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Biomedical subjects

W T Longstreth

Publications and source records attributed to W T Longstreth.

At least 55 records · Page 3Linked to original sources

Plasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons: the Cardiovascular Health Study.

BACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI). DESIGN: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype. RESULTS: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P =.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P =.07 for linear trend). CONCLUSION: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.

Aged↗

DNA sequence analysis of monoamine oxidase B gene coding and promoter regions in Parkinson's disease cases and unrelated controls.

The allele G of the intron 13 G/A polymorphism of the monoamine oxidase B gene (MAO-B) has been associated with Parkinson's disease (PD) in several studies. Apart from a potential direct effect on splicing processes, the association of this intronic polymorphism with PD is due possibly to linkage disequilibrium with other mutations in the coding or promoter regions of the gene. We addressed this latter hypothesis by determining the DNA sequence of the entire MAO-B coding region comprising 15 exons and partial intronic sequences flanking each exon, in 33 cases with idiopathic PD and 38 unrelated controls. The promoter region of MAO-B gene up to base -1,369 from ATG (start point of mRNA translation) was also sequenced to identify variants with potential functional effects on gene transcription. In the promoter region, a new polymorphism consisting of a C to T single base change was detected in position -1,114 from ATG, with an allelic frequency of 3.5%, but it was not associated with PD risk. No commonly occurring (>10%) polymorphisms were found in the exons or the intronic sequences flanking the exons, although several rare variants were detected in the coding and promoter regions.

Aged↗

Family history as a risk factor for stroke in young women.

BACKGROUND: Family history of stroke (FHS) is associated with risk of stroke in middle-aged to elderly populations. However, few studies have examined this association in younger women or by stroke type. A population-based, case-control study was conducted to examine the association of FHS and risk of stroke in young women, and to determine whether the association is independent of other stroke risk factors. METHODS: Cases were women aged 18 to 44 years, with first, nonfatal ischemic (n =49) and hemorrhagic (n = 63) strokes in western Washington State in 1991 to 1995. Demographically similar community controls (n = 446) were identified through random-digit telephone dialing. Information on FHS in first-degree relatives (parents and siblings) and other risk factors was obtained through an interview. Person-years (P-Y) at risk of stroke for relatives of each subject were included in polytomous logistic regression models to adjust for family size. The analysis was conducted between 1999 and 2000. RESULTS: After adjustment for age and P-Y, FHS in first-degree relatives was significantly associated with an increased risk of hemorrhagic (odds ratio [OR]=2.6, 95% confidence interval [CI]=1.5-4.3) and ischemic stroke (OR=2.1, 95% CI=1.2-3.9). FHS remained associated with risk of hemorrhagic stroke (OR=2.4, 95% CI=1.4-4.1) and ischemic stroke (OR=1.8, 95%CI=0.9-3.5) after further adjustment for diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, smoking, alcohol, and family history of myocardial infarction. Findings were similar when associations with parental and sibling FHS were examined separately. CONCLUSIONS: Family history of stroke is a risk factor for both hemorrhagic and ischemic strokes among young women.

Adolescent↗

Self-reported alcohol consumption and falls in older adults: cross-sectional and longitudinal analyses of the cardiovascular health study.

OBJECTIVES: To assess the cross-sectional and longitudinal associations between alcohol consumption and risk of falls in older adults. DESIGN: Cross-sectional and longitudinal analyses. SETTING: Four U.S. communities. PARTICIPANTS: A total of 5,841 older adults enrolled in the Cardiovascular Health Study, an ongoing, population-based, prospective cohort study, participated. MEASUREMENTS: Self-reported alcohol consumption at baseline, self-reported frequent falls at baseline, and the 4-year risk of falls of participants who denied frequent falls at baseline. RESULTS: Cross-sectional analysis indicated an apparent inverse association between alcohol consumption and risk of frequent falls (adjusted odds ratio in consumers of 14 or more drinks per week=0.41; 95% confidence interval (CI)=0.14-1.17; P for trend=.06), but longitudinal analysis indicated a similar 4-year risk of falls in abstainers and light to moderate drinkers but a 25% higher risk in consumers of 14 or more drinks per week (95% CI=3-52%; P for trend=.07). Similar results were found in analyses stratified by age, sex, race, and physical activity. CONCLUSION: Consumption of 14 or more drinks per week is associated with an increased risk of subsequent falls in older adults. Cross-sectional studies may fail to identify this risk of heavier drinking, perhaps because older adults at risk for falls decrease their alcohol use over time or because heavier drinkers at risk for falls tend not to enroll in cohort studies. However, because this study relied upon annual reporting of falls, further prospective studies should be conducted to confirm these findings.

Accidental Falls↗

Increased pelvic vein thrombi in cryptogenic stroke: results of the Paradoxical Emboli from Large Veins in Ischemic Stroke (PELVIS) study.

BACKGROUND AND PURPOSE: Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT). METHODS: At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans. RESULTS: The 95 patients who met entry criteria were scanned. Their mean+/-SD age was 46+/-10 years, and time from stroke onset to pelvic MRV scan was 49+/-16 hours. Compared with those with stroke of determined origin (n=49), patients with cryptogenic stroke (n=46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P<0.03), with most having an appearance of a chronic DVT. CONCLUSIONS: In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke.

Adolescent↗

Parkinson's disease risks associated with dietary iron, manganese, and other nutrient intakes.

BACKGROUND: Dietary influences on oxidative stress have been thought to play important role in the etiology of PD. OBJECTIVE: To examine associations of PD with dietary nutrients, including minerals, vitamins, and fats. METHODS: A population-based case-control study was conducted among newly diagnosed case (n = 250) and control subjects (n = 388) identified between 1992 and 2002 from enrollees of the Group Health Cooperative health maintenance organization in western Washington state. Controls were frequency matched to cases on sex and age. In-person interviews elicited data on food frequency habits during most of adult life. Nutrient intakes were calculated and analyzed by adjusting each person's nutrient intake by their total energy intake (the nutrient density technique). RESULTS: Subjects with an iron intake in the highest quartile compared with those in the lowest quartile had an increased risk of PD (odds ratio = 1.7, 95% CI: 1.0, 2.7, trend p = 0.016). There was an apparent joint effect of iron and manganese; dietary intake above median levels of both together conferred a nearly doubled risk compared with lower intakes of each nutrient (odds ratio = 1.9, 95% CI: 1.2, 2.9). No strong associations were found for either antioxidants or fats. CONCLUSION: A high intake of iron, especially in combination with high manganese intake, may be related to risk for PD.

Adult↗

Prospective study of alcohol consumption and risk of dementia in older adults.

CONTEXT: Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. OBJECTIVE: To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. MAIN OUTCOME MEASURES: Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. RESULTS: Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term =.001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E epsilon4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. CONCLUSIONS: Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.

Aged↗

Prognosis in amyotrophic lateral sclerosis: a population-based study.

BACKGROUND: Accurate information on prognosis of ALS is useful to patients, families, and clinicians. METHODS: In a population-based study of ALS in western Washington, the authors assembled a cohort of 180 patients with incident ALS between 1990 and 1994. Information on potential prognostic factors was collected during an in-person interview. Patients also completed the Medical Outcomes Study Short Form 36 (SF-36). Vital status through December 1999 was known for all patients. RESULTS: Median survival was 32 months from onset of symptoms and 19 months from diagnosis. The 5-year survival after diagnosis was 7%. Older age and female sex were strongly associated with poor survival. In multivariable Cox proportional hazards regression models, factors significantly and independently associated with a worse prognosis included older age, any bulbar features at onset, shorter time from symptom onset to diagnosis, lack of a marital partner, and residence in King County. Recursive partitioning identified age, time from symptom onset to diagnosis, and marital status as the strongest predictors of survival. Good summary scores for physical health on the SF-36, but not for mental health, were significantly associated with longer survival than poor scores. CONCLUSION: These findings are consistent with other population-based studies of ALS and confirm its pernicious nature. Older age, female sex, any bulbar features at onset, short time from symptom onset to diagnosis, lack of a marital partner, and disease severity are key prognostic factors. Serial measurement of severity would likely improve predictions.

Adult↗

Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.

Oxidative stress is widely thought to contribute significantly to the pathogenesis Parkinson's disease (PD). Given the role of glutathione S-transferases (GSTs) in the conjugation of electrophiles and protection against reactive oxygen species, genes encoding the GSTs have been considered candidates for association studies of PD. We tested for associations between genotypes of GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non-deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of 214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of Caucasian ethnicity. No significant associations with any of the GST genotypes were observed. However, there was a marginally significant difference in the distribution of GSTP1 104 genotypes between cases and controls (P=0.07), with an excess of Ile104Val heterozygotes found among cases (odds ratio (OR)=1.43; 95% Confidence Interval (CI): 0.98-2.08). This difference in the genotype distribution was strongest among smokers (OR for heterozygote=1.92; 95% CI: 1.12-3.29) versus non-smokers and among males (OR for heterozygote=1.99; 95% CI: 1.24-3.19) versus females. The distribution of GSTP1 Ile104Val and Ala113Val haplotypes did not differ between cases and controls. Taken together, these results suggest a potentially minor role of GSTP1 in PD, but do not give evidence for associations with either GSTM1 or GSTT1.

Adult↗

Hypertension and cognitive function: pathophysiologic effects of hypertension on the brain.

Accumulating evidence supports a causal role of hypertension for cognitive decline above and beyond its relationship to frank stroke. Hypertension-associated pathologic changes in the brain and its vasculature include vascular remodeling, impaired cerebral autoregulation, cerebral microbleeds, white matter lesions, unrecognized lacunar infarcts, and Alzheimer-like changes such as amyloid angiopathy and cerebral atrophy. White matter lesions and retinal vascular changes, both of which can be imaged noninvasively, may reveal the general condition of the cerebral vasculature or the presence of arteriosclerotic or hypertensive encephalopathy. These noninvasive indicators may also identify a subgroup in whom infarct prevention, particularly via blood pressure reduction, is of paramount importance. Optimal control of blood pressure on a population-wide basis, but particularly in those prone to cognitive loss, is thus a critically important but as yet elusive goal that should be fully exploited for its potential to reduce future cognitive impairment.

Alzheimer Disease↗

Serum potassium and stroke risk among treated hypertensive adults.

BACKGROUND: In prospective studies, hypokalemia has been shown to be associated with a subsequent increase in stroke risk in treated hypertensive adults after 4 to 16 years of follow-up. Stroke risk associated with more recent assessments of hypokalemia has not been examined. METHODS: We used data from an on-going, population-based, case-control study of incident stroke at Group Health Cooperative (GHC). Cases were treated hypertensive adults, 30 to 79 years old, who sustained an incident ischemic or hemorrhagic stroke between July 1989 and December 2000. Controls were GHC members without a history of stroke who met same inclusion criteria as cases. Serum potassium (K(+)) levels were collected from GHC laboratory database. Hypokalemia (< or =3.4 mM/L) was defined using the most recent serum K(+) measure in the year before the index date (event date for cases; random date within calendar year of identification for controls). Multivariate logistic regression estimated the relative risk of ischemic and hemorrhagic stroke. RESULTS: Among 593 ischemic and 125 hemorrhagic stroke cases, and 2397 controls, few subjects were hypokalemic: 3%, 6%, and 2%, respectively. Using the normal range of serum K(+) as a reference (3.5 to 5.0 mM/L), hypokalemia was associated with an elevated risk of ischemic (odds ratio [OR]: 2.04; 95% confidence interval [CI]: 1.14-3.64) and hemorrhagic stroke (OR: 3.29; 95% CI: 1.45-7.48) in adjusted analyses. Associations were not modified by diuretic use. CONCLUSIONS: In adults with treated hypertension, hypokalemia in the year before a stroke was associated with an increased risk of incident ischemic and hemorrhagic stroke independent of diuretic use when compared to normal serum K(+) levels.

Aged↗

Elevated risk of stroke among patients with end-stage renal disease.

BACKGROUND: Although end-stage renal disease (ESRD) has been associated with accelerated vascular disease of the cerebral circulation, there are no prior studies that have estimated the risk of hemorrhagic and ischemic stroke among the United States dialysis population relative to the general population. METHODS: We performed a population-based cohort study to compare rates of hospitalized ischemic and hemorrhagic stroke among incident dialysis patients in the United States Renal System database and non-ESRD subjects from the general population identified in the National Hospital Discharge Survey. RESULTS: After adjustment for age, gender, and race, estimated rates of hospitalized stroke were markedly higher for dialysis patients compared to the general population. The age-adjusted relative risk (RR) of stroke among dialysis patients compared to the general population was 6.1 [95% Confidence Interval (95% CI) 5.1, 7.1] for Caucasian males, 4.4 (95% CI 3.3, 5.5) for African American males, 9.7 (95%CI 8.2, 11.2) for Caucasians females and 6.2 (95%CI 4.8, 7.6) for African American females. When considered as separate outcomes, hospitalization rates for hemorrhagic and ischemic stroke were both markedly elevated for subjects treated with dialysis (ischemic, RR = 4.3 to 10.1; hemorrhagic, RR = 4.1 to 6.7). CONCLUSION: Incident dialysis patients are at markedly higher risk for hospitalized stroke when compared to the general population. Although prior public health initiatives have focused primarily on cardiac disease among patients treated with dialysis, our data suggest that new initiatives are needed to control the high risk of stroke in this population.

Black or African American↗

Apolipoprotein E genotypes and outcome from out of hospital cardiac arrest.

Genetic factors may influence outcome from cardiac arrest. In Seattle, WA, paramedics collected blood specimens from patients who had suffered cardiac arrest outside of a medical institution (out of hospital cardiac arrest). We examined associations between apolipoprotein E (APOE) genotype and outcome in 134 who died "in the field", 131 who died in the hospital, 198 patients who were discharged from hospital alive, and 64 control subjects. APOE genotype was not significantly related to outcome, including being alive at and being independent by 3 months after the arrest. Specifically, having one or two alleles of APOE epsilon4 or having APOE epsilon3/epsilon3 was not related to outcome, even after controlling for age, sex, race, and initial rhythm. We failed to confirm previous studies and found no significant associations between APOE genotype and outcome from out of hospital cardiac arrest.

Aged↗

Hormone replacement therapy and associated risk of stroke in postmenopausal women.

BACKGROUND: There is little information about the risk of stroke in relation to time since initiation of hormone therapy and in relation to estrogen dose. METHODS: We conducted a population-based case-control study at Group Health Cooperative (GHC), a health maintenance organization in the greater Seattle (Wash) area, to assess the association of hormone replacement therapy with the risks of incident ischemic and hemorrhagic stroke. Cases were all postmenopausal women with incident stroke at GHC during July 1989 through December 1998 (726 ischemic strokes and 213 hemorrhagic strokes). Controls were randomly selected from GHC enrollees and frequency matched to cases on age and calendar year (n = 2525). Hormone use was assessed from computerized pharmacy data. We reviewed the medical record to confirm eligibility and assess other risk factors. RESULTS: After risk factor adjustment, ischemic stroke was not associated with current use of estrogen with progestin (odds ratio [95% confidence interval]: 0.97 [0.69-1.37]) or without (0.94 [0.72-1.23]) compared with never use. Similarly, hemorrhagic stroke was not associated with current use of estrogen with progestin (0.74 [0.43-1.28]) or without (1.06 [0.71-1.56]). However, the risks of ischemic stroke and hemorrhagic stroke were increased 2-fold during the first 6 months of hormone use (ischemic stroke: 2.16 [1.04-4.49], hemorrhagic stroke: 2.20 [0.83-5.81]). Risk of ischemic stroke also increased with estrogen dose (P for trend =.03). CONCLUSION: The transitory increase in risks of ischemic stroke and hemorrhagic stroke associated with initiation of hormone replacement therapy merits further investigation.

Adult↗

Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of interventions aimed at improving neurologic outcome after cardiac arrest. METHODS: The authors conducted a double-blind, placebo-controlled, randomized clinical trial with factorial design to see if magnesium, diazepam, or both, when given immediately following resuscitation from out-of-hospital cardiac arrest, would increase the proportion of patients awakening, defined as following commands or having comprehensible speech. If the patient regained a systolic blood pressure of at least 90 mm Hg and had not awakened, paramedics injected IV two syringes stored in a sealed kit. The first always contained either 2 g magnesium sulfate (M) or placebo (P); the second contained either 10 mg diazepam (D) or P. Awakening at any time by 3 months was determined by record review, and independence at 3 months was determined by telephone calls. Over 30 months, 300 patients were randomized in balanced blocks of 4, 75 each to MD, MP, PD, or PP. The study was conducted under waiver of consent. RESULTS: Despite the design, the four treatment groups differed on baseline variables collected before randomization. Percent awake by 3 months for each group were: MD, 29.3%; MP, 46.7%; PD, 30.7%; PP, 37.3%. Percent independent at 3 months were: MD, 17.3%; MP, 34.7%; PD, 17.3%; PP, 25.3%. Significant interactions were lacking. After adjusting for baseline imbalances, none of these differences was significant, and no adverse effects were identified. CONCLUSIONS: Neither magnesium nor diazepam significantly improved neurologic outcome from cardiac arrest.

Activities of Daily Living↗