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Biomedical subjects

A Dhar

Publications and source records attributed to A Dhar.

At least 19 recordsLinked to original sources

Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells.

This paper investigates the presence and functionality of retinoid signaling pathways in human urinary bladder carcinoma and SV40-immortalized uroepithelial cell lines. Only two of eight cell lines were proliferation-inhibited by 10 microM of either all-trans or 13-cis-retinoic acid. Transactivation of the CAT gene under control of a retinoid-responsive element demonstrated functionality of the signaling pathway in both sensitive cell lines and four of six resistant cell lines. Relative RT-PCR analysis of a panel of retinoid-responsive and inducible genes demonstrated changes in expression levels of all the genes in response to-retinoic acid treatment together with numerous aberrations dysregulations. We conclude that retinoid signaling may be a target for inactivation during tumorigenesis by uncoupling gene expression, proliferation and differentiation. Therefore retinoids are more likely to be effective for chemoprevention than for treatment of bladder carcinomas.

Apoptosis

Alu elements in a Plasmodium vivax antigen gene.

Plasmodium vivax is a very common human malaria parasite but it is poorly characterized at the molecular level. Here, we describe the isolation and characterization of an antigen coding gene of P. vivax which contains Alu elements. This gene, called Pv-Alu, is expressed during the erythrocytic phase of the parasite. The encoded 200 amino acid long polypeptide is highly hydrophobic, contains transmembrane domains, and is rich in leucine (19.4%), serine (15.9%), proline (15.4%) and phenylalanine (15.4%). The 5'-untranslated region and part of the 3'-end coding region of Pv-Alu show significant homology to different Alu families. The presence of Alu elements in the coding region of a parasite antigen gene is significant from a functional and evolutionary viewpoint.

Amino Acid Sequence

Real-time intraoperative transesophageal echocardiography--how useful? Experience of 5,016 cases.

OBJECTIVE: To evaluate transesophageal echocardiography (TEE) as an intraoperative monitoring modality and to assess its safety, reliability, and overall utility in real-time use during cardiac surgery. DESIGN: Prospective, observational cohort study performed from January 1993 to June 1997. SETTING: Operating room of a tertiary care hospital for cardiology and cardiovascular surgery. PARTICIPANTS: Five thousand and sixteen adult patients with acquired heart disease, who underwent 1,356 valve procedures and 3,660 coronary artery bypass graftings (CABGs). INTERVENTIONS: All patients were monitored with radial artery and pulmonary artery catheters, along with continuous TEE monitoring with a multiplane transducer. MEASUREMENTS AND MAIN RESULTS: Prebypass imaging yielded unsuspected findings that either helped or modified the surgical plan in 158 of 1,356 valve procedures (11.65%) and in 993 of 3,660 CABGs (27.13%). There were 3,217 TEE-guided hemodynamic interventions in 944 patients (25.79%) in the CABG group and 629 in 142 patients (10.47%) in the valve group. TEE was the sole guiding factor in initiating therapy in 23.53% of events, whereas it was supportive to other monitoring modalities in 76.46% of events. Postbypass TEE identified the need for graft revision in 29 patients (0.8%), intra-aortic balloon pump (IABP) requirement in 29 patients (0.8%), and inadequate valve repair in 28 patients (2.08%). For the entire series, 38.78% of patients benefited from prebypass and 39.16% from postbypass use of TEE. There were no complications attributable to the use of TEE in the entire series. There was 87% concordance between online interpretation by a trained anesthesiologist and offline analysis by a cardiologist. CONCLUSION: Intraoperative TEE is useful in formulating the surgical plan, guiding various hemodynamic interventions, and assessing the immediate results of surgery. It is safe and the results are reliable in the hands of trained anesthesiologists.

Cardiac Surgical Procedures

Lansoprazole and secnidazole with clarithromycin, amoxycillin or pefloxacin in the eradication of Helicobacter pylori in a developing country.

BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined. AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer. METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication. RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks. CONCLUSIONS: High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.

2-Pyridinylmethylsulfinylbenzimidazoles

Pulmonary tuberculosis treated with directly observed therapy: serial changes in lung structure and function.

OBJECTIVES: (1) To correlate structure (CT) with function in pulmonary tuberculosis (TB), and (2) to describe the evolution of structural and functional abnormalities when pulmonary TB is treated with directly observed therapy. SUBJECTS AND METHODS: Twenty-five patients with drug-susceptible pulmonary TB, 15 cavitary and 10 noncavitary, were studied prospectively. Conventional CT and pulmonary function testing (spirometry, diffusing capacity, and arterial blood gases) were performed at baseline, and after 1 and 6 months of directly observed therapy. RESULTS: All but one patient with noncavitary miliary TB had CT evidence of endobronchial disease, and all patients with cavitary disease had coexistent reduced lung attenuation, the latter presumably a result of gas trapping, hypoxic vasoconstriction, and vascular injury. Functional impairment was minimal and in proportion to the number of diseased segments and cavitary volume. Bronchiectasis was significantly more likely to complicate cavitary than noncavitary disease (64 vs 11%; p<0.05). CONCLUSIONS: CT findings correlate well with function in pulmonary TB. Physiologic data were consistent with the concept that pulmonary TB is an endobronchial disease that causes parallel reductions in ventilation and perfusion. This concurrent involvement of both airways and contiguous pulmonary blood supply offers an explanation for the minimal respiratory limitation experienced by these patients despite often extensive lung disease. Supervised therapy of drug-susceptible disease results in minimal structural and functional residua.

Adult

Effect of immunization against the amino-terminal peptide (alpha N) of the alpha 43-subunit of inhibin on follicular atresia and expression of tissue inhibitor of matrix metalloproteinase (TIMP-1) in ovarian follicles of sheep.

Ewes actively immunized against alpha N, the N-terminal peptide of inhibin alpha 43 precursor, have lowered fertility associated with ovulation failure, restricted tissue remodelling and reduced matrix metalloproteinase-2 activity in the follicular fluid at the time of expected ovulation. This could be due to altered ratios of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase (TIMP-1), or to the onset of atresia in antral follicles destined to ovulate. The objectives of the present study were to investigate the effects of immunization against alpha N on the localization of TIMP-1 in ovine follicles, and on follicular growth and atresia in the follicular phase. Ewes were either immunized against alpha N or remained as controls and the ovaries were removed before (0, n = 4) and at 12 h (n = 4) and 24 h (n = 4) after hCG administration in a synchronized follicular phase, 48 h after removal of intravaginal pessaries. Observations were made on a single section taken through the largest follicle present in the ovaries of each ewe. There were no healthy antral follicles > 1 mm in immunized ovaries (0/29) compared with controls (16/31) (P < 0.001), whereas the proportion of healthy antral follicles < 1 mm was the same in each group (9/19 versus 5/12). TIMP-1 immunoactivity was localized in large luteal cells, smooth muscle and endothelial cells, and in all antral follicles, including oocytes. At the time of hCG administration, no TIMP-1 immunoreactivity was detected in the apical region of the follicular wall of large follicles (> 6 mm) compared with the rest of the follicle wall, but staining appeared in the apical granulosa layer 24 h later. In newly formed corpora lutea, TIMP-1 expression was found along the invaginating vascular layer. There was no effect of immunization on the patterns of TIMP-1 immunoreactivity, suggesting that changes in TIMP-1 are not involved in the effects of alpha N. These data are consistent with a paracrine role for alpha N in the selection and atresia of antral follicles, and for TIMP-1 in tissue reorganization and steroidogenesis at the time of ovulation.

Analysis of Variance

HLA association and occurrence of autoantibodies in Asian-Indian patients with ulcerative colitis.

OBJECTIVES: The purpose of the present study was to determine the profile of HLA class I antigens, antinuclear antibodies (ANA), and antineutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis (UC) patients from Northern India. METHODS: The study consisted of 100 UC patients with or without extraintestinal manifestations. Data on HLA, ANA, and ANCA were analyzed with respect to age at onset, sex, duration of disease, and occurrence of extraintestinal manifestations, and data were correlated with those of healthy controls from the same population. RESULTS: The most common extraintestinal manifestations in order of occurrence were arthralgia (53.8%), ocular lesions (18%), sacroiliitis (12.7%), hepatobiliary (7.7%), cutaneous (5%), and vascular (2.6%). ANA and ANCA were positive in only 3% of cases. Of the HLA class I antigens, HLA-A19 was significantly increased in UC patients compared with controls (63.4% vs. 33.5%, p < 0.001, RR = 3.4), particularly its subtype HLA-A33 (20.7% vs. 4%, p < 0.001, RR = 6.3). There was no deviation in the frequency of HLA-B locus antigens, whereas HLA-Cw6 was increased significantly in patients compared with controls (14.6% vs. 3.5%, p < 0.001, RR = 4.4). CONCLUSIONS: The occurrence of extraintestinal manifestations in Indian patients with UC is similar to that reported elsewhere, although ANA and ANCA positivity is lower. HLA studies revealed that A19(33) and Cw6 are associated with UC.

Adolescent

Eradication of H. pylori in a developing country: comparison of lansoprazole versus omeprazole with norfloxacin, in a dual-therapy study.

OBJECTIVES: Lansoprazole, a newer benzimidazole, is more potent than omeprazole in its anti-Helicobacter pylori effect in vitro. The present study was aimed at assessing its efficacy in a developing country. METHODS: Fifty patients were randomized to receive either lansoprazole or omeprazole, with norfloxacin for 2 wk; the ulcer healing rates, H. pylori eradication rates, and recurrence rates were compared over a 6-month period. RESULTS: Both lansoprazole and omeprazole were equally effective in inducing healing of ulcer (96.1 vs 95.5%, p > 0.05) and eradicating H. pylori (76.9 vs 63.9%, p > 0.05), with very low recurrence rates over a 6-month follow-up period. CONCLUSIONS: Either lansoprazole or omeprazole combined with norfloxacin is effective in eradicating H. pylori in a high percentage of cases of duodenal ulcer, with little difference between the two proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles

Changes in adenine nucleotides during hemorrhagic shock and reperfusion.

Certain tissues are known to be susceptible to shock-induced damage: liver, small bowel mucosa, and small bowel wall. This study was done to assess the changes in adenine nucleotides induced by hemorrhagic shock. Male Sprague-Dawley rats (n = 21; 300-350 g) were anesthetized with sodium pentobarbital (50 mg/kg, ip) and mechanically ventilated. The external jugular vein and common carotid artery were cannulated. Laparotomy was done. Hemorrhagic shock was induced by withdrawing blood into a heparinized syringe until a mean arterial blood pressure of 40 mm Hg was obtained and was maintained for 30 min by continued withdrawals. Shed blood was then reinfused through the venous catheter. No additional fluid was administered. The animals were observed for another 60 min. Throughout the procedure, biopsies were taken of liver and small bowel. The small bowel biopsies were separated into mucosal and wall fractions. Nucleotides were extracted. ATP, ADP, AMP, adenosine, inosine, xanthine, and hypoxanthine were measured with gradient HPLC. Cellular ATP concentrations decreased significantly during shock (P < 0.05). Liver ATP dropped from 8.93 +/- 0.55 to 2.91 +/- 0.16 micromol/g dry tissue (mean +/- SEM) (33%), small bowel mucosal ATP from 9.40 +/- 1.04 to 3.26 +/- 0.21 (35%), and small bowel wall ATP from 5.47 +/- 0.36 to 2.74 +/- 0.18 (50%). The nucleotide response to shock in small bowel mucosa was closer to that of liver than to that of small bowel wall. After reperfusion, ATP levels were partially restored in liver, small bowel mucosa, and small bowel wall, but not to preshock values. All of the metabolites (adenosine, inosine, hypoxanthine, and xanthine) increased during shock (P < 0.05), and did not return to preshock levels after reperfusion. The abnormalities in ATP and its metabolites, and their persistence after reperfusion, suggest a possible mechanism for the production of postshock damage.

Adenine Nucleotides

Role of platelet-activating factor in skeletal muscle ischemia-reperfusion injury.

These studies indicate that PAF, a known stimulator of aggregation, secretory and/or contractile activity of platelets, neutrophils, smooth muscle and other cells, is produced by skeletal muscle during IRI. The maximum increase occurs at 10 to 15 minutes and continues for at least an hour. Infusions of PAF into skeletal muscle subjected to 20 minutes of ischemia and 20 hours of reperfusion resulted in tissue necrosis similar to that produced by 5 hours of ischemia and 20 hours of reperfusion. 25 mg/kg of pentoxifylline, infused immediately prior to reperfusion of ischemic skeletal muscle, decreased PAF production and muscle necrosis. It was also demonstrated that skeletal muscle necrosis can be reduced by infusion of PAF antagonists (WEB-2086) into the muscle immediately prior to reperfusion. Thus, PAF has an important role in skeletal muscle IRI and additional studies of PAF inhibition during IRI are warranted.

Animals

Intensive care unit admission following successful cardiopulmonary resuscitation: resource utilization, functional status and long-term survival.

A retrospective review of consecutive admissions (n = 285) to a university hospital intensive care unit (ICU) following cardiopulmonary resuscitation was conducted to determine long-term outcome, length of stay (LOS), and ICU resource consumption. Ninety-four patients (33%) survived to hospital discharge. Hospital survivors had longer ICU LOS than non-survivors (5.1 +/- 0.8 vs. 2.8 +/- 0.4 days, P < 0.001) and longer hospital stays (22.5 +/- 3.7 vs. 2.9 +/- 1.2 days, P < 0.001). Average laboratory and pharmacy costs per admission were greater in hospital survivors than non-survivors. Most patients returned to their pre-arrest homes functionally independent and 58% of hospital survivors were alive 2 years after discharge. It is possible that attempts to appropriately limit therapy in patients with poor prognosis may help direct resources towards patients who will benefit.

Activities of Daily Living

The human ovarian granulosa cell: a stereological approach.

The human ovarian granulosa cell is perhaps the most widely studied endocrine cell, but little quantitative structural information exists for this cell. In the present study new and traditional stereological probes have been employed to provide quantitative structural information on these functionally important cells. Granulosa cells were obtained from follicular aspirations from 10 women during in vitro fertilisation procedures. Initially 2 methods were used to estimate the mean nuclear volume of these cells: the mean number weighted nuclear volume was estimated by the Selector and the mean volume weighted nuclear volume by the point sampled intercept method. It was found that the difference between the 2 volume estimates was only 8.5%. The volume weighted mean nuclear volume was used as an estimate of nuclear volume. This was subsequently corrected (taking the percentage difference as the empirical bias) and combined with fractional cell volumes (Vv) to produce estimates of cell, mitochondrial, lipid and nucleolar volume. The proportion of the cell occupied by the nucleus had a remarkably low interindividual variation (CV = 7.6%). The proportion of the nucleus occupied by euchromatin also had a striking low variation (CV < 6%). All other cellular parameters had CVs of less than 35%. The lipid composition of these cells showed the greatest interindividual variability, with a CV of 42% for relative and 54% for absolute volume. The present study outlines a simple protocol for the quantitation of granulosa cell structure using new unbiased stereological probes and providing baseline structural information.

Cell Nucleus

Pancrease divisum: five years' experience in a teaching hospital.

AIM: To study the frequency and significance of pancreas divisum. METHODS: Retrospective analysis of all pancreatograms carried out between July 1989 and June 1994. RESULTS: The 809 pancreatograms performed included 207 in patients with pancreatitis (acute 74, chronic 133), 330 with biliary disease, 238 with obscure abdominal pain and 34 with pancreatic malignancy. Of these, 30 patients (3.7%) were diagnosed to have pancreas divisum - 26 had type I variant, one had type II variant and three had type III variant. Accessory papillary cannulation was attempted in 10 patients; 8 were successful, with dorsal ductography confirming pancreas divisum in all of them. Two of these 8 patients had changes of chronic pancreatitis in the dorsal duct. The frequency of pancreas divisum in patients with pancreatitis (19 of 207, 9.2%) was significantly higher than in patients with biliary diseases and those with obscure abdominal pain (11 of 568, 1.9%; p < 0.001). CONCLUSIONS: Pancreas divisum is not an uncommon condition in India and its frequency in patients with idiopathic pancreatitis is higher than that in patients with other abdominal conditions. It should be looked for in any case of idiopathic pancreatitis.

Biliary Tract Diseases

Biliary obstruction due to pancreatic insulinoma.

Pancreatic insulinomas are rare tumors and their association with polycystic disease of the liver is uncommon. We report here a patient with pancreatic insulinoma with hepatic metastasis and biliary obstruction presenting with neuroglycopenic symptoms and cholestasis on a background of polycystic liver disease.

Cholangiopancreatography, Endoscopic Retrograde

Effect of pentoxifylline on tissue injury and platelet-activating factor production during ischemia-reperfusion injury.

PURPOSE: Pentoxifylline lessens the metabolic derangements associated with ischemia-reperfusion injury. This study evaluated the effects of pentoxifylline on platelet-activating factor (PAF) production and tissue injury during skeletal muscle ischemia-reperfusion injury. METHODS: The isolated canine gracilis muscle model was used. Group 1 muscles were subjected to 5 hours of ischemia and 20 hours of reperfusion (n = 10); group 2 muscles received pentoxifylline, 15 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6); group 3 muscles received pentoxifylline, 25 mg/kg, systemic infusion 10 minutes before reperfusion (n = 6). PAF was measured from muscle venous effluent by the scintillation proximity assay method. Muscle injury was assessed by vital staining and planimetry. RESULTS: PAF levels in group 2 were decreased at 10, 15, and 30 minutes of reperfusion compared with group 1 but did not reach significance. PAF levels in group 3 were decreased at all times of reperfusion compared with group 1 but attained significance only at 10 minutes of reperfusion (p < 0.05). No significant differences in muscle weight were noted among the three groups. No differences in the extent of muscle necrosis was observed between group 1 (77.26% +/- 20.38%) and group 2 (60.49% +/- 23.97%) (p = 0.08); there was a significant reduction in the extent of muscle necrosis in group 3 (44.55% +/- 21.47%) compared with group 1 (p < 0.05). CONCLUSIONS: The administration of pentoxifylline at 25 mg/kg before reperfusion of ischemic skeletal muscle decreased significantly the extent of muscle necrosis and PAF levels in the venous effluents at all times of reperfusion (significantly at 10 minutes). These results suggest that pentoxifylline may decrease tissue injury of ischemia-reperfusion by inhibiting the production of PAF during critical periods of reperfusion.

Animals