Biomedical subjects

M L Thompson

Publications and source records attributed to M L Thompson.

At least 19 recordsLinked to original sources

PubMed1995

Repeatability and validity of a field kit for estimation of cholinesterase in whole blood.

OBJECTIVES: To evaluate a spectrophotometric field kit (Test-Mate-OP) for repeatability and validity in comparison with reference laboratory methods and to model its anticipated sensitivity and specificity based on these findings. METHODS: 76 farm workers between the age of 20 and 55, of whom 30 were pesticide applicators exposed to a range of organophosphates in the preceding 10 days, had blood taken for plasma cholinesterase (PCE) and erythrocyte cholinesterase (ECE) measurement by field kit or laboratory methods. Paired blinded duplicate samples were taken from subgroups in the sample to assess repeatability of laboratory and field kit methods. Field kits were also used to test venous blood in one subgroup. The variance obtained for the field kit tests was then applied to two hypothetical scenarios that used published action guidelines to model the kit's sensitivity and specificity. RESULTS: Repeatability for PCE was much poorer and for ECE slightly poorer than that of laboratory measures. A substantial upward bias for field kit ECE relative to laboratory measurements was found. Sensitivity of the kit to a 40% drop in PCE was 67%, whereas that for ECE was 89%. Specificity of the kit with no change in mean of the population was 100% for ECE and 91% for PCE. CONCLUSION: Field kit ECE estimation seems to be sufficiently repeatable for surveillance activities, whereas PCE does not. Repeatability of both tests seems to be too low for use in epidemiological dose-response investigations. Further research is indicated to characterise the upward bias in ECE estimation on the kit.

Adult↗

PubMed1994

Effect of chronic DDC treatment on LHRH and substance P amidation processes in the rat.

We examined the effects of chronic diethyldithiocarbamate (DDC) treatment on the concentrations of methionine-enkephalin, mature and unamidated forms (-Gly) of luteinizing hormone releasing hormone (LHRH) and substance P (SP) in various regions of the central nervous system (CNS). Chronic DDC treatment resulted in elevations of LHRH-Gly like immunoreactivity in the preoptic area (POA) and the medial basal hypothalamus (MBH), as well as elevations in SP-Gly like immunoreactivity in all areas of the CNS examined. Castration altered the ratios of SP-G-like/SP-like immunoreactivity in the pons, and LHRH-Gly like immunoreactivity in the MBH. Met-enkephalin concentrations were significantly elevated in the pons and medulla of intact DDC-treated animals, and in the POA of both intact- and castrated DDC-treated animals. Results demonstrate that it is possible to detect basal levels of unamidated LHRH and SP in many areas of the CNS, with ratios of unamidated/amidated peptides representing a unique and sensitive method for determining altered posttranslational processing of these transmitters, especially under altered endocrine states such as castration. Pharmacological blockade of terminal enzymatic processing of these peptides may be useful in studying upstream regulatory events in peptidergic neurons.

Amides↗

PubMed1993

The usefulness of weight gain in predicting pregnancy complications.

The usefulness of recently constructed centile charts for weight gain during pregnancy was studied. The association of weight gain in pregnancy with pregnancy complications was investigated. The incidence of pre-eclampsia and small for gestational age babies both had a significant relationship with weight gain. Use of the charts to screen for pregnancy complications on a selected population had both a sensitivity and specificity of about 50 per cent. The positive and negative predictive values of the charts ranged from 49 to 53 per cent. The question arises as to whether the routine recording of maternal weight at each antenatal visit is necessary.

Birth Weight↗

PubMed1993

A role for the ecological study in the developing world.

Retrospective case-control or prospective (follow-up) studies are important epidemiological tools and have provided useful information on exposure disease associations. Prospective studies would be the ideal option, but many countries (particularly in the developing world) do not have the necessary infrastructure to follow people up. Both retrospective and prospective studies are, however, sometimes conducted without due regard for their own limitations. These limitations are exacerbated when measures of exposure or disease are based on a single measurement and where the population under study is homogeneous with regard to exposure. The former is responsible for regression dilution bias and the latter for a lack of contrasts between exposure groups. Both factors would attenuate any relationship between exposure and disease. Ecological studies in epidemiology are weaker in design than case-control or prospective studies, but in some circumstances an ecological approach, which looks at the prevalence of an exposure or disorder in a number of areas of varying disease rates, may offer some advantages.

China↗

PubMed1992

Kinetics, brain uptake, and receptor binding of tandospirone and its metabolite 1-(2-pyrimidinyl)-piperazine.

Tandospirone is an azaspirodecanedione derivative under investigation as an antidepressant. Metabolism of tandospirone in humans and rodents leads to 1-(2-pyrimidinyl)-piperazine (1-PP), presumed to have pharmacologic activity. To determine the relative contributions of tandospirone and 1-PP after tandospirone administration, we evaluated open-field activity, pharmacokinetics, and receptor binding of tandospirone and 1-PP in a mouse model. Tandospirone significantly reduced open-field activity during 30 minutes at doses of 1-20 mg/kg. 1-PP had no significant effect on activity except for a trend toward reduction at 20 mg/kg. At 30 minutes after administration, plasma and cortex concentrations of tandospirone and 1-PP increased in proportion to dose. Plasma protein binding (free fraction) for tandospirone was 30.4%, and for 1-PP, 87.5%. Receptor binding studies indicated that tandospirone bound with high affinity to serotonin1A sites, and with low affinity to serotonin2, alpha 1, alpha 2, and benzodiazepine sites. 1-PP bound with high affinity to alpha 2 sites and with low affinity to the other sites evaluated. A "receptor occupancy index" of tandospirone cortex concentrations divided by receptor affinity suggests that after acute administration of tandospirone, effects are likely to be due to the parent compound rather than to the metabolite. Similar conclusions are likely to be correct for other azaspirodecanediones, including buspirone.

Animals↗

PubMed1991

Persistent elevation in GABAA receptor subunit mRNAs following social stress.

Stress is associated with alterations in GABA/benzodiazepine binding and function. We evaluated effects of social stress on GABAA receptor subunit (alpha 1 and gamma 2) mRNAs by Northern hybridization. In cortex, no change was observed in either subunit mRNA immediately after stress, but a 4 hours mRNAs for both subunits were increased. These changes persisted for 72 hours after stress, and returned to baseline levels at 7 days. No changes in mRNAs were observed in sham-treated mice. No changes in either subunit mRNA were observed in stressed or sham-treated mice in cerebellum or hippocampus. In undefeated resident mice, mRNAs for both subunits in cortex were unaffected at 24 hours after the stress episode. Social stress is associated with increases in GABAA receptor alpha 1 and gamma 2 subunit mRNAs in cortex.

Animals↗

PubMed1991

Cochlear efferent neurones and protection against acoustic trauma: protection of outer hair cell receptor current and interanimal variability.

We have measured the changes in neural and microphonic sensitivity in the basal turn of the guinea-pig cochlea produced by intense acoustic overstimulation (10 kHz, 115 dB SPL for 60 s and 150 s). As reported previously, the drop in neural and microphonic sensitivities observed after overstimulation were highly correlated [Patuzzi et al. (1989) Hear. Res. 39, 189-202]. Presentation of a non-traumatizing pure-tone to the contralateral ear (10 kHz, 80 dB SPL) during acoustic overstimulation reduced the amount of acoustic trauma measured using the neural response or the microphonic response. Transection of the medial olivo-cochlear system of efferent fibres at the floor of the fourth ventricle abolished this protective effect of contralateral sound and dramatically reduced the variability in the data. Since the low-frequency microphonic is a simple measure of the receptor current through the outer hair cells, and this current probably plays a part in enhancing the mechanical sensitivity of the cochlea, the protection of the microphonic we have observed suggests that the efferent system protects neural sensitivity by protecting the mechano-electrical transduction of outer hair cells. The drop in variability after sectioning the efferents also suggests that inter-animal variations in susceptibility to noise trauma may be a consequence of differing tonic activity of the efferents, and/or a variation in the sensitivity of the efferent pathway.

Action Potentials↗

PubMed1991

Benzodiazepine receptor binding response to acute and chronic stress is increased in aging animals.

Benzodiazepine receptor binding in vivo, as determined by the uptake of the high-affinity specific benzodiazepine receptor ligand [3H]Ro15-1788, was examined following acute and chronic defeat stress in male mice aged 6 weeks, 7 months and 1 year. Specific uptake in 6-week-old mice was increased from control values only in the cerebellum following acute but not chronic stress. Specific uptake in the cortex and hypothalamus was unchanged from control values following both acute and chronic stress. Seven-month-old mice demonstrated an increased specific uptake in the cortex and cerebellum when measured immediately following both acute stress and the final session of chronic stress. This enhanced binding returned to baseline levels by 24 h after stress. One-year-old mice demonstrated no change in specific uptake when measured after acute stress, while binding was enhanced in all brain regions after the final session of chronic stress. This increased binding was still evident at 24 h after the cessation of chronic stress. Changes in benzodiazepine binding differ as a response to acute and chronic stress, and this response varies markedly with age.

Acute Disease↗

PubMed1990

Choice of coronary heart disease risk factor variables in a cross-sectional study of white South Africans.

This report explores the possibility of redefining risk factors so as to improve their observed associations with prevalent coronary heart disease (CHD). A large cross-sectional community study of 5,895 white males and females aged 25-64 years yielded 240 cases of confirmed angina pectoris and 361 of confirmed myocardial infarction. Odds ratios for CHD end-points by level of risk factors when risk factors were expressed in the conventional manner (e.g. total cholesterol, systolic and diastolic blood pressure or current smoking) were often low and not statistically significant. Redefinition of risk factor variables in a manner that improved their specificity or compensated to some extent for the decreased risk factor exposure as a result of a CHD event (e.g. stopping smoking after a myocardial infarct) improved the strength of association. In this study, the most useful cholesterol variable was total cholesterol minus high-density lipoprotein cholesterol; for blood pressure the most useful variable was a blood pressure of 160/95 mmHg or above and/or being on anti-hypertensive treatment; and for smoking the most useful variable was the total duration of smoking (previous and current). Strong associations with CHD end-points were also found for conventionally expressed serum uric acid, diabetes prevalence (females) and family history of CHD. The study suggests that appropriate redefinition of risk factor variables and CHD end-points in cross-sectional studies yields associations similar in strength and direction to those found in prospective studies.

Adult↗

PubMed1990

Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain.

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.

Animals↗

PubMed1990

Socio-economic status, risk factors and coronary heart disease. The CORIS baseline study.

The relationship of socio-economic status (SES) indicators and coronary risk factors (RFs) with coronary heart disease (CHD) prevalence was examined in 5 620 subjects aged 20-60 years who participated in the Coronary Risk Factor (CORIS) baseline study. Education and income (with some exceptions in males) were strongly and inversely related to hypercholesterolaemia, low high-density lipoprotein cholesterol, hypertension, smoking, overweight and prevalence of angina pectoris. In contrast, type A behaviour was positively associated with higher income and education. Females showed stronger SES-RF relationships than males. Town-dwelling females were more likely to be smokers, and had a higher prevalence of angina pectoris and myocardial infarction. The lowest overall prevalence of RFs, angina pectoris and myocardial infarction was found in the professional and managerial categories for both males and females. The SES indicators had little or no independent effect on CHD prevalence in multivariate logistic analyses after inclusion of the standard RFs. We conclude that these indicators relate to RFs, and through them to CHD.

Adult↗

PubMed1990

Disulfiram administration affects substance P-like immunoreactive and monoaminergic neural systems in rodent brain.

The biosynthetic enzyme peptidylglycine alpha-amidating monooxygenase catalyzes the formation of a variety of biologically active alpha-amidated peptides from respective COOH-terminal glycine-extended peptide precursors. Peptidylglycine alpha-amidating monooxygenase activity is dependent on copper, ascorbate, and molecular oxygen and is inhibited by the relatively selective copper chelator N,N-diethyldithiocarbamate or its disulfide dimer disulfiram (Antabuse). In the present study, chronic disulfiram treatment (100 mg/kg/day, for 12-25 days) resulted in significant changes in several neurochemical parameters in the mouse central nervous system, including levels of substance P-like, unamidated substance P-Gly-like, and protease-generated substance P-Gly-Lys-like immunoreactivities (SP-LI, SP-G-LI, and SP-G-K-LI, respectively). Combined high performance liquid chromatography/radioimmunoassay analyses of the extracted SP-LI, SP-G-LI, and SP-G-K-LI species indicated very similar chromatographic and immunochemical behavior as demonstrated for chemically authentic peptide standards. Additionally, changes in levels of monoamines and their metabolites were observed after drug administration. Complementary immunohistochemical analyses using affinity-purified anti-SP-G sera localized these drug-induced changes in levels of immunoreactive unamidated precursor to neural elements that normally express SP. As a functional corollary to alterations in neurochemical parameters, we observed significant disulfiram-induced increases in pain thresholds, potentiated by capsaicin treatment. Overall, our results indicate that the observed changes in steady state levels of immunoreactive SP and of the immature COOH-terminal extended forms of SP may reflect compensatory biosynthetic and posttranslational processing events in SP-containing neural systems after pharmacological challenge.

Amino Acid Sequence↗

PubMed1990

Maximum likelihood estimation of reference centiles.

We propose the use of centile estimates which are based on the fitting of appropriate densities by maximum likelihood. In the case of cross-sectional centile estimation, we show that this approach will generally lead to more precise estimates than would result from the use of non-parametric centile estimates. When longitudinal data are available or a series of cross-sectional data at different time points, the maximum likelihood approach can be used to simultaneously fit densities to each cross-section, subject to constraints (for example, smoothness constraints) on the parameters. The variances of these centile estimates are readily obtained and missing values and unequally spaced records are easily accommodated. We illustrate the procedure by means of an application using the Johnson family of densities to a study of weight gain in pregnancy.

Adult↗

PubMed1990

Chronic morphine administration augments benzodiazepine binding and GABAA receptor function.

Behavioral and neurochemical evidence indicates links between the opioid and GABA neurotransmitter systems. To assess effects of chronic opiates on the major site of postsynaptic GABAergic activity, the GABAA receptor, we administered chronic morphine and naltrexone to mice and evaluated binding at the benzodiazepine and t-butylbicyclophosphorothionate (TBPS) sites and GABA-dependent chloride uptake. After morphine (3 days), benzodiazepine receptor binding in vivo but not in vitro was increased in cortex compared to placebo-treated mice. TBPS binding was unchanged in cortex, but muscimol-stimulated chloride uptake was increased at low doses of muscimol. Benzodiazepine and TBPS binding and muscimol-stimulated chloride uptake were unchanged in naltrexone-(8 days) compared to placebo-treated mice. When naltrexone was administered previously to block opiate sites, the increases in benzodiazepine binding and chloride uptake observed with chronic morphine were reversed. These results indicate that chronic morphine but not naltrexone enhances benzodiazepine binding and GABAA receptor function, perhaps by an action at opioid receptors.

Animals↗

PubMed1990

A centile chart for weight gain in pregnancy for the urban population of the Western Cape, South Africa.

Weight gain during pregnancy was studied. Women with low body mass index (BMI) gained significantly more weight than women with high BMI. Older women gained significantly less weight than younger women. Centile charts were constructed using a maximum likelihood procedure. The centile charts for patients who are less than or equal to 25 years or with a BMI = less than or equal to 24 kg/m2 cannot be regarded as differing significantly, however the chart for patients greater than 25 years with a BMI greater than 24 kg/m2 does lie significantly below the others. For practical purposes the process of weight gain can be regarded as independent of gestational age. These charts can thus be used without knowledge of gestational age.

Adolescent↗

PubMed1990

Innate and adaptive immune responses in a social conflict paradigm.

Social conflict stress was examined for its effects on in vitro and in vivo immunity in mice. Adaptive immunity, as measured by the generation of primary IgM antibody responses to the T-dependent antigen keyhold limpet hemocyanin, was suppressed following chronic (greater than 1 day), but not acute (less than 1 day), stress periods while the IgM response to the T-independent antigen polyvinylpyrrolidone was not affected. In vitro proliferative responses of splenocytes to the T cell mitogen concanavalin A and the B cell mitogen lipopolysaccharide were unaffected. Acute (less than 1 day) stress dramatically increased innate immunity as measured by a luminol-dependent chemiluminescence assay of phagocytic cell function. DBA/2J mice averaged a 269% increase in phagocytosis as compared to a 412% increase in C57BL/6J. This differential effect of stress on immune responsiveness indicates that alterations in innate immunity in addition to adaptive immunity should also be considered when evaluating neuroendocrine and immune interactions in response to stress.

Animals↗

PubMed1990

Acid-base-electrolyte balance responses to catecholamine antagonists in Ambystoma tigrinum.

Neotenic larval Ambystoma tigrinum were subjected to hypercapnia (3% CO2, 22 Torr) for 24 h under different conditions: alpha-adrenergic blockade using phentolamine, beta-adrenergic blockade using propranolol, and sham treatments. The sham animals were able to carry out a partial extracellular pH compensation that consisted of an increase in extracellular [HCO3-]. Animals treated with catecholamine antagonists did not compensate to the same extent. Analysis of plasma samples by high-performance liquid chromatography with electrochemical detection revealed a significant increase in circulating norepinephrine, but not epinephrine, during the high-CO2 exposure. Measurements of cutaneous ion transport showed that beta-antagonists block the increased Na+ influx associated with hypercapnia, whereas alpha-antagonists inhibited the decrease in cutaneous Cl- influx that is also associated with respiratory acidosis. Additionally, both alpha- and beta-blockers inhibited the increase in transcutaneous potential difference that accompanied the respiratory acidosis. The results are consistent with a role for circulating catecholamines in compensatory ion transport responses to respiratory acidosis in this species.

Acid-Base Equilibrium↗

PubMed1989

Doppler ultrasonography of the fetoplacental circulation--normal reference values.

Normal reference values for the resistance index, A/B ratio and pulsatility index of the umbilical artery obtained by Doppler ultrasonography are presented. The resistance index and A/B ratio values are very similar to those previously published, indicating no need to formulate normal values for different populations. The pulsatility index differed from other published values, probably reflecting different calculation methods built into the spectrum analysers rather than differences in waveforms. The resistance index had the lowest coefficient of variation and showed least inter-observer variation. For routine use the resistance index is preferable to other indices.

Adult↗