Biomedical subjects
Publications and source records attributed to N H Brooks.
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Different groups of cytokines may initiate or inhibit the rejection process. We used the polymerase chain reaction to study the expression of cytokine mRNA for interleukin (IL)-2, -4, -6 and -10, tumor necrosis factor-alpha, and interferon-gamma in 187 biopsy specimens from 24 human cardiac transplant recipients 5-555 days after transplantation. Cytokine levels in the serum were also measured. Cytokine mRNA was detected in 38.5% of biopsy specimens. IL-10 mRNA was detected more frequently with mild or absent rejection (11.6% in grades 0 and 1 - vs. 1.4% in grades 2 and 3, P=0.01). Up to 90 days after transplantation, IL-2 mRNA was detected more frequently with moderate rejection (13% in grades 2 and 3 vs. 0% in grades 0 and 1, P=0.076), and IL-4 mRNA was detected more frequently with mild or absent rejection (16% in grades 0 and 1 - vs. 0% in grades 2 and 3, P=0.061). More than 90 days after transplantation, IL-2 mRNA was detected more frequently with mild or absent rejection (10% in grades 0 and 1 vs. 0% in grades 2 and 3, P=0.078). Serum IL-4 levels corresponding to biopsy specimens positive for IL-4 mRNA were higher than those corresponding to specimens negative for IL-4 mRNA (59 pg/ml vs. 32 pg/ml medians, P=0.028). Our results suggest that IL-10 and possibly IL-4 (T helper 2 cytokines) may suppress graft rejection, whereas IL-2 (T helper 1 cytokine) may promote cellular rejection. In addition, cytokine profiles may change with length of time after transplantation. The association of elevated serum levels of IL-4 with increased expression of intragraft IL-4 mRNA may suggest release of this cytokine from the graft into the circulation.
Cytokines are important in the pathogenesis of allograft rejection. Some studies have suggested a positive relationship between serum levels of cytokines and rejection, so this study was designed to investigate the presence of a range of cytokines in a large cohort of cardiac transplant recipients. We used enzyme linked immunosorbent assays (ELISA) to examine sequential serum samples from 28 consecutive heart transplant recipients; length of follow up varied between 2 and 566 days (median 357 days). Serum levels of IL-2, 4, 6, 10, TNF-alpha, and IFN-gamma were measured. We compared these results with detailed data on patients' clinical courses, including histological rejection, infection, and therapeutic use of antithymocyte globulin (ATG). No significant relationship was found between rejection and serum cytokine levels for samples taken more than 30 days after transplantation. Prior to this cytokine levels were significantly disturbed by the use of cytolytic therapy for induction immunosuppression. Serum cytokine levels sometimes showed peaks that appeared to be related to rejection, or occasionally to infection, but these relationships were not consistent. Serum TNF-alpha and IL-6 were consistently elevated within a few days of administration of ATG. We conclude that there is no systematic relationship between serum cytokine levels and histological rejection or infection in cardiac transplant recipients.
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BACKGROUND: Right and left atrial configuration is more normal when the donor left atrium is anastomosed to a recipient left atrial cuff with direct anastomoses of the donor and recipient vena cavas on the right side. The right atrium and sinus node may be less disturbed by the technique of bicaval anastomosis than by the standard procedure. OBJECTIVE: To compare the incidence of atrial arrhythmias and pacing after bicaval and standard anastomoses. METHODS: 75 patients had heart transplants between January 1991 and December 1993. The notes were reviewed. Nine patients who died within the first 30 days were excluded from further analysis (seven patients with standard anastomoses, one with bicaval anastomosis, and one with a hybrid technique). RESULTS: 66 patients survived for more than 30 days. Thirty five patients had standard anastomoses and 31 bicaval anastomoses. Atrial tachyarrhythmias (atrial fibrillation, atrial flutter, atrial tachycardia, or supraventricular tachycardia) occurred on four days in three patients in the bicaval group compared with 27 days in 13 patients in the standard group (P = 0.009). The relative risk of atrial tachyarrhythmias with standard anastomosis was 5.52 (P = 0.015) compared with that of bicaval anastomosis. Atrial tachyarrhythmias requiring treatment occurred less often in the bicaval group (four episodes in three patients in the bicaval group and eight episodes in four patients in the standard group), and fewer patients with a bicaval anastomosis required temporary pacing (pacing on 20 days in 10 patients in the bicaval group, but pacing on 49 days in 16 patients in the standard group) and late permanent pacing (no patients in the bicaval group and three patients in the standard group), although these differences were not statistically significant. Patients in the bicaval group were discharged from hospital sooner than those in the standard group (mean 24.1 v 29.1 days, P = 0.024). CONCLUSIONS: The technique of bicaval anastomosis, in addition to theoretical advantages from maintaining a more normal atrial configuration, has a lower incidence of postoperative atrial tachyarrhythmias, may reduce the need for pacing, and allows earlier discharge from hospital.
Two patients died following heart transplantation from failure of the donor right ventricle. Histological examination of the lungs showed occlusion of pulmonary veins. A more reliable method is required to predict the outcome for potential heart transplant recipients with a "borderline" pulmonary vascular resistance.
OBJECTIVE: This article reviews the role of counseling, education, dietary modifications, and exercise for patients with heart failure due to left ventricular systolic dysfunction. DATA SOURCE: We reviewed studies published in English between 1966 and 1993 and referenced in MEDLINE or EMBASE. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific areas of interest. Where data were lacking, we relied on opinions of panel members and peer reviewers. STUDY SELECTION AND DATA SYNTHESIS: Studies were reviewed to determine whether patients had heart failure due to systolic dysfunction (left ventricular ejection fraction, < 0.35 to 0.40) and whether clinical outcomes were reported. Studies that reported only intermediate outcomes (eg, hemodynamics) were not reviewed. CONCLUSION: Counseling and education can improve patient outcomes and decrease unnecessary hospitalizations. Patients with mild to moderate heart failure should be restricted to 3 g/d of sodium initially. Those who are unresponsive to this dosage or who have more severe disease should be advised to consume 2 g/d or less. Patients should be strongly advised to drink no more than 30 mL/d of alcohol or, preferably, to abstain completely. Exercise training is safe and can improve exercise duration and symptoms. Adherence to the treatment plan should be stressed and monitored at each visit. Clinicians should inform patients of the seriousness of their disease and their prognosis, but they should emphasize that patients can continue to remain active and enjoy a reasonable quality of life.
It is well established that incompatible HLA antigens presented by donor tissue readily evoke an immune response. Prospective HLA matching policies, widespread in European kidney transplant centers have reduced the level of HLA mismatching and have significantly improved graft survival. The influence of HLA incompatibility in heart transplantation remains controversial, and prospective HLA matching is seldom achieved. We examined the role of HLA antigen mismatching on transplant rejection by analyzing 2569 endomyocardial biopsies (EMB) from 157 consecutive orthotopic heart transplants performed from April 1987 to August 1993 in our own center. Biopsies were graded according to the accepted International Classification, with grade 2 and higher indicating rejection. Among 91 patients who received a 2 HLA-DR mismatch transplant 34% of 1624 biopsies analyzed were graded as > or = 2. This frequency fell to 29% of 797 biopsies for 53 patients with a one-HLA-DR mismatch and to 18% of 148 biopsies for 13 patients in the zero-HLA-DR-mismatch group (P < 0.00005). No significant effect on EMB grade frequencies was observed using the same method of analysis with transplants mismatched at the HLA-A or HLA-B loci apart from analysis of HLA-B matched transplants at 3 months posttransplant (P = 0.02). The close linkage of the HLA-B and HLA-DR loci may account for this observation. The results of this study show that heart transplants matched at the HLA-DR locus have a significantly reduced incidence of EMB grades indicative of rejection requiring augmented immunosuppressive therapy. We propose that prospective HLA-DR matching should be adopted for allocation of donor hearts for more efficient use of this precious and limited resource.
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BACKGROUND: The aetiology of idiopathic dilated cardiomyopathy is believed to have an immunological component. Association with human leucocyte antigens (HLAs) has been previously reported, particularly with HLA-DR4. AIM: To determine the association of HLA type with diagnosis in a group of patients assessed for heart transplantation. METHODS: A comparison was made of frequencies of HLA types in patients with a diagnosis of idiopathic dilated cardiomyopathy or (n = 98) ischaemic heart disease (n = 170) and in controls from the North Western region (n = 857). RESULTS: Neither the patients with idiopathic dilated cardiomyopathy nor those with ischaemic heart disease showed a significant increase or decrease in any HLA frequency compared with the controls. CONCLUSION: These results suggest that there is no HLA association with idiopathic dilated cardiomyopathy or ischaemic heart disease. This conflicts with the results of some previous studies.
Three cases of Wegener's granulomatosis with cardiac complications are described and the relevant published reports are reviewed. The first case of Wegener's granulomatosis was associated with aortic regurgitation and required aortic valve replacement. The second and third cases were associated with pericardial disease requiring pericardiectomy for constructive pericarditis in one case, and haemorrhagic pericarditis with pericardial effusion in the other. Aortic valve involvement in Wegener's granulomatosis is uncommon and valve replacement has been described on only one previous occasion. Pericardial involvement is relatively common pathologically, but pericardial surgery has been described in this condition only twice, once for tamponade and once for constrictive pericarditis after pericardiocentesis. Cardiac involvement is not uncommon in patients with Wegner's granulomatosis and may be clinically important. Diagnosis is aided by estimation of the anti-neutophil cytoplasmic antibody titre.
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The objective of this study was to assess the changes in outcome of cardiac arrest due to ventricular fibrillation, asystole and electromechanical dissociation in relation to the changing guidelines for drug therapy set by the U.K. Resuscitation Council. It was a retrospective study of 667 resuscitation records for the years 1982, 1986, 1988, 1989, 1990 and 1991. It took place in a large district general hospital with a regional cardio-thoracic centre. We have audited the asystolic cardiac arrests (N = 271) which occurred outside the cardiac care unit (CCU). Adrenaline (intravenous 1 mg) is now the first line drug followed by atropine at an increased dose (2 mg intravenously); calcium is no longer recommended and sodium bicarbonate should be reserved for cases in which an acidosis has been documented. Atropine use has increased over the 9-year period. Bicarbonate use did not change from 1982 to 1986 but fell progressively to no use at all in 1991. Calcium use has declined since 1982. Adrenaline use has remained unchanged. Survival from asystolic arrests (hospital discharge) has remained unchanged at 0-5.5%. Asystole as a primary event in the CCU was uncommon (N = 17) and no patient was discharged. Over the same period, 60% of patients (N = 92) with a cardiac arrest on CCU due to ventricular fibrillation (VF) were discharged and 55% were alive after 6 months. For VF on the wards (N = 192), only 20% of patients were discharged from hospital. A similar proportion was successful for each year.(ABSTRACT TRUNCATED AT 250 WORDS)
BACKGROUND: Carcinoid heart disease typically results in pulmonary stenosis and tricuspid incompetence. Percutaneous balloon dilatation is an effective treatment for congenital pulmonary stenosis and has been applied successfully to tricuspid stenosis caused by carcinoid heart disease. The value of balloon dilatation of the pulmonary valve in carcinoid pulmonary stenosis was assessed. METHODS: Two patients with severe congestive heart failure secondary to carcinoid heart disease and with documented pulmonary stenosis had balloon dilatation of the pulmonary valve. In both cases tricuspid regurgitation was also present together with reduced cardiac output. RESULTS: The procedure was technically successful in both patients. One patient experienced symptomatic benefit for two months and the other experienced no improvement. Both patients subsequently required combined tricuspid and pulmonary valve replacement from which good results and symptomatic improvement were obtained. CONCLUSION: Though balloon dilatation of the pulmonary valve is technically feasible it is unlikely to provide useful palliation in carcinoid heart disease. Valve surgery should be considered in patients in whom the malignancy is controlled but carcinoid heart disease is producing drug resistant congestive heart failure.
BACKGROUND: Raised pulmonary vascular resistance is associated with decreased survival after orthotopic heart transplantation and patients with this risk factor are usually denied transplantation. In a proportion of cases raised pulmonary vascular resistance may fall with time and medical treatment. METHODS: Seven patients with high pulmonary vascular resistance (range 3.9-6.6 Wood units) at initial assessment for cardiac transplantation were restudied by right heart catheterisation after a period of seven to 17 months. RESULTS: In five of the seven patients the pulmonary vascular resistance had fallen, allowing orthotopic heart transplantation to be performed in four. In one patient the resistance was static and in one it had risen. The mean fall in pulmonary vascular resistance for the group was (mean (SD)) 2.6 (2.7) Wood units, p < 0.05. CONCLUSION: Patients who have been denied transplantation on the basis of their raised pulmonary vascular resistance should be reassessed after four to six months if they remain otherwise clinically suitable.