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J Leonard

Publications and source records attributed to J Leonard.

156 records · Page 9Linked to original sources
PubMed1970

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Educational Measurement↗
PubMedDate not supplied

Association of demyelination with deficiency of cerebrospinal-fluid S-adenosylmethionine in inborn errors of methyl-transfer pathway.

Long-term deficiency of cobalamin or folate causes a demyelinating disease of the brain and spinal cord. A reduced supply of methyl groups has been implicated as its cause. To examine the mechanisms of demyelination in human beings, we have studied three children with sequential inborn errors of the methyl-transfer pathway. One child had abnormal methylfolate metabolism, one abnormal methylcobalamin metabolism, and one hypermethioninaemia probably caused by methionine adenosyltransferase deficiency. Magnetic resonance imaging of the brain and measurement of cerebrospinal-fluid concentrations of 5-methyltetrahydrofolate, methionine, and S-adenosylmethionine were carried out before and after 6-12 months of appropriate treatment. Each patient had abnormal myelination before treatment; the scans suggested demyelination. The only consistent biochemical abnormality in the cerebrospinal fluid was a low concentration of S-adenosylmethionine. Treatment led to substantial clinical improvement, apparent remyelination, and increases in cerebrospinal-fluid S-adenosylmethionine concentration into the normal range. Cerebrospinal-fluid concentrations of S-adenosylmethionine and methionine were significantly lower in eight other children with errors of the methyl-transfer pathway than in an age-matched reference population (mean [95% confidence interval] standard deviation score -1.81 [0.57], p less than 0.001 for S-adenosyl methionine and -1.82 [0.19], p less than 0.001 for methionine). The concentrations of these metabolites increased to within the reference range on treatment. We have shown that demyelination is associated with cerebrospinal-fluid S-adenosylmethionine deficiency and that restoration of S-adenosylmethionine is associated with remyelination.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMedDate not supplied

When does metoclopramide facilitate transpyloric intubation?

Postpyloric feeding probably reduces the incidence of tracheobronchial aspiration and improves feeding tolerance. However, duodenal intubation is often unsuccessful in critically ill patients due to gastric atony. Metoclopramide improves gastric emptying. In a pilot study, 12 adult patients were administered 10 to 20 mg of intravenous metoclopramide after weighted nasal feeding tubes had failed to spontaneously pass distal to the pylorus. In no patient did metoclopramide induce transpyloric passage of the tube. A randomized prospective study involving 10 adult patients was conducted to examine the effect of preinsertion intravenous metoclopramide on transpyloric intubation. All patients had failed to achieve spontaneous duodenal intubation. Five patients received 20 mg of metoclopramide 10 min prior to nasal insertion of a weighed feeding tube. Five control patients received no premedication. Four metoclopramide patients achieved duodenal intubation immediately. In none of the control patients did transpyloric intubation occur (p = 0.048). Metoclopramide, administered after nasogastric intubation, is ineffective in promoting transpyloric advancement of feeding tubes. There is a significant increase in transpyloric intubation when metoclopramide is administered prior to tube insertion.

Adult↗
PubMedDate not supplied

Somatosensory evoked potential peak latencies and amplitudes in contralateral and ipsilateral hemispheres in normal and severely traumatized brain-injured subjects.

The purpose of this study was to compare in normal and traumatic brain injury (TBI) subjects long latency cortical brain-evoked potential patterns obtained upon stimulation of the median nerves. Quantitative data were analysed involving nine peak latencies and eight amplitudes obtained simultaneously contralaterally and ipsilaterally. Left-right hemispheric differences were also analysed. The following was found: TBI latencies were significantly longer for five of nine peaks (N30, P40, N60, P185, P285). TBI amplitudes were significantly smaller for two of eight amplitudes (P185-N240 and N240-P285). A significant contralateral-ipsilateral latency difference occurred only at P40 where latencies in the contralateral hemisphere are shorter for both normals and TBIs. Significant contralateral-ipsilateral amplitude differences occurred in the four early amplitudes (N30-P40, P40-N60, N60-P105, P105-N140) with amplitudes being smaller on the ipsilateral side. A differential effect, however, was found for amplitudes N30-P40 and P40-N60 where the difference is significantly larger in the contralateral hemisphere for normals but not for TBIs. This suggests that contralateral-ipsilateral amplitude difference can be a marker of extent and severity of injury and may also be helpful in localizing site of injury, particularly interhemispheric or corpus callosal injury. The differential latency and amplitude responses for later peaks occurring in the P300 region suggest sensitivity to detecting impairments in pre-cognitive and early cognitive activities.

Adult↗
PubMedDate not supplied

The surgical management of nontraumatic ectopic lenses.

We report the results of limbal lensectomy for ectopia lentis in 50 eyes of 30 children over a period of 7 years. The reasons for surgery were poor visual acuity in 47 eyes and dislocation of the lens into the anterior chamber in three. Best-corrected visual acuity improved in all except two patients, both of whom had glaucoma: in one (with an unusual syndrome), a vitreous hemorrhage occurred that resulted in light-perception-only vision; in the other, a persistent uveitis developed that eventually required secondary vitrectomy. Visual acuity was unchanged in two patients. Peaked pupil occurred in seven. We conclude that, unless there are associated ocular diseases, limbal lensectomy in childhood ectopia lentis effectively improves visual acuity with few complications.

Child↗
PubMedDate not supplied

Ursolic acid-induced changes in tumor growth, O2 consumption, and tumor interstitial fluid pressure.

The anti-tumor effect of ursolic acid (UA) and UA-induced changes in tumor physiology in tumor-bearing mice were examined. MTT colorimetric assay, clonogenic assay, and growth-delay assay for the determination of tumoricidal effects of UA were evaluated. UA-induced apoptosis was measured by fluorescent microscopy, stained by propidium iodide. Oxygen consumption (QO2) after treatment with UA was measured using a Clark-type electrode chamber. Systemic toxicity in mice was assayed by LD50(30). We also measured UA-induced changes in several tumor physiological parameters. Inhibitory effect of UA on various tumor cell lines was observed using MTT and clonogenic assays in vitro. UA-induced apoptosis significantly increased in a dose-dependent manner. Cellular QO2 values were significantly reduced by UA. In animal studies, UA significantly reduced tumor interstitial fluid pressure (TIFP) to approximately 40% of the control values at 2-3 days post-treatment (P<0.05). An i.p. administration of 100 mg/kg of UA significantly (P<0.01) inhibited tumor growth of FSaII. In conclusion, UA showed anti-tumor effect on various tumor cells in vitro as well as a moderate retardation of growth in two tumor models in vivo. We gained some insight regarding the pathophysiological benefits of UA (i.e., reduction in TIFP) as a cancer therapeutic agent. Consequently, these observations can be used for further study of UA or to facilitate clinical applications of UA for treating cancer patients.

Animals↗
PubMedDate not supplied

Betahistine dihydrochloride treatment facilitates vestibular compensation in the cat.

Unilateral lesion of the vestibular system induces posturo-locomotor deficits that are compensated for with time. Drug therapy is currently used to improve the recovery process and to facilitate vestibular compensation. Betahistine dihydrochloride is an histamine-like substance that has been employed in vestibular pathology; it was found effective in many forms of vertigo and in vestibular-related syndromes. Investigations performed in animal models have shown betahistine-induced neuronal modulations in the vestibular nuclei complex and interactions with the H1 and H3 histamine receptors. Potentially, this substance is therefore capable to interfere with some recovery mechanisms and to improve the behavioral adaptations. But there is at present a total lack of data concerning the influence of betahistine treatment on vestibular compensation in animal models. The aim of this study was to understand the pharmacological activity of betahistine in the restoration of posture and locomotor balance functions in unilateral vestibular neurectomized cats. Posture recovery was assessed by quantifying the surface reaction of the cat's support as measured while standing erect on its four legs, at rest. Locomotor balance recovery was determined using the rotating beam test, by measuring the maximal performance (max. P.) of the cat and its locomotion speed regulation during the postoperative time period. We have compared the recovery profile and time course of these static (posture) and dynamic (equilibrium) functions in three groups of cats. Two experimental groups were treated at daily doses of 50 mg/kg and 100 mg/kg, respectively. Betahistine dihydrochloride was given orally until complete recovery of posturolocomotor functions. One untreated control group served as the reference. Results showed that postoperative treatment strongly accelerated the recovery process in both treated groups, inducing a time benefit of around 2 weeks as compared to the controls. Maximum performance of the cats on the rotating beam as well as locomotion speed regulation were highly correlated to the postoperative development of the cat's support surface, indicating that compensation of the static vestibulospinal deficits conditioned the subsequent locomotor balance recovery. These behavioral data showed that betahistine dihydrochloride constitutes a useful drug therapy for the symptomatic treatment of central vestibular disorders in our animal model of unilateral vestibular lesion. Improvement of vestibular compensation under betahistine postoperative treatment, as evidenced here for the posture and locomotor balance functions, is discussed both in terms of aspecific effect (histamine-induced increase of the level of vigilance) or more direct action in the vestibular nuclei (histamine-induced rebalance of neuronal activity on both sides).

Administration, Oral↗