Influence of food on the intravenous and oral dose kinetics of propranolol in the dog

The intravenous and oral dose kinetics of propranolol were studied in the dog both in a fasted state and immediately after a meal consisting of 100 g of cooked beef liver. Fifty Ci of³H-propranolol was administered intravenously simultaneously with a 40-mg oral dose of unlabeled propranolol. Plasma³H-propranolol was measured by specific extraction and liquid scintillation spectrometry, and unlabeled plasma propranolol was determined by gas chromatography-mass spectrometry. Feeding significantly reduced (25%) the elimination half-life and increased (52%) the systemic clearance of intravenous propranolol. The increase in the systemic clearance of propranolol after feeding was mostly due to an increase (60%) in apparent hepatic blood flow, which appeared to remain elevated for 5–7 hr. The meal had no influence on the apparent volume of distribution or plasma binding. Feeding did not affect the area under the concentration-time curve of oral propranolol, but significantly delayed the rate of oral propranolol absorption, shifting the time to reach peak plasma levels from 60 to 158 min. The results of this study suggest that feeding alters the disposition of propranolol in the dog by producing a sustained increase in hepatic blood flow.This work was supported by National Institute of Health grants GM 07534, GM 20387, and HL 29566.     

催经止孕药Ru-486的临床药代动力学

应用高效液相色谱法(HPLC)研究了抗孕激素药,Ru-486的临床药代动力学。六名志愿受试者,一次口服Ru-486 50毫克后测得该药的药代动力学各项参数,血药半寿期t 1/2 33.0小时,一级消除速率常数Kel 0.021 hr~(-1),血药表观容积Vd 120.1 Liter,体内血药总廓清率Cl2.5 Liter/hr,药-时曲线下面积Auc 19825.1 ng/ml/hr。实验表明,服药后一小时血药浓度迅即达高峰,随后转入消除期,血浆药物浓度在消除相的头4～8小时消除较快,而后逐渐减慢,持续24小时,到48小时血药浓度已较低(0.15±0.07μg/ml)。     

香烟烟雾提取物致小鼠生殖细胞的遗传学损伤

目的：研究香烟烟雾提取物对小鼠生殖细胞染色体和精子的影响,方法：给雄性小鼠腹腔注射不同剂量的香烟烟雾提取物,观察其精原细胞染色体畸变及精子畸形的情况,结果：精原细胞染色体畸变率及精子畸形率均增高,精子畸形率增高的程度大于精原细胞染色体畸变率。结论：香烟烟雾提取物可致雄性小鼠生殖细胞染色体畸变和精子畸形。     

Outcomes and factors associated with early mortality in pediatric postcardiotomy veno‐arterial extracorporeal membrane oxygenation

Mortality and morbidity of children received veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) support after cardiac surgery remain high despite remarkable advances in medical management and devices. The purpose of this study was to describe outcomes and risk factors of applying VA‐ECMO in the surgical pediatric population. We retrospectively analyzed 85 consecutive pediatric patients (aged <18 years) who received postcardiotomy VA‐ECMO from January 2010 to December 2018. Median (IQR) age at ECMO implantation in this cohort was 12.7 (6.4, 43.2) months, median weight was 8.5 (6.0, 12.8) kg, mean ECMO duration was 143.2 ± 81.6 hours and mean hospital length of stay was 48.4 ± 32.4 days. Seventy‐five patients (88.2%) were indicated for postcardiotomy cardiogenic shock. The successful ECMO weaning rate was 70.6% and in‐hospital mortality was 52.9%. The most common diagnosis was transposition of great arteries (n = 18, 21.2%), while acute kidney injury occurred most often (n = 64, 75.3%). Multivariate logistic regression analysis showed that thrombocytopenia, hemolysis, and nosocomial infection were positively correlated with in‐hospital mortality. Multivariate Cox proportional hazard regression analysis presented that thrombocytopenia significantly increased the 180‐day mortality in patients with successful weaning. Therefore, multiple factors had adverse effects on prognosis. Patient selection and procedures from ECMO implantation to weaning need to be closely monitored and performed in a timely manner to improve outcome.     

Approach selection and outcomes of craniopharyngioma resection: a single-institute study

Neurosurgical Review - Since there are many approaches for successful craniopharyngioma resection, how to choose a suitable approach remains problematic. The aim of this study was to summarize...     

Pyriform sinus fistula in children: A comparison of endoscopic-assisted surgery and endoscopic radiofrequency ablation

BackgroundPyriform sinus fistula (PSF) is a rare congenital anomaly, and the preferred definitive treatment is yet to be verified. In this study, we investigated the treatment outcomes of PSF specifically comparing endoscopic-assisted surgery and endoscopic radiofrequency ablation (RA).MethodsThe medical records of patients treated for PSF at the Shanghai Children's Hospital between October 2016 and September 2019 were retrospectively evaluated.ResultsThere were 93 girls and 98 boys. The median age at onset and operation was 3 years and 5 years, respectively. Endoscopic-assisted surgery was performed in 143 patients. During the same period, RA was performed in 48 patients, and 10 of them concurrently underwent incision and drainage of neck abscesses. Longer hospital stay was found in the endoscopic-assisted surgery group than in the RA group (10.50 ± 3.93 vs. 5.02 ± 3.30 days, P < 0.001). Postoperative complications were not significantly different between the two groups, except for neck infection (0 vs. 8.3%, P = 0.004). After a median follow-up period of 21 months, no significant difference was found between the two groups in terms of recurrence (1.4% vs. 0, P = 0.560).ConclusionPatients treated with RA had a significantly shorter hospital stay than those treated with endoscopic-assisted surgery. Outcomes of endoscopic-assisted surgery and RA were not significantly different for the management of PSF and treatment method should be tailored to the patient.Level of evidenceIV.     

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway

Hepatic ischemia–reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H₂O₂-induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H₂O₂ group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl-2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB-1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.