放射性肾图及肾有效血浆流量对移植肾功能监测的临床价值

对 16例肾移植术后病人进行肾图及肾有效血浆流量 (Effectiverenalplasmaflow ,ERPF)测定 ,同时收集临床资料及血生化检查结果进行比较。结果 9例正常肾图 ,其ERPF正常 ,临床资料也正常 ;5例肾图呈梗阻图形 ,ERPF减少 ,血生化异常 ;2例肾图呈低水平延长型 ,ERPF明显减少 ,血肌酐、尿素氮明显升高。表明肾图和ERPF能较好反映移植肾的功能状况 ,是监测移植肾功能的敏感指标 ,是肾移植术后监测病情变化的好方法     

低剂量电离辐射对小鼠免疫器官Bcl-2蛋白表达的影响

目的 :研究低剂量电离辐射对小鼠胸腺、脾和肠系膜淋巴结 Bcl- 2蛋白表达的影响 ,以揭示辐射诱导细胞凋亡 J型曲线的分子机理。方法 :采用免疫组织化学及图像分析定量方法。结果 :假照组各免疫器官存在 Bcl- 2蛋白的基础表达 ;而照射组随着照射后时间的推移 ,Bcl- 2蛋白表达逐渐增高 ,2 4 h达峰值 ,且差异显著 ;72 h回复至假照水平。结论 :上述结果为揭示低剂量辐射免疫兴奋效应和辐射诱导细胞凋亡 J型曲线的分子机理提供了有意义的数据     

负荷量苯巴比妥预防新生儿缺氧缺血性脑病及颅内出血

观察重度窒息儿静注苯巴比妥预防新生儿缺氧缺血性脑病及颅内出血的效果。方法：选择本院产科出生的重度窦息儿６０例为观察对象,随机分为用药组和对照组各３０例。用药组转入我科后即给予苯巴比妥钠荷量２０ｍｇ／ｋｇ,１２小时后给予维持量５ｍｇ／ｋｇ．ｄ,共７天。     

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of γ-rays (0.01 Gy) 4 or 20 hrs prior to high dose γ-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose γ-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose γ-ray irradiation to high dose γ-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.     

Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs

1. Several unrelated drugs have pro-arrhythmic activity associated with an ability to prolong the QT interval of the ECG. The aim of this work was to examine the effects of the antimalarial drug halofantrine in vivo and in vitro.
2. In anaesthetized guinea-pigs consecutive bolus doses of halofantrine (0.3, 1, 3, 10 and 30 mg kg⁻¹, i.v.) at 25 min intervals caused dose-dependent prolongation of the rate corrected QTc interval and bradycardia. The change in heart rate became significant after administration of 10 mg kg⁻¹ halofantrine (−23±9 beats min⁻¹) whereas the increase in QTc was significant with only 1 mg kg⁻¹ halofantrine (22±10 ms). It was only with the highest dose of halofantrine that the PR interval was increased (from 52±3 to 67±4 ms) and second degree atrioventricular (AV) block (type 1 Mobitz) occurred in all animals. No changes were observed in any parameters in a separate group of guinea-pigs which received vehicle (dimethylacetamide 60% propylene glycol 40%) at equivalent time points.
3. The blood concentrations of halofantrine ranged from 0.26±0.17 μM after administration of 0.3 mg kg⁻¹ to 2.79±0.87 μM after 30 mg kg⁻¹, i.v. There was a significant correlation between the blood concentrations of halofantrine and the changes in QTc interval.
4. In guinea-pig left papillary muscles the effective refractory period was increased significantly 60 min after addition of halofantrine; from 161±4 to 173±6 ms with 10 μM, 156±8 to 174±6 ms with 30 μM and 165±6 to 179±5 ms with 100 μM halofantrine. However, the vehicle (0.1% Tween 80 in DMSO; final concentration of vehicle in Krebs, 1%) also increased the effective refractory period from 164±5 to 173±6 ms. Similar results were obtained in right ventricular strips but left atrial effective refractory periods were not altered by either the vehicle or halofantrine.
5. The results of these experiments suggest that any direct effects that halofantrine may have had on the effective refractory period of cardiac muscle cannot be separated from those of the vehicle. The prolongation of QTc and consistent observation of AV block with halofantrine in anaesthetized guinea-pigs suggest that in vivo models may be more useful for further studies investigating the mechanisms underlying the cardiotoxicity of halofantrine.

     

Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients

Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three- compartment model and linear kinetics. After a single IV bolus, the mean initial volume of distribution (V1) was 0.4811·kg^–1, and the steady-state volume of distribution (V_ss) was 2.16 1·kg^–1. The distribution (t_1/2) and elimination (t_1/2) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml·min^–1·kg^–1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CV_intra) as it was between patients (CV_inter). The steady-state trough plasma concentration (C_min obs) ranged from 4.8 to 30 mg·1^–1 (mean 16.0 mg·1^–1 and median 14.3 mg·1^–1). Peak concentrations (C_max obs) ranged from 8.35 to 45 mg·1^–1 (25.4 mg·1^–1, and median 23.3 mg·1^–1). The values of V1 and V_ss were similar to those obtained after a single dose. For V1, the mean was 0.333 1·kg^–1. The mean V_ss was 2.68 1·kg^–1, with a CV_intra of 12.6 to 56% and a CV_inter of 13.2%. A shorter distribution half-life t_1/2 was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t_1/2 and the mean residence time became longer due to a decrease in clearance. For t_1/2 the mean value was 16.3 h. The mean MRT was 21.9 h, CV_intra 9.19 to 48.5%, and the CV_inter 35.3%. The mean clearance was 2.16 ml·min^–1·kg^–1, CV_intra 7.28 to 25.5%, and the CV_inter 20.4%. This value is 50% lower than after a single dose.Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.     

KD306型耐硫甲烷化催化剂有效扩散系数的测定

基于开发的计算机取样系统,采用ＳＰＳＲ法脉冲动态测试ＫＤ３０６型耐硫甲烷化催化剂的有效扩散系数。线性化和参数估值的结果吻合较好,证实：线性化简化是合理的,参数估值是可用于有效扩散系数。ＫＤ３０６型耐硫甲烷化催化剂的曲折因子为７．２。     

A cost-effective thoracoscopic treatment strategy for pediatric spontaneous pneumothorax

Background: Recent data suggest that children have a higher incidence of recurrence than adults after nonoperative treatment of primary spontaneous pneumothorax (PSP). Video-assisted thoracoscopic surgery (VATS) allows efficacious therapy with significantly less morbidity. We attempt to define the most cost-effective clinically efficacious strategy using VATS to manage pediatric PSP. Methods: We retrospectively reviewed all admissions to a tertiary care children's hospital for PSP between January 1, 1991 and June 30, 1996. Results: Fifteen children had 29 primary or recurrent PSPs. Mean patient age was 14.8 ± 1.1 years, boy–girl ratio 4:1, median body mass index 18 (normal, 20–25), and 67% of pneumothoraces left sided. All patients were managed initially nonoperatively: 14 with tube thoracostomy drainage and 1 with oxygen alone. Of the children initially managed nonoperatively, 57% had a recurrent pneumothorax, and 50% of these patients eventually developed contralateral pneumothoraces. Nonoperative treatment for recurrence resulted in a 75% second recurrence rate. In contrast, eight children who underwent operative management had a 9% incidence of recurrence. The total for charges accrued in treating 29 pneumothoraces in these 15 patients was approximately $315,000. In the same population, the estimated charges for initial nonoperative therapy followed by bilateral thoracoscopy after a single recurrence would be $230,000. Conclusions: A cost-effective treatment strategy for pediatric primary spontaneous pneumothorax is tube thoracostomy at first presentation, followed by VATS with thoracoscopic bleb resection and pleurodesis for patients who experience recurrent pneumothorax. Received: 15 May 1998/Accepted: 15 January 1999     

Auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy in genitourinary cancer patients

To determine the auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy, pure tone hearing thresholds were measured prior to therapy and repeated before each subsequent treatment. CDDP was given by a slow intravenous drip method at a low dose of 1 mg/kg body weight, with 37.5 gm mannitol, once a week for six treatments and every 3 weeks thereafter. From a group of 173 genitourinary cancer patients treated, 50 male patients were selected who received at least 12 months of CDDP with no active conductive ear pathology, and whose audiograms obtained at baseline, 6th weeks, 26th weeks, and 52nd weeks of treatment were all available for comparison. Pure tone threshold levels deteriorated across time particularly by the 52nd week and at the higher frequencies. Threshold differences across time were statistically significant and within a linear trend. Of the 50 cases, 30% showed suspect or no ototoxicity, 26% mild, 32% moderate, 2% marked, and 4% showed severe ototoxic changes. Of the two cases who developed severe ototoxicity, one showed complete recovery. There was partial recovery in 26% and no recovery in 54%. Individual variability in susceptibility to and recovery from ototoxicity necessitates systematic audiometric monitoring throughout the therapy.     

Analysis of the pharmacokinetics of lithium in man

Summary An analysis of the single and multiple dose pharmacokinetics of lithium in 7 healthy volunteers is presented. A solution of lithium chloride was administered in single dose experiments and the same solution and a sustained release preparation were employed in multiple dose experiments, which were carried out at steady state. A fixed dose of 24 mmol was used in the single dose experiments and in the subsequent multiple dose experiments in the same subjects the same dose was administered once daily for a week. Distinct two-compartment characteristics were found, with a mean disposition rate constant () of 0.035 h^–1±0.010 SD, corresponding to a mean biological half-life of about 19.8 h. The mean half-time of the distributory -phase was about 1.15 h. The absorption of lithium from an orally administered solution took place with a half-time of about 0.15 h in the single dose experiments. The apparent volume of distribution of the central compartment (V_c) was 0.307 1 kg^–1±0.046 SD, less than half that of V_de at equilibrium. V_d (V_darea) was 0.8291 kg^–1±0.184 SD and mean total body clearance was 27.6 ml kg^–1 h^–1±4.7 SD.