Pharmacokinetic and pharmacodynamic studies with mitoxantrone in the treatment of patients with nasopharyngeal carcinoma.

The pharmacokinetics and pharmacodynamics of mitoxantrone were studied in 15 patients with advanced nasopharyngeal carcinoma (NPC) after single intravenous rapid infusion (12 to 14 mg/m2). Mitoxantrone plasma concentrations and urinary excretion were measured specifically with the use of a high-performance liquid chromatographic method with ultraviolet detection at 242 and 658 nm. The pharmacokinetic parameters are described adequately by a three-compartment model with a terminal half-life of 71.5 +/- 40.1 hours and a volume of distribution of 5037 +/- 2377 l. The total plasma clearance was 743 +/- 462 ml/minute, and the renal clearance was 18.8 +/- 8.49 ml/minute. Within 72 hours, 1.8 +/- 0.6% of the administration dose was excreted in urine as mitoxantrone parent compound. From the urinary excretion rate data, glomerular filtration and possible tubular reabsorption were the mechanisms involved in the urinary excretion of mitoxantrone. The values for unbound fraction (%) in plasma at time 0 and 5 minutes were 2.88 +/- 0.91% and 3.25 +/- 1.19%, with an average of 3.04 +/- 1.01%. The degree of protein binding of mitoxantrone was not affected by concentration (P greater than 0.05) in Chinese patients with NPC. The response rate for mitoxantrone was poor in this study. Clinical studies have demonstrated that mitoxantrone was generally well tolerated. Only very low incidences of nausea, vomiting, and alopecia were observed. The mild and rapidly reversible dose-limiting hematologic toxic effects have proven leukopenia. Although the toxicities reported here were tolerated for most patients, other combination regimens including mitoxantrone or other administration routes may be considered and need to be evaluated carefully.     

Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.     

Menstrual cycle and gonadal steroid effects on symptomatic hyperammonaemia of urea-cycle-based and idiopathic aetiologies

Summary We report two female patients, one with a known inborn error of ureagenesis and the other of unknown cause, in whom recurrent, transient episodes of severe hyperammonaemia increased in frequency and severity with sexual maturity and parturition. Both responded to ovarian steroids administered continuously to suppress ovulation and menstruation, and ultimately to simple hysterectomy. These studies suggest a new therapeutic approach to defective ureagenesis in female patients and a relationship between ammonia production or disposal and the menstrual cycle.     

Subclinical neurotoxicity of mercury vapor revealed by a multimodality evoked potential study of chloralkali workers

Pattern visual, brainstem auditory, and somatosensory evoked potential (EP) studies were performed on 26 chloralkali workers. The intensity of mercury vapor exposure in these workers was estimated from the individual working history. Mercury levels in blood, urine, and hair were determined with atomic absorption spectrometry. The EP findings were compared with those from individually matched normal subjects. In brainstem auditory and somatosensory EP studies, prolonged neural conduction times in the central nervous system (CNS) were found in workers exposed to mercury vapor. In the pattern visual EP study, mercury workers had higher interpeak amplitudes. Findings of this study suggested that chronic exposure to mercury vapor would affect the CNS functions. A multimodality EP study is a useful adjunct in evaluation of chronic mercury neurotoxicity, especially in an epidemiological study.     

Demand feeding for healthy premature newborns: a randomized crossover study.

BACKGROUND AND PURPOSE: In hospitals, preterm infants are routinely fed specified amounts of formula on a fixed schedule. This results in the baby's intake volume being regular and easily confirmed, but does not consider the individual baby's needs. The purpose of this study was to compare the effects of demand feeding and fixed schedule feeding for healthy premature newborn babies. METHODS: A 2-feeding-type, 2-period crossover study design was employed, in which each period consisted of 2 days, the first of which was a washout period, comprising a self-comparison protocol designed to identify any differences in the feeding characteristics of premature infants on demand or scheduled bottle-feeding. Eleven preterm infants were included. The sample size was monitored during the observation period by power calculation. The mean weight at study entry was 1897.27 +/- 175.94 g and the mean postconceptional age was 35.34 +/- 1.54 weeks. RESULTS: Compared with scheduled feeding, demand feeding was associated with a longer daily mean interval (4.17 vs 3.02 hours; p = 0.00), greater volume per feed for demand feeding (67.28 vs 51.11; p = 0.00), greater feeding speed (5.73 vs 4.51 mL/min; p = 0.00), but a similar daily total duration of feeding. There was no significant difference in the daily total feeding volume. CONCLUSIONS: Demand feeding provides superior volume per feed, and feeding speed and shortens the duration of feeding compared to feeding on a routine schedule. It is suitable and feasible for healthy premature newborns.     

肾移植2,3,5年患者的免疫抑制用药分析

目的：分析肾移植后免疫抑制剂对长期存活的影响，寻找移植后不同时间合适的免疫抑制用药方案及其用药剂量。 方法：对肾移植一年以上、肾功能正常的４９７例患者进行５年连续随访。根据移植后２、３、５年的不同免疫抑制用药将患者分为三联、二联、传统二联治疗三组。统计各组的排异发生率，排异和无排异患者免疫抑制用药的种类、剂量及ＣｓＡ浓度，对排异患者追踪排异发生前１２个月内的药物更动情况。 结果：肾移植后２、３、５     

Post-prostatectomy urinary incontinence: response to behavioral training

Urinary incontinence after prostatectomy can be psychologically and socially disabling. We reviewed our experience with 27 patients who were incontinent between 5 and 198 months after either radical retropubic, total perineal or transurethral prostatectomy. These patients were entered into our bladder behavior clinic, which was administered by nursing staff with physician supervision. Patients were strongly encouraged to discontinue the incontinence devices, and were then evaluated for the type and extent of incontinence. Perineal exercises were demonstrated in detail, tested for their correct use via simultaneous rectal and abdominal examination, and applied to the pattern of incontinence. Patients were evaluated frequently for compliance and their progress was followed with instruction repeated as needed. Pharmaceutical agents were not used. Among the 24 patients evaluable over-all improvement in the number of incontinent episodes was 56.6% (p less than 0.001). Two patients (8.3%) achieved total continence, 10 (42%) improved greatly, 4 showed moderate improvement and 8 (33%) showed essentially no change. Transurethral and perineal prostatectomy patients improved by 74 and 61%, respectively, versus only 33% in the radical retropubic group (p = 0.14). In addition, patients who previously underwent transurethral resection before total prostatectomy did worse (18%) than did those who did not (67%). We conclude that a significant number of patients who are incontinent after prostatectomy (especially those without a prior transurethral resection) can improve dramatically with a behavioral training program that provides a strong support system.     

A closed loop microprocessor controller for treatment of hypertension after cardiac surgery

Hypertension after cardiac surgery is common and requires accurate control by carefully regulated infusions of drugs such as sodium nitroprusside. A microprocessor-based controller has been designed to close the loop between the blood pressure response and the infusion rate of a hypotensive drug. This system has been refined by computer simulation of the blood pressure response to sodium nitroprusside and by experience gained in using the controller in eleven patients in the early recovery period after cardiac surgery. The controller was able automatically to maintain blood pressure within 10% of a specified value. Provision of sophisticated safety features in automatic drug infusion controllers is essential for patient protection.