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W H Abelmann

Publications and source records attributed to W H Abelmann.

At least 19 recordsLinked to original sources
PubMed1997

Generation of physician-scientists manpower: a follow-up study of the first 294 graduates of the Harvard-MIT Program of Health Sciences and Technology.

BACKGROUND: The MD program of the Harvard-MIT Division of Health Sciences and Technology was founded in 1970. One of its goals was the application of the academic resources of the two universities to the education of leaders in academic medicine and biomedical sciences. METHODS: The first MD class was admitted in 1971. Prerequisites for admission are a strong background in quantitative sciences and demonstrated interest in research. Research and a thesis are obligatory. Enrollment in a PhD program is elective. Questionnaires were sent to 293 alumni who graduated from the MD program between 1975 and 1988, followed up by letters and telephone calls. RESULTS: By 1988, 296 students had graduated, 207 with an MD only, 89 with MD-PhD degrees. Follow-up by questionnaires of 293 living graduates (92%), plus indirect data on 11 others, revealed that 212 (75%) held faculty appointments in 64 medical schools. Overall, 73.5% of respondents were engaged in research: 68% of MDs and 86% of MD-PhDs. One hundred and four (38%) respondents spent more than 50% of their time on research: 54 (29%) of MDs and 50 (60%) of MD-PhDs. Seventy-five percent of respondents were active in teaching. CONCLUSION: Our experience indicates that both an MD-PhD program and a research-oriented MD program are effective in producing physician-scientists and leaders in academic medicine.

Career Choice↗
PubMed1993

Producing physician-scientists: a survey of graduates from the Harvard--MIT Program in Health Sciences and Technology.

BACKGROUND: The Harvard-MIT Program in Health Sciences and Technology (HST) is a flexible, preclinical curriculum, taught by members of the faculties of both Harvard University and the Massachusetts Institute of Technology, that stresses a rigorous, scientific, quantitative approach, small classes (usually fewer than 50 students), and student-faculty interaction. The program is aimed at students with strong backgrounds in quantitative and biological sciences who are interested in careers as physician-scientists. METHOD: The first 234 students of the program, who graduated between 1975 and 1985, were asked to participate in a 1990 follow-up study by completing a four-page questionnaire and submitting curricula vitae and lists of publications, if available. Data were analyzed quantitatively and qualitatively. RESULTS: Of the 234 graduates, 211 (90%) responded. Sixty-three (30%) had received both MD and PhD degrees. The graduates were twice as likely to describe their primary professional roles as academic than as clinical practice; 94 held full-time faculty positions at 50 medical schools. The 154 (73%) in research spent an average of 51% of their time on this activity. According to the 179 graduates (85%) who stated that they would choose HST again, the most frequently mentioned reasons were the quantitative approach that emphasized integration of basic science and clinical practice (49%) and the small class size (37%). CONCLUSION: The HST MD curriculum, with its emphasis on basic science and research experience, has been successful in preparing carefully selected students for careers as physician-scientists, without necessarily requiring the completion of a PhD degree.

Career Choice↗
PubMed1993

Myocardial fibrin deposition in experimental viral myocarditis that progresses to dilated cardiomyopathy.

Myocardial fibrosis is a characteristic late feature in cases of viral myocarditis that progress to dilated cardiomyopathy. However, the pathogenesis of the myocardial fibrosis in such cases is unknown. Prior studies have shown that in healing wounds and tumor stroma generation, interstitial fibrin deposition precedes the development of fibrosis. Therefore, interstitial fibrin deposition in the myocardium was investigated in a murine model of myocarditis in which dilated cardiomyopathy develops. Inbred male C3H/He mice inoculated with coxsackievirus B3 were killed 0, 3, 7, 14, 21, 30, and 60 days after infection. Paraffin sections of hearts were stained with hematoxylin-eosin, Masson's trichrome stain, and antibodies to fibrinogen/fibrin by use of an immunoperoxidase technique. Pretreatment of all mice with anticoagulants and antifibrinolytics 5 minutes before death was used to prevent artifactual fibrin deposition and fibrinolysis during tissue manipulation. Tissue fixation in formalin supplemented with acetic acid served to extract non-cross-linked fibrin, fibrinogen, and fibrinogen and fibrin degradation products, thus ensuring that clotted and cross-linked fibrin was the major immunoreactant. Myocardial fibrin deposition and fibrosis were each quantitated by computer-assisted image analysis. Myocardial fibrin deposition first appeared on day 3, was maximal on day 14, and disappeared by day 30. Conversely, myocardial fibrosis was not detectable until day 14 and was maximal at day 60. Thus, as in healing wounds and developing tumor stroma, fibrin deposition preceded fibrosis in this murine model of myocarditis that progresses to dilated cardiomyopathy.

Animals↗
PubMed1992

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

Cardiomyopathy, Dilated↗
PubMed1992

An experimental model of acute and subacute viral myocarditis in the pig.

Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST-T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions.

Animals↗
PubMed1991

Natural evolution of cardiac function, cardiac pathology and antimyosin scan in a murine myocarditis model.

Serial technetium-99m radionuclide ventriculograms, indium-111 antimyosin antibody scans and tissue biodistribution studies were performed in C3H/He mice with experimentally induced viral encephalomyocarditis and the results were compared with pathologic assessments of myocardial necrosis. Postinfection ejection fraction decreased on days 10 (20.7 +/- 5.5%, n = 6), 20 (18.6 +/- 15.2%, n = 5), 30 (18.5 +/- 7.7%, n = 5) and 150 (30.0 +/- 18.7, n = 6) (p less than 0.001) in comparison with that in uninfected control mice (63.3 +/- 3.1%, n = 6). In the same group of animals, indium-111 antimyosin antibody scans showed intense positive myocardial accumulation on day 10 (in six of six mice) and only slight accumulation on day 20 (in one of five mice). In the chronic stage, two of five mice on day 30 and two of six mice on day 150 still showed positive uptake. The antimyosin scan myocardium to lung uptake ratio (expressed as mean count density [mean counts/pixel of the region] ratio) increased greatly on day 10 (p less than 0.001 versus values in uninfected control mice) but not subsequently. Biodistribution studies of the indium-111 antimyosin antibody showed that the heart to blood count ratio was significantly higher on day 10 (p less than 0.001 versus values in control mice) but not on days 20, 30 and 150. Pathologic examination showed active and ongoing severe myocardial necrosis with dilated ventricles on day 10. On day 20, there was less active necrosis and healing had appeared to begin. On days 30 and 150, myocardial fibrosis increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Immunosuppression with high doses of cyclophosphamide reduces the severity of myocarditis but increases the mortality in murine Coxsackievirus B3 myocarditis.

To test the therapeutic efficacy of immunosuppression with cyclophosphamide (CYP) on coxsackievirus B3 (CB3) myocarditis, 2-week-old DBA/2 mice were inoculated with 3 X 10(2) plaque-forming units of CB3 virus. CYP (100 mg/kg/day s.c.) was administered daily on days 0-8 (experiment 1; group 2), days 8-21 (experiment 2; group 4), and days 21-34 (experiment 3; group 6). Groups 1, 3, and 5 were infected control groups for each experiment. Spleen, thymus, and body weights were measured. In experiment 1, survival rate in group 2 on day 8 was low compared with group 1 (nine of 51 versus eight of 28; p = NS), and myocardial virus titers in group 2 on day 8 were higher (p less than 0.05) compared with group 1; however, cellular infiltration and myocardial necrosis in group 2 were less severe (p less than 0.05), and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 2, survival rate in group 4 on day 21 was significantly lower (six of 24 versus 12 of 16; p less than 0.01), but cellular infiltration, myocardial necrosis, and calcification in group 4 were significantly less severe, and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 3, survival rate, cardiac histopathology, and serum neutralizing antibody titers did not differ between groups 5 and 6. In experiments 1, 2, and 3, the treated groups were characterized by lower spleen-to-body-weight and thymus-to-body-weight ratios and by marked cellular depletion in spleen and thymus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

In vivo significance of T cells in the development of Coxsackievirus B3 myocarditis in mice. Immature but antigen-specific T cells aggravate cardiac injury.

Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with coxsackievirus B3 (CB3) or encephalomyocarditis virus (EMC). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu/+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3- or EMC-infected nu/+ mice. Acute myocarditis occurred in both nu/nu and nu/+ mice. Severe myocarditis, however, developed only in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogenesis of ongoing myocarditis.

Animals↗
PubMed1989

Characteristics of lymphocytes cultured from murine viral myocarditis specimens: a preliminary and technical report.

Long-term culture of lymphocytes from myocardial biopsy specimens has been reported. To test the usefulness of this technique in experimental models of murine myocarditis, the culture and characterization of lymphocytes from mice infected with encephalomyocarditis virus or coxsackievirus B3 were studied. Lymphocytes were successfully cultured from three hearts of encephalomyocarditis virus-infected mice in interleukin 2-containing culture. After approximately 10 days, lymphocytes migrated out of myocardium in the chronic stage of myocarditis and gradually increased in numbers. More than half of the exuding cells were Thy 1.2-positive. None of the myocardial samples from coxsackievirus B3-infected mice grew out lymphocytes. Pathologic examination of all specimens showed myocardial necrosis with lymphoid infiltration. Although further studies are needed, this preliminary study suggests that the technique of lymphocyte culture may promote new insights into the pathogenesis of experimental myocarditis.

Animals↗
PubMed1989

The challenge of cardiomyopathy.

The combined clinical and pathophysiologic characteristics and diagnostic features as well as current concepts of pathogenesis, therapy and prevention of the principal forms of cardiomyopathy are reviewed. These include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy and specific cardiac muscle disease. Emphasis is placed on recent developments and unresolved questions requiring application of newer techniques of molecular biology and genetics and adult myocyte culturing.

Cardiomyopathy, Dilated↗
PubMed1989

Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice.

The efficacy of monoclonal antibodies against T cell subsets in the therapy of experimental myocarditis caused by coxsackievirus B3 (CB3) was investigated. Two-week-old male C3H/He mice were inoculated with CB3 virus. Treatment was begun in the viremic stage (starting on the day of inoculation) in experiment 1 and in the later aviremic stage (starting on day 10) in experiment 2. Rat anti-mouse monoclonal antibodies, Lyt 1 (helper/inducer T) at 1 microgram/mouse (group 2 in experiment 1; group 6 in experiment 2), Lyt 2 (suppressor/cytotoxic T) at 1 microgram/mouse (group 3 in experiment 1; group 7 in experiment 2), and Lyt 1 at 1 microgram plus Lyt 2 at 1 microgram/mouse (group 4 in experiment 1; group 8 in experiment 2), were administered subcutaneously daily for 2 weeks. The treatment groups were compared with infected controls (group 1 in experiment 1; group 5 in experiment 2). In experiment 1, the survival rate in group 4 was higher (p less than 0.01) than in group 1. In experiment 2, mice treated with Lyt 1 plus Lyt 2 (group 8) survived significantly longer (p less than 0.05) than did controls (group 5). In experiment 1, myocardial virus titers on days 5 and 6 did not show any significant differences among the four groups. Serum-neutralizing antibody titers between group 1 and group 4 in experiment 1 or between group 5 and group 8 in experiment 2 did not differ significantly. Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups: there was less infiltration in group 4 and in group 8 and less severe necrosis in group 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Absence of effects of cyclosporine on myocardial lymphocyte subsets in Coxsackievirus B3 myocarditis in the aviremic stage.

To test the therapeutic efficacy of immunosuppression with cyclosporine upon the aviremic stage of coxsackievirus B3 (CB3) myocarditis, 2-week-old BALB/c mice were inoculated with 3 x 10(2) plaque-forming units of CB3, and the effects of cyclosporine on peripheral, splenic, and myocardial lymphocyte subsets were investigated. Cyclosporine, 25 mg/kg/day, was administered subcutaneously daily on days 10-31 (experiment 1) and days 30-51 (experiment 2). Treated groups were compared with infected controls for each experiment. In experiment 1, the survival rate of the cyclosporine-treated group was low (17/25 vs. 24/25, p less than 0.05). The severity of myocardial lesions and the distribution of lymphocyte subsets in myocardium and spleen on days 15-18 did not differ between treated and control groups; on the other hand, the percentages of peripheral Thy 1.2+ (pan T) and L3T4+ (activated helper T) cells on days 15-18 were decreased in the treated group, and those of B, Lyt 1+ (helper/inducer T), and Lyt 2+ (suppressor/cytotoxic T) subsets did not differ significantly. Notably, myocardial interleukin-2 receptor (IL-2R) positive cells, through which cyclosporine is considered to act, were scarce in both groups. In experiment 2, survival rates of two groups did not differ (treated, 32/34; untreated, 34/34; p = NS). The severity of myocardial lesions and the distribution of splenic lymphocyte subsets on days 35-38 also were not different between two groups. The percentages of peripheral lymphocyte subsets (Thy 1.2+ and L3T4+) were decreased in the treated group; those of B, Lyt 1+, and Lyt 2+ subsets did not differ significantly. In experiments 1 and 2, the thymus/body weight ratio in the treated groups was smaller than in the untreated group, but the spleen/body weight ratio in the treated group did not differ from the untreated group; histologically, medullary cellular depletion was evident in the thymus, not in the spleen, of the treated groups. We conclude that cyclosporine failed to change the distribution of lymphocyte subsets in the spleen as well as in the myocardium in CB3 myocarditis although it had effects on the peripheral blood and thymus, which may account for the higher mortality in the treated groups. The absence of beneficial effects of cyclosporine upon the CB3-infected myocardium may be related to the paucity of cyclosporine-sensitive cells (IL-2R, L3T4, and Lyt 2 positive cells) in the myocardium.

Animals↗
PubMed1989

Echocardiographic assessment of cardiac chamber size and functional performance in swine.

Ninety nonanesthetized 7- to 16-week-old pigs were studied, using 2-dimensional echocardiography that permits orientation of a targeted M-mode beam perpendicular to structures being studied and allows serial studies of the same cardiac regions. Normative data were obtained and included body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and left ventricular fractional shortening. A positive correlation was found between body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and fractional shortening. A correlation was found between body weight and age. Best-fit analysis resulted in all measurements fitting either a first- or second-degree polynomial.

Age Factors↗