Search PubMed⌕ Search

Biomedical subjects

L Richardson

Publications and source records attributed to L Richardson.

At least 73 records · Page 4Linked to original sources

Cancer risks associated with 10 inorganic dusts: results from a case-control study in Montreal.

A multicancer site, multifactor case-control study was undertaken to generate hypotheses about possible occupational carcinogens. Probing interviews were carried out with eligible cases, comprising all incident cases of 20 types of cancer who were male, aged 35-70 years, and a resident in Montreal. The interview was designed to obtain detailed lifetime job histories and information on potential confounders. Each job history was reviewed by a team of chemists and industrial hygienists who translated it into a history of occupational exposures. These occupational exposures were then analyzed as potential risk factors in relation to the sites of cancer included; 3,726 cases were interviewed. For each site of cancer analyzed, controls were selected from among the other sites in the study. This report concerns the associations between the 12 main types of cancer in our series and 10 inorganic dusts that are found mainly in construction and metal industries. All site-exposure combinations were investigated. After intensive control for confounding, nonadenocarcinoma (NAC) of the lung was associated with long duration-high level exposure to silica (odds ratio [OR] = 1.4), excavation dust (OR = 1.9), concrete dust (OR = 2.5), abrasives dust (OR = 1.4), and alumina (OR = 1.5). It was difficult to disentangle the relative effects of those substances, and confounding among them was a distinct possibility. Although residual confounding by some uncontrolled factors may explain the elevated ORs, the results were compatible with the hypothesis of a nonspecific relation between NAC of the lung and respirable inorganic dusts as a class. Other associations that remained suggestive after in-depth analysis were silica and stomach cancer (OR = 1.2) and concrete dust and lymphoma (OR = 2.9).

Adult↗

Costs and statistical power associated with five methods of collecting occupation exposure information for population-based case-control studies.

The ascertainment of information on past occupational exposure of study subjects is perhaps the main problem in case-control studies of occupational risk factors. Several methods have been proposed and used but little is known of their relative merits. The present study, undertaken in the context of a large ongoing case-control study of occupational cancer in Montreal, was designed to compare the costs of and statistical power to be derived from five plausible methods of data collection: 1) job titles abstracted from routine records, 2) job titles abstracted from routine records and processed through a job exposure matrix to derive exposure data, 3) job titles obtained by interview, 4) job titles obtained by interview and processed through a job exposure matrix to derive exposure data, and 5) job descriptions obtained by interview and processed by a team of experts to derive exposure data. Statistical power of the five methods was derived for 160 hypothetical risk factors, partly on the basis of empirical data from the data set and partly on the basis of some theoretical constructs. The design based on interview and expert evaluation was used as a reference, and the degree of misclassification of other methods was estimated in relation to this reference. For fixed sample size the interview and expert evaluation design was estimated to be much more costly than the others, but it provides much greater statistical power for detecting risks. Under the conditions of this investigation, this design was the most cost-effective. However, it is not clear to what extent this finding is generalizable.

Case-Control Studies↗

Evaluation of reproductive function of female rats exposed to radiofrequency fields (27.12 MHz) near a shortwave diathermy device.

In recent years, there has been increased concern regarding effects of operator exposure to the electromagnetic (EM) field associated with shortwave diathermy devices. The present study was designed to investigate the effects, on rats, of repeated exposure to such an EM field. Following repeated exposure for 5 wk, a reduction in fertility occurred as indicated by a reduced number of matings in exposed rats compared to sham-irradiated rats and a reduction in the number of rats that conceived after mating. The data suggest that female operators could experience reduced fertility, if they remained close to the console for prolonged periods. This has particular significant for the physiotherapy profession.

Animals↗

Sexually dimorphic characteristics of clonidine-induced growth hormone release and autofeedback.

The mechanism underlying the sexually dimorphic pattern of GH secretion in the rat has not been clearly elucidated. In this study differences in the regulation of GH secretion in males and females were analyzed by examining their sensitivity to alpha 2-adrenergic (alpha 2) stimulation and GH autofeedback. The model used in testing this system was the capacity of ovine (o) GH, injected into the third ventricle, to suppress the endogenous GH surge induced by clonidine (CLON), an alpha 2-agonist. In morning experiments, CLON (30 micrograms/kg BW, iv) was injected between 1000-1100 h in males. oGH (20 micrograms in 2 microliters vehicle) injected 3 h earlier inhibited the GH surge, which peaked 15 min after CLON injection in control animals receiving CLON alone. In females there was both no change in plasma GH levels and no difference between treatment groups in animals receiving 30, 50, 100, or 150 micrograms/kg CLON and saline controls. Preinjection of 20 micrograms oGH in proestrous or diestrous animals or 30 micrograms oGH in diestrous animals 3 h before CLON treatment did not depress plasma GH levels below those found in animals receiving CLON alone. Further, neither reducing the preinjection time to 2 h nor injecting 7, 13, or 20 micrograms oGH at this preinjection period suppressed basal or CLON-induced GH release. To facilitate comparisons in subsequent experiments the male protocol was followed. In evening experiments, CLON (injected between 2210-2240 h) stimulated a significant GH surge in diestrous females. However, preinjected oGH lowered basal GH levels but failed to suppress the CLON-induced GH surge. In somatostatin (SRIF) antiserum (anti-SRIF; 0.5 ml, iv)-treated adult diestrous animals, CLON induced a significant GH surge that was suppressed by oGH preinjection. In normal sheep serum-treated animals there was no significant response to either CLON alone or in combination with oGH. To determine the influence of ovarian hormones on GH release females were ovariectomized (OVXed) either pre- or postpubertally. After adult OVX, CLON induced an increase in GH release that was not suppressed by oGH pretreatment. In prepubertally OVXed animals CLON induced a substantial GH surge that was suppressed in animals preinjected with oGH. In prepubertally OVXed animals implanted with testosterone capsules the response to CLON and oGH was not significantly different from that after prepubertal OVX alone. Sham-operated animals responded to treatment in a manner similar to unoperated cycling females.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Characterization of proteins secreted by sheep oviduct epithelial cells and their function in embryonic development.

The role in early development of proteins secreted by oviduct epithelial cells has been investigated. Secreted proteins devoid of serum contamination have been produced by the surgical removal and immediate incubation of oviduct cells in [35S]methionine-containing medium. After electrophoretic separation, secreted polypeptides could be divided into those that were secreted uniformly throughout the oestrous cycle and a second class that showed a cyclical pattern of secretion. The first class of proteins represented a small proportion of total output whilst the predominant second class was composed mainly of polypeptides of Mr 92 and 46 x 10(3), respectively. Both of these polypeptide species, referred to as sheep oviduct proteins 92 and 46 (SOP 92, SOP 46), are detected only during the first 4 to 5 days after oestrus when the embryos are located in the oviduct. Oviduct cells collected at oestrus and maintained thereafter in culture secrete the same pattern of proteins and follow the same time course as their counterparts in vivo. The interaction between the oviduct proteins and the developing embryo was studied firstly by determining whether any of the secreted proteins bound to the zona pellucida. The results of iodination studies showed that two polypeptides of Mr 92 and 46 x 10(3), respectively, were bound to the zona pellucida of eggs removed from the oviduct but were absent from eggs that had not had contact with the oviduct epithelium. That these newly acquired proteins represent SOP 92 and 46 is suggested by their electrophoretic mobility and their ability to bind to the zona of follicular eggs when added in vitro and by the fact that they both disappear from the zonae of embryos after exit from the oviduct. The collection of unlabelled secreted proteins enabled us to produce a monoclonal antibody, which was used in the second series of experiments on oviduct-embryo interactions. The results confirmed that SOP 92 binds to the zona pellucida and moreover showed that this protein crosses the zona and becomes associated with the individual blastomeres of the developing embryo. These findings provide evidence that the mammalian oviduct probably plays a direct role in supporting embryonic development through specific polypeptides produced by its epithelium.

Animals↗

Smoking and degree of occupational exposure: are internal analyses in cohort studies likely to be confounded by smoking status?

Occupational cohort studies are usually carried out without the benefit of information on smoking habits of cohort members. One common approach to avoid confounding bias related to smoking habits is to carry out an internal analysis, comparing workers with different degrees of occupational exposure. The premise behind this approach is that within a cohort there is unlikely to be correlation between degree of exposure and smoking habits. If this were untrue, smoking could confound the disease-exposure relationships. Our purpose was to verify the premise. The study sample consisted of 857 French-Canadian men born between 1910 and 1930, with 11 or fewer years of education, and interviewed around 1980 in the context of an occupational cancer case-control study. For each man we had information on smoking habits, job history, and a history of the chemicals he was exposed to in each of his jobs. We computed two indices of the dirtiness of workers' job histories: one based on the job titles held by the man and a second based on the degree of exposures to workplace substances. There was no correlation between these indices of job dirtiness and smoking history. We also examined the smoking-exposure relationship among the subsets of men who had been occupationally exposed to ten especially noticeable substances. Within the subsets, there was no indication of a consistent difference among the smoking subgroups in level or duration of exposure to these index substances. These findings do not support the view that nonsmokers sought out cleaner job environments than smokers; they imply that internal analyses of "dose-response" in cohort studies are unlikely to be seriously confounded by smoking habits.

Adult↗

Isolation and characterization of epididymal epithelial cell plasma membranes.

Sperm maturation and storage occur in a unique milieu created in large part by the epididymal epithelium. To learn more about the interaction of the epididymal epithelial cell with both luminal and systemic environments, we now report on the preparation and characterization of epididymal epithelial cell plasma membranes. A preparation enriched for epididymal epithelial cell plasma membranes was isolated from collagenase-digested epididymal tubule fragments by hand-Dounce homogenization, differential centrifugation, and sucrose gradient centrifugation. The final membrane fraction was enriched 11-fold for the plasma membrane marker 5'-nucleotidase; 2.6-fold for the lysosomal marker acid phosphatase, and 3-fold for the Golgi marker thiamine pyrophosphatase. No enrichment was observed for mitochondrial or endoplasmic reticulum enzyme markers. Specific and saturable transferrin-binding activity was also detected in the final preparation. Electron microscopy revealed the presence of vesicles and sheets of membranes as well as an occasional Golgi apparatus. The plasma membrane fraction was used to generate monoclonal antibodies. Of 102 wells exhibiting growth, 12 were positive by immunofluorescent staining of frozen sections. Ten of these recognized determinants in epithelial cells, and 2 stained peritubular smooth muscle cells. Most of the epithelial cell-specific antibodies stained brush border alone or in combination with the basolateral plasma membrane. Three antibodies stained the Golgi apparatus. Most antibodies were specific for particular epididymal regions, 3 also recognized determinants in the kidney, and 1 stained residual bodies in the testis.

Animals↗

Degree of confounding bias related to smoking, ethnic group, and socioeconomic status in estimates of the associations between occupation and cancer.

In occupational cancer epidemiology, many studies are carried out without access to information on smoking and other potential confounding variables. It is unclear whether such deficiencies are likely to cause serious bias in estimates of cancer-occupation associations. An empiric investigation was carried out to determine the effect of inclusion or exclusion of three variables--smoking, ethnic group, and socioeconomic status--on estimates of odds ratios (OR) between 25 occupations and three types of cancer--lung, bladder, and stomach. Of the 75 associations studied, only one OR was distorted by more than 40% when comparing unadjusted with adjusted estimates; three were distorted by between 30% and 40%; four others by between 20% and 30%. Of the eight associations which were distorted by more than 20%, seven involved lung cancer and one involved bladder cancer; none involved stomach cancer. An additional analysis was carried out on the 25 lung cancer-occupation associations to determine whether the nature of the stratification on smoking (ie, whether crude or "precise" categories were used) gave different OR estimates. The differences in ORs induced by different parametrizations of the smoking variable were relatively small. Our results support the view that relative risks between lung cancer and occupation in excess of 1.4 are unlikely to be artifacts due to uncontrolled confounding. For bladder and stomach cancer, the corresponding cut point may be as low as 1.2. In studies of occupation and cancer, uncontrolled confounding due to smoking and social class may not be as serious a threat to the integrity of results as is sometimes feared.

Adult↗

Associations between several sites of cancer and ten types of exhaust and combustion products. Results from a case-referent study in Montreal.

A population-based case-referent study provided information on the associations between several types of cancer and 10 types of exhaust and combustion products. All site-exposure combinations were investigated. An increased lung cancer risk, in particular squamous-cell cancers, due to exposure to gasoline and diesel exhausts was found. Among the associations that have not been subject to previous attention, the most promising leads for further investigation are the possible relations between gasoline and diesel exhaust and colorectal cancers, gasoline exhaust and kidney cancer, coal combustion products and pancreatic cancer (and possibly nonadenocarcinoma lung cancer), combustion products of heating oil and prostatic cancer, and natural-gas combustion products and bladder cancer.

Adult↗

Associations between several sites of cancer and twelve petroleum-derived liquids. Results from a case-referent study in Montreal.

A population-based case-referent study provided information on the associations between several types of cancer and 12 petroleum-derived liquids. All site-exposure combinations were investigated. The most interesting results concerned the following combinations: leaded gasoline-stomach cancer, aviation gasoline-kidney cancer (and the possible implications of this association for a similar effect of unleaded automotive gasoline), mineral spirits-squamous-cell cancer of the lung, diesel fuel-nonadenocarcinoma lung cancer, lubricating oils-squamous-cell lung cancer, cutting fluids-bladder cancer, other mineral oils-bladder cancer, mineral spirits-prostate cancer, diesel fuel-prostate cancer, and lubricating oils-prostate cancer.

Humans↗

Discovering carcinogens in the occupational environment. Methods of data collection and analysis of a large case-referent monitoring system.

A multi-cancer site, multi-factor, case-referent study was undertaken to generate hypotheses about possible occupational carcinogens. About 20 types of cancer were included. Incident cases among men aged 35-70 years and diagnosed in any of the major Montreal hospitals were eligible. Probing interviews were carried out for 3 726 eligible cases. The interview was designed to obtain detailed lifetime job histories and information on potential confounders. Each job history was reviewed by a team of chemists who translated it into a history of occupational exposures. These occupational exposures were then analyzed as potential risk factors in relation to the sites of cancer included. For each site of cancer analyzed, referents were selected from among the other sites in the study. The analysis was carried out in stages. First a Mantel-Haenszel analysis was undertaken of all cancer-substance associations, stratifying on a limited number of covariates, and, then, for those associations which were noteworthy in the initial analysis, a logistic regression analysis was made taking into account all potential confounders. This report describes the fieldwork and analytical methods.

Carcinogens, Environmental↗

Associations between several sites of cancer and nine organic dusts: results from an hypothesis-generating case-control study in Montreal, 1979-1983.

A multi-cancer site, multi-factor case-control study was undertaken to generate hypotheses about possible occupational carcinogens. Probing interviews were carried out with over 2,000 subjects. All incident cases of 19 sites of cancer in males aged 35-70 and resident in Montreal were eligible. The interview was designed to obtain detailed lifetime job histories, and information on potential confounders. Each job history was reviewed by a team of chemists who translated it into a history of occupational exposures. These occupational exposures were then analyzed as potential risk factors in relation to the sites of cancer included. For each site of cancer analyzed as a case series, controls were selected from among the other cancer sites in the study. This report concerns the associations between sites of cancer for which there were over 100 cases processed (stomach; colorectal, also analyzed by subsites; lung; prostate; bladder; kidney; non-Hodgkin's lymphoma) and nine organic dusts (wood; paper; grain; flour; fabrics; cotton; wool; synthetics; fur). All site-exposure combinations were investigated. The ones that provided the most interesting leads were lung-wood dust (odds ratio (OR) = 1.5), stomach-wood dust (OR = 1.5), colorectal-synthetic fiber (OR = 1.5), bladder-synthetic fiber (OR = 1.8), non-Hodgkin's lymphoma-cotton dust (OR = 1.9), colon-grain dust (OR = 2.6), prostate-grain dust (OR = 2.2), and prostate-paper dust (OR = 2.0). Only the associations with wood dust, synthetic fibers and cotton dust showed some evidence of "dose-response" with duration of exposure. Because it is such a common exposure and appears to increase lung and stomach cancer risks, wood dust may be responsible for a great deal of occupational cancer.

Adult↗

Incidence of hepatitis A virus (HAV) infection in rural Liberia.

To provide background for future hepatitis A vaccine trials, sera were collected from 0- to 4-year-old Liberian infants and their mothers on two occasions an average of 14.75 months apart and tested for antibody to hepatitis A virus (anti-HAV). The prevalence of anti-HAV rose from 2.5% in infants 0-6 months of age to 70% in children 3-4 years of age and did not differ between male and female infants. The annual incidence of new infections was slightly lower in the first year of life (35%) than in the subsequent 3 years, when it averaged 45%. The presence of HBV infection did not affect the incidence of HAV seroconversion. No clinical hepatitis was recognized in the subjects who seroconverted. Dual hepatitis A and B virus infection were observed; these were all clinically inapparent. The extraordinary incidence of HAV infection documented in the present study offers an opportunity for vaccine efficacy trials requiring minimal numbers of subjects.

Adolescent↗

Further evidence of inactivity of hypothalamo-pituitary-thyroid axis in Snell dwarf mice.

The effects of hemithyroidectomy (hemiTX) and complete thyroidectomy (TX) on the cellular composition and the mitotic activity of the anterior pituitary gland were examined in genetically thyrotropin (TSH)-deficient female Snell dwarf mice (dw/dw) and in phenotypically normal female mice (?/+) from the same strain. In normal (nondwarf) mice, both hemiTX and TX reduced the percentage of acidophilic (orange G-positive) cells and increased the percentage of thyrotropic (aldehyde fuchsin [AF]-positive) cells, whereas the percentage of gonadotrophs (PAS-positive cells) and chromophobes (unstained cells) was not affected. Both interventions increased the mean mitotic activity rate (MMAR) of the anterior pituitary lobe. This effect was related to the enhancement of the MMAR of acidophilic cells and, particularly, thyrotropic cells. The MMAR of thyrotrophs in thyroidectomized normal mice was significantly higher than that in sham-TX controls or in hemithyroidectomized animals. In Snell dwarf mice, neither hemiTX nor TX affected the percentage of the various cell categories (PAS-positive, unstained, and extremely rare AF-positive cells) in the anterior pituitary lobe. Furthermore, neither hemiTX nor TX substantially influenced the MMAR of the gland. No mitotic figures were found in the AF-positive cells. Since the AF-positive cells in the anterior pituitary of dwarf mice completely failed to respond to hemiTX or TX, we believe they are not true thyrotropic cells. Using electron microscopy, we confirmed a lack of somatotrophs, mammotrophs, and normal thyrotrophs in the anterior pituitary of Snell dwarf mice. The results provide morphological evidence of inactivity of the hypothalamo-pituitary-thyroid axis in Snell dwarf mice.

Animals↗

Quality of response in different population groups in mail and telephone surveys.

Mail and telephone survey methods, with follow-up by other methods, can provide high response rates. However, it is not clear whether different population groups provide responses of different quality, thus creating risk of biased comparisons. A closely related problem is whether proxy response adequately substitutes for self-response. This study addressed these issues in the context of parallel mail and telephone health surveys carried out in Montreal. In the telephone survey, proxy respondents provided lower estimates of morbidity and health care utilization than self-respondents; in the mail survey, there was no difference between proxy and self-response. Response validity was assessed by comparing reported physician visits with those recorded by the government-run universal health insurance plan. In general, mail responses were more valid than telephone responses. In both methods, there were suggestive but not persuasive differences in validity among sociodemographic subgroups. In both methods, those reporting illness or medication use had less underreporting of physician visits than those not reporting such things.

Adolescent↗

Inactivation of hepatitis B and Hutchinson strain non-A, non-B hepatitis viruses by exposure to Tween 80 and ether.

Titrated stocks of hepatitis B virus and Hutchinson strain non-A, non-B hepatitis virus were diluted in normal serum to contain, respectively, greater than or equal to 10(6) and greater than or equal to 10(4) chimpanzee infectious doses (CID50) per milliliter and exposed to 1% Tween 80 and 20% ether at 4 degrees C for 18 h. After evaporation of the ether, the treated sera were each inoculated into two chimpanzees. The animals remained free of serologic and biochemical evidence of hepatitis during a 6-month follow-up period, and were then shown to be susceptible to infection by challenge with the original untreated inocula. To assess the effect of exposure to Tween 80/ether on coagulation factors, four lots of antihemophilic factor (AHF) concentrate and 2 lots of commercial factor IX concentrate were treated as above. For the AHF concentrate there was an average of 70% recovery of factor VIII procoagulant activity, 93% recovery of factor VIII-related antigen, and 73% recovery of fibronectin opsonin activity and no detectable change in ristocetin cofactor activity or in fibronectin antigen. Crossed immunoelectrophoresis revealed no change in migration rate of fibrinogen, fibronectin, and von Willebrand factor (vWF), although the quantity of fibrinogen was reduced. Factor VIII procoagulant activity and vWF activity remained associated during chromatography on BioGel A15.

Animals↗

Nickel and cancer associations from a multicancer occupation exposure case-referent study: preliminary findings.

Since 1979 our group has been engaged in a case-referent study of 12 tumour types (oesophagus, stomach, colon, rectum, liver, pancreas, lung, melanoma of skin, prostate, bladder, kidney, lymphoid tissue) and occupational exposure. The study covers the entire Montreal population of males aged 35-70; cases are ascertained in all major hospitals. The interview concerns various sociodemographic variables and a detailed job history. Each job history is evaluated by a team of chemists who infer for each job what the possible physical and chemical exposures were. The list of exposures thus inferred is added to the subject's data file. Each site and each exposure noted in any patient's history are statistically evaluated for possible association. Until June 1982, 1 343 cancer cases and 144 general population subjects had been thus interviewed. For the present purpose, all 1 487 files were reviewed to assign exposure to nickel, and nickel exposure was attributed to 79 subjects. Mantel-Haenszel analyses were carried out comparing each site with a referent group consisting of all other interviewees (other sites and healthy controls). Only the nickel-lung association turned out to be remarkable, with an odds ratio of 3.1, 95% confidence limits 1.9-5.0, and some indication of dose-response effect. The risk was particularly high among stainless-steel welders, though other nickel-exposed workers were also at risk. These findings probably reflect a real risk; however, we cannot be certain that nickel is responsible. Exposure to chromium compounds was so highly correlated with nickel that the observed nickel association may simply have reflected a confounding effect of chromium. Confounding with other occupational exposures is also possible.

Adult↗