Mary Catherine Schumacher

Occupation, cadmium exposure, and prostate cancer.

A population-based case-control study was used to investigate associations between prostate cancer and cadmium exposure, longest industry held, and longest occupation held. The study included 358 men with newly diagnosed prostate cancer and 679 control men identified from the Utah population. Occupational exposures to cadmium were ascertained from self-reported data, through several a priori suspect industries and occupations, through an occupation-exposure linkage system, and through dietary food frequency questionnaires. Overall, cadmium exposure appeared to result in a small increased relative risk for prostate cancer, most apparent for aggressive tumors (OR = 1.7, CI = 1.0–3.1 for any occupational exposure, high dietary intake, or smoking cigarettes). Cases were more likely to have worked in the following industries: mining, paper and wood, medicine and science, and entertainment and recreation. Among men younger than 67, cases were also more likely to have worked in the food and tobacco industries (OR = 3.6, CI = 1.0–12.8). Cases were less likely to have worked in industries involved with glass, clay and stone, or rubber, plastics, and synthetics. Men employed as janitors and in other building service occupations showed increased relative risk for aggressive tumors (OR = 7.0, CI = 2.5–19.6). Agricultural occupations did not appear to be related to prostate cancer, although an increased relative risk for aggressive tumors was detected among younger men (OR = 2.6, CI = 0.6–12.1).

Major Gene Effect for Insulin Levels in Familial NIDDM Pedigrees

Insulin resistance and hyperinsulinemia are familial traits that may precede and predict the onset of non-insulin-dependent diabetes mellitus (NIDDM). In some populations, the distribution of fasting insulin levels and measures of in vivo insulin action suggest the effects of a single major gene. We previously noted hyperinsulinemia among unaffected members of 16 large white pedigrees ascertained through two or more NIDDM siblings. To examine the hypothesis that insulin levels are determined by a single major genetic locus, we used segregation analysis to examine fasting insulin levels in 206 family members and 65 spouses who had normal glucose tolerance tests by World Health Organization criteria. Segregation analysis supported a major locus determining fasting insulin levels and segregating as an autosomal recessive allele with a frequency of 0.25. Thus, homozygotes represented 6.25% of the population, and homozygosity for the hyperinsulinemia allele elevated the mean fasting insulin level from 70.3 to 211.1 pM (11.7–35.2 μU/ml). The analysis apportioned the variance in fasting insulin as 33.1% due to the major autosomal locus, 11.4% due to polygenic inheritance, and 55.5% due to unmeasured effects. Homozygotes for the recessive allele had higher 1-h insulin levels than all others (911.7 vs. 427.2 pM [152.0 vs. 71.2 μU/ml]). We also found evidence for a major locus determining 1-h-stimulated insulin levels, with codominant inheritance as the most likely pattern in inheritance. The causal relationship between these findings and NIDDM has not been determined, and segregation of direct measures of insulin action remains to be demonstrated. However, we have found evidence for a major gene locus that may contribute to the observed familial aggregation of impaired insulin action in relatives of NIDDM individuals and the inherited predisposition to NIDDM.

Physical activity and colon cancer: A comparison of various indicators of physical activity to evaluate the association

We compare categories of physical activity, based upon self-reported leisure time and occupational activity, with categories of activity based upon coded job titles using the Dictionary of Occupational Titles. For people under 65 years of age, self-reported total activity, total nonintense activity, and occupational activity were not strongly associated with coded occupational activity in men (Spearman r = 0.36, 0.27, and 0.32, respectively); even weaker associations were noted in women (r = 0.23, 0.27, and 0.10). Associations between total activity and coded occupational activity were generally weaker for people who were 65 or older. Despite these weak associations, all indicators of physical activity assessed were associated with a decreased risk for colon cancer in men. Comparing those in the highest category of activity with those in the lowest, the OR for total self-reported activity was 0.7; for self-reported occupational activity, 0.7; and for coded occupational activity, 0.6. Whereas self-reported total activity was associated with colon cancer among women, estimates of activity based upon occupation (both self-reported and coded from job titles) were not.

Type III dyslipoproteinemia in patients heterozygous for familial hypercholesterolemia and apolipoprotein E2. Evidence for a gene-gene interaction.

In four large pedigrees with heterozygous familial hypercholesterolemia (FH) genetically linked to the low density lipoprotein receptor locus, we have observed a strong interaction between the presence of FH and a single apolipoprotein (apo) E2 allele, resulting in a markedly increased prevalence of type III dyslipoproteinemia (DLPIII). DLPIII was defined by chemical criteria. None of the patients with DLPIII had tuberous or palmar xanthomas characteristic of classically defined type III hyperlipoproteinemia. After exclusion of four persons with apo E 2-2 phenotype, there were 89 FH patients and 110 non-FH subjects. Definite DLPIII (defined as a very low density lipoprotein [VLDL] cholesterol to plasma triglyceride ratio greater than 0.30 with plasma triglycerides greater than or equal to 150 mg/dl) was present in 26% of 43 FH patients with a single E2 allele compared with only 3.4% of 29 non-FH subjects with an E2 allele (p = 0.003). To further characterize this interaction we performed a two-way analysis of covariance, after adjustment for age, sex, and body mass index, to test for any interaction between FH and the apo E loci. There was a statistically significant interaction between FH and the presence of a single E2 allele for the ratio of VLDL cholesterol to plasma triglycerides and for a newly derived estimate of beta-VLDL cholesterol concentration. Estimated beta-VLDL cholesterol level was strongly correlated with age in the subgroup with FH and an E2 allele but not in other subgroups. There was no difference in estimated beta-VLDL cholesterol between sexes. Correlation between estimated beta-VLDL cholesterol level and body mass index in persons older than 18 years was of only marginal significance and of similar magnitude in persons with or without an apo E2 allele. Present knowledge suggests that beta-VLDLs are highly atherogenic; if so, then a sizable subset of FH patients having at least one apo E2 allele and DLPIII may be at increased risk for premature coronary heart disease.

Treatment of the elderly hypertensive patient

It is generally accepted that increased blood pressure, especially high systolic blood pressure, is a major risk indicator in people over 60 years of age. Retrospective analyses of published trials show that when the elevation in arterial pressure has been firmly established by repeated blood pressure measurements, antihypertensive treatment should be considered for the following subgroups (1) All elderly hypertensive patients with grade III or IV retinopathy, congestive heart failure or cerebral infarction or hemorrhage should be treated regardless of age or degree of blood pressure elevation (2) In elderly patients with established mild hypertension and no symptoms or complications, non-pharmacological treatment should be started in patients less than 80 years of age, with antihypertensive drugs prescribed if diastolic pressure reaches lOOmmHg or more over 3 months or 95mmHg or more over 6 months of follow-up. The therapeutic benefit of pharmacologic antihypertensive treatment has not yet been established in hypertensive patients over 80 years of age or in those with isolated systolic hypertension All things considered, the indication to intervene pharmacologically should be viewed as becoming gradually more compelling as blood pressure rises. The more closely a patients characteristics match those of a subset of elderly hypertensive patients in whom therapeutic benefit has been proven, the greater the need for pharmacologic treatment

Smoking and bladder cancer. The modifying effect of cigarettes on other factors

A population‐based, incidence case‐control study was used to assess the effect of cigarette smoking on other risk factors for the development of bladder cancer. White men (n = 332) between the ages of 21 and 84 with bladder cancer were compared with 686 population‐based controls. Cigarette smokers were classified by current smoking status as well as by amount, duration, inhalation patterns, age at first having smoked, and years since having stopped smoking. These variables were associated with a change in the risk for bladder cancer. The population‐attributable risk associated with cigarette smoking was 48.5%. Risks from the use of other tobacco products such as cigars, pipes, snuff, and chewing tobacco, and from caffeinated coffee, tea, and alcoholic beverages were evaluated in light of cigarette smoking status. Cigarette smoking was shown to be both a confounder and an effect modifier. Risk estimates for bladder cancer associated with caffeinated coffee and alcoholic beverages were decreased after controlling for the effects of cigarette smoking. However, an increased risk of developing bladder cancer from cigar smoking (Odds ratio [OR] = 2.46) and tea drinking (OR = 3.14) was only seen in men who never smoked cigarettes. An increased but not significant risk was also seen for pipe, snuff, and chewing tobacco use in noncigarette smokers. The population‐attributable risk from cigars and tea in the population of white men who had never smoked was 6.3% and 18.9%, respectively. Our results suggest that cigarette smoking may obscure other risk factors unless those who never smoked are separately studied.

Dyslipidemias Among Normoglycemic Members of Familial NIDDM Pedigrees

OBJECTIVE To examine the hypothesis that hyperinsulinemia among relatives of NIDDM probands will increase the prevalence of DLPs, we measured insulin levels and examined the frequency of DLPs among NIDDM pedigree members. RESEARCH DESIGN AND METHODS We performed 2-h 75-g OGTTs and measured lipid and insulin levels of 287 family members and 86 spouses from 16 large Utah pedigrees ascertained for ≥ 2 siblings with NIDDM. RESULTS One-hour insulin levels were higher among 206 family members with NGT than among 65 NGT spouses (483.3 vs. 361.7 pM, P = 0.05). Among the NGT family members, 32% had cholesterol levels at or above the age- and sex-specific 90th percentile level defined by the LRC studies, 33% had HDL levels ≤ 10th percentile, and 20% had triglyceride levels ≥ 90th percentile. DLP (any of the three abnormalities) was found among 58% of NGT family members, which was significantly higher than the expected 27% (P < 0.00001) and the prevalence among spouses of 45% (P < 0.05). By NCEP criteria for hyperlipidemia, 40% of family members met criteria for diet and/or pharmacological therapy. CONCLUSIONS Normoglycemic members of NIDDM pedigrees have a high prevalence of DLPs, which approaches the prevalence in patients with NIDDM. Our data suggest that members of NIDDM pedigrees should be screened carefully for lipid abnormalities.

Platelet-derived growth factor — A growth factor with an expanding role in health and disease

Platelet-derived growth factor (PDGF) is the principal mitogen for connective tissue-derived cells such as fibroblasts, smooth muscle cells, and glial cells. It is synthesized by a variety of cell types and the synthesis of PDGF and its receptors is tightly controlled. Accumulating evidence obtained in vitro and in vivo suggests that PDGF plays important roles in the pathogenesis of clinically important diseases such as atherogenesis and cancer. Moreover, PDGF is an important research tool to study the signal transmission pathway of growth factors and other hormones.SummaryPlatelet-derived growth factor (PDGF) is the principal mitogen for connective tissue-derived cells such as fibroblasts, smooth muscle cells, and glial cells. It is synthesized by a variety of cell types and the synthesis of PDGF and its receptors is tightly controlled. Accumulating evidence obtained in vitro and in vivo suggests that PDGF plays important roles in the pathogenesis of clinically important diseases such as atherogenesis and cancer. Moreover, PDGF is an important research tool to study the signal transmission pathway of growth factors and other hormones.

Current knowledge regarding the genetics of human hypertension

Observations over 11 years from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are reviewed to illustrate research approaches, developing results and prospects for future studies. Strong associations with hypertension have been found for several biochemical tests that show substantial genetic determination. Suggestions of recessive major gene effects and significant polygenic background determinations have been found for several variables, including urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport and sodium-potassium cotransport. Each of these variables is related in some way to sodium or potassium metabolism, or both, and may help to improve the understanding of a possibly inherited susceptibility to hypertension that is related to dietary electrolyte intake. A second major group of factors involving familial predisposition to hypertension include lipid abnormalities (increased very-low- and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol); increased fasting insulin levels or insulin resistance, or both; obesity (especially central or upper body obesity); and multiple environmental factors influencing these metabolic systems, including dietary fat, carbohydrate and calorie intake; physical exercise; and certain antihypertensive medications that adversely affect lipid metabolism and glucose tolerance. Some studies even suggest a possible link between these two large groups of factors (electrolyte metabolism and lipid-insulin metabolism). Hypertriglyceridaemia and hyperinsulinaemia are both significantly correlated with increased levels of several cation-flux tests. It is recommended that studies of human hypertension apply these biochemical profiles to study sibships with two or more hypertensive siblings as a cost-effective initial approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Interpretation and uses of data collected in poison control centres in the United States.

SummaryClinical toxicology and poison control have not benefited from the same epidemiological and demographical scrutiny that other health care disciplines have, because of the lack of a meaningful, appropriate database from which to undertake those analyses. Since the creation of the American Association of Poison Control Centers National Data Collection System in 1982 many of the former obstacles of data collection have been overcome. A system has been devised which apparently meets the needs of busy regional poison control centres willing to participate in data collection, and thus provide a large database of human poisoning experience. The data collected by poison control centres and maintained in the National Data Collection System afford a new, powerful tool with which to address issues of demography, epidemiology, risk assessment, product surveillance and regulatory affairs. While the system affords these potentials, certain limitations of the data must be understood so that the data are not misinterpreted. Additionally, we have attempted to identify strengths of the system as well as areas in need of improvement and refinement.