Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post-discharge death in an independent data set.

OBJECTIVE: To determine the validity of the GRACE (Global Registry of Acute Coronary Events) prediction model for death six months after discharge in all forms of acute coronary syndrome in an independent dataset of a community based cohort of patients with acute myocardial infarction (AMI). DESIGN: Independent validation study based on clinical data collected retrospectively for a clinical trial in a community based population and record linkage to administrative databases. SETTING: Study conducted among patients from the EFFECT (enhanced feedback for effective cardiac treatment) study from Ontario, Canada. PATIENTS: Randomly selected men and women hospitalised for AMI between 1999 and 2001. MAIN OUTCOME MEASURE: Discriminatory capacity and calibration of the GRACE prediction model for death within six months of hospital discharge in the contemporaneous EFFECT AMI study population. RESULTS: Post-discharge crude mortality at six months for the EFFECT study patients with AMI was 7.0%. The discriminatory capacity of the GRACE model was good overall (C statistic 0.80) and for patients with ST segment elevation AMI (STEMI) (0.81) and non-STEMI (0.78). Observed and predicted deaths corresponded well in each stratum of risk at six months, although the risk was underestimated by up to 30% in the higher range of scores among patients with non-STEMI. CONCLUSIONS: In an independent validation the GRACE risk model had good discriminatory capacity for predicting post-discharge death at six months and was generally well calibrated, suggesting that it is suitable for clinical use in general populations.

Self-help care in older African Americans with arthritis.

Arthritis is the third most common health problem among African Americans and the leading cause of activity limitations. Some of the obstacles facing people who are experiencing health care problems fall disproportionately on older racial and ethnic minority populations. Receiving care, which is perceived as racially and ethnically relevant, is an important factor in overcoming these obstacles. The Arthritis Self-Help Course (ASHC) was successfully used with 150 impoverished African-American elders living in public housing to bolster their confidence in managing their arthritis symptoms.

Obesity and hyperleptinemia in metallothionein (-I and -II) null mice.

Metallothionein (MT) has several putative roles in metal detoxification, in Zn and Cu homeostasis, in scavenging free radicals, and in the acute phase response. Mice of mixed 129/Ola and C57BL/6J background with targeted disruption of MT-I and MT-II genes are more sensitive to toxic metals and oxidative stress. We noted that these animals were larger than most strains of mice, and we systematically studied aspects of their physiology and biochemistry relating to energy metabolism. During the first 2 weeks after weaning, the growth rates of MT-null and C57BL/6J mice were similar, but the transgenic mice became significantly heavier at age 5-6 weeks. At age 14 weeks, the body weight and food intake of MT-null mice was 16 and 30% higher, respectively, compared with C57BL/6J mice. Most 22- to 39-week-old male MT-null mice were obese, as shown by increased fat accretion, elevated obese (ob) gene expression, and high plasma leptin levels, similar to those recorded in Zucker fatty (fa/fa) rats. Seven-week-old MT-null mice also had significantly higher levels of plasma leptin and elevated expression of ob, lipoprotein lipase, and CCAAT enhancer binding protein alpha genes as compared with age-matched C57BL/6J mice. These observations indicate that abnormal accretion of body fat and adipocyte maturation is initiated at 5-7 weeks of age, possibly coincident with sexual maturation. Targeted disruption of MT-I and MT-II genes seems to induce moderate obesity, providing a new obese animal model. A link between MT and the regulation of energy balance is implied.

The HIV information project for transfusion recipients a decade after transfusion.

OBJECTIVE: To gather information on which to base decisions about a general notification program for pediatric patients a decade after their receiving transfusions. DESIGN: The physicians of a cohort of 1793 patients who underwent cardiac surgery were sent letters asking them to contact and counsel patients identified from cardiovascular surgery and blood bank databases about their risk for human immunodeficiency virus (HIV) infection. Questionnaires were used to collect data about physicians' HIV practices; telephone interviews were conducted to collect information about patients' and parents' knowledge and attitudes about HIV and transfusions. Because of unexpected media interest, questionnaires and interviews were modified to include questions about the source of information. The HIV-testing status of patients reported by physicians was anonymously cross-referenced with specimens received by the Laboratory Services Branch, Ontario Ministry of Health, Toronto. SETTING: A large Canadian pediatric tertiary care hospital in Toronto. PARTICIPANTS: Seven hundred ninety-three patients undergoing cardiopulmonary bypass between 1980 and 1985. RESULTS: The HIV Information Project successfully reached most (approximately 75%) of this cohort and, with the help of the media, many other at-risk transfusion recipients. The information was new for many; almost all informed wanted to undergo testing. The seroprevalence of this group that received multiple transfusions was, at minimum, 8.5 patients in 1000. Six previously unsuspected HIV-seropositive cases were diagnosed. CONCLUSIONS: Although we had assumed that most patients receiving transfusions would be aware of their risk for HIV infection, our results indicate that, even a decade after the transfusion, many recipients were not aware of the risk and wanted to undergo testing. Testing identified asymptomatic infected patients.

Protein synthesis in splanchnic tissues of sheep offered two levels of intake.

Protein synthesis rates were measured in liver and gastrointestinal tract (GIT) sections of fattening sheep offered lucerne (Medicago sativa) pellets at either 1.25 or 2 times energy maintenance. The measurement technique involved a large dose of [1-13C]valine over 60 min. Animals on the higher intake had a larger mass of liver protein (143 v. 100 g, P = 0.02), similar fractional synthesis rates (ks; 22.5 v. 22.1%/d, not significant) and greater absolute amounts of protein synthesis (32 v. 23 g/d; P = 0.016) compared with those on the smaller amount of ration. The ks values and RNA: protein in the GIT sections also tended to increase with food intake. Estimated total GIT protein synthesis was approximately three-fold that in liver and probably constituted 25-35% of whole body synthesis. All splanchnic tissues measured had lower translational efficiencies (g protein synthesized/d per g total RNA) than reported for milk-fed and newly-weaned lambs and this may relate to the decline in the rate of protein deposition as lambs progress to the fattening condition.

After menopause.

Women of 50 today have roughly the same number of years to look forward to as they have already lived as reproductive women. Many women will live 30,40 or even 50 years post menopause. This very important period in women's lives has been studied little and viewed negatively by the medical profession and society at large. The purpose of this paper is to examine the psychological and physiological concerns of women at menopause. Self-help measures that are effective in managing the physical and psychological aspects of menopause are discussed. Hormone replacement therapy as a method of managing menopause is examined. Women are challenged to sort out the myths surrounding menopause, to take charge of their health and to move into this second season of their lives filled with vitality and joy.

Cancer mortality among immigrant populations in Ontario, 1969 through 1973.

Ontario is home to a sizeable, recently established immigrant population whose cancer mortality has until now remained unexamined. The province's six largest immigrant groups (British, Italian, German, Dutch, Polish and Soviet) were investigated to compare their cancer mortality experience with that prevailing in Ontario and in their countries of birth for the period 1969 through 1973. Standardized mortality ratios (SMRs) were computed from data from Statistics Canada and the World Health Organization (for 1971) for five sites of cancer. The rates of death from stomach cancer were significantly higher for the immigrant groups (except the Germans) than for the Canadian-born (SMRs 158.6 to 256.1) and were significantly lower for the immigrants (except the Dutch) than for the populations of their countries of birth (SMRs 26.5 to 72.9). The rates of death from colorectal cancer and cancer of the breast tended to be lower among the immigrants. Most male immigrants had high rates of death from lung cancer relative to the Canadian-born, whereas their female counterparts had relatively low rates. For most of the immigrant groups the rates of death from prostate cancer closely resembled those prevailing in the country of birth. Displacement of cancer mortality experience towards that in Ontario was most evident for Polish immigrants. It may have been too soon to see trends among the more recent immigrants (Italian, German and Dutch), who, for the most part, had not yet reached the age of highest cancer risk. Ontario should provide a valuable resource for further studies of lifestyle and environmental determinants of cancer.

PIP: Cancer mortality among the six largest immigrant groups in Ontario, Canada (British, Italian, German, Dutch, Polish, and Soviet), is investigated and compared with cancer mortality for the population of Ontario as a whole and with cancer mortality in the immigrants' countries of birth. Standardized mortality ratios for five major cancer sites are calculated for 1971 using official Canadian data and data from the World Health Organization. (summary in FRE)

Cancer mortality following cardiac catheterization: a preliminary follow-up study on 4,891 irradiated children.

A retrospective cohort study was conducted on the risk of radiation-induced cancer mortality following cardiac catheterization. The study included 4,891 children with congenital heart disease who were assessed by cardiac catheterization during 1946 to 1968 at The Hospital for Sick Children, Toronto. The cohort was matched against the Ontario cancer death file from 1950 to 1975. The average period of follow-up was 13 years and more than 66,000 person-years have been accrued from the cohort. No deaths from breast cancer or thyroid cancer were identified. Five cancer deaths were observed and compared with 4.8 expected deaths based on Ontario cancer death rates. The five cancer deaths resulted from three leukemias, one Wilms' tumor, and one unspecified nervous system tumor. The preliminary findings did not demonstrate a significant leukemia risk arising from diagnostic cardiac catheterizations. Continued follow-up of this cohort is required to evaluate the risk of breast and thyroid cancers which can occur more than 20 years following radiation exposure.

Smoking as a risk factor in cancer of the cervix: additional evidence from a case-control study.

The results of a case-control study in Toronto, Canada, demonstrated a two-fold risk of invasive squamous cell carcinoma of the cervix among current smokers relative to women who had never smoked. This significant effect of smoking was not diminished by simultaneously adjusting for age, education, and indices of sexual behavior. This association was further supported by the observations that ex-smokers were at a lower risk than current smokers (1.7 versus 2.3), and that the risk increased with the amount of cigarettes smoked (2.2 for less than half a pack per day to 2.9 for more than one pack per day).

Exogenous estrogens and endometrial cancer: a case-control study and assessment of potential biases.

Eighty-eight cases with newly diagnosed carcinoma of the endometrium and 177 age-matched neighborhood controls were interviewed to test the hypothesis that exogenous estrogens lead to an increased risk of endometrial cancer. Forth-five per cent of the cases and 22% of the controls reported a history of estrogen use which yielded an odds ratio of 2.9 (confidence interval (Cl) 1.7-5.1). Women with five or more years of estrogen use had an odds ratio of 8.6 (Cl 3.2-23.0). Approximately 80% of the estrogen users had used conjugated equine estrogens. For these women the odds ratio was 4.0 (Cl 1.9-8.4) for daily dosages of more than 1 mg of estrogen. Several sources of bias which might affect the estrogen association were investigated. These included comparability of cases and controls, selection procedures, difference between estrogen users and nonusers, exclusion of controls who had hysterectomy, source of estrogen information, and differential recall. The concept or medical surveillance was evaluated by access to medical care and prior history of dilatation and curettage. The strong association between exogenous estrogen use and endometrial cancer remained after consideration for the effects of these biases.

Replication of double-stranded RNA of the virus-like particles in Saccharomyces cerevisiae.

The mode of replication of the L double-stranded RNA (dsRNA) present in virus-like particles in Saccharomyces cerevisiae was examined by density transfer experiments. After transfer to light medium, significant amounts of fully heavy dsRNA persisted over a number of cell doublings. In addition, very little material of hybrid density was ever formed, and the accumulation of fully light material began as early as 0.5 doubling after transfer to light medium. Our results are compatible with a conservative mode of replication or with a semiconservative mode of replication carried out by a small portion of the total dsRNA population. In additional experiments the synthesis of dsRNA relative to the cell cycle was studied. This was done by determining the ratio of short-term to long-term radioactive label in size-separated cell fractions of a prelabeled exponential culture. The ratio of short-term to long-term label remained constant for all fractions, implying that dsRNA is synthesized throughout the cell cycle, increasing through the cell cycle at an exponential rate.