Procainamide therapy, physical performance and energy expenditure in the Schwartz-Jampel syndrome

The effects of procainamide administration were assessed in a 5-yr-old boy with Schwartz-Jampel syndrome (chondrodystrophic myotonia). Without procainamide the resting metabolic rate was found to be significantly higher than in an age-matched control group. With a serum level of 3.8 mg l-1 procainamide a reduction of the resting metabolic rate of 22% was observed, and times needed to climb stairs and to re-open eyes after forceful contraction (blepharospasm) were significantly reduced.     

Cognitive and neuroradiological findings in myotonic dystrophy.

Cognitive functions were investigated in 37 patients with myotonic dystrophy (MD) and correlated with clinical and neuroradiological variables. The whole cognitive performance was at a low-average level; in about 1/3 of the subjects, in fact, the scores at the neuropsychological tests were below the normal range. There was a consistent trend for patients with inheritance on maternal side to perform worse on Wechsler verbal score and to present cerebral atrophy. In 7 out of 12 subjects focal white matter lesions were found at nuclear magnetic resonance. The significance of these findings and its relation to cognitive performance are discussed.     

Increased bone turnover during the third trimester of pregnancy and decreased bone mineral density after parturition in adolescents as compared to age-matched control patients.

To evaluate the impact of pregnancy on bone, we studied bone turnover at the first (T1) and third (T3) trimester of gestation in 58 adolescents and 28 healthy adolescents who had never been pregnant. Total body (TB) and lumbar spine (LS) bone mineral density (BMD) and body composition were evaluated by dual-energy X-ray absorptiometry in all control patients (C) and after parturition in 28 pregnant patients (G). Paired and unpaired t tests, Mann-Whitney and Pearson correlation tests were used. Bone turnover markers were above the reference range for adult women in more than 80% of the adolescents, with no difference between C and G patients at T1. Increase in urinary N-telopeptide crosslinks of type I collagen and serum bone-specific alkaline phosphatase, markers of bone turnover, was seen during pregnancy ( p < 0.0001). Body composition did not differ between groups, but LS BMD, percentage of expected LS BMD, LS Z-score, percentage of expected TB BMD and TB Z-score were lower in G than C patients ( p < 0.05). TB BMD was positively correlated with LS BMD (r2 = 0.52). The inverse correlations between bone markers and LS BMD suggest that the increased bone turnover during pregnancy probably explains the low bone density after parturition. The impact on future peak bone mass must be studied.     

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.     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

Isolated complete orbital infarction: a common carotid artery occlusion syndrome

When blood flow through the internal and external carotid arteries is completely interrupted by ipsilateral common carotid artery occlusion, the arterial orbital circulation may be more compromised than the brain supply. We studied a pure and extreme example of this situation in a patient who presented with acute orbital infarction, but no cerebral ischemia on clinical, CT and single-photon emission computerized tomography (SPECT) grounds. Ipsilateral blindness corresponded to retinal, choroidal and optic nerve infarction. The pattern of ophthalmoplegia, with relative sparing of adduction, was more compatible with a muscle than a nerve dysfunction, but a reactive dilated pupil, corneal anesthesia, and orbital pain suggested that the intraorbital branches of the ocular motor nerves and ophthalmic division of the trigeminal nerve were not spared. In addition, signs of widespread ocular ischemia were present. Sequential examinations documented the evolution pattern over 1 year. The absence of an orbital collateral supply from the contralateral external carotid and muscular cervical arteries systems, which contrasted with an adequate middle cerebral artery supply via the contralateral internal carotid artery, may explain this isolated and complete form of orbital ischemia due to common carotid artery occlusion.     

Brain and spinal cord hemorrhage in long-term survivors of malignant pediatric brain tumors: a possible late effect of therapy

Three children with malignant primary CNS tumors treated with craniospinal radiotherapy developed intraparenchymal hemorrhages a median of 5 years following therapy in sites distant from the primary tumor. Radical surgical procedures disclosed fresh and old hematoma, gliosis, and necrosis in all 3 patients and an aggregation of abnormal microscopic blood vessels in two. No tumor was found. All 3 patients remain in long-term (greater than 10 years) continuous remission.     

Evidence that dopamine in the nucleus accumbens is involved in the ability of rats to switch to cue-directed behaviours.

Recently we have reported that injections of d-amphetamine into the nucleus accumbens enhanced the number of switches to cue-directed behaviours without an effect on the number of switches to non-cue-directed behaviours in a swimming test. In the present study we investigated to what extent this effect is mediated via the dopaminergic system in the nucleus accumbens. For that purpose drugs selective for D1- and D2-receptors were studied in this swimming test. It was found that the selective D2-agonist LY 171 555 (50 ng/0.5 microliters) enhanced the number of different cue-directed behaviours. The selective D2-antagonist raclopride (50 ng/0.5 microliters) decreased it. Furthermore an ineffective dose of raclopride attenuated the effect of LY 171 555. Both the selective D1-antagonist SCH 23390 (400 ng/0.5 microliters) and the selective D1-agonist SKF 38393 (50-400 ng/0.5 microliters) decreased the number of different cue-directed behaviours. The effect induced by SCH 23390 could not be blocked by SKF 38393. Similarly the effect induced by SKF could not be attenuated by SCH 23390. These data point to a role for dopamine D2-receptors in the ability to switch to cue-directed behaviours. The present findings do not yet allow the conclusion that D1-receptors are involved.     

A survey of hospitals in New York State treating psychiatric patients with chemical abuse disorders.

Eighty-eight of 143 hospitals in New York State providing psychiatric inpatient treatment responded to a mailed questionnaire designed to determine the size of three subgroups of chemical abusers--alcohol abusers, drug abusers, and polychemical abusers--among inpatients with psychiatric diagnoses, as well as the availability of services for these patients. Data for New York City and its metropolitan area were analyzed separately. In 1987 almost one-third of psychiatric admissions both in and outside the metropolitan area had comorbid chemical abuse disorders. Seventy-five percent of patients in the metropolitan area with comorbid chemical abuse had a drug abuse disorder; in rural areas 88 percent of patients with chemical abuse disorders abused alcohol. Both hospital- and community-based aftercare services, especially in the metropolitan area, were less available to psychiatric patients with chemical abuse than to patients without these disorders.