Simultaneous Determination of (R)- and (S)-Brefanolol in Human Plasma: High-Performance Liquid Chromatographic Assay on a Chiral Stationary Phase

A new method for the quantitative enantiospecific determination of rac-brefanolol, a vasodilating β-adrenoceptor blocking agent, in human plasma is described. After an alkaline liquid-liquid extraction from biological material and a preseparation on a silica gel column with fractional collection of the eluate, the separation of the underivatized enantiomers is performed by high-performance liquid chromatography on cellulose tris-4-methylbenzoic acid polymer coated on silica gel. The UV-absorbance of the eluate was monitored at 254 nm. Determination limits are 10 ng enantiomer per ml plasma and allow the performance of pharmacokinetic studies after the aimed therapeutic dosages.     

The Incidence of Myocardial Contusion in 160 Patients with Blunt Chest Trauma Diagnostic Criteria and Outcome

The incidence of myocardial contusion after blunt chest trauma has been reported in 8.2 to 75% of trauma patients. We performed this study to report on the incidence of myocardial contusion in order to determine the frequency and to describe the type of complications in these patients. We conducted a retrospective analysis over a period of 4 years. There were 160 patients with a blunt chest trauma which were admitted to our hospital. Myocardial contusion occurred in 27 of our patients with blunt chest trauma (16.9%). In all these patients typical ECG-changes could be found during hospitalization (100%). The incidence of further pathological findings in the 27 patients was 30% for the auscultation, 37% for cardiac enzymes (MB-fraction), and 41% for the echocardiography. Cardiac complications like arrhythmias, cardiac failure and tamponade occurred in 20 patients (74%). Early diagnosis of myocardial contusion in patients with blunt chest trauma is important to prevent and to treat possible complications. ECG-controls have the highest sensitivity to detect a myocardial contusion, whereas cardiac enzymes and echocardiograms seem to be poor markers of blunt myocardial injury.     

Understanding the recent evolution of the human genome: insights from human-chimpanzee genome comparisons

The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome.     

Physical activity and prevalence and incidence of mental disorders in adolescents and young adults

BACKGROUND: Although positive effects of physical activity on mental health indicators have been reported, the relationship between physical activity and the development of specific mental disorders is unclear. METHOD: A cross-sectional (12-month) and prospective-longitudinal epidemiological study over 4 years in a community cohort of 2548 individuals, aged 14-24 years at outset of the study. Physical activity and mental disorders were assessed by the DSM-IV Composite International Diagnostic Interview (CIDI) with an embedded physical activity module. Multiple logistic regression analyses controlling for age, gender and educational status were used to determine the cross-sectional and prospective associations of mental disorders and physical activity. RESULTS: Cross-sectionally, regular physical activity was associated with a decreased prevalence of any and co-morbid mental disorder, due to lower rates of substance use disorders, anxiety disorders and dysthymia. Prospectively, subjects with regular physical activity had a substantially lower overall incidence of any and co-morbid mental disorder, and also a lower incidence of anxiety, somatoform and dysthymic disorder. By contrast, the incidence of bipolar disorder was increased among those with regular physical activity at baseline. In terms of the population attributable fraction (PAF), the potential for preventive effects of physical activity was considerably higher for men than for women. CONCLUSIONS: Regular physical activity is associated with a substantially reduced risk for some, but not all, mental disorders and also seems to reduce the degree of co-morbidity. Further examination of the evidently complex mechanisms and pathways underlying these associations might reveal promising new research targets and procedures for targeted prevention.     

ABO mismatch increases transplant-related morbidity and mortality in patients given nonmyeloablative allogeneic HPC transplantation

BACKGROUND: ABO mismatch has not been thought to affect the outcome of patients undergoing myeloablative conditioning and allogeneic HPC transplantation. Data on transplant-related complications after ABO-mismatched transplantation after nonmyeloablative conditioning are limited. STUDY DESIGN AND METHODS: Therefore, 40 patients were analyzed after nonmyeloablative conditioning with regard to ABO compatibility. Eleven received a minor and bidirectional and 8 a major ABO-mismatched graft. RESULTS: Four patients had evidence of hemolysis during engraftment, being lethal in one, and three developed pure RBC aplasia. Six patients in the ABO-mismatched group developed thrombotic microangiopathy, and three of them died. ABO-identical and ABO-mismatched patients had a similar incidence of GVHD. Viral infections occurred in both groups in equal shares. Patients with an ABO-mismatch had to be rehospitalized until Day 100 for a median of 19 days versus 0 days in the identical group (p < 0.05). Overall survival was 60 and 57 percent in the ABO-identical and ABO-mismatch groups, respectively. The probability of transplant-related mortality was 0 versus 28 percent in the identical group compared to patients with an ABO mismatch (p < 0.05). The probability of relapse or progression was 76 versus 25 percent in the ABO-identical group compared to the ABO-mismatched group, respectively. CONCLUSION: Significantly more patients with ABO mismatch showed transplant-associated complications and died as a result of transplant-related causes.     

Serological, epidemiological and molecular aspects of hepatitis C virus infection in a population from Londrina, PR, Brazil, 2001-2002

Serological, epidemiological and molecular aspects of hepatitis C virus (HCV) infection were evaluated in 183 subjects from Londrina, Paraná, Brazil, and adjacent areas. Serum samples which tested anti-HCV positive by microparticle enzyme immunoassay (MEIA) obtained from eight patients with chronic hepatitis C, 48 blood donors, and 127 patients infected with the human immunodeficiency virus (HIV) were submitted to another enzyme immunoassay (ELISA) and to the polymerase chain reaction (PCR). About 78.7% of samples were also reactive by ELISA, with the greater proportion (70.8%) of discordant results verified among blood donors. A similar finding was observed for HCV-RNA detection by PCR, with 111/165 (67.3%) positive samples, with higher rates among HIV-positive subjects and patients with chronic hepatitis than among blood donors. Sixty-one PCR-positive samples were submitted to HCV genotyping, with 77.1, 21.3 and 1.6% of the samples identified as types 1, 3 and 2, respectively. Finally, analysis of some risk factors associated with HCV infection showed that intravenous drug use was the most common risk factor among HIV/HCV co-infected patients, while blood transfusion was the most important risk factor in the group without HIV infection. The present study contributed to the knowledge regarding risk factors associated with HCV infection and the distribution of HCV genotypes in the population evaluated.     

Wide QRS-complex tachycardia with variable VA-conduction: what is the mechanism?

We describe the case of a 16-year-old woman with a surgically corrected tetralogy of Fallot presenting with recurrent wide-QRS-complex tachycardia. The tachycardia could be induced and terminated with ventricular stimulation only. QRS morphology during sinus rhythm and tachycardia was identical and variable VA-conduction was observed. Mapping of the tachycardia showed that variations of HH intervals preceded VV intervals. Therefore, a mechanism involving re-entry within the bundle branches was suggested. However, detailed mapping showed cranial to caudal depolarization of the His bundle, leading to the diagnosis of atrioventricular node re-entrant tachycardia. The tachycardia was abolished by radiofrequency catheter ablation of the slow AV nodal pathway. We conclude that variable VA conduction can occur in patients with atrioventricular node re-entrant tachycardia. The atrial tissue is not always an integral part of the re-entrant circuit.     

Long-term survival in patients with different combinations of evidence-based medications after incident acute myocardial infarction: results from the MONICA/KORA Myocardial Infarction Registry

Background

Use of the four evidence-based medications [EBMs: antiplatelet agent, beta-blocker, statin and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEI/ARB)] after acute myocardial infarction (AMI) has a clear impact on 1-year survival. Aim of this study was to evaluate the association between different EBM combinations at discharge and long-term survival after AMI.

Methods

From a German population-based AMI registry, 2,886 men and 958 women were included, aged 28–74 years, hospitalized with an incident AMI between 2000 and 2008. All data were collected by standardized interviews and chart review. All-cause mortality was assessed for all registered persons in 2010. Median follow-up time was 6.0 years (interquartile range 4.1 years). Survival analyses and multivariate Cox regression analysis were conducted.

Results

Of the 3,844 patients, 70.3 % were prescribed all four EBMs; 23.8 % received three, 4.6 % two, and 1.3 % were discharged with one or no EBM. Long-term survival was 71.7 % [95 % confidence interval (CI) 55.4–82.9 %], 64.7 % (95 % CI 59.2–69.6 %) and 60.2 % (95 % CI 51.9–67.5 %) in patients with four, three and <3 EBMs, respectively. Patients prescribed three or less EBMs without ACEI/ARB showed similar long-term survival to those receiving four EBMs. In Cox regression analysis after adjustment for confounding variables, the hazard ratio for long-term mortality in patients with four EBMs versus three or less EBMs was 0.63 (95 % CI 0.53–0.74).

Conclusions

Prescribing of a combination of all four EBMs appeared to improve clinical outcomes in AMI patients by significantly reducing long-term mortality. Hospital discharge is a critical time for optimal long-term management.