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Biomedical subjects

K L Baughman

Publications and source records attributed to K L Baughman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Refining the treatment of women with unstable angina--a randomized, double-blind, comparative safety and efficacy evaluation of Integrelin versus aspirin in the management of unstable angina.

BACKGROUND: Although women typically develop coronary artery disease several years after men, once they have symptomatic disease their thromboembolic complications are worse than in men. The mechanism mediating this gender difference in outcome after thromboembolic events is unknown. We previously studied platelet functions in siblings from patients with premature coronary artery disease. We observed that platelets from women are responsive than their male counterparts. In particular, platelets from women stimulated ex vivo with various agonists bind more fibrinogen molecules than platelets from men. HYPOTHESIS: We hypothesized that in patients with acute coronary events, the control of platelet activity might require stronger antagonists in women than in men. METHODS: To test this hypothesis, we investigated retrospectively the results of a trial on Integrelin in unstable angina. RESULTS: We report that platelet aggregation and Holter-detected ischemic episodes are significantly reduced in women with unstable angina treated with the specific GPIIb-IIIa inhibitor, Integrelin, compared with the standard platelet inhibitor aspirin. In contrast, both platelet aggregation and Holter-detected ischemic events are well controlled in men with unstable angina treated with standard therapy including aspirin. CONCLUSION: Integrelin does provide protection in men, but, in contrast with women, not beyond what can be achieved with aspirin. Our data are consistent with the concept that the platelets from women require stronger and more specific inhibitors to limit their activity, and that platelets may play a more important role in women with acute coronary syndromes than in men. Most important, specific GPIIb-IIIa inhibitors may represent a therapeutic option which provides as much suppression of ischemic events in women as they do in men with coronary artery disease.

Aged↗
PubMed1996

The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients.

It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.

Coronary Artery Disease↗
PubMed1996

Dehydroepiandrosterone and cardiac allograft vasculopathy.

BACKGROUND: Tissue culture, animal model, and epidemiologic studies suggest that dehydroepiandrosterone may inhibit atherosclerosis through its potent antiproliferative effects. Because cardiac allograft vasculopathy is predominantly a proliferative abnormality of intimal and medial smooth muscle cells, plasma levels of dehydroepiandrosterone may play an important role in the development of this disease. METHODS: Sixty-one cardiac allograft recipients who survived for 1 year or more and had at least one annual follow-up cardiac catheterization were included in the study. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and free dehydroepiandrosterone (dehydroepiandrosterone not bound to sex hormone-binding globulin) were measured in all 61 subjects and compared with the presence or absence of cardiac allograft vasculopathy as defined by angiography. RESULTS: Plasma levels of total and free dehydroepiandrosterone were lower in subjects in whom cardiac allograft vasculopathy developed (p = 0.005 and 0.003, respectively). Furthermore, the time to development of cardiac allograft vasculopathy was shorter in subjects with low levels of total and free dehydroepiandrosterone (p = 0.062 and 0.046, respectively). This relationship was maintained after adjusting for age, gender, cholesterol, prednisone use, and blood pressure. CONCLUSIONS: Low plasma levels of dehydroepiandrosterone may facilitate and high levels may retard the development of cardiac allograft vasculopathy.

Adult↗
PubMed1995

Respiratory illness, beta-agonists, and risk of idiopathic dilated cardiomyopathy. The Washington, DC, Dilated Cardiomyopathy Study.

An epidemiologic study was carried out to examine the possible role of beta-agonists and other respiratory medications in the development of idiopathic dilated cardiomyopathy. Associations with respiratory medications, bronchial asthma, emphysema, and chronic bronchitis were examined by comparing newly diagnosed cases (n = 129) ascertained from five Washington, DC, area hospitals for the period 1990-1992 with neighborhood controls (n = 258) identified by using a random digit dialing technique. The cases and controls were matched on sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of emphysema or chronic bronchitis (adjusted odds ratio (OR) = 4.4, 95% confidence interval (CI) 1.6-12.4). The association with bronchial asthma was of borderline significance (adjusted OR = 1.9, 95% CI 0.9-4.2). Associations were also observed with use of oral beta-agonists (adjusted OR = 3.4, 95% CI 1.1-11.0) and beta-agonist inhalers or nebulization (adjusted OR = 3.2, 95% CI 1.4-7.1), as well as with use of oral corticosteroids, inhaled corticosteroids or cromolyn, and theophylline medications. A total of 20.0% (23 of 115) of the cases had a reported history of beta-agonist inhaler use compared with 6.7% (17 of 254) of the controls. The strength of these associations was diminished when the temporal relation between exposure to beta-agonist inhalers or oral preparations and clinical diagnosis of idiopathic dilated cardiomyopathy was taken into account, however, and the associations with duration of beta-agonist medication use were not statistically significant (p > 0.05). The results of this study suggest, but do not prove, that use of beta-agonists has an etiologic role in idiopathic dilated cardiomyopathy.

Adrenergic beta-Agonists↗
PubMed1995

Reverse remodeling from cardiomyoplasty in human heart failure. External constraint versus active assist.

BACKGROUND: Cardiomyoplasty (CM) is a novel surgical therapy for dilated cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around the heart and chronically paced synchronously with ventricular systole. While studies have found symptomatic improvement from this therapy, the mechanisms by which CM confers benefit remain uncertain. This study sought to better define these mechanisms by means of serial pressure-volume relation analysis. METHODS AND RESULTS: Serial pressure-volume studies were performed by the conductance catheter method in three patients (total to date) with dilated cardiomyopathy (New York Heart Association class III) who underwent CM. Data were measured at baseline (before surgery) and at 6 and 12 months after CM. Chronic left ventricular (LV) systolic and diastolic changes induced by CM were evaluated with the stimulator in its stable pacing mode (every other beat) and after temporarily suspending pacing. CM-stimulated beats were compared with pacing-off beats to evaluate active systolic assist effects of CM. In each patient, CM resulted in a chronic lowering of cardiac end-diastolic volume and an increased ejection fraction. Most notably, the end-systolic pressure-volume relation shifted leftward, consistent with reversal of chronic chamber remodeling. In contrast, the diastolic pressure-volume relation was minimally altered, and the loops shifted down along the same baseline relation. These marked chronic changes in LV function measurable with CM stimulation off contrasted to only minor acute effects observed when the muscle wrap was activated. This suggests that the benefit of CM derived less from active systolic assist than from remodeling, perhaps because of an external elastic constraint. CONCLUSIONS: These data, while limited to a small number of patients, suggest that CM can reverse remodeling of the dilated failing heart. While systolic squeezing assist effects of CM may play a role in some patients, our study found that this was not required to achieve substantial benefits from the procedure. We speculate that CM may act more passively, like an elastic girdle around the heart, to help reverse chamber remodeling.

Adult↗
PubMed1995

Dilated heart muscle disease associated with HIV infection.

As more effective therapies have produced longer survival times for HIV-infected patients, non-infectious complications of late stage HIV infection such as the development of severe global left ventricular dysfunction (dilated heart muscle disease) have emerged. The demographic and clinical characteristics of HIV-infected patients who develop dilated heart muscle disease as well as potential risk factors are, as yet, poorly characterized. Of 174 patients enrolled in a prospective longitudinal study, a total of nine patients, all with CD4 T cell counts < 200 mm-3, developed symptomatic heart disease (congestive heart failure n = 7, sudden cardiac death n = 1 and cardiac tamponade n = 1); three of these patients developed progressive cardiac dysfunction leading to primary cardiac failure and death. An additional 55 HIV-infected patients referred to our Cardiomyopathy Service were found to have global left ventricular dysfunction, with 84% having New York Heart Association Class III or IV congestive heart failure on presentation. Clinical characteristics associated with severe symptomatic cardiac dysfunction included low CD4 T cell counts, myocarditis associated with non-permissive cardiotropic virus infection on endomyocardial biopsy and persistent elevation of anti-heart antibodies. No relationships to any specific HIV risk factor or opportunistic infection were found. These findings suggest that a severe form of HIV-related dilated heart muscle disease is largely a disease of late stage HIV infection. Virus-related myocarditis and cardiac autoimmunity may play a role in the pathogenesis of progressive cardiac injury. Long-term longitudinal studies of larger HIV-infected cohorts are warranted to identify clinical, behavioral and immunologic risk factors.

Adult↗
PubMed1995

Intimate association of eosinophils to collagen bundles in eosinophilic myocarditis and ranitidine-induced hypersensitivity myocarditis.

BACKGROUND: Eosinophilic myocarditis is an inflammatory condition of the heart in which the infiltrate is composed predominately of eosinophils. DESIGN: We identified three cases of eosinophilic myocarditis in which the infiltrating eosinophils showed a remarkable intimate association with bundles of collagen. Two of the hearts examined were explants from heart transplant recipients with hypersensitivity myocarditis at the time of transplant and the third was from an autopsied patient with Churg-Strauss syndrome. These hearts were examined using light and electron microscopy. The cellular infiltrate in all three cases was characterized using immunoperoxidase stains with a panel including antibodies against myeloperoxidase, common leukocyte antigen (CD45), B lymphocytes (CD20), T lymphocytes (CD3), active-memory T lymphocytes (CD45RO), inactive T lymphocytes (CD45RA), and macrophages (CD68). RESULTS: Ultrastructural examination in all three cases confirmed the apposition of eosinophils to both large bundles of collagen and smaller aggregates of collagen fibrils. The eosinophils and the bundles of collagen stained strongly for myeloperoxidase, suggesting at least partial degranulation of the eosinophils. A KP-1 stain (CD68) revealed macrophages admixed with the eosinophils adjacent to the collagen bundles, and stains for CD45RA (naive lymphocytes) and CD45RO (memory T cells) showed an interstitial infiltrate of predominantly CD45RO-positive cells. Clinically, the cardiac decompensation of one of the transplant patients was most likely due to ranitidine-induced hypersensitivity myocarditis. CONCLUSIONS: These results suggest that some cases of eosinophilic myocarditis may be caused by the expression of novel antigens bound to collagen bundles. In one of the patients awaiting cardiac transplant, cardiac decompensation was temporally associated with ranitidine therapy, an agent not previously implicated as a cause of hypersensitivity myocarditis.

Adult↗
PubMed1994

The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients.

OBJECTIVES: The purpose of this study was to document the various causes of dilated cardiomyopathy in a large group of adult patients with congestive heart failure. BACKGROUND: Previous reports of the causes of dilated cardiomyopathy have usually been case reports of a single specific etiology or review articles. The frequency of any single specific heart muscle disease is largely unknown. METHODS: We evaluated 673 patients referred for congestive heart failure due to dilated cardiomyopathy. The evaluation included medical history, physical examination, routine blood chemistry and hematologic measurements, electrocardiography and echocardiography. Thyroid function tests, antinuclear antibody tests and urinary vanillylmandelic acid and metanephrine levels were also obtained. Endomyocardial biopsy with right heart catheterization was performed in every patient. Coronary arteriography was performed in patients who had at least two standard cardiovascular risk factors or a history suggestive of myocardial ischemia. The cases were retrospectively reviewed, and a final cause for dilated cardiomyopathy was listed for each patient. RESULTS: The most common causes of dilated cardiomyopathy were idiopathic origin (47%), idiopathic myocarditis (12%) and coronary artery disease (11%). The other identifiable causes of dilated cardiomyopathy made up 31% of the total cases. CONCLUSIONS: Idiopathic dilated cardiomyopathy is a common cause of congestive heart failure. Specific heart muscle diseases occur with much less frequency.

Biopsy↗
PubMed1994

Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus.

OBJECTIVES: The purpose of this study was to characterize the histologic and immunopathologic results of 37 endomyocardial biopsy samples from patients infected with human immunodeficiency virus type 1 (HIV-1) who were evaluated for unexplained global left ventricular dysfunction. BACKGROUND: Recent studies have identified a growing number of patients infected with HIV-1 who develop unexplained left ventricular dysfunction and congestive heart failure. Myocarditis has been confirmed at autopsy in small numbers of such patients, although a pathogenic opportunistic infectious agent can rarely be identified. METHODS: All patients had moderate to severe global left ventricular hypokinesia on two-dimensional echocardiography. Endomyocardial biopsy samples were evaluated by standard histologic studies, immunoperoxidase staining and in situ hybridization for cytomegalovirus and HIV-1 gene sequences. RESULTS: Twenty-eight patients presented with New York Heart Association functional class III or IV congestive heart failure. Four patients had myocarditis secondary to known etiologies (opportunistic infection n = 2; drug-induced hypersensitivity myocarditis n = 2). Of the remaining 33 samples, 17 (51%) showed histologic evidence of idiopathic active or borderline myocarditis. Immunohistologic findings revealed induced expression of major histocompatibility class I antigen on myocytes and increased numbers of infiltrating CD8+ T lymphocytes. Specific hybridization within myocytes was observed in 5 of 33 samples with the HIV-1 antisense riboprobe and in 16 of 33 samples with the cytomegalovirus immediate early (IE-2) antisense riboprobe. All but one patient with specific myocyte hybridization presented with congestive heart failure; all patients had myocarditis and CD4+ cell counts < 100/mm3. CONCLUSIONS: This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.

AIDS-Related Opportunistic Infections↗
PubMed1994

Diabetes mellitus and risk of idiopathic dilated cardiomyopathy. The Washington, DC Dilated Cardiomyopathy Study.

An epidemiologic study was carried out to examine the possible role of diabetes mellitus and other factors in the development of idiopathic dilated cardiomyopathy. Possible associations with diabetes and other factors were examined by comparing newly diagnosed case patients (n = 129) ascertained from five Washington, DC area hospitals with neighborhood control subjects (n = 258) identified using a random-digit dialing technique. The case patients and control subjects were matched by sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of diabetes (relative odds = 2.2; 95% confidence interval: 1.5 to 3.3). The association with diabetes was not explained by race, income, cigarette usage, or hypertension. A total of 28.7% (37/129) of the case patients had a reported history of diabetes, as compared with 13.6% (35/258) of the control subjects (P < 0.05). A possible interactive effect was also observed between diabetes and history of hypertension (P > 0.05). These findings support the view that diabetics, particularly those with a history of hypertension, may be at increased risk of idiopathic dilated cardiomyopathy.

Adult↗
PubMed1994

Peritransplant injury to the myocardium associated with the development of accelerated arteriosclerosis in heart transplant recipients.

Accelerated arteriosclerosis is now the major long-term complication of heart transplantation. Defining the risk factors associated with the development of accelerated arteriosclerosis will provide not only a means of identifying patients at risk for this complication but also clues to the etiology of accelerated arteriosclerosis. The purpose of this study was to examine the relationship between peritransplant myocardial ischemic injury and the development of accelerated arteriosclerosis. In a case-control study we examined the first three endomyocardial biopsies from 50 heart transplant recipients and graded the degree of ischemic injury present in these biopsies. The histologic changes graded in the biopsies included contraction band necrosis, coagulative necrosis, and macrophagic removal of ischemically injured myocytes. Of the 50 recipients included in the study, 25 had angiographic evidence of accelerated arteriosclerosis and 25 did not. In multivariate analysis, which included the number of class I major histocompatibility (MHC) antigen mismatches between the donor and the recipient, the recipient's post-transplant cytomegalovirus status, the donor's age, and the number of rejection episodes, the histologic degree of ischemic injury present in the biopsies emerged as the strongest predictor of the development of accelerated arteriosclerosis (RR 2.6, 95% CI 1.2-5.8, p = 0.02). These results suggest that ischemic injury to the heart during the peritransplant period significantly contributes to the development of accelerated arteriosclerosis in heart transplant recipients and that histologic changes in early posttransplant biopsies can be used to identify recipients at risk of developing accelerated arteriosclerosis.

Adolescent↗
PubMed1994

Black-white differences in mortality in idiopathic dilated cardiomyopathy: the Washington, DC, dilated cardiomyopathy study.

Racial, socioeconomic, and clinical factors were examined as predictors of survival in idiopathic dilated cardiomyopathy using cases from five Washington, DC-area hospitals. One hundred three (80.5%) of the patients were black and 25 (19.5%) were white. The black patients were less likely to have private health insurance, less educated on average, and more likely to have a household income of $15,000 or less (P < or = .05). No racial differences were found in cardiac medication usage, with the exception of beta blockers and antiarrhythmics. The cumulative survival among black patients at 12 and 24 months was 71.5% and 63.6%, respectively, as compared with 92.0% and 86.3% among whites. The 12-month survival of black patients with ventricular arrhythmias or an ejection fraction of less than 25% was particularly poor. Age, ventricular arrhythmias, ejection fraction, and cigarette usage were significant predictors of survival in univariate analysis using the proportional hazards model. The univariate association with black race was of borderline significance (P < or = .07). In multivariate analysis, age and race were statistically significant independent predictors of survival. A strong association with black race was observed with an estimated relative risk of mortality of 5.41 (P < or = .02) after adjustment for age, ejection fraction, ventricular arrhythmias, and educational attainment. Poorer survival among blacks may be caused by a greater severity of disease at the time of diagnosis or by racial differences in cardiac care, comorbid conditions, or biologic factors affecting survival.

Adult↗
PubMed1993

Prevalence and incidence of left ventricular dysfunction in patients with human immunodeficiency virus infection.

The prevalence and incidence of left ventricular (LV) dysfunction was examined in patients infected with the human immunodeficiency virus (HIV). Sixty-nine randomly selected patients diagnosed with HIV infection who were followed in HIV clinics were prospectively evaluated by 2-dimensional echocardiography. Mean follow-up duration was 11 months. Additionally, 39 consecutive HIV-infected patients referred to the Cardiomyopathy Service and found to have LV dysfunction by 2-dimensional echocardiography were also studied. Of the 39 referred patients, 34 (87%) were referred for recent onset, unexplained, congestive heart failure. During this time, the HIV clinic population comprised 1,819 alive and actively followed patients; the 39 cardiomyopathy referrals therefore constituted a crude rate of 2.1% for this population. Of the 69 prospectively studied patients without clinical heart disease, a 14.5% prevalence of global LV hypokinesia and an incidence of 18%/patient-year were found. During a maximal 18-month follow-up period, 4 prospective patients (5.8%) developed symptoms of congestive heart failure. A greater proportion of prospective and referred patients with LV dysfunction had CD4 counts < 100/mm3 (62 and 79%, respectively) than did that of those without LV dysfunction (35%). In conclusion, the high rate of unexpected LV dysfunction in this HIV-infected population suggests that early cardiac contractile abnormalities may involve a significant number of patients, most of whom have low CD4 counts. A subgroup of these patients appears to progress to symptomatic congestive heart failure.

Adult↗
PubMed1993

Demographic features and prevalence of idiopathic myocarditis in patients undergoing endomyocardial biopsy.

From January 1985 through December 1990, 534 patients underwent endomyocardial biopsy at Johns Hopkins Hospital for suspected myocarditis. One hundred thirty-eight (26%) biopsy specimens were diagnosed histologically by 2 cardiac pathologists as either active (n = 85, 16%) or borderline (n = 53, 10%) myocarditis. Of the 138 patients, 60 were excluded based on either specific concurrent clinical conditions or noncongestive heart failure presentations. Immunohistochemical staining for common leukocyte antigen infiltrating cells performed on the remaining 78 specimens confirmed the presence of focal or multifocal inflammatory infiltrates in 58, of which 49 had histologic evidence of active myocarditis. All 49 patients presented with congestive heart failure and left ventricular ejection fractions of < 40%. Compared with patients with either idiopathic dilated cardiomyopathy (n = 207) or ischemic cardiomyopathy (n = 44), these patients with myocarditis had a less striking male predominance (58 vs 69 and 83%, respectively) (p = 0.02) and were younger (43 +/- 16 vs 50 +/- 17 and 55 +/- 13 years, respectively, p = 0.005). Racial distributions were similar. A recent history of a discrete flu-like illness was obtained in 52%, two-thirds of which were clustered between the months of December and March. Onset of heart failure peaked between December and April (63% and was low between May through September (22%). A peak in the proportion of patients found to have active myocarditis on biopsy occurred in 1986 (17 vs 7 to 10% in other years).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Descriptive epidemiology of idiopathic dilated cardiomyopathy in Washington County, Maryland, 1975-1991.

Estimates of the incidence of idiopathic dilated cardiomyopathy (IDC) were obtained by identifying cases from Washington County, Maryland who were hospitalized at local and regional hospitals over a recent 17 year period. All of the verified cases had evidence of ventricular dilatation and hypokinesis, with a left ventricular ejection fraction of less than 40%. A total of 26 cases were hospitalized over the period 1975-1991. The average age of the cases at the time of diagnosis was 55.5 years (range 22-80 years of age). About 58% of the subjects were males. A marked increase in newly diagnosed cases of IDC occurred in this population in recent years; 38% of the cases (10 of 26) were newly diagnosed during 1991 alone. Over the period 1975-1991, the average annual incidence rate of hospitalized cases was 1.6 per 100,000 among men and 1.2 per 100,000 among women. During the last 7 years of the case ascertainment period (1985-1991), the average annual incidence rate was 3.5 per 100,000 among men and 2.5 per 100,000 among women. These results provide additional evidence that IDC is being increasingly recognized by clinicians, and underscore the need for an improved understanding of the distribution and determinants of this often fatal condition.

Adult↗
PubMed1993

Myocarditis associated with doxorubicin cardiotoxicity.

In contrast to previous reports, the authors were impressed by the frequency of myocarditis in the endomyocardial biopsy specimens of patients treated with anthracyclines. To examine this, they reviewed the histologic and electron microscopic results and immunoperoxidase stains of myocardial biopsy specimens from 11 patients with doxorubicin cardiotoxicity grades 1.0-3.0. Immunoperoxidase stains for lymphocytes, macrophages, and endothelial cells and induced expression of Class II antigen were performed using the avidin-biotin complex procedure. A full panel of monoclonal antibodies was employed on fresh-frozen tissue; a smaller panel was used with formaldehyde-fixed paraffin-embedded material. Four of the 11 endomyocardial biopsy specimens showed myocarditis, and 2 showed borderline myocarditis by the Dallas criteria. The infiltrating lymphocytes were generally characterized as T lymphocytes and were associated with induced Class II antigen expression by arterial endothelial cells. In addition, foci of replacement fibrosis, suggesting a chronic process, were identified. Although this association does not prove a causal relationship, these results suggest that myocarditis can be a component of doxorubicin-induced myocardial injury.

Adult↗