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Biomedical subjects

V K Sharma

Publications and source records attributed to V K Sharma.

At least 127 records · Page 7Linked to original sources
PubMed1999

A survey of gastroenterologists' perceptions and practices related to Helicobacter pylori infection.

OBJECTIVE: The aim of this study was to assess the current practice of gastroenterologists in the United States concerning Helicobacter pylori (H. pylori) infection. METHODS: We mailed a structured questionnaire to 1000 gastroenterologists chosen at random from a national database. We asked about personal and practice demographics and practices relating to testing for, and treating, H. pylori infection. RESULTS: A total of 922 questionnaires were delivered, from which we received 286 responses (31%). Respondents used many different tests for H. pylori infection, but only 10% each had used either the 13C- or 14C-urea breath test. Testing for H. pylori infection was usually for appropriate reasons, although 21% indicated that they might not treat a patient with a positive test result. Different multiple treatment regimens were used; the most frequent were combinations of a proton pump inhibitor, clarithromycin, and either amoxicillin or metronidazole. Estimates of the prevalence of antibiotic resistance were highly variable and often inaccurate. Most respondents would not check asymptomatic individuals for the infection; however, in the absence of symptoms, 38% would personally undergo testing and treatment if positive. CONCLUSIONS: Gastroenterologists usually test for H. pylori infection in appropriate conditions, but may not always treat the infection based on a positive test result. Most use efficacious regimens to treat the infection although many have inaccurate information on resistance rates, which may adversely influence prescribing. Many would have testing and, if positive, treatment in the absence of symptoms or a specific diagnosis, but do not recommend this for their patients.

Amoxicillin↗
PubMed1999

Metaanalysis of randomized controlled trials of endoscopic retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis.

OBJECTIVE: Endoscopic retrograde cholangiography with endoscopic sphincterotomy (ERC+ES) has been advocated for the management of acute biliary pancreatitis. However, it is also viewed as dangerous. Our objective was to review published randomized, controlled trials (RCTs) of ERC+ES in patients with acute biliary pancreatitis and, by metaanalysis, to estimate the overall efficacy and safety of this approach. METHODS: We performed a fully recursive literature search for published RCTs of ERC+ES in gallstone-related acute pancreatitis. RCTs were pooled. Individual and overall mortality and complication rates were calculated, together with their 95% confidence intervals (CI), absolute risk reduction (ARR), relative risk reduction (RRR), and numbers needed to treat (NNT) for avoidance of complications or death. RESULTS: Four published RCTs had a numerically lower complication rate, and three had a numerically lower mortality rate, in the treated groups than in controls. After pooling, there were 460 treated patients and 374 controls. Complications occurred in 115 (25.0%) treated patients and 143 (38.2%) controls (z = 4.10; p < 0.001). Twenty-four treated patients (5.2%) and 34 controls (9.1%) died (z = 2.15; p < 0.05). ERC+ES had a 34.6% RRR for complications and a 42.9% RRR for death; ARR for complications and death was 13.2% (95% CI: 6.9-19.5%) and 3.9% (95% CI: 0.35-7.45%), respectively. The NNT for avoidance of complications and death was 7.6 and 25.6, respectively. CONCLUSIONS: ERC+ES reduces morbidity and mortality in patients with acute biliary pancreatitis. Treating 26 such patients with ERC+ES is predicted to save one life.

Acute Disease↗
PubMed1999

Immunological defect in leprosy patients: altered T-lymphocyte signals.

The early events of activation were studied in paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients by stimulation of their lymphocytes with mitogenic agents (calcium ionophore A23187/PMA) and Micobacterium leprae antigen (PGL-1). Maximum proliferation in response to PMA/A23187 and PGL-1 was observed in the BT/TT patients and the control group, respectively. Inositol triphosphate (IP3) and calcium were constitutively elevated in BT/TT and LL/BL patients. PMA/A23187 caused an increase in both IP3 and [Ca2+]i in BT/TT patients and controls. PGL-1 marginally increased IP3 levels in BT/TT patients. In the LL/BL patients, although PMA/A23187 increased IP3 levels, but no change was seen in [Ca2+]i, PGL-1 had no effect. Protein kinase C levels were seen to be associated with particulate fractions in BT/TT patients and were found to increase further in response to PMA/A23187. PGL-1 did not increase translocation of protein kinase C in controls or LL/BL patients. A preactivated and sensitised state of T-lymphocytes was observed in BT/TT patients, responsive to antigen and mitogens, whereas the cells of LL/BL patients were unresponsive to PGL-1. The altered signal transduction events characterised in the MB patients thus correlate well with the anergic state of their cells.

Calcium↗
PubMed1999

Spontaneous apoptosis in peripheral blood mononuclear cells of leprosy patients: role of cytokines.

Peripheral blood mononuclear cells from leprosy patients underwent spontaneous apoptosis upon culture for 24 h. The apoptosis was inhibited by anti-TNFalpha antibodies and to a certain extent by anti-IL-1alpha and IL-6, thus showing that T(H)2-type cytokines (mainly TNFalpha) are responsible for inducing apoptosis. This cytokine-mediated apoptosis could be inhibited by ionomycin and zinc, thereby suggesting that these metal ions can be used to decrease the levels of these inflammatory cytokines in various diseases.

Antibodies↗
PubMed1999

In the field mouse Mus booduga melatonin phase response curves (PRCs) have a different time course and wave form relative to light PRC.

The phase shifting effects of the pineal hormone melatonin on the circadian locomotor activity rhythm of the field mouse. Mus booduga was examined at various phases of the circadian cycle using single melatonin injections of two concentrations (10 mg/kg, high dose; and 1 mg/kg, low dose) and two phase response curves (PRCs) were constructed. A single dose of melatonin administered during the early subjective day evoked maximum phase delays, and during the late subjective night evoked phase advances in the locomotor activity rhythm. Other phases of the circadian cycle also responded to melatonin. The interval between circadian time 19 (CT19) and CT2 of the high dose melatonin PRC is marked by significant phase advances, whereas the interval between CT2 and 19 is marked by significant phase delays. A single dose of melatonin of strength 10 mg/kg was found to evoke phase shifts that were of comparable magnitude to those of the phase shifts evoked by natural daylight pulses. Control animals, treated with 50% dimethyl sulfoxide (DMSO), did not respond with phase shifts significantly greater than zero. Significant differences between the shapes of the two melatonin PRCs exist. Further melatonin PRCs appear to have a different time course and wave form relative to light-induced PRC.

Activity Cycles↗
PubMed1999

Health of the Nation Outcome Scales: a case study in general psychiatry.

BACKGROUND: Health of the Nation Outcome Scales (HoNOS) were incorporated in a data set recording the routine clinical activities of a mental health team in Liverpool. AIMS: To evaluate the use of HoNOS in general adult psychiatry. METHOD: All consecutive patients who came in contact with the mental health team were administered HoNOS by the consultant psychiatrist. A cohort (n = 204) of patients was identified over a period of 8 months. All patients (n = 156) who had a repeat HoNOS after an interval of 6 months were included in the study. RESULTS: There was an overall reduction in HoNOS scores after an interval of 6 months, more so among patients with psychotic and affective disorders. Patients scoring on other disorders showed no change on HoNOS. The measured change in clinical state based on the Clinical Global Impression scale was broadly consistent with HoNOS scores. CONCLUSIONS: It was feasible to administer HoNOS during routine assessments, but HoNOS data were of limited value in care-planning in day-to-day clinical practice. The widespread adoption of HoNOS for use in routine clinical practice would be premature.

Adolescent↗
PubMed1999

CT findings in involvement of the paranasal sinuses by lepromatous leprosy.

The role of nasal infection in the transmission of leprosy has been extensively studied. Leprosy can affect the paranasal sinuses due to mucosal continuity and bacillaemia. This prospective study was performed on 25 untreated patients with lepromatous leprosy. 5 mm contiguous axial and coronal CT sections of paranasal sinuses, on soft tissue and bone windows, were obtained in all patients. Each sinus was examined for mucosal thickening, soft tissue densities and bony outlines. Representative biopsies were taken from ethmoid sinus to confirm the radiological diagnosis in 12 patients with multiple paranasal sinus involvement. Ethmoid aircells were involved in 20 patients (80%). Maxillary, frontal and sphenoid sinuses showed abnormalities in 12, four and three patients, respectively. The ethmoid biopsy showed involvement by lepromatous leprosy in seven of 12 patients (58.3%). Involvement of paranasal sinuses is common in lepromatous leprosy and is of considerable epidemiological significance.

Adolescent↗
PubMed1999

Timely administration of melatonin accelerates reentrainment to phase-shifted light-dark cycles in the field mouse Mus booduga.

The effect of melatonin on the rate of reentrainment after a 6 h phase delay and a 6 h phase advance in the light-dark (LD) cycle was assayed in the nocturnal field mouse Mus booduga. After a phase delay of 6 h in the LD cycle, a single dose of melatonin (1 mg/kg) was administered for three consecutive days at about CT4 (circadian time 4). After a phase advance of 6 h in the LD cycle, melatonin was administered for three consecutive days at about CT22. Melatonin was found to accelerate reentrainment in both cases. Melatonin-treated animals took significantly fewer cycles to reentrain compared to vehicle-treated (50% dimethylsulfoxide [DMSO]) and nontreated control animals.

Animals↗
PubMed1999

Presence of M. leprae in tissues in slit skin smear negative multibacillary (MB) patients after WHO-MBR.

This study looked for M. leprae in the lymph node, nerve and skin of multibacillary (MB) leprosy patients who become slit skin smear negative after the completion of WHO-MBR. Twenty-five WHO-MBR-treated multibacillary leprosy patients were studied; borderline lepromatous (BL) leprosy (n = 11) and lepromatous (LL) leprosy (n = 14)). Fifteen patients had reaction (erythema nodosum leprosum 11, upgrading reaction 4) either at presentation or during therapy. All patients attained slit skin smear negativity after WHO-MBR (range 24-39 months. Sixteen (64%) patients with multibacillary leprosy showed fragmented bacilli in skin and nerve biopsy or lymph node aspirates after WHO-MBR. Lymph node aspirates alone revealed M. leprae in seven patients, followed by nerve in two and skin in one patient. Four cases showed M. leprae at all sites followed by nerve and skin or lymph node in one case each. A pretreatment bacteriological index (BI) of 4+ or more was significantly associated with the presence of M. leprae at the end of treatment. Also, significantly more lymph node aspirates contained M. leprae in comparison with nerve or skin biopsies. All seven cases in whom treatment was extended beyond 24 months showed M. leprae in tissues even after attaining slit smear negativity. In conclusion, M. leprae persist in tissues after 2 years of WHO-MBR and patients with an initial BI of 4+ or more need to be closely followed up after stopping MDT.

Adolescent↗
PubMed1999

Diagnosis of hydatid disease of abdomen and thorax by ultrasound guided fine needle aspiration cytology.

Five cases of hydatid disease of abdomen and thorax were diagnosed by fine needle aspiration cytology (FNAC) under ultrasound guidance. The age of patients ranged from 25-50 years, with a median age of 37 years. Male to female ratio was 2:3. None of the cases were clinically diagnosed as hydatid disease, but ultrasonography raised suspicion in two cases. The location of cyst in four cases was liver and one aspiration was done from lung. Smears from all cases showed features consistent with hydatid disease. None of the patients showed any untoward allergic reaction following FNAC.

Adult↗
PubMed1998

Signaling mechanisms underlying muscarinic receptor-mediated increase in contraction rate in cultured heart cells.

We have investigated the mechanisms by which stimulation of cardiac muscarinic receptors result in paradoxical stimulatory effects on cardiac function, using cultured neonatal rat ventricular myocytes as a model system. Application of low concentrations of carbachol (CCh) (EC50 = 35 nM) produced an atropine-sensitive decrease in spontaneous contraction rate, while, in cells pretreated with pertussis toxin, higher concentrations of CCh (EC50 = 26 microM) elicited an atropine-sensitive increase in contraction rate. Oxotremorine, an m2 muscarinic acetylcholine receptor (mAChR) agonist, mimicked the negative but not the positive chronotropic response to CCh. Reverse transcription followed by polymerase chain reaction carried out on mRNA obtained from single cells indicated that ventricular myocytes express mRNA for the m1, m2, and, possibly, m4 mAChRs. The presence of m1 and m2 mAChR protein on the surface membranes of the cultured ventricular myocytes was confirmed by immunofluorescence. The CCh-induced positive chronotropic response was significantly inhibited by fluorescein-tagged antisense oligonucleotides directed against the m1, but not the m2 and m4, mAChR subtypes. The response was also inhibited by antisense oligonucleotides against Gqalpha protein. Finally, inhibition of CCh-induced phosphoinositide hydrolysis with 500 microM neomycin or 5 microM U73122 completely abolished the CCh-induced positive chronotropic response. These results are consistent with the stimulatory effects of mAChR activation on the rate of contractions in cultured ventricular myocytes being mediated through the m1 mAChR coupled through Gq to phospholipase C-induced phosphoinositide hydrolysis.

Animals↗
PubMed1998

Age-dependent modulation of circadian parameters in the field mouse Mus booduga.

The locomotor activity of the field mouse Mus booduga was monitored under continuous darkness (DD) for extended periods of 275 to 388 days. Free-running period (tau), activity time (alpha) and rest time (rho) were computed from the activity records for all the animals (n = 10). Decreases in the circadian period (tau) with age were observed in some of the animals at an early age (< ca. 100 days) and then tau remained relatively constant for rest of their life span. The activity time (alpha), rest time (rho), and their ratio (alpha/rho), however, did not show any consistent trend of increase/decrease. The initial decrease in tau is consistent with previous models suggesting a time-dependent increase in the number of cells generating oscillations in the suprachiasmatic nucleus (SCN) and/or increase in the strength of coupling between these cells. In such models, after an optimal number of cells launch themselves into a state of self-sustained oscillation, tau stabilizes, achieving relative constancy, a pattern similar to the one observed in our study.

Aging↗
PubMed1998

Protein-lipid interactions and enzyme requirements for light subtype generation on cycling reconstituted surfactant.

Surfactant convertase is required for conversion of heavy density (H) natural surfactant to light density (L) subtype during cycling in vitro, a technique that reproduces surfactant metabolism. To study mechanisms of H to L conversion, we prepared liposomes of dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG), or the phospholipids (PL) in combination with either surfactant protein A (SP-A), surfactant protein B (SP-B), or both SP-A and SP-B. Phospholipids alone showed time-dependent conversion from heavy to light subtype on cycling in the absence of convertase, which was decreased by adding SP-B, but not SP-A, to phospholipids (p < 0.01 for PL+SP-B, or PL+SP-A+SP-B vs. PL, or PL+SP-A). The ultrastructure, surface activity, buoyant density, and L subtype generation on cycling PL+SP-A+SP-B with partially purified convertase or with phospholipase D were similar to those of natural TM. In conclusion, a reconstituted surfactant mimics the behavior of natural surfactant on cycling, and reveals that interaction of SP-B with phospholipids decreases L subtype generation. In addition, esterase/ phospholipase D activity is required for conversion of heavy to light subtype on cycling.

Animals↗
PubMed1998

In vivo expression of transforming growth factor-beta1 in humans: stimulation by cyclosporine.

BACKGROUND: Transforming growth factor-beta1 (TGF-beta1) is an immunoregulatory and fibrogenic cytokine. In an earlier in vitro study, we demonstrated that cyclosporine (CsA) increases TGF-beta1 transcription rate in human T lymphocytes. Herein, we explored whether CsA augments the in vivo expression of TGF-beta1 in humans. METHODS: The inherent difficulty in studying the in vivo effect of CsA in humans was circumvented by investigating stable end-stage renal disease patients who were preconditioned with CsA before their living donor renal transplantation. Sera and peripheral blood mononuclear cells were obtained from CsA-preconditioned patients and quantified for TGF-beta1 expression at the mRNA (by competitive polymerase chain reaction) and protein (sandwich enzyme-linked immunosorbent assay) levels. RESULTS: Our studies demonstrated a significant increase in TGF-beta1 expression after CsA therapy. The stimulatory effect was unique to TGF-beta1, and CsA did not increase interleukin (IL)-10, IL-6, IL-2, or tumor necrosis factor-alpha expression. CONCLUSIONS: Our first-time demonstration of a TGF-beta1-selective in vivo stimulatory effect of CsA in humans: (1) advances a TGF-beta1-centered hypothesis for the beneficial (immunosuppression) and detrimental (fibrosis, hypertension) effects of CsA use, and (2) broadens the mechanism of immunosuppressive action of CsA to include heightened expression of an endogenous immunosuppressive cytokine.

Cyclosporine↗
PubMed1998

Alterations in early biochemical events following T cell activation in leprosy patients.

The early events of activation and cytokine profiles (IL-2, 4, and 6) were studied in lymphocytes of paucibacillary (TT/BT) and multibacillary (BL/LL) leprosy patients after stimulation with PMA/A23187 and Mycobacterium leprae antigen (PGL-1). Lymphocytes from BT/TT patients showed proliferation in response to both PMA/A23187 and PGL-1 compared to BL/LL. The levels of early activation signaling molecules such as IP3, calcium, and protein kinase C (PKC) in the particulate fraction were found to be elevated in BT/TT and BL/LL patients and showed a further significant increase after stimulation with PMA/A23187 in BT/TT patients. PGL-1 marginally increased the IP3 levels in BT/TT patients, whereas in BL/LL patients, it had no effect. The levels of IL-2 were enhanced in lymphocytes of BT/TT leprosy patients and were further augmented by PPD and PGL-1, while the levels of IL-4 and IL-6 were increased in LL/BL lymphocytes and further augmented by PGL-1. Thus PGL-1 seems to be a major culprit in inducing the TH2-type cytokine response observed in lepromatous leprosy patients.

Antigens, Bacterial↗