Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: An analysis of 12,082 prostate cancer cases.

BACKGROUND: Prostate cancer (PCa) is a leading cause of mortality and genetic factors can influence tumour aggressiveness. Several germline variants have been associated with PCa-specific mortality (PCSM), but further replication evidence is needed. METHODS: Twenty-two previously identified PCSM-associated genetic variants were genotyped in seven PCa cohorts (12,082 patients; 1544 PCa deaths). For each cohort, Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for risk of PCSM associated with each variant. Data were then combined using a meta-analysis approach. RESULTS: Fifteen SNPs were associated with PCSM in at least one of the seven cohorts. In the meta-analysis, after adjustment for clinicopathological factors, variants in the MGMT (rs2308327; HR 0.90; p-value = 3.5 × 10-2) and IL4 (rs2070874; HR 1.22; p-value = 1.1 × 10-3) genes were confirmed to be associated with risk of PCSM. In analyses limited to men diagnosed with local or regional stage disease, a variant in AKT1, rs2494750, was also confirmed to be associated with PCSM risk (HR 0.81; p-value = 3.6 × 10-2). CONCLUSIONS: This meta-analysis confirms the association of three genetic variants with risk of PCSM, providing further evidence that genetic background plays a role in PCa-specific survival. While these variants alone are not sufficient as prognostic biomarkers, these results may provide insights into the biological pathways modulating tumour aggressiveness.

Evaluation of sampling locations in pregnant women and newborns for the detection of colonisation with antibiotic-resistant bacteria.

Up to now, little has been known about the prevalence and clinical relevance of colonisation of asymptomatic pregnant women with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) or extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. In this two-centre cross-sectional study, we evaluated the performance and importance of screening at different times and different locations for colonisation in pregnant women and newborns. Between October 2013 and December 2015, four samples were collected from pregnant women, two from newborns at birth and three from 3-day-old newborns. Samples were screened on culturing media and were confirmed with molecular methods. MSSA was used as a surrogate for MRSA, as the two share most microbiologic characteristics and colonisation patterns. Of 763 pregnant women, 14.5% (111) were colonised with MSSA, 0.4% (3) with MRSA and 2.6% (20) with ESBL-producing E. coli. Of 658 newborns, 0.9% (10) were colonised with MSSA at birth and 13.1% (70) at 3 days old, 0.5% (3) were colonised with MRSA and 2.6% (17) with ESBL-producing E. coli. Nasal sampling identified 91.0% of MSSA-colonised pregnant women and 60.0% of newborns. In newborns, nasal and umbilical sampling at 3 days after birth discovered 84.0% of colonised cases. For ESBL-producing E. coli, the perianal region was positive in all colonised pregnant women and in 88.2% of colonised newborns. Combining nasal and perianal swabs is optimal when screening for antibiotic-resistant bacteria in pregnant women. Nasal, perianal and umbilical sample collection from 3-day-old newborns significantly increased the sensitivity compared to screening immediately after birth.

[Exposure of Pupils to Recreational Noise from Portable Listening Devices and Possible Preventive Measures]. / Freizeitlärmbelastung durch tragbare Musikabspielgeräte bei Schülern und Präventionsmöglichkeiten.

Background and Objectives: Exposure to recreational noise is becoming increasingly important due to a change in leisure behavior amongst children and adolescents. The aim of this pilot study was to assess exposure of 6th grade pupils to recreational noise from portable listening devices (PLD). Furthermore, preventive measures to reduce recreational noise exposure should be identified. Methods: In "Ohrkan Kids", 38 Bavarian pupils aged 11 to 14 were interviewed regarding their music listening behavior using a standardized questionnaire. In addition, measurements of commonly used volume settings on the children's portable listening devices were carried out. Furthermore, the German Social Accident Insurance (DGUV), health insurance companies as well as health and education ministries of the German federal states were surveyed regarding their activities in the prevention of recreational noise exposure. Results: Based on the questionnaire data for weekly usage, 10 out of 31 children (32.3%) exceeded the upper exposure value of 85 dB recommended by labor protection law. Taking actually measured values, 9 out of 31 children (29%) exceeded this level. The DGUV and some federal states carry out specific projects for the prevention of recreational noise exposure. Conclusion: The large number of children with hazardous music consumption indicates that measures for the prevention of noise-induced hearing loss are already required for 11 to 14 year olds. To maximize the number of children addressed, age-appropriate and target-group-specific preventive measures are needed. As there are only few studies which examined the effectiveness of awareness campaigns for the prevention of recreational noise, any future prevention projects should be evaluated with an increased focus on estimating their effectiveness.

[Taking Care of Asylum Seekers: Occupational Health Aspects with a Special Focus on Vaccination]. / Arbeitsmedizinische Aspekte und Impfschutz beim Umgang mit Asylbewerbern.

Employees and volunteers often feel insecure about the potential transmission of infectious diseases when taking care of asylum seekers. It could be shown that overall only a minor risk of infection emanates from asylum seekers. However, aspects of occupational health and vaccination should be kept in mind.Besides the standard vaccination the Standing Committee on Vaccination (STIKO) recommends for occupational indication, which is given for employees and volunteers in asylum facilities, vaccination against hepatitis A, hepatitis B, polio (if the last vaccination was more than 10 years before) as well as influenza (seasonal).According to the German Occupational Safety and Health Act taking care of the employer has to determine which exposures might occur at the workplace (risk assessment) and define necessary protection measures. Depending on task and exposure when taking care of asylum seekers different acts (e. g. biological agents regulation) and technical guidelines for the handling biological agents (e. g. TRBA 250 or TRBA 500) have to be applied.The Bavarian Health and Food Safety Authority (LGL) has published several information sheets regarding "asylum seekers and health management" for employees and volunteers from the non-medical as well as the medical area (www.lgl.bayern.de search term "Asylbewerber"). With theses publications insecurities in taking care of asylum seekers should be prevented. Furthermore the employer gets support in the implementation of legal obligations to ensure occupational safety for the employees.

[Preoperational study for the improvement of hygiene conditions in long-term care facilities]. / Modellprojekt zur Verbesserung der Hygiene in stationären Pflegeeinrichtungen.

Hygiene is becoming more and more important in long-term care facilities. Long-term care facilities are subject to monitoring by the Public Health Service (PHS) and other authorities. For the PHS in Bavaria the Bavarian Health and Food Safety Authority (Landesamt für Gesundheit und Lebensmittelsicherheit, LGL) published a hygiene monitoring concept and there exists an inspection guide developed by a specialist department for nursing homes and institutions for the handicapped (Fachstelle für Pflege und Behinderteneinrichtungen, FQA). Because inspections are performed in multiprofessional teams, it makes sense to use a coordinated inspection catalog. The aim was to integrate hygienic requirements specified in the Bavarian guidelines for hygiene by the LGL into the inspection guide published by the FQA to obtain a quality assured surveillance. The involved parties were questioned about the inspection guide and their hygiene management and then the hygiene criteria of the LGL were implemented into the inspection guide. Questions dealing with hygiene requirements concerning intensive care, management of multidrug resistant bacteria and interviews with the person responsible for infection control in the facility itself were developed for the first time and were integrated into the inspection guide. The revised inspection guide was tested for its applicability. With the revised inspection guide there now exists a tool which allows not only comprehensive inspections of the facilities including hygiene issues but also a good cooperation of the various parties involved. There are many actions which have to be conveyed into the future, especially programs to train staff to apply the inspection guide and to enhance the ability of all participants to act in cooperation. The guide will also allow the facilities to cooperate more easily and more closely, as the guide takes the respective problems and challenges of the different facilities into consideration. Additionally the development of legal guidelines regarding hygiene can support general healthcare of residents.

First detection of Borrelia burgdorferi-antibodies in free-living birds of prey from Eastern Westphalia, Germany.

Borrelia (B.) burgdorferi sensu lato, the causative agent of Lyme disease, is the most important arthropod-borne zoonosis-pathogen in the Northern hemisphere. Besides small mammals, birds, primarily Passeriformes and sea birds, play an important role in the transmission, distribution and maintenance of this disease. Previous studies on birds have focused mainly on the detection of Borrelia-infected ticks. However, the presence or absence of an infected tick cannot be taken as an indicator of the infective status of the avian host; to date this area of research has not been explored. In this study, serological analyses of blood collected from free-living birds of prey (n = 29) at the rehabilitation centre in Eastern Westphalia, Germany, highlights that birds of prey are also susceptible to B. burgdorferi and react immunologically to an infection. Increased antibody-levels could be found by using a modified Indirect Immunofluorescent-testing in two common buzzards, Buteo buteo, and two eagle owls, Bubo bubo. Further research regarding the serological diagnostics of B. burgdorferi within the avian host is required. In the future, it should be taken into account that birds of prey can be reservoirs for B. burgdorferi, as well as carriers of infected ticks; although at present their epidemiological importance is still to be confirmed.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

The predictive value of OCT characteristics for the visual outcome in neovascular AMD.

BACKGROUND: The intravitreal injection of an anti-VEGF compound is the current standard of care in neovascular AMD. The response to this therapy varies greatly. To date it was not possible to determine clear predictive factors in regard to therapy response, thus making it difficult when counselling patients regarding the probability for visual improvement. The aim of this study was to evaluate baseline OCT characteristics in regard to their predictive value on the outcome of visual acuity (VA) after 12 months. PATIENTS AND METHODS: A retrospective analysis of 75 eyes with neovascular AMD treated with intravitreal anti-VEGF injections at the University Hospital of Zurich with a documented follow-up of at least 12 months. Measurement and comparison of the following OCT structures were undertaken: central retinal thickness (CRT), integrity of the IS/OS junction, and presence of intra- or subretinal fluid. VA at baseline and after 12 months was evaluated. OCT findings were compared between eyes that gained ≥ 5 letters ETDRS (group 1) and eyes that did not (group 2). RESULTS: 75 eyes with a mean baseline VA of 57.2 ± 15 letters and a mean baseline CRT of 430 ± 226 µm were analyzed. Although baseline VA did not differ statistically significantly, eyes in group 2 had a higher VA than eyes in group 1 (60.2 ± 16.2 vs. 54.9 ± 13.6, p = 0.123). In group 1 the change of VA after 12 months was 12.6 ± 8.0 letters while it was -5.0 ± 7.8 letters in group 2. No statistically significant differences between the two groups with respect to the analyzed OCT parameters were found. None of the analyzed OCT factors had a predictive value regarding the VA outcome at month 12. CONCLUSIONS: Our study was not able to find baseline OCT parameters that could predict the course of VA after 12 months. However, eyes with a thicker central retinal thickness at presentation showed a greater reduction in CRT during the analyzed period. This was associated with a more favourable course in VA. Perhaps this might be due to a less pronounced initial morphological retinal damage.

Development of a suspicion index to aid diagnosis of Niemann-Pick disease type C.

OBJECTIVES: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive lysosomal lipid storage disorder that is invariably fatal. NP-C diagnosis can be delayed for years due to heterogeneous presentation; adult-onset NP-C can be particularly difficult to diagnose. We developed a Suspicion Index tool, ranking specific symptoms within and across domains, including family members who have NP-C, to provide a risk prediction score to identify patients who should undergo testing for NP-C. METHODS: A retrospective chart review was performed in 5 centers in Europe and 2 in Australia (n = 216). Three patient types were selected: classic or variant filipin staining NP-C cases (n = 71), NP-C noncases (confirmed negative by filipin staining; n = 64), or controls with at least 1 characteristic symptom of NP-C (n = 81). NP-C signs and symptoms were categorized into visceral, neurologic, or psychiatric domains. Logistic regression was performed on individual signs and symptoms within and across domains, and regression coefficients were used to develop prediction scores for NP-C. Internal validation was performed with the bootstrap resampling method. RESULTS: The Suspicion Index tool has good discriminatory performance with cutpoints for grading suspicion of NP-C. Neonatal jaundice/cholestasis, splenomegaly, vertical supranuclear gaze palsy, cataplexy, and cognitive decline/dementia were strong predictors of NP-C, as well as symptoms occurring in multiple domains in individual patients, and also parents/siblings or cousins with NP-C. CONCLUSIONS: The Suspicion Index tool is a screening tool that can help identify patients who may warrant further investigation for NP-C. A score ≥70 indicates that patients should be referred for testing for NP-C.

Trends in the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds metropolitan area, 2005-2010.

AIM: This study reports the incidence of visual impairment certification due to diabetic retinopathy in Leeds between 2008 and 2010 and makes a comparison with data from 2005, immediately before the introduction of a comprehensive screening service. METHODS: The primary causes of visual impairment certification between 2008 and 2010 were collected and reviewed. Mid-year population estimates and a diabetes prevalence model were used to determine the incidence of certification secondary to diabetic retinopathy. RESULTS: Diabetic retinopathy was the primary cause of visual impairment certification in 33 of 446 (7.4%) certificates in 2008, 34 of 410 (8.3%) certificates in 2009 and 24 of 392 (6.1%) in 2010. For the total population in 2008, 2009 and 2010, the combined incidence of either sight impairment or severe sight impairment due to diabetic retinopathy was 42.3, 43.2 and 30 per million per year, respectively. For the population with diagnosed diabetes mellitus, the combined incidence of either sight impairment or severe sight impairment secondary to diabetic retinopathy was 1227, 1192 and 796 per million per year, respectively. For each year, the incidence of visual impairment was lower than the corresponding figure for 2005. CONCLUSION: Following the introduction of a comprehensive retinal screening service, the incidence of visual impairment certification secondary to diabetic retinopathy in the Leeds Metropolitan area appears to be decreasing. However, a multifaceted approach, addressing all the avoidable risk factors, may be required to maintain this trend in view of the increasing prevalence of Type 2 diabetes.

Mutant small heat shock protein B3 causes motor neuropathy: utility of a candidate gene approach.

OBJECTIVE: Idiopathic peripheral neuropathy is common and likely due to genetic factors that are not detectable using standard linkage analysis. We initiated a candidate gene approach to study the genetic influence of the small heat shock protein (sHSP) gene family on an axonal motor and motor/sensory neuropathy patient population. METHODS: The promoter region and all exonic and intronic sequences of the 10 sHSP genes (HSPB1-HSPB10) were screened in a cohort of presumed nonacquired, axonal motor and motor/sensory neuropathy patients seen at the Ohio State University Neuromuscular Clinic. RESULTS: A missense mutation in the gene encoding small heat shock protein B3 (HSPB3, also called HSP27, protein 3) was discovered in 2 siblings with an asymmetric axonal motor neuropathy. Electrophysiologic studies revealed an axonal, predominantly motor, length-dependent neuropathy. The mutation, HSPB3(R7S), is located in the N-terminal domain and involves the loss of a conserved arginine. CONCLUSIONS: The discovery of an HSPB3 mutation associated with an axonal motor neuropathy using a candidate gene approach supports the notion that the small heat shock protein gene family coordinately plays an important role in motor neuron viability.

e-Learning strategies in occupational legal medicine based on problem solving through "CASUS" system.

The use of online teaching tools facilitate the incorporation of self-learning methods. With a view to encouraging convergence in teaching tools and methods in Occupational Legal Medicine, an initiative was set up within the classes of Legal and Forensic Medicine at Saragossa University, as part of the EU funded NetWoRM project, which has been led since 1999 by Ludwig-Maximilians-Universität in Munich (Germany). The interest of medical students in Occupational Legal Medicine has so far been low and in addition different aspects complicate the teaching of Occupational Legal Medicine at medical schools: One reason for the low interest is the limited availability of bedside teaching, one of the students' most favourite and effective way to learn. The reason for that is that most medical schools with occupational departments only have outpatient clinics. "Interesting" patients who be need for educational purposes are therefore only available for a limited part of the day. However, in order to recognize and prevent occupational disorders each medical student and physician needs profound clinical knowledge in Occupational Legal Medicine. This project has proven to be highly efficient in permitting the creation and validation of teaching tools which cover and improve the traditional training of the Occupational Legal Medicine programme imparted in the degree of Medicine.

Thyroid testing in Sloughis.

BACKGROUND: Thyroid hormone concentrations were found to be different in Greyhounds and Whippets compared with nonsight hound dogs. HYPOTHESIS: In Sloughis, thyroid hormone concentration is lower than in nonsight hounds and comparable to Greyhounds. ANIMALS: Fifty-one Sloughis with no evidence of disease and a mean age of 4 years (range, 1-12 years). METHODS: Thyroid profiles consisting of total thyroxine (tT4), free thyroxine (fT4), free thyroxine after equilibrium dialysis (fT4 after ED), canine thyroid stimulation hormone (cTSH), and thyroglobulin antibodies as well as CBC and serum biochemistry results of Sloughis were compared with those of normal dogs. In 8 Sloughis, TSH stimulation tests were performed. RESULTS: In Sloughis, tT4 concentrations and fT4 concentrations measured by chemiluminescence were lower than those of controls (1.13+/-0.65 microg/dL compared with 2.9+/-0.8 microg/dL, P< .0001 and 11+/-4.3 pmol/L compared with 16.7+/-5.2 pmol/L, P< .0001, respectively). Concentrations of fT4 after ED and TSH were increased in Sloughis, when compared with controls (41.3+/-26.9 pmol/L compared with 20.98+/-10.29 pmol/L, P< .0001 and 0.22 +/- 0.15 pmol/L compared with 0.15+/-0.13 pmol/L, P= .0138, respectively). T4 concentration after TSH stimulation increased from 1.5 microg/dL (range, 0.2-2.7 microg/dL) to 2.7 microg/dL (range, 1.2-4.7 microg/dL); the recommended post-TSH T4 concentration was achieved by only 3 of 8 Sloughis. Hemoconcentration was found in 84.3% and hypoglobulinemia in 80.3%. CONCLUSIONS AND CLINICAL IMPORTANCE: When evaluating Sloughis for hypothyroidism, veterinarians should be aware that these dogs have different thyroid hormone concentrations than nonsight hound dogs.

The phosphatidylserine receptor mediates phagocytosis by vascular smooth muscle cells.

Apoptosis participates in every step of atherogenesis, but the process of clearance of apoptotic cells by phagocytosis has been underestimated. Rapid removal of apoptotic cells is critical for tissue homeostasis, in order to avoid accumulation of necrotic material and subsequent inflammation in the pathological vascular wall. We have demonstrated by RT-PCR, western blot and immunocytofluorescence that vascular smooth muscle cells (VSMCs) express the phosphatidylserine receptor (PSR). We then tested the involvement of PSR in the ability of VSMCs to bind and engulf apoptotic cells. We used a model of senescent erythrocytes, which expose PS after 4 days of culture (85% of cells relative to 8% in freshly isolated erythrocytes). The pseudo-peroxidase activity of haemoglobin contained within erythrocytes allowed us to quantify per se both binding and phagocytosis by VSMCs. We have also shown by light and confocal microscopy that VSMCs were able to ingest aged erythrocytes. Addition of a blocking antibody or transfection of VSMCs by a siRNA directed against PSR reduced the binding and engulfment of aged erythrocytes by more than 90%. These results suggest that PSR is involved in phagocytosis of PS-presenting cells. Incubation of aged erythrocytes with VSMCs also significantly increased the expression of PSR, suggesting that the tethering/ingestion of apoptotic cells triggers this process. Immunostaining for PSR in complicated atherosclerotic plaques shows positivity in the media and macrophage-rich areas. The mechanisms underlying phagocytosis and involving PSR in vivo, within the pathological arterial wall, deserve further investigation.

European dissemination of a web- and case-based learning system for occupational medicine: NetWoRM Europe.

OBJECTIVE: Occupation has a large impact on health in Europe. In order to prevent and recognize occupational diseases, medical students and physicians should know about the potentially causal relationship between profession and diseases as well as the basic legal aspects of occupational medicine (OM). However, the opportunity of bedside teaching, the students' most favoured way of teaching, is limited. METHODS: One possibility to complete and improve traditional training in OM is computer-oriented case-based learning. Using the authoring system "CASUS" (INSTRUCT AG) cases can be created and handled without knowledge in computer sciences. RESULTS: So far, 19 cases have been created and evaluated by students of German universities. Due to the great efforts arising from the creation of such multimedia cases it is desirable and cost-effective to use the existing cases at several medical universities. Therefore, the Net-based Training in Work-Related Medicine (NetWoRM) project shares cases on an international base. In February and April 2005, 13 case-authors from 12 centres were trained in the basics of case creation during a 3 week programme in Munich. The overall evaluation of the participants indicated that this way of teaching case creation is very efficient. Up to now, nine cases were translated into English and five into Spanish. First implementation of the cases in Spain and Finland showed a good acceptance by the students but more evaluation has still to be done. CONCLUSION: Based on these results we conclude that exchange of case-based e-learning in OM is feasible and rewarding on an international base.

SMN mRNA and protein levels in peripheral blood: biomarkers for SMA clinical trials.

BACKGROUND: Clinical trials of drugs that increase SMN protein levels in vitro are currently under way in patients with spinal muscular atrophy. OBJECTIVE: To develop and validate measures of SMN mRNA and protein in peripheral blood and to establish baseline SMN levels in a cohort of controls, carriers, and patients of known genotype, which could be used to follow response to treatment. METHODS: SMN1 and SMN2 gene copy numbers were determined in blood samples collected from 86 subjects. Quantitative reverse transcription PCR was used to measure blood levels of SMN mRNA with and without exon 7. A cell immunoassay was used to measure blood levels of SMN protein. RESULTS: Blood levels of SMN mRNA and protein were measured with high reliability. There was little variation in SMN levels in individual subjects over a 5-week period. Levels of exon 7-containing SMN mRNA and SMN protein correlated with SMN1 and SMN2 gene copy number. With the exception of type I SMA, there was no correlation between SMN levels and disease severity. CONCLUSION: SMN mRNA and protein levels can be reliably measured in the peripheral blood and used during clinical trials in spinal muscular atrophy, but these levels do not necessarily predict disease severity.

Maternal predictors of subcutaneous fat in the term newborn.

AIM: To determine the relative influences of some maternal factors on skinfold thickness. The effects of age, parity, height, body mass index (BMI) and pregnancy weight gain (PWG) of the mother on the subscapular skinfold thickness (SST) of the newborn were estimated, and compared with their effects on birthweight (BW), crown-heel length (CHL) and head circumference (HC). METHODS: A sample of 13, 972 healthy, term singletons was selected at the Clamart Maternity Hospital (France). Stepwise regressions were used to determine the most predictive maternal factors for each parameter in the newborn. The respective effects of the mother's age and parity on each newborn dimension were tested by analysis of variance. RESULTS: The SST is a singular parameter, influenced by the mother's BMI and PWG, but not by her height. In contrast, the main predictor of BW, CHL and HC is the height of the mother, and to a lesser extent her PWG and BMI. Parity and maternal age have a smaller effect, except on SST, and essentially between the first and second pregnancies. CONCLUSION: These results clearly separate SST from other newborn dimensions. The skinfold thickness depends only on the nutritional status of the mother, while other dimensions are markedly influenced by the genetic background. This study is the first to demonstrate the singularity of skinfold thickness in newborn infants as a marker of the mother's nutritional status.

[IUD-associated pseudoactinomycotic gradiate granules (Spendore-Hoeppli phenomenon) in uterine curettage]. / Pseudoaktinomykotische Granula (Splendore-Hoeppli-Phänomen) im Korpusabradat bei IUP.

Pseudoactinomycotic radiate granules, also known as the Splendore-Hoeppli phenomenon represent a response to organic and in-organic foreign substances and can be found at various locations in the body. They are frequently observed in uterine curettages, where they can be misinterpreted as actinomycotic sulfur granules. Here we report a case with Splendore-Hoeppli phenomenon in an intrauterine device (IUD)-associated genital actinomycosis. The morphological features of this phenomenon are presented using special staining methods and electron microscopy and the literature is reviewed.

Clinical characteristics of prostate cancer in an analysis of linkage to four putative susceptibility loci.

PURPOSE: Hereditary prostate cancer is an etiologically heterogeneous disease with six susceptibility loci mapped to date. We aimed to describe a collection of high-risk prostate cancer families and assess linkage to multiple markers at four loci: HPC1 (1q24-25), PCaP (1q42.2-43), HPCX (Xq27-28), and CAPB (1p36). EXPERIMENTAL DESIGN: Medical record data on 505 affected men in 149 multiply-affected prostate cancer families were reviewed, and correlations of clinical traits within each family were calculated. Logarithm of odds (LOD) score and nonparametric (NPL) linkage analyses were performed; white families were stratified by age of diagnosis, grade and stage of disease, and evidence of linkage to the other loci to increase genetic homogeneity. RESULTS: Age at diagnosis was the most correlated clinical trait within families. A maximum NPL score of 2.61 (P = 0.007) appeared to confirm HPC1 linkage for families that had a prevalence of high-grade or advanced-stage prostate cancer and which were not likely to be linked to PCaP, HPCX, or CAPB. Because the NPL scores improved when families more likely to be linked to the other loci were excluded, HPC1 may act independently of the other loci. The relationship of HPC1 and aggressive disease was strongest in families with median age at diagnosis > or =65 years (NPL, 3.48; P = 0.0008). CONCLUSIONS: The current results suggest that HPC1 linkage may be most common among families with more severe prostate cancer. Stratification by clinical characteristics may be a useful tool in prostate cancer linkage analyses and may increase our understanding of hereditary prostate cancer.

Germline mutations in the p73 gene do not predispose to familial prostate-brain cancer.

BACKGROUND: Analysis of high-risk prostate cancer (PC) families with at least one confirmed case of primary brain cancer (BC) has identified a region of genetic linkage on chromosome 1p36 termed CAPB. The p36 region of chromosome one has been reported to have frequent loss of heterozygosity (LOH) in brain and central nervous system (CNS) tumors and epidemiological studies have shown an increased relative risk of BC and tumors of the CNS in PC families. In 1997 a reported tumor suppressor with high homology to p53, termed p73, was mapped to the p36 region of chromosome one. Here, we examine the p73 gene as a potential candidate for CAPB. METHODS: Ninety-four members from the 12 prostate-brain cancer families in which linkage was originally found were examined. The complete coding region and intron-exon boundaries of the p73 gene were analyzed for germline mutations by Single Stranded Conformational Polymorphism analysis (SSCP) and direct DNA sequencing. RESULTS: Silent nucleotide substitutions only were detected within the coding regions of the gene in affected individuals. Nucleotide changes were detected in introns 1, 6, 8, 9, and 10, but all were located >or=16 base pairs from the splice site, and are thus unlikely to be deleterious mutations. CONCLUSIONS: Germline mutations in the p73 gene are unlikely to be critical for inherited susceptibility to PC in this specified subset of families.