Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.     

Non-response to maprotiline caused by ultra-rapid metabolism that is different from CYP2D6?

In this historical prospective study using sera stored for 22 years, we investigated the effect of HTLV-I infection on survival in a population of leprosy patients in the Democratic Republic of the Congo (formerly Zaire). We also determined the distribution of HTLV-I by subpopulation, age, and gender. Stored sera taken from a population of leprosy patients and controls in 1969 were tested for HTLV-I. Follow-up survival data on these patients were obtained in 1991. The sera collected in 1969 from 520 individuals was used to determine the prevalence of HTLV-I. Included in this number were 328 patients resident in the sanatorium. Survival and other data were available for 327 of these. A multivariate survival analysis using a logistic regression model was performed to evaluate the influence of HTLV-I status, age, type of leprosy, gender, duration of hospitalization, and ethnic group on survival. The overall prevalence of HTLV-I among the 520 individuals in the prevalence study was 34%, with 37.4% in the leprosy group and 25.2% in the control group (p < 0.01). Multivariate analysis using logistic regression showed that females of the Mongo and Ngombe ethnic group taken together were significantly more likely to be infected than the other groups (OR = 3.67, 95% CI: 2.14 to 6.30). A comparison of the death rates directly standardized for age and sex showed that the rate was significantly higher for HTLV-I positive (5.5/100 person-years of observation) compared with HTLV-I negative (3.6/100 person-years of observation). A survival analysis using the Cox model showed a risk ratio of 1.4 (CI: 1.04 to 1.89) for those infected with HTLV-I. An increase in the death rate was associated with HTLV-I infection in leprosy inpatients. The decreased survival associated with HTLV-I infection may result from an increased susceptibility to a variety of diseases.     

A case-mix classification system for medical rehabilitation

Dissatisfaction with Medicare's current system of paying for rehabilitation care has led to proposals for a rehabilitation prospective payment system, but first a classification system for rehabilitation patients must be created. Data for 36,980 patients admitted to and discharged from 125 rehabilitation facilities between January 1, 1990, and April 19, 1991, were provided by the Uniform Data System for Medical Rehabilitation. Classification rules were formed using clinical judgment and a recursive partitioning algorithm. The Functional Independence Measure version of the Function Related Groups (FIM-FRGs) uses four predictor variables: diagnosis leading to disability, admission scores for motor and cognitive functional status subscales as measured by the Functional Independence Measure, and patient age. The system contains 53 FRGs and explains 31.3% of the variance in the natural logarithm length of stay for patients in a validation sample. The FIM-FRG classification system is conceptually simple and stable when tested on a validation sample. The classification system contains a manageable number of groups, and may represent a solution to the problem of classifying medical rehabilitation patients for payment, facility planning, and research on the outcomes, quality, and cost of rehabilitation.     

The interaction of peripheral blood leukocytes with alpha1-acid glycoprotein, its carbohydrate chains and neoglycoconjugates

The interaction of human peripheral blood leukocytes with alpha 1-acid glycoprotein (AGP), its glycoforms as well as neoglyco-conjugates representing carbohydrate chains of AGP or its fragments was studied by flow cytometry. It was shown that the main target cells for AGP as well as for conjugates of its carbohydrate chains with polyacrylamide (PAA) are monocytes and polymorphonuclear leukocytes but not lymphocytes. The interaction of AGP with monocytes and granulocytes are mediated by its carbohydrate chains: the binding of AGP with cells was inhibited by AGP, AGP oligosaccharides as well as conjugates of oligosaccharides and its fragments with PAA. The data obtained show the existence of monocyte (and granulocyte) receptors which interact with complex type sialooligosaccharides of AGP.     

Acetylation of core histones causes the unfolding of 30 nm chromatin fiber: analysis by agarose gel electrophoresis

In the present work it was directly demonstrated that increased acetylation level of histones causes the decompactization of 30 nm chromatin fiber, as revealed by low-percentage agarose gel electrophoresis. In the light of obtained results the possible molecular mechanism of the decompactization of acetylated fiber is discussed.     

Perceived equity and intimacy in marriage

The extent to which perceived inequity is related to perceived marital intimacy was examined. Sixty-six couples married five years or less were randomly selected from marriage license records in a western rural community. Equity/inequity was assessed using the Walster global measure of equity. Levels of overall intimacy, conflict resolution, affection, cohesion, sexuality, identity, compatibility, autonomy, and expressiveness were measured using the Waring Intimacy Questionnaire (WIQ). Inequity was associated with lower levels of overall intimacy, compatibility, identity, and expressiveness among the wives. Among the husbands, inequity was not associated with any types of intimacy. When comparing husbands in inequitable relationships to wives in inequitable relationships, the wives reported lower scores for only one kind of intimacy--identity. Explanations and implications for marriage therapy are discussed.     

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.