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Biomedical subjects

D W Jones

Publications and source records attributed to D W Jones.

At least 55 records · Page 3Linked to original sources
PubMed1999

What is the role of obesity in hypertension and target organ injury in African Americans?

Hypertension is the most common reversible risk factor for cardiovascular disease. It is especially common in African Americans. One of the factors that may contribute to the high rates of hypertension and target organ injury in African Americans is obesity. Hypertension and obesity are common among African Americans. Obesity is particularly common in African American women. About 75% of African American women are obese. Regulation of both body weight and blood pressure are complex, involving an interaction of genetic and environmental factors. Most research thus far has focused on blood pressure control systems studied in other forms of hypertension, including the sympathetic nervous system, the renin angiotensin system, and metabolic factors-primarily insulin resistance. Proposed mechanisms that are unique to obesity-associated hypertension include: 1) intrarenal physical forces associated with obesity-induced changes in the renal medulla; 2) genetic/metabolic factors; and 3) metabolic effects of abdominal visceral fat. The Jackson Heart Study provides a unique opportunity to address unresolved questions in the relationship of body weight, blood pressure, and cardiovascular disease.

Adult↗
PubMed1999

Antibodies to factor XII associated with lupus anticoagulant.

Falsely low levels of factor XII (FXII) have been documented in patients who are lupus anticoagulant positive (LA+). In addition, we have previously noted a surprisingly high incidence (20.9%) of apparently true FXII deficiency in patients who were LA+. We have hypothesised that this may be partly due to the presence of antibodies to FXII. The aim of the present study was to investigate whether LA+ patient plasmas contain antibodies directed either against FXII or FXII in association with phospholipids. Plasma samples from 60 blood donors, all LA negative, and 51 LA+ patients were tested using ELISA assays employing purified FXII, phosphatidylserine (PS) and phosphatidylethanolamine (PE). We have identified seven patients whose plasma contained either IgG or IgM that reacted with purified FXII in the absence of PS or PE. When PS was included in the assay system four additional patient plasmas were shown to contain either IgG or IgM that reacted with FXII. The plasma of one patient contained IgG that reacted with FXII both in the presence and absence of PS. There was no reactivity to FXII with either IgG or IgM when PE was included in the assay system. Affinity purified IgG from three patients whose plasma reacted with FXII in the ELISA assay in the absence of PS, gave a positive reaction in an immunoblot assay. These results suggest that FXII antibodies are present in a significant proportion of LA+ patients and may lead to an erroneous diagnosis of FXII deficiency.

Antibody Specificity↗
PubMed1999

Exposure or absorption and the crucial question of limits for mercury.

Health Canada recently lowered the recommended maximum daily exposure of mercury from all sources for women of child-bearing age and for children less than 10 years. This new exposure guideline does not seem to be based on any new scientific finding of human toxicity. The average daily intake of methylmercury (mainly from fish) that may cause demonstrable health effects in the most sensitive individual is 300 micrograms/day, or 4.3 micrograms Hg/day/kg body weight. The new, lower Health Canada limit is 95% below the level that may cause health effects. A number of studies have looked at methylmercury in human breast milk (where maternal consumption of fish is high), but no strong evidence of toxicity has been reported. The amount of mercury released from dental amalgam is minimal; a person would have to have 490 amalgam surfaces for there to be enough mercury vapour and ionic mercury given off from amalgam fillings to meet the maximum exposure guidelines. The uptake of food-related organic mercury is six times higher than the uptake of mercury from amalgam; moreover, food-related mercury is significantly more toxic. Many studies of amalgam-related mercury are flawed by confusion between exposure and absorption for the various forms of mercury, a limited selection of data, the ignoring of confounding variables or the misclassification of data.

Absorption↗
PubMed1998

A Canadian perspective on the dental amalgam issue.

This article provides a view of government reaction in Canada to public concern over the use of dental amalgam. It also addresses the basis of the irrational fears the general public may have regarding the impact of external factors on their health.

Air Pollution, Indoor↗
PubMed1998

Psychomotor slowing, negative symptoms and dopamine receptor availability--an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients.

Anhedonia and psychomotor slowing in schizophrenia have been attributed to a dysfunction of dopaminergic neurotransmission. To differentiate between disease and drug-induced negative symptoms, we examined eight drug-free and eight neuroleptic-treated schizophrenic patients. Positive and negative symptoms and extrapyramidal side effects were assessed using standardized rating scales (PSAS, AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer-aided system and striatal dopamine D2/D3 receptor availability was assessed using [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening and avolition were increased in treated patients relative to the untreated cohort and were negatively correlated with dopamine D2/D3 receptor availability. Significant positive correlations were found between parkinsonism and affective flattening and between psychomotor slowing and avolition. Positive symptoms were not significantly associated with striatal IBZM binding. These findings support the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum can mimic certain negative symptoms, such as affective flattening and avolition, and indicates that psychomotor testing may be helpful in differentiating between disease and drug-induced negative symptoms.

Acute Disease↗
PubMed1998

In vivo imaging of brain nicotinic acetylcholine receptors with 5-[123I]iodo-A-85380 using single photon emission computed tomography.

The distribution and kinetics of 5-[123I]iodo-A-85380, a novel ligand for brain nicotinic acetylcholine receptors (nAChRs), were evaluated in the Rhesus monkey using single photon emission computed tomography (SPECT). Peak levels of radioactivity were measured in brain at 90 min after injection of the tracer. Accumulation of radioactivity was highest in the thalamus, intermediate in the frontal cortex and basal ganglia, and lowest in the cerebellum. The ratio of specific to nonspecific binding (V3") in the thalamus, estimated from the (thalamic-cerebellar)/cerebellar radioactivity ratio, reached a value of 6 at 4 h post-injection. Specific binding was reduced by subcutaneous injection of 1 mg/kg cytisine at 2.25 h after injection of radiotracer. At 2.5 h after cytisine administration, radioactivity in the thalamus was reduced by 84%, in the frontal cortex, by 76%, and in the basal ganglia, by 57% of the level measured at the time of cytisine administration, demonstrating that the binding was reversible. On the basis of these findings, together with other data indicating high affinity, receptor subtype selectivity, low nonspecific binding and lack of toxicity in animals, 5-[123I]iodo-A-85380 appears to be a promising ligand for SPECT imaging of nAChRs in the human brain.

Animals↗
PubMed1998

The evaluation of resin composite consistency.

OBJECTIVE: To evaluate a method for the assessment of the consistency of unset resin composite. METHODS: Fourteen commercial resin composites were selected, which had a range of consistencies as assessed subjectively. The material was placed in a cylindrical mold with 8 mm diameter and 8 mm depth, and a glass rod with 4.37 mm diameter driven into the composite at 24.4 mm min-1 for 6 s, i.e., to a depth of 2.44 mm. The maximum force reached during the 6 s period was recorded, and used as a measure of consistency. RESULTS: Consistency values ranged from 0.33 N to 31.3 N, with the highest values being found for some of the recently introduced 'packable' materials. The reliability of the test was high. SIGNIFICANCE: The test may be useful as a standard method of assessing resin composite consistency.

Analysis of Variance↗
PubMed1998

The effect of two different 18-week walking programmes on aerobic fitness, selected blood lipids and factor XIIa.

Forty-nine previously sedentary or low active individuals aged 40-71 years were allocated to three groups. The long walking group participated in an 18-week walking programme which consisted of walks lasting 20-40 min; the repetitive short walking group completed walks of between 10 and 15 min, up to three times a day, with no less than 120 min between each walk; and the control group maintained their low level of activity. Both walking programmes began at a prescribed 60 min x week(-1), which increased steadily up to 200 min x week(-1) by week 12. During the study, the long walking group walked for an estimated 2514 min (139 min x week(-1)), expending an estimated 67.5 MJ (3.72 MJ x week(-1)) at an estimated 73% of their age-predicted maximum heart rate and 68% of their estimated VO2max. The repetitive short walking group walked for an estimated 2476 min (135 min x week(-1)), expending an estimated 58.5 MJ (3.17 MJ x week(-1)) at an estimated 71% of their age-predicted maximum heart rate and 65% of their estimated VO2max. The results showed a statistically significant reduction in heart rate during a standardized step test (pre- vs post-intervention) in both walking groups, indicating an improvement in aerobic fitness, although the control group showed a higher average heart rate during the post-intervention test, indicating reduced fitness. When compared with the male subjects pre-intervention, the females possessed more favourable levels of high-density lipoprotein (HDL) cholesterol (P< 0.001), apolipoprotein (apo) AI (P < 0.001) and ratios of total cholesterol:HDL cholesterol (P< 0.02) and low-density lipoprotein (LDL) cholesterol: HDL cholesterol (P< 0.02). Compared with the controls post-intervention, the walking groups showed no statistically significant changes in total cholesterol, LDL cholesterol, HDL cholesterol, apo AI, apo AII, apo B, or the ratios of total cholesterol: HDL cholesterol, LDL cholesterol: HDL cholesterol, apo AI: apo B or apo AI: apo AII (P > 0.05). Relative to the walking groups, factor XIIa increased in the control group (P < 0.05). We conclude that, although both walking programmes appeared to improve aerobic fitness, there was no evidence of improvements in the blood lipids or associated apolipoproteins of the walking groups. Further analysis indicated that this apparent lack of change may have been related to the subjects' relatively good pre-intervention blood lipid profiles, which restricted the potential for change. The implications of the observed changes in the coagulation/fibrinolytic factors remain unclear.

Adult↗
PubMed1998

An automated chromogenic peptide substrate assay for coagulation factor XII.

We have developed an automated chromogenic peptide substrate assay for factor XII (FXIIcs) on a Cobas Mira S Plus clinical chemistry analyser using a new commercially available kit. This was used to determine factor XII (FXII) levels in plasma samples from 320 blood donors, 206 patients with a history of venous thrombosis and 74 lupus anticoagulant positive (LA+) patients. Results were compared with those obtained in a clotting assay for FXII (FXIIct) and an immunochemical assay (FXIIag). A satisfactory correlation coefficient of 0.92 and a regression line equation of y = 7.898 + 0.871x was obtained between FXIIcs and FXIIct in the 320 blood donors. Levels of FXII below the calculated normal range were found in nine blood donors (2.8%) and 16 venous thrombosis patients (7.8%). The blood donors and patients with venous thrombosis with low FXIIcs values had FXII levels below our lower limits of normal for both FXIIct and FXIIag; all were lupus anticoagulant negative. When FXII levels were determined in the 74 LA+ patients, 27 (36.5%) gave markedly lower FXII values in the FXIIct when compared with the FXIIcs. FXIIag levels corresponded with FXIIcs. The automated FXIIcs assay is therefore lupus anticoagulant insensitive and allows us to measure FXII levels accurately and routinely in large numbers of patient samples.

Autoanalysis↗
PubMed1998

Reduced central serotonin transporters in alcoholism.

OBJECTIVE: Dysfunction of monoamine uptake mechanisms has been implicated in the pathogenesis of alcohol dependence. The authors explored whether serotonergic dysfunction is associated with anxiety and depression, which increase the risk of relapse in alcoholics. METHOD: The availability of serotonin and dopamine transporters in 22 male alcoholics and 13 healthy male volunteers was measured with the use of [123I] beta-CIT and single photon emission computed tomography, and psychopathological correlates were assessed. RESULTS: A significant reduction (a mean of about 30%) in the availability of brainstem serotonin transporters was found in the alcoholics, which was significantly correlated with lifetime alcohol consumption and with ratings of depression and anxiety during withdrawal. CONCLUSIONS: The findings support the hypothesis of serotonergic dysfunction in alcoholism and in withdrawal-emergent depressive symptoms.

Adult↗
PubMed1998

In vivo association between alcohol intoxication, aggression, and serotonin transporter availability in nonhuman primates.

OBJECTIVE: Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence. METHOD: The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly. RESULTS: In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding. CONCLUSIONS: In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.

Adult↗
PubMed1998

Tourette's syndrome: [I-123]beta-CIT SPECT correlates of vocal tic severity.

OBJECTIVE: To examine in vivo the density of brain monoaminergic transporters in Tourette's syndrome (TS). BACKGROUND: TS is a heritable neuropsychiatric disorder characterized by chronic vocal and motor tics and is often associated with obsessive-compulsive symptoms. Hyperstimulation of dopamine receptors and dysfunction of serotonergic transmission have been implicated in its pathogenesis, but direct evidence of involvement of these neurochemical systems has been limited. METHODS: Symptom severity and the availability of presynaptic monoaminergic transporters in the basal ganglia, midbrain, and thalamus were measured using SPECT and the radioligand [I-123]2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([I-123]beta-CIT) in 10 patients with TS and in 10 age- and sex-matched normal volunteers. RESULTS: A significant negative correlation was found between a measure of overall tic severity and beta-CIT binding in the midbrain (r = -0.73, p = 0.02) and the thalamus (r = -0.82, p < 0.01). When examined post hoc, these correlations were determined largely by vocal tic severity. No other significant correlations were found between symptom severity and beta-CIT binding in the striatum or cortex. CONCLUSIONS: These findings indicate that serotonergic neurotransmission in the midbrain and serotonergic or noradrenergic neurotransmission in the thalamus may be important factors in the expression of TS and may suggest novel targets for treatment.

Adult↗
PubMed1998

Factor XII determinations in the presence and absence of phospholipid antibodies.

Factor XII (FXII) levels were determined in plasma samples from 29 normal donors, 10 patients with inherited FXII deficiency (all lupus anticoagulant [LA] negative) and 67 LA positive patients, using clotting (FXIIct), chromogenic substrate (FXIIcs) and immunochemical (FXIIag) assays. Excellent correlations were obtained in the three FXII assays with the LA negative samples and between the FXIIcs and FXIIag assays in the LA positive samples. Correlations between both the FXIIcs and FXIIag with FXIIct in the LA positive patients were poor. Of 67 LA positive samples studied, 25 (37.3%) showed lower values in the FXIIct assay; 13 (19.4%) of these patients were pseudo FXII deficient with values of FXII below the lower limit of normal. These results indicate that a diagnosis of FXII deficiency can be made inappropriately in the presence of phospholipid antibodies and that such a diagnosis should not be made by FXIIct assay alone.

Antibodies, Antiphospholipid↗
PubMed1997

Cortical abnormality in schizophrenia: an in vivo application of the gyrification index.

To investigate the hypothesis that patients with schizophrenia exhibit gross cortical abnormalities of developmental origin, we utilized the gyrification index (GI) (ratio of inner to outer cortical contours), a measure of overall cortical folding, in an in vivo magnetic resonance imaging study of young, strongly right-handed male patients and controls. The two groups did not differ with respect to whole-brain volume, age, or handedness. In an examination confined to the left hemisphere, mean GI values were significantly reduced in the patient group in both anterior and posterior regions. Neither age nor length of illness were found to be significant predictors of GI variance in the patients group, suggesting that GI reductions do not result from an ongoing atrophic process. Rather, these results are consistent with the hypothesis of neurodevelopmental abnormalities in schizophrenia that result in an overall reduction in cortical folding.

Adult↗