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Biomedical subjects

M Gillespie

Publications and source records attributed to M Gillespie.

At least 37 records · Page 2Linked to original sources
PubMed1992

Failure of buspirone and verapamil to improve spasmodic torticollis.

The effects of buspirone and verapamil on spasmodic torticollis were investigated in two double-blind, placebo-controlled crossover studies. Buspirone was given in doses of 20-100 mg/day for 4 weeks to 14 patients; verapamil was given in doses of 40-100 mg/day for 3 weeks to 8 patients. Neither drug improved symptoms of the movement disorder (posture, motility, rigidity, tremor), pain, perceived stress, or mood, either in the whole group or in any individual patient.

Adult↗
PubMed1991

Bilirubin as an antioxidant: effect on group B streptococci-induced pulmonary hypertension in infant piglets.

Bilirubin scavenges toxic oxygen radicals in vitro, but it is not known whether this potential salutary effect can be extended to the intact animal. Accordingly, the present experiments tested the hypothesis that bilirubin protects against oxygen radical-dependent pulmonary hypertension and arterial hypoxemia in piglets infected with group B streptococci (GBS). Piglets ranging in age and weight from 7 to 14 days and 1.5 to 2.0 kg, respectively, were infused for 60 min with 108 cfu GBS/kg/min. One group of 7 animals was pretreated with a bolus infusion of 15 mg/kg of bilirubin followed by a continuous bilirubin infusion. A second group of 7 animals was given the vehicle. While plasma bilirubin levels in control animals were negligible, administration of exogenous bilirubin was associated with plasma levels of 13.0 +/- 0.74 mg%. Piglets treated with exogenous bilirubin exhibited GBS-induced increases in pulmonary arterial pressure and decreases in PaO2 of 16.1 +/- 2.0 and 46.5 +/- 4.3 torr, respectively. In control animals, GBS increased pulmonary arterial pressure and decreased PaO2 by 17.5 +/- 1.6 and 47.9 +/- 3.2 torr, respectively. Neither the peak changes in pulmonary arterial pressure or PaO2 nor the time courses of these alterations differed between treatment groups. These observations indicate that bilirubin fails to prevent GBS-induced pulmonary hypertension and arterial hypoxemia in infant piglets and suggests that in this particular model bilirubin does not exhibit appreciable oxygen radical scavenging activity.

Animals↗
PubMed1990

Schizosaccharomyces U6 genes have a sequence within their introns that matches the B box consensus of tRNA internal promoters.

The gene for the U6 small nuclear RNA (snRNA) in the fission yeast Schizosaccharomyces pombe is interrupted by an intron whose structure is similar to those found in messenger RNA precursors (pre-mRNAs) (1). This is the only known example of a split snRNA gene from any organism--animal, plant, or yeast. To address the uniqueness of the S. pombe U6 gene, we have investigated the structures of the U6 genes from five Schizosaccharomyces strains and three other fungi. A fragment of the U6 coding sequence was amplified from the genomic DNA of each strain by the polymerase chain reaction (PCR). The sizes of the PCR products indicated that all of the fission yeast strains possess intron-containing U6 genes; whereas, the U6 genes from the other fungi appeared to be uninterrupted. The sequences of the Schizosaccharomyces U6 gene fragments revealed that each had an intron of approximately 50 base pairs in precisely the same position. In addition to the splice sites and putative branch point regions, a sequence immediately upstream of the branch point consensus was found to be conserved in all of the Schizosaccharomyces U6 genes. This sequence matches the consensus for the B box of eukaryotic tRNA promoters. These results raise the interesting possibility that synthesis of U6 RNA in fission yeast might involve the use of internal promoter elements similar to those found in other genes transcribed by RNA polymerase III.

Base Composition↗
PubMed1989

Physostigmine treatment of progressive supranuclear palsy.

Cognitive and extrapyramidal effects of cholinomimetic therapy were evaluated in 8 patients with progressive supranuclear palsy. Each was randomized to a 10-day double-blind crossover trial of physostigmine and placebo. Physostigmine treatment was associated with marginal and inconsistent changes in long-term memory, suggesting that cholinergic therapy alone is insufficient to restore cognitive function. Motor scores remained unchanged.

Aged↗
PubMed1986

Audit of the Medical Audit Committee.

We reviewed 39 medical audits started in one institution between 1981 and 1985 to determine whether they monitored the quality of health care in a scientific manner, whether recommendations were made that could improve the quality of health care and, if so, whether the recommendations were acted on. Thirty-three audits (85%) were completed; 21 (64%) failed to state their objectives, 30 (91%) failed to compare their results with those in the literature, 9 (27%) made no recommendations that could improve the quality of health care, and 9 were poorly researched and written. The number of patients in each audit was usually adequate. Feedback was rarely received by the Medical Audit Committee concerning the Medical Advisory Committee's response to the audit. Information concerning the implementation of recommendations was available for 17 of the 24 audits that made recommendations; 7 (41%) had failed to implement half or more of the recommendations. Despite these problems, 8 (24%) of the audits were considered to be of a quality that could improve health care. We present recommendations to improve the audit procedure and foster the growing confidence among doctors in the medical audit.

Canada↗
PubMed1986

Muscarinic agonist therapy of Alzheimer's disease. A clinical trial of RS-86.

Cholinergic projections to the cerebral cortex from certain basal forebrain nuclei degenerate in Alzheimer's disease. Nevertheless, attempts to alleviate this disorder through the administration of drugs that increase the availability of acetylcholine to postsynaptic receptor sites have generally yielded disappointing results. In an attempt to evaluate the therapeutic efficacy of cholinomimetics that act independently of the presynaptic cholinergic terminals, a double-blind, placebo-controlled trial of the muscarinic agonist RS-86 (2-ethyl-8 methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) was undertaken. Eight patients with Alzheimer's disease with mild to moderately advanced dementia received RS-86 orally at maximum individually tolerated dose levels for eight days. Although some verbal and visuospatial tests showed slight alterations, no consistent overall change in cognitive performance could be discerned. These results lend further support to the view that short-term administration of cholinomimetic monotherapies may fail in the symptomatic treatment of Alzheimer's dementia.

Aged↗
PubMed1986

GABA-agonist therapy for Alzheimer's disease.

Evidence suggesting a reduction of cerebral gamma-aminobutyric acid (GABA) neurons in Alzheimer's disease has been reported. To evaluate the possible contribution of GABA system dysfunction to the intellectual decline associated with this disorder, a controlled therapeutic trial of a potent and specific GABA agonist, THIP [4,5,6,7-tetrahydroisoxazolo(5,4,-c)pyridin-3-ol], was undertaken. Six Alzheimer patients with mild to moderately severe dementia and low spinal-fluid GABA levels received THIP at maximum individually tolerated dosage. No significant change in cognitive function could be discerned, despite attainment of dose levels that produced centrally mediated adverse effects similar to those of other GABA agonists. The results support the views that pharmacologic attempts to stimulate central GABA-mediated synaptic function may not confer therapeutic benefit to patients with Alzheimer's disease and that a GABA system deficit may not serve as a critical determinant of the dementia that characterizes this disorder.

Alzheimer Disease↗
PubMed1986

Buspirone, Parkinson's disease, and the locus ceruleus.

Buspirone is a novel anxiolytic whose pharmacological profile differs from that of the benzodiazepines and includes dopaminergic agonist effects. Because of these properties, buspirone's usefulness in the management of idiopathic Parkinson's disease was evaluated in a controlled study of 16 outpatients with stage I-IV disease. At doses of 10 to 60 mg/day, no significant group or individual effects could be discerned on standardized disability, dyskinesia, anxiety, or depression scales. At high dose levels (100 mg/day) however, there was a significant worsening of disability ratings and a decrease in dyskinesia scores; anxiety ratings were also significantly increased. The results indicate that buspirone is well tolerated by parkinsonian patients at conventional antianxiety doses of 10 to 40 mg. Clinical effects of high dose treatment, on the other hand, resemble those associated with a reduction in central dopamine mediated synaptic function. Since buspirone reportedly produces dose-dependent stimulation of norepinephrine containing neurons in the locus ceruleus and behavioral symptoms of such activation were observed, these clinical observations support the concept that central noradrenergic stimulation can adversely affect parkinsonian symptoms.

Anti-Anxiety Agents↗
PubMed1986

Structural and functional studies of Gilles de la Tourette syndrome.

Preliminary studies with PET-scanner and nuclear magnetic resonnance have shown no abnormalities in Gilles de la Tourette syndrome. Estimation of homovanillic acid, the main metabolic of dopamine, in the cerebrospinal fluid of patients with Gilles de la Tourette disease suggests that brain dopaminergic receptors are hypersensitive. Such an hypersensitivity of dopamine receptors is in agreement with the clinical improvement of patients treated with neuroleptic drugs. The study with PET-scanner presented here suggests the existence of a neuronal hypofunction in some striatal and corticolimbic area in patients.

Adult↗
PubMed1978

Twin study of multiple sclerosis: an epidemiologic inquiry.

The National Research Council Twin Registry comprises 16,000 pairs of white male twins, both members of which had been in military service, mainly in World War II. All their available military and Veterans Administration records and their responses to a 1965 to 1970 NRC questionnaire have been coded as to disease. Upon review we found 16 cases of multiple sclerosis (MS) among 15 pairs of twins, for an age-specific prevalence rate of 51 per 100,000 veterans aged 43 to 53--about half the expected frequency. Of the 15 sets, three sets refused cooperation and three were unavailable for study. Nine sets were examined and interviewed together with the mother. One of five monozygotic twin pairs was concordant for MS and in another the co-twin of an MS case had had a solitary episode of retrobulbar neuritis; all others were discordant. There were more definable environmental events (as noted below) among the affected twins than among the unaffected co-twins. The greatest excess was within the 20 years before onset. Summing events across the four 5-year periods before onset, among the 10 MS versus the eight not-MS individuals, there were 5:1 instances of trauma, 8:2 or operation, 7:1 of ether anesthesia, 7:1 of allergy, 10:5 of infection, and 9:0 of animal exposure. Summing these same events within each 5-year period, the MS:control ratios were 9:1, 10:2, 12:3, and 15:4, respectively, for 0 to 4, 5 to 9, 10 to 14, and 15 to 19 years before onset.

Adolescent↗
PubMedDate not supplied

A case of paraquat poisoning and subsequent fatality presenting to an emergency department.

Paraquat (1,1'-dimethyl-4,4'-dipyridylium) is an herbicide associated with both accidental and intentional ingestion, leading to severe and often fatal toxicity. Prognosis is largely dependent on the amount of paraquat absorbed. Rapid identification of the symptoms of paraquat toxicity (burns or ulceration at the site of ingestion or injection, acute respiratory distress, and renal failure) can facilitate early treatment intervention to limit absorption. We report a case of a 71-year-old man with a suicidal ingestion of paraquat 2 days prior to presentation. Serum paraquat levels, time elapsed since ingestion, and clinical symptoms all indicated poor prognosis. The patient developed severe respiratory distress and progressive renal failure, and died 6 days after admission to the hospital.

Aged↗
PubMedDate not supplied

Continuous transdermal dopaminergic stimulation in advanced Parkinson's disease.

The objective of the study was to determine the safety and efficacy of increasing doses of Rotigotine CDS in patients with advanced Parkinson's disease. The development of motor complications in Parkinson's disease has been linked to intermittent stimulation of dopamine receptors. Continuous, noninvasive, dopaminergic stimulation has not been available to date. Rotigotine CDS is a lipid-soluble D2 dopamine agonist in a transdermal delivery system that could fill this void. This inpatient study consisted of a 2-week dose escalation phase followed by a 2-week dose maintenance phase at the highest dose (80 cm2). Each individual's L-Dopa dose was back-titrated as feasible. The primary outcome measure was L-Dopa dose, and secondary outcome measures included early morning "off"-L-Dopa Unified Parkinson's Disease Rating Scale motor scores by a blinded evaluator and motor fluctuation data obtained from patient diaries ("on" without dyskinesia, "on" with dyskinesia, and "off"). Seven of 10 subjects provided data that could be evaluated. There were two administrative dropouts, and one individual was eliminated from the study because of recrudescence of hallucinations. The median daily L-Dopa dose decreased from 1,400 to 400 mg (p = 0.018, Wilcoxon test). Unified Parkinson's Disease Rating Scale motor scores were unchanged. Although diary variables improved in most individuals, only the reduction in "off" time attained statistical significance. Adverse effects were mild and consisted mainly of dopaminergic side effects and local skin reactions. The data suggest that Rotigotine CDS is an effective treatment for advanced Parkinson's disease and permits patients to substantially lower L-Dopa doses without loss of antiparkinsonian efficacy. Full-scale controlled clinical trials are warranted. In addition to potential therapeutic benefits, this drug can be used to test the hypothesis that continuous dopaminergic stimulation from the initiation of Parkinson's disease therapy will limit the development of motor complications.

Administration, Cutaneous↗