Early detection of ovarian cancer: preliminary results of the Yale Early Detection Program.

Eighty-four women at high risk for ovarian cancer by having first-degree relatives with epithelial ovarian cancer participated in a newly established, early ovarian cancer detection program at Yale University. Participants were to be evaluated with physical examinations and circulating tumor markers at entry and every six months thereafter. Endovaginal ultrasound and color Doppler flow studies were to be performed at three and nine months following entry into the program. In addition, women were encouraged to follow American Cancer Society guidelines for mammography. Stool was checked for occult blood. Endometrial sampling was offered to post-menopausal women. No participant has developed an ovarian cancer since entering the program. One woman has been diagnosed to have breast cancer. False-positive levels of circulating tumor markers (CA 125, 4/84 [4.8 percent]; lipid-associated sialic acid in plasma, 13/84 [15.5 percent]; NB/70K, 4/84 [4.8 percent]; and urinary gonadotropin fragment, 1/65 [1.5 percent]) were observed on entry into the program. Low resistive indices (less than 0.5) were documented in 8/91 (8.8 percent) ovaries studied by the color Doppler flow technique. One participant underwent a laparotomy based on a false-positive endovaginal ultrasound examination. Tests now being employed in community practice have a high likelihood of being associated with false-positive results. Therapeutic interventions based on isolated abnormal tumor markers or ultrasound studies obtained from women with family histories of ovarian cancer may lead to inappropriate surgery. It is necessary for cancer centers to develop expertise in ovarian cancer detection techniques to advise physicians in their geographic areas appropriately about the significance of the abnormal screening test.     

Early and late results of resection of abdominal aortic aneurysms.

Resection of the abdominal aortic aneurysm is being performed with decreasing operative mortality and morbidity. Among 190 patients undergoing this procedure at the Ottawa Civic Hospital between 1970 and 1975, 53 (28%) had a ruptured aneurysm and 137 (72%), a nonruptured aneurysm. Mean age of the patients was 66.2 years. Concomitant disease was frequent, 73% of patients having two or more associated diseases; the average number of associated diseases per patient was 2.25. Operative mortality in the group with ruptured aneurysms was 51%, and in the group with nonruptured aneurysms, 4%. Postoperative morbidity was 85% among those with a ruptured aneurysm, 67% among those with imminent rupture before operation and 34% among the others with a nonruptured aneurysm. Graft complications occurred in 15% of those with a ruptured aneurysm and 9% of those with a nonruptured aneurysm. Among survivors of the operation 73% and 81% of those with a ruptured and a nonruptured aneurysm, respectively, are known to be alive. In both groups causes of late death included infection or thrombosis of the graft and mesenteric thrombosis, as well as causes unrelated to the operation. Surgical management of the abdominal aortic aneurysm is advocated in all but patients at poor risk for operation who have asymptomatic aneurysms less than 6 cm in diameter.     

Management of childhood illness in Africa. Early evaluations show promising results

This article reports the positive evaluation results of the integrated management of childhood illness (IMCI) strategy for the last 3 years of operation in 28 countries in Africa. The strategy aimed to improve case management skills of health workers through training with locally adapted guidelines such as the use of clinical algorithms to detect the most common causes of childhood illnesses. In addition, the strategy was designed to improve the health system of the region, including the provision of essential drugs. A final component of the program seeks to optimize family and community practices in relation to child health, particularly care seeking behavior. Overall, the benefits include more rational drug use, increased attendance, improved provider morale, and improved perceptions of quality of care by mothers. Although its initial effects are rather small, it should be recognized that the proper implementation of IMCI should contribute to a steady reduction in childhood mortality in Africa.     

Aesthetic results following partial mastectomy and radiation therapy

This study was undertaken to determine the aesthetic changes inherent in partial mastectomy followed by radiation therapy in the treatment of stage I and stage II breast cancer. A retrospective analysis of breast cancer patients treated according to the National Surgical Adjuvant Breast Project Protocol B-06 was undertaken in 57 patients from 1984 to the present. The size of mastectomy varied between 2 x 1 cm and 15 x 8 cm. Objective aesthetic outcome, as determined by physical and photographic examination, was influenced primarily by surgical technique as opposed to the effects of radiation. These technical factors included orientation of resections, breast size relative to size of resection, location of tumor, and extent and orientation of axillary dissection. Regarding cosmesis, 80 percent of patients treated in this study judged their result to be excellent or good, in comparison to 50 percent excellent or good as judged by the plastic surgeon. Only 10 percent would consider mastectomy with reconstruction for contralateral disease. Asymmetry and contour abnormalities are far more common than noted in the radiation therapy literature. Patients satisfaction with lumpectomy and radiation, however, is very high. This satisfaction is not necessarily based on objective criteria defining aesthetic parameters, but is strongly influenced by retainment of the breast as an original body part.     

Progesterone therapy results in partial reversibility of uterine abnormalities of the adult anovulatory rat.

The effects of progesterone therapy (5 mg, administered subcutaneously daily for 6 days) on the abnormal uterus of adult anovulatory Wistar rats have been studied. These rats, rendered anovulatory by neonatal treatment with testosterone propionate or clomiphene citrate, displayed severe hyperplasia and metaplasia of the uterine luminal epithelium and a disproportionately high content of nuclear oestrogen receptor, as a result of constant oestrogen stimulation unrelieved by progesterone [White, Moore, Elder & Lim (1981) Biochem. J. 196, 557-565]. Progesterone therapy resulted in the virtual elimination of the hyperplasia and metaplasia and a corresponding decrease in the content of nuclear oestrogen receptor with the proportion of the unoccupied nuclear receptor being increased to values exhibited by normal cyclic females. There was also a decrease in the content of progestin receptors, a putative index of oestrogenic stimulation. Further, in the testosterone-treated group, progesterone therapy resulted in the restoration of oestrogen receptor translocational responses to oestradiol stimulation. Progesterone treatment of these anovulatory rats thus provides a model system for investigating the biochemical mechanisms underlying progestin antagonism and regulation of oestrogen-stimulated cell proliferation.     

Heterogeneous capture-recapture models with covariates: a partial likelihood approach for closed populations

In practice, when analyzing data from a capture-recapture experiment it is tempting to apply modern advanced statistical methods to the observed capture histories. However, unless the analysis takes into account that the data have only been collected from individuals who have been captured at least once, the results may be biased. Without the development of new software packages, methods such as generalized additive models, generalized linear mixed models, and simulation-extrapolation cannot be readily implemented. In contrast, the partial likelihood approach allows the analysis of a capture-recapture experiment to be conducted using commonly available software. Here we examine the efficiency of this approach and apply it to several data sets.     

Mechanism of AMPA receptor activation by partial agonists: disulfide trapping of closed lobe conformations

The mechanism by which agonist binding to an ionotropic glutamate receptor leads to channel opening is a central issue in molecular neurobiology. Partial agonists are useful tools for studying the activation mechanism because they produce full channel activation with lower probability than full agonists. Structural transitions that determine the efficacy of partial agonists can provide information on the trigger that begins the channel-opening process. The ligand-binding domain of AMPA receptors is a bilobed structure, and the closure of the lobes is associated with channel activation. One possibility is that partial agonists sterically block full lobe closure but that partial degrees of closure trigger the channel with a lower probability. Alternatively, full lobe closure may be required for activation, and the stability of the fully closed state could determine efficacy with the fully closed state having a lower stability when bound to partial relative to full agonists. Disulfide-trapping experiments demonstrated that even extremely low efficacy ligands such as 6-cyano-7-nitroquinoxaline-2,3-dione can produce a full lobe closure, presumably with low probability. The results are consistent the hypothesis that the efficacy is determined at least in part by the stability of the state in which the lobes are fully closed.     

Early chromosome condensation without cell fusion. I. Preliminary results with allogeneic and xenogeneic cells.

Early chromatin condensation in interphase cells (G1) of human peripheral blood lymphocytes has been induced without virus or cell fusion by exposure to allogeneic or xenogeneic mitotic cells. The event, although similar in some ways to the phenomenon described as "premature chromosome condensation," "chromosome pulverization," and "prophasing," differs in that it does not require the presence of viruses and cell fusion before mitosis proceeds in the G1 cell. Early chromatin condensation in interphase cells induced by mitotic cells only, consists of chromatids in the early or late G1 phase of the cell cycle that are not pulverized or fragmented at mitosis. Some of the chromosomes are twice as long as the metaphase chromosomes and exhibit natural bands. Almost twice as many of these bands are produced as by trypsin treatment of metaphase chromosomes. The nuclear membrane is intact and nucleoli are present, to which some chromosomes are attached. The DNA content of the precocious chromosomes in G1 is half the amount of the metaphase complement.