Comorbid psychiatric disorders among patients with narcolepsy

Sleep and Breathing - This case-control study assessed the prevalence of psychiatric disorders in Arab (Saudi) patients with narcolepsy using a structured clinical interview. The study...     

Loose anagen hair syndrome in children of Upper Egypt

Background  Loose anagen hair (LAH) syndrome is a phenomenon in early childhood characterized by the presence of easily pluckable hair, where hair tufts can be pulled out easily and painlessly.
Aims  All reports in the English literature described mainly white patients with blond hair. We present the first report of LAH syndrome in dark-skinned children of Upper Egypt.
Patients and methods  Twenty-eight children with LAH were diagnosed and examined from 1996 to 2007. The main complaints were patchy or diffuse alopecia and/or slow growth of hair. Clinical examination, hair pull test, trichogram, and scanning electron microscopy (SEM) were performed.
Results  Children with LAH included 21 girls (75%) and seven boys (25%). Light microscopy of hair pull tests and trichograms disclosed a striking predominance of anagen hairs (90–100%) with misshapen hair bulbs and absent inner and outer root sheaths. SEM confirmed the misshapen anagen bulbs with ruffled appearance of cuticle and the longitudinal groove parallel to the long axis of the hair shaft. Most children improved spontaneously within few years, however, hair shed continued.
Conclusion  LAH syndrome occurs in dark-skinned children and could be under-diagnosed. The condition is of cosmetic concern and does not affect the general health.     

'Choose and Book' in ENT: the GP perspective

OBJECTIVES: 'Choose and Book' is a UK government initiative devised to allow a greater freedom of choice for National Health Service patients. The system is designed to give patients a choice of hospitals and appointment times, as well as giving their general practitioner (GP) more responsibility for appropriate prioritization. We set out to determine the attitudes of UK GPs to the new Choose and Book project and to assess the impact that these changes are likely to have on ENT practice. DESIGN: Postal questionnaire survey. METHODS: Five hundred GPs were sent a questionnaire about the planned Choose and Book referral project. RESULTS: Three hundred and eighty GPs (76 per cent) replied to the questionnaire after reminders were sent. Most were aware of the project and had been sent information about it. Of those who had heard of it, 61.5 per cent did not think it was a good thing. Most stated that both they and their patients were satisfied with current prioritization practices. Many GPs would be willing to delegate responsibility for prioritization to non-clinical staff. Important time and responsibility issues were identified. CONCLUSIONS: The majority of GPs were not in favour of Choose and Book. Many cited difficulties with time constraints and an inflexible system as factors that made Choose and Book unacceptable.     

Safety and immunogenicity of a candidate vaccine for visceral leishmaniasis (Alum-precipitated autoclaved Leishmania major + BCG) in children: an extended phase II study

BACKGROUND: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions. METHODS: A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity.RESULTS: The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (>or=5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL. CONCLUSION: Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers.     

A brief history of tendon and ligament bioreactors: Impact and future prospects

Bioreactors are powerful tools with the potential to model tissue development and disease in vitro. For nearly four decades, bioreactors have been used to create tendon and ligament tissue-engineered constructs in order to define basic mechanisms of cell function, extracellular matrix deposition, tissue organization, injury, and tissue remodeling. This review provides a historical perspective of tendon and ligament bioreactors and their contributions to this advancing field. First, we demonstrate the need for bioreactors to improve understanding of tendon and ligament function and dysfunction. Next, we detail the history and evolution of bioreactor development and design from simple stretching of explants to fabrication and stimulation of two- and three-dimensional constructs. Then, we demonstrate how research using tendon and ligament bioreactors has led to pivotal basic science and tissue-engineering discoveries. Finally, we provide guidance for new basic, applied, and clinical research utilizing these valuable systems, recognizing that fundamental knowledge of cell-cell and cell-matrix interactions combined with appropriate mechanical and chemical stimulation of constructs could ultimately lead to functional tendon and ligament repairs in the coming decades.     

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

Several pharmacokinetic studies have suggested that dabigatran possesses a number of ideal properties for expedited removal via extracorporeal methods. However, this practice has not been prospectively evaluated in patients with life-threatening bleeding or requiring emergency surgery secondary to dabigatran-associated coagulopathy. The purpose of this literature review is to evaluate the published evidence surrounding extracorporeal removal of dabigatran in the setting of emergency surgery or life-threatening bleeding. A query of MEDLINE, Web of Science, International Pharmaceutical Abstracts, and Google Scholar using the terms dabigatran, dabigatran etexilate, hemodialysis, renal replacement therapy, hemorrhage, and atrial fibrillation was used to retrieve relevant literature. Furthermore, a manual search of the references of the identified literature was performed to capture additional data. Current evidence suggests that extracorporeal removal of dabigatran may play a role in the setting of life-threatening bleeding and emergent surgery. Conflicting evidence exists with regard to the potential for redistribution based on serum dabigatran concentrations. In addition, a number of practicalities must be considered before incorporating this technique in the clinical setting. Extracorporeal removal of dabigatran may be a treatment modality in selected patients who require emergency reversal.     

Global structural motions from the strain of a single hydrogen bond

The origin and biological role of dynamic motions of folded enzymes is not yet fully understood. In this study, we examine the molecular determinants for the dynamic motions within the β-barrel of superoxide dismutase 1 (SOD1), which previously were implicated in allosteric regulation of protein maturation and also pathological misfolding in the neurodegenerative disease amyotrophic lateral sclerosis. Relaxation-dispersion NMR, hydrogen/deuterium exchange, and crystallographic data show that the dynamic motions are induced by the buried H43 side chain, which connects the backbones of the Cu ligand H120 and T39 by a hydrogen-bond linkage through the hydrophobic core. The functional role of this highly conserved H120–H43–T39 linkage is to strain H120 into the correct geometry for Cu binding. Upon elimination of the strain by mutation H43F, the apo protein relaxes through hydrogen-bond swapping into a more stable structure and the dynamic motions freeze out completely. At the same time, the holo protein becomes energetically penalized because the twisting back of H120 into Cu-bound geometry leads to burial of an unmatched backbone carbonyl group. The question then is whether this coupling between metal binding and global structural motions in the SOD1 molecule is an adverse side effect of evolving viable Cu coordination or plays a key role in allosteric regulation of biological function, or both?