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PubMed2004

Two-year infant neurodevelopmental outcome after single or multiple antenatal courses of corticosteroids to prevent complications of prematurity.

OBJECTIVE: This study was undertaken to evaluate the effect of exposure to multiple antenatal steroid courses on short-term neonatal morbidity and 2-year infant neurodevelopmental outcome. STUDY DESIGN: This was a prospective observational study of 201 preterm singleton infants who received 1 or more courses of corticosteroids to prevent complications of prematurity and were delivered between 24 and 34 weeks' gestation at a single institution. Neurodevelopmental outcome of the infants was evaluated at 2 years corrected age. Logistic regression analysis was used to perform multivariate analyses of associations and trends. RESULTS: One hundred thirty-eight subjects (68.7%) received at least 1 complete course of betamethasone, whereas 63 (31.3%) patients were treated with dexamethasone. The prevalence of multiple steroid doses exposure was 26.8% (37/138) in betamethasone and 52.4% (33/63) in dexamethasone group. The prevalence of infant leukomalacia, including both prolonged echogenicity and cystic leukomalacia, was 25.9% (34/131) after a complete corticosteroid course, 40% (6/15) after 1, 42.3% (12/28) after 2, and 44.4% (12/27) after more than 2 additional courses, respectively (adjusted P for trend=.011). In the same categories of steroid exposure, the corresponding prevalences of 2-year infant neurodevelopmental abnormalities were 18% (20/111), 21.4% (3/14), 29.2% (7/24), and 34.8% (8/23), respectively (adjusted P for trend=.038). Multivariate study of first grade interaction suggested that the risk of leukomalacia and 2-year infant neurodevelopmental abnormalities associated with multiple doses exposure was confined to dexamethasone. In fact, compared with betamethasone, exposure to multiple doses of dexamethasone was associated with an increased risk of leukomalacia (19/33 compared with 11/37; odds ratio [OR]=3.21, 95% CI=1.07-9.77) and overall 2-year infant neurodevelopmental abnormalities (12/28 compared with 6/35; OR=3.63, 95% CI=1.03-13.58). CONCLUSION: In this study, multiple antenatal courses of dexamethasone but not betamethasone were associated with an increased risk of leukomalacia and 2-year infant neurodevelopmental abnormalities.

Betamethasone↗
PubMed2004

Occupation, pesticide exposure and risk of multiple myeloma.

OBJECTIVES: This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk.

Adult↗
PubMed1988

Acute toxicity of helenalin in BDF1 mice.

The acute toxicity of helenalin, a sesquiterpene lactone isolated from Helenium microcephalum, was examined in male BDF1 mice. The 14-day LD50 for a single ip dose of helenalin in male mice was 43 mg/kg. A single ip injection of 25 mg helenalin/kg increased serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea nitrogen (BUN), and sorbitol dehydrogenase within 6 hr of treatment. Multiple helenalin exposures, ip injection of 25 mg helenalin/kg for 3 days, increased differential polymorphonuclear leukocyte counts and decreased lymphocyte counts. Serum ALT, BUN, and cholesterol levels were also increased by multiple helenalin exposures at 25 mg helenalin/kg/day. Helenalin significantly reduced liver, thymus, and spleen relative weights and histologic evaluation revealed substantial effects of multiple helenalin exposures on lymphocytes of the thymus, spleen, and mesenteric lymph nodes. No helenalin-induced histologic changes were observed in the liver or kidney. Multiple helenalin exposures (25 mg/kg/day) significantly inhibited hepatic microsomal enzyme activities (aminopyrine demethylase and aniline hydroxylase) and decreased microsomal cytochromes P-450 and b5 contents. Three concurrent days of diethyl maleate (DEM) pretreatment (3.7 mmol DEM/kg, 0.5 hr before helenalin treatment) significantly increased the toxicity of helenalin exposure. The present studies indicate that the hepatic microsomal drug metabolizing system and lymphoid organs are particularly vulnerable to the effects of helenalin. In addition, helenalin toxicity is increased by DEM pretreatments which have been shown to decrease glutathione concentrations.

Animals↗
PubMed1995

Reducing donor exposure in preterm infants requiring multiple blood transfusions.

Preterm infants frequently require multiple blood transfusions. Traditionally, 'fresh' (less than seven days old) blood has been used but this often results in transfusions from multiple donors. To reduce donor exposure the policy for top-up transfusions was changed. A unit of blood under five days old with additional satellite packs was ordered for each infant and used up to its expiry date, allowing up to eight transfusions from a single donation to be given. The mean (SD) number of transfusions per infant in 43 infants transfused according to previous policy and in 29 transfused according to the new policy was similar at 5.6 (4.0) and 5.3 (3.1), respectively. However, donor exposure fell following the change in policy from 4.9 (3.5) to only 2.0 (0.9). Only one infant was exposed to more than three donors compared with 24 infants in the control group. Plasma potassium concentrations were not significantly different following transfusion of blood stored for up to 33 days. This simple change in policy has reduced donor exposure in infants requiring multiple top-up transfusions.

Blood Donors↗
PubMedDate not supplied

Food safety: risk assessment methodology and decision-making criteria.

As our scientific technology grows, risk assessment methods become more complex and, therefore, open to greater scientific debate. Risk assessment has always been a part of the regulatory notification and approval process for foods. However, the methodologies applied to risk assessment and decision-making have become diverse, dependent on a number of features, including the areas of the world in which one operates, the need to use cumulative risk assessment for pesticides and other ingredients or alternative risk assessment considerations for evaluating nontraditional or bioengineered foods. Diverse institutional structures within a single federal regulatory authority may tend to lead to diversity in risk outcomes that creates policy decisions that complicate and confuse the risk management process. On top of this challenge, decisions become more complicated by the need to examine beneficial factors of foods rather than the adverse effects of foods and food additives. Foods are a complex mixture of ingredients. Regulatory groups recognize the need to use new approaches for evaluating the safety and risks associated with foods and food additives, and to do so in a timely manner. The United States Food and Drug Administration (US FDA) in its need to ensure standards of "reasonable certainty of no harm" continues to explore alternative means to be responsive to petitioners as well as continue to examine scientifically validated means, e.g., quantitative structure-activity relationship (QSAR), and computer-assisted programs, within the approval process to assist in the evaluation of risks. Another means to improve the risk management process would include the cumulative risk assessment of pesticides that will, no doubt, be the beginning of more intensive efforts to understand cumulative exposures and the inherent risks from multiple pathways of exposure. The passage of the Food Quality Protection Act (FQPA) resulted in developing additional risk assessment methodologies and approaches to assess the potential for multiple exposures and risks. Addressing the international criteria used in decision-making related to foods safety assessment has resulted in acceptable intake values for food ingredients for carcinogens and noncarcinogens that, in general, tend to be more stringent in the United States compared to Europe. Clearly, the need for harmonization of risk assessment criteria and the impact of the decision process on regulatory approvals and safety assessment is a future need for the continued assurances of food safety. The topics presented in this paper are based on a symposium held in November 2002 at the annual meeting of the American College of Toxicology.

Animals↗
PubMed2003

Balloon dilatation in children for oesophageal strictures other than those due to primary repair of oesophageal atresia, interposition or restrictive fundoplication.

BACKGROUND: Balloon dilatation of the oesophagus in children has been performed predominantly for treating strictures, which are the result of primary repair of oesophageal atresia, interposition surgery or restrictive Nissen's fundoplication. Reports of the use of this technique for alternative causes of stricture are few. OBJECTIVE: To report our experience and success with balloon dilatation of strictures due to caustic ingestion, achalasia, oesophagitis, congenital stenosis, and epidermolysis bullosa (EB) and to make comparisons with our treatment of patients with primary repair of oesophageal atresia (OA), as well as with reports in the English language literature. MATERIALS AND METHODS: Retrospective review of fluoroscopically guided balloon oesophageal dilatation procedures in 19 patients over a 5-year period, and comparison of those performed for OA repair complications with those due to other diseases. The average radiation dose, per procedure, was calculated by a medical physicist. RESULTS: Ten patients had strictures as a result of primary repair of OA. Three patients had stricture as a result of EB, two from achalasia, two from caustic injury, one due to an oesophageal web and one from reflux oesophagitis. Our results show that the technique can also be curative for the last group and that it may be used intermittently to alleviate symptoms in ongoing diseases. We have not experienced any complications and have also calculated that, even with prolonged use of multiple procedures, the radiation exposure is comparable to other radiological techniques. CONCLUSIONS: Patients with alternative causes for oesophageal stricture may be treated to resolution within 2 years using balloon dilatation. Ongoing diseases such as EB require ongoing dilatation, but balloon dilatation of strictures has been successful in alleviating swallowing difficulty. Patients with stricture from OA repair sometimes need ongoing dilatation. Radiation exposure for multiple procedures, over an extended period, is comparable to that from a single abdominal CT, and can be considered acceptable when repeat complex surgery is the alternative treatment option, or when ongoing incurable disease is the cause of the stricture.

Adolescent↗
PubMed2003

Bioaccumulation of trace metals in the Antarctic amphipod Paramoera walkeri (Stebbing, 1906): comparison of two-compartment and hyperbolic toxicokinetic models.

Bioaccumulation of Cd, Pb, Cu and Zn in the Antarctic gammaridean amphipod Paramoera walkeri (Stebbing, 1906) was investigated at Casey station (Australian Antarctic Territory). The main goals were to provide information on accumulation strategies of the organisms tested and to verify toxicokinetic models as a predictive tool. The organisms accumulated metals upon exposure and it was possible to estimate significant model parameters of two-compartment and hyperbolic models. These models were successfully verified in a second toxicokinetic study. However, the application of hyperbolic models appears to be more promising as a predictive tool for metals in amphipods compared to compartment models, which have failed to adequately predict metal accumulation in experiments with increasing external exposures in previous studies. The following kinetic bioconcentration factors (BCFs) for the theoretical equilibrium were determined: 150-630 (Cd), 1600-7000 (Pb), 1700-3800 (Cu) and 670-2400 (Zn). We find decreasing BCFs with increasing external metal dosing but similar results for treatments with and without natural UV radiation and for the combined effect of different exposure regimes (single versus multiple metal exposure) and/or the amphipod collective involved (Beall versus Denison Island). A tentative estimation showed the following sequence of sensitivity of P. walkeri to an increase of soluble metal exposure: 0.2-3.0 microg Cd l(-1), 0.12-0.25 microg Pb l(-1), 0.9-3.0 microg Cu l(-1) and 9-26 microg Zn l(-1). Thus, the amphipod investigated proved to be more sensitive as biomonitor compared to gammarids from German coastal waters (with the exception of Cd) and to copepods from the Weddell Sea inferred from literature data.

Amphipoda↗
PubMed1996

Direct and indirect exposure to air pollution.

Hazardous substances that originally are discharged as air pollutants may find their pathway to human exposure through multiple routes, including ingestion and dermal contact, as well as direct inhalation. The mechanisms for modeling and understanding the fate of air pollutants through atmospheric transport, deposition into water and soil, bioaccumulation, and ultimate uptake to receptor organs and systems in the human body are complex. Pollution prevention programs can be better engineered, pollution priorities can be identified, and greater environmental public health gains (attributable to pollution prevention) can be achieved by evaluating the multiple pathways to human exposure and through improved dosage calculations. A single contaminant source often may represent only a fraction of a total body pollutant burden. Further research is needed on source culpability and attributable risk, long-range transport of air pollutants, human dose contributions by various pathways, better techniques for health risk assessment, and an identification of human behavior patterns that affect exposure and dose.

Air Pollutants↗
PubMed1999

Genetic subtyping of Escherichia coli O157 isolates from 41 Pacific Northwest USA cattle farms.

Escherichia coli O157 (n = 376) from 41 cattle farms were subtyped using pulsed field gel electrophoresis of endonuclease cleaved chromosomal DNA. Cleavage with XbaI resulted in 81 subtypes. Fifty-one isolates from subtypes found in more than one herd, or in herds on multiple sample collection dates were compared using the endonuclease NotI, resulting in 23 additional subtypes. Up to 11 XbaI subtypes were found per farm with up to 7 subtypes/farm identified from a single date. Indistinguishable subtypes (both XbaI and NotI) were found to persist on 4 farms for 6-24 months. Five subtypes were found on more than one farm separated by up to 640 km. Dairy farms where cattle had moved onto the farm had a similar number of subtypes as farms with no movement of cattle, and feedlots had more subtypes than dairy farms. These data indicate that there is a mechanism for multiple herd exposure to specific subtypes, there are multiple sources of exposure for cattle on farms, and on-farm reservoirs other than cattle may exist.

Animals↗
PubMed1998

Hepatitis C: controversies, strategies and challenges.

Risk factors for hepatitis C infection include I.V. drug use (42%); history of blood transfusion (6%); exposure to multiple heterosexual partners (6%); exposure to a household contact (3%); health care employment (2%); or hemodialysis (1%). Forty percent of patients have no identifiable risk factors. The HCV is a single-stranded, positive-sense RNA virus. Six major genotypes have been identified; each contains a series of subtypes. In the U.S., prevalences are type 1 (74%); type 2 (15%); type 3 (6%); and type 4 (1%). Within an infected individual, HCV also exists as a spectrum of closely related genotypes referred to as a quasispecies, and more complex quasispecies correlate with longer duration of disease, higher levels of viremia, genotype 1 infection, and poorer response to interferon therapy. Diagnosis is made by measuring anti-HCV by EIA, with confirmation by RIBA or HCV RNA. Patients with chronic HCV infection, with or without aminotransferase elevation, have detectable serum RNA by PCR. Standard therapy is interferon alfa 2b (Intron A) at a dosage of 3 million units 3 times a week for 6 months. This results in a 40%-50% complete response at the end of treatment (normal aminotransferases and undetectable HCV RNA), but relapse occurs in 60%-80% of cases over the next six months. Longer (12 month to 18 month) courses are now widely advocated. Better patient selection, e.g., those with low serum HCV RNA levels and absence of cirrhosis, and increased duration of therapy may lead to better response rates. Combination therapy with other antiviral agents, such as ribavirin, has dramatically reduced relapse rates.

Hepatitis C↗
PubMed1987

Further studies of patients with both honeybee- and yellow-jacket-venom-specific IgE.

Twenty-five sera from patients with high titers of both honeybee- and yellow-jacket-venom-specific IgE were analyzed in RAST inhibition experiments, using each venom as the coupling and inhibiting antigen. Eight sera had unique antibody activity with no cross-reactivity between yellow-jacket- and honeybee-venom-specific IgE. In 5 sera, the IgE antibody activity was directed at a major allergen in yellow jacket venom cross-reacting with a minor allergen in honeybee venom. Honeybee venom inhibited only the honeybee venom RAST; yellow jacket venom inhibited both the honeybee and the yellow jacket venom RAST. Five sera showed the opposite pattern with IgE antibody directed at a major allergen in honeybee venom cross-reacting with a minor allergen in yellow jacket venom. The fourth newly observed pattern was that of extensive IgE antibody cross-reaction found with 7 sera. Both honeybee venom and yellow jacket venom inhibited both the honeybee and yellow jacket venom RASTs. There were no clinical features such as age, sex, atopy or type of anaphylactic symptoms which could distinguish patients in each group. All but one patient had a history of multiple sting exposures. These data suggest multiple allergens in honeybee and yellow jacket venom with differing patterns of cross-reactivity and have important implications for proper venom immunotherapy.

Adolescent↗
PubMed1995

Helicobacter pylori infection in dentists--a case-control study.

To test the null hypothesis that frequent and multiple salivary exposure is not a risk factor for developing H. pylori infection, serum anti-H. pylori IgG from 179 dentists and dental students and 179 age-, sex- and socioeconomic-matched controls were assayed using an ELISA. Seroprevalence in dentists was 16% (11/70); clinical dental students 6% (3/47); and pre-clinical dental students 10% (6/62). There were no differences in H. pylori seropositivity between cases and controls. There was an increase in H. pylori seropositivity with age (chi (trend)2 9.04, p = 0.003). These data provide evidence that adults are not at high risk of developing H. pylori infection as a result of exposures to saliva from multiple sources.

Adolescent↗
PubMed1985

Drug and environmental exposure histories in selective patient populations.

Drug histories and environmental exposures are an important part of all medical histories and are particularly significant in specific at-risk primary care patient populations such as obstetrical patients, primary care genetic referrals, and pediatric patients being evaluated in developmental centers. A review of genetic referrals made by primary care physicians to a satellite genetics clinic over a one-year period showed that 29 percent of all referrals had a significant history of single drug exposure, single environmental exposure, or multiple environmental and drug exposures. Drug and environmental exposures must be an important consideration in all at-risk groups.

Drug Prescriptions↗
PubMed2004

Lowering fear-avoidance and enhancing function through exposure in vivo. A multiple baseline study across six patients with back pain.

This study investigated the effects of an exposure in vivo treatment for chronic pain patients with high levels of fear and avoidance. The fear-avoidance model offers an enticing explanation of why some back pain patients develop persistent disability, stressing the role of catastrophic interpretations; largely fueled by beliefs and expectations that activity will cause injury and will worsen the pain problem. Recently, an exposure in vivo treatment was developed that aims to enhance function by directly addressing these fears and expectations. The purpose of this study was to describe the short-term, consequent effect of an exposure in vivo treatment. The study employed a multiple baseline design with six patients who were selected based on their high levels of fear and avoidance. The results demonstrated clear decreases in rated fear and avoidance beliefs while function increased substantially. These improvements were observed even though rated pain intensity actually decreased somewhat. Thus, the results replicate and extend the findings of previous studies to a new setting, with other therapists and a new research design. These results, together with the initial studies, provide a basis for pursuing and further developing the exposure technique and to test it in group designs with larger samples.

Adult↗
PubMed1981

Acute ammonia intoxication complicating multiple trauma.

Exposure to ammonia gas causes severe tissue damage to skin, lungs, and eyes. Toxic effects, both immediate and delayed, can alter the response to other injuries. We report a 14-year-old boy who suffered multiple trauma in a vehicular accident and at the same time was exposed to anhydrous ammonia. He exhibited severe pulmonary and ocular damage in addition to other severe injuries, and despite aggressive treatment, died of respiratory failure.

Accidents, Traffic↗
PubMed1993

Measurements of year-long exposure to tree nursery workers using multiple pesticides.

A year-long nurseryworker pesticide exposure study was designed to measure and evaluate the exposure occurring to workers who had the potential for simultaneous exposure to multiple pesticides. This four-State study was conducted in five nurseries (four USDA Forest Service and one State) involved in conifer seedling production. Primary comparisons were made among nursery workers in the Pacific northwest and south central United States. Worker exposure was assessed by using patches attached to clothing, handrinse samples and urine excreted from potentially exposed workers. In addition, dislodgeable residue in rinsate from a water wash of pesticide-treated seedlings was also evaluated. Four different groups of field workers, designated as applicators, weeders, scouts and packers, were included. The pesticide absorbed dose, assessed by urine analysis of pesticide metabolites and the deposition of pesticide on patches attached to the clothing of field workers, was monitored as they performed their duties under normal conditions (e.g., typical clothing, pesticide application). Monitoring was performed for the 14 different pesticides which were used in these nurseries. Seven pesticides were studied in more detail using biological monitoring. For these compounds, metabolites known to be excreted in the urine of exposed humans or other mammals were used to estimate the dose of pesticide absorbed by the exposed workers. The highest percentage of positive samples came from dislodgeable residue samples (8.3%) followed by patch samples (3.2%), handrinse (2.9%), and urine samples (1.3%). To summarize the conclusions from the urinary excretion data, 12 of the 73 nursery workers in the study received a low absorbed dose of pesticide. Biological monitoring revealed that three pesticides (benomyl, bifenox and carbaryl) were found in the urine of some of the workers. Of the 3,134 urine samples analyzed there were 42 positive; 11 urine samples were positive for benomyl, while bifenox was responsible for 13 positives and carbaryl accounted for the remaining 18. The 12-week continuous monitoring of urine showed that metabolites of these materials were rapidly excreted; thus, no build-up in the body is anticipated. Margins of Safety (MOS) calculations were made to provide an assessment of the significance of the exposure. Based on the low frequency of positive urine samples in the study, the low levels of metabolites when they were found, their apparent rapid excretion rate and the No Observed Effect Level (NOEL) data, furnished from other sources, nursery worker exposure to pesticides in these conifer nurseries is below health threatening levels.

Adult↗
PubMed1992

Expression of monocyte activation antigen Mo3 on the surface of peripheral blood monocytes from patients with multiple sclerosis.

Exposure of human peripheral blood monocytes (PBM) to phorbol esters, bacterial products, and cyclic adenosine monophosphate agonists is known to stimulate expression of a plasma membrane antigen ([Ag]; Mo3). Mo3 is recognized by two monoclonal antibodies, Mo3e (IgM), and Mo3f (IgG). Surface Mo3 is barely detectable by indirect immunofluorescence flow cytometry in nonstimulated monocytes. Mo3-positive monocytes have been found in inflammatory tissues, but increased surface expression of Mo3 in PBM has not been seen in any patient group. We report that PBM from patients with chronic progressive MS (CPMS) express increased Mo3. PBM from patients with other neurologic diseases and healthy controls express little measurable Mo3. No difference was seen in class II major histocompatibility complex Ag expression and in Mo2 (CD14) expression. Exposure of PBM to lipopolysaccharide (10 mg/ml) enhanced Mo3 expression in both MS patients and controls. Mo3 expression on CPMS PBM was not dependent on culture conditions. Taken together, our observations suggest that monocytes from patients with MS are stimulated in vivo to express activation Ag Mo3, but that Mo3-positive monocytes need not be upregulated for HLA-DR.

Cell Separation↗
PubMed2002

Hsp25 regulates the expression of p21(Waf1/Cip1/Sdi1) through multiple mechanisms.

Exposure of cells to external stresses leads to the induction or activation of certain proteins. Expression of heat shock proteins (Hsps) is induced in response to these stresses. Hsps are known to have molecular chaperone activities; but recent studies have shown that Hsps have a variety of functions such as the triggering of proliferation, differentiation, and apoptosis of cells. Previously, we found that overexpression of a 25 kDa Hsp (Hsp25) induced expression of cell cycle inhibitory protein p21 (Waf1/Cip1/Sdi1) in murine fibroblastoid L929 cells. However, the mechanisms underlying the induction of p21 by Hsp25 are unknown. In the present study, we investigated the mechanisms underlying the regulation of p21 expression by Hsp25 in these cells. The introduction of Hsp25 cDNA stimulated the accumulation of p21 transcripts through transcriptional but not posttranscriptional regulation in these cells. We also found that overexpression of Hsp25 markedly increased the translational rate of p21 and stabilized the protein. Studies involving proteasome inhibitors and Western blot analysis for ubiquitination of p21 demonstrated that the stabilization of p21 is regulated through a ubiquitin-independent pathway. However, no direct association of Hsp25 with p21 was observed. These findings suggest that Hsp25 induces p21 expression through multiple mechanisms, and that transcriptional, translational, and post-translational regulation are important in the regulation of p21.

Animals↗