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Biomedical subjects

M Kramer

Publications and source records attributed to M Kramer.

At least 127 records · Page 7Linked to original sources

A dose response study of the hypnotic effectiveness of alprazolam and diazepam in normal subjects.

One group of eight normal young males was administered three doses of alprazolam (0.25, 0.5 and 1.0 mg) and placebo, while a second group of eight normal young males was given three doses of diazepam (2, 5, and 10 mg) and placebo in the same design. All subjects slept in the sleep laboratory for 10 nights, 2 consecutive nights each week for 5 consecutive weeks. The first 2 nights served as adaptation. During the next 4 weeks subjects received a random dose of alprazolam (or placebo) or a random dose of diazepam (or placebo) each week. Similar dose-related benzodiazepine effects were found on sleep with both medications. Alprazolam reduced percent stage 4 and REM sleep and increased stage 2 sleep and latency to REM. Diazepam decreased percent stage 1 and increased percent stage 2 sleep. No drug by dose interactions were found. It was concluded that, while both drugs had similar effects on sleep, alprazolam showed significant effects on REM sleep parameters and might be evaluated for possible antidepressant effect.

Adolescent

Gastroesophageal reflux in infants: relation to apnea.

The temporal relationship between apnea and gastroesophageal reflux was examined in 14 infants with abnormal GER scores and histories of prolonged apnea. Simultaneous polysomnographic and intraesophageal pH recordings were performed for each infant. GER episodes were compared to control segments of the recording (without GER) for frequency and type of apnea. Apnea was equally likely to occur during the control segments as during the GER episodes. Brief obstructive apneic episodes were more common during the onset of GER episodes than the onset of control segments. GER duration appeared prolonged during sleep. GER and apnea were not temporally related in the majority of instances, and may be two manifestations of a more general developmental delay.

Apnea

Dose-related effects of phenobarbitone on human sleep-waking patterns.

1 Twenty-four healthy male subjects had two consecutive drug nights at 2-week intervals using placebo and 80, 140 and 240 mg doses of phenobarbitone in a double-blind cross-over design. 2 Phenobarbitone produced significant dose-related decreases in sleep latency and number of awakenings, along with increased total sleep time. 3 Both subjective and objective measures of sleep indicated the presence of cumulative (first v second night) effects of phenobarbitone, especially decreases in the number of awakenings and in delta waveform activity. 4 Measures of REM sleep were highly sensitive to phenobarbitone. The high dose decreased REM density to 30% of baseline on the first night and to 18% on the second night. 5 EEG alpha activity was decreased, beta activity was increased and sigma spindle activity was unaffected by phenobarbitone during sleep. 6 Subjects experienced some impairment of cognitive performance along with residual sedation the following morning.

Adult

The interaction of age, performance and hypnotics in the sleep of insomniacs.

Scant attention has been paid to the objective evaluation of insomnia as a function of age, particularly with reference to increased drug sensitivity and resulting loss in balance performance. Therefore, the electroencephalographic sleep and the balance-board performance of 10 young and 12 geriatric insomniacs were studied under baseline and hypnotic drug (ketazolam) conditions. In terms of objectively measured sleep, the geriatric insomniacs had worse sleep on every dimension except sleep latency and percentage of stage-2 sleep. These differences between aged and young insomniacs, however, were no greater than might be expected as a function of normal aging. Drug-age interactions indicated that ketazolam differentially increased sleep efficiency, decreased the percentage of REM sleep, and eliminated any learning improvement on the balance board in geriatric versus young insomniacs. The findings indicate that the geriatric subjects were more sensitive to the hypnotic drug, in that their sleep improved to a greater extent. However, an important loss in balance performance was also observed.

Adult

The acute effect of quazepam on the sleep of chronic insomniacs. A dose-response study.

The present study investigated the effects of the benzodiazepine, 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1,4-benzodiazeepine-2-thione (quazepam), on hypnotic efficacy and sleep staging in chronic insomniacs. We evaluated the acute withdrawal effects of several doses (0, 7.5, 30 and 45 mg) of quazepam. The effects of the different doses were assessed using both objective (polysomnographic) and subjective sleep parameters in a double blind repeated measures design (n = 15). The results indicated that daily administration of quazepam over three nights produced increased effects on sleep which suggested drug accumulation. Lower doses (7.5 and 15 mg) only had significant effects on sleep (sleep induction and maintenance and sleep architecture) with three days of administration, while 45 mg of quazepam produced significant effects on the first night of drug administration. Contrary to previous research investigating longer periods of administration, acute administration of low doses of quazepam did not produce carryover effects on withdrawal, while higher doses did. The accumulation of the parent compound or its active metabolites thus seemed to mediate these effects on sleep in a dose related fashion.

Adolescent

[Haemodynamic effect of naloxone during electrostimulation analgesia with special reference to the role of endorphin (author's transl)].

10 persons undergoing cardiac surgery in electro-stimulation analgesia (ESA) with controlled ventilation were given 5 microgram/kg bodyweight and 10 microgram/kg body-weight respectively of naloxone during the operation and the effects of the drug on the circulation were registered over a period of 10 minutes. The observations do not support the view that endorphin plays a part in ESA. Other possible modes of action are discussed.

Dose-Response Relationship, Drug

Guanosine polyphosphate production of Escherichia coli stringent and relaxed strains in the stationary phase of growth.

Stringent and relaxed Escherichia coli strains grown on minimal and on differently enriched media produced guanosine polyphosphates in the stationary phase of growth. On transition from the logarithmic to the stationary phase, stringent strains started to produce guanosine 5' triphosphate 3' diphosphate (pppGpp). and guanosine 5' diphosphate 3' diphosphate (ppGpp), while relaxes strains accumulated only ppGpp. When the stringent strain was cultivated on media enriched with Casamino Acids the leve of pppGpp decreased, while with yeast extract an almost twofold increase could be observed. The concentration of ppGpp increased with both nutrients as compared to that measured in minimal medium. Readdition of glucose to the stationary phase culture did not result in the slightest decrease of the nucleoside polyphosphate levels. In contrast, addition of a mixture of 20 L-amino acids or Casamino Acids or yeast extract to the medium caused an abrupt decrease in the guanosine polyphosphate levels. Qualitatively similar results were obtained with the relaxed strains except that the amounts of ppGpp were smaller than in the case of the stringent counterpart and the responses to the resupplementation were slower. Some possible mechanisms regarding the occurrence of guanosine polyphosphates in the stationary phase are discussed.

Culture Media

[Cardiac and vascular effects of midazolam during induction of anesthesia prior to and during extracorporeal circulation in coronary-surgical patients (author's transl)].

8-Chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) is a new benzodiazepine which, when compared with its predecessors diazepam (Valium) and flunitrazepam (Rohypnol), has several outstanding advantages: We conducted hemodynamic investigations with 0.15 mg/kg b.w. midazolam in a total of 28 coronary patients divided into 3 groups. The new water-soluble benzodiazepine is at the dose given useful in the induction of and as an adjuvant to anesthesia because of its hemodynamic effect.

Anesthetics

The effects of flurazepam, lorazepam, and triazolam on sleep and memory.

This study evaluated the effects of flurazepam 30 mg, lorazepam 4 mg, triazolam 0.5 mg, and placebo upon sleep and memory in eleven normal male subjects continuously monitored for nighttime EEG, EOG, and EMG recording. Subjects received each drug or placebo for two consecutive nights per week for 4 weeks in a repeated measures, double-blind, Latin Square design. Three hours post-administration, subjects were awakened and presented with a series of tasks. Recall was assessed immediately following task presentation and after the final morning awakening. The results showed that every drug significantly decreased stage 1, increased stage 2, and produced no change in stage 3--4 sleep in comparison to placebo. Only lorazepam significantly decreased REM percent. Post-drug recall was significantly decreased in comparison to placebo at night and was further decreased in the morning. Morning recall was significantly poorer when the return to sleep was 2.5 min or less than when the return to sleep was greater than 5 min following the nighttime awakening in all drug conditions. These results indicate that 1. failure of memory consolidation rather than failure of retrieval is the most likely explanation for the morning memory loss and 2. hypnotic drug properties, measured by latency to fall back asleep, affect memory consolidation.

Adult

The lifetime prevalence of mental disorders: estimation, uses and limitations.

The age-specific lifetime prevalence rate of a disease is the proportion of persons surviving to a given age who have experienced the disease at any time during their lives. This measure of morbidity has been used to report findings in many of the epidemiological surveys of mental disorders of the last 30 years. This paper presents a life-table method for estimating age-specific lifetime prevalence rates from incidence and mortality data. The method is applied to Monroe County, New York, case register data on the incidence of schizophrenia. Using this method, we estimate that at least 3% of the White population surviving to age 55 have experienced an episode of schizophrenia at some time during their lives. The difficulties of producing valid estimates of lifetime prevalence and the difficulties in interpreting differences reported in such rates make this morbidity measure of secondary importance to incidence and point-prevalence data.

Actuarial Analysis

Chronic toxicity of pyrazolones: the problem of nitrosation.

1 During 6-month oral toxicity studies of dipyrone in rats and dogs, there was an increase in the number of reticulocytes and Heinz bodies at the highest dose, and a slight haemosiderosis was induced. 2 Similar results were obtained after parenteral administration (intravenously and subcutaneously). 3 These studies fail to contribute to the knowledge of the mechanism of allergic reactions in man. 4 In vitro studies in conditions imitating the physiological environment, show to what extent nitrosation of dipyrone takes place. 5 Subsequent toxicological investigations with the two reaction compounds, or the nitrosation product itself, are powerful instruments to show whether the nitrosamine or nitrosamide formed is dangerous. 6 In the case of pyrazolones, only aminopyrine forms a carcinogenic nitrosamine.

Animals

The efficacy of triazolam and chloral hydrate in geriatric insomniacs.

A double-blind crossover study was performed to evaluate the efficacy of hypnotics in geriatric insomniacs. Twenty-seven patients with a mean age of 70 years (range 60-94 years) received each of five treatments on 5 consecutive nights. The treatment conditions, consisting of chloral hydrate 250 and 500 mg, triazolam 0.25 and 0.50 mg, and placebo, were administered using a Latin Square design. Subjective estimates of sleep were collected in the morning following each treatment night. The patients' global evaluation of effectiveness indicated that triazolam 0.25 mg and 0.50 mg improved sleep more than placebo, while chloral hydrate 250 and 500 mg were not better than placebo. Triazolam 0.50 mg was felt to be significantly better than either dose of chloral hydrate. In addition, triazolam 0.50 mg was found to significantly decrease the patients' estimates of their sleep latency. Patients estimated their total sleep time to be longer following the use of triazolam 0.25 mg as compared to choral hydrate 500 mg, and their estimates of the number of awakenings was significantly lower on triazolam 0.50 mg than it was on chloral hydrate 500 mg or placebo.

Aged