Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers

Palonosetron (Aloxi(R), Onicit(R)) is a potent, single stereoisomeric 5-HT(3) receptor antagonist developed to prevent chemotherapy-induced nausea and vomiting. The pharmacokinetics and metabolic disposition of a single intravenous [(14)C]-palonosetron (10 microg/kg, 0.8 microCi/kg) bolus dose were evaluated in six healthy volunteers (three males, three females) using serial blood, plasma, urine and fecal samples obtained over 10 days. The safety, tolerability and cardiac effects were assessed. Radiolabeled metabolic characterization revealed that unchanged palonosetron accounted for 71.9% of the total radioactivity in plasma over 96 h, with an extensive distribution volume (8.34 l/kg) and mean plasma elimination half-life of 37 h. Approximately 83% of the dose was recovered in urine ( approximately 40% as unchanged drug, with 50% metabolized; M9 and M4 were the major metabolites) and 3.4% in feces. Hydrolysis of urine samples suggests that the metabolites are not beta-glucuronide or sulfate conjugates of the parent drug or metabolites. The blood to plasma concentration ratio of the total radioactivity was 1.2, on average, indicating little selective partitioning in erythrocytes. Palonosetron was generally well tolerated; headache was the most frequently reported adverse event. Electrocardiograms and 72 h Holter monitoring revealed no clinically significant changes. Palonosetron circulates in plasma mainly as the parent drug. Renal elimination is the primary excretion route, with parent drug and metabolites M9 and M4 accounting for the majority of palonosetron disposition. These results indicate that both renal and hepatic routes are involved in the elimination of palonosetron from the body.     

先天性无肛直肠舟状窝瘘手术186例

1临床资料1988-06/2003-12我院共186例,均为女性,无肛门,其中0～6月龄21例,0.5～1岁96例,1～3岁53例,3～8岁15例,13岁1例.以大便从会阴部舟状窝瘘口处排出而就诊,患儿有不同程度的排便困难,严重时伴腹胀呕吐,多数患儿有营养不良性贫血.瘘口直径0.3～0.6 cm,直肠盲端到肛穴皮肤之间的距离1.0～2.5 cm,属于中、低位肛门直肠畸形.本组有3例合并先天性心脏病-室间隔缺损,2例合并骶前囊肿,1例合并脐疝.     

Radiation‐induced brain disorders in patients with pituitary tumours

Radiation‐induced brain disorders (RIBD) are uncommon and they are grave sequelae of conventional radiotherapy. In the present report, we describe the clinical spectrum of RIBD in 11 patients who received post‐surgery conventional megavoltage irradiation for residual pituitary tumours. Of these 11 patients (nine men, two women), seven had been treated for non‐functioning pituitary tumours and four for somatotropinomas. At the time of irradiation the age of these patients ranged from 30 to 59 years (mean, 39.4 ± 8.3; median, 36) with a follow‐up period of 6?96 months (mean, 18.3 ± 26.4; median, 11). The dose of radiation ranged from 45 to 90 Gy (mean, 51.3 ± 13.4; median, 45), which was given in 15?30 fractions (mean, 18.6 ± 5.0; median, 15) with 2.8 ± 0.3 Gy (median, 3) per fraction. The biological effective dose calculated for late complications in these patients ranged from 78.7 to 180 Gy (mean, 99.1 ± 27.5; median, 90). The lag time between tumour irradiation and the onset of symptoms ranged from 6 to 168 months (mean, 46.3 ± 57.0; median, 57). The clinical spectrum of RIBD included new‐onset visual abnormalities in five, cerebral radionecrosis in the form of altered sensorium in four, generalized seizures in four, cognitive dysfunction in five, dementia in three and motor deficits in two patients. Magnetic resonance imaging (MRI)/CT of the brain was suggestive of radionecrosis in eight, cerebral oedema in three, cerebral atrophy in two and second neoplasia in one patient. Associated hormone deficiencies at presentation were hypogonadism in eight, hypoadrenalism in six, hypothyroidism in four and diabetes insipidus in one patient. Autopsy in two patients showed primitive neuroectodermal tumour (PNET) and brainstem radionecrosis in one, and a cystic lesion in the left frontal lobe following radionecrosis in the other. We conclude that RIBD have distinctive but varying clinical and radiological presentations. Diabetes insipidus and PNET as a second neoplastic disorder in adults following pituitary irradiation have not been reported previously.     

学报发展之我见

国家最新的统计数据显示,在我国5000种科技期刊中,高等院校所办的期刊已经达到1347种,其中绝大多数为学报;在我国1124种医学期刊中,学报也占有较大的比例．尽管学报的数量不少,但从期刊的综合评价体系来看,其中高质量者寥寥无几;而获得过“首届国家期刊奖,第二届国家期刊奖提名奖”的第四军医大学学报无疑是其中的佼佼者、尽管我们取得过辉煌的成绩,但依旧无法回避今日严峻的现实．要使学报能够健康地发展,我认为以下几点不容忽视．     

Victoria Symptom Validity Test performance in acute severe traumatic brain injury: implications for test interpretation.

Effort testing has become commonplace in clinical practice. Recent research has shown that performance on effort tests is highly correlated with performance on neuropsychological measures. Clinical application of effort testing is highly dependent on research derived interpretive guidelines. The Victoria Symptom Validity Test (VSVT) is one of many measures currently used in clinical practice. The VSVT has recommended interpretive guidelines published in the test manual, but the samples used in developing interpretive guidelines are small and heterogeneous and concern has been expressed regarding high false negative rates. In this study, a homogeneous sample of acute, severely brain injured persons were used to assess the sensitivity of the VSVT. Results confirmed that acute, severely brain injured persons (N=71) perform very well on the VSVT. The severe brain injury population is 99% likely to have between 44.1 and 46.8 correct VSVT Combined Score responses. While the VSVT was insensitive to memory dysfunction, the presence of severe visual perceptual (Benton Visual Form Discrimination Score<21) and verbal fluency (Controlled Oral Word Association Score<15) deficits predicted poor performance on the VSVT. These results provide further evidence that performance expectations currently incorporated in the VSVT manual interpretative criteria are too conservative. Empirically based alternative criteria for interpreting VSVT Combined Scores in the TBI population are presented.