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D W Jones

Publications and source records attributed to D W Jones.

At least 37 records · Page 2Linked to original sources
PubMed2000

Genotype influences in vivo dopamine transporter availability in human striatum.

In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3' untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]beta-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.

3' Untranslated Regions↗
PubMed2000

In vivo olanzapine occupancy of muscarinic acetylcholine receptors in patients with schizophrenia.

Olanzapine is an atypical antipsychotic with potent antimuscarinic properties in vitro (K(i) = 2-25 nM). We studied in vivo muscarinic receptor occupancy by olanzapine at both low dose (5 mg/dy) and high dose (20 mg/dy) in several regions of cortex, striatum, thalamus and pons by analyzing [I-123]IQNB SPECT images of seven schizophrenia patients. Both low-dose and high-dose olanzapine studies revealed significantly lower [I-123]IQNB binding than that of drug-free schizophrenia patients (N = 12) in all regions except striatum. [I-123]IQNB binding was significantly lower at high-dose than low-dose in the same regions. Muscarinic occupancy by olanzapine ranged from 13% to 57% at 5 mg/dy and 26% to 79% at 20 mg/dy with an anatomical pattern indicating M(2) subtype selectivity. The [I-123]IQNB data indicate that olanzapine is a potent and subtype-selective muscarinic antagonist in vivo, perhaps explaining its low extrapyramidal side effect profile and low incidence of anticholinergic side effects.

Adult↗
PubMed2000

Neuropharmacological studies with SPECT in neuropsychiatric disorders.

The last decade saw a rapid development of single photon emission computed tomography (SPECT) from a tool to assess cerebral blood flow to the study of specific neurotransmitter systems. Because of the relatively long half-life of SPECT radioisotopes, it is practical to measure the availability of neuroreceptors and transporters in conditions approaching equilibrium. The cost-efficiency of SPECT allowed studies in relatively large samples of patients with various neuropsychiatric disorders. We have applied this approach in studies of dopaminergic, serotonergic, and muscarinergic neurotransmission in patients with dementia, extrapyramidal disorders, schizophrenia, and alcoholism. No simple associations were observed between a single defect in one neurotransmitter system and a certain neuropsychiatric disease. Instead, complex dysfunction of several neurotransmitter systems in multiple, partially connected brain circuits have been implicated. Treatment effects also have been characterized. Microdialysis and neurotransmitter depletion studies showed that most radioligands and endogenous neurotransmitters compete for binding at receptors and transporters. Future research directions include the assessment of endogenous neurotransmitter concentrations measured by depletion studies and of genetic effects on neuroreceptor and transporter expression.

Brain↗
PubMed2000

Reduced factor XII levels in patients with the antiphospholipid syndrome are associated with antibodies to factor XII.

Antibodies to factor XII (FXII) have previously been identified in some patients who were lupus anti-coagulant-positive. The relationship between these antibodies and FXII levels appeared to be variable. The aim of the present study was to confirm the presence of antibodies to FXII in patients with well characterized antiphospholipid syndrome (APS) and to establish their potential effect on levels of FXII. Forty-two patients with APS were studied; 21 patients were found to have either immunoglobulin (Ig)G or IgM antibodies to FXII by enzyme-linked immunosorbent assay (ELISA) using a highly purified preparation of FXII (> 99% pure). Levels of FXII were statistically significantly lower (P = 0.02) in patients with antibodies to FXII when compared with patients without antibodies to FXII (median = 91 micro/dl, s.d. = 39.1, median = 122 micro/dl, s.d. = 41.1 respectively). Four of the 21 patients with antibodies to FXII were found to have FXII levels below the laboratory normal range. Antibodies to FXII are present in significant numbers of patients with APS and may lead to acquired FXII deficiency.

Adult↗
PubMed2000

The importance of locally derived reference ranges and standardized calculation of dilute Russell's viper venom time results in screening for lupus anticoagulant.

Three commercial dilute Russell's viper venom time (DRVVT) kits were evaluated at four UK centres experienced at performing lupus anticoagulant (LA) tests. Each centre established a normal reference range for the DRVVT ratio calculated against local pooled normal plasma from 20 healthy normal subjects. Plasma from LA-positive patients and LA-negative thrombophilia patients was also tested. DRVVT ratios and the degree of correction were assessed in a variety of ways to reflect not only the UK national Guidelines, but also the manufacturers' recommendations. The reference range data showed a normal distribution in each case, but considerable variation in the mean and SD between the centres and reagents, with the mean +2SD value ranging from 1.06 to 1.19. The use of an arbitrary DRVVT ratio of < 1.1 as the cut-off value for normality, which is applied in many laboratories, is therefore inappropriate. Although no single kit had a clear overall advantage in terms of sensitivity and specificity, the way in which the screen and confirmation data were analysed had a major impact on the interpretation of the results. A data analysis method employing a mean plus two standard deviations (SDs) cut-off for normality, and judgement regarding confirmation of LA based on a percentage correction of DRVVT ratio, was the simplest and most consistent, with overall sensitivity and specificity values of 81% and 94%, respectively, for uncomplicated LA-positive and LA-negative thrombophilia samples. We conclude that the 1991 BSCH Guidelines are in need of revision, each laboratory should establish its own normal reference range for the DRVVT ratio and a common method should be used for calculating the degree of correction with confirmation reagents, so that LA results can be correctly interpreted between laboratories. Standardizing DRVVT interpretation in this way should improve the consistency of LA detection.

Humans↗
PubMed2000

Rising levels of cardiovascular mortality in Mississippi, 1979-1995.

BACKGROUND: Cardiovascular disease rates are improving in the United States, but not for certain subgroups, especially some African Americans. The objective of the study is to assess current levels and trends in cardiovascular disease mortality in Mississippi. METHODS: Mortality statistics from the U.S. vital statistics system for the period 1979-95 were used. Comparison of age-adjusted mortality rates in Mississippi with the other states for the year 1995 and with the nation as a whole over the period of 1979-95 was performed. RESULTS: Mississippians had the highest age-adjusted cardiovascular disease morality rates in the nation in 1995. Overall, the cardiovascular rates in Mississippi were 37% higher than for the U.S. African American men and women from Mississippi had especially high cardiovascular mortality rates, approximately 50% and 70% higher than their white counterparts, respectively. The higher burden of cardiovascular disease in African Americans from Mississippi was especially marked in the younger age groups. Since about 1984-85, cardiovascular mortality rates in Mississippi have been increasing for African Americans, whereas nationally they have been decreasing. In contrast, cardiovascular mortality rates for whites in Mississippi have been declining, but at a much slower rate than seen nationally. The wide divergence in trends for African American and white men and women over that period in Mississippi has lead to an estimated 19,400 excess cardiovascular deaths. Virtually identical trends were found for heart disease. CONCLUSIONS: Cardiovascular diseases are a major public health problem in Mississippi that is especially severe in African American residents, and the problem is growing worse each year. It is important to identify the determinants of and solutions for this enormous public health problem in Mississippi.

Adult↗
PubMed2000

Adenosine preconditions against endothelin-induced constriction of coronary arterioles.

Myocardial hypoperfusion is accompanied by concomitant increases in adenosine and endothelin-1 (ET-1) production, but the vasodilatory effect of adenosine prevails over that of ET-1. Therefore, we hypothesized that adenosine-induced or ischemic preconditioning reduces the vasoconstrictive effect of ET-1. Coronary arteriolar diameter in vivo was measured using fluorescence microangiography in anesthetized open-thorax dogs. ET-1 (5 ng. kg(-1). min(-1) administered intracoronary, n = 10) induced progressive constriction over 45 min [25 +/- 6% (SE)]. The constriction was blocked by preconditioning with adenosine (25 microgram. kg(-1). min(-1) administered intracoronary) for 20 min and 10 min of washout (n = 10) or attenuated by ischemic preconditioning (four 5-min periods of ischemia, 9 +/- 5% at 45 min). To investigate the receptor involved in this process, coronary arterioles (50-150 micrometer) were isolated and pressurized at 60 mmHg in vitro. The ET-1 dose-response curve (1 pM-5 nM) was rightward shifted after preconditioning with adenosine (1 microM) for 20 min and 10 min of washout (n = 11). Blockade of A(2) receptors [8-(3-chlorostyryl)caffeine, 1 microM, n = 9] but not A(1) receptors (8-cyclopentyl-1,3-dipropylxanthine, 100 nM, n = 7) prevented this shift. These results suggest that adenosine confers a vascular preconditioning effect, mediated via the A(2) receptor, against endothelin-induced constriction. This effect may offer a new protective function of adenosine in preventing excessive coronary constriction.

Adenosine↗
PubMed2000

Aging and word-finding: a comparison of spontaneous and constrained naming tests.

This study compared the word-finding abilities of 26 young adults (ages 18-22 years), 26 young-old adults (ages 58-74 years), and 26 old-old adults (ages 75-93 years) on a confrontational naming test (Boston Naming Test) and a more spontaneous discourse test. The groups were matched in terms of gender (7 male, 19 female) and estimated IQ (M = 114). When participants were asked to narrate what they perceived in pictures (discourse test), the older adult groups committed significantly more word-retrieval errors than the younger adults. In contrast, results from the picture-naming test surprisingly revealed higher naming accuracy by the older adult groups. Subsequent examination of the picture-naming items revealed that four items appeared to be influenced by generational familiarity with the item. These results suggest that selection of cohort-free items for picture-naming tests is important when comparing across age-groups, and that tests of discourse may be better measures for assessing everyday word-finding difficulties in healthy older adults.

Journal Article↗
PubMed1999

Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.

Adult↗
PubMed1999

Sleep-disordered breathing and periodic limb movements in sleep in older patients with schizophrenia.

BACKGROUND: Since the prevalence of both sleep-disordered breathing (SDB) and periodic limb movements in sleep (PLMS) increase with age, we explored whether older schizophrenia patients would have a high incidence of SDB and PLMS. Correlations between sleep and clinical variables were also examined. METHODS: Fifty-two patients (mean age = 59.6 years, SD = 8.9) had their sleep/wake, respiration, and leg movements recorded using a modified Medilog/Respitrace portable recording system plus oximetry. A battery of clinical, psychosocial, and motor disturbance variables were collected by research center staff. RESULTS: Forty-eight percent of these patients had at least 10 respiratory events per hour of sleep. These patients reported more symptoms of daytime sleepiness than patients with fewer than 10 events per hour. The relatively high prevalence of SDB in this group may contribute to overall sleep disturbances, and does not appear to be a result of high body mass index. Only 14% of the patients had at least five limb movements per hour of sleep, suggesting the prevalence of PLMS is much lower than expected in this age group. The number of leg jerks was inversely related to symptoms of tardive dyskinesia. CONCLUSIONS: The disturbance of sleep in these patients may be due, in part, to SDB, but is unlikely due to PLMS.

Age Factors↗
PubMed1999

A chromogenic substrate assay kit for factor XII: evaluation and use for the measurement of factor XII levels in cardiopulmonary bypass patients.

Factor XII levels were determined in plasma samples from 75 patients before undergoing aortocoronary bypass grafting and from 40 healthy age-matched donors by using a microtitre plate adaptation of a new chromogenic peptide substrate assay kit for factor XII. The chromogenic peptide substrate assay values for factor XII correlated well with those obtained in clotting (r=0.90; y= 15.811+0.8236x) and immunochemical (r=0.88; y=17.90+0.817x) assays in the normal donor samples. Factor XII levels in the patients were significantly lower than those in the normal donors (83.3+/-23.2% versus 103.4+/-23.1: p=0.004), and nine patients (12%) had factor XII values below 50% compared with only one of the normal donors (2.5%). Factor XII levels and kallikrein-like activities (a measure of contact system activation) were followed before, during, and one day after cardiopulmonary bypass in 20 patients. Factor XII levels were significantly reduced, and kallikrein-like activities significantly elevated after 5 and 30 minutes cardiopulmonary bypass. One day after cardiopulmonary bypass both factor XII levels and kallikrein-like activities were significantly lower than preoperation values.

Adult↗
PubMed1999

Striatal dopamine receptors and transporters in monkeys with neonatal temporal limbic damage.

Developmental cortical damage has been implicated in the basic neurobiology of schizophrenia. Adult rhesus monkeys with neonatal temporal limbic damage show a stimulus-dependent disinhibition of subcortical dopamine (DA) release. We measured dopamine D2 receptors and transporters in vivo in rhesus monkeys with neonatal and adult mesial temporal limbic lesions and control monkeys to explore further the effects of this developmental lesion on striatal DA function. All monkeys were studied with [I-123]IBZM SPECT to assess the availability of striatal dopamine D2 receptors and with [I-123]beta-CIT SPECT to measure the availability of dopamine transporters in the striatum. IBZM binding was significantly reduced in monkeys with neonatal limbic lesions. No group difference in beta-CIT binding was found. The reduction in IBZM binding was significantly correlated with subcortical dopamine release after monoaminergic prefrontal stimulation as determined with in vivo microdialysis. Our findings imply specific interactions between age at lesion and the availability of DA transporter and receptors in non-human primates, and suggest that stimulus-dependent DA activity affects the expression of DA receptors.

Age Factors↗
PubMed1999

Corrosion and cytotoxicity evaluation of thermafil endodontic obturator carriers.

The purpose of this study was to evaluate the in vitro cytotoxicity of two metallic and two plastic Thermafil carrier materials, and to separately evaluate the in vitro corrosion behavior of the two metallic carriers. Stainless-steel, Ti-6AI-4V, Polysulfone, and Vectra carriers were evaluated for cytotoxicity using the ISO-recommended agar overlay test. The two metallic carriers were additionally corrosion tested in 0.9% NaCl solution for 174 wk, at 37 degrees C. Elemental analyses of the corrosion solutions were periodically conducted using inductively coupled plasma-mass spectroscopy. Agar overlay results showed that the four carrier materials were not cytotoxic to L929 fibroblasts. Inductively coupled plasma-mass spectroscopy results showed that the metallic materials had small mass loss rates. Scanning electron microscopy showed no evidence of pitting or crevice corrosion.

Alloys↗
PubMed1999

FXII levels, FXIIa-like activities and kallikrein activities in normal subjects and patients undergoing cardiac surgery.

A new chromogenic peptide substrate assay kit was used to measure factor XII (FXII) levels in plasma samples from 115 male patients with heart disease awaiting cardiac surgery, 40 age-matched normal healthy male blood donors and 20 patients before, during and after cardiopulmonary bypass surgery (CPB). Kallikrein-like and FXIIa-like activities were also determined in the CPB patient group. FXII levels were significantly lower (p = 0.0049) in the heart disease patients awaiting surgery when compared with values for the healthy donors and 13 patients (11.3%) had FXII levels below 50% compared with 1 normal donor (2.5%). During CPB significant decreases in FXII levels and significant increases in FXIIa-like and kallikrein-like activities were found indicating activation of the FXII-plasma kallikrein pathway during CPB.

Adult↗
PubMed1999

The effect of weight loss intervention on antihypertensive medication requirements in the hypertension Optimal Treatment (HOT) study.

Obesity is a significant risk factor for hypertension and the cardiovascular sequelae of hypertension. Weight loss has been shown to be effective in lowering blood pressure in overweight individuals. The purpose of this study was to show the impact of a weight loss intervention on overall medication requirements for obese, hypertensive patients. This was a substudy of the Hypertension Optimal Treatment (HOT) study. HOT study patients who had a body mass index > or =27 kg/m2 were randomized to receive either the weight loss intervention, which included dietary counseling and group support, or to serve as the control group. Patients' weights and number of medication steps (per HOT protocol) required to achieve target diastolic blood pressure were measured at 3, 6, 12, 18, 24, and 30 months. Patients in the weight loss group lost significantly more weight than the control group only at 6 months (-3.2+/-4.3 v. -1.8+/-2.7 kg [mean +/- SD] for weight loss group versus control, respectively, P = .05). The weight loss group tended to regain weight after the first 6 months of the study. However, patients in the weight loss group used a significantly fewer number of medication steps than the control group at all time intervals except 3 months. Weight loss appears to be a useful tool in blood pressure management in patients who require medication to control their blood pressure.

Adrenergic beta-Antagonists↗
PubMed1999

The efficacy of accumulated short bouts versus single daily bouts of brisk walking in improving aerobic fitness and blood lipid profiles.

Fifty-six subjects (19 men and 37 woman) aged between 40 and 66 completed the study. They were allocated into three walking groups and a control group (C). The three walking groups performed the same total amount of walking for 18 weeks, but completed it in bouts of differing durations and frequencies. These were Long Walkers (LW; 20-40 min/bout), Intermediate Walkers (IW; 10-15 min/bout) and Short Walkers (SW; 5-10 min/bout); with the IW and SW performing more than one bout of walking a day. Following the 18 week walking programme, compared to the C group all walking groups showed similar improvements in fitness as determined by a reduction in blood lactate during a graded treadmill walking test (LW 1.0 mmol/l; IW 0. 8 mmol/l; SW 1.2 mmol/l; C 0.2 mmol/l; P = 0.003) and reduction in final heart rate (LW 8 beats/min; IW 6 beats/min; SW 10 beats/min; C 0 beats/min; P = 0.056). Also compared to the C group, the LW and IW groups recorded statistically significant decreases in low-density lipoprotein cholesterol (LW 0.29 mmol/l; IW 0.41 mmol/l; P = 0.024), whereas the control group showed a mean increase of 0.22 mmol/l. The LW and IW groups also showed significant reductions in apolipoprotein (apo) A-II (LW 0.05 g/l; IW 0.02 g/l; SW 0.01 g/l; C 0.00 g/l; P = 0.012) with the LW recording a statistically significant increase in the ratio of apo A-I/A-II (LW, 0.19, P = 0. 044). In conclusion, some health benefits were achieved from all walking programmes. However, whilst the changes in aerobic fitness were similar, the effects upon blood lipid profiles were not. The findings from this study suggest that the LW regimen was most effective in benefiting blood lipid profile, followed by the IW regimen, with the SW being least potent. Nevertheless, for the sedentary/low-active members of society, any improvement in health may be considered as important. Therefore accumulated bouts of moderate intensity exercise, which according to theories of exercise behaviour may be more easily incorporated into an individual's lifestyle than single prolonged bouts, may be advocated for health promotion but may not be as effective as the traditionally prescribed 20-40 min bouts.

Adult↗