noticed a various degree of hematuria postoperatively, none required blood transfusion or further intervention. Mean hospitalization was 1.1 days. CONCLUSIONS: Endoscopic repair of distal ureteral stenosis using a cutting balloon catheter is a viable option in patients with complete ureteral obstruction. This technique results in low morbidity, a short hospital stay and excellent long-term patency. Endoscopic treatment using a cutting balloon catheter may be a therapeutic option in many patients with complete distal ureteral obstruction at or near the ureterovesical junction.

Adult↗
PubMed2001

Creutzfeldt-Jakob disease : report of 10 cases from North India.

Creutzfeldt-Jakob disease (CJD) is increasingly being reported over the last three decades as a result of heightened awareness of the disease. Various studies have reported annual incidence of 0.5-1.5 cases of CJD per million of general population. In India, the disease is still under reported. Over the period spanning from 1968-1997, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore recorded 69 cases of CJD from different parts of India in the CJD registry. This paper describes the clinical experience with cases of CJD managed at the Department of Neurology, G.B. Pant Hospital, New Delhi from 1990-1998. In this series, the mean age of the patients was 53.80 (+/- 7.32) years and there were 5 females and 5 males. Myoclonus was present in all the cases and abnormal behaviour with or without other features was the presenting complaint in 7 of the 10 patients, while one patient of CJD had cerebellar ataxia as the presenting feature. One patient with occipital variant of CJD presented with acute onset cortical blindness and myoclonic jerks. One of the patients had acute psychosis precipitated by emotional stress at the onset. Extrapyramidal features were noted in 7 of the 10 patients before death. The mean duration of symptoms from the onset of disease to death was 6.6 (+/- 6.11) months. Classical EEG changes were observed in all the patients, except in one possible case of occipital variant of CJD, where we did not have access to EEG record. Brain biopsy could be undertaken in 3 patients, and in 2 patients the features of subacute spongiform encephalopathy (SSE) were noted.

Adult↗
PubMed2001

Topiramate: a new safe and effective antiepileptic.

Twenty patients of either sex, with refractory partial epilepsy with or without secondary generalisation were entered in an open label study to evaluate the efficacy and safety of topiramate in them. Topiramate was used as an adjunctive therapy with an initial starting dose of 50 mg/day. The dose was then titrated upwards with increments of 50 mg per week, till a time the most effective and the best tolerated dose was reached. This most effective/tolerated dose was then continued for 6 months. Of the 17 patients entering the maintenance phase, 4 patients (24%) became seizure free, while a total of 14 patients (83%) out of 17 cases responded with a reduction in monthly seizures rate by 50% or more. Mean reduction of 68.9% was observed in monthly seizure rate during the maintenance phase. The median effective dose of topiramate was 600 mg per day. Five patients dropped out of the study due to adverse events such as anxiety, aggressiveness, rash, lethargy, etc. The central nervous system (CNS) related side effects such as dizziness, headache, and tremor were reported, which are commonly seen with other presently available antiepileptics like carbamazepine, phenytoin sodium, sodium valproate, etc, as well. Most adverse events, however, were mild and transient and did not interfere with the day to day activity of the patients. Topiramate was not associated with any abnormality in laboratory or neurological examination findings. The excellent response with topiramate therapy in Indian patients, uncontrolled with the available antiepileptics, as well as its good safety profile endorse the international efficacious and safe image of topiramate.

Adolescent↗
PubMed2000

Expression of angiotensin II type I receptor on erythroid progenitors of patients with post transplant erythrocytosis.

BACKGROUND: The pathogenesis of posttransplant erythrocytosis (PTE) has been elusive. Angiotensin converting enzyme inhibitors (ACEI) are efficacious in lowering the hematocrit of patients with PTE and angiotensin II (AII) type I receptors (AT1R) were recently detected on red blood cell precursors, burst-forming unit-erythroid- (BFU-E) derived cells. The purpose of this study was to determine whether there is increased expression of the AT1R on BFU-E-derived cells of patients with PTE, which might contribute to the pathogenesis of PTE. METHODS: Twelve healthy volunteers and 25 transplant recipients (13 patients with and 12 without PTE) were studied. BFU-E from peripheral blood were cultured in methylcellulose and BFU-E-derived colonies were harvested on day 10. Western blotting was used to detect AT1R and erythropoietin receptor (EpoR) expression. Intracellular free calcium in response to AII and erythropoietin (Epo) was measured with digital video imaging. RESULTS: There were no differences between transplant patients, with and without PTE, with respect to weight, age, sex, blood pressure, serum creatinine, circulating renin, angiotensin II, and Epo levels. Hematocrit, red blood cell number, BFU-E-derived colony number,and size were significantly increased in PTE compared with other two groups. AT1R expression was increased by 44% on the erythroid progenitors of PTE versus non posttransplant erythrocytosis patients and by 32% in PTE patients versus normal volunteers. AT1R expression correlated significantly with the hematocrit in PTE (Spearman r=0.68, P=0.01). In contrast, EpoR expression was equivalent in all groups. The AT1R was functional since a significant increase in [Ca(i)] was observed in Fura-2 loaded day 10 cells when stimulated with AII (182%, P<0.0001). CONCLUSION: An increase in AT1R density was observed in erythroid precursors of transplant patients with PTE compared to those without PTE and normal volunteers, and the level of AT1R expression in PTE correlated significantly with the hematocrit. In contrast, EpoR expression was not different in PTE compared with non posttransplant erythrocytosis or normal controls. This study supports a role for the AT1 receptor signaling pathway in the pathogenesis of PTE.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Protein kinase-A dependent phosphorylation of transcription enhancer factor-1 represses its DNA-binding activity but enhances its gene activation ability.

The cAMP-dependent signaling pathway has been implicated in cardiac cell growth/differentiation and muscle gene transcription. Previously, we have identified a cAMP-inducible E-box/M-CAT hybrid motif in the cardiac alpha-myosin heavy chain (alpha-MHC) gene promoter. The two factors, TEF-1 and Max, that bind to this motif are found to physically associate with each other and exert a positive cooperative effect for gene regulation. Here we show that TEF-1, but not Max, is a substrate for protein kinase-A (PK-A)-dependent phosphorylation. TEF-1 is phosphorylated by PK-A at residue serine-102. This post-translational modification of TEF-1 repressed its DNA-binding activity, but not its ability to interact with the Max protein. Replacement of serine-102 in TEF-1 by a neutral or a charged amino acid did not abolish its DNA-binding ability, suggesting that changing a charge at the 102 amino-acid position of TEF-1 was not sufficient to inhibit its DNA-binding activity. We also show that PK-A response of the alpha-MHC gene is stimulated by the presence of wild-type TEF-1 but not by mutant TEF-1 having serine-102 replaced by alanine, suggesting that phosphorylation at this residue accounts for the cAMP/PK-A response of the gene. Thus, these data demonstrate that TEF-1 is a direct target of cAMP/PK-A signaling in cardiac myocytes.

Amino Acid Sequence↗
PubMed2000

TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha.

TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the 3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To determine the functional significance of this interaction, we used homologous recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce significantly more TNF-alpha protein than wild-type controls. The half-life of TNF-alpha transcripts is similar in wild-type and TIA-1(-/-) macrophages, indicating that TIA-1 does not regulate transcript stability. Rather, the absence of TIA-1 significantly increases the proportion of TNF-alpha transcripts that associate with polysomes, suggesting that TIA-1 normally functions as a translational silencer. TIA-1 does not appear to regulate the production of interleukin 1 beta, granulocyte-macrophage colony-stimulating factor or interferon gamma, indicating that its effects are, at least partially, transcript specific. Mice lacking TIA-1 are hypersensitive to the toxic effects of LPS, indicating that this translational control pathway may regulate the organismal response to microbial stress.

3' Untranslated Regions↗
PubMed2000

A new transacting factor that modulates hypoxia-induced expression of the erythropoietin gene.

Hypoxia is a strong stimulus for the transcription of a set of genes, including erythropoietin and vascular endothelial growth factor. Here we report on the cloning, functional significance, and expression of a complementary DNA (cDNA) that is involved in hypoxia-mediated expression of these 2 genes. The full-length cDNA encodes a predicted protein of 806 amino acids that contains a leucine zipper motif. This protein, termed HAF for hypoxia-associated factor, binds to a 17-base pair (bp) region of the erythropoietin promoter, which was shown earlier to participate in hypoxia-induced expression of the erythropoietin gene. In Hep3B cells, clones modified to express HAF antisense RNA showed an attenuated response to hypoxia-mediated induction of both erythropoietin and vascular endothelial growth factor transcription. HAF showed sequence-specific interaction with a DNA element in the 5' untranslated region of VEGF gene. The HAF 2.6-kilobase (kb) messenger RNA (mRNA) is expressed in most adult tissues. The highest expression occurs in fetal liver and the least in adult liver. HAF is the murine homolog of Sart-1, a 125-kd human protein expressed in the nuclei of normal and malignant cells. (Blood. 2000;96:491-497)

Animals↗
PubMed2000

Antitumor activity of methanolic extract of Cassia fistula L. seed against Ehrlich ascites carcinoma.

Effects of methanolic extract (ME) of Cassia fistula seed on the growth of Ehrlich ascites carcinoma (EAC) and on the life span of tumor bearing mice were studied. ME treatment showed an increase of life span, and a decrease in the tumor volume and viable tumor cell count in the EAC tumor hosts. Cytological studies have revealed a reduction in the mitotic activity, and the appearance of membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells. Improvement in the hematological parameters following ME treatment, like hemoglobin content, red blood cell count and bone marrow cell count of the tumor bearing mice have also been observed. The results of the present study suggest that ME of C. fistula seed has an antitumor activity.

Animals↗
PubMed2000

The vitamin D3 analog EB 1089 enhances the antiproliferative and apoptotic effects of adriamycin in MCF-7 breast tumor cells.

Exposure of MCF-7 breast tumor cells to the vitamin D3 analog, EB 1089 enhances the response to adriamycin. Clonogenic survival studies indicate that EB 1089 shifts the dose-response curve for sensitivity to adriamycin by approximately six-fold in p53 wild-type MCF-7 cells; comparative studies in MCF-7 cells with a temperature-sensitive dominant negative p53 mutation show less than a two-fold shift in adriamycin sensitivity in the presence of EB 1089. The combination of EB 1089 with adriamycin also promotes apoptotic cell death in the p53 wild-type MCF-7 cells but not in the MCF-7 cells expressing mutant p53. EB 1089 treatment blocks the increase in p21waf1/cip1 levels induced by adriamycin and interferes with induction of MAP kinase activity by ionizing radiation, effects which could be related to the capacity of EB 1089 to promote secretion of insulin-like growth factor binding protein. Taken together with our previous findings that EB 1089 enhances breast tumor cell sensitivity to ionizing radiation, there studies further support the concept that vitamin D3 analogs could have utility in combination with conventional chemotherapy and/or radiotherapy in the treatment of breast cancer.

Anti-Bacterial Agents↗
PubMed2000

Dexamethasone induced cardiac hypertrophy in newborn rats is accompanied by changes in myosin heavy chain phenotype and gene transcription.

Cardiac hypertrophy has been observed in newborn infants treated with dexamethasone (DEX). This study was undertaken to examine whether DEX-induced hypertrophy in newborn rats is associated with redistribution of cardiac myosin heavy chain (MHC) isoforms and, if so, the effects involve transcriptional regulation. Newborn rats were injected with either DEX (1 mg/kg/day; s.c.) or equivalent volume normal saline for 1, 3, 5, 7 or 9 days. Hypertrophy was quantified by heart dry/wet wt ratios, heart/body wt ratios, and total protein content of the myocardium. Changes in the expression of cardiac MHC mRNA were characterized by northern blot and slot blot analyses, using isoform specific probes for alpha- and beta-MHC genes. DEX effect on alpha-MHC gene transcription was analyzed by transiently transfecting various alpha-MHC promoter/CAT reporter constructs into primary cultures of cardiac myocytes derived from one day old rat pups. DEX administration into newborn rats produced significant cardiac hypertrophy ranging from 23% at day 1 to 59% at 9 days. The hypertrophy was accompanied by immediate increase (83%) in steady state level of the alpha-MHC mRNA within one day and a maximum increase (148%) at 7 days of treatment. The steady state level of beta-MHC mRNA declined by 25% at day 1 and a maximum decrease of 54% at day 7 of DEX treatment. The changes in MHC mRNA were also reflected in their protein levels as determined by V1 and V3 isozyme analysis. DEX treatment of primary cultures of cardiomyocytes following transfection with alpha-MHC promoter/CAT reporter constructs resulted in increased CAT expression in a dose dependent manner. The minimum alpha-MHC gene sequences responding to DEX treatment were located between the -200 to -74-bp region of the gene, resulting in 2-fold and 6-fold activation of CAT reporter after 0.05 and 0.1 mM doses of DEX, respectively. Our data indicate that DEX induced cardiac hypertrophy in newborn rats is accompanied by increased expression of alpha-MHC and decreased expression of beta-MHC. The alpha-MHC effects are mediated in part through transcriptional mechanisms.

Animals↗
PubMed2000

Comparison of functional efficacy of surfactant protein B analogues in lavaged rats.

Leakage of plasma proteins into the alveoli inhibits pulmonary surfactant function and worsens respiratory failure. Surfactant protein B (SP-B), is essential for surfactant function, but the N-terminal domain of human SP-B (residues 1.25, SP-B1-25) can mimic the biophysical properties of full length SP-B1-78 in vitro. The authors compared the function and inhibition resistance of synthetic surfactant preparations containing SP-B analogues to a natural bovine surfactant preparation "Survanta". Eight groups of eight rats were lavaged to induce surfactant deficiency, fibrinogen was instilled as a surfactant inhibitor, and then they were rescued with exogenous surfactant. Five experimental surfactants were formulated by mixing 3% SP-B1-78, or an equimolar amount of SP-B1-25 and/or 1% palmitoylated surfactant protein C (SP-C)1-35, into a standard phospholipid (PL) mixture: B1-78, B1-25, C1-35, B1-78+C1-35, and B1-25+C1-35 surfactant preparations. Survanta was used as a positive control and PL and no treatment as a negative control. Lung function was assessed during a 2-h period using arterial blood gas and lung compliance measurements. Rats treated with B1-25+C1-35 surfactant and Survanta maintained the highest oxygenation and lung compliance values throughout the experiments. The surfactants could be ranked as B1-25+C1-35 surfactant and Survanta >B1-25 and B1-78+C1-35 surfactants >others. Because the N-terminal domain of surfactant protein B1-25 can improve inhibition resistance, it may be able to substitute for surfactant protein B in exogenous surfactant preparations.

Animals↗
PubMed2000

Successful teaching in evidence-based medicine.

OBJECTIVES: Several published articles have described the importance of exposing medical trainees to the 'new paradigm' of evidence-based medicine (EBM). Recognizing this, we sought to develop and objectively evaluate a mini-course in EBM for third-year medical students. DESIGN: We developed a mini-course consisting of four sessions in which students learn to derive sequentially focused questions, search MEDLINE, review articles critically and apply information from the literature to specific clinical questions. To evaluate the teaching intervention, we performed a controlled educational study. Students at the intervention site (n=34) attended the EBM mini-course, while students at the control site (n=26) received more 'traditional' didactic teaching on various clinical topics. Intervention and control students were surveyed immediately before and after the mini-course to assess changes in reading and literature searching skills, as well as a tendency to use the literature to answer clinical questions. SETTING: Boston University School of Medicine. SUBJECTS: Third-year medical students. RESULTS: The intervention was associated with significant changes in students' self-assessed skills and attitudes. MEDLINE and critical appraisal skills increased significantly in the intervention group relative to the control group (significance of between group differences: P=0.002 for MEDLINE and P=0.0002 for critical appraisal), as did students' tendency to use MEDLINE and original research articles to solve clinical problems (significance of between group differences: P=0.002 and P=0.0008, respectively). CONCLUSIONS: We conclude that this brief teaching intervention in EBM has had a positive impact on student skills and attitudes at our medical school. We believe that the key elements of this intervention are (1) active student involvement, (2), clinical relevance of exercises and (3) integrated teaching targeting each of the component skills of EBM.

Education, Medical, Undergraduate↗
PubMed2000

Co-teaching: a faculty development strategy.

It has been stated that faculty development programmes which are closely linked to particular teaching contexts are most likely to be effective. Over the past 10 years we have developed a model of 'co-teaching' for faculty development which is based upon this premise and which can be applied to any clinical rotation. In this paper we describe our model, in which paired physicians focus on developing their teaching skills while sharing the clinical supervision of residents and medical students. Through iterative phases of teaching, debriefing and planning, co-teachers gain experience in analysing teaching encounters and develop skills in self-evaluation. Teaching occurs in the usual clinical settings such as attending (consultant) teaching rounds, clinic precepting, and case conferences. We discuss our model in the context of educational theory and related literature. We support our positive assessment of the co-teaching model through the precepts of collaborative inquiry and case study methodology. Vignettes, taken from the experiences of the authors, are used to demonstrate how the model is used to develop effective solutions to problems and to help in the maturation of one's skill as an educator. Successful implementation of the model is predicated on the development of a truly collaborative process between co-teachers. We share lessons we have learned from our experience of implementing the model in different clinical venues, such as the contrast between teaching on a hospital ward or in the clinic. This collaborative process has been well received by junior and senior faculty participants in our institution for more than a decade.

Education, Medical, Graduate↗
PubMed2000

Laparoscopic-assisted renal biopsy: an alternative to open approach.

An open renal biopsy frequently is performed when the conventional percutaneous approach is contraindicated. Although many of the surgical procedures, previously performed by a traditional open technique, are now successfully accomplished by laparoscopic technique, there remains a paucity of reports on laparoscopic kidney biopsy. We describe the use of laparoscopic technique in performing native kidney biopsy in three patients and review the potential safety and accuracy of this approach. To date, laparoscopic-assisted renal biopsy has been reported in six patients. The average length of stay in our small series was 1.3 days, and there were no major or catastrophic complications. Adequate numbers of glomeruli for confirmation of microscopic diagnosis were obtained in all cases. The review of literature, in addition to our encouraging preliminary results of a small group of patients, shows a possible role of laparoscopic-assisted renal biopsy in place of an open renal biopsy.

Aged↗