Friedreich's ataxia cardiomyopathy: case based discussion and management issues.

Cardiac involvement is common in Friedreich's Ataxia and is a common cause of premature death. Evidence regarding treatment of congestive heart failure in patients with Friedreich's Ataxia is lacking. The case of a 31-year-old male with advanced Friedreich's Ataxia who presented with an acute diarrhoeal illness and features of acute heart failure is discussed. We then review the reported cardiac manifestations of Friedreich's Ataxia and discuss management options.

Age at any full-term pregnancy and breast cancer risk.

The authors analyzed data from two multistate, population-based case-control studies to investigate the association between age at any full-term pregnancy (FP) and breast cancer risk. Study subjects included breast cancer cases aged 20-79 years identified from four statewide cancer registries and randomly selected controls interviewed from 1988 to 1996. Complete information on a comprehensive set of risk factors for breast cancer was available for 9,891 cases and 12,271 controls. The large number of subjects enabled simultaneous adjustment of the covariates and efficient application of various modeling approaches. Overall, each 5-year increase in age at first FP was associated with an odds ratio of 1.07 (95% confidence interval (CI): 1.01, 1.13) for breast cancer. The corresponding estimates were odds ratio = 1.02 (95% CI: 1.00, 1.05) for age at second through ninth FPs. For age at last FP, the effect estimate (odds ratio = 1.01, 95% CI: 0.97, 1.06) was indistinguishable from that for other FPs after the first. In this analysis, a modest and transient increase in breast cancer risk after childbirth was also observed. The relatively greater effect of age at first FP is consistent with the existence of a long-term effect of early first FP on the differentiation of mammary cells, causing them to become less susceptible to carcinogenesis.

Overview of studies on endometrial cancer and other types of cancer in humans: perspectives of an epidemiologist.

The epidemiologic studies relevant to the hypothesis that exposure to tamoxifen is associated with risk of cancer of the endometrium and perhaps other organs are described, summarized, and evaluated. One large body of data comes from the randomized trials of tamoxifen as a therapeutic agent against established breast cancer. With respect to endometrial cancer, these studies suggest that an association with tamoxifen use exists. However, the evidence is far from conclusive: the association is not seen in all the reported randomized trials, there appears to be a deficit of endometrial cancer in the comparison groups in two of the most important studies, none of the studies has adequately addressed the problems of confounding by prior hysterectomy and/or hormone replacement therapy, and none addresses the issue of detection bias. One nonrandomized cohort study shows findings similar to those from the randomized studies but also has similar problems, in addition to the problems associated with the lack of randomization of exposure. Case control studies were also considered, with the conclusion that they show results similar to those from the cohort studies (randomized and nonrandomized); that is, that the evidence leans toward the view that there is an association between tamoxifen use and endometrial cancer risk, but that it is incomplete and inconclusive. The issues of detection bias and potential confounding variables are better dealt with in the case control studies than in the cohort studies. One important question raised in one of the major case control studies is whether the apparent association is stronger with total dose of tamoxifen or with duration of use. Some investigators have reported an association between tamoxifen use and cancers other than those of the endometrium, but for none of these cancers is the evidence consistent between studies and the associations lack the theoretical underpinning that might be invoked for endometrial cancer, if in fact the existence of an association were established empirically for the latter site.

Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion.

The authors assess the randomization strategy that had been used in the Canadian National Breast Screening Study (NBSS). Document experts at a private investigation and security company were hired to assist in reviewing instances in which names of subjects were altered in the "allocation books" (the basic instrument used to assign, at random, participants to either the mammography or the usual-care arm). The review was restricted to records from 3 NBSS centres where women assigned to the mammography arm had a distinctly higher (not necessarily significant) number of deaths from breast cancer than those assigned to the usual-care arm, and to records from 2 centres where, for limited periods, administrative problems were reported. In most cases the underlying, original name could be identified. The document experts found no evidence of a deliberate attempt to conceal the alterations. A search of the NBSS database for the underlying and superimposed names revealed that only 1 of the women whose name had been deleted or superimpsed died of breast cancer. She was in the mammography arm. The authors' thorough review of ways in which the randomization could have been subverted failed to uncover credible evidence of it. They conclude that even if there had been acts of subversion, they could only have been few in number and, given that there was only 1 death from breast cancer in the group reviewed, the alterations could have had only a trivial effect on the study findings as reported in 1992.

Risk of breast cancer in relation to lifetime alcohol consumption.

BACKGROUND: Although an association between alcohol consumption and risk of breast cancer has been observed in many studies, questions of major importance remain, including the nature of the dose-response relationship and the effects of drinking at various periods in life. PURPOSE: Our goal was to address the issues listed above with a large case-control study. METHODS: We conducted a population-based case-control study in Maine, Massachusetts (excluding the four counties that include metropolitan Boston), New Hampshire, and Wisconsin. Case patients were eligible if their diagnosis of invasive breast cancer was first reported to one of the four statewide cancer registries during the period of 1988 through 1991. During the accrual period, 11,879 potentially eligible case patients and 16,217 control subjects were identified. After excluding ineligible women from the study, telephone interviews were obtained from 6888 case patients and 9424 control subjects. Complete data for recent alcohol consumption, and thus final eligibility for study participation, were determined for 6662 case patients and 9163 control subjects. The average age at time of interview was 58.7 years. The questions on alcohol use addressed average consumption during five periods of the subjects' lives: ages 16-19, 20-29, 30-39, 40-59, and 60-74 years. Similar responses from 211 control subjects upon reinterview 6-12 months later were taken to be indicative of the reliability of the questionnaire used in this study. RESULTS: Lifetime average alcohol consumption (measured as the average grams per day consumed from age 16 to the recent past) and recent alcohol consumption (average grams per day consumed in the previous age interval) were associated with risk of developing breast cancer. The multivariate relative risk of breast cancer, in those who drink compared with abstainers, associated with average lifetime consumption of 12-18 g/day of alcohol (about one drink) was 1.39 (95% confidence interval [CI] = 1.16-1.67), of 19-32 g/day (about two drinks) was 1.69 (95% CI = 1.36-2.10), of 33-45 g/day (about three drinks) was 2.30 (95% CI = 1.51-3.51), and of greater than or equal to 46 g/day (four or more drinks) was 1.75 (95% CI = 1.16-2.64) (P for trend < .0001). The multivariate relative risk per 13 g/day (about one drink) of alcohol consumed before 30 years of age was 1.09 (95% CI = 0.95-1.24), whereas the relative risk associated with recent consumption of 13 g/day was 1.21 (95% CI = 1.09-1.34). CONCLUSIONS: In these data, alcohol consumption was clearly related to breast cancer risk. Risk appeared to increase even at moderate levels of consumption. For women of all ages combined, consumption before 30 years of age was not an important determinant of risk.

The epidemiological evidence on the carcinogenicity of beryllium in humans.

Authoritative reviews of the question of whether occupational exposure to beryllium compounds is associated with increased risk of respiratory cancer were published in 1987 and were critical of the quality of the evidence available up to that time. No clear conclusion could be drawn from it as to the carcinogenicity of beryllium to humans. If studies published since 1987 are to lead to a revision of the regulatory status of beryllium compounds they must clearly be of high quality and scientific validity. These studies, as well as the earlier reports, are reviewed here. I argue that the small and inconsistent excess of lung cancer deaths in employees of one or two plants seen in two post-1987 studies is compatible with a number of explanations other than that they are attributable to occupational exposure to beryllium. Specifically, information on cigarette smoking is poor, and the data do not exist to rule out the possibility that the small number of excess deaths results from residual confounding by cigarette smoking patterns in the populations studied. Indeed, excess deaths from emphysema and ischemia heart disease in the same cohort suggest that confounding by cigarette smoking is a more likely explanation of the lung cancer excess than is occupational exposure to beryllium compounds.

Lactation and a reduced risk of premenopausal breast cancer.

BACKGROUND: The evidence of an association of lactation with a reduction in the risk of breast cancer among women has been limited and inconsistent. The effect of lactation appears to be confined to premenopausal women with a history of long lactation, but most studies of this relation have been limited in statistical power. We conducted a multicenter, population-based, case-control study with a sample large enough for us to describe more precisely the association between lactation and the risk of breast cancer. METHODS: Patients less than 75 years old who had breast cancer were identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly selected from lists of licensed drivers if the case subjects were less than 65 years old, and from lists of Medicare beneficiaries if they were 65 through 74 years old. Information on lactation, reproductive history, and family and medical history was obtained by means of telephone interviews. After the exclusion of nulliparous women, 5878 case subjects and 8216 controls remained for analysis. RESULTS: After adjustment for parity, age at first delivery, and other risk factors for breast cancer, lactation was associated with a slight reduction in the risk of breast cancer among premenopausal women, as compared with the risk among women who were parous but had never lactated (relative risk, 0.78; 95 percent confidence interval, 0.66 to 0.91); the relative risk of breast cancer among postmenopausal women who had lactated, as compared with those who had not, was 1.04 (95 percent confidence interval, 0.95 to 1.14). With an increasing cumulative duration of lactation, there was a decreasing risk of breast cancer among premenopausal women (P for trend < 0.001) but not among postmenopausal, parous women (P for trend = 0.51). A younger age at first lactation was significantly associated with a reduction in the risk of premenopausal breast cancer (P for trend = 0.003). As compared with parous women who did not lactate, the relative risk of breast cancer among women who first lactated at less than 20 years of age and breast-fed their infants for a total of six months was 0.54 (95 percent confidence interval, 0.36 to 0.82). CONCLUSIONS: There is a reduction in the risk of breast cancer among premenopausal women who have lactated. No reduction in the risk of breast cancer occurred among postmenopausal women with a history of lactation.

A case-control study of oral cancer in Beijing, People's Republic of China. Associations with nutrient intakes, foods and food groups.

A case-control study of oral cancer was conducted in Beijing, People's Republic of China to examine the association between dietary nutrient intake and risk of oral cancer, both in terms of estimated intake of nutrients and micro-nutrients, and in terms of specific foods and food groups. The study was hospital-based and controls were hospital in-patients matched for age and sex with the cases. The response rate for cases and controls was 100% and 404 case/control pairs were interviewed. The results suggest that increased protein and fat intake are related to a decreased risk of oral cancer. Carbohydrate intake, however, showed a moderate increased risk for oral cancer. Total carotene intake and carotene intake from fruits and vegetables are inversely associated with risk of oral cancer. A similar pattern was observed for dietary vitamin C intake. Dietary fibre derived from fruits and vegetables showed a strong negative association with oral cancer risk, but fibre derived from other sources did not exhibit any protective effect. At the level of foods and food groups, increased consumption of fresh meat, chicken and liver was significantly associated with a reduction in oral cancer risk: the tests for trend were all statistically significant at the P < 0.01 level. Consumption of common carp, hairtail, shrimp and lobster were also associated with decreased risk. Risk was found to increase with increasing consumption of millet and corn bread (P < 0.01) but to decrease with increasing consumption of rice (P < 0.01). Increased consumption of grapes, bananas, oranges, tangerines, peaches and pears were associated with reduced risk.(ABSTRACT TRUNCATED AT 250 WORDS)

The reliability of self-reported alcohol consumption in the remote past.

We examined the reliability of self-reported alcohol consumption in past age periods of women's lives. As part of a case-control study of breast cancer conducted in Massachusetts and Wisconsin in 1988-1991, the same questionnaire was administered for a second time to 211 controls (mean age = 54 years) after an interval of 6-12 months. The Spearman correlation coefficients between the average number of grams of alcohol consumed daily reported in the two interviews, by age period of consumption, were: 16-19 years, r = 0.81; 20-29 years, r = 0.84; 30-39 years, r = 0.75; and for recent consumption, r = 0.77. Self-reported alcohol consumption throughout adult life was reported with precision sufficient to make the ranking of subjects' intake consistent between interviews.

The quantification of alcohol-caused morbidity and mortality in Australia: a critique.

One of the more controversial conclusions of the Commonwealth Department of Community Services and Health's report on The quantification of drug caused morbidity and mortality in Australia 1988 is that alcohol "causes" about 5% of all deaths in Australia. Against the background of this conclusion, this paper reviews current concepts of what constitutes a causal relationship and how the existence of causation is diagnosed in a nonexperimental setting. The conclusion of the report appears to rest on the assumption that all differences in disease rates between users and non-users of alcohol (or other drugs) are causal in nature--an assumption which is tantamount to equating statistical association with causation. Moreover, the estimate of alcohol-caused deaths, derived from the summation of alcohol-caused deaths from a large number of medical conditions, is at considerable variance with an estimate of total alcohol-caused deaths computed directly from total death rates. The latter estimate actually indicates that alcohol prevents more deaths than it causes in the population as a whole, a conclusion that is compatible with the findings of several recent large cohort studies, from which it is in fact derived. The discrepancy between the two estimates casts doubt on the validity of the assumptions underlying the methodology that has been applied.

Is acute lymphoblastic leukemia in children virus-related?

The sharp peak in incidence of acute lymphoblastic leukemia at ages 2 and 3 years strongly suggests the effect of an agent, whether viral or not, to which either exposure occurs only in the earliest months of life or to which immunity develops very rapidly. Suspected clusters of childhood leukemia in the neighborhoods of two British nuclear reprocessing facilities led Leo Kinlen to postulate that large-scale immigration into areas that had previously been remote and isolated offers opportunities for spread of viral infections to which most urban populations become immune at a very early age: leukemia may be a rare manifestation of infection by one or more of such viruses. He and his group have presented evidence in support of this hypothesis. Lack of increase in childhood leukemia in the contexts of the massive evacuation of mothers and children from British cities during the Second World War, and of the considerable immigration into previously isolated islands of Greece during the last several decades, indicates that some large movements of children have occurred without providing the circumstances postulated by Kinlen. The marked inverse association of leukemia risk with birth order, noted almost 30 years ago, remains unexplained and deserves to be recalled when considering the possibility of viral involvement in the etiology of acute lymphoblastic leukemia of children.

A prospective cohort study of nutrient intake and age at menarche.

A cohort of 213 girls (aged 10 y, range +/- 9 mo) whose parents reported their dietary intakes (including nutritional supplements) using a semiquantitative food frequency questionnaire, was followed for 4 y until 82% of the 194 parents who responded to follow-up letters had reported that their daughters had had their first menstrual periods. The relative risk (RR) of menarche before age 12.5 y was 2.0 [95% confidence interval (CI) = 1.1-3.8] for the tallest girls (greater than 150 cm) compared with the shortest girls (less than 130 cm). The RR was 2.1 (95% CI = 1.1-3.8) for the fattest girls [Quetelet's index of relative weight (in kg/m2) greater than 19] vs the leanest girls (less than 15). After adjusting for height and Quetelet's index, menarcheal age was not associated with intake of energy nor energy-adjusted intake of protein, fat, or carbohydrate. The overall results are consistent with the hypothesis that nutritional factors influence age at menarche mainly through their effects on accumulation of adipose tissue.

A code of ethical conduct for epidemiologists?

The absence of a written code of ethics in epidemiology does not imply that epidemiologists have been behaving unethically. Rather, there are unwritten standards taught by precept and enforced at the level of science (e.g. through funding, publication, etc.) and the courts. The question is whether it would be desirable to have a set of guidelines in written form. Those epidemiologists pressing for a written code perceive the theoretical advantage of one. Those opposed are concerned with the feasibility of developing an effective, enforceable code. Although I do not underestimate the difficulty of the task, the benefit of having written guidelines seems to me comparable to that of having written laws, albeit incomplete and imperfect--i.e. to inform the individual how his or her actions would be viewed in terms of professional norms. Steps have already been taken by the Society for Epidemiologic Research in cooperation with the American College of Epidemiology to draft a code of ethics for epidemiologists. Broad participation in this endeavor will be required if it is to succeed.