The pharmacokinetics of lignocaine in humans during a computer-controlled infusion.

Several types of chronic pain syndromes are effectively treated with sodium channel blockers such as lignocaine. Further investigation of this therapeutic modality would be facilitated by refinement of the parameters describing lignocaine distribution and elimination. This would allow precise lignocaine infusion by a computer-controlled infusion to attain and maintain stable target lignocaine concentrations. Arterial blood samples were obtained at frequent intervals during a computer-controlled infusion of lignocaine in 12 adult human volunteers. Plasma lignocaine concentrations of 1, 2, 3, 4 and 5 microg/ml were targeted for 15 min at each concentration. A three-compartment mammillary pharmacokinetic model best described the resulting concentration vs time profile. A population pharmacokinetic analysis was performed using three different techniques; the two-stage, pooled and mixed effects modelling. There was marked overshoot of the plasma concentration above the target prior to refinement of the pharmacokinetic parameters. The best parameters of a three-compartment mammillary model fit to the measured concentration using the pooled data approach were: V(1) = 7.44, V(2) =11.5 and V(3) = 97.71; Cl(1) = 0.585, Cl(2) = 2.23 and Cl(3) =1.64 l/min. Similarly calculated parameters using NONMEM were V(1) = 6.99, V(2) =12.2 and V(3) =1341; Cl(1) = 0.703, Cl(2) =1.24 and Cl(3) =1.49 l/min. The addition of age as a covariate of the pharmacokinetic parameters improved the model in both cases. Height, lean body mass and body surface area as covariates of the pharmacokinetic parameters did not improve the predicted value of the model. Prospective testing of the pharmacokinetic parameters will be required to define whether they function well. The refinement of pharmacokinetic parameters for the computer-controlled intravenous infusion of lignocaine will facilitate further research in pain therapy. Published lignocaine pharmacokinetic values have a relatively large central volume of distribution, and hence, when implemented as a computer-controlled infusion, result in dramatic overshoot shortly after targeting a higher plasma concentration. In light of the long-lasting pain relief provided by sodium channel blockade in neuropathic pain states, overshoot of plasma concentrations must be avoided if the concentration vs effect relationship is to be defined.     

Breakdown of gastric mucus in presence of Helicobacter pylori.

The potential of Helicobacter pylori to degrade gastric mucus was examined. Colonies of H pylori cultured from antral mucosal biopsy specimens of patients with non-autoimmune gastritis were washed with sterile saline, passed through a sterilisation filter, and the filtrate examined for urease, protease, and mucolytic activity. The filtrate failed to hydrolyse bovine serum albumin, or to degrade stable mucus glycoprotein structures of high particle weight that had been separated from human gastric mucus on Sepharose 2B. The high particle weight mucus glycoprotein was, however, extensively degraded when incubated with H pylori filtrate (which possessed urease activity) in the presence of 2 M urea, to release fragments of Mr approximately 2 X 10(6). The high particle weight mucus glycoprotein was also broken down to a comparable extent when incubated with Jack bean urease in the presence of 2 M urea, or 1 M ammonium carbonate, or 40 mM carbonate-bicarbonate buffer (pH 8.7), but not when treated with 4 M urea alone, or Jack bean urease alone. These results indicate that the loss of high particle weight mucus glycoprotein in gastric mucus from patients with gastritis and gastric ulcers is unlikely to be due to the mucolytic action of an extra-cellular protease produced by H pylori, but it may result from the destabilising effects of a carbonate-bicarbonate buffer, generated at the mucosal surface when H pylori urease hydrolyses transuded plasma urea.     

Risk factors of acute pancreatitis]

A total of 689 operative cases of acute necrotic pancreatitis (ANP) were collected from 42 hospitals all over the country by the ANP Cooperative Study Group in the years of 1987 to 1989. General data, laboratory findings, pathology of the pancreas and the type of surgical treatment were analysed according to the outcome of the patient. The results showed that 37% of the cases were related to cholelithiasis, the highest incidence was in age above 60, and female patients were predominant and with higher mortality. Laboratory findings at admission, WBC greater than 20,000/mm3, Hb greater than 15 g%, blood sugar greater than 200 mg%, serum bilirubin greater than 5 mg%, BUN greater than 20 mg%, and serum calcium less than 7 mg% were related to the markedly elevated mortality rate. Operative findings noted in patients with bloody or cloudy peritoneal fluid, necrotic changes up to 75% of the pancreas, more than 2 areas of extrapancreatic involvements and resection of a large portion of the pancreas was found to be necessary were all related to a higher mortality. And emergency operations performed within 24 hours after the onset of the disease was also related with a highest mortality rate.     

Study on the pathogenicity of Campylobacter jejuni by modifying the medium

Campylobacter jejuni has been documented as one of the major aetiological agents of diarrhoeal illness all over the world. Studies revealed its pathogenicity by different assay methods, but none could be strongly recommended as a tool for differentiating toxigenic strains of C. jejuni. This study was an attempt to demonstrate better its pathogenicity by media modification. Fifteen isolates of C. jejuni recovered from diarrhoeal patients at the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka Hospital were included in this study. The standard medium for C. jejuni was modified by the incorporation of FeCl3 at different concentrations. The pathogenicity of the test isolates were studied by rabbit ileal loop assay; Chinese hamster ovary (CHO), human epithelial cervical carcinoma (HeLa); Y-1 adrenal cell lines and suckling mouse assay. Sonicated extracts of the test organisms, grown with FeCl3 supplement, were also assayed. An enhanced growth of C. jejuni was obtained with the increasing concentration of FeCl3 supplementation in the medium. Only five isolates of C. jejuni produced cytotoxic effect on HeLa cell monolayer. Other cell lines were not affected by the test specimens or sonicates. Rabbit ileal loop assay did not reveal any fluid accumulation but on dissection, the test loops were found highly haemorrhagic. No heat-stable (ST) toxin could be detected. Cell-free culture supernatant of patients' isolates of C. jejuni had an effect on HeLa cell monolayer. Sonicated extracts of patients' extracts had a greater effect on HeLa cell monolayer. Pathogenic strains of C. jejuni might be distinguished on HeLa cell monolayer using its sonicated extracts.     

非瓣膜病心房颤动病人华法林抗凝治疗安全性评价

目的:评价非瓣膜病心房颤动(房颤)用华法林抗凝治疗的安全性。方法:选择符合该研究抗凝标准的98例心房颤动病人随机分为两组,华法林治疗组(治疗组)46例,给予华法林3mg/d开始监测凝血酶原时间(PT)及国际标准化比值(INR),7～15天使INR达到2.0～3.0范围内,以后每月查1次INR。若病人增加或减少药物、有出血倾向时随时再测INR。阿司匹林对照组(对照组)52例,给予阿司匹林100mg/d口服2次,密切随访。结果:治疗组9～15d(平均10.1±2.2)INR达2.0～3.0(平均2.25±0.11),其中INR在1.8～2.5(平均1.92±0.23)之间者占90.7%,治疗组未出现脑梗死,而对照组有3例发生脑梗死,两组总不良反应率差异无显著性.。结论:非瓣膜病房颤病人选择华法林3mg/d加强服药后监测及各药物间的相互作用,使INR保持在2.0～3.0之间是有效、安全的。     

N-乙酰半胱氨酸对慢性阻塞性肺疾病患者血淋巴细胞DNA损伤的影响

目的　探讨N -乙酰半胱氨酸 (NAC)治疗不同病期慢性阻塞性肺疾病 (COPD)的疗效。方法　 49例稳定期、急性发作期COPD患者 ,随机分为观察组 (2 5例 )和对照组 (2 4例 ) ,观察组除给予常规治疗外 ,加用NAC(每次 2 0 0mg ,3/d ,连用 2个月 ) ;对照组仅给予常规治疗。治疗前后观察所有患者外周血淋巴细胞DNA损伤程度。结果　治疗前后比较 ,观察组稳定期、急性发作期DNA损伤明显降低 ,差异有显著性 (P <0 .0 5)。对照组稳定期DNA损伤程度亦有一定程度的改善 ,但差异无显著性 (P >0 .0 5) ,急性发作期DNA损伤程度降低 ,差异有显著性 (P <0 .0 5)。结论　COPD患者体内存在氧化 -抗氧化失衡 ,抗氧化治疗可降低COPD患者外周血淋巴细胞DNA损伤程度 ,急性发作期出现氧化应激。     

Reactivity of hydroxybenzoic acids in the hydrogen-isotope exchange reaction.

The hydrogen-isotope exchange reaction (T-for-H exchange reaction) between tritiated water vapor (HTO vapor) and 3-hydroxy-4-methoxybenzoic acid (and it's analog; 4-hydroxy-3-methoxybenzoic acid) were observed at 50 and 70 degrees C in a gas-solid system to reveal the reactivity of a functional group in an aromatic compound having two substituents in the aromatic ring. Further, it was shown that (a) the reactivity of the compounds used in this work follows the Hammett's rule, and (b) the reactivity of trisubstituted aromatic compound could be analyzed by applying the additive property of the Hammett's rule even if the compound contains a substituent at the ortho-position.     

规范化介入治疗方案在肝癌经导管介入治疗中的指导意义

目的探讨规范化介入治疗方案在肝癌经导管介入治疗中的意义。方法回顾性分析实施规范化方案治疗前后患者生存率的变化。结果实施规范化方案后能明显提升患者生存率。结论规范化方案在肝癌经导管介入治疗中具有重要的指导意义。