Reduction in Internal Carotid Arterial Blood Flow Velocity in Children During Antiepileptic Drug Therapy with Clinical Dosages

Summary: We studied the effect of antiepileptic drugs (AEDs) on internal carotid artery (ICA) blood flow velocity, as an index of total cerebral blood flow (CBF). The subjects were 45 newly diagnosed children with febrile convulsion or epilepsy who were seizure-free for a period long enough not to affect the results. They had no neurologic deficit, received fixed monotherapy, and were examined by a noninvasive Doppler ultrasound method, in comparisonwith 13 age-matched normal volunteers with no AED. In 30 patients, the measurements were performed before and after AED administration [10 with phenobarbital (PB), 10 with carbamazepine (CBZ), and 10 with valproate (VPA)], and performed before and after AED discontinuation in the remaining 15 patients (all with PB). Normal volunteers underwent the two consecutive examinations with a mean interval equal to that of the entire patient group, and there was no difference in velocity values between the measurements. In patients receiving CBZ or VPA, a significant reduction was noted in blood flow velocity after drug administration. Although velocity values in the patients receiving PB did not change after drug administration, they were significantly increased after complete discontinuation. In the present study, a slight but significant reduction in CBF caused by AED administration at therapeutic doses in children was suggested.     

Characterization of Aerosols of Human Recombinant Deoxyribonuclease I (rhDNase) Generated by Jet Nebulizers

Recombinant human deoxyribonuclease I (rhDNase) is a new therapeutic agent developed to improve clearance of purulent sputum from the human airways. It is delivered by inhalation. Four jet nebulizers, T Up-Draft II (Hudson), Customized Respirgard II (Marquest), Acorn II (Marquest), and Airlife Misty (Baxter), were evaluated in vitro for their ability to deliver aerosols of rhDNase. The aerosols were generated from 2.5-mL aqueous solutions of rhDNase, at concentrations of either 1 or 4 mg/mL. In all experiments, the Pulmo-Aide Compressor (De Vilbiss) was used to supply the air to the nebulizers. Between 20 and 28% of the rhDNase dose initially placed in the nebulizers was delivered to the mouthpiece in the respirable range (1-6 µm). Evaluation of the rhDNase following nebulization in all four devices indicated that there was no loss in enzymatic activity and no increase in aggregation. Circular dichroism spectrophotometry indicated there was no change in either the secondary or the tertiary structure in rhDNase following nebulization. These results show that all four nebulizers are essentially equivalent in their ability to deliver respirable doses of rhDNase in an intact, fully active form. Changing the concentration of the solution in the nebulizer from 4 to 1 mg/mL rhDNase leads to a proportional reduction in the respirable dose delivered to the mouthpiece.     

Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.     

善宁治疗顽固性大咯血疗效观察

目的 评价善宁对顽固性大咯血的疗效。方法 将55例传统药物抢救无效或有禁忌的大咯血分为治疗组（善宁）与对照组（立止血组），观察24—72h的止血效果。结果 治疗组总有效率为92％，对照组为70％，两组比较有显著差异p〈0．05（x^2=4．125）。结论 善宁治疗大咯血疗效显著，使用安全，不良反应少，值得临床推广应用。     

Flumazenil, a GABA antagonist, may improve features of Parkinson's disease.

Manipulation of gamma-aminobutyrate (GABA) system has been little studied in Parkinson's disease, despite the fact that GABA subserves a large part of the basal ganglia, including the outflow tracts. To test whether antagonism of GABA could improve features of PD, we administered open label intravenous flumazenil to eight practically defined off patients and assessed UPDRS scores, bilateral 1-minute hand-tapping speed, and timed gait tests. Patients demonstrated significantly greater tapping speed, which peaked 40 minutes after injection (P < 0.05). Total motor Unified Parkinson's Disease Rating Scale scores modestly improved (P < 0.05). There were no adverse events. Mechanisms by which flumazenil could improve PD are discussed.     

Partially Reversible Chronic Renal Failure Due to Long-term Use of Non-steroidal Anti-inflammatory Drugs

A case of partially reversible chronic renal failure due tolong-term NSAID use is discussed. An analysis of this and similarcases recently reported indicates many similarities betweenchronic NSAID nephropathy and analgesic nephropathy.     

Inhibition or enhancement of kindling evolution by antiepileptics

Summary The influence of antiepileptics on the evolution of rat amygdaloid kindling was studied.Under placebo conditions clonic convulsions and a spike-wave EEG pattern developed. Diazepam, clonazepam, clobazam and phenobarbital were most effective in suppressing the evolution of kindling; the effects of valproate sodium, ethosuximide and acetazolamide were somewhat less pronounced in this respect. Carbamazepine, oxcarbazepine and phenytoin, on the other hand, enhanced kindling development, i.e. the increase in duration of after-discharge was faster than in the placebo group. The results indicate that under the above experimental conditions drugs with no anti-absence component can be distinguished from those with an anti-absence component. The mechanism of action underlying the observed effects is not yet known; the hypothesis that under special conditions protective inhibitory neuronal activity can develop to absence type seizures is proposed.     

法莫替丁治疗消化性溃疡60例

60例(男50,女10,年龄43±8a)经内窥镜证实的活动性消化性溃疡患者,口服法莫替丁40mg,qn,疗程2-4wk或延至6-9wk。溃疡愈合率DU2,4,6 wk分别为50％,84％,92％,SU2,4,6,8 wk分别为40％,68％,73％,82％。服药后3,7,14 d上腹痛缓解率DU为50％,80％,100％,SU为40％,75％,95％。未见严重不良反应。故法莫替丁对溃疡病,尤其是DU是一有效和安全药物。     

Evaluating therapeutic outcome in epileptic patients using the changes of interval and duration

BACKGROUND: Seizure frequency is in abnormal distribution, and it is not enough to express the trend of concentration using means, and its median loses a lot of information, thus it lacks of a standard for evaluating the therapeutic effects based on seizure frequency. OBJECTIVE: To establish a method for evaluating the therapeutic effects on anti-epileptic drugs using changes of interval and duration of seizure. DESIGN: A prospective cohort study. SETTING: Zhumadian Psychiatric Hospital. PARTICIPANTS: Outpatients and inpatients suffering from epilepsy attending firstly visited Zhumadian Psychiatric Hospital from June 2001 to June 2002 were enrolled. They were diagnosed as epileptic according to the International Classification of Epileptic Seizure by International League Against Epilepsy (1981) based on the clinical history, physical examination, and investigations. The interval time was no more than 6 months. Informed consent was obtained from all the subjects, and the study was approved by the hospital ethical committee. METHODS: ① For the first visit and each follow-up, the following data were recorded, including general demographic information, seizure type, the date and time of ictus, the duration of ictus, and inducement or situation related, according to which the following indexes could be calculated, including seizure styles, interval, duration, cluster frequency and cluster duration. The information from the first review was noted as annals A. The second interview was taken at the end of the evaluating period; the information from the second review was noted as annals B. The third interview was taken within two weeks after the second one; the information from the third review was noted as annals C. The annals B or the annals C were respectively compared with the annals A in the light of the same types or the same styles of the same patient. Summation of the scores of interval change and duration change of the same type or the same style and 5 of basic score was the score of a corresponding seizure type or a corresponding style of one patient. In order to test its reliability and validity, the score of change of frequency or duration plus 5 scores respectively was the score of frequency or duration. ② Reliability and validity were tested by calculating corresponding correlation coefficient with SPSS 11.0. ROC curve was used for developing diagnostic criterion of predicting therapeutic effects with SPSS 11.0. MAIN OUTCOME MEASURES: ① Reliability and validity; ② Diagnostic criterion for predicting therapeutic effects one year later. RESULTS: Totally 28 patients were involved in the final analysis of results. ① Reliability and validity were high: rinter-rater=0.98, rtest-retest=0.99, rconstruct validity=0.83. ② A total score > 6 was the optimal diagnostic criteria for predicting therapeutic effects one year later, in other words, a patient who scored more than 6 at the evaluating period may be seizure-free one year later. CONCLUSION: It is a potential tool for evaluating epileptic therapeutic outcome, and it can be diffusely used in interrelated fields after being further validated.     

Cholinergic therapy in dementia

After reviewing the evidence for cholinergic pathology in Alzheimer's disease and related disorders, this paper reviews strategies for treating dementia using cholinomimetic drugs. Special attention is paid to cholinesterase inhibitors, particularly tacrine, the drug recently approved by the FDA. New studies suggesting that muscarinic and nicotinic cholinergic receptor active drugs may be more effective will be reviewed. Brief mention will be made of strategies to slow the progression of Alzheimer's disease.