Molecular epidemiology of hepatitis B virus infections in Denmark.

BACKGROUND: Denmark has a low incidence of acute hepatitis B (HBV) infections but the impact of an increasing number of immigrants with chronic HBV infection on HBV transmission is unknown. OBJECTIVES: To characterise individuals with chronic and acute HBV infection in a defined region and to examine the importance of different risk groups for the current HBV transmission. METHODS: During 2000-2001 all consecutive HBV infected individuals routinely diagnosed through the regional HBV serology laboratory in the County of Funen were classified according to ethnicity, presumed route of transmission and stage of infection based on clinical data mainly supplied by the requesting physician. HBV DNA was sequenced and subjected to phylogenetic analysis. RESULTS: Of 309 identified cases, 91 (29%) were classified as acute infection. HBV DNA sequencing was possible in 54 (59%) of these cases. Phylogenetic analysis showed that HBV isolated from injecting drug users (IDUs) was identical or closely related. Among acute cases acquired in Denmark 89% (74/83) were seen in IDUs (65) or in individuals presumably exposed to IDUs (nine) and phylogenetic analysis corroborated the assumption of IDU related transmission in every case with available sequence data. Among 83 ethnic Danes who acquired their HBV infection in Denmark, no new cases of transmission from immigrants were detected. CONCLUSION: Injecting drug use was the single most important factor for hepatitis B transmission in Denmark. The current Danish vaccination strategy is unable to protect IDUs from HBV infection and IDUs pose a greater risk of HBV transmission to the general population than immigrants.     

DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure.

Thirteen marker loci localised on the short arm of the X chromosome are available for use in genetic studies for Duchenne muscular dystrophy (DMD). This large number of probes detecting about 20 RFLPs encouraged us to set up a standard procedure using a sequence of selected probes and restriction enzymes for the diagnosis of DMD families. The application of DNA probe analysis for carrier detection and prenatal diagnosis, involving 61 pedigrees of both familial and isolated cases, has yielded the following results. Carrier detection using flanking markers was possible in more than 75% of the cases (104 out of 136 females) with a reliability of better than 98%. Prenatal diagnosis was possible in 95% of the cases (65 out of 68 proven carriers or women at risk). Twenty-three prenatal diagnoses were performed on male fetuses; 13 appeared to have a low risk for DMD (less than 1%) and thus the pregnancies continued. Seven have since come to term and the male infants have normal CK levels. The genetic distances of the loci relative to the DMD locus and their order on the short arm of the X chromosome were deduced from our total DMD family material and are not significantly different from those reported earlier. For 754 (DXS84) we found a genetic distance of 5 cM with a lod score of +12.4 and 95% confidence limits between 2 and 12 cM. Similar data were obtained for pERT87 (DXS164), suggesting that in our family material both loci are tightly linked. Multiply informative recombination showed that both 754 and pERT87 map proximal to the DMD mutations in the cases studied. The high frequency of DMD mutations and its relation to the observed instability in this part of the genome will be discussed. Unequal crossing over is proposed as one of the mechanisms contributing to the high mutation frequency.     

Studies in stress-relaxation and distensibility characteristics of small skin veins in vivo by a combined photoelectric-photographic and plethysmographic technique

Summary The phenomena of stress-relaxation and capillary outward filtration were studied in the isolated rabbit ear, perfused with blood at constant flow. The volume increase, as measured by the plethysmograph, following elevation of venous outflow pressure to 20 mm Hg for 4 min was predominantly due to capillary outward filtration in the norepinephrine constricted vascular bed (0.5 g/min). With papaverine induced dilatation (0.08 mg/min) this persistent volume increase could be attributed mainly to stress-relaxation of the veins. Engorgement of venous vessels as well as capillary outward filtration led to an increase of the ear volume that is measured by the plethysmographic technique. The photographic-photoelectric measurement of venous diameter changes was used in these experiments to distinguish intravascular from extravascular volume changes. The moduli of volume elasticity were calculated for smaller and larger veins (mean diameter 0.133 mm and 0.553 mm) with norepinephrine constriction. It has been demonstrated that the smaller veins were about seven times less distensible than the larger veins.This investigation was supported by Contract F44620-71-C-0117 of the USAF School of Aerospace Medicine, European Office of Aerospace Research (OAR), U.S. Air Force and Deutsche Forschungsgemeinschaft.This work was presented in part at the 39. Tagung der Deutschen Physiologischen Gesellschaft, Erlangen, April 1972 [Pflügers Arch. Suppl.332, R 54 (1972)].     

Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10-20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids.     

A fractal analysis of pyramidal neurons in mammalian motor cortex.

Pyramidal neurons in the mammalian cerebral cortex can be described by a fractal dimension (Mandelbrot, 1982), which is an objective, quantitative measure of the complexity of their soma/dendritic borders. In the cat, the fractal dimensions of lamina V cells, which include pyramidal tract neurons (PTN), indicate that these cells are more complex than other pyramidal neurons (PN) in the same region of motor cortex. The lamina V cells of the cat are also more complex than those in motor cortex of the monkey. Moreover, lamina III neurons in the monkey are more complex than monkey lamina V neurons. The fractal dimension of the intracortical axon collateral arborizations of the same pyramidal neurons indicated, in all cases, that the branching of these terminals is less complex than the branching of the dendrites of the same cells. In line with the observation that the fractal dimensions of some homologous cellular populations are different in different species, it is suggested that the fractal dimension and the degree of morphological complexity may relate to the requirement for the number of separable functions to be accommodated within one neuron. For example, as the size of the cortex and the number of neurons in a region increase, the opportunity exists within a given cortical zone, for individual functions to be segregated and for functional specialization to be accommodated with less morphological complexity of the individual neurons performing each of these functions.     

über die antikörperinaktivierende Wirkung der Antirheumatica

Zusammenfassung Die Antirheumatica Prednisolon, Phenylbutazon, Resochin, Natriumgentisinat und Natriumsalicylat hemmen die durch hämolytischen Hammelblutamboceptor und Komplement bewirkte Hammelbluthämolyse.Diese Wirkung der Antirheumatica kommt durch eine Inaktivierung des Amboceptors (Antikörpers) zustande. Das Komplement und die Hammelblutkörperchen werden bei diesen Versuchen von den Antirheumatica nicht beeinflußt.Es besteht eine strenge quantitative Beziehung zwischen Amboceptorkonzentration und Antirheumaticumkonzentration. Je höher die Konzentration des Amboceptors ist, um so stärkere Antirheumaticakonzentrationen sind zu seiner Inaktivierung nötig.Bezogen auf die wirksamen molaren Endkonzentrationen sind Prednisolon 8,5, Phenylbutazon 6,5, Resochin 5,0 und Gentisinsäure 1,5mal stärker wirksam als Salicylsäure.Wird der Amboceptor mit bestimmten Konzentrationen von Phenylbutazon, Natriumgentisinat oder Natriumsalicylat vorbehandelt, so kann mit diesem Amboceptor der Forssman-Schock (invers-anaphylaktischer Schock) nicht mehr beim Meerschweinchen ausgelöst werden. Phenylbutazon und Natriumgentisinat sind dabei etwa gleichstark wirksam, während Natriumsalicylat wesentlich schwächer wirkt als die beiden anderen Substanzen.     

Pattern and persistence of the epitope-specific IgM response against human cytomegalovirus in renal transplant patients.

The humoral immune response against human cytomegalovirus (HCMV) was evaluated in immunocompromised patients by Western blotting (WB) based on recombinant viral envelope (gB and gH) and tegument (pp150 and pp65) proteins. Three groups of patients were investigated: (a) 74 renal transplant recipients; (b) 24 hemodialysis patients, both groups without clinical evidence of viral infections; and (c) 19 renal transplant patients with manifest HCMV infections. The results obtained suggest that (i) the WB is considerably more sensitive, recognizing the HCMV-specific IgM response rather than the enzyme-linked immunosorbent assays. An IgM response was detected in one-third of all clinically asymptomatic renal patients. (ii) The virus-specific IgM response is primarily directed against the pp150 epitope. (iii) In patients with clinically manifest HCMV disease, additional IgM reactivities are most frequently directed against the glycoprotein B epitope. (iv) The severity of HCMV infections correlates with the extent of the IgM antibody response, i.e. with the number of specific epitopes involved. (v) After transplantation, IgM reactivity and its epitope-specific pattern persist for years.