Clinical picture and treatment of 2212 patients with common variable immunodeficiency.

Background: Common variable immunodeficiency (CVID) is an antibody deficiency with an equal sex distribution and a high variability in clinical presentation. The main features include respiratory tract infections and their associated complications, enteropathy, autoimmunity, and lymphoproliferative disorders.

Objective: This study analyzes the clinical presentation, association between clinical features, and differences and effects of immunoglobulin treatment in Europe.

Characterization of animal models for primary sclerosing cholangitis (PSC).

Primary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies.

Detection of E6-AP as a potential therapeutic target in cervical specimen of HPV-infected women.

Purpose: Silencing of HPV oncogenes or their human host client proteins using topically applied small interfering RNA (siRNA) may be an attractive nonsurgical strategy for CIN treatment. An exploratory clinical investigation was designed to evaluate E6-AP mRNA expression levels in different stages of cervical intraepithelial neoplasia and during the menstrual cycle.

Methods: In 38 premenopausal women aged 18-45 years referred to colposcopy clinic, analysis of serum hormones, cervical smears for cytology and HPV DNA, cervical biopsy, p16 immunohistochemistry and E6-AP mRNA expression levels in cervical smears and biopsies were performed.

Reproductive medicine and the law: egg donation in Germany, Spain and other European countries.

This paper analyzes the key legal issues raised by Reproductive Medicine practiced in Europe, with special attention to the rules prevailing in countries such as Germany and Spain. Thus, the paper involves a detailed study of the regulation in force in those countries, comparing their solutions with the rules adopted in other EU countries. It also highlights the high risk of com-modification in oocyte donation.

First clinical experiences with a direct acoustic cochlear stimulator in comparison to preoperative fitted conventional hearing aids.

Objective: Patients with moderate-to-severe mixed hearing losses (MHLs) are hard to provide sufficient benefit with currently available conventional hearing aids. Here, the long-term safety of a direct acoustic cochlear stimulator (DACS) and the effectiveness compared with conventional "high-performance" hearing aids were investigated.

Study Design: Prospective, within patient reference, nonrandomized, interventional multicenter clinical study performed at these 3 centers: Medical University Hannover, University of Heidelberg, and Helios Hospital Krefeld.

Neural representation in the auditory midbrain of the envelope of vocalizations based on a peripheral ear model.

The auditory midbrain implant (AMI) consists of a single shank array (20 sites) for stimulation along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) and has been safely implanted in deaf patients who cannot benefit from a cochlear implant (CI). The AMI improves lip-reading abilities and environmental awareness in the implanted patients. However, the AMI cannot achieve the high levels of speech perception possible with the CI.

Do we really need a Coupler for the round window application of an AMEI?

Objective: Implanting active middle ear implants (AMEI) at the round window has become a standard procedure to restore hearing for patients with moderate inner ear or mixed hearing loss. The round window (RW)-Coupler was developed as an alternative coupling aid to fit smaller RW diameters and require less drilling in the RW niche. The question arises whether using the RW-Coupler is useful and a safe procedure compared with the nonuse of the RW-Coupler

Materials And Methods: Forty-nine German-speaking patients were implanted with either a RW-Coupler attached to an AMEI floating mass transducer (FMT) or without coupler.

The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients.

Objective: According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients.

Design: Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis.

A case of instantaneous rigor?

The question of whether instantaneous rigor mortis (IR), the hypothetic sudden occurrence of stiffening of the muscles upon death, actually exists has been controversially debated over the last 150 years. While modern German forensic literature rejects this concept, the contemporary British literature is more willing to embrace it. We present the case of a young woman who suffered from diabetes and who was found dead in an upright standing position with back and shoulders leaned against a punchbag and a cupboard.

Increased hospital length of stay attributable to Clostridium difficile infection in patients with four co-morbidities: an analysis of hospital episode statistics in four European countries.

Hospital-onset Clostridium difficile infection (CDI) places a significant burden on health care systems throughout Europe, estimated at around €3 billion per annum. This burden is shared between national payers and hospitals that support additional bed days for patients diagnosed with CDI while in hospital or patients re-admitted from a previous hospitalisation. This study was performed to quantify additional hospital stay attributable to CDI in four countries, England, Germany, Spain, and The Netherlands, by analysing nationwide hospital-episode data.

Autoantibodies against CD74 in spondyloarthritis.

Background: Spondyloarthritis (SpA) is a common debilitating inflammatory disorder. Establishing the diagnosis is often difficult, since abnormalities in conventional X-ray develop with a latency of several years and only HLA-B27 is used as a laboratory marker. The goal of our study was to identify new autoantibodies as diagnostic markers of SpA.

Epitope mapping of antibodies against ferritin heavy chain in giant cell arteritis and polymyalgia rheumatica.

Objectives: In a previous study we found an association between antibodies against the human ferritin heavy chain (HFC) protein and giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), especially in GCA/PMR patients prior to glucocorticoid treatment. Antibodies against the N-terminal part of ferritin were present in 92% of untreated patients, 69% of patients with disease flare, and 13% of patients in remission. These antibodies appeared to be markers for the early detection of a disease complex usually diagnosed with considerable delay.

Mesenchymal stem cells maintain long-term in vitro stemness during explant culture.

The advantage of mesenchymal stem cells (MSC) in view of cell and/or tissue replacement after transplantation and their prolonged clinical use raises heavy debates not only in the fields of tissue engineering and regenerative medicine to date. Explant culture of umbilical cord (UC) tissue pieces for more than 190 days demonstrated a similar morphology and proliferation rate of outgrowing MSC as compared to UC tissue cultured for 15 days. Flow cytometric analysis revealed the expression of the typical UC-MSC markers CD73, CD90, and CD105 with concomitant absence of CD14, CD31, CD34, and CD45 in all MSC populations.

The effect of static force on round window stimulation with the direct acoustic cochlea stimulator.

The Direct Acoustic Cochlea Stimulator Partial Implant (DACS PI, Phonak Acoustic Implants SA, Switzerland) is intended to stimulate the cochlea by a conventional stapedotomy piston that is crimped onto the DACS PI artificial incus. An alternative approach to the round window (RW) is successfully done with other devices, having the advantage of being also independent of the existence of middle ear structure (e.g.

Nanosecond laser pulse stimulation of the inner ear-a wavelength study.

Optical stimulation of the inner ear, the cochlea, is discussed as a possible alternative to conventional cochlear implants with the hypothetical improvement of dynamic range and frequency resolution. In this study nanosecond-pulsed optical stimulation of the hearing and non-hearing inner ear is investigated in vivo over a wide range of optical wavelengths and at different beam delivery locations. Seven anaesthetized guinea pigs were optically stimulated before and after neomycin induced destruction of hair cells.

Mesenchymal stem cells as all-round supporters in a normal and neoplastic microenvironment.

Mesenchymal stem cells (MSC) represent a heterogeneous population exhibiting stem cell-like properties which are distributed almost ubiquitously among perivascular niches of various human tissues and organs. Organismal requirements such as tissue damage determine interdisciplinary functions of resident MSC including self-renewal, migration and differentiation, whereby MSC support local tissue repair, angiogenesis and concomitant immunomodulation. However, growth of tumor cells and invasion also causes local tissue damage and injury which subsequently activates repair mechanisms and consequently, attracts MSC.

Development of brainstem-evoked responses in congenital auditory deprivation.

To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs) and hearing controls (HCs) were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed.

No association of SIDS with two polymorphisms in genes relevant for the noradrenergic system: COMT and DBH.

Aim:   Recent research suggests that genetic variance determining the strength of noradrenergic transmitting might contribute to the aetiology of SIDS. We have typed 2 functional polymorphisms of relevance for both biosynthesis and catabolism of noradrenalin: The Val158Met single-nucleotide polymorphism (SNP) of the Catechol-O-methyl transferase gene (COMT) and the 1021C/T SNP of the dopamine dehydroxylase gene (DBH).

Methods:   COMT and DBH were typed in 171 and 196 SIDS cases and 213 and 244 controls, respectively, using PCR followed by digestion with restriction enzymes.

A device for patterned electrical stimulation of cultivated cells: preliminary tests with rat auditory neurons.

The number of surviving spiral ganglion neurons (SGNs) is important for the function of cochlear implants. Electrical stimulation has been discussed controversially regarding its protective effects on SGNs both in vivo and in vitro. The aim of this study was to develop a device for electrical stimulation of cultured SGNs.

Association between a functional polymorphism in the MAOA gene and sudden infant death syndrome.

Objectives: Abnormalities in the serotonergic as well as the noradrenergic neuronal systems are believed to contribute to sudden infant death syndrome (SIDS). The X-chromosomal monoamine oxidase A (MAOA) gene is of importance for both systems and up to now no systematic study on a functional polymorphism in this gene has been performed in a sufficiently large group.

Methods: We investigated a functional MAOA promoter length polymorphism in 156 white SIDS cases and 260 gender- and age-matched control subjects by using capillary electrophoresis and fluorescence dye labeled primers.

Variable disease progression after successful stem cell transplantation: prospective follow-up investigations in eight patients with Hurler syndrome.

We report the results of a prospective, standardized follow-up programme of eight children (median age at SCT 1.2 yr) with mucopolysaccharidosis (MPS1H, M. Hurler) transplanted using a fludarabine-based SCT.

Developmental neuroplasticity after cochlear implantation.

Cortical development is dependent on stimulus-driven learning. The absence of sensory input from birth, as occurs in congenital deafness, affects normal growth and connectivity needed to form a functional sensory system, resulting in deficits in oral language learning. Cochlear implants bypass cochlear damage by directly stimulating the auditory nerve and brain, making it possible to avoid many of the deleterious effects of sensory deprivation.