The efficacy and safety of estriol to treat vulvovaginal atrophy in postmenopausal women: a systematic literature review.

OBJECTIVES: To evaluate the efficacy and safety of estriol for the treatment of vulvovaginal atrophy in postmenopausal women. METHODS: A systematic literature review was performed. We searched the following electronic databases: Medline, Cochrane, Embase, Lilacs, CINHAL and Google Scholar. The studies selected included controlled clinical trials and quasi-experimental studies. Selections were made in pairs and independently, first by title and abstract and then complete texts. RESULTS: We identified 188 studies, 22 of which met the inclusion criteria; 13 were controlled clinical trials and nine were quasi-experimental, and 1217 women were included. These studies confirmed the efficacy of local estrogens to treat symptoms of vulvovaginal atrophy with few adverse effects reported. Following treatment, serum estriol levels rose, peaking at 1 h. At the 6-month follow-up, there was no increase in serum estriol in treated women. CONCLUSIONS: The available evidence (of low and moderate quality) shows that, when administered vaginally, estriol preparations appear to be safe for women who have risk factors related to systemic estrogen therapy.

Copepod parasites of Curimatella lepidura (Characiformes, Curimatidae) from the Três Marias Reservoir, Brazil / Copépodes parasitos de Curimatella lepidura (Characiformes, Curimatidae) do reservatório de Três Marias, Brasil

Copépodes ergasilídeos coletados nas brânquias de Curimatella lepidura do reservatório de Três Marias, alto rio São Francisco, Minas Gerais, Brasil e identificados como Miracetyma etimaruya e Ergasilus sp., constituem o primeiro registro de parasitos nesse peixe forrageiro e endêmico. A ocorrência foi independente do sexo e do tamanho dos peixes. A distribuição geográfica conhecida das espécies de Miracetyma Malta, 1993, restrita à bacia do rio Amazonas, é ampliada neste estudo para a bacia do rio São Francisco.

Genetic monitoring of malathion-exposed agricultural workers.

The aerial application of malathion over large urban populations in Southern California during the early 1990s raised concerns about adverse health effects, including the potential to cause genetic damage. Workers in the Mediterranean fruit fly eradication program, which involved application of malathion as ground treatment, were studied to examine micronucleus formation and mutation frequencies assessed by the glycophorin A (GPA) assay. In the 1992 pilot project the mean micronuclei level appeared higher in lymphocytes of exposed workers (n = 13) compared to controls (n = 4) (20.1 +/- 7.1 vs 14.3 +/- 7.2 respectively, P = 0.09). During the 1993 season, neither of the cohorts examined showed a higher level of micronuclei in workers exposed to malathion compared to unexposed, nor did the pooled total (n = 53; means = 17.8 +/- 7.2 vs 18.5 +/- 6.3, respectively), even after adjustment by multiple regression. The GPA variant frequency was not associated with malathion exposure in any of the cohorts. These results suggest that any potential risk of genotoxic damage from exposure to malathion is relatively low, but other assays may be more sensitive, and the sample size was small.

Assessment of reproductive disorders and birth defects in communities near hazardous chemical sites. III. Guidelines for field studies of male reproductive disorders.

Exposures to environmental toxicants can have detrimental effects on several aspects of human male reproduction: fertility, sexual function, hormone status, and pregnancy/birth outcomes. However, no simple prescreening methods are available for reliably identifying potential hazards; questionnaires alone are relatively imprecise and inefficient in the absence of field data. Multidisciplinary field studies are required that include detailed exposure information, health and reproductive histories, physical examinations, semen analyses, and possibly, hormone analyses. Semen analysis is a critical component of field studies for evaluating two aspects of male reproduction: 1) changes in sperm or seminal content, which may be indicative of adverse effects on the male reproductive system with possible implications for fertility potential; and 2) defects in sperm DNA or chromosomes, which may be associated with subsequent changes in viability during embryonic development and health risks to the offspring. Semen analyses may be tiered: 1) initially, each semen study may include conventional semen assays (concentration, motility, and morphology) as well as specific biomarkers indicated by the health effect of concern in the study cohort: and 2) archived samples (i.e., frozen, videotaped, or smeared) may be utilized in later second-tier analyses to further characterize specific findings. Before initiating any field study, it is cost effective to critically evaluate the suitability of the cohort by confirming exposure and determining that there are adequate numbers of male participants in each exposure category. Such evaluations must be based on the statistical sensitivities of the specific tissue biomarkers and health endpoints for detecting changes. This article summarizes the components of the ideal field study and identifies research needs for improving field studies of male effects and for understanding the mechanisms of male reproductive toxicity. Several promising semen methods currently under development are also discussed.

Genotoxicity of malathion in human lymphocytes assessed using the micronucleus assay in vitro and in vivo: a study of malathion-exposed workers.

The aerial application of malathion, a widely used organophosphate insecticide, has raised public concerns about potential adverse health effects. We therefore studied micronucleus formation in human lymphocytes as a biomarker of genotoxicity both in vitro and in vivo. Lymphocytes were cultured either as whole blood or after Ficoll isolation and treated with malathion in doses from 5 to 100 micrograms/ml for 48 h. A significant increase in micronucleated cells (47.5/1000 versus 16.0/1000 in DMSO control, p < 0.001) was found in isolated lymphocytes at high dose levels (75-100 micrograms/ml), concurrent with cytotoxicity and a strong inhibition of proliferation (p < 0.001). Many of the treated cells also possessed multiple micronuclei. Antikinetochore-antibody staining revealed that the majority of malathion-induced micronuclei were kinetochore-negative. A significant dose-response was also observed in whole blood cultures, although the increase in micronucleated cells was lower than in isolated lymphocyte cultures (p = 0.03). When the same technique was applied to lymphocytes of 38 intermittently malathion-exposed workers involved in the Mediterranean Fruit Fly Eradication Program in California, no change in either proliferation or micronucleus level was observed compared with an unexposed control group. We conclude that malathion has a relatively low potential to cause chromosome damage in vitro, and corresponding doses are much higher than ones that even professional applicators are likely to be exposed to in vivo. The potential risk of chromosome damage for malathion exposure in vivo is therefore relatively low. More studies are needed to assess the possibility of interaction of malathion with other pesticides through combined exposure.

Lead poisoning in construction.

Ways to prevent lead poisoning and regulations intended to eliminate exposures to lead are the topics here. Lead registries and other studies are described that were designed to evaluate the extent of the problem and to address the lack of routine blood-lead monitoring in the industry.

Lead exposure in a tank demolition crew: implications for the new OSHA construction lead standard.

The Federal Occupational Safety and Health Administration (OSHA) has recently extended the basic health and safety provisions of the OSHA lead standard for general industry to workers in the construction industry. In this report we describe a tank demolition worksite that midway through the project strengthened its lead exposure control activities to a level that approximated the current lead standard. Of 12 tested ironworkers and laborers who worked at the site before the change, zinc protoporphyrin levels increased and seven developed blood lead levels (BLL) > 50 micrograms/dL. After the change these workers' BLLs declined. Six workers hired after the change did not experience increases in zinc protoporphyrin and none developed BLL > 25 micrograms/dL. The experience at this worksite demonstrates the usefulness and feasibility of implementing the current lead standard in construction settings.

Carpal tunnel syndrome among grocery store workers.

The California Department of Health Services evaluated carpal tunnel syndrome (CTS), a median nerve entrapment condition associated with forceful and repetitive wrist motion, among grocery store workers at a large California supermarket where a CTS cluster had been reported. Forceful and repetitive wrist motion was measured, in three exposure levels, through a job classification scheme based upon type of work tasks and average time per week spent performing these tasks. A medical questionnaire and measurements of median sensory nerve conduction were used to measure CTS. CTS prevalence was 23% based upon a sample of 56 participants drawn from a workforce of 69 employees. A relative risk of 8.3 (95% confidence interval 2.6-26.4) for a history of CTS-like symptoms between the high and low exposure level groups held up after adjustment for the potential confounders of age, sex, alcohol consumption, and high-risk medical history. It was concluded that the basic principles of good ergonomic design should be used to prevent or diminish the risk of musculoskeletal injury in the workplace.

4,4'-Methylene-bis(2-chloroaniline)-DNA adduct analysis in human exfoliated urothelial cells by 32P-postlabeling.

4,4'-Methylene-bis(2-chloroaniline) (MOCA) is an aromatic amine used widely in industry, and human exposure to this compound is well documented. MOCA induces lung and liver tumors in rodents and urinary bladder tumors in dogs, and it is regarded as a suspect urinary bladder carcinogen in humans. In this pilot study, we investigated the occurrence of MOCA-DNA adducts in exfoliated urothelial cells of a MOCA-exposed worker by 32P-postlabeling analysis. Urine samples were collected from the worker at various times after accidental acute exposure to MOCA. DNA isolated from exfoliated urothelial cells collected from each urine sample was enzymatically digested and postlabeled with excess [32P]ATP. Thin-layer chromatographic analysis of the labeled digests revealed the presence of a single, major DNA adduct that cochromatographed with the major N-hydroxy-MOCA-DNA adduct, N-(deoxyadenosin-8-yl)-4-amino-3-chlorobenzyl alcohol, formed in vitro. The MOCA-DNA adduct was detected in samples obtained between 4 and 98 h after initial exposure but not in samples collected at later times. The level of DNA adducts 4 h after exposure was determined to be 516 adducts/10(8) nucleotides. A 5-fold decrease in adduct level was observed 14 h later, followed by a gradual decrease over subsequent days. The results indicate that MOCA is potentially genotoxic to human urinary bladder in vivo and that 32P-postlabeling analysis of exfoliated urothelial cells provides a noninvasive means for biomonitoring the formation of MOCA-DNA adducts resulting from occupational exposure.

Lead exposure in the construction industry: results from the California Occupational Lead Registry, 1987 through 1989.

The construction industry is exempt from the medical monitoring portions of the US Federal Occupational Safety and Health Administration General Industry Lead Standard. Of 28 construction workers reported to the California Occupational Lead Registry through March 1989, 11 (39%) had blood lead levels of 2.90 mumol/L (60 micrograms/dL) or greater, the level at which immediate removal from lead exposure is mandated in nonconstruction industries. Many workers had not been warned of possible lead exposure. The exemption of the construction industry from the General Industry Lead Standard should be reconsidered.

Investigation of a fatality among parathion applicators in California.

Staff of the California Department of Health Services investigated the death of a parathion applicator in California that was thought to be pesticide-related. A crew of eleven workers (including six sprayers, three mixer/loaders, one mixer/sprayer and one foreman) had been applying 0.125% parathion spray to almond orchards for approximately three weeks. On the day of the fatality, a sprayer rapidly developed symptoms of salivation, sweating, and convulsions after a half-day of work. Despite aggressive medical treatment, the worker died within one hour of his initial symptoms. Significant laboratory results for the decreased case included: parathion residue on the inner and outer garments worn by the worker, parathion in the post-mortem gastric contents, and elevated urinary metabolites consistent with acute parathion intoxication. Interviews with the work crew revealed that three of the 10 workers had complaints of headaches, vomiting, and/or sore throat; yet, subsequent plasma and red cell cholinesterase tests of the co-workers did not show any significant depressions in comparison with pre-season baseline values. This worker death is consistent with prior reports of parathion-related sprayer/applicator intoxications and is the first worker-related parathion death in California since 1972. Substitution of pesticides with less toxic active ingredients or the elimination of parathion is recommended.

Screening workers exposed to 4,4'-methylenebis(2-chloroaniline) for bladder cancer by cystoscopy.

A bladder cancer incidence study was conducted among 540 workers exposed to the potential bladder carcinogen 4,4'-methylenebis(2-chloroaniline) from 1969 to 1979. Among the 385 workers who participated in a urine screening examination, none had suspicious or positive cytology. Twenty-one workers had at least one reading of atypia and 60 had either a positive dipstick for heme or greater than five red blood cells per low power field. The study protocol initially involved referral to private physicians for follow-up of any suspicious laboratory results. However, the diagnosis by cystoscopy of a bladder tumor in a nonsmoking man less than 30 years old with low-level hematuria prompted us to offer cystoscopy to all members of the cohort. A total of three tumors were identified in 200 persons who received cystoscopy. All were low-grade, papillary tumors and two occurred in men with completely normal urine screening results. These findings suggest that cystoscopy of asymptomatic persons should be considered in designing bladder cancer screening programs in high-risk cohorts.

Biological monitoring of a worker acutely exposed to MBOCA.

A 30 year-old male polyurethane worker was exposed to an accidental spill of 4,4'-methylene-bis-2-chloroaniline (MBOCA) at a plant producing MBOCA-cured plastic products. Exposure to MBOCA is significant in that this compound is a known animal carcinogen and a suspected human carcinogen. The employee was sprayed over his upper body and extremities with molten MBOCA while cleaning out a clogged hose from a MBOCA and polymer mixing machine. The subsequent environmental and medical evaluation of this episode included serial urinary MBOCA samples from the worker over a 2 week period to allow the calculation of a biological half-life for this compound. This worker experienced a very high dose of MBOCA as judged by his urinary MBOCA levels (peak value of 1,700 ppb 4 hours after exposure). There were no acute symptoms or other laboratory abnormalities noted. The kinetic evaluation resulted in a biological half-life for MBOCA in urine of approximately 23 hours. Assuming a one-compartment model, approximately 94% of an initial MBOCA dose will be eliminated within four days. This is the first report of kinetic analysis on urinary MBOCA excretion in humans. This information suggests that biological monitoring of the urine MBOCA concentrations in exposed workers may miss peak levels following an acute exposure unless the analyses of the urinary MBOCA are performed in a timely fashion. Recommendations to the company included: 1) installation of a warning system or lock-out device on the mixing machine to prevent the opening of the MBOCA hose prior to the release of pressure; and 2) annual medical surveillance of this individual for bladder cancer with urinalysis and urine cytology.

Nephropathy in cadmium workers: assessment of risk from airborne occupational exposure to cadmium.

To assess the quantitative relation between exposure to airborne cadmium and various markers of renal tubular and glomerular function, 45 male workers employed at a plant that recovers cadmium from industrial waste and 32 male hospital workers of similar age and geographical location were examined. Cumulative external exposure to airborne cadmium (dose) was estimated from historical air sampling data, adjusted for respirator use. Increasing cadmium dose was associated with multiple renal tubular functional abnormalities, including reduced reabsorption of beta-2-microglobulin (beta-2), retinol binding protein (RBP), calcium, and phosphate. Serum creatinine concentration also increased with cadmium dose, suggesting impaired glomerular function. Mean systolic and diastolic blood pressures were higher in the cadmium workers than in the unexposed (134 v 120 mm Hg and 80 v 73 mm Hg respectively), but only systolic blood pressure was significantly associated with cadmium dose in multivariate analyses. Cadmium dose remained the most important predictor of serum creatinine concentration after controlling for age, blood pressure, body size, and other extraneous factors. Logistic regression to model the probability (prevalence) of various renal abnormalities with increasing dose of cadmium was used. The probability of multiple tubular abnormalities and raised serum creatinine concentration increased sharply at cumulative cadmium exposures exceeding 300 mg/m3 days, corresponding to working for 4.3 years at the current permissible United States exposure limit for cadmium dust.

Bladder tumors in two young males occupationally exposed to MBOCA.

MBOCA (4,4' methylenebis (2-chloroaniline) is a structural analogue of benzidine and is carcinogenic in mice, rats, and dogs. MBOCA has not yet been demonstrated to be carcinogenic in humans and is not regulated as an occupational carcinogen in the United States. We report two noninvasive papillary tumors of the bladder identified in a screening study of 540 workers exposed to MBOCA during its production at a Michigan chemical plant from 1968 to 1979. Both tumors occurred in men under 30 years old who had never smoked. Although the prevalence of grade 1-2 tumors among asymptomatic males in this age group is unknown, the incidence of clinically apparent tumors on U.S. males aged 25-29 is only 1 per 100,000 per year. The detection of the two tumors in young, nonsmoking males is consistent with the hypothesis that MBOCA induces bladder neoplasms in humans.

A case-control study of bladder cancer using city directories as a source of occupational data.

Commercial city directories, currently produced in 1,250 United States cities, potentially provide yearly information on occupation and employer for all city residents over age 18 years. To investigate the usefulness of these occupational data, the authors have conducted a case-control study of male bladder cancer mortality in Hamilton County, Ohio (which includes Cincinnati). A total of 731 bladder cancer cases who died during 1960-1982 were matched on age, sex, race, date-of-death, and residence at death to two controls per case. Risks of bladder cancer death were calculated by occupation, industry, and specific employer, using both city directories (multiple statements) and death certificates (single statement). Four companies showed a significant excess bladder cancer risk when using city directories. Only one would have been identified using death certificates, which ask for usual lifetime type of industry rather than a specific company name. Using city directories, significant positive associations were found between bladder cancer and occupation as an engineer, tailor, carpenter, furnace operator, blending machine operator, chemist, pressing machine operator, house cleaner, or salesman. For industry, the authors found significant positive associations for the textile, chemical, grain mill, foundry, petroleum, building service, entertainment, and advertising industries. A significant increase in risk for those with 20 or more years of employment was seen for those employed as truck drivers and furnace operators, or those employed in the railroad industry. A check of the validity of city directory data indicated that 77 per cent of the listings agreed with Social Security earnings reports for employer in any given year. One limitation of Hamilton County city directory data was the fairly large number of yearly listings without any occupational data (15 per cent for occupation, 36 per cent for employer). While city directory data do provide work history over time, unlike death certificates, such data are available only for years of residence in the city in question.

Silica and glomerulonephritis: case report and review of the literature.

A 54-year-old foundry worker with extensive silica exposure, but no pulmonary disease, developed the nephrotic syndrome and renal failure over a 3-month period. Renal biopsy demonstrated a proliferative glomerulonephritis; energy dispersive x-ray analysis detected silicon within the renal tubules. Measurements of respirable silica at the foundry revealed levels up to 2.5 times the current occupational standard. Similar glomerular disease has been reported in silica-exposed animals and workers with silicosis. This case suggests that clinicians should include silica exposure in the differential diagnosis of unexplained diffuse proliferative glomerulonephritis, renal disease may occur without clinically evident pulmonary disease in silica exposure, and silica-induced glomerulonephritis warrants further clinical and epidemiologic research.

Investigation of lung cancer among female cosmetologists.

Using a population-based cancer registry to identify subjects, a case-control study of female cosmetologists in Los Angeles County was conducted to investigate possible occupational and environmental causes for the elevated lung cancer risk found in this group. A standardized questionnaire was administered to proxy informants for decreased lung cancer patients and decreased nonpulmonary cancer control patients. No associations between lung cancer and specific beauty shop tasks, beauty product use, or environmental exposures were observed in the crude analysis or after controlling for smoking status. Case subjects had held more jobs outside of cosmetology than control subjects, but these jobs did not appear to be associated with any known hazardous exposures. Despite the elevated risk of lung cancer among female cosmetologists, researchers were unable to relate this excess to any specific occupational tasks or exposures. The excess of lung cancer in cosmetologists is most likely accounted for by a higher frequency of smoking in this occupational group.