Fluoropyrimidine chemotherapy in a rat model: comparison of fluorouracil metabolite profiles determined by high-field 19F-NMR spectroscopy of tissues ex vivo with therapy response and toxicity for locoregional vs systemic infusion protocols

A Sprague-Dawley rat model with DS sarcoma transplanted in the thigh was used to compare transcatheter locoregional i.a. and systemic i.v. administration of 5-fluorouracil (FU) at 12 dose-rate schedules: 25, 50 and 100 mg/kg; bolus, 1, 5 and 24 h infusions. In experiment A tumor (62/67 animals) as well as liver and kidney (56/67 animals) were excised 1 h after a single bolus or 1 h infusion or at the end of 5 and 24 h infusions. (19)F-NMR spectroscopy at 11.7 T was used to quantitate FU and its metabolites in ca. 1 g of tissue at 4 degrees C. In experiment B analogous FU treatments were repeated for 5 days (rats 80+11 controls). Tumor volumes vs time, various blood parameters and survival times were recorded, and a log growth rate parameter log GR, a response index RI, and a toxicity index TI were calculated. The i.a. vs i.v. ratios for tumor concentrations of FU and total anabolites (F-Nucl) were >1 for nearly all treatments and increased with infusion time at the higher doses. F-Nucl in tumor correlated linearly with total fluorine concentration (Tot. F range 30-1100 nmol/g) over all treatments (r=0.92, slope=0.45, p<0.0001). For non-bolus i.v. treatments [FU+F-Nucl] decreased linearly with decreasing FU dose rate (r(2)=0.74, zero intercept), while i.a. treatments showed non-linear behavior. For non-bolus treatments the mean log GR per treatment group showed a negative correlation (r=-0.87) with log[F-Nucl]. The most effective non-toxic treatments were 25 mg/kg over 5 or 24 h; the i.a. route was superior to i.v. on the basis of [FU+F-Nucl], RI, the reduction in log GR, and Kaplan-Meier survival statistics. For liver and kidney Tot. F (>83% FU catabolites) reached ca. 3-4 and 6-7 micromol/g, respectively, at the highest dose rates for either route; F-Nucl were detected only for Tot. F>500 nmol/g and increased exponentially as Tot. F increased (toxic treatments). The concentrations of the main catabolite (alpha-fluoro-beta-alanine, FBAL) in tumor did not correlate with Tot. F but rather with FBAL levels in kidney (r=0.90, all treatments), indicating that uptake of liver-derived FBAL from the circulation is the major source of FBAL in tumor.     

Nutrient composition: effects on appetite in monkeys with oral factors held constant

The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.     

Spread of epidural analgesia following a constant pressure injection

(1) The spread of epidural analgesia following injection of 15ml of 2% mepivacaine was 17.3 ± 0.6, 14.3 ± 0.4, and 13.3 ± 0.7 spinal segments in cervical, thoracic, and lumbar epidural analgesia, respectively. The patients age showed significant correlation with the spread of epidural analgesia in cervical (r = 0.5776, p < 0.001), thoracic (r = 0.3758, p < 0.01), and lumbar area (r = 0.8195, p < 0.001). The spread of cervical epidural analgesia was more caudad than cephalad (p < 0.05), but in lumbar epidural analgesia it was more cephalad than caudad (p < 0.05). There was no difference between the cephalad and caudad spread in thoracic epidural analgesia.(2) The epidural pressure immediately after injection of 15ml of 2% mepivacaine into the lumbar epidural space at a constant pressure (80mmHg) correlated to the patients age (r = –0.5714, p < 0.001) and the spread of analgesia (r = –0.3904, p < 0.05). The lower epidural pressure associated with higher age, the wider spread of analgesia. There was no significant correlation between the residual pressure at 60 seconds and the age or the spread of analgesia.(Hirabayashi Y et al.: Spread of epidural analgesia following a constant pressure injection: an investigation of relationships between locus of injection, epidural pressure and spread of analgesia. J Anesth 1: 44–50, 1987)     

双水止负压输液器的应用研究

为改进一次性输液器因回血量少 ,影响穿刺成功率。我们将输液器改装为双水止负压输液器 ,产生管内负压。经临床试验 ,负压组总回血长度 3 90 .4cm ,平均回血长度 8.76cm/例。对照组总回血长度 3 9.9cm ,平均回血长度 0 .89cm/例。经方差处理p <0 .0 0 1 ,有明显临床意义。其优点 :增加穿刺回血量 ,提高了穿刺成功率 ,减少病人的痛苦。操作简单易行 ,减少了中间环节 ,避免了污染的输液反应     

胃癌术中动脉区域灌注化疗与全身静脉化疗的临床疗效比较

目的　评价胃癌术中动脉区域灌注化疗药物的临床疗效。方法　对 40例经病理确诊的胃癌患者 (治疗组 )于术中经供应肿瘤的区域动脉行插管化疗 ,同时进行手术治疗 ,并与同期术中行全身静脉化疗的 2 4例胃癌患者 (对照组 )进行临床疗效比较。结果　术后病理检查显示 ,治疗组原发灶中的癌细胞均有不同程度地变性坏死 ,其近期有效率为 95 % ,对照组有效率为 41.6 7% ,两组比较差异显著 (P<0 .0 5 )。结论　胃癌患者术中经动脉灌注化疗 ,其近期抗癌效果好 ,毒副反应轻 ,对减少或防止术中癌细胞的医源性扩散与种植以及术后复发 ,均有重要的临床意义     

Incomplete Administration of Intravenous Vancomycin Prophylaxis is Common and Associated With Increased Infectious Complications After Primary Total Hip and Knee Arthroplasty

BackgroundVancomycin is often used as antimicrobial prophylaxis in patients undergoing total hip or knee arthroplasty. Vancomycin requires longer infusion times to avoid associated side effects. We hypothesized that vancomycin infusion is often started too late and that delayed infusion may predispose patients to increased rates of surgical site infections and prosthetic joint infections.MethodsWe reviewed clinical data for all primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients at our institution between 2013 and 2020 who received intravenous vancomycin as primary perioperative gram-positive antibiotic prophylaxis. We calculated duration of infusion before incision or tourniquet inflation, with a cutoff of 30 minutes defining adequate administration. Patients were divided into two groups: 1) appropriate administration and 2) incomplete administration. Surgical factors and quality outcomes were compared between groups.ResultsWe reviewed 1047 primary THA and TKA patients (524 THAs and 523 TKAs). The indication for intravenous vancomycin usage was allergy (61%), methicillin-resistant staphylococcus aureus colonization (17%), both allergy and colonization (14%), and other (8%). 50.4% of patients began infusion >30 minutes preoperatively (group A), and 49.6% began infusion <30 minutes preoperatively (group B). Group B had significantly higher rates of readmissions for infectious causes (3.6 vs 1.3%, P = .017). This included a statistically significant increase in confirmed prosthetic joint infections (2.2% vs 0.6%, P = .023). Regression analysis confirmed <30 minutes of vancomycin infusion as an independent risk factor for PJI when controlling for comorbidities (OR 5.22, P = .012).ConclusionLate infusion of vancomycin is common and associated with increased rates of infectious causes for readmission and PJI. Preoperative protocols should be created to ensure appropriate vancomycin administration when indicated.     

温热清对小鼠腹腔巨噬细胞吞噬功能的影响

本文对温热清冲剂(柴胡、黄芩、生石膏、重楼、公英、连翘、厚朴、甘草)对小鼠腹腔巨噬细胞吞噬功能的影响进行实验观察,结果表明:温热清对巨噬细胞的各噬功能有显著的促进作用,与对照组相比较,有显著差别(P<0.01)。由此说明中药祛邪亦可实现扶正。     

Increased sodium requirement following early postnatal surgical correction of congenital uropathies in infants

Serum electrolyte equilibrium and plasma aldosterone concentrations were monitored in 19 infants who had severe obstructive uropathy or grade 5 vesico-ureteral reflux and were undergoing surgical correction in the first 2 months of life. Before surgery high plasma aldosterone levels were observed in 8 patients, but serum sodium and potassium concentrations were normal. Plasma concentrations of aldosterone were elevated in all patients during the week following surgery and 7 patients developed severe hyponatraemia, hyperkalaemia and weight loss despite very high plasma aldosterone concentrations. As a consequence 5 infants were infused with sodium chloride (4 mEq/kg per day) before and for 36h after surgery; this prevented metabolic imbalance. We conclude that infants undergoing surgical correction of uropathies may require a high sodium intake to maintain electrolyte balance and adequate growth.     

超声引导下行输卵管通液术在原发性不孕中的应用

通过57例原发性不孕症病人在B超引导下行输卵管通液术,术后随访观察,输卵管不通畅治愈率达89．5％(51／57);妊娠率达63。2％(36／57)。因此,B超引导下行输卵管通液术不仅是诊断和治疗输卵管不通所致原发性不孕症的一条好途径,而且是对传统输卵管通液术的进一步发展。