Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure

BACKGROUND: Congestive heart failure (CHF) has previously been shown to be associated with insulin resistance and hyperinsulinemia. A beneficial effect of the non-selective beta-blocker carvedilol has been demonstrated in patients with CHF. However, whether the drug affects the insulin sensitivity (S(i)) is unknown. AIMS: To investigate whether treatment with carvedilol alters the S(i) in patients with CHF during a prospective, double-blinded, placebo-controlled study. METHODS AND RESULTS: The patients were randomized to receive either carvedilol (n=29) or matched placebo (n=17). Insulin and glucose responses were measured during a 0.3 g/kg intravenous glucose tolerance test, and S(i) was calculated according to Bergman's Minimal Model. Baseline S(i) values correlated significantly with body mass index (r=-0.42, P=0.002), plasma urate (r=-0.42, P=0.002), plasma HDL-cholesterol (r=0.39, P=0.003), maximal oxygen uptake (r=0.35, P=0.009), plasma triglycerides (r=-0.34, P=0.01) and weight (r=-0.29, P=0.03). During the study the insulin sensitivity was unchanged in the carvedilol group compared with placebo (2.63+/-1.45 to 2.38+/-1.64 vs. 2.81+/-2.36 to 2.48+/-1.84x10(-4) min(-1)/mUl(-1), P=0.83). CONCLUSION: Additional treatment with carvedilol is neutral with regard to influence the insulin sensitivity in patients with mild to moderate CHF.     

Treatment of fibromyalgia (Fibrositis syndrome): A parallel double blind trial with carisoprodol,paracetamol and caffeïne (Somadril comp®) versus placebo

Summary Forty-three of fifty-eight (74.1%) female patients with fibromyalgia completed an eight-week treatment period testing the combination of carisoprodol, paracetamol (acetaminophen) and caffeine versus placebo. Twenty-three patients received placebo and twenty active medication. In the placebo group 56.5% of the patients used additional analgesics or nonsteroidal anti-inflammatory drugs compared to only 20% in the active treatment group (p=0.015). Forty-three percent of the patients in the placebo group and none of the patients in the active treatment group used tricyclic antidepressants, anxiolytics or sedatives (p=0.0008). Active treatment gave statistically significant improvement after treatment for pain (p<0.01), for sleep quality (p<0.01) and for the general feeling of sickness (p<0.05). In the active treatment group increased pressure pain threshold after eight weeks was found at 70% of the sites measured, while the pressure pain threshold was increased at only 30% of the sites in the placebo group. In the placebo group improvement was found for the pain and sleep quality (p<0.05). This improvement may in part be due to the large amounts of extra medication in this group. Thus, the combination of carisoprodol and paracetamol (acetaminophen) and caffeine are effective in the treatment of fibromyalgia.     

Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases.

Protein phosphatase 1 and protein phosphatase 2A contain potential phosphorylation sites for cyclin-dependent kinases. In the present study we found that rabbit skeletal muscle protein phosphatase 1, as well as recombinant protein phosphatase 1 alpha and protein phosphatase 1 gamma 1, but not protein phosphatase 2A, was phosphorylated and inhibited by cdc2/cyclin A and cdc2/cyclin B. Phosphopeptide mapping and phospho amino acid analysis suggested that the phosphorylation site was located at a C-terminal threonine. Neither cdc2/cyclin A nor cdc2/cyclin B phosphorylated an active form of protein phosphatase 1 alpha in which Thr-320 had been mutated to alanine, indicating that the phosphorylation occurred at this threonine residue. Furthermore, protein phosphatase 1, but not protein phosphatase 2A, activity was found to change during the cell cycle of human MG-63 osteosarcoma cells. The observed oscillations in protein phosphatase 1 activity during the cell cycle may be due, at least in part, to phosphorylation of protein phosphatase 1 by cyclin-dependent kinases. Together, the results suggest a mechanism for direct regulation of protein phosphatase 1 activity.     

Serum lipids of Greenland Inuit in relation to Inuit genetic heritage, westernisation and migration

BACKGROUND: The reputed low prevalence of cardiovascular disease among the Inuit has recently been challenged. Studies have shown total cholesterol among the Inuit to differ little from that of western populations and the association between cholesterol and atherosclerosis to be inconsistent. METHODS: We studied serum lipids in a population survey among 2114 Inuit living in Denmark or in West Greenland. Blood tests were supplemented by structured interviews, anthropometry and measurements of blood pressure. FINDINGS: Compared with the general population of Denmark, total cholesterol was higher among Inuit women, while HDL-cholesterol was higher among Inuit men. Triglyceride was lower among Inuit of both sexes. Cholesterol and triglyceride varied according to westernisation, diet, alcohol consumption and smoking. In a multivariate analysis, serum lipids also differed significantly between pure and genetically mixed Inuit: HDL-cholesterol was higher among the genetically pure Inuit, while among men triglyceride was lower and among women total and LDL-cholesterol were higher. INTERPRETATION: Among the Inuit, serum lipids are significantly associated with westernisation and genetic heritage. The effect of westernisation is to some extent due to dietary changes. From a cardiovascular health point of view, westernisation within Greenland is associated with unfavourable lipid changes while migration to Denmark is associated with favourable lipid changes.     

Respiratory symptoms and obstructive pulmonary disease in a population aged over 70 years

STUDY QUESTION: What is the prevalence of respiratory symptoms and obstructive pulmonary disease by age, sex, and smoking history in a population aged 70 years and older? What is the association between selected comorbidities and obstructive pulmonary disease? PATIENTS AND METHODS: A questionnaire on respiratory symptoms and disease, selected comorbidities, and smoking history was mailed to a cross-sectional, sex- and age-stratified, random sample of the population 70 years and older of Bergen, Norway. RESULTS: About 11% of these elderly persons reported having at least one current obstructive pulmonary disease, 8% reported daily wheezing, and 12% reported significant dyspnea. The only respiratory symptom or disorder to show any clear age-related pattern was dyspnea, which increased through age 89 before declining. Dyspnea, current asthma, and current chronic bronchitis were about half as likely in males as females, after adjusting for smoking pack-years. Persons with obstructive pulmonary disease reported problems with walking, heart disease, and muscle/joint disease more frequently than those without. CONCLUSIONS: The prevalence of respiratory symptoms and obstructive pulmonary disease has been estimated. Only dyspnea was associated with age in this elderly population. Female sex was a predictor of dyspnea, current asthma, and current chronic bronchitis.     

Peridevice Leak Following Amplatzer Left Atrial Appendage Occlusion: Cardiac Computed Tomography Classification and Clinical Outcomes

ObjectivesThis study aimed to investigate cardiac computed tomography (CT) and transesophageal echocardiography (TEE) peridevice leak (PDL) assessments, and the clinical relevance of PDL.BackgroundPDL assessment is integral during follow-up after left atrial appendage (LAA) occlusion. Comparative studies of TEE and cardiac CT are sparse, and the clinical relevance of PDL is uncertain.MethodsThis was a single-center observational study of consecutive patients undergoing LAA occlusion with Amplatzer devices (Amplatzer Cardiac Plug/Amulet) between 2010 and 2018 (N = 415). Patients with both 8-week CT and TEE were included for analysis (n = 346). Images were analyzed by blinded investigators (K.K. and A.S.). PDL on cardiac CT was classified from grade 1 to 3, based on PDL at the device disc, device lobe, and LAA contrast patency. Primary clinical outcome was a composite of ischemic stroke, transient ischemic attack, systemic embolism, or all-cause death.ResultsPDL was present in 110 patients (32%) by TEE, with 29 (8%) >3 mm. By cardiac CT, 210 patients (61%) had PDL at the disc, with contrast patency in 204 patients (59%). A grade 3 PDL (gap at disc, lobe, and LAA contrast patency) was present in 63 patients (18%). Bland-Altman analysis showed poor agreement between CT and TEE for leak sizing. CT and TEE detected PDL was not significantly associated with worse outcome, hazard ratio: 1.82 (95 % confidence interval: 0.95 to 3.50); p = 0.07 and hazard ratio: 1.43 (95% confidence interval: 0.74 to 2.76); p = 0.28, respectively.ConclusionsPDL occurrence is substantially higher with CT compared with TEE, with a large discrepancy between modalities in leak quantification. A novel CT-based classification is proposed, yet PDL was not associated with worse clinical outcome.     

Zur Aetiologie,Klinik und Therapie des Aneurysma dissecans der Aorta

Zusammenfassung Anhand von fünf eigenen Beobachtungen von dissezierendem Aneurysma der Aorta ascendens (de Bakey Typ II) werden allgemeine Gesichtspunkte zur Aetiologie, Pathogenese, Klinik und Therapie der Aortendissektion dargestellt. Die große Streuung der anamnestischen Angaben, der Symptome und klinischen Zeichen können zu mannigfaltigen Fehlinterpretationen Anlaß geben. Indessen ist es heute in den meisten Fällen möglich, innert nützlicher Frist das dissezierende Aortenaneurysma zu diagnostizieren und eine Großzahl der Patienten mit den modernen Verfahren der Herz- und Gefäßchirurgie mit gutem Resultat zu operieren.

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Summary Five cases of dissecting aneurysm of the ascending aorta (de Bakey type II) are presented and a review is given concerning etiology, pathogenesis, clinical signs and therapy of this disease. Because of considerable differences in case history, symptoms and findings, early and correct diagnosis has been difficult to reach in the past. Thanks to recent advances in the diagnostic field, however, the majority of these cases can now be recognized in time and operated with success.

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Mit 21 Abbildungen und 2 Tabellen