The management of the type 2 diabetic patient with hypertension - too late and too little: suggested improvements

Patients with comorbid hypertension and type 2 diabetes are common, have a greatly increased risk of premature cardiovascular and renal morbidity and mortality, and are likely to increase substantially in number over the next 10-15 years. We suggest the need for more aggressive management strategies for these patients, regardless of their baseline blood pressure, including the early use of combination therapy with blockers of the renin-angiotensin system.

Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo points to a novel mechanism involving nonstructural protein 4B.

Intravenous silibinin (SIL) is an approved therapeutic that has recently been applied to patients with chronic hepatitis C, successfully clearing hepatitis C virus (HCV) infection in some patients even in monotherapy. Previous studies suggested multiple antiviral mechanisms of SIL; however, the dominant mode of action has not been determined. We first analyzed the impact of SIL on replication of subgenomic replicons from different HCV genotypes in vitro and found a strong inhibition of RNA replication for genotype 1a and genotype 1b. In contrast, RNA replication and infection of genotype 2a were minimally affected by SIL. To identify the viral target of SIL we analyzed resistance to SIL in vitro and in vivo. Selection for drug resistance in cell culture identified a mutation in HCV nonstructural protein (NS) 4B conferring partial resistance to SIL. This was corroborated by sequence analyses of HCV from a liver transplant recipient experiencing viral breakthrough under SIL monotherapy. Again, we identified distinct mutations affecting highly conserved amino acid residues within NS4B, which mediated phenotypic SIL resistance also in vitro. Analyses of chimeric viral genomes suggest that SIL might target an interaction between NS4B and NS3/4A. Ultrastructural studies revealed changes in the morphology of viral membrane alterations upon SIL treatment of a susceptible genotype 1b isolate, but not of a resistant NS4B mutant or genotype 2a, indicating that SIL might interfere with the formation of HCV replication sites. CONCLUSION: Mutations conferring partial resistance to SIL treatment in vivo and in cell culture argue for a mechanism involving NS4B. This novel mode of action renders SIL an attractive candidate for combination therapies with other directly acting antiviral drugs, particularly in difficult-to-treat patient cohorts.

Assessing patient's belief on HIV testing before elective surgery: room for improvements in Switzerland !

Background: ln Switzerland no HIV test is performed without the patient's consent based on a Voluntary Counseling and Testing policy (VCT). We hypothesized that a substantial proportion of patients going through an elective surgery falsely believed that an HIV test was performed on a routine basis and that the lack of transmission of result was interpreted as being HIV negative. Method: All patients with elective orthopedic surgery during 2007 were contacted by phone in 2008. A structured questionnaire assessed their belief about routine preoperative blood analysis (diabetes, coagulation function, HIV test and cholesterol level) as well as result awareness and interpretation. Variables included age and gender. Analysis were conducted using the software JMP 6.0.3. Results: 1123 patients were included. 130 (12 %) were excluded (Le. unreachable, unable to communicate on the phone, not operated). 993 completed the survey (89 %). Median age was 51 (16-79). 50 % were female. 376 (38 %) patients thought they had an HIV test performed before surgery but none of them had one. 298 (79 %) interpreted the absence of result as a negative HIV test. A predictive factor to believe an HIV test had been done was an age below 50 years old (45 % vs 33 % for 16-49 years old and 50-79 years old respectively, p < 0.001). No difference was observed between genders. Conclusion: ln Switzerland, nearly 40 % of the patients falsely thought an HIV test had been performed on a routine basis before surgery and were erroneously reassured about their HIV status. These results should either improve the information given to the patient regarding preoperative exams, or motivate public health policy to consider HIV opt-out screening instead of VCT strategy.

Selection on age at first and at last reproduction in the long-lived Alpine Swift Apus melba

The way an organism spreads its reproduction over time is defined as a life-history trait, and selection is expected to favour life-history traits associated with the highest fitness return. We use a long-term dataset of 277 life histories to investigate the shape and strength of selection acting on the age at first reproduction and at last reproduction in the long-lived Alpine Swift. Both traits were under strong directional selection, but in opposite directions, with selection favouring birds starting their reproductive career early and being able to reproduce for longer. There was also evidence for stabilising selection acting on both traits, suggesting that individuals should nonetheless refrain from reproducing in their first 2 years of life (i.e. when inexperienced), and that reproducing after 7 years of age had little effect on lifetime fitness, probably due to senescence.

Winter habitat selection by two sympatric forest grouse in western Switzerland: implications for conservation

Two endangered tetraonids, the capercaillie (Tetrao urogallus) and the hazel grouse (Bonasa bonasia rupestris), are sympatric throughout part of their distribution range in central Europe. Precise information on their specific habitat requirements is needed if the coexistence of both species in exploited forests is to be maintained. We quantified winter habitat selection for both species in the upper part (1100-1600 m) of the Jura mountains (Switzerland). No preference for altitude or exposure could be detected. Capercaillie preferred open forests (including grazed forests) with a sparse canopy dominated by spruce (Picea abies) and fir (Abies alba), and avoided dense undercanopy and understorey, especially when dominated by spruce and beech (Fagus sylvatica). By contrast, hazel grouse preferred feeding sites with a dense understorey of rowan (Sorbus aucuparia), willow (Salix sp.), beech and spruce. These preferences can be related to the feeding habits and predator avoidance behaviour of both species. Coexistence thus requires a mosaic distribution of habitat types, with a matrix of open forests (30% canopy cover) where fir is favoured, and understorey kept sparse (20%). Group-cuts of mature trees should allow regeneration patches, where a dense understorey (50% cover) should provide suitable habitats for hazel grouse

Additional effect of hypnosis in an in-patient detoxification program: results of a pilot clinical trial

The present study aims to examine the additional effects of hypnosis in the reduction of withdrawal syndrome in an inpatient detoxification treatment program. Thirty-two in-patients aged between 18 and 65 meeting the DSM-IV criteria for multiple substance dependence were randomly assigned to hypnosis condition (two sessions of standardized Ericksonian technique) or control condition (two sessions of standardized support interview). The primary outcome measures were the Short Opiate Withdrawal Scale (SOWS) and Visual Analogue Scales (withdrawal symptoms, craving, depressive mood, anxiety and nervousness). Significant reductions for most outcome measures were found for the total sample. Hypnosis was effective in reducing withdrawal symptoms, however, without significant differences compared to control group.

Electroencephalogram changes during inhalation with nitric oxide in the pediatric intensive care patient--a preliminary report.

OBJECTIVES: Although endogenous nitric oxide (NO) is an excitatory mediator in the central nervous system, inhaled NO is not considered to cause neurologic side effects because of its short half-life. This study was motivated by a recent case report about neurologic symptoms and our own observation of severe electroencephalogram (EEG) abnormalities during NO inhalation. DESIGN: Blind, retrospective analyses of EEGs which were registered before, during, and after NO inhalation. EEG was classified in a 5-point rating system by an independent electroencephalographer who was blinded to the patients' clinical histories. Comparisons were made with the previous evaluation documented at recording. Other EEG-influencing parameters such as oxygen saturation, hemodynamics, electrolytes, and pH were evaluated. SETTING: Pediatric intensive care unit of a tertiary care university children's hospital. PATIENTS: Eleven ventilated, long-term paralyzed, sedated children (1 mo to 14 yrs) who had EEG or clinical assessment before NO treatment and EEG during NO inhalation. They were divided into two groups according to the NO-indication (e.g., congenital heart defect, acute respiratory distress syndrome). MEASUREMENTS AND MAIN RESULTS: All 11 patients had an abnormal EEG during NO inhalation. EEG-controls without NO showed remarkable improvement. EEG abnormalities were background slowing, low voltage, suppression burst (n = 2), and sharp waves (n = 2) independent of patients' age, NO-indication, and other EEG-influencing parameters. CONCLUSIONS: These preliminary data suggest the occurrence of EEG-abnormalities after application of inhaled NO in critically ill children. We found no correlation with other potential EEG-influencing parameters, although clinical state, medication, or hypoxemia might contribute. Comprehensive, prospective, clinical assessment regarding a causal relationship between NO-inhalation and EEG-abnormalities and their clinical importance is needed.