Benefical effects of reteplase in combination with abciximab: platelet/leukocyte interactions and coagulation system

Pathophysiological aspects of acute myocardial infarction include altered hemostatic and fibrinolytic systems as well as platelet activation. Treatment with thrombolytics and GP IIb/IIIa antagonists has been described as having an additional influence on these systems. We investigated the effects of a new thrombolytic regimen with half-dose double-bolus reteplase (2 x 5 IU, 20 patients) combined with abciximab versus full dose reteplase (2 x 10 IU, 18 patients) on platelet-granulocyte complexes and on thrombin-antithrombin III complexes in patients with acute ST-segment elevation myocardial infarction. In vivo, the thrombolytic regimen with half-dose reteplase in combination with abciximab caused fewer platelet-granulocyte aggregates (measured as percentage of CD41-positive granulocytes) and a lower paradoxical activation of the coagulation system (measured as thrombin-antithrombin III complex) compared with the reteplase regimen. The combination regimen could therefore have benefical effects on platelet-induced leukocyte activation and leukocyte-mediated proinflammatory/cytotoxic effects as well as on granulocyte-induced effects on endothelium, tissue damage and coagulation. This could be, at least in part, a possible explanation for the significantly lower rates of reinfarction, recurrent ischaemia and percutaneous coronary interventions observed during the early phase after an acute myocardial infarction in the combination group in the GUSTO-V trial.     

Complex encounters at the macrophage-mycobacterium interface: studies on the role of the mannose receptor and CD14 in experimental infection models with Mycobacterium avium

The initial interactions between mycobacterial cell wall components and receptor structures on the surface of macrophages may be critical in determining the outcome of infection. They may trigger the ingestion and digestion of microorganisms, but they may also promote the intracellular persistence and growth of mycobacteria. Using Mycobacterium avium as a model system, three approaches of different complexities were used to analyse some structural features and some functional consequences of M. avium interacting with the macrophage mannose receptor or CD14, a pattern recognition receptor. Binding specificities of a recombinant, truncated extracellular portion of the mannose receptor were assayed in a novel ELISA-formatted system using viable M. avium cells as ligands. Infection with M. avium strains differing in their virulence were performed in murine bone marrow-derived macrophages and in mice with a targeted deletion of the CD14 gene. These parallel and converging approaches not only help define the molecular basis for understanding early events in the pathogenesis of mycobacterial infections, but are also necessary to ultimately determine the relevance of in vitro findings in the context of actual manifestations of disease in vivo.     

Auditory P3 findings in mission Indian youth.

OBJECTIVE: Native Americans have some of the highest rates of alcohol abuse and dependence, yet potential biological risk factors associated with the problem drinking seen in many tribes remain relatively unknown. In this study, the amplitude of the P3 component of the event-related potential (ERP), a measure associated with risk for alcoholism in European-American youth, was investigated in Mission Indians. METHOD: The study participants were Mission Indian children and adolescents (N = 68, 37 male) between the ages of 7 and 13 years. ERPs were collected using two auditory "oddball" paradigms: an easy and a difficult discrimination task. P3 amplitude and latency were statistically evaluated as a function of age, gender, degree of Native American heritage (NAH) and family history (FH) of alcohol dependence. RESULTS: P3 latency was found to vary as a function of age and gender, with girls demonstrating greater decreases in latency with age than boys. suggesting a faster maturation time. Whereas there were no significant relationships between NAH and P3 latency, those participants with at least one alcoholic parent had longer P3 latencies elicited by the difficult auditory task. No significant relationships were found between P3 amplitude generated to the target tones and any of the variables (age, gender, FH, NAH). CONCLUSIONS: Mean P3 amplitudes and latencies obtained from these Mission Indian youth were within the range of those values reported in the literature for samples of children and adolescents of other ethnicities. Although the amplitude of the P3 ERP measure has been associated with FH of alcoholism in studies of predominantly European-American individuals, P3 amplitudes generated in response to these auditory tasks did not robustly differentiate Mission Indian children and adolescents who may be at higher risk for alcoholism from those presumed to be at lower risk.     

Myocardial troponin T release is associated with enhanced fibrinolysis in patients with acute coronary syndromes

Patients with acute coronary syndromes (ACS) frequently present with signs of disturbed fibrinolysis. The present study investigates the correlation of alterations in the fibrinolytic system and the amount of myocardial damage characterized by troponin release. In 85 patients with ACS markers of plasmin activation, plasminogen activator system and troponin T (TnT) were measured initially and after 48 h. Patients with TnT release (> or = 0.01 microg/l) at admission had higher TPA levels than those without release (10.2+/-0.7 ng/ml vs. 7.6+/-0.5 ng/ml; p <0.01). Additionally, patients with positive TnT had higher D-dimer levels initially (457+/-39 ng/ml vs. 316+/-22 ng/ml; p <0.01) and 48 h later (451+/-42 ng/ml vs. 275+/-37 ng/ml; p <0.01). The association of myocardial damage with a prothrombotic state and an enhanced fibrinolysis may explain the high prognostic value of troponin measurements in respect to future coronary events.     

Diet and cancer prevention: the fiber first diet

Diet can play a major role in cancer prevention. The international differences in cancer incidence are largely accounted for by lifestyle practices that include nutrition, exercise, and alcohol and tobacco use. About 50% of cancer incidence and 35% of cancer mortality in the U.S., represented by cancers of the breast, prostate, pancreas, ovary, endometrium, and colon, are associated with Western dietary habits. Cancer of the stomach, currently a major disease in the Far East, relates to distinct, specific nutritional elements such as excessive salt intake. For these cancers, information is available on possible initiating genotoxic factors, promoting elements, and prophylactic agents. In general, the typical diet in the United States contains low levels of the potent carcinogenic agents, heterocyclic amines, formed during the cooking of meats. It provides only about half the potent appropriate fiber intake and is high in calories. About twice as many calories as would be desirable come from fat, certain kinds of which enhance the development of cancers. Other foods with functional properties, such as soy products and tea, can be beneficial. To achieve reduction in risk of certain cancers, diet must be optimized, primarily to reduce caloric intake and the fat component. The latter should be 20% or less of total caloric intake and fiber should be increased to 25- 35 g per day for adults. One approach to achieving these goals is the Fiber First Diet, a diet designed around adequate fiber intake from grains, especially cereals, vegetables, legumes, and fruits, which thereby reduces both calorie and fat intake. Such dietary improvements will not only reduce cancer and other chronic disease risks, but will contribute to a healthy life to an advanced age. A corollary benefit is a lower cost of medical care.      

Trans?sophageale Echokardiographie Perioperative Beurteilung der Herzklappen Perioperative Beurteilung der Herzklappen

Der hohe Stellenwert der trans?sophagealen Echokardiographie (TEE) in der perioperativen Medizin ist unumstritten. Die TEE gestattet eine direkte bildgebende Darstellung von pathologischen Ver?nderungen des Herzens. Daher ist die TEE das Verfahren der Wahl zur Diagnose und Graduierung von Herzklappenerkrankungen. über die direkte bildliche Darstellung hinaus erlaubt die TEE eine objektivierbare h?modynamische Beurteilung der Klappen- und Ventrikelfunktion. Durch Messung von Blutflussgeschwindigkeiten werden Druckgradienten über stenotischen Klappen ermittelt. Unter Anwendung der Kontinuit?tsgleichung oder der Planimetrie lassen sich Klappen?ffnungsfl?chen bestimmen. Bei einer Klappeninsuffizienz wird der Schweregrad mittels color flow, continuous oder pulsed-wave Doppler abgesch?tzt.     

Evaluation of EEG alpha activity in sons of alcoholics

The results of computer-analyzed electroencephalographic (EEG) data from 24 sons of alcoholics (family history positive [FHP]) and their matched controls (family history negative [FHN]) were compared before and 90 minutes following alcohol and placebo challenge. Blind analysis of the data revealed that FHP men had more energy in the fast-frequency alpha range (9 to 12 Hz) of their EEG than did FHN subjects at baseline. EEG response to ethanol was also found to differ between the two groups. FHN but not FHP subjects evidenced a decrease in fast-frequency alpha energy following ethanol challenge. These data support other evidence of a less intense reaction to ethanol in FHPs as measured by subjective response, body sway, and hormone levels. In addition, these findings suggest that certain normal alpha wave variants may be more common in sons of alcoholics.