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排序方式: 共有778条查询结果,搜索用时 31 毫秒
1.
R. Watson T. Kozlowski V. Nickeleit J. T. Woosley J. L. Schmitz S. L. Zacks J. H. Fair D. A. Gerber K. A. Andreoni 《American journal of transplantation》2006,6(12):3022-3029
Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d. 相似文献
2.
BACKGROUND: The QT interval on the ECG is prolonged by more than 50 marketed drugs, an effect that has been associated with syncope and/or sudden cardiac death due to an arrhythmia. Because changes in heart rate also change the QT interval, it has become standard practice to use a correction formula, such as the Bazett formula, to normalize the QT interval to a heart rate of 60 bpm, that is, the rate-corrected QT or QTc. Numerous other formulas have been devised to make this correction, including the Fridericia, Hodges, and Framingham formulas. OBJECTIVES: The purpose of this study was to investigate how the Bazett formula and three other formulas influence assessment of the QT-prolonging effect of the potassium channel-blocking drug ibutilide. METHODS: Using a standardized physical activity protocol, the QT interval was assessed over a broad range of heart rates before and after an infusion of ibutilide (4.75 microg/kg) that produced a stable 15- to 20-ms QT prolongation in consenting normal subjects (9 men and 9 women). The QT interval was measured digitally over a range of heart rates from 60 to 120 bpm, and then four correction formulas (Bazett, Fridericia, Framingham, or Hodges) were applied. The uncorrected change in QT interval due to ibutilide was compared with the change using each of the formulas by repeated measures analysis of variance. RESULTS: At heart rates from 60 to 120 bpm, the Bazett and Fridericia correction formulas overestimated the change in QT in both men and women (P <.001). However, the Framingham and Hodges formulas did not alter the accuracy of the assessment of QT interval change. CONCLUSION: Rate correction of QT intervals using the standard Bazett and Fridericia formulas can introduce significant errors in the assessment of drug effects on the QT interval. This has implications for the clinical assessment of drug effects and for the safety assessment of new drugs under development. 相似文献
3.
Golli M; Van Nhieu JT; Mathieu D; Zafrani ES; Cherqui D; Dhumeaux D; Vasile N; Rahmouni A 《Radiology》1994,190(3):741
4.
Genetically-determined interaction between propafenone and low dose quinidine: role of active metabolites in modulating net drug effect. 总被引:2,自引:2,他引:0 下载免费PDF全文
C Funck-Brentano H K Kroemer H Pavlou R L Woosley D M Roden 《British journal of clinical pharmacology》1989,27(4):435-444
1. Quinidine is a potent inhibitor of the genetically-determined debrisoquine 4-hydroxylation. Oxidation reactions of several other drugs, including the 5-hydroxylation of the new antiarrhythmic drug propafenone, depend on the isozyme responsible for debrisoquine 4-hydroxylation. 2. The effect of quinidine on the debrisoquine phenotype-dependent 5-hydroxylation and the pharmacological activity of propafenone was studied in seven 'extensive' metabolizers and two 'poor' metabolizers of the drug receiving propafenone for the treatment of ventricular arrhythmias. 3. In patients with the extensive metabolizer phenotype, quinidine increased mean steady-state plasma propafenone concentrations more than two fold, from 408 +/- 351 (mean +/- s.d.) to 1096 +/- 644 ng ml-1 (P less than 0.001), decreased 5-hydroxypropafenone concentrations from 242 +/- 196 to 125 +/- 97 ng ml-1 (P less than 0.02) and reduced propafenone oral clearance by 58 +/- 23%. 4. Despite these changes in plasma concentrations, electrocardiographic intervals and arrhythmia frequency were unaltered by quinidine coadministration, indicating that 5-hydroxypropafenone contributes to the pharmacologic effects of propafenone therapy in extensive metabolizers. 5. In contrasts, plasma concentrations of propafenone and 5-hydroxypropafenone remained unchanged in the two patients with the poor metabolizer phenotype. 6. Biotransformation of substrates for the debrisoquine pathway can be markedly perturbed by even low doses of quinidine; interindividual variability in drug interactions may have a genetic component. 相似文献
5.
6.
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
7.
Richard C. Semelka Suvipapun Worawattanakul Nikolaos L. Kelekis Gesine John John T. Woosley Mark Graham William G. Cance 《Journal of magnetic resonance imaging : JMRI》1997,7(6):1040-1047
This study compares liver lesion detection, characterization, and effect on patient management between single-phase spiral CT and MRI using spoiled gradient echo (SGE), T2-weighted fat-suppressed spin echo, and serial post gadolinium SGE. All patients with suspected liver lesions who underwent spiral CT and MRI within a 1-month period between January 1993 and September 1996 were included in the study. Spiral CT and MRI were interpreted prospectively in a blinded fashion by separate individual experienced investigators, and lesion detection and characterization were determined. Confirmation was obtained by surgery (6 patients), biopsy (18 patients), imaging follow-up (36 patients), or combined reading of all imaging studies and clinical follow-up (29 patients). Effect on patient management was determined by combined chart review and interview of the patients' physicians and by retrospective clinical assessment performed by a surgical oncologist and medical oncologist separately. Eighty-nine patients were included in the study. Regarding true positive lesion detection, 295 and 519 lesions were detected on spiral CT and MR images, respectively, which was significantly different on a patient-by-patient basis (P < .001). More lesions were detected on MR than on spiral CT in 44 of 89 patients (49.4%), and 11 of these 44 patients had lesions shown on MRI in whom no lesions were apparent on CT images. No patients had true positive lesions shown on spiral CT that were not shown on MRI. Regarding lesion characterization, 129 and 466 lesions were characterized on spiral CT and MRI images, respectively, which was significantly different on a patient-by-patient basis (P < .001). More lesions were characterized on MR than CT images in 67 patients (75.3%). Regarding effect on patient management, chart review with physician interview demonstrated that findings on MRI provided information that altered patient management as compared with findings on spiral CT in 57 patients. Retrospective clinical evaluation by the surgical and medical oncologist showed that MRI was considered to have a greater effect on patient management than spiral CT in 58 and 55 patients, respectively. Comparing current MRI technique to single-phase spiral CT, MRI detected more lesions in 49.4% and characterized more lesions in 75.3% of patients investigated for focal liver disease. MRI had a greater effect on patient management in each of the three methods than singlephase spiral CT in more than 61% of patients. 相似文献
8.
Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant. 相似文献
9.
Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system 总被引:8,自引:0,他引:8
Hwu YM; Lee RK; Chen CP; Su JT; Chen YW; Lin SP 《Human reproduction (Oxford, England)》1998,13(7):1916-1921
Recently, in-vitro maturation (IVM) of immature human oocytes recovered
from non-stimulated follicles has been applied in the treatment of
infertility. However, in previous reports, very few embryos cultured in
conventional medium have reached the expanded blastocyst stage following
in-vitro maturation and fertilization (IVM/IVF). The objective of this
study was to investigate whether the developmental competence of human
embryos following IVM/IVF could be enhanced by the use of a human ampullary
cell co-culture system. Immature human oocytes were aspirated from small
follicles at Caesarean section and then cultured in medium containing human
menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes
were randomly cultured either in conventional culture medium alone or in
the co-culture system. Of 48 embryos cultured in conventional medium alone,
all arrested at the 2-16- cell stage on day 3 after insemination. Of 46
embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at
the 2-16-cell stage. Six embryos (13%) developed to the morula stage.
Fourteen embryos (30.4%) developed to expanded blastocysts and two
blastocysts were hatching on day 7 after insemination. We conclude that
co-culture significantly enhances the development of blastocysts in embryos
resulting from IVM/IVF.
相似文献
10.
The ratio of 2nd to 4th digit length: a predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen 总被引:19,自引:2,他引:19
Manning JT; Scutt D; Wilson J; Lewis-Jones DI 《Human reproduction (Oxford, England)》1998,13(11):3000-3004
The differentiation of the urinogenital system and the appendicular
skeleton in vertebrates is under the control of Hox genes. The common
control of digit and gonad differentiation raises the possibility that
patterns of digit formation may relate to spermatogenesis and hormonal
concentrations. This work was concerned with the ratio between the length
of the 2nd and 4th digit (2D:4D) in humans. We showed that (i) 2D:4D in
right and left hands has a sexually dimorphic pattern; in males mean 2D:4D
= 0.98, i.e. the 4th digit tended to be longer than the 2nd and in females
mean 2D:4D = 1.00, i.e. the 2nd and 4th digits tended to be of equal
length. The dimorphism is present from at least age 2 years and 2D:4D is
probably established in utero; (ii) high 2D:4D ratio in right hands was
associated with germ cell failure in men (P = 0.04); (iii) sperm number was
negatively related to 2D:4D in the right hand (P = 0.004); (iv) in men
testosterone concentrations were negatively related to right hand 2D:4D and
in women and men LH (right hand), oestrogen (right and left hands) and
prolactin (right hand) concentrations were positively correlated with 2D:4D
ratio and (v) 2D:4D ratio in right hands remained positively related to
luteinizing hormone and oestrogen after controlling for sex, age, height
and weight.
相似文献