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The sublingual form of the benzodiazepine hypnotic lormetazepam was developed with the aim of attaining greater flexibility in the treatment of sleep disorders. The object is to achieve rapid onset of hypnotic effect and provide patients with a Form of medication which they can take after having gone to bed and only if they have difficulty in falling asleep. In a placebo-controlled crossover double-blind study the hypnotic effect, side-effects and acceptance of lormetazepam sublingual (1 mg) were investigated in 60 patients with sleep disorders receiving treatment from physicians in independent practices. The study was conducted over a total of 2 weeks, the patients receiving lormetazepam and placebo for 7 days respectively, changing over in the second week. The results show that in the sublingual form lormetazepam (1) is distinctly better than placebo as regards hypnotic efficacy, particularly with respect to the reduction of steep latency: (2) does not lead to a significantly higher rate of concomitant symptoms than placebo; and (3) is well accepted by the patients in the wafer form. [ABSTRACT FROM AUTHOR]

Background: Human retinal pigment epithelial (RPE) cells produce levodopa and their transplantation into the striatum might improve continuity of administration compared with that achieved with oral levodopa. We aimed to assess the safety, tolerability, and efficacy of transplantation of microcarrier-bound human RPE cells versus a sham surgery control in patients with advanced Parkinson's disease., Methods: In this randomised, double-blind study eligible patients were aged 36-70 years, had been symptomatic for at least 5 years, were in Hoehn and Yahr stage 3-4 and had unified Parkinson's disease rating scale (UPDRS) motor scores of 38-70 when off medication (off state), and had symptoms that responded to oral levodopa but were insufficiently controlled by optimised pharmacotherapy. Randomisation was done in a 1:1 ratio. Only the neurosurgical team was aware of treatment assignments. During stereotactic transplantation around 325,000 cells per side were injected into the postcommissural putamen; sham surgery patients received partial burr holes. The primary efficacy endpoint was change in UPDRS off-state motor score at 12 months. This study is registered with ClinicalTrials.gov, number NCT00206687., Findings: Of 71 enrolled patients, 35 underwent cell transplantation and 36 sham surgery. Change in mean motor scores did not differ significantly between groups (-10.5 [SD 10.26] for transplantation vs -10.1 [SD 12.26] for sham surgery, p=0.9). The overall rate of adverse events was similar in the two study groups, although the number attributable to surgery or RPE cells (mostly neurological or psychiatric) was higher in transplant recipients. Two and seven patients died in the sham surgery and transplantation group, respectively; one death in the latter group was possibly related to surgery or RPE cells., Interpretation: Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery., Funding: Bayer HealthCare AG., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

It has been suggested from pharmacological studies in animals that ZK 93426 may improve memory and other cognitive processes in humans. Scopolamine has been used to model aspects of memory impairment. To test the effects of ZK 93426 alone and in combination with scopolamine, ZK 93426 (0.04 mg/kg) or vehicle (Intralipid R) was administered intravenously (i.v.) to normal controls, pre-treated with either scopolamine 0.5 mg administered subcutaneously (s.c.) or the same volume of saline. A visual (presentation of pictures) and a verbal (words list) memory test were applied. Both drugs on their own and in combination were found to be safe and well tolerated. ZK 93426 did not antagonize the scopolamine-induced impairment of acquisition of the words list. Scopolamine did not impair delayed recall of visual or verbal material. ZK 93426 alone improved performance in delayed recall of visual material presented after drug application, whereas it impaired performance in delayed recall of visual material presented before drug administration.

Serum prolactin, growth hormone, and alpha-fetoprotein were determined in women taking a new oral contraceptive, consisting of 2 mg cyproterone acetate and 50 microgram of ethinylestradiol. Because these women were suffering from acne vulgaris they were taking this contraceptive containing a gestagen with antiandrogenic activity. Prolatin and growth hormone were determined because both may favour the development and the growth of mammary tumors and because their secretion may be stimulated by estrogenic compounds. Alpha-fetoprotein is a marker of hepatocellular carcinoma, which may be associated with long-term use of oral contraceptives. During one year of treatment with cyproterone acetate and ethinylestradiol there was a continuous rise of serum concentrations of prolactin. However, this rise did not exceed the normal range. In contrast, serum concentrations of growth hormone did not change significantly. Serum alpha-fetoprotein levels remained below the detection limit of the method.

Unlike conventional antidepressants, rolipram stimulates both the presynaptic as well as the postsynaptic component of monoaminergic transmission. Several double-blind comparative trials are on the way to assess the clinical efficacy and safety of this novel compound. The present study was a randomized double-blind double-dummy comparison with imipramine in inpatients with major, "minor" and atypical depressions (DSM III). Results show no relevant differences between rolipram and imipramine regarding efficacy and safety.

In order to determine whether the clinically used frequency bands of the EEG can also be obtained by a mathematical system we did a factor analysis with 480 EEG recordings, 5 minutes each, in 60 healthy male volunteers. A power spectrum analysis was done and 57 frequency bands between 1.5 and 30.0 Hz in a half Hz steps were calculated. The factor structure obtained made the following frequency bands (Hz) reasonable: deltaF = 1.5 - 6.0, thetaF = 6.0 - 8.5, alpha1F = 8.5 - 10.5, alpha2F = 10.5 - 12.5, beta1F = 12.5 - 18.5, beta2F = 18.2 - 21.0, beta3F = 21.0 - 30.0. Except for alpha1F all other 6 frequency bands were represented by one general factor with the complexity 1. The variance of the alpha1F band is explained by several of the 6 factors. The clinically known and the by factor analysis obtained frequency bands in the beta-range are similar. The clinically alpha-band is subdivided into two frequency bands alpha1F and alpha2F by the factor analysis. The clinically known border line between delta- and theta-band of 3.5 Hz cannot be found by factor analysis.

Solutions of different low osmolar contrast media (CM) obviously show clinically relevant differences in the osmolality despite equal iodine concentrations and similar molecular structure. To obtain precise and comparable data, the osmolality of five batches (usually) each of contrast media, iopamidol, iohexol, iopromide, and ioxaglate-all preparations commercially available-were measured by means of the vapor pressure method. The osmolality of the solutions of sodium meglumine ioxaglate with the same iodine concentration is lower than that of the nonionic CM examined. Iopromide showed the lowest osmolality and iohexol the highest value of the nonionic preparations. The differences are statistically significant as a rule. They are attributed to a varying association and hydration of the CM molecules in the solution.

The effect of the following vasoactive substances, which are used in the treatment of peripheral arterial occlusive diseases, was investigated in a randomized study in 36 patients with normal and 52 patients with diabetic carbohydrate metabolism by intravenous infusion on the behaviour of blood sugar and serum insulin (IMI) during simultaneous oral glucose tolerance tests (100 g oligosaccharides). The substances used and the doses given were as follows: protein-free calf-blood extract (Actihaemyl, 0,5 ml per kg body weight), bencyclane (Fludilat, 200 mg), naftidrofuryl (Dusodril, 200 mg, pentoxifyllin (Trenal, 200 mg). The results obtained with the simultaneous treatment and oral glucose tolerance test were compared with a second OGTT carried out at an interval of 3-4 days under the same conditions but without administration of the substances (in a cross-over procedure) and the results of these experiments were compared with those obtained from an untreated control group. In subjects with a diabetic metabolic state, Actihaemyl led to a significant reduction of the blood sugar after oral glucose load (p less than 0,05) without producing any change in serum insulin. The same behaviour was exhibited by Fludilat for the total area integral and by Trental for the first 60 min after the oral glucose load. The change in the blood sugar behaviour was only significantly different from the untreated controls with Actihaemyl (p less than 0,05). In subjects with a normal metabolic state neither blood sugar nor serum insulin (IMI) were altered by any of the substances investigated.

Lormetazepam (1 mg) and diazepam (5 mg) were compared in a double-blind study of 100 patients with sleep disorders associated with a medical illness. Assignment to one of two treatment groups was at random. Lormetazepam had a greater hypnotic effect than diazepam in all significant variables (P less than 0.05). There was no hangover effect or other side effects with lormetazepam, which was thus superior to diazepam also in this respect (P less than 0.05).

The longtime application of oral contraceptives is assumed to elevate serum prolactin levels under non-stimulated conditions. We therefore examined whether oral contraceptives also will augment prolactin secretion after stimulation, e.g. by thyrotropin releasing hormone (TRH). After TRH stimulation the time sequence of secretion both of prolactin (HPRL) and thyroid stimulating hormone (TSH) was determined. Three groups of women were tested in a non-randomized study: group 1 without any hormonal medication (= controls), group 2 taking an oral contraceptives containing cyproterone acetate, group 3 using an oral contraceptive containing d-norgestrel. HPRL secretion was similar in all three groups, the same held true for TSH. A possible correlation between the secretion of HPRL and TSH was examined in the control group. No such correlation was found. The secretion patterns of both hormones also were different. In addition, the basic levels of both HPRL and TSH did not seem to influence the response after stimulation.

In a controlled double-blind trial 2X12 healthy male volunteers were tested during treatment with lithium sulphate (24--36 mval/d) or placebo. Volunteers were tested after one and two weeks' drug intake using the following tests: Quantitative pharmaco EEG, psychological performance and mood scales. In comparison to pacebo, lithium shows increased mistake duration of the pursuit rotor (MLS), decreased flicker fusion threshold and an impairment of mood. The EEG effects (decrease 7--9 cps, increase 20--50 cps) require further clarification.

The hypnotic action of a soporific may be of limited use in populations who live in contradiction to their "internal biological clock". In order to test the assumption 60 nurses who had a disturbance in their sleep-waking rhythm due to shift work participated in an one-week double blind study. Nurses were randomly assigned to receive either lormetazepam 1 mg (Noctamid) or placebo (n = 30 per group). In the nurses with disturbance of falling asleep, a normalization of the duration of falling asleep occurred in 15 of 17 cases under lormetazepam as compared to ten of 17 under placebo. In the nurses who slept too little the length of the sleeping time normalized in 15 of 16 cases under lormetazepam as compared to the nine of 16 under placebo. With simultaneous consideration of the duration of falling asleep, total duration of sleep and depth of sleep, a distinction was made between "normalization in all three parameters", "normalization in one or two parameters, but no deterioration in any parameter" and "no normalization" for evaluation of the therapy comparison. The action of lormetazepam was shown in higher improvement rates (p less than 0,05). Neurophysiological and social medical implications are being discussed.

The role of preoperative anxiety in perioperative adaptation is viewed in two different ways. Janis suggested that anxiety is a drive that evokes the cognitive work of worrying. Leventhal stresses the importance of coping behavior for adaptation, while anxiety may or may not accompany this coping process. Both theories have empirical support. The aim of this study was to determine whether both theories could show empirical support because the scientists chose different methods: Janis used interviews, Leventhal and Lazarus anxiety scales. The study analyzed the pre- and postoperative emotional reactions of surgical patients with three different methods of anxiety measurement: an anxiety scale, a fear thermometer, and a psychoanalytic interview (Gottschalk-Gleser content analysis method). The different methods were compared and related to the adaptation behavior (Table 3). The data showed a clear interaction between the selected methods and respective theories about the effects of preoperative anxiety on intra- and postoperative adaptation. The anxiety scales showed no correlation with adaptation behavior (blood pressure and heart rate during surgery; postoperative pain medication) and were not related to the anxiety scores obtained from the interview (content analysis). On the other hand, the interview anxiety measurements showed a clear relationship between separation anxiety (and also shame anxiety), physiological excitement during surgery (increase in heart rate), and postoperative medication (increased analgesics and tranquilizers). The patients who worried about the risks of surgery (Verletzungsangst, see Fig. 3) had very good perioperative adjustment, so that the quality of anxiety measured in the interview was very important for the prediction of adaptation.

Lormetazepam (Noctamid) at a dosage of 1 mg was compared with diazepam (Valium) at a dosage of 5 mg in a 7-day double-blind study. The study involved fifty patients in the lormetazepam group and fifty patients in the diazepam group. All the patients were suffering from sleep disorders as a concomitant symptom of general diseases. Lormatazepam was significantly better than diazepam in the: -Reduction of the time taken to fall asleep (p less than 0.05) -Prolongation of the duration of uninterrupted sleep (p less than 0.05) -Reduction of the frequency of awakening (p less than 0.05). Lormetazepam displayed no hang-over effects or other side-effects and, in this respect too, was significantly superior to diazepam (p less than 0.05).

Based on a sample of 953 subjects without known metabolic abnormalities and a sample of 186 diabetics a classification rule was developed by a quadratic discriminant analysis. The measurements of blood glucose 1 and 2 h after the oral administration of 100 g oligosaccharids are used to classify the patients into the categories of "healthy", "suspect" and "diabetic". The rates of false positive and false negative classification were estimated from a second sample of 128 non-diabetic and 73 diabetics. By administration of 100 g oligosaccharids these rates were found to be 3.1% and 0%, respectively. An analogous study for the administration of 100 g glucose was based on a different sample of N = 472, 99 diabetics included. Misclassification rates were found to be 1.6% and 2.7%, respectively. For practical application of the rules two-dimensional netplanes are given.

The purpose of this study was to determine the arousal effect of physostigmine after lormetazepam sedation on the human EEG. 12 male volunteers received 2 mg/kg bm lormetazepam and 30 minutes later physostigmine 2 mg preceded by atropine 1 mg. Generally an arousal effect of physostigmine could be clinically observed and more objectively demonstrated by reduced sleep stages in the vigilosomnogram (p less than 0.05). 2 volunteers did not fall asleep. 9 volunteers were awake 5-12 minutes after termination of physostigmine injection. 1 volunteer did not show any effect. Resedation and parasympathetic side effects did not occur. In earlier studies deep sleep stages after lormetazepam 1 or 2 mg/70 kg bm lasted 70 to 120 minutes. Physostigmine is recommended to counteract undesirable benzodiazepine induced sedation.

Lormetazepam (0.5, 1, 2, 4, 8 mg)--a new benzodiazepine--was tested versus Pentobarbital (100 mg) under double blind conditions on 240 preoperative inpatients for night-time sedative and side effects after acute oral intake. Results are based on p less than 0.05. Additionally p less than 0.125 in binomial-two-sample-tests was accepted. Lormetazepam shows dose dependent increase in hypnotic effects (e.g. reduction in sleep latency and number of awakenings, increase of total sleep duration), and side effects (e.g. dopiness, dizziness), but no relevant change in vital signs. About 0.5 mg of Lormetazepam are equivalent to 100 mg of Pentobarbital. 2 mg of Lormetazepam seem to be the optimum dose regarding the relation between hypnotic and side effects. In the view of anaesthesists Lormetazepam is preferable to Pentobarbital because of more favorable safety aspects.