Comparison of the effect of beta adrenergic antagonists with different ancillary properties on isolated canine and human coronary arteries

Experiments were performed on canine and human isolated coronary arteries to characterise human coronary beta adrenoceptors and to determine whether or not beta blocking agents with different ancillary properties unmask the alpha adrenergic effect of noradrenaline in a similar way. The inhibitory effects of atenolol (a beta1 selective antagonist), epanolol (a beta1 selective antagonist with modest intrinsic sympathetic activity), and propranolol (a non-selective antagonist) were assessed on isoproterenol concentration-response curves. Regression analysis provided slopes not significantly different from unity and similar pA2 values for each agent in both preparations. In a second group of experiments, the effects of noradrenaline (10 mumol.litre-1) were assessed in the absence and presence of beta blockade. At equipotent doses (1 log or 2 log units from the pA2 values) each beta blocking agent unmasked the alpha effect of noradrenaline in the same way. This alpha effect of noradrenaline (10 mumol.litre-1) was completely abolished by prazosin 1 mumol.litre-1 in canine coronary arteries but only partially antagonised in human coronary arteries. Thus the property of a beta blocking agent to unmask the alpha adrenergic effect of adrenaline is mainly related to its affinity for the coronary smooth muscle beta adrenoceptors. These beta adrenoceptors were very similar in both preparations and appear to be mainly beta1. The alpha adrenoceptors seem, nevertheless, to be different and resistant to prazosin in human preparations.     

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up.

We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.     

Differential diagnosis and prognosis of cirrhosis: role of liver biopsy

Histopathological examination of needle biopsies of the liver is a cornerstone in the diagnostic work-up on a patient with symptoms of chronic liver disease. It allows to confirm whether cirrhosis is present or not. In a considerable number of cases, this confirmation is definitive. In some cases, only a diagnostic level of suspicion is reached. In these cases, close collaboration between clinician and pathologist may increase the degree of diagnostic certainty. A reliable diagnosis of cirrhosis on liver biopsies requires careful consideration of differential diagnostic alternatives. Application of the full battery of histopathological techniques, including special stains, polarizing light and immunohistochemistry, allows to specify (or to help to specify) the aetiology in a substantial number of cases. The histopathologist should further look for information which bears on prognosis, and evaluate the stage, the activity and eventual complications by search of the corresponding histological changes.     

Distributional Properties and Criterion Validity of a Shortened Version of the Social Responsiveness Scale: Results from the ECHO Program and Implications for Social Communication Research

Prior work proposed a shortened version of the Social Responsiveness Scale (SRS), a commonly used quantitative measure of social communication traits. We used data from 3031 participants (including 190 ASD cases) from the Environmental Influences on Child Health Outcomes (ECHO) Program to compare distributional properties and criterion validity of 16-item “short” to 65-item “full” SRS scores. Results demonstrated highly overlapping distributions of short and full scores. Both scores separated case from non-case individuals by approximately two standard deviations. ASD prediction was nearly identical for short and full scores (area under the curve values of 0.87, 0.86 respectively). Findings support comparability of shortened and full scores, suggesting opportunities to increase efficiency. Future work should confirm additional psychometric properties of short scores.

     

A randomised controlled trial of intravenous dexamethasone combined with interscalene brachial plexus blockade for shoulder surgery

We recruited patients scheduled for shoulder rotator cuff repair or subacromial decompression under general anaesthesia and interscalene brachial plexus blockade (30 ml ropivacaine 0.5%). We allocated 240 participants into four groups of 60 that were given pre‐operative saline 0.9% or dexamethasone 1.25 mg, 2.5 mg or 10 mg, intravenously. We recorded outcomes for 48 h. The median (IQR [range]) time to first postoperative analgesic request after saline was 12.2 (11.0–14.1 [1.8–48]) h, which was extended by intravenous dexamethasone 2.5 mg and 10 mg to 17.4 (14.9–21.5 [7.2–48]) h, p < 0.0001, and 20.1 (17.2–24.3 [1.3–48]) h, p < 0.0001, respectively, but not by dexamethasone 1.25 mg, 14.0 (12.1–17.7 [2.1–48]) h, p = 0.05. Postoperative analgesia was given sooner after rotator cuff repair than subacromial decompression, hazard ratio (95% CI) 2.2 (1.6–3.0), p < 0.0001, but later in older participants, hazard ratio (95% CI) 0.98 (0.97–0.99) per year, p < 0.0001.     

"Once apical ballooning, always apical ballooning?"

It is important that a cardiologist knows and recognizes the entity of takotsubo cardiomyopathy or apical ballooning, but remains aware that a subsequent similar episode is not necessarily a recurrence of this syndrome. Relapse may be caused by "classical" coronary atherosclerosis, as described in this case report.     

Lack of hepatic transferrin receptor expression in hemochromatosis

The major part of hepatocellular iron is derived from uptake of transferrin-bound iron by means of nonspecific fluid-phase endocytosis and specific, saturable binding on high-affinity transferrin receptors. We investigated the expression of transferrin receptors on hepatocytes in liver biopsies of 22 cases of hemochromatosis (21 primary hemochromatosis and 1 secondary hemochromatosis), using immunohistochemical demonstration of the human transferrin receptor with the specific monoclonal antibody OKT9. Fifty liver biopsies (normal and pathological) without demonstrable iron storage (Perls' stain negative) served as controls. In the controls, membranous and/or cytoplasmic transferrin receptor expression was always present on hepatocytes, albeit in variable numbers and patterns without obvious relation to the underlying liver disease. In 19 of 22 hemochromatosis cases with severe iron overload, OKT9 immunoreactivity on hepatocytes was completely absent. Three hemochromatosis cases showed few hepatocytes positive for OKT9. One showed mild iron overload, while the second, a successfully treated case, was free of iron. The remaining hemochromatosis case was a known alcoholic with severe iron overload. Since OKT9 binding to the transferrin receptor is not blocked by previous binding of transferrin, the findings show that in advanced hemochromatosis hepatocytes do not express transferrin receptors. This finding is in keeping with the inverse relation between transferrin receptor expression and exogenous iron supply in various cell cultures. These results indicate that in hemochromatosis,apparently as a result of progressive iron overload,transferrin receptor expression on hepatocytes disappears.(ABSTRACT TRUNCATED AT 250 WORDS)     

Artemisinins,New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

Mucosal biofilm-related fungal infections are very common, and the incidence of recurrent oral and vulvovaginal candidiasis is significant. As resistance to azoles (the preferred treatment) is occurring, we aimed at identifying compounds that increase the activity of miconazole against Candida albicans biofilms. We screened 1,600 compounds of a drug-repositioning library in combination with a subinhibitory concentration of miconazole. Synergy between the best identified potentiators and miconazole was characterized by checkerboard analyses and fractional inhibitory concentration indices. Hexachlorophene, pyrvinium pamoate, and artesunate act synergistically with miconazole in affecting C. albicans biofilms. Synergy was most pronounced for artesunate and structural homologues thereof. No synergistic effect could be observed between artesunate and fluconazole, caspofungin, or amphotericin B. Our data reveal enhancement of the antibiofilm activity of miconazole by artesunate, pointing to potential combination therapy consisting of miconazole and artesunate to treat C. albicans biofilm-related infections.     

Clinical characteristics of impaired trunk control in children with spastic cerebral palsy

This study aimed to identify clinical characteristics of impaired trunk control in hundred children with spastic CP (mean age 11.4 ± 2.1 years, range 8–15 years). Assessment of trunk control was performed with the Trunk Control Measurement Scale (TCMS). Trunk control was clearly impaired, indicated by a median total TCMS score of 38.5 out of 58 (66%). Median subscale scores were 18 out of 20 (90%) for the subscale static sitting balance, 16 out of 28 (57%) for the subscale selective movement control and 6 out of 10 (60%) for the subscale dynamic reaching. Total TCMS and subscale scores differed significantly between topographies and severity of motor impairment according to the Gross Motor Function Classification System (GMFCS). Children with hemiplegia obtained the highest scores, followed by children with diplegia and children with quadriplegia obtained the lowest scores. TCMS scores significantly decreased with increasing GMFCS level. In conclusion, trunk control is impaired in children with CP to a various extent, depending on the topography and severity of the motor impairment. The findings of this study also provide specific clues for treatment interventions targeting trunk control to improve their functional abilities.