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Biomedical subjects

M Paik

Publications and source records attributed to M Paik.

18 recordsLinked to original sources
PubMed1999

Serum transferrin receptor as a marker of erythropoiesis suppression in patients on chronic transfusion.

In the management of patients requiring chronic transfusion, various parameters may be used to evaluate the degree of erythroid marrow suppression. The aim of our study was to assess which of these parameters provide the most useful assessment of erythropoiesis. We studied 27 chronically transfused patients, 19 with sickle cell disease (SS patients) and 8 with thalassemia. Thirty-one nonchronically transfused SS patients and 74 healthy children served as controls. We measured serum transferrin receptor levels, reticulocyte counts, hemoglobin (Hb) concentrations and erythropoietin levels. The serum transferrin receptor levels were very elevated in control SS patients and remained significantly elevated in those on transfusion therapy, but were normal in thalassemia patients, indicating a more complete suppression of erythropoiesis. The reticulocyte counts were elevated in all SS patients, even when on chronic transfusion, but were in the normal range in patients with thalassemia. Erythropoietin levels were elevated in patients with thalassemia and in all the SS patients. Hb levels negatively correlated with serum transferrin receptor and erythropoietin in all SS patients. In the transfused SS patients, a higher HbS level correlated with higher reticulocyte counts, transferrin receptor, and erythropoietin levels. In thalassemia patients, erythropoiesis was more completely suppressed, as reflected both by normal reticulocyte counts and near-normal transferrin receptor levels. Though the reticulocyte counts were not significantly different in the transfused SS patients, the serum transferrin receptor levels were less elevated than in SS patients not on transfusion. The serum transferrin receptor level appears to be the most useful marker of marrow erythropoietic activity in chronically transfused SS patients. We recommend that reticulocyte counts be integrated with periodic measurements of serum transferrin receptor levels.

Adolescent↗
PubMed1997

Contribution of genetic and nutritional factors to DNA damage in heavy smokers.

Prior epidemiological evidence suggests that genes controlling the metabolism of carcinogens and antioxidant/nutritional status are associated with lung cancer risk, possibly through their ability to modulate DNA damage by carcinogens. We performed a cross-sectional analysis of 159 heavy smokers from a cohort of subjects enrolled in a smoking cessation program. A total of 159 blood samples were analyzed to determine the relative contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in smokers was affected by genetic polymorphisms and nutritional status. Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher (2-fold, P < or = 0.03) levels of DNA damage than those without. In parallel models, PAH-DNA adducts were inversely associated with plasma levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P = 0.09), and alpha-tocopherol (beta = -0.28, P = 0.21) in 159 subjects. The association between smoking-adjusted plasma beta-carotene levels and DNA damage was only significant in those subjects lacking the GSTM1 detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a statistical interaction between beta-carotene and alpha-tocopherol; when beta-carotene was low, alpha-tocopherol had a significant protective effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with retinol (r = 0.20, P = 0.0005). These results suggest that several micronutrients may act in concert to protect against DNA damage and highlight the importance of assessing overall antioxidant status. In conclusion, a subset of smokers may be at increased risk of DNA damage and possibly lung cancer due to the combined effect of low plasma micronutrients and genetic susceptibility factors. The use of biological markers to assess efficacy of interventions and to study mechanisms of micronutrients is timely given the current debate regarding the use of chemopreventive agents in high risk populations.

Adult↗
PubMed1997

Cardiac autonomic control is inversely related to blood pressure variability responses to psychological challenge.

Blood pressure exhibits variability (BPV) at low (0.02- to 0.07-Hz), mid (0.07- to 0.15-Hz)-, and high (0.15- to 0.50-Hz) frequencies. Evidence suggests that BPV responses to challenge are inversely related to cardiac autonomic control. We tested this hypothesis by examining the BPV responses to psychological stressors in 22 normal subjects who differed in cardiac control, operationalized as resting heart period variability (HPV). HPV and BPV were measured noninvasively or a beat-to-beat basis. The stressors produced a significant increase in heart rate and a small but significant increase in diastolic blood pressure. As predicted, the changes in BPV in response to the stressors were inversely related to resting HPV. The results are interpreted in terms of a model of cardiovascular control that holds that BPV originates from feedforward effects of central control of the heart, feedback effects mediated through the baroreflexes, and direct sympathetic vascular effects.

Adult↗
PubMed1997

Blood pressure variability responses to tilt are buffered by cardiac autonomic control.

Variability in blood pressure (BPV) is influenced by vascular sympathetic drive as well as autonomic control of the heart. Evidence suggests that elimination of cardiac autonomic control, as measured by heart period variability (HPV), produces a reduction in BPV at rest but an increase in BPV during challenge. We recently showed that the BPV response to psychological challenge, which principally produces cardiac parasympathetic withdrawal, was inversely related to the subject's level of cardiac control. In the current study we examined the BPV response to orthostatic tilt, a sympathetic stressor. Subjects were 22 healthy men and women who differed in cardiac control due in part to differences in aerobic capacity. HPV and BPV were measured noninvasively on a beat-to-beat basis. Tilt produced significant increases in heart rate and diastolic blood pressure and a significant decrease in high frequency HPV. As predicted, changes in BPV in response to tilt were inversely related to resting HPV. Results are interpreted in terms of a model of cardiovascular control which holds that BPV originates from feedforward effects of central control of the heart, feedback effects mediated through the baroreflexes, and direct sympathetic vascular effects.

Adult↗
PubMed1995

Aggregatory characteristics and expression of the collagen adhesion receptor in fetal porcine platelets.

Fetal wound healing differs significantly from that of the adult by its rapidity, the paucity of an inflammatory response, and the lack of scarring. In the adult, activation and aggregation of platelets at the site of injury result in the release of cytokines and inflammatory mediators that stimulate wound healing by initiating an acute inflammatory response. The aim of this study was to characterize the activity of midtrimester (day 60) and third-trimester (day 95) fetal porcine platelets (full term, 114 days) compared with that of adults in an attempt to understand the lack of inflammation in fetal wounds. The aggregatory capabilities of adult and fetal platelets were analyzed after exposure to adenosine diphosphate (ADP) concentrations of 10 mumol/L and 40 mumol/L concentrations, collagen of 0.19 mg/mL, and arachidonic acid of 0.5 mg/mL. Expression of the alpha 2 subunit of the collagen receptor (alpha 2 beta 1) was evaluated by Western blot analysis. The aggregation of day-60 fetal platelets when exposed to ADP (10 mumol/L and 40mumol/L) and collagen was significantly lower than that of the adult. The aggregation of third-trimester platelets to 10 mumol/L of ADP was similar to that of the adult and significantly greater than that of midtrimester fetuses at higher concentrations (40 mumol/L). Both fetal groups responded suboptimally to collagen, and the response was significantly less than that of adults. In contrast, arachidonic acid caused rapid and complete aggregation of both fetal platelet groups, suggesting that both mid- and late-trimester fetal platelets possessed the ability to fully aggregate with the appropriate stimulus. The different aggregatory responses to collagen could not be explained by differences in collagen receptor expression, because these were found to be similar in adults and midtrimester fetuses. It is concluded that although fetal platelets have the potential to aggregate effectively, they aggregate poorly to collagen and exhibit improved aggregation to ADP with increasing maturity. There is a transition to "adultlike" platelet aggregatory activity in the third trimester, which correlates with the period of transition to adultlike wound healing in utero. Similar expression of the alpha 2 beta 1 collagen receptor in the fetus and adult cannot explain the differences observed in their responses to collagen.

Animals↗
PubMed1994

Experience with 500 prenatal diagnoses of sickle cell diseases: the effect of gestational age on affected pregnancy outcome.

Prenatal diagnosis of sickle cell diseases is obtained rapidly and precisely by polymerase chain reaction (PCR) with Ddel restriction analysis and dot-blotting with allele-specific oligonucleotides (ASO). Prenatal diagnosis of HgbSS and HgbSC was performed in 500 pregnancies, 196 by Southern blot and 304 by PCR. PCR drastically shortened the interval from sampling to reporting, allowing acceptance even of samples with unknown paternal phenotype, and resulted in an overall four-fold increase in diagnoses. In 108 pregnancies, the diagnosis was an affected fetus; 25 were HgbSC: 3 (12 per cent) were terminated; 83 were HgbSS: four ended in miscarriage; 40/79 (51 per cent) were terminated. The gestational age at the time of report to the mother appeared to be a major outcome determinant when the fetal diagnosis was HgbSS. The change-point in the maternal decision was found at 20 weeks of gestation. Before the 20th week, most mothers (64 per cent) chose termination; thereafter, the majority (72 per cent) chose continuation. The odds ratio of termination in earlier relative to later reporting was 4.7. In order to offer a choice to the mothers at risk of delivering a fetus affected by sickle cell disease, the diagnosis should be reported before the 20th week of gestation.

Amniocentesis↗
PubMed1994

Effect of mental stress throughout the day on cardiac autonomic control.

Although many laboratory studies have demonstrated changes in cardiac autonomic control during psychological stress, few have attempted to demonstrate this effect in ambulatory subjects. To address this issue, 24-h electrocardiographic recordings of 33 healthy subjects were analyzed for RR interval and heart period variability (HPV) responses associated with periodic diary entries measuring physical position, negative effect, and time of day. A total of 362 diary entries were made during the 24-h sessions, each in response to a device which signaled on an average of once per hour. HPV was analyzed in the frequency domain, yielding estimates of spectral power in low (LF) and high (HF) frequency bands, as well as the LF/HF ratio. Because of the high correlations of the measures of negative affect (alpha = 0.91), they were combined to create a single index of stress. Multivariate analysis was used to assess the effect of individual subject differences, physical position, and stress on RR interval and HPV. Results revealed significant effects of individual differences, stress, and physical position on RR interval, with increases in stress associated with decreases in RR interval as expected. HF power was significantly lower and the LF/HF ratio significantly higher in the standing compared with the sitting position. Psychological stress was significantly associated with an increase in the LF/HF ratio, suggesting increases in the relative predominance of sympathetic nervous system activity during stressful periods of the day. Overall, these findings suggest that in ambulatory normal subjects, cardiac autonomic control varies throughout the day as a function of self-reported stress.

Adult↗
PubMed1994

Cognitive impairment after stroke: frequency, patterns, and relationship to functional abilities.

Cognitive function was examined in 227 patients three months after admission to hospital for ischaemic stroke, and in 240 stroke-free controls, using 17 scored items that assessed memory, orientation, verbal skills, visuospatial ability, abstract reasoning, and attentional skills. After adjusting for demographic factors with standardised residual scores in all subjects, the fifth percentile was used for controls as the criterion for failure on each item. The mean (SD) number of failed items was 3.4 (3.6) for patients with stroke and 0.8 (1.3) for controls (p < 0.001). Cognitive impairment, defined as failure on any four or more items, occurred in 35.2% of patients with stroke and 3.8% of controls (p < 0.001). Cognitive domains most likely to be defective in stroke compared with control subjects were memory, orientation, language, and attention. Among patients with stroke, cognitive impairment was most frequently associated with major cortical syndromes and with infarctions in the left anterior and posterior cerebral artery territories. Functional impairment was greater with cognitive impairment, and dependent living after discharge either at home or nursing home was more likely (55.0% with, v 32.7% without cognitive impairment, p = 0.001). In a logistic model examining the risks related to dependent living after stroke, cognitive impairment was a significant independent correlate (odds ratio, OR = 2.4), after adjusting for age (OR = 5.2, 80 + v 60-70 years) and physical impairment (OR = 3.7, Barthel index < or = 40 v > 40). It is concluded that cognitive impairment occurs frequently after stroke, commonly involving memory, orientation, language, and attention. The presence of cognitive impairment in patients with strike has important functional consequences, independent of the effects of physical impairment. Studies of stroke outcome and intervention should take into account both cognitive and physical impairments.

Cerebrovascular Disorders↗
PubMed1994

Dementia after stroke is a predictor of long-term survival.

BACKGROUND AND PURPOSE: The aim of this study was to determine whether dementia after stroke adversely influences long-term survival. METHODS: Subjects were 251 patients > or = 60 years of age with ischemic stroke who were given neurological, neuropsychological, and functional examinations 3 months after hospitalization and were followed up prospectively. Using criteria modified from the Diagnostic and Statistical Manual of Mental Disorders-III-R, dementia was found in 66 (26.3%) patients at the 3-month baseline examination. Life-table methods were used to estimate mortality rates in the groups with and without dementia after 1 to 5 years of follow-up, Kaplan-Meier curves to estimate the cumulative proportion surviving with and without dementia, and Cox proportional-hazards analysis to compute the relative risk of mortality associated with dementia at baseline, after adjusting for other potential predictors of stroke mortality. RESULTS: The mortality rate was 19.8 deaths per 100 person-years with dementia compared with 6.9 deaths per 100 person-years without dementia. The cumulative proportion surviving after a median follow-up of 58.6 months was 38.9 +/- 0.08% for those with dementia and 74.5 +/- 0.04% for those without dementia. The relative risk associated with dementia was 3.11 (95% confidence interval, 1.79 to 5.41) after adjusting for the effects of demographic factors, cardiac disease, severity of stroke (Barthel Index), stroke type (lacunar versus nonlacunar), and recurrent stroke (examined as a time-dependent variable). When the Mini-Mental State Examination score at baseline was examined instead of the diagnosis of dementia, the results of the model were similar. CONCLUSION: Our study is the first to demonstrate that dementia or cognitive impairment adversely influences long-term survival after stroke, even after adjusting for other commonly accepted predictors of stroke mortality. Impairment in intellectual function after stroke, independent of physical disability, has a significant impact on prognosis. Both cognitive and physical functions should be assessed in clinical studies of stroke outcome.

Aged↗
PubMed1994

Risk of dementia after stroke in a hospitalized cohort: results of a longitudinal study.

Stroke is considered the second most common cause of dementia, but the magnitude of the risk posed by stroke has not been fully clarified. The aim of this study was to determine the long-term risk of developing dementia after stroke onset in a hospitalized cohort. We prospectively examined 185 nondemented patients aged > or = 60 years hospitalized with ischemic stroke and 241 age-matched nondemented controls without stroke from the same community using neurologic, neuropsychological, and functional assessments given annually. Using criteria modified from the DSM-III-R, we diagnosed incident dementia based on the annual examination findings. We used life-table methods to estimate incidence in the two groups, Kaplan-Meier analysis to determine the proportion surviving without dementia, and Cox proportional-hazards analysis to compute the relative risk (RR) of dementia after 1 to 4 years of follow-up. The incidence of dementia was 8.4 per 100 person-years in the stroke group and 1.3 per 100 person-years in the control group. After 52 months of follow-up, the cumulative proportion (+/- SE) surviving without dementia was 66.3 +/- 5.5% for stroke and 90.3 +/- 4.3% for control subjects. The RR of dementia associated with stroke compared with controls was 5.5 (95% CI, 2.5 to 11.1) after adjusting for demographic factors. Older age at stroke onset and fewer years of education were significant covariates, but sex and race were not. A low score on the Mini-Mental State Examination at baseline was a significant predictor when added to this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort.

We investigated the relationship between risk factors for cerebrovascular disease and cognitive function in 249 stroke-free community volunteers (age, 70.8 +/- 6.7 years; education, 12.3 +/- 4.6 years) who were given tests of memory, language, visuospatial, abstract reasoning, and attentional skills. Using logistic regression analyses, we examined hypertension, diabetes mellitus, myocardial infarction, angina, hypercholesterolemia, and cigarette smoking as potential correlates of performance within these cognitive domains. Controlling for demographic factors within the logistic models, diabetes mellitus was a significant independent correlate of abstract reasoning deficits (odds ratio, 10.9; 95% confidence interval, 2.2 to 54.9) and visuospatial dysfunction (odds ratio, 3.5; confidence interval, 1.2 to 10.7), while hypercholesterolemia was a significant independent correlate of memory dysfunction (odds ratio, 3.0; confidence interval, 1.4 to 6.6). Prolonged exposure to vascular risk factors such as diabetes mellitus and hypercholesterolemia may lead to atherosclerotic disease, possibly resulting in "silent" infarctions or impaired cerebral blood flow and a decline in cognitive functioning.

Aged↗
PubMed1993

Clinical determinants of dementia related to stroke.

Among 251 patients examined 3 months after the onset of acute ischemic stroke, we diagnosed dementia in 66 (26.3%) by using modified DSM-III-R criteria based on neuropsychological, neurological, functional, and psychiatric examinations. We used a logistic regression model to derive odds ratios (ORs) for clinical factors independently related to dementia in this cross-sectional sample. Dementia was significantly associated with age, education, and race. A history of prior stroke (OR = 2.7) and diabetes mellitus (OR = 2.6) was also independently related to dementia, but hypertension and cardiac disease were not. Stroke features associated with dementia included lacunar infarction compared with all other subtypes combined (OR = 2.7) and hemispheric laterality in relation to brainstem or cerebellar location. There was a predominance of dementia in patients with left-sided lesions (OR = 4.7), an effect not explained by aphasia. Dementia was especially common with infarctions in the left posterior cerebral and anterior cerebral artery territories. A major dominant hemispheral syndrome (reflecting size and laterality) was also independently associated with dementia (OR = 3.9). We suggest that dementia after ischemic stroke is a result of multiple independent factors, including both small subcortical and large cortical infarcts especially involving the left medial frontal and temporal regions, with additional contributions by demographic and vascular risk factors.

Age Factors↗
PubMed1992

Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort.

We determined the frequency of dementia in a cohort of 251 patients aged greater than or equal to 60 years hospitalized with acute ischemic stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa = 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 (p less than 0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 (p less than 0.001) with significant age and race effects. We conclude that ischemic stroke significantly increases the risk of dementia, with independent contributions by age, education, and race.

Aged↗
PubMed1991

A study of inter- and intra-examiner reliability of pocket depth and attachment level.

Factors affecting inter- and intra-examiner variability for probing pocket depth and periodontal attachment level were studied on a sample of 20 patients, each given six full-month examinations, two by each of 3 examiners. The major determinant of both dimensions of variability was the degree of periodontal destruction, measured as either pocket depth or level of attachment: the greater the degree of destruction, the greater the disagreements within and between examiners. Differences in variability were generally minor between sites on anterior and sites on posterior teeth, between midsites and proximal sites, and between sites on the facial and sites on the lingual surface. When differences were found between the average variances for different kinds of sites, they may have been due to corresponding differences between the average depths, and not to any inherently greater difficulty in measuring one kind of site than another.

Adolescent↗
PubMed1987

Some effects of cigarette smoking, arsenic, and SO2 on mortality among US copper smelter workers.

Previous studies of the relationship between arsenic levels and respiratory cancer among copper smelter workers have not directly accounted for possible effects of SO2 exposure and cigarette smoking. This is a report on the 1949-1980 mortality experience of 6,078 white male workers who worked at least 3 years between 1 January 1946 and 31 December 1976 at one or more of eight US copper smelters. The completeness of the cohort was verified statistically, and worker exposures to arsenic, SO2, dust, nickel, cadmium, and lead were estimated from retrospective industrial hygiene surveys reported elsewhere. By using internal controls, a dose-response relationship for lung cancer was observed with exposure to arsenic and SO2. When cigarette smoking data were included with arsenic and SO2 exposure data in a nested case-control analysis, only smoking and arsenic were statistically significant factors. The arsenic-lung cancer relationship was confined to a single smelter associated with high content feed. In the remaining smelters mortality for all causes of death and for all cancer was not high based on comparisons with national, state, and local rates.

Air Pollutants, Occupational↗
PubMedDate not supplied

Stressful life events and seizure frequency in patients with epilepsy.

We tested whether unpleasant life events increased seizure occurrence in persons with epilepsy. Forty-six subjects maintained daily diaries for 10-36 weeks in which they recorded seizures and life events. Mean age of subjects was 39 years; 78% were female; 83% had complex partial seizures (CPS). On the average, subjects reported 3.3 seizures a week. Analyses first were conducted within each subject and then in the sample overall. For each person, we tested whether seizure frequency increased within 24 h of the occurrence of unpleasant events, using Poisson regression analyses that adjusted for daily antiepileptic medication, sleep duration and quality, alcohol intake, menstrual status, and pleasant events. Rarity of events precluded analyses in 9 subjects. Events increased seizure frequency in 5 subjects (14%) (p < 0.05). Events decreased seizure frequency in 2 subjects (p < 0.05). When individual risk ratios were aggregated across subjects, unpleasant events were significantly associated with seizure increase only in men (RR = 1.67, 95% Confidence interval 1.09, 2.54). However, this finding must be interpreted with caution because of the limited number of men in the sample. In other aggregate analyses, events and seizures were not associated in subjects grouped by seizure type, age of seizure onset, current age, ethnicity, educational level, or marital status. Identification of factors that distinguish patients with and without event-triggered seizures requires further study.

Adolescent↗
PubMedDate not supplied

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗