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Biomedical subjects

J A Simpson

Publications and source records attributed to J A Simpson.

At least 73 records · Page 4Linked to original sources

Selected risk factors in adolescent suicide attempts.

This study examined stress, depression, attempted suicide, and knowledge of common signs of potential suicide in Alabama adolescents. A modified version of the National Adolescent Student Health Survey (NASHS) was administered to 3,803 eighth- and tenth-grade public school students during the fall of 1988. The incidence of stress, depression, and attempted suicide was analyzed by gender, ethnicity, locale (urban vs. rural), and participation in sexual intercourse and use of alcohol. Chi-square tests were used to determine if there were significant differences between groups. Findings indicated that females were at greater risk than were males. Both males and females who engaged in sexual intercourse and alcohol consumption were at greater risk than were abstainers. When analyzed by ethnicity, white adolescents who engaged in these behaviors were at significantly greater risk than were those who abstained; differences were not as pronounced for black youth. Comparisons on the knowledge scale indicated that females scored better than males, whites scored better than blacks, and urban students scored better than rural students. The data suggest that many adolescents are having difficulty coping with stress and depression, and that those who are engaging in various types of risk-taking behavior are at greater risk for depression and suicide.

Adolescent↗

Long-term double masked trial of early treatment with L-dopa plus bromocriptine versus L-dopa alone in Parkinson's disease. Interim results.

The quality and duration of control in two groups of parkinsonian patients under treatment with an L-dopa-based drug alone or L-dopa-based drug which has been partially substituted with bromocriptine are being compared over a 5-year period using a double-blind placebo-controlled study design. The aim is to establish whether early addition of bromocriptine will minimise late L-dopa complications. Results are presented after 1 year. Of 31 patients randomised, 13 were treated with combined L-dopa/bromocriptine and 14 with L-dopa/placebo. 4 patients were withdrawn for various reasons. In both groups any dose adjustments were aimed at maintaining the pre-entry clinical condition. In the group receiving bromocriptine combination therapy, progressive reduction of L-dopa was possible without deterioration of the patients' condition. In patients receiving L-dopa alone, the dose of L-dopa at 12 months was almost similar to that recorded on entry to the study. The total number of patients reporting adverse events in the L-dopa/bromocriptine combination and L-dopa alone groups were 8 and 7, respectively. At the present interim stage of the study it is not possible to compare the incidence of L-dopa long-term complications in either group.

Bromocriptine↗

Stimulatory and inhibitory actions of proteins and amino acids on copper-catalysed free radical generation in the bulk phase.

The effect of a variety of proteins and amino acids was investigated on oxygen free radical activity as assessed by copper/hydrogen peroxide induced benzoate hydroxylation as well as copper-catalysed ascorbate autoxidation. Serum albumins from a variety of species (human, bovine and dog) had both inhibitory and stimulatory effects depending on the molar copper to protein ratio; low ratios were inhibitory and high stimulatory. Some other proteins tested (lysozyme, soybean trypsin inhibitor and conalbumin) also had dual (inhibitory and stimulatory) effects, as did both histidine and polyhistidine, but all effects occurred at different molar ratios presumably dependent on the relative affinities for the copper ions. In contrast, metallothionein and caeruloplasmin, proteins specialised to bind copper in vivo had no stimulatory effects. In this paper we show that in addition to their fairly well documented inhibitory effects, under certain conditions some proteins also stimulate radical reactions. The possible role of this phenomenon in vivo is discussed.

Amino Acids↗

Scavenging by alginate of free radicals released by macrophages.

Failure to eradicate mucoid forms of P. aeruginosa has implicated bacterial alginate in a local evasion of host defence mechanisms within the lung of Cystic Fibrosis (CF) patients. We have found that purified bacterial alginate scavenges free radicals released by triggered macrophages as detected by lucigenin amplified chemiluminescence (CL) and reduction of cytochrome c. In agreement with this, alginate was also able to scavenge radicals generated by a chemical system (hydrogen peroxide and copper; detected by benzoate hydroxylation and chemiluminescence), and by an enzymatic system (hypoxanthine and xanthine oxidase; detected by chemiluminescence). All inhibitions were dose-related. Oxygen consumption by neutrophils (unlike that of macrophages) could be detected in a Clark electrode, and was not reduced by alginate, confirming that scavenging of radicals was responsible for the earlier observations. These data suggest that bacterial alginate by scavenging free radicals, may favour the survival of mucoid forms of P. aeruginosa, particularly in the CF lung.

Alginates↗

Exercise stress alters murine lymphocyte subset distribution in spleen, lymph nodes and thymus.

Our previous work indicated that exercise stress in mice was associated with reduced splenic lymphocyte proliferation to T cell mitogens. The purpose of this study was to determine the effect of acute exercise stress and exercise training on the phenotype distribution of murine lymphocytes in the spleen, lymph nodes and thymus. In mice given an exhaustive bout of treadmill exercise, the percentage of Thy 1.2 and Lyt2 antigen bearing cells decreased in the thymus, but the percentage of L3T4-positive cells did not change significantly. Acute exercise did not alter the percentage of Thy1.2, L3T4 or Lyt2-positive cells in the secondary lymphoid compartments (nodes, spleen). By contrast, in mice given a chronic exercise training programme (8 weeks duration; 30 m/min, 8 degrees slope, 30 min/session, 5 daily sessions/week) followed by a 72 h rest period, the percentage of L3T4-positive cells increased by 53% in the spleen, 19% in the lymph nodes and 29% in the thymus compared with sedentary controls; no parallel increase in the percentage of Thy1.2 antigen bearing cells was observed. These results suggest that the effect of exercise on the frequencies of lymphocyte subpopulations in murine lymphoid compartments is dependent upon the chronicity of the stress and probably on the accompanying physiological adaptations to the stress.

Animals↗

Free-radical generation by copper ions and hydrogen peroxide. Stimulation by Hepes buffer.

Hydroxyl radicals (OH.), generated by a phosphate-buffered Cu2+/H2O2 system, were detected by lucigenin-amplified chemiluminescence, deoxyribose degradation and benzoate hydroxylation. In each system the buffer, Hepes, was found to stimulate radical generation significantly. There are two main reasons for this effect: Hepes increases Cu2+ solubility in phosphate-buffered systems, and forms a complex with Cu2+ that is effective in generating OH. from H2O2. Pipes, a structurally similar buffer, and histidine, a known Cu2+ chelator, were found to have a similar effect. These data suggest that the crucial factor in such free-radical-generating systems is the availability of Cu2+, and that these actions of Hepes should be considered in the design of studies utilizing such systems.

Benzoates↗

Hydroperoxide-mediated fragmentation of proteins.

1. Chemiluminescence and benzoic acid hydroxylation were used to detect oxygen-centred free-radical production by 2.5 mM-H2O2 and 100 microM-Cu2+. Free radicals could not be detected by these methods when H2O2 was replaced with 10 mM-t-butyl hydroperoxide (TBH) or 10 mM-cumene hydroperoxide (CH). The inclusion of the thiol compound dithioerythritol (DTET; 100 microM) increased radical production by H2O2 and Cu2+ as judged by both assays. Mannitol scavenged radicals in the chemiluminescence system in a dose-dependent manner. 2. H2O2, TBH and CH, each with Cu2+, gave rise to substantial fragmentation of the protein bovine serum albumin (BSA). This fragmentation could be increased by the inclusion of DTET. Omission of Cu2+ or the addition of the chelator DETAPAC (diethylenetriaminepenta-acetic acid; 1 mM) lead to virtual abolition of fragmentation. Autoxidized lipid in the presence of Cu2+ caused protein fragmentation by reactions of lipid hydroperoxides. 3. Polyacrylamide-gel electrophoresis in the presence of SDS confirmed that production of fragments had occurred. 4. Susceptibility of BSA to enzymic hydrolysis by two different proteinases acting at pH 5 and pH 7.2 was increased after a limited exposure to hydroperoxides in the presence of Cu2+. 5. These results may have biological significance, particularly for proteins in lipid environments (e.g. membrane proteins and lipoproteins).

Benzoates↗

Abetalipoproteinaemia in adults: role of vitamin therapy.

The retinal and neurological complications of abetalipoproteinaemia may be preventable by replacing vitamins A and E from an early age, but their role in adult presentations is less clear. Two adult females with abetalipoproteinaemia have received 8 and 10 years respectively of replacement therapy with vitamins A, E and linoleic acid. In Case 1, visual function improved objectively on commencing therapy but has subsequently deteriorated and her neuropathy has slowly progressed. The rate of progression of neurological impairment in Case 2 was slowed but not halted by therapy, and her severe visual disturbance was unaffected. Replacement by fat soluble vitamins has only a limited role in the management of abetalipoproteinaemia once irreversible neurological/retinal damage has occurred.

Abetalipoproteinemia↗

Alginate inhibition of the uptake of Pseudomonas aeruginosa by macrophages.

Pseudomonas aeruginosa alginate was purified and characterized in terms of uronic acid, carbohydrate and protein content, as well as by infra-red spectroscopy and gel electrophoresis. Added exogenous bacterial alginate inhibited the uptake and degradation of both viable and non-viable radiolabelled non-mucoid P. aeruginosa by resident mouse peritoneal macrophages. Alginic acid (from seaweed) inhibited the same parameters to almost the same degree. Bacterial alginate also inhibited the uptake of fluorescent-labelled zymosan and latex particles. Starch, at equivalent viscosity to the alginate, inhibited the uptake and degradation of radiolabelled nonviable P. aeruginosa to a greater extent, but Dextran T500 had no effect. This suggests that the viscous nature of alginate exerts a non-specific inhibitory effect on the uptake and subsequent degradation of phagocytosible particles.

Alginates↗

An improved method for rapid measurement of accommodation and firing frequency of single motor units in man.

A stimulator is described producing trapezoid wave forms with accurately defined linear rise and fall at pre-determined slopes independent of the maximum current which is limited at the threshold for a motor unit recorded by discriminative electrodes. The stimulation threshold, measured in rheobase units, is directly proportional to the latency of response and is more accurately measured by sweep expansion (by computer). Thresholds to linearly rising currents of pre-selected slopes are rapidly measured and plotted on a grid calibrated to allow immediate measurement of the time-constant of accommodation.

Electric Stimulation↗

Fasciculation and focal loss of nerve accommodation in peripheral neuropathies.

Fasciculation of muscle and repetitive response of single motor units to brief electric stimuli in diffuse demyelinative and focal (compression) neuropathies are associated with localised loss of accommodation of motor nerve fibres. The pathogenesis of spontaneous and triggered repetitive firing of neurones is discussed and it is proposed that the discrete sites of abnormally low accommodation may be in regenerating (sprouting) neurones. An improved rapid method for measuring single fibre accommodation may be used to identify regenerating neurones.

Alcoholism↗

Local sites of low accommodation of peripheral motor axons and the pathogenesis of fasciculation in amyotrophic lateral sclerosis.

There is no generalized disturbance of accommodation of peripheral motor axons in amyotrophic lateral sclerosis. Local sites of reduced accommodation are found proximally and distally with apparent correlation to spontaneous fasciculation. The possible mechanism of fasciculation provoked by acetylcholine is discussed and it is suggested that the local sites of low accommodation represent nodal sprouts with growth cones in extra-muscular as well as intra-muscular parts of peripheral motor axons.

Amyotrophic Lateral Sclerosis↗

Readiness potential of cortical area 6 preceding self paced movement in Parkinson's disease.

The vertex Readiness Potential (RP) (Bereitschaftspotential) preceding self paced voluntary movements is reduced in duration and amplitude in patients with Parkinsonism. It cannot be used as an index for delayed initiation of movement. The negative potential is commonly replaced by a positive slow wave. In hemi-Parkinsonism, the abnormal RP is more apparent on moving the affected limb. The abnormal RP is related to the severity but not to the duration of Parkinsonism. Short-term fluctuations of akinesia and rigidity, spontaneous or caused by levodopa are associated with changes of RP duration and amplitude. The abnormality does not correlate with reaction or movement times. It is suggested that the Readiness Potential is a diffuse response of area 6 cortex (especially Supplementary Motor Area) evoked by pallido-thalamo-cortical afferents under dopaminergic control. It is not obligatory for pre-programming of voluntary movement. The authors postulate a dendritic potential of basket cells associated with a pallidal activated gate control of postural set.

Adult↗

Treatment of myasthenia gravis: an audit.

Although treatment of myasthenia gravis with anticholinesterase drugs and thymectomy was based on wrong models of pathogenesis the resulting saving of life has not been improved by immunosuppressive treatment based on a current autoimmune model. Immunosuppression with steroids or azathioprine may reduce morbidity but as these drugs can rarely be withdrawn without causing relapse, the long-term hazards are serious, including increased mortality.

Autoimmune Diseases↗

Aggressive thyroid cancer in low-risk age population.

Seventy-eight patients under the age of 40 (low-risk patients) who had undergone surgical treatment for well-differentiated thyroid carcinoma were referred from 1979 to 1986 to our hospital for adjuvant therapy. A subgroup of 37 patients, 14 with apparent aggressive cancer, was studied. This study group consisted of 27 female and 10 male patients with mixed papillary and follicular cancer, who ranged in age from 11 to 40 years. Nodal disease occurred in 27 (73%) patients and invasiveness in 30 (81%) patients and involved multiple areas in 9 (24%) patients. Recurrence occurred in 14 (38%) patients and visceral metastases occurred in eight (22%) patients. All patients underwent appropriate surgery, but microscopic residual disease was seen in 15 patients and gross residual disease in seven patients, so that 31 patients underwent iodine-131 therapy, and 17 of these patients also underwent external radiation therapy. Three patients died of their disease, whereas 24 (65%) patients are free of disease and 9 (24%) patients are alive with disease. An additional 7 (19%) patients were initially seen in the fifth to seventh decade after decades of neglected thyroid disease, which culminated in residual cancer and death. Although low-risk categorization for thyroid cancer appears valid, its rigid application in support of conservative treatment may lead to inadequate primary treatment and underdiagnosis of cancer in thyroid nodule disease in the low-risk age population.

Adenocarcinoma↗

Beta-lactamase-producing isolates of Neisseria gonorrhoeae in Cape Town.

Isolates of Neisseria gonorrhoeae from patients attending the sexually transmitted disease clinics of the Cape Town Municipal Health Department were examined for beta-lactamase (penicillinase) production by a chromogenic cephalosporin test. Of the 208 isolates, 4 (less than 2%) produced beta-lactamase. When grown on chocolate blood agar plates 3 isolates showed no inhibition of growth around a penicillin disc; the 4th had a markedly reduced zone of inhibition. The minimum inhibitory concentrations of penicillin for these 4 strains were from 1 to 4 micrograms/ml.

Gonorrhea↗

High-dose radiation and the emergence of thyroid nodular disease.

High-dose radiation (in excess of 2500 rads or centiGray) to the head and neck area is reputedly infrequently associated with the emergence of thyroid nodular disease. Thirty-three patients who underwent high-dose radiation and who developed thyroid nodular disease have been described. Radiation was originally administered for hyperthyroidism in 11 patients, postmastectomy in five, oral cancer in three, Hodgkin's disease in three, facial hirsutism in three, hemangioma in three, cancer of the larynx in one, skin cancer in one, desmoid tumor of the neck in one, Ewing's tumor in one, and pituitary tumor in one. Treatment included radioiodine in 11, external radiation in 21, interstitial radiation in one, and combined radiation in one. Associated head and neck neoplasms included four parathyroid tumors, one osteogenic sarcoma of the maxilla, two basal cell cancers of the facial skin, and one parotid gland carcinoma. The study group consisted of five men and 26 women varying in age from 22 to 75 years, with a duration of latency of effect varying from 1.5 to 50 years. Thyroid disease consisted of 21 cancers, six adenomas, four colloid goiters, and two cases of thyroiditis resulting in four deaths caused by cancer, for a 20% mortality rate. Consideration of radiation beam behavior showed that isodose curve, penumbra effect, back scatter, and special field resulted in the thyroid gland receiving a low dose, namely under 2500 rads. Clinical factors such as an overlooked goiter, coincidental carcinoma, error in presumption of dose, and second primary malignancy were also considerations. True biologic radiation oncogenesis may have been seen in our radioiodine-treated group with hyperthyroidism as well as the group with Hodgkin's disease who underwent mantle irradiation. It is apparent that for whatever reason and by whatever means and by whatever mechanism, high-dose radiation to the head and neck area can result in significant thyroid disease, and patients undergoing such radiation should be followed with this in mind and considered for thyroid feeding on a prophylactic basis.

Adenocarcinoma↗