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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 181 records · Page 10Linked to original sources
PubMed1996

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating-factor support for dose-intensive cyclophosphamide, etoposide, and cisplatin.

This is a double-blind randomized placebo-controlled trial to evaluate the efficacy and safety of granulocyte-macrophage colony-stimulating-factor (GM-CSF) after dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). Fifty-six patients with lymphoma or breast carcinoma were randomized to receive GM-CSF 250 microg/m2 or placebo subcutaneously (SC) every 12 hr after each course of DICEP until recovery of absolute neutrophil count (ANC) of 1.5 x 10(9)/L. Each patient was to receive three courses of DICEP. There were 28 patients in each group. The median duration of ANC below 0.5 x 10(9)/L was 10 versus 12 days for Course 1 (P = 0.010), 10 versus 12 days for Course 2 (P = 0.248), and 16.5 versus 15 days for Course 3 (P = 0.126); platelet counts below 20 x 10(9)/L was 4 versus 4 days for Course 1 (P = 0.586), 8.5 versus 7 days for Course 2 (P = 0.013), and 23.5 versus 10.5 days for Course 3 (P = 0.104); hospitalization for patients readmitted with cytopenic fever were 4 versus 8 days for Course 1 (P = 0.035); 7 versus 6 days for Course 2 (P = 0.692); and 8 versus 12 days for Course 3 (P = 0.884) in the GM-CSF and placebo group, respectively. GM-CSF significantly shortens the duration of neutropenia and readmission only during the first course of DICEP. There was a delay in platelet recovery and an increase in transfusion requirement during subsequent courses in the GM-CSF group. The result cautions the routine use of lineage specific hematopoietic growth factors in supporting repeated cycles of dose-intensive chemotherapy.

Adult↗
PubMed1996

Protective effects of GSH, vitamin E, and selenium on lipid peroxidation in cadmium-fed rats.

Increased intake of Cd results in its retention and in peroxidative damage in soft tissues. Coadministration of antioxidants, viz., glutathione (GSH), alpha-tocopherol, and Se, restricted the uptake and distribution of Cd in liver and kidney of rats. Moreover, no rise in malondialdehyde was recorded. Although possible antioxidative mechanisms manifested by GSH, alpha-tocopherol, and Se have been discussed, it is hypothesized that GSH functions as a Cd chelator. Glutathione yielded favorable effects in comparison to Se and alpha-tocopherol.

Animals↗
PubMed1996

Defective endothelium-dependent relaxation in fructose-hypertensive rats.

The present study examined the endothelium-dependent and -independent responses of isolated mesenteric arteries to acetylcholine and the endothelium-independent vasodilator sodium nitroprusside in mesenteric arteries from fructose-induced hypertensive rats. Fructose feeding resulted in hyperinsulinemia and elevated blood pressure when compared to controls (plasma insulin, 5.9 +/- 0.4 v control 3.6 +/- 0.4 ng/mL, P < .05; systolic blood pressure, 154 +/- 5 v control 127 +/- 7 mm Hg, P < .05). The maximum contractile response of mesenteric arteries to norepinephrine did not differ between the control and fructose groups, either with or without the endothelium. In arteries with intact endothelia, precontracted with the approximate ED50 of norepinephrine, the percent maximum relaxation produced by acetylcholine in hypertensive rats was lower than the control arteries (62 +/- 7 v control 95 +/- 5, P < .05) without any change in sensitivity. In arteries precontracted with norepinephrine, the endothelium-independent vasodilator sodium nitroprusside produced a dose-dependent relaxation in arteries obtained from control and fructose groups, both with and without the endothelium. The maximum relaxation produced by sodium nitroprusside did not differ between control and fructose arteries, either with or without the endothelium; however, removal of the endothelium caused an increase in sensitivity of this agonist. These data suggest that in the insulin resistant and hyperinsulinemic fructose-hypertensive rats, there is a defective endothelium-dependent yet preserved endothelium-independent relaxation.

Acetylcholine↗
PubMed1996

Decreased vascular reactivity in metformin-treated fructose-hypertensive rats.

We have previously demonstrated that long-term metformin treatment prevents the development of hyperinsulinemia and hypertension in fructose-hypertensive (FH) rats; however, the exact nature of its antihypertensive effects remains elusive. Since hyperinsulinemia has been proposed to be a strong stimulus for norepinephrine (NE) release, the present study examined the effects of long-term metformin treatment (500 mg/kg/d for 10 weeks) on the reactivity of superior mesenteric arteries to NE in FH rats. Metformin treatment prevented the development of hyperinsulinemia and hypertension in FH rats. Mesenteric arteries from FH rats exhibited an increased cross-sectional area ([CSA] 0.45 +/- 0.07 mm2 v 0.32 +/- 0.05 in controls, P < .05), which was prevented by long-term metformin treatment (0.34 +/- 0.04 mm2, p > .05 v untreated FH). Interestingly, mesenteric arteries from metformin-treated fructose and control rats exhibited a reduction in maximum responsiveness to NE both with and without the endothelium. These data suggest that metformin directly reduces catecholamine constrictor responses in resistance arteries of rats, which may contribute to its antihypertensive effects in rats.

Animals↗
PubMed1996

An in vivo investigation of the structures responsible for corneal haze after photorefractive keratectomy and their effect on visual function.

PURPOSE: To make serial measurements of corneal haze and microscopic anatomy after photorefractive keratectomy (PRK) and compare the results with visual function measured at the same time points in the same single group of human subjects. METHODS: Ten patients underwent -6.00-diopter, 6-mm PRK. The patients were reviewed frequently for 12 months. Corneal haze was measured objectively in two ways: (1) an opacification index was determined from the variance in digitized retroillumination images; and (2) light reflected and scattered back from the cornea was assessed by gray-scale analysis of video slit images. In vivo confocal microscopy recorded the anatomic changes occurring in the cornea, and computer analysis of the images quantified the keratocytes and subepithelial deposit. Visual performance was assessed by Snellen visual acuity, contrast sensitivity, and glare-induced visual dysfunction. RESULTS: In the first week, epithelial irregularity resulted in a transient reduction in all aspects of visual function. In the first month, keratocyte disturbances reduced contrast sensitivity at high frequencies and produced glare. Over the next couple of months, the subepithelial deposit resulted in a more prolonged loss of contrast sensitivity at low frequencies and glare-induced visual dysfunction due to the scattering of light. In several patients, these visual defects persisted after 1 year. CONCLUSIONS: Epithelial and keratocyte disturbances only transiently affect visual function. The subepithelial deposit is more persistent and can have a lasting effect on visual performance. Therefore, attempts to improve the visual outcome of PRK must be aimed at controlling the synthesis of subepithelial material.

Adult↗
PubMed1996

Hemodynamic predictors of early intolerance and long-term effects of propranolol in dilated cardiomyopathy.

BACKGROUND: Fifty-six patients with dilated cardiomyopathy (DCM) (aged 14-68 years) and background therapy of angiotensin-converting enzyme inhibitors, diuretics, and digoxin were given an initial challenge of propranolol in gradually increasing doses. These patients were studied noninvasively and hemodynamically and subjected to right ventricle biopsy. METHODS AND RESULTS: Forty-four patients tolerated propranolol and received the drug for 6 months; 12 patients deteriorated after starting the drug with worsening of congestive heart failure and/or hypotension. The patients who did not tolerate propranolol had higher left ventricular end-diastolic dimension (73 +/- 8 vs 66 +/- 8 mm, P < .05), and severe mitral regurgitation was more common. Hemodynamically these patients had higher heart rate, right ventricular end-diastolic pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and left ventricular end-diastolic pressure (102 +/- 16 vs 89 +/- 12 beats/min, 15 +/- 7 vs 9 +/- 4, 39 +/- 16 vs 31 +/- 12, 28 +/- 8 vs 21 +/- 8, 28 +/- 8 vs 22 +/- 8 mmHg, respectively, P < .01). These patients had a significantly lower cardiac index (1.9 +/- 0.6 vs 2.5 +/- 0.6 L/min/m2, P < .01). Forty patients completed 6 months follow-up evaluation and were further subjected to repeat noninvasive and hemodynamic study. There was a significant improvement in New York Heart Association class, cardiothoracic ratio, and left ventricular end-diastolic dimension (68% vs 62%, 66 +/- 8 vs 62 +/- 7 mm, respectively, P < .01), while the ejection fraction (EF) rose from 23 to 35% (P < .001). Hemodynamically, there was a significant decrease in heart rate, right ventricular end-diastolic pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure, and left ventricular end-diastolic pressure (91 +/- 14 vs 71 +/- 5 beats/min, 9 +/- 4 vs 5 +/- 3, 32 +/- 11 vs 22 +/- 7, 25 +/- 9 vs 17 +/- 8, 21 +/- 7 vs 14 +/- 4 mmHg, P < .05). The cardiac index rose from 2.3 +/- 0.6 to 3.2 +/- 0.7 L/min/m2 (P < .01). CONCLUSIONS: Propranolol in dilated cardiomyopathy is associated with significant intolerance. Those who tolerate propranolol seem to have long-term beneficial effects. This study is limited as it is uncontrolled and nonrandomized.

Adolescent↗
PubMed1996

Effect of immunization with human SP-10 in male rodents.

PROBLEM: Over the years immunocontraception has emerged as a promising modality. Theoretically it is possible to intercept fertility using a panel of antigens expressed along the entire pituitary, hypothalamus and gonadal axis. One such sperm antigen designated as SP-10 is in advanced stages of development. Its gene has been cloned by Wright et al. (Biol Reprod 1990; 42:693-701). It is envisaged that immunization with SP-10 would induce antisperm antibodies in females and hence interrupt fertility. However, the in vivo effect of SP-10 immunization has been assessed in male rodents with particular reference to spermatogenesis and effect of such immunization in various tissues. The SP-10 antigen was a generous gift from Dr. John Herr. METHODS: A group of male Wistar rats and BALB/c mice were immunized with a total dose of 175 micrograms of SP-10 glutathione transferase fusion protein. Anti-SP-10 antibodies generated were detected by ELISA, immunofluorescence, flow cytometry and western blot assay. Histopathology of all the organs was conducted with particular reference to assess their effect on sperm maturation in testicular sections. RESULTS: All the animals immunized with SP-10 depicted a significant antibody response. DNA analysis by flow cytometry did not reveal any arrest of spermatogenesis, which was confirmed by histological studies. CONCLUSIONS: It is concluded that conventional immunization generating significant antibody titers does not induce arrest of spermatogenesis in male rodents.

Acrosome↗
PubMed1996

Duration and fundamental frequency correlates of phrase boundaries in productions by children and adults.

Two experiments examined how children and adults produce acoustic correlates for phrase boundaries during speech. Adult and children (ages 5 and 7) were asked to describe groupings of colored blocks, first in a relatively spontaneous manner and next under more structured conditions designed to elicit grouping information concerning "which blocks go together." In the spontaneous condition, adults gave elaborate descriptions of block positions and color, whereas children produced short descriptions such as "pink, green, white;" "pink, green, and white;" and "pink and green and white." In the structured condition, all subjects produced utterances corresponding to three syntactic bracketings of the phrase "pink and green and white:" [pink and (green and white)]; [(pink and green) and white]; and [pink and green and white]. Acoustic analyses indicated that adults reliably control both duration and fundamental frequency (F0) to signal phrase boundaries, whereas children of both age groups demonstrate little evidence of either type of information being used. We interpret these finding as suggesting that children as old as age 7 do not produce prosodic cues for this type of standing ambiguity in their everyday speech. Possible reasons for this lack of phrase boundary prosodic correlates are examined.

Adult↗
PubMed1996

Effect of ablation profile on wound healing and visual performance 1 year after excimer laser photorefractive keratectomy.

BACKGROUND: Early photorefractive keratectomy ablations were of limited diameter and depth to maintain the integrity of the globe and to minimise postoperative haze. This study evaluated the effects of deeper, larger diameter wounds on refractive stability and corneal haze, and investigated the effects of ablation profile on wound healing and visual performance. METHODS: One hundred patients undergoing -3.00D and -6.00D corrections were randomised to receive 5 mm, 6 mm, or multizone treatments. The multizone treatment was 6 mm in diameter, but only the depth of the 5 mm treatment. Outcome was measured by Snellen visual acuity, residual refractive error, objective techniques for haze and halos, pupil diameter, subjective night vision, and requirement for retreatment. RESULTS: Overall, the results of 6 mm treatments were superior to those of 5 mm and multizone treatments: they had a smaller hyperopic shift (p < 0.01), a more predictable (p < 0.001) and stable refractive outcome, less haze (p < 0.05), smaller halos (p < 0.05), fewer subjective night vision problems, and fewer patients required retreatment. CONCLUSIONS: Analysis of these data and a literature review of corneal wound healing demonstrated that the improved outcome associated with the 6 mm beam did not relate to the depth of ablation. The factor with greatest apparent influence on the development of haze and regression was the slope of the wound surface over the entire area of the ablation. Tapering the wound edge provided no additional benefit, and contributed to night vision problems. It is, therefore, recommended that small diameter or multizone treatments should not be used in low and moderate myopia.

Adult↗
PubMed1996

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Adult↗
PubMed1995

Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation.

The adenovirus type 2/5 E1A proteins transform primary baby rat kidney (BRK) cells in cooperation with the activated Ras (T24 ras) oncoprotein. The N-terminal half of E1A (exon 1) is essential for this transformation activity. While the C-terminal half of E1A (exon 2) is dispensable, a region located between residues 225 and 238 of the 243R E1A protein negatively modulates in vitro T24 ras cooperative transformation as well as the tumorigenic potential of E1A/T24 ras-transformed cells. The same C-terminal domain is also required for binding of a cellular 48-kDa phosphoprotein, C-terminal binding protein (CtBP). We have cloned the cDNA for CtBP via yeast two-hybrid interaction cloning. The cDNA encodes a 439-amino acid (48 kDa) protein that specifically interacts with exon 2 in yeast two-hybrid, in vitro protein binding, and in vivo coimmunoprecipitation analyses. This protein requires residues 225-238 of the 243R E1A protein for interaction. The predicted protein sequence of the isolated cDNA is identical to amino acid sequences obtained from peptides prepared from biochemically purified CtBP. Fine mapping of the CtBP-binding domain revealed that a 6-amino acid motif highly conserved among the E1A proteins of various human and animal adenoviruses is required for this interaction. These results suggest that interaction of CtBP with the E1A proteins may play a critical role in adenovirus replication and oncogenic transformation.

Adenovirus E1A Proteins↗
PubMed1995

Pharmacology, relative bioavailability, and toxicity of three different oral cyclophosphamide preparations in a randomized, cross-over study.

Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, and toxicity of three different oral formulations of cyclophosphamide (Cytoxan, Endoxan, and an investigational direct compression tablet). Patients were randomized with respect to the order in which they received the different oral cyclophosphamide preparations, and received each one for two weeks followed by a two week washout period. Concurrent chemotherapy was allowed provided it remained constant across all 3 courses of cyclophosphamide. Plasma concentrations of cyclophosphamide and phosphoramide mustard were measured by gas chromatography with electron capture detection. Peak plasma cyclophosphamide concentrations and times to peak plasma cyclophosphamide and phosphoramide mustard preparations were significantly greater for Endoxan than for Cytoxan and the investigational direct compression tablet. Drug area under the concentration-time curve (AUC), bioavailability, and plasma elimination half-life could not be reliably calculated for Endoxan but were similar for Cytoxan and the investigational formulation. Based on AUC comparisons, bioavailability of parent compound (relative to an oral cyclophosphamide solution) was 85% for Cytoxan and 69% for the investigational formulation. This difference was not significant. There were no significant differences between the 3 formulations with respect to any individual type of toxicity, although the investigational formulation tended to be associated with somewhat less overall toxicity (p = 0.08).

Administration, Oral↗
PubMed1995

A prospective, randomized, double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy.

PURPOSE: To investigate the role of 1% tetracaine in controlling pain after photo-refractive keratectomy (PRK) and determining its effect, if any, on epithelial healing, refractive outcome, and visual performance. METHODS: In this study, 44 patients were randomized to receive either Gutt. 1% tetracaine or placebo after undergoing PRK. Drops were instilled at 30-minute intervals during waking hours for 24 hours postoperatively. In addition, all patients received two coproxamol (paracetamol + dextropropoxyphene) tablets every 6 hours for 2 days. Visual Analogue Pain Charts were used to record pain levels for 4 days after surgery. Serial digitized retro-illumination photography was used to assess rates of epithelial healing, and surface epithelial quality was monitored using topography. At fixed intervals over a 6-month period visual performance was assessed by measuring refractive outcome, best-corrected visual acuity, objective haze, halo, and glare. RESULTS: Patients in the tetracaine group had significantly less pain (P < 0.0001). Both groups demonstrated full epithelial closure within 72 hours. Similar numbers of patients in both groups at 1 week showed topographic irregularity that completely resolved by 1 month. No statistically significant difference was seen in any of the parameters monitoring visual performance. CONCLUSIONS: Tetracaine in conjunction with coproxamol is effective in reducing pain after PRK without adversely affecting corneal wound healing or visual performance.

Acetaminophen↗
PubMed1995

Effect of chronic endothelin blockade in hyperinsulinemic hypertensive rats.

Evidence suggests that hyperinsulinemia may be causally related to the development of high blood pressure (BP) in fructose-hypertensive (FH) rats. Because plasma insulin has been shown to modulate endothelin (ET) release in vivo, we hypothesized that hyperinsulinemia may provide a continual stimulus for ET release, which could increase BP by altering plasma or blood vessel ET levels. To test this hypothesis, we studied the effect of chronic ET-receptor blockade (by using bosentan, a noncompetitive ET antagonist) on plasma insulin levels, plasma ET levels, blood vessel ET content, and BP in FH rats. Chronic oral bosentan treatment (100 mg.kg-1.day-1) was initiated in 6-wk-old Sprague-Dawley rats. One week after bosentan treatment was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma insulin, plasma glucose, and systolic BP were measured weekly. At termination (in 15-wk-old rats), plasma ET levels and total mesenteric ET content were determined. Bosentan treatment caused a sustained decrease in BP in the FH rats (treated 130 +/- 4 vs. untreated 149 +/- 2 mmHg, P < 0.001) but had no effect in the normotensive control group. FH rats had a higher total mesenteric ET content compared with the control group (21.5 +/- 3.2 vs. 14.1 +/- 2.1 fmol, P < 0.05). Bosentan treatment did not alter total mesenteric ET content (treated 18.8 +/- 5 fmol, P > 0.05 vs. untreated) nor did it affect plasma insulin or ET levels in any group. These data suggest that ET may be involved in the development of high BP in FH rats. Whether ET represents an intermediate, linking hyperinsulinemia to hypertension in rats, or is an independent hypertensinogenic mechanism remains to be determined.

Animals↗
PubMed1995

IgG & IgM antibodies against measles virus in unvaccinated infants from Pune: evidence for subclinical infections.

IgG and IgM class of antibodies to measles virus were estimated in the plasma samples of 211 unvaccinated infants living under overcrowded conditions in Pune, Maharashtra. IgG antibodies to measles virus, in high titres, were detected in 52.1 per cent and IgM antibodies in 31.3 per cent of the infants studied. Most of the infants with IgM antibodies to measles virus had not suffered from an attack of measles. A history of contact with an older child with overt measles was available for 13.3 per cent of the 211 infants studied. Among these infants with such a contact history, 82.1 per cent had IgM antibodies to measles virus. These observations suggest that many infants studied by us, had experienced subclinical measles infections and many times older children with measles at home or in the neighbourhood might have transmitted such infections.

Antibodies, Viral↗