Asthmaanfälle unter niedrigdosierter Heparinprophylaxe bei einem Mann mit Schenkelhalsfraktur und Aortenaneurysma

Summary Hypersensitivity reactions to heparin preparations with a wide spectrum of clinical manifestations have been reported frequently in the past, but are a rarity now. A 88 year old man was admitted for physical therapy of a collum femoris fracture. Treatment with a diuretic, Reserpine and Verapamil was continued. Chest x-ray revealed a large thoracic aortic aneurysm. From the 12th to the 18th day of low dose heparin prophylaxis with calcium heparin, 7500 U twice daily, at least eight attacks of asthma or cyanosis were observed, starting about two hours after heparin injection. The last attack began suddenly with wheezing, tachypnoea and cough and was associated with apprehension, a sudden blood pressure increase and severe cyanosis. Ventilation improved with oxygen and a ₂-stimulator, but hypertension and cyanosis lasted for three hours. After discontinuation of heparin no further attacks occurred. Causes other then heparin could not be found. Despite the use of porcine mucosa heparin, avoidance of preservatives and use of low doses a hypersensitivity reaction occurred in our case. The delayed onset after preceeding subcutaneous application as well as difficulties in separating the reaction from complications of underlying disease may delay heparin discontinuation.

---

Abkünzungen BWS Brustwirbelsäule - p.a. posterior-anterior     

Dose to patients through nuclear medicine procedures in a department in northern Greece

Diagnostic nuclear medicine procedures in a large hospital in northern Greece during 1984–1988 have been surveyed in order to estimate the radiation burden to the patients. The mean effective dose equivalent (EDE) was found to be 1.96 mSv/examination and 2.46 mSv/patient, allowing for the fact that a number of patients underwent more than one examination. Apart from EDE, absorbed dose has been calculated for bone marrow, thyroid, gonads, kidneys and bladder. Patients undergoing multiple examinations have been used to calculate true patient dose distribution as well as patient time-weighted dose distribution. Because of the predominance of renal examinations, 8.5 fatal renal malignancies are expected per 100000 patients.     

Evidence for an Interaction Between the β-Blocker Pafenolol and Bile Salts in the Intestinal Lumen of the Rat Leading to Dose-Dependent Oral Absorption and Double Peaks in the Plasma Concentration–Time Profile

Pafenolol is a -blocker with unusual oral absorption properties. The blood concentration–time profile exhibits two peaks, and the bioavailability is low and dose dependent because of incomplete and nonlinear intestinal uptake. We addressed the question whether the intestinal absorption of pafenolol was affected by bile depletion in the gut lumen of rats. Further, the hypothesis that variable gastric emptying accounts for double peaks in blood was tested by duodenal administration of pafenolol. Following intraduodenal administration to rats with intact bile secretion, double peaks were observed in the blood concentration–time curve. The bioavailability was 6.8 ± 0.7% for the low dose (1 µmol/kg) and increased significantly to 28 ± 10% following the high duodenal dose (25 µmol/kg). These blood concentration–time profiles exclude interrupted gastric emptying as cause of the twin peaks. In bile duct-cannulated rats the intestinal absorption of the low dose (1 µmol/kg) was still poor (F = 10.7 ± 5.5%) and the blood concentration–time profile contained two peaks. Following administration of a high duodenal dose (25 µmol/kg) to rats with an almost bile-free small intestine, the absorption rate increased and the double-peak phenomenon disappeared in five of seven rats, while the bioavailability increased significantly, to 62 ± 27%. These results suggest that the low bioavailability of pafenolol is due to a complexation between bile and pafenolol in the gut lumen, preventing intestinal uptake in the major part of the small intestine. Further, such complex formation in the intestinal lumen may be the underlying mechanism of the double peaks observed in the blood concentration–time profile.     

Optimum dose of epidural morphine for postsurgical analgesia

To determine the optimum dose of epidural morphine for postoperative pain control, 0.5–4.0mg of morphine was administered to 198 patients who had undergone operations on lower abdomen or lower extremities under continuous epidural anesthesia. Analgesic effect of morphine and incidence of nausea or vomiting were studied using linear discriminant analysis. As explanatory variables, age and dose of morphine were statistically significant in discriminating analgesic effect of morphine. Among indices for physique of patients, height was the most useful for predicting the analgesic effect. The dose which made the discriminant function zero corresponded to the minimum effective dose (MED) of morphine and it was expressed as follows; MED (mg·meter^–1) = –0.0107 × age + 1.85. Predicting the incidence of nausea or vomiting in relation to the dose of morphine did not reach a level of statistical significance.(Ochi G, Yamane C, Arai T: Optimum dose of epidural morphine for postsurgical analgesia. J Anesth 4: 35–39, 1990)     

Effect of low dose radiation on subpopulations of lymphocytes and T cell subsets in mice

<正> The effect of radiation on lymphocyte subpopulations and T cell subsets of peripheral blood was studied in mice after X- and y-irradiation.lt was found that (1) there were neither marked changes in the percentage and absolute number of acid alpha-naphthol acetyl esterase "positive(ANAE + )cells of different granular patterns, nor significant lowering of the T11/Ts ratio after single whole body X-irradiation in the dose range of 25-250 mGy with a dose rate of 12.5mGy/min. At the same time no significant changes were found at different time intervals after irradiation. After continuous low level irradiation with 60Co γ-rays with a dose rate of 5.4 mGy/6h.d,the ANAE grauular pattern of lymphocytes showed no significant changes with cumulative doses of 32.4 -520 mGy. (3)There was no decrease in the "splenocyte Ts index in Kunming mice after low dose X-irradiation. The results suggest that the stimulatory effect of low dose radiation on the PFC reaction can not be explained on the basis of a decrease in num     

Pharmacokinetics and pharmacodynamics of cicaprost in healthy volunteers after oral administration of 5 to 20 μG

Summary In a Phase I study, the tolerability, pharmacodynamics and pharmacokinetics of cicaprost have been investigated in 6 male volunteers given 5, 10, 15 and 20 g as tablets of the -cyclodextrin clathrate.Individual inhibition of platelet aggregation and changes in facial colour (measured by chromametry) were dose-dependent and reached a maximum 30 to 60 min post-dose. The maximum inhibition of platelet aggregation was about 40%. After 3 to 4 h pre-treatment values had returned. Blood pressure remained within the normal range. The peak plasma level of cicaprost was reached within 15 to 90 min after drug intake. Both C_max-and AUC were individually dose-dependent. The terminal half-life in plasma of cicaprost was approx. 1 h, and its total clearance amounted to 4–7 ml·min^–1·kg^–1. The time courses of the plasma levels and of the pharmacodynamic actions were in agreement. Interindividual differences were observed in the occurrence of unwanted effects (e.g. headache).Thus, cicaprost is an orally available PGI₂-mimetic, for which effects on platelet aggregation and vascular perfusion have been demonstrated in healthy volunteers after doses of 5 to 15 g.The results will form part of the M.D. thesis of T.Staks. Some of the findings were presented at the CPT meeting, Mannheim/Heidelberg, 1989     

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     

术中经胆囊管胆道造影的应用价值

目的：探讨胆囊切除术时经胆囊管作胆道造对胆道结石病人的应用价值。方法回顾分析442例患有胆囊胆道结石的病人经胆囊管胆道造影的情况。结果442例病人中,假阳性3例,假阴性1例,诊断准确率达99．1％,结论对胆囊胆道结石病人,特别具有胆总管相对探查指征的病人,常规作术中经胆囊管胆道造影可降低胆道残余结石发生率,减少胆道损务,避免不必要的胆总管探查。     

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.     

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.