Two cases of Kallmann syndrome associated with empty sella

Kallmann syndrome (KS) is a developmental disease characterized by the association of isolated hypogonadotropic hypogonadism and anosmia/hyposmia. We report an unusual presentation of two females with KS and empty sella. These females, aged at 20 and 29-year-old, presented primary amenorrhea with prepubertal estradiol and low gonadotropin levels. No other significant clinical signs were observed. Empty sella was observed on MRI in both cases. Sequencing of FGFR1 gene, recently implicated in autosomal form of KS, was performed and one splicing mutation (IVS14 + 1G > A) was identified in one patient.     

Virus associated glomerulonephritis

Virus associated glomerulonephritis is considered to be a para- or post-infectious autoimmune phenomena. The disease is mediated by immune complexes which usually contain the viral antigen. Virus associated glomerulonephritis due to chronic viral infection with hepatitis B or C virus, or with human immunodeficiency virus (HIV) shows a typical histomorphological picture for each virus. Hepatitis B virus usually leads to a membranous glomerulonephritis, while hepatitis C virus is associated with a membranoproliferative glomerulonephritis due to cryoglobulins, and HIV is associated with a focal segmental sclerosing glomerulonephritis. Knowledge of the relationship between the primary viral infection and secondary glomerulonephritis is important, as a primary immunosuppressive therapy might lead to more severe viral disease. On the other hand, a primary reduction in the viral load due to antiviral therapy with immunostimulants or inhibitors of viral replication could lead to an amelioration of the secondary glomerulonephritis.     

Impaired TRAIL-dependent cytotoxicity of CD1c-positive dendritic cells in chronic hepatitis C virus infection

Dendritic cells (DCs) play a central role in antiviral immunity. Conflicting data on DC function have been reported for hepatitis C virus (HCV) infection. In addition to antigen presentation and cytokine secretion, a subset of human DCs displays direct cytotoxic activity. It has been suggested that measles virus and human immunodeficiency virus (HIV) may enhance cytotoxicity of DCs potentially leading to apoptosis of activated T cells and subsequent down-regulation of antiviral immune responses. We demonstrate that CD1c-positive myeloid DCs, but not BDCA-4-positive plasmacytoid DCs, are able to kill different target cells mainly via tumour necrosis factor-related apoptosis-inducing ligand. The ability of CD1c+ DCs to lyze target cells was found to be completely impaired in patients with chronic hepatitis C (10 chronic HCV patients vs 10 healthy controls; P < 0.001) but not in patients with primary biliary cirrhosis. Successful antiviral therapy of chronic hepatitis C rescued the cytotoxicity of DCs. Myeloid DCs of HCV patients and healthy controls had a similar phenotype and endocytotic activity, however, the frequency of mDCs in the peripheral blood was lower (P = 0.004) and the allostimulatory function was weaker (P < 0.001) in chronic hepatitis C. Thus, in contrast to HIV and measles virus studies on monocyte-derived DCs, freshly isolated myeloid DCs of patients with hepatitis C do not show an increased but a completely abolished cytotoxic activity. The impaired DC cytotoxicity could represent a novel mechanism for the increased prevalence of autoimmunity in HCV infection.     

Nongenomic cardiovascular effects of triiodothyronine in euthyroid male volunteers

T(3) has been shown to exert cardiovascular effects. These effects have not yet been defined with regard to the mode of action (nongenomic vs. genomic) and with regard to an interaction with the adrenergic system in humans. To address these issues we conducted a randomized, double blind, 6-fold cross-over trial in 18 healthy male volunteers. After pretreatment with the beta-agonist dobutamine, the beta-blocking agent esmolol, or placebo (0.9% NaCl), 100 microg T(3) or placebo were injected. Primary target variables were systemic vascular resistance (SVR) and cardiac output (CO) within 45 min after injection of T(3) vs. placebo after placebo pretreatment. Sympatho-vagal balance was assessed by measurement of heart rate variability. T(3) caused a lower SVR and a higher CO than placebo (P < 0.001) after pretreatment with placebo. An increased low frequency (LF)/high frequency (HF) ratio (power in LF/power in HF band) after T(3) compared with placebo (P = 0.004) suggests an increase in sympathetic tone. After pretreatment with dobutamine, the effects of T(3) on SVR and CO were abolished, and the effect on LF/HF ratio was reversed. After pretreatment with esmolol, the effects on SVR and LF/HF ratio were reversed. Our data show, for the first time, nongenomic cardiovascular effects of T(3) in humans.     

Increased PLA2 activity in individuals at ultra-high risk for psychosis

European Archives of Psychiatry and Clinical Neuroscience - Phospholipase A2 is the main enzyme in the metabolism of membrane phospholipids. It comprises a family of enzymes divided into iPLA2,...     

Real-time assessment of acute myocardial ischaemia by an intra-thoracic 6-lead ECG: evaluation of a new diagnostic option in the implantable defibrillator.

AIM: In the presence of coronary artery disease, implantable cardioverter-defibrillators (ICD) are used effectively for treating life-threatening tachyarrhythmias. Continuous monitoring of myocardial ischaemia would provide a new diagnostic option in future ICD generations. METHODS AND RESULTS: In 22 selected patients undergoing coronary angioplasty, percutaneous transluminal coronary angioplasty (PTCA), three electrodes, similar to those used in the ICD, were inserted aiming to create six intra-thoracic ECG (IT-ECG) leads according to Einthoven and Goldberger. In total, 27 PTCA were conducted. The diagnostic efficacy for ischaemia assessment was compared with the surface ECG. The IT-ECG proved to be more sensitive than conventional ECG in early and overall ischaemia assessment. At 30 s of coronary artery occlusion, ischaemic ST-segment alterations (> or =0.25 mV) were present in the IT-ECG 2.3 times more often (23 vs. 10/27 PTCA attempts, P<0.01) and at 90 s 1.4 times more often compared with conventional ECG leads (18 vs. 26/27, P<0.05). Intra-thoracic Einthoven 2 (SVC+RVA vs. ICD-housing) and Goldberger 3 (SVC+ICD-housing vs. RVA) had the highest sensitivity (88/85%). Using > or =4 IT-ECG, ischaemia monitoring was independent of severity and site of origin. IT-ECG signals showed double ST-T signal amplitude (4.19+/-0.6 vs. 2.15+/-0.3 mV, ratio: 1.95, P<0.01) at a QRS/ST amplitude ratio similar in the two ECG techniques. CONCLUSION: This study provides strong evidence that the ICD-based IT 6-lead ECG would provide a new and efficient means of assessing a patient's daily ischaemic burden.     

Structural insights into the biogenesis and biofilm formation by the Escherichia coli common pilus

Bacteria have evolved a variety of mechanisms for developing community-based biofilms. These bacterial aggregates are of clinical importance, as they are a major source of recurrent disease. Bacterial surface fibers (pili) permit adherence to biotic and abiotic substrates, often in a highly specific manner. The Escherichia coli common pilus (ECP) represents a remarkable family of extracellular fibers that are associated with both disease-causing and commensal strains. ECP plays a dual role in early-stage biofilm development and host cell recognition. Despite being the most common fimbrial structure, relatively little is known regarding its biogenesis, architecture, and function. Here we report atomic-resolution insight into the biogenesis and architecture of ECP. We also derive a structural model for entwined ECP fibers that not only illuminates interbacteria communication during biofilm formation but also provides a useful foundation for the design of novel nanofibers.