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21.
MGC Hendriks P Dogterom JT Ebels B Oosterhuis LR Geertsema T Hulot G Bianchetti and JHG Jonkman 《Fundamental & clinical pharmacology》1998,12(5):559-565
Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)1, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (cmin), the maximum plasma concentration (cmax), the time to reach that concentration (tmax), the time interval during which the plasma concentration exceeds 50% of cmax (t50), the area under the plasma concentration-time curve (AUC72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC72–96 (AUCNDM and AUCDAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated. 相似文献
22.
Effect of elevated prolactin levels on the synthesis and release of catecholamines from the adrenal medulla in female rats 总被引:1,自引:0,他引:1
J Fernandez-Ruiz M Cebeira C Agrasal J A Tresguerres A I Esquifino J A Ramos 《Neuroendocrinology》1987,45(3):208-211
Recent evidence suggests that increased plasma prolactin (PRL) levels could be modifying the synthesis and release of catecholamines (CA) from the adrenal medulla. In order to study this possibility, female rats bearing an anterior pituitary gland, from a litter-mate donor, under the right kidney capsule since day 30 of life and their sham-operated controls were sacrificed by decapitation 45 days after the transplant operation. Plasma PRL and CA levels and CA content in the adrenal medulla were analyzed. A significant increase in plasma PRL levels was shown in grafted (22 +/- 2 micrograms/l) when compared to control rats (6 +/- 0.3 micrograms/l), together with a significant increase in plasma norepinephrine (NE) (4.2 +/- 1.1 micrograms/l vs. 1.7 +/- 0.7 micrograms/l) and epinephrine (E) (2.9 +/- 0.6 micrograms/l vs. 1.6 +/- 0.2 micrograms/l). Similar plasma dopamine (DA) levels were found in both groups (0.6 +/- 0.2 micrograms/l vs. 0.8 +/- 0.3 micrograms/l). An increase in adrenal DA content (29.1 +/- 6.8 ng/mg protein), together with a decrease in NE (33.3 +/- 6.8 ng/mg protein) and E content (65.9 +/- 11.8 ng/mg protein) was detected in grafted as compared to control rats (DA: 12.0 +/- 3.6 ng/mg protein; NE: 79.3 +/- 22.1 ng/mg protein; E: 184.2 +/- 39.2 ng/mg protein). We can conclude from these data that the elevation of circulating PRL levels induced by a pituitary graft is able to increase the synthesis and release of CA from the adrenal medulla in female rats. 相似文献
23.
Monitoring of the rejection of intrasplenic hepatocyte allografts and xenografts in the rat using technetium 99m-imidoacetic acid scanning 总被引:2,自引:0,他引:2
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A validity study of the Brazilian version of the 15-item Short Psychiatric Evaluation Schedule (SPES), included in the mental health assessment of Older Americans Resources and Services (OARS), designed to detect psychiatric disorders in the elderly, against the "caseness" criterion suggested by Cooper and Schwarz was carried out with a community sample, as part of a survey to study health and living conditions of the elderly in a large urban center of a developing country, S?o Paulo, Brazil. The screening questionnaire was completed by 292 subjects, and 91 were selected for the psychiatric interview. The validity coefficients were as follows: sensitivity 61%, specificity 89%, positive predictive value 66%, negative predictive value 87% and misclassification rate 18%. A discriminant analysis using a stepwise procedure was then applied to select the best item discriminators of the screening questionnaire. The best set of discrimination comprised six items leading to the following validity coefficients: sensitivity 82%, specificity 77%, positive predictive value 58%, negative predictive value 92% and misclassification rate 21%. The possible factors related to false positive and false negative responses on the screening are discussed. 相似文献
27.
A reduced version of the Face-Hand Test (FHT), the FHT-R, was applied to a random sample of 91 elderly subjects living in the community (S. Paulo-Brazil), to study the instrument's ability to detect Organic Brain Syndrome (OBS). The scores of the FHT-R test were then compared with a psychiatric assessment using the Clinical Interview Schedule. Five persons were regarded as OBS "cases" and 86 as OBS "non cases". At the cut-off point 0/1 the validity coefficients were as follows: Sensitivity 60%, Specificity 94%, Positive Predictive Value 38%, Negative Predictive Value 98% and Overall Misclassification Rate 8%. The usefulness of this clinical test to screen for OBS in epidemiological surveys is discussed. 相似文献
28.
Performance of the TechLab C. DIFF CHEK-60 enzyme immunoassay (EIA) in combination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea 下载免费PDF全文
We compared a recently marketed enzyme immunoassay for glutamate dehydrogenase (GDH), TechLab's C. DIFF CHEK-60 (TL-GDH), in combination with the C. difficile Tox A/B II enzyme immunoassay (Tox-A/B) with (i) the Triage C. difficile test, which detects both GDH (TR-GDH) and toxin A (TR-Tox-A); (ii) an in-house cytotoxin assay (C-Tox); and (iii) stool cultures for C. difficile. All C. difficile isolates were tested for the presence of the toxin genes by PCR. If a toxin gene-positive strain of Clostridium difficile was recovered and a toxin was detected by any method, the result was considered to be truly positive. Eighty-seven of 93 and 79 of 93 C. difficile culture-positive samples were also TL-GDH and TR-GDH positive, respectively. No test was able to detect toxin in all samples with true-positive results. Tox-A/B and TR-Tox-A in combination with the GDH detection tests and C-Tox were able to identify 52 and 50 samples with true-positive results. Tox-A/B and TR-Tox-A would have missed 15 and 31% of cases of C. difficile-associated diarrhea, respectively, if used alone. 相似文献
29.
David Tarrag Julio Casal Jesús Ruiz-Contreras J. Toms Ramos Pablo Rojo Harm Snippe Wouter T. M. Jansen 《Clinical and Vaccine Immunology : CVI》2005,12(1):165-170
We investigated antibody responses against pneumococci of serotypes 6B, 14, and 23F in 56 children and adolescents with perinatal human immunodeficiency virus (HIV) infection who were vaccinated with 7-valent pneumococcal conjugate vaccine. Overall immune responses differed greatly between serotypes. Correlation coefficients between immunoglobulin G (IgG) measured by enzyme-linked immunosorbent assay (ELISA) and functional antibodies measured by a flow cytometry opsonophagocytosis assay (OPA) varied with serotype and time points studied. After 3 months of administering a second PCV7 dose we got the highest correlation (with significant r values of 0.754, 0.414, and 0.593 for serotypes 6B, 14, and 23F, respectively) but no significant increase in IgG concentration and OPA titers compared to the first dose. We defined a responder to a serotype included in the vaccine with two criteria: frequency of at least twofold OPA and ELISA increases for each serotype and frequency of conversion from negative to positive OPA levels. Responders varied from 43.9% to 46.3%, 28.5% to 50.0%, and 38.0% to 50.0% for serotypes 6B, 14, and 23F, respectively, depending on the response criterion. The present research highlights the importance of demonstrating vaccine immunogenicity with suitable immunological endpoints in immunocompromised patients and also the need to define how much antibody is required for protection from different serotypes, since immunogenicity differed significantly between serotypes. 相似文献
30.
J.?Macías J.?A.?PinedaEmail author F.?Lozano J.?E.?Corzo A.?Ramos E.?León J.?A.?García-García J.?Fernández-Rivera J.?A.?Mira J.?Gómez-Mateos 《European journal of clinical microbiology & infectious diseases》2003,22(11):675-680
Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is highly prevalent in southern Europe. However, there are few and contradictory data about the effect of HCV carriage on the response to highly active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T cells following HAART among antiretroviral-naïve patients seropositive for HIV with and without HCV coinfection was investigated. Two hundred one HIV-infected patients without previous exposure to antiretroviral drugs were included in the study. HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/µl was longer in the HCV-positive group (P<0.001). In a Cox model, HCV infection and lack of persistent HIV viremia (defined as <200 copies/ml) were associated with the time to recover 200 CD4+ cells/µl. The mean increase in CD4+ cell counts was lower in the HCV-positive group during the first year of therapy. HIV/HCV-coinfected patients naïve for antiretroviral therapy show a delayed recovery of CD4+ cell counts after starting HAART. 相似文献