BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial

Vitamin D receptor (VDR) gene polymorphisms could be considered one of the factors influencing the efficacy of the anti-osteoporotic treatments. In this multicenter, prospective, randomized and controlled trial we evaluated whether BsmI vitamin D receptor (VDR) genotypes influence the efficacy of antiresorptive treatment regimes (administered alone or in combination) in postmenopausal osteoporotic women. Using restriction endonuclease, we identified the BsmI VDR polymorphism in 1,100 postmenopausal women with osteoporosis. The women were randomized, taking account of genotype, into five treatment groups: (1) alendronate (Aln, 10 mg/day) plus raloxifene (Rlx, 60 mg/day); (2) Aln plus hormone replacement therapy (HRT, 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate); (3) Aln alone; (4) HRT alone; and (5) Rlx alone. Lumbar-spine bone mineral density (BMD) and bone turnover markers were measured at study entry and after 1 year of treatment. Using the general linear model (GLM) repeated-measures procedure, the means of BMD and bone turnover markers significantly differed from baseline after a period of treatment. In particular, the mean change from baseline for BMD was –0.034 (95% confidence interval [CI]: –0.037 to –0.031, P <0.001); for serum osteocalcin (OC) it was 1.369 (95% CI: 1.289 to 1.448, P <0.001); and for urinary deoxypyridinoline (DPD) it was 1.322 (95% CI: 1.242 to 1.401, P <0.001), indicating a considerable variation before and after treatment of these indicators. In all three cases these effects appeared significantly influenced by treatments, genotypes, and the treatments*genotypes interaction term (P <0.001 each, except for the BMD and genotype effect with P =0.02), and not by the investigational centers involved in the study. In conclusion, in postmenopausal osteoporotic women, BsmI VDR genotypes influence the efficacy of antiresorptive drugs particularly when used in combination.     

Splenectomy prolongs in vivo survival of erythrocytes differently in spectrin/ankyrin- and band 3-deficient hereditary spherocytosis

Red cell (RBC) deformability and membrane-bound immunoglobulin G (IgG) were studied to better understand premature clearance of erythrocytes in hereditary spherocytosis. Averaged deformability profiles from cells having comparable cell age revealed that splenectomy was more beneficial for spectrin/ankyrin-deficient than for band 3-deficient RBCs. Splenectomy prevented an early loss of young cells in both types of deficiencies. It had an additional beneficial effect on spectrin/ankyrin-deficient but not band 3-deficient RBCs. It prolonged the survival of mature spectrin/ankyrin-deficient RBCs such that they lost their deformability more slowly than RBCs from patients who had not undergone splenectomy. Band 3-deficient RBCs lost their deformability at the same rate before and after splenectomy. In HS patients with band 3 deficiency who underwent splenectomy, RBC deformability inversely correlated with the number of RBC-bound IgG (up to 140 molecules per cell). In spectrin/ankyrin deficiency, RBC-bound IgG remained at control levels (60 IgG or less per cell). It appears that spectrin/ankyrin-deficient RBCs escaped opsonization by releasing band 3-containing vesicles because their band 3 content and deformability dropped in parallel with increasing cell age. Band 3-deficient RBCs did not lose band 3 with increasing cell age. Hence, it is possible that band 3 clusters required for bivalent binding of low-affinity-IgG, naturally occurring antibodies were retained in band 3-deficient RBCs with a relative excess of skeletal proteins but were released from spectrin/ankyrin-deficient RBCs, in which vesicle budding was facilitated by an impaired skeleton.     

Mechanisms and predictors of transient left ventricular dysfunction early after successful percutaneous balloon mitral valvuloplasty.

BACKGROUND: The immediate effects of balloon mitral valvuloplasty (BMV) on left ventricular (LV) function in patients with mitral stenosis are still controversial. The aim of this study was to investigate the mechanisms and potential clinical, echocardiographic and hemodynamic predictors of transient LV dysfunction occurring in patients with mitral stenosis early after successful percutaneous BMV. METHODS: Sixty patients without residual mitral regurgitation were divided into two groups according to the changes in the left atrial (LA) pressure 15 min after successful BMV: 18 patients (group A) did not present with any reduction in LA pressure, and underwent nitroglycerin administration (0.4 mg, sublingually). The remaining 42 patients (group B) presented with a decrease in LA pressure. RESULTS: At baseline, both the mitral valve gradient and area assessed at echocardiography and during cardiac catheterization were similar in groups A and B. Group A patients presented with, however, higher LV early- and end-diastolic pressures and peak V waves during cardiac catheterization both prior to and 15 min after BMV than group B patients (all p values < 0.05). In group A, nitroglycerin administration was associated with a decrease in LV end-diastolic pressure (p = 0.049), LA pressure (p < 0.001), and peak V wave (p < 0.001) that was still persistent 30 min after its administration, reaching values similar to those observed in group B early after BMV. At multivariate analysis, the only independent predictors of LV dysfunction early after BMV were found to be LV early- (p = 0.015) and end-diastolic (p = 0.023) pressures at baseline and the Wilkins' score (p = 0.004). CONCLUSIONS: After successful BMV a transient lack of LV adaptation to the increased LV preload resulting in a persistently elevated LA pressure is predicted by higher baseline LV diastolic filling pressures and higher Wilkins' scores. It is promptly and steadily reversed by nitroglycerin administration through a transient LV unloading, thus allowing a correct hemodynamic evaluation of the immediate results of the procedure.     

Podoplanin expression as a predictive marker of dysplasia in oral leukoplakia

Purpose

Recent studies have emphasized the role of podoplanin in oral lesions at risk of malignant transformation. We investigated a group of oral leukoplakias (OLs) to determine a possible relation between altered podoplanin expression and dysplasia, and to compare the results with those obtained by other, widely used biomarkers.