The Long‐Term Use of a Low‐Phenylalanine Diet in Late‐Treated Phenylketonuria: A Single Case Report

Background When phenylketonuria (PKU) is not diagnosed and long‐term treatment commenced within the first few weeks of life, permanent brain damage will occur. There is some evidence to show that late diagnosed or untreated people with PKU who have severe challenging behaviours may benefit from a low phenylalanine diet [ Harper & Reid (1987) Journal of Mental Deficiency Research vol. 31, pp. 209–212; Hoskins et al. (1992) Journal of Intellectual Disability Research vol. 36, pp. 183–191; Baumeister & Baumeister (1998) Clinical Neuropharmacology vol. 21, pp. 18–27; Fitzgerald et al. (2000) Journal of Intellectual Disability Research vol. 44, pp. 53–59]. Method In the light of this evidence, a woman with late‐diagnosed PKU was treated with a low‐phenylalanine diet in an attempt to reduce her severe challenging behaviour. Results A reduction in challenging behaviours was observed when phenylalanine levels were maintained within a specific narrow range. Data are reported over a 2‐year period. A dramatic rise in severe challenging behaviour was noticed when her blood phenylalanine levels fell below a certain level. Conclusions This case report suggests that blood phenylalanine levels need to be maintained within a specific range for maximum benefit.     

Neural signature of behavioural inhibition in women with bulimia nervosa

BackgroundImpaired inhibitory control is considered a behavioural phenotype in patients with bulimia nervosa. However, the underlying neural correlates of impaired general and food-specific behavioural inhibition are largely unknown. Therefore, we investigated brain activation during the performance of behavioural inhibition to general and food-related stimuli in adults with bulimia nervosa.MethodsWomen with bulimia and healthy control women underwent event-related fMRI while performing a general and a food-specific no-go task.ResultsWe included 28 women with bulimia nervosa and 29 healthy control women in our study. On a neuronal level, we observed significant group differences in response to general no-go stimuli in women with bulimia nervosa with high symptom severity; compared with healthy controls, the patients showed reduced activation in the right sensorimotor area (postcentral gyrus, precentral gyrus) and right dorsal striatum (caudate nucleus, putamen).LimitationsThe present results are limited to adult women with bulimia nervosa. Furthermore, it remains unclear whether impaired behavioural inhibition in patients with this disorder are a cause or consequence of chronic illness.ConclusionOur findings suggest that diminished frontostriatal brain activation in patients with bulimia nervosa contribute to the severity of binge eating symptoms. Gaining further insight into the neural mechanisms of behavioural inhibition problems in individuals with this disorder may inform brain-directed treatment approaches and the development of response inhibition training approaches to improve inhibitory control in patients with bulimia nervosa. The present study does not support greater behavioural and neural impairments to food-specific behavioural inhibition in these patients.     

Absorbent products for incontinence: 'treatment effects' and impact on quality of life

Abstract Aim. This study aimed to determine how the use and characteristics of absorbent products for incontinence impact on women's quality of life, and to examine the concept of ‘treatment effects’ in the context of pad use. Method. Key pad performance characteristics were identified from the literature and focus group work. Semi‐structured interviews with 99 women with light incontinence were used to investigate the impact of pad use on women's quality of life, including both positive and negative ‘treatment effects’, and to rank pad characteristics by their importance. Results. Achieving effective and discrete containment of urine was the dominant factor impacting on women's lives. Sub‐themes embraced physical effects, psychological impact and social functioning. The five pad characteristics ranked most important for day time use were: ‘to hold urine, to contain smell, to stay in place, discreteness, and comfort when wet. For night use discreteness was replaced by to keep skin dry’. High levels of reported anxiety were associated with perceived risk of poor pad performance, lack of discreteness and need for complex regimes for pad management. Conclusion. Insufficient attention has been paid to the balance between the beneficial and negative treatment effects of absorbent pads to date. Existing continence‐related quality of life measures are not designed for conditions where change in symptoms is not an outcome measure. The study findings provide the basis for developing a more sensitive, patient‐oriented, quality of life measure for pad‐users which can aid product selection, new product development and inform future evaluative comparisons between products/products and treatments. Relevance to clinical practice. This paper illustrates the complex influence on quality of life caused by using absorbent pads to contain incontinence. It raises awareness of the importance of careful selection of the most appropriate pad for each individual to minimize unfavourable side effects, and the need for a new quality of life measure designed for pad‐users.     

Pain management: setting up a nurse-led femoral nerve block service

Managing pain following a fractured neck of femur is challenging for a number of reasons. This group of patients are typically older people and frail with multiple co-morbidities and are often on numerous medications. In addition to a hip fracture, they commonly present with acute medical problems. Fractures cause significant pain, which can be difficult to manage safely and effectively with the traditional analgesics. A femoral nerve block has been shown to be a safe and effective preoperative intervention for managing pain in this patient group while they wait for surgery. This article describes how an acute pain team have developed protocols and training to establish a nurse-led service for providing preoperative femoral nerve blocks to patients with fractured neck of femur.     

A multicenter study evaluating the current strategies for isolating Staphylococcus aureus strains with reduced susceptibility to glycopeptides

Glycopeptide-intermediate Staphylococcus aureus (GISA) and heterogeneous GISA (hGISA) strains are notoriously difficult to detect in the diagnostic laboratory. The clinical importance of GISA, and particularly hGISA, will only be obvious when a definitive detection method is available. A few novel GISA and hGISA detection methods have been proposed; however, their validity has never been tested on a significant scale and in different laboratories. This study compares three screening methods for detecting GISA and hGISA strains in 12 laboratories, using a blind panel of 48 strains with known glycopeptide susceptibilities. The three screening methods used were brain heart infusion agar with 6 mg/liter vancomycin (BHIA6V) (CDC/CLSI), Mueller-Hinton agar with 5 mg/liter teicoplanin (MHA5T) (European Antimicrobial Resistance Surveillance System [EARSS]), and the macrodilution method Etest (MET) (EARSS), with population analysis profile-area under the curve analysis as the gold standard. Sensitivity and specificity were highest for MHA5T and MET, which identified 82.5% and 85.9% of strains, respectively. BHIA6V had poor sensitivity, particularly for hGISA (11.5% of strains were detected), and gave the largest interlaboratory variation in performance. MET exhibited the least interlaboratory variation. It is essential that laboratories use appropriate methods to detect GISA/hGISA strains so that the prevalence and clinical importance of these strains can be assessed properly.     

Meta-analysis of genome-wide linkage studies for multiple sclerosis, using an extended GSMA method

Many genome-wide linkage studies in multiple sclerosis (MS) have been performed, but results are disappointing, with linkage confirmed only in the HLA region. We combined results from all available, non-overlapping genome-wide linkage studies in MS using the Genome Search Meta-Analysis method (GSMA). The GSMA is a rank-based analysis, which assesses the strongest evidence for linkage within bins of traditionally 30 cM width on the autosomes and X chromosome. Genome-wide evidence for linkage was confirmed on chromosome 6p (HLA region; P=0.00004). Suggestive evidence for linkage was found on chromosomes 10q (P=0.0077), 18p (P=0.0054) and 20p (P=0.0079). To explore how these results could be affected by bin definition, we analysed the data using different bin widths (20 and 40 cM) and using a shifted 30 cM bin by moving bin boundaries by 15 cM. Consistently significant results were obtained for the 6p region. The regions on 10q and 18p provided suggestive evidence for linkage in some analyses, and, interestingly, a region on 6q, that showed only nominal significance in the original analysis, yielded increased, suggestive significance in two of the additional analyses. These regions may provide targets to focus candidate gene studies or to prioritise results from genome-wide association studies.     

The link between IL-23 and Th17 cell-mediated immune pathologies

IL-23--produced by dendritic cells--and Th17 cells have both been identified as major factors involved in autoimmune inflammation, yet their relationship with each other remains controversial. This review aims to describe the initial discovery of Th17 cells, their subsequent characterization as a unique T helper subset in mouse and man, as well as the mechanisms involved in regulating these cells. Finally, the roles of IL-23 in inflammatory diseases in relation to Th17 function will be discussed.