Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

Correlation between eosinophilic oesophagitis and aeroallergens

Aliment Pharmacol Ther 31 , 509–515

Summary

Background Aeroallergens have been implicated in the pathogenesis of eosinophilic oesophagitis. Aim To determine whether a seasonal variation exists in the diagnoses of eosinophilic oesophagitis and whether there is a correlation with seasonal pollen count. Methods A retrospective review was performed from January 2006 to November 2008 to identify eosinophilic oesophagitis patients. Cases were classified by endoscopic date. Daily pollen counts for grass, trees and weeds were obtained from a certified counting station. Per cent of eosinophilic oesophagitis cases were collated seasonally and compared with mean pollen counts for grass, trees and weeds during the same time period. Results A total of 127 eosinophilic oesophagitis cases were identified (median age 41, range 19–92 years, 84% men). The highest percentage of cases (33.0%; Binomial P = 0.022) was diagnosed in the spring, while the least percentage (16%; Binomial P = 0.0.010) occurred in the winter. There was a significant association between per cent eosinophilic oesophagitis cases diagnosed seasonally and mean grass pollen count (r_s = 1.000, P < 0.01), but not with trees (r_s = 0.400, P = 0.600) or weeds (r_s = 0.800, P = 0.200). Conclusions A seasonal variation was seen in the diagnosis of eosinophilic oesophagitis which correlated with pollen counts. These findings have important implications regarding the pathogenesis of eosinophilic oesophagitis, suggesting a potential role for aeroallergens.     

Five‐year outcome in COPD patients after their first episode of acute exacerbation treated with non‐invasive ventilation

Background and objective: Little is known about long‐term survival of patients surviving the first episode of type II respiratory failure requiring non‐invasive ventilation (NIV). We aimed to determine the 1‐, 2‐ and 5‐year survival, cause of death and potential prognostic indicators in this patient cohort. Methods: We retrospectively identified 100 sequential COPD patients (mean age 70, mean FEV₁ 37% predicted) treated with NIV for the first time. Mortality and data on hospital morbidity and potential prognostic factors were collected from patient records and a State Health Data Linkage Service. Results: Survival at 1, 2 and 5 years was 72%, 52% and 26%, respectively. Respiratory failure secondary to COPD was the commonest cause of death (56.8%), followed by cardiovascular events (25.7%). Readmission rate at 1 year was 60% for those who survived 2 years or more and 52% for those deceased within 2 years. Recurrent respiratory failure requiring NIV was observed in 31% of the cohort. Only advance age (P = 0.04), BMI (P = 0.014) and prior domiciliary oxygen use (P = 0.03) correlated with death within 5 years. Severity of respiratory failure did not correlate with mortality. Conclusions: The 2‐ and 5‐year mortality rates for patients with COPD surviving their first episode of respiratory failure requiring NIV are high. Physiological measures of the severity of respiratory failure at presentation do not predict subsequent survival and nor does the time interval between first and second admissions requiring NIV. Age, BMI and prior need for domiciliary oxygen are the main predictors of mortality at 5 years.     

Smoking attenuates the vasoconstrictor response to noradrenaline in type I diabetic patients and normal subjects: possible relevance to diabetic nephropathy

Abstract Exaggerated vascular reactivity has been implicated in the pathogenesis of diabetic nephropathy, and several studies suggest that smoking accelerates its progression. We therefore assessed the vasoactive effects of smoking by comparing noradrenaline-induced vasoconstriction in dorsal hand-veins between smoking and non-smoking groups of Type I diabetic patients with and without microalbuminuria and in non-diabetic subjects. Smokers had a significantly higher dose causing 50% vasoconstriction (reduced sensitivity to noradrenaline) in all three groups: microalbuminuric diabetic smokers vs. non-smokers, 20·2(4·6) (SEM) vs. 6·6(2·3) ng min^-1 (P = 0·02); normoalbuminuric, 76·9(29·4) vs. 22·8(9·1) ng min^-1 (P = 0·03); non-diabetic subjects, 97·8(30·0) vs. 38·0(12·8) ng min^-1 (P = 0·01). Both microalbuminuric diabetic groups showed significantly greater sensitivity to noradrenaline-induced vasoconstriction than the other smoking and non-smoking groups, respectively (P<0·01).
Vasoconstrictor responses to noradrenaline are attenuated in smokers, possibly due to α-adrenoceptor down-regulation. Smoking could increase urinary albumin losses and accelerate renal damage through catecholamine surges which raise systemic and, perhaps, intraglomerular blood pressure. This hypothesis deserves further consideration.     

Evidence of Chemical Stimulation of Hepatic Metabolism by an Experimental Acetanilide (FOE 5043) Indirectly Mediating Reductions in Circulating Thyroid Hormone Levels in the Male Rat

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide(FOE 5043) is a new acetanilide-type herbicide undergoing regulatorytesting. Previous work in this laboratory suggested that FOE5043-induced reductions in serum thyroxine (T₄) levels weremediated via an extrathyroidal site of action. The possibilitythat the alterations in circulating T₄ levels were due to chemicalinduction of hepatic thyroid hormone metabolism was investigated.Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixturewas found to significantly increase the clearance of [¹²⁵I]T₄from the serum, suggesting an enhanced excretion of the hormone.In the liver, the activity of hepatic uridine glucuronosyl transferase,a major pathway of thyroid hormone biotransformation in therat, increased in a statistically significant and dose-dependentmanner; conversely, hepatic 5'-monodeiodinase activity trendeddownward with dose. Bile flow as well as the hepatic uptakeand biliary excretion of [¹²⁵I]T₄ were increased following exposureto FOE 5043. Thyroidal function, as measured by the dischargeof iodide ion in response to perchlorate, and pituitary function,as measured by the capacity of the pituitary to secrete thyrotropinin response to an exogenous challenge by hypothalamic thyrotropinreleasing hormone, were both unchanged from the controlled response.These data suggest that the functional status of the thyroidand pituitary glands has not been altered by treatment withFOE 5043 and that reductions in circulating levels of T₄ arebeing mediated indirectly through an increase in the biotransformationand excretion of thyroid hormone in the liver.     

Hepatic Glycogen Storage Disease: CLINICAL AND LABORATORY FINDINGS IN 23 CASES

Clinical and laboratory findings and the results of enzyme studiesmade on tissue samples from 23 children with hepatic glycogenstorage disease are described. Two-thirds of the patients had glycogenosis associated withdeficiency of glucose-6-phosphatase, amylo 1,6-glucosidase,or hepatic phosphorylase. No enzyme defect could be found toaccount for excessive glycogen deposition in the others, whowould have been incorrectly diagnosed as suffering from oneof the recognized enzyme deficiencies, if samples of affectedtissue had not been examined for specific enzyme activities. The treatment of glycogen storage disease has been limited toregulating the blood sugar level and preventing hypoglycaemia.In most patients this was achieved by simple dietary management.Two children who did not respond to dietary control have beentreated with diazoxide.     

Allergic drug reactions: an in vitro model using a mixed function oxidase complex to demonstrate antibodies with specificity for a practolol metabolite

Reactive metabolite products of the drug practolol were generated in vitro using the rat liver mixed function oxidase complex. The metabolites were spontaneously coupled to a non-agglutinating rabbit antibody to human O red blood cells, so forming a metabolite–antibody reagent. This reagent was then used to passively sensitize human O red cells which subsequently acted as indicator cells for detecting anti-metabolite antibodies.     

Junctional epidermolysis bullosa and pyloric atresia: a distinct entity. Clinical and pathological studies in five patients

Summary functional epidermolysis bullosa (JEB) associated with pyloric atresia (PA) is a distinct entity which is inherited as an autosomal recessive disorder. We describe five patients with this association: tour died in the neonatal period and one is still alive at 4 years of age. The cutaneous lesions in these patients are identical or similar to those in other JEB subtypes. Urinary tract involvement is part of the syndrome and presents a problem for long-term survival. Using the monoclonal antibody GB3 we investigated skin biopsies from three of our patients and showed normal expression in all of them, unrelated to the outcome of their disease. This indicates that the GB3 monoclonal antibody is without prognostic significance in this syndrome. It is clear that JEB with PA is a distinct entity. The molecular basis as yet is unknown.