Mutations in six nephrosis genes delineate a pathogenic pathway amenable to treatment.

No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG) activity, and demonstrate deficiency for mutants of pTSNS patients.

Whole Exome Sequencing of Patients with Steroid-Resistant Nephrotic Syndrome.

Background And Objectives: Steroid-resistant nephrotic syndrome overwhelmingly progresses to ESRD. More than 30 monogenic genes have been identified to cause steroid-resistant nephrotic syndrome. We previously detected causative mutations using targeted panel sequencing in 30% of patients with steroid-resistant nephrotic syndrome.

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality.

Mutations in nuclear pore genes NUP93, NUP205 and XPO5 cause steroid-resistant nephrotic syndrome.

Nucleoporins are essential components of the nuclear pore complex (NPC). Only a few diseases have been attributed to NPC dysfunction. Steroid-resistant nephrotic syndrome (SRNS), a frequent cause of chronic kidney disease, is caused by dysfunction of glomerular podocytes.

Defects of CRB2 cause steroid-resistant nephrotic syndrome.

Nephrotic syndrome (NS), the association of gross proteinuria, hypoalbuminaemia, edema, and hyperlipidemia, can be clinically divided into steroid-sensitive (SSNS) and steroid-resistant (SRNS) forms. SRNS regularly progresses to end-stage renal failure. By homozygosity mapping and whole exome sequencing, we here identify recessive mutations in Crumbs homolog 2 (CRB2) in four different families affected by SRNS.

A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome.

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of ESRD in the first two decades of life. Effective treatment is lacking. First insights into disease mechanisms came from identification of single-gene causes of SRNS.

Cardiac Troponin I elevation after epileptic seizure.

Background: Cardiac troponin-I (cTNI) is highly specific biomarker to prove myocardial damage, e.g. in acute coronary syndrome (ACS).

Factors associated with shunt dynamic in patients with cryptogenic stroke and patent foramen ovale: an observational cohort study.

Background: As previously reported there is evidence for a reduction in right to left shunt (RLS) in stroke patients with patent foramen ovale (PFO). This occurs predominantly in patients with cryptogenic stroke (CS). We therefore analysed factors associated with a shunt reduction on follow-up in stroke patients suffering of CS.

Cerebral vein thrombosis: clinical manifestation and diagnosis.

Background: Cerebral venous thrombosis (CVT) is a disease with a wide spectrum of symptoms and severity. In this study we analysed the predictive value of clinical signs and symptoms and the contribution of D-dimer measurements for diagnosis.

Methods: We evaluated consecutive patients admitted with suspected CVT receiving non-invasive imaging.

High frequency of silent pulmonary embolism in patients with cryptogenic stroke and patent foramen ovale.

Background And Purpose: Deep vein thrombosis and pulmonary embolism (PE) prove venous embolic activity and enforce the suspicion of paradoxical embolism in patients with stroke with patent foramen ovale. Because it has implications in secondary prevention, we investigated the frequency of silent PE in such a cohort of patients.

Methods: Patients with cryptogenic stroke or transient ischemic attack and patent foramen ovale who underwent a ventilation perfusion scintigraphy were identified from a stroke registry.

Decrease in shunt volume in patients with cryptogenic stroke and patent foramen ovale.

Background: In patients with patent foramen ovale (PFO) there is evidence supporting the hypothesis of a change in right-to-left shunt (RLS) over time. Proven, this could have implications for the care of patients with PFO and a history of stroke. The following study addressed this hypothesis in a cohort of patients with stroke and PFO.

Effects of gentamicin and gentamicin-RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: an experimental study in rabbits.

Antimicrobial coatings are of interest as a means to improve infection prophylaxis in cementless joint arthroplasty. However, those coatings must not interfere with the essential bony integration of the implants. Gentamicin-hydroxyapatite (gentamicin-HA) and gentamicin-RGD (arginine-glycine-aspartate)-HA coatings have recently been shown to significantly reduce infection rates in a rabbit infection prophylaxis model.

No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing--remitting multiple sclerosis patients.

We investigated the expression of intercellular adhesion molecules ICAM-1 and ICAM-3 on peripheral blood mononuclear cells in a subgroup of 34 patients with relapsing-remitting multiple sclerosis who were treated orally with the chemokine receptor 1 antagonist BX 471 in a 16-week, randomised, double-blind, placebo-controlled phase II study. ICAM-1 and ICAM-3 expression was measured by flow cytometry at different time points during and after therapy and compared using multivariate analysis of variance and non-parametric Mann Whitney test. ICAM-3 expression on CD14( +) peripheral blood mononuclear cells was increased in the verum group under therapy, but did not differ significantly between the verum and placebo groups.

Prevalence of enteroaggregative Escherichia coli among children with and without diarrhea in Switzerland.

In a prospective study between July 1999 and September 2000, stool specimens of children below the age of 16 years with (n = 187) and without (n = 137) diarrhea were tested for the presence of enterovirulent bacteria by standard culture methods and by PCR. Targets for the PCR were the plasmid pCVD432 for enteroaggregative Escherichia coli (EAEC), the verotoxin 1 and verotoxin 2 genes for enterohemorrhagic E. coli, ipaH for enteroinvasive E.

Significance of inflammation on standard semen analysis in chronic prostatitis/chronic pelvic pain syndrome.

The impact of defined urogenital inflammations on standard ejaculate parameters is still a matter of controversial debate. Basic spermiogram parameters has been analysed in patients with inflammatory and noninflammatory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-NIH IIIA/IIIB) with regard to indicators of inflammation in prostatic secretions and/or the ejaculate. A total of 112 consecutive patients symptomatic for chronic pelvic pain were included in the study.

Chronic prostatitis/chronic pelvic pain pyndrome): seminal markers of inflammation.

The new prostatitis classification proposes the inclusion of seminal leukocytes in the diagnosis of inflammatory chronic pelvic pain syndrome (CPPS). The present study has been performed to clarify the role of seminal leukocytes and inflammatory seminal plasma parameters in order to contribute to the differential diagnosis between inflammatory (category IIIA) and non-inflammatory (category IIIB) CPPS. A total of 112 consecutive symptomatic patients (mean age 37.

Expression analysis of the glucocorticoid receptor and the nuclear factor-kB subunit p50 in lymphocytes from patients with rheumatoid arthritis.

Objective: To study a possible relationship between expression of the transcription factor glucocorticoid receptor (GR), which mediates antiinflammatory effects, and the transcription factor p50, which mediates proinflammatory effects, in peripheral blood mononuclear cells (PBMC) of patients with rheumatoid arthritis (RA).

Methods: Expression analysis of GR and nuclear factor-kB subunit p50 in PBMC was performed by semiquantitative immunoblotting.

Results: GR and p50 expression in PBMC were significantly increased in patients with RA who had never received corticosteroids.

Seminal secretory capacity of the male accessory sex glands in chronic pelvic pain syndrome (CPPS)/chronic prostatitis with special focus on the new prostatitis classification.

Objective: The aim of the study was to evaluate the secretory dysfunction of the male accessory glands in men with inflammatory versus non-inflammatory chronic pelvic pain syndrome (CPPS).

Methods: One hundred and twelve consecutive patients symptomatic for chronic pelvic pain were included into the study. All underwent a combined granulocyte analysis in expressed prostatic secretions (EPS) and a four-glass-test followed by ejaculate analysis.

Impaired glucose effectiveness in chronic progressive external ophthalmoplegia.

Mitochondrial gene mutations have been recognized to be associated with diabetes mellitus. The incidence of diabetes mellitus in patients with other mitochondrial diseases, such as chronic progressive external ophthalmoplegia (CPEO), seems to be several times higher than in the normal population. The aim of the present investigation was to study insulin sensitivity index (SI), insulin secretion (AIR(Glucose)), and glucose effectiveness (Sg) in patients with CPEO.

Enhanced lymphocyte proliferation in patients with adrenoleukodystrophy treated with erucic acid (22:1)-rich triglycerides.

Lymphocytopenia and depression of natural killer cells have been observed in patients with adrenoleukodystrophy (ALD) treated with glycerol trioleate and glycerol trierucate ('Lorenzo's oil'). To investigate possible alterations of cellular immunoreactivity, we measured lymphocyte proliferation in response to mitogens (PHA, Con A, PWM, OKT3) in 27 patients on treatment and in 14 patients without treatment. In patients on treatment, lymphocyte proliferation in response to the mitogens PHA and Con A was significantly higher than in patients without treatment.

[Left ventricular heart volume determination with fast MRI in breath holding technique: how different are quantitative heart catheter, quantitative MRI and visual echocardiography?].

Goal: Comparison of fast MRI, echocardiography (Echo), and ventricular angiography (Cath) in the assessment of left ventricular global function.

Methods: Fast MRI in short axis plane, biplane Cath, and 2D Echo were performed in 62 patients [35 coronary artery diseases, 16 acquired valvular diseases (VD), 9 dilated cardiomyopathies (DCM), 1 congenital heart disease and 1 heart transplantation]. Enddiastolic (EDV), endsystolic (ESV), stroke volumes (SV), cardiac output (CO), and ejection fraction (EF) were compared in MRI and Cath.

Right ventricular volumes and ejection fraction with fast cine MR imaging in breath-hold technique: applicability, normal values from 52 volunteers, and evaluation of 325 adult cardiac patients.

Our goal was to establish right ventricular (RV) volume and ejection fraction (EF) values in normal volunteers with fast magnetic resonance (MR) imaging using a breath-hold technique, to assess the frequency and severity of RVEF abnormality in cardiac patients and to compare RV with left ventricular (LV) data. We performed simultaneously derived RV and LV fast cine measurements in 52 normals and 325 patients with coronary artery disease (CAD), acquired valvular disease (VD), cardiomyopathy (CM), or congenital heart disease (CHD). RVEF was reduced in 31% (102) of all patients, in 50% dilated CM, 39% CHD, 34% CAD, and 22% acquired VD patients.

[The determination of left and right ventricular ejection and filling functions of the heart by fast cine MRT in the breath-hold technic in subjects].

Purpose: Evaluation and comparison of localized and global left and right ventricular ejection and filling with fast cine MR imaging in the breath-hold technique.

Materials And Methods: 10 healthy volunteers were examined with a 1.5 Tesla unit and phased-array-coil using a segmented FLASH-2D sequence in breath-hold technique.