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Biomedical subjects

J M Mann

Publications and source records attributed to J M Mann.

At least 19 recordsLinked to original sources
PubMed1992

Assessment of rejection in orthotopic human heart transplantation using proliferating cell nuclear antigen (PCNA) as an index of cell proliferation.

Myocardial biopsies taken during the management of cardiac transplantation were stained for proliferating cell nuclear antigen (PCNA). Counts of PCNA-positive interstitial cells were compared, in retrospect, with the reported histological grade of rejection. Biopsies without rejection had negligible numbers of PCNA-positive cells. Ascending grades of rejection were paralleled by an increase in the number of PCNA-positive cells [grade 1, 13 +/- 35 (mean +/- SD); grade 2a, 38 +/- 40; grade 2b, 91 +/- 75; grade 3, 170 +/- 78]. While highly significant, in statistical terms, the overlap in the counts between different grades means that prediction of rejection from the PCNA count alone is not feasible. Biopsies graded as 0 or 1 and which immediately preceded more severe rejection episodes showed no increase in PCNA-positive cells. The majority of PCNA-positive cells are fibroblasts, although in grade 2b and 3 rejection a small population of PCNA-positive T lymphocytes occurs. PCNA staining is also seen in cardiac myocytes immediately after transplantation, during rejection episodes, and late after transplantation in the absence of rejection. The positive PCNA staining of cardiac myocytes probably reflects DNA synthesis that occurs with the shift toward polyploidy in hypertrophy.

Autoantigens↗
PubMed1992

Myocardial magnesium depletion associated with prolonged hypomagnesemia: a longitudinal study in heart transplant recipients.

OBJECTIVES: This study was carried out to establish prospectively the incidence and relation of hypomagnesemia and myocardial magnesium depletion after heart transplantation. BACKGROUND: No serial in vivo study of the relation of serum with tissue magnesium has been described. Myocardial magnesium depletion is associated with intracellular calcium overload, an increased incidence of cardiac arrhythmia and changes in coronary vasculature similar to those seen in the accelerated atherosclerosis that compromises graft survival after transplantation. METHODS: In a prospective study in 19 consecutive patients, serum and myocardial magnesium content were measured serially for 9 months after heart transplantation. Blood cyclosporine was assayed simultaneously. RESULTS: The incidence of hypomagnesemia was 100% during the 9-month study period, with lowest levels at 3 months (mean 0.80 vs. 0.64 mmol/liter, p less than 0.002). Myocardial magnesium depletion developed in 94% and was persistent in 55%; the lowest levels occurred at 6 months (mean 33.6 vs. 30.1, mumol/g, p less than 0.04). Hypomagnesemia predated decreases in myocardial magnesium by 2 to 6 weeks. Peak cyclosporine levels correlated positively with the decrease in serum magnesium. Clinical events were rare. CONCLUSIONS: This is the first report of serial measurement of tissue magnesium. Persistent hypomagnesemia is invariably accompanied by myocardial magnesium depletion in the transplanted heart. Reciprocal calcium overload and adverse changes in coronary vasculature would be expected from previous studies and merit further investigation. Should the implications of this study extend to the native heart, myocardial magnesium depletion may contribute to the high incidence of fatal arrhythmic events observed in patients with heart failure, who commonly have persistent hypomagnesemia.

Cyclosporine↗
PubMed1992

AIDS--the second decade: a global perspective.

The human immunodeficiency virus (HIV) and AIDS epidemic merits its designation as a pandemic: AIDS cases are reported to the World Health Organization from 163 countries, and at least 10 million adults have been infected with HIV. The pandemic is a relatively new phenomenon, and therefore it remains dynamic, unstable, and volatile. Transmission continues in all already-affected countries; HIV is spreading, sometimes quite rapidly, to previously unaffected or little-affected areas of the world; and the epidemic becomes more complex and differentiated. The major impact of the pandemic is yet to come: In the 1990s, a 10-fold increase is anticipated in the numbers of adults (to 10 million) and children (to 5 million) developing AIDS. The social, cultural, economic, and political impacts of the pandemic are also increasing. The community, national, and international approach to control of the pandemic must continue to evolve, taking into account the specific conditions of the modern world, of which the global interdependence of health has become the major new factor.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Myocardial disarray in Noonan syndrome.

OBJECTIVE: To characterise the histopathology of the left ventricular hypertrophy commonly associated with Noonan syndrome by assessing the extent of myocyte disarray and therefore to define one aspect of the relation between this disease and idiopathic hypertrophic cardiomyopathy. DESIGN: Blinded histological analysis. SETTING: Hospital medical school. PATIENTS: Six hearts of children with the Noonan phenotype and isolated ventricular hypertrophy were compared with age and sex matched controls. METHODS: Histological analysis was performed with an image analyser under light microscopy. Representative sections from the entire left ventricular free wall were examined. Results were expressed as the percentage of fields showing disarray related to the number of fields evaluated: 100 fields were examined for each patient. RESULTS: In the patients with Noonan syndrome myocardial disarray was present in the ventricular septum in 24 (5.7)% (mean (SD)) of fields and in the free wall in 22.2 (6.8)%. In the controls disarray was present in the septum in 3.8 (2.3)% of fields and in the free wall in 2.4 (2.8)%. In both regions the extent of disarray was significantly greater in patients with Noonan syndrome (p < 0.0005; 95% confidence interval 14 to 26.3 for the septum: p < 0.005, 95% confidence interval 11.4 to 28.2 for the free wall). CONCLUSIONS: The ventricular hypertrophy associated with Noonan syndrome is histologically similar to hypertrophic cardiomyopathy but whether the two diseases are the expression of the same genetic defect remains to be determined.

Child↗
PubMed1992

Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy.

BACKGROUND: Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform. METHODS AND RESULTS: We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) using indirect immunofluorescence. To identify the autoantigen(s) recognized by heart-specific autoantibodies in human disease, we tested, by Western blotting, sera from 26 DCM patients, 14 of whom were cardiac antibody-positive and 12 antibody-negative, as well as sera from 12 patients with cardiac failure from ischemic or valvular heart disease and from 13 normal subjects who were cardiac antibody-negative. Crude myofibrillar proteins and myosin preparations extracted from human atrial or ventricular specimens were used as antigens. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed. The proteins were electrophoretically transferred to nitrocellulose sheets. The paper strips were incubated in sera from patients or controls at 1:100 dilution; the reaction was revealed with a peroxidase-labeled second antibody against human immunoglobulin. Twelve of the 14 DCM sera (86%) containing heart-specific antibodies reacted with both the alpha- (atrial specific) and beta- (ventricular and slow skeletal) myosin heavy chain isoforms; none of the 13 normal sera (p = 0.0001) and one of the 24 heart failure-negative control sera (4%, p = 0.0001) contained antibodies against myosin heavy chain. CONCLUSIONS: These findings indicate that alpha- and beta-cardiac myosin heavy chain isoforms as in the murine model of autoimmune heart disease are major autoantigens in patients with idiopathic DCM.

Adult↗
PubMed1991

Experimental model of left ventricular failure.

A model of chronic cardiac failure has undergone extensive hemodynamic investigation. Under anesthesia the homonymous and second diagonal coronary arteries of sheep have been ligated. The resulting myocardial infarction caused significant acute hemodynamic impairment (paired two-tailed t tests), mean pulmonary artery pressure increasing from 7.31 +/- 0.94 to 13.80 +/- 1.19 mm Hg (p less than 0.001), pulmonary artery diastolic pressure increasing from 4.94 +/- 1.03 to 11.13 +/- 1.27 mm Hg (p less than 0.001), and directly measured left ventricular end-diastolic pressure increasing from 9.31 +/- 1.52 to 17.42 +/- 1.82 mm Hg (p less than 0.001) after infarction documented with invasive monitoring. There was a hemodynamically significant left ventricular aneurysm (paired two-tailed t tests) in animals studied 3 months later, with increased mean pulmonary artery pressure from 7.20 +/- 1.15 to 13.80 +/- 2.00 mm Hg (p = 0.009), an increase in pulmonary artery diastolic pressure from 4.60 +/- 1.30 to 12.10 +/- 2.06 mm Hg (p = 0.006), and an increase in left ventricular end-diastolic pressure from 11.00 +/- 1.94 mm Hg before infarction to 17.00 +/- 2.69 mm Hg (p = 0.038). We conclude that this is a useful model of chronic left ventricular failure that is reproducible and applicable to investigations of therapeutic options in chronic heart failure.

Animals↗
PubMed1991

Global AIDS: critical issues for prevention in the 1990s.

A review of the first decade of global experience with the struggle against HIV/AIDS suggests that prevention will require both full application of existing approaches and fundamental changes in concepts and values. The critical deeper issues can be grouped under three headings: behavior, societal action, and globalism. Behavior, individual and collective, will be increasingly recognized as the major challenge for public health. However, for purposes of HIV prevention (and other issues) a sufficient understanding of behavior has not yet been developed. At the societal level, the activism of community organizations has shifted the balance of initiative in public health toward the community. The long-term implications of this evolution for roles and responsibilities at the community, national, and international levels must be explored. Finally, an understanding of global solidarity, based on respect for human rights and on the objective conditions of the modern world, will be critical for the future capability to deal effectively with HIV/AIDS. In summary, the future of HIV/AIDS prevention and control cannot be separated from the major public health and social issues of our time.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Human T cell lymphotropic virus type I (HTLV-I) among female prostitutes in Kinshasa, Zaire.

Three hundred seventy-seven prostitutes from Kinshasa, Zaire, were enrolled in a study to determine associated risk factors for human immunodeficiency virus type 1 (HIV-1) and human T cell lymphotropic virus type I (HTLV-I) infection. Twelve samples (3.2%) were seropositive for HTLV-I; results for HIV-1 (101 [26.8%]) are reported elsewhere. HTLV-I prevalence increased with age, and seven of the seropositive women originated from the Equateur region, a remote area in northwestern Zaire. The prevalence among women from Equateur (7.2%) was higher than that of women from all other regions (1.8%, P = .02). Presence of HTLV-I antibodies was not associated with frequency or type of sex practice. In a subsequent study, 350 serum samples were obtained from a variety of subjects in the Equateur region in 1986. Nineteen (5.4%) showed antibodies to HTLV-I. These data and a recent report of a cluster of patients with tropical spastic paraparesis from this region suggest that HTLV-I is endemic in the Equateur region of Zaire.

Adult↗
PubMed1990

Cerebrovascular accidents in infective endocarditis: role of anticoagulation.

Anticoagulation is still a matter of debate in infective endocarditis, since it can increase the risk of complications, mostly neurological. In our series of 269 patients with native valve endocarditis studied between 1970 and 1982, 35 were anticoagulated. We observed 14 patients with brain infarcts, of whom five died, and 12 patients with cerebromeningeal or brain haemorrhage of whom six died. In a similar series of 63 patients with prosthetic valve endocarditis, all of whom were on anticoagulation and were studied between 1972 and 1987, we observed five patients with brain infarcts, three of whom died, and two patients with brain haemorrhage, one of whom died. The frequency of cerebrovascular accident (CVA) was similar for both groups (11.1% in prosthetic endocarditis vs 11.5% in native valve endocarditis, P = ns), as was mortality rate (57% vs 48.4%, P = ns). CVA are significantly more frequent among anticoagulated patients (19/94 vs 19/238: P less than 0.01), but the mortality rate in CVA is similar for anticoagulated and non-anticoagulated patients (11/19 vs 8/19: P = ns). The indications for anticoagulation in infective endocarditis remain similar to those in valvular heart disease. In patients with infective endocarditis, anticoagulation with heparin should be maintained whenever a brain infarct is present, unless it is large and/or haemorrhagic.

Adolescent↗
PubMed1990

Projections of HIV infections and AIDS cases to the year 2000.

After the recognition of AIDS (acquired immunodeficiency syndrome) in the early 1980s, uncertainty about the present and future dimensions of HIV (human immunodeficiency virus) infection led to the development of many models to estimate current and future numbers of HIV infections and AIDS cases. The Global Programme on AIDS (GPA) of the World Health Organization (WHO) has developed an AIDS projection model which relies on available HIV seroprevalence data and on the annual rate of progression from HIV infection to AIDS for use in areas where reporting of AIDS cases is incomplete, and where scant data are available to quantify biological and human behavioural variables. Virtually all models, including the WHO model, have projected large increases in the number of AIDS cases by the early 1990s. Such short-term projections are considered relatively reliable since most of the new AIDS cases will develop in persons already infected with HIV. Longer-term prediction (10 years or longer) is less reliable because HIV prevalence and future trends are determined by many variables, most of which are still not well understood. WHO has now applied the Delphi method to project HIV prevalence from the year 1988 to mid-2000. This method attempts to improve the quality of the judgements and estimates for relatively uncertain issues by the systematic use of knowledgeable "experts". The mean value of the Delphi projections for HIV prevalence in the year 2000 is between 3 and 4 times the 1988 base estimate of 5.1 million; these projections have been used to obtain annual estimates of adult AIDS cases up to the year 2000. Coordinated HIV/AIDS prevention and control programmes are considered by the Delphi participants to be potentially capable of preventing almost half of the new HIV infections that would otherwise occur between 1988 and the year 2000. However, more than half of the approximately 5 million AIDS cases which are projected for the next decade will occur despite the most rigorous and effective HIV/AIDS prevention efforts since these AIDS cases will develop in persons whose HIV infection was acquired prior to 1989. The Delphi projections of HIV infection and AIDS cases derived from the WHO projection model need to be periodically reviewed and modified as additional data become available. These projections should be viewed as the first of many attempts to develop estimates for planning strategies to combat the HIV/AIDS pandemic in the 1990s.

Adult↗
PubMed1990

International travel and HIV infection.

Although human immunodeficiency virus (HIV) infection is a worldwide problem, its prevalence and pattern vary from country to country. Accordingly, the risk to international travellers of acquiring HIV infection also varies widely in different parts of the world, and depends principally on their behaviour. The risk of sexual acquisition of HIV infection can be virtually eliminated by avoiding penetrative sexual intercourse with intravenous drug users and persons who have had multiple sexual partners (such as prostitutes) or reduced by the use of condoms. The risk of parenteral exposure to HIV can be reduced by avoiding parenteral drug use and behaviour that is likely to lead to injury (with its attendant risk of requiring blood transfusion) and by seeking medical facilities with adequate capabilities to screen blood donors for HIV and to sterilize instruments. HIV screening of international travellers is an ineffective, costly, and impractical public health strategy for limiting the worldwide spread of HIV infection. Travellers infected with HIV require specialized advice regarding health precautions, prophylactic medications, and immunization.

Acquired Immunodeficiency Syndrome↗