[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

Side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of tennis elbow.

Apart from a few observational reports, there are no studies on the side-effects of extracorporeal shock wave therapy (ESWT) in the treatment of insertion tendopathies. Within the framework of a randomised, placebo-controlled, single-blind, multicentre study to test the effectiveness of ESWT in the case of lateral epicondylitis (LE), side-effects were systematically recorded. A total of 272 patients from 15 centres was allocated at random to active ESWT (3 x 2000 pulses, energy flux density ED(+) 0.04 to 0.22 mJ/mm(2) under local anaesthesia) or placebo ESWT. In all, 399 ESWT and 402 placebo treatments were analysed. More side-effects were documented in the ESWT group (OR = 4.3, CI = [2.9; 6.3]) than in the placebo group. Most frequently, transitory reddening of the skin (21.1%), pain (4.8%) and small haematomas (3.0%) were found. Migraine was registered in four and syncopes in three instances after ESWT. ESWT for LE with an energy flux density of ED(+) 0.04 to 0.22 mJ/mm(2) is a treatment method which has very few side-effects. The possibility of migraine being triggered by ESWT and the risk of a syncope should be taken into account in the future. No physical shock wave parameters could be definitely identified as the cause of the side-effects observed.

Patterns of cerebrospinal fluid pathology correlate with disease progression in multiple sclerosis.

Multiple sclerosis is a chronic inflammatory and demyelinating disease of the CNS with, as yet, an unknown aetiology. Temporal profile, intensity and treatment responses are highly variable in multiple sclerosis suggesting pathogenetic heterogeneity. This hypothesis has been supported by histopathological studies disclosing at least four different subtypes of acute demyelinating lesions. Although stratification of multiple sclerosis patients into these categories would be extremely helpful for clinical studies, this approach is impractical as it requires brain biopsy. In this study we investigated CSF cytology from 60 multiple sclerosis patients by flow cytometry. We identified different patterns of CSF cytology, which were independent of immunological parameters in the peripheral blood. The most variable CSF parameter was the B cell to monocyte ratio, which remained stable during different phases of disease in selected patients. The ratio correlated with disease progression but not with disability or disease duration in a retrospective, consecutive analysis. A high ratio (predominance of B cells) was associated with more rapid disease progression, whereas a low ratio (predominance of monocytes) was found in patients with slower progression. Our study demonstrates the existence and potential clinical relevance of different CSF cytology patterns. We hypothesize that CSF cytology patterns may reflect the heterogeneity in the pathogenesis of multiple sclerosis.

Further evidence for linkage of low-mid frequency hearing impairment to the candidate region on chromosome 4p16.3.

We have investigated a three-generation family with an autosomal dominant low-mid frequency hearing loss. Audiograms show consistently a hearing threshold of 50+/-20 db hearing loss (HL) between 250 Hz and 1-2 kHz. Normal hearing level was reached between 3 and 6 kHz in all examined children. Adult patients show an additional hearing impairment (HI) in the mid and higher frequencies that seems to differ from presbyacusis. The HI is always bilateral and symmetrical. Genes causing non-syndromic autosomal-dominant deafness with HI in the low and mid frequencies were previously mapped to chromosome 4p16.3 (DFNA6, DFNA14) and chromosome 5q31 (DFNA1). After exclusion of linkage to DFNA1 on chromosome 5, we mapped the candidate gene region to the DFNA14 and DFNA6 loci, between the genetic markers D4S432 and D4S431, located on chromosome 4. This is a further family in which evident linkage of low-mid frequency HI to the candidate region on chromosome 4p16.3 has been found.

Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population.

Neural tube defects (NTD) are likely to result from an interaction of several genes and environmental factors. Because periconceptional folate intake reduces the NTD risk in the fetus, and because mothers of children with NTD showed elevated plasma homocysteine levels, gene polymorphisms of the folate and homocysteine pathway, such as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C and cystathionine beta-synthase (CBS) 844ins68, have been implicated in the etiology of NTD. Several studies have demonstrated that these polymorphisms may indeed be associated with NTD in some populations. In order to evaluate the role of these polymorphisms and their interaction in NTD, we genotyped 417 individuals for case-control studies and 129 families for transmission disequilibrium tests. We are the first to present detailed data on MTHFR haploid genotypes in combination with CBS 844ins68. The MTHFR risk genotype 677CT/1298AC, known to be associated with decreased enzyme activity and increased homocysteine, was found significantly more often in patients than in controls (P = 0.02). A CBS insertion allele in addition to MTHFR 677CT/ 1298AC heterozygosity or MTHFR 677TT/1298AA homozygosity did not result in an increased risk for NTD. This is in agreement with the recently reported homocysteine-lowering effect of the CBS 844ins68 allele in carriers of MTHFR variants.

Expression of mast cell growth modulating and chemotactic factors and their receptors in human cutaneous scars.

In order to explore possible mechanisms involved in the previously documented turnover of mast cell subpopulations in human cutaneous scars, we have examined selected factors known to stimulate and/or modulate mast cell hyperplasia (SCF, NGF, TGFbeta1, GM-CSF) and their receptors in human cutaneous scar tissue. On immunohistochemistry, numbers of SCF- and TGFbeta1-positive cells were significantly increased in the epidermis and throughout the dermis in scars (n = 27) of varying ages (4-369 d old), compared with normal skin (n = 12). Furthermore, TRbetaRI, II, and the NGF-p75 receptors were significantly increased in the epidermis, TRbetaRI and NGF-TrkA throughout the dermis, and TRbetaRII, NGF-p75, and GM-CSFR only in the mid- and lower dermis of scars. NGF and GM-CSF expression was in contrast scarce and weak, with no differences between normal skin and scars. In tissue extracts, mRNA levels of SCF, TGFbeta1, TRbetaI and II, and both NGF-receptors, but not GM-CSFR, were significantly increased as well. TRbetaI and II were identified in up to 90% and 83%, respectively, of isolated normal skin mast cells on flow cytometry, and GM-CSFR and NGFR-p75 were identified on 70% and 73%, respectively, of avidin-positive normal mast cells on double immunofluorescence microscopy. As described before for the SCF receptor KIT, GM-CSFR and NGFR-p75 were partly or entirely downregulated on avidin-positive mast cells in scars. The marked upregulation of TGFbeta1, its type I and II receptors, and SCF suggest that these factors play a major role in the orchestration of mast cell increase in human cutaneous scars whereas the role of NGF and GM-CSF is less clear, despite the significant upregulation of their receptors.

A bivariate Haseman-Elston method and application to the analysis of asthma-related phenotypes on chromosome 5q.

We propose a bivariate combination of different Haseman-Elston (HE) methods for model free linkage analysis of quantitative traits. Adjustments for correlations of phenotypes and sibship sizes > 2 are performed using generalized estimating equations (GEE). All calculations are carried out with freely available software packages. We illustrate the application of standard HE methods, the unified HE method, and our novel approach to asthma-associated quantitative traits from the COAG-Perth data set [Palmer et al., 1998, Am J Respir Crit Care Med 158:1825-30]. Our multipoint analyses provide evidence for linkage between log IgE levels adjusted for age, gender and antigen-specific IgE titers. Our results are consistent with previous findings that suggest the existence of loci regulating asthma-associated quantitative traits in the 5q31-33 chromosomal region. Simulation studies are required to compare the power of our novel bivariate HE with other HE approaches and the variance component method.

The use of sequential designs in genome scans for asthma susceptibility loci with affected sib pairs.

We use optimized group sequential study designs to analyze data from two genome scans (German and CSGA) for asthma susceptibility loci with affected sib pairs from Genetic Analysis Workshop (GAW) 12. Results are compared with those from a fixed sample design and the sequential probability ratio test (SPRT). The SPRT does not reach significance at any position. Using the fixed sample design, evidence for linkage is found on chromosomes 6 and 9 in the German and on chromosome 1 in the CSGA scan. The group sequential designs identify the same regions on chromosomes 1 and 6 with a reduced sample size.

Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to xp22.3.

PURPOSE: There is an ongoing discussion whether Lisch corneal dystrophy (band-shaped and whorled microcystic dystrophy of the corneal epithelium) represents a disorder that is different from Meesmann corneal dystrophy. The purpose of this study was to evaluate at the molecular level if Lisch and Meesmann corneal dystrophies are genetically distinct. METHODS: We examined at the slit lamp a total of 48 members of a family with an aggregation of Lisch corneal dystrophy. Genomic DNA was extracted from leukocytes of the peripheral blood of seven affected and six unaffected members of this family. Mutational hotspots in the cornea-specific keratin genes K3 and K12 were scanned for mutations by single-strand conformation analysis. To test for linkage to the keratin K3 or K12 loci or for X-chromosomal inheritance, six (K3) and four (K12) microsatellite markers each flanking the keratin loci as well as 22 microsatellite markers covering the X-chromosome were typed. Linkage was analyzed using the MLINK and FASTMAP procedures. RESULTS: A total of 19 trait carriers were identified in six generations of the family. No hereditary transmission from father to son was observed. Linkage was excluded for the keratin K3 and K12 genes. Furthermore, single-strand conformation analysis detected no mutations in these genes. Multipoint linkage analysis revealed linkage with a maximum likelihood of the odds (LOD) score of 2.93 at Xp22.3. Linkage was excluded for Xp22.2 to Xqter. CONCLUSIONS: Lisch corneal dystrophy is genetically different from Meesmann corneal dystrophy. Evidence was found for linkage of the gene for Lisch corneal dystrophy to Xp22.3.

[Extracorporeal shockwave therapy in treatment of epicondylitis humeri radialis. A current overview]. / Die extrakorporale Stosswellentherapie zur Behandlung der Epicondylitis humeri radialis. Ein aktueller Uberblick.

In the past, extracorporeal shock-wave therapy (ESWT) has been used increasingly as a treatment for conservatively unsuccessfully treated radiohumeral epicondylitis. However, published reviews of clinical trials on the efficacy of ESWT have led to inconsistent results and are outdated or methodologically inadequate. As a consequence, a systematic literature search was conducted which yielded 20 relevant papers that described trials on the efficacy of ESWT in the treatment of radiohumeral epicondylitis. These were rated according to biometrical criteria for the conduct of therapeutic trials. None of the rated trials fulfilled all of the criteria, and it is concluded that the efficacy of ESWT in the treatment of epidondylitis can presently be neither confirmed nor excluded.

Altered expression of mast cell chymase and tryptase and of c-Kit in human cutaneous scar tissue.

In order to explore a possible involvement of mast cells during human wound healing, we studied sections from scars (4-369-d-old) (N = 20) and normal skin (N = 10) for mast-cell-specific tryptase and chymase by enzyme histochemistry, for the stem cell factor receptor c-Kit and the melanosomal marker TA99 by immunohistochemistry, and for simultaneous c-Kit expression and avidin fluorescence by double staining. Enzyme activities and mRNA expression were also studied in tissue extracts. Chymase-reactive mast cell numbers as well as chymase activity and mRNA expression were reduced in all scars, whereas overall numbers of tryptase-reactive cells did not differ from normal skin, although tryptase activity and mRNA expression were increased in scar extracts. In contrast, numbers of c-Kit positive cells were significantly increased in old scars, and in the mid and lower dermis of all scars. A marked reduction of c-Kit reactivity was noted, however, in avidin-positive dermal mast cells and in epidermal basal cells, despite unchanged numbers of melanosome-positive cells, with an associated overall decrease of c-Kit mRNA in scar extracts. These data thus show that numbers of resident mast cells are very low in human cutaneous scars, suggesting massive mediator release from these cells into fresh wounds. Downregulation of stem cell factor receptors may also prevent these cells from increasing in number even in old scars. Instead, scar tissue is populated by a mast cell subpopulation that is chymase-, avidin-, tryptase +, c-Kit +, reflecting most probably an increased immigration and/or proliferation of immature mast cells and their precursors.