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Biomedical subjects

A Shetty

Publications and source records attributed to A Shetty.

At least 37 records · Page 2Linked to original sources
PubMed2000

Liver transplantation improves cirrhosis-associated impaired oral glucose tolerance.

BACKGROUND: Thirty-five percent to 80% of cirrhotic patients have impaired glucose tolerance (IGT) or diabetes mellitus (DM). Diabetic cirrhotics have higher morbidity and mortality than nondiabetics. Therefore, it would be worthwhile to determine whether liver transplantation improves glucose homeostasis in these patients. METHOD: A total of 26 patients awaiting liver transplantation were evaluated for impaired glucose homeostasis by fasting blood glucose and/or oral glucose tolerance tests (OGTT). Five patients underwent transplant surgery within 1 year of OGTT and had a repeat OGTT 3-6 months after transplantation. RESULTS: Sixty-five percent (17/26) of the patients had abnormal glucose homeostasis. Twenty-three percent (6/26) met American Diabetes Association criteria for DM, and another 42.3% (11/26) had IGT. All patients had normal HbA1C levels. After transplantation, the 2-hr blood glucose improved in four patients and the mean 2-hr glucose level was reduced (204 +/- 94 vs. 132 +/- 53 mg/dl [mean +/- SD, P=0.051]). CONCLUSION: Liver transplantation can reverse cirrhosis-associated impaired glucose tolerance.

Adult↗
PubMed2000

Effect of IL-5, glucocorticoid, and Fas ligation on Bcl-2 homologue expression and caspase activation in circulating human eosinophils.

IL-5 is a potent eosinophil viability-enhancing factor that has been strongly implicated in the pathogenesis of IgE-mediated inflammation in vivo. Recently published data have suggested that IL-5 (and related cytokines) may act by altering the expression of the anti-apoptotic regulator Bcl-2 or its homologues, but this is controversial. The behaviour of the recently described pro-apoptotic cysteine proteases (caspases) in eosinophils after IL-5 treatment has not been explored. We examined the effect of IL-5 on the expression of four major Bcl-2 homologues, as well as on the expression/activation of key members of the caspase cell death cascade in cultured circulating human eosinophils. The effect of relevant inducers of eosinophil apoptosis (glucocorticoid and Fas ligation) on these regulatory proteins was also examined. We observed baseline expression of the anti-apoptotic Mcl-1 and pro-apoptotic Bax proteins in immunoblots of eosinophil lysates, but not Bcl-x, Bcl-2. IL-5 treatment had the effect of maintaining this basal level of expression over time without altering the balance of Bcl-2 homologues. The (upstream) caspase 8 and (downstream) caspase 3 proenzymes were detected in eosinophils at baseline, and were processed during spontaneous and stimulated eosinophil death. IL-5 completely blocked caspase processing in spontaneous and dexamethasone-induced cell death, and significantly slowed processing during Fas ligation. Our data do not support the theory that IL-5 acts by altering the balance of anti-apoptotic and pro-apoptotic Bcl-2 homologues, but suggest that it may act by regulating activation of the caspase cell death cascade.

Apoptosis↗
PubMed1999

Renal failure and multiple myeloma: pathogenesis and treatment of renal failure and management of underlying myeloma.

Renal impairment is a common complication of multiple myeloma occuring in 50% of patients at some stage in their disease. Pathogenesis is multifactorial. Nephrotoxic manifestations of monoclonal immunoglobulin overexpression include the 'myeloma kidney', light chain deposition disease, AL amyloid, plasma cell infiltration and glomerulonephritis. Other factors, such as hypercalcaemia, hyperuricaemia, infection, hyperviscocity and nephrotoxic drugs can precipitate or exacerbate acute and chronic renal failure. Aggressive treatment has dramatically improved outcome in patients who present with acute or acute-on-chronic renal failure. Dialysis has become an accepted treatment acutely and in end stage renal disease due to myeloma. Conventional therapy with melphalan and prednisolone is still advocated for elderly patients. However, renal failure is not a contraindication to aggressive cytoreduction, stem cell collection, double hemibody radiotherapy and autologous transplantation in those otherwise fit to tolerate these procedures. Prognosis is primarily determined by the response of the myeloma clone to chemotherapy. Outcome in chemosensitive patients approaches that of patients with equivalent disease stage without renal dysfunction.

Humans↗
PubMed1997

Long-term clinical results and quality of life after insertion of a self-expanding flexible endourethral prosthesis.

OBJECTIVE: To evaluate the safety and efficacy of the Urolume self-expanding flexible endourethral stent, based on a long-term follow-up, and to determine its role amongst the various modalities of treatment available for the relief of bladder outlet obstruction (BOO) arising from benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: From January 1991 to April 1992, the Urolume wallstent (American Medical Systems, USA) was placed successfully in each of 62 patients (aged 50-89 years) who had significant subjective and objective evidence of BOO. The stent was placed as a daycase procedure under general anaesthesia. Pre-operatively, each patient was assessed fully in an out-patient clinic by symptoms, a flow rate measurement and a rectal examination. Post-operatively, patients were assessed using transrectal ultrasonography, cystoscopy, symptoms and flow rate measurement, and after 5 years, the International Prostate Symptom Score and satisfaction score were obtained. RESULTS: After 5 years, 27 (39%) patients survived and 10 (14%) died with their Urolume stent intact; 22 (32%) completed the follow-up and five refused or were lost to follow-up. Day and night-time frequencies and flow rates improved continuously. Complete epithelialization occurred in 16 of the 22 patients assessed. Of those in whom the Urolume was removed, 20 are alive and five dead. CONCLUSION: The effectiveness of the Urolume in improving symptoms and flow rates in patients with BPH was confirmed. However, the high failure rate arose largely from inexperience in selection and deployment. There are no absolute criteria to predict a successful outcome. This study confirms the Urolume as a safe device. Most patients whose symptoms settled in the first year maintained a good flow rate and a significant improvement in symptoms for 5 years; their quality of life at the last follow-up was good.

Aged↗
PubMed1996

Hypotension on continuous ambulatory peritoneal dialysis.

Hypotension in patients on CAPD is almost an unexplored area in the literature. This retrospective analysis of 525 patients treated at the Toronto Hospital. Toronto over the last five years, of whom 65 were hypotensive, describes the possible causes of hypotension, the response to treatment, morbidity and mortality rates. The incidence of hypotension was 12% in our CAPD population. The mean age of these patients was 58 +/- 17 years with a male to female ratio of 1.25:1. The distribution of various comorbid conditions such as, insulin-dependent diabetes mellitus, neoplasia coronary/cerebro/peripheral vascular diseases was similar to nonhypotensive patients. There was a higher proportion of malignancies, noninsulin-dependent diabetes mellitus and chronic obstructive pulmonary disease (CAPD) in hypotensive group. Hypotension was attributed to hypovolemia in 16 (25%), heart failure in 15 (23%) and antihypertensive medications in 12 (18%) patients. In 26 (34%) patients the exact cause of hypotension was unclear. Five patients had malignancies and 4 had severe autonomic neuropathy. Among 16 hypovolemic patients, 14 responded to volume expansion and 2 did not because of concurrent administration of coronary vasodilators. Seven out of 12 patients with hypotension due to antihypertensive medications improved. In 3 patients, blood pressure increased marginally after stopping the drugs and 2 remained hypotensive because of continuation of the drugs. Of the patients with heart failure, 40% (6/15) responded to a decrease to the target weight. Two patients treated with captopril did not respond. Of the patients from the unknown category, 50% (13/26) improved. One out of 4 patients treated with midodrine responded. The mortality rate was higher among hypotensive patients than among the nonhypotensives on CAPD.

Adult↗
PubMed1996

Successful use of continuous ambulatory peritoneal dialysis in octogenarians.

Clinical data and outcomes of 18 patients, aged 80 or older, on continuous ambulatory peritoneal dialysis (CAPD) during the last five years were reviewed. There were 12 males and 6 females, with a mean age of 85 (range 82-91 years) and median duration on CAPD of 31.5 months (range 2-58 months). End-stage renal disease was caused by nephrosclerosis in 9, diabetes mellitus and light chain disease in 2 each, and chronic glomerulonephritis, membranous nephropathy, and IgA nephropathy in 1 each, with the cause unknown in yet another 2 patients. Hypertension and angina were the commonest comorbid conditions observed. Peritonitis episodes occurred one per 10.8 patient-months, and necessitated catheter removal in 7 patients and reinsertion in 6 of them. Fourteen episodes of exit-site infections were seen in 8 patients, 2 developed pericatheter leak, and 1 had tunnel infection. Nine patients are continuing CAPD successfully, with a median duration of 29 months (range 11-57 months). One patient was transferred to hemodialysis, and 8 died. The causes of death were peritonitis (3/8), cerebrovascular accident (2/8), pneumonia (1/8), and septicemia (1/8), with the cause not known in 1 patient. Our survival rate of 80% at three years is encouraging, and we advocate CAPD as a successful alternative treatment modality in octogenarians.

Aged↗
PubMed1995

Hypotension in CAPD: role of volume and sodium depletion.

The prevalence of hypotension in continuous ambulatory peritoneal dialysis (CAPD) patients varies between 10% and 16%. The main causes of hypotension in these patients include hypovolemia, antihypertensive medications, myocardial failure, and a variety of poorly understood causes, viz, severe autonomic neuropathy, amyloidosis, malignancies, adrenal insufficiency, removal of vasopressor substances by dialysis and steroid withdrawal. In addition, there are a large number of patients with hypotension due to unknown causes. Between 1989 and 1994 we had 65 of 525 CAPD patients suffering from persistent hypotension. Sixteen (25%) patients were hypovolemic, 14 improved after increasing the target weight, but 2 did not because of concurrent administration of coronary vasodilators. The various steps in the treatment of this group include fluid repletion after discontinuing anti-hypertensive medications and excluding myocardial failure, oral sodium supplementation and possibly increasing the dialysate sodium. Preventive measures include frequent assessment of the hydration status. Judicious use of diuretics is also important. Bioelectrical impedance and inferior vena caval ultrasound are two promising tools to assess the fluid status and supplement careful clinical examination.

Blood Volume↗
PubMed1995

Discrepancy between weekly KT/V and weekly creatinine clearance in patients on CAPD.

Currently, weekly KT/V and weekly creatinine clearance (WCC) are used to quantitate continuous ambulatory peritoneal dialysis (CAPD), the minimum recommended requirements being 1.7/week and 50 L/week, respectively. There is no substantial evidence that one index is better than the other, and there is no clear recommendation what one should do if there is a discrepancy between these two values. We performed a cross sectional analysis of 68 patients in whom we measured weekly KT/V, WCC, residual clearances, and a 4-hr peritoneal equilibration test (PET). The correlation between KT/V and WCC in the whole group was highly significant (p < 0.0001); when patients were divided in the four PET groups, there was a significant correlation (p < 0.05) in the low-average (n = 22) and high-average (n = 21) PET groups, but the correlation was not significant in the high (n = 13) and low (n = 12) PET groups. Fourteen of 68 patients (20%) showed a discrepancy between KT/V and WCC: 7 patients had a KT/V < 1.7 and WCC > or = 50 (group 1), and 7 patients had a KT/V > or = 1.7 and WCC < 50 (group 2). Those in group 1 with a WCC > 50 had a higher residual renal function (0.82 vs 0.11 mL/min, p < 0.05) than those in group 2 and therefore had a higher tubular secretion of creatinine and reabsorption of urea. Those in group 2 with a KT/V > 1.7 had lower creatinine equilibration than those in group 1 (D/Pcr 0.56 vs 0.75, p < 0.05) and therefore a better removal of urea than creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B.

Human neutrophils are highly responsive to the chemokine interleukin-8 (IL-8) owing to high levels of expression of two related receptors encoded by the single copy genes il8ra and il8rb located on chromosome 2q34-q35. To identify nuclear factors that regulate the expression of IL-8 receptors, we have first defined the organization of both genes and characterized their functional promoters. il8ra and il8rb span approximately 4 and 12 kilobase pairs of genomic DNA, respectively. In both cases, the open reading frame resides on a single exon. In contrast, the 5'-untranslated regions are more complex. For il8ra, it is formed from two exons, whereas for il8rb, seven distinct neutrophil mRNAs are formed by alternative splicing of 11 exons. One of the splice variants, designated IL8RB3, is the predominant form for il8rb. Two equally abundant mRNAs for il8ra, 2.0 and 2.4 kilobases in length, are expressed in neutrophils and arise from usage of two alternative polyadenylation signals. Primer extension analysis identified two major transcription start points for il8ra and 11 for il8rb. Regions extending 300 base pairs (bp) upstream from exon 1 of il8ra and 81 bp upstream from exon 3 of il8rb have limited sequence similarity but had strong constitutive promoter activity when cloned upstream from a chloramphenicol acetyltransferase-encoding reporter gene and transiently transfected into surrogate myeloid (HL-60, and U-937) and lymphoid (Jurkat) cell lines. Neither of these regions has sequences corresponding to classic promoter elements. In contrast, a region 643 base pairs upstream from exon 1 of il8rb had relatively low levels of constitutive promoter activity in all three cell environments, and a conserved TATA element is located 47 bp upstream of the 5'-end of exon 1. Thus, despite marked differences in the complexity of their genomic organization, il8ra and il8rb encode products that are similar in structure, function, and the major cell type of expression.

Base Sequence↗
PubMed1994

Penetrating atherosclerotic ulcers of the aorta.

PURPOSE: This study investigates the natural history and optimal imaging modality of penetrating atherosclerotic ulcers of the aorta. METHODS: We reviewed our experience with 29 penetrating ulcers in 18 patients. Computed tomography (17 patients), magnetic resonance imaging (nine patients), and aortography (five patients) were used for diagnosis and follow-up. Patients were typically elderly (average age 74 years) and had hypertension and coronary artery disease. Ulcers were most common in the distal descending thoracic aorta (31%) and were characterized by a discrete ulcer crater (100%) and thickened aortic wall (89%). Modes of presentation included chest or back pain in four patients, distal embolization in two patients, and abnormal chest radiography results in one; the remaining were incidental findings. RESULTS: Follow-up was available in ten patients with 17 ulcers from 1 to 7 years. Recurrent pain occurred in two patients, recurrent embolization occurred in one patient, and seven patients remained symptom free. Progression to saccular pseudoaneurysm occurred in five ulcers, and fusiform aneurysm occurred in two ulcers. Two ulcers were associated with an increase in aortic diameter, and nine ulcers did not change. There were no cases of aortic dissection or rupture in the follow-up period. There were no deaths and only one patient underwent resection. CONCLUSION: The natural history of penetrating atherosclerotic ulcers is one of progressive aortic enlargement, with saccular and fusiform aneurysms the result if follow-up is sufficient. Aortic dissection, aortic rupture, and embolization can also occur but are less common. Contrast-enhanced computed tomography is the primary imaging modality.

Aged↗
PubMed1989

Disruption of stromal niches by diffusible factors in the conditioned media of leukemic cell-lines and sera of chronic myelogenous leukemia patients.

The bone-marrow microenvironment has a decisive role in maintaining haemopoietic stem cells and regulating their differentiation. In diseases of the haemopoietic system, viz. anaemias and leukemias, the microenvironment has been shown to play a key role. In this paper we show that leukemic cell conditioned medium and sera from CML patients, interact with the in vitro bone-marrow environment and bring about changes which affect the maintenance of normal stem cells.

Animals↗
PubMed1988

Sodium NMR imaging of lung water in rats.

Coronal proton and sodium images of control rats and rats with either increased permeability edema produced by intravenous alloxan (300 mg/kg) or increased pressure edema produced by saline infusion (2 ml/min) were obtained. Axial chest CT images were used to monitor the development of pulmonary edema. Immediately after the imaging session compartmental lung water was measured gravimetrically. The sodium and proton imagings were done sequentially in a 31-cm-bore 1.9-T magnet without moving the animal. The anatomical boundaries of the lung on the proton images were transferred to the sodium images for calculation of the average sodium signal intensity which was determined by extrapolating the mean values from five echoes to time zero. The sodium signal intensity was correlated (r = 0.7) with the total water fraction. There was poor correlation (r = 0.56) with the extravascular water due to confounding by the sodium vascular signal.

Animals↗
PubMed1988

Experimental radiation injury: combined MR imaging and spectroscopy.

A model of radiation injury to the brain was developed in the cat. Definite radiation changes were demonstrated at magnetic resonance (MR) imaging in four of six cats. These changes consisted of high-intensity abnormalities on images obtained with a long repetition time (TR) and a long echo time (TE), which were initially noted 208-285 days after irradiation. These changes were associated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement on short TR and inversion-recovery (IR) pulse sequences. Gd-DTPA enhancement and the high intensity on the long TR/TE images were identified at the same time and became more prominent throughout the study. Chemical-shift imaging and phosphorus spectroscopy demonstrated no notable changes despite clear-cut MR evidence of abnormalities. Sodium imaging was positive in one case. Correlation of MR and pathologic findings revealed areas of radiation necrosis and wallerian degeneration that corresponded to areas of Gd-DTPA enhancement on short TR and IR images and to areas of high intensity on long TR/TE images. Peripheral to the areas of Gd-DTPA enhancement were nonenhanced zones of high-signal-intensity abnormality on long TR/TE images, which represented regions of demyelination without necrosis. Gd-DTPA-enhanced proton imaging was the most sensitive method for detecting radiation damage in this animal model.

Animals↗