[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery.

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.

Analysis of federal process of care data reported from hospitals in rural westernmost North Carolina.

OBJECTIVE: To evaluate standardized process of care data collected on selected hospitals serving a remote, rural section of westernmost North Carolina. MATERIALS & METHODS: Centers for Medicare & Medicaid Services (CMS) data were retrospectively analyzed for 21 clinical parameters at Fannin Regional Hospital (FRH), Murphy Medical Center (MMC), and Union General Hospital (UGH). A binomial test was used to compare each study site to state (NC) and national (U.S.A.) average. RESULTS: Summary data showed FRH to have higher scores on a significant number of standardized clinical process of care measures compared to state (p < 0.05) and national (p < 0.005) averages. Too few process of care measures at UGH were significantly higher than state and national averages to conclude that differences were not due to Type I error. Similarly, at MMC too few process of care measures were significantly higher than national averages to conclude that observed differences were not attributable to Type I error. MMC did not achieve a significantly higher score on any process of care measure when compared to state averages. CONCLUSION: Despite limitations associated with summary data analysis, the CMS "Hospitals Compare" information suggests that process of care scores at FRH are significantly higher than the state and national average. As these hospital quality data are freely available to patients, it remains to be determined what impact this may have on hospital volume and/or market share in this region. Additional research is planned to identify process of care trends in this geographical area.

Head and neck carcinoma models. In vivo reproduction in athymic mice and in vitro culture.

683 tumour fragments from 63 head and neck carcinoma patients were cultured in vitro. Two laryngeal carcinomas and two salivary gland carcinomas were established into permanent cell lines. Malignancy of these cultured cells was proved by cloning, by chromosomal analysis and by transplantation into athymic (nu/nu) mice. Experiments demonstrating preservation of histological, biochemical and antigenic properties in the tumour models counter the objection that tumour-specific characteristics may be lost.

[Histochemical and electron microscopical changes in the kidney of pregnant rats at the time of partus (author's transl)]. / Uber Nierenveränderungen bei der Ratte zur Zeit des Werfens. Histochemische und elektronenmikroskopische Untersuchungen

In the convoluted proximal tubules of the kidney of pregnant rats alkaline phosphatase activity decreases from 21 days gestation till the 2nd day after birth. During the same time the reaction product of the histochemical succinate dehydrogenase assay exhibits an atypical granular character in some of the proximal tubules, which sometimes additionally contain sudanophilic structures. Electron microscopy reveals dilated mitochondria, an increased number of autophagosomes and big lipid vacuoles of low density.

[On the lysosomal pattern in the kidney of normal rats with special reference to the protein excretion(author's transl)]. / Uber das lysosomenmuster normaler Rattennieren unter Berücksichtigung der EiweiBausscheidung

Using the histochemical reaction for acid phosphatase the lysosomal pattern of the proximal renal tubule has been investigated in virginal female rats, in the course of pregnancy, and in females following pretreatment with progesterone. Furthermore the stage of gestation, phases of sexual cycle, the urinary output as well its protein concentration and the protein excretion have been taken into account. From the metabolic studies it becomes clear, that the urine values depend on the sexual phase and the duration of gravidity. On the basis of our histochemical results strong evidence occurs, that the lysosomes in the proximal renal tubule are influenced by both, the proteins in the primary urine and by sex hormones. In all collectives investigated an increase of the protein concentrations in the urine runs always parallel to an increase of the number of small and medium-sized lysosomes; the big ones disappear. At the end of pregnancy and after pretreatment with progesterone acid phosphatase seems to diffuse out of the lysosomes in the epithelial cells of the S1- and S2-segments.

[Fine-needle biopsy in tumor diagnosis of the head and neck region. A method for general practice]. / Die Feinnadelpunktion zur Tumordiagnostik im Kopf-Halsbereich. Eine Methode für die Praxis.

During the last 4 years over 1500 thin-needle aspiration biopsies from tumors in the head and neck region were carried out in the University-ORL-Clinic of Würzburg. 306 cytological results were compared with the histological diagnoses. None of the benign tumors was classified cytologically as malignant (false positive = 0%). 84% of the malignancies were attached to the groups III, IV or V according to the so called Pap.-staging. The rest could not be detected by this method because of technical mistakes as well as accidental false punctions. Some types of tumors could be classified histogenetically in high percentage of cases, especially the pleomorphic adenoma of the glandula parotis and carcinoma metastases.

[Total and partial sleep deprivation in the treatment of depression: preliminary communication]. / Totaler und partieller Schlafentzug in der Behandlung von Depressionen: Vorläufige Mitteilung

Sleep deprivation (SD) has been proved to be an effective measure of antidepressive treatment (especially in endogenous depression). In a new study, 125 SD were examined on 93 depressed patients. The therapeutic benefit of SD on endogenous depression consists not only of the nightly clear up but also of provoking or improving a typical day wave the day after DS. A period of at least 36 h is necessary to survey the total effect of this method. The best results are achieved in patients with severe endogenous depression, especially in those with the typical day wave and distinct somatic symptoms. The effect of partial SD (for the second half of the night) is almost the same as that of total SD. The advantages of partial SD are: the patient can stand it easier, more often, and - in the company of a suited person - even at home. Finally, it is less complicate in clinical routine than selective REM-deprivation.

[Circulatory function in depression with the circadian rhythm uninfluenced or modified (author's transl)]. / Kreislauffunktionen im unbeeinflussten und modifizierten zirkadianen Rhythmus bei Depressionen: Vorläufige Mitteilung

The effect of sleep deprivation (SD) on the altered circadian rhythm of endogenous-depressed patients has been investigated. 61 patients (39 endogenous- and 22 neurotic-depressed) with normal cardio-circulatory activities were tested: During SD-night pulse rate is less lowered in endogenous than in neurotic depression. The increase of systolic blood pressure is quicker and higher in endogenous than in neurotic depression. - Surveying the patients for 72 h (before, during and after SD), pulse rate in endogenous- and neurotic-depressed is less markedly fluctuating than in normal individuals. There is a close connection between the circadian fluctuationsof the depressive symptoms and of the pulse rates. The more SD improves depressive symptoms the more it also flattens the wave of pulse rates. - The circadian courses of systolic blood pressure in endogenous- and neurotic-depressed and in normal subjects are nearly the same. SD markedly flattens the circadian rhythm of blood pressure. In neurotic depression, SD does not clearly alter the course of pulse and blood pressure rates.

Role of the electrochemical proton gradient in genetic transformation of Haemophilus influenzae.

The uptake of homologous DNA by Haemophilus influenzae was studied as a function of the proton motive force in completely competent cultures in the pH range of 6 to 8. The composition and magnitude of the proton motive force were varied by using the ionophores valinomycin and nigericin (in the presence of various potassium ion concentrations) and by using protonophores. No interaction of the ionophores with the DNA transformation system itself was observed. Either component of the proton motive force, the electrical potential or the pH gradient, can drive the uptake of DNA, and the extent of the uptake of DNA is ultimately determined by the total proton motive force. The transformation frequency increases with the proton motive force, which reaches a maximum value at around -130 mV. These results are consistent with an electrogenic proton-DNA symport mechanism, but direct evidence for such a system is not available. The proton motive force was followed during competence development of H. influenzae at pH 8. In the initial phase (up to 50 min), the proton motive force remained constant at about -90 mV, whereas the transformation frequency rose steeply. In the second phase, the proton motive force increased. The transformation frequency in this phase increased with the proton motive force, as in completely competent cultures. These observations and the observed inhibition by NAD of both the proton motive force and the transformation frequency indicate that structural components of the competent state are formed in the initial phase of competence development, whereas the second phase is characterized by an increase of the proton motive force.

Sequence analysis of a split gene involved in fruiting from the fungus Schizophyllum commune.

The sequence of a gene and its mRNA, which is abundantly expressed during fruiting body initiation in the Basidiomycete Schizophyllum commune, is described. This gene (1G2), the first to be analyzed in this group of fungi, contains an open reading frame coding for a polypeptide of 94 amino acids and a mol. wt. of 9842. A possible signal peptide of 20 residues and one glycosylation site were found. The sequence analysis was hampered by a sequence rearrangement in one of the cDNA clones, probably due to base pairing between short complementary sequences present at the 5' and 3' ends of the mRNA. The 5' untranslated leader sequence is 57 bp long and harbors a possible ribosome binding site close to the AUG start codon. A TATA box is found at position -31 upstream of transcription initiation. The 3' untranslated sequence is 200 bp long and contains the sequence -TATATAAT-, which most likely represents the polyadenylation signal. Some heterogeneity as to the site of addition of the poly(A) tail was observed. The coding region of the gene is interrupted by three very small introns of 53, 49 and 49 bp, respectively. The 5' and 3' splice junctions are conserved: GTGAGT- and -AG-, respectively. Each intron contains a sequence complementary to the 5' end of the intron. These sequences are compared with internal conserved sequences in yeast and filamentous fungi with regard to their possible role in splicing.