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Biomedical subjects

J Donaldson

Publications and source records attributed to J Donaldson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes.

Duodenal Ulcer↗
PubMed1984

Increased cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in Kleine-Levin syndrome.

A 17-year-old man with the Kleine-Levin syndrome died unexpectedly of cardiopulmonary arrest during a period of autonomic instability that followed an episode of megaphagia. At autopsy, the only pertinent finding was mild depigmentation of the locus ceruleus and substantia nigra. Premortem CSF levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were elevated. These findings indicate that many symptoms of the Kleine-Levin syndrome are a result of a neurotransmitter imbalance in the serotonergic pathway of the brainstem.

Adolescent↗
PubMed1984

The effects of manganese on the cholinergic receptor in vivo and in vitro may be mediated through modulation of free radicals.

Incubation of rat brain tissue in the presence of catecholamine autoxidation products catalysed by manganese led to a dose-dependent decrease in high-affinity binding of 3H-QNB. Such effects may be due to receptor destruction or inactivation through membrane damage mediated by free radicals or cytotoxic quinones arising from the powerful in vitro effects in catalysing dopamine autoxidation. In contrast, administration of manganese to neonatal rats for fourteen days resulted in an increase in 3H-QNB binding in the striatum but not in other brain regions. Inhibition of lipid peroxidation by manganese treatment was also most pronounced in the striatum. Thus, manganese can display remarkable dichotomy in acting both as pro-oxidant or powerful antioxidant. The prevailing state may be dictated under pathological conditions by the redox status of a particular region of brain as well as by the amount of manganese deposited there. Under physiological conditions endogenous manganese may subserve a neuromodulatory role in specific neural areas related to control of redox bioenergetics.

Animals↗
PubMed1983

Prooxidant properties of vanadate in vitro on catecholamines and on lipid peroxidation by mouse and rat tissues.

Vanadate (Na3VO4) in micromolar concentrations enhanced the in vitro formation of adrenochrome from epinephrine, and of aminochrome from dopamine. Lipid peroxides in various tissues of the mouse and rat, particularly brain, were increased. Products of both catecholamine oxidation and lipid peroxidation may be the basis of the cardiotoxic and neurotoxic effects of vanadium.

Adrenochrome↗
PubMed1982

Manganese neurotoxicity: a model for free radical mediated neurodegeneration?

In man, manganese neurointoxication is characterised in the early phase by behavior reminiscent of that observed in schizophrenia. During chronic manganese intoxication the neuropsychiatric symptoms manifested earlier disappear and are followed by a permanent neurological phase typified by extrapyramidal symptoms similar to those of Parkinson's disease. Study of manganese intoxication in animals may provide important clues towards elucidation of the biochemical defect underlying neuropsychiatric as well as extrapyramidal disease. Investigations in our laboratory suggest that neurotoxicity of manganese is an exaggeration of function in normal neuronal homeostasis. Manganese neurointoxication in neonatal rats resulted in significant depression of lipid peroxidation in several rat brain regions examined. In the striatum, lipid peroxidative activity was abolished, an effect which may be related to alteration in neurotransmitters often observed in the striatum of manganese treated rats. The chronic, extrapyramidal stage of manganism, may ensue when excess Mn2+ is oxidised to higher valency forms where it can potentiate the autoxidation of catecholamines, like dopamine, resulting in concomitant formation of free radicals and cytotoxic quinones. This latter effect may arise preferentially in the substantia nigra, where neuromelanin is formed nonenzymatically by autoxidation of dopamine.

Animals↗
PubMed1982

Treatment of persistent eustachian tube dysfunction in children with aerosolized nasal dexamethasone phosphate versus placebo.

Forty-five children aged two to 10 years with persistent eustachian tube dysfunction received a three-week course of aerosolized nasal dexamethasone phosphate or placebo. Patients were randomly assigned to the drug or placebo group and received one spray in each nostril three times a day for three weeks. Middle ear pressure and gradient were assessed with tympanometry. Tympanic membrane mobility, position and presence of middle ear fluid were assessed by the investigators initially and at weekly intervals during the study. Fasting morning plasma cortisol levels were obtained prior to starting the study and at its conclusion. The dexamethasone-treated group showed a significant increase in patients with normal middle ear pressure compared to placebo after one week and a significant increase in the number of patients with normal middle ear gradient at the second week. By the conclusion of the study there were no significant differences between the groups. Within the dexamethasone group, however, there were statistically significant increases in patients achieving normal middle ear pressure, tympanic membrane mobility and position in one or both ears. Plasma cortisol levels fluctuated widely from one determination to another and did not show an over-all declining trend for the dexamethasone group. However, two dexamethasone patients had a transient fall in cortisol level to below the normal range. These results support some therapeutic efficacy for nasal aerosolized dexamethasone but also point out the therapeutic value of time alone. The observation that most improvement occurred in the first two weeks and that some worrisome cortisol changes occurred suggests that dexamethasone therapy should be limited to two weeks and be undertaken with caution.

Administration, Intranasal↗
PubMed1981

Energy requirements of antarctic sledge dogs.

1. Eighteen male sledge dogs were weighed immediately on removal from their sheltered winter quarters at Halley Bay, Antarctica (75 degrees 31' s, 26 degrees 42' W) and weekly thereafter for 14 weeks. The first 2 weeks they were tethered and inactive and the following 12 weeks travelled an average of 10.9 km/d fully laden. Daily energy intake during winter and while tethered averaged 18-25 MJ/d and while travelling 13.9 MJ/d. 2. Mean weight loss during the 2 weeks of inactivity was 2.3 kg despite an energy intake almost twice the recommended requirement. During the 12 weeks travelling energy intake decreased to 13.9 MJ/d but the weight loss stopped. Weather conditions at this time were becoming progressively milder. 3. The evidence suggests that sledge dogs are capable of high levels of cold-induced and possibly diet-induced thermogenesis and that these factors, particularly the former should be taken into account when designing dog rations and feeding schedules.

Animals↗
PubMed1981

Enhanced autoxidation of dopamine as a possible basis of manganese neurotoxicity.

Autoxidation of dopamine as measured by its aminochrome formation at 480 nm was considerably potentiated by Mn++ in comparison to other biologically-important divalent cations such as Cu++, Zn++, Ni++, Ca++ and Mg++. Effectiveness of autoxidation by metal ions tested was closely related to their redox potential. Manganese-enhanced autoxidation of dopamine was associated with increased generation of the free radicals O2-, H2O2, and HO as suggested by the inhibitory effects of superoxide dismutase, catalase and ethanol. Manganese, by enhancing the oxidation of dopamine, may augment considerably the production of neurotoxins emanating from this process and, under in vivo conditions, could be expected to contribute significantly to the neurodegenerative changes that accompany manganese dyskinesia in man.

Animals↗
PubMed1979

Lymphocyte adherence in multiple sclerosis.

It has been reported that peripheral blood lymphocytes from patients with multiple sclerosis (MS) adhere to measles-infected human epithelial cells in significantly greater numbers than do lymphocytes from healthy volunteers or patients with other neurologic diseases. We have confirmed this observation in three separate studies, and have investigated the relationship of lymphocyte adherence to the clinical state. Lymphocyte adherence determination values correlated with the degree of certainty of the clinical diagnosis of MS, and lymphocyte adherence values in individual patients increased during clinical exacerbations. Judicious use of this test may facilitate the diagnosis of MS.

Epithelium↗
PubMed1978

Enhancement by hyperthermia of the effect of BCNU against the EMT6 mouse tumor.

The combination of moderate hyperthermia (43 degrees C water bath for 1 hour) and BCNU against the EMT6 mouse tumor has been studied. The effect was found to be much greater than could have been predicted from the effects of the single modalities and this is true whether the endpoint is tumor cure, growth delay, or in vitro assay of clonogenic fraction. The results indicate that inhibition of "recovery from potentially lethal drug damage" is not the mechanism by which heating potentiates the action of BCNU.

Animals↗