Association between motor proficiency and oral health in people with intellectual disabilities.

BACKGROUND: People with intellectual disabilities (IDs) may be at increased risk of developing periodontal diseases and dental caries due to poor oral hygiene. Our aim was to investigate motor proficiency factors associated with presence of visible plaque and gingival bleeding in people with IDs. We were particularly interested in the level of dependence, manual coordination and fine manual control of people with ID, as well as the level of exhaustion of the primary caregiver. METHODS: In this cross-sectional study, 299 people with ID were evaluated for oral hygiene using the simplified Visible Plaque Index and for gum inflammation using the Gingival Bleeding Index. The Bruininks-Oseretsky Motor Proficiency Test assessed motor proficiency through fine manual control (fine motor integration and fine motor precision) and manual coordination (manual dexterity and upper limb coordination). The level of dependence was assessed by the Katz dependency index, and the caregiver was tested for exhaustion using the fatigue severity scale. Prevalence ratios [and 95% confidence intervals (CI)] were calculated using crude and adjusted Poisson regression with robust variance. RESULTS: The exhaustion of the caregiver was associated positively to visible plaque [prevalence ratio (PR) = 1.36; 95% CI 1.06-1.65]. For gingival bleeding, people with IDs that had better fine motor integration (PR = 0.49; 95% CI 0.33-0.75) and precision (PR = 0.50; 95% CI 0.26-0.94), as well as manual dexterity (PR = 0.62, 95% CI 0.49-0.77), presented better results. CONCLUSION: Poor oral hygiene and gum inflammation were associated with motor proficiency of people with IDs and caregivers' exhaustion. Interventions to improve the oral health of people with IDs should take into account such conditions.

High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection.

BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/µL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

Association between oropharyngeal dysphagia, oral functionality, and oral sensorimotor alteration.

OBJECTIVE: To evaluate whether the oral functionality and the oral sensorimotor alterations are associated with oropharyngeal dysphagia in community-dwelling older persons and long-term care older residents. METHODS: An exploratory study with 265 independent older persons of the southern state of Brazil. The diagnosis of dysphagia, as well as the condition of the oral sensorimotor system, was assessed by a speech-language therapist and the oral health status by a dentist. Poisson Regression with robust variance was used to calculate the crude and adjusted Prevalence Ratios (PR) and their respective confidence intervals of 95%. RESULTS: The mean age was 73.5 (±8.9) years, women represented 59.2% of the sample. The frequency of dysphagia in the studied population was 45.3% (n = 120), being more frequent in the long-term care older residents (62.5%; n = 75) than in the community-dwelling older persons (37.5%; n = 45). Individuals with four or more oral sensorimotor alterations (PR = 2.01; 95% CI 1.27-3.18), as well as those who presented a non-functional oral status (PR = 1.61; 95% CI 1.02-2.54) presented a higher frequency of dysphagia. Subgroup analysis indicates the same trend of results, when stratified by community-dwelling older persons and long-term older residents. CONCLUSION: A non-functional oral health status and oral sensorimotor alterations are associated with a higher prevalence of oropharyngeal dysphagia.

HIV-positive men who have sex with men are at high risk of development of significant liver fibrosis after an episode of acute hepatitis C.

Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection. Liver fibrosis was estimated by Fibroscan® and Fibrotest® . Liver-related and non-liver-related outcomes were documented. Overall 213 episodes of acute HCV infection in 178 men were documented. Median follow-up for all included patients was 38.7 months. Spontaneous HCV clearance was found in 10.8% of patients, which was significantly associated with older age, lower HCV RNA levels, and higher ALT levels upon initial acute HCV diagnosis. Treatment with interferon-based therapy was initiated in 86.3% of cases, resulting in a sustained virological response(SVR) rate of 70.7%. After 3 years' follow-up, significant liver fibrosis of METAVIR F2 stage or higher was found in 39.4% of patients after first acute HCV diagnosis. Higher age, physician-declared alcoholism, and nonresponse to acute HCV therapy were independently associated with higher fibrosis stages. Ten patients died during the observation period (IR 1.4/100 patient-years) and four during interferon treatment. Significant liver fibrosis is a common finding in HIV-positive MSM following acute HCV infection despite high treatment uptake and cure rates, suggesting the need for close liver disease monitoring particularly if HCV treatment is deferred.

Real-world experience with the all-oral, interferon-free regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus infection in the German Hepatitis C Registry.

Real-world studies are relevant to complement clinical trials on novel antiviral therapies against chronic hepatitis C; however, clinical practice data are currently limited. This study investigated effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r)±dasabuvir (DSV)±ribavirin (RBV) for treatment of HCV genotype (GT) 1 and GT4 infection in a large real-world cohort. The German Hepatitis C Registry is an observational cohort study prospectively collecting clinical practice data on direct-acting antiviral therapies. Patients with GT1/4 infection treated with OBV/PTV/r±DSV±RBV were analysed. Effectiveness was assessed by sustained virologic response in 558 patients who reached post-treatment week 12 (SVR12). Safety is reported in 1017 patients who initiated treatment. Of the patients, 892 (88%) had GT1 and 125 (12%) had GT4 infection. Prior treatment experience and cirrhosis were reported in 598 (59%) and 228 (22%) patients, respectively. Overall, SVR12 (mITT) was 96% (486/505) in GT1- and 100% (53/53) in GT4 patients. SVR12 rates were high across subgroups including patients with cirrhosis (95%, 123/129), patients with moderate to severe renal impairment (100%, 34/34), and subgroups excluded from registrational trials like patients ≥70 years (96%, 64/67) and failures to prior protease inhibitor treatment (96%, 46/48). Adverse events (AEs) and serious AEs were reported in 52% (525/1017) and 2% (21/1017) of patients, respectively, and led to treatment discontinuation in 1.5% (15/1017) of patients. OBV/PTV/r±DSV±RBV was effective and generally well tolerated for treatment of HCV infection in clinical practice.

Peginterferon-alfa mono-therapy in the treatment of acute hepatitis C in HIV-infection.

The ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal treatment outcome in HIV co-infected individuals. Cohort study of 105 HIV-infected patients with AHC infection from five centres in two European countries was carried out. Choice of treatment with pegIFN-alfa alone (group 1; n = 36) or pegIFN-alfa and ribavirin (RBV) (group 2; n = 69) was at the discretion of the investigator. Outcome was evaluated as RVR and SVR. Fisher's exact and Mann Whitney U tests were used for statistical analysis. All patients were male, median age was 39 years, main route of transmission MSM (91%). In 69% of patients, clinical signs of acute hepatic infection were missing, dominant HCV genotypes were 1 (64%) and 4 (16%) and mean baseline HCV-RNA was 3.559.085 IU/mL. 60% received HAART and CD4 cell count was 469/mm(3) . Overall SVR rate was 64.8% (68/105). SVR was reached in 69% of treated patients in group 1 and in 63% of treated patients in group 2 (P = 0.67) while RVR was seen in 61% and 49%, respectively (P = 0.35). Interestingly, by univariate analysis, SVR rates in group 1 were significantly higher in patients initiating therapy within 4 weeks of AHC diagnosis compared to patients initiating therapy within 5-36 weeks after diagnosis (P = 0.03). PegIFN-alfa alone or in combination with ribavirin results in similar response rates in HIV-infected patients with AHC. In particular, when treatment is initiated within 4 weeks of diagnosis, pegIFN mono-therapy might be sufficient to allow for an optimal treatment response.

Multiple hepatitis C virus (HCV) reinfections in HIV-positive men who have sex with men: no influence of HCV genotype switch or interleukin-28B genotype on spontaneous clearance.

OBJECTIVES: The incidence of sexually transmitted hepatitis C virus (HCV) reinfection is on the rise in HIV-infected men who have sex with men (MSM). Data on natural history of acute hepatitis C and possible factors associated with spontaneous clearance are limited. The aim of this study was to analyse the outcome of HCV reinfections in HIV-positive MSM. METHODS: A retrospective analysis was carried out on patients with more than one sexually acquired HCV infection who were diagnosed at four major German HIV and hepatitis care centres. Reinfection was defined by genotype or phylogenetic clade switch, detectable HCV RNA after a sustained virological response (SVR) or after spontaneous clearance (SC). RESULTS: In total, 48 HIV-positive MSM were identified with HCV reinfection, among them 11 with a third episode and one patient with four episodes. At the first episode, 43 and five patients had an SVR and SC, respectively. The second episode was accompanied by a genotype switch in 29 patients (60%). Whereas 30 and nine patients showed an SVR and SC, respectively, eight patients developed chronic hepatitis. Neither HCV genotype switch nor interleukin-28B genotype was associated with SC. However, SC rates at the second episode were higher for patients with SC at the first episode compared with patients without SC (60 vs. 14%, respectively; P = 0.03). Two patients with SC at the first episode were reinfected with the same genotype. CONCLUSIONS: Multiple reinfections in HIV-infected MSM do occur, with or without genotype switch, and with prior SC of previous episodes. In this large case series, except for SC at the first episode, no factor was of value in clinical decision-making for early therapeutic intervention in acute HCV reinfection.

High rates of quinolone-resistant strains of Shigella sonnei in HIV-infected MSM.

PURPOSE: There is increasing evidence that shigellosis is a predominantly sexually transmitted disease among men who have sex with men (MSM) and that infection with the human immunodeficiency virus (HIV) is a risk factor for shigellosis. METHODS: Retrospective analysis of antibiotic resistance profiles of Shigella species isolated from stool specimens of patients presenting with diarrhea from January 2010 to July 2012 in three German outpatient clinics specialized in HIV care. RESULTS: Among 79 cases of Shigella sonnei, 56 occurred in HIV-infected MSM, while 23 were observed in HIV-negative MSM. High resistance rates (>90%) were found for doxycycline, tetracycline, aminoglycosides, all cephalosporins of first and second generations tested, and trimethoprim/sulfamethoxazole. In total, 54% of cases were resistant to ciprofloxacin. Compared to negative subjects, HIV-infected MSM had a significantly higher rate of quinolone resistance. For ciprofloxacin, the resistance rates were 66 versus 24%, respectively (p = 0.0016). Individual resistance patterns did not indicate that this was due to a limited outbreak. Rates of resistance to other antibiotics than quinolones showed no differences between HIV-infected and HIV-negative cases. No resistance was found for carbapenems or newer cephalosporins such as ceftriaxone. CONCLUSIONS: The high rates of S. sonnei isolates resistant to quinolones and other traditional antibiotics are of concern. Innovative prevention efforts are urgently needed. The empirical use of quinolones in HIV-infected patients presenting with S. sonnei infection is no longer recommended.

[Current diagnostics and therapy of B cell Non Hodgkin Lymphoma]. / Aktuelle Diagnostik und Therapie bei B-Zell Non Hodgkin Lymphomen.

New diagnostic tools and therapeutic options for Non Hodgkin Lymphoma (NHL) contributed to several improvements in the understanding and treatment of this hematological malignancies. In diffuse large cell lymphoma (DLBCL) gene expression profiling and molecular analyses of myc and bcl-2 gene rearrangements resulted in the description of new DLBCL entities with significant differences in outcome. Combination immunochemotherapy according to the R-CHOP protocol remains the mainstay for treatment of DLBCL in younger and older patients. Mantle cell lymphoma is characterised by the overexpression of cyclin D1. While older patients should be treated with R-CHOP with rituximab maintenance therapy, first line treatment of younger patients should also include AraC containing regimens and autologous stem cell transplantation. Cases with follicular lymphoma very often show the t(14; 18) translocation resulting in overexpression of BCL2 and diminished apoptosis. Compared to R-CHOP treatment new combinations with R-Bendamustin have shown high efficacy with reduced toxicity and should therefore be regarded as standard in patients in need for therapy.

Changes of platelet function and blood coagulation during short-term storage of CPDA-1-stabilised ovine blood.

The objective of this study was to detect the influence of short-term storage on the haemostatic function in whole citrated ovine blood at different storage temperatures. Ovine blood was collected in a commercial transfer bag system containing CPDA-1 and stored on a wobbler at room (20-25 °C; n=5) or refrigerator temperature (4 °C; n=5). The following analyses were performed initially and after 1, 2, 3, 4, 5, 6, 8, 12, 24, 48 and 72 h of storage: platelet count and (spontaneous) aggregates, agonist-induced platelet aggregation with two methods (impedance aggregometry, turbidimetric method), prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration and resonance thrombography. Platelet count remained stable at room temperature, whereas a significant decrease was detected after 48 h storage at 4 °C. The latter was associated with the formation of a high percentage of platelet aggregates (50-60%) after 5h storage. Decrease in platelet aggregation was significantly more pronounced when blood was stored at 4°C. The plasmatic coagulation tests were stable within the observation period. Results indicate that platelet count and aggregability of CPDA-1-stabilised ovine blood is better preserved at room temperature and provides adequate haemostatic function for ex vivo experiments for one working day. Functional loss and high percentage of platelets within aggregates which were observed in ovine blood stored at refrigerator temperature have to be considered in blood transfusion in sheep.

Estimating the likelihood of sustained virological response in chronic hepatitis C therapy.

The likelihood of a sustained virological response (SVR) is the most important factor for physicians and patients in the decision to initiate and continue therapy for chronic hepatitis C (CHC) infection. This study identified predictive factors for SVR with peginterferon plus ribavirin (RBV) in patients with CHC treated under 'real-life' conditions. The study cohort consisted of patients from a large, retrospective German multicentre, observational study who had been treated with peginterferon alfa-2a plus RBV or peginterferon alfa-2b plus RBV between the years 2000 and 2007. To ensure comparability regarding peginterferon therapies, patients were analysed in pairs matched by several baseline variables. Univariate and multivariate logistic regression analyses were used to determine the effect of nonmatched baseline variables and treatment modality on SVR. Among 2378 patients (1189 matched pairs), SVR rates were 57.9% overall, 46.5% in HCV genotype 1/4-infected patients and 77.3% in genotype 2/3-infected patients. In multivariate logistic regression analysis, positive predictors of SVR were HCV genotype 2 infection, HCV genotype 3 infection, low baseline viral load and treatment with peginterferon alfa-2a. Negative predictors of SVR were higher age (≥40 years), elevated baseline gamma-glutamyl transpeptidase (GGT) and low baseline platelet count (<150,000/µL). Among patients treated with peginterferon plus RBV in routine clinical practice, genotype, baseline viral load, age, GGT level and platelet levels all predict the likelihood of treatment success. In patients matched by baseline characteristics, treatment with peginterferon alfa-2a may be a positive predictor of SVR when compared to peginterferon alfa-2b.

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive Individuals.

OBJECTIVE: This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated. METHODS: Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2). RESULTS: 168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209). CONCLUSIONS: Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.

Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study.

In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P < or = 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b.

Measurement of platelet function in dogs using a novel impedance aggregometer.

The aim of this study was to optimise the technique and establish reference values for whole blood aggregometry in dogs using a novel multiplate analyser. Measurements were performed on the hirudin-anticoagulated blood of healthy dogs using a wide range of agonists. Optimal agonist concentrations were 10 micromol/L of adenosine diphosphate, 5 microg/mL of collagen and 1 mmol/L of arachidonic acid. Ristocetin (at 0.2 and 1 mg/mL) and thrombin receptor activating peptide (TRAP-6 at 32 and 160 micromol/L) did not consistently induce platelet aggregation. Coefficients of variance for within-run imprecision (n=10 repetitions) varied from 5% to 18%. Measurement signals were significantly higher when analyses were performed on standard samples (hirudin-anticoagulated blood) compared to citrated blood or blood samples anticoagulated with citrate buffer, regardless of whether or not re-calcification was performed (P<0.05). The findings indicate that the analyser is suitable for the investigation of platelet aggregation in dogs and analysis should be performed on hirudin-anticoagulated blood using optimised agonist concentrations.

The ubiquitin ligase APC(Cdh1) is required to maintain genome integrity in primary human cells.

Ensuring precise DNA replication and chromosome segregation is essential during cell division in order to provide genomic stability and avoid malignant growth. Proteolytic control of cell cycle regulators by the anaphase-promoting complex, activated by Cdh1 (APC(Cdh1)), is responsible for a stable G1 phase after mitotic exit allowing accurate preparation for DNA replication in the following S phase. APC(Cdh1) target proteins are frequently upregulated in tumor cells and the inactivation of human Cdh1 might interfere with genome integrity by target stabilization. Here we show that APC(Cdh1) is required for maintaining genomic integrity in primary human cells. Lentiviral-delivered strong and stable suppression of Cdh1 by RNA interference (RNAi) causes aberrant accumulation of several APC(Cdh1) target proteins, such as cyclin A, B, Aurora A or Plk1, which control accurate and equal distribution of the genetic information to daughter cells. This induces a premature and prolonged S phase, mitotic-entry delay and defects in chromosome separation and cytokinesis. Cell cycle deregulation by stable knockdown of Cdh1 leads to activation of p53/p21 and genomic instability, which is further increased by codepletion of p53. Thus, stabilization of APC(Cdh1) targets may initiate aberrant DNA replication and chromosome separation, and trigger a p53 response by deregulating G1 in primary human cells.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) in HIV-1 infected individuals on HAART.

BACKGROUND: Studies suggest that highly active anti-retroviral therapy (HAART) prolongs life in HIV infected individuals and that HIV infected individuals increasingly suffer from cardiovascular complications. NT-proBNP has been shown to represent an indicator of cardiac function. METHODS: 495 HIV infected individuals under HAART and 1980 blood donors (BD) were tested for N-terminal pro-B-type natriuretic peptide (NT-proBNP). NT-proBNP was performed by an automated electrochemiluminescence immunoassay (ECLIA) method. RESULTS: HIV infected individuals had significantly higher NT-proBNP levels than age matched blood donors (18-29 y: median: 33 pg/ml HIV vs. 5 pg/ml BD; p = 0.0247; 30-39 y: median: 25 pg/ml HIV vs. 5 pg/ml BD; p = 0.0351; 40-49 y: median: 35.5 pg/ml HIV vs. 5 pg/ml BD; p < 0.0001; 50-59 y: median: 42 pg/ml HIV vs. 36 pg/ml BD; p = 0.3665; 60-69 y: median: 82.5 pg/ml HIV vs. 46 pg/ml BD; p = 0.0055) the effect was consistently found in all age and both gender groups. HIV infected individuals differed from the blood donor control group with respect to cardiovascular risk factors (hypertension, cardiovascular (CV) medication, diabetes mellitus, smoking status). In HIV infected individuals NT-proBNP levels did not correlate to cardiovascular risk factors including GFR except for C-reactive protein (CRP) levels using multivariate analysis. There was also no evidence for cardiotoxic effects due to HAART or specific antiretroviral drugs. High NT-proBNP levels were found in Hepatitis C virus (HCV) infected individuals who had received alpha-interferon therapy. CONCLUSIONS: HIV infected individuals had higher NT-proBNP levels than age matched blood donors possibly as a result of a higher prevalence of general cardiovascular risk factors and HIV associated risk factors, the finding is consistent with an increased incidence of cardiovascular events described in HIV infected individuals. Further studies on the relationship to cardiovascular outcome are warranted.

[Smoking behavior during pregnancy of women with type 1 or gestational diabetes]. / Rauchverhalten während der Schwangerschaft bei Frauen mit Typ-1-Diabetes oder Gestationsdiabetes.

BACKGROUND AND OBJECTIVE: Smoking and diabetes mellitus (DM) are both risk factors for complications during pregnancy and disorders in the newborn. Smoking behavior during pregnancy was investigated in German families where either the pregnant woman or her spouse had diabetes. The relationship between maternal smoking during pregnancy, her metabolic state and the child's birth weight was analysed. PATIENTS AND METHODS: Data on smoking behavior during pregnancy of women and their spouses were obtained by questionnaire. 2 498 families were included: 1,439 women and 1,010 men with type 1 diabetes (T1D) and 1,059 women and 1,488 men without T1D, deliveries having taken place between 1989 and 2005 (no account was taken of the amount smoked or whether stopped during pregnancy). Also collected were data on 308 women with gestational diabetes (GDM), who delivered a baby between 1989 and 1997. RESULTS: Significantly more pregnant women with T1D and GDM smoked than pregnant women without diabetes (13.2% and 15.2% vs 8.7%, p=0.001). Children of smoking pregnant women with T1D had a significantly lower birth weight than those of non-smoking pregnant women with T1D (median 54th percentile vs 71st percentile, p<0.001), although smoking pregnant women had a higher HbA (1c) than non-smoking pregnant women with T1D (median 6.1% vs 5.7%, p<0.001). The number of women and men who smoked during pregnancy declined between 1989 and 2005 (women: 17.5% vs. 8.9%, p=0.02, men: 38.0% vs 24.7%, p<0.001). CONCLUSIONS: The lower birth weight of children of mothers who smoked demonstrates the detrimental consequences of smoking during pregnancy. Pregnant woman with diabetes are a high risk group that should be targeted with programmes that aim to stop smoking during pregnancy.

Treatment of acute hepatitis C infection in HIV-infected patients: a retrospective analysis of eleven cases.

Studies on hepatitis C virus (HCV) monoinfected patients suggest high sustained treatment response rates of up to 98% when interferon monotherapy is administered during the acute phase of HCV-infection. To clarify whether early treatment of acute hepatitis C is similarly efficient in human immunodeficiency virus (HIV) positive patients, we conducted a retrospective survey of HIV-positive patients with acute HCV infection. Eleven HIV-positive patients who had been treated with interferon or interferon/ribavirin were identified at eight HIV-specialty outpatient clinics. The patients had been treated over a median 25 weeks with standard interferon (two patients), pegylated interferon (four patients) and pegylated interferon in combination with ribavirin (five patients). A post-treatment response (negative serum HCV-RNA at the end of treatment) was seen in 10 of 11 patients and HCV-RNA remained undetectable 24 weeks after the end of treatment in all the 10 responders. Alanine aminotransferase (ALT) normalized in eight patients while two virological responders and one nonresponder showed persistent mild ALT elevations. In conclusion, early treatment of acute hepatitis C seems to achieve high sustained virological treatment response rates also in patients with HIV-infection.