Distribution of oral nimesulide in female genital tissues

Nimesulide is a non-steroidal anti-inflammatory agent which has proved to be effective in reducing menstrual discomfort in dysmenorrhoeaic women. To determine the concentrations of this drug in the uterus (fundus, cervix), oviduct, and ovaries and to correlate these findings with plasma concentrations, a single oral dose of 100 mg nimesulide was administered 1 to 6 h before surgery to 12 women undergoing hysterectomy and salpingo-oophorectomy, mainly for fibroids. Tissue samples were taken, concentration of nimesulide measured by HPLC, and findings compared with plasma concentrations. One patient not undergoing treatment served as control. Nimesulide concentration in the tissues studied was highest 3 h after administration, as expected from the drug's pharmacokinetic profile. The highest tissue/plasma ratio (0.5) was also found at that time. Average tissue concentrations at 1, 2, 3, and 6 h after drug intake ranged from 0.3 to 1.8 micrograms g-1, and plasma concentrations from 2.6 to 4.1 micrograms ml-1. Nimesulide was evenly distributed in the tissues studied.     

抗痫灵在大鼠肝脏中代谢的研究

用离体大鼠肝脏灌流法,研究了抗痫灵在肝脏灌流过程中的代谢规律。用高效液相色谱法由灌流液中分离、制备得到了两种代谢物,经紫外吸收光谱与质谱鉴定,确定代谢物的结构为3,4-次甲基二氧桂皮酰羟基哌啶及阿魏酰哌啶,后者经化学合成得到了进一步的确证。本文还研究了肝循环过程中抗痫灵的代谢动力学,揭示了大部份抗痫灵以原形结合贮存于肝脏中。     

Jejunal access loop cholangiogram and intervention using image guided access

Jejunal access loop is fashioned in patients who undergo Roux en Y hepaticojejunostomy and biliary intervention is anticipated on follow up. Post-operative study of the biliary tree through the access loop is usually done under fluoroscopic guidance. We present a series of 20 access loop cholangiograms performed in our institution between August 2004 and November 2008. We aimed to evaluate the safety and efficacy of the procedure and to highlight the role of CT guidance in procuring access. Access loop was accessed using CT (n = 13), ultrasound (n = 3) or fluoroscopic guidance (n = 4). Fluoroscopy was used for performing cholangiograms and interventions. Twelve studies had balloon plasty of the stricture at anastomotic site or high up in the hepatic ducts. Seven studies showed normal cholangiogram. Plasty was unsuccessful in one study. Technical success in accessing the jejunal access loop was 100%; in cannulation of anastomotic site and balloon plasty it was 95%. One case required two attempts. Procedure-related complications were not seen. All patients who underwent balloon plasty of the stricture were doing well for variable lengths of time. Access loop cholangiogram and interventions are safe and effective. CT guidance in locating/procuring the access loop is a good technique.     

成纤维细胞生长因子对兔纤维环细胞转化生长因子β2的调节

目的:观察成纤维细胞生长因子对培养兔纤维环细胞转化生长因子β2表达的调节作用。方法:实验于2005-03/2006-04在华中科技大学同济医学院附属协和医院骨科实验室完成。培养4月龄雌性日本大白兔的纤维环细胞,在每次换液时加入成纤维细胞生长因子100μg/L,铺满后收集细胞,作纤维环细胞转化生长因子β2常规免疫组织化学研究,细胞呈棕黄色染色为阳性表达信号,同时为进一步明确纤维环细胞转化生长因子β2的定位进行免疫胶体金标记电镜观察。结果:光镜下细胞明显呈棕色,电镜下细胞膜表面有明显的胶金颗粒粘附。结论:成纤维细胞生长因子能促进纤维环细胞转化生长因子β2的表达。     

Long-term follow-up of a phase III study of recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancies

One hundred and twenty-eight patients with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), and acute lymphoblastic leukemia (ALL) previously reported from a phase III trial of rhGM-CSF or placebo following autologous bone marrow transplantation (ABMT) were investigated for the development of late toxicities. Median follow-up is 36 months. No apparent long-term deleterious effects on BM function were observed. Moreover, disease-free survival and overall survival were similar for patients on both treatment arms, arguing for the long- term safety of recombinant human granulocyte macrophage-colony- stimulating factor (rhGM-CSF). The only factors predictive for both a high risk of relapse over time and mortality were having the diagnosis of ALL and/or undergoing ABMT in resistant relapse. We attempted to identify clinical variables before BM harvest, at the time of marrow infusion, or events within the first 100 days posttransplant, which might predict speed of neutrophil recovery in the setting of placebo or rhGM-CSF administration after ABMT. Only previous exposure to agents that deplete stem cells led to a significant delay in neutrophil recovery, suggesting their avoidance in patients who may undergo ABMT. Nevertheless, even those patients benefited from rhGM-CSF. For all patients, rhGM-CSF and agents that deplete stem cells were the strongest independent predictors for neutrophil engraftment. With the increasing use of newer hematopoietic growth factors both alone and in combination, long-term follow-up is essential to confirm the same safety that we report with rhGM-CSF.     

Relationships among premorbid alcohol use, acute intoxication, and early functional status after traumatic brain injury

Vickery CD, Sherer M, Nick TG, Nakase-Richardson R, Corrigan JD, Hammond F, Macciocchi S, Ripley DL, Sander A. Relationships among premorbid alcohol use, acute intoxication, and early functional status after traumatic brain injury.

Objective

To investigate the relationships among intoxication at time of injury, preinjury history of problem drinking, and early functional status in patients with traumatic brain injury (TBI).

Design

Prospective cohort study.

Setting

Acute inpatient TBI rehabilitation.

Participants

Participants were 1748 persons with TBI.

Interventions

Not applicable.

Main Outcome Measures

Blood alcohol levels (BALs) were obtained at admission to the emergency department, and a history of problem drinking was obtained through interview. Study outcomes, Disability Rating Scale (DRS), and FIM instrument scores were gathered at admission to inpatient rehabilitation.

Results

Multivariate regression analysis revealed that BAL and a history of binge drinking were predictive of DRS, but not FIM, scores. A higher BAL was associated with poorer functional status on the DRS. Paradoxically, a history of binge drinking was associated with more intact functional status on the DRS.

Conclusions

The relationships among intoxication at time of injury, history of problem drinking, and early outcome after TBI were modest. Injury severity had a more significant association with TBI functional status.