Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

A measurement of the efficacy of nosocomial infection control using the 95 per cent confidence interval for infection rates

From 1981 through 1985, the authors studied the changes in monthly nosocomial infection rates at the University of Virginia Hospital in Charlottesville, Virginia using the 95% confidence interval for infection rates as a marker of the efficacy of infection control activities. For a 99-month baseline period, monthly infection rates were calculated and the 95% confidence interval was established. In the 60 study months, each monthly rate was compared with the 95% confidence interval for that particular month. At the end of each study year, the monthly infection rates were incorporated into the existing confidence interval. Of 60 monthly rates during the study period, 30 were below the confidence interval (p less than 0.00001), two were above the confidence interval (p = 0.23), and 28 were within the confidence interval. Since there was no reduction in surveillance activity, patient case-mix index, or laboratory sensitivity for organism recovery, these results suggest that monthly nosocomial infection rates at this hospital have decreased when compared with the baseline period. The use of the 95% confidence interval may provide a measure of the efficacy of infection control activities, suggest temporal intervals requiring more intensive infection surveillance, and provide a method for examining the variability in monthly infection rates.     

Extended-release divalproex in bipolar and other psychiatric disorders: A comprehensive review

Bipolar disorder can be a devastating disease state for individuals with the disease and also for family members. Proper recognition and treatment is vital to the successful management of this disease state. Through increased community and practitioner awareness, along with efforts to increase awareness for proper assessment, the rate of diagnosed bipolar disorder is increasing. Recent years have brought about the introduction of several new medications with approved indications for the treatment of bipolar disorder. In addition to new agents, traditional mood stabilizing medications have also been released in different formulations to better enhance tolerability without jeopardizing efficacy. One particular product is extended-release divalproex sodium. In the following article, we review the clinical presentation of bipolar disorder, its epidemiology, and the pharmacokinetics and mechanism of action for divalproex. In addition, we specifically review the role of extended-release divalproex in bipolar disorder through a critical analysis of the currently available published primary literature.     

Affective neural circuitry during facial emotion processing in pediatric bipolar disorder.

BACKGROUND: Facial emotions are central to human interaction. Identifying pathophysiology in affect processing circuitry that supports the ability to assess facial emotions might facilitate understanding of affect regulation in pediatric bipolar disorder. METHODS: Ten euthymic, unmedicated pediatric bipolar patients and 10 healthy control subjects matched for age, gender, race, socioeconomic status, and IQ were scanned with functional magnetic resonance imaging. Angry, happy, and neutral faces were presented in 30-sec blocks, with a 20-sec rest period between blocks. Subjects were asked to press a button when each face appeared, to ensure that attention was maintained on-task. RESULTS: In bipolar patients, in response to both angry and happy faces relative to neutral faces, we observed reduced activation of right rostral ventrolateral prefrontal cortex together with increased activity in right pregenual anterior cingulate, amygdala, and paralimbic cortex. Bipolar patients also showed reduced activation of visual areas in occipital cortex together with greater activation in higher-order visual perceptual areas, including superior temporal sulcus and fusiform gyrus with angry faces and posterior parietal cortex with happy faces. CONCLUSIONS: Findings document a disturbance in affective neurocircuitry in pediatric bipolar disorder. Reduced activation in ventrolateral prefrontal cortex might reflect diminished top-down control that leads to the observed exaggerated activation in amygdala and paralimbic areas. Changes in occipital areas might represent an effort to gate sensory input when affective responses to the faces could not be successfully modulated. Disturbances in affect processing circuitry could contribute to emotional dysregulation and social cognitive difficulties in bipolar youth.     

Adenocarcinoma Metastasis of the Intertransversarius Cervicis Muscle Eliciting a Right Forelimb Lameness in a Dog

This article describes identification of a metastatic adenocarcinoma to the intertransversarius cervicis muscle using magnetic resonance imaging (MRI) in a dog that presented with chronic lameness of the right forelimb. Magnetic resonance imaging revealed a right sided, ovoid signal abnormality within the intertransversarius cervicis muscle lateral to the sixth cervical (C6) vertebra. The lesion was uniform, hyperintense on T2‐ and isointense on T1‐weighted images to muscle and exhibited uniform contrast enhancement on T1‐weighted images. The MRI findings were consistent with a neoplasia. Surgical excision was performed. Histopathological diagnosis was metastatic fibrous adenocarcinoma. The dog recovered rapidly but 6 months post‐operatively he was killed because of lung metastases. Necropsy was declined and the primary tumour could not be identified.     

Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome.

BACKGROUND: There are limited studies of large cohorts of patients with specific polysaccharide antibody deficiency (SPAD) syndrome. OBJECTIVE: To study the clinical and laboratory characteristics of patients with specific polysaccharide antibody deficiency syndrome. METHODS: We retrospectively studied 75 patients with total IgG levels of at least 500 mg/dL and fewer than 9 of 12 responses to vaccination with pneumococcal vaccine polyvalent. Exclusion criteria included an IgG level less than 500 mg/dL, established immunodeficiency syndrome, and secondary immunodeficiency. RESULTS: The most common clinical presentation was frequent infections (n = 69; 92%), including sinusitis (n = 53; 77%), pneumonia (n = 29; 42%), ear infections (n = 18; 26%), and bronchitis (n = 19; 28%). Other presentations were systemic infections (n = 5; 7%), autoimmune or rheumatic diseases (n = 6; 8%), and chronic diarrhea (n = 4; 5%). The median IgG2 level of patients with no response to pneumococcal vaccine polyvalent tended to be lower than that of patients with at least 1 response (150 vs 193 mg/dL, respectively; P = .06). There was no association between total IgG level (categorized as 500-600 or > or = 600 mg/dL) and frequency of infection (P = .43). Patients with fewer responses to pneumococcal vaccine polyvalent and a higher frequency of infections were more likely to receive intravenous immunoglobulin (IVIG) therapy (P = .01 and .003, respectively). Treatment with IVIG significantly reduced the number of infections (P < .001). CONCLUSION: Patients with no response to pneumococcal vaccine polyvalent tended to have lower IgG2 levels; those with fewer responses were more likely to receive IVIG therapy.     

The Washington University-Barnes Hospital experience with lung transplantation. Washington University Lung Transplantation Group

OBJECTIVE.--To review our experience with lung transplantation, emphasizing recipient selection, choice of procedure, functional results, and outcome. DESIGN.--Retrospective review of patients who received lung transplants at Barnes Hospital, St Louis, Mo, between July 1, 1988, and January 31, 1991. SETTING.--Washington University School of Medicine, St Louis, Mo, and Barnes Hospital, a medical school and its affiliated referral hospital, respectively. PATIENTS.--Sixty-nine lung transplant procedures were performed in 66 recipients. Patients with clinically and physiologically severe lung disease were selected according to predetermined guidelines. Underlying diseases in the recipients included chronic obstructive pulmonary disease, alpha 1-antitrypsin deficiency emphysema, cystic fibrosis, pulmonary fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome associated with an atrial septal defect, bronchiectasis, eosinophilic granuloma, and lymphangiomyomatosis. INTERVENTION.--Double-lung, bilateral sequential, and single-lung transplantations were performed. Eight patients underwent en bloc double-lung transplantations or a modification of this procedure with separate bronchial anastomoses. Thereafter, the bilateral sequential approach to replacement of both lungs was performed in 26 patients. Thirty-two patients underwent single-lung transplantations. MAIN OUTCOME MEASURES.--Pulmonary function tests, arterial blood gas levels, pulmonary artery pressure, pulmonary vascular resistance, and actuarial survival. RESULTS.--Actuarial survival at 1 year for the 66 lung transplant recipients was 79%. Actuarial survival at 1 year was 82% for the bilateral lung transplant recipients and was 90% for the single-lung transplant recipients. In patients with either restrictive or obstructive lung disease, pulmonary function tests and arterial blood gas levels improved markedly after lung transplantation. In patients with primary pulmonary hypertension or Eisenmenger's syndrome, the pulmonary artery pressure decreased and the cardiac index increased into the normal range after single-lung transplantation. CONCLUSIONS.--In carefully selected patients with end-stage lung disease, single-lung and bilateral lung transplantations can significantly improve functional capacity, with promising early actuarial survival statistics after 1 year.     

227. Der gestielte Peronaeus-Insellappen als Alternative zum freien Gewebetransfer am distalen Unterschenkel und Fuß

Zusammenfassung Der distal gestielte Peronaeus-Insellappen, erstmals 1984 von Yoshimura publiziert, ist ein fasciocutaner Lappen, der über einen Hautast der A. peronea ernährt wird. Die A. peronea weist distal, ca 5 cm oberhalb des Sprunggelenkes, einen Ramus perforans zur A. tibialis anterior auf und über einen Ramus communicans besteht eine Verbindung zur A. tibialis posterior. Unterbindet man die A. peronea proximal der Abgangsstele der Hautarterie, so kommt es über die distalen Anastomosen zur retrograden Durchblutung. Der distal gestielte Peronaeuslappen besitzt einen großen Schwenkbereich bis hin zum Fußrücken. Die Durchgängigkeit der drei Unterschenkelarterien ist die Voraussetzung für die Durchführbarkeit. Die Indikation ergibt sich bei oberflächlichen Knochen- und Hautdefekten im distalen Unterschenkeldrittel, der Malleolengabel, der Ferse und des Fußrückens.