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W Stewart

Publications and source records attributed to W Stewart.

At least 19 recordsLinked to original sources
PubMed1995

Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers.

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.

Adult↗
PubMed1995

Expression of insulin-like growth factor II in spontaneously immortalized rat mesothelial and spontaneous mesothelioma cells: a potential autocrine role of insulin-like growth factor II.

Insulin-like growth factors (IGFs) are polypeptides that play an important role in cellular proliferation and differentiation. The present study examines the role of IGFs in the growth of mesothelial cells. Cell lines derived from normal rat mesothelium as well as lines derived from spontaneous rat mesotheliomas were found to express RNA transcripts for IGF-II. In contrast, cell lines derived from asbestos-induced rat mesotheliomas did not express this growth factor. All cell lines expressed receptors for IGF-I and IGF-II, as well as insulin receptors. Coexpression of IGF-II and its cognate receptor suggested that IGF-II was acting as an autocrine growth factor in the spontaneously immortalized cells and the cells derived from the spontaneous tumors. The biological activity of IGF-II secreted by the cell lines into conditioned medium could be neutralized using an IGF-II-specific antibody. Growth was inhibited in a dose-dependent manner; at the highest antibody concentration used (100 micrograms anti-IGF-II/ml), cell growth was decreased to 47% of control values. This inhibition was partially reversible by treatment of the cultures with IGF-II (91% of the control). These data suggest that IGF-II expression may be involved in the spontaneous alteration of rat mesothelial cells and may function as an autocrine or paracrine growth factor to modulate the growth of these cells in vitro and in vivo. Ubiquitous expression of IGF-II by cells that have not been exposed to asbestos and the lack of IGF-II expression by asbestos-transformed cells suggest that the mechanisms of changes in growth factor expression differ in mesothelial cells transformed by different pathways.

Animals↗
PubMed1995

Autocrine growth stimulation by transforming growth factor alpha in asbestos-transformed rat mesothelial cells.

Although the association between asbestos exposure and mesothelioma development has been established for decades, very little is known regarding the molecular mechanism(s) by which asbestos fibers induce this disease. In this series of experiments, the potential for transforming growth factor alpha (TGF-alpha) to act as an autocrine growth factor in transformed mesothelial cells was examined in rats, a model system frequently used to assess the tumorigenic potential of fibrous particulates. Both asbestos-transformed cells and spontaneously transformed cells expressed functional EGF receptors, although only the asbestos-transformed cells expressed TGF-alpha. Expression of TGF-alpha transcripts was correlated with secretion of picogram amounts of growth factor into conditioned medium by the asbestos-transformed cells. In addition, whereas TGF-alpha inhibited the growth of spontaneously transformed mesothelial cells, it stimulated the growth of asbestos-transformed cells. Neutralizing antibody that recognized TGF-alpha secreted by the asbestos-transformed cells was able to inhibit the growth of these cells. Taken together, these data indicate that TGF-alpha acts as an autocrine growth factor for asbestos-transformed rat mesothelial cells. Therefore, in asbestos-transformed mesothelial cells, altered production and responsiveness to TGF-alpha distinguish these cells from spontaneously transformed mesothelial cells. These data suggest that differences in mesothelioma etiology may be reflected in differences in the molecular alterations present in these tumors.

Animals↗
PubMed1995

Comparison of neurobehavioral function in workers exposed to a mixture of organic and inorganic lead and in workers exposed to solvents.

The neurobehavioral effects of lead (organic and inorganic) and organic solvents were compared in 386 U.S. workers (52 reference, 190 lead, and 144 solvent workers). The association between neurobehavioral test performance and duration of exposure to lead or solvents was also examined and compared. The neurobehavioral test battery consisted of examiner and computer-administered neurobehavioral tests, a test of olfactory function, and questionnaires that assessed neuropsychiatric symptoms. Adjusted mean differences on the neurobehavioral test scores were estimated by comparing the exposed group to the referent group using linear regression and adjusting for premorbid intellectual ability, age, and race. Both lead and solvents were associated with diminished neurobehavioral performance in all neurobehavioral areas tested. Specifically, while lead and solvent exposure had the same magnitude of adverse effects on tests of manual dexterity, lead exposure was associated with greater adverse effects on memory and learning tests but with less adverse effects on executive/motor tests and on a test of olfaction than solvent exposure. An elevated number of neuropsychiatric symptoms was reported by 7% of the referent group, 43% of the lead group, and 15% of the solvent group. For exposure duration of < or = 10 years, more neurobehavioral decrements were found in the solvent group relative to the lead group. However, for exposure duration of > or = 18 years, the lead group showed more decrements than the solvent group. Overall, these data suggest differences in neurobehavioral functioning between the lead (organic and inorganic) and solvent exposed workers examined in this study.

Adult↗
PubMed1995

A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers.

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.0 mg/k). Subjects were monitored for adverse events, vital sign and laboratory alterations, and changes in electrocardiographic (ECG) intervals and electroencephalographic (EEG) patterns. Overall, the percentage of subjects reporting adverse events was similar in those receiving dolasetron (44/64; 68.8%) or placebo (10/16; 62.5%); most adverse events were mild in severity. Subjects receiving dolasetron reported a higher incidence of central nervous system (headache and dizziness/lightheadedness), gastrointestinal (increased appetite and nausea), and visual adverse events and taste alterations. No clinically significant changes in laboratory variables were observed. Transient and asymptomatic ECG changes (small mean increases in PR interval and QRS complex duration versus baseline) were noted in several subjects at 1 to 2 hours after infusion at doses > or = 3.0 mg/kg. Transient, mild blood pressure decreases were observed in five subjects, including one on placebo. Dolastron mesylate was well tolerated in single intravenous doses up to 5.0 mg/kg in healthy male volunteers. Clinical studies of the drug are ongoing for antiemetic indications.

Adolescent↗
PubMed1995

Predictors of blood lead levels in organolead manufacturing workers.

The relations between recent and cumulative exposure to organic and inorganic lead and blood lead levels were examined in 222 organolead manufacturing workers. Personal monitoring data grouped by 29 exposure zones were used to derive estimates of recent and cumulative occupational exposure. Recent exposure to organic lead and recent combined exposure to organic and inorganic lead were significantly and positively associated with blood lead levels. Exposure duration was found to modify the relation between recent inorganic lead exposure and blood lead levels. Age and cigarette smoking were positively associated with blood lead levels, whereas alcohol use was associated with lower blood lead levels. This is in notable contrast to the influence of alcohol consumption on blood lead levels among inorganic lead workers or the general population. Furthermore, the data suggested that current alcohol use modified the relation between recent organic lead exposure and blood lead levels (P = .08): current alcohol users evidenced less of an increase in blood lead levels with increasing recent organic lead exposures than did workers who did not currently use alcoholic beverages. The data suggest that organic lead exposure affects blood lead levels, probably after dealkylation to inorganic lead. The associations with alcohol consumption may be evidence for differences in enzyme-mediated metabolism of organolead compounds. Finally, the data suggest that recent external lead exposure and internal lead stores both influenced blood lead levels in these workers.

Adult↗
PubMed1995

Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites.

OBJECTIVES--To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. METHODS--34 male lead workers in the Republic of Korea were given a single oral dose of 10 mg/kg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours. RESULTS--Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0.76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSA-chelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper dose-response relation between these two measures. CONCLUSIONS--The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead.

Adult↗
PubMed1995

Cumulative exposure to inorganic lead and neurobehavioural test performance in adults: an epidemiological review.

OBJECTIVES: To evaluate the current evidence that cumulative exposure to inorganic lead is associated with decreased performance in neurobehavioural tests in adults. METHODS: 21 unique studies were reviewed from 28 published manuscripts. An algorithm was developed to determine the usefulness of each study on the basis of exposure assessment, control of confounding variables, methods of subject selection, test conditions, and data analysis. Highest emphasis was placed on the use of cumulative measures of exposure or absorption. RESULTS: Only three studies used a measure of cumulative exposure to or absorption of lead, and two others used duration of exposure as a surrogate for cumulative exposure. All other studies used a measure that did not adequately estimate cumulative exposure to lead, most often current blood lead concentration. 20 of the studies controlled for age as a confounding variable, although in several studies the possibility for residual confounding by age remained. 16 studies controlled for intellectual ability before exposure; all of them used educational level for this purpose. Of the five studies that used direct or surrogate measures of cumulative exposure to or absorption of lead, two were thought to be of low usefulness because of inadequate duration of exposure. The three remaining studies found stronger associations of neurobehavioural performance with recent exposure measures than with those of cumulative exposure. CONCLUSION: The current scientific literature provides inadequate evidence to conclude whether or not cumulative exposure to or absorption of lead adversely affects performance in neurobehavioural tests in adults. The current evidence is flawed because of inadequate estimation of cumulative exposure to or absorption of lead and inadequate control for age and intellectual ability before exposure.

Age Factors↗
PubMed1994

Rater agreement for the Rey-Osterrieth Complex Figure Test.

This report assesses the intrarater and interrater reliability of quantitatively scoring the Rey-Osterrieth Complex Figure Test (RCF). The intrarater correlation coefficients were .96, .99, and .96, and the interrater correlation coefficients were .88, .97, and .96 for the Copy, Immediate Recall, and Delayed Recall, respectively. However, statistically significant mean differences in score were found between raters on the Copy, Immediate, and Delayed Recall. Though the majority of structural units within the RCF are reliably scored, several units had a greater magnitude of observed scoring differences compared to the other units after adjusting for expected differences. Overall, reliability estimates demonstrate high intrarater reliability and acceptable interrater reliability except for the potential for systematic scoring differences.

Adolescent↗
PubMed1994

Molecular cytogenetic analysis of a duplication Xp in a male: further delineation of a possible sex influencing region on the X chromosome.

We describe a male infant with severe mental retardation and autism with a duplication of the short arm of the X chromosome. Chromosome painting confirmed the origin of this X duplication. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified one copy of the zinc finger protein on the X chromosome (ZFX) and two copies of the steroid sulfatase gene (STS), further delineating the breakpoints. Based on cytogenetic and molecular comparisons of cases from the literature of sex-reversal in dup(X),Y patients and our patient, we suggest that a possible secondary sex-influencing gene involved in the regulation of sex determination or testis morphogenesis is present at the distal Xp21.1 to p21.2 region.

Autistic Disorder↗
PubMed1994

Comparison of measures of lead exposure, dose, and chelatable lead burden after provocative chelation in organolead workers.

OBJECTIVES: To describe 6 h urinary lead excretion (6 h PbU) after 1 g intravenous ethylene diamine tetraacetic acid (EDTA) in organolead manufacturing workers with mixed exposure to organic and inorganic lead; to determine the predictors of lead excretion (PbU); and to determine the extent to which internal lead stores and ongoing external exposure govern blood concentrations of lead (PbB). METHODS: A case series of 21 active workers were studied. Personal industrial hygiene data, grouped by 29 exposure zones, in combination with personal interviews about work location and times were used to derive several measures of recent and cumulative exposure to organic and inorganic lead. The average exposure intensities assigned to the 29 zones ranged from 4 to 119 micrograms/m3 (0.02-0.57 mumol/m3 as lead) for organic lead and from 1 to 56 micrograms/m3 (0.004-0.27 mumol/m3) for inorganic lead. RESULTS: After controlling for age, 6 h PbU was significantly and positively correlated with summary measures of PbB--for example, lifetime peak PbB, time weighted PbB--and zinc protoporphyrin concentrations--for example, lifetime peak zinc protoporphyrin, time weighted zinc protoporphyrin--but not with measures of estimated external exposure--for example, duration of exposure and cumulative exposure to inorganic or organic lead. Among workers with higher chelatable lead burdens (6 h PbU > or = 212.4 micrograms (1.03 mumol) divided at the median), there was no apparent relation between recent inorganic lead exposure and PbB at the time of chelation. Among workers with lower chelatable lead burdens (6 h PbU < 212.4 micrograms (1.03 mumol) however, there was a significant relation between exposure and effect between recent exposure to inorganic lead and PbBs. CONCLUSION: These findings are consistent with the concept of physiological dampening. The high chelatable lead burden, a source of internal exposure, dampens the effect of external exposure on PbBs. The data suggest that in organolead workers with high chelatable lead burdens, PbBs may be more influenced by internal lead stores than by variations in airborne exposure to organic and inorganic lead.

Adult↗
PubMed1994

Comorbidity of migraine and panic disorder.

Clinical and epidemiologic evidence suggests that migraine co-occurs with psychopathology, including specific anxiety disorders. To examine this association, survey data from a population-based study of more than 10,000 respondents were used to determine if individuals with a history of panic attacks were at greater risk of having specific headaches in the week preceding an interview. Four types of headache were defined. Of these, only migraine was strongly associated with panic attacks. Given the high prevalence of both migraine and panic attacks and evidence that they often co-occur, treatment implications are discussed for this comorbidity.

Adolescent↗
PubMed1993

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) associated with interstitial deletion of band 3q22: review and gene assignment to the interface of band 3q22.3 and 3q23.

We report on a child with blepharophimosis, ptosis, and epicanthus inversus (BPES), developmental delay and an interstitial deletion of band q22 of chromosome 3. A review of chromosome 3q anomalies associated with eye abnormalities, specifically blepharophimosis and ptosis, strongly suggests that a locus for eyelid development is present at the interface of bands 3q22.3 and 3q23.

Blepharophimosis↗
PubMed1993

Decrements in neurobehavioral performance associated with mixed exposure to organic and inorganic lead.

In 1990, 222 current employees of a chemical facility in the eastern United States that manufactured tetraethyl lead were administered a neurobehavioral test battery, tests of olfactory function and peripheral vibration threshold, and questionnaires that assessed neuropsychiatric symptoms. A cumulative variable of exposure to inorganic and organic lead was derived from 12 years of personal industrial hygiene sampling data and an occupational history interview that assessed work in each of 29 exposure zones in the lead area. The range of assigned exposure intensities in these 29 zones was 4-119 micrograms/m3 for organic lead and 1-56 micrograms/m3 for inorganic lead. Cumulative lead exposure and exposure duration were defined as categorical variables (four groups) in multiple linear regression models. The adjusted mean differences in neurobehavioral test scores were estimated by comparing the average scores of the moderate, high, and highest exposure groups with the low exposure (reference) group. After adjustment for premorbid intellectual ability, age, race, and alcohol consumption, neurobehavioral test scores were poorer as measures of both cumulative lead exposure and exposure duration increased; many of the associations evidenced dose-response relations. Associations were observed in most cognitive and functional domains tested, but were most common in two domains: manual dexterity and verbal memory/learning. On the affected neuropsychologic measures, the groups with the highest exposure averaged scores 5-22% lower than those of the reference groups. Overall, the data revealed generally consistent and coherent associations between two measures of lead exposure and poorer neurobehavioral test performance.

Adult↗
PubMed1993

Work activities and the onset of first-time low back pain among New York City fire fighters.

In a prospective study of first-time low back pain among New York City fire fighters, a total of 115 cases and 109 randomly selected controls were interviewed by telephone between December 1988 and July 1989 to examine the role of recent work activities in the onset of first-time low back pain. After adjusting for known risk factors and off-duty activities, statistically significant high-risk work activities included operating a charged hose inside a building (odds ratio (OR) = 3.26), climbing ladders (OR = 3.18), breaking windows (OR = 4.45), cutting structures (OR = 6.47), looking for hidden fires (OR = 4.32), and lifting objects > or = 18 kg (OR = 3.07). Low-risk activities included connecting hydrants to pumpers (OR = 0.36), pulling booster hose (OR = 0.19), and participating in drills (OR = 0.09) or physical training (OR = 0.16). When further adjusted for exposure to smoke (OR = 13.59), a surrogate for severity of alarms, the ORs associated with high-risk activities were no longer significant. This, however, does not diminish the role of activities in the onset of low back pain. Instead, it suggests an inseparable role for activities and environmental hazards. To examine this, the risk of low back pain was measured within five work zones sequential in time relative to location and distance from a structural fire. The risk gradually increased as the fire fighter moved away from the firehouse (OR = 0.10) and closer to the site of fire (OR = 3.91).

Case-Control Studies↗
PubMed1993

Consistent lack of association between breast cancer and oral contraceptives using either hospital or neighborhood controls.

BACKGROUND: Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls. METHODS: To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years. RESULTS: Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol. CONCLUSIONS: Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years.

Adolescent↗
PubMed1993

Do patients with less than 'echo-perfect' results from mitral valve repair by intraoperative echocardiography have a different outcome?

BACKGROUND: Not all valve repairs for mitral regurgitation (MR) have a perfect result, with no MR on postpump intraoperative echocardiography. Although more than 2+ MR by postpump echocardiography has led to second pump runs for further surgery in 6% to 8% of our patients, those left with 1+ or 2+ MR, traditionally an acceptable result, have not previously been evaluated for clinical outcome. METHODS AND RESULTS: Among 530 patients undergoing mitral repair during 1987 to 1989, 76 patients with 1+ or 2+ MR by postpump intraoperative echocardiography were compared with 76 patients who had equivalent age, sex, left ventricular function, and concomitant surgery but who had no MR by postpump echo. In-hospital morbidity measured by the frequency of respiratory complications, strokes, time in intensive care unit, and duration of hospital stay was actually higher in the patients with no MR after repair. Hospital mortality was not significantly different. There were no significant differences in posthospital mortality (4-year survival estimate of 86% in both groups), thromboembolic events, hospitalizations for heart failure, or functional class, although more patients in the group with no MR after repair were using diuretics. There was a trend toward more reoperations in patients with 1+ or 2+ MR compared with those with no MR by intraoperative echocardiography after repair (4-year estimates of freedom from reoperation, 83% versus 94%; adjusted risk ratio, 3.30). CONCLUSIONS: The presence of 1+ or 2+ MR by postpump intraoperative echocardiography does not confer increased morbidity or mortality. However, the trend toward more reoperations suggests the need for close follow-up for possible recurrence of MR. These data support our low threshold for performing further surgery during second pump runs.

Female↗