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31.
Juan Carlos Gómez-Esteban Juan Jose Zarranz Elena Lezcano Fernando Velasco Roberto Ciordia Idoia Rouco Jose Losada Iker Bilbao 《Movement disorders》2006,21(7):983-988
The aim of this research was to quantify sleep problems in patients suffering from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale (PDSS) and to correlate such problems with the possible influence of current drug treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75 and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75 (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355, P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc = -0.416, P < 0.001). Motor conditions, mental state, and drug complications influence sleep quality. Although this effect was significant, it was not of a great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a whole, sleep quality in patients who took dopaminergic agonists did not differ from that of patients who took levodopa in monotherapy. 相似文献
32.
33.
Dagmar Busse Jose Cosme Philippe Beaune Heyo K. Kroemer Michel Eichelbaum D. Busse H. K. Kroemer M. Eichelbaum 《Naunyn-Schmiedeberg's archives of pharmacology》1995,353(1):116-121
The calcium channel blocker verapamil [2,8-bis-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] undergoes extensive biotransformation in man. We have previously demonstrated cytochrome P450 (CYP) 3A4 and 1A2 to be the enzymes responsible for verapamil N-dealkylation (formation of D-617 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile]), and verapamil N-demethylation (formation of norverapamil [2,8-bis(3,4-dimethoxyphenyl)-2-isopropyl-6-azaoctanitrile]), while there was no involvement of CYP3A4 and CYP1A2 in the third initial metabolic step of verapamil, which is verapamil O-demethylation. This pathway yields formation of D-703 [2-(4-hydroxy-3-methoxyphenyl)-8-(3,4-dimethoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)6-methyl-2-isopropyl-6-azaoctanitrile]. The enzymes catalyzing verapamil O-demethylation have not been characterized so far. We have therefore identified and characterized the enzymes involved in verapamil O-demethylation in humans by using the following in vitro approaches: (I) characterization of O-demethylation kinetics in the presence of the microsomal fraction of human liver, (II) inhibition of verapamil O-demethylation by specific antibodies and selective inhibitors and (111) investigation of metabolite formation in microsomes obtained from yeast strain Saccharomyces cerevisiae W(R), that was genetically engineered for stable expression of human CYP2C8, 2C9 and 2C18.In human liver microsomes (n=4), the intrinsic clearance (CLint), as derived from the ratio of V
max/Km, was significantly higher for O-demethylation to D-703 compared to formation of D-702 following incubation with racemic verapamil (13.9±1.0 vs 2.4±0.6 ml*min-1
*g-1 mean±SD; p<0.05), S-Verapamil (16.8±3.3 vs 2.2±1.2 ml* mini*g-1, p<0.05) and R-verapamil (12.1±2.9 vs 3.6 ±1.3 ml*min-1
* g-1; p<0.05), thus indicating regioselectivity of verapamil O-demethylation process. The CLint of D-703 formation in human liver microsomes showed a modest but significant degree of stereo selectivity (p<0.05) with a S/R-ratio of 1.41±0.17. Anti-LKM2 (anti-liver/kidney microsome) autoantibodies (which inhibit CYP2C9 and 2C19) and sulfaphenazole (a specific CYP2C9 inhibitor) reduced the maximum rate of formation of D-703 by 81.5±4.5% and 45%, that of D-702 by 52.7±7.5% and 72.5%, respectively. Both D-703 and D-702 were formed by stably expressed CYP2C9 and CYP2C18, whereas incubation with CYP2C8 selectively yielded D-703.In conclusion, our results show that enzymes of the CYP2C subfamily are mainly involved in verapamil O-demethylation. Verapamil therefore has the potential to interact with other drugs which inhibit or induce these enzymes. 相似文献
34.
Prospective assessment of biofeedback for the treatment of paradoxical puborectalis contraction 总被引:25,自引:18,他引:7
Steven D. Wexner M.D. John D. Cheape M.D. Jose M. N. Jorge M.D. Steve Heymen B.A. David G. Jagelman M.D. 《Diseases of the colon and rectum》1992,35(2):145-150
Eighteen patients with chronic constipation were diagnosed as having paradoxical puborectalis contraction (PPC) as the cause for their constipation. The diagnosis of PPC was made after office evaluation, colonic transit study, manometry, cinedefecography, and electromyography (EMG). These 18 patients had a mean duration of symptoms of 26.9 years; none of these patients had unassisted bowel movements. Fourteen patients had a mean of 4.6 laxative-induced bowel evacuations per week, and 11 patients had a mean of 4.4 enema-induced bowel evacuations per week. Patients underwent a mean of 8.9 one-hour EMG-based biofeedback sessions. At a mean follow-up of 9.1 (range, 0.5–12) months, these 18 patients had a mean of 7.3 unassisted bowel actions per week (
P
<0.0001). In addition, persistent laxative use was reported by only two patients, and, in both cases, this was once a week or less (
P
<0.001). Similarly, enema use was reported by only three patients, one once weekly and the other two thrice weekly (
P
<0.002). No biofeedback-related complications were identified. EMG-based biofeedback is a valuable technique associated with an 89 percent success rate in the treatment of PPC.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991. 相似文献
35.
Alicia Bas Ignacio Lopez Jose Perez Mariano Rodriguez Escolastico Aguilera-Tejero 《Journal of bone and mineral research》2006,21(3):484-490
VC is an important clinical entity; however, very little information is available on its resolution. Induction and regression of calcitriol-induced VC was studied in 47 rats. After calcitriol withdrawal, there was a relatively rapid regression of VC mediated by an active cellular process. INTRODUCTION: Vascular calcifications (VCs) represent an important risk factor for cardiovascular death. Although VCs are prevalent in relevant diseases (e.g., chronic kidney disease, osteoporosis, diabetes), the reversibility of extraskeletal calcifications is an unresolved issue. This study was conducted to investigate (1) the in vivo effect of calcitriol on VC and (2) whether calcitriol-induced VC would regress after suppression of calcitriol treatment. MATERIALS AND METHODS: The calcifying effect of calcitriol was studied in four groups of rats (n = 8) that received calcitriol (1 mug/kg, IP) for 2, 4, 6, and 8 days. The reversibility of VC was studied in three additional groups (n = 5) treated with 1 mug/kg of calcitriol for 8 days that were subsequently killed 1, 2, and 9 weeks after the last calcitriol dose. Aortic VC was assessed by histology and by quantification of aortic calcium and phosphorus content. The aortic wall was studied by histology and immunohistochemistry. Statistical analysis was performed by ANOVA and t-tests. RESULTS: Calcitriol administration resulted in a time-dependent induction of VC, with aortic calcium and phosphorus being significantly increased at 6 and 8 days. Treatment with calcitriol for 8 days resulted in massive medial calcification of the aorta with a 10- to 30-fold increase in the aortic Ca and P content. After suppressing calcitriol administration, a progressive decrease in von Kossa staining and aortic Ca (from 32.8 +/- 2.5 to 9.3 +/- 1.8 mg/g of tissue, p < 0.001) and P (from 11.9 +/- 1.2 to 2.7 +/- 1.8 mg/g of tissue, p = 0.001) content was evidenced. Histology of the aortic wall showed monocytes adhered to the aortic endothelium and macrophages involved in the reabsorption of calcium deposits. CONCLUSIONS: Our results show that calcitriol treatment induces time-dependent VC. After calcitriol withdrawal, VC regress rapidly with aortic calcium and phosphorus decreasing by 75% in the course of 9 weeks. An active cellular process seems to be involved in regression of VC. 相似文献
36.
37.
The clinicopathological and immunohistochemical properties of 6 examples of arteriovenous hemangioma, including 2 intraoral lesions, were reviewed. This distinct benign, acquired vascular lesion, infrequently encountered in the literature, is characterized by multiple thick- and thin-walled vascular spaces resembling arteries and veins, respectively. In our study, we performed elastic stains that revealed a prominent venular component, whereas the arterial aspect was inconspicuous to absent. Our aim was also lo elucidate the possible histogenesis of this lesion. Previous reports suggest as pathogenetic mechanisms hamartomatous proliferation either of the subpapillaiy vascular plexus or of the Suquet-Hoyer canal of the true glomus. Our immunohistochemical studies failed to identify typical glooms cells. In addition, we investigated the mast cell count in all lesions and it was found increased. These findings, as well as recent evidence directly implicating mast cells in angiogenesis, can support the theory of hamartomatous proliferation of the subpapillary plexus. One should also not exclude the possibility of a reactive process resulting in the characteristic features of arteriovenous hemangioma. 相似文献
38.
39.
Fixation of cementless acetabular cups: A radiographic 4-8-year study of 102 porous-coated components 总被引:2,自引:0,他引:2
We studied fixation changes over time in 113 porous-coated Howmedica (PCA) cementless acetabular cups inserted in 90 patients 1984-1988. The mean follow-up was 5 years. Radiographic fixation was classified as stable, fibrous-stable, or unstable. 9 cups, 3 in neutral position and 6 vertical, were revised. At follow-up, 40/75 neutral cups were stable versus 7/27 vertical cups. Most stable cups and two thirds of the unstable cups were clinically good. After the first 2 years, 28/75 neutral cups and 10/27 vertical cups changed their fixation: 12 had improved fixation and 26 had a worse one. 相似文献