Differential diagnosis of jaundice: a pocket diagnostic chart

Based on extensive clinical and clinical chemical information (107 different items) from 1002 jaundiced patients, we developed a diagnostic algorithm which was evaluated on a test sample of another 110 jaundiced patients. A primary classification into categories of obstructive jaundice (probability of obstruction greater than or equal to 0.80), non-obstructive jaundice (probability of obstruction less than or equal to 0.20), and of doubtful causes of jaundice (probability of obstruction: 0.20-0.80) was attempted. Among 234 patients in the data base who were classified as obstructive, 220 (94%) proved to be so, as did 36 (97%) of 37 in the test sample. The corresponding figures for non-obstructive jaundice were 463 (96%) of 483 patients correctly classified in the data base and 47 (92%) of 51 patients in the test sample. Altogether 69% of the patients in the data base and 75% of those in the test sample were correctly classified, in 27% and 20% the cause of jaundice was doubtful, and only 4% and 5%, respectively, were misclassified. A slight majority of the patients in whom the algorithmic diagnoses were doubtful proved obstructive. A close correlation was found between the preliminary diagnoses made by the algorithm and by the clinicians. A secondary classification of the patients by the algorithm into benign versus malignant causes of obstructive jaundice performed equally well in the data base and the test sample.     

Commonly recommended daily intake of vitamin D is not sufficient if sunlight exposure is limited

OBJECTIVES: Sunlight exposure of the skin is known to be the most important source of vitamin D. The aims of this study were: (i) to estimate vitamin D status amongst sunlight-deprived individuals (veiled Arab women, veiled ethnic Danish Moslem women and Danish controls); and (ii) through food intake analysis to estimate the oral intake of vitamin D necessary to keep a normal vitamin D status in sunlight-deprived individuals. DESIGN: Cross-sectional study amongst randomly selected Moslem women of Arab origin living in Denmark. Age-matched Danish women were included as controls. To control for racial differences, a group of veiled ethnic Danish Moslem women (all Caucasians) was included. SETTING: Primary Health Care Centre, City Vest and Department of Endocrinology and Metabolism C, University Hospital of Aarhus, Aarhus Amtssygehus, Aarhus, Denmark. SUBJECTS: Sixty-nine Arab women (60 veiled, nine non-veiled) and 44 age-matched Danish controls were randomly selected amongst patients contacting the primary health care centre for reasons other than vitamin D deficiency. Ten ethnic Danish Moslem women were included through a direct contact with their community. MAIN OUTCOME MEASURES: Serum levels of 25-hydroxyvitamin D were used as estimates of vitamin D status. Intact parathyroid hormone (PTH) was used to control for secondary hyperparathyroidism. Alkaline phosphatase and bone-specific alkaline phosphatase were used as markers for osteomalacic bone involvement. Oral intake of vitamin D and calcium were estimated through a historical food intake interview performed by a trained clinical dietician. RESULTS: Veiled Arab women displayed extremely low values of 25-hydroxyvitamin D: 7.1 +/- 1.1 nmol L-1, compared with 17.5 +/- 2. 3 (P < 0.002) in ethnic Danish Moslems and 47.1 +/- 4.6 (P < 10-17) in Danish controls. PTH was increased amongst veiled Arab women: 15. 6 +/- 1.8 pmol L-1, compared with 5.7 +/- 1.4 in ethnic Danish Moslems and 2.7 +/- 0.3 (P < 10-6) in Danish controls. The vitamin D intake (including food supplementation) was very low amongst Arab women: 1.04 microg day-1, compared with 13.53 amongst ethnic Danish Moslems and 7.49 amongst Danish controls (P < 0.0005). CONCLUSIONS: Severe vitamin D deficiency is prevalent amongst sunlight-deprived individuals living in Denmark. In veiled Arab women, vitamin D deficiency is the result of a combination of limitations in sunlight exposure and a low oral intake of vitamin D. The oral intake of vitamin D amongst veiled ethnic Danish Moslems was, however, very high, at 13.53 microgram (approximately 600 IU), but they were still vitamin D-deficient. Our results suggest that the daily oral intake of vitamin D in sunlight-deprived individuals should exceed 600 IU; most probably it should be 1000 IU day-1 to secure a normal level of 25-hydroxyvitamin D. This finding is in contrast with the commonly used RDA (recommended daily allowance) for adults in Europe: 200 IU day-1.     

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.