Effects of after-midnight intake of zolpidem and temazepam on driving ability in women with non-organic insomnia.

BACKGROUND: Occasionally, insomniac patients may take a sleeping pill after midnight. This may have consequences on their ability to drive a car and result in an increased risk of car accidents. METHODS: This double-blind, randomized, placebo-controlled, three-treatment three-period cross-over study investigated the effects of two frequently prescribed hypnotics of different classes in a real life condition on driving performance and psychomotor skills in insomniac women. Single doses of zolpidem 10 mg (Z), temazepam 20 mg (T) or placebo (P) were administered at 2:00 a.m. to 19 women aged 35-60 years in three treatment periods separated by wash-out periods of 3-14 days. After polysomnography at baseline and each treatment night, patients underwent, 5.5 h after drug intake at 7:30 a.m. on the next morning, a STISIM driving simulator test, and a subsequent neuropsychological test (FePsy). RESULTS: Eighteen insomniac women were included in the analysis (mean age 50 years, mean weight 69 kg, mean BMI 25.6 kg/m2). There were no differences between treatments for the primary outcome measure (mean time to collision; baseline: 0.120 s, P: 0.124, T: 0.118, Z: 0.124; P> or =0.12 for all pairwise comparisons). No differences were recorded for speed deviation and reaction time to tasks for the verum treatments, however, lane position deviation was greater after administration of zolpidem in comparison to both placebo and temazepam (P=0.025 and 0.05, respectively). There were no differences between treatments in the FePsy test. Both medications were well tolerated. CONCLUSIONS: 5.5 h after drug administration there were no major differences in psychomotor performances between both zolpidem and temazepam compared to placebo, which indicates the absence of significant residual effects at that time. However, certain patients were more susceptible than others to the drug effects (two patients with high number of collisions). This underlines the necessity to strongly advocate against the late intake of hypnotics if patients intend to drive a car early the next morning.

Genomic hypomethylation in human chronic lymphocytic leukemia.

DNA samples from patients with chronic lymphocytic (CLL), chronic myelocytic (CML), acute myelocytic (AML), and acute lymphocytic leukemia (ALL), as well as samples from patients with multiple myeloma (MM) and healthy volunteers, were analyzed for their genomic methylation status using Hpa II and Msp I digestions followed by a simple gel electrophoresis and ethidium bromide staining. A densitometric method was developed to measure more accurately the extent of methylation in genomic DNA samples and the results were confirmed by high-performance liquid chromatography (HPLC) analysis of hydrolyzed DNA. Southern analysis with ornithine decarboxylase (ODC) gene probe was also employed, and the levels of ODC mRNA were determined with the aid of polymerase chain reaction (PCR). The results indicated that a general genomic hypomethylation was present in almost all of the samples obtained from patients with B-cell CLL. This hypomethylation was most striking among the patients who were freshly diagnosed and among untreated chronic patients. CML appeared to be a heterogenous group, comprising patients with normal methylation status in addition to patients with slight hypomethylation. Patients with ALL, AML, or MM did not show any signs of DNA methylation changes in comparison to healthy volunteers. Although all analyzed samples from patients with B-CLL showed hypomethylation of ODC sequences, little correlation existed between the mRNA levels and the extent of hypomethylation of ODC gene.

A double-blind group comparison of mianserin and clomipramine in the treatment of mildly depressed psychiatric out-patients.

The effects of mianserin 30-60 mg and clomipramine 75-150 mg were compared in a randomized double-blind study of 62 mildly depressed out-patients. Treatment was continued for three to four weeks, after which approximately 50% of patients left the study clinically much improved. Significant benefits for mianserin were apparent at days 7 and 21 on the Hamilton Depression Rating Scale (HDRS) total score and at day 7 on the HDRS anxiety-somatization factor score. No difference in overall antidepressant activity was found in those patients treated for four weeks. There was a significantly greater number of side-effects in the clomipramine treated group. It is suggested that mianserin is a more rational treatment than clomipramine in this group of patients because of a greater anxiolytic action and a lower incidence of side-effects.

Myelographic versus clinical diagnostics in lumbar disc disease.

The series consisted of 200 patients on whom lumbar myelography was performed for sciatica. After myelography, a disc operation was carried out on 95 patients. The episode of sciatica was the first for 90 patients. Objective neurologic signs were present in 185 patients, while 15 had only subjective symptoms. Definite or possible disc herniation was revealed by myelography in 66%. Most positive findings were located at the L4-L5 interspace. The clinical diagnostic accuracy rate was assessed from the patients' histories. As confirmed by operation, the accuracy of the clinical diagnostics was 52%, and the accuracy rate of myelography was 90%. The rate of false positive findings in myelography was 4%, that of false negative findings 6%. When the clinical or myelographic diagnosis was definitive, a disc herniation or protrusion was always found at operation. Almost one fourth of the clinically diagnosed definite herniations were not treated surgically because myelography proved negative. One fifth of those patients in whom myelography revealed an unequivocal disc herniation were not operated on because these patients had clinically improved before being admitted to myelography. The results of this study justify the following conclusions: the clinical level diagnostics of a disc herniation is rather unreliable, and myelography is therefore always indicated before operation; myelography should only be performed in those cases in which there is a clear clinical indication for surgery; myelography ought to be performed within 1 week; an unequivocal positive finding in myelography predicts a good operative result.

Effect of rifampicin treatment on the kinetics of mexiletine.

To study the effects of enzyme induction on its pharmacokinetics, a single oral dose of the new antiarrhythmic agent mexiletine hydrochloride 400 mg was administered to 8 healthy volunteers before and after treatment with rifampicin 300 mg b.i.d. for ten days. The absorption and distribution of mexiletine were not changed after rifampicin, but its elimination half-life fell from 8.5 +/- 0.8 h (mean +/- SE) to 5.0 +/- 0.4 h (p less than 0.01), and its nonrenal clearance increased from 435 +/- 68 ml/min to 711 +/- 101 ml/min (p less than 0.01). The mean renal clearance of mexiletine did not change, but it showed an exponential correlation with urinary pH. The amount of unchanged mexiletine excreted in urine over two days decreased from 32 +/- 7 to 18 +/- 3 mg (p less than 0.01). The half-life of antipyrine fell from 11.8 +/- 0.4 to 5.5 +/- 0.3 h and its clearance increased from 40 +/- 3 ml to 74 +/- 3 ml/min (p less than 0.01). There was a significant (p less than 0.05) positive linear correlation between both the half-lives and the clearances of antipyrine and mexiletine. The clearances were positively correlated with serum gamma-glutamyl transpeptidase. The results suggest that the dosage of mexiletine should be adjusted when enzyme inducing drugs are started or stopped during therapy with it.