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1.
Stanislas Grassin‐Delyle Michaela Semeraro Frantz Foissac Naim Bouazza Haleema Shakur‐Still Ian Roberts Jean‐Marc Treluyer Saïk Urien 《Fundamental & clinical pharmacology》2019,33(6):670-678
Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV. 相似文献
2.
C Lee R Salim D Ofili-Yebovi J Yazbek A Davies D Jurkovic 《Ultrasound in obstetrics & gynecology》2006,28(6):837-841
OBJECTIVE: To determine the intraobserver and interobserver reproducibility of measurement of the percentage of protrusion of submucous fibroids into the uterine cavity using three-dimensional saline contrast sonohysterography (3D-SCSH). METHODS: Women diagnosed with submucous uterine fibroids on B-mode two-dimensional (2D) ultrasound scan were invited to join the study and 3D-SCSH was carried out. 3D volume datasets were stored digitally and were examined later using the technique of planar reformatted sections. The reproducibilities of the measurement of fibroid diameter and protrusion ratio into the uterine cavity (ratio of the size of the segment of the fibroid protruding into the cavity to the total diameter of the fibroid) were examined by two independent observers who were unaware of the initial 2D scan findings. Interobserver reproducibility was assessed by calculating the difference between measurements taken by the two operators (limits of agreement) and interclass correlation coefficient. Intraobserver repeatability was assessed by calculating the difference between two measurements for each variable (limits of agreement) and further expressed as an intraclass correlation coefficient. RESULTS: Thirty-three 3D ultrasound volumes were examined. There was a good agreement between the observers in classifying the fibroids as greater or less than 50% confined to the myometrium (Cohen's kappa 0.81). There was no bias in measurements for both variables either between observers or with repeated measurements by each observer. For fibroid diameter and protrusion ratio the inter- and intraclass correlation coefficients were high (0.984-0.995), with narrow limits of agreement. CONCLUSION: 3D-SCSH is a reproducible method for the quantification of the percentage of a submucous fibroid protruding into the uterine cavity. 相似文献
3.
4.
A S Salim 《Clinical science (London, England : 1979)》1991,80(1):59-64
1. Reserpine (5 mg/kg intraperitoneally) produced gastric mucosal vasoconstriction and injury in all rats within 6 h (injury score 38.8 +/- 2.1 mm2, mean +/- SEM). Coeliac ganglionectomy or the beta-adrenoceptor-blocking drug propranolol (5-15 mg/kg) did not influence these effects of reserpine, but vagotomy protected the rats against them. The alpha-adrenoceptor-blocking drugs phenoxybenzamine and phentolamine at 5 mg/kg were protective against injury. However, a 10 mg/kg dose of either blocker was more effective (2.2 +/- 0.5 mm2 and 3 +/- 0.8 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM, P less than 0.01) and a dose of 15 mg/kg afforded complete protection. 2. Methysergide, a 5-hydroxytryptamine receptor antagonist, produced a dose-dependent increase in the reserpine-induced injury; a significant (P less than 0.05) increase was noted with 15 and 20 mg/kg (47.5 +/- 2.9 mm2 and 49.4 +/- 2.2 mm2, respectively, versus 38.8 +/- 2.1 mm2, mean +/- SEM). 3. The results suggest that, in the rat, reserpine causes vagal alpha-adrenoceptor stimulation producing gastric mucosal vasoconstriction and injury. 5-Hydroxytryptamine is not implicated in the mechanism of this injury and affords protection against it. 相似文献
5.
A S Salim 《Journal of pharmaceutical sciences》1992,81(7):698-700
Reserpine (intraperitoneal, 5 mg/kg every day for 5 days) produced chronic ulceration of the rat stomach 2 weeks postdose. Gavage with 1% DL-cysteine or DL-methionine-S-methylsulfonium chloride at 1 mL/day for 2 weeks and 5 days protected against ulceration in 30% of the rats, and this protection extended to 80% of cases with 2% solutions. Similar gavage with 5% solutions protected all rats against ulceration without significantly influencing the basal H+ output [13.1 +/- 0.3 and 14.2 +/- 0.2 mumol for DL-cysteine and DL-methionine-S-methylsulfonium chloride, respectively, versus 15.1 +/- 0.4 mumol (mean +/- standard error of the mean; n = 10)]; that is, cytoprotection was achieved. 相似文献
6.
7.
A S Salim 《The Journal of pharmacy and pharmacology》1990,42(1):64-67
Rats infused for 24 h with pentagastrin (4 micrograms kg-1 min-1) and carbachol (0.8 microgram kg-1 min-1) developed acute duodenal ulceration (100%) and hyperchlorhydria (69 +/- 5.3 mumol h-1 vs 14 +/- 0.9 mumol h-1, P less than 0.001, n = 10). The animals were then given daily by gavage, saline, allopurinol with dimethyl sulphoxide (DMSO) or cysteine with methyl methionine sulphonium bromide (MMSB). Two days after the infusion, 10 rats (100%) given saline and 7 rats (70%) given allopurinol and DMSO, or cysteine and MMSB, showed duodenal ulceration. Five days after the infusion, 8 rats (80%) given saline, 3 rats (30%) given allopurinol and DMSO, and 2 rats (20%) given cysteine and MMSB had duodenal ulceration. Seven days after the infusion, only 5 rats (50%) given saline still had duodenal ulceration. Daily intramuscular injection of reserpine (0.1 mg kg-1) for 6 weeks produced chronic duodenal ulceration (90%) and hyperchlorhydria (47 +/- 3.1 mumol h-1 vs 12 +/- 0.9 mumol h-1, P less than 0.001, n = 10). Animals were then given daily by gavage, saline, allopurinol and DMSO, or cysteine and MMSB. Five days after reserpine, 10 rats (100%) given saline, 8 rats (80%) given allopurinol and DMSO, and 7 rats (70%) given cysteine and MMSB showed duodenal ulceration. Ten days after reserpine, 9 rats (90%) given saline, 3 rats (30%) given allopurinol and DMSO, and 4 rats (40%) given cysteine and MMSB had duodenal ulceration. Fifteen days after reserpine, 8 rats (80%) receiving saline and only one rat (10%) receiving allopurinol and DMSO or cysteine and MMSB had duodenal ulceration.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
The validity and use of psychosocial assessments in occupational therapy are ongoing concerns (Moyer, 1984) and were the focus of this study. Fifty African patients with schizophrenia and 10 nondysfunctional African volunteers took an an assessment battery that included the Schroeder, Block, Campbell Adult Psychiatric Sensory Integration Evaluation (SBC) (Schroeder, Block, Trottier, & Stowell, 1978), a daily activity, work, and leisure activity interview based on the Model of Human Occupation (Kielhofner, 1985), and a culture-specific test of functional performance. Data on subjects' psychiatric histories and demographics were collected. Rationale for the assessments used, methods for devising the functional assessment, methods and procedures for data collection, and analysis are presented. A stronger relationship was found to exist between subjects' performances on the SBC and the functional activity test than between interviews based on the Model of Human Occupation and the functional activity test, both for patients and for the whole sample. All assessments were found to differentiate between patients and nonpatients, although the SBC was the best discriminator. Among psychiatric history variables, the strongest relationships were between measures of seriousness of illness and both the SBC and functional activity assessment. The most effective way to measure performance dysfunction and seriousness of illness in persons with schizophrenia was to measure the underlying sensorimotor impairment or to use a culture-specific test of functional performance. 相似文献
9.
Salim H. Khalil Mohammed H. Qari John M. Jackson Robert Haywood Pyle Hassan El-Solh Abdallah Al-Nasser 《Leukemia research》1994,18(12):881-883
Geographical variations in the incidence of disease are of considerable theoretical and practical importance. It has been claimed that the distribution of acute lymphoblastic leukemia (ALL) phenotypes in Saudi Arabia is different from that recorded in the Western literature. One hundred and twelve (112) patients under 15 years of age, diagnosed as ALL between January 1992 and May 1994 had immunophenotypes performed on their blast cells. Common ALL (cALL) together with pre-B-ALL, formed 86.5% of the total; B-cell 3%, T-cell 6% and null cell 4.5%. These figures are not significantly different from the Western literature. A previous claim from this institution in 1990, that both null and B-cell ALL were significantly increased compared with elsewhere, is not supported by the present figures. Age and sex distribution, and FAB classification, L1 77%, L2 20% and L3 3%, were also of the same order as described elsewhere and, in particular, there was no increase in the frequency of L3 subtype. 相似文献
10.
Tension development in response to direct and indirect electrical stimulation was studied in an isolated phrenic nerve hemidiaphragm preparation of the mouse. β-Endorphin (β-EP) caused an increase in the preparation of the mouse. β-Endorphin (β-EP) caused an increase in the response to low frequency stimulation of the nerve. Upon direct stimulation of the muscle the peptide had no effect. The actions of β-EP were abolished in the presence of the opioid antagonist naloxone and mimicked by β opioid agonists. Upon high frequency stimulation of the nerve, β-EP caused an increase in the initial, maximum, and mean tension. It also prevented the fall in the final tension seen in the control preparations with repeated periods of stimulation. The findings are consistent with β-EP having a role to improve neuromuscular function and deley fatigue, and indicate the possible therapeutic potential of opioid substances in conditions where muscle weakness is present. © John Wiley & Sons, Inc. 相似文献