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Biomedical subjects

K Phadke

Publications and source records attributed to K Phadke.

At least 19 recordsLinked to original sources
PubMed2000

Use of nitric oxide inhalation in chronic obstructive pulmonary disease.

BACKGROUND: Inhalation of nitric oxide with oxygen could be a promising treatment in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension. However, the current methods of delivery of NO are cumbersome and unsuitable for long term use. The present study was undertaken to investigate the safety and efficacy of a mixture of nitric oxide (NO) and oxygen administered via a nasal cannula for 24 hours in patients with oxygen dependent COPD. METHODS: Twenty five parts per million (ppm) of NO was administered by inhalation combined with supplemental oxygen at a flow rate of 2 l/min via a nasal cannula for 24 hours to 11 ambulatory men with stable, oxygen dependent COPD. Room air with supplemental oxygen at 2 l/min was administered in an identical manner for another 24 hours as control therapy in a randomised, double blind, crossover fashion to all patients. Pulmonary function tests, exercise tolerance, dyspnoea grade, and lung volumes were measured at baseline, 24, and 48 hours. Pulmonary artery pressure (PAP), cardiac output (CO), pulmonary vascular resistance (PVR), arterial blood gas tensions, and minute ventilation were measured at baseline, after 30 minutes and 24 hours of breathing NO and oxygen. Venous admixture ratio (Qs/Qt) and dead space ratio (Vd/Vt) were also calculated. Concentrations of nitrogen dioxide (NO(2)) and NO in the inhaled and ambient air were monitored continuously. Differences in pulmonary function, arterial blood gas tensions, pulmonary haemodynamics, exercise tolerance, and dyspnoea between oxygen and NO breathing periods were analysed for significance using paired t tests. RESULTS: A significant (p<0.05) fall was observed in PVR (183.1 (116.05) and 137.2 (108.4) dynes.s.cm(-3) before and after breathing NO for 24 hours, respectively) with NO administration without significant changes in symptoms, pulmonary function, arterial oxygen tension, or exercise tolerance. CONCLUSIONS: NO at a concentration of 25 ppm blended with oxygen can be safely administered by nasal cannula for 24 hours without significant adverse effects and lowers PVR in stable patients with COPD receiving long term oxygen therapy.

Administration, Inhalation↗
PubMed1998

Cyclosporine experience in nephrotic syndrome.

OBJECTIVE: To analyze the use of Cyclosporine (CyA) in nephrotic syndrome. METHODS: Thirty five children of mean age of 5.9 years with steroid dependent (n = 26) or steroid resistant (n = 9) primary nephrotic syndrome with normal renal functions and who received CyA were studied. CyA was used at a dosage of 6-7 mg/kg/day orally in two divided doses. The mean duration of therapy was 9.6 weeks. All received a minimum of 8 weeks of CyA therapy. In a few who received longer therapy, the dose was reduced to 4 mg/kg/day. All patients were monitored serially for hepatotoxicity and nephrotoxicity. The nephrotic state was evaluated serially with biochemical tests and followed up for a mean period of 2.55 years. RESULTS: Thirty one patients completed the study. The response to therapy was categorized into 5 groups-no response (4 patients), good response (4 patients), partial response (4 patients), cyclosporine dependence (16 patients), and infrequent relapsers (3 patients). Good response was defined as complete remission lasting for at least one year after cessation of therapy. Patients who showed partial response had reduction in quantitative proteinuria and needed less diuretics. Sixteen patients went into complete remission while on therapy but relapsed within 3 months of discontinuation (CyA dependence). The response to CyA correlated more with steroid-responsiveness than with the underlying histopathology. The drug was well tolerated. CONCLUSION: In steroid-dependent or steroid-resistant nephrotic children with normal renal functions, CyA therapy may be considered as one of the possible therapeutic options. Our results suggest that a longer duration of CyA therapy may possibly be indicated in these cases.

Administration, Oral↗
PubMed1998

Pediatric renal transplantation--Indian experience.

OBJECTIVE: To analyze our experience with renal transplantation in children with end-stage renal disease (ESRD) in India. DESIGN: Retrospective study. METHODS: Over the last 7.5 years, 27 renal transplants were performed on children below 12 years of age, 8 children were less than 6 years old, 19 were between 6 and 12 years of age. Sixteen children had underlying glomerular disease while eleven had tubulointerstitial renal disease. Transperitoneal approach was used in smaller recipients weighing less than 12 kg. Extraperitoneal approach was used in the remainder. Triple immunosuppression with Cyclosporine, Azathioprine and Steroids was used in all cases. RESULTS: Follow-up period ranged from 6 months to 7.5 years (mean 3.7 years). There were 10 episodes of acute rejection. Three cases of acute rejection failed to respond to therapy. No surgical complications were encountered. Graft survival was 73.2% at one year and 71% at two years. Satisfactory rehabilitation was achieved in children with functioning grafts. CONCLUSIONS: Renal transplantation in children in India offers an acceptable choice in ESRD as anywhere in the world.

Child↗
PubMed1995

Conditioned media from a cell strain derived from a patient with mastocytosis induces preferential development of cells that possess high affinity IgE receptors and the granule protease phenotype of mature cutaneous mast cells.

We have demonstrated for the first time that a conditioned medium from a human cell strain can induce morphologically mature mast cells that express Fc epsilon RI and three mast cell-specific proteases from normal bone marrow progenitor cells. In contrast, recombinant human Kit ligand induced the differentiation of mast cells that were tryptase-positive but negative for chymase, carboxypeptidase, and Fc epsilon RI. This data indicates that factors other than Kit ligand are critical for inducing the differentiation and maturation of mast cells in the human. The HBM-M cell was originally derived from a patient with mastocytosis. As mastocytosis is thought to represent a reactive hyperplasia rather than a mast cell malignancy, the factor secreted by the HBM-M cell strain could well be responsible for the mast cell hyperplasia seen in some patients with mastocytosis.

Base Sequence↗
PubMed1995

A randomized trial of cimetidine with 5-fluorouracil and folinic acid in metastatic colorectal cancer.

Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant therapy for gastric cancer. We have demonstrated expression of histamine receptors on colon cancer cell lines and inhibition of their growth with cimetidine. Cimetidine also activates suppressor T cells and stimulates cell-mediated immunity. We therefore performed a randomized controlled clinical trial to determine the effect of cimetidine 400 mg given twice daily in conjunction with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized and 35 patients were eligible for further analysis. Both groups were well matched for pre-treatment characteristics. There was no difference in overall response. There was, however, a significantly increased rate of CEA response in the cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA response compared to none of eight in the control. Meaningful comparisons of overall survival cannot yet be made. This study demonstrates that cimetidine has encouraging activity in increasing CEA response in patients with metastatic colorectal cancer treated with chemotherapy. This observation needs to be extended in a larger randomized study, which is currently underway.

Adult↗
PubMed1993

Atenolol or nicardipine alone is as efficacious in stable angina as their combination: a double blind randomised trial.

BACKGROUND: Beta blockers and calcium antagonists are widely used in the management of angina pectoris in the belief that the combination is more efficacious than either drug alone. METHODS: This double blind randomised crossover placebo controlled study compares the effects of nicardipine, atenolol and their combination in 30 patients with chronic stable angina. Each treatment period lasted 6 weeks with dose titration after 3 weeks. Symptom limited treadmill exercise testing and radionuclide ventriculography at rest was carried out at the end of each treatment period. RESULTS: Total exercise duration and time to 1-mm ST-segment depression was significantly prolonged by nicardipine and atenolol when compared to placebo, the combination offered no additional benefit. Time to onset of angina was significantly prolonged by nicardipine and the combination but not by atenolol. Indices of left ventricular function were not significantly affected by any treatment other than an increase in left ventricular end diastolic volume on atenolol and the combination. CONCLUSIONS: Nicardipine and atenolol are equally effective in prolonging exercise duration and time to onset of ischemia in patients with chronic stable angina while the combination appeared to offer no additional benefit. Nicardipine prolonged the time to onset of angina significantly; again there was no further improvement with the combination. Neither drug appears to have an important effect on the parameters of diastolic function studied in patients with chronic stable angina.

Adult↗
PubMed1993

Balloon angioplasty of adult aortic coarctation.

OBJECTIVE: To examine the use of balloon angioplasty in the treatment of native adult aortic coarctation. DESIGN: Haemodynamic and angiographic studies to establish the diagnosis of aortic coarctation were established before carrying out the procedure in all patients. SETTING: All the studies and angiographic procedures were performed in a large district general hospital within the departments of cardiology and radiology. There was careful perioperative monitoring. The mean hospital stay was three days. PATIENTS: 15 adult patients (with clinical, haemodynamic, and angiographic evidence of native aortic coarctation) were considered for this treatment. 13 were offered balloon angioplasty. One was excluded, as there was no significant gradient across the lesion. One patient had complete atresia at the site of the coarctation. INTERVENTIONS: Percutaneous transluminal balloon angioplasty was carried out with balloon catheters diameter 2 mm less than the diameter of the aorta immediately below the left subclavian artery to minimise the possibility of tearing the aortic wall. MAIN OUTCOME MEASURES: Abolition or significant reduction of the preoperative gradient was achieved in all 13 patients treated. Reduction in blood pressure of the upper limb was also achieved in all of the patients. Only four patients required continued antihypertensive treatment. Two patients developed false aneurysms after the procedure and required surgery. No deaths occurred. These results compare favourably with conventional surgery and are much more economical. CONCLUSIONS: Balloon angioplasty could become the first line treatment for all patients with native adult aortic coarctation, but longer term follow up is required to validate this.

Adolescent↗
PubMed1992

Effects of coronary artery bypass surgery and angioplasty on the total ischemic burden: a study of exercise testing and ambulatory ST segment monitoring.

To assess the effects of standard therapeutic interventions on the total ischemic burden, 86 patients with stable angina underwent 48 hours of ambulatory ST segment monitoring and treadmill exercise testing before and at a mean of 10 weeks after coronary artery bypass surgery (CABG) (group 1, N = 46) or percutaneous transluminal coronary angioplasty (PTCA) (group 2, N = 40). There were 72 male and 14 female patients with a mean age of 56.4 years. All patients had documented coronary artery disease (24, single-vessel; 28, two-vessel; 34, three-vessel disease). Both groups were characteristically similar apart from more severe coronary artery disease (p less than 0.001) and more previous myocardial infarctions (p less than 0.05) in group 1. Groups with CABG and PTCA had significant prolongation of exercise time after intervention (group 1: 7.6 to 9.8 minutes, p less than 0.0001; group 2: 8.1 to 10.0 minutes, p less than 0.001), and both interventions led to a significant reduction in ischemic responses (group 1: 33 to 4, p less than 0.001; group 2: 20 to 13, p less than 0.05) to exercise. During a total of 7643 hours of ST segment monitoring, 253 episodes of ischemia were recorded in 3768 hours before and 44 ischemic episodes in 3875 hours after intervention (group 1, 113 episodes in 24 patients and 21 episodes in 10 patients; group 2, 140 episodes in 13 patients and 23 episodes in six patients). Both interventions reduced the mean frequency of ischemia per 24 hours (group 1: 1.24 to 0.22 episodes per 24 hours; p less than 0.01; group 2: 1.9 to 0.3 episodes per 24 hours; p less than 0.05). Almost 28% (N = 24) of resting electrocardiographic findings were altered as a result of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1991

Clinical validation of four solid state ambulatory monitoring devices in detecting shift of the ST segment.

Continuous monitoring for detection of changes in the ST segment during daily life in patients with stable angina has received increasing attention in recent years. Various reports testify to its role in the detection of silent ischaemia, and its potential usefulness in stratification of risk. Frequency modulated recorders, using magnetic tape for recording with subsequent visual analysis, have been previously validated for the detection of such changes. Analysis, however, is time consuming, and is subject to technical faults due to the presence of moving parts. Several new solid state devices have become available in recent years which provide real-time automated analysis, and have theoretically ideal recording capabilities with frequency response down to 0.05 Hz and linear phase integrity which may be as good, or better than, tape based recorders. We compared each of four solid state devices with a previously validated frequency modulated recording device in patients with angina in order to assess whether such devices correlate well in detecting changes in the ST segment.

Angina Pectoris↗
PubMed1988

Interleukin-1-induced alterations in proteoglycan metabolism and matrix assembly.

In cartilage, the large chondroitin sulfate proteoglycan exists as aggregates by interacting with link protein and hyaluronic acid. In diseases associated with cartilage degeneration, the proteoglycan does not aggregate because of a defect in the hyaluronate-binding activity. Since interleukin-1 (IL-1) is a secretory product of activated macrophages and may influence the cartilage function in joints, we studied the effects of IL-1 on the synthesis and assembly of proteoglycan by rabbit articular chondrocytes in culture. IL-1-treated cells showed a modest increase in the total proteoglycan synthesis, but also showed a more pronounced decrease in the incorporation of extracellular matrix. Affinity chromatography of the conditioned media on hyaluronic acid-Sepharose revealed that all of the proteoglycan of control cells strongly bound to hyaluronate. The IL-1-treated medium contained two fractions: one that was strongly bound to the column and a second that did not bind. The results demonstrate that the IL-1-treated cells cannot incorporate proteoglycan into the matrix partly because of a defect in the proteoglycan molecules and partly due to other mechanisms regulating proteoglycan assembly.

Animals↗
PubMed1988

Regulation of cellular and humoral immune responses to collagen type I or collagen type II.

We have investigated the characteristics of antigen-specific reductions in murine immune responses to rat collagen type I (R-CI), chick collagen type II (C-CII) or bovine collagen type II (B-CII). Intravenous pretreatment with the appropriate soluble collagen or collagen-coupled spleen cells led to the development of antigen-specific reduced immune responses, the former treatment being more effective than the latter. In the case of CII, pretreatment with R-CI or non-related antigens was ineffective. However, pretreatment with denatured bovine-CII, native bovine-CII or chick-CII led to immune hyporesponsiveness for either the homologous or heterologous CII molecule. A delayed development of the diminished immune responses was observed for the cell-mediated immune response (CMI), as measured by in vivo delayed-type hypersensitivity (DTH), in that no reduction was evident at Day 7 but a significantly decreased response was observed at Day 14. Collagen-specific IgG and IgM antibody responses were consistently reduced by the pretreatment and remained reduced during the study period. The antigen-specific hyporesponsive state was not sensitive to cyclophosphamide treatment and was not transferable with hyporesponsive spleen cells. Additionally, we have induced unresponsiveness to CII by treating mice with an antibody directed to T helper cells (GK1.5). This treatment led to profound reductions in CII CMI responses as well as CII antibody levels. However, this unresponsive state is not permanent and not transferable with spleen cells from treated mice. These two types of procedures, soluble B-CII i.v. or GK1.5 treatment, not only resulted in CII hyporesponsive states, but also produced delayed onset and decreased incidence of arthritis in the appropriate strains.

Animals↗
PubMed1987

Fibroblast growth factor enhances the interleukin-1-mediated chondrocytic protease release.

The unfractionated macrophage-conditioned medium stimulates the chondrocytes to produce high levels of proteases. Purified IL-1 preparations exhibit significantly lower activity towards chondrocytes. This IL-1 mediated effect can be enhanced in presence of fibroblast growth factor, suggesting that other factors may collaborate with IL-1, in events leading to the cartilage destruction in vivo.

Animals↗
PubMed1987

Paucity of minimal-change lesion in children with early frequently relapsing steroid-responsive nephrotic syndrome.

It is widely believed that the most common morphological lesion in children with the idiopathic nephrotic syndrome who manifest a frequently relapsing steroid-responsive course is the minimal-change lesion. However, there are no prospective renal biopsy studies in such patients to substantiate this assertion. We performed a renal biopsy in all children with early frequently relapsing steroid-responsive nephrotic syndrome during the years 1980-1984. In 16 affected children, only 4 (25%) had minimal-change lesion, 7 had IgM nephropathy, 3 had diffuse mesangial hypercellularity, and 2 had focal segmental glomerulosclerosis. Fourteen of these patients have required immunosuppressive therapy with cyclophosphamide. Long-term follow-up revealed that 10 patients have remained protein free, 4 have persistent proteinuria despite cyclophosphamide therapy, 1 had progressed to end-stage renal disease, and 1 is lost to follow-up. On the basis of these findings, we recommend that all children with nephrotic syndrome and an early frequently relapsing steroid-responsive course undergo a prompt renal biopsy. Such patients constitute a high-risk group with a spectrum of renal histopathological lesions characterized by an unpredictable response to therapy and an unfavorable prognosis.

Child↗
PubMed1987

A second Australian family with hemoglobin North Shore (beta 134 Val----Glu).

A second Australian family is reported with Hemoglobin North Shore (beta 134 Val----Glu), an unstable hemoglobin, causing no clinical symptoms. All affected family members showed only mild reticulocytosis and microcytosis on the blood film, despite the strongly positive isopropanol test for Hb (hemoglobin) stability and numerous red cell inclusions. Hb North Shore constituted 31-38% of the total hemoglobin and migrated on the anodal side of Hb A at pH 8.9. The association of a mildly raised Hb A2 level and thalassemic phenotype with Hb North Shore previously reported, is confirmed in this study.

Adult↗