The spectrum of bone disease in predialysis and dialysis patients has changed during the last decade. The incidence of aplastic bone disease has increased and this can not be attributed to bone aluminum deposition; moreover, low bone cellular activity is present despite a moderate elevation in PTH levels. This study compares PTH levels and types of bone disease in both predialysis and dialysis patients from the same geographical area. We prospectively studied 119 unselected end-stage renal disease patients: 38 were immediately predialysis (PreD), 49 on hemodialysis (HD), and 32 on CAPD. A bone biopsy was performed in all patients. Aplastic bone disease with < 5% bone surface aluminum was a common finding (48%, 32%, and 48%, in PreD, HD, and CAPD, respectively). In all groups, an intact PTH level below 120 pg/ml was highly predictive of low bone turnover. Conversely, a PTH level above 450 pg/ml was always associated with histologic features of hyperparathyroid bone disease. Among the bone histomorphometric parameters, osteoblast surface showed the best correlation with intact PTH in each group, and the slope of the regression line for this correlation was significantly steeper in HD and CAPD than PreD patients. Thus, the range of PTH (95% confidence limit bands) needed to obtain a normal osteoblast surface of 1.5% was greater in preD than in HD and CAPD patients (300 to 500 vs. 75 to 260 pg/ml, respectively). In all groups some degree of marrow fibrosis was observed when PTH levels were greater than 250 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular epidemiological studies suggest that particular Mycobacterium tuberculosis strains have an enhanced capacity to spread within a community. One strain, the Beijing genotype, has been associated with outbreaks in a number of communities throughout the world. IS6110 restriction fragment length polymorphism (RFLP) analysis was performed on M. tuberculosis isolates from 566 of the 721 patients (78.5%) diagnosed with tuberculosis (TB) on Gran Canaria Island from 1993 to 1996, as well as 35% of isolates from 1991-1992 (85 strains). RFLP identification of the family of strains of the Beijing genotype was confirmed by spoligotyping. Medical records of all patients were reviewed and epidemiological links were identified. Of 566 M. tuberculosis isolates from 1993 to 1996 with RFLP available, 72% belonged to clusters. The largest contained 75 cases and was caused by a strain of the Beijing genotype that was introduced to the island in 1993. It was found in 10 patients in 1993 (5.5%), 12 in 1994 (8.1%), 18 in 1995 (16.4%), and 35 in 1996 (27.1%). Epidemiological linkage was confirmed for 68% of cases. This study has demonstrated rapid dissemination of this strain of the Beijing genotype. This genotype might play an important role in the future of the worldwide tuberculosis epidemic.

Blood vessels respond to injury by initiating cell proliferation and migration that result in vascular lesion formation. To determine the roles of thrombin and the thrombin receptor in this process, we characterized thrombin receptor expression in normal and injured arteries, thrombin receptor-mediated smooth muscle cell mitogenesis, and the regulation of thrombin receptor mRNA expression in vitro. Thrombin receptor mRNA was not detected in normal rat or baboon arteries by in situ hybridization. Immunohistochemistry using an antithrombin receptor antibody (TR-R9), directed against the thrombin cleavage site of the rat aortic smooth muscle cell thrombin receptor, revealed low-level staining for thrombin receptor protein in endothelial cells and smooth muscle cells of normal arteries. In contrast, balloon catheter injury increased thrombin mRNA expression in medial smooth muscle cells within 6 hours. This increased thrombin receptor expression continued within the media and in neointimal cells throughout vascular lesion formation, predominantly in areas of active cell proliferation. In vitro, alpha-thrombin stimulates rat aortic smooth muscle cell proliferation in a concentration-dependent manner. That thrombin receptor activation is required for the mitogenic response was confirmed by demonstrating that the polyclonal antibody TR-R9 inhibits thrombin-induced cell proliferation. Thrombin receptor mRNA synthesis was induced by both basic fibroblast growth factor (maximal stimulation of 1.8-fold at 1 hour) and platelet-derived growth factor (maximal stimulation of 2.4-fold at 8 and 24 hours) in quiesced cultured rat aortic smooth muscle cells. In summary, upregulation of smooth muscle cell thrombin receptor expression occurs very early after vascular injury and continues throughout neointimal development.(ABSTRACT TRUNCATED AT 250 WORDS)