Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.

Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.

Outcome after injections of crushed tablets in intravenous drug abusers in the Helsinki University Central Hospital.

OBJECTIVE: To retrospectively analyse injection drug users (IDUs) with complications after intra- or extra-vasal administration of dissolved tablets. DESIGN: A retrospective study. METHODS: The hospital discharge registers were used to identify the patients admitted in different clinics in Helsinki University Central Hospital during 2000-2005. The patient demographics and social background were clarified. The type of the crushed drugs, the injection route and the timing of administration were registered. Medical interventions, examinations and surgical procedures were recorded. RESULTS: Between January 2000 and December 2005, 24 patients had been treated on 30 occasions for manifestations caused by injecting crushed tablets. The main types of manifestations were acute limb ischaemia (16 patients) and infection (eight patients), and eight cases led to distal or proximal amputations. Men (19 of 24) were affected more frequently than were women (5 of 24). Their ages ranged between 20 and 39 years (mean: 26 years). All the patients had a previous history of intravenous drug abuse, and they lived in Greater Helsinki region. The incidence of seropositivity for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) was 33% (n=8), 88% (n=21) and 4% (n=1), respectively. The time between injection and presentation to the Emergency Department varied between 3h and 10 days (mean: 62 h). Buprenorphine was the most commonly used drug in 10 of the 24 patients, and benzodiazepine derivatives were also used in 11 of the 24 patients. CONCLUSIONS: Intra- or extra-vasal administration of dissolved tablets leads to serious consequences, including limb amputations. Vascular and soft-tissue imaging may be helpful in the diagnosis. Prompt drainage of any abscess and fasciotomies for compartment syndrome treatment are essential. Controversy exists over the best medical therapy.

TICAREX: Exposiciones laborales a agentes cancerígenos y plaguicidas en Costa Rica / TICAREX: occupational exposure to carcinogens and pesticides in Costa Rica

El sistema europeo de datos CAREX (CARcinogen Exposure) considera la fuerza laboral de un país agrupada en 55 sectores económicos según la Clasificación Internacional de Actividades Económicas de las Naciones Unidas, segunda revisión de 1968, y mediante la aplicación de proporciones de trabajadores expuestos a partir de datos generados en estudios de higiene industrial para 139 agentes carcinógenos, los convierte en fuerza laboral expuesta y número de trabajadores expuestos a agentes carcinogénicos, según rama de actividad. En este artículo se describe una modificación y extensión del sistema CAREX para calcular los números de trabajadores expuestos a agentes cancerígenos y plaguicidas en Costa Rica. Esta primera aplicación de CAREX fuera de Europa (TICAREX) fue realizada en Costa Rica, Centroamérica, para 27 agentes cancerígenos y 7 grupos de plaguicidas, considerados de interés para el país, realizando estimaciones por separado para mujeres y hombres. Los agentes cancerígenos más frecuentes a los que se expone la fuerza laboral de Costa Rica de 1.3 millones fueron la radiación solar (333,000 trabajadores), las emisiones de diesel (278,000), paraquat y diquat (175,000), el humo de tabaco ambiental (71,000), los compuestos de cromo hexavalente (55,000), el benceno (52,000), mancozeb, maneb y zineb (49,000), clorotalonil (38,000), el polvo de madera (32,000), el cuarzo (27,000), benomil (19,000), el plomo y sus compuestos inorgánicos (19,000), tetracloroetileno (18,000), y los compuestos aromáticos policíclicos (17,000). En los hombres, la distribución se mantuvo muy ajustada a los anteriores rangos, sin embargo en las mujeres, debido a su diferente distribución en los sectores, el formaldehído, el radón y el cloruro de metileno superaron a los plaguicidas, el cromo (VI), el polvo de madera y el cuarzo. La agricultura, la construcción, los servicios personales y domésticos, el transporte terrestre y acuático y los servicios asociados al transporte, la fabricación de productos cerámicos y similares, la manufactura de productos de madera, la minería, la silvicultura, la pesca, la fabricación de maquinaria y aparatos eléctricos, bares y restaurantes fueron sectores de donde las exposiciones son frecuentes. Una reducción drástica de exposiciones laborales y ambientales a estos agentes daría por resultado mejoras sustanciales en los niveles de salud pública y ocupacional. La vigilancia de las exposiciones laborales y de la salud en el trabajo son esenciales para el control de la contaminación y de las exposiciones a los agentes cancerígenos

The European data system CAREX takes the workforce of a country grouped into 55 economic sectors according to the International Economic Activity Classification of the United Nations, the second 1968 revision and through the application of proportions of workers exposed to 139 carcinogenic agents based on data from industrial hygiene studies, converting it into the total workforce exposed to carcinogens by sector. . In this article we describe a modification and extension of of the CAREX system in order to calculate the number of workers exposed to carcinogens in Costa Rica. It is the first use of CAREX outside Europe (TICAREX) in Costa Rica, Central America, for 27carcinogens and 7 groups of pesticides thought to be of interest for the country, with separate estimations for men and women. The most frequent agents of exposure for the 1.3 million workers of Costa Rica were solar radiation (333,000 workers); diesel exhaust (278,000); paraquat and diquat (175,000); environmental tobacco smoke (71,000); hexavalent chromium compounds (55,000); benzene (52,000); mancozeb, maneb and zineb (49,000); chlorothalonil (38,000); wood dust (32,000); quartz (27,000); benomyl (19,000); lead and its inorganic compounds (19,000); tetrachloroethylene (18,000); and polycyclic aromatic hydrocarbons (17,000). Owing to the different occupational distribution between the genders, exposures to formaldehyde, radon and methylene chloride were more frequent than pesticides, hexavalent chromium, wood dust, and quartz in women. Agriculture, construction, personal and domestic services, manufacture of wood products, mining, forestry, fishing, manufacture of electrical products, and bars and restaurants were sectors with frequent exposures. Substantial reduction of occupational and environmental exposures to these agents would significantly improve public and occupational health. Reduction of occupational exposures is usually also followed by improvement of environmental quality. Monitoring of exposures and health of workers and the general public is an essential element in the control of environmental contamination and human exposures

Risk of fatal industrial accidents and death from other external causes among asphalt workers.

The hypothesis that asphalt workers are at increased risk of mortality from industrial accidents and other external causes was tested. Mortality rates for external and violent causes of death in a cohort of asphalt industry employees from seven European countries and Israel were compared to that of the general population. There was no evidence that mortality from external causes was increased among long term employees in asphalt application and mixing. There was an increased risk for mortality due to external causes among short term workers. However, none of the fatal accidents among short term workers appear to have occurred during employment in the studied asphalt companies. Overall, no evidence was found supporting the hypothesis that asphalt workers are at increased risk of fatal industrial or road accidents. Mortality from other external causes did not increase in this population as a whole, but increased risks among short term workers deserve further attention.

[Employees attitudes to workplace health promotion programs for cancer prevention]. / Actitudes de los trabajadores frente a los programas de promoción de la salud para la prevención del cáncer en el lugar del trabajo.

OBJECTIVE: [corrected] We describe a method for feasibility assessment of workplace health promotion (WHP) programs as a necessary prerequisite of any WHP program. METHODS: A total of 167 employees from five workplace communities participated in the study. A questionnaire on the basic components of feasibility (risk factors, attitudes to workplace health promotion interventions, and social-occupational context) was administered. RESULTS: Risk behaviours were common among the employees interviewed. Health promotion in the workplace was favorably viewed by 79% of subjects but reported participation would be lower. Interventions on diet and physical activity received the highest acceptance. Participation would be greatest among local administration employees. CONCLUSIONS: The method demonstrated its utility in obtaining useful data for designing workplace health promotion interventions.

Actitudes de los trabajadores frente a los programas de promoción de la salud para la prevención del cáncer en el lugar del trabajo / Employees attitudes to workplace health promotion programs for cancer prevention

Objetivo: Presentamos un método para evaluar la factibilidad de los programas de promoción de la salud en el trabajo como paso previo a su diseño. Métodos: Un total de 167 trabajadores de cinco ramas de actividad económica participaron en el estudio. Se administró un cuestionario con preguntas sobre los componentes básicos de la factibilidad (factores de riesgo de cáncer, actitudes hacia los programas de promoción de la salud y entorno sociolaboral). Resultados: Las conductas de riesgo para el cáncer son frecuentes entre los trabajadores entrevistados. Un 79 por ciento demostró interés por los programas de promoción de la salud, pero la participación sería inferior. Dieta y ejercicio físico serían los factores de riesgo más susceptibles a la intervención. La participación más alta se hallaría entre los trabajadores de la administración local. Conclusiones: La información obtenida parece válida y útil para orientar el objeto y la planificación de un programa promoción de la salud en el trabajo (AU)

Objetive: We describe a method for feasibility assessment of workplace health promotion (WHP) programs as a necessary prerequisite of any WHP program. Methods: A total of 167 employees from five workplace communities participated in the study. A questionnaire on the basic components of feasibility (risk factors, attitudes to workplace health promotion interventions, and social-occupational context) was administered. Results: Risk behaviours were common among the employees interviewed. Health promotion in the workplace was favorably viewed by 79% of subjects but reported participation would be lower. Interventions on diet and physical activity received the highest acceptance. Participation would be greatest among local administration employees. Conclusions: The method demonstrated its utility in obtaining useful data for designing workplace health promotion interventions (AU)

Knowledge, attitudes and practices (KAP) among agricultural extension workers concerning the reduction of the adverse impact of pesticides in agricultural areas in Tanzania.

BACKGROUND: Extension workers are educated locally to enable them to train farmers in using improved local farming methods and imported technology, such as pesticides, to increase crop production. However, the extension workers are not adequately trained in health aspects of pesticides and hence are unable to provide adequate services to farmers with regard to safe use of pesticides. OBJECTIVE: The present study assessed the knowledge, attitudes and practices of agricultural extension workers with respect to health effects of pesticides in order to develop strategies for the control of pesticide exposure and prevention of pesticide poisoning in Tanzania. METHODS: A survey of Tanzanian agricultural extensionists was undertaken in 1991-1994 using a standardized questionnaire in face-to-face interviews. Extensionists who were district agricultural officers, assistant agricultural officers, agricultural assistants, and field assistants, working in the coffee and cotton growing areas (N = 61) within a radius of 15 km of farm, estate or village under farm worker study (reported elsewhere) were included in the survey. RESULTS: The majority of extensionists knew that pesticides could enter the human body but only a quarter perceived pesticides as a major problem in the community they served. The majority showed awareness of potential health hazards of the different pesticides used in their service areas, but they did not recognize what pesticides were responsible for poisoning. A high proportion was familiar with first aid procedures in case of pesticide poisoning; however, many procedures described were not appropriate for pesticide poisoning. CONCLUSIONS: The survey indicated that training of agricultural workers in health aspects of pesticide exposure is an important task for adequate provision of service to farmers with regard to safe use of pesticides in Tanzania. Nevertheless, the appropriate role of extensionists in reducing the health impact of pesticides would be to advocate pesticides of low toxicity or non-chemical pest control.

VEGFR-3 in adult angiogenesis.

Vascular endothelial growth factor receptor 3 (VEGFR-3, Flt-4), the receptor for vascular endothelial growth factors (VEGFs) C and D, is expressed on lymphatic endothelium and may play a role in lymphangiogenesis. In embryonic life, VEGFR-3 is essential for blood vessel development. The purpose of this study was to investigate whether VEGFR-3 is also involved in blood vessel angiogenesis in the adult. This was studied in human tissues showing angiogenesis and in a model of VEGF-A-induced iris neovascularization in the monkey eye, by the use of immunohistochemistry at the light and electron microscopic level. VEGFR-3 was expressed on endothelium of proliferating blood vessels in tumours. In granulation tissue, staining was observed in the proliferative superficial zone in plump blood vessel sprouts, in the intermediate zone in blood vessels and long lymphatic sprouts, and in the deeper fibrous zone in large lymphatics, in a pattern demonstrating that lymphangiogenesis follows behind blood vessel angiogenesis in granulation tissue formation. At the ultrastructural level, VEGFR-3 was localized in the cytoplasm and on the cell membrane of endothelial cells of sprouting blood vessels and sprouting lymphatics. In monkey eyes injected with VEGF-A, blood vessel sprouts on the anterior iris surface and pre-existing blood vessels in the iris expressed VEGFR-3. In conclusion, these results support a role for VEGFR-3 and its ligands VEGF-C and/or VEGF-D in cell-to-cell signalling in adult blood vessel angiogenesis. The expression of VEGFR-3 in VEGF-A-induced iris neovascularization and in pre-existing blood vessels exposed to VEGF-A suggests that this receptor and possibly its ligands are recruited in VEGF-A-driven angiogenesis.

Lymphatic versus blood vascular endothelial growth factors and receptors in humans.

Three different growth factor systems have been described acting via endothelial cell-specific receptor tyrosine kinases (RTKs). These are vascular endothelial growth factors (VEGFs), angiopoietins, and ephrins. Recent studies on gene targeting suggest that they play critical roles in embryonic development and contribute to the integrity and responses to environmental factors in the adult vasculature. Coagulation, inflammation, immune response regulation, vascular tone, stromal component synthesis, and angiogenesis are all dependent on the physiological and pathological events that affect endothelial cells in the heart, arteries, veins, and lymphatic vessels. Angiogenesis, the formation of new blood vessels from preexisting ones, takes place in adults only during hormonal control of female reproduction. All other activation of angiogenesis in adulthood occurs in response to injury or pathological processes such as tumorigenesis, diabetes, or inflammatory conditions. Insufficient growth of collateral vessels is a major problem in atherosclerotic cardiovascular disease. Controlled stimulation of angiogenesis would be of therapeutic value. Lymphangiogenesis, the mechanisms involved in the development of lymphatic vessels, was studied intensively nearly a century ago, although since then it has been neglected, perhaps because, unlike the disorders of blood vessels, those of the lymphatic vessels are seldom life-threatening. Interrupting this one-way system can cause severe disorders, including liver dysfunction, genetic disease (e.g., Milroys disease), and degenerative disease (e.g., primary lymphangiosclerosis). Recently, novel growth factors, receptors, cell surface proteins, and transcription factors have been found which play a role in the lymphatic endothelium. These are VEGF-C, VEGF-D, VEGFR-3, LYVE-1, podoplanin, and Prox-1. Until recently lymphatic vessels have been difficult to study due to a lack of appropriate tools. Monoclonal antibodies raised against VEGFR-3 and against its ligands, VEGF-C and VEGF-D, have offered an insight into expression studies in tissues. In this review, we summarize the recent data on VEGFs in the human vasculature.

Acute health effects of organophosphorus pesticides on Tanzanian small-scale coffee growers.

Acute health effects of organophosphorus (OP) pesticides on coffee farmworkers in 1991-1992 in Tanzania are reported to provide a basis for concern over farmworkers being overexposed during application. Workers exposed to OP pesticides (N=133) were drawn from a population of about 240,000 coffee farmers. They were interviewed on symptoms and personal protection, and their erythrocyte acetylcholinesterase (AChE) activity was determined during both spraying and nonspraying period. AChE activities during spraying and nonspraying period were comparable (mean 32.0, SD 7.8 vs. 33.0, SD 8.7 U/g HgB, P=0.26). The prevalence of cough, headache, abdominal pain, excessive sweating, nausea, excessive salivation, diarrhea, and vomiting did not differ significantly between spraying and nonspraying periods. There was no suggestion of decreased AChE in exposed subjects who complained of OP-related symptoms compared to symptomless exposed subjects. Use of gloves, long boots, head cover, face cover, and coverall was not significantly associated with AChE activity. No marked AChE depression was found during spraying season, which may explain the lack of association between symptoms and AChE. The fact that only moderately toxic OP pesticides were used may indicate that toxicity was not sufficiently high to cause depression. Experience, however, suggests that occupational poisoning remains a potential serious danger in coffee cultivation in Tanzania.

Occupational exposures and cancers of the endometrium and cervix uteri in Finland.

BACKGROUND: Endometrial cancer incidence rates are low in Asia and Africa and high in North America and Northern Europe. Cervical cancer is often the most common female cancer in developing countries, and infection with human papillomavirus (HPV) is its main risk factor. However, other factors, such as occupational exposures may modify the HPV-related risk. We conducted an exploratory register-linkage study in Finland to assess the role of occupational exposures on incidence rates of cancers of the endometrium and cervix uteri. METHODS: Occupational risk factors for endometrial and cervical cancers were explored in a 25-year follow-up of female workers born 1906-1945 (N = 413,877) identified through the Population Census of Finland of 1970. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socio-economic status. For each agent, the product of level and probability of exposure was calculated and subdivided in three categories: zero, low, and medium/high. Adjustment at the job title level was done for the turnover rate (endometrial and cervical cancers), mean parity, and age at first birth (endometrial cancer). RESULTS: Endometrial cancer (2,833 cases) was associated with exposure to animal dust (RR 1.2, low level, 174 cases) and sedentary work (RR 1.3, high level, 145 cases). Cervical cancer (1,101 cases) was associated with exposure to aliphatic and alicyclic (RR 1.3, low level, 91 cases), aromatic (RR 1.2, low level, 318 cases; RR 1.4, high level, 41 cases), and chlorinated hydrocarbon solvents (RR 1.3, low level, 50 cases), silica dust (RR 1.2, low level, 251 cases), and wood dust (RR 1.2, low level, 249 cases). CONCLUSIONS: This study suggests that occupational exposures may be associated with increased risk of endometrial and cervical cancers.

Occupational health and safety in the least developed countries--a simple case of neglect.

In many of the least developed countries, working people are significantly exposed to a number of occupational problems that may result in a deterioration of their health, safety and well being. These work-related problems are untenable, not only because of the occupational problems itself but also because of the simultaneous exposure to heat, dusts, noise, organo-chemicals, and biological and environmental pollution. This situation has existed for a long time due to various socio economic,geographical, cultural and local factors. The deteriorating situation of health and safety in the workplace may perhaps exist due to the inadequate resource facilities, economic constraints and lack of opportunity to conduct research and studies on the assessment of exposure-diseases associations. Officials, who are employed by the state, are not able to implement work regulations and labour legislation easily. Generally, they are not professionally trained and expert in the occupational health, industrial hygiene and/or safety fields, and thus, successful application and implementation of control measures are lacking. Steps to control work exposure limits have been ineffective, since national policies have been rare, owing to the multiple obstacles in preventing occupational problems. However, the major focus is on practical solutions to differing workers' needs, consideration of which is very important, depending on the what the industrial entrepreneurs could reasonably to be expected to afford. Why there is a lack of motivation and effort regarding the development of health and safety-this paper explores some important issues, aiming to focus public attention on the legacy of national and international efforts. Examples are likewise given to show the real situation of health and safety in the least developed countries.

Lymphangiogenesis and the vascular endothelial growth factor receptor (VEGFR)-3 in gastric cancer.

Vascular endothelial growth factor C (VEGF-C) is the only factor known to cause lymphangiogenesis. We studied the correlation between VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression of 85 primary gastric cancers by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry, and the results were correlated with the number of lymphatic vessels, stained with anti-VEGFR-3 antibody. RT-PCR and immunohistology demonstrated that VEGF-C was mainly produced from cancer cells, but not from stromal elements. Morphologically, VEGFR-3 expression was detected in the endothelial cells of the stromal lymphatic vessels. There was a statistically positive correlation between the incidence of VEGF-C and VEGFR-3 mRNA expression in the primary tumours (P=0.0002). The number of VEGFR-3-positive lymphatic vessels in VEGF-C mRNA positive tumours was significantly larger than that in VEGF-C-negative tumours. The number of VEGFR-3-positive vessels in the tumour stroma was closely related to the grade of lymphatic invasion of gastric cancer. These results strongly indicate that VEGF-C may induce the proliferation of lymphatic vessels in the stroma of primary gastric cancer via activation of VEGFR-3, expressed on the endothelial cells of lymphatic vessels. In these circumstances, cancer cells can easily invade the lymphatic vessel, because of the increase of the contact points of cancer cells with the lymphatic vessels.

Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents and related compounds: a meta-analysis.

This is a meta-analysis of occupational exposures to chlorinated hydrocarbon (CHC) solvents and pancreatic cancer, based primarily on studies that addressed exposure directly (agent studies) and secondarily on studies that reported data without verification of individual CHC exposures (job title studies), all of which were listed in databases for the period January 1969 to May 1998. Standardized extraction of data and double-checking of consistency of data extraction by five extractors were done. Simple random models estimated meta-relative risks. Suggestive weak excesses were found for trichloroethylene (meta-relative risk (MRR) = 1.24, 95% confidence interval (CI): 0.79, 1.97), polychlorinated biphenyls (MRR = 1.37, 95% CI: 0.56, 3.31), methylene chloride (MRR = 1.42, 95% CI: 0.80, 2.53), and vinyl chloride (MRR = 1.17, 95% CI: 0.71, 1.91) but not for carbon tetrachloride. One study addressed tetrachloroethylene (MRR = 3.08, 95% CI: 0.63, 8.99); another investigated chlorohydrin production (MRR = 4.92, 95% CI: 1.58, 11.4). Exposure-response meta-analyses for trichloroethylene and methylene chloride failed to reveal trends. Job title studies on metal degreasing and dry cleaning revealed significant MRRs (2.0 and 1.4, respectively). Publication bias was unlikely. Confounding may have remained insufficiently controlled. Unless the results are seriously biased by exposure or endpoint misclassification or by confounding, strong causal associations between CHC compounds and pancreatic cancer can be judged unlikely. Interactions between environmental and occupational agents, lifestyle factors, and genetic susceptibility remain a possibility, but the data for this meta-analysis did not address interactions.

Paraquat in developing countries.

The herbicide paraquat is considered safe by industry and the bulk of regulators worldwide. However, determinants of exposure from 30 years ago persist in developing countries. Little is known about systemic absorption from occupational exposures. The relationships between exposure determinants, levels of external exposure, biomarkers of exposure, and outcomes are not clear. High rates of severe acute poisonings have been documented. In addition, topical injuries occur in as many as 50% of exposed workers. Non-worker populations are also at risk, particularly children. Long-term and delayed health effects include Parkinson's disease, lung effects, and skin cancer. Regulatory agencies have not fully recognized either the inherent toxicity of paraquat or the particular risks derived from exposures in developing countries. Independent risk assessment in the developing-country context and application of the precautionary principle are necessary to prevent adverse effects of dangerous pesticides in susceptible populations.

Pesticide-handling practices in agriculture in Tanzania: observational data from 27 coffee and cotton farms.

The practices of pesticide handling in agriculture were surveyed in 1991-1993 in Tanzania, to identify hazardous practices and farms where they occurred. The study involved 23 coffee farms with 246 persons exposed to hazardous practices, and four cotton farms with 45 exposed. An observation form addressed locations of important places with respect to pesticide spraying, storage, disposal, and equipment; personal protection; and hygiene. More pesticide formulations were used for coffee compared with cotton and by individual rather than cooperative farms. Coffee farms more often had unlabeled pesticide containers and missing mixing instructions, while cotton pesticides were stored in bedrooms, near food, and near open fires, and pesticide leftovers were often present. Hazardous practices were more pronounced at individual than cooperative farms, with significant differences in pesticide storage areas, as well as unlabeled and non-original containers. The study demonstrated the need to train farmers in pesticide safety, strengthen advisory and regulatory services, and extend protection to farm workers' families.

Hazardous pesticides in Central America.

Pesticides are an extensively documented occupational and environmental hazard in Central America. Yet, severe problems persist. Toxic pesticide use in the Region increased during 1985-1999. High exposure levels and ineffectiveness of personal protective equipment evidence the difficulties for risk reduction. Acute poisonings remain a severe problem. Delayed and/or long-lasting health effects include dermatoses, cancer, and genotoxic, neurotoxic, and respiratory effects. The use of hazardous pesticides persists through deficiencies in government-driven assessment and risk management; excessive focus on regional harmonization; short-term economic interests; strong links between industry and governments; aggressive marketing; weak trade unions; and failure of universities to reach decision makers. Regulation based on local data is lacking. An agreement of the Ministries of Health for restricting the most toxic pesticides in Central America has potential for progress. The most effective way to reduce risk is to greatly reduce pesticide use. Actions needed include development of multidisciplinary strategies for local studies on health and environmental impact of pesticides; development of sustainable nonchemical agricultural technologies; evaluation of interventions; extending and sharing of expertise within the Region; strengthening of unions and communities; and redefining the role of industry toward development of safer products, with responsible marketing and reliable information.

Assessment of the ability of health care providers to treat and prevent adverse health effects of pesticides in agricultural areas of Tanzania.

A survey of Tanzanian health care providers in agricultural areas was undertaken in 1991-1994 to assess their knowledge of toxic effects of pesticides, experiences and practices, as well as of their needs for appropriate information in order to develop effective strategies for reducing pesticide poisoning. Face-to-face interviews were conducted with 104 physicians, clinical officers and nurses at health care facilities in the coffee and cotton growing areas. Eighty percent of respondents reported to have seen one and nine of them two to four cases of pesticide poisoning in the preceding three months. A significantly higher annual number of poisonings were observed in coffee than in cotton area (GM 0.5 vs 0.1). Also the number of cases registered in hospitals was considerably higher than that in the out-patient health care (GM 1.7 vs 0.2). Pesticide poisoning was regarded as a major problem in the community by 63% of health care providers, including 77% of hospital staff. One third of health care providers thought that a certain percent of pesticide poisoning cases remain unrecognized, and that this percentage is higher in cotton than in coffee growing areas. The respiratory tract was the major route for pesticide to enter the human body; this was followed by gastrointestinal tract, skin, and eyes. Only one percent of the respondents could identify the groups of pesticides (organophosphate vs organochlorine) mostly used in the study areas. The survey indicated that training of hospital staff in toxicity of pesticide exposure is an important task and a prerequisite for efficient recognition, diagnosis and treatment of pesticide poisoning cases in Tanzania.

Cancer risk in laboratory workers: an emphasis on biological research.

BACKGROUND: At the end of the 1980s, several cancer clusters were observed in biological research laboratories. Over time, biological research and the technologies used have been diverse and have involved a wide range of mutagenic or carcinogenic chemical, physical and biological agents. METHODS: We reviewed 45 published studies on cancer risk among biological research personnel and workers in closely related fields, and numerous reports based on routinely collected data. RESULTS: Biological research could be associated with an elevated risk for pancreatic cancer, brain tumors, and certain hemopathies. A common limitation of available studies was low statistical power and the absence or inaccuracy of data on individual past exposure. CONCLUSIONS: Overall, this study suggests a low overall risk of cancer, albeit a higher risk may be suggested for cancers of the pancreas (risk ratios ranging from 0.5 to 6.3) and brain (0.7-9.4), and for non-Hodgkin's lymphoma (0.6-51.5). We suggest ways in which multiple past exposures could be assessed more precisely and emphasize a pressing need to take into account known confounders.

VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues.

Recently, vascular endothelial growth factor receptor 3 (VEGFR-3) has been shown to provide a specific marker for lymphatic endothelia in certain human tissues. In this study, we have investigated the expression of VEGFR-3 and its ligands VEGF-C and VEGF-D in fetal and adult tissues. VEGFR-3 was consistently detected in the endothelium of lymphatic vessels such as the thoracic duct, but fenestrated capillaries of several organs including the bone marrow, splenic and hepatic sinusoids, kidney glomeruli and endocrine glands also expressed this receptor. VEGF-C and VEGF-D, which bind both VEGFR-2 and VEGFR-3 were expressed in vascular smooth muscle cells. In addition, intense cytoplasmic staining for VEGF-C was observed in neuroendocrine cells such as the alpha cells of the islets of Langerhans, prolactin secreting cells of the anterior pituitary, adrenal medullary cells, and dispersed neuroendocrine cells of the gastrointestinal tract. VEGF-D was observed in the innermost zone of the adrenal cortex and in certain dispersed neuroendocrine cells. These results suggest that VEGF-C and VEGF-D have a paracrine function and perhaps a role in peptide release from secretory granules of certain neuroendocrine cells to surrounding capillaries.