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
Studies have shown a high correlation between measurements of bone mineral density (BMD) obtained on differentdual-energy X-ray absorptiometry machines. Challenger osteodensitometers (Diagnostic Medical System [DMS],Montpellier, France) are becoming widely used but little is known about their clinical performance. The aim of this study was to compare BMD measurements and the resulting patient classification based on T-scores obtained on a DMS Challenger device to those obtained on Hologic 4500A (Bedford, MA) device. Fifty-three volunteers were studied.The BMD of the spine and of the hip were simultaneously measured on both densitometers. BMD values obtained on the Challenger were significantly higher than those obtained with the Hologic QDR4500 (p<0.001). The correlations coefficients between the Hologic QDR4500 and the DMS Challenger measured BMDs were r=0.70 at the femoral neck, r=0.70 at the trochanter, and r=0.83 at the spine (p<0.001). Among the 35 postmenopausal women, there was discordance in the WHO T-score-based classification in 28 subjects (80%) at the spine, 18 subjects (52%) at the femoral neck, and 14 subjects (42%) at the trochanter. The intermachine agreement was low: The kappa score was -0.10 at the spine, 0.2 at the femoral neck, and 0.3 at the trochanter. In conclusion, this study cautions against the use of non established densitometers that leads to underdiagnosis of patients and, subsequently, to inappropriate treatment strategies. 相似文献
Synovial sarcoma demonstrates epithelial differentiation, either by light microscopy (biphasic synovial sarcoma) or by immunohistochemical/ultrastructural methods only (monophasic) and poorly differentiated synovial sarcoma. Although the glands of synovial sarcoma are known to have tight junction-like structures, far less is known about junction formation in the spindled component of synovial sarcomas. Additionally, it is unknown whether the tight junctions of synovial sarcoma are normally constituted. The tight junction is a multiprotein complex consisting of numerous proteins that include ZO-1, claudin-1 and occludin. A total of 35 cases of synovial sarcoma (13 biphasic, 14 monophasic and eight poorly differentiated) were immunostained for ZO-1, claudin-1 and occludin using commercially available antibodies, heat-induced epitope retrieval and standard avidin-biotin technique. When available, corresponding electron micrographs were reviewed. For five cases, the presence of either an SYT-SSX1 (three cases) or SYT-SSX2 (two cases) gene fusion was known. Positive cases showed particulate membrane staining. The glands of biphasic synovial sarcomas expressed ZO-1 (13/13), claudin-1 (12/13) and occludin (11/13) in a manner identical to normal glandular epithelia, at the apical portion of the lateral membrane. The spindle cells of biphasic synovial sarcomas showed abnormal circumferential membranous expression of ZO-1 (12/13), claudin-1 (6/13) and occludin (3/13). Monophasic synovial sarcomas expressed ZO-1 in a circumferential pattern (13/14) but less often claudin-1 (4/14) or occludin (3/14). Poorly differentiated synovial sarcomas expressed ZO-1 (8/8) and claudin-1 (6/8) but only rarely occludin (2/8). By electron microscopy, recognizable tight junctions were seen only in glands. No correlation was seen between histologic subtype or fusion type and expression of tight junction proteins. We conclude that the glands of biphasic synovial sarcomas show well-organized, true epithelial tight junctions. In contrast, the spindled cells of all synovial sarcomas show significant abnormalities in the expression and localization of tight junction proteins, suggesting partial and/or aberrant epithelial differentiation. 相似文献
The development of T- or B-membrane determinants on human foetal lymphoid cells was studied by the direct immunofluorescence technique, using a tetramethyl rhodamine isothiocyanate (TRITC) labelled horse antihuman T-cell conjugate (ATC) for the detection of T lymphocytes and a fluorescein isothiocyanate (FITC) labelled goat antihuman Fab conjugate for the demonstration of Ig-bearing B lymphocytes. Human foetal lymphocytes were also tested for spontaneous rosette formation with sheep red blood cells (SRBC).
Cell suspensions of liver, spleen, thymus, bone marrow and blood of twenty-five human foetuses of 5·5–26 weeks of gestational age have been investigated. ATC-positive lymphoid cells were first seen in the liver at 5·5 weeks; E rosette-forming cells (ERFC) and Ig-bearing lymphoid cells were first found at 9 weeks. ERFC were also present in the thymus at 9 weeks. By 12 weeks, fluorescent B and T lymphocytes were found in bone marrow and spleen. ERFC were also found in bone marrow at this age, but not in spleen. At 15 weeks, more than 80% of blood lymphoid cells had T or B determinants.
A difference in the reactivity of lymphoid cells with the ATC and their capacity to form E rosettes was observed. In liver and spleen, the ATC determinant was detectable before the SRBC receptor. In bone marrow, blood and thymus the ATC determinant was found on a higher percentage of lymphoid cells than was the SRBC receptor when those organs were first investigated. During the entire investigated period of gestation, the majority of lymphoid cells in liver and bone marrow did not react with either of the conjugates, nor did they form E rosettes. In all organs investigated, except in the thymus, lymphoid cells were occasionally seen which reacted with both conjugates. By the 16th week of foetal age, more than 90% of lymphoid cells in thymus, spleen and blood had acquired T- or B-membrane determinants.
The synthesis and transportation proteins of the Vi capsular polysaccharide of Salmonella enterica serovar Typhi (serovar Typhi) are encoded by the viaB operon, which resides on a 134-kb pathogenicity island known as SPI-7. In recent years, Vi-negative strains of serovar Typhi have been reported in regions where typhoid fever is endemic. However, because Vi negativity can arise during in vitro passage, the clinical significance of Vi-negative serovar Typhi is not clear. To investigate the loss of Vi expression at the genetic level, 60 stored strains of serovar Typhi from the Faisalabad region of Pakistan were analyzed by PCR for the presence of SPI-7 and two genes essential for Vi production: tviA and tviB. Nine of the sixty strains analyzed (15%) tested negative for both tviA and tviB; only two of these strains lacked SPI-7. In order to investigate whether this phenomenon occurred in vivo, blood samples from patients with the clinical symptoms of typhoid fever were also investigated. Of 48 blood samples tested, 42 tested positive by fliC PCR for serovar Typhi; 4 of these were negative for tviA and tviB. Three of these samples tested positive for SPI-7. These results demonstrate that viaB-negative, SPI-7-positive serovar Typhi is naturally occurring and can be detected by PCR in the peripheral blood of typhoid patients in this region. The method described here can be used to monitor the incidence of Vi-negative serovar Typhi in regions where the Vi vaccine is used. 相似文献
BACKGROUND: Maintaining asthma control is a major objective of therapy. Traditionally, the effectiveness of asthma therapy has been judged primarily by its effect on airway function rather than on multiaspect asthma control. OBJECTIVE: An inhaled corticosteroid and a leukotriene receptor antagonist were compared to determine whether they provided equivalent effects, as judged by days of asthma control. METHODS: In a randomized, multicenter, double-blind, placebo-controlled, parallel-group study, asthmatic patients (n = 782) with FEV(1) percent predicted values of between 50% and 85% and a weekly average beta-agonist use of more than 2 puffs per day were randomized to receive montelukast (10 mg daily), beclomethasone (200 microg twice daily), or placebo treatment for 6 weeks in a double-dummy fashion. We examined the distribution of the primary end point: percentage of days of asthma control. Secondary end points included FEV(1), albuterol use, occurrence of an asthma attack, asthma flare-up, rescue corticosteroid use, sustained asthma control, and adverse experiences. RESULTS: The percentage of days of asthma control was almost identical between the montelukast and beclomethasone groups (98% overlap in the distribution). Montelukast was at least equal to beclomethasone, and both were greater than placebo on the basis of frequency of asthma attacks, asthma flare-ups, and rescue corticosteroid use. Beclomethasone had a greater effect than montelukast and both treatments were better than placebo at improving FEV(1). CONCLUSIONS: Montelukast was as effective as beclomethasone, as judged by indices of clinical control other than FEV(1). When evaluating the outcome of montelukast therapy, FEV(1) might underestimate clinical effectiveness. 相似文献
Introduction: Tunisia is experiencing a double burden of morbidity, characterized by the explosion of cardiovascular diseases and their risk factors including arterial Hypertension. The objective of this study, based on the HSHS cohort (Hammam Sousse Sahloul Heart Study), was to determine the prevalence of hypertension in the general population and to identify its predisposing factors. Methods: HSHS is a cardiovascular health promotion initiative in the city of Hammam Sousse (Tunisia). The study was conducted via a random sample of households, using the WHO PEV technique, made up of 33 clusters, of 33 households each. All people aged 20 and over, included, benefited from a questionnaire, a physical examination and a biological assessment. The Systolic Blood Pressure (SBP) and the Diastolic Blood Pressure (DBP) were measured from the average of the last two measurements, by an OMRON type tensiometer, of suitable width. These prevalences were adjusted according to sex and age group, by their weighting coefficients in the general population, and they were accompanied by their 95% CIs. Binary logistic regression was conducted to identify independent factors associated with hypertension. Results: The study population was composed of 481 men (33.4%) and 960 women (66.6%), with an average age of 49.6±16.35 years in males (M) and 46.6±16.18 in females (F). In addition to the family history of hypertension, the sufficient weekly consumption of vegetables and fruits was low (M: 32.4%, F: 24.9%). The adjusted rate of hypertension in the adult study population was 32.5%, 95%CI[31.9-33.1] (M: 36.4%, 95%CI[35, 5-37.3]; F: 28.4%; 95% CI[27.6-29.2]), reaching in the age group of 60 years and above: M: 74.6% (95%CI[66.9-82.3], F: 82.7% (95%CI[73.8-83.6]) Multivariate analysis identified five independent factors significantly associated with hypertension: male sex (ORa=1.55 [1.18-2.03]), age over 40 years (ORa=6.54[4.70-9.11]), low level of schooling (ORa=1.80 [1.36-2.38]), low physical activity (ORa=1.42[1.07-1.88]) and high socio-economic level (ORa=1 .84 [1.30-2.63]). Conclusion: The HSHS study confirmed the high prevalence of hypertension, and the extent of its low detection and control. Hence the need for a universal approach to health promotion, oriented towards the general population, piloted by its local organizations, based on the adoption of a healthy lifestyle, and centered on physical activity. 相似文献
Primary retroperitoneal cavernous hemangioma is an extremely rare disease in clinical practice. It is classified as a vascular tumor. Only three cases have been reported in the literature. The diagnosis is uncommon due to the lack of specific radiological features. It becomes symptomatic as a consequence of its enormous size or complications like rupture or compression. We herein report a unique case of primary retroperitoneal cavernous hemangioma treated with conventional surgery in a 35‐year‐old male patient admitted to our department for chronic abdominal pain. Retroperitoneal cavernous hemangioma is an extremely rare vascular tumor in adulthood. Confirmation is made by histopathological examination after total surgical resection. 相似文献
We report a case of a patient who presented for ACTH‐dependent Cushing after a confirmed hypercortisolism and an inadequate normal ACTH. A transsphenoidal surgery of a pituitary picoadenoma has been done. After surgery, the patient showed the persistence of hypercortisolism. CT scan revealed adrenal adenomas removed surgically and improved the patient. 相似文献