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Biomedical subjects

L Richardson

Publications and source records attributed to L Richardson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Are the apparent effects of cigarette smoking on lung and bladder cancers due to uncontrolled confounding by occupational exposures?

It has been suggested that the well known associations between smoking and cancer may in part reflect inadequately controlled confounding due to occupational exposures. The purpose of the present analysis is to describe the association between cigarette smoking and both lung and bladder cancers, taking into account the potential confounding effects of over 300 covariates, most of which represent occupational exposures. A population-based case-control study was undertaken in Montreal to investigate the associations between a large variety of environmental and occupational exposures, on the one hand, and several types of cancer, on the other. Interviews were carried out with male incident cases of several sites of cancer, including 857 lung cancers and 484 bladder cancers. A group of non-smoking-related cancers, comprising 1,707 interviewed subjects, was used as one control group. Additionally, 533 population controls were interviewed and constituted a second control group. Interview information included detailed lifetime smoking histories, job histories, and other potential confounders. Each job history was reviewed by a team of experts who translated it into a history of occupational exposures. These occupational exposures, as well as nonoccupational covariates, were treated as potential confounders in the analysis of cigarette smoking effects. Regardless of whether population controls or cancer controls were used, the odds ratio (OR) between smoking and lung cancer (ranging from 12 to 16 for ever vs never smokers) was not materially affected by adjustment for occupational exposures. The odds ratios for bladder cancer (ranging from 2 to 3) were also unaffected by confounding due to occupational exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The pharmacokinetics, tissue localization, and metabolic processing of recombinant human hepatocyte growth factor after intravenous administration in rats.

Hepatocyte growth factor (HGF) is a pluripotent mitogen thought to be involved in liver regeneration. It is synthesized as a single chain promitogen and requires proteolytic processing to a two-chain heterodimeric form for biological activity. The pharmacokinetics and tissue distribution of radioiodinated single chain recombinant human HGF ([125I]rhuHGF) were studied in male Sprague-Dawley rats after an iv bolus dose. Pharmacokinetic parameters were determined from trichloroacetic acid-precipitable radioactivity in serum samples. There was a rapid distribution phase (t1/2 alpha = 3.1 min) and a slower elimination phase (t1/2 beta = 114 min). Tissue distribution was assessed by whole body autoradiography 5, 60, and 1440 min after an iv bolus dose. rhuHGF rapidly distributed to the liver, kidney, adrenal gland, and spleen. The importance of the liver in the rapid clearance and subsequent conversion of single chain pro-rhuHGF to the mitogenically active two-chain form was demonstrated using an isolated rat liver perfusion system. TCA-precipitable radioactivity excreted into the bile (1.0 +/- 0.1%) and released into the venous effluent (38.9 +/- 6.1%) was monitored for 60 min after a portal vein injection. The appearance of radioactivity in both the bile and venous effluent was maximal between 20-35 min. Further characterization of the reduced samples by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed that the two-chain form of [125I]rhuHGF was the predominant form after hepatic perfusion. These studies suggest that the liver plays a major role in the rapid clearance and subsequent activation of pro-rhuHGF in vivo.

Animals↗
PubMed1994

High plasma insulin-like growth factor-II and low lipid content in transgenic mice: measurements of lipid metabolism.

Transgenic mice were made by introducing extra copies of the mouse insulin-like growth factor-II (IGF-II) gene driven by the bovine keratin 10 promoter (BKVI). The adult plasma IGF-II levels were elevated at least three times in one line. In this line, there was a lower lipid content of both brown and white adipose depots at 2-4 months of age, and 40% less fat in the carcass at 7-9 months. The low lipid phenotype was not detected in the carcass at 2 weeks after birth. The lean characteristic was attributed to circulating IGF-II because the transgene was not expressed in fat. At 2-4 months of age, the transgenes oxidized more oral lipid, and less of this lipid was incorporated into the whole body and the epididymal fat. In contrast, the interscapular brown adipose tissue maintained lipid incorporation and lipoprotein lipase activity despite its reduced size. The altered activity of the brown adipose tissue may account for the gradual onset and persistence of the lean feature of the transgenic mice. There were no substantial changes in lipogenesis which could account for the low fat content. The plasma levels of IGF-I, insulin, glycerol, non-esterified fatty acids, triacylglycerols and glucose were not greatly changed and the pituitary GH content was within the normal range.

Adipose Tissue↗
PubMed1993

Linkage analysis of DRD2, a marker linked to the ataxia-telangiectasia gene, in 64 families with premenopausal bilateral breast cancer.

Recent reports suggest that subjects who are heterozygous for the ataxia-telangiectasia gene are at increased risk of breast cancer. We conducted linkage analyses of 64 families with premenopausal bilateral breast cancer using DRD2, a marker linked to the ataxia-telangiectasia locus at 11q22-23. We assumed a model with dominant transmission of breast cancer. Lod scores summed over all families provided strong evidence against tight linkage (e.g., a lod score of -6.08 at theta = 0.00001), although a single family provides suggestive evidence of tight linkage to DRD2. Evidence against linkage to 11q was strongest among families that may involve the BRCA1 breast cancer susceptibility gene on 17q21. However, we did not observe evidence of linkage to 11q among the remaining subgroup with neither a family history of ovarian cancer nor the appearance of linkage to 17q21.

Adult↗
PubMed1993

A linkage analysis of D17S74 (CMM86) in thirty-five families with premenopausal bilateral breast cancer.

We report here results of a linkage analysis of a marker in 35 families in which the proband had premenopausal bilateral breast cancer. This group is of particular interest given their high family risk and the question of etiological heterogeneity. Probands were ascertained from cancer registries in Los Angeles County and Connecticut and major hospitals in Montréal and Québec. Assuming no residual heterogeneity and summing lod scores over all families, we obtained strong evidence against tight linkage (e.g., lod score at theta = 0.000001 is -3.39). To address the issue of heterogeneity, we performed admixture and predivided sample analyses. Using an admixture model we were able to reject the hypothesis of no linkage versus that of linkage with homogeneity (P = 0.045). However, we were unable to reject the hypothesis of no linkage versus linkage with heterogeneity (P = 0.119) or to distinguish between linkage with homogeneity and linkage with heterogeneity (P = 0.500). Predivided sample analyses based upon age of onset, pathological characteristics, time between diagnoses of the breast cancers in each bilateral proband, and the span of ages at diagnoses within a family did not discriminate between apparently linked and unlinked families.

Age Factors↗
PubMed1993

Characterization of radioiodinated recombinant human TGF-beta 1 binding to bone matrix within rabbit skull defects.

Bone healing is regulated in part by the local production of TGF-beta 1 and other growth factors produced by cells at the site of injury. The single application of recombinant human TGF-beta 1 (rhTGF-beta 1) to calvarial defects in rabbits induces an accelerated recruitment and proliferation of osteoblasts within 3 days. This ultimately results in the formation of new bone and the complete closure of the defect within 28 days. The persistence and localization of [125I]rhTGF-beta 1 within an osseous defect was investigated after applying a single dose of [125I]rhTGF-beta 1 formulated in a 3% methylcellulose vehicle. Normal bone encompassing the defect site, the periosteum, and the gel film covering the dura were harvested at 0, 4, 8, and 24 h and 3, 7, and 16 days after [125I]rhTGF-beta 1 application. The defect site-associated radioactivity was quantitated, visualized by autoradiography, and characterized by TCA precipitation and SDS-PAGE. Radioactivity was observed in autoradiographs of gross specimens, histologic sections of the bone matrix, and periosteal tissue surrounding the defect. There was a time-dependent decrease in TCA-precipitable radioactivity; however, radioactivity was still associated with the bone matrix 16 days after application of [125I]rhTGF-beta 1. SDS-PAGE and autoradiography of the radioactivity in homogenized bone and periosteal samples revealed a 25 kD band, suggesting that the radioactivity remaining at the defect site represented intact [125I]rhTGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

An intraoral splint for the prevention of microstomia from facial burns.

Microstomia may be a disfiguring complication of severe burn injuries of the soft tissues of the face. The constriction of the perioral myocutaneous tissues following such trauma poses several problems and usually necessitates major plastic and reconstructive intervention. A novel technique is described which limited the anticipated constriction of perioral tissues in a 21-year-old female who suffered full skin thickness burns to 65 per cent of her body, including her face, following a self-induced petrol burn.

Adult↗
PubMed1991

Gastrointestinal health effects associated with the consumption of drinking water produced by point-of-use domestic reverse-osmosis filtration units.

During a prospective epidemiological study of gastrointestinal health effects associated with the consumption of drinking water produced by reverse-osmosis domestic units, a correlation was demonstrated between the bacterial counts on R2A medium incubated at 35 degrees C and the reported gastrointestinal symptoms in families who used these units. A univariate correlation was found with bacterial counts on R2A medium at 20 degrees C but was confounded by the bacterial counts at 35 degrees C. Other variables, such as family size and amount of water consumed, were not independently explanatory of the rate of illness. These observations raise concerns for the possibility of increased disease associated with certain point-of-use treatment devices for domestic use when high levels of bacterial growth occur.

Canada↗
PubMed1991

A randomized trial to evaluate the risk of gastrointestinal disease due to consumption of drinking water meeting current microbiological standards.

BACKGROUND: This project directly and empirically measured the level of gastrointestinal (GI) illness related to the consumption of tapwater prepared from sewage-contaminated surface waters and meeting current water quality criteria. METHODS: A randomized intervention trial was carried out; 299 eligible households were supplied with domestic water filters (reverse-osmosis) that eliminate microbial and chemical contaminants from their water, and 307 households were left with their usual tapwater without a filter. The GI symptomatology was evaluated by means of a family health diary maintained prospectively by all study families over a 15-month period. RESULTS: The estimated annual incidence of GI illness was 0.76 among tapwater drinkers compared with 0.50 among filtered water drinkers (p less than 0.01). These findings were consistently observed in all population subgroups. CONCLUSION: It is estimated that 35% of the reported GI illnesses among the tapwater drinkers were water-related and preventable. Our results raise questions about the adequacy of current standards of drinking water quality to prevent water-borne endemic gastrointestinal illness.

Adolescent↗
PubMed1990

The expression of IgG allotypes on platelets and immunization to IgG allotypes in multitransfused thrombocytopenic patients.

We investigated whether the platelet-membrane surface carries IgG allotypic antigens and whether these determinants may be important in platelet transfusion therapy. Using a hemagglutination inhibition assay, we showed that the G1m IgG allotypes (a, x, f) and K1m and K3m light-chain allotypes are expressed on the surface of platelets, whereas G3m allotype antigenic determinants were not detectable. In 146 multitransfused thrombocytopenic patients, 35 (24%) patients were found to have antiallotypic antibodies. To study the effect of antiallotypic antibodies on platelet transfusion outcome, patients received platelet transfusions from donors, either positive or negative for the IgG allotype to which patients were immunized. Of the 19 antigen-positive and 19 antigen-negative platelet transfusions given, respectively, the mean platelet count increments at 1 hour were 8,402 +/- 6,402 +/- 6,721 (1 SD) and 9,799 +/- 5,559 (1 SD) P less than .2. Transfusion reactions were not more common when antigen-positive platelet transfusions were given. Despite the presence of IgG allotypic determinants on platelets, allotypic antibodies do not decrease platelet transfusion recovery. Furthermore, passive administration of plasma containing IgG allotypes to patients with antiallotypic antibodies does not lead to innocent bystander-mediated platelet destruction.

Blood Platelets↗
PubMed1990

Cancer incidence and risk factors among Montreal residents of Italian origin.

Cancer risks associated with Italian ethnicity were investigated using data from a large case-control study on the aetiology of several cancer sites in the male population of Montreal. Two approaches were taken. First, incidence rates were computed for Italians and for others in the Montreal area using our ascertained cases as numerators and census-derived denominators. Secondly, for respondents to the case-control study, an analysis was carried out with Italian ethnicity as the risk factor and a number of covariates as potential confounders. Out of 4553 incident cases in men aged 35-69, 301 were of Italian origin. As compared with other Montreal males, those of Italian origin had higher incidence rates for cancers of the stomach (p = 0.016, based on 31 cases) and of the colon and rectum (p = 0.102, based on 75 cases) and lower rates for cancer of the lung (p = 0.006) and prostate (p = 0.102, based on 24 cases). For other sites the differences between Montrealers of Italian and non-Italian origins were small. Montreal Italians manifested risks similar to those of the country of origin for cancer of the prostate and similar to the host country for cancers of the colon, rectum and liver. For other sites it was difficult to characterize the pattern because of wide variations among Italian registries. Over 80% of the study subjects in Montreal were interviewed and odds ratios (OR) for Italian ethnicity were estimated for each cancer site using all other sites as controls, adjusting for five potential confounders.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Interaction between norepinephrine and serotonin in the neuroendocrine control of growth hormone release in the rat.

Both alpha 2-adrenergic (alpha 2) and serotonergic (5HT) neurons are associated with stimulation of GH secretion via GRH release. The object of this study was to determine whether the 5HT system is involved in the stimulation of GH secretion by alpha 2-receptor agonists. There are two parts of this study. In the first, the relationship between alpha 2-5HT systems were analyzed by determining if alpha 2-stimulated GH release is mediated by 5HT. In this model, systemically administered alpha 2-agonists [clonidine (CLON) or UK14,304] were tested against 5HT antagonists (meterogoline or cyproheptadine) or 5HT synthesis inhibitors (p-chlorophenylalanine methylester hydrochloride). In the second, sites of 5HT-GRH interaction were determined by testing the response to CLON after 5HT neurotoxin [5,7-dihydroxytryptamine (5,7-DHT)] microinjection at specific hypothalamic nuclei. In both experiments sequential blood samples were withdrawn from silastic jugular cannulas in unanesthetized, freely moving animals. Metergoline (0.045 and 0.135 mg/kg, iv) and cyproheptadine (0.969 micrograms/kg, iv) suppressed, in a dose-dependent manner, the CLON (33 or 66 micrograms/kg, iv)-induced GH surge that was detected 15-30 min after injection in control animals. Both cyproheptadine (0.969 micrograms/kg, iv) and p-chlorophenylalanine (300 mg/kg, ip) effectively suppressed the UK14,304 (220 micrograms/kg, iv)-induced GH surge that occurred 15-30 min after injection in control animals. These data suggest that an intact 5HT system is required for alpha 2-stimulated GH release. 5,7-DHT neurotoxin microinjected into the midline arcuate nucleus (6 micrograms/mg,iv) or bilaterally into the ventromedial nucleus or perifornical area (4 micrograms/0.2 microliter) 5 days previously suppressed the CLON (30 micrograms/kg)-induced GH surge only in animals with arcurate nucleus lesions. To determine if the suppression was mediated by inhibition of GH-releasing hormone (GRH) or stimulation of somatostatin (SRIF), an additional experiment was conducted including 5,7-DHT arcuate nucleus-lesioned animals injected with anti-SRIF. Inasmuch as anti-SRIF failed to reverse the 5,7-DHT suppression of GH secretion, the results of this experiment suggest that GRH mediates NE-5HT-induced GH secretion. In conclusion, these data suggest that alpha 2 activation of GH secretion requires intact serotonergic terminals in the arcuate nucleus and most likely involves GRH rather than SRIF, release.

5,7-Dihydroxytryptamine↗
PubMed1990

Silica and cancer associations from a multicancer occupational exposure case-referent study.

A multicancer site, multifactor case-control study was undertaken to generate hypotheses about possible occupational carcinogens. Eligible cases, comprising all incident cases of cancer at 14 sites who were male, aged 35-70 and resident in Montreal, were subjected to probing interviews 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 analysed as potential risk factors in relation to the sites of cancer included. Over 3700 cases were interviewed and processed. For each site of cancer analysed as a case series, controls were selected from subjects with cancer at the other sites covered in the study. This report concerns the associations between silica exposure and each site of cancer. In initial screening analyses, there were significantly elevated odds ratios for silica and stomach cancer and for silica and non-adenocarcinoma lung cancer. More detailed analyses confirmed these associations, though there was no evidence of a dose-response relationship for stomach cancer. For lung cancer, there were significantly elevated risks in those with high-level long-term exposure. These results, which took into account several potential confounders including cigarette smoking and asbestos exposure, lend credence to the hypothesis that silica exposure increases the risk of lung cancer, and suggest the possibility of an effect on stomach cancer.

Adult↗