[Incidence of coercive measures as an indicator of quality in psychiatric hospitals. Problems of data recording and processing, preliminary results of a benchmarking study]. / Die Inzidenz von Zwangsmassnahmen als Qualitätsindikator in psychiatrischen Kliniken. Probleme der Datenerfassung und -verarbeitung und erste Ergebnisse.

OBJECTIVE: The clinical practice concerning the use of coercive measures in psychiatry should be compared. METHOD: A common documentation of physical restraint, seclusion, and medication by coercion was introduced among 10 hospitals. RESULTS: 8.4 % of cases treated within the first 6 months of 2004 were exposed to coercive measures with the highest percentage among patients with psychoorganic disorders (32.1 %). The incidence of coercive measures varied highly between different diagnostic groups and hospitals. DISCUSSION: The processing of the large multi-site data sets yields considerable technical problems. Data interpretation should consider confounding factors such as case mix and hospital structure characteristics.

Diagnosis-related frequency of compulsory measures in 10 German psychiatric hospitals and correlates with hospital characteristics.

OBJECTIVE: To investigate the incidence of coercive measures in standard psychiatric care in different psychiatric hospitals. METHODS: We developed a common documentation of mechanical restraint, seclusion, and medication by coercion, and introduced it in 10 participating hospitals. We developed software able to process the data and to calculate four key indicators for routine clinical use. RESULTS: 9.5% of 36,690 cases treated in 2004 were exposed to coercive measures with the highest percentage among patients with organic psychiatric disorders (ICD-10 F0) (28.0%). Coercive measures were applied a mean 5.4 times per case and lasted a mean 9.7 h each. The incidence and duration of coercive measures varied highly between different diagnostic groups and different hospitals. Use of detailed guidelines for seclusion and restraint was associated with a lower incidence of coercive measures. DISCUSSION: Data interpretation should consider numerous confounding factors such as case mix and hospital characteristics. Suggestions on how to cope with ethical and technical problems in the processing of large multi-site data sets in routine clinical use are made.

Bathing suit ichthyosis is caused by transglutaminase-1 deficiency: evidence for a temperature-sensitive phenotype.

Bathing suit ichthyosis (BSI) is a striking and unique clinical form of autosomal recessive congenital ichthyosis characterized by pronounced scaling on the bathing suit areas but sparing of the extremities and the central face. Here we report on a series of 10 BSI patients. Our genetic, ultrastructural and biochemical investigations show that BSI is caused by transglutaminase-1 (TGase-1) deficiency. Altogether, we identified 13 mutations in TGM1-among them seven novel missense mutations and one novel nonsense mutation. Structural modeling for the Tyr276Asn mutation reveals that the residue is buried in the hydrophobic interior of the enzyme and that the hydroxyl side chain of Tyr276 is exposed to solvent in a cavity of the enzyme. Cryosections of healthy skin areas demonstrated an almost normal TGase activity, in contrast to the affected BSI skin, which only showed a cytoplasmic and clearly reduced TGase-1 activity. The distribution of TGase-1 substrates in the epidermis of affected skin corresponded to the situation in TGase-1 deficiency. Interestingly, the expression of TGase-3 and cathepsin D was reduced. Digital thermography validated a striking correlation between warmer body areas and presence of scaling in patients suggesting a decisive influence of the skin temperature. In situ TGase testing in skin of BSI patients demonstrated a marked decrease of enzyme activity when the temperature was increased from 25 to 37 degrees C. We conclude that BSI is caused by TGase-1 deficiency and suggest that it is a temperature-sensitive phenotype.

Novel and recurrent mutations in keratin KRT5 and KRT14 genes in epidermolysis bullosa simplex: implications for disease phenotype and keratin filament assembly.

Epidermolysis bullosa simplex (EBS) is a group of autosomal dominant genetic skin disorders caused by mutations of the keratin genes KRT5 and KRT14. It is characterised by lysis of basal keratinocytes leading to the development of intraepidermal blisters upon minor mechanical trauma. We investigated 27 EBS patients and families of mainly German origin by sequence analysis of the entire coding sequences of KRT5 and KRT14 and identified 12 novel and seven previously reported mutations within the KRT5 and KRT14 genes. The study discusses possible implications of the novel mutations on protein structure, keratin intermediate filament (KIF) formation and the corresponding phenotype, and summarises the spectrum of mutations reported so far in EBS. Detailed knowledge of the spectrum of EBS mutations and their genotype-phenotype correlation is essential for accurate genetic counselling and prenatal diagnosis.

Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris.

The gene for solute carrier family 12 member A8 has recently been proposed as a candidate gene for psoriasis susceptibility (PSORS5) on chromosome 3q based on association of five single nucleotide polymorphisms (SNP) in Swedish patients. To investigate whether this locus is relevant for German psoriasis vulgaris (PsV) patients, we analyzed a group of 210 trios and a case-control group including 375 patients. Based on our investigation of the linkage disequilibrium (LD) structure of SLC12A8, we assayed 35 haplotype tag SNP and grouped them into nine LD-blocks. In the case-control study, we detected an association for six SNP and three LD-based haplotypes. Association was strongest for ss35527511 (chi2 = 11.224, p = 0.0008) and haplotype E-2 (chi2 = 11.788, p = 0.00059) and independent of the presence of an HLA-associated PSORS1 risk allele. Through extended haplotype analysis, we could show that two independent association signals exist in SLC12A8, suggesting allelic heterogeneity. None of the SNP showed association in trios, apart from a weak association of rs2228674 (transmission disequilibrium test statistics p = 0.048), probably due to insufficient power. We conclude that SLC12A8 is a susceptibility locus for PsV. In order to establish the exact nature of this association, efforts to identify the disease-causing variants are ongoing.

Mutation spectrum and functional analysis of epidermis-type lipoxygenases in patients with autosomal recessive congenital ichthyosis.

Autosomal-recessive congenital ichthyosis (ARCI) is a clinically and genetically heterogeneous group of severe hereditary keratinization disorders characterized by intense scaling of the whole integument, and differences in color and shape. It is often associated with erythema. To date, six loci for ARCI have been mapped. Mutations in ALOXE3 and ALOX12B on chromosome 17p13, which code for two different epidermal lipoxygenases, were recently found in patients with ichthyosiform erythroderma from Turkey, France, and North Africa. Here we describe molecular and clinical findings in 17 families with ARCI originating from Central Europe, Turkey, and the Indian subcontinent, with mutations in ALOXE3 or ALOX12B. We identified 11 novel point mutations in ALOX12B (one nonsense mutation and 10 missense mutations) and four different inactivating mutations in ALOXE3. The gene products of ALOX12B and ALOXE3, the epidermal lipoxygenases 12R-LOX and eLOX3, respectively, are preferentially synthesized in the skin. They act in sequence to convert arachidonic acid via 12(R)-HPETE to the corresponding epoxyalcohol, 8(R)-hydroxy-11(R),12(R)-epoxyeicosatrienoic acid. To assess the impairment of enzyme activity, we expressed the mutated genes in vitro and determined the activity of the recombinant proteins toward their genuine substrates. All but one of the recombinant mutants were enzymatically inactive. The characterization of disease-causing mutations in ALOXE3 and ALOX12B and the resulting ARCI phenotypes did not result in clear diagnostic criteria; however, we found a first correlation between the genetic findings and the clinical presentation of ichthyosis.

Lack of evidence for genetic association to RUNX1 binding site at PSORS2 in different German psoriasis cohorts.

A DNA variant, rs734232, altering a RUNX1 binding site was recently reported as susceptibility allele at PSORS2 (17q25) in cohorts of psoriasis patients from the US. A testing of this variant in psoriasis patients from Germany did not confirm this association in 300 trios nor in two case-control studies with 281 patients with psoriasis vulgaris and 375 patients with psoriatic arthritis, respectively. These results fail to support rs734232 as a psoriasis susceptibility factor in German psoriasis patients.

German adaptation of the Skindex-29 questionnaire on quality of life in dermatology: validation and clinical results.

BACKGROUND: Health-related quality of life (HRQOL) has increasingly been recognized as an important aspect of a comprehensive clinical assessment in dermatology. OBJECTIVE: The aim of the present study was to translate and validate one of the most frequently used and established skin disease-specific HRQOL questionnaires originally developed in English for the German language area: the Skindex-29. METHODS: 295 in-patients with psoriasis and atopic dermatitis completed the German translation of the Skindex as well as a number of additional skin disease-specific questionnaires. Data from 2 subsamples were analysed separately to test for the robustness of results. RESULTS: Results from principal component analyses supported the scale structure of the original Skindex. Internal consistency coefficients were high for all scales. Further analyses supported the convergent validity of the German adaptation of the Skindex-29 as well as its sensitivity to change. CONCLUSION: The study provides evidence for the validity and reliability of the Skindex-29.

A new family with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer.

We describe a new family with the rare genodermatosis keratosis punctata palmo-plantaris Buschke-Fischer-Brauer (keratoma disseminatum). In all, 3 family members in 3 generations were affected, a pattern consistent with autosomal dominant inheritance. Clinical symptoms started in the third decade with disseminated, small, round, hyperkeratotic papules on the palms and soles. Punctate keratoses coalesced into hyperkeratotic plaques on pressure points. Identification of additional families is necessary to permit definitive genetic classification of this genodermatosis.

47 patients in 14 families with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer.

We summarize the clinical data of 47 patients with the rare genodermatosis keratosis punctata palmoplantaris Buschke-Fischer-Brauer. The pedigrees of 14 German families were studied. In three families there was only one member affected, two or more affected members were found in the other families. These family pedigrees were consistent with autosomal dominant inheritance. Variable expression of the disease was noted in members within one family. Over pressure points punctate keratoses coalesced into hyperkeratotic plaques. There was palmoplantar hyperhidrosis in 3 families associated with keratosis. Continuous systemic retinoid treatment can clear symptoms. Future genetic classification on a molecular basis may reveal the existence of more than one entity of this clinically heterogeneous genodermatosis.

Lipid composition of outer stratum corneum in hereditary palmoplantar keratodermas.

BACKGROUND: The analysis of lipid composition of the outer stratum corneum is a promising approach to study the pathophysiology of inherited disorders of keratinization. OBJECTIVE: The purpose of the study was the search for biochemical alterations of stratum corneum lipids in hereditary palmoplantar keratoderma (PPK). METHODS: Using high-performance thin-layer chromatography, we performed an analysis of all major stratum corneum lipid classes in scales of 29 patients with 8 different types of hereditary PPK. RESULTS: In comparison to the controls, slight differences in the lipid pattern were found in all keratodermas. Reduced amounts of total ceramides and increased levels of free fatty acids were noted in nearly all types. CONCLUSIONS: The study indicates that the abnormal composition of stratum corneum lipids in PPK is probably not caused by genetic defects of the epidermal lipid metabolism, but it appears to represent an epiphenomenon of a disturbed cornification.

Influences on human internal exposure to environmental platinum.

Different influences on internal exposure to platinum are investigated and for the first time weighted in environmentally exposed subjects as far as individual internal platinum concentrations are concerned. Detailed medical and environmental histories as well as oral cavity status were assessed in 84 dermatological patients, and internal platinum exposure was determined by analyzing platinum in urine using adsorptive voltammetry (AV). Platinum concentrations ranged from <0.9 (detection limit) to 65.5 ng Pt/l urine. Influence of different types and age of alloy restorations and therefore relevance of the exposure pathway due to solubilization of platinum in saliva could be demonstrated. No platinum-related health effects (contact stomatitis, asthma or kidney conditions) were observed. Analysis of covariance showed the number of noble dental alloy restorations (P<0.0001) and to a lesser extent age (P=0.0017) to independently influence internal platinum exposure. Even though spread of environmental platinum has increased, internal platinum exposure is low in subjects without assessable medical or dental devices (usually <4.5 ng/l urine) and not related to adverse health effects. For the first time, detailed individual information on possible exposure pathways to platinum were considered in an analysis of relevant influential factors: Car traffic exposure and dermatological condition showed no association with internal platinum exposure. Uptake from platinum containing noble metal dental alloy restorations (NMDAR) is of greatest relevance, surmounting the influence of each year of lifetime on platinum body load by more than 10-fold.

Epidermolytic palmoplantar keratoderma of Vörner: re-evaluation of Vörner's original family and identification of a novel keratin 9 mutation.

In 1901, Hans Vörner observed a family with a diffuse non-transgredient palmoplantar keratoderma of autosomal dominant inheritance. Histopathologically, he found epidermolytic hyperkeratosis as a characteristic sign and diagnostic criterion of this disorder. We performed a follow-up study of the family originally seen by Vörner in 1901 with clinical, histopathological, and molecular investigations. Clinically, affected family members showed the typical diffuse keratoses over the entire surface of the palms and soles sharply bordered by red margins. A mycotic infection was additionally found in two patients examined. Histopathological investigations confirmed epidermolytic hyperkeratosis. Molecular studies revealed a novel mutation in keratin 9, N160I, in patients from the family. The mutation in the coil-1A domain is thought to have a dominant negative effect on the assembly of keratin intermediate filaments, explaining the dominant inheritance of the phenotype. These findings give further evidence that palmoplantar keratoderma of Vörner represents the same entity as palmoplantar keratoderma of Thost, which was recently re-evaluated in Thost's original family and shown to be caused by a similar mutation, R162 W, in the same segment of keratin 9.