Correlation of serum and CSF magnesium levels of normal newborns with maternal serum magnesium.
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Biomedical subjects
Publications and source records attributed to M Gupta.
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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.
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.
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.
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.
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.
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.
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.
Leakage of plasma proteins into the alveolar space can inhibit pulmonary surfactant function and worsen respiratory failure in ventilated preterm infants. We tested the effect of intratracheal instillation of fetal calf serum (FCS) and fresh frozen plasma (FFP) on lung function in ventilated rats who were made surfactant-deficient by saline lavage. Post lavage, the rats were treated with air placebo, Survanta, FCS or FFP, air placebo + FCS or FFP 1 hour post lavage, or Survanta + FCS or FFP 1 hour post lavage. After 2 hours of ventilation, pressure volume curves were performed and the lungs relavaged. FCS instillation rapidly improved oxygenation when given immediately post lavage or 1 hour after placebo or Survanta instillation, whereas FFP instillation never improved oxygenation. FCS instillation increased post-treatment lavage phospholipid values, but FFP did not. Both FCS and FFP decreased lung volume, but the negative effect of FFP exceeded that of FCS. Surfactant aggregate sizing of the final lung lavages by dynamic light scattering showed a definite shift towards smaller aggregates after FFP, but not after FCS, instillation. These data suggest that intratracheal instillation of FCS improves oxygenation and preserves the alveolar presence of phospholipids and large surfactant aggregates, whereas FFP decreases oxygenation and surfactant aggregate size in surfactant-deficient lavaged rats.
It has been proposed that successful pregnancy is a T helper 2-type phenomenon, and that T helper (Th)1-type reactivity is deleterious to pregnancy. The objective of this study was to compare the concentrations of Th1 and Th2 cytokines produced by peripheral blood mononuclear cells from women undergoing unexplained recurrent spontaneous abortion (RSA) with those produced during normal pregnancy at a similar gestational stage. The control group consisted of 24 women with a history of successful pregnancies and the abortion group comprised of 23 women with a history of unexplained RSA. Blood from the control group was obtained at the end of the first trimester as gestational age controls for the abortion group from whom blood was collected at the time of abortion. Phytohaemagglutinin-stimulated peripheral blood cell culture supernatants were analysed for concentrations of cytokines. Significantly higher concentrations of Th2 cytokines were produced by the first trimester normal group than by the RSA group, while significantly higher concentrations of Th1 cytokines were produced by the abortion group as compared to first trimester normal pregnancy, indicating a distinct Th2-bias in normal pregnancy and a Th1-bias in unexplained RSA.
A young girl developed extensive striae while on Depo Provera injections. She had gained some weight during the treatment. Endocrinal investigations were negative. The development of striae was attributed to her weight gain.
Short-term treatment with oral steroids is very effective in control ling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV1] and concentration of histamine causing a 20% reduction FEV1 [PD20 FEV1]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD20 FEV1 values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean +/- SD time for 95% recovery from histamine-induced bronchospasm was 33.00 +/- 19.47 min before treatment and decreased significantly to 18.00 +/- 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.
A 43 year old male presented with slowly progressive weakness of limbs and hypertrophy of triceps, brachioradialis and calf muscles for four years. There was thinning of quadriceps muscles in both thighs. Histological study was compatible with Becker muscular dystrophy (BMD). Genomic DNA analysis showed a deletion of the Hind III fragments, spanning exons 45-47. A junction fragment of 11.0 kb was observed along with a deletion of a 3.4 kb PstI fragment containing exon 51 in the patient, and in one of his two sisters. The clinical and laboratory characteristics in this patient are in keeping with what has been described 'quadriceps myopathy' and fall within the phenotypic variants of BMD as has been shown by others.
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The term 'congenital myasthenic syndrome' (CMS) encompasses a number of heterogeneous disorders characterised by myasthenic symptoms since birth, usually with positive family history and absence of acetyl choline receptor antibodies. Recent advances in electrophysiology and ultrastructural analysis of neuromuscular junction have made it possible to identify the various defects underlying these disorders. We report four cases of CMS, with a review of literature.
BACKGROUND: Temporal changes in baseline characteristics, treatment and clinical outcomes of patients presenting with acute ST elevation myocardial infarction in Canada and the United States have not been examined comprehensively over time. OBJECTIVES: To evaluate baseline characteristics, process of care and clinical outcomes. Also, to explore whether earlier process-of-care differences between Canada and the United States had changed and, if so, whether they influenced clinical outcomes. PATIENTS AND METHODS: A total of 13, 888 American and 3011 Canadian patients enrolled in 184 American and 38 Canadian hospitals that participated in both the Global Utilization of Streptokinase and Tissue Plasminogen Activator (alteplase) for Occluded Coronary Arteries (GUSTO-I) trial (1990 to 1993) and the Global Utilization of Strategies to Open Occluded Coronary Arteries (GUSTO-III) trial (1995 to 1997) were studied. Logistic regression was used to identify significant prognostic factors, to assess illness severity at hospital presentation and to classify trends between Canada and the United States. RESULTS: In both countries, illness severity on admission increased, door-to-needle time for thrombolysis was reduced, intensive care unit stay was shortened and hospital stay decreased from GUSTO-I to GUSTO-III. Whereas the administration of oral nitrates, calcium blockers and beta-blockers at discharge converged over time between countries, the disparity in the use of angiography and revascularization widened; the rise in American revascularization rate was most evident in patients without in-hospital ischemia. The 30-day and one-year mortality rates were comparable and declined nonsignificantly in both countries. CONCLUSIONS: Despite increased illness severity and varying medication and procedure rates, there was no increase over time in 30-day or one-year mortality; this remained comparable between countries throughout the seven-year observation period.
L-Deprenyl (Selegeline) introduced for use in parkinson's disease, is implicated to show beneficial effects in epilepsy, alzheimer's disease, cognition, depression and other age related neurological diseases. In this study, we investigated the CNS effects of L-deprenyl with special reference to epilepsy, anxiety and cognition and memory in mice. L-deprenyl (10, 20 and 40 mg/kg) showed a significant anticonvulsant activity against pentylenetetrazole (PTZ)-induced convulsions. Combination of L-deprenyl (10 mg/kg) with the sub-protective dose of diazepam (1 mg/kg) showed potentiation of the anticonvulsant effect. In the maximal-electroshock (MES)-induced convulsions, L-deprenyl (10 mg/kg) significantly delayed the onset and decreased the duration of extensor phase. Its combination with the lower dose of phenytoin (10 mg/kg) showed potentiation in response compared to the per se effect of both the drugs. However, L-deprenyl did not show any protective effect in lithium-pilocarpine induced status epilepticus. Acute treatment with L-deprenyl had no effect on learning and memory. In chronic treatment, L-deprenyl per se showed no effect on learning and memory but did improve the condition in mice with scopolamine induced memory deficit. L-Deprenyl per se was anxiogenic though in combination with diazepam (1 mg/kg) it potentiated the antianxiety effect of the latter. The above observations suggest that in epilepsy, L-deprenyl might be acting partially by influencing the GABAA/benzodiazepine mechanism in the brain (similar to diazepam and phenytoin), and in cognition enhancing effect, the cholinergic system might be playing a role. Thus, L-deprenyl could prove to be an adjuvant in the antiepileptic therapy and beneficial in dementia associated with epilepsy.