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Biomedical subjects

J B O'Connell

Publications and source records attributed to J B O'Connell.

At least 19 recordsLinked to original sources
PubMed2000

The economic burden of heart failure.

Heart failure, a major cause of morbidity and mortality among the elderly, is a serious public health problem. As the population ages and the prevalence of heart failure increases, expenditures related to the care of these patients will climb dramatically. As a result, the health care industry must develop strategies to contain this staggering economic burden. Strategies may include adopting approaches for preventing heart failure and implementing new treatment modalities with proven efficacy into large-scale clinical practice. Successful implementation of these strategies will require intensive physician and patient education and development of innovative approaches to fund support services.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The repetitive histologic pattern of vascular cardiac allograft rejection. Increased incidence associated with longer exposure to prophylactic murine monoclonal anti-CD3 antibody (OKT3).

While vascular cardiac allograft rejection increases morbidity and mortality following transplantation, factors predisposing to its development have not been completely elucidated. To evaluate the influence of the duration of early rejection prophylaxis with the murine monoclonal anti-CD3 antibody (OKT3) on the development of a repetitive histologic pattern of vascular cardiac allograft rejection, endomyocardial biopsies from 344 heart transplant recipients were prospectively evaluated. The influence of clinical characteristics was assessed. Eighty-three patients (24%) developed and 261 patients (76%) did not develop a repetitive histologic pattern of vascular cardiac allograft rejection. The vascular rejection pattern was more common in patients with a positive crossmatch (89% versus 11%, P<0.0001) and OKT3 sensitization (73% versus 27%, P<0.0001), and was positively correlated with the duration of OKT3 treatment (P<0.0001). The correlation persists even after excluding patients with a positive crossmatch or OKT3 sensitization. Patients developing a repetitive histologic pattern of vascular cardiac allograft rejection early after transplantation had decreased allograft survival (P=0.0008). The development of a repetitive histologic pattern of vascular cardiac allograft rejection is positively correlated with the duration of OKT3 treatment. Judicious use of OKT3 in early rejection prophylaxis in cardiac transplantation is warranted.

Adult↗
PubMed1996

Implications of the Myocarditis Treatment Trial for clinical practice.

Active myocarditis, a common precursor of dilated cardiomyopathy, is defined as myocardial inflammation and injury in the absence of ischemia. Many agents may cause myocarditis and the exact manifestation of the disease depends on the interplay between the inciting agent and host response. Widespread belief that myocarditis is an autoimmune disorder has led to the possible overuse of endomyocardial biopsy and immunosuppressive agents. Their use is further complicated by the observation that many patients improve with conservative management alone. The Myocarditis Treatment Trial was designed to address the role of immunosuppression in the treatment of myocarditis, define the natural history of the disease, and increase understanding of the immunologic mechanisms involved in the pathogenesis of the disease. Enrollment began in October 1986 and was completed in October 1990 with follow-up completed in 1991. The study failed to show a significant benefit for immunosuppressive agents. Conventional medical regimens should be used to alleviate symptoms and immunosuppressive agents should be reserved for patients with progressive deterioration and biopsy-proven disease.

Adult↗
PubMed1996

Community-based internal medicine residency training--a report on our first two years.

Since August, 1993, internal Medicine Associates Foundation, Inc. of Tupelo and the Department of Medicine, University of Mississippi Medical Center, have been cooperating in a program of community-based Internal Medicine residency training, the first effort of its kind in the state. We are pleased to report the program an unqualified success, for the residents themselves, the participating private physicians, and the Department as a whole. As one of only a handful of ambulatory care private practice relationships in the country (approximately five percent of Internal Medicine departments have such at present), we feel that ours can serve as a model for other programs to emulate. We therefore present a report on our program's background, organizational structure, curriculum, and future plans.

Ambulatory Care↗
PubMed1996

Exercise capacity after heart transplantation: influence of donor and recipient characteristics.

BACKGROUND: For incompletely understood reasons, cardiac transplant recipients achieve only 60% to 70% of predicted values for maximal exercise capacity. The objective was to determine the characteristics of cardiac transplant recipients that are predictive of exercise capacity. METHODS: One hundred ten patients underwent maximal exercise testing using a modified Naughton protocol 26 +/- 1 months after transplantation. Recipient characteristics, resting hemodynamic variables and exercise parameters were compared using univariate and multivariate analyses. RESULTS: The average maximum heart rate was 85% of predicted, and the average peak oxygen consumption (Vo2) was 17.7 +/- 0.3 ml/kg/min (64% of predicted). Pretransplant status, etiology of heart failure, ischemic time, degree of HLA disparity, cumulative corticosteroid exposure, and number of rejection episodes failed to correlate with any exercise parameter. Older recipient age and female gender were associated with greater values for the proportion of the predicted peak Vo2 (p < 0.001 for age; p = 0.001 for gender). Older donor age was the strongest independent predictor of a decreased chronotropic response (p < 0.001) and was a weak predictor of decreased peak Vo2 (p = 0.014). Even in the multivariate analysis, maintenance prednisone dose negatively impacts exercise duration (p = 0.05), peak Vo2 (p = 0.035) and percent of predicted peak Vo2 (p = 0.032). Of all characteristics tested, pulmonary vascular resistance within 24 hours of exercise most powerfully predicts exercise duration (p = 0.002) and peak Vo2 (p = 0.001). CONCLUSIONS: Female recipients and older recipients have a lower absolute exercise capacity, but achieve a greater proportion of their predicted capacity. Recipients of older donor hearts and those receiving chronic corticosteroids have decreased exercise capacity. Pulmonary vascular resistance is inversely correlated with exercise capacity.

Adolescent↗
PubMed1996

Improved long-term survival after heart transplantation predicted by successful early withdrawal from maintenance corticosteroid therapy.

BACKGROUND: Short-term studies suggest that cardiac transplant immunosuppression without maintenance corticosteroids is feasible in selected patients. However, concern exists as to the long-term effects, specifically the possibility of increased morbidity and mortality because of late allograft rejection and allograft coronary artery disease. METHODS: We retrospectively reviewed the records from 441 consecutive heart transplantation procedures done in 416 patients with use of an immunosuppressive protocol that attempted corticosteroid withdrawal within 2 months of transplantation. forty-two patients died or underwent retransplantation during the first 3 months and were excluded from further analysis. Analysis focused on demographic and long-term outcome variables (including death, rejection, retransplantation, and infection). RESULTS: Thirty percent (111) of eligible patients (374) met the definition of successful early steroid withdrawal. Only male gender independently predicted successful withdrawal. Mortality, both short and long term, was significantly lower in patients in whom successful early withdrawal from corticosteroids was achieved than in patients in whom the early attempts failed (1.7% per year versus 4.7% per year; p < 0.0001). The prevalence of late acute allograft rejection (more than 1 year after transplantation) was lower in patients successfully withdrawn from steroid therapy early after transplantation (0.07 pt-yr of follow-up versus 0.15 pt-yr; p = 0.002). Multivariate analysis of the entire group identified incidence of infection (p = 0.001), older age (p = 0.001), failed early steroid withdrawal (p = 0.006), and female gender (p = 0.016) as independent predictors of mortality. CONCLUSIONS: Successful early corticosteroid withdrawal identifies a subgroup of "immunologically privileged" patients with a low risk for long-term mortality and is not associated with an increased prevalence of late rejection or clinically significant coronary artery disease.

Case-Control Studies↗
PubMed1996

Cyclophosphamide in cardiac transplant recipients with frequent rejection: a six-year retrospective review.

Allograft rejection remains a major cause of morbidity and mortality. Cyclophosphamide, a nitrogen mustard, is a potent immunosuppressive agent with effects on both T- and B-lymphocytes, and thus may be effective in preventing further cellular and/or humoral rejection in cardiac transplant recipients with recurrent or recalcitrant rejection. We retrospectively reviewed the records of 320 surviving cardiac transplant recipients. Cyclophosphamide was substituted for azathioprine in 28 patients because of frequent allograft rejection. We then reviewed the rejection history of these 28 patients, specifically looking at rejection frequency, type (cellular, vascular or mixed), and treatment. Cyclophosphamide was substituted for azathioprine at an average of 8.4 +/- 2.8 months after transplantation. Despite a 56.0% reduction in prednisone dose (p < 0.001), at least a threefold reduction in rejection frequency (p < 0.001) was observed, while cyclosporine levels were unchanged. Twenty-eight percent of the patients did not experience even mild rejection after beginning therapy with cyclophosphamide, 55% had 1 or 2 subsequent mild or moderate rejection episodes, and only 17% had more than two subsequent episodes of mild or moderate rejection. Overall, the number of treated rejection episodes decreased from 0.37 episodes per patient month with azathioprine to 0.10 episodes per patient month on therapy with cyclophosphamide. Separating the patients into two groups based on the predominant rejection type (cellular vs. vascular) occurring at the time of cyclophosphamide substitution revealed a similar reduction in cellular and vascular rejection in each respective group. While white blood cell count decreased by 16%, cyclophosphamide was not discontinued in any patient due to leukopenia, and no change was noted in hematocrit. Cyclophosphamide appears to be safe and effective in maintenance immunosuppression and may reduce rejection frequency in some patients with frequently occurring allograft rejection without necessitating the augmentation of either corticosteroids or cyclosporine.

Azathioprine↗
PubMed1995

Role of beta-adrenergic receptor downregulation in the peak exercise response in patients with heart failure due to idiopathic dilated cardiomyopathy.

The effect of beta-adrenergic receptor downregulation on peak exercise response in patients with heart failure has not been directly investigated. Seventy-two patients with idiopathic dilated cardiomyopathy who had a mean ejection fraction of 23 +/- 1% (mean +/- SEM) and New York Heart Association class II or III symptoms were investigated. Subjects underwent maximal exercise testing on a bicycle or a treadmill, hemodynamic assessment by right heart catheterization, and measurement of total beta-adrenergic receptor density by 125I-iodocyanopindolol binding performed in the right ventricular endomyocardial biopsy tissue and in peripheral lymphocytes. Endomyocardial biopsy beta-adrenergic receptor density (Bmax) was markedly decreased (45 +/- 2 fmol/mg), and significantly lower than lymphocytes Bmax (107 +/- 14 fmol/mg; p < 0.05). By univariate analysis, all exercise variables correlated significantly with biopsy tissue Bmax but not with lymphocyte Bmax. Maximal exercise oxygen consumption (VO2max) yielded the highest correlation with Bmax (r2 = 0.61, p < 0.001). By stepwise regression analysis, VO2 max, delta heart rate x systolic blood pressure, and ejection fraction were all independently related to Bmax. Myocardial beta-adrenergic receptor downregulation is likely to be partially responsible for the reduced chronotropic and inotropic responses to peak exercise in patients with mild to moderate symptomatic heart failure due to idiopathic dilated cardiomyopathy.

Adult↗
PubMed1995

Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.

Improved outcome of heart failure in response to medical therapy, coupled with a critical shortage of donor organs, makes it imperative to restrict heart transplantation to patients who are most disabled by heart failure and who are likely to derive the maximum benefit from transplantation. Hemodynamic and functional indexes of prognosis are helpful in identifying these patients. Stratification of ambulatory heart failure patients by objective criteria, such as peak exercise oxygen consumption, has improved ability to select appropriate adult patients for heart transplantation. Such patients will have a poor prognosis despite optimal medical therapy. When determining the impact of individual comorbid conditions on a patient's candidacy for heart transplantation, the detrimental effects of each condition on posttransplantation outcome should be weighed. Evaluation of patients with severe heart failure should be done by a multidisciplinary team that is expert in management of heart failure, performance of cardiac surgery in patients with low left ventricular ejection fraction, and transplantation. Potential heart transplant candidates should be reevaluated on a regular basis to assess continued need for transplantation. Long-term management of heart failure should include continuity of care by an experienced physician, optimal dosing in conventional therapy, and periodic reevaluation of left ventricular function and exercise capacity. The outcome of high-risk conventional cardiovascular surgery should be weighed against that of transplantation in patients with ischemic and valvular heart disease. Establishment of regional specialized heart failure centers may improve access to optimal medical therapy and new promising medical and surgical treatments for these patients as well as stimulate investigative efforts to accelerate progress in this critical area.

Adolescent↗
PubMed1995

A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators.

BACKGROUND: Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis and to examine measures of the immune response as predictors of the severity and outcome of disease. METHODS: We randomly assigned 111 patients with a histopathological diagnosis of myocarditis and a left ventricular ejection fraction of less than 0.45 to receive conventional therapy alone or combined with a 24-week regimen of immunosuppressive therapy. Immunosuppressive therapy consisted of prednisone with either cyclosporine or azathioprine. The primary outcome measure was a change in the left ventricular ejection fraction at 28 weeks. RESULTS: In the group as a whole, the mean (+/- SE) left ventricular ejection fraction improved from 0.25 +/- 0.01 at base line to 0.34 +/- 0.02 at 28 weeks (P < 0.001). The mean change in the left ventricular ejection fraction at 28 weeks did not differ significantly between the group of patients who received immunosuppressive therapy (a gain of 0.10; 95 percent confidence interval, 0.07 to 0.12) and the control group (a gain of 0.07; 95 percent confidence interval, 0.03 to 0.12). A higher left ventricular ejection fraction at base line, less intensive conventional drug therapy at base line, and a shorter duration of disease, but not the treatment assignment, were positive independent predictors of the left ventricular ejection fraction at week 28. There was no significant difference in survival between the two groups (P = 0.96). The mortality rate for the entire group was 20 percent at 1 year and 56 percent at 4.3 years. Features suggesting an effective inflammatory response were associated with less severe initial disease. CONCLUSIONS: Our results do not support routine treatment of myocarditis with immunosuppressive drugs. Ventricular function improved regardless of whether patients received immunosuppressive therapy, but long-term mortality was high. Patients with a vigorous inflammatory response had less severe disease.

Adult↗
PubMed1995

The OKT3 Antibody Response Study: a multicentre study of human anti-mouse antibody (HAMA) production following OKT3 use in solid organ transplantation.

Human anti-murine antibody titres following patient exposure to the monoclonal antibody Orthoclone OKT3 (muromonab-CD3) are determined by laboratories using diverse analytical methods which are not standardized and whose concordance is not established. A multicentre study group therefore compared testing for IgG anti-OKT3 antibody among seven laboratories. A set of 270 sera was obtained from 30 heart, 30 kidney and 30 liver transplant recipients with no previous exposure to OKT3 who were receiving OKT3 for induction immunosuppression. Sera were collected from each patient prior to and at 24 +/- 2 days and 31 +/- 2 days following initial OKT3 exposure. Identical aliquots of all 270 sera were tested for IgG anti-OKT3 antibody by each laboratory. In addition, the limit of detection of each laboratory's method was estimated by titration of an affinity-purified IgG anti-OKT3 reference material of known concentration. Anti-OKT3 antibody formation differed greatly among the three organ groups. Cardiac patients demonstrated the least sensitization and almost exclusively lower titres, while kidney recipients had more frequent and higher titre antibody formation. Liver recipients yielded the highest sensitization rate and the most frequent high titre sera. Importantly, the seven laboratories differed widely in the number of pretreatment sera reported as positive (ranging from 0% to 41% among laboratories), the number of post-OKT3 sera reported as positive (17-63%), the number of post-OKT3 samples with titre > or = 1000 (2-31%), and the number of patients sensitized 19-69%). Concordance among laboratories was highly variable, with interlaboratory agreement ranging from 38% to 83% on the sample titres assigned to 180 post-OKT3 sera. Many of the discordant results were consistent with differences in the limit of detection of the analytical methods, which ranged from 0.19 microgram/ml to > or = 15 micrograms/ml, a nearly 100-fold difference among laboratories. This study demonstrated the presence of both good concordance and significant discordance among laboratories in determining human anti-mouse antibody titres, and demonstrated that common titre categories (100, 1000, 10,000) were not equivalent among laboratories. The level of concordance among methods should be considered when comparing anti-OKT3 antibody results from different centres and their correlation with clinical events. Universal comparative testing, patterned after proficiency testing programmes, is needed to assess differences among laboratories and to bring uniformity and a sound interpretative basis to this field of testing.

Adult↗
PubMed1995

Myocarditis and idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.

Cardiomyopathy, Hypertrophic↗