Value and limitations of human myocardial biopsy.

Twenty-three myocardial biopsies from 22 patients with various cardiological diseases were examined by light and electron microscopy. The amount of fibrosis, endocardial thickening, “whorling of myofibers”, “irregular running of myofibers”, fat infiltration and lipofuscein granules were compared to cardiological parameters such as the function group of the patients, cardiac index, stroke index and the pulmonary capillary wedge pressure. The histological grading showed a weak correlation to the function group of the patients and the pulmonary capillary wedge pressure, but not to the cardiac index or stroke index. While patients with an almost normal heart function had a normal histology, both normal and abnormal histology were seen in patiens with severe heart disease. It was not possible to relate any morphological changes in the myocardium, neither at the light microscopical nor at the ultrastructural level to specific heart diseases as for example primary or alcoholic cardiomyopathy. However, severe contraction artefacts disturbed both the light microscopical and especially the ultrastructural evaluation of the specimens.This problem is discussed and in order to diminish the risk of misinterpretation of myocardial biopsy specimens, recommendations are given with regard to fixation, mincing and embedding of the specimens as well as to the evaluation of both the light microscopic slides and the ultrathin sections.     

Asphyxia homicides in Denmark 1992–2016

In this retrospective study , we present the findings in 250 homicides by asphyxia in Denmark in a 25-year period, with a particular focus on the autopsy findings in strangulation. Our intention is for the results to be used in future death investigations, where difficulties in interpretation of findings in potential asphyxial deaths arise. Asphyxia homicides showed a strong bias with respect to sex, age, and homicide type. The frequent female victim was typically an adult, whereas the rarer male victim was most often a child. Female offenders most often killed their children, and male offenders most often killed their female partner. Generally, most asphyxia homicides took place in a domestic setting. Manual strangulation and ligature strangulation were the most common mechanisms of asphyxia homicides (81.6%). A lack of petechial hemorrhages, especially in the conjunctiva, was rare in homicidal strangulation, but there were exceptions, especially when there was postmortem decomposition, making it impossible to verify them. Most victims of strangulation had skin lesions in the face (including the jawline) or on the neck, with accompanying hemorrhages in muscle and connective tissue, but the findings could be subtle or compounded by decomposition. Fractures of the laryngo-hyoid complex were common in strangulation, particularly in manual strangulation (chi-sq = 4.0993, df = 1, P < 0.05) and were clearly related to the age of the victim (chi-sq = 82.193, df = 4, P < 0.001). In children and young adults dying from homicidal strangulation, a lack of fractures is to be expected, while a lack of fractures is unusual, but not entirely unexpected, for adults and aged people.

     

A decision tree for early differentiation between obstructive and non-obstructive jaundice

We present a method for early differentiation between obstructive and non-obstructive jaundice. On the basis of 14 variables (clinical data and clinical chemical tests, all available within 48 h) a simple decision tree or flow chart has been constructed. The diagnostic yield was as follows: 857 of 982 consecutive jaundiced patients (87%) in a data base and 98 of 108 patients in an independent test sample (91%) were correctly classified. Decision trees for the differentiation between benign or malignant causes within the obstructive group and between acute or chronic causes within the non-obstructive group are also presented. The resulting four-way classification was correct for 77% of the patients in the data base and for 72% of the patients in the test sample. The decision trees are compared with previous methods founded on Bayes' rule and logistic discrimination. The decision trees enable a quick and reliable classification of jaundiced patients, thus providing a valid basis for rational planning of the further diagnostic study.     

HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus

Summary Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n=164), and a subset (n=93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR4 was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system. Note. A list with detailed data on all patients is available from the authors on request.     

Pulsed doppler echocardiography in diagnosis of pulmonary regurgitation: Its value and limitations

Ninety-eight patients were studied with two dimensional echocardiography combined with pulsed Doppler echocardiography to assess the usefulness and limitations of the Doppler technique in the diagnosis of pulmonary regurgitation. The diagnosis of pulmonary regurgitation by pulsed Doppler echocardiography depended on subjective interpretation of the audio signal and objective interpretation of the time interval histogram for the presence of wide frequency dispersion. During cardiac catheterization in 53 of the 98 patients, indocyanine green was injected into the pulmonary artery, and simultaneous sampling was performed from the right ventricle and femoral artery to diagnose pulmonary regurgitation. Pulmonary regurgitation was confirmed by pulmonary arteriogram in one patient. Among 62 patients with adequate pulsed Doppler echocardiographic studies, diastolic turbulence was noted in 21. When diastolic turbulence was less than 50 percent of the period of diastole, no pulmonary regurgitation was demonstrated in patients studied by indicator-dilution technique. However, three of the four patients with diastolic turbulence greater than 50 percent had positive evidence of pulmonary regurgitation. Audio output was more sensitive than the time interval histogram, and only five patients' findings suggested pulmonary regurgitation. Three of these patients underwent dye-dilution studies; two studies were positive for pulmonary regurgitation and one was negative.Thus, interpretation of pulmonary regurgitation based on the time interval histogram alone produces a large number of false positive results. When diastolic turbulence is greater than 50 percent of the period of diastole, both the sensitivity and specificity of diagnosis of pulmonary regurgitation are increased. Combining audio output and the time interval histogram results in improved diagnostic capability.     

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.     

Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis

Mannan-binding protein is synthesized by the liver and functions in first-line host defence by opsonizing mannose-rich microorganisms due to activation of the classical complement pathway independent of Clq, and by an intrinsic ability to opsonize and mediate phagocytosis. We have investigated whether the increased susceptibility to bacterial infections in patients with cirrhosis could be explained by low plasma concentrations of mannan-binding protein and impaired complement-dependent opsonization. We examined 51 patients with compensated alcoholic cirrhosis, 34 who were decompensated and 16 healthy controls. Irrespective of group, we found a significant correlation (p<0.05) between plasma mannan-binding protein concentration and deposition of the complement opsonin C4 on mannan from baker's yeast. In contrast to what was expected, this kind of opsonization and plasma levels of mannan-binding protein were significantly increased in the patients with decompensated cirrhosis (p=0.01 and p=0.007, respectively). A significant correlation (0<0.05) was found between mannan-binding protein and erythrocyte sedimentation rate, fibrinogen and haptoglobin in these patients. Though the correlations were weak (rho=0.49, rho=0.48 and rho=0.40, respectively), the elevated levels of mannan-binding protein in the patients with decompensated cirrhosis may reflect an acute phase reaction. It is concluded that plasma levels of mannan-binding protein are increased in patients with decompensated cirrhosis and that complement-dependent opsonization of mannan does not seem to be compromized in patients with alcoholic cirrhosis.     

Risk factors for asthma in adult twins

Introduction: This PhD thesis was conducted at the Respiratory and Allergy Research Unit, Department of Respiratory Medicine, Bispebjerg University Hospital, Copenhagen, Denmark. Objective: This study was conducted in a population of adult twins to: (i) determine the incidence of asthma; (ii) identify the risk factors for asthma; and (iii) estimate to what extent genetic and environmental factors influence asthma, wheeze, rhinitis, positive skin‐prick test (posSPT) and airway hyper‐responsiveness (AHR). Materials and Methods: The study population was based on the twin cohorts born between 1953 and 1982 that were ascertained from the nationwide Danish Twin Registry. Questionnaire data on multiple traits including asthma and possible risk factors for asthma was collected in 1994 and 2002, defining a population of 19 349 subjects (6090 intact twin pairs) at risk of new asthma. Furthermore, a total of 575 subjects (256 intact pairs and 63 single twins), who either themselves and/or their co‐twins reported a history of asthma at the 2002 questionnaire, were clinically examined. Results: The incidence of asthma was 4.5 and 6.4 per 1000 person‐years, respectively, among males and females (Odds Ratio (OR) = 1.49, P < 0.001). There was a positive association between increasing body mass index (BMI) and risk of asthma for both sexes (OR = 1.05 per unit, P < 0.001). A history of hay fever (OR = 4.2 for males and OR = 3.7 for females, P < 0.001), eczema (OR = 3.5 for males and OR = 2.0 for females, P < 0.001) and both (OR = 6.9 for males and OR = 8.0 for females, P < 0.001) were significant predictors of asthma. Physical exercise was weakly associated with asthma (OR for inactivity = 0.35, P = 0.02), whereas smoking and educational status was not significantly associated with asthma. There was a high genetic similarity between asthma and wheeze (genetic correlation, ρ_A = 0.96), asthma and rhinitis (ρ_A = 0.94), wheeze and rhinitis (ρ_A = 0.95), wheeze and AHR (ρ_A = 0.85), and rhinitis and posSPT (ρ_A = 0.92), whereas lower genetic correlations were observed between rhinitis and AHR (ρ_A = 0.43) and between AHR and posSPT (ρ_A = 0.59). Traits with a high degree of environmental sharing were asthma and wheeze (environmental correlation, ρ_E = 0.82), rhinitis and posSPT (ρ_E = 0.92), and wheeze and posSPT (ρ_E = 0.71), whereas lower environmental correlations were observed between asthma and rhinitis (ρ_E = 0.19) and between wheeze and rhinitis (ρ_E = 0.25). Conclusions: The incidence of asthma in adulthood is high, especially among females. In both sexes, increasing levels of BMI increase the risk of asthma. A substantial portion of adult‐onset asthma is preceded by hay fever and eczema. Asthma, wheeze, rhinitis, AHR and posSPT share, to a large extent, a common genetic aetiology. In particular, asthma and rhinitis are genetically similar, but environmentally distinct. Furthermore, genetic factors mainly explain the co‐occurrence of asthma and posSPT, and rhinitis and posSPT, whereas asthma, but not rhinitis, is closely genetically related to AHR. Finally, asthma and posSPT, and rhinitis and posSPT show similar environmental architectures. These results provide new insights into the aetiology of asthma and may be used to guide the choice of traits for genetic linkage analysis.