Journal of International Medical Research

The possible synergistic effect of valproic acid and ethosuximide in combination on pentylenetetrazole-induced epilepsy was investigated in rats. Valproic acid and ethosuximide administered intraperitoneally both showed dose-dependent anti-epileptic activity towards pentylenetetrazole-induced myoclonias and tonic – clonic seizures. The valproic acid – ethosuximide combination had a synergistic pharmacological effect. Against myoclonias combined valproic acid – ethosuximide produced a non-significant decrease in the effective dose of both drugs compared with treatment with either drug alone. In the case of tonic – clonic seizures the protective effect against the seizures was significantly increased by combined treatment compared with treatment with either drug alone. Neither plasma concentrations nor any other pharmacokinetic parameters were significantly changed when the same doses of valproic acid and ethosuximide were given, singly or in combination.

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, inflammatory neurodegenerative disease. This study investigated the relationships of clinical stage with epidemiological and magnetic resonance imaging (MRI) findings in SSPE by retrospective review of 76 cases (57 male) diagnosed by typical periodic electroencephalographic features, clinical symptoms and elevated measles antibody titre in cerebrospinal fluid. Clinical stage at diagnosis was I or II in 48 patients, III in 25 and IV in three. Prominent findings at presentation were atonic/myoclonic seizures (57.9%) and mental deterioration with behaviour alteration (30.3%). Frequent MRI findings (13 – 32 patients) were subcortical, periventricular and cortical involvement and brain atrophy; the corpus callosum, basal ganglia, cerebellum and brainstem were less frequently involved. Five patients had pseudotumour cerebri. Cranial MRI at initial diagnosis was normal in 21 patients (19 stage I/II, two stage III/IV). Abnormal MRI findings were significantly more frequent in the later stages, thus a normal initial cranial MRI does not exclude SSPE, which should, therefore, be kept in mind in childhood demyelinating diseases even when the presentation is unusual.

A 30-year-old man presented with a left undescended testis, right testicular deficiency and azoospermia. Testicular biopsy revealed an absence of spermatocytes and increased numbers of Leydig cells in the undescended testis. Additional comparative analyses were undertaken to explore Sonic Hedgehog (Shh) immunostaining in the testis of juvenile and adult mice, in the testis of the patient with cryptorchidism, and in archival testicular tissue from a patient with obstructive azoospermia and a patient with prostate cancer. Shh immunostaining was demonstrated in spermatocytes in juvenile and adult mouse testis and in the patients with obstructive azoospermia and prostate cancer, suggesting that Shh signalling is involved in normal spermatogenesis. In the patient with cryptorchidism, Shh immunostaining was localized to the Leydig cells, which suggests that Shh might be involved in the abnormal expansion of the Leydig cell population in the testis. These preliminary data on the appearance of Shh protein during normal spermatogenesis might provide the basis for further investigations to clarify the role of Shh signalling in spermatogenesis during normal and pathogenic testis development.

OBJECTIVE: To determine risk factors associated with drug resistant tuberculosis (TB) in mainland China. METHODS: PubMed and Chinese BioMedical databases were searched. Cohort, case—control and cross-sectional studies providing effect estimates of risk factors for any-drug resistant or multidrug resistant (MDR) TB were included. RESULTS: The meta-analysis included 16 studies. Any-drug resistant TB was significantly associated with poor quality directly observed treatment, short-course (DOTS) (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.22, 5.79), long term illness > 1 year (OR 2.71, 95% CI 1.34, 5.48), poor treatment adherence (OR 2.00, 95% CI 1.17, 3.40), previous treatment (OR 4.54, 95% CI 2.71, 7.61) and age 40 – 60 years (OR 1.62, 95% CI 1.10, 2.38). MDR-TB was significantly associated with poor quality DOTS (OR 1.84, 95% CI 1.36, 2.49), poor treatment adherence (OR 4.39, 95% CI 2.97, 6.50), previous treatment (OR 3.83, 95% CI 2.12, 6.89) and poverty (OR 1.87, 95% CI 1.38, 2.52). CONCLUSIONS: Previous treatment, poor quality DOTS, poor treatment adherence, long term illness, age 40 – 60 years and poverty are associated with a greater risk of drug resistant TB in mainland China.

One hundred and four patients suffering from insomnia took part in four different two-night double-blind crossover trials of triazolam. In three separate studies, triazolam 0·5 mg was compared to placebo, flurazepam 30 mg and chloral hydrate 500 mg. Triazolam 0·5 mg was found to be preferred and to be superior to placebo, flurazepam and chloral hydrate in the treatment of insomnia. Analysis of sleep questionnaire data showed triazolam to be superior to the other treatments on the following: How much did the medication help you sleep, onset of sleep, duration of sleep and number of awakenings. Additionally, triazolam was superior to chloral hydrate on the feeling in the morning parameter. In another comparison of triazolam 0·25 mg to flurazepam 15 mg, triazolam was not significantly better than flurazepam on any of the efficacy parameters except that the patients felt more alert the morning following triazolam than following flurazepam. On all efficacy endpoints, trends for all parameters favoured triazolam 0·25 mg over flurazepam 15 mg. Untoward side-effects in these four studies were minimal.

The short-term hypnotic efficacy of triazolam was compared to that of flurazepam and placebo in 120 out-patient insomniacs. Each patient was studied with a two-night, double-blind crossover trial. Triazolam (0.5 mg) was compared to placebo and flurazepam (30 mg). Triazolam (0.25 mg) was compared to flurazepam (15 mg and 30 mg). Triazolam (0.5 mg) was preferred to both placebo and flurazepam (30 mg). Triazolam (0.5 mg) was superior to placebo in improving quality of sleep, shortening sleep onset, increasing sleep duration, and reducing the number of night-time awakenings. Triazolam (0.5 mg) was superior to flurazepam (30 mg) in speeding sleep onset and increasing the quality of sleep. Triazolam (0.25 mg) was preferred to flurazepam (15 mg) and was significantly better than flurazepam on all sleep questions. Triazolam (0.25 mg) was preferred by more patients than flurazepam (30 mg) and was judged equally efficacious on indivdual sleep questions. Reports of side-effects were minimal for both drugs.

The safety and efficacy of 10 or 20 mg/day zolpidem, a new hypnotic belonging to the imidazopyridine class, were studied over a 180-day period in 96 patients with sleep disorders. The treatment was continued for a further 180 days by 49 of these patients. Follow-up information from 21 patients who discontinued treatment after 180 days showed no rebound insomnia or withdrawal signs. Efficacy of treatment with respect to reduction of sleep onset latency and number of nocturnal wakenings, and improvement in duration of sleep, quality of sleep and morning wakenings was found in nearly 90% of patients and was maintained in those patients who continued treatment for 360 days. This efficacy was achieved with a stable percentage of patients receiving 10 mg/day and 20 mg/day zolpidem from day 30 to the final visit. Zolpidem, therefore, has been shown to be an effective and safe hypnotic, and to be devoid of rebound and withdrawal effects.

La sécurité d'utilisation et l'efficacité du 10 ou 20 mg par jour de zolpidem, un nouvel hypnotique appartenant à la classe des imidazopyridines, ont été étudiées sur une période de 180 jours chez 96 patients souffrant de troubles du sommeil. Le traitement s'est poursuivi pendant 180 jours supplémentaires chez 49 de ces patients. Le suivi de 21 patients ayant cessé le traitement au bout de 180 jours n'a montré ni rebond d'insomnie, ni syndrome de sevrage. L'efficacité du traitement se mesure par la reduction du temp d'endormissement et le nombre de réveils noctures, ainsi que l'amélioration de la durée du sommeil, de la qualité du sommeil et du réveil au matin ont été retrouvés chez près de 90% des patients; ces effets se sont maintenus chez les patients qui ont poursuivi le traitement pendant 360 jours. Cette efficacité a été obtenue pour un pourcentage assez constant de patients qui ont reçu 10 mg par jour de zolpidem, puis 20 mg par jour du 30 ème jour à la fin du traitement. Pour ces raisons, le zolpidem, s'est donc révélé être un hypnotique efficace et sûr, dépourvu d'effets de rebond et de sevrage.

The efficacy and tolerability of the imidazopyridine hypnotic, zolpidem, were investigated in 119 elderly psychiatric inpatients complaining of insomnia in a double-blind, parallel-group, placebo-controlled trial. After a 7-day placebo washout period, patients were randomized to receive 10 or 20 mg/day zolpidem, or placebo for 21 days; thereafter, all patients received placebo for 7 days. Sleep was assessed by patient observation on days 0, 1, 7, 14, 21, 22 and 28. Compared with placebo, 20 mg/day zolpidem significantly improved total duration of sleep between day 0 and day 21, and this was maintained at day 28. After 10 or 20 mg/day zolpidem, there was also a trend towards improvement in all other sleep parameters, which remained above baseline at day 28. Zolpidem was well tolerated with no withdrawal symptoms during the second 7-day placebo treatment period. Daytime drowsiness was reported in three patients receiving 20 mg/day zolpidem and in one receiving 10 mg/day zolpidem, but there was no significant increase in daytime drowsiness between days 0 and 21. Ataxia occurred in two, one and one patient, respectively, treated with 20 mg/day zolpidem, 10 mg/day zolpidem and placebo. The incidences of other adverse events or effects on clinical and laboratory parameters were minimal and similar in all three treatment groups. It is concluded that, in elderly psychiatric patients, 10 mg/day zolpidem can be used to treat insomnia and can be safely added to concomitant psychotropic treatment without inducing daytime drowsiness.

L'efficacité et la tolérabilité du zolpidem, hypnotique de la classe des imidazopyridines ont été étudiées chez 119 patients âgés hospitalisés souffrant de troubles psychiatriques et se plaignant d'insomnie dans une étude en double aveugle à groupes parallèles, contrôlée par placebo. Après une période de washout par placebo de 7 jours, les patients ont été randomisés de manière à recevoir d'abord 10 ou 20 mg par jour de zolpidem ou du placebo pendant 21 jours; puis tous les patients recevèrent du placebo pendant 7 jours. Le sommeil a pu être évalué par l'observation des patients aux jours 0, 1, 7,14, 21, 22 et 28. Comparé au placebo, le zolpidem à la dose de 20 mg par jour a significativement augmenté la durée totale du sommeil entre le 1er et le 21ème jour, et cet effet était toujours présent au 28ème jour. Après 10 ou 20 mg par jour de zolpidem, on a également relevé une tendance à l'amélioration de tous les autres paramètres du sommeil, qui étaient toujours au-dessus de leurs valeurs de base au 28ème jour. Le zolpidem a été bien toléré et on n'a pas observé de syndrome de manque sevrage lors de la seconde période de traitement de 7 jours par placebo. Une somnolence diurne a été observée chez trois patients recevant 20 mg par jour de zolpidem, et chez un patient recevant 10 mg par jour, mais il n'y pas eu d'augmentation significante de la somnolence diurne entre jour 0 et jour 28. Une ataxie est apparue chez duex patients traité par 20 mg par jour de zolpidem, un patient traiteá par 10 mg par jour de zolpidem, et un patient traité par placebo. Les incidences des autres effets secondaires ou l'action sur les paramètres cliniques ou biologiques s'est révélée minime et similaire pour les trois groupes de patients. L'étude a conclu que, chez les patients âgés souffrant de troubles psychiatriques, un traitement par 10 mg par jour de zolpidem pouvait être utilisé pour traiter l'insomnie et peut être adjoint en toute sécurité à un traitement psychotrope concomitant sans induire de somnolence diurne.