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PubMed1992

Persistence of platinum-ammine-DNA adducts in gonads and kidneys of rats and multiple tissues from cancer patients.

The persistence of platinum-DNA adducts was investigated using normal rats as well as tissues from cancer patients receiving either cisdiamminedichloroplatinum(II) (cisplatin) or diamminecyclobutanedicarboxylatoplatinum(II) (carboplatin) for cancer chemotherapy. These studies used an enzyme-linked immunosorbent assay, established with a rabbit anti-cisplatin-DNA that is specific for intrastrand platinum-DNA adducts. The gonads and kidneys of male and female rats, sites for antitumor activity and toxicity, respectively, were monitored for cisplatin-DNA adduct formation after a single dose of drug and during multiple-dose exposures (once a wk for 3 wk). DNA adducts were measured by enzyme-linked immunosorbent assay 4 h and 2, 4, 7, and 14 days after administering a single i.v. injection of 8 mg/kg of cisplatin. Adduct profiles in renal tissues were similar in both males and females with adduct levels increasing between 4 h and 2 days, decreasing between Days 2 and 7, and stable between Days 7 and 14. In both sexes, levels of kidney DNA adduct measured 7 to 14 days after cisplatin injection comprised about 30% of the highest (Day 2) value. In testes and ovaries, adduct removal was complete by 4 days, and 40 to 50% of adducts present at Day 2 persisted until Days 7 and 14. A study of multiple dosing showed that adducts in renal and testicular DNA from rats given three weekly doses of 5 mg/kg of cisplatin had different accumulation profiles. In the testis there was a 2-fold accumulation of adduct after the third dose, while in the kidney adducts dropped with repeated dosing. In humans, the persistence of platinum-DNA adducts was studied in tissues from eight cancer patients who received their last dose of cisplatin or carboplatin chemotherapy between 1 day and 15 mo before autopsy. The patients had either ovarian cancer, breast cancer, or lymphoma, and the tissues studied included ovarian tumor, bone marrow, kidney, liver, spleen, lymph node, peripheral nerve, and brain. When samples were available from tumor tissues and from bone marrow within the same patient, adduct levels were similar in the two tissues. In addition, adducts were persistent for many months, since half of the individuals received their most recent platinum-drug therapy 7 to 15 mo before death. Overall, these studies demonstrate a widespread distribution and high degree of platinum-DNA adduct persistence in both animal and human tissues subsequent to cisplatin or carboplatin treatment.

Adult↗
PubMed2004

[Prediction of 29-years mortality rate from initial and emerging risk factors during follow-up in a Warsaw population].

Searching for clues through cohort studies requires introducing initial values of predictors likely to forecast future morbid events. This may put the end points on unequal footing, due to different timing of preceding exposures. A long follow-up mortality study of an urban population with repeated measurements in the midst of the observation enabled splitting predictors of death into time-related components making comparisons more alike with regards to time. A random sample of 1898 Warsaw adult population was interviewed in 1970 on a variety of demographic, social, behavioural and morbid circumstances as well as the use of health services. The 29-year-long search for death events was instituted with 751 (39.5%) deaths ascertained till the end of 1999 and 166 persons not traced (8.7%). In 1979 the inquiry was repeated in 1366 respondents alive and ready to take part, with the same set of questions asked. Beyond base-line values of traits in question, the estimates of change (possible predictors both times; appearance or vanishing of a trait; no trait whatsoever; no answer) were arranged as dummy variables tested for creating an excess risk against double absence of exposure. Cox multiple regression models were used for assessing relative odds of death. The base-line '70 predictions limited the risk of death for women mainly to non-structured evidence of disease whereas among men they included social circumstances, smoking & bronchitis, and possession of a personal doctor. With the '79 base-line recent hospital discharge was added to the prediction of remaining ('80-'99) mortality experience of both sexes, and disability appeared as a risk factor in men. Using time-related variables disclosed the mortality-boosting influence of twice-confirmed smoking in both sexes, as well as the excess death following the so far absent protracted illness among men and women. The appearance of the excess risk of death due to addition of hitherto neutral exposures was more frequent among men than women. The same pattern of the new exposures emerged for recent hospital discharge vs. no hospitalization. It seems that arranging exposure in the time-related fashion discloses a newly evolving excess risk of death which may pave the way towards death in more vulnerable fraction of a population in largely non-specific fashion.

Adult↗
PubMed1997

Impact of multiple antenatal doses of betamethasone on growth and development of mice offspring.

OBJECTIVE: Our purpose was to determine in a randomized, placebo-controlled manner whether multiple antenatal doses of betamethasone affect long-term growth and development of exposed mouse offspring. STUDY DESIGN: Sixty pregnant CD-1 mice received either two, four, or eight antepartum doses of 0.1 mg betamethasone or placebo. Perinatal outcomes, growth, and development of the offspring were compared in a blinded manner. Variables were compared by analysis of variance or chi 2 testing. RESULTS: Betamethasone-exposed subjects gained less weight during pregnancy and were delivered of fewer live pups, with fewer male survivors and lower birth weights. These trends were dose related. Growth measurements were similar after the neonatal period. No differences in functional development and physical maturation in the offspring were noted. The reproductive capability, perinatal outcomes, and growth and development of the second-generation offspring were unaffected by betamethasone exposure. CONCLUSION: Multiple antenatal dosings of betamethasone, reaching toxic levels, did not have an impact on the long-term growth and development of the surviving mouse offspring.

Animals↗
PubMed1996

Bloodborne pathogens risk and precautions among urban fire-rescue workers.

Health care workers are exposed to various infectious agents that can lead to disease transmission during patient care. Emergency first-responders, paramedics, and emergency medical technicians (EMTs) are a subgroup of health care workers particularly at risk for occupational exposure to bloodborne pathogens. The Centers for Disease Control and Prevention has recommended universal precautions to prevent occupational transmission of bloodborne pathogens among health care workers. This cross-sectional study evaluates risks and behaviors for occupational exposure to bloodborne pathogens among urban paramedics and EMTs in Dade County, Florida. Reported exposure via multiple routes was common, especially among paramedics. Knowledge of universal precautions was high, but reported practices were suboptimal because of inadequate information, as well as logistical and access issues. Additional research, administrative effort, and regulation are needed to increase the application of universal precautions in the prehospital setting.

Adult↗
PubMed2003

Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin.

The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P < 0.005-0.001), catalase (51-92%, P < 0.001) and glutathione level (87-100%, P < 0.005). Treatment of EGCG or GTP also inhibited UVB-induced oxidative stress when measured in terms of lipid peroxidation (76-95%, P < 0.001), and protein oxidation (67-75%, P > 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P < 0.01-0.001), oxidative stress (33-71%, P < 0.01) and phosphorylation of ERK1/2, JNK and p38 proteins of MAPK family but the photoprotective efficacy was comparatively less than that of topical treatments of EGCG and GTP. Lesser photoprotective efficacy of GTP in d.w. in comparison with topical application may be due to its less bioavailability in skin target cells. Together, for the first time a cream based formulation of green tea polyphenols was tested in this study to explore the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans.

Animals↗
PubMed2005

Application and impact of population pharmacokinetics in the assessment of antiretroviral pharmacotherapy.

Population pharmacokinetics has been an important technique used to explore and define relevant sources of variation in drug exposure and response in patient populations. This has been especially true in the area of antiretroviral therapy where the assurance of adequate and sustained drug exposure of multiple agents is highly correlated with therapeutic success. Population pharmacokinetic analyses across the four drug classes and 20 US FDA-approved products used to treat HIV have been published to date. The published reports were predominantly based on actual clinical trials conducted in HIV-infected patients with one or more agents administered. Modelling and simulation approaches have been used in the evaluation of antiretroviral agent outcomes incorporating problematic design and analysis factors such as sparse plasma sampling, data imbalance and censored data. Additional benefits of population modelling approaches applied to the investigation of antiretroviral agents include the ability to assess dosing compliance, understanding and quantifying drug-drug interactions in order to select dosing regimens and the screening of new drug candidates. Pharmacokinetic/pharmacodynamic models have been used to characterise the relationship between drug exposure and virological and immunological response, and to predict clinical outcome. These models offer the best opportunity for individualising and optimising patient therapy, particularly when adjusted for adherence/compliance. The impact of population pharmacokinetics in the area of antiretroviral therapy can be directly assessed by its role in the validation of surrogate markers such as viral RNA load, therapeutic drug monitoring and the management of individual patient outcomes via exposure-toxicity relationships. Each of these population pharmacokinetic outcomes has contributed to the current regulatory environment, specifically in the area of accelerated approval of new antiretroviral agents.

Anti-HIV Agents↗
PubMed1990

Isobolographic characterization of drug interactions incorporating biological variability.

Isobolograms have been widely used to characterize the nature of the interaction between combinations of drugs or chemicals. Some authors have applied this technique without accounting for the variability in the data or without adjusting for multiple comparisons to the line of additivity. This paper develops a graphical procedure which takes into account the variability of the data and which maintains favorable statistical properties. The isobolographic procedure utilized is illustrated by using three classical pharmacological drug combinations in female ICR mice. An additive relationship is illustrated with the loss of righting reflex after combinations of doses of sodium hexobarbital with itself. An antagonistic relationship is illustrated with the protection by mecamylamine of nicotine-induced lethality. A synergistic relationship is illustrated with the loss of righting reflex after combinations of ethanol and chloral hydrate. The procedure's statistical properties (level of significance and power) were determined using a simulation study. The isobolographic procedures developed here are applicable for quantal, continuous and count data. These procedures are applicable for identifying beneficial drug combinations, or conversely, identifying hazards resulting from exposure to multiple toxicants.

Animals↗
PubMed1994

A six-hour in vitro virulence assay for Listeria monocytogenes using myeloma and hybridoma cells from murine and human sources.

An in vitro cell culture assay using myeloma cells and hybrid lymphocytes was developed which detected pathogenic Listeria strains in just 6 h. Three separate hybridoma cell lines, murine Ped-2E9 and EM-7G1 and human RI.37 and murine myeloma NS1 cells, proved equally sensitive in responding to virulent Listeria species. Listeria monocytogenes along with other Listeria spp., collected from food and clinical sources, were inoculated at 10(8) cfu/ml into a suspension of Ped-2E9 (10(6)/ml). Pathogenic Listeria spp. killed 80% of hybridoma cells by 4 h, as determined by trypan blue exclusion test. Conversely, none of all nonpathogenic Listeria spp. killed the hybridoma cells. Ped-2E9 cells exposed to three strains of L. monocytogenes strains showed 96-97.5% death in 6 h measured by trypan blue staining and release of 91-97% of lactate dehydrogenase (LDH) enzyme. RI.37 cells showed similar results. A multiplicity of exposure (MOE) of 100 L. monocytogenes to 1 hybridoma cell or of 10:1 killed about 80% of the hybridoma cells in 4 or 6 h respectively. The in vitro virulence assay of L. monocytogenes with hybridoma cells compared favorably with the immunocompromised mouse model, yielding results in 6 h instead of 3 days. Intracellular L. monocytogenes and L. innocua were not recovered from Ped-2E9 hybridoma cells after 2 or 4 h of exposure. However, attachment of both L. monocytogenes and L. innocua cells on Ped-2E9 cell surfaces were observed under epifluorescence microscopy. Direct contact of hemolysin positive L. monocytogenes with hybridoma cells is essential to cause death, since hybridoma cells were not killed when they were separated from the growing bacteria by a 0.45 microns filter.

Animals↗
PubMed1992

Conceptual problems in identifying risk factors for functional decline in the elderly: a commentary.

Assessment of risk factors for chronic disease and disability among the elderly is a complex issue. Findings may be affected by the age at which the putative risk factor was measured, interval between the time of measurement of risk and outcome, possibility of changing patterns of exposure throughout the life span, and selective survival. We illustrate the complexity of risk assessment with findings from the Iowa 65+ Rural Health Study on the relationship between body mass and changing physical function. In baseline cross-sectional analyses, both high and low body mass were associated with poorer function. In 6-year longitudinal analyses limited to persons who were functionally intact at baseline, high body mass was associated with poorer lower-extremity function but relatively preserved upper-extremity function. High body mass was also associated with elevated rates of transient impairments. Extremes of teenage body habitus were associated with impaired physical function in old age. Function was poorest among those with a lifetime history of high body mass, and changes in body mass were complexly associated with subsequent function. Thus conceptual and analytic models of chronic illness and disability need to consider multiple, changing exposures over the lifetime, as well as the impact of illness, disability, and their treatment on subsequent risk factor exposure.

Activities of Daily Living↗
PubMed2007

Neurocognitive characteristics of DUI recidivists.

Individuals who drive under the influence (DUI) of alcohol may be at greater risk for neurocognitive impairment because of their exposure to multiple sources of neurological risk. This could contribute to the persistence of DUI behaviour and influence the effectiveness of remedial interventions. The objectives of this study were to clarify the neurocognitive characteristics of DUI recidivists and the nature of potential impairments, and to explore relationships between these characteristics and the frequency of past DUI convictions. One hundred male recidivists were evaluated for visuospatial constructional abilities and visual memory, verbal fluency, attention skills, cognitive flexibility, spatial planning, and verbal and movement inhibition. Results indicated that a majority of recidivists showed signs of neurocognitive impairment on several dimensions. Impairment was most marked on visuospatial constructional abilities and visual memory. In contrast to previous studies, no participants were found to have impulse control problems. Measures of memory and cognitive efficiency were significantly associated with the frequency of past convictions. Finally, exploratory analyses of two potential sources of impairment, alcohol exposure and head trauma, suggested the role of excessive alcohol use as the most obvious associated factor. Overall, the findings indicate that neurocognitive impairments are a common feature in recidivists and may contribute to DUI persistence. Development of a DUI-specific neurocognitive assessment and greater understanding of how neurocognitive status influences DUI risk could lead to remediation strategies better adapted to the individual characteristics of recidivists.

Adult↗
PubMed2003

Randomized, single-blind, placebo-controlled study of topical application of the immune response modulator resiquimod in healthy adults.

Resiquimod is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent inducer of alpha interferon (IFN-alpha) and other cytokines. The effects of multiple applications of resiquimod gel were assessed in a randomized, single-blind, dose-ranging, placebo-controlled study with 41 healthy subjects. Over a 3-week period, 1-g doses of resiquimod or vehicle gel (3:1 randomization) were applied to a 50-cm2 area of the upper arm according to the following regimens: 0.25% applied for 8 h two times per week, 0.05% applied for 8 h two times per week, 0.05% applied for 8 h three times per week, and 0.01% applied for 24 h three times per week. Skin biopsy specimens were obtained prior to the application of the first dose and after the completion of application of the last dose. Dosing with 0.01 and 0.05% resiquimod was well tolerated, but that with 0.25% was not; a dose-response relationship for local adverse effects was observed. The level of systemic exposure during multiple topical dosings was <1% of the applied dose. A significant increase in responders after completion of application of the last dose was observed for serum IFN and the interleukin-1 (IL-1) receptor antagonist (P<0.01, Fisher's exact test). Increased levels of mRNA for IL-6, IL-8, IFN-alpha, and Mx (an IFN-alpha-inducible protein) were seen in posttreatment biopsy specimens from the group receiving 0.25% resiquimod compared to the levels seen in specimens from the group receiving vehicle only (P<0.01, Wilcoxon rank sum test). A dose-response-related increase in CD3-positive cells consistent with T-lymphocyte infiltration and a decrease in CD1a-positive cells, consistent with emigration of Langerhans' cells, were observed in treated skin. This study suggests that resiquimod is a potent topically active immune response modifier that significantly enhances the cutaneous immune response.

Adjuvants, Immunologic↗
PubMed2003

Analysis of gene expression profiles in largemouth bass exposed to 17-beta-estradiol and to anthropogenic contaminants that behave as estrogens.

Novel molecular based methods are being developed to study changes in gene expression in wildlife exposed to anthropogenic chemicals. Gene arrays, in particular, are useful tools that can be used to simultaneously monitor hundreds to thousands of genes within a single experiment, giving an investigator the ability to determine how exposure affects multiple metabolic pathways. These methods are thought to be both sensitive and able to reveal biochemical mechanisms of action. A largemouth bass (LMB) array containing 132 genes has been designed to study the impact of gene expression in male fish exposed to 17-beta estradiol or to the compounds 4-nonylphenol (4-NP) or 1,1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p,p'-DDE). The results of these experiments demonstrate distinct gene expression patterns in LMB exposed to these compounds.

Animals↗
PubMed2004

Neurologic and immunologic effects of exposure to corticosterone, chlorpyrifos, and multiple doses of tri-ortho-tolyl phosphate over a 28-day period in rats.

An animal (rat) model of chronic stress (corticosterone in the drinking water) was used to study the interaction of stress and the organophosphorus (OP) neurotoxicants chlorpyrifos (60 mg/kg subcutaneously in a single dose) and tri-ortho-tolyl phosphate (TOTP, at 75, 150, or 300 mg/kg given 7 times orally in a 2-wk period). Adult male Long-Evans rats were provided with corticosterone in drinking water (400 microg/ml, w/v) for a total of 28 d, which led to significantly decreased weight and decreased cellularity of the thymus and spleen. Seven days after initiation of corticosterone treatment, half of the rats were given chlorpyrifos, and an additional 7 d later the 2-wk, 7-dose treatment of TOTP was initiated. During the 28-d test period, behavior of rats was evaluated using a functional observational battery (FOB), motor activity, and passive avoidance. Reductions in body weight, grip strength, and ambulatory movements occurred as a result of corticosterone treatment. Decreased body weight and grip strength were also elicited by TOTP, and the interactions of corticosterone and TOTP enhanced the effects on body weight and grip strength. Blood cholinesterase levels were obtained during the 28-d study period and found useful for monitoring OP exposure. At the end of the 28-d testing period, rats were sacrificed and activities of cholinesterase, neurotoxic esterase (neuropathy target esterase), and/or carboxylesterase were evaluated in blood, liver, and/or brain regions (basal forebrain, caudate putamen, cerebral cortex, hippocampus). All these esterases in brain were inhibited in a dose-related manner by TOTP, with some enhancement in rats drinking corticosterone-containing water. In addition, choline acetyltransferase, glial acidic fibrillary protein (GFAP), glutathione peroxidase, and superoxide dismutase were evaluated in one or more of the brain regions already identified. Choline acetyltransferase, glutathione peroxidase, and superoxide dismutase activities were unaffected by treatments. However, GFAP was elevated above control levels in the cerebral cortex of rats by all treatments (corticosterone, chlorpyrifos, TOTP). Neuropathological examination revealed early stages of dose-related increased distal myelinated fiber axonal degeneration seen in the medullary fasciculus gracilis at only the highest dose of TOTP (300 mg/kg).

Animals↗
PubMed1983

Evaluation of mixed exposure to carcinogens and correlations of in vivo and in vitro systems.

The biological evaluation of air pollutants is an example of the difficulties of evaluating the effects of mixed concurrent exposures to multiple agents, such as combinations of carcinogens with other carcinogens of the same or different chemical class, with incomplete carcinogens and cocarcinogens, with particulate materials and other factors that modify tissue distribution and retention, and with modifiers of metabolic pathways of activation and detoxication. A research approach is outlined to investigate such interactions in a series of biological systems of increasing complexity but closely related to each other in a step-by-step sequence, e.g., bacterial mutagenesis; mammalian cell mutagenesis, toxicity and neoplastic transformation, including embryo cells, fibroblasts and epithelial cells; organ cultures of target epithelia; in vivo animal systems for short-term and long-term studies, including animal models closely comparable to human pathology; observational studies of human pathology and histopathogenesis; experimental studies of corresponding human target tissues using organ and cell culture methods for metabolism, toxicity, mutagenicity and possibly neoplastic cell transformation. Respiratory carcinogenesis models were successfully used for studies of mixed exposures to different carcinogens and cofactors. The role of particulates has been found to be important but needs to be further characterized. Quantitative variations in the response to carcinogens and cofactors among different biological test systems and among different individuals in the human population make quantitative risk estimation very difficult, but studies in a sequence of related biological systems including human tissues indicate the importance of qualitative risk evaluation.

Air Pollutants↗
PubMed2002

Nickel(II)-induced apoptosis in murine T cell hybridoma cells is associated with increased fas ligand expression.

Nickel(II) exposure has multiple effects on the immune system, including thymic involution, decreased T cell number in the spleen, and decreased natural killer cell activity. Using a murine T cell hybridoma cell line (KMls 8.3.5.1) to model nickel-induced cell death in immune cells, we found that nickel(II) acetate treatment rapidly induced apoptosis in these cells, as signified by membrane blebbing, chromatin condensation, increased annexin V staining, and an increased proportion of cells with hypodiploid DNA. Preceding these morphological changes, nickel(II) treatment increased expression of Fas ligand (FasL) mRNA and protein levels and also increased caspase-3-like protease activity. Coincubation with caspase inhibitors markedly inhibited nickel(II)-induced apoptosis, with Z-IETD-FMK, an inhibitor of caspase-8 and granzyme B, nearly as effective as less selective caspase inhibitors. Agents that generate reactive oxygen species (ROS) cause apoptosis in a variety of cells by inducing expression of FasL. Given that nickel(II) can directly generate ROS, exposure to nickel(II) may lead to apoptosis through a similar mechanism.

Animals↗
PubMed2001

Invasive infections due to vancomycin-resistant enterococci in adult patients.

Since 1990, vancomycin-resistant enterococci have emerged as important nosocomial pathogens. Invasive infections caused by these organisms have challenged most physicians because they are resistant to multiple antibiotics. We analyzed the clinical characteristics of adult patients with invasive vancomycin-resistant enterococci infections in the National Taiwan University Hospital from January 1993 through December 2000. A total of 11 adult patients were identified, 9 of whom had bacteremia (7 caused by vancomycin-resistant Enterococcus faecalis and 2 by vancomycin-resistant Enterococcus faecium) and one each had thoracic empyema (vancomycin-resistant E. faecium) and peritonitis (vancomycin-resistant E. faecium). Five patients had rectal swab cultures positive for vancomycin-resistant enterococci; 4 of them had underlying malignancies. The majority (91%) of these patients had prolonged hospitalization and prior long-term use of broad-spectrum cephalosporins (ceftriaxone, ceftazidime, or cefepime) or anti-anaerobic agents (clindamycin or metronidazole). The crude mortality rate was 64%. In conclusion, invasive infection caused by vancomycin-resistant enterococci is an emerging problem among hospitalized patients in Taiwan, particularly those with severe underlying diseases and exposure to multiple antibiotics.

Adult↗
PubMed2003

Occupational contact dermatitis to nickel: experience of the British dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes.

AIMS: To examine, from occupational surveillance reporting data, whether scheme reporters considered nickel exposure to play a role in occupational contact dermatitis (OCD) in the UK. METHODS: Data on occupational skin disease in the UK are collected by two occupational disease surveillance schemes, EPIDERM and OPRA. Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or OPRA from February 1993 to January 1999 were studied. RESULTS: An estimate of 1190 cases of occupational contact dermatitis thought to have relevant nickel exposure (12% of total estimated OCD) was derived from reports by dermatologists, an average of 198 per year. The highest incidence rates were seen in hairdressers (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash and checkout operators (2.8), and catering assistants (2.5). From May 1994 to January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases) were estimated; the most frequently reported occupations were electronic assemblers, nurses, sales assistants, and general assemblers. From July 1997 to January 1999, 547 positive patch tests to nickel were reported; in 195 cases (36%), nickel was felt to be a relevant occupational allergen (for example, coin handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually considered, if relevant at all, to be only one of several causes of dermatitis. CONCLUSIONS: Up to 12% of total estimated cases of OCD were thought to be due in part to nickel. Results suggest that nickel hypersensitivity is one of several contributors to OCD in subjects with multiple occupational exposures. Coin handling may be a source of OCD to nickel.

Adolescent↗
PubMed1993

Lung responses to ultrasound-guided fetal treatments with corticosteroids in preterm lambs.

Maternal corticosteroid treatments augment lung function in the human preterm infant. However, not all fetuses respond, the response requires > or = 48 h of exposure, and multiple maternal doses expose the mother to potential risks. To evaluate the potential of direct fetal therapy, we used ultrasound to direct fetal intramuscular or intravascular injections of corticosteroids or saline in sheep and subsequently delivered the preterm lambs at 128 days gestational age to assess postnatal lung function. Relative to saline-injected controls, 0.5 or 2 mg/kg betamethasone given as a single intramuscular dose 48 h before delivery increased compliance and the efficiency of ventilation (as measured by an indicator that included ventilatory pressures and CO2 values) nearly twofold (P < 0.05). Lung volumes, measured from deflation pressure-volume curves, also increased (P < 0.05). However, the 2 mg/kg dose caused severe pulmonary interstitial emphysema in 5 of 13 lambs, suggesting adverse effects. An intravascular fetal dose of 12.5 mg/kg hydrocortisone or an intramuscular dose of 0.1 mg/kg betamethasone had no effect on postnatal lung function. In separate studies, the 2 mg/kg dose improved all indicators of lung function almost twofold after only 24 h of fetal exposure and delivery at 128 days gestational age (P < 0.01). There was a dose-dependent suppression of the postnatal cortisol surge in treated animals, although fetal treatment did not alter cord cortisol levels. Single-dose fetal hormone treatments can cause large and rapid improvements in postnatal lung function in preterm lambs.

Adrenal Cortex Hormones↗