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Biomedical subjects

J Parameshwar

Publications and source records attributed to J Parameshwar.

At least 37 records · Page 2Linked to original sources
PubMed1999

The utility of pacemaker evoked T wave amplitude for the noninvasive diagnosis of cardiac allograft rejection.

Previous work suggested that pacemaker evoked T wave amplitude (ETWA) may be a sensitive noninvasive marker of cardiac allograft rejection. A Topaz QT sensing rate responsive pacemaker (Vitatron Medical) was implanted at transplantation using epicardial ventricular leads in 45 recipients (35 males; median age 51 years, range 20-63). The median duration of follow-up was 129 days (range 4-327). The ETWA at a paced rate of 100 beats/min was measured daily during hospitalization and at each outpatient attendance (900 readings). Endomyocardial biopsies were at routine intervals or when otherwise clinically indicated (257 biopsies with concurrent ETWA data). There were 58 episodes of rejection > or = grade 3a in 28 patients. The biopsies were classed as either no rejection (grade < 3a) or rejection requiring treatment (grade > or = 3a). The median normalized ETWA was 100.8% (range 24.6-239.7) without rejection and 89.9% (17.0-189.7) with rejection (Mann-Whitney U Test: P = 0.028). The performance of ETWA monitoring as a diagnostic test for the individual recipient was evaluated with exponentially weighted moving average quality control charts. For the diagnosis of all rejection episodes, ETWA monitoring had a sensitivity of 55%, a specificity of 62%, a positive predictive value of 30%, and negative predictive value of 83%. It is concluded that although analysis of pooled data showed a significant reduction in normalized ETWA with biopsy proven rejection, ETWA monitoring requires further refinement to improve sensitivity before it can be considered a clinically useful technique for the non-invasive diagnosis of cardiac allograft rejection in individual recipients.

Adult↗
PubMed1998

Evaluating the donor pool: impact of using hearts from donors over the age of 49 years.

The shortage of hearts for transplantation has led to the use of organs from older donors in many centres. Despite the lack of coronary angiography on potential organ donors, hearts from carefully selected donors over 49 years of age have been used at this centre since 1988. In the study reported here looked at the impact of this strategy on morbidity and mortality. Between May 1988 and August 1996, 400 first heart transplants were performed, 35 recipients (31 male, 4 female; age 51 +/- 5.9 years) received hearts from donors over 49 years of age (group 1) while 365 (310 male, 55 female; age 49 +/- 9.7 years) had younger donors (group 2). The mean ischaemic time was 189 min (+/- 63.1) in group 1 and 180 min (+/- 59.2) in group 2 (n.s.). The main aetiology of heart failure in groups 1 and 2 was coronary artery disease in 46% and 51%, and dilated cardiomyopathy in 40% and 45% respectively (n.s.). There were no differences in the duration of stay on the intensive care unit or in hospital between the groups. One-year survival was 79% in group 1 and 82% in group 2 (n.s.) and actuarial 5-year survival 69% and 67%, respectively. Six patients in group 1 (17%) and 45 patients in group 2 (12%) died in the first 3 months; of these primary donor organ failure accounted for 50% in group 1 and 13.3% in group 2 (n.s.). Episodes of acute rejection (in the first 3 months) were similar in the two groups: 1.4 and 1.6 per 100 patient days, respectively. Infection rates were also similar: 0.5 and 0.6 per 100 patient days, respectively. The prevalence of coronary artery disease on surveillance coronary angiography at 2 years was 23% in group 1 and 9% in group 2 (P < 0.005). There was a greater proportion of CMV antibody donors in the older donor group, but the association between donor age and coronary artery disease persisted after adjusting for CMV status in multivariate analysis. Too few patients underwent angiography thereafter for valid comparisons. In summary, recipients of organs from donors aged 49 years and over can expect comparable survival rates and morbidity levels to recipients of organs from younger donors, at least in the first 2 years postoperation. There is evidence that older donors confer a significantly higher risk of cardiac allograft vasculopathy which may result in a greater attrition rate thereafter. Careful follow-up of these patients after 2 years is required.

Age Factors↗
PubMed1997

Left ventricular assist devices: current status and future applications.

Despite the advances in the medical management of heart failure over the last 20 years it remains a major cause of morbidity and mortality. While cardiac transplantation has evolved into an established mode of therapy, the number of patients with severe heart failure who could benefit from cardiac transplantation far exceeds the supply of donor organs. The development of an implantable left ventricular assist device (LVAD) began in the early 1970s in centres such as the Texas Heart Institute and was funded by the National Heart, Lung, and Blood Institute. Clinical trials of these devices began in the mid 1980s and several hundred patients have now been supported with one or other of these devices. Most patients have had an LVAD implanted as a bridge to cardiac transplantation. Recently there has also been interest in the use of an LVAD for (a) permanent ventricular support and (b) as a bridge to recovery in patients with potentially reversible causes of heart failure.

Heart Failure↗
PubMed1997

Human leukocyte antigen compatibility in heart transplantation: evidence for a differential role of HLA matching on short- and medium-term patient survival.

BACKGROUND: Studies of the influence of human leukocyte antigen (HLA) matching on cardiac transplant outcome have proved inconclusive, mainly due to the lack of well-matched grafts. However, a growing number of studies report improved clinical course and patient survival in cases with increased HLA compatibility. Opelz et al. believe these benefits justify the introduction of prospective HLA-matching strategies. METHODS: We performed univariate and multivariate analyses to examine the short- and medium-term influence of HLA matching on 556 consecutive primary heart transplants performed at a single center between 1983 and 1994. Overall graft survival at 1, 3, and 5 years was 80%, 74%, and 67% respectively. Sixteen (2.9%) grafts failed within 5 days and were not considered in the analysis of the HLA matching and graft survival data. RESULTS: Complete HLA-A, -B, and -DR typing data were available on 477 transplant pairs. The results demonstrate a 12% 1-year survival advantage for 31 patients with zero to two HLA antigen mismatches compared with three to six mismatches. The influence of each individual locus was 6.1%, 8.4%, and 5.4% for zero HLA-A, -B, and -DR mismatches, respectively, compared with two mismatches. However, when outcome from 1 to 5 years was considered, analysis of the role of each locus revealed marked differences. HLAA-matched grafts (n=45) had a 24% lower survival rate compared with two-antigen-mismatched grafts (n=148; 88% [SE 3.1] vs. 64% [SE 8.2], respectively; P=0.009). Furthermore, 34% of HLA-A-matched grafts failed between 1 and 5 years, compared with only 5% of HLA-B-matched grafts (P=0.013). CONCLUSIONS: These data suggest that although HLA matching is effective at reducing acute graft loss, in the longer term, HLA-A matching may impair survival. HLA-A may serve as a restriction element for indirect presentation of allopeptides or tissue-specific minor histocompatibility antigens, facilitating chronic graft loss. Therefore, we advocate a differential role for HLA matching over two epochs. A blanket approach to prospective matching for heart transplants may be premature for optimal long-term survival.

Adolescent↗
PubMed1996

Lipids, lipoprotein (a) and coronary artery disease in patients following cardiac transplantation.

Cardiac allograft vascular disease (CAVD) is the most important cause of late mortality in cardiac transplant recipients. While the pathogenesis of the disease is believed to be immunological, other factors like hyperlipidaemia may contribute. Total cholesterol, LDL cholesterol. HDL cholesterol, triglycerides, apolipoprotein A1 and B and Lp(a) levels were measured in 174 cardiac transplant recipients attending our clinic for routine follow-up. Univariate and multivariate logistic regression analysis was carried out to assess the relationship of the variables studied to the presence of CAVD diagnosed with coronary angiography. CAVD was present in 42 of the 174 patients. The group with CAVD had a higher total cholesterol (6.8 vs 6.3 mmol/l), lower HDL cholesterol (0.8 vs 0.9 mmol/l), higher triglyceride (2.8 vs 2.0 mmol/l) and higher Lp(a) level (317.5 vs 95 mg/l) than the group without CAVD. In multivariate analysis, after adjusting for gender, hypertension, time from transplantation, preoperative diagnosis and lipid-lowering therapy, Lp(a), total cholesterol, HDL cholesterol and triglycerides remained significantly correlated with CAVD. The results indicate a significant association between hyperlipidaemia, Lp(a) levels and allograft vascular disease. Further studies are needed to show whether treatment of hyperlidaemia in this population delays the onset or slows the progression of CAVD.

Adult↗
PubMed1996

The management of post-cardiac transplantation coronary artery disease.

OBJECTIVE: Allograft coronary artery disease remains the single greatest limitation to long term survival after cardiac transplantation. It is peculiarly aggressive in its behavior and diffuse in its nature. The role of conventional approaches to coronary artery revascularisation were studied in a selected group of cardiac transplant recipients. METHODS: Of the 557 patients undergoing cardiac transplantation at our unit between January 1979 and December 1993, all were screened for the development of allograft coronary artery disease routinely after 2 years and yearly thereafter or after 4 years. Twenty patients with allograft coronary artery disease were considered suitable for treatment by conventional means 17 of whom had undergone transplantation for ischaemic cardiomyopathy and the others for dilating cardiomyopathy. Percutaneous transluminal coronary angioplasty was performed in 18, 25-103 months after transplantation (mean 60 months) all of whom had severe proximal stenoses and reversible defects on perfusion scans. None suffered chest pain. Coronary artery bypass grafting was performed in 5, 95-105 months after transplantation (mean 101 months) 2 of whom had post-infarction unstable angina and 3 had severe triple vessel disease, dyspnoea, and perfusion abnormalities. RESULTS: The primary success rate for PTCA was 84% (16/19). Two lesions restenosed and 3 patients had progressive disease which necessitated coronary revascularisation. No patient died. Of the 5 patients undergoing coronary artery surgery 2 died perioperatively, one from acute left ventricular failure and one from acute rejection. All 18 survivors have improved perfusion scans. Following surgery, all survivors had improvement in dyspnoea and relief of angina. Five late deaths a mean of 89 months after transplantation were from coronary artery disease (4) and lung malignancy (1). CONCLUSIONS: Revascularisation by PTCA and CABG is feasible and successful in selected cardiac transplant recipients. Further study is required to determine the effect of revascularisation on prognosis.

Adult↗
PubMed1996

Objective assessment of the response to treatment of severe heart failure using a 9-minute walk test on a patient-powered treadmill.

BACKGROUND: No previous studies have demonstrated the changes in exercise capacity that occur during treatment of decompensated severe heart failure. The authors assessed the efficacy and safety of using a patient-powered treadmill to objectively measure exercise capacity and its relationships, if any, to symptom scores and body weight. METHODS AND RESULTS: Changes in time-limited exercise capacity on a patient-powered treadmill were assessed during inpatient treatment of 12 patients with decompensated chronic heart failure (New York Heart Association classes III and IV). Patients performed a 9-minute walk test daily for 7 days and again at the 6-week follow-up examination. They also completed a 24-item symptom score questionnaire. After treatment, there was a rapid, significant increase in total distance walked, with the increase beginning as early as the second day after admission (mean distance walked +/- SEM, 54 +/- 27 m and 174 +/- 54 m on admission and on day 2, respectively, P < .05). Improvement was maintained throughout the period in the hospital and at 6 weeks (P < .001). Patients reported symptomatic improvement, but this did not reach significance until 4 days after admission (P < .05). Weight loss was not significant. Improved exercise capacity correlated with reduced symptoms and weight loss, but preceded these by several days. CONCLUSIONS: In patients with decompensated chronic heart failure, this exercise test provides a safe, practical, inexpensive, and objective assessment of functional capacity, providing certain advantages over other indices of response to therapy, such as symptom scores and weight loss. Improvement of exercise capacity does not occur concurrently with relief of symptoms and weight loss.

Adult↗
PubMed1996

Serological and molecular evidence of enterovirus infection in patients with end-stage dilated cardiomyopathy.

OBJECTIVE: To study the relative diagnostic value of enterovirus-specific molecular biological and serological assays in patients with end-stage dilated cardiomyopathy, and to investigate the possible role of other cardiotropic viruses in dilated cardiomyopathy. DESIGN: Analysis of recipient myocardial tissue and serum from patients with dilated cardiomyopathy and controls undergoing cardiac transplantation for end-stage cardiac disease. SETTING: University virology department and transplantation unit. METHODS: Reverse transcriptase-polymerase chain reaction and nucleotide sequence analysis of myocardial RNA and DNA; enterovirus-specific in situ hybridization; enterovirus-specific immunoglobulin M detection. RESULTS: Enterovirus RNA was detected in myocardial tissue from only a small proportion of (five of 75) hearts. However, although enterovirus-specific immunoglobulin M responses were detected in 22 (28%) of 39 controls patients, a significantly higher prevalence was observed among patients with dilated cardiomyopathy (22 (56%) of 39 patients; P < 0.005). All enteroviruses detected in myocardium showed greatest nucleotide sequence homology with coxsackievirus type B3. Detection of enterovirus RNA in myocardium by the polymerase chain reaction and by in situ hybridisation gave comparable results. Other potentially cardiotropic virus genomes, including human cytomegalovirus, influenzaviruses, and coronaviruses were not detected in myocardium. CONCLUSION: This study found that enterovirus-specific immunoglobulin M responses provided the strongest evidence of enterovirus involvement in patients with end-stage dilated cardiomyopathy. However, the high background prevalence of these responses limits their diagnostic value. The finding that enteroviruses detected in myocardium were coxsackievirus type B3 accords with recent findings in patients with acute myocarditis, and indicates that this serotype is the major cardiotropic human enterovirus.

Antibodies, Viral↗
PubMed1994

Transmission of hepatitis C virus by organ transplantation in the United Kingdom.

This study employed a second-generation anti-HCV ELISA, and a second-generation recombinant immunoblot assay and hepatitis C virus RNA detection by polymerase chain reaction to investigate the anti-HCV prevalence in 554 British organ donors and the transmission of hepatitis C virus to heart, liver and kidney recipients between 1984 and 1991. Serum samples from six (1.08%) donors were reactive in the second-generation anti-HCV ELISA and four (67%) of these gave positive or indeterminate results in the recombinant immunoblot assay-2. Of the 15 recipients of these organs from hepatitis C virus-confirmed positive/indeterminate donors, 14 (93%) acquired hepatitis C virus infection and seven (47%) had evidence of hepatitis C virus-related liver disease after transplantation and no evidence of blood transfusion-related transmission. Only six of the 15 (40%) recipients had detectable anti-HCV after transplantation, while 12 of 14 (86%) patients tested had hepatitis C virus RNA in their serum detectable by "nested" polymerase chain reaction. These data indicate a very high rate of transmission with a major risk of the development of liver disease. We believe our study supports the testing of all British organ donors for anti-HCV and that organs from anti-HCV-positive patients should not be transplanted unless the recipient has life-threatening disease and there is a donor shortage, when their use may be justified. Since there are time constraints on organ donor testing, which may frequently be done on call during unsocial hours, we would recommend second-generation ELISA as the current screening test of choice.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Assessment of functional capacity in chronic heart failure: time-limited exercise on a self-powered treadmill.

OBJECTIVES: To assess the efficacy of a 9-minute walking test on a self-powered treadmill in a group of patients with various degrees of heart failure, to investigate the reproducibility of the technique, and to establish the safety of the technique. PATIENTS AND METHODS: 24 controls and 37 patients with various grades of heart failure were studied. Peak oxygen consumption was measured in patients and controls. The distance walked in 9 minutes on a self-powered treadmill was measured in all groups and the test was repeated to assess reproducibility. RESULTS: The distance walked in 9 minutes correlated with peak oxygen consumption in patients, controls, and both groups combined. There was a significant difference in the distance walked by controls and patients and in the distance walked by patients with severe rather than with mild or moderate heart failure. There was no significant difference between the results of successive 9-minute walking tests in any group. No serious adverse reaction was seen in any patient during or after the test. CONCLUSION: The 9-minute walking test on a self-powered treadmill is a sensitive, reproducible, safe, and inexpensive method of assessing functional capacity in patients with all grades of heart failure.

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

The role of calcium antagonists in the treatment of chronic heart failure.

Calcium antagonists have been widely used for the treatment of angina and hypertension. Because of vasodilator and anti-ischaemic properties, calcium antagonists might be expected to bring benefit to patients with heart failure, particularly when the heart failure is due to coronary heart disease. Eight trials of calcium antagonists, fulfilling specific criteria, have been reviewed. The evidence at present does not support the use of calcium antagonists in established heart failure. Some benefit may accure from the use of the newer calcium antagonists but further trials are awaited. Calcium antagonists appear to improve diastolic fraction in patients with coronary heart disease, no overt heart failure but a reduced ejection fraction.

Calcium Channel Blockers↗
PubMed1992

Predictors of prognosis in severe chronic heart failure.

A total of 127 patients with chronic heart failure referred to our exercise laboratory were studied retrospectively to identify parameters predictive of prognosis. Patients were followed for a mean of 14.6 months. The group as a whole had severe ventricular dysfunction with a median ejection fraction of 17% and a median peak rate of oxygen consumption of 13.7 ml/kg/min. During the follow-up period 23 patients (18%) died and 18 (14%) underwent cardiac transplantation. The effect of the following variables on outcome (death or transplantation) were examined: age, cause of heart failure, cardiothoracic ratio on chest radiography, left ventricular end-systolic dimension on echocardiography, left ventricular ejection fraction on radionuclide ventriculography, mean dose of diuretic, plasma sodium and urea concentrations, and peak oxygen consumption during exercise. Although all variables except cause of heart failure affected outcome on univariate analysis, multivariate analysis identified three variables that were statistically significant and independent predictors of outcome. In order of importance these were plasma sodium level, left ventricular ejection fraction and peak oxygen consumption. Even in this group of patients with severe heart failure, these variables were predictive of outcome.

Exercise Test↗