The Effect of Antiepileptic Drugs on Cognition: Patient Perceived Cognitive Problems of Topiramate versus Levetiracetam in Clinical Practice

Summary:  Introduction: Neurocognitive complaints may interfere with long-term antiepileptic drug (AED) treatment and are an important issue in clinical practice. Most data about drug-induced cognitive problems are derived from highly controlled short-term clinical trials. We analyzed such cognitive complaints for the two most commonly used AEDs in a clinical setting using patient perceived problems as primary outcome measure.
Method: All patients of the epilepsy center Kempenhaeghe that received topiramate (TPM) or levetiracetam (LEV) from the introduction to mid 2004 were analyzed using a medical information system, an automated medical file. Patients were analyzed after 6, 12, and 18 months of treatment.
Results: Four hundred and two patients used either TPM (n = 260) or LEV (n = 142); 18 months retention showed a statistically significant difference, revealing 15% more patients that continued LEV compared to TPM: 18 months retention 46% for TPM and 61% for LEV [F (1.400) = 3.313, p = 0.043]. Neurocognitive complaints accounted for a significant number of drug discontinuations and especially the high frequency of neurocognitive complaints in the first period of TPM treatment appeared to be significant different from LEV [F(2,547) = 3.192, p = 0.042]. In the remaining patients, the difference in neurocognitive complaints was not statistically significant.
Conclusion: cognitive complaints are common in TPM treatment and frequently lead to drug withdrawal. The impact of LEV on cognitive function is only mild. This leads to a much higher (15%) drug discontinuation rate for TPM compared to LEV.     

LEEP刀治疗与护理相结合治疗宫颈疾病的作用

目的探讨LEEP刀治疗与护理相结合在治疗宫颈疾病中的作用。方法选择应用LEEP刀治疗与红外光治疗两组患者各60例。比较其疗效和护理作用。结果LEEP刀治疗比红外光治疗宫颈疾病效果要好。结论LEEP刀治疗与护理相结合对宫颈疾病的治疗值得推广应用。     

Eye movement quantitative evaluation before and after high-dose 6-methylprednisolone in multiple sclerosis

We studied saccadic and smooth pursuit eye movements in 24 patients suffering from multiple sclerosis during disease worsening, before and after high-dose 6-methylprednisolone infusions. Quantitative evaluation of saccades was based on amplitude/duration and amplitude/peak velocity relationships, precision (i.e. the ratio of actual to desired saccade amplitude) and the latency, whereas smooth pursuit eye movements were studied using target velocity/performance index relationship. At basal recordings, 22/24 (91.7%) of the patients showed at lest one abnormality. Eleven of the 24 patients (45.8%) showed modification of one or several parameters: improvement in 6 patients, worsening in 2, coexistence of both trends in 3. Latency improvement was the only significant modification when patients were considered as a group. Neurophysiological modifications did not correspond to clinical changes.     

The Testes in Cadmium Intoxication: Morphological and vascular aspects

Cadmium toxicity was tested on young male Wistar rats by injecting 1 mg/ml of cadmium chloride (CdCl2) intra-peritoneally. Post-mortem examination was done 4 hours, 24 hours and 14 days after cadmium administration to observe time-sequence cadmium-induced alterations in vascular permeability of the mesothelium in the pleura, peritoneum and tunica vaginals. This paper mainly reports the alterations observed in the testes. Vascular permeability was assessed by the colloidal carbon technique. Vascular labelling was evidenced as early as 4 hours after CdCl2, injection; 24 hours later severe oedema with leakage of particles to the interstitium and also into the tubules was patent. Fourteen days after CdCl2 administration atrophy of the testes with necrosis of the tubules, fibrosis of the interstitium and vascular thrombosis was found, compatible with chemical castration.     

Nasal nicotine spray: a rapid nicotine delivery system

Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed.     

Quantitation of T2′ anisotropic effects on magnetic resonance bone mineral density measurement

In this paper, the authors quantitate the anisotropy of susceptibility effects in an uniaxial trabecular bone model and show its relevance to clinical MR bone mineral density measurements. A physical model is described that quantitates the anisotropic MR behavior of uniaxial trabecular bone. To test the model, a phantom of parallel polyethylene filaments was scanned every 15° between 0° and 90° with respect to the system's main magnetic field (B₀). The distal radial metaphysis of a healthy female volunteer was scanned in orthogonal projections. The signal from each phantom image and each radial image was separated in a pixel-wise fashion into R₂ and R₂′ maps. As predicted, R₂′ relaxation showed anisotropic behavior and changed according to sin² (?), confirming that columnar structures parallel with B₀ will cause no MR susceptibility effects. Scans of the distal radius showed that R₂′ relaxation was twice as great with the forearm perpendicular to B₀ as when it was parallel to it, demonstrating different contributions from struts and columns. For both phantom and radial bone scans, R₂ relaxation was isotropic and did not change with object orientation.     

Controlling for occasion-specific effects when assessing the test–retest reliability of self-report health questionnaires

OBJECTIVE: This study proposes a method for self-report health questionnaires to adjust test-retest reliability for changes during the test-retest interval based on an external measure, and to distinguish such changes from random response errors. METHODS: In our application, eighty participants completed the Symptoms of Illness Checklist (SIC) on two occasions, two weeks apart, immediately before interviews given on each occasion by one of two physicians in a crossover design. The physician interview scores served as external measures, and structural equation modeling was used to estimate the parameters of a model that corrected for the occasion-specific effect of participants' responses using information from the interviews. RESULTS: Correcting for changes in symptoms during the test-retest interval increased SIC test-retest reliability from .744 to .804 and significantly improved model fit (chi2(diff)(1) = 30.78, p < .001). CONCLUSIONS: The results suggest methods that can improve the evaluation of self-report health questionnaire test-retest reliability by identifying changes using an external measure, and distinguishing these from random response errors; these increased the estimated SIC test-retest reliability and indicated that the SIC was indeed able to measure changes over the studied time interval. This method can be applied across a broad range of questionnaires.     

Effect of concomitant food intake on absorption kinetics of fenoldopam (SK&F 82526) in healthy volunteers

Summary Eight healthy volunteers participated in an open crossover study to assess the effect of a standardised meal on the systemic availability of a single oral dose of fenoldopam mesylate 100 mg. Subjects were studied on four separate occasions, twice fasting and twice fed in randomised, balanced order. Plasma and urine samples were obtained before and at regular intervals up to 25 h post dose. Measurement of fenoldopam (SK&F 82526) and its 8-sulphate metabolite (SK&F 87782) were by means of HPLC-EC analysis. Area under the plasma concentration time curve (AUC) and maximum detected plasma concentration (C_max) for fenoldopam and SK&F 87782 were significantly reduced whereas time to maximum concentration was significantly increased with food. Using AUC's for fenoldopam and SK&F 87782, mean relative bioavailabilities were 35% and 81% respectively under fed compared with fasting conditions. Twenty-four hour excretion of fenoldopam was significantly reduced with food, but excretion of SK&F 87782 was apparently unchanged. Mean relative bioavailabilities calculated from these data were 83% and 86% respectively. Relatively large inter-subject variability in AUC and C_max were seen, but intra-subject variability was not marked. Mild symptoms associated with vasodilation were reported on all study days.     

微波与X线联合辐射对人体血液系统的影响

本文调查了微波与X线同时接触工人49名(联合组)、单微波接触工人48名(微波组)以及两者均不接触的工人46名(对照组)。联合组和微波组工人的微波辐射剂量每日平均约300μw/cm~2,联合组工人接触的X线剂量,每年小于5rem。结果显示:联合组中性粒细胞ACP、AKP活性以及中性粒细胞核棘突出现率均较微波组和对照组明显增高(P<0.01),糖原含量则较其它两组明显下降(P<0.01)。调查表明,低强度微波与低剂量X线联合辐射比单独微波辐射对人体的潜在危害更大。因此,对雷达等发射设备周围的工作人员,除必要的微波防护外。同时需要对X线进行防护。