Postcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation

The contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.     

An Atypical Recurrence of Endometrial Carcinoma Following Estrogen Replacement Therapy

Following an abdominal hysterectomy and bilateral salpingoophorectomy wherein a superficial (1.6 mm) well-differentiated endometrial cancer and bilateral ovarian serous cystadenomas were discovered, estrogen replacement was given. One year later the patient presented with a 9 × 7-cm left groin recurrence. Patients with endometrial carcinoma may request estrogen replacement. The benefits of such replacement are well recognized; however, these patients also need to be counselled that hormonal replacement may be complicated by recurrence. Physicians need to be cognizant of symptoms or signs which would suggest disease recurrence at unusual sites in these patients who are perceived as being at low risk for recurrent disease.     

Genetic mediation of infanticide and parental behavior in male and female domestic and wild stock house mice

Infanticide is a reproductive strategy found in many mammals, especially rodents. The proportion of male and female house mice (Mus domesticus) that are either infanticidal or noninfanticidal is strain specific and varies widely from stock to stock. Male house mice also show strain-specific variation in the behavioral mechanisms that inhibit infanticidal individuals from killing their own offspring. The adult offspring generated from reciprocally crossed CF-1 and Wild stock house mice were tested for their behavior toward newborn pups. In male CF-1xWild hybrids, the proportion of infanticidal and noninfanticidal males matched with their maternal phenotype, whereas female CF-1xWild hybrids exhibited a proportion of behaviors typical of the CF-1 phenotype, regardless of their mother's genotype. Our results suggest three conclusions: first, that infanticide is a highly labile and heritable behavior in both sexes; second, that there is a sex difference in the genetic substrate that regulates the inheritance of infanticidal behavior; and third, that selection pressures in male mice may operate independently on the mechanisms that promote spontaneous infanticidal behavior versus the mechanisms that inhibit infanticide.     

Detection of N-myc gene amplification by fluorescence in situ hybridization. Diagnostic utility for neuroblastoma.

We assessed fluorescence in situ hybridization (FISH) as an alternative to Southern blot analysis for determination of N-myc gene amplification in neuroblastoma. In the 44 pediatric solid tumor cell lines examined (20 neuroblastomas), the mean number of N-myc copies determined by FISH correlated closely with Southern blot results. There was wide intercellular variability in gene copy number in tumors that had evidence of amplification; however, tumors judged to be non-amplified completely lacked any cells with high N-myc copy number. FISH provided reliable estimates of N-myc amplification in 12 clinical samples even when the percentage of tumor was low. The other advantages of FISH over Southern blot analysis were speed and technical simplicity, ability to discern heterogeneous gene amplification among tumor cells in the same specimen, and capacity to determine the source of the amplified N-myc signal, whether extrachromosomal double-minute chromosomes, expanded intrachromosomal regions, or chromosome 2 aneuploidy. We conclude that FISH would refine the analysis of N-myc amplification in neuroblastoma and thus improve the assignment of patients to prognostic groups based on this unfavorable risk factor.     

Clinical importance of near-diploid tumor stem lines in patients with osteosarcoma of an extremity

We determined the clinical value of flow-cytometric measurement of tumor-cell DNA content, which reflects the chromosome number (ploidy), in patients with osteosarcoma of an extremity. Hyperdiploid stem lines were identified in 25 of 26 tumor samples obtained at diagnosis from patients who did not have clinically overt metastases. Near-diploid tumor stem lines coexisted with hyperdiploid lines in 15 of these 25 cases; an isolated near-diploid line was present in the 26th case. All 26 patients underwent definitive surgery and then were treated uniformly with intensive adjuvant combination chemotherapy. Kaplan-Meier analysis of both relapse-free and overall survival times showed that the presence of a near-diploid tumor stem line was associated with improved outcome (P = 0.003 for each comparison). After a median follow-up time of three years, pulmonary metastases developed in only 2 patients in the group with near-diploid lines, in contrast to 7 of the 10 with hyperdiploid lines exclusively. Near diploidy remained significantly associated with improved relapse-free survival after adjustment for the influence of age, the only clinical variable that showed prognostic strength in this analysis (P less than 0.01; relative risk, 0.08; 95 percent confidence interval, 0.02 to 0.48). Our findings demonstrate the usefulness of flow-cytometric determination of tumor-cell ploidy for predicting the sensitivity of histologically high-grade osteosarcoma to chemotherapeutic agents. Patients with a near-diploid tumor stem line can be expected to respond favorably to adjuvant chemotherapy as used in this study, whereas those with only hyperdiploid lines should be considered as candidates for alternative therapy.     

Relationship Between Breast and Axillary Pathologic Complete Response in Women Receiving Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology - We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer....     

Hormone and fertility drug use and the risk of neuroblastoma: a report from the Children's Cancer Group and the Pediatric Oncology Group.

Previous epidemiologic studies have suggested an association between maternal sex hormone use during pregnancy, including infertility medication, and an increased risk of neuroblastoma in the offspring. The authors conducted a case-control interview study from 1992 to 1996 that included 504 children less than 19 years of age whose newly diagnosed neuroblastoma was identified by two national collaborative clinical trials groups in the United States and Canada, the Children's Cancer Group and the Pediatric Oncology Group. Controls, matched to cases on age, were identified by random digit dialing. No association was found for use of oral contraceptives before or during pregnancy (first trimester odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.5, 2.1). The odds ratio was slightly elevated for history of infertility (OR = 1.4, 95% CI: 0.9, 2.1) and ever use of any infertility medication (OR = 1.2, 95% CI: 0.7, 2.2). Specifically, ever use of clomiphene was associated with a 1.6-fold increased risk (95% CI: 0.8, 3.0) but not periconceptionally or during the index pregnancy. A suggestive pattern was found for gender of the offspring, with an increased risk for males but not for females after exposure to oral contraceptives or clomiphene. This study did not find consistent and large increased risks for maternal use of hormones, but the suggestion of an association for male offspring requires further consideration.     

Age-Specific Native Hawaiian Mortality: A Comparison of Full, Part, and Non-Hawaiians

PURPOSE OF THE PAPER: The purpose of this paper is to test if the previously identified disparity in mortality rates among full Hawaiians, part Hawaiians, and non­Hawaiians in the state of Hawaii has continued into the 1990s. SUMMARY OF METHODS UTILIZED: Based on Hawaii vital records and population data, standardized age­specific mortality rates by cause and 95% confidence intervals were estimated. PRINCIPAL FINDINGS: The most striking finding was the significant differences in mortality rates in four age strata ­­ 45­54, 55­64, 65­74, and 75­84 ­­ with mortality rates highest for full Hawaiians, lowest for non­Hawaiians, and intermediate for part Hawaiians. CONCLUSIONS: Findings suggest that Native Hawaiians continue to be at greater risk of death compared with non­Hawaiians, with full Hawaiians at greatest risk. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS: Asian and Pacific Islander Americans have been called the model minority. These data provide evidence that Native Hawaiians, especially full Hawaiians, have dramatically higher mortality rates than non­Hawaiians and merit special attention.