Patterns of adaptation to children's food allergies.

BACKGROUND: Families with food allergy (FA) are at risk of reduced quality of life and elevated anxiety. A moderate level of anxiety may be beneficial to sustain vigilance for food avoidance; however, excessive anxiety may increase risk for burden and maladjustment. The current study presents a framework for understanding the patterns of adaptation to FA across families and to identify typologies of families that would benefit from intervention. METHODS: Participants included 57 children, 6-12 years old with documented FA, and their mothers. Families were assessed using the Food Allergy Management and Adaptation Scale. Families also completed measures of quality of life, anxiety, FA management, and psychosocial impairment. RESULTS: A hierarchical cluster analysis revealed that 56 of the 57 families of food-allergic children were categorized into four groups that differed on their adequacy of family FA management, levels of anxiety, and balanced psychosocial functioning: balanced responders (n = 23; 41%), high responders (n = 25; 45%), and low responders (n = 3; 5%). The fourth group, anxious high responders (n = 5; 9%), was characterized by extremely high maternal FA anxiety scores and low scores for balanced integration of FA management and psychosocial functioning. Families in clusters differed across illness and psychosocial outcome variables. CONCLUSION: Families with FA were characterized by patterns of FA management, anxiety, and ability to integrate FA demands into daily life. Identified adaptation patterns correspond with clinical impressions and provide a framework for identifying families in need of intervention.

[Carcinoid tumor of the testis]. / Insuläres Karzinoid des Hodens.

A 69-year-old man presented with a 2.4 cm painless mass in his right testis. Inguinal orchiectomy was performed. Histologically a carcinoid tumor of the testis was diagnosed. These neuroendocrine, noninvasive tumors are very rare, representing 0.23% of all testicular neoplasms. In 10% these tumors are associated with carcinoid syndrome and in 20% with metastatic disease.

Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications.

Conditions associated with identification of mentally ill youths in juvenile detention.

The current study examines the prevalence and severity of psychiatric symptoms in incarcerated youth. A random sample of youth ages 13-17 who were referred for mental health services (n=120) and not referred for services (n=120) at a juvenile detention facility were studied. Psychopathology was evaluated using the Diagnostic Interview Schedule for Children and the Child Behavior Checklist. Ninety-six percent of referred youth and 69% of non-referred youth had one or more psychiatric diagnoses. Co-morbidity was common in both groups. The findings suggest that youths in the juvenile justice system have noteworthy psychopathology that often remains unidentified.

Laser microdissection and microarray analysis of breast tumors reveal ER-alpha related genes and pathways.

About 70-80% of breast cancers express estrogen receptor alpha (ER-alpha), and estrogens play important roles in the development and growth of hormone-dependent tumors. Together with lymph node metastasis, tumor size, and histological grade, ER status is considered as one of the prognostic factors in breast cancer, and an indicator for hormonal treatment. To investigate genes and pathways that are associated with ER status and epithelial cells in breast tumor, we applied laser capture microdissection (LCM) technology to capture epithelial tumor cells from 28 lymph node-negative breast tumor samples, in which 17 patients had ER-alpha+ tumors, and 11 patients have ER-alpha- tumors. Gene expression profiles were analysed on Affymetrix Hu133A GeneChip. Meanwhile, gene profiles using total RNA isolated from bulk tumors of the same 28 patients were also generated. In total, 146 genes and 112 genes with significant P-value and having significant differential expression between ER-alpha+ and ER-alpha- tumors were identified from the LCM data set and bulk tissue data set, respectively. A total of 61 genes were found to be common in both data sets, while 85 genes were unique to the LCM data set and 51 genes were present only in the bulk tumor data set. Pathway analysis with the 85 genes using Gene Ontology suggested that genes involved in endocytosis, ceramide generation, Ras/ERK/Ark cascade, and JAT-STAT pathways may play roles related to ER. The gene profiling with LCM-captured tumor cells provides a unique approach to study epithelial tumor cells and to gain an insight into signaling pathways associated with ER.

Intracellular signaling pathways involved in mediating the effects of lead on the transcription factor Sp1.

It has been well established that exposure to Pb during critical periods of brain development results in both cognitive and behavioral deficits. Although the mechanism by which Pb induces developmental neurotoxicity is unknown, it may involve alterations in transcription of genes that are essential for growth and differentiation. Recent studies reveal that Pb interferes with growth and differentiation by acting on the transcription factor Sp1. Pb-induced changes in the activity of Sp1 may be consequent to alterations in intermediates in signal transduction pathways. This study examines both in vivo and in vitro the role of signaling factors in mediating the effects of Pb on Sp1 DNA-binding. Hippocampal developmental profiles of Sp1 DNA-binding, PKC, and MAPK protein levels were monitored in Pb-exposed rats. Pb exposure resulted in an induction of Sp1 DNA-binding during PND 5-10 followed by a subsequent decline on PND 15-20. The protein expression profiles for PKCalpha and MAPK followed a relatively similar pattern. To examine the interdependence between Sp1 DNA-binding, PKCalpha, and MAPK, PC12 cells were exposed to Pb and/or NGF. Pb or NGF exposure increased Sp1 DNA-binding. Addition of the PKC inhibitor (staurosporine) diminished NGF and Pb-induced Sp1 DNA-binding, while the MAPK inhibitor (PD 98059), completely abolished both basal and induced Sp1 DNA-binding. These findings demonstrate that Sp1 DNA-binding is regulated by PKC and MAPK, which may serve as mediators through which Pb may indirectly modulate Sp1 DNA-binding.

[Intraoperative histological sections in obstetric brachial plexus lesions--comparison of macroscopic appearance, HE staining and toluidine blue staining]. / Intraoperative Schnellschnittdiagnostik bei der geburtstraumatischen Plexusläsion - Gegenüberstellung von Makroskopie, HE-Schnellschnitten und Semidünnschnitten mit Toluidinblau-Färbung.

In brachial plexus lesions and their revision, evaluation of nerve stumps is very important for the reconstructive strategy. We intraoperatively perform cryostat sections, Haematoxilin-Eosin (HE) stained, and compare the clinical appearance of the nerves to the microscopic results. Toluidine blue staining is later used to validate the structural details. Intraneural fibrosis can be traced safely with both staining methods, in root avulsions a histology is helpful, too. For more proximal, intraforaminal lesions semithin section stained with toluidine-blue are less informative than are HE-stained cryostat sections. In these lesions the clinical control by electrical stimulation and evoked potentials is superior.

Variation in melanin content and composition in type V and VI photoexposed and photoprotected human skin: the dominant role of DHI.

A combination of techniques, including high-performance liquid chromatography (HPLC), spectrophotometric measurements, and a novel method for quantifying melanosome morphology, were applied to the analysis of melanin content and composition in highly pigmented (Fitzpatrick type V and VI) human skin. We found that total epidermal melanin content is significantly elevated in photoexposed type V and VI skin (approximately 1.6 x), while analysis of individual melanin components suggests that pheomelanin content increases only slightly, whereas 5,6-dihydroxyindole-2-carboxylic acid (DHICA)-eumelanin and to a greater extent 5,6-dihydroxyindole (DHI)-eumelanin content are both markedly elevated. Analysis of the relative composition of epidermal melanin in these subjects revealed that DHI-eumelanin is the largest single component (approximately 60-70%), followed by DHICA-eumelanin (25-35%), with pheomelanin being a relatively minor component (2-8%). Moreover, there was a comparative enrichment of DHI-eumelanin at photoexposed sites, with a corresponding decline in the relative contributions from DHICA-eumelanin and pheomelanin. There was also a good correlation and close agreement between the concentration of spheroidal melanosomes determined by morphological image analysis and the concentration of pheomelanin determined by a combination of HPLC and spectrophotometric analysis (r = 0.89, P < 0.02). This study demonstrates the usefulness of melanosome morphology analysis as a sensitive new method for the quantification of melanin composition in human skin. The data also suggest that DHI-eumelanin formation is the dominant pathway for melanin synthesis in heavily pigmented (Fitzpatrick V and VI) skin types in vivo, and is the favoured pathway when melanin production is increased in chronically photoexposed skin.

Long-term survival after mitral valve replacement in children aged <5 years: a multi-institutional study.

BACKGROUND: Short- and long-term outcomes after prosthetic mitral valve replacement (MVR) in children aged <5 years are ill-defined and generally perceived as poor. The experience of the Pediatric Cardiac Care Consortium (45 centers, 1982 to 1999) was reviewed. METHODS AND RESULTS: MVR was performed 176 times on 139 patients. Median follow-up was 6.2 years (range 0 to 20 years, 96% complete). Age at initial MVR was 1.9+/-1.4 years. Complications after initial MVR included heart block requiring pacemaker (16%), endocarditis (6%), thrombosis (3%), and stroke (2%). Patient survival was as follows: 1 year, 79%; 5 years, 75%; and 10 years, 74%. The majority of deaths occurred early after initial MVR, with little late attrition despite repeat MVR and chronic anticoagulation. Among survivors, the 5-year freedom from reoperation was 81%. Age-adjusted multivariable predictors of death include the presence of complete atrioventricular canal (hazard ratio 4.76, 95% CI 1.59 to 14.30), Shone's syndrome (hazard ratio 3.68, 95% CI 1.14 to 11.89), and increased ratio of prosthetic valve size to patient weight (relative risk 1.77 per mm/kg increment, 95% CI 1.06 to 2.97). Age- and diagnosis-adjusted prosthetic size/weight ratios predicted a 1-year survival of 91% for size/weight ratio 2, 79% for size/weight ratio 3, 61% for size/weight ratio 4, and 37% for size/weight ratio 5. CONCLUSIONS: Early mortality after MVR can be predicted on the basis of diagnosis and the size/weight ratio. Late mortality is low. These data can assist in choosing between MVR and alternative palliative strategies.

Metal distribution in Clark Fork River sediments.

Accurate sampling of pore waters and sediments in gravel river beds is problematic because cobbles preclude most coring techniques, while the angularity of sand grains destroys the membranes of standard pore water samplers. In the Clark Fork River, the recipient of over 100 years of mining activity, a modified single tube core-freezing device was used to profile bed sediment (approximately 65% cobbles and 35% gravel substrate), and a novel pore water sampler was developed to collect interstitial water. In the sediment, the <63 microm fraction comprised <4 wt % yet contained approximately an order of magnitude higher metal concentrations compared to the 63 microm-2 mm fraction (constituting approximately 20% of the mass). However, on a mass basis the sand fraction contained 60% of the metals, compared to 40% in the clay/silt fraction in the gravels, while in point bars the distribution was approximately 50:50. The metals occur predominantly in sulfides frequently armored with an oxide rim and other sparingly soluble phases that may explain the low pore water metal concentrations. These data demonstrate that consideration of multiple particle size cutoffs is necessary to accurately characterize fluvial bed sediment metal conditions and that the form of the metal is important in understanding metal solubility in the benthos.

Priorities among recommended clinical preventive services.

BACKGROUND: Many recommended clinical preventive services are delivered at low rates. Decision-makers who wish to improve delivery rates, but face competing demands for finite resources, need information on the relative value of these services. This article describes the results of a systematic assessment of the value of clinical preventive services recommended for average-risk patients by the U.S. Preventive Services Task Force. METHODS: The assessment of services' value for the U.S. population was based on two dimensions: burden of disease prevented by each service and cost effectiveness. Methods were developed for measuring these criteria consistently across different types of services. A companion article describes the methods in greater detail. Each service received 1 to 5 points on each of the two dimensions, for total scores ranging from 2 to 10. Priority opportunities for improving delivery rates were determined by comparing the ranking of services with what is known of current delivery rates nationally. RESULTS: The highest ranked services (scores of 7+) with the lowest delivery rates (< or =50% nationally) are providing tobacco cessation counseling to adults, screening older adults for undetected vision impairments, offering adolescents an anti-tobacco message or advice to quit, counseling adolescents on alcohol and drug abstinence, screening adults for colorectal cancer, screening young women for chlamydial infection, screening adults for problem drinking, and vaccinating older adults against pneumococcal disease. CONCLUSIONS: Decision-makers can use the results to set their own priorities for increasing delivery of clinical preventive services. The methods provide a basis for future priority-setting efforts.

Methods for priority setting among clinical preventive services.

Methods used to compare the value of clinical preventive services based on two criteria-clinically preventable burden (CPB) and cost effectiveness (CE)-are described. A companion article provides rankings of clinical preventive services and discusses its uses for decision-makers; this article focuses on the methods, challenges faced, and solutions. The authors considered all types of data essential to measuring CPB and CE for services recommended by the U.S. Preventive Services Task Force and developed methods essential to ensuring valid comparisons of different services' relative value.

Normalization of ventricular repolarization with flecainide in long QT syndrome patients with SCN5A:DeltaKPQ mutation.

BACKGROUND: The Long QT Syndrome (LQTS) is a genetic channelopathy with life-threatening implications. The LQT3 form of this disease is caused by mutations of the SCN5A sodium-channel gene. A specific mutation, SCN5A:DeltaKPQ, is associated with repetitive reopenings of the sodium channel and prolonged inward current. This dominant inward current is manifest on the electrocardiogram as QT prolongation. Flecainide is a potent blocker of the open sodium channel. METHODS AND RESULTS: The effect of flecainide on the duration of the QT-interval and the T-wave morphology was systematically evaluated in five male patients age 2-64 years having the SCN5A:DeltaKPQ mutation. After baseline electrocardiograms were obtained, low-dose oral flecainide was administered for 48 hours. Serial electrocardiograms and blood flecainide levels were obtained during flecainide therapy. The QTc interval decreased on average by 104 ms, from a baseline value of 565 +/- 60 ms to 461 +/- 23 ms (P < 0.04) at a mean flecainide level of 0.28 +/- 0.08 mg/L, with shortening of the QTonset interval (P < 0.003) and normalization of T-wave morphology. The effects of flecainide were compared with oral mexiletine in two patients, with flecainide showing greater QTc shortening and more complete normalization of repolarization. No adverse side effects or proarrhythmia were observed with flecainide in this study. CONCLUSION: Low-dose, oral flecainide consistently shortened the QTc interval and normalized the repolarization T-wave pattern in five LQT3 patients with SCN5A:DeltaKPQ mutation. This preliminary study indicates that low-dose flecainide is a promising therapeutic agent for LQTS patients with the SCN5A:DeltaKPQ sodium channel mutation.

Is arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias.

BACKGROUND: Use of automatic external defibrillators (AEDs) in children aged <8 years is not recommended. The purpose of this study was to develop an ECG database of shockable and nonshockable rhythms from a broad age range of pediatric patients and to test the accuracy of the Agilent Heartstream FR2 Patient Analysis System for sensitivity and specificity. METHODS AND RESULTS: Children aged

Lead exposure in pheochromocytoma (PC12) cells alters neural differentiation and Sp1 DNA-binding.

Previous studies have revealed that lead modulates the DNA-binding profile of the transcription factor Sp1 both in vivo and in vitro (Dev Brain Res 1998;107:291). Sp1 is a zinc finger protein, that is selectively up-regulated in certain developing cell types and plays a regulatory role during development and differentiation (Mol Cell Biol 1991;11:2189). In NGF-stimulated PC12 cells, Sp1 DNA-binding activity was induced within 48 h of exposure of NGF naïve cells. Exposure of undifferentiated PC12 cells to lead alone (0.1 microM) also produced a similar increase in Sp1 DNA-binding. Since lead altered the DNA-binding profile of Sp1 in newly differentiating cells, neurite outgrowth was assessed as a morphological marker of differentiation to determine whether or not the effects of lead on differentiation were restricted to the initiation phase (unprimed) or the elaboration phase of this process (NGF-primed). NGF-primed and unprimed PC12 cells were prepared for bioassay following exposure to various concentrations of NGF and/or lead. Neurite outgrowth was measured at 48 and 72 h during early stages of NGF-induced differentiation and at 14 h in NGF primed/replated cells. In the absence of NGF, exposure to lead alone (0.025, 0.05, 0.1 microM) promoted measurable neurite outgrowth in unprimed PC12 cells at 48 and 72 h. A similar phenomenon was also observed in primed/replated PC12 cells at 14 h. However, this effect was two to five times greater than unprimed control cells. In the presence of NGF, a similar trend was apparent at lower concentrations, although the magnitude and temporal nature was different from lead alone. In most cases, the administration of higher lead concentrations (1 and 10 microM), in both the absence or presence of NGF, was less effective than the lower concentrations in potentiating neurite outgrowth. These results suggest that lead alone at low doses may initiate premature stimulation of morphological differentiation that may be related to lead-induced alterations in Sp1 binding to DNA.