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Biomedical subjects

G Sexton

Publications and source records attributed to G Sexton.

At least 37 records · Page 2Linked to original sources

Motor slowing precedes cognitive impairment in the oldest old.

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

Aged↗

Persistent inflammatory response in stroke survivors.

OBJECTIVE: Goals were to determine how long acute-phase markers remain elevated after ischemic stroke and how marker levels relate to stroke risk factors, stroke mechanism, and subsequent vascular events. METHODS: Fibrinogen (FIB), C-reactive protein (CRP), leukocytes (WBC), neutrophils (PMN), interleukin-6, and interleukin-1 receptor antagonist were measured at stroke onset and at 6 weeks, 6 months, and 1 year after enrollment, or until a vascular event occurred in 136 acute ischemic stroke patients, 76 patients with comparable risk factors for stroke, and 48 age-balanced healthy subjects. RESULTS: Multivariate logistic analysis showed that prior stroke and FIB level predicted new events in stroke patients (p < 0.04 for both), whereas congestive heart failure (p < 0.02) and creatinine level (p < 0.006) were predictive in at-risk patients. After controlling for infection, FIB, CRP, and PMN levels at baseline were higher in at-risk but not in stroke patients with recurrent events (p < 0.05 for all). At 1 year, FIB levels remained elevated in event-free stroke survivors compared with levels in the risk and control groups (p < 0.001 for both). FIB also remained higher in stroke survivors who had atheroembolism (AE) compared with non-AE stroke survivors (381+/-72 versus 342+/-78 mg/dL, p < 0.02). Peripheral vascular disease was an independent predictor (p < 0.0001) of longitudinal FIB in stroke survivors. Of note, both WBC and PMN levels were chronically elevated in patients with stroke risk factors and in stroke survivors (p < 0.0001 for both) compared with healthy elderly subjects. CONCLUSIONS: Most acute-phase markers decline gradually after stroke, but FIB remains significantly elevated and is associated with increased risk for recurrent vascular events.

Acute-Phase Proteins↗

Brain volume preserved in healthy elderly through the eleventh decade.

OBJECTIVE: To determine which brain regions lose volume with aging over time in healthy, nondemented elderly. BACKGROUND: Cross-sectional studies suggest widespread loss of brain volume with aging. These studies may be biased by significant numbers of preclinically demented elderly in the oldest comparison groups. Longitudinal studies may allow closer determination of the effect of aging unaffected by dementia. METHODS: Quantitative volumetric MRI was performed annually on 46 healthy subjects older than age 65 who had maintained cognitive health a mean of 5 years. Comparisons (analysis of variance) were made of rates of volume loss (slopes) divided into 11 young-old (mean age, 70 years), 15 middle-old (mean age, 81 years), and 20 oldest-old (mean age, 87 years) subjects. Regions of interest included CSF spaces, lobar regions, and limbic-subcortical regions. RESULTS: There were significant differences between groups in intracranial, total brain, left hemisphere, right hemisphere, temporal lobe, basilar-subcortical region, and hippocampus volumes, with oldest-old subjects showing the smallest volumes, followed by middle-old and young-old subjects. Oldest-old subjects had significantly greater subarachnoid volumes than the younger groups. There were no significant differences in rates of change of regions of interest across age groups. CONCLUSIONS: After age 65 there is minimal brain volume loss observed over time in healthy elderly. Brain volume differences seen cross-sectionally, at any age, likely reflect small, constant rates of volume loss with healthy aging. Healthy oldest-old subjects do not show greater rates of brain loss compared with younger elderly, suggesting that large changes seen in cross-sectional studies reflect the presence of preclinical dementia in older groups.

Aged↗

Differential permeability of a human brain tumor xenograft in the nude rat: impact of tumor size and method of administration on optimizing delivery of biologically diverse agents.

To assess how to maximize drug delivery to intracerebral tumors and surrounding brain, this study examined the effects of route and method of administration and tumor size on the distribution of three agents in a nude rat intracerebral tumor xenograft model. Aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), and dextran 70 (M(r) 70,000) were administered i.v. or intra-arterially (i.a.) with or without osmotic blood-brain barrier disruption (BBBD) at 8, 12, or 16 days after tumor cell inoculation (n = 72). A 2.2- to 2.5-fold increase in delivery to tumor and surrounding brain was observed when i.a. was compared with i.v., and a 2.5- to 7.6-fold increase was observed when BBBD was compared with the saline control. The combined effect of i.a. administration and BBBD was to increase delivery 6.3-16.7-fold. The greatest benefit of BBBD was seen in animals with 8-day tumors, whereas BBBD had less benefit in improving delivery to intracerebral tumor and brain around tumor as the tumors grew larger. Regional delivery decreased as the molecular weight of the agent increased. Based on these results, we suggest that i.a. administration of antitumor agents may be adequate to obtain initial responses in large, very permeable, intracerebral tumors. However, in smaller, less permeable tumors or after an initial response to treatment, there may be a significant therapeutic advantage to i.a. agent administration and BBBD.

Aminoisobutyric Acids↗

Long-term toxicity and neuropathology associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery.

OBJECTIVE: The goal was to evaluate, at 1 year, 75 Long-Evans rats for survival rates and toxicity associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery. METHODS: Seventy-five Long-Evans rats were randomized into four groups and evaluated at 1 year for survival rates and toxicity associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery. Radiation (2,000 cGy) was administered as a single fraction, by using parallel opposed portals, 30 days before chemotherapy (Group 1), 24 hours before chemotherapy (Group 2), 30 days after chemotherapy (Group 3), or without chemotherapy or without radiation (control group, Group 4). Five subgroups within each treatment group included rats receiving intra-arterially administered methotrexate (1 g/m2) or intravenously administered etoposide (200 mg/m2) combined with intra-arterially administered carboplatin (200 mg/m2), administered with or without osmotic blood-rain barrier disruption, and a group receiving normal saline solution after blood-brain barrier disruption. RESULTS: There was a significant increase in total toxic effects when the three experimental groups were compared with the control group (P = 0.001, 0.006, and 0.013 for Groups 1, 2, and 3, respectively). All groups receiving radiation and chemotherapy (particularly carboplatin and etoposide) had an increased incidence of hind limb paralysis, resembling experimental allergic neuritis (P = 0.053). Statistical analysis showed a trend toward increased mortality rates in Group 1 (antecedent radiation), compared with the control group (P = 0.082), and an increased incidence of intracerebral calcification (P = 0.019). No differences in mortality rates were observed for Group 2 or 3, compared with the control group. CONCLUSION: Radiation before chemotherapy was a more toxic sequence and, surprisingly, carboplatin/etoposide administered in combination with radiotherapy was more detrimental than methotrexate. Additional studies are in progress to evaluate the toxicity and efficacy of sequences of cranial irradiation and enhanced chemotherapy in tumor-bearing rats.

Animals↗

Cognitive markers preceding Alzheimer's dementia in the healthy oldest old.

OBJECTIVE: To look for preclinical markers of Alzheimer's dementia in a sample of healthy, oldest old individuals. DESIGN: Prospective, longitudinal study of individuals examined at yearly intervals with neuropsychological tests selected to be sensitive to the early detection of dementia. PARTICIPANTS: One hundred and thirty-nine community-dwelling, functionally independent, healthy individuals 65 to 106 years of age who met strict criteria for lack of dementia at entry. Incident dementia cases consisted of 16 volunteers all 80 years old or older who developed dementia of the Alzheimer's type and 31 volunteers 80 years old and older showing no evidence of dementia during a mean 2.8-year follow-up interval. MEASUREMENTS: Scores on 10 neuropsychological measures were analyzed for the initial examination when none of the volunteers showed clinical evidence of dementia and for the two subsequent yearly examinations. RESULTS: Individuals who subsequently developed dementia showed evidence of verbal memory impairment at their initial examination, which was a mean of 2.8 years before clinical evidence of dementia. The average yearly incidence rate for dementia in those 80 years of age and older was 12%. Performance of individuals who did not development dementia remained relatively stable during follow-up for up to 5 years. CONCLUSION: Alzheimer's disease has a preclinical stage in which verbal memory decline is the earliest sign. Dementia in the oldest old is distinguishable from age-related cognitive decline.

Aged↗

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia.

OBJECTIVE: To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. BACKGROUND: Postmortem studies suggest that the earliest changes in Alzheimer's disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. METHODS: 30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. RESULTS: NoD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NoD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. CONCLUSIONS: Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Aged↗

A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype.

The oldest old are the fastest-growing segment of our population and have the highest prevalence of dementia. Little is known about the genetics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD)--namely, apolipoprotein E (APOE) epsilon4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genetic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects who were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psychometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon4 and a family history of dementia (independent of epsilon4) were associated with an earlier age at onset of dementia. Subjects who had epsilon4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those who had neither epsilon4 nor a family history of dementia. These observations suggest that the rate of cognitive decline increases with age and that APOE and other familial/genetic factors influence the onset age throughout life.

Age of Onset↗

Beta-carotene in HIV infection: an extended evaluation.

OBJECTIVE: Several small short-term intervention studies have suggested that beta-carotene supplementation in HIV-infected patients can increase the number of various immune cells including CD4 cells. This prospective double-blinded study was designed to investigate whether beta-carotene supplementation would result in this immuno-enhancement in a larger number of patients over a longer time period. METHODS: HIV-positive patients were randomly assigned to receive either 60 mg beta-carotene orally three times daily or a matched placebo. In addition, all patients received a multivitamin supplement. Patients were evaluated at baseline, 1 month, and 3 months for T-cell quantitative subsets, natural killer cells, HIV p24 antigen, beta-carotene levels, complete blood counts and chemistry batteries. Body weights and Karnofsky scores were evaluated at each visit. RESULTS: Seventy-two patients signed informed consent forms and entered the study. Except for serum beta-carotene concentration, there were no statistically significant differences (P < 0.05) between the treatment (60 mg beta-carotene three times daily and multivitamins) and placebo (placebo and multivitamins) groups at baseline or after either 1 or 3 months of treatment. DISCUSSION: Earlier studies suggesting that beta-carotene supplementation increased levels of immune cells in HIV-infected patients were not replicated in this study. The addition of a multivitamin supplement to both arms of this study may have masked any difference between the two groups. However, on the basis of the results of this study, we would not recommend supplementation with high doses of beta-carotene for HIV-infected patients.

Administration, Oral↗

Incorporation of dietary n-3 fatty acids into the fatty acids of human adipose tissue and plasma lipid classes.

The consumption of n-3 fatty acids from seafood has been related to a lower incidence of coronary artery disease. Adipose tissue composition has served as a biological marker of chronic ingestion of many dietary polyunsaturated fatty acids. However, the incorporation of n-3 fatty acids into the fat depots has not been studied in humans. Daily dietary supplementation with > or = 10 g n-3 fatty acids from fish oil for > 12 mo resulted in significantly greater 20:5n-3, 22:5n-3, and 22:6n-3 concentrations in fatty acids of adipose tissue, and a greater 20: 5n-3 fatty acid content in plasma lipid classes (cholesterol esters, phospholipids, and free fatty acids) of supplemented subjects compared with nonsupplemented control subjects. Combined values for all subjects indicated that fatty acid concentrations of n-3 plasma lipid classes, including 20:5n-3, 22:5n-3, 22:6n-3, and total n-3, significantly correlated with corresponding concentrations of fatty acids in adipose tissue. These findings indicate that the long-term ingestion of large amounts of n-3 fatty acids in humans resulted in their incorporation into the adipose tissue fatty acids. Incorporation of the fatty acids into adipose tissue warrants consideration for use in clinical studies requiring precise documentation of long-term n-3 fatty acid consumption.

Adipose Tissue↗

Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat.

This study characterized agent differential permeability, three-dimensional tumor volume, and survival in an LX-1 human small cell lung carcinoma intracerebral xenograft model in the nude rat. The percent accessible tissue space (distribution volume) and the permeability x capillary surface product for aminoisobutyric acid (M(r) 103), methotrexate (M(r) 454), dextran 10 (M(r) 10,000), and dextran 70 (M(r) 70,000) were measured between 8 and 16 days after inoculation of tumor. Magnetic resonance imaging and histology were used to quantitate intracerebral tumor volume (mm3). Accessible tissue space (ml/g) and permeability x capillary surface product in intracranial tumor, surrounding brain, and subcutaneous tumor decreased with increasing molecular weight of the agent, regardless of the number of days after inoculation. Accessible tissue space in intracranial tumor increased between 8 and 16 days for all agents except dextran 70. There was little change in the subcutaneous tumor or other tissues with time. Tumor volume calculations from imaging studies correlated with volumetric measurements from histological sections (r2 = 98.5%) and illustrated natural tumor progression (9 to 225 mm3). These results provide a basis for therapeutic design based on differential permeability of specific agents and the ability to quantitatively measure brain tumor volume for accessing tumor response.

Animals↗

Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence.

The sequence of chemotherapy administered prior to cranial irradiation rather than the more traditional order of radiation followed by chemotherapy is currently being evaluated. This rodent study was designed to assess the sequencing of radiation therapy and chemotherapy administered with osmotic blood-brain barrier disruption (BBBD). Drug delivery and acute toxicity were evaluated. Two clinically relevant chemotherapy regimens were given with BBBD: intraarterial methotrexate (MTX, 1 g/m2), or a combination of intraarterial carboplatin (200 mg/m2) and i.v. etoposide (200 mg/m2). In a randomized protocol, the standard rodent model of 2000 cGy as a single fraction using parallel opposed portals was administered 30 days prior to, concurrent with (24 h prior), or 30 days after these two chemotherapeutic regimens. A total of 72 animals was evaluated in this study. The administration of external beam radiation therapy either prior to or concurrent with the administration of a high molecular weight marker 14C-labeled dextran 70 (Mr 70,000), or a low molecular weight marker 3H-labeled MTX (Mr 456) resulted in a statistically significant (P < 0.01) decrease in drug delivery when compared to animals not receiving cranial irradiation. Seizures were observed in 26% of the animals that received radiation prior to the administration of intraarterial MTX after BBBD. It did not matter whether the radiotherapy was administered 30 days prior to or concurrent with MTX. Seizures were not seen in any other group. The mortality in animals receiving radiotherapy 30 days prior to chemotherapy was significantly (P = 0.03) higher than the mortality in control animals receiving chemotherapy after osmotic BBBD, but no radiation. Drug delivery was significantly decreased when the animals received prior radiotherapy; the administration of radiation prior to MTX with BBBD resulted in an increased incidence of seizures, and there was a significant increase in mortality when cranial irradiation was given 30 days prior to chemotherapy administered with BBBD. With regard to delivery and toxicity, chemotherapy with BBBD administered prior to radiotherapy may have advantages over the other sequences utilizing chemotherapy and cranial irradiation.

Analysis of Variance↗

Antiphospholipid antibodies in vascular surgery patients. A cross-sectional study.

BACKGROUND: Autoantibodies to phospholipid (aPL) have been associated with vascular thromboses in cerebral, coronary, and peripheral venous and arterial sites. To date, no large cross-sectional study has examined the incidence of occurrence of aPL in patients with peripheral arterial disease. METHODS: A cross-sectional study was performed with patients admitted for vascular surgery procedures to treat peripheral arterial disease for 23 months between January 1, 1990 and November 1, 1991. Consecutive patients were evaluated for the presence of aPL. Medical records for each patient were reviewed in detail, and historic, operative, and postoperative parameters were tabulated for relationship to the presence of aPL. RESULTS: Two hundred thirty-four patients underwent complete testing for aPL. All patients were receiving chronic aspirin therapy. This represented 86% of admissions. Antiphospholipid antibodies were detected in 60 patients (26%). No differences in age, sex, operation performed, or postoperative outcome were found between patients with and without aPL. However, patients with aPL were 1.8 times more likely to have undergone previous lower extremity (LE) vascular surgery than patients without aPL (95% confidence interval = 1.0 - 3.6, p = 0.047). Patients with aPL and previous LE vascular surgery were 5.6 times more likely to have had occlusion of that procedure than patients without aPL (95% confidence interval = 1.9 - 16.8, p = 0.03). The occluded previous LE procedures had a shorter duration of patency before occlusion in patients with aPL than in those without (mean duration of patency 17 months vs. 50 months, p < 0.003). Patients with occluded previous LE procedures and aPL were 4 times more likely to be female (95% C.I. = 1.4 - 11.3, p = 0.018). CONCLUSIONS: The incidence of aPL in vascular surgery patients is substantial. Vascular surgery patients with aPL are more likely to have failure of previous LE bypass procedures and to be female and the bypass failure occurs significantly more rapidly than in patients without aPL. Based on these data, testing of vascular surgery patients for aPL and investigation of alternative antithrombotic treatment regimens in patients with aPL appears warranted.

Aged↗

Effects of naloxone infusions on pulsatile thyrotropin secretion.

Endogenous opioids are known to modulate the secretion of some anterior pituitary hormones, but they are not thought to have significant effects on TSH secretion. However, dynamic TSH secretion has not been characterized during naloxone infusions. Therefore, we measured TSH levels every 15 min over 24 h in nine healthy young men at baseline and during infusions of naloxone at 2 mg/h. A TRH test was performed after each study. TSH pulses were located by Cluster analysis. Naloxone infusions decreased 24-h mean TSH levels by 28%, from 1.68 +/- 0.20 to 1.21 +/- 0.19 mU/L. Mean daytime TSH levels did not change, but nocturnal TSH levels were decreased by 39%, from 2.21 +/- 0.30 to 1.35 +/- 0.21 mU/L. There were no changes in TSH pulse frequency, but naloxone infusions decreased 24-h TSH pulse amplitude by 32%, from 2.02 +/- 0.26 to 1.37 +/- 0.21 mU/L. Daytime TSH pulse amplitude was relatively unaffected (1.27 +/- 0.15 vs. 1.16 +/- 0.21 mU/L), whereas nocturnal TSH pulse amplitude was decreased by 42%, from 2.72 +/- 0.40 to 1.57 +/- 0.23 mU/L. TSH responses to acute TRH administration were decreased after naloxone infusions (12.38 +/- 1.93 vs. 9.17 +/- 1.36 mU/L). Serum T3 levels fell by 21% during naloxone infusions, from 1.9 +/- 0.1 to 1.5 +/- 0.1 nmol/L, whereas other thyroid hormone levels and cortisol levels were unchanged. These findings suggest that endogenous opioids have significant stimulatory effects on TSH secretion, predominantly during the nocturnal TSH surge.

Adult↗

Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox.

BACKGROUND: For decades, the coronary heart disease (CHD) mortality rate has been four or more times higher in Finland than in France despite comparable intakes of dietary cholesterol and saturated fat. A potential answer to this paradox is provided by this study of 40 countries and the analyses of other nutrients in the diets besides cholesterol and saturated fat. METHODS AND RESULTS: CHD death rates for men aged 55 to 64 years were derived from the World Health Organization annual vital statistics. Dietary intakes were gathered from the Food and Agriculture Organization of the United Nations database. Forty countries at various levels of economic development and 40 dietary variables were investigated, including a lipid score that combined the intakes of cholesterol and saturated fat (Cholesterol-Saturated Fat Index [CSI]). The CSI was significantly and positively related to CHD mortality in the 40 countries. The countries with low CSIs had low CHD death rates. Countries with high CSIs had a wide range of CHD death rates. France, Finland, and other Western industrialized countries had similar CSIs. After adjusting for cholesterol and saturated fat, milk and many components of milk (butterfat, milk protein, calcium from milk, and riboflavin) and total calcium remained positively related to CHD mortality for all 40 countries. There were differences in the consumption of these foods and nutrients in France and Finland. Milk and butterfat (fat from milk, cream, cheese, and butter) consumption was higher in Finland than in France. The consumption of plant foods, recently shown to be protective against CHD (vegetables and vegetable oils containing monounsaturated and polyunsaturated fatty acids), was greater in France than in Finland. CONCLUSIONS: Over the years, France and Finland, with similar intakes of cholesterol and saturated fat, consistently have had very different CHD mortality rates. This paradox may be explained as follows. Given a high intake of cholesterol and saturated fat, the country in which people also consume more plant foods, including small amounts of liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of CHD mortality. On the other hand, milk and butterfat were associated with increased CHD mortality, possibly through their effects on thrombosis as well as on atherosclerosis.

Cholesterol, Dietary↗

Fibrinogen and the albumin-globulin ratio in recurrent stroke.

BACKGROUND AND PURPOSE: In following patients initially recruited for a cross-sectional study of blood viscosity in ischemic cerebrovascular disease, it was noted that those having a low albumin-globulin ratio appeared to experience the majority of subsequent vascular events. Accordingly, a prospective study in which subjects were assigned to a high or low albumin-globulin cohort was undertaken to examine the relation between a low albumin-globulin ratio, the presence of clinical risk factors for stroke, and the occurrence of subsequent stroke, myocardial infarction, or vascular death. METHODS: Three groups of subjects were followed for an average of 1.5 +/- 0.8 years to ascertain vascular end points. Group 1 consisted of 126 patients with acute ischemic stroke; group 2 included 109 subjects matched with group 1 for age, medications, and recognized clinical risk factors for stroke; and group 3 was composed of 84 healthy volunteers, matched for age with groups 1 and 2. The median albumin-globulin ratio for group 1 at enrollment, 1.45, was used to dichotomize patients into two cohorts: all subjects with an albumin-globulin ratio of 1.45 or less were assigned to the "low" albumin-globulin cohort; those whose ratio was greater than 1.45 were assigned to the "high" albumin-globulin cohort. The occurrence of vascular end points was verified during subsequent hospitalizations and outpatient clinic visits and by telephone interviews of patients and providers. RESULTS: A total of 51 vascular events occurred, including 39 in group 1, 8 in group 2, and 4 in group 3. Subjects in either group 1 or 2 who were in the low albumin-globulin cohort had at least double the risk for a subsequent vascular event compared with their counterparts in the high albumin-globulin cohort (P < .01 and P < .03, respectively). In comparison with the high albumin-globulin cohort, significantly more patients in the low albumin-globulin cohort in group 1 had a history of prior stroke (P < .03). When groups 1 and 2 were combined, both a low albumin-globulin ratio and diabetes had a significant independent association with increased risk for subsequent vascular events in a Cox proportional-hazards model (P < .01 and P < .03, respectively). CONCLUSIONS: The results of this study indicate that significantly increased risk for subsequent vascular events in stroke patients and in subjects with clinical risk factors for stroke is associated with a shift in the concentrations of blood proteins to a prothrombotic environment characterized by lower levels of albumin and an increased concentration of globulins and fibrinogen.

Aged↗

Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.

Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives.

Adult↗

The Diet Habit Survey: a new method of dietary assessment that relates to plasma cholesterol changes.

The Diet Habit Survey was designed to identify eating habits and measure dietary changes made over time by 442 adults in the Family Heart Study, a coronary heart disease prevention project. Reliability was determined by test-retest analysis. Validity was assessed by comparison with 24-hour dietary recalls and by comparing changes in diet with changes in plasma cholesterol levels. At baseline, 89% of the subjects were classified as eating the current American diet (37% fat), 10% reported eating Diet 1 (30% fat), and 1% reported eating Diet 2 (25% fat). After 5 years of dietary intervention, the population's eating habits had shifted; 48% reported eating the current American diet, 37% reported Diet 1, 14% reported Diet 2, and 1% reported Diet 3 (20% fat). Significant plasma cholesterol lowering was associated with changes in Diet Habit Survey scores reflecting lower cholesterol and saturated fat and higher complex carbohydrate intakes. This questionnaire is an inexpensive, reliable, and valid instrument for rapid assessment of eating habits and diet composition and, thus, is an important new tool for dietetics researchers and practitioners.

Adult↗