Hyperprolinemia type II: identification of the glycine conjugate of pyrrole-2-carboxylic acid in urine.

The urinary organic acids were studied in two cases of hyperprolinemia Type II, using various combinations of chromatographic, electrophoretic and mass spectrometric techniques. In both cases N-(pyrrole-2-carboxylic acid) was idenfitied as a major urinary metabolite. While there was evidence for an additional conjugate of this pyrrolic acid, no free pyrrole-carboxylate could be detected in the urine from either case.

A cluster-focus of multiple sclerosis at Henribourg, Saskatchewan.

This study presents the clinical characteristics of 8 victims of multiple sclerosis from the hamlet of Henribourg, Saskatchewan with a population of less than 75 people. A diligent victim of the disease had observed that six female classmates from the early 1940's had later developed multiple sclerosis. Two male military personnel who had also resided briefly in close proximity, during the same common exposure time, also later developed multiple sclerosis. The mean onset time of developing the disease after leaving the area was 20 years. This cluster-focus suggests a common exposure to an environmental factor or a common infective agent in the etiology of multiple sclerosis.

Prevalence of antinuclear antibodies in a rural population.

Exposure to environmentally and occupationally encountered toxicants can be associated with the development of certain autoimmune diseases and with the induction of antinuclear antibodies (ANA). Some chemicals used in the agricultural industry are known to affect immune function but their roles in the induction of autoimmunity in general, and ANA in particular, have not been reported previously. This study was undertaken to establish the prevalence of ANA in a rural population and to determine environmental and occupational exposures with which they are associated. This cross-sectional study represented one component of an interdisciplinary project (Prairie Ecosystem Study [PECOS], Eco-Research Program, Tri-Council Secretariat of Canada) designed to explore, in a rural population, the roles of environmental exposures as determinants of human health status. Information regarding lifetime, current, and main occupational exposures in the rural-dwelling study population was derived from a self-administered questionnaire. Sera from consenting subjects, collected during the months of February and March 1996, were assayed for ANA by indirect immunofluorescence on HEp-2 cells. The study population comprised 322 adult subjects (mean age 49.3+/-14.7 yr; range 16-87 yr). Statistical analyses adjusted for age and sex revealed that the presence of ANA among the participants was associated with a current agricultural occupation that included oilseed production, hog production, or poultry production. There was a significant association between ANA positivity and a current main farming operation of crop production. There was also an association among individual participants between lifetime exposure to the insecticide class of pesticides and the presence of ANA. In this rural study population, ANA positivity was significantly associated with lifetime exposure specifically to carbamate, organochlorine (including aldrin, chlordane, dieldrin, endrin, heptachlor, and lindane, but excluding DDT and methoxychlor), and pyrethroid insecticides and to phenoxyacetic acid herbicides, including 2,4-D. After adjustment for age, sex, and other insecticide exposures, multivariate analyses indicated that ANA positivity was associated with current oilseed production and with lifetime exposure to pyrethroid insecticides. In a rural population, ANA were associated with production of certain crops and certain animals and exposure to specific pesticides. The data indicate that some occupational exposures related to the agricultural industry are associated with the presence of ANA, a serologic expression of autoimmunity.

Seasonal changes in lung function in a farming population.

OBJECTIVE: To assess the changes in respiratory health from winter to summer seasons in a rural population. DESIGN: A longitudinal design was used in the study. SETTING: A population-based study was conducted as part of the Environmental Pesticide Exposure and Human Health component of the Prairie Ecosystem Study (PECOS) in southwestern Saskatchewan. PATIENTS: In the winter season, 358 patients participated in the study. Of these patients, 234 returned for the second assessment during the summer season. After excluding 34 children aged 17 years and under, 200 adult patients were available for analysis. MEASUREMENTS: Questionnaires were used to obtain information on demographic factors, smoking habits, occupational and environmental exposures, and respiratory conditions. Pulmonary function measurements were obtained using a volume displacement spirometer. RESULTS: Mean ages (+/- SD) of the 106 men and 94 women participating in the study were 50.1+/-13.3 and 49.0+/-13.1 years, respectively. Mean percentage changes in maximal midexpiratory flow rate from winter to summer assessments indicated an improvement for town residents and a decline for farm residents. Mean percentage changes in the ratio of forced expiratory volume in 1 s to forced vital capacity indicated an improvement for town residents who were not engaged in farming, and increasing declines for town residents engaged in farming, farm residents not engaged in farming and farm residents engaged in farming. CONCLUSIONS: Seasonal changes occurred in measurements of pulmonary function between winter and summer seasons; these changes may be related to the environmental or occupational exposures experienced by the participants during the study.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, Cluster Focus. I. The water.

Some childhood-related, geographically-linked factor predisposes towards (or protects against) multiple sclerosis (MS). It is quite plausible that this factor could be one or more chemicals in the environment, and that chemical study of the environment or "focus" of an MS cluster might maximize the chances of detecting such an etiological link. The water chemistry of such a focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of water from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. Overall, the results suggest that an environment predisposing to MS may have a number of water chemistry characteristics such as: relative deficiency of selenium and sulfate, but relative abundance of barium, calcium, chloride, chromium, magnesium, manganese, molybdenum, nitrate plus nitrite, strontium and zinc. Possible explanations for the apparent link between the excess rate of MS and the water geochemistry findings at Henribourg are discussed.

Geotoxicology of multiple sclerosis: the Henribourg, Saskatchewan, cluster focus. II. The soil.

The childhood-related, geographically-linked factor which predisposes towards (or protects against) multiple sclerosis (MS) could be one or more chemicals in the environment. Chemical study of the environment or "focus" of an MS cluster may maximize the chances of detecting such an etiological link. The soil chemistry of an MS focus (Henribourg, Saskatchewan) was compared with North American norms, and with the chemistry of soil from a nearby control area with a near-zero incidence of MS and of childhood homes of MS cases. A combination of our present results with those reported in the literature suggests that an environment predisposing to MS may have a number of the following chemical characteristics: Calcareous; with soils (but not necessarily waters) generally low in copper, iron and vanadium; with excess lead, nickel and zinc in the upper soil layer; with waters relatively high in chloride, chromium, molybdenum, nitrate plus nitrite, and zinc; but low in selenium and sulfate. One possible causal pathway to explain the apparent link between the excess rate of MS and some of the curious geochemical findings at Henribourg is presented. Many other possible explanations could equally well be advanced, and methods for testing such alternative hypotheses are proposed.

Autotransfer chromatography in the characterization of pyrroles. Chemistry of multiple-spot phenomena.

A characteristic pattern of five interconverting "component" zones is obtained on autotransfer chromatography when pure kryptopyrrole (KP) is adsorbed from aqueous solution onto charcoal and then eluted with methanol. Specific oxidation products (lactams) derived from synthetic KP matched four of the five zones. Zone 1 was obtained directly from the a'-hydroxy-a-lactam. Zone 3 was produced directly by the a'-methoxy-a-lactam, while zones 2 and 5 were formed as a consequence of its acid hydrolysis during equilibration and chromatographic development. The formation of the methoxy lactam itself depended upon the presence of added methanol in the extraction process. In the absence of methanol during extraction only zone 1 (sometimes accompanied by zone 4) was formed.

Quality assessment of external data: a further means of reducing animal use for toxicity testing--a case study.

One overlooked area of quality assurance (QA) is the critical, in-depth reassessment of toxicity data from secondary compilations. Such retrospective QA may play a role in avoiding needless additional or repeated animal testing, as this case study shows. Initially, the task was simply to carry out toxicity testing of a chemical for LD50 determination for regulatory purposes. The impetus for this proposed (re-)testing was the erroneously calculated low LD50 value for just one species and one route of administration. Examination of the original literature cited as the source of the seemingly anomalous LD50 value revealed that a combination of conceptual and transcriptional errors had been made when the results were translated from the original German research paper and were put into two widely used secondary compilations: RTECS and HSDB. Correcting these errors rendered the true value for LD50, which was no longer out of step with values for other species, nor was it sufficiently low to cause any concern in the work place. The critical reassessment removed the need to use any further animal studies to assess the situation. It is concluded that, in some cases, "reassessing" existing data can be added to the established list of "refining, reducing, and replacing" as a means of decreasing animal use in toxicological evaluation.

Health and environment of rural families: results of a Community Canvass survey in the Prairie Ecosystem Study (PECOS).

This cross-sectional survey was conducted as Phase I of the Prairie Ecosystem Study (PECOS): Environmental Pesticide Exposure and Human Health. In November of 1995, community volunteers delivered a self-administered household questionnaire to 1185 rural households in southern Saskatchewan, Canada. The survey provided a broad description of the general health and the physical environment of 511 men, 499 women, and 393 children (< 18 years of age) residing in 549 respondent households in the rural study area (population density of about one person/km2). Families in the respondent households resided on a farm, in town or both. Of the 369 households that operated a farm, 25.2% of the households did not list the farm as their primary household. Residents of both farming and non-farming households reported contact with pesticides and fertilizers through home or garden use. History of smoking was greater among men and women from non-farming households. The most commonly reported health problems among the children were a history of bronchitis, asthma, skin allergies, pneumonia, and hay fever. The most frequently reported health problems among the men were a history of high blood pressure, bronchitis, pneumonia, hearing problems, and stress; and among the women were a history of bronchitis, high blood pressure, shortness of breath, and pneumonia. Compared to farming households, more members of non-farming households reported a history of respiratory problems, particularly bronchitis among the women and children. Overall, there were important differences in the smoking history, the occupational use of pesticides and fertilizers, and the general health status between the farming and non-farming households and individuals in this rural population.