Implications of birth cohort patterns in interpreting trends in breast cancer rates.

BACKGROUND: Most investigations of trends in cancer rates are based on a cross-sectional approach, i.e., an examination of trends in rates by year of diagnosis or death. When there are longitudinal effects (i.e., trends in rates with successive birth cohorts), interpretation of cross-sectional trends can be misleading. Based on cross-sectional comparisons, U.S. breast cancer mortality rates have been reported to be decreasing over the last 20 years in younger women but to be increasing during the same period in older women. PURPOSE: To examine the impact of longitudinal effects on the divergence of cross-sectional trends in breast cancer mortality with age, we examined breast cancer mortality rates from 1969 to 1988 by birth cohort for White women in the United States. METHODS: By using a novel, nonparametric, permutational method to analyze 2-year, age-specific mortality rates for women aged 30-89 years, we identified trends in rates with successive birth cohorts. RESULTS: The divergence in trends with age is shown to be consistent with an increase in breast cancer risk with successive birth cohorts from 1900 to 1916 and with a decrease in breast cancer risk with successive birth cohorts beginning around 1926. CONCLUSION: Longitudinal effects have a significant impact on cross-sectional trends in breast cancer mortality. IMPLICATIONS: Continuation of the birth cohort trend in younger women, which could correspond to changes in reproductive patterns accompanying the "baby boom," would result in decreasing cross-sectional trends in women 60-69 years of age over the next decade and in women 70-79 years of age in the subsequent decade. Longitudinal effects must be taken into consideration when monitoring and evaluating the effects of early detection, treatment, and intervention programs using national rates.     

Side effects during continuous epidural infusion of morphine and fentanyl

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Statistical issues in interpretation of chronic bioassay tests for carcinogenicity.

The interpretation of chronic bioassay tests for carcinogenicity requires that the data be appropriately recorded. A "case history" for each animal links the pathology data for each organ of each animal to the length of its life. This information can be used in interpretation of the tumor incidences in light of the survival information. The role of historical controls was discussed, and the use of significance tests in a multidisciplinary approach to the assessment of the pattern of tumor response was suggested. Multiple comparison methods valid for the interpretation of continuous (or measurement) data do not apply to the discrete data analyses used in these studies. The ideas and methods of these studies were applied to an animal study of chloroform.     

Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial.

To examine whether endogenous androgens influence the occurrence of prostate cancer, we conducted a nested case-control study among participants enrolled in the Carotene and Retinol Efficacy Trial. We analyzed serum samples of 300 cases diagnosed between 1987 and 1998, and 300 matched controls. Higher concentrations of testosterone (T) were not associated with increased prostate cancer risk. Relative to men with levels in the lowest fourth of the distribution, men in the upper fourth of total T had a risk of 0.82 [95% confidence interval (CI), 0.52-1.29]. The corresponding relative risks for free T (0.72; 95% CI, 0.45-1.14), percentage of free T (0.74; 95% CI, 0.46-1.19), and total T:sex hormone binding globulin ratio (0.52; 95% CI, 0.32-0.83) similarly were not elevated. Higher concentrations of androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were weakly associated with risk. Relative risks associated with being in the highest fourth for androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were 1.20 (95% CI, 0.76-1.89), 1.38 (95% CI, 0.86-2.21), and 1.27 (95% CI, 0.80-2.00), respectively. Men in the upper fourth of total estradiol (E2), free E2 and percentage of free E2 had relative risks of 0.71 (95% CI, 0.42-1.13), 0.52 (95% CI, 0.33-0.82), and 0.65 (95% CI, 0.40-1.05), respectively. The inverse association between E2 and prostate cancer risk was largely restricted to men with blood collection within 3 years of diagnosis. Our results add to the evidence that serum testosterone is unrelated to prostate cancer incidence. The suggestions that intraprostatic androgen activity may increase risk and that serum estrogens may decrease risk, warrant additional study.     

The effect of Rhodiola capsules on oxygen consumption of myocardium and coronary artery blood flow in dogs]

It has been proved that Rhodiola Capsules can obviously decrease the oxygen consumption of myocardium and oxygen consumption index in anesthetic dogs, decrease the coronary artery resistance, but have no marked effect on the coronary artery blood flow. The Capsules also have the function of decreasing blood presure and slowing heart rate.     

Three clusters of ciguatera poisoning: clinical manifestations and public health implications

Between July 1997 and August 1998 we investigated three clusters (26 cases) of ciguatera poisoning in the inner Sydney area. Tropical reef fish were implicated in each cluster. Most of those affected had musculoskeletal, neurological and gastrointestinal symptoms. The clusters raise questions about the need for rapid diagnosis and enhanced surveillance mechanisms, the regulation of fish supply, and the lack of testing facilities for ciguatera toxin.     

Incidence of adverse events after I.V injection of MR contrast agents in a Chinese population. A comparison between gadopentetate and gadodiamide

PURPOSE: To study the incidence of adverse events after i.v. injection of MR contrast agents in a Chinese population. A comparison was made between an ionic contrast agent (dimeglumine gadopentetate, Magnevist) and a non-ionic contrast agent (gadodiamide, Omniscan). MATERIAL AND METHODS: During a 24-month period, 2,049 Chinese patients who randomly received an i.v. bolus injection of either Magnevist or Omniscan were investigated. All patients were questioned for the presence of any generalized or localized adverse reaction on the following day after the MR examination according to a standardized questionnaire. RESULTS: Three hundred and nine out of 2,049 patients (15%) reported an adverse event. There was a higher incidence of adverse events in patients receiving Magnevist as compared to those receiving Omniscan injection. All reported adverse events were clinically mild and required neither treatment nor hospitalization. CONCLUSION: There was a higher incidence of adverse reaction in patients receiving Magnevist than in those receiving Omniscan.     

Immunohistochemical analysis of survivin expression in primary breast cancers.

BACKGROUND AND PURPOSE: Survivin, an inhibitor of apoptosis, is expressed in fetal tissues but undetectable in normal adult tissues. It is also expressed in most common human cancers. This study evaluated the expression of survivin in breast cancers. METHODS: A monoclonal anti-survivin antibody B1 was generated. Immunohistochemical staining was performed in 226 paraffin sections of primary breast cancers and correlated with the patients' clinicopathological characteristics. RESULTS: Survivin was expressed in the cytoplasm of tumor cells in 59.3% of breast cancers. Expression of survivin was associated with high histologic grade (p = 0.027), high mitotic count (p = 0.014), positive p53 immunostaining (p = 0.012), neu overexpression (p = 0.018), and with bcl-2 (p = 0.001) and bak (p < 0.001) expression. No correlation was found between survivin expression and age, tumor size, estrogen receptor, progesterone receptor or Bax expression. Survivin expression was not significantly associated with overall or disease-free survival. CONCLUSIONS: Survivin expression is correlated with high histologic grade, high mitotic count, p53 overexpression, and bcl-2 expression in breast cancer. It does not have significance as a marker in predicting overall or disease-free survival.     

Neuroleptic malignant syndrome after the use of venlafaxine in a patient with generalized anxiety disorder.

Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse reaction to neuroleptics, which is characterized by hyperthermia, extrapyramidal symptoms, altered consciousness and autonomic dysfunction. Although NMS is most commonly induced by the high-potency neuroleptics, its development has also been associated with the use of non-neuroleptic agents that block central dopamine pathways. A 68-year-old man with generalized anxiety disorder and depressive symptoms presented at the emergency department (ED) with high fever, tremor, muscle rigidity, rhabdomyolysis and altered mental status. NMS was considered to have been caused by the recent addition and subsequent dose increase in his treatment regimen of venlafaxine, a serotonin norepinephrine reuptake inhibitor. He was successfully treated with bromocriptine, lorazepam, and fluid hydration in the ED and intensive care unit.