Biomedical subjects
Publications and source records attributed to S Lal.
A one year old male child presented with a perianal growth of two months' duration. Clinical and histopathological findings confirmed the diagnosis of condylomata acuminata, which regressed completely following topical treatment with podophyllin.
Nedocromil sodium (FPL 59002) is a pyranoquinoline dicarboxylic acid that has been developed for the management of bronchial asthma. We report the results of a double blind group comparative trial in which the disodium salt of nedocromil delivered by pressurised aerosol and a placebo were compared in the management of patients with a diagnosis of bronchial asthma who entered the double blind period on a minimum dose of beclomethasone dipropionate. In almost all the assessments of clinical activity nedocromil sodium was shown to be more effective than placebo. These include improvements in diary card symptom scores, reduction in concomitant use of a bronchodilator aerosol, and patients' and investigators' assessments of efficacy. Unwanted effects were few and mild. No patients were withdrawn from the trial.
Melatonin was given orally to patients undergoing diagnostic pneumoencephalography and various compounds were measured in the lumbar and cisternal CSF. Melatonin markedly increased plasma and CSF melatonin concentrations. The plasma: CSF melatonin ratios were similar in patients who received, and in those who did not receive, melatonin. This supports the idea that melatonin is released from pineal to blood and gets into the CSF via the blood. Melatonin did not affect CSF 5-hydroxyindoleacetic acid, which indicates that it has no effect on 5-hydroxytryptamine metabolism. Melatonin increased CSF indoleacetic acid significantly, indicating increased metabolism of tryptamine. Melatonin did not affect CSF cAMP levels, but increased cGMP levels. The effect on indoleacetic acid and cGMP was seen in both lumbar and cisternal CSF, suggesting that melatonin can have generalized actions throughout the CNS.
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Buspirone produces a dose-dependent but short-lived elevation in striatal dopamine (DA) metabolites in the rat. In vitro, buspirone possesses an affinity similar to sulpiride for DA receptors (3H-spiperone). A moderate affinity for alpha 1 receptors was also observed while buspirone was inactive at alpha 2, beta, muscarinic and serotonin2 receptors. This pharmacological profile as well as previous behavioral data indicate that buspirone may be a potential "atypical" neuroleptic.
Assessment of neurochemical markers in the frontal cortex indicates that choline acetyltransferase is significantly decreased in Alzheimer's and Gerstmann-Straussler dementias but not in Pick's dementia. It therefore appears that the cholinergic innervation of the cortex from the basal forebrain is intact in Pick's disease. Cortical somatostatin was decreased only in Alzheimer's disease (AD), indicating that loss of somatostatin is not a constant feature in different forms of dementia. Muscarinic binding sites were unaltered in Pick's disease and Gerstmann-Straussler syndrome but were decreased in a subpopulation of AD patients. These data suggest that in some cases of AD a significant loss of cholinoceptive neurones in the cortex is evident.
CCK-33 (225 Ivy Dog Units iv) antagonized the growth hormone response to the dopamine receptor agonist, apomorphine HCl (0.5 mg sc), and increased basal prolactin secretion in normal male volunteers. A stress mediated prolactin effect could not be excluded. CCK-8 (5 ug iv) antagonized the growth hormone response to apomorphine but had no effect on basal prolactin or plasma homovanillic acid. Ceruletide (0.3 ug/kg im) had no effect on basal prolactin or apomorphine-induced growth hormone secretion. CCK-33, CCK-8 and ceruletide had no effect on basal growth hormone secretion which suggests that they do not inhibit the release of growth hormone. These findings are compatible with an inhibitory effect of CCK-33 and CCK-8 (or fragments) on dopaminergic function in man, at least in the hypothalamic-pituitary axis and point to a simple way to study the effect of peptides on dopaminergic function in man including those which may not cross the blood brain barrier.
Choline acetyltransferase activity was decreased in the frontal cortex in Alzheimer's and Gerstmann-Straussler dementias but not in Pick's disease. Cortical somatostatin was only decreased in Alzheimer's dementia. Postsynaptic muscarinic binding sites appeared to be decreased in a subpopulation of Alzheimer's patients. Our data indicate that a loss of cholinergic innervation of the cortex is not common to all dementias.
The classical neuroleptics haloperidol, perphenazine and chlorpromazine increase both dopamine metabolism and release in the mouse striatum. The atypical agents clozapine and thioridazine increase dopamine metabolism with no increase in release. At high doses, sulpiride increases both dopamine metabolism and release. These data suggest that atypical neuroleptics act to inhibit dopamine release and indicate that sulpiride may not be an atypical agent.
Pituitary function studies were performed in two patients with pseudocyesis, one of whom was reinvestigated during a recurrent episode. There was an exaggerated prolactin response to thyrotropin-releasing hormone, an aberrant growth hormone increase, and an impaired growth hormone response to dopamine receptor agonists (apomorphine or bromocriptine). These findings point to a derangement in hypothalamic-pituitary function in pseudocyesis and may indicate an underlying impairment in dopaminergic function in this disorder.
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Mice infected with Mycobacterium bovis, BCG, were shown to be highly susceptible to subsequent challenge with Pseudomonas aeruginosa. The susceptibility was characterized by the enhanced mortality and shortened survival after challenge with P. aeruginosa. BCG-treated mice did not show any enhanced susceptibility to challenge with Gram-positive bacteria such as Staphylococcus aureus or Listeria monocytogenes. BCG-treated mice eliminated P. aeruginosa from their organs in a pattern similar to that in untreated mice. There was no significant difference in the bactericidal activities of polymorphonuclear cells and macrophages between BCG-treated and untreated mice. An equal amount of endotoxin was detected by the Limulus lysate assay in the blood of both BCG-treated and untreated mice after challenge with P. aeruginosa. The enhanced susceptibility induced by BCG pretreatment could be decreased when the mice were rendered LPS-tolerant by injections of small amounts of LPS. These results suggest that BCG-induced susceptibility to P. aeruginosa can be ascribed to an enhanced susceptibility to the lethal effect of LPS produced by challenge bacteria, and not to the impairment of the ability to eliminate infected bacteria.
The effect of clonidine (0.075 mg given intravenously) on subjectively experienced menopausal flushes, skin temperature and luteinizing hormone (LH) secretion was investigated in eight women in a double-blind, saline-controlled cross over study. Subjects were monitored over a 5-hour period. The number and magnitude of temperature peaks (increment greater than 1 degree C) was unaffected by clonidine. Clonidine significantly decreased the number of subjectively experienced flushes as well as the intensity of the flushes. Clonidine had no effect on the number of LH secretory pulses or on total LH secretion. These results indicate that the therapeutic effect of clonidine is independent of factors responsible for episodic skin temperature changes or factors regulating LH secretion.
Clonidine (0.15 mg intravenously), an alpha-adrenergic receptor agonist, was administered to 13 male chronic schizophrenics, who had been withdrawn from chronic neuroleptic therapy, and to 18 normal male controls. There was no significant difference in growth hormone (GH) response between the two groups. There was no significant correlation between duration of psychosis, duration of neuroleptic therapy or length of neuroleptic withdrawal and GH response. These results suggest that postsynaptic alpha-adrenergic receptor function in the hypothalamic-pituitary axis is unaltered in chronic schizophrenia or by prior chronic neuroleptic therapy.
Concordance is reported of Gilles de la Tourette syndrome in a male twin pair in whom phenotyping revealed a >98·7% probability that they were monozygotic. The development and extent of the illness differed markedly in the two subjects. Our findings are compatible with the view that there is a genetic form of Gilles de la Tourette syndrome.
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