Clomipramine discontinuation-emergent dystonia.
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Biomedical subjects
Publications and source records attributed to S Dutta.
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BACKGROUND & OBJECTIVES: The rapid spread of multidrug resistant (MDR) typhoid fever has posed a great challenge for the treatment of these cases the world over. After the emergence of chloramphenicol resistant Salmonella typhi strains, ciprofloxacin has become the drug of choice for the treatment of typhoid fever even in the paediatric age group. This study evaluated the role of ceftriaxone therapy in bacteriologically confirmed MDR typhoid cases who did not respond to 12-14 days of ciprofloxacin therapy. Attempts have also been made to investigate the in vitro susceptibility of isolated S. typhi strains to chloramphenicol, ciprofloxacin and ceftriaxone. METHODS: A total of 140 children, aged 3-10 yr, clinically diagnosed as having typhoid fever, without any clinical response after 12-14 days of ciprofloxacin therapy were screened for S. typhi by blood culture. In the bacteriologically positive children the treatment was changed to intravenous ceftriaxone for 14 days. The isolated strains of S. typhi were tested for in vitro antimicrobial susceptibility. RESULTS: Clinical and bacteriological cure was observed with intravenous ceftriaxone therapy in all the 32 bacteriologically positive patients. All isolated S. typhi strains were uniformly (100%) susceptible to ciprofloxacin and ceftriaxone but 50 per cent of the strains were resistant to chloramphenicol. The MIC values of chloramphenicol, ciprofloxacin and ceftriaxone ranged between 125-500, 0.0625-0.5 and < 0.0625 microgram/ml respectively. INTERPRETATION & CONCLUSION: The study indicates that although the S. typhi strains were susceptible to ciprofloxacin in vitro, the patients did not respond clinically and bacteriologically to ciprofloxacin therapy. Hence, ciprofloxacin may not represent a reliable and useful option for treating MDR typhoid fever; ceftriaxone may be an effective alternative for the treatment of such cases.
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A series of title compounds has been synthesized and evaluated by the cytotoxicity assays conducted in vitro in seven human tumor cell lines, initially in MT-4 and H-9, followed by U-937, PM-1, MCF-7, Hep-3B, and K-562. These compounds were simultaneously compared with the existing clinical drug, busulfan and also with an experimental drug, hepsulfam. IC(50) values of these agents in T-cell lymphoma and leukemic cell lines indicate that two of these agents hexsulfamyl and octsulfamyl (compounds 3 and 4) were significantly more potent than busulfan and were comparable in antileukemic activity with hepsulfam. In order to determine the effect of these agents on normal proliferating cells, the toxicity of 3 and 4 was also determined in vitro against human peripheral blood mononuclear cells (PBMC) and against murine bone marrow progenitor cells. PBMC assay data indicate that these agents were generally less toxic than hepsulfam. The results of the colony forming unit-erythroid (CFU-E) and granulocyte-macrophage colony forming unit (CFU-GM) assays, however, indicate that these agents were more toxic than hepsulfam to erythroid progenitor cells than to granulocyte-macrophage progenitors. The toxicity of octsulfamyl was further assessed in vivo in normal Swiss mice by measuring drug-induced changes in hematological parameters, femoral bone marrow cellularity and splenic cellularity as well as hepatotoxicity and nephrotoxicity on day 7 and 14 following drug treatment at the dose of 1.0 mg/kg body weight from days 1 to 5. The results indicate that the compound did not adversely affect hematopoiesis. Marginal bone marrow suppression was observed on day 7, which gradually tends to reach normalcy on day 14. The other parameters were within normal limit.
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The changes in the free amino acid (FAA) levels, the rate of efflux of FAAs from the perfused liver, and the activity of some enzymes related to amino acid metabolism such as glutamate dehydrogenase (GDH, both reductive amination and oxidative deamination), glutamine synthetase (GS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were studied in the liver of a freshwater air-breathing teleost, the walking catfish, Clarias batrachus, perfused with 5 and 10 mM NH(4)Cl. The level of the various non-essential FAAs increased significantly, with a total increase of about 150%, which was accompanied by a significant increase of both ammonia and urea-N in the perfused liver both with 5 and 10 mM NH(4)Cl. The rate of efflux of these non-essential FAAs from the perfused liver also increased significantly with a total increase of about 115% and 160% at 5 and 10 mM NH(4)Cl, respectively. The activity of the mentioned amino acid metabolism-related enzymes in the perfused liver also got stimulated, except for GDH in the ammonia forming direction and ALT, under a higher ammonia load. The activity (both tissue and specific) of GDH in the glutamate forming direction increased maximally, followed by AST and GS in a decreasing order. Owing to these physiological adaptive strategies related to amino acid metabolism along with the presence of a functional and regulatory urea cycle (reported earlier), it is believed that this catfish is able to survive in very high ambient ammonia or in the air or in the mud during habitat drying.
Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, reduces the requirements for anesthetic, analgesic, sedative, and hypnotic drugs. Dexmedetomidine pharmacokinetics were characterized in healthy subjects after intravenous administration by means of a computer-controlled infusion pump. A series of seven stepwise increasing pseudo-steady-state plasma concentrations were targeted. The influence of cardiac output on the pharmacokinetics was investigated by use of a compartmental modeling approach in which the elimination clearance was characterized as being either cardiac output independent or dependent. At dexmedetomidine concentrations of 0, 0.6, and 1.2 ng/mL, mean (SD) estimated cardiac outputs were 5. 6 (0.85), 5.1 (0.67), and 4.5 (0.83) L/min, and mean (SD) clearances were 40 (10), 38 (9.0), and 35 (8.5) L/h, respectively. Dexmedetomidine V(SS) and elimination half-life were 72 (19) L and 1. 9 (0.62) h, respectively. The approximately 3 to 19% decrease in cardiac output observed within the anticipated therapeutic range of 0.3 to 1.2 ng/mL was similar to that observed for clonidine. The decrease in cardiac output with increasing plasma concentrations of dexmedetomidine resulted in a corresponding decrease in drug elimination clearance of < or =12% within the therapeutic range; however, this decrease in dexmedetomidine clearance is likely not clinically relevant.
Cytogenetic and molecular analyses have shown that the chromosome band 12q22 is recurrently deleted in male germ cell tumors (GCTs), indicating the presence of a candidate tumor suppressor gene (TSG) in this region. To identify the TSG, we mapped the APAF1 gene, a proapoptotic mammalian homologue of ced-4, to chromosomal band 12q22, that suggested that this might be the candidate deleted gene in GCTs. We further localized the gene between the polymorphic markers D12S1671 and D12S1082 at 12q22 to determine the role of APAF1 in the pathogenesis of GCT, and we characterized its normal genomic structure and analyzed its alterations in GCTs. The APAF1 gene comprises 27 exons, with the coding region spanning 26. The region containing APAF1 was found to be deleted in GCT by fluorescence in situ hybridization analysis, but without evidence of coding sequence alterations. RT-PCR and Western blot analysis showed APAF1 gene expression at detectable levels in all GCT cell lines analyzed. An aberrant-sized APAF1 protein was seen in one cell line. This and 2 other cell lines carrying APAF1 deletions also exhibited defects in dATP-mediated caspase-3 activation. Caspase-3 activity was effectively restored by addition of recombinant caspase-9 and APAF1 proteins, and to a lesser extent by caspase-9 alone, but not by APAF1 alone. These data do not support a TSG role for APAF1, but defects in other components of the apoptotic pathway that may be related to 12q22 deletion cannot be ruled out. Genes Chromosomes Cancer 28:258-268, 2000.
BACKGROUND: Surgeons who have demonstrated excellence through extensive publication in the medical education literature can provide valuable guidance for new surgeons interested in educational research. METHODS: National databases identified members of the Association for Surgical Education (ASE) who have accumulated the greatest number of peer-reviewed, original educational research publications. The top 15 surgeons completed an open-ended survey exploring surgical education research issues. RESULTS: The top three factors contributing to success in this field were (1) chair support, (2) collaboration with peers and mentors, and (3) participation in the ASE. The top three barriers were (1) perception at their institution of educational research as lacking credibility, (2) lack of adequate funding, and (3) lack of time. Eighty-five percent (11 of 13) reported having tenure or equivalent, of which 45% reported educational research as playing a significant role. All respondents advised formal training in education. CONCLUSIONS: Credibility of educational research is bolstered by quality research and a supportive chair. Scholarly work in this field can form the basis for an academic career.
BACKGROUND: Surgical education peer-reviewed publications have markedly increased over the last decade. The purpose of this study was to review the surgical education literature published over the last 10 years and address the following questions: What subjects in surgical education tend to be studied? What are the most to least commonly employed research designs and statistics? Has there been a change in how research data are collected? Where are these studies published? METHODS: A literature search encompassing surgical education papers published between January 1988 and August 1998 was performed. Four investigators coded qualifying abstracts on journal type, subject of research, data collection methods, research design, and statistics. Each investigator was asked to code 10 articles at the start of the study to assess interrater reliability. RESULTS: A total of 420 abstracts were evaluated. Interrater reliability yielded percent agreements ranging from 82% to 96%. Curriculum and teaching were the most frequent topics studied (40%), followed by assessment (23%) and program evaluation (18%). Most research designs used were descriptive (41%). Experimental design has progressively increased from 2% in 1988-89 to 16% in 1998. A total of 551 statistical methods were accounted for in the 420 abstracts. The most common statistical analyses used were descriptive statistics (32%). The predominant mode of data collection was through testing or direct observations (34%). Survey instruments followed closely as a popular data collection method at 27%. The majority of papers were published in peer-reviewed surgical journals (64%),followed by medical education journals (22%) and "other" journals (14%). CONCLUSIONS: An analysis of the surgical education literature demonstrates the growing emphasis on the use of educational research to explore relevant issues and problems. Descriptive research is most popular, with an increasing trend in experimental research. Publication of educational research in peer-reviewed surgical journals is becoming more popular. This study informs those interested in the surgical education research literature of current trends, and what they need to know for a more critical appraisal of this body of literature.
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Effects of daily evening (just before the onset of darkness in a 24 h light dark cycle) administration of graded doses (25, 50, or 100 microg/100 g body wt./day for 30 days) of melatonin on the concentrations of blood glucose and adrenal catecholamines were studied in sexually active male roseringed parakeets under natural (NP; approximately 12L: 12D) and artificial long (LP; 16L: 8D) and short (SP; 8L: 16D) photoperiods. Blood samples and adrenal glands were collected from each bird during the mid-day on the following day of the last treatment. The concentrations of glucose in blood and epinephrine (E) and norepinephrine (NE) in the adrenals were measured. The results of the study indicated that exogenous melatonin induces hypo- or hyperglycemia depending on the dose of hormone administered as well as to the length of photoperiod to which birds were exposed. The levels of E and NE in the adrenals were shown also to vary in relation to photoperiod and the dose of melatonin administered. But the nature of the influence of melatonin becomes different under altered photoperiodic conditions. It appears that short photoperiods are more effective than long photoperiods as a modulator of glycemic and adrenal catecholaminergic responses to exogenous melatonin. A statistically significant correlation between the levels of blood glucose and that of E and NE in the adrenals was found in the control birds, but not in the melatonin treated birds. The results suggested that the responses of blood glucose and adrenal catecholamines to the treatment with melatonin in the roseringed parakeets may not be dependent on each other.
UNLABELLED: A double-blind, randomized, controlled trial was conducted to compare the clinical efficacy of hypo-osmolar oral rehydration salts (ORS) solution (224 mmol/L) and standard ORS solution (311 mmol/L) in children with persistent diarrhoea who were prone to develop dehydration. Initially, 95 children aged between 3 and 24 mo were included in the study for overnight observation. Of these, 70 children who passed stool more than 2 g/kg/h were finally enrolled in the study and were randomly assigned either standard ORS or hypo-osmolar ORS. After decoding the identity of ORS, it was observed that 37 children were in the standard ORS group and 33 in the hypo-osmolar ORS group. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrolment. Total stool output (2.5+/-1.1 vs 3.2+/-1.6 kg; p = 0.04), duration of diarrhoea (114.8+/-38.3 vs 145.4+/-40.0 h; p = 0.002), total intake of ORS (5.4+/-1.6 vs 7.8+/-1.8 l; p = 0.002) and total fluid intake (7.9+/-2.6 vs 10.0+/-4.1 l, p = 0.01) were significantly less in the hypo-osmolar ORS group compared to the standard ORS group. However, the percentage of weight gain on recovery in the hypo-osmolar group was less compared to that of the standard ORS group, though the difference was statistically insignificant. Thirty-five (95%) children in the standard ORS and 33 (100%) children in the hypo-osmolar group recovered within 10 d of initiation of therapy and modified dietary management. CONCLUSION: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating persistent diarrhoea.
A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhoea to evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). After decoding it was observed that 44 children received zinc sulphate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrollment. All the children (100 per cent) in the zinc supplemented group and 32 (89 per cent) children in the placebo group recovered within 5 days of hospitalization (p = 0.04). The zinc supplemented group had a significantly shorter duration of diarrhoea (70.4 +/- 10.0 vs. 103.4 +/- 17.1 h; p = 0.0001), passed less liquid stool (1.5 +/- 0.7 vs. 2.4 +/- 0.7kg; p=0.0001), consumed less oral rehydration solution (2.5 +/- 1.0 vs. 3.6 +/- 0.8 litre; p = 0.0001) and other liquids (867.0 +/- 466.1 vs. 1354.7 +/- 675.6 ml; p = 0.0001) as compared to the placebo group. Our findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhoea.
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The toxicity of beta-tethymustine, a potential anticancer compound 1 ((Cancer Lett., 119 (1997) 7-12) was assessed in normal as well as in Ehrlich ascites carcinoma (EAC), Sarcoma-180 (S-180) and Dalton' s Lymphoma (DL) tumour-bearing Swiss male mice by measuring drug-induced changes in haematological parameters, femoral bone marrow cellularity and splenic cellularity on days 9, 15 and 21 following drug treatment at the optimum dose of 8.0 mg/kg body weight from days 1 to 7. Detailed studies were also made by noting sequential changes in the above parameters in normal and EAC-bearing mice on days 12 and 18, respectively. The results indicate that the compound did not adversely affect haematopoiesis as it was observed that no significant decrease in haematological parameters and femoral marrow cellularity occurred in treated groups. Initial hyposplenic activity was, however, noted in EAC and normal treated groups on day 9 which soon reached normal count within 7-10 days after termination of drug therapy. Drug-induced hepatotoxicity and nephrotoxicity were also sequentially evaluated in normal and tumour-bearing mice on days 9, 15 and 21 but no such toxicities were detected. Also, body weight, skin and hair texture, and behavioural pattern (food and water intake and activity) did not reflect any toxic reaction in host mice at this optimum dose.