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Biomedical subjects

S Ashton

Publications and source records attributed to S Ashton.

17 recordsLinked to original sources
PubMed2001

Preventive care of older urban American Indians and Alaska natives in primary care.

Little is known about prevention among elderly or urban American Indian/Alaska Native (AI/AN) populations. We reviewed the medical records of 550 older urban AI/AN primary care patients to evaluate how frequently preventive measures were received. Adherence to guidelines was examined by a culturally appropriate (> or =50 years) and standard age threshold (> or =65 years), and by performance of preventive measures at any time ("ever") and in the past year. Lifetime performance was inadequate for the many measures, including mammograms (56%), fecal occult blood testing (37%), audiometry (33%), visual acuity testing (50%), smoking cessation counseling (50%), and pneumococcal (22%) and influenza (49%) vaccinations. Performance of the measures was less frequent in the prior year, but did not differ by age threshold. Predictors of adherence included female gender, having insurance, and having more health problems and medications. Nonadherence infrequently resulted from patients' failure to comply with recommendations. We conclude that use of most preventive services among elderly urban AI/ANs is suboptimal and should be improved.

Age Factors↗
PubMed2001

Monozygotic twins discordant for chronic fatigue syndrome: regional cerebral blood flow SPECT.

PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS. MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors. RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging. CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.

Adult↗
PubMed2001

Cognitive compromise following exercise in monozygotic twins discordant for chronic fatigue syndrome: fact or artifact?

This study examined the effects of exhaustive exercise on cognitive functioning among 21 monozygotic twin pairs discordant for chronic fatigue syndrome (CFS). The co-twin control design adjusts for genetic and family environmental factors not generally accounted for in more traditional research designs of neuropsychological function. Participants pedaled a cycle ergometer to exhaustion; maximum oxygen output capacity (VO2max) as well as perceived exertion were recorded. Neuropsychological tests of brief attention and concentration, speed of visual motor information processing, verbal learning and recognition memory, and word and category fluency were administered with alternate forms to participants pre- and postexercise. The preexercise neuropsychological test performance of CFS twins tended to be slightly below that of the healthy twin controls on all measures. However, twins with CFS did not demonstrate differential decrements in neuropsychological functioning after exercise relative to their healthy co-twins. Because exercise does not appear to diminish cognitive function, rehabilitative treatment approaches incorporating exercise are not contraindicated in CFS.

Adult↗
PubMed2001

Comorbid clinical conditions in chronic fatigue: a co-twin control study.

OBJECTIVES: Chronically fatiguing illness, defined as fatigue for at least 6 months, has been associated with various physical health conditions. Our objective was to determine whether there is a significant relationship between chronically fatiguing illness and 10 clinical conditions that frequently appear to be associated with fatigue, adjusting for the potentially confounding effects of psychiatric illness. DESIGN: A co-twin control study controlling for genetic and many environmental factors by comparing chronically fatigued twins with their nonfatigued co-twins. SETTING: A nationally distributed volunteer twin registry. PARTICIPANTS: The study included 127 twin pairs in which one member of the pair experienced fatigue of at least 6 months' duration and the co-twin was healthy and denied chronic fatigue. Fatigued twins were classified into 3 levels using increasingly stringent diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: Twins reported on a history of fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, temporomandibular disorder, interstitial cystitis, postconcussion syndrome, tension headache, chronic low back pain, chronic pelvic pain (women), and chronic nonbacterial prostatitis (men). The prevalence of these comorbid clinical conditions was significantly higher in the fatigued twins compared to their nonfatigued co-twins. Most notably, compared to their nonfatigued co-twins, the chronically fatigued twins had higher rates of fibromyalgia (> 70% vs < 10%) and irritable bowel syndrome (> 50% vs < 5%). The strongest associations were observed between chronic fatigue and fibromyalgia (odds ratios > 20), irritable bowel syndrome, chronic pelvic pain, multiple chemical sensitivities, and temporomandibular disorder (all with odds ratios > or = 4). Regression analysis suggested that the number of comorbid clinical conditions associated with chronic fatigue could not be attributed solely to psychiatric illness. CONCLUSIONS: Chronically fatiguing illnesses were associated with high rates of many other clinical conditions. Thus, patients with chronic fatigue may present a complex clinical picture that poses diagnostic and management challenges. Nonetheless, clinicians should assess such patients for the presence of comorbid clinical conditions. Future research should provide a better understanding of the temporal relationship of the onset of fatigue and these conditions, and develop strategies for early intervention.

Adult↗
PubMed2000

Use of alternative treatments by chronic fatigue syndrome discordant twins.

Background: Patients with chronic fatigue syndrome (CFS) have been faced with difficulties in diagnosis and lack of effective treatments. Anecdotal evidence suggests that use of alternative treatments may be common in these patients. Our primary objective was to compare the prevalence and patterns of alternative medicine use among twins who met the Centers for Disease Control and Prevention (CDC) CFS criteria to that of their non-CFS co-twins. Secondary goals were to assess how often alternative medicine use was discussed with physicians and the perceived benefit of these therapies. Methods: Sixty-three twin pairs discordant for CFS completed a survey about their use of 22 alternative therapies. Matched pair odds ratios and 95% confidence intervals were used to examine differences in the use between CFS twins and their non-CFS co-twins. Results: 91% of twins with CFS and 71% of non-CFS twins had used at least 1 alternative treatment in their lifetime. Twins with CFS were more likely to use homeopathy, mega-vitamins, herbal therapies, biofeedback, relaxation/meditation, guided imagery, massage therapy, energy healing, religious healing by others, and self-help groups than their non-CFS counterparts. A large proportion of all twins found alternative therapies helpful; however, only 42% of those with CFS and 23% of those without CFS discussed their use of alternative medicine with a physician. Conclusions: Individuals with CFS frequently used alternative medical treatments yet rarely communicated this use to their medical doctor. Future research should ascertain the usefulness of alternative practices in the management of CFS.

Journal Article↗
PubMed1999

Tolerance to LPS decreases macrophage G protein content.

The effects of tolerizing doses of LPS on mRNA and protein levels of three different G protein subunits were investigated to understand the mechanism(s) responsible for the reduction in Gialpha protein content in LPS tolerance. Tolerance was induced in rats using Salmonella enteritidis LPS (intraperitoneal route) with a single dose of 100 microg/kg. Peritoneal macrophages were harvested 6 and 24 h later. In some studies, a second dose of LPS 500 microg/kg was given on the following day, and peritoneal macrophages were harvested 5 days after the first injection. Macrophage RNA or a crude membrane fraction was prepared from macrophages, and the mRNA level or the protein content for Gialpha3, Gialpha2, and Gsalpha was analyzed using Northern or Western blots, respectively. Compared with the control levels, the message for Gialpha3 was reduced (p < .025) at 6 and 24 h and 5 day time periods after LPS treatment. The Gialpha2 mRNA was increased relative to the control levels (p < .05) at 6 h and 5 days after LPS treatment, respectively, and Gsalpha message was not significantly changed. The half-life of Gialpha3 mRNA was not significantly different in control versus tolerant macrophages. The Gialpha3 mRNA and membrane protein were not significantly changed by incubation with LPS for intervals up to 6 h in vitro. Macrophage membrane Gialpha3 and Gialpha1 and 2 protein content from tolerant rats were reduced compared with the controls at 6 and 24 h, respectively (p < .05). These studies are consistent with our previous observations of selective changes in macrophage Gialpha protein content in LPS tolerance and raise the possibility that this may affect signal transduction events in these cells.

Animals↗
PubMed1999

The Chronic Fatigue Twin Registry: method of construction, composition, and zygosity assignment.

Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue are conditions of unknown etiology. The Centers for Disease Control and Prevention (CDC) define CFS as an illness characterized by > or = 6 months of disabling fatigue associated with muscle pain, pharyngitis, and alterations in mood, sleep and neurocognition. We constructed a registry of twins with chronic fatigue to facilitate research on the impact of illness, the associated medical and psychosocial factors, and the heterogeneous proposed mechanisms for these conditions. We have recruited 204 twin pairs in which one or both members reported persistent fatigue through patient support group newsletters (60%), clinicians/researchers familiar with CFS (12%), notices placed on electronic bulletin boards for CFS (11%), twin organizations and researchers (6%), relatives and friends (3%) and other sources (8%). Complete data are available for 177 pairs (87%). Twins completed an extensive questionnaire booklet that included measures of physical and mental health, functional status, and psychosocial factors; a structured psychiatric interview was also conducted by telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic fatigue: 1) > or = 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured interview (69 discordant pairs and 25 concordant pairs). Despite the limitations of a volunteer registry, the Chronic Fatigue Twin Registry promises to be an important resource for research on CFS and chronic fatigue.

Diseases in Twins↗
PubMed1998

Suppressed thromboxane production in endotoxin-desensitized THP-1 cells is not a result of decreased prostaglandin H synthase activity.

Pre-exposure of THP-1 cells to low concentrations of endotoxin (lipopolysaccharide, LPS) down-regulates thromboxane (Tx) A2, an arachidonic acid (AA) metabolite, production in response to a subsequent LPS stimulation. To further delineate the mechanisms of LPS-induced down-regulation of TxA2, we examined expression of prostaglandin H synthase (PGHS)-2 mRNA, changes in PGHS activity, and content of PGHS-1 and -2. Pre-exposure to LPS (1 microg/mL for 18 h to desensitize cells) inhibits production of TxB2, the stable metabolite of TxA2, in response to secondary stimulation of LPS (10 microg/mL), when compared with LPS-stimulated naive cells (p < .05, n=5). LPS (10 microg/mL) induced expression of PGHS-2 mRNA at 1 and 2 h in naive cells, but this expression was decreased in the LPS-desensitized cells. However, exogenous AA (16 microM) or phorbol myristic acid (PMA), 3 microM) stimulated greater TxB2 production in the LPS-desensitized cells than in the naive cells (p < .05). Protein content of PGHS-1 and -2 were examined by Western blot analysis, using antibodies specific for PGHS-1 and PGHS-2. Densitometric analysis demonstrated a significant increase in PGHS-2 induction in LPS-stimulated naive cells (405+/-174%) over its respective basal group (p < .05, n=5). PGHS-1 was constitutively present, but there was no significant difference in quantity between naive and LPS-desensitized basal or LPS-stimulated groups. Thus, despite the reduction in expression of PGHS-2 mRNA, these composite data demonstrate that down-regulation of PGHS activity (assessed with exogenous AA or PMA) cannot be responsible for the inhibition of AA metabolism observed in LPS desensitization.

Arachidonic Acid↗
PubMed1992

Use of the neural cell adhesion molecule VASE exon by neurons is associated with a specific down-regulation of neural cell adhesion molecule-dependent neurite outgrowth in the developing cerebellum and hippocampus.

The development of the CNS is associated with an increasing use of the 30-bp variable alternative, spliced exon (VASE) in neural cell adhesion molecule (NCAM). We have assessed the relative usage of VASE by reverse transcriptase-linked polymerase chain reaction in the developing cerebellum and hippocampus at times when neurons isolated from these tissues can respond to substrate-associated NCAM by increased axonal growth and also at later developmental stages, when they are no longer responsive to substrate-associated NCAM. Neurons isolated from the developing cerebellum at postnatal day 6 respond to NCAM with increased neurite growth. NCAM transcripts from these cells were found to have negligible levels of VASE usage. In contrast, neurons that are isolated at later stages of development (postnatal days 8, 10, and 11) and do not respond to NCAM were found to synthesise a much higher proportion of NCAM transcripts containing VASE. In the hippocampus, embryonic day 18 neurons, which are responsive to NCAM, express low levels of VASE, whereas postnatal days 4 and 5 neurons, which are not responsive to NCAM, have a greater proportion of transcripts containing VASE. Thus, the level of NCAM VASE exon usage by neurons appears to be a good indicator of the ability of these cells to respond to non-VASE-containing NCAM (expressed in a cellular substratum) by increased neurite outgrowth.

Alternative Splicing↗
PubMed1991

Effect of the LTD4 receptor antagonist LY203647 on endotoxic shock sequelae in the rat.

This study investigated the effect of a novel LTD4 receptor antagonist LY203647 on Salmonella enteritidis endotoxin-induced shock sequelae in anesthetized rats. LY203647 (30 mg/kg i.v.) or vehicle was given 10 min prior to endotoxin (10 mg/kg i.v.) or its vehicle, and the hematocrit, mean arterial pressure and circulating leukocyte counts were determined. LY203647 significantly inhibited endotoxin-induced hemoconcentration up to 90 min post-endotoxin (46.7 +/- 1.3 vs. 51.9 +/- 2.4% at 30 min post-endotoxin, 45.9 +/- 1.1 vs. 53.1 +/- 1.4% at 90 min post-endotoxin, N = 8-9, P less than 0.05). The endotoxin-induced decreases in mean arterial pressure were also attenuated by LY203647, -29 +/- 5 vs. -56 +/- 9 mm Hg at 60 min post-endotoxin and -42 +/- 4 vs. -60 +/- 9 mm Hg at 90 min post-endotoxin (N = 9-10, P less than 0.05). LY203647 also attenuated endotoxin-induced decreases in leukocyte count in arterial blood. A study of differential counts in circulating leukocytes (N = 3) showed that endotoxin induced complete disappearance in circulating neutrophils. The circulating lymphocyte count was decreased by 30 +/- 10 and 41 +/- 1% at 15 and 30 min post-endotoxin, respectively. LY203647 inhibited endotoxin-induced lymphopenia (P less than 0.05) but failed to alter endotoxin-induced neutropenia. These data suggest that LTD4 may play an important role in mediating hemoconcentration, hypotensive and lymphocytopenic sequelae of endotoxin shock.

Acetophenones↗
PubMed1990

Phenylethylamine metabolism in Tourette's syndrome.

Beta-phenylethylamine, phenylalanine, and phenylacetic acid were examined in 24-hour urine samples and/or plasma samples obtained from 28 medication-free patients with Tourette's syndrome and 20 control subjects matched for age and education. Statistical analyses revealed that Tourette patients had lower plasma phenylalanine and urinary free beta-phenylethylamine compared with the controls, but did not differ on urinary total levels of phenylacetic acid. Fifty percent of the Tourette patients had a urinary beta-phenylethylamine level that was lower than the lowest control subject. In addition, urinary beta-phenylethylamine levels were inversely related to several scores from the Tourette Syndrome Global Scale. These data suggest that abnormalities in synthesis or metabolism of beta-phenylethylamine may be involved in the etiology of some patients with Tourette's syndrome.

Child↗
PubMed1976

Drivers use of seat belts as a function of attitude and anxiety.

It is shown that drivers' reported and actual use of seat belts are predictable from their opinions about the comfort and effectiveness of belts. These relationships are, however, moderated by anxiety about possible accidents, in that low-anxiety drivers exhibit a stronger association between attitude and behaviour than do high-anxiety drivers.

Accidents, Traffic↗
PubMedDate not supplied

Results of isoproterenol tilt table testing in monozygotic twins discordant for chronic fatigue syndrome.

BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is unknown. Neurally mediated hypotension (NMH) has been suggested as a common comorbid condition or a potential underlying cause. METHODS: We conducted a cotwin control study of 21 monozygotic twins who were discordant for CFS. One twin met the 1994 Centers for Disease Control and Prevention criteria for CFS, and the other twin was healthy and denied chronic fatigue. The twins were selected from a volunteer twin registry in which at least 1 member reported persistent fatigue. As part of a 7-day clinical evaluation, all 21 twin pairs were evaluated with a 3-stage tilt table test with isoproterenol hydrochloride for the assessment of NMH. The presence of NMH was defined as syncope or presyncope associated with a decrease of 25 mm Hg in blood pressure and no associated increase in heart rate. RESULTS: A positive tilt table test result was observed in 4 twins with CFS (19%) and in 4 healthy twins (19%). This difference was not statistically significant (matched pair odds ratio, 1.0; 95% confidence interval, 0.2-5.4; P>.90). Compared with the healthy twins, the twins with CFS reported more severe symptoms of CFS and NMH both in the week before and during the tilt table test. CONCLUSIONS: These results do not support a major role for NMH in CFS. They highlight the importance of selecting well-matched control subjects, as well as the unique value of the monozygotic cotwin control design in the study of this illness. Arch Intern Med. 2000;160:3461-3468.

Adult↗
PubMedDate not supplied

Urinary excretion of MHPG and normetanephrine in attention deficit hyperactivity disorder.

Twenty-four-hour excretion (expressed per gram of creatinine) of the norepinephrine metabolites 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and normetanephrine (NME) was measured in children with attention deficit hyperactivity disorder (ADHD) and in normal subjects matched for age and education. In contrast to findings with Tourette syndrome patients, in the ADHD patients there was no significant difference in excretion of MHPG and NME from control values.

Attention Deficit Disorder with Hyperactivity↗
PubMedDate not supplied

Transforming growth factor beta 1 alters rat peritoneal macrophage mediator production and improves survival during endotoxic shock.

Transforming Growth Factor beta 1 (TGF-beta 1) is a potent anti-inflammatory cytokine involved in wound healing. Because of its anti-inflammatory actions, the effects of TGF-beta 1 were studied in vitro on rat macrophage inflammatory mediator production and in vivo on Salmonella enteritidis endotoxin (LPS) induced lethality. TGF-beta 1's effect on stimulated rat peritoneal macrophage (MO) production of prostacyclin and nitric oxide were assessed via measurement of their stable metabolites, 6-keto-PGF-1 alpha and nitrite, respectively. TGF-beta 1 (10 ng/ml) pretreatment (3 hours) resulted in significant reductions (p < 0.05) of LPS (50 micrograms/ml) stimulated, lipid A (1 and 10 micrograms/ml) stimulated, arachidonic acid (16 microM) stimulated, and Ca++ ionophore (10 microM) stimulated MO 6-keto-PGF 1 alpha production. These data suggest that TGF-beta 1 inhibits LPS stimulated MO 6-keto-PGF-1 alpha production by acting at, or distally to, phospholipase A2, possibly at the level of cyclooxygenase in the arachidonic acid cascade. In a similar study, TGF-beta 1 pretreatment led to a significant (p < 0.05) reduction of LPS stimulated MO nitrite production. In subsequent studies, the effects of TGF-beta 1 were studied in vivo on rats challenged with lethal doses of LPS. Rats pretreated with TGF-beta 1 (250 ng/rat i.v.) exhibited a significant increase (p < 0.01, n = 15 rats/group) in mean survival time compared to control rats. The increased survival time of TGF-beta 1 pretreated rats with LPS shock may be due, in part, to altered production of MO mediators.

6-Ketoprostaglandin F1 alpha↗