Advances in the care of children with heart disease

As we enter the next millennium, we are encouraged by the progress that has been made in the care of neonates, infants, and children with heart disease. Surgical repair can be offered at an earlier age with excellent results. Diseases that were uniformly fatal in the past have improved outcomes. Research continues in the area of interventional devices such that surgical repair might be eliminated or delayed. We continue to look forward to advances in the next several years that will allow for future improvement in outcome, better quality-of-life and better long-term results.     

A double-blind randomized comparison of combined aspirin and ticlopidine therapy versus aspirin or ticlopidine alone on experimental arterial thrombogenesis in humans

No randomized study comparing the effect of combined ticlopidine and aspirin therapy versus each drug alone in reducing poststenting thrombotic complications has been performed. To compare these three antiplatelet regimens versus placebo, we conducted a double-blind randomized study using an ex vivo model of thrombosis. Sixteen healthy male volunteers were assigned to receive for 8 days the following four regimens separated by a 1-month period: aspirin 325 mg/d, ticlopidine 500 mg/d, aspirin 325 mg/d + ticlopidine 500 mg/d, and placebo. At the end of each treatment period, native nonanticoagulated blood was drawn directly from an antecubital vein over collagen- or tissue factor (TF)-coated coverslips positioned in a parallel-plate perfusion chamber at an arterial wall shear rate (2, 600 s-1 ) for 3 minutes. Thrombus, which formed on collagen in volunteers treated by placebo, were rich in platelets and poor in fibrin. As compared with placebo, aspirin and ticlopidine alone reduced platelet thrombus formation by only 29% and 15%, respectively (P > .2). In contrast, platelet thrombus formation was blocked by more than 90% in volunteers treated by aspirin + ticlopidine (P < .01 v placebo or each treatment alone). Furthermore, the effect of the drug combination therapy was significantly larger than the sum of the two active treatments (P < .05). Thrombus, which formed on TF-coated coverslips in volunteers treated by placebo, were rich in fibrin and platelets. Neither of the three antiplatelet treatments significantly inhibited fibrin deposition and platelet thrombus formation on this surface (P > .2). Thus, the present study shows that combined aspirin and ticlopidine therapy dramatically potentiates the antithrombotic effect of each drug alone, but that the antithrombotic effect of the combined treatment depends on the nature of the thrombogenic surface.     

Contingent tolerance, compensatory responses, and physical dependence in diazepam-treated amygdala-kindled rats

Three groups of amygdala-kindled rats received 10 bidaily treatment trials: On each trial, the drug-before group received a diazepam (2.5 mg/kg i.p.) injection 1 hr before a convulsive stimulation, the drug-after group received a diazepam injection 1 hr after a stimulation, and the vehicle control group received a vehicle injection either 1 hr before or 1 hr after a stimulation. After treatment, only the drug-before group displayed significantly longer forelimb clonus under the influence of diazepam (that is, they displayed contingent tolerance to diazepam's anticonvulsant effect) and significantly longer forelimb clonus while drug free. Following a 14-day retention period, the rats in the drug-before group retained significant levels of contingent tolerance but did not display significant increases when tested drug free. These data suggest that compensatory responses do not play a causal role in the expression of contingent tolerance.     

Nervous system lupus mimics limbic encephalitis

A 28-year-old woman with systemic lupus erythematosus (SLE) suffered recent onset fever, headache, encephalopathy followed by severe, repeated generalized seizures. Investigations revealed limbic encephalitis. Tests for Herpes simplex encephalitis and paraneoplastic encephalomyelitis were negative. High titers anti-ribosomal-P antibodies in the cerebrospinal fluid (CSF) suggested an association with nervous system lupus. No brain biopsy was performed. Treatment was with anti-seizure, anti-viral, and immunomodulating medication.     

Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus

Transient neonatal diabetes mellitus occurs in growth-retarded infants, has an incidence of 1 in 400000 live births and has been associated with both paternal uniparental disomy of chromosome 6 and paternal duplications of 6q. We analysed samples from our cohort of patients with transient neonatal diabetes mellitus for uniparental disomy of chromosome 6 using polymorphic microsatellite repeat analysis. We report here the fifth case of paternal uniparental disomy of chromosome 6 associated with classic transient neonatal diabetes mellitus and estimate that uniparental disomy of chromosome 6 accounts for approximately one fifth of cases of transient neonatal diabetes mellitus.     

The effects of oral liarozole on epidermal proliferation and differentiation in severe plaque psoriasis are comparable with those of acitretin

The imidazole derivative liarozole is a potent inhibitor of cytochrome P450-dependent 4-hydroxylation of endogenous all-trans retinoic acid, thereby increasing the levels of all-trans retinoic acid in both plasma and skin. As part of a large, double-blind, randomized clinical study, we investigated the cell biological alterations in uninvolved and lesional skin of 20 patients with severe plaque psoriasis, who were treated with either liarozole or acitretin. The extent and severity of the skin lesions, as recorded by the Psoriasis Area and Severity Index score, was significantly reduced (P 相似文献   

French consensus conference on hepatitis C: screening and treatment

CORRESPONDENCE TO: Professor J P Galmiche, Hépato-Gastroentérologie, H?tel Dieu, CHU de Nantes, 44035 Nantes Cedex, France (email: galmiche@easynet.fr). This consensus conference followed the rules developed by the French Agence Nationale pour le Développement de l'Evaluation Médicale (ANDEM). Briefly, this required an organising committee, a working group whose task was to make a comprehensive critical review of the literature before the conference was held, a panel of experts, and a jury. The conference was held over two days and included (a) a public session with presentations by experts working in areas relevant to the consensus questions, (b) questions and statements from conference attendees, and (c) deliberation by the jury, followed by the drafting of conclusions and recommendations. (GUT 1998;:892-898)