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Biomedical subjects

B Krishnan

Publications and source records attributed to B Krishnan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Urinary obstruction causes irreversible renal failure by inducing chronic tubulointerstitial nephritis.

Obstruction of urinary tract is a frequent cause of transient renal dysfunction, which, in the majority of cases, is reversible. Urinary obstruction can occasionally cause chronic renal failure, in spite of successful relief of the obstruction. Sonographic and pathologic studies show renal atrophy, interstitial fibrosis, and interstitial inflammation, which explain the loss of renal function. Herein, we report two cases of bilateral obstructive nephropathy due to prostatic hyperplasia, in which renal ultrasound demonstrated hydronephrosis and normal cortical thickness. In both cases, the renal failure persisted even after urinary obstruction was relieved by continuous catheter drainage. Renal biopsy showed that in each case the cause of the irreversible renal failure was chronic tubulointerstitial nephritis. It is concluded that renal biopsy can be of diagnostic, as well as of prognostic value in obstructive nephropathy, especially when relief of the obstruction is not followed by restoration of the renal function.

Aged↗
PubMed1996

Lack of importance of respiratory muscle load in ventilatory regulation during heavy exercise in humans.

1. Seven active subjects (24 +/- 1 years; maximal oxygen uptake (VO2,max), 3.77 +/- 0.2 l min-1; mean +/- S.E.M.) performed constant work rate heavy exercise (CWHE, approximately 80% of maximal incremental work rate) to exhaustion on 2 days, one with (unload) and one without (control) respiratory muscle unloading. 2. With unloading, a special device applied flow-proportional mouth pressure assist (positive with inspiratory (I), negative with expiratory (E) flows) throughout each breath. No pressure assist occurred during control CWHE. To confirm unloading, respiratory muscle pressures (Pmus) were derived (n = 5) from measured pleural pressure and chest wall elastic and resistive pressures. 3. Other than minor differences in early exercise, the temporal course of minute ventilation (VE) was similar in both tests as exercise progressed. The fall in estimated mean alveolar CO2 (PA,CO2) throughout CWHE was identical in both tests. There were no significant differences (ANOVA) in VE, tidal volume, frequency, oxygen consumption rate (VO2), heart rate or PA,CO2, between unload and control CWHE, at matched times (at 50% of control duration and at the end of exercise). Unloading reduced Pmus significantly throughout CWHE; at 50% control duration, peak Pmus,I and Pmus,E fell by 24 and 41%, respectively, with unloading, as did mean Pmus,I and Pmus,E (21 and 44%). 4. The lack of any significant changes in VE, PA,CO2 or breathing pattern, despite a marked reduction in respiratory muscle load throughout CWHE, indicates that the load on the respiratory muscles has only a minor role in the regulation of ventilation during heavy exercise. 5. The absence of improvement in CWHE duration (control, 11.4 +/- 1.2 min; unload, 12.6 +/- 2.1 min, n.s.) with unloading implies that respiratory muscle function does not limit endurance exercise performance during cycling in healthy humans.

Adult↗
PubMed1996

Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism.

BACKGROUND: Previous studies have demonstrated that a moderate dose of ethanol induced a significant increase in the plasma beta-endorphin content of subjects from families with a history of alcoholism (high risk (HR)), but not subjects from families without a history of alcoholism (low risk (LR)). The objective of this study was to examine the response of the pituitary beta-endorphin and adrenal cortisol systems to various concentrations of ethanol in male and female subjects at high and low risk of the future development of alcoholism. METHODS: All subjects participated in four experimental sessions. In each session the subjects were given a drink containing one of the following doses of ethanol: 0, 0.25, 0.50, and 0.75 g of ethanol per kilogram of body weight (for a 60- to 70-kg individual). Blood samples were taken at 0 minutes and at 15, 45, 120, and 180 minutes after the drink for estimation of the blood alcohol, plasma beta-endorphin, and plasma cortisol levels. RESULTS: The concentration of alcohol in the blood at various intervals after the drink was similar among the subjects, regardless of the risk group. Ethanol increased the plasma level of beta-endorphin-related peptides of the HR but not of the LR subjects in a dose-dependent manner. All subjects showed a small decrease in plasma cortisol level with time, but ethanol ingestion did not significantly alter the plasma cortisol levels. CONCLUSION: This study indicates that the pituitary beta-endorphin system, but not the adrenal cortisol system, of the HR subjects shows an enhanced sensitivity to ethanol, which may be an important factor in controlling ethanol consumption.

Adult↗
PubMed1996

Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa.

BACKGROUND & AIMS: Helicobacter pylori is not usually found in areas of intestinal metaplasia. Thus, the development of intestinal metaplasia has been viewed as a mechanism by which the stomach eliminates H. pylori. The aim of this study was to evaluate the frequency of H. pylori adherence to intestinal metaplasia in different populations. METHODS: Mapped gastric biopsy specimens from 378 H. pylori-positive subjects from various geographical regions were examined. Intestinal metaplasia was typed by staining with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue. RESULTS: In 32 patients, H. pylori was found in intimate contact with intestinal metaplasia. This was documented by electron microscopy. All areas of intestinal metaplasia showing adherence contained sulfomucins and had no brush border. Posttreatment biopsy specimens from 4 patients whose infection was not cured showed persistence of H. pylori in intestinal metaplasia. CONCLUSIONS: These patients may have a strain of H. pylori with unusual adhesion characteristics, or their type of intestinal metaplasia may have biochemical properties that make it hospitable for H. pylori. The exclusive association of H. pylori adherence with incomplete intestinal metaplasia (a putative precursor of carcinoma) and its greater frequency in Koreans (a population at risk for gastric cancer) suggest that this phenomenon may play a role in the hypothetical sequence metaplasia > dysplasia > carcinoma.

Bacterial Adhesion↗
PubMed1996

The effect of Yohimbine, an alpha2 adrenergic receptor antagonist, on the growth hormone response to apomorphine in normal subjects.

Yohimbine HCl (16 mg po) administered 30 min before clonidine (CLON) (2 ug/kg infused over 10 min) (N = 5) or apomorphine HCl (Apo) (0.5 mg sc) (N = 10) antagonized the growth hormone (GH) response to CLON but had no effect on the GH response to Apo in normal men. This finding suggests that in humans, alpha2 adrenergic mechanisms do not modulate dopaminergic function, at least not in the hypothalamic-pituitary axis, and that the GH response to Apo is not mediated via an alpha2 adrenergic link.

Adrenergic alpha-Antagonists↗
PubMed1995

Renal neoplasm in acquired cystic kidney disease.

The development of renal cell neoplasms ranging from adenoma to metastatic carcinoma is the most serious complication of acquired cystic kidney disease (ACKD). A comprehensive review of the pertinent literature shows that there is up to 50-fold increased risk of renal cell carcinoma in ACKD compared to the general population. The ACKD-associated renal cell carcinoma is seen predominantly in males, occurs approximately 20 years earlier than in the general population, and is frequently bilateral (9%) and multicentric (50%). Acquired cystic kidney disease-associated renal cell carcinoma is frequently asymptomatic (86%), but may be associated with bleeding, abrupt changes in hematocrit, fever, and flank pain or rarely with hypoglycemia, hypercalcemia, or metastases at presentation. Computed tomography seems to provide a better diagnostic yield than sonography or magnetic resonance imaging; nevertheless, large (up to 8 cm) tumors not visualized by any imaging techniques have been reported. It is generally agreed that there is a need for regular screening of symptomatic ACKD patients for early detection of renal cell carcinoma; however, whether screening is needed for asymptomatic patients remains controversial. Nephrectomy is indicated for tumors larger than 3 cm. Management for tumors smaller than 3 cm with persistent symptoms, such as back pain or hematuria, remains controversial, but nephrectomy may be recommended since many of these tumors turn out to be unequivocal renal cell carcinoma. Asymptomatic tumors smaller than 3 cm should be serially screened, and tumor enlargement may be an indication for nephrectomy. Acquired cystic kidney disease-associated renal cell carcinoma accounts for approximately 2% of deaths in renal transplant patients. A median length of survival of approximately 14 months and a 5-year survival rate of 35% are comparable to the same data for renal cell carcinoma in the general population. Successful renal transplant probably decreases the risk of renal cell carcinoma in ACKD patients, but this preliminary observation needs confirmation. The development of ACKD-associated renal carcinoma is a continuous process with evolving phenotypic expression, including damaged renal tubule, simple cyst, cyst with atypical lining, adenoma, and, finally, carcinoma. The pathogenesis of this continuous process is not entirely known, but growth factor-induced compensatory growth of tubular epithelium initiated by the changes of end-stage kidney disease, and probably perpetuated by activation of proto-oncogenes, seems to be the most significant factor.

Adult↗
PubMed1995

Cadmium accumulation in follicular fluid of women in in vitro fertilization-embryo transfer is higher in smokers.

OBJECTIVE: To assess cadmium, a heavy metal in cigarette tobacco, in follicular fluid (FF) of women in IVF-ET, who smoke. DESIGN: Controlled clinical study. SETTING: Infertile patients in a hospital IVF-ET program. PATIENTS: Fifty-one women selected in groups according to smoking habits: nonsmokers (n = 10), passive smokers (n = 17), light smokers (< 15 cigarettes per day, n = 19), and heavy smokers (> or = 15 cigarettes per day, n = 5). INTERVENTIONS: Ovarian hyperstimulation with GnRH agonist. RESULTS: The mean +/- SEM level of FF cadmium was higher in smokers (7.93 +/- 0.16 ng/mL) than in nonsmokers (6.73 +/- 0.31 ng/mL), and with a dose-effect of smoking. The individual levels in passive, light, and heavy smoking women also were higher than in nonsmoking women. CONCLUSIONS: Despite lack of vascularization of the follicle, cadmium accumulation was detectable in FF. Cadmium also could accumulate in oocytes of smokers; it does so, in a dose-dependent manner, in oocytes of cadmium-treated rats. Access to cadmium and other contaminants of cigarette smoke in FF may compromise the quality of oocytes, becoming a risk factor.

Adult↗
PubMed1995

Inspiratory muscle weakness in chronic heart failure: role of nutrition and electrolyte status and systemic myopathy.

Inspiratory muscle weakness has been demonstrated in ambulatory, stable chronic heart failure (CHF) and may contribute to dyspnea during daily living. However, the mechanisms underlying this weakness are unknown. Malnutrition and electrolyte depletion are recognized complications of CHF that may impair skeletal muscle function, and limb muscle weakness and myopathic changes have also been demonstrated in CHF. We examined whether nutrition and electrolyte status contribute to the reduced skeletal muscle strength and whether inspiratory muscle weakness in CHF is part of general skeletal muscle weakness. We measured maximum inspiratory and expiratory mouth pressures as indices of respiratory muscle strength, maximum hand-grip strength as an index of limb muscle strength, anthropometric indices, serum albumin, and total lymphocyte count as indices of nutritional status, and serum electrolytes in 15 stable patients with chronic cardiac pump failure who had no evidence of primary lung disease, and in 15 age-and-sex-matched healthy controls. As compared with the matched controls, the CHF patients had reduced inspiratory muscle strength (p < 0.0025), but their expiratory and limb muscle strength were not significantly reduced. CHF patients were not malnourished; they were heavier than matched controls because of increased body fat (p < 0.05). Serum sodium was significantly lower in the CHF patients than in the controls (p < 0.01), but was within the normal range in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Phenotypic and functional changes in peripheral blood monocytes during progression of human immunodeficiency virus infection. Effects of soluble immune complexes, cytokines, subcellular particulates from apoptotic cells, and HIV-1-encoded proteins on monocytes phagocytic function, oxidative burst, transendothelial migration, and cell surface phenotype.

We postulated that changes in the cell surface display of molecules that facilitate cell-cell and cell-matrix adhesions may reflect the changing immunosurveillance capacity of blood monocytes during progression of human immunodeficiency virus (HIV) infections. In Centers for Disease Control (CDC) stage A patients, whose monocytes' ability to phagocytose bacteria and generate reactive oxygen intermediates is often increased, the frequency of monocytes expressing CD49d, HLA-DP, HLA-DQ, and an activation epitope of CD11a/CD18 was increased and monocyte transendothelial migration was unimpaired. In CDC stage B/C patients, whose monocytes' ability to phagocytose bacteria and migrate across confluent endothelial monolayers was diminished, surface expression of CD49e and CD62L and the percentage of monocytes expressing CD18, CD11a, CD29, CD49e, CD54, CD58, CD31, and HLA-I were significantly decreased. Incubating normal donor monocytes with immune complexes in vitro reproduced the phenotypic and functional abnormalities seen in stage B/C patients. By contrast, in vitro stimulation with subcellular particulates released by apoptotic lymphocytes reproduced changes seen in stage A patients' monocytes. Although circulating monocytes appear to be activated at all stages, these data suggest that the high levels of circulating immune complexes, found predominantly in the later stages of HIV infection, may be particularly instrumental in reducing the monocyte's capacity to maintain surveillance against infection.

Antigen-Antibody Complex↗
PubMed1995

Induction of senescent cell-derived inhibitor of DNA synthesis gene, SDI1, in hepatoblastoma (HepG2) cells arrested in the G2-phase of the cell cycle by 9-nitrocamptothecin.

BACKGROUND: Recent studies have demonstrated that the plant-derived alkaloid camptothecin (CPT) and its derivative, 9-nitro-CPT (9NC), are cytotoxic in tumorigenic cells but cytostatic in nontumorigenic cells in vitro and in vivo. Also, CPT induces differentiation of human leukemia cells in vitro along specific lineages. In this study, we have investigated the effects of 9NC on nontumorigenic HepG2 cells derived from human hepatoblastoma. A newly discovered senescent cell-derived inhibitor (SDI1) plays a critical role in the cell cycle, so we evaluated the effect of 9NC on the expression of the SDI1 gene. EXPERIMENTAL DESIGN: The effects of 9NC on HepG2 cells were evaluated by monitoring DNA synthesis, morphologic and ultrastructural changes of cells, and perturbation in the cell cycle and by assessing the levels of p53 protein and SDI1 mRNA. RESULTS: Treatment of HepG2 cells with 9NC results in a dose-dependent inhibition of cell proliferation and DNA synthesis. Flow cytometric analysis of DNA content showed that 9NC-treated HepG2 cells are arrested in the G2-phase of the cell cycle. Light and electron microscopic examination revealed that 9NC at low concentrations induces morphologic and growth features that resemble properties highly differentiated or senescent cells, i.e., increased cell size and decreased nuclear/cytoplasmic ratio, as well as enlarged numbers of lysosomes, mitochondria, and lipid in the cytoplasm. No significant alteration in the p53 protein level was noted in 9NC-treated cells. In contrast to untreated, logarithmically grown HepG2 cells, 9NC-treated cells arrested at the G2-phase of the cell cycle and contained increased levels of SDI1 mRNA. Kinetic studies revealed gradual increases in SDI1 mRNA synthesis. CONCLUSIONS: Induction of SDI1 mRNA by 9NC represents the first documentation that the SDI1 gene can be overexpressed in the G2-phase of the cell cycle and provides a valuable cell culture system to dissect the events controlling the G2 checkpoint. In addition, this finding corroborates the hypothesis that genes up-regulated in senescent cells can also be induced in tumor-derived immortalized cells.

Antineoplastic Agents↗
PubMed1994

Differential ventilatory control during constant work rate and incremental exercise.

The purpose of this study was to determine whether the tachypneic breathing pattern of constant work rate, heavy exercise (CWE) is unique to CWE or whether it represents the usual pattern of the respiratory control system at high levels of ventilation (VI). We compared breathing pattern in ten healthy subjects (age 20-29 years) during CWE and maximal incremental exercise (MIE) on a bicycle ergometer. Work rate was constant at 76% of maximum work rate in CWE and progressively increased by 25 watts/minute until exhaustion during MIE. Breathing pattern was examined at matched levels of VI equivalent to 80% and about 100% of maximum VI during CWE (97.1 and 121.4 L.min-1, respectively). Exercise duration (mean+standard deviation) was 13 +/- 6 and 12 +/- 1 min during CWE and MIE, respectively (P = NS). Tidal volume (VT) fell by an average of 0.20 L towards the end of CWE, but was maintained relatively high and constant towards the end of MIE. At high, but not lower, matched levels of VI breathing pattern during CWE was significantly more rapid and shallow than that during MIE. The tachypnoea of CWE did not correlate with the progressive rise in VI, oxygen uptake or cardiac frequency during CWE. We conclude that (1) CWE is associated with a tachypneic influence that is absent or less during incremental exercise; this tachypnea is most marked at the end of CWE. (2) The tachypnoea of CWE is not part of a generalized rate accelerating process during CWE. The mechanism(s) underlying the tachypnoea are unclear but it may be related to inspiratory muscle fatigue, pulmonary oedema, and/or altered respiratory mechanics.

Adult↗
PubMed1994

Glial cell nuclear hypertrophy in complex partial seizures.

The white matter of resected temporal lobes from patients with intractable complex partial seizures shows increased cellularity which appears to be related to glia and neurons. This study, using quantitative methods, defines an increase in glial cell numbers and a significant increase in glial nuclear size within a defined area of white matter in the lateral temporal lobe. Evaluation was made on specimens from ten patients with complex partial seizures compared with two patients with non-epileptic brain lesions and five autopsy patients with no neurologic disease. The importance of recognizing these alterations in glia and the possible relevance to the pathoetiology of epilepsy are discussed.

Adolescent↗
PubMed1994

Prolonged penile erections induced by hydroxyzine: possible mechanism of action.

We describe a subject who developed prolonged penile erections on hydroxyzine. Molecular modelling showed that the hydroxyzine metabolite, norchlorcyclizine, has structural and conformational similarities to the trazodone metabolite, m-chlorophenylpiperazine. This suggests that a common pharmacological mechanism may underlie the ability of trazodone and hydroxyzine to induce erections.

Adult↗
PubMed1993

Resolution of chlorpromazine-induced cutaneous pigmentation following substitution with levomepromazine or other neuroleptics.

Eleven chronic schizophrenic patients with abnormal skin pigmentation associated with neuroleptic treatment were withdrawn from chlorpromazine (CPZ), which was replaced by levomepromazine (n = 4), trifluoperazine (n = 1) or thioproperazine (n = 1) as the sole neuroleptic, by a combination of these phenothiazines (n = 4) or with haloperidol plus pipotiazine (n = 1). Seven patients showed complete resolution of abnormal skin pigmentation over a period of 1-5 years and 4 markedly improved over 2.0-2.6 years of follow-up. Our observations suggest that neuroleptic-induced abnormal skin pigmentation is (i) predominantly, if not exclusively, a side effect of CPZ and (ii) reversible, providing that CPZ is withdrawn and sufficient time is allowed to elapse.

Adult↗
PubMed1993

Effect of scopolamine on spontaneous yawning in men.

The effect of scopolamine hydrobromide (0.4 mg s.c.) on spontaneous yawning was studied in 16 male volunteers in a double-blind study. Scopolamine (or placebo) was given 60 min before (-60 min) placebo (physiological saline s.c.) (time 0 min) and yawning monitored from -15 to +60 min by recording displacement of the lower jaw and storing the traces on diskettes. After placebo, the number of yawns was 5.3 +/- 1.4 (means +/- SE) and after scopolamine pretreatment 4.3 +/- 1.6 (p = NS). Drowsiness was assessed with the Stanford Sleepiness Scale and the Analog Sleepiness Scale at -15, 0, +20, +40, +60 min. There was no significant correlation between total sleepiness scores (area under the curve, 0 min to +60 min), peak sleepiness score or peak increment in sleepiness score and number of yawns on either scale. These data suggest that (a) spontaneous yawning in man is not mediated by a central muscarinic cholinergic link, and (b) the assumed relationship between drowsiness and yawning remains to be verified experimentally.

Adult↗
PubMed1993

Replacement of chlorpromazine with other neuroleptics: effect on abnormal skin pigmentation and ocular changes.

This paper describes the outcome of 15 patients with chlorpromazine (CPZ)-induced abnormal skin pigmentation (ASP) in whom CPZ was replaced with other neuroleptics for three to 13 years. Complete resolution of ASP occurred over a period of six months to five years following substitution with haloperidol (four patients), levomepromazine (three patients), trifluoperazine (one patient), thioproperazine (one patient) as the sole neuroleptic, by a combination of two of the three phenothiazines (four patients) or haloperidol plus pipotiazine (one patient). Resolution was maintained during the remainder of the follow-up period. In one patient, at final follow-up, marked improvement was present three years after CPZ was replaced with levomepromazine. Bilateral lenticular pigmentary deposits persisted in all eight patients examined 3.3 to 13 years after replacing CPZ and less than three months to nine years after resolution of ASP; improvement was noted in only one of these patients. Bilateral endothelial corneal deposits, present in five patients while on CPZ therapy, had disappeared in two patients seven and 13 years, respectively, after replacing CPZ; improvement was noted in two other patients. These findings indicate that: 1. CPZ-induced ASP is completely reversible in most, if not all, patients if CPZ is withdrawn; 2. a variety of neuroleptics including other phenothiazines can be used to replace CPZ without risk of re-emergence of ASP; 3. CPZ-induced lenticular changes persist whereas corneal changes may resolve slowly over a period of many years following replacement of CPZ; 4. ASP and ocular changes induced by CPZ may be subserved by two different pathophysiological mechanisms.

Adult↗
PubMed1992

Aluminum-binding serum proteins: desferrioxamine alters serum aluminum speciation.

The aluminum content of four size classes of protein (high and low molecular weight, transferrin/albumin and a fraction provisionally termed albindin) in sera from healthy volunteers (group I) and from aluminum workers with normal (group II) and high (group III) total serum aluminum was compared using size exclusion chromatography and electrothermal atomic absorption spectroscopy. In the absence of any drug treatment the transferrin/albumin fraction was the major carrier, containing 29% to 33% of the aluminum recovered, in all three subject groups. Desferrioxamine treatment of groups II and III significantly decreased the proportion of aluminum bound by albumin/transferrin (P less than 0.05 in group III) and increased that bound by albindin (P less than 0.05 in groups II and III). The albindin fraction contained over 40% of the aluminum recovered from sera of group III subjects during desferrioxamine treatment. We conclude that the albindin fraction contains a protein or proteins that can form stable complexes with aluminum which may be important in preventing aluminum toxicity.

Adult↗