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Biomedical subjects

W T Longstreth

Publications and source records attributed to W T Longstreth.

At least 37 records · Page 2Linked to original sources

Intracranial meningioma and ionizing radiation in medical and occupational settings.

In a population-based case-control study of 200 cases and 400 controls in western Washington State, the authors assessed associations between meningioma and ionizing radiation in medical and occupational settings. No significant associations were observed for diagnostic studies or occupational settings, but associations were observed for radiation therapy to head or neck (odds ratio 3.7, 95% CI 1.5 to 9.5), especially for neoplastic conditions. Only four patients (2%) had meningiomas that followed high-dose cranial radiation.

Adolescent↗

Fish consumption and stroke risk in elderly individuals: the cardiovascular health study.

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential. METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained. RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55-0.98) and 30% lower risk with intake of 5 or more times per week (HR, 0.70; 95% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke. CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.

Age Distribution↗

Pesticides and risk of Parkinson disease: a population-based case-control study.

BACKGROUND: Pesticide exposures are suspected risk factors for Parkinson disease (PD), but epidemiological observations have been inconsistent. OBJECTIVE: To investigate associations between pesticide exposures and idiopathic PD. DESIGN: Population-based case-control study. SETTING: Group Health Cooperative, a health care system in western Washington State, and the University of Washington. PARTICIPANTS: Two hundred fifty incident PD case patients and 388 healthy control subjects (age- and sex-matched). We assessed self-reported pesticide exposures using a structured interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression models, controlling for age, sex, and smoking. RESULTS: Odds ratios for occupational exposures were not significant but suggested a gradient that paralleled occupational exposures (pesticide worker: OR, 2.07; 95% CI, 0.67-6.38; crop farmer: OR, 1.65; 95% CI, 0.84-3.27; animal and crop farmer: OR, 1.10; 95% CI, 0.60-2.00; and dairy farmer: OR, 0.88; 95% CI, 0.46-1.70). Odds ratios for organophosphates paralleled the World Health Organization hazard classifications, with parathion much higher than diazinon or malathion. We also found elevated ORs from herbicides (OR, 1.41; 95% CI, 0.51-3.88) and paraquat (OR, 1.67; 95% CI, 0.22-12.76). We found no evidence of risk from home-based pesticide exposures. We found significantly increased ORs from lifelong well water consumption (OR, 1.81; 95% CI, 1.02-3.21). CONCLUSIONS: The findings for occupational pesticide exposures are consistent with a growing body of information linking pesticide exposures with PD. However, the lack of significant associations, absence of associations with home-based exposures, and weak associations with rural exposures suggest that pesticides did not play a substantial etiologic role in this population.

Adult↗

Hypothesis: a motor neuron toxin produced by a clostridial species residing in gut causes ALS.

We hypothesize that a yet-to-be-identified motor neuron toxin produced by a clostridial species causes sporadic amyotrophic lateral sclerosis (ALS) in susceptible individuals. This clostridial species would reside undetected in the gut and chronically produce a toxin that targets the motor system, like the tetanus and botulinum toxins. After gaining access to the lower motor neuron, the toxin would be transported back to the cell body, as occurs with the tetanus toxin, and destroy the lower motor neuron - the essential feature of ALS. Again like the tetanus toxin, some of the toxin would cross to neighboring cells and to the upper motor neuron and similarly destroy these motor neurons. Weakness would relentlessly progress until not enough motor neurons remained to sustain life. If this hypothesis were correct, treatment with appropriate antibiotics or antitoxins might slow or halt progression of disease, and immunization might prevent disease.

Amyotrophic Lateral Sclerosis↗

Quantitative assessment of spasticity in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

People with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develop spasticity. The authors examined 34 patients with HAM/TSP in Perú using a device that measures tone in the gastroc-soleus-Achilles tendon unit and provides a quantitative spasticity assessment (QSA). Tone in the 34 patients was more than double that of women with asymptomatic HTLV-I infection. The device may help to track progression in HTLV-I infection.

Adult↗

Dopamine transporter (SLC6A3) 5' region haplotypes significantly affect transcriptional activity in vitro but are not associated with Parkinson's disease.

The dopamine transporter (DAT) plays a critical role in dopaminergic neurotransmission and is also the major site of action for some drugs of abuse. The coding region of the DAT gene, SLC6A3, is well conserved, but non-coding regions are more variable, most notably a variable number of tandem repeats (VNTR) polymorphism in the 3' untranslated region, which has been studied in a number of dopamine-related neurological disorders, including Parkinson's disease (PD). We aimed to characterize variation in the 5' region of SLC6A3 because little is known about the extent of variation in this region and potential consequences of such variation on gene expression. We identified multiple single nucleotide polymorphisms (SNPs) covering approximately 5000 bp 5' of exon 1 through the start of exon 2 (+2106). These SNPs segregated as eight haplotypes, six of which were common. These haplotypes differed significantly in activity in a reporter gene activity assay. However, we did not observe associations between common SNPs or haplotypes and PD in a case-control study of 261 incident cases and 376 age- and gender-matched unrelated controls. By contrast, we did observe a modest association of the 3' VNTR 9-repeat allele with PD (odds ratio=1.45; 95% confidence interval=1.04-2.03). This association was limited to subjects 60 years of age and greater versus those less than 60 years of age. We conclude that although DAT 5' region SNPs haplotypes significantly alter in vitro transcriptional activity, they are not related to PD risk. In addition, our findings provide further evidence supporting an association of PD with the VNTR polymorphism.

3' Untranslated Regions↗

Ventricular cerebrospinal fluid hypocretin-1 inversely correlates with glucose levels in cerebrospinal fluid and serum from patients with neurological injuries.

INTRODUCTION: Hypocretin-1 is a hypothalamic neuropeptide that may help regulate arousal and feeding behavior and is quantifiable in cerebrospinal fluid (CSF). In this retrospective pilot study, hypocretin-1 levels obtained from ventricular CSF of neurologically injured patients were correlated with clinical and laboratory results to test whether arousal or metabolic factors might be related to the level of hypocretin-1. METHODS: CSF samples from a heterogeneous group of neurosurgical patients with externally draining intraventricular catheters were assayed in a standard manner for hypocretin-1 and other routine laboratories. Associations were sought between hypocretin-1 and clinical data such as body mass index (BMI), temperature, and Glasgow Coma Scale (GCS) score and between hypocretin-1 and laboratory data such as serum and CSF glucose, protein, and cell counts. RESULTS: Lower levels of ventricular CSF hypocretin-1 were correlated with higher levels of serum (p = 0.020) and ventricular CSF glucose (p = 0.001). Clinical findings such as BMI, temperature, and GCS failed to correlate with hypocretin-1. CONCLUSIONS: In a group of neurologically injured patients, hypocretin-1 and glucose levels are inversely correlated. More studies are needed to investigate these associations, particularly in a homogenous patient sample.

Adult↗

Active and passive cigarette smoking and risk of intracranial meningioma.

Motivated by prior studies, we examined associations between cigarette smoking and risk of intracranial meningioma in a population-based case-control study, including 200 cases and 2 controls matched to each case on age and sex. Subjects were asked to recall their history of active and passive cigarette smoking occurring 10 or more years before the date of meningioma surgery. Ever active smoking was associated with an increased risk of meningioma in men (OR = 2.1; 95% CI 1.1-4.2) but not in women (OR = 0.7; 95% CI 0.5-1.1). The statistical interaction by gender was significant (p = 0.01). In men, risk increased with increasing number of cigarettes smoked daily (p for trend = 0.04). In women, the trend was opposite (p for trend = 0.08). Among never active smokers, passive smoking from a spouse was associated with increased risk in both sexes (OR 2.0; 95% CI 1.1-3.5), and risk increased with increasing duration of exposure (p for trend = 0.02). Uncertain is whether these findings reflect a true biological phenomenon or result from chance or uncontrolled confounding.

Adolescent↗

No associations between Parkinson's disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes.

Reactive oxygen species derived from dopamine metabolism can induce oxidative stress and thus may contribute to Parkinson's disease (PD) pathogenesis. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) detoxify quinones and quinonoid compounds. We investigated associations of genetic polymorphisms of NQO1 (C609T) and NQO2 (I/D, 29 base pairs) with PD in a population-based case-control study of 190 idiopathic PD cases and 305 unrelated controls matched on age and sex. No associations were detected for either gene variant or for any allele combinations.

Aged↗

Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging. METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade. RESULTS: Worsening was evident in 538 participants (28%), mostly (85%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk. CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

Aged↗

Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups.

OBJECTIVE: To perform a health maintenance organization-based case-control study to evaluate the association of total and high density lipoprotein (HDL) cholesterol with the risk of stroke subtypes and in patient subgroups. METHODS: Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke (n = 313). Controls (n = 6,455) were identified in a companion myocardial infarction study. Risk of stroke was modeled using logistic regression. RESULTS: The highest total cholesterol quintile was associated with an increased risk of ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0) with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated with a decreased risk of ischemic stroke compared to the lowest quintile (OR = 0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol association was more important for patients < 66 years of age and those with HDL < 50 mg/dL; the HDL association was more important for patients without diabetes or atrial fibrillation. The second through fourth total cholesterol quintiles were associated with a decreased risk of hemorrhagic stroke compared to the lowest quintile (OR = 0.7, CI 0.5 to 1.0). CONCLUSIONS: Higher total and lower HDL cholesterol levels were associated with increased risk of ischemic stroke, especially certain stroke subtypes and patient subgroups. The lowest levels of total cholesterol were associated with an increased risk of all hemorrhagic strokes.

Adult↗

Stroke risk factors and loss of high cognitive function.

BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition. METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS). RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction). CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.

Aged↗

Human T cell lymphotropic virus type 1 infection and early neurologic development: a pilot study of 48 children.

To determine whether human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with delayed neurological development, we examined 48 Peruvian children with exposure to HTLV-1 who were identified at the Instituto Materno-Perinatal. Compared with 38 HTLV-1-seronegative children, the 10 seropositive children did not have higher rates of neurodevelopmental delay. Long-term follow-up is planned.

Antibodies, Viral↗

White matter hyperintensity on cranial magnetic resonance imaging: a predictor of stroke.

BACKGROUND AND PURPOSE: We have previously reported that several "silent" infarcts found on magnetic resonance imaging (MRI) were a risk factor for stroke. Several recent reports have shown that high white matter grade (WMG) and increasing WMG over time were risk factors for stroke. We tested the hypothesis that high WMG > or =2 was a predictor of risk for stroke, independent of other risk factors. METHODS: We examined the extent of white matter hyperintensity on cranial MRI of 3293 participants from the Cardiovascular Health Study (CHS). The degree of white matter hyperintensity was graded from least severe (grade=0) to most severe (grade=9). Participants were followed-up for an average of 7 years for the occurrence of a stroke. Clinical stroke diagnoses were based on hospital records reviewed by an adjudication committee expert in stroke diagnosis. During this period, 278 strokes occurred. Results The relative risk of stroke increased significantly as the WMG increased. The risk of stroke was 2.8% per year for participants with high WMG (grades > or =5), compared with only 0.6% for participants with grades 0 to 1.Conclusions The risk of stroke with high WMG is independent of traditional stroke risk factors and persists when controlling for MRI infarcts, another subclinical imaging marker of cerebrovascular disease. Assessment of white matter disease may be valuable in assessing future risk of stroke.

Aged↗

Dental X-rays and the risk of intracranial meningioma: a population-based case-control study.

BACKGROUND: Ionizing radiation is a likely cause of intracranial meningioma. The authors determined whether the risk of intracranial meningioma was associated with past dental X-rays-specifically, posterior bitewings, full-mouth series, and lateral cephalometric and panoramic radiographs. METHODS: The authors conducted a population-based case-control study of residents of King, Pierce, and Snohomish counties in western Washington State. Case patients (n = 200) had an incident intracranial meningioma that was confirmed histologically during life between January 1995 and June 1998. The authors used random-digit dialing and Medicare eligibility lists to identify two control subjects to be matched to each case patient based on age and gender. Exposures were determined during an in-person interview. The authors compared self-report and dental records in a subset of study participants. RESULTS: Of the 4 dental X-ray procedures evaluated, only the full-mouth series (specifically, > or = 6 over a lifetime) was associated with a significantly increased risk of meningioma (odds ratio, 2.06; 95% confidence limits, 1.03-4.17). However, evidence for a dose-response relation was lacking (P for trend = 0.33). The risk was elevated with the aggregate number of full-mouth series in 10-year periods from approximately 15-40 years before diagnosis, with significant elevations in the 10-year periods beginning 22-30 years before diagnosis. The risks in these analyses were even greater when only women were considered. CONCLUSIONS: Dental X-rays involving full-mouth series performed 15-40 years ago, when radiation exposure from full-mouth series was much greater than it is now, were associated with an increased risk of meningioma. The authors did not observe an increased risk with bitewings, lateral cephalometric, and panoramic radiographs.

Adult↗

Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease.

BACKGROUND: Whether carotid artery disease is a cause of cognitive impairment in persons who have not had stroke is unknown. If this is the case, diminished performance on the Modified Mini-Mental State Examination should be more common in persons with left carotid artery disease than in those with right carotid artery disease. OBJECTIVE: To determine whether left carotid artery disease is associated with cognitive impairment. DESIGN: Cross-sectional and cohort study. SETTING: Four U.S. communities participating in the Cardiovascular Health Study. PATIENTS: 4006 right-handed men and women 65 years of age or older without history of stroke, transient ischemic attack, or carotid endarterectomy. MEASUREMENTS: Internal carotid artery stenosis and intima-media thickness of the common carotid artery were assessed by using duplex ultrasonography. Cognitive impairment was defined as a score less than 80 on the Modified Mini-Mental State Examination, and cognitive decline was defined as an average decrease of more than 1 point annually in Modified Mini-Mental State Examination score during up to 5 years of follow-up. Multivariate logistic regression models were used to estimate the risk for cognitive impairment and decline associated with left internal carotid artery stenosis and intima-media thickness, after adjustment for measures of right-sided disease and risk factors for vascular disease. RESULTS: After adjustment for right-sided stenosis, high-grade (> or =75% narrowing of diameter) stenosis of the left internal carotid artery (32 patients) was associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1] compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to 6.3]). Intima-media thickness of the left common carotid artery was associated with cognitive impairment and decline in univariate analysis, but this effect did not persist after adjustment. CONCLUSIONS: Cognitive impairment and decline are associated with asymptomatic high-grade stenosis of the left internal carotid artery. The persistence of the association after adjustment for right-sided stenosis indicates that the association is not due to underlying vascular risk factors or atherosclerosis in general.

Aged↗