Tolerance of soya lecithin in children with non-immunoglobulin E-mediated soya allergy: a randomised, double-blind, cross-over trial.

BACKGROUND: Soya lecithin is present in a wide variety of foods regularly consumed by children, in the form of an emulsifier or stabiliser. Children with non-immunoglobulin (Ig)E-mediated allergies who commonly have to avoid milk and soya will have a significantly restrictive diet with reduced alternative foods if soya lecithin also has to be eliminated. The present study aimed to establish whether children with non-IgE-mediated gastrointestinal soya allergy react to soya lecithin in food products. METHODS: A double-blind, cross-over study was performed in soya-allergic children aged between 8 months and 5 years. Eligible children had their soya allergy status confirmed with a home challenge. Children were randomly assigned to either placebo or challenge dose of soya lecithin (1.5 g per day) in a custom-made biscuit. This was followed by a 1-week washout period and cross-over to another 1 week of challenge or placebo dose. Symptoms were recorded prior to commencing the study and at the end of each week's challenge. RESULTS: Twenty-two children, 16 boys, with a median age of 44 months (range 21-58 months) were recruited, although only 20 completed the full study. The median number of foods avoided in addition to soya was 3. Over the challenge period, the parents reported reactions in six cases: five cases (23%) to the placebo and one case (5%) to the challenge dose. There was no statistical difference (P = 0.025) between the groups. CONCLUSIONS: One child with a non-IgE-mediated gastrointestinal allergy had a slight reaction to soya lecithin. Although single cases may react to soya lecithin, we suggest that soya lecithin should be included in children with this delayed allergy, unless they have a confirmed reaction to traces of soya within this emulsifier.

Parental perception of their child's quality of life in children with non-immunoglobulin-E-mediated gastrointestinal allergies.

BACKGROUND: Food allergy can have a significant impact on health-related quality of life (HRQoL). Parental proxy questionnaires are commonly used when children are too young to complete questionnaires themselves. Little data are available on HRQoL in children with non-IgE-mediated gastrointestinal food allergy (GIFA). The aim of this study was to evaluate HRQoL in these children by parent proxy. METHODS: A cross-sectional questionnaire study was conducted with children aged 2-16 years with confirmed GIFA. Parents of these children completed the Pediatric Quality of Life Inventory (PedsQL™ ) and the family impact module of the PedsQL. The PedsQL scores were compared to two published cohorts: functional abdominal pain (FAP) and IgE-mediated food allergy. RESULTS: Fifty-two parents of children with GIFA completed the PedsQL™ parent proxy. The GIFA cohort had significantly better overall HRQoL compared with the FAP cohort, but lower emotional functioning scores. The GIFA cohort also had poorer physical QoL compared with the IgE cohort (all p < 0.05). The more foods excluded, comorbidity of nasal congestion, abdominal pain, back arching, the persistence of flatus and gastrointestinal symptom severity after elimination diet were related to poorer QoL in this non-IgE cohort. Regression analyses showed that number of foods and nasal congestion significantly predicted total QoL score as perceived by parents. CONCLUSIONS: This study has shown that different areas of HRQoL of children with GIFA are affected compared with children with FAP or IgE-mediated food allergy, highlighting the need for a specific GIFA HRQoL questionnaire to better understand the impact on these children.

Multiple-strain colonization in nasal carriers of Staphylococcus aureus.

Staphylococcus aureus is a commensal that can also cause invasive infection. Reports suggest that nasal cocolonization occurs rarely, but the resources required to sequence multiple colonies have precluded its large-scale investigation. A staged protocol was developed to maximize detection of mixed-spa-type colonization while minimizing laboratory resources using 3,197 S. aureus-positive samples from a longitudinal study of healthy individuals in Oxfordshire, United Kingdom. Initial typing of pooled material from each sample identified a single unambiguous strain in 89.6% of samples. Twelve single-colony isolates were typed from samples producing ambiguous initial results. All samples could be resolved into one or more spa types using the protocol. Cocolonization point prevalence was 3.4 to 5.8% over 24 months of follow-up in 360 recruitment-positives. However, 18% were cocolonized at least once, most only transiently. Cocolonizing spa types were completely unrelated in 56% of samples. Of 272 recruitment-positives returning ≥12 swabs, 166 (61%) carried S. aureus continuously but only 106 (39%) carried the same single spa type without any cocolonization; 31 (11%) switched spa type and 29 (11%) had transient cocarriage. S. aureus colonization is dynamic even in long-term carriers. New unrelated cocolonizing strains could increase invasive disease risk, and ongoing within-host evolution could increase invasive potential, possibilities that future studies should explore.

Extraintestinal manifestations in children with gastrointestinal food allergy.

OBJECTIVES: The presence of extraintestinal manifestations (EIM) in children with gastrointestinal (GI) food allergy (GIFA) is greatly debated. In the present study we assessed the prevalence of EIM in children with GIFA and investigated whether their presence is helpful in the allergy-focused history-taking process. METHODS: The medical records of all children with a proven diagnosis of GIFA were reviewed along with those of children diagnosed as having inflammatory bowel disease (IBD) as controls. Data regarding age at onset, age at diagnosis, atopic family history, atopic comorbidities, GI symptoms, and EIM were recorded. RESULTS: Data from 436 children with GIFA and 74 children with IBD were included in the analysis. EIM were documented in 368 children with GIFA, including fatigue (53.0%), allergic shiners (49.1%), mouth ulcers (39.0%), joint pain/hypermobility (35.8%), poor sleep (34.4%), night sweats (34.4%), headache (22.7%), and bed-wetting (17.7%). The proportion of patients with EIM was higher in the GIFA group compared with that in the IBD group (368/436 [84.4%] vs 40/74 [54.1%]; P < 0.001). Segregating the GIFA group into children with and without atopic comorbidities, both atopic (276/30; 89.9%) and nonatopic (93/130; 71.5%) children showed higher proportion of EIM than children with IBD ([40/74; 54.1%], P < 0.01 and <0.05, respectively). CONCLUSIONS: GIFA are commonly associated with a wide range of EIM, which appear to represent important and specific clinical features of this group of conditions. Their recognition in taking an allergy-focused history may play an important role for both diagnosis and management.

A study of matrix metalloproteinase expression and activity in atopic dermatitis using a novel skin wash sampling assay for functional biomarker analysis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition that is characterized by a defective skin barrier. Despite the well-recognized role of proteases in skin barrier maintenance, relatively little is known of the contribution made by matrix metalloproteinases (MMPs) to the inflammatory process in AD. OBJECTIVES: To test a simple, novel ex vivo bioassay technique in an analysis of the MMPs present in wash samples taken from the skin surface of patients with AD. METHODS: Saline wash samples were collected from eczematous and unaffected areas of the skin of patients with AD and from the skin of normal controls. Wash samples were analysed for their MMP content using a functional peptide cleavage assay, gelatin zymography and an antibody array. RESULTS: Using a functional substrate cleavage assay, skin wash samples from AD lesions were shown to contain 10- to 24-fold more MMP activity than those from normal control skin (P < 0.02) and fivefold more than those from unaffected AD skin (P < 0.05); this activity was inhibited by a broad-spectrum MMP inhibitor Ro 31-9790. Gelatin zymography and antibody array analysis revealed substantial levels of MMP-8 (neutrophil collagenase) and MMP-9 (92-kDa gelatinase) in AD skin wash samples as well as lower levels of MMP-10 (stromelysin 2) and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2; low levels of MMP-1 (fibroblast collagenase), MMP-3 (stromelysin 1) and TIMP-4 were also detected. CONCLUSIONS: A simple skin wash technique suitable for the quantitative and functional analysis of biomolecules in AD is described. Using this method we show that MMPs, and in particular MMP-8 and MMP-9, represent an important potential component of the pathology of AD. The method is expected to prove useful in advancing our understanding of AD and in identifying biomarkers for the evaluation of new therapies.

In vivo transplantation of fetal human gut-derived enteric neural crest cells.

The prospect of using neural cell replacement for the treatment of severe enteric neuropathies has seen significant progress in the last decade. The ability to harvest and transplant enteric neural crest cells (ENCCs) that functionally integrate within recipient intestine has recently been confirmed by in vivo murine studies. Although similar cells can be harvested from human fetal and postnatal gut, no studies have as yet verified their functional viability upon in vivo transplantation. We sought to determine whether ENCCs harvested from human fetal bowel are capable of engraftment and functional integration within recipient intestine following in vivo transplantation into postnatal murine colon. Enteric neural crest cells selected and harvested from fetal human gut using the neurotrophin receptor p75NTR were lentivirally labeled with either GFP or calcium-sensitive GCaMP and transplanted into the hindgut of Rag2- /γc- /C5- -immunodeficient mice at postnatal day 21. Transplanted intestines were assessed immunohistochemically for engraftment and differentiation of donor cells. Functional viability and integration with host neuromusculature was assessed using calcium imaging. Transplanted human fetal gut-derived ENCC showed engraftment within the recipient postnatal colon in 8/15 mice (53.3%). At 4 weeks posttransplantation, donor cells had spread from the site of transplantation and extended projections over distances of 1.2 ± 0.6 mm (n = 5), and differentiated into enteric nervous system (ENS) appropriate neurons and glia. These cells formed branching networks located with the myenteric plexus. Calcium transients (change in intensity F/F0 = 1.25 ± 0.03; 15 cells) were recorded in transplanted cells upon stimulation of the recipient endogenous ENS demonstrating their viability and establishment of functional connections.

Multi-site and nasal swabbing for carriage of Staphylococcus aureus: what does a single nose swab predict?

BACKGROUND: Carriage of Staphylococcus aureus is a risk for infections. Targeted decolonization reduces postoperative infections but depends on accurate screening. AIM: To compare detection of S. aureus carriage in healthy individuals between anatomical sites and nurse- versus self-swabbing; also to determine whether a single nasal swab predicted carriage over four weeks. METHODS: Healthy individuals were recruited via general practices. After consent, nurses performed multi-site swabbing (nose, throat, and axilla). Participants performed nasal swabbing twice-weekly for four weeks. Swabs were returned by mail and cultured for S. aureus. All S. aureus isolates underwent spa typing. Persistent carriage in individuals returning more than three self-swabs was defined as culture of S. aureus from all or all but one self-swabs. FINDINGS: In all, 102 individuals underwent multi-site swabbing; S. aureus carriage was detected from at least one site from 40 individuals (39%). There was no difference between nose (29/102, 28%) and throat (28/102, 27%) isolation rates: the combination increased total detection rate by 10%. Ninety-nine patients returned any self-swab, and 96 returned more than three. Nasal carriage detection was not significantly different on nurse or self-swab [28/99 (74%) vs 26/99 (72%); χ2: P=0.75]. Twenty-two out of 25 participants with first self-swab positive were persistent carriers and 69/71 with first self-swab negative were not, giving high positive predictive value (88%), and very high negative predictive value (97%). CONCLUSION: Nasal swabs detected the majority of carriage; throat swabs increased detection by 10%. Self-taken nasal swabs were equivalent to nurse-taken swabs and predicted persistent nasal carriage over four weeks.

The biological chemistry of lead.

Recent biophysical studies on the interactions between lead and recombinant proteins and peptides that naturally bind zinc or calcium have provided unparalleled insights into the biological chemistry and molecular toxicology of lead. These studies lay the foundation for the rational design of improved methods for detecting and treating lead poisoning.

Eye movements during visual search for emotional faces in individuals with chronic headache.

BACKGROUND: Attentional biases for pain-related information have been frequently reported in individuals with chronic pain. Recording of participants' eye movements provides a continuous measure of attention, although to date this methodology has received little use in research exploring attentional biases in chronic pain. The aim of the current investigation was to explore the specificity of attentional orienting bias using a novel visual search task while recording participant eye movement behaviours. This also allowed for the investigation of whether attentional biases for pain-related information exist in the presence of multiple stimuli competing for attention. METHODS: Twenty-three participants with chronic headache and 24 pain-free, healthy control participants were engaged in a visual search task where pain, angry, happy and neutral faces were used as both target and distractor stimuli. While completing this task, participants' eye movements were recorded. RESULTS: Supporting the adopted hypothesis, participants with chronic headache, relative to healthy controls, demonstrated a significantly higher proportion of initial fixations to target pain expressions when the pain expressions were presented in displays containing neutral-distractor faces. No significant differences were found between groups in the time taken to fixate target pain expressions (localization time). CONCLUSIONS: Individuals with chronic headache show facilitated initial orienting towards pain expressions specifically when used as targets in a visual search task. This study adds to a growing body of research supporting the presence of pain-related attentional biases in chronic pain as assessed via different experimental paradigms, and shows biases to exist when multiple stimuli competing for attention are presented simultaneously.

Refocusing on history-taking skills during internal medicine training.

Recognizing that skilled history-taking is in danger of becoming a lost art, the American Board of Internal Medicine calls attention to the urgent need for internal medicine residency programs to ensure that these skills are taught and assessed. Although the Board's certification examination contains standardized items that test the physician's ability to use information from a patient's medical history, the written examination cannot assess the physician's ability to elicit that history. The Board believes that history-taking skills will become even more crucial as health care delivery changes, requiring more cost efficiency without sacrificing quality. By highlighting the skills of effective history-taking and strategies for assessment, the Board offers specific recommendations for its promotion as a key element of quality patient care.

Harvey A. K. Whitney Lecture. To a new beginning from converging paths.

The implementation of the pharmaceutical care concept is discussed. Current activities of professional pharmacy organizations are laying the groundwork for the new emphasis on patient outcomes, which is seen in the mission statements of the American Pharmaceutical Association (APhA) and the Joint Commission of Pharmacy Practitioners (JCPP). APhA is revalidating its standards of practice; the American Association of Colleges of Pharmacy (AACP) has formed a Commission to Implement Change in Pharmaceutical Education; the American Council on Pharmaceutical Education (ACPE) is revising its standards to be consistent with entry-level practitioners' ability to provide pharmaceutical care and seeking ways in which pharmacists currently practicing in all sites can upgrade their skills. These groups are called on to implement pharmaceutical care: To make known the "value-added services" encompassed in pharmaceutical care, JCPP should market to the public its concept of pharmacists' mission. APhA should analyze pharmaceutical services currently provided and promote postgraduate training programs in pharmaceutical care. ACPE must focus on ways pharmacists can achieve the competencies required for pharmaceutical care, and AACP must ensure that academic programs are consistent with the needed competencies. ASHP should hold a national conference on implementation of pharmaceutical care, create a commission for this purpose, direct more effort at pharmacists practicing in nonhospital settings, and accelerate its clinical skills development program. Employers should put less emphasis on "clinical" designations and Pharm.D. degrees and more on the ability to provide pharmaceutical care. Implementation of pharmaceutical care is imperative.

P & T Committee interview: communication and education contribute to an effective formulary system.

In this exclusive Hospital Formulary interview, Daniel Hinthorn, MD, and Harold Godwin, MS, chairman and secretary of the University of Kansas Medical Center P & T Committee, share that evolution, not revolution, has made for smooth transition in changes of formulary policy at their institution. They attribute the success of their P & T Committee to the collective experience of their members, to an educational rather than a confrontational approach, and to the active role of clinical pharmacists on the floors. Members of the University of Kansas Medical Center's P & T Committee view their involvement as a forum for valuable interaction, one which helps them stay at the forefront of important therapeutic advancements.

Pharmacy and therapeutics committee review of the parenteral cephalosporins.

The process by which a 530-bed university hospital reduced, from three to one, the number of parenteral cephalosporins in its formulary is discussed. In January 1975, cephapirin sodium was added to the formulary which already included cefazolin sodium and cephalothin sodium. Nine months later, the pharmacy and therapeutics committee decided to delete cephapirin and cephalothin from the formulary. The pharmacy department had supplied background information to the committee, and infectious disease specialists advised the committee. The decision was ratified by the executive committee of the medical staff. The rationale for the decision and its implementation, including staff communications, are discussed.