[Dysphagia and tonsillitis in a 25-year-old male patient : The nearly forgotten severe complication of a common ailment]. / Dysphagie und Angina tonsillaris bei einem 25-jährigen Patienten : Die fast vergessene schwere Komplikation einer häufigen Krankheit.

We report the case of a patient with a severe dysphagia accompanying progressive tonsillitis. The clinical examination supported the possibility of a severe septic soft tissue infection. The blood cultures revealed a largely anaerobic sepsis with Fusobacterium necrophorum. This unusual pathogen is the most common cause of Lemierre's syndrome. A duplex sonogram and magnetic resonance imaging (MRI) of the neck region and vessels suggested a thrombophlebitis of the left internal jugular vein with partial occlusion, so that Lemierre's syndrome could be diagnosed. The patient was treated with appropriate antibiotics according to the resistogram and also with rivaroxaban.

Fatal human metapneumovirus infection following allogeneic hematopoietic stem cell transplantation.

Respiratory viruses are an important yet underestimated cause of infectious morbidity and mortality in immunocompromised children and adolescents. Here, we report the occurrence of fatal lower respiratory tract disease associated with human metapneumovirus (HMPV) infection in a 10-year-old girl with chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (HSCT) for secondary chronic myeloid leukemia. Symptoms occurred 8 months after HSCT while on immunosuppression with 0.2 mg/kg/day of prednisone, and presented as dry cough, bilateral pneumonitis, and progressive respiratory distress. Non-invasive and invasive microbiological investigations revealed HMPV type B as the sole pathogen. Histopathological findings showed interstitial and intra-alveolar pneumonitis with profound alveolar cell damage. The patient was treated with intravenous and oral ribavirin and polyvalent immunoglobulins, but ultimately died from respiratory failure. The case reflects the potentially fatal impact of infections by respiratory viruses in immunocompromised patients and the need for effective approaches to their prevention and treatment.

[Neonatal enterovirus meningitis: transmission via parents during rooming-in and current epidemiology in Germany]. / Neonatale Enterovirus-Meningitis: Transmission durch die Eltern beim familiären Rooming-in und derzeitige Epidemiologie der Erkrankung in Deutschland.

INTRODUCTION: Non-polio-enterovirus infections are common in children and adults and usually lead to a mild, self-limiting disease. Perinatally acquired enterovirus infections, however, may lead to a severe disease including meningitis, encephalitis, hepatitis, coagulopathy or myocarditis. The mode of transmission may be not obvious. METHODS: 2 cases of neonatal enterovirus meningitis are presented. The disease was probably transmitted by the parents after birth during rooming-in within the hospital. The frequency of neonatal enterovirus infections in Germany was determined by analysing data of the enterovirus surveillance system of the national commission for polio eradication. RESULTS: In both cases, the parents suffered from a febrile infection. In case 1, transmission by the febrile mother was suspected. In case 2, transmission of Coxsackie B5-virus by the father was confirmed by viral culture. Both neonates exhibited fever, one patient had the typical clinical signs of meningitis. Levels of inflammatory indicators in blood (CRP, IL-6) were remarkably low. From 2006 to 2009, 322 neonates were included within the voluntary, passive enterovirus surveillance system. In 81 patients (25%) an enterovirus was detected via RT-PCR. The yearly frequency of infections was between 8 and 21. In 58 of 322 specimens (18%) serotyping was possible. CONCLUSION: Infections with enterovirus are both clinically and epidemiologically relevant during the neonatal period. Predominantly in the typical season, from June to October, enteroviral infections may be an important differential diagnosis to neonatal sepsis. The infection may be transmitted via infected parents during rooming-in within the hospital.

Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity.

Low HDL cholesterol increases the risk of coronary heart disease. Treatment of postmenopausal women with tibolone lowers HDL cholesterol. We elucidated the consequences of this unwanted side effect in a randomized, double-blind study, where 12 women received 2.5 mg tibolone per day and 6 women, placebo. Blood samples were collected on days -1 (i.e. baseline), 28, 56, and 84 for the analysis of various parameters of lipid metabolism and HDL function. Compared to placebo, treatment with tibolone led to statistically significant decreases of HDL cholesterol (-22% to -32%), apoA-I (-14% to -22%), and HDL subclass LpA-I (-30% to -40%) but to no significant changes in apoA-II and HDL subclass LpA-I,A-II. These changes were not associated with statistically significant changes in the activity of plasma to release 3H-cholesterol from radiolabeled fibroblasts or in the serum activity of the anti-oxidative enzyme paraoxonase/arylesterase. There were no significant changes in either serum levels of triglycerides, LDL cholesterol, apoB, and leptin, or in LDL size. We conclude that changes in insulin do not contribute to the lowering of HDL cholesterol by tibolone. Despite decreased HDL cholesterol, putatively anti-atherogenic activities of HDL remained unchanged.

Cholesterol efflux from normal and Tangier disease fibroblasts into normal, high-density lipoprotein-deficient, and apolipoprotein E-deficient plasmas.

Tangier disease (TD) fibroblasts have defective cholesterol release in the presence of lipid-free apolipoproteins. We compared normolipidemic probands and patients with apolipoprotein A-I (apoA-I) deficiency, apoE deficiency, or TD in terms of the plasma capacity to induce the efflux of [3H]-cholesterol from normal and TD fibroblasts and to esterify this cell-derived cholesterol. Compared with normal fibroblasts, TD fibroblasts released a significantly smaller fraction of [3H]-cholesterol into normal, high-density lipoprotein (HDL)-deficient, and apoE-deficient plasmas. Supplementation of apoE-deficient plasma with exogenous apoE normalized the cholesterol efflux from normal cells but did not fully restore the reduced cholesterol efflux from TD fibroblasts. Compared with control plasma, HDL- and apoE-deficient plasmas had a significantly reduced activity to esterify cell-derived cholesterol. Cholesterol derived from TD fibroblasts was less available for esterification in either patient or normal plasmas than cholesterol derived from normal cells. The esterification defect of TD cell-derived cholesterol was more pronounced in patient plasmas than in control plasma. We conclude that (1) apoA-I and, to a lesser degree, apoE are important determinants of the cholesterol efflux and esterification capacity of plasma, (2) TD fibroblasts have a reduced capacity to release cholesterol into the plasma, and (3) TD cell-derived cholesterol is less available for esterification in plasma than cholesterol from normal fibroblasts. The absence of distinct apoA-I- or apoE-containing subclasses aggravates the defective efflux and esterification of cholesterol derived from TD cells.

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, thyroid-stimulating hormone, insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone-binding globulin (SHBG). After adjustment for age, body mass index, and waist-to-hip ratio, 92 patients with >/=1 stenoses >70% differed from 97 patients without such focal lesions by higher serum levels of glucose, total and LDL cholesterol, and apolipoprotein (apo) B, as well as by lower serum levels of IGFBP-3. Multivariate analyses revealed significant and independent correlations of all 3 coronary scores with LDL cholesterol (or apoB) and IGFBP-3; of 2 coronary scores with age, glucose, and insulin; and of 1 score with IGF-I. No significant correlations existed for waist-to-hip ratio (or body mass index) and DHEAS (or testosterone or SHBG). IGFBP-3 explained 9% to 14% and 3.5% to 10% of the variances of focal and diffuse lesions, respectively. In conclusion, IGFBP-3 and, with much less strength and consistency, insulin and IGF-I, but not markers of hypothyroidism, adrenopause, and andropause, have statistically significant and independent associations with coronary arteriosclerosis in men.

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, thyroid-stimulating hormone, insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone-binding globulin (SHBG). After adjustment for age, body mass index, and waist-to-hip ratio, 92 patients with >/=1 stenoses >70% differed from 97 patients without such focal lesions by higher serum levels of glucose, total and LDL cholesterol, and apolipoprotein (apo) B, as well as by lower serum levels of IGFBP-3. Multivariate analyses revealed significant and independent correlations of all 3 coronary scores with LDL cholesterol (or apoB) and IGFBP-3; of 2 coronary scores with age, glucose, and insulin; and of 1 score with IGF-I. No significant correlations existed for waist-to-hip ratio (or body mass index) and DHEAS (or testosterone or SHBG). IGFBP-3 explained 9% to 14% and 3.5% to 10% of the variances of focal and diffuse lesions, respectively. In conclusion, IGFBP-3 and, with much less strength and consistency, insulin and IGF-I, but not markers of hypothyroidism, adrenopause, and andropause, have statistically significant and independent associations with coronary arteriosclerosis in men.

Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I.

Plasmas of patients with Tangier disease (TD) lack lipid-rich alpha-HDL which, in normal plasma, constitutes the majority of high density lipoprotein (HDL). Residual amounts of apolipoprotein (apo)A-I in TD plasma occur as lipid-poor or even lipid-free prebeta-HDL. By contrast to normal plasma, TD plasma does not convert prebeta-HDL into alpha-HDL. Moreover, fibroblasts of TD patients were found to be defective in secreting cholesterol or phospholipids in the presence of lipid-free apoA-I. We have therefore hypothesized that both defective conversion of prebeta-HDL into alpha-HDL and defective lipid efflux from TD cells onto lipid-free apoA-I result from a disturbance in phospholipid transfer occurring in both cellular and extracellular compartments. To test this hypothesis we established an assay that measures the activity of plasma, cells, and cell culture media to transfer radiolabeled phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI) from vesicles onto apoA-I, apoA-II, albumin, or reconstituted HDL. Plasmas, HDL, and lipoprotein-depleted plasma of normolipidemic probands as well as cell homogenates and culture media of normal fibroblasts were active at 37 degrees C but not at 4 degrees C in transferring radiolabeled PC, PI, and PE dose- and time-dependently onto either lipid-free apoA-I or reconstituted HDL. Transfer of glycerophospholipids onto apoA-II was much lower than onto apoA-I; transfer onto albumin was close to background. Compared to ten normolipidemic plasmas and four apoA-I-deficient plasmas, plasmas of six TD patients were significantly reduced by 40-50% in their glycerophospholipid transfer activities. Compared to eight normal fibroblast cell lines, homogenates and culture media of four TD fibroblast cell lines were reduced by 40-50% and 30-35%, respectively, in their activity to transfer PC, PI, or PE onto apoA-I. Our data suggest that in TD the same mechanism underlies both defective conversion of prebeta-HDL into alpha-HDL and impaired efflux of cellular lipids, namely a defective phospholipid transfer.