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Biomedical subjects

M H Lader

Publications and source records attributed to M H Lader.

At least 55 records · Page 3Linked to original sources
PubMed1981

Comparative effects of diazepam and buspirone on subjective feelings, psychological tests and the EEG.

12 normal subjects were tested on a battery of tests both before and 1, 3 and 5 h after 10 mg diazepam, 10 and 20 mg buspirone hydrochloride and a placebo. The test included self-ratings of mood and bodily symptoms, the electroencephalogram, reaction time, tapping, digit symbol substitution and the symbol copying test. Diazepam showed a clear profile of action, producing EEG changes, pronounced sedation and psychological impairment. Buspirone had less effect on the EEG and produced less cognitive impairment. Its sedative effects were similar to those of diazepam but it also produced some dysphoria in the higher dose.

Acoustic Stimulation↗
PubMed1981

Benzodiazepine derivatives--side effects and dangers.

The benzodiazepines are generally safe and effective drugs with usually only minor side effects, dose-related sedation being the most common. A range of paradoxical effects can occur of which release of aggressive and hostile feelings has excited most attention. These responses are idiosyncratic however, as most patients report decrease of such feelings while taking benzodiazepines. Dependence on benzodiazepines with escalation of dosage and/or social abuse is uncommon set against their widespread use. Recently though, evidence has accumulated that patients on normal doses for prolonged periods can commonly experience withdrawal symptoms, often unpleasant and even severe. These drugs should be reserved for patients suffering from defined clinical anxiety syndromes and not used indiscriminately in patients with normal stress responses.

Aggression↗
PubMed1980

Diazepam and N-desmethyldiazepam concentrations in saliva, plasma and CSF.

1 Salivary and plasma diazepam and nordiazepam concentrations were measured in 51 paired samples from four experimental situations. In seven of the patients CSF samples were estimated. 2 Correlation of 0.89 (P less than 0.001) was observed between salivary and plasma diazepam and 0.81 (P less than 0.001) between salivary and plasma nordiazepam. 3 Mean salivary diazepam was 1.6% (+/- 0.3%) of the plasma diazepam. It was found to vary markedly in an acute dosage study. Mean salivary nordiazepam was 2.9% (+/- 1%) of the plasma measure and was dependent on salivary flow rate. 4 CSF diazepam was in equilibrium with unbound plasma diazepam and salivary diazepam. 5 Mean protein binding of diazepam in vitro was 99.3% with no variations as a function of concentration. 6 The results suggest salivary diazepam and nordiazepam measures to be of value in epidemiological studies. However, they do not predict accurately the plasma total or unbound drug concentration from a salivary sample in an individual.

Adult↗
PubMed1980

High and very high dosage antipsychotics: a critical review.

Since antipsychotic drugs were introduced over 25 years ago, controversy has continued concerning the relative effectivness of standard and high dosage. Uncontrolled studies suggested that some psychotic patients responded to high but not to low drug dosage. Extrapyramidal effects seemed the same as with standard dosage. Our review of 14 controlled trials suggests some superiority of the high dosage over standard antipsychotic drug dosage but that extrapyramidal effects are more common. It is concluded that a minority of pychotic patients may benefit from high doses of neuroleptic medication, pharmacokinetic factors possibly being important.

Animals↗
PubMed1979

Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients.

A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression.

Adult↗
PubMed1979

Bodily reactions to people and events in schizophrenics.

Schizophrenic patients were tested on psychophysiologic measures within their homes and in the laboratory. Sweat gland activity and heart rate changes when patients encounter novel situations such as life events, together with the home atmosphere generated by a critical or overinvolved relative, confirmed objectively the importance of previous social measures of these factors in determining relapse. Drug effects were also found to be modified by these social factors. Environmental and socially induced changes found in the home were undetectable in the laboratory situation.

Antipsychotic Agents↗
PubMed1979

The effect of temporal lobe surgery on electrodermal activity: implications for an organic hypothesis in the aetiology of schizophrenia.

It has recently been suggested that the bilateral asymmetry of electrodermal activity (EDA) reported in schizophrenia may be related to unilateral temporal lobe dysfunction. To test this hypothesis, 3 aspects of EDA--skin conductance level (SCL), number of spontaneous fluctuations (SF), and skin conductance response (SCR)--were measured bilaterally in 10 patients who had undergone unilateral temporal lobectomy. No differences could be detected between the operated and non-operated sides within the patient group, nor between the patient and control groups. The implications of these findings are discussed.

Adult↗
PubMed1979

Tryptophan disposition in psychiatric patients before and after stress.

Non-esterified fatty acid and total and free tryptophan were determined in the plasma of psychiatric patients unselected with respect to psychiatric diagnosis and in the plasma of normal subjects before and after physiological and psychiatric tests. Retarded patients had significantly low total and free tryptophan values which correlated negatively with agitation. Total tryptophan fell significantly after testing in the non-retarded subjects. The only biochemical abnormality significantly associated with a diagnosis of primary depression was the rise of plasma non-esterified fatty acid after testing. Thus, tryptophan abnormalities were associated more with psychiatric rating scores than with diagnoses.

Adult↗
PubMed1979

Salivary secretion in the affective disorders and schizophrenia.

Salivary secretion was measured in 54 psychiatric patients comprising four diagnostic groups: schizophrenia, mania, depression and anxiety state. Detailed psychometric assessment was carried out at the time of measurement. Although salivary flow failed to show an association with either diagnostic category or mental state at the time of examination, it was positively correlated with a subjective rating of appetite. The implications of these findings are discussed.

Adult↗
PubMed1978

Acute and chronic effects of lithium chloride on physiological and psychological measures in normals.

In the acute experiment six healthy volunteers were given orally two doses of lithium chloride, 16 and 32 mmol, and placebo sodium chloride 32 mmol in a double-blind standardized procedure, with a 1-week interval between treatments. Compared to sodium, lithium produced a decrease in subjective well-being, decrease of skin conductance fluctuations, and increase in plasma calcium concentrations. Dose-related effects were maximal at the first hour after ingestion, decreasing or disappearing at 3--5 h. Most effects did not correlate with plasma or erythrocyte lithium concentrations, but drug effects and feelings of nausea were highly correlated. Accordingly, most acute effects seemed due to peripheral drug effects. In the chronic experiment six healthy volunteers were given orally 16 mmol of lithium chloride or sodium chloride (placebo) twice a day for 1 week in a double-blind standardized procedure with a 2-week interval between treatment weeks. Compared to placebo, lithium produced feelings of subjective impairment, an increase in EEG slow waves and of auditory evoked response variability, a deficit in long-term memory, and an increase in plasma magnesium concentrations. Most lithium effects did not correlate with plasma or erythrocyte lithium concentrations.

Adult↗
PubMed1978

The EEG's of chronic schizophrenic patients in hospital and in the community.

EEG's were recorded from chronic schizophrenic inpatients, remitted patients living in the community and normal controls, during resting and auditory stimulation conditions. Chronic impatients had more energy in the slower and fastest wave bands than either remitted patients or normal controls. No differences were found in overall EEG energy and variability between groups of subjects or between sides of the head. It was concluded that any abnormalities were associated with behavioural differences and not with schizophrenic process changes.

Adult↗
PubMed1978

The clinical pharmacology of oxazepam.

The benzodiazepines have been available now for about 15 years but new aspects of their actions are being elucidated all the time. Oxazepam has a short half-life and inactive metabolites and therefore differs from most other benzodiazepines. Some aspects of its clinical pharmacology are reviewed in outline. Firstly, the effects of the drug on psychological functioning is discussed. Next, the controversy regarding benzodiazepines and aggression is examined. Oxazepam appears exceptional here in that it is not associated with paradoxical release of aggression in patients. Finally, the ethical implications of the widespread use of these drugs is commented on, and the problem of dependence, physical and psychological, discussed. It appears that oxazepam is less likely than other benzodiazepines to induce dependence.

Aggression↗
PubMed1978

Electrodermal and heart-rate measurements in chronic and partially remitted schizophrenic patients.

Electrodermal activity and heart-rate were recorded in the laboratory from partially remitted schizophrenic patients living in the community, chronic schizophrenic inpatients and normal controls. Althoug all patients had faster heart-rates, no consistent electrodermal differences between patient groups and normals were evident, nor was there a bimodal distribution of responding within the patient group. Laboratory recordings did not reflect differences in community patients tested in their homes and associated with environmental and social factors. This emphasized the limitations of laboratory testing in investigating a disorder such as schizophrenia whose course may be markedly influenced by environmental and social factors.

Galvanic Skin Response↗
PubMed1977

Is nicotine important to tobacco smoking?

Tobacco smoking is generally regarded as a form of nicotine dependence, but the evidence for this is slender. Two experiments are described here which examine the hypothesis that habitual smokers need nicotine and that they regulate their intakes of this drug. A laboratory test for smoking was devised which permitted the continuous monitoring of puffing as well as of selected physiologic variables; the procedure was also designed to reduce the influence of smoking habits and rituals. In the first experiment, inhaled amounts of tobacco smoke reduced subsequent ad libitum smoking in a dose-related way. In the second experiment comparable doses of nicotine were given intravenously to the same subjects, but they failed to affect ongoing smoking. However, both the inhaled and intravenous doses of the drug produced very similar physiologic effects. These experiments do not, therefore, support the nicotine-dependence hypothesis; thus the ways, if any, in which this drug sustains the tobacco-smoking habit merit further examination.

Adult↗
PubMed1977

Effects of adrenaline injection on human plasma tryptophan and non-esterified fatty acids.

1. Subcutaneous injection of adrenaline into normal male volunteer subjects caused large increases of plasma non-esterified fatty acids and free tryptophan, but plasma total tryptophan fell considerably. Therefore increases of the percentage of plasma tryptophan in the free state were more marked than absolute increases of free tryptophan. 2. Plasma tyrosine fell slightly and plasma phenylalanine and cortisol were unaffected. 3. It is suggested that catecholamine release could lead to abnormalities of tryptophan disposition in stress and psychiatric illness.

Epinephrine↗
PubMed1977

Plasma concentrations of benzodiazepines.

1. Twenty anxious patients were treated with medazepam, diazepam, chlordiazepoxide, amylobarbitone and placebo, each given in flexible dosage for 2-4 weeks. 2. At the end of each treatment, a series of clinical, physiological and behavioural variables were measured and plasma samples were taken for estimation of the appropriate drug and metabolite concentrations. 3. Nordiazepam was shown to be an important metabolite of both medazepam and diazepam: the ratio of medazepam to noradiazepam was 0.14 and the ratio of diazepam to nordiazepam following diazepam administration was 0.72. 4. No significant correlations were found between the plasma concentrations of any of the treatments and the clinical ratings or behavioural measures. 5. Some relationship was shown between levels of medazepam and its physiological effects.

Amobarbital↗
PubMed1976

The effects of adrenaline injections on human platelet monoamine oxidase and related measures.

A double-blind, placebo-controlled, cross-over study in ten normal volunteers assessed the effects of the subcutaneous administration of adrenaline on platelet MAO activity, in an attempt to replicate previous findings of increased MAO activity following adrenaline. Platelet counts, cortisol plasma concentrations, and uptake of metaraminol by the platelets were also determined to elucidate possible mechanisms of action. Blood pressure and heart rate were used as indices of the concentration of adrenaline effectively in circulation. MAO activity towards benzylamine was significantly increased by adrenaline. Non-significant increases were noted in the deamination of tyramine and tryptamine, in platelet counts, cortisol concentrations and metaraminol uptake. Increases in MAO activity were also noted early in the experimental sessions suggesting that other experimental variables such as venepuncture may affect platelet MAO activity. Possible mechanisms for this adrenaline effect are discussed and it is suggested that variables such as "arousal" and "stress" must be taken into account when interpreting clinical data on platelet MAO.

Adult↗