Infantile autism—fragile X: Molecular findings support genetic heterogeneity

Twenty-two members of 18 families with autism have been examined for the presence of mutations and abnormal methylation in the FMR-1 region at Xq27.3. All patients fulfilled diagnostic criteria of infantile autism. A characteristic pattern of insertion and methylation were detected after Southern blot analysis in 7 autistic individuals expressing the fragile site at Xq27.3. Normal DNA patterns were observed in 15 autistic boys cytogenetically negative for the fragile site. The results indicate a lack of involvement of the FMR-1 region in infantile autists negative for fragile X expression. © 1992 Wiley-Liss, Inc.     

Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes

We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine.     

Children With Chronic Physical Disorders: Maternal Reports of Their Psychological Adjustment

Advances in biomedical science have resulted in dramatic improvementsin the medical care of chronically ill and handicapped children.Past measurement problems have resulted in a lack of clarityregarding the psychological adjustment of these children. Themothers of 270 chronically ill and handicapped children wereadministered the Child Behavior Checklist in an attempt to identifypatterns of behavioral functioning across six pediatric chronicdisorders: juvenile diabetes, spina bifida, hemophilia, chronicobesity, juvenile rheumatoid arthritis, and cerebral palsy.In general, it was found that children in all chronic disordergroups were perceived by their mothers as evidencing on theaverage more behavioral and social competence problems thanexpected based on norms for children in general. However, theirbehavioral and social adjustment was reported as better thanthat of a normative sample of children referred to mental healthclinics. There were essentially no differences between childrenwith different chronic disorders in terms of behavior problemsand social competence. The results were taken to support theview that these children were as a group at risk for adjustmentproblems. They were also discussed in terms of the noncategorialapproach, which suggests that similar psychosocial challengesare faced across pediatric chronic physical disorders.     

Oral session 1: General neurology

Oral session 1: General neurology     

Human spumaretrovirus antibody reactivity in multiple sclerosis

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.     

Combined action of phthalocyanine photosensitization and gamma-radiation on mammalian cells

The response of Chinese hamster cells and human lymphocytes to the combined action of photosensitization by chloroaluminium phthalocyanine tetrasulfonate and gamma-radiation was studied using colony-forming ability and [3H]thymidine incorporation following mitogenic stimulation respectively, as endpoints. The action of both treatments was usually additive regardless of the sequence of application. However, in human lymphocytes irradiated at low temperature, the photosensitization interacted synergistically with the subsequent ionizing radiation; in this experiment the initial photosensitization reduced the yield of micronuclei produced by gamma-radiation.     

Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.

This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.     

Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers.

Ampakines act as positive allosteric modulators of AMPA-type glutamate receptors and facilitate hippocampal long-term potentiation (LTP), a mechanism associated with memory storage and consolidation. The present study investigated the acute effects of farampator, 1-(benzofurazan-5-ylcarbonyl) piperidine, on memory and information processes in healthy elderly volunteers. A double-blind, placebo-controlled, randomized, cross-over study was performed in 16 healthy, elderly volunteers (eight male, eight female; mean age 66.1, SD 4.5 years). All subjects received farampator (500 mg) and placebo. Testing took place 1 h after drug intake, which was around Tmax for farampator. Subjects performed tasks assessing episodic memory (wordlist learning and picture memory), working and short-term memory (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Information processing was assessed with a tangled lines task, the symbol digit substitution test (SDST) and the continuous trail making test (CTMT). Farampator (500 mg) unequivocally improved short-term memory but appeared to impair episodic memory. Furthermore, it tended to decrease the number of switching errors in the CTMT. Drug-induced side effects (SEs) included headache, somnolence and nausea. Subjects with SEs had significantly higher plasma levels of farampator than subjects without SEs. Additional analyses revealed that in the farampator condition the group without SEs showed a significantly superior memory performance relative to the group with SEs. The positive results on short-term memory and the favorable trends in the trail making test (CTMT) are interesting in view of the development of ampakines in the treatment of Alzheimer's disease and schizophrenia.     

User satisfaction with a real-time automated feedback system for general practitioners: a quantitative and qualitative study.

OBJECTIVE: The GRIF automated feedback system produces real-time comments on the appropriateness of diagnostic tests ordered by general practitioners (GPs) based on recommendations from accepted national and regional practice guidelines. We investigated the experiences of GPs with this system and, more specifically, with the recommendations produced by the system as well as their views on using this system in daily practice. SETTING: We tested the GRIF system in an experiment in a laboratory setting and in a daily practice trial. STUDY PARTICIPANTS: General practitioners. INTERVENTION: In the laboratory experiment, GPs used the GRIF system to assess the appropriateness of 30 request forms. Each of the GPs was confronted with requests they had submitted to the diagnostic unit of the hospital in the past. In the field trial, the GRIF system was applied during patient consultations for 1 year. MAIN OUTCOME MEASURES: We measured GPs' satisfaction with the system using a questionnaire, and also conducted group discussions (in the laboratory experiment) and in-depth interviews (in the field trial) to elicit GPs' opinions of and experiences with the system. In addition, we explored GPs' reasons for not accepting the comments offered by the GRIF system. RESULTS: The results show that the GPs in the laboratory experiment had more positive attitudes towards the system compared with participants in the field trial. All discussion groups and most of the GPs in the field trial regarded receiving the immediate feedback during the test ordering process as an important advantage. The most frequently mentioned reason to reject the recommendation was disagreement with the content and/or the recommendations in the practice guidelines. CONCLUSION: Apart from securing agreement on guideline content, a prerequisite for using GRIF in daily practice on a large scale is that more attention is paid to promotion of the guidelines and their adoption, and stimulation of a positive attitude towards the practice guidelines among the users.