Breast cancer among women exposed to polybrominated biphenyls

We conducted a nested case-control study with 1,925 women enrolled in a polybrominated biphenyl (PBB) registry to examine the association between breast cancer and serum PBBs. Twenty women who developed breast cancer were matched to 290 control subjects on sex, race, and age. Women with serum PBB levels of 2.0-3.0 parts per billion (ppb) [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 0.9-13] or 4.0 ppb or greater (OR = 3.1; 95% CI = 0.8-12) had a higher estimated risk for breast cancer than women with less than 2.0 ppb. The odds ratios were unchanged when available breast cancer risk factors were included in the analysis.     

Erythroid precursor cells in a tissue culture from subjects exposed to ionizing radiation

Cloning efficiency of erythroid progenitor cells in gel diffusion chambers from patients irradiated as a result of the Chernobyl accident was studied. Stimulation of erythroid progenitor cells, activation of enzymatic activity in peripheral blood cells and an increase of 2,3-D Ph G were detected. These data supplement the notion about the development of adaptative processes in the erythron system as a response to effects of radiation.     

Breast cancer risk and alcohol consumption: results from a large case-control study

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.     

Potentiation of the antitumor effect of ionizing radiation by brief concomitant exposures to angiostatin

Angiostatin, a proteolytic fragment of plasminogen, inhibits the growth of primary and metastatic tumors by suppressing angiogenesis. When used in combination with ionizing radiation (IR), angiostatin demonstrates potent antitumor synergism, largely caused by inhibition of the tumor microvasculature. We report here the temporal interaction of angiostatin and IR in Lewis lung carcinoma (LLC) tumors growing in the hind limbs of syngeneic mice. Tumors with an initial mean volume of 510 +/- 151 mm3 were treated with IR alone (20 Gy x 2 doses on days 0 and 1), angiostatin alone (25 mg/kg/day divided twice daily) on days 0 through 13, or a combination of the two as follows: (a) IR plus angiostatin (days 0 through 13); (b) IR plus angiostatin (days 0 and 1); and (c) IR followed by angiostatin beginning on the day after IR completion and given daily thereafter (days 2 through 13). By day 14, tumors in untreated control mice had grown to 6110 +/- 582 mm3, whereas in mice treated with: (a) IR alone, tumors had grown to 2854 +/- 338 mm3 (P < 0.05 compared with untreated controls); and (b) angiostatin alone, tumors had grown to 3666 +/- 453 mm3 (P < 0.05 compared with untreated controls). In combined-treatment groups, in mice treated with: (a) IR plus longer-course angiostatin, tumors reached 2022 +/- 282 mm3 (P = 0.036 compared with IR alone); (b) IR followed by angiostatin, tumors reached 2677 +/- 469 mm3 (P > 0.05 compared with IR alone); and (c) IR plus short-course angiostatin, tumors reached 1032 +/- 78 mm3 (P < 0.001 compared with IR alone). These findings demonstrate that the efficacy of experimental radiation therapy is potentiated by brief concomitant exposure of the tumor vasculature to angiostatin.     

Hierarchical analysis of genetic structure in native fire ant populations: results from three classes of molecular markers

We describe genetic structure at various scales in native populations of the fire ant Solenopsis invicta using two classes of nuclear markers, allozymes and microsatellites, and markers of the mitochondrial genome. Strong structure was found at the nest level in both the monogyne (single queen) and polygyne (multiple queen) social forms using allozymes. Weak but significant microgeographic structure was detected above the nest level in polygyne populations but not in monogyne populations using both classes of nuclear markers. Pronounced mitochondrial DNA (mtDNA) differentiation was evident also at this level in the polygyne form only. These microgeographic patterns are expected because polygyny in ants is associated with restricted local gene flow due mainly to limited vagility of queens. Weak but significant nuclear differentiation was detected between sympatric social forms, and strong mtDNA differentiation also was found at this level. Thus, queens of each form seem unable to establish themselves in nests of the alternate type, and some degree of assortative mating by form may exist as well. Strong differentiation was found between the two study regions using all three sets of markers. Phylogeographic analyses of the mtDNA suggest that recent limitations on gene flow rather than longstanding barriers to dispersal are responsible for this large-scale structure.     

Rejoining of DNA single- and double-strand breaks in human white blood cells exposed to ionizing radiation

PURPOSE: To characterize inter- and intra-individual differences in X-ray-induced DNA strand break rejoining kinetics in human peripheral white blood cells (WBC) obtained from 10 healthy volunteers. MATERIALS AND METHODS: The alkaline and neutral versions of the comet assay were used to measure the rate of rejoining of predominantly single-strand breaks (ssb) following exposure to 8 Gy and double-strand breaks (dsb) following 75 Gy. RESULTS: All cells within a population responded in a similar fashion to induction of ssb and dsb; however, a subset of the WBC appeared to rejoin ssb more rapidly. For the 10 individuals examined, the percentage of ssb rejoined by the rapid component(s) was 47 +/- 16% and the rejoining half-time for the slow component was 1.3 +/- 0.4 h. By 24 h after 8 Gy, 4.9 +/- 3.8% of the initial ssb remained. For dsb rejoining, 58 +/- 11% of the initial damage was still present 4h after 75 Gy and by 24 h 32% of the initial level of damage was still detected. Heavily damaged cells present 24 h after 75 Gy varied from 4% to 50% and were excluded from the analysis of repair rates. CONCLUSIONS: Inter-individual variability exceeded intra-individual variability for 2 of 4 endpoints examined for ssb repair, but not for dsb repair. It was concluded that DNA damage measured using the comet assay could identify a range in the X-ray repair responses of WBC from different normal individuals. Whether these differences correlate with differences in cell killing by radiation remains to be determined.     

p53-mediated regulation of proliferating cell nuclear antigen expression in cells exposed to ionizing radiation

BACKGROUND: The complications associated with anterior craniofacial resections for benign and malignant tumors were reviewed in 104 patients treated between January 1981 and June 1996. METHODS: Information regarding patient characteristics, histologic type, history of prior therapy, extent of the disease, extent of surgical procedure, and type of reconstruction were entered in a microcomputer database. To better understand and stage postoperative complications, we divided them into early (<14 days) and late (>14 days) according to the time of presentation, into major and minor depending on the morbidity potential of complication, and into local and systemic ones. Comparison between risk factors associated with complications was made using chi-square analysis with Yates' correction for continuity. Survival analysis was performed using the Kaplan-Meier product limit method. RESULTS: There were 8 (7.6%) postoperative deaths, with only 1 occurring from systemic complications. Complications occurred in 53 (48.6%) patients. Local major complications occurred in 49 (45%) patients, local minor in 29 (26.6%), and systemic in 11 (10%). Early complications occurred in 40 (38.5%) patients and late complications in 13 (12.5%) patients. These complications developed during a period ranging from 1 day to 5 months. More than one complication occurred in a number of patients. Bacterial contamination leading to local septic complications was the principal cause of morbidity, accounting for 54.7% (29/53) of complications. Major complications included meningitis in 8 patients associated with cerebrospinal fluid leak in 7, cerebral abscess in 2, sepsis in 1, and subdural hemorrhage in 1, all of which resulted in death except for one case. The extent of the craniofacial resection (p = .011) was the most important factor associated with major complications. Invasion of the dura and the type of reconstruction of the anterior skull base were the most important factors related to cerebrospinal fluid leakage (p = .048 and p = .032) and meningitis (p = .011). CONCLUSION: Contemporary surgical approaches and methods of reconstruction have enabled skull base surgeons to extend their cranial base resections and increase the 5-year survival rates of patients. Nevertheless, significant complications persist. Knowledge and high index of suspicion together with early recognition of these complications are essential for effective management of patients undergoing craniofacial resection. The factors related to major complications found in this study stressed the need to develop more effective methods to prevent contamination of intracranial structures.     

The nature of the development of autoimmune hemolytic anemia in thymectomized animals exposed to the action of ionizing radiation

To study the character of the experimental autoimmune haemolytic anaemia formation in thymectomized mice, which were irradiated in 1.0 Gy dose. Shown, autoimmune process is result in most aggressive course in thymectomized irradiated mice with autoimmune anaemia than in irradiated mice with autoimmune anaemia. This pathology was connected with decrease of the T-suppressor function. Via 20th weeks the autoimmune process was practically depressed.     

Calculation of radiation exposures from patients to whom radioactive materials have been administered

Spreadsheet templates which calculate cumulative exposures to other persons from patients to whom radioactive materials have been administered have been developed by the authors. Calculations can be based on any specified single-, bi- or tri-exponential whole-body clearance rate and a diurnal (or any other periodic) contact pattern. The time (post-administration) during which close contact should be avoided in order to constrain the radiation exposure and exposure rates to selected limits is also calculated using an iterative technique (Newton's method), and the residual activity at the time when contact can resume is also calculated. These templates find particular application in the calculation of exposures to persons who are in contact with patients who have received 131I for therapeutic purposes. The effect of changing dose limits, contact patterns and using individually derived clearance rates may be readily modelled.     

The Special Surveillance Breast Program: a model of intervention for women at high risk for breast cancer

The Special Surveillance Breast Program (SSBP) is a long-term, comprehensive, multidisciplinary program for women determined to be at high risk for the development of breast cancer. Because the women who attend this program are otherwise healthy but concerned about their risk for breast cancer, current and relevant information is required to address their concerns regarding the possibility of developing breast cancer. The purpose of this article is to describe the risk factors that indicate eligibility for the program, the structure of the program, and the results of an assessment that identified the needs of this special population.     

Breast cancer screening of the medically underserved: results and implications

Socioeconomic status is the most significant factor influencing the decreased survival associated with breast cancer in minority groups in the United States. Barriers to the use of early detection programs by low-income women often result in the detection of breast cancer at stages too advanced to assure optimum outcomes. In an effort to increase accessibility of breast cancer screening among such individuals, the Early Detection Program (EDP) was initiated in 1987. The program provided breast cancer screening to women 40 years of age and older who attended eight primary healthcare centers located in low-income neighborhoods throughout Dade County, Florida. From its inception in October 1987 through December 1993, 23,866 medically underserved women had mammography examinations, with more than 17,000 of these women undergoing baseline mammograms. Since the program's inception, 126 cancers were diagnosed in 123 women. A dramatic shift from later to earlier stage breast cancers was observed. These results warrant a greater inclusion of medically underserved and lower socioeconomic status women in screening programs for the early detection of breast cancer.     

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.     

Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland

Several lines of evidence suggest that sex hormones may be involved in the etiology of prostate cancer. We conducted a prospective nested case-control study to evaluate the relationships of serum androgens and estrogens to prostate cancer using serum collected at baseline for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The 29,133 male smokers who participated in the trial were 50-69 years old at baseline. During 5-8 years of follow-up, 246 men were diagnosed with prostate cancer, and 116 of these were randomly selected for inclusion in the current study. For each case, two controls matched on age, date of blood collection, intervention group, and study center were selected. Hormones were measured in serum by RIA using standard procedures. None of the individual androgens or estrogens was significantly related to prostate cancer. These findings were unaltered by simultaneous evaluation of serum androgen and estrogen concentrations in multivariate models. These results do not support a strong relationship of serum androgens and estrogens with prostate cancer in smokers. Within-person variation in concentrations of some hormones may have contributed to the lack of significant associations.     

Assessment of chronic radiation exposure as one of risk factors of the development of cancer in industrial city residents exposed to radioactive pollution

In previous studies we have shown that injection of the insect growth regulator Azadirachtin (AZA) into young vitellogenic females induces inhibition of vitellogenesis in a dose-dependent manner. Juvenile hormone treatment rescues vitellogenin synthesis and ovarian growth. The cytopathological effects on ovaries and fat body are not linked to an inhibition of feeding. In this work we investigated the effects of AZA on the endocrine and neuroendocrine system. Enzyme immunoassay reveals that ovarian ecdysteroid levels are drastically reduced, in a dose-dependent fashion, by AZA. Ultrastructural study indicates that corpus allatum cells exhibit signs of inactivity and degenerative changes after AZA exposure. Using an antibody against allastostatin-3 of Blatella germanica (BLAST-3), we show the appearance of strong immunoreactivity of numerous cells and axons in the brain of AZA-injected females. We conclude that vitellogenesis inhibition by AZA consists of a direct cytotoxic effect as well as a generalized disruption of endocrine and neuroendocrine functions.     

The use of bee and plant products in the treatment and rehabilitation of subjects exposed to the effect of ionizing radiation]

The necessity is substantiated for use of apiphytoproducts in patients with duodenal ulcer who had become victims of Chernobyl accident. Apiphytoproducts were found out to accelerate the natural elimination of cesium radionuclides from the body, to normalize the indices for lipid peroxidation; they can be used on a monotherapy basis or combined with antisecretory or anti-Helicobacter drug preparations.     

A mathematical analysis of the mortality kinetics of Drosophila melanogaster exposed to gamma radiation

Being interested in factors stabilizing neurotubules (NTs) in situ, we decided to immerse short segments of fresh rat peripheral nerves in buffered solutions containing ZnCl2 in final concentrations up to 10-2 m prior to fixation with buffered osmium or glutaraldehyde, both containing ZnCl2. Zinc treatment resulted in a remarkable structural preservation of NTs after fixation with osmium, though they are not preserved by osmium fixation alone. Cross sections of myelinated nerve fibres show NTs arranged predominantly in compact groups. Within the groups NTs are surrounded or embedded in an electron dense fine granular material. The occurrence of incomplete C-shaped NTs and NT-like densities can be seen. NTs exhibit relatively constant distances and sometimes geometric patterns of arrangement. A lot of intertubule cross bridges and NTs with arms could be observed. In longitudinal section the bridge and arm spacing is seen to be periodic along the tubule axis at about 500 A. Zinc treatment of nerves fixed in glutaraldehyde resulted in the same ultrastructural alterations described above. The resistance of zinc-stabilized NTs to degradation by osmium and the ultrastructural changes induced by zinc are discussed. The results suggest that in the presence of zinc ions osmium-labile NTs are transformed--by disassembly and reassembly--to osmium-stabile microtubules that are not identical with preexisting ones.     

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Breast cancer and heredity: results of a population case-control study in Girona

BACKGROUND: To characterise the relationship between breast cancer and different aspects of the reproductive life, use of drugs and alcohol by family history of breast cancer. PATIENTS AND METHODS: From the cancer registry of Girona, Spain, 330 women were identified with histologically confirmed breast cancer during 1986-1989. For each case, a control woman was selected from a random sample of the population living in the matched area to the case by age (+/- 5 yr.). The information was collected by a personal interview and included: family history of breast cancer, reproductive history, presence of acne during the teenage years, use of oral contraceptives and drugs for sleep and anxiety disorders, and alcohol consumption. RESULTS: 18.5% of breast cancer cases and 8.9% of all controls had a family history of breast cancer. Family history on a first degree relative (mother or sister) was present in 10.6% of the cases and 2.8% of controls, which represented an odds ratio for breast cancer of 3.7 (95% CI, 1.8-7.8) higher than the general population. Women with a first degree family history of breast cancer were at higher risk for breast cancer if they had a history of acne during the teenage period (OR = 2.4; 95% CI, 1.1-5.2) and if they referred long menstrual periods in the early years of menarche (OR = 3.1; 95% CI, 1.3-7.0). Women with no family history had a higher breast cancer risk if they had a late menarche, long menstrual periods, late first full term pregnancy, and history of acne during puberty. Alcohol consumption and use of drugs for anxiety and sleep disorders were associated with a decreased risk of breast cancer. CONCLUSIONS: First degree family history of breast cancer seems to be the best risk indicator for developing breast cancer. Long menstrual periods and presence of acne during puberty may indicate hormonal imbalance that act independently of the family history in breast cancer development.