Activation of the cortical pain network by soft tactile stimulation after injection of sumatriptan

The anti-migraine drug sumatriptan often induces unpleasant somatosensory side effects, including a dislike of being touched. With a double-blind cross-over design, we studied the effects of sumatriptan and saline on perception (visual analogue scale) and cortical processing (functional magnetic resonance imaging) of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6) was less pleasant (p<0.04) and evoked less activation of posterior insular cortex in the sumatriptan compared to the saline condition. Soft brushing activated pain processing regions (anterior insular, lateral orbitofrontal, and anterior cingulate cortices, and medial thalamus) only in the sumatriptan condition, whereas activation of somatosensory cortices was similar in both conditions. Soft brush stroking on the palm (n=6) was equally pleasant in both conditions. One possible mechanism for the activation of pain processing regions by brush stroking is sensitization of nociceptors by sumatriptan. Another possibility is inhibition of a recently discovered system of low-threshold unmyelinated tactile (CT) afferents that are present in hairy skin only, project to posterior insular cortex, and serve affective aspects of tactile sensation. An inhibition of impulse transmission in the CT system by sumatriptan could disinhibit nociceptive signalling and make light touch less pleasant. This latter alternative is consistent with the observed reduction in posterior insular cortex activation and the selective effects of stimulation on hairy compared to glabrous skin, which are not explained by the nociceptor sensitization account.     

Vitamin A abuse: development of cirrhosis despite cessation of vitamin A. A six-year clinical and histopathologic follow-up

ABSTRACT— We report the case of a 35-year-old man who contracted vitamin A-induced liver cirrhosis. Five years before, he had been investigated for vitamin A-induced non-cirrhotic portal hypertension. In this case, the clinical and histopathologic evolution from non-cirrhotic portal hypertension to cirrhosis was documented. In spite of the cessation of pharmaceutical vitamin A intake, the disease progressed. Therapy with colchicine and phenobarbital apparently did not influence evolution to cirrhosis. This suggests that vitamin A can trigger largely unknown mechanisms of liver fibrosis which seem to be self-perpetuating.     

Feasibility of an accelerated PVAL method for the collection of GSR and biological traces

International Journal of Legal Medicine - The polyvinyl alcohol method (PVAL) is known as an effective technique to thoroughly collect traces of gunshot residue (GSR) from different surfaces, e.g.,...     

Pattern of microbial translocation in patients living with HIV-1 from Vietnam,Ethiopia and Sweden

Introduction

The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

Methods

Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

Results

All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

Conclusions

Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.     

A 5-year follow-up study of adolescents who sought treatment for substance misuse in Sweden

Previous studies have shown that substance misuse in adolescence is associated with increased risks of hospitalizations for mental and physical disorders, convictions for crimes, poverty, and premature death from age 21 to 50. The present study examined 180 adolescent boys and girls who sought treatment for substance misuse in Sweden. The adolescents and their parents were assessed independently when the adolescents first contacted the clinic to diagnose mental disorders and collect information on maltreatment and antisocial behavior. Official criminal files were obtained. Five years later, 147 of the ex-clients again completed similar assessments. The objectives were (1) to document the prevalence of alcohol use disorders (AUD) and drug use disorders (DUD) in early adulthood; and (2) to identify family and individual factors measured in adolescence that predicted these disorders, after taking account of AUD and DUD in adolescence and treatment. Results showed that AUD, DUD, and AUD + DUD present in mid-adolescence were in most cases also present in early adulthood. Prediction models detected no positive effect of treatment in limiting persistence of these disorders. Thus, treatment-as-usual provided by the only psychiatric service for adolescents with substance misuse in a large urban center in Sweden failed to prevent the persistence of substance misuse. Despite extensive clinical assessments of the ex-clients and their parents, few factors assessed in mid-adolescence were associated with substance misuse disorders 5 years later. It may be that family and individual factors in early life promote the mental disorders that precede adolescent substance misuse.     

Evaluation of safety and efficacy as an adjuvant for the chitosan-based vaccine delivery vehicle ViscoGel in a single-blind randomised Phase I/IIa clinical trial

ViscoGel, a chitosan-based hydrogel, has earlier been shown to improve humoral and cell-mediated immune responses in mice. In this study, a Phase I/IIa clinical trial was conducted to primarily evaluate safety and secondarily to study the effects of ViscoGel in combination with a model vaccine, Act-HIB to Haemophilus influenzae type b, administered as a single intramuscular injection. Healthy volunteers of both sexes, ages 22–50 and not previously vaccinated to HIB, were recruited. The trial had two phases. In Phase A, three ascending dose levels of ViscoGel (25, 50 and 75 mg) were evaluated for safety in 3 × 10 subjects. Phase B had a single-blind, randomised, parallel-group design evaluating safety and efficacy in five groups, 20 subjects/group, comparing vaccination with 0.2 μg or 2 μg Act-HIB alone or combined with ViscoGel (50 mg) and one group receiving the standard Act-HIB dose (10 μg). No safety or tolerability concerns were identified. Local, transient reactions at the injection site were the most common adverse events. These were more frequent in groups receiving Act-HIB + ViscoGel, while other AEs were recorded at similar frequency in Act-HIB and Act-HIB + ViscoGel groups. Efficacy was evaluated by measuring serum anti-HIB antibodies and cellular responses in peripheral blood mononuclear cells (PBMC). There was a large variation in baseline anti-HIB antibody titres and no adjuvant effect was observed on the anti-HIB antibody production in groups vaccinated with Act-HIB + ViscoGel. ELISpot analyses revealed increased interferon-γ (IFN-γ) responses to Act-HIB in PBMCs from subjects vaccinated with Act-HIB in combination with ViscoGel, compared to groups receiving Act-HIB alone. Moreover, ViscoGel counteracted an inhibitory effect of Act-HIB vaccination on the IFN-γ response to both the vaccine itself and an irrelevant influenza antigen. In summary, ViscoGel was found to be safe and well-tolerated, supporting further examination of ViscoGel as a new innovative vehicle for vaccine development.