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N Thomas

Publications and source records attributed to N Thomas.

At least 73 records · Page 4Linked to original sources
PubMed1999

Dopaminergic activities in the human striatum: rostrocaudal gradients of uptake sites and of D1 and D2 but not of D3 receptor binding or dopamine.

The human striatum, which receives dopaminergic innervation from the substantia nigra and ventral tegmental area (cell groups A8, A9 and A10), has structural and functional subdivisions both rostrocaudally and dorsoventrally. These relate to motor and non-motor origins of cortical projections and the specific areas of the substantia nigra and ventral tegmental area providing dopaminergic innervation. In the present study, we have evaluated the distribution of a number of dopaminergic parameters in the caudate, putamen and nucleus accumbens at separate coronal levels in a post mortem study in a series of elderly normal individuals aged 55-94 years, with analysis of the effect of post mortem variables. Dopamine D1 receptor density displayed a rostrocaudally declining gradient in the putamen but not in the caudate, such that at levels posterior to the anterior commissure, there was significantly lower D1 binding in the putamen compared to the caudate. The density of dopamine D2 receptors was similar in the putamen and caudate, increasing rostrocaudally. The density of dopamine uptake sites exhibited an increasing rostrocaudal gradient in the caudate, especially ventrally, but not in the putamen, where binding was more constant. The dopamine D3 receptor was concentrated in the ventral striatum, particularly the nucleus accumbens, although there was no evidence of a rostrocaudal gradient. With respect to striosome-matrix compartmentalization, there was no complete segregation, although D1 and D3 receptors were concentrated in striosomes, whereas D2 receptors and uptake sites showed higher density in the matrix. Levels of dopamine were similar in the caudate and putamen, and were significantly elevated at levels including the nucleus accumbens and the anterior commissure. Homovanillic acid and the metabolic index (homovanillic acid/dopamine ratio) were significantly higher in the putamen compared to the caudate, especially at levels from and caudal to the anterior commissure. These distributions of dopamine receptors and metabolic indicators, reflecting the different functional domains of the striatum, are relevant to the interpretation of current in vivo imaging of the dopamine transporter and receptors in neurological and psychiatric disorders. They provide information to assist in the detection of perturbations in expression, in specific diseases, at particular points on rostrocaudal, lateromedial and dorsoventral axes, a level of resolution beyond current neuroimaging capability.

Aged↗
PubMed1999

Neonatal Group B Streptococcal bacteraemia in India: ten years' experience.

Group B Streptococcus (GBS) is an infrequent cause of neonatal septicaemia in many developing countries. In a perinatal centre in India with 60,119 live births between 1988 and 1997, GBS was isolated from blood cultures of 10 babies. Thus the incidence of GBS bacteraemia was 0.17 per 1000 live births. Lethargy, respiratory distress and poor perfusion were the presenting features in eight symptomatic babies. Two babies had meningitis, three required ventilatory support and one died. There were no cases of late onset disease. The low incidence could be due to the low rate of colonisation and high prevalence of protective antibody in the mothers.

Bacteremia↗
PubMed1999

Relationships between age, dehydro-epiandrosterone sulphate and plasma glucose in healthy men.

BACKGROUND: dehydro-epiandrosterone sulphate (DHEAS) has been reported to ameliorate diabetes mellitus in rats. AIM: we investigated the relationships between plasma glucose, age, serum DHEAS and weight in healthy men. METHODS: we measured the serum DHEAS, fasting plasma glucose, plasma cortisol and body mass index in 169 subjects (mean age 46.5 years). RESULTS: there was a significant decline in serum DHEAS with age (P < 0.0001). Multiple linear regression showed significant relationships with plasma glucose for all measured variables. Age was not a significant determinant of plasma glucose after adjusting for log serum DHEAS, body mass index and log serum cortisol. CONCLUSIONS: a lowered serum DHEAS is paralleled by an elevated plasma glucose within the normal reference interval, and this may contribute to the rise in fasting plasma glucose which occurs with ageing.

Adult↗
PubMed1999

Striatal dopaminergic markers in dementia with Lewy bodies, Alzheimer's and Parkinson's diseases: rostrocaudal distribution.

Dementia with Lewy bodies (DLB) is a neuropsychiatric disease associated with extrapyramidal features which differ from those of Parkinson's disease, including reduced effectiveness of L-dopa and severe sensitivity reactions to neuroleptic drugs. Distinguishing Alzheimer's disease from DLB is clinically relevant in terms of prognosis and appropriate treatment. Dopaminergic activities have been investigated at coronal levels along the rostrocaudal striatal axis from a post-mortem series of 25 DLB, 14 Parkinson's disease and 17 Alzheimer's disease patients and 20 elderly controls. [(3)H]Mazindol binding to the dopamine uptake site was significantly reduced in the caudal putamen in DLB compared with controls (57%), but not as extensively as in Parkinson's disease (75%), and was unchanged in Alzheimer's disease. Among three dopamine receptors measured (D1, D2 and D3), the most striking changes were apparent in relation to D2. In DLB, [(3)H]raclopride binding to D2 receptors was significantly reduced in the caudal putamen (17%) compared with controls, and was significantly lower than in Parkinson's disease at all levels. D2 binding was significantly elevated at all coronal levels in Parkinson's disease compared with controls, most extensively in the rostral putamen (71%). There was no change from the normal pattern of D2 binding in Alzheimer's disease. The only significant alteration in D1 binding ([(3)H]SCH23390) in the groups examined was an elevation (30%) in the caudal striatum in Parkinson's disease. There were no differences in D3 binding, measured using [(3)H]7-OH-DPAT, in DLB compared with controls. A slight, significant decrease in D3 binding in the caudal striatum of Parkinson's disease (13%) patients and an increase in Alzheimer's disease (20%) in the dorsal striatum at the level of the nucleus accumbens were found. The concentration and distribution of dopamine were disrupted in both DLB and Parkinson's disease, although in the caudate nucleus the loss of dopamine in DLB was uniform whereas in Parkinson's disease the loss was greater caudally. In the caudal putamen, dopamine was reduced by 72% in DLB and by 90% in Parkinson's disease. The homovanillic acid : dopamine ratio, a metabolic index, indicated compensatory increased turnover in Parkinson's disease, which was absent in DLB despite the loss of substantia nigra neurons (49%), dopamine and uptake sites. These differences between DLB, Parkinson's disease and Alzheimer's disease may explain some characteristics of the extrapyramidal features of DLB and its limited response to L-dopa and severe neuroleptic sensitivity. The distinct changes in the rostrocaudal pattern of expression of dopaminergic parameters are relevant to the interpretation of the in vivo imaging and diagnosis of DLB.

Aged↗
PubMed1999

Carotid plaque characterization by duplex scanning: observer error may undermine current clinical trials.

BACKGROUND AND PURPOSE: Clinical studies currently in progress are using subjective methods to characterize plaque morphology from ultrasound images. However, there are few studies on the intraobserver and interobserver variability of these classifications. This study was designed to assess these variables. METHODS: Grading of plaque morphology from ultrasound images, stored both digitally and to hard copy, was performed by 2 classification schemes. Interobserver agreement was determined by 4 observers. Within-observer agreement was performed at intervals for up to 6 months. Accuracy of the 2 methods was determined by comparison with histology. RESULTS: Within- and between-observer agreement was moderate to good for full-color digital image analyses, with pooled kappa values of kappap=0.49+/-0.10 and kappap=0.62+/-0.07 for the 2-category method and kappap=0.53+/-0.06 and kappap=0.52+/-0.05 for the 4-category method, respectively. Hard copy data analyses gave lower kappa values. The more experienced observers produced higher within-observer agreements and higher correlation with histology. CONCLUSIONS: Reproducible grading of ultrasound images is not consistently achievable among experienced observers, and within-observer agreement may vary with time. The current subjective ultrasound characterization of carotid plaque morphology used in clinical trials may be associated with unacceptable levels of reproducibility in some centers. Variability between observers may be reduced by using the simpler 2-category grading of plaque morphology to interrogate full-color digitally stored images. Observer agreement should be audited regularly.

Aged↗
PubMed1998

Intra-aortic balloon counterpulsation in patients with severe cardiac dysfunction undergoing abdominal operations.

OBJECTIVE: To assess the effectiveness of intra-aortic balloon counterpulsation (IABC) as adjunctive treatment in patients undergoing abdominal operations. DESIGN: Retrospective review of patient medical records to determine the incidence of mortality following abdominal surgery and the incidence of complications from IABC. SETTING: University-based, tertiary care hospital. PATIENTS: Sixty-eight patients who underwent an abdominal operation and IABC during the same hospitalization were divided into the following groups: Group 1, IABC initiated prior to operation to enhance perioperative cardiac function; group 2, IABC used to treat cardiogenic shock in a patient who subsequently required an operation while undergoing IABC; and group 3, IABC device inserted and removed for treatment of cardiogenic shock in a patient who subsequently required an operation within 30 days of removal of the device. MAIN OUTCOME MEASURES: The incidence of mortality in IABC-supported patients and IABC-related complications. RESULTS: In group 1, excluding 3 patients who died following emergency operation, 26 patients underwent nonemergency procedures and had a 12% mortality rate. In group 2, 5 of 6 patients who underwent emergency operations died, whereas 3 of 4 patients who required only urgent operations survived. In group 3, 18 (62%) of 29 patients who underwent urgent or emergent operations died postoperatively. Thirteen patients experienced complications related to IABC; there were no deaths and no limbs were lost to ischemia. CONCLUSIONS: This is the largest reported series looking at the utility of IABC as adjunctive treatment for patients undergoing abdominal operations. The outcome for those patients requiring emergency operations remains poor, but it is likely that more liberal use of IABC in patients with severe cardiac dysfunction who require nonemergency operations may improve patient outcome.

Abdomen↗
PubMed1998

Differential translation of the alpha-1 isoforms of L-type calcium channel in rat brain and other tissues.

L-Type voltage operated calcium channel plays an important role in the contraction-relaxation of muscle cells. The alpha-1 subunit of this pentameric protein performs catalytic functions. Multiple mRNA isoforms of this subunit are generated by alternative splicing. For example, an exon encoding 11 amino acids (aa) between the third and fourth transmembrane domains produces two mRNA isoforms in gastrointestinal (GI) tract. The corresponding exon in brain encodes 15 aa. Whether the alpha-1 mRNA isoforms are translated into the corresponding isozymes remain unknown. To address this issue and to characterize the exon in brain, isozymes specific anti-peptide polyclonal antibodies were raised. Both the antibodies reacted with a protein of Mr 180 kDa in the heart and GI-tract, while no reaction was obtained in the kidney or liver. Brain expressed the isoform containing the same exon encoding 11 amino acids present in GI-tract, but the corresponding isozymes were of Mr 145-150 kDa. These findings suggest a tissue-specific translation of the alpha-1 isozymes.

Alternative Splicing↗
PubMed1998

Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use.

Reports of a reduction in the risk of developing Parkinson's disease and Alzheimer's disease in tobacco smokers, together with the loss of high-affinity nicotine binding in these diseases, suggest that consequences of nicotinic cholinergic transmission may be neuroprotective. Changes in brain dopaminergic parameters and nicotinic receptors in response to tobacco smoking have been assessed in this study of autopsy samples from normal elderly individuals with known smoking histories and apolipoprotein E genotype. The ratio of homovanillic acid to dopamine, an index of dopamine turnover, was reduced in elderly smokers compared with age matched non-smokers (P<0.05) in both the caudate and putamen. Dopamine levels were significantly elevated in the caudate of smokers compared with non-smokers (P<0.05). However there was no significant change in the numbers of dopamine (D1, D2 and D3) receptors or the dopamine transporter in the striatum, or for dopamine D1 and D2 receptors in the hippocampus in smokers compared with non-smokers or ex-smokers. The density of high-affinity nicotine binding was higher in smokers than non-smokers in the hippocampus, entorhinal cortex and cerebellum (elevated by 51-221%) and to a lesser extent in the striatum (25-55%). The density of high-affinity nicotine binding in ex-smokers was similar to that of the non-smokers in all the areas investigated. The differences in high-affinity nicotine binding between smokers and the non- and ex-smokers could not be explained by variation in apolipoprotein E genotype. There were no differences in alpha-bungarotoxin binding, measured in hippocampus and cerebellum, between any of the groups. These findings suggest that chronic cigarette smoking is associated with a reduction of the firing of nigrostriatal dopaminergic neurons in the absence of changes in the numbers of dopamine receptors and the dopamine transporter. Reduced dopamine turnover associated with increased numbers of high-affinity nicotine receptors is consistent with attenuated efficacy of these receptors in smokers. A decrease in striatal dopamine turnover may be a mechanism of neuroprotection in tobacco smokers that could delay basal ganglia pathology. The current findings are also important in the interpretation of measurements of nicotinic receptors and dopaminergic parameters in psychiatric conditions such as schizophrenia, in which there is a high prevalence of cigarette smoking.

Age Factors↗
PubMed1998

Search for life on Mars.

A multi-user integrated suite of instruments designed to optimize the search for evidence of life on Mars is described. The package includes: -Surface inspection and surface environment analysis to identify the potential Mars landing sites, to inspect the surface geology and mineralogy, to search for visible surficial microbial macrofossils, to study the surface radiation budget and surface oxidation processes, to search for niches for extant life. -Subsurface sample acquisition by core drilling -Analysis of surface and subsurface minerals and organics to characterize the surface mineralogy, to analyse the surface and subsurface oxidants, to analyse the mineralogy of subsurface aliquots, to analyse the organics present in the subsurface aliquots (elemental and molecular composition, isotopes, chirality). -Macroscopic and microscopic inspection of subsurface aliquots to search for life's indicators (paleontological, biological, mineralogical) and to characterize the mineralogy of the subsurface aliquots. The study is led by ESA Manned Spaceflight and Microgravity Directorate.

Europe↗
PubMed1997

Results from the Mars Pathfinder camera.

Images of the martian surface returned by the Imager for Mars Pathfinder (IMP) show a complex surface of ridges and troughs covered by rocks that have been transported and modified by fluvial, aeolian, and impact processes. Analysis of the spectral signatures in the scene (at 440- to 1000-nanometer wavelength) reveal three types of rock and four classes of soil. Upward-looking IMP images of the predawn sky show thin, bluish clouds that probably represent water ice forming on local atmospheric haze (opacity approximately 0.5). Haze particles are about 1 micrometer in radius and the water vapor column abundance is about 10 precipitable micrometers.

Atmosphere↗