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Biomedical subjects

P Boyle

Publications and source records attributed to P Boyle.

At least 145 records · Page 8Linked to original sources

Epidemiology of sociodemographic characteristics, lifestyle, medical history, and colon cancer: a case-control study among French Canadians in Montreal.

Colon cancer is the second most common cancer in both men and women in North America and other developed countries. In a population-based case-control study of colon cancer among French Canadians in greater Montreal, a total of 402 cases and 668 controls were interviewed. The cancer cases were identified through the admission offices of five major Francophone teaching hospitals in Montreal from 1989 to 1993. The controls, matched by age, sex, place of residence, and language, were selected by a modified random digit dialing method. The results show that subjects who had ever been married had a lower risk for colon cancer (odds ratio [OR]: 0.58; 95% confidence interval [95% CI]: 0.48-0.84) than did individuals who had never been married. A significant association (OR: 1.90; p for trend = 0.003) was found between the height of subjects and the risk of colon cancer. The OR for individuals with a family history of colorectal cancer was 2.78 with a p value of 0.01. A direct and significant association (OR: 2.01) was found among constipation, use of laxatives (OR: 1.41), and the risk of colon cancer. Among women, a suggestive inverse association was detected between the number of full-term pregnancies and the risk of colon cancer in female subjects (the OR for five or more pregnancies was 0.58 with a p for trend of 0.08). There was also a suggestive linear trend (increased age-decreased risk) between age at menarche and the risk of colon cancer. No association was apparent between other sociodemographic characteristics and the risk of colon cancer. In conclusion, married individuals had lower risk for colon cancer, perhaps due to food habits or other characteristics of being single. Higher height and weight history 10 years before the diagnosis of cancer are risk factors for breast cancer, while both current weight and body mass index seem to be protective. Positive family history of colon cancer increased the risk of colon cancer significantly.

Adult↗

Sociodemographic characteristics, smoking, medical and family history, and breast cancer.

The relationship between sociodemographic characteristics, lifestyle, family history of cancer, medical history, and reproductive factors and breast cancer was investigated in a population-based case-control study of French Canadians in Montreal. In this study, a total of 414 French-Canadian cases and 429 age- and language-matched population controls were interviewed. Ever-married women showed significantly lower risk (OR: 0.64 [0.45-0.92]) for breast cancer, as did smokers (OR: 0.73 [0.55-0.98]), particularly of nonfilter cigarettes (OR: 0.36 [0.17-0.72]). Weight history, both for the year before the diagnosis of breast cancer and 10 years previously, was associated with risk for the disease. A strong inverse relationship was found between the number of full-term pregnancies (OR: 0.48 [0.28-0.82]) and the risk of breast cancer, while the p trend for late age at first pregnancy (p = 0.02) and menopause (p = 0.004) was statistically significant. A history of breast problems (OR: 1.87 [1.34-2.60]) and a history of breast cancer in relatives (OR: 2.95 [1.63-5.34]) were strongly associated with risk. This study confirms the risk factors of late age at first full-term pregnancy, nulliparity, late age at menopause, and positive family history of breast cancer in the etiology of this disease. Perhaps the protective effect of smoking against breast cancer could be due to its antiestrogenic influence.

Adult↗

Migration and housing tenure in South East England.

"A substantial literature has developed regarding the relationship between migration and housing tenure in Britain.... It is important to control for individual characteristics before the independent effect of tenure on mobility can be determined. This paper is a report of an investigation of this relationship in the South East of England, in which the Sample of Anonymised Records, a unique individual-level British data source for this type of study, were used. The study continues with a consideration of the influence of housing on migration into the South East from the North of Britain for those in manual and nonmanual occupations."

Demography↗

Genetic polymorphism of N-acetyltransferases, glutathione S-transferase M1 and NAD(P)H:quinone oxidoreductase in relation to malignant and benign pancreatic disease risk. The International Pancreatic Disease Study Group.

Carcinogens present in cigarette smoke and diet have been associated with pancreatic cancer. We hypothesized that heterocyclic and aromatic amines implicated in these exposures could be involved as causative agents and that therefore genetic variation in enzymes metabolizing these carcinogens could modify the risk of developing malignant and benign pancreatic disease. The effect of the genetic polymorphism of acetyltransferases (NAT1) and NAT2), glutathione S-transferase M1 (GSTM1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) on the risk of pancreatic diseases (cancer, pancreatitis) was examined in a case-control study. PCR-based assays were used for genotype analysis of genomic DNA from whole blood cells. Samples collected from Caucasian patients with diagnosed pancreatic cancer (n = 81), with non-alcoholic (n = 41) and alcoholic pancreatitis (n = 73) and from asymptomatic control subjects (n = 78) were analysed. The prevalence of GSTM1 null genotype and of NAT2 fast and slow acetylator genotypes and the distribution of frequencies for NQO1 genotypes did not differ in subjects with pancreatic diseases vs controls. For NAT1 slow acetylators a non-significant excess (P = 0.18) was found among pancreatic cancer cases vs controls. There was a significant over-representation of the GSTM1 AB or B genotype in all pancreatic disease cases combined (OR = 2.6; P < 0.05). When concurrent controls were pooled with literature controls (n = 1427), OR was 1.4 (P = 0.08). The results of this study, requiring confirmation, suggest that the polymorphism of GSTM1 and NAT1 enzymes may be associated with a modest increase in susceptibility to pancreatic diseases.

Acetyltransferases↗

Pure endotoxin does not pass across the intestinal epithelium in vitro.

Numerous reports suggest that endotoxin (LPS) may play a central role in triggering the inflammatory cascade that leads to the systemic inflammatory response syndrome. Although conditions that promote bacterial translocation in vivo may also facilitate direct translocation of LPS, the exact mechanisms by which LPS crosses the intestinal barrier to reach the systemic circulation are unknown. This study was designed to determine whether pure endotoxin could pass across injured rat ileal mucosa in the Ussing chamber. Sprague-Dawley rats were subjected to mild or severe hemorrhagic shock following carotid artery cannulation, and then resuscitated. Control animals underwent carotid artery cannulation only (sham-shock). Bacterial translocation to the mesenteric lymph nodes, liver, or spleen was measured after 24 h. Transmucosal passage of fluorescein isothiocyanate (FITC)-labeled E. coli C-25, or FITC-conjugated LPS was measured in the Ussing chamber. Intestinal membranes were examined by light and confocal laser microscopy. Severe hemorrhagic shock resulted in a 60% mortality rate and a 100% incidence of bacterial translocation in surviving animals. Sham-shock rats had a 100% survival rate and a 33% incidence of bacterial translocation. Transmucosal passage of FITC-E. coli C-25 was similar in both groups; however, passage of FITC-LPS was never detected. Histologic analysis confirmed mucosal injury to the intestinal epithelium of rats subjected to severe hemorrhagic shock, and confocal laser microscopy demonstrated passage of FITC-E. coil C-25, but not of FITC-LPS across the ileal membranes. Disruption of the intestinal epithelium with a potent mucolytic agent did not result in significant increase in transmucosal passage of FITC-LPS. We conclude that pure LPS does not pass across the intestinal mucosa in vitro. Transmucosal passage of LPS in vivo may be due, at least in part, to the release of bacterial cell wall fragments containing LPS from killed bacteria that had previously translocated.

Animals↗

Chemoprevention of colorectal cancer.

Colorectal cancer is the fourth commonest form of cancer in men with 678 000 estimated new cases per year worldwide, representing 8.9% of all new cancers. The disease is most frequent in Occidental countries and particularly so in North America, Australia, New Zealand, and parts of Europe. Prospects for colorectal cancer control are bright and a number of possible approaches could prove fruitful. Among these, pharmaceutical measures seem to be valid and logical approaches to the prevention of colorectal cancer and diminishing its impact. Such approaches could concentrate in primary prevention in at-risk subjects or be applied in altering the course of precursor or established disease. Treatments used must fulfil basic requirements of biological plausibility and safety in continued use in large numbers of subjects. Those available include vitamins and minerals, and other drugs with potential as antioxidants, immune modulators or promoters of cell differentiation or apoptosis. Of the various regimens suggested, vitamin A supplementation may even predispose to adverse outcomes, and antioxidant vitamins in general have no coherent body of evidence to support their use. N-acetylcysteine and ursodeoxycholic acid have promising characteristics but there are as yet no clinical data to support the use of the former in gut epithelial cancer, and formal dose ranging studies must be carried out before the latter is submitted to large scale trial. Folate shows promising characteristics but non-steroidal anti-inflammatory drugs and vitamin D seem the most promising agents. Both seem to reduce the incidence of disease, and to reduce growth rates and/or induce differentiation or apoptosis in gut epithelial cancer cells. Both are also well understood pharmacologically. They may be preferred to newer selective compounds in the same class until these newer compounds are confirmed as safe for widespread long term use.

Anti-Inflammatory Agents, Non-Steroidal↗

Some remarks on the epidemiology of acute urinary retention.

Acute urinary retention is an unpleasant, painful experience which requires immediate medical, and frequently surgical intervention. Population studies reveal that acute urinary retention is a common event: a 60 year-old man who survives a further 20 years has a 23 per cent probability of experiencing an acute episode of urinary retention. About half of acute retention episodes appear to be linked to general anaesthesia and a further large population due to the natural history of benign prostatic hyperplasia. The risk of acute urinary retention increases with increasing age. There are a number of other risk factors with risk increased in men with moderate and severe urinary symptoms, low peak urinary flow rates (less than 12 ml/sec) and among men with large prostates. Recent placebo-controlled randomised trials reveal that finasteride is associated with a 57 per cent reduction in the hazard ratio of acute urinary retention when used for at least two years. Since finasteride acts in a positive manner on the major risk factors (finasteride use increases peak urinary flow rate, reduces symptom scores in moderately symptomatic men and reduces prostate volume), this result is not too surprising. It remains to be determined what the risk factors for anaesthesia-induced acute retention are and how they can be altered. Nevertheless, the improvement of our knowledge of the epidemiology of acute urinary retention in the past 12 months is impressive.

Acute Disease↗

Immunoglobulin A supplementation abrogates bacterial translocation and preserves the architecture of the intestinal epithelium.

BACKGROUND: Breast milk has been shown to prevent gut-origin infections in neonates through undefined mechanisms. Putative protective factors in breast milk include immunoglobulin (Ig)A, IgG, and lactoferrin. We examined their role in bacterial translocation in neonatal rabbits. METHODS: IgA, IgG, and lactoferrin were isolated from rabbit breast milk through gel filtration and ion-exchange chromatography. Neonates were randomized to receive breast milk, formula alone, or formula supplemented with IgA, IgG, or lactoferrin. Quantitative cultures were performed on day 7 for bacterial translocation. Hematoxylin-eosin-stained sections of distal ileum were examined by light microscopy. Transmucosal bacterial passage was determined in vitro, and the ileal mucosal membranes were examined by confocal microscopy. RESULTS: IgA supplementation abrogated bacterial translocation. IgG and lactoferrin had no significant effect. Neonates that received IgA or breast milk gained more weight than those in the other groups. IgA reduced transmucosal bacterial passage in vitro. In contrast to the normal-appearing distal ileum of neonates fed breast milk, intestinal epithelium from neonates that received formula or formula with IgG or IgA demonstrated prominent vacuoles by light microscopy. Those fed formula alone or formula with lactoferrin had slightly shortened villi. CONCLUSIONS: IgA supplementation prevents bacterial translocation by enhancing gut mucosal barrier function.

Animals↗

Effect of parity and age at delivery on breast cancer risk in Slovenian women aged 25-54 years.

In 1988, a case-control study on breast cancer and oral contraceptives with 624 cases and 624 matched controls in the age range 25-54 years was undertaken in Slovenia. This analysis assesses the relationship between parity and breast cancer risk: the relative importance of age at first birth, age at subsequent births and total parity. We also evaluate whether a dual effect of an increased risk immediately after childbirth followed by a long-term benefit exists. Three logistic regression models were used. Age at first delivery is an important breast cancer risk factor: among parous women it was associated with a 5.3% increase/year in the odds of breast cancer. Multiparity was not shown to be an independent risk factor. Age at subsequent deliveries was associated with a 1% increase in risk for every 1 year increase of age at any birth, but this contribution to the risk was not significant. In the analysis stratified by parity the most important influence is with the age at first birth. We find no evidence of an effect on the odds of breast cancer associated with the age at the second, or later, births. We do find that there is an increased risk associated with the birth of the first child followed by a longer term protective effect. A post-menopausal woman has a reduced breast cancer risk compared with a pre-menopausal woman of the same age, adjusting for the same number of deliveries and ages at these deliveries.

Adult↗

Nutritional factors and colon carcinoma: a case-control study involving French Canadians in Montréal, Quebec, Canada.

BACKGROUND: In a population-based case-control study of colon carcinoma and nutrition involving the francophone community in Greater Montreal, a total of 402 cases (200 males and 202 females) and 668 controls (239 males and 429 females) were interviewed. METHODS: Cases from 1989-1993 were identified through the admission offices of 5 major francophone teaching hospitals in Montreal and were ages 35-79 years. Controls matched by age, place of residence, and language were selected by a modified random digit dialing method. Information on dietary intake was collected with a quantitative food frequency questionnaire. RESULTS: No associations were evident between colon carcinoma and total energy, protein, or carbohydrate consumption, whereas a suggestive inverse association was found with total fat intake, with an odds ratio (OR) of 0.78 (P = 0.0637), and with saturated fat intake as well (OR = 0.71, P = 0.0893). A strongly significant inverse association was found with dietary fiber (OR = 0.50, P = 0.0018). The strongest inverse association concerning fiber was found with fiber from vegetable sources (OR = 0.57, P = 0.0096), and a suggestive (although nonsignificant) inverse association (OR = 0.74, P = 0.0687) was found with fiber from fruits. Calcium was inversely associated with risk (OR = 0.69, P = 0.0411), as was dietary intake of vitamin A (OR = 0.67, P = 0.0162), retinol, (OR = 0.069, P = 0.0409), vitamin E (OR = 0.53, P = 0.0028), and alphatocopherol (OR = 0.63, P = 0.0256). Although there was no association demonstrated between dietary beta-carotene intake and risk, a suggestive (although nonsignificant) inverse association with intake of other types of carotene was observed (OR = 0.76, P = 0.0740). No association was found between intake of other nutrients investigated in this study and risk of colon carcinoma. CONCLUSIONS: There is strong evidence from epidemiologic studies that high intake of fat and meat are risk factors for colorectal carcinoma in humans, whereas high intake of vegetable and fruit are inversely associated with risk of colon carcinoma. The findings from this study are in agreement with this observation.

Adult↗

Epidemiologic aspects of gallbladder cancer: a case-control study of the SEARCH Program of the International Agency for Research on Cancer.

BACKGROUND: There are few previous epidemiologic studies of gallbladder cancer, a rare but nearly always lethal gastrointestinal cancer with a demonstrated greater frequency in adult women and older subjects of both sexes, and also in the members of populations throughout central and eastern Europe and certain racial groups such as native American Indians. Unfortunately, the prospects for the prevention of this form of cancer are poor. PURPOSE: Our purpose in conducting this study was to investigate possible new risk factors for gallbladder cancer and to strengthen our understanding of established causal agents that may be involved in this disease. METHODS: A large, collaborative, multicenter, case-control study of cancer of the gallbladder was conducted in five centers located in Australia (Adelaide), Canada (Montreal and Toronto), The Netherlands (Utrecht), and Poland (Opole) from January 1983 through July 1988. Case subjects with gallbladder cancer were accrued by the centers from hospital pathology records and from reports to regional cancer registries. Cancer diagnosis was confirmed by either biopsy, cholecystectomy, or at the time of autopsy. Control subjects were randomly assigned at each center from the population. The pooled analysis included 196 case subjects and 1515 control subjects (who did not report previous cholecystectomy). Ninety-eight percent of the subjects were white. Personal interviews of case subjects, control subjects, and surrogates (spouse or next of kin) were conducted by trained personnel. RESULTS: After adjusting for potential confounding factors (age, sex, center, type of interview, years of schooling, alcohol intake, and lifetime cigarette smoking), a history of gallbladder symptoms requiring medical attention (e.g., reduced bile secretion from the gallbladder into the small intestine due to obstructions of the common bile or cystic ducts) was the major risk factor associated with this form of cancer (odds ratio [OR] = 4.4; 95% confidence interval [CI] = 2.6-7.5). This association was present even in subjects who had their first gallbladder examination because of symptoms present more than 20 years earlier (OR = 6.2; 95% CI = 2.8-13.4). Other variables associated with gallbladder cancer risk included an elevated body mass index, high total energy intake, high carbohydrate intake (after adjustment for total energy intake), and chronic diarrhea. All of these risk factors have been previously associated with gallstone disease. CONCLUSIONS: These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

Adult↗

The increase of Hodgkin's disease incidence among young adults. Experience in Connecticut, 1935-1992.

BACKGROUND: Recent studies have indicated an increase in young adulthood Hodgkin's disease incidence, particularly among females, since 1970. However, no studies have examined the long term trends and period-cohort patterns of Hodgkin's disease incidence. METHODS: The current study reported time trends and age-period-cohort patterns of Hodgkin's disease incidence during the period 1935-1992, with an emphasis on incidence rate changes among young adults, using data from the Connecticut Tumor Registry. RESULTS: A total of 4997 incidences of Hodgkin's disease were included in the study. The authors found that the incidence of Hodgkin's disease had increased among young adults age 20-44 years. Incidence had increased dramatically among females since 1970 but less significantly among males. These observed trends were primarily associated with nodular sclerosis histologic type. Age-period-cohort analyses indicated that these observed increases in young adults were cohort phenomena, suggesting possible changes in exposure to risk factors. CONCLUSIONS: Currently identified major risk factors, including social status, Epstein-Barr virus infection, and human immunodeficiency virus infection, cannot adequately explain the observed trends. Analytical epidemiologic studies are urgently needed to identify risk factors that will not only elucidate the etiology of Hodgkin's disease but also explain the rapid increase in Hodgkin's disease incidence among young females.

Adult↗

Craniofacial abnormalities in mice carrying a dominant interference mutation in type X collagen.

Type X collagen is a short, non-fibril forming collagen restricted to hypertrophic cartilage, and has been hypothesized to play a role in endochondral ossification. The purpose of the study was to investigate the consequences resulting from the interference of type X collagen function on the growth and development of the craniofacial skeleton through analysis of transgenic mice with a dominant interference mutation for type X collagen. The craniofacial tissues of 21-day-old transgenic mice were examined by: cephalometric and radiographic densitometry analyses, conventional histology, and immunohistochemistry using antibodies specific for either endogenous mouse type X collagen or the transgene product. Genotypically positive mutant mice showed moderate but statistically significant craniofacial skeletal abnormalities, including the underdevelopment of the chondrocranium and mandible, but no cleft palate. Mean radiographic optical densities of the mutant condylar cartilage and the subchondylar areas were 32% less than the corresponding areas of normal mandibles, while mean radiographic optical density measured at the incisor tooth point remained constant. Histologically, transgene-positive mice revealed compressed hypertrophic cartilage zones and reduced trabeculae in both the mandibular condyle and the synchondroses of the chondrocranium. In the normal condyle, mouse type X collagen was localized by the monospecific antibody against a synthetic rat type X collagen NC1 peptide throughout the hypertrophic cartilage layer; in the mutant condyle, immunoreactivity to endogenous type X collagen was only seen sporadically. The truncated type X collagen transgene product, identified with the monoclonal antibody against an epitope within the chick type X collagen NC2 domain, persisted in the lower hypertrophic cartilage layer and the primary spongiosa, rather than being removed by subsequent endochondral ossification. The data suggested that the expression of the chick type X collagen transgene product was strongly associated with the craniofacial skeletal abnormalities that were distinct from other cartilage-related phenotypes.

Animals↗

Public housing and migration: a multi-level modelling approach.

"This paper...[analyzes] the distance moved by one-year migrants using a multi-level modelling approach. Controlling for a range of socio-economic variables, derived from the 1991 British Census Sample of Anonymised Records (SAR), at both the individual and area level, the distance moved by household heads in public, privately rented and owner-occupied housing within Britain is assessed.... It is confirmed that migrants in public housing are less likely to migrate long distances than owner-occupiers and that the proportion of public housing in a SAR area, and the absolute reduction in public housing in a SAR area between 1981 and 1991, does not have a significant effect on the distance that in-migrants have moved."

Demography↗

Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia.

OBJECTIVES: A pooled analysis of all available randomized trials with 2-year follow-up data with finasteride and placebo was undertaken to further investigate recent observations that finasteride use may reduce the occurrence of acute urinary retention (AUR) and benign prostatic hyperplasia (BPH)-related surgical intervention. METHODS: Occurrences of AUR and surgical intervention were examined by treatment group in a pooled series of 4222 men with moderately symptomatic BPH. RESULTS: In total, 81 occurrences of AUR were reported, 24 (1.1%) of 2113 in the finasteride group and 57 (2.7%) of 2109 in the placebo group. The hazard ratio was consistent in all three studies, with a 57% decrease in the hazard rate for occurrence of AUR with finasteride compared with that for placebo present in the pooled data set over the 2-year study period (P < 0.001). Additionally, 227 surgical interventions were recorded over the 2-year study period, 89 (4.2%) of 2113 in the finasteride group and 138 (6.5%) of 2109 in the placebo group. The hazard ratio was consistent across the three studies, with a 34% reduction in the hazard rate for occurrence of surgery with finasteride compared with that for placebo (P < 0.002). Overall, there was 35% reduction in the two BPH-related end points (ie, AUR or surgery). CONCLUSIONS: Treatment with finasteride for up to 2 years more than halves the frequency of AUR and reduces surgical intervention by over one third relative to placebo in patients with moderate BPH. This is the first demonstration that long-term medical therapy can reduce clinically significant end points such as AUR or surgery, and these data have important implications for the long-term management of patients with BPH.

Acute Disease↗