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Biomedical subjects

V K Sharma

Publications and source records attributed to V K Sharma.

At least 91 records · Page 5Linked to original sources
PubMed2000

Working memory dysfunction in major depression: an event-related potential study.

OBJECTIVES: To study working memory function in untreated major depression using a digit probe identification and matching task. METHODS: We compared behavioural performance and event-related potentials during processing of the Sternberg working memory task in 14 depressed patients and 14 healthy matched control subjects. RESULTS: Patients made more mistakes than controls as the memory load was increased from one to 5 digits and had significantly slower reaction times at all levels of memory load. The patients' event-related potentials (ERPs) differed significantly from controls. Pathological changes were similar for auditory and visual presentation. Surface negative activity in the 157-210 ms section of the waveform was reduced for all levels of memory load, suggesting abnormal sensory/perceptual processing in the modality-specific association cortices, possibly due to a failure of selective attention mechanisms. In the 375-840 ms epoch, the patients' responses showed large amplitude sustained negative activity, maximal at Cz and a reduced late positive wave. The large prolonged negativity in the patients' ERPs suggests activation of additional neuronal assemblies than those normally participating in the task. This could reflect either compensatory mechanism or dysfunction of inhibitory systems. These changes were sensitive to memory load, suggesting that they reflect alterations of memory-related processes. CONCLUSIONS: This study provides objective evidence that major depression significantly affects working memory. The ERP changes in depression could be accounted for by dysfunction of the central executive control of working memory.

Adult↗
PubMed2000

Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes.

Studies with electron microscopy have shown that sarcoplasmic reticulum (SR) and mitochondria locate close to each other in cardiac muscle cells. We investigated the hypothesis that this proximity results in a transient exposure of mitochondrial Ca2+ uniporter (CaUP) to high concentrations of Ca2+ following Ca2+ release from the SR and thus an influx of Ca2+ into mitochondria. Single ventricular myocytes of rat were skinned by exposing them to a physiological solution containing saponin (0.2 mg/ml). Cytosolic Ca2+ concentration ([Ca2+]c) and mitochondrial Ca2+ concentration ([Ca2+]m) were measured with fura-2 and rhod2, respectively. Application of caffeine (10 mM) induced a concomitant increase in [Ca2+]c and [Ca2+]m. Ruthenium red, at concentrations that block CaUP but not SR release, diminished the caffeine-induced increase in [Ca2+]m but not [Ca2+]c. In the presence of 1 mM BAPTA, a Ca2+ chelator, the caffeine-induced increase in [Ca2+]m was reduced substantially less than [Ca2+]c. Moreover, inhibition of SR Ca2+ pump with two different concentrations of thapsigargin caused an increase in [Ca2+]m, which was related to the rate of [Ca2+]c increase. Finally, electron microscopy showed that sites of junctions between SR and T tubules from which Ca2+ is released, or Ca2+ release units, CRUs, are preferentially located in close proximity to mitochondria. The distance between individual SR Ca2+ release channels (feet or ryanodine receptors) is very short, ranging between approximately 37 and 270 nm. These results are consistent with the idea that there is a preferential coupling of Ca2+ transport from SR to mitochondria in cardiac muscle cells, because of their structural proximity.

Animals↗
PubMed2000

Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated doses as intact capsules or as suspensions in sodium bicarbonate.

BACKGROUND: Omeprazole and lansoprazole can be given in sodium bicarbonate as, respectively, simplified omeprazole suspension and simplified lansoprazole suspension. We previously found the antisecretory effect of omeprazole 20 mg given as simplified omeprazole suspension to be lower than with intact capsules. However, lansoprazole 30 mg as simplified lansoprazole suspension produced an effect similar to that seen with intact capsules. AIM: To evaluate the absorption of both drugs when given orally as capsules or as suspensions in sodium bicarbonate. METHODS: In random order, we gave 5-day courses of omeprazole 20 mg and lansoprazole 30 mg as capsules and as suspensions in sodium bicarbonate to 12 healthy women. Serial blood samples were taken on days 1 and 5 of each course for pharmacokinetic measurements. RESULTS: There was impairment of omeprazole absorption when given as simplified omeprazole suspension. Maximum plasma concentration and area under the concentration/time curve were lower with simplified omeprazole suspension than with omeprazole capsules (P=0.034 and 0.013, respectively, on day 5). No differences were found in lansoprazole absorption when simplified lansoprazole suspension was compared with its standard capsule formulation. Relative bioavailability of omeprazole from simplified omeprazole suspension compared to the capsule was 58.4% on day 5. The corresponding value for lansoprazole was 84.7%. CONCLUSIONS: Simplified omeprazole suspension 20 mg does not supply adequate omeprazole for systemic absorption. Lansoprazole absorption from simplified lansoprazole suspension is maintained.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Probing the circadian oscillator of a mammal by two-pulse perturbations.

When organisms are maintained under constant conditions of light and temperature, their endogenous circadian rhythms free run, manifesting their intrinsic period. The phases of these free-running rhythms can be shifted by stimuli of light, temperature, and drugs. The change from one free-running steady state to another following a perturbation often involves several transient cycles (cycles of free-running rhythm drifting slowly to catch up with the postperturbation steady state). Although the investigation of oscillator kinetics in circadian rhythms of both insects and mammals has revealed that the circadian pacemaker phase shifts instantaneously, the phenomenon of transient cycles has remained an enigma. We probed the phases of the transient cycles in the locomotor activity rhythm of the field mouse Mus booduga, evoked by a single light pulse (LP), using LPs at critically timed phases. The results of our experiments indicate that the transient cycles generated during transition from one steady state to another steady state do not represent the state of the circadian pacemaker (basic oscillator) controlling the locomotor activity rhythm in Mus booduga.

Animals↗
PubMed2000

Presence of circadian rhythms in the locomotor activity of a cave-dwelling millipede Glyphiulus cavernicolus sulu (Cambalidae, Spirostreptida).

The locomotor activity of the millipede Glyphiulus cavernicolus (Spirostreptida), which occupies the deeper recesses of a cave, was monitored in light-dark (LD) cycles (12h light and 12h darkness), constant darkness (DD), and constant light (LL) conditions. These millipedes live inside the cave and are apparently never exposed to any periodic factors of the environment such as light-dark, temperature, and humidity cycles. The activity of a considerable fraction of these millipedes was found to show circadian rhythm, which entrained to a 12:12 LD cycle with maximum activity during the dark phase of the LD cycle. Under constant darkness (DD), 56.5% of the millipedes (n = 23) showed circadian rhythms, with average free-running period of 25.7h +/- 3.3h (mean +/- SD, range 22.3h to 35.0h). The remaining 43.5% of the millipedes, however, did not show any clear-cut rhythm. Under DD conditions following an exposure to LD cycles, 66.7% (n = 9) showed faint circadian rhythm, with average free-running period of 24.0h +/- 0.8h (mean +/- SD, range 22.9h to 25.2h). Under constant light (LL) conditions, only 2 millipedes of 11 showed free-running rhythms, with average period length of 33.3h +/- 1.3h. The results suggest that these cave-dwelling millipedes still possess the capacity to measure time and respond to light and dark situations.

Animals↗
PubMed2000

Correction of cubitus varus by French or dome osteotomy: a comparative study.

BACKGROUND: The purpose of this study was to compare the outcomes of two different techniques of supracondylar osteotomy, French osteotomy and dome osteotomy, for the correction of posttraumatic cubitus varus. METHODS: A comparative randomized study was undertaken of 25 patients (average age 10 years) with an established posttraumatic cubitus varus deformity (mean time from injury to corrective osteotomy, 1.7 years). Patients were followed-up with for 1 year, and carrying angle, Baumann's angle, and internal rotation deformity were measured. Postoperative complications were assessed. RESULTS: A significant (p < 0.01) correction of carrying angle and Baumann's angle was achieved with both techniques, with no statistically significant differences between them. Although internal rotation deformity was corrected by both techniques, the correction was significantly greater with the dome osteotomy (p < 0.01). However, the persistence of internal rotation did not seem to affect the final outcome. There was a higher incidence of postoperative complications in the dome osteotomy group, including infection (1), inadequate correction (1), nerve palsy (1), loss of motion (5), and circulatory compromise (1). CONCLUSION: The dome osteotomy is technically more difficult than the French osteotomy and has a higher incidence of complications. We suggest that the French osteotomy be used for the correction of cubitus varus after supracondylar fractures of the elbow in children.

Adolescent↗
PubMed2000

Colorectal cancer screening and surveillance practices by primary care physicians: results of a national survey.

OBJECTIVE: Screening for colorectal cancer reduces its morbidity and mortality and is cost-effective. Screening is usually the responsibility of primary care physicians who may be unsure about its implementation. We aimed to assess primary care physicians' knowledge and practice regarding colorectal cancer screening, and to compare their responses with those of three national experts and with published guidelines. METHODS: We mailed a postal questionnaire to 2,310 primary care physicians regarding demographics, nature of practice, use of screening tests, and six hypothetical patients who may have been candidates for screening or surveillance. We used published national guidelines and the collective opinions of the three external experts as the so-called "gold standard." RESULTS: Of all respondents, 85.1% offered colorectal cancer screening. Most used suitable tests, starting at an appropriate age; 49.8% continued screening indefinitely irrespective of patients' age and 43.6% performed fecal occult blood testing without appropriate dietary advice to patients. Also, respondents frequently performed this test for inappropriate indications. Only 51.8% would follow a positive fecal occult blood test with colonoscopy. CONCLUSIONS: Colorectal cancer screening practices by primary care physicians vary considerably from those recommended. Many offer screening to individuals in whom it is not appropriate, and continue it into advanced age. Frequent, inappropriate use of fecal occult blood tests will produce many false positives. Primary care physicians often do not appropriately follow a positive test. Further educational efforts are needed in an attempt to improve practice and further reduce the morbidity and mortality from colorectal cancer.

Colorectal Neoplasms↗
PubMed2000

Survey of internal medicine residents' use of the fecal occult blood test and their understanding of colorectal cancer screening and surveillance.

OBJECTIVE: Primary care physicians have imperfect understanding of current colorectal cancer screening guidelines and recommendations. Furthermore, compliance with colorectal cancer screening by internal medicine residents has been demonstrated to be poor. We sought to identify whether current trainees in internal medicine had adequate understanding of colorectal cancer screening and surveillance and test utilization. METHODS: We applied a structured questionnaire about colorectal cancer screening and the use of fecal occult blood tests to 168 internal medicine residents at four accredited programs in the U.S. They were also asked for recommendations about six hypothetical patients who may have been candidates for screening or surveillance. RESULTS: Seventy-one percent identified 50 yr as the currently recommended age to commence screening in an average-risk individual; 64.3% would begin screening with fecal occult blood testing and flexible sigmoidoscopy and 4.8% with colonoscopy. Most perform fecal occult blood testing on stool obtained at digital rectal exam and without prior dietary restrictions. Many use fecal occult blood testing for indications other than colorectal cancer screening. Only 29% recommended colonoscopy to evaluate a positive fecal occult blood test. Most residents plan to be screened for colorectal neoplasia at the appropriate age; significantly more opted for colonoscopy than recommended it for their patients. CONCLUSIONS: Internal medicine residents have many misperceptions regarding colorectal cancer screening and the utility of the fecal occult blood test. Educational efforts should be directed at internal medicine residents, many of whom plan careers in primary care, where most colorectal cancer screening is currently performed.

Adult↗
PubMed2000

A survey of internal medicine residents' knowledge about Helicobacter pylori infection.

OBJECTIVE: Despite recently published national guidelines, many physicians have only limited knowledge about Helicobacter pylori infection. We conducted this study to assess internal medicine residents' knowledge about H. pylori. METHODS: Two hundred and nineteen residents in seven accredited internal medicine training programs completed a self-administered questionnaire on personal demographics and practices related to testing for-and treating-H. pylori infection. RESULTS: Noon conferences (82%), ward teaching (66%), journals (70%), and sponsored symposia (27%) were their major sources of H. pylori-related information. Forty-eight percent had used office-based tests for the infection. Testing for (and treatment of) Helicobacter pylori infection was recommended by 97% (97%) for newly diagnosed duodenal ulcer, but by only 61% (63%) for a past history of duodenal ulcer. Many recommended testing in unproven conditions and might not have offered treatment to an infected patient. A proton pump inhibitor-based triple-drug regimen was the treatment of first choice of 55%; 20% recommended proton pump inhibitor-based dual regimens. Sixty-six percent and 80%, respectively, underestimated the rates of resistance to clarithromycin and metronidazole. In the absence of gastrointestinal symptoms, 22% would have ordered Helicobacter pylori testing but only 33% of these would undergo treatment if positive. CONCLUSIONS: Internal medicine residents usually test for Helicobacter pylori infection in appropriate conditions, but may not always treat the infection when the result is positive. Most use efficacious treatment regimens although many have inaccurate knowledge of resistance rates, which may adversely influence prescribing. Education should focus on practical issues surrounding Helicobacter pylori testing and treatment such as those contained in the American College of Gastroenterology's 1998 practice guidelines.

Adult↗
PubMed2000

Meta-analysis of randomized, controlled trials of antibiotic prophylaxis before percutaneous endoscopic gastrostomy.

OBJECTIVES: We sought to review the published literature on the value of antibiotic prophylaxis for the prevention of wound infection that occurs after percutaneous endoscopic gastrostomy. We also sought by meta-analysis to estimate the efficacy of antibiotic prophylaxis in preventing wound infection. METHODS: We performed a fully recursive literature search for randomized, controlled trials of antibiotic prophylaxis against wound infection occurring after percutaneous endoscopic gastrostomy. Relative and absolute risk reductions and the numbers needed to treat were derived for individual trials and pooled data. RESULTS: We identified seven trials, two of which did not find a statistically significant benefit of antibiotic prophylaxis. After pooling, antibiotic prophylaxis was found to reduce the relative and absolute risk of wound infection by 73% and 17.5%, respectively. The number needed to treat to prevent one wound infection was 5.7 (95% confidence interval = 4.4-8.0). CONCLUSION: A single intravenous dose of a broad-spectrum antibiotic, given approximately 30 min before percutaneous endoscopic gastrostomy is effective in reducing the incidence of peristomal wound infections.

Antibiotic Prophylaxis↗
PubMed2000

Changes in colorectal cancer over a 15-year period in a single United States city.

OBJECTIVE: The aim of this study was to identify colorectal cancer trends in different patient groups in one region. METHODS: We reviewed the records of all patients with colorectal cancer who were seen at two hospitals in Columbia, SC, between 1981 and 1995. Patients were divided into three 5-yr cohorts (cohort 1, 1981-1985; cohort 2, 1986-1990; and cohort 3, 1991-1995). We recorded demographic data, histological type, tumor stage, grade, and survival. RESULTS: A total of 1395 patients were diagnosed, of whom 1252 had adenocarcinoma. Mean age of diagnosis was 64.5 yr in black and 66 in white patients (p = 0.036). Adenocarcinoma proximal to the splenic flexure was found in 62% of women and 49% of men (p < 0.001), and in 51% of black and 44% of white patients (p = 0.08). Proximal cancers accounted for 61%, 48%, and 32% of cohorts 1, 2, and 3, respectively. The proportions of patients with advanced stage (III and IV) adenocarcinoma in the three cohorts were 54%, 47%, and 40%, respectively (p = 0.001). Median survival for adenocarcinoma was 23.7, 23.5, and 23.1 months in cohorts 1, 2, and 3 (p = 0.9). CONCLUSIONS: The prevalence and demographics of colorectal cancer have been fairly stable at this center. There has been a significant decrease in proximal cancers. Although adenocarcinoma is being diagnosed at an earlier stage, this has not affected survival. Colonoscopy may be the most appropriate screening method in women and in black patients, in whom proximal cancers are more often found.

Adenocarcinoma↗
PubMed2000

Survey of the opinions, knowledge, and practices of gastroenterologists regarding colorectal cancer screening and use of the fecal occult blood test.

OBJECTIVES: Primary care physicians and internal medicine residents have poor understanding of colorectal cancer screening and the use of fecal occult blood tests. If acceptance and implementation of colorectal cancer screening is to improve, gastroenterologists may have to take a more leading role in the education of their primary care colleagues, physicians in training, and the general public. However, before this can be recommended, it is necessary to determine how closely gastroenterologists follow currently recommended guidelines and how they use fecal occult blood tests. METHODS: We mailed a two-page, structured questionnaire about colorectal cancer screening and use of fecal occult blood tests to 8000 randomly selected gastroenterologists in the United States. RESULTS: We received responses from 24% of the gastroenterologists. Almost all used fecal occult blood tests in the office setting, 86% on stool obtained at rectal examination. The test was frequently used for reasons other than colorectal cancer screening, and often without adequate patient instruction on dietary and medication restrictions. Of the respondents, 98% commenced screening at age < or = 50 yr, whereas 37% either continued screening into advanced age or never stopped. Annual fecal occult blood testing with flexible sigmoidoscopy every 5 yr was the screening strategy recommended by 71% of the respondents, whereas 25% recommended colonoscopy every 10 yr. However, 77% of the gastroenterologists chose colonoscopy for personal colorectal cancer screening. CONCLUSIONS: Gastroenterologists usually give appropriate advice on colorectal cancer screening but often misuse fecal occult blood tests. This may produce excessively high false-positive screening rates, leading to unnecessary diagnostic testing without apparent benefit.

Attitude of Health Personnel↗
PubMed2000

Simultaneous detection of Salmonella strains and Escherichia coli O157:H7 with fluorogenic PCR and single-enrichment-broth culture.

A multiplex fluorogenic PCR assay for simultaneous detection of pathogenic Salmonella strains and Escherichia coli O157:H7 was developed and evaluated for use in detecting very low levels of these pathogens in meat and feces. Two sets of primers were used to amplify a junctional segment of virulence genes sipB and sipC of Salmonella and an intragenic segment of gene eae of E. coli O157:H7. Fluorogenic reporter probes were included in the PCR assay for automated and specific detection of amplified products. The assay could detect <10 CFU of Salmonella enterica serovar Typhimurium or E. coli O157:H7 per g of meat or feces artificially inoculated with these pathogens and cultured for 6 to 18 h in a single enrichment broth. Detection of amplification products could be completed in </=4 h after enrichment.

Animals↗
PubMed2000

The effect of different light regimes on adult life span in Drosophila melanogaster is partly mediated through reproductive output.

The effects of different light regimes on the fitness of organisms have typically been studied using mean or median adult life span as the sole index of physiological well-being. It is, however, known that life span is inversely related to reproductive output in many species. Moreover, the effects of a given environmental treatment on life span can be due to effects on either age-independent mortality or the "rate of aging," or a combination of both. Drawing evolutionary inferences from the effects of light regime on mean or median adult life span alone is difficult and, at best, speculative. We examined the effects of constant light (LL), alternating light-dark cycles (LD 12:12 h), and constant darkness (DD) on the life span of reproducing and virgin flies in four populations of Drosophila melanogaster and also estimated lifetime fecundity in the three light regimes. The light regime effects on life span were further dissected by examining the age-independent mortality and the Gompertz rate of aging under the three light regimes. While mean adult life span of reproducing males and females and virgin females was significantly shorter in LL compared to LD 12:12 h and DD, life-time egg production was highest in LL. Life span of virgin males was not significantly affected by light regime. The rate of aging in reproducing females was higher in LL as compared to DD, whereas age-independent mortality was higher in DD. As reproductive output, especially early in life, is a far more significant contributor to fitness than is life span, our results suggest that the earlier reported deleterious effects of LL on fitness are partly an artifact of examining life span alone, without considering other components of adult fitness that trade off with life span. Our results suggest that detailed investigation of the effects of light regime on the physiological and behavioral processes that accompany reproduction is necessary to fully understand the effects of different light regimes on adult fitness in Drosophila.

Aging↗
PubMed2000

Probing the circadian pacemaker of a mouse using two light pulses.

In two separate sets of experiments, the phases of the locomotor activity rhythm of the nocturnal field mouse Mus booduga were probed using two light pulses (LPs). In the first set of experiments, the circadian pacemaker underlying the locomotor activity rhythm was perturbed at circadian time 14 (CT 14) using a resetting light pulse LP1 of 1000 lux intensity and 15 min duration. The phases of the resetting pacemaker were then probed at all even CTs between CT 16 and CT 14 using a PRC probing light pulse LP2 of equal strength. The "LP2 PRC" thus obtained was then compared with the single light pulse PRC in terms of the area under delay (D) and advance (A) zones of the PRCs. The time course and waveform of the two LP PRCs suggest that the LP2 PRC resembled the single LP PRC, displaced by 2 h toward the right. The LP1 PRC had smaller D compared to the single LP PRC (p = 0.007), whereas both the PRCs had A of equal magnitude (p = 0.23). This suggests that the pacemaker phase shifts rapidly after LP perturbations. In the second set of experiments, the LP1 was administered at CT 14. The phase of the pacemaker was then perturbed on day 1 (next cycle after LP1) either 2 h after activity onset (at ca. CT 14 of the transient cycle) or 8 h after activity onset (at ca. CT 20 of the transient cycle) using an LP2 of equal strength. It was observed that the steady-state phase shifts evoked by positioning an LP2, 2 h after activity onset, were positively correlated with the phase shifts observed on day 1. The steady-state phase shifts observed, when the LP2 was positioned, 8 h after activity onset, were negatively correlated with the phase shifts observed on day 1. These results suggest that the transient cycles do not mirror the state of the pacemaker oscillator.

Animals↗