A pharmacokinetic comparison of cyclosporin oral solution and cyclosporin capsules in heart and lung transplant recipients

Pharmacokinetic profiles were obtained for 16 heart or lung recipients following the administration of identical doses of cyclosporin as oral solution and capsules on consecutive days. A comparison of pharmacokinetic parameters (AUC, C_max, C_min and t_max) showed that there were no significant differences between the two formulations except for the t_max, which was significantly longer for the capsules. The mean variation in day-to-day trough levels produced by the two different forms was 25.6%. A retrospective study was carried out of consecutive cyclosporin levels in patients at steady state on oral solution. The mean variation in day-to-day trough levels was 32.3%. This was not significantly different from the variation in consecutive trough levels seen in the oral solution/capsule comparison. This study shows that cyclosporin capsules can be substituted for oral solution without causing acute changes in cyclosporin blood levels, and that the pharmacokinetics of the two formulations are similar.This work was carried out in partial fulfillment of the requirements for the Master of Science Degree in Clinical Pharmacy, University of London     

Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment

Background: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retionic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. Methods: After treatment with 1 μg all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). Results: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. Conclusions: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves. © 1995 Wiley-Liss, Inc.     

Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P<0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased form 78.1 to 93.6 bpm on average (P<0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.     

慢性重症病毒性肝炎并发医院内曲霉菌感染

1976～1991年我院收治慢性重症病毒性肝炎并发曲霉菌感染15例,感染于住院后3～112天,<30天9例。以血性痰液、胸水、腹水、脑脊液为特点。多数周围血象白细胞不增高,中性粒细胞增高,IgG增高,曲霉菌( );感染后2～10天均死亡。感染前咽部检出白色念珠菌6例,滥用抗生素者占80％。     

Sulpiride in negative schizophrenia: A placebo-controlled double-blind assessment

Twenty-four chronic schizophrenic long-stay hospital patients were identified, who had not received neuroleptic drugs for 8–30 (average 8 months) and met or exceeded a minimum criterion of severity of negative symptoms. They were rendomly alocated to either sulpiride 200 mg twice daily or matching placebo, on a double-blind basis for 12 weeks. The results showed that low-dose sulpiride was significantly better than placebo in relation to improvements in negative symptoms. The changes in social behaviour were complex and not obviously related to symptom improvement; exhibited abnormal behaviour, a major factor in preventing successful return to the community, consistently improved only on the active drug.     

Inhibition of rat heart allograft rejection by a PUVA treatment of the graft recipient

Treatment of rat heart grafts with PUVA, the combination of the photosensitizer 8-methoxypsoralen and longwave ultraviolet light, leads to a prolonged transplant survival in allogeneic recipients. A PUVA treatment of the recipient rats, performed for 7 consecutive days after transplantation, prolonged graft survival even more effectively. This may be due to the systemic immunomodulatory effects of PUVA in the recipient. One of the mediators is urocanic acid, which is transformed by ultraviolet light in the skin from its trans- to the cis-isomer, which, in turn, acts as a mediator on the immune system. An injection of cisurocanic acid into graft recipients for 7 consecutive days after transplantation resulted in prolonged graft survival; in 40% of the rats, permanent graft acceptance was observed. The significance of these results for clinical organ transplantation is discussed.     

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

The chronotropic effect of acetylcholine in the presence of vecuronium and atracurium A study in the isolated perfused rabbit heart

The bradycardia produced by 1 microgram acetylcholine in the isolated perfused rabbit heart, in the presence of vecuronium and atracurium, was studied and compared with control. Vecuronium at a concentration of 2.5 micrograms/litre and atracurium 6 micrograms/litre did not enhance the negative chronotropic effect of acetylcholine. Atracurium produced a statistically significant inhibition of the negative chronotropic effect of acetylcholine.     

Interruption of pulmonary arterial flow with inadequate ventilation leads to pulmonary infarction

We examined the effect of interruption of pulmonary arterial flow and inadequate ventilation on the development of pulmonary infarction in rats. Pulmonary arterial flow was blocked by the injection of agar into the inferior vena cava and inadequate ventilation was produced by obstructing the left main bronchus with a polypropylene tip. Histological and angiographic examination of the lung demonstrated that: pulmonary artery embolism alone does not induce pulmonary infarction; obstruction of a bronchus does not induce significant changes, but that pulmonary infarction develops when pulmonary artery embolism and obstruction of a bronchus occur simultaneously. It has been thought that pulmonary infarction is caused by acute obstruction of a pulmonary artery, however, the alveolar walls are supplied with oxygen by both the pulmonary circulation and by ventilation. Interruption of pulmonary arterial flow alone is probably not sufficient to induce pulmonary infarction, which is probably caused by deficiency of oxygen supply to the alveolar walls by a synergy between interruption of pulmonary arterial flow and inadequate ventilation.     

生物反馈技术治疗慢性盆底疼痛综合征及慢性前列腺炎

目的：评估生物反馈刺激治疗对慢性盆底疼痛综合征(CPPS)及慢性前列腺炎(CP)的效果。方法：评估30例患者治疗前后，前列腺液(EPS)及精液(SF)和临床症状的变化，包括每日排尿次数、尿急、疼痛和生活质量。使用侵入型的生物反馈刺激治疗仪，治疗周期5～15d，每次20min。结果：30例患者中的14例进行了5次生物反馈治疗，10例进行了10次，6例进行了15次治疗(平均每位患者治疗8．6次)，追踪生物反馈治疗后0～2个月，并比较治疗前和治疗后的结果，显示病情有明显好转。结论：生物反馈刺激治疗对CP或CPPS患者能明显改善疼痛、尿频、尿急和生活质量，对CP患者能减少EPS或SF中的WBC。