Twiddler's syndrome and pectoral stimulation in a patient with dual-site unipolar atrial pacing.

Twiddler's syndrome is a rare condition of pacemaker rotation; when associated with unipolar pacing it could provoke extracardiac muscular stimulation. We report a case of an obese woman who unintentionally reversed her triple-chamber, dual-site unipolar atrial pacemaker, implanted for the prevention of paroxysmal atrial fibrillation. The extracardiac pectoral stimulation was due to unipolar atrial stimulation. The polarity mode was not programmable and output reduction was unsuccessful. Thus, the problem was resolved noninvasively by means of external manual rotation of the pacer. At 24 months of follow-up, the patient was still free of symptoms.     

The use of methotrexate in rheumatoid arthritis

OBJECTIVE: To address the long-term efficacy and toxicity issues related to methotrexate (MTX) and compare it with other disease-modifying antirheumatic drugs (DMARDs). METHODS: Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease. RESULTS: MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival. The toxicity profile of MTX is well established and includes serious and sometimes fatal liver disease, pneumonitis, and cytopenias. Hence, regular and careful monitoring of patients taking MTX is essential, particularly when MTX is combined with other DMARDs. Folate supplementation can reduce some of the most common side effects of MTX, but it has not yet been established whether this translates into a reduced risk of serious disease. Another potential approach to reducing the toxicity of MTX is therapeutic drug monitoring and dose individualization. However, correlations between pharmacokinetics and clinical response have been addressed in only a few studies and with conflicting results. CONCLUSIONS: MTX is an effective DMARD with a relatively safe profile compared with other therapies. Folate supplementation can significantly reduce the risk of MTX toxicity. Finally, it is essential that patients be monitored carefully to reduce the potential serious toxicities of MTX.     

Effect of inhibitors of myeloperoxidase on the development of aortic atherosclerosis in an animal model

Our earlier studies have shown that some steroids increase myeloperoxidase enzyme (MPO) release from human granulocytes, and that MPO plasma levels are significantly lower in postclimacteric people. Moreover, we have proven that MPO inhibits production of atherogenic free radical superoxide anion and MPO-inhibitors increase superoxide release. The aim of the present study was to investigate the effect of MPO-inhibitors on the early phase of aortic atherosclerosis, namely the extent of intimal plaques and the thickening of the medial layer. Adult male rabbits were fed with lipid rich food (cholesterol: 1.3%, peanut oil: 8%) for 8 weeks. During this period MPO-inhibitors were also given (4-aminobenzoicacid-hydrazide/ABAH/-13.3 mg/kg/day or indometacin-5 mg/kg/day). All animals developed intimal lipid plaques (raised fatty streaks). The relative plaque-covered areas of the aortas were compared and the media thickness of the aorta was measured on plaque-free as well as plaque-containing areas. The medial smooth muscle density and peroxidase activity of the aortic media were also determined. The media thickness increased (p<0.05) in the cholesterol+ABAH as well as in the cholesterol+indometacin groups up to 375.7 (+/-60.5) and 442.5 (+/-123.4) microm, respectively, compared to the control group (cholesterol feeding alone) where it measured only 308.4 (+/-51.67) microm. The medial peroxidase activity decreased significantly in the indometacin treated group and showed a decreasing tendency using ABAH. In parallel to this there was a tendency of increase in the relative plaque covered areas. The smooth muscle density showed no significant modifications, while inhibitors of the MPO seemed to enhance aortic medial thickness, i.e. the grade of a pre-atherosclerotic lesion, in our animal model. Collectively, the anti-atherogenic effect of certain steroid hormones might be realized through the impact on MPO activity.     

Gastric mucosal histamine storing cells

Gastric mucosal histamine content, enterochromaffin-like cell density, and mast cell density were studied in 13 subjects under omeprazole therapy, 13 partially gastrectomized subjects with a Billroth II reconstruction, 10 partially gastrectomized subjects with a Roux-en-Y reconstruction, and 9 control subjects. Histamine content was significantly greater both in the subjects with higher gastrinemic levels (omeprazole-treated subjects) and those with more abundant enterogastric reflux (Billroth II subjects) than in controls. Enterochromaffin-like cell density was significantly greater in the omeprazole subjects than in each of the other groups. Mast cell density was significantly greater in Billroth II subjects than in controls. Serum gastrin levels, mucosal histamine content, and enterochromaffin-like cell density were positively correlated. Gastrin was not correlated to mast cell densilty. These results support the existence of different control pathways for enterochromaffin-like and mast cells. Moreover, they suggest that enterochromaffin-like cells and mast cells are involved in the regulation of gastric secretion and in gastric mucosal injury-repair mechanisms, respectively, due to histamine release.     

Enculturation,perceived stress,and physical activity: implications for metabolic risk among the Yup'ik – The Center for Alaska Native Health Research Study

Objectives. American Indians and Alaska Natives (ANs) report among the lowest levels of physical activity in the USA, but there is very little systematic research examining the determinants of physical activity patterns in these populations. This study investigated the relationships between enculturation (or cultural traditionality), psychosocial stress, and physical activity in a community-based sample of Yup'ik women and men living in rural AN communities. Associations between these variables and several metabolic risk factors were also examined.

Design. A sample of 488 Yup'ik participants (284 women and 204 men) from six villages in the Yukon-Kuskokwim Delta region completed a wellness survey and an array of physiological assessments [e.g., body mass index (BMI), blood pressure]. A subset of 179 participants also completed a 3-day pedometer assessment of physical activity.

Results. Multivariate linear regression models indicated that participants who were more enculturated (i.e., living more of a traditional lifestyle) and who experienced lower levels of psychosocial stress were significantly more physically active. In turn, both lower levels of psychosocial stress and higher levels of physical activity were associated with lower BMI, lower percent body fat, and lower waist circumference.

Conclusions. Findings underscore the importance of gaining a culturally specific understanding of physical activity patterns in indigenous groups in order to inform effective health promotion strategies.     

Comparison of cardiovascular aquaporin-1 changes during water restriction between 25- and 50-day-old rats

Purpose

Aquaporin-1 (AQP1) is the predominant water channel in the heart, linked to cardiovascular homeostasis. Our aim was to study cardiovascular AQP1 distribution and protein levels during osmotic stress and subsequent hydration during postnatal growth.

Methods

Rats aged 25 and 50 days were divided in: 3d-WR: water restriction 3 days; 3d-WAL: water ad libitum 3 days; 6d-WR+ORS: water restriction 3 days + oral rehydration solution (ORS) 3 days; and 6d-WAL: water ad libitum 6 days. AQP1 was evaluated by immunohistochemistry and western blot in left ventricle, right atrium and thoracic aorta.

Results

Water restriction induced a hypohydration state in both age groups (40 and 25 % loss of body weight in 25- and 50-day-old rats, respectively), reversible with ORS therapy. Cardiac AQP1 was localized in the endocardium and endothelium in both age groups, being evident in cardiomyocytes membrane only in 50-day-old 3d-WR group, which presented increased protein levels of AQP1; no changes were observed in the ventricle of pups. In vascular tissue, AQP1 was present in the smooth muscle of pups; in the oldest group, it was found in the endothelium, increasing after rehydration in smooth muscle. No differences were observed between control groups 3d-WAL and 6d-WAL of both ages.

Conclusion

Our findings suggest that cardiovascular AQP1 can be differentially regulated in response to hydration status in vivo, being this response dependent on postnatal growth. The lack of adaptive mechanisms of mature animals in young pups may indicate an important role of this water channel in maintaining fluid balance during hypovolemic state.     

A qualitative assessment of health seeking practices among and provision practices for men who have sex with men in Malawi

Background

In the context of a generalized epidemic and criminalization of homosexuality, men who have sex with men (MSM) in Malawi have a disproportionate burden of HIV compared to other adults. Past research has documented low uptake of HIV prevention and health services among MSM, self-reported fear of seeking health services, and concerns of disclosure of sexual orientation and discrimination in health settings. Qualitative research was conducted among MSM and health service providers in Blantyre, Malawi to understand underlying factors related to disclosure and health seeking behaviors and inform the development of a community-based comprehensive HIV prevention intervention.

Methods

Using peer recruitment, eight MSM participants representing a range of ages, orientations, and social and behavioral characteristics were enrolled for in-depth interviews. Five service providers were recruited from the district hospital, local health and STI clinics, and a HIV prevention service organization. We use the Health Belief Model as a framework to interpret the influential factors on 1) health seeking and uptake among MSM, and 2) influences on provision of services by healthcare providers for MSM.

Results

Results highlight disclosure fears among MSM and, among providers, a lack of awareness and self-efficacy to provide care in the face of limited information and political support. Service providers reported concerns of adverse repercussions related to the provision of services to men in same sex sexual relationships. Some MSM demonstrated awareness of HIV risk but believed that within the wider MSM community, there was a general lack of HIV information for MSM, low awareness of appropriate prevention, and low perception of risks related to HIV infection.

Conclusions

Qualitative research highlights the need for appropriate information on both HIV risks and acceptable, effective HIV prevention options for MSM. Information and educational opportunities should be available to the wider MSM community and the health sector. Health sector interventions may serve to increase cultural and clinical competency to address health problems experienced by MSM. To ensure availability and use of services in light of the criminalization and stigmatization of same sex practices, there is need to increase the safety of uptake and provision of these services for MSM.

     

Real-life experience with switching TNF-α inhibitors in ankylosing spondylitis

Background

Published economic evaluations of trastuzumab for the treatment of HER2-positive metastatic breast cancer have arrived at different conclusions regarding the cost-effectiveness of trastuzumab, despite comparative efficacy being demonstrated by a small set of randomised controlled trials (RCTs).

Objectives

This article aims to provide insight into the quality of the evaluations and explore the possible drivers of the conflicting conclusions.

Methods

A systematic literature review was conducted to identify all published economic evaluations that compared the incremental costs and outcomes of trastuzumab versus a comparator.

Results

Fifteen economic evaluations were identified. In the evaluations that estimated efficacy using an RCT, the key drivers of the conclusions regarding cost-effectiveness were: the approach used to estimate overall survival in the control group given crossover to trastuzumab following progression in the trials; the inclusion of treatment beyond progression; inclusion of wastage due to unused vial portions, adverse events, and the cost of HER2 testing. Four evaluations used non-randomised approaches to estimate efficacy, thus introducing the potential for confounding. As a result these evaluations reported relatively optimistic estimates of comparative effectiveness. Finally the evaluations used different thresholds to determine whether treatment with trastuzumab was cost-effective.

Conclusion

There were numerous drivers of the different conclusions regarding the cost-effectiveness of trastuzumab, many of which are due to judgements made by the authors when translating data from RCTs. Many of the potential drivers were not identified by the published systematic reviews of economic evaluations and perhaps more remain unidentified because of inconsistent and limited reporting.     

Cortisol modifies extinction learning of recently acquired fear in men

Exposure therapy builds on the mechanism of fear extinction leading to decreased fear responses. How the stress hormone cortisol affects brain regions involved in fear extinction in humans is unknown. For this reason, we tested 32 men randomly assigned to receive either 30 mg hydrocortisone or placebo 45 min before fear extinction. In fear acquisition, a picture of a geometrical figure was either partially paired (conditioned stimulus; CS+) or not paired (CS−) with an electrical stimulation (unconditioned stimulus; UCS). In fear extinction, each CS was presented again, but no UCS occurred. Cortisol increased conditioned skin conductance responses in early and late extinction. In early extinction, higher activation towards the CS− than to the CS+ was found in the amygdala, hippocampus and posterior parahippocampal gyrus. This pattern might be associated with the establishment of a new memory trace. In late extinction, the placebo compared with the cortisol group displayed enhanced CS+/CS− differentiation in the amygdala, medial frontal cortex and nucleus accumbens. A change from early deactivation to late activation of the extinction circuit as seen in the placebo group seems to be needed to enhance extinction and to reduce fear. Cortisol appears to interfere with this process thereby impairing extinction of recently acquired conditioned fear.     

Quantitative Validation of the n-Butanol Sniffin’ Sticks Threshold Pens

Odorant pens are used by medical practitioners and researchers to assess olfactory dysfunction. Despite their routine use, there are currently no data on the gas-phase odorant concentrations released from the pen tips or whether these concentrations scale linearly with the aqueous-phase concentrations inside the pens. The commercially available Sniffin’ Sticks odor threshold test containing n-butanol was chosen for evaluation. The gas-phase concentration of n-butanol at the tip of each pen was measured directly in a new set of pens via proton-transfer-reaction mass spectrometry (PTR-MS). Measurements were additionally made on the same pens after 6 months and two older pen sets, namely a 3-year-old (used) and 4-year-old (new) set. Furthermore, application-related tests were made to determine the performance of the pens during routine use and under stress. These data demonstrate that the gas-phase n-butanol concentrations of the threshold pens are linear over the entire set, both for brand-new pens and 6 months later; this reflects the expected performance that was previously only assumed. Furthermore, the application–simulation tests demonstrated a good performance of the pens when used according to their intended protocol. Measurements of the older pen sets suggest that storage conditions are more critical than usage for pen stability. The present findings confirm that the n-butanol odorant pens are an appropriate tool for threshold testing, provided they are stored and handled correctly.