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32.
R Dixon AM Hughes K Nairn M Sellers JV Kemp RA Yates 《Cephalalgia : an international journal of headache》1998,18(7):468-475
Zolmitriptan (ZomigTM ) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination. 相似文献
33.
Analyses of T-cell differentiation from hemopoietic stem cells in the G0 phase by an in vitro method. 总被引:1,自引:0,他引:1
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J Toki T Kumamoto H Ogata M Kawamura M Fukumoto Cherry Y Yamamoto S Than M Inaba Y Himeno et al. 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(17):7548-7551
Using differential radiation sensitivity of components of mouse embryonal thymus, an in vitro method for studying T-cell differentiation from hemopoietic stem cells (HSCs) in the G0 phase was established. Intrathymic T-cell precursors present in embryonal thymus were found to be quite radioresistant (up to 20 Gy), and consequently 25-Gy-irradiated embryonal thymic lobes were used. Thymic lobes (25-Gy irradiated) taken from mouse fetuses (gestation day 15) were placed in Millipore-HA culture plates supported on squares of gelatin foam sponge in 24-well culture plates in which neonatal thymus stromal cells were cultured. HSCs (10(5) cells per well) in the G0 phase were added to these thymic lobes and cocultured at 37 degrees C in a 5% CO2/95% air incubator. Half the culture medium was changed every week. After 3 weeks, a large number of colonies had formed. Immunohistochemical studies and fluorescence-activated cell sorter analyses revealed that the colonizing cells regularly develop and exhibit surface markers characteristic of T cells (Thy-1, IL-2R, L3T4, Lyt-2, etc.). In situ hybridization analyses revealed that mRNA expression for T-cell receptor (TCR) beta chains occurred within colonizing cells. Using a monoclonal antibody (F23.1), expression of TCR beta-chain variable domain (V beta 8) on the surface of these developing T cells was demonstrated. These cells responded to interleukin 2 and/or anti-CD3 monoclonal antibody, indicating functional T cells. This method will be useful in studying T-cell differentiation pathways from pluripotent HSCs and in clarifying the mechanisms involved in negative and positive selection of T cells within the thymus. 相似文献
34.
Jean M. Panneton MD Peter Gloviczki MD Linda G. Canton RN BSN Thomas C. Bower MD Matthew S. T. Chow MD Peter C. Pairolero MD Hartzell V. Schaff MD John W. Hallett Jr. MD Kenneth J. Cherry Jr. MD 《Annals of vascular surgery》1996,10(2):97-108
Renal transplantation has increased the longevity of patients with uremia. An increasing number undergo aortic reconstruction, which exposes the transplanted kidney to ischemic injury. To evaluate the risk for renal failure, loss of the transplant, and methods of renal protection, we reviewed our experience. Clinical data were reviewed for 10 consecutive patients (7 men, 3 women; mean age 52.7 years [range 32 to 75 years]) with a transplanted kidney who underwent aortic reconstruction between 1977 and 1994 at our institution. Mean interval between renal transplantation and aortic reconstruction was 5.9 years (range 1 month to 12.7 years). Seven patients required emergency repair because of dissection (2 patients), aneurysm rupture (4 patients), or symptomatic aneurysm (1 patient); three underwent elective repair. Reasons for reconstruction included aortic dissection (2 patients), aneurysm of the descending thoracic (2 patients), thoracoabdominal (1 patient), or abdominal aorta (3 patients), and aortoiliac occlusive disease (2 patients). Patients with thoracic or thoracoabdominal reconstructions underwent repair with atriofemoral, aortofemoral, or femorofemoral shunt placement or bypass. Of the five abdominal aortic reconstructions, the kidney was protected with aortofemoral shunt placement in one patient and cold renal perfusion in three. In two of them, topical cooling of the kidney also was used. One patient with acute aortic dissection died at 39 days as a result of respiratory failure. Loss of the recently transplanted kidney was caused by acute rejection. One patient had a transient increase in serum creatinine concentration. Eight had no worsening of renal function, and none of the nine survivors lost the transplanted kidney. We conclude that aortic reconstruction can be safely performed in kidney transplant recipients. Patients in whom thoracic or thoracoabdominal aortic reconstruction was required were protected with an atriofemoral or aortofemoral bypass or shunt. Patients undergoing abdominal aortic reconstruction did well when cold renal perfusion with or without local cooling of the transplant was used for renal protection. Transplanted kidneys appeared to tolerate ischemic injury similarly to native kidneys.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995. 相似文献
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Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy 总被引:3,自引:0,他引:3
Kelsell RE; Gregory-Evans K; Payne AM; Perrault I; Kaplan J; Yang RB; Garbers DL; Bird AC; Moore AT; Hunt DM 《Human molecular genetics》1998,7(7):1179-1184
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to
within an 8 cM interval on chromosome 17p12-p13. The retinal- specific
guanylate cyclase gene (RETGC-1), which maps to within this genetic
interval and previously was implicated in Leber's congenital amaurosis, was
screened for mutations within this family and in a panel of small families
and individuals with various cone and cone- rod dystrophy phenotypes. A
missense mutation (E837D) was identified in affected members of the CORD6
family, as well as a second missense mutation (R838C) in three other
families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene
to be implicated in cone-rod dystrophy and this is the first report of
dominant mutations in this gene.
相似文献
38.
Localization of a gene for otosclerosis to chromosome 15q25-q26 总被引:5,自引:0,他引:5
Tomek MS; Brown MR; Mani SR; Ramesh A; Srisailapathy CR; Coucke P; Zbar RI; Bell AM; McGuirt WT; Fukushima K; Willems PJ; Van Camp G; Smith RJ 《Human molecular genetics》1998,7(2):285-290
Among white adults otosclerosis is the single most common cause of hearing
impairment. Although the genetics of this disease are controversial, the
majority of studies indicate autosomal dominant inheritance with reduced
penetrance. We studied a large multi- generational family in which
otosclerosis has been inherited in an autosomal dominant pattern. Five of16
affected persons have surgically confirmed otosclerosis; the remaining nine
have a conductive hearing loss but have not undergone corrective surgery.
To locate the disease- causing gene we completed genetic linkage analysis
using short tandem repeat polymorphisms (STRPs) distributed over the entire
genome. Multipoint linkage analysis showed that only one genomic region, on
chromosome 15q, generated a lod score >2.0. Additional STRPs were typed
in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and
D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis
gene.
相似文献
39.
40.
Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women 总被引:1,自引:0,他引:1
Croxatto HB; Salvatierra AM; Fuentealba B; Massai R 《Human reproduction (Oxford, England)》1998,13(12):3297-3302
The effectiveness of a sequential regimen consisting of mifepristone, 10
mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for
the next 13 days, for inhibiting ovulation and maintaining regular bleeding
cycles was assessed in 10 surgically sterilized volunteers who were
followed for one pretreatment and three treated cycles. Hormonal
determinations in blood and urine, ovarian ultrasonography, bleeding
records in all cycles and an endometrial biopsy taken on day 22-25 of the
third treatment cycle were used to monitor the effects of treatment. During
treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l)
and six biphasic cycles were recorded. Nine follicular ruptures were
detected echographically in these 30 treated cycles, five of which occurred
in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA
treatment. Echographic and endocrine features of ovulatory cycles were both
present in only four treated cycles (13.3%). Development of a secretory
endometrium was achieved in all cases, but it was always irregular. Regular
withdrawal bleeding occurred in all subjects and no adverse reactions were
recorded. The ovarian and endometrial effects of this regimen justify
testing its contraceptive effectiveness in phase 2 clinical trials.
相似文献