Inherited antithrombin (AT) deficiency is a rare autosomal dominant disorder, caused by mutations in the AT gene (SERPINC1). Considering that the genotype phenotype relationship in AT deficiency patients remains unclear, especially in pediatric patients, the aim of our study was to evaluate genotype phenotype correlation in a Serbian pediatric population. A retrospective cohort study included 19 children younger than 18 years, from 15 Serbian families, with newly diagnosed AT deficiency. In 21% of the recruited families, mutations affecting exon 4, 5, and 6 of the SERPINC1 gene that causes type I AT deficiency were detected. In the remaining families, the mutation in exon 2 causing type II HBS (AT Budapest 3) was found. Thrombosis events were observed in 1 (33%) of those with type I, 11 (85%) of those with AT Budapest 3 in the homozygous respectively, and 1(33%) in the heterozygous form. Recurrent thrombosis was observed only in AT Budapest 3 in the homozygous form, in 27% during initial treatment of the first thrombotic event. Abdominal venous thrombosis and arterial ischemic stroke, observed in almost half of the children from the group with AT Budapest 3 in the homozygous form, were unprovoked in all cases.
Conclusion: Type II HBS (AT Budapest 3) in the homozygous form is a strong risk factor for arterial and venous thrombosis in pediatric patients.
What is Known:
• Inherited AT deficiency is a rare autosomal dominant disorder, caused by mutations in the SERPINC1gene.
• The genotype phenotype correlation in AT deficiency patients remains unclear, especially in pediatric patients.
What is New:
• The genetic results for our paediatric population predominantly showed the presence of a single specific mutation in exon 2, that causes type II HBS deficiency (AT Budapest 3).
• In this group thrombosis mostly occurred as unprovoked, in almost half of them as abdominal thrombosis or stroke with high incidence of recurrent thrombosis, in 27% during initial treatment.
The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990–1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RTT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries. 相似文献
Postoperative nausea and vomiting (PONV) continues to be a \"big little problem\" despite recent advances in anesthesia. Because of an increased interest in, and the abundant publications on this topic, guidelines for the management of PONV were published in 2003. Several key but controversial issues regarding PONV prophylaxis were left unaddressed, however. These included whether clinical differences exist between the 5-hydroxytryptamine subtype 3 (5-HT3) receptor antagonists, concern over optimal dosage and timing of administration, optimal 5-HT3 receptor antagonist combination therapy, and whether rescue therapy is effective after prior administration of the same or a different 5-HT3 receptor antagonist. The application of these antiemetics in clinical practice has raised questions regarding the role of the 5-HT3 receptor antagonists in the treatment of postdischarge nausea and vomiting and opioid-induced nausea and vomiting. A brief overview of the incidence, risk factors and current management recommendations for PONV and current controversies with special emphasis on the 5-HT3 receptor antagonists, is discussed. 相似文献
Generalized tendomyopathy (GTM), or fibromyalgia (FM), is a disease characterized by wide-spread pain in the musculoskeletal system which usually begins at a single site, e.g., as low-back pain or cervical syndrome, and develops into generalized pain over months or years. The disorder affects primarily women, beginning around the age of 35 and reaching its peak during or after the menopause. Its etiology is still unknown. Secondary forms are observed particularly in rheumatoid arthritis. In order to get more information on FM we determined the local metabolic rate of glucose in vivo in the skeletal muscle (lumbar region) with dynamic 18F-FDG positron emission tomography (PET). 2 healthy volunteers and 6 female patients with FM reaching in age from 31 to 53 years were scanned. As 18F-FDG PET scanning is a metabolic tool, it is crucial to observe standardized conditions of metabolic steady-state. We used, therefore, the hyperinsulinemic euglycemic insulin clamp technique to stimulate the myogenic glucose uptake under stable plasma-glucose levels. The local metabolic rates of glucose utilization were estimated with a non-linear least squares fit on the 3 compartment 18F-FDG-model. A lumped constant of 0.67 was assumed. Under glucose clamp conditions patients with FM showed a significantly (p < 0.001) lower metabolic rate of glucose (4.3 +/- 1.1) mumol/100 g tissue/min compared with normal volunteers (8.5 +/- 2.3 mumol/100 g/min). Due to a significantly (p < 0.005) increased glucose backflow from tissue into the vascular space (k2 in the kinetic model) the rate of phosphorylation was markedly reduced in patients with FM.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
