Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.

Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].     

Benefits and risks of simvastatin in patients with familial hypercholesterolaemia.

Familial hypercholesterolaemia is a frequent, inherited, monogenic disorder, associated with accelerated development of atherosclerotic disease leading to coronary artery disease. Life expectancy of patients with familial hypercholesterolaemia is reduced by 15-30 years unless they are adequately treated with lipid-lowering therapy. Given the chronic nature of this disease, the selection of a therapeutic approach should be strongly based on its long-term safety and tolerability. The introduction of HMG-CoA reductase inhibitors has revolutionised the treatment of familial hypercholesterolaemia.Simvastatin 40-80 mg/day effectively reduces serum low density lipoprotein (LDL)-cholesterol levels. Furthermore, simvastatin reduces triglycerides and mildly raises high density lipoprotein-cholesterol levels. In addition to the hypolipidaemic effect, other potentially important effects, such as improvement of endothelial function and reduction of LDL oxidation and vascular inflammation, have been associated with HMG-CoA reductase inhibitor therapy. Simvastatin has also been shown to abolish the progression, and even facilitate the regression, of existing human atherosclerotic lesions.The good safety and tolerability profile of simvastatin is clearly highlighted by the low rate of therapy discontinuation observed in several population-based clinical trials. The most common adverse events leading to the discontinuation of therapy are gastrointestinal upset and headache. Asymptomatic elevations in liver transaminase levels and myopathy are uncommon.The overwhelming clinical evidence regarding the long-term use of HMG-CoA reductase inhibitor therapy in patients with familial hypercholesterolaemia together with the long-term safety data (particularly relating to simvastatin) provide support for the use of this drug as a first-line agent when pharmacological treatment is indicated. Early intervention with simvastatin treatment can be successfully implemented with favourable economic benefits.     

Hantaviral antigens and antibodies in wild rodents in Portugal.

Small rodents of the species Rattus norvegicus and Rattus rattus have been captured between 1986 and 1988 in several areas of Southern Portugal. A total of 135 animal specimens were examined for hantaviral antigens in lung sections and 5 have been found positive. Some of the rodents were shown to have serum antibodies as detected by immunofluorescence in titres up to 1:256. This investigation proves for the first time the presence of Hantavirus in wild rodent populations of Portugal.     

Effects of methylphenidate and behavior modification on the social and academic behavior of children with disruptive behavior disorders: the moderating role of callous/unemotional traits.

This study examined whether response to behavior modification with and without methylphenidate differed for children with attention-deficit/hyperactivity disorder (ADHD) and conduct problems (CP) depending on the presence of callous/unemotional (CU) traits. Participants were 37 children ages 7 to 12, including 19 with ADHD/CP-only and 18 with ADHD/CP-CU, referred to a university-based summer treatment program. Results showed that ADHD/CP-CU children had worse behavior in the behavior-therapy-only (BT-only) condition, especially on measures of CP, noncompliance, and rule violations, but these differences largely disappeared when medication was added to BT. Children with ADHD/CP-CU were also less likely to be normalized by treatment than were children with ADHD/CP-only. These findings, though tentative, suggest that children with ADHD/CP-CU may not show a sufficient positive response to BT alone and that the combination of medication and BT may be especially important for them.     

Effect of voice rehabilitation on oral communication of Parkinson's disease patients

Voice and speech disorders are common in Parkinson's disease patients and may lead to social isolation. We employed routine clinical voice therapy measures to evaluate the effect of voice rehabilitation. Twenty patients with a stable drug regimen participated in this study. The patients were assessed before and after a program of voice rehabilitation consisting of 13 group therapy sessions during 1 month, with emphasis on the increase in laryngeal sphincteric activity. Voice rehabilitation produced an increase in maximal phonation times, decrease in the values of s/z ratio and air flow, increase in vocal intensity, decrease in the complaints of weak and strained-strangled voice and monotonous and unintelligible speech and elimination of complaints of swallowing alterations. These data indicate a greater glottic efficiency after voice rehabilitation reflecting a more functional oral communication.     

Adenosine 5′-triphosphate,uridine 5′-triphosphate,bradykinin, and lysophosphatidic acid induce different patterns of calcium responses by human articular chondrocytes

Small calcium-mobilizing inflammatory mediators have been implicated in joint pathology. Here we demonstrate that bradykinin, adenosine 5′-triphosphate, uridine 5′-triphosphate, and lysophosphatidic acid raise the intracellular calcium concentration ([Ca²⁺]_i) in human articular chondrocytes. Heterologous cross-desensitization experiments showed that the uridine 5′-triphosphate response was abolished by prior treatment with adenosine 5′-triphosphate and conversely, that the adenosine 5′-triphosphate response was abolished by prior treatment with uridine 5′-triphosphate: this indicated competition for the same receptor site, whereas bradykinin and lysophosphatidic acid did not compete with other ligands. Pretreatment with thapsigargin abolished ligand-mediated Ca²⁺ responses but not vice versa: this confirmed that Ca²⁺ release occurred from intracellular stores. Single-cell analysis of Fura-2 acetoxymethyl ester loaded chondrocytes showed mediator-dependent patterns of oscillatory Ca²⁺ changes in a subset of cells when challenged with submaximal concentrations of bradykinin, adenosine 5′-triphosphate, or uridine 5′-triphosphate in the presence of extracellular Ca²⁺. However, no oscillatory responses were seen after a challenge with lysophosphatidic acid. Therefore, although a number of different Ca²⁺-mobilizing ligands activate chondrocytes, the differences that occur in the temporal patterning of Ca²⁺ responses may result in unique mediator-dependent changes in cellular activity.     

A Double-Blind Comparison of Sinusoidal Wave and Brief-Pulse Electroconvulsive Therapy in Endogenous Depression

In a double-blind prospective study, 29 endogenously depressed patients (RDC) were randomized into sinusoidal wave (SW) and brief-pulse (BP) electroconvulsive therapy (ECT) groups. Bilateral modified treatments were administered on alternate days, three per week, and the treatment variables of current dosage and seizure duration were monitored for each treatment. Significantly more patients responded to SW than to BP ECT, but a comparable number of treatments was required to produce this response in the two groups. There was no difference in clinical or treatment variables between the SW and the BP groups, nor between ECT responders and nonresponders, with the exception that the SW-treated patients received larger doses of current per treatment than did the BP patients. For endogenous depression treated with ECT, we conclude that cumulative seizure duration may not be a parameter of significance, that overall rate of recovery in ECT responders is independent of stimulus waveform, and that some depressives may respond to SW but not to BP ECT. We suggest that the antidepressant effect of the ECT seizure may be characterized by a therapeutic window in current requirements; alternatively, a putative response threshold (again in terms of current requirement) may exist, which is higher in some patients than in others.     

Mania as a Side Effect of Electroconvulsive Therapy

Thirty-two endogenous depressed patients (RDC) were treated with electroconvulsive therapy. Four patients (12.5%) developed a transient manic reaction; in two cases, this reaction occurred in mid-depression. Mania is not a generally recognized side effect of ECT; we detail the clinical characteristics, but fail to define clinical predictors of vulnerability.     

Expression microdissection: operator-independent retrieval of cells for molecular profiling.

Tissue microdissection is an important method for the study of disease states. However, it is difficult to perform high-throughput molecular analysis with current techniques. We describe here a prototype version of a novel technique (expression microdissection) that allows for the procurement of desired cells via molecular targeting. Expression microdissection (xMD) offers significant advantages over available methods, including an increase in dissection speed of several orders of magnitude. xMD may become a valuable tool for investigators studying cancer or other disease states in patient specimens and animal models.     

Performance characteristics of a rapid new immunochromatographic test for detection of antibodies to human immunodeficiency virus

A new immunochromatographic rapid test (Rapid Check HIV 1 and 2; Núcleo de Doen?as Infecciosas) for the detection of antibodies to human immunodeficiency virus type 1 and type 2 in human samples (whole blood, serum, and plasma) was evaluated and compared to the commercially available Determine (Abbott Laboratories). When whole-blood samples were evaluated, the specificity and sensitivity of both tests were 100%. However, when plasma samples were used, sensitivity for the Rapid Check HIV 1&2 and the Determine tests were 100 and 98.58%, respectively. The observed specificity for plasma samples was 98.94% for the Rapid Check HIV 1&2 and 96.97% for the Determine test. The results presented here are encouraging and support the adoption of both tests as an alternative to enzyme-lined immunosorbent assay and/or Western blots in regions where laboratorial infrastructure is not available or for use in the management of occupational accidents for healthcare workers.