Clinical significance of intrinsic sympathomimetic activity of the beta blocker carteolol. II: Comparative studies of carteolol and pindolol in patients with bradycardia

Completing previous studies in patients with sinus bradycardia (Med. Klin. 82 [1987], 647-650) we compared metoprolol with carteolol and pindolol, pindolol with carteolol, no treatment with carteolol (in two groups) in five series of the paired comparisons of Holter-ECG each. With change from metoprolol to carteolol or pindolol (dose ratio 10:1) lowest heart rate on Holter-ECG increased by 28 or 29% without change of exercise heart rate. Direct comparison of pindolol and carteolol revealed a very similar heart rate profile, indicating equipotent beta blockade and ISA. In patients with previous beta blocker induced bradycardia, carteolol did not change a normal resting heart rate off treatment. However, in patients with spontaneous sinus bradycardia carteolol increased lowest heart rate (+14%, due to overriding ISA) and lowered exercise heart rate (-15%, due to overriding beta blockade). A beta blocker induced sinus bradycardia consistently improved with change of treatment to carteolol and pindolol. With caution carteolol and pindolol may also be used despite spontaneous sinus bradycardia.     

Combined endurance and muscle strength training in female and male patients with chronic heart failure

BACKGROUND: Exercise training has now become established practice in patients with chronic heart failure. Women are often under-represented in intervention studies compared to men. For this reason it was our aim to conduct a combined endurance and muscle strength training program to evaluate its effect on clinical performance data and health-related psychosocial factors in women and men. METHODS: One hundred and sixteen women, mean age 69 +/- 9 years, body mass index (BMI) 25.8 +/- 4.9, and 169 men, mean age 66 +/- 9 years, BMI 26.6 +/- 3.6 underwent combined endurance/resistance training. The training program lasted 29 +/- 7 days and comprised bicycle ergometer training, a 6-min walk test as a training unit and muscle strength training for the lower and upper extremities. RESULTS: Differences between women and men were found in clinical parameters. In particular, statistically significant differences were revealed between the women and men with regard to cardiopulmonary performance. Quality of life was significantly improved on discharge with regard to both physical and mental health, whereas anxiety and depression showed no significant alteration. CONCLUSION: A specialized in-hospital program for women and men combining endurance/resistance training and education is feasible. But our program revealed a very low level of cardiopulmonary performance in women. Women need to be encouraged and motivated to participate in such programs.     

Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis

BACKGROUND/AIMS: Severe alcoholic hepatitis (AH) is associated with high mortality. Tumor necrosis factor-alpha (TNFalpha) has been demonstrated to play an important role in its pathophysiology. METHODS: Twelve patients with biopsy-confirmed AH and a Maddrey discriminant factor >32 were treated with a single infusion of the anti-TNF monoclonal antibody Infliximab at a dose of 5mg/kg body weight. Serial measurements were made for various cytokines using specific enzyme-linked immunoassays (ELISA). In four patients, liver biopsy samples were available pretreatment and on day+28 of therapy. RESULTS: Ten of the 12 patients are alive at a median of 15 (12-20) months. Two patients died within 30 days from septicemia. Serum bilirubin levels, Maddrey score, neutrophil count and C-reactive protein fell significantly within the first month. There was an early, though not significant, decrease in plasma levels of proinflammatory cytokines (interleukins (IL)-1beta, IL-6, IL-8, interferon-gamma), whereas plasma levels of TNFalpha remained near the sensitivity limit of the assay throughout the treatment course. While TNFalpha mRNA expression in the liver did not change, expression of IL-8, a cytokine regulated mainly by TNFalpha, was almost absent on day+28. CONCLUSIONS: Our data suggest that randomized controlled trials of anti-TNF antibody in severe AH are warranted.     

Failure on voxilaprevir,velpatasvir, sofosbuvir and efficacy of rescue therapy

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Early viral load and recipient interleukin-28B rs12979860 genotype are predictors of the progression of hepatitis C after liver transplantation

There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL-28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL-28B genotyping for identifying HCV recipients at risk for severe HCV recurrence.     

Awareness of HIV/AIDS among primary school pupils in north central region of Nigeria

ObjectiveTo determine the knowledge of HIV/AIDS among primary school pupils in north central area of Nigeria.Methods2000 randomly selected primary school pupils in and around eastern part of Idoma area of Benue state were interviewed using an open-ended questionnaire. Data analysis was done with EPI-INFO 2000. The Chi-square test was used for statistical analysis and the 0.05 level of significance was adopted.ResultsA totle of 1010 males and 990 females at ages between five and sixteen years were drawn from 10 primary schools in the area. Pupils in the higher classes were more knowledgeable and sex difference was not statistically significant. Certain misconceptions were noted.ConclusionsThere is need for health education for all cadres of primary school pupils in the area, which will increase the awareness of the disease.     

Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease

Type III protein S deficiency is characterized by a low plasma level of free protein S, whereas the total concentration of protein S is normal. In contrast, both free and total protein S levels are low in type I deficiency. To elucidate the molecular mechanism behind the selective deficiency of free protein S in type III deficiency, the relationship between the plasma concentrations of beta-chain containing isoforms of C4b-binding protein (C4BP beta+) and different forms of protein S (free, bound, and total) was evaluated in 327 members of 18 protein S- deficient families. In normal relatives (n = 190), protein S correlated well with C4BP beta+, with free protein S (96 +/- 23 nmol/L) being equal to the molar excess of protein S (355 +/- 65 nmol/L) over C4BP beta+ (275 +/- 47 nmol/L). In protein S-deficient family members (n = 117), the equimolar relationship between protein S (215 +/- 50 nmol/L) and C4BP beta+ (228 +/- 51 nmol/L), together with the high affinity of the interaction, resulted in low levels of free protein S (16 +/- 10 nmol/L). Free protein S levels were distinctly low in protein S- deficient members, whereas in 47 of the protein S-deficient individuals, the concentration of total protein S was within the normal range, which fulfils the criteria for type III deficiency. The remaining 70 had low levels of both total and free protein S and, accordingly, would be type I deficient. Coexistence of type I and type III deficiency was found in 14 families, suggesting the two types of protein S deficiency to be phenotypic variants of the same genetic disease. Interestingly, not only protein S but also C4BP beta+ levels were decreased in orally anticoagulated controls and even more so in anticoagulated protein S-deficient members, suggesting that the concentration of C4BP beta+ is influenced by that of protein S. In conclusion, our results indicate that type I and type III deficiencies are phenotypic variants of the same genetic disease and that the low plasma concentrations of free protein S in both types are the result of an equimolar relationship between protein S and C4BP beta+.