Excessive daytime somnolence in Japanese patients with Parkinson''s disease

To investigate the prevalence and severity of excessive daytime somnolence (EDS) in Japanese patients with Parkinson's disease (PD) and to examine the main cause of EDS. Fifty-three Japanese patients with PD (PDs: 32 females and 21 males) and 17 controls (10 females and seven males) were evaluated using the Epworth Sleepiness Scale (ESS). The severity of the disease was evaluated by Unified Parkinson's disease Rating Scale (UPDRS), and information about quality and quantity of medications was collected. The correlations amongst EDS and age, severity of PD, duration of illness and medications were analyzed. The mean ESS score was significantly higher in advanced PDs than in controls, and correlated with the UPDRS score (r(s) = 0.743, P < 0.0001). Age, duration of illness and the dose of levodopa weakly correlated with ESS score. The intake of dopamine agonists did not affect the severity of EDS. The mean ESS score in PDs was lower than that reported in PD in European and American studies. EDS in Japanese patients with PD was milder compared with Caucasian patients, which might be due to the lower doses of the medications used in Japan. The results suggest that EDS in PD is mainly because of neuropathological changes of the disease itself.     

冻干水痘减毒活疫苗最小免疫剂量的研究

通过临床研究确定冻干水痘减毒活疫苗的最小免疫剂量 ,为制定规程中的免疫剂量提供科学依据。观察对象接种不同免疫剂量的冻干水痘减毒活疫苗后 ,于接种前和接种后 6周采血 ,采用荧光抗膜抗体 (FAMA)法检测其抗体阳转率和几何平均滴度 (GMT)。接种不同免疫剂量的疫苗 ,抗体阳转率差异无显著的统计学意义。疫苗中抗原含量在 2 5 0 0 0PFU/ml和 2 0 0 0PFU/ml之间 ,GMT差异无显著的统计学意义 ,但 2 5 0 0 0PFU/ml、2 0 0 0PFU/ml与 2 0 0PFU/ml之间抗体GMT的差异有极显著的统计学意义。研究结果表明 ,2 0 0 0PFU/ml为冻干水痘减毒活疫苗的最小免疫剂量。     

复方卡托普利片中氢氯噻嗪的含量及均匀度测定

用紫外分光度法直接溯定复方卡托普利片中氢氯噻嗪的含量及均匀度。测定波长为272±1nm,平均回收率100.2%,变异系数0.3%,吸收度与氢氯噻嗪的浓度在1～10μg/ml 范围内具有线性关系。     

Different molecular forms of cholecystokinin and CCKB receptor binding in the rat brain after chronic antidepressant treatment

Cholecystokinin (CCK) is a neuropeptide recently implicated in affective disorders. This study aimed at measuring the levels of different molecular forms of CCK and the binding characteristics of CCK_B receptors in the rat brain after three weeks of treatment with four different antidepressants, imipramine, amitriptyline, desipramine, and citalopram (all at the dose of 10 mg/kg once per day i.p.). Chronic treatment with imipramine and desipramine had a significant immobility-reducing effect in the Porsolt‘s swim test. The effect of amitriptyline, albeit in the same direction, was not significant, and citalopram had no effect in this test. In the elevated plus-maze test of anxiety, all drugs tended to increase the number of open arm entries and the ratio open/total arm entries, but only the effects of imipramine were statistically significant. None of the treatments affected the total levels of CCK or the levels of CCK-8-sulphated, CCK-8-nonsulphated, CCK-5, or CCK-4 in the frontal cortex. There was no effect of the treatments on CCK_B receptor binding in the frontal cortex, hippocampus, or striatum. Imipramine and amitriptyline, however, increased the affinity of CCK_B receptor binding in the hypothalamus. Thus, no consistent effect of chronic antidepressant treatment on the CCK-ergic neurotransmission in the rats was found. Received: 4 June 1996 / Accepted: 26 August 1996     

Dosage guidelines for the use of vancomycin based on its pharmacokinetics in infants

Summary The purpose of this study was to characterize the pharmacokinetics of vancomycin and to develop optimal dosage guidelines in infants. Thirteen infants between the ages of 13 to 183 days were enrolled. All had been born prematurely, and average gestational age, postconceptional age, and actual body weight were 29.8 weeks, 38.2 weeks, and 2.1 kg respectively. Multiple blood samples were obtained from each patient after 72 h of therapy. Serum inhibitory and bactericidal titres were determined for peak and trough samples.There were good correlations between total body clearance of vancomycin and both postconceptional age (r=0.86) and actual body weight (r=0.87). This information was used to develop vancomycin dosage guidelines in premature infants. The regression line for vancomycin daily dosage requirements vs postconceptional age may be useful for determining initial dosage recommendations.There were also good correlations between vancomycin serum concentrations and serum inhibitory and cidal titres. Peak and trough concentrations in the therapeutic range (peak, 25–35 µg/ml; trough, 5–10 µg/ml) corresponded to titres of 1:8 and 1:2 to 1:8 respectively.Based on these data we suggest the following dosage guidelines for vancomycin: 10 mg/kg 12 hourly for 30–34 weeks postconceptional age and <1.2 kg actual body weight; 10 mg/kg 8 hourly for 30–42 weeks postconceptional age and >1.2 kg actual body weight; 10 mg/kg 6 hourly for >42 weeks postconceptional age and >2.0 kg actual body weight.Thus, doses which are lower than currently recommended are needed for infants born prematurely. Furthermore, the initial dose of vancomycin can easily be determined using an infant's postconceptional age.SML was a Fellow at Children's Hospital at the time of study and is now at Rutgers University, College of Pharmacy, Piscataway, NJ, USA     

Dosage compensation, the origin and the afterlife of sex chromosomes

Over the past 100 years Drosophila has been developed into an outstanding model system for the study of evolutionary processes. A fascinating aspect of evolution is the differentiation of sex chromosomes. Organisms with highly differentiated sex chromosomes, such as the mammalian X and Y, must compensate for the imbalance in gene dosage that this creates. The need to adjust the expression of sex-linked genes is a potent force driving the rise of regulatory mechanisms that act on an entire chromosome. This review will contrast the process of dosage compensation in Drosophila with the divergent strategies adopted by other model organisms. While the machinery of sex chromosome compensation is different in each instance, all share the ability to direct chromatin modifications to an entire chromosome. This review will also explore the idea that chromosome-targeting systems are sometimes adapted for other purposes. This appears the likely source of a chromosome-wide targeting system displayed by the Drosophila fourth chromosome.     

A homozygous MITF mutation leads to familial Waardenburg syndrome type 4

Waardenburg syndrome (WS) is a genetic disorder characterized by hearing loss and pigmentary abnormalities with variable penetrance. Though heterozygous mutations in MITF are a major cause for Waardenburg syndrome type 2 (WS2), homozygous mutations in this gene and the associated phenotype have been rarely characterized. In this study, we identified a novel p.R223H mutation in MITF in a Chinese Han family with variable WS features. Both parents carried a heterozygous p.R223H mutation. They had normal hearing, and premature greying of the hair is their only pigmentary abnormality. In contrast, their two children both carried a homozygous p.R223H mutation and had classic WS features including profound hearing loss, heterochromia irides and marked pigmentary abnormalities in hair and skin. Interestingly, the two affected children also have persistent chronic constipation since the neonatal period, symptoms suggestive of Waardenburg syndrome type 4 (WS4). Our study revealed a likely association between homozygous mutations in MITF and WS4, which implies a dosage effect for the underlying pathogenesis mechanism.     

Charcot-Marie-Tooth phenotype produced by a duplicated PMP22 gene as part of a 17P trisomy-translocation to the X chromosome

The Charcot-Mane-Tooth disease type 1A (CMTlA) phenotype is most often associated with a 1.5 megabase (mb), tandem duplication of chromosome 17 band p12 (17˜12). The prevailing hypothesis is that the demyelinating neuropathy results from a dosage effect of the peripheral myelin protein gene PMP22 which is included within this duplication. We present a patient with clinical and electrophysiological features ofCMTlA in whom an extra PMP22 gene resulted from a rare unbalanced translocation of 17p to the X chromosome. This finding further supports the hypothesis of gene dosage as the basis for CMTlA. More-over, this case highlights the importance of fluorescence in siiu hybridization (FISH) as an alternative molecular technique in the diagnosis of CMTlA.     

诊断X线机辐射剂量的测量

为提高诊断X线机的诊断质量,促进放射防护工作的开展,根据"国际辐射单位和测量委员会"(International Commission on Radiological Units and Measurements,ICRU),"国际放射防护委员会"(International Commission on Radiation Protection,ICRP)关于辐射对人体的损害之划分标准,作者对岛津制作所90年代中期生产的XEB150L-20型500mA X线机按照国家规定的要求及有关标准,分别对辐射空气释动能率,半价层,输入量重复性,输出量线性,高对比分辨率,光野与照射野一致性及X线管的焦点等参数进行了测试。分析了测试的数据与结果,并进行了简要的评价。     

Relationships among genotypes, virulence and clinical forms of Sporothrix schenckii infection

This study explored the relationships among genotypes, virulence and clinical forms of Sporothrix schenckii. Genomic DNA from isolates of S. schenckii, collected from different clinical forms of sporotrichosis, was amplified by randomly amplified polymorphic DNA (RAPD). Suspensions of different isolates of S. schenckii were inoculated into healthy BALB/c mice to compare their virulence, and the numbers and distribution of spores were determined by histological analysis. RAPD analysis indicated that the isolates from different clinical forms of sporotrichosis belonged to different genotypes. The mice inoculated with isolates from disseminated sporotrichosis showed an earlier onset of illness and more severe lesions than those inoculated with isolates from lymphocutaneous sporotrichosis, which, in turn, showed an earlier onset of illness and more severe lesions than those inoculated with isolates from fixed cutaneous sporotrichosis. Healthy BALB/c mice injected with isolates from disseminated sporotrichosis died within 10 days, whereas isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis failed to cause death. Histologically, mice inoculated with isolates from disseminated sporotrichosis had more spores than those inoculated with isolates from lymphocutaneous sporotrichosis and fixed cutaneous sporotrichosis. Thus, different genotypes may be associated closely with the virulence of different clinical forms of S. schenckii infection.