Beta-blockers and primary prevention of coronary heart disease in patients with high blood pressure

We conducted a population-based, case-control study to determine whether beta-blockers, used for the treatment of hypertension, prevent first events of coronary heart disease. Cases were patients who had high blood pressure treated with medicines and who presented in 1982 to 1984 with angina or fatal or nonfatal myocardial infarction. Controls were a probability sample of health maintenance organization patients with pharmacologically treated hypertension and free of coronary heart disease. Blinded to case-control status, we reviewed the medical records of the 248 cases and 737 controls. The health maintenance organization's computerized pharmacy database was used to ascertain the use of beta-blockers. Fewer cases than controls were taking beta-blockers. This difference was confined to those with nonfatal infarctions. After adjustment for confounding, the estimated relative risk was 0.62 (95% confidence interval, 0.39 to 0.99). Higher doses of beta-blockers conferred greater protection. We conclude that beta-blockers may prevent first events of nonfatal myocardial infarction in patients with high blood pressure.     

Marknagelung bei der Humerusschaftfraktur

Zusammenfassung Die Humerusschaftfraktur ist in 10–18% der Fälle durch primäre Radialisparese kompliziert. Sekundäre Radialisläsionen treten iatrogen bei intramedullären Verfahren in 3%, bei Plattenosteosynthesen in 15,5% auf. In der überwiegenden Mehrzahl der Fälle (80%) ist der Radialisschaden rückläufig. Eine Verletzung der A. radialis ist eher selten; sie erfordert ein offenes Vorgehen mit lokaler Revision des Gefäßes und Frakturversorgung mittels Plattenosteosynthese. Die Marknagelosteosynthese ist bei einfachen, komplexen oder pathologischen Schaftfrakturen primär oder als Verfahrenswechsel nach primärer Fixateuranlage indiziert. Während auch ausgewählte Frakturen im Collum chirurgicum mit einem Nagel versorgt werden können, sind Frakturen im distalen Viertel des Humerus ausgeschlossen. Frakturen bei kleinen Kopffragmenten weisen ein erhöhtes Komplikationsrisiko auf. Zur Vermeidung von Läsionen der Rotatorenmanschette stehen wir der anterograden Nagelung noch zurückhaltend gegenüber. Bei differenzierter Indikationsstellung und Nachbehandlung erwies sich die retrograde Marknagelung als ein schonendes Verfahren mit hohem Patientenkomfort und gutem funktionellem Ergebnis.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.     

Gallstone pancreatitis: a prospective randomized trial of the timing of surgery

The correct timing of surgery in cases of gallstone pancreatitis is debatable. To delineate more clearly the influence of the timing of surgery in the treatment of the disease, a prospective randomized clinical study of early surgery (less than 48 hours after admission) and delayed surgery (more than 48 hours after admission) was conducted in 165 patients. Ranson's prognostic signs of severity of disease were used to classify the patients into two risk groups: mild pancreatitis (three or fewer positive signs) and severe pancreatitis (more than three positive signs). In patients with three or fewer positive Ranson's signs, the time of surgery appeared to have little effect on the outcome, whereas in patients with more than three positive signs, early surgery resulted in a significant increase in rates of morbidity and mortality. Controlled randomization showed that in patients with gallstone pancreatitis, edematous or hemorrhagic necrotizing pancreatitis can develop, with or without impacted stones, early or late in the progression of the disease, during early or delayed surgery. These findings suggest that (1) although a gallstone initiates a bout of pancreatitis, it does not cause the progression of the disease; (2) the fate of the progression of pancreatitis is decided early by the amount of digestive enzymes being activated; (3) early removal of an impacted stone does not ameliorate the progression of pancreatitis; and (4) surgery should be performed during the initial hospital admission after the pancreatitis has subsided.     

Erection and ejaculation in man. Assessment of the electromyographic activity of the bulbocavernosus and ischiocavernosus muscles

Electromyographic (EMG) recordings were obtained by concentric needle electrodes from the bulbocavernosus (BC) and ischiocavernosus (IC) muscles in 7 human volunteers during excitement to erection and subsequent ejaculation. Simultaneous registration of the time course and volume of each expressed spurt of semen was obtained using an aluminium pan suspended in front of the subject's penis on a force transducer the output of which was charted with the EMG activity. The BC and IC muscles showed no EMG activity during erection and detumescence cycles induced by visual sex stimulation. In 5 of 7 subjects, the first EMG burst of the BC in ejaculations induced by masturbation was not correlated with an expelled spurt of semen as were subsequent bursts. However, only 26 to 60% of the total number of EMG bursts were accompanied by expulsion of a spurt of semen. There thus appears to be a large safety factor in the striated muscle expulsive mechanism. Oral phenoxybenzamine treatment in 2 subjects did not significantly affect either the number of EMG bursts of the BC or the subjective pleasure of the orgasm but did significantly reduce the volume of semen expelled. Semen volume does not appear to be a unique determinant of the pleasure felt or the trigger for ejaculation.     

Effect of conjugated estrogens on platelet function and prostacyclin generation in CRF

In a double-blind, randomized, placebo-controlled cross-over study, we investigated in seven patients with chronic renal failure the effect of conjugated estrogens (0.6 mg/kg/day for 5 days) on template bleeding time and on thromboxane A2 (TxA2), beta-thromboglobulin (beta-TG) and prostacyclin (PGI2) concentrations in blood emerging from the template bleeding time incisions. Administration of conjugated estrogens resulted in a significant shortening of the bleeding time in six out of seven patients with a maximum effect 7 and/or 14 days following treatment. Both TxA2 (measured as thromboxane B2, TxB2) and beta-TG release in bleeding time blood were significantly higher following administration of conjugated estrogens as compared to placebo administration. No difference was seen in endothelial PGI2 (measured as 6-keto-prostaglandin F1 alpha) formation when patients were treated with conjugated estrogens as compared to placebo administration over the 28 day observation period. We conclude that in patients with chronic renal failure, infusion of conjugated estrogens results in a significant shortening of the bleeding time together with an increase in platelet reactivity, as indicated by an increase of TxA2 and beta-TG concentration in the microvasculature. No effect was seen on PGI2 production, thereby excluding a major effect on vascular prostaglandin metabolism.