Cancer risk after evaluation for infertility

To evaluate cancer risk by various causes of infertility, the authors conducted a retrospective cohort study among 2,335 women evaluated for infertility at the Mayo Clinic between 1935 and 1964. Most cancers occurred at expected frequencies, with the exception of cancers of the thyroid (standardized incidence ratio (SIR) = 2.6) and other endocrine glands (SIR = 6.7), although analyses were based on small numbers. Patients with progesterone deficiencies (31 per cent of the study subjects) had a 20 per cent higher cancer risk than did those with other causes of infertility, with excesses deriving primarily from cancers of the lung, cervix, ovary, and thyroid and from melanoma. Breast cancer risk, however, was not elevated in either patients with progesterone deficiencies (SIR = 0.9) or patients with other causes of infertility (SIR = 1.0). Examination of other parameters of infertility, including age at evaluation, type of infertility (primary vs. secondary), and years of attempted conception, showed no elevated risks of breast cancer in any subgroup. These results fail to support previous studies that have linked progesterone deficiencies among infertile women to elevated breast cancer risk. However, the data suggest a possible involvement of a progesterone deficiency in the etiology of other cancers, particularly thyroid cancer and melanoma.     

Synthesis of antimicrobial agents. 1. Syntheses and antibacterial activities of 7-(azole substituted)quinolones

A series of 6-fluoro- and 6,8-difluoro-7-(azole substituted)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids were prepared. Structure-activity relationship studies indicated that the antibacterial potency was better when the 6,8-substituents were fluorine atoms and the 7-substituent was either 1-imidazolyl, 20, or 4-methyl-1-imidazolyl, 25. From the results of studies on pharmacokinetic profile and toxicity, 20 and 25 were found to possess excellent antibacterial activities and to show high blood levels after oral administration to mice with low toxicity.     

The use of pericardium for the management of recurrent tracheoesophageal fistula

Correction of congenital esophageal atresia and tracheoesophageal fistula (TEF) with either a primary or staged repair may result in recurrence of the TEF, most often at the site of esophageal anastomosis. Definitive operative repair of a recurrent TEF involves isolation and resection of the fistula with closure of the tracheal and esophageal defects. A technique is described, whereby mobilization of a vascularized pedicle of pericardium allows further enhancement of the standard repair of a recurrent TEF. The vascularized pedicle of pericardium serves to isolate the tracheal and esophageal suture lines from each other, as well as aid in sealing leaks at either or both suture lines. This may dramatically reduce the incidence of second recurrences and lower the overall operative mortality, reportedly as high as 59%.     

Impaired insulin receptor binding and postbinding defects of adipocytes from normal and diabetic pregnant women

To evaluate the relative contribution of insulin binding and postbinding defects of glucose utilization in peripheral tissue during normal and diabetic pregnancy, we have studied the in vitro insulin action of isolated adipocytes from eight nondiabetic pregnant women and nine pregnant women with insulin-dependent diabetes mellitus who were undergoing cesarian section. The pregnant women were compared with a matched group of normal nonpregnant women undergoing gynecologic surgery. Insulin binding to adipocytes measured at tracer insulin concentration was reduced by 45% (P less than 0.01) in normal pregnant women and by 30% (P less than 0.02) in pregnant women with diabetes. In contrast, no changes were found between the three groups in insulin binding to pure monocytes and erythrocytes. The glucose transport system in fat cells from both groups of pregnant women was characterized by impaired maximal (P less than 0.05) and half-maximal (P less than 0.05) response to insulin. When fat cell glucose metabolism was studied, pregnant diabetic women exhibited decreased basal lipogenesis (P less than 0.05) and decreased maximal responses of lipogenesis and glucose oxidation to insulin stimulation (P less than 0.05). Similar but less pronounced abnormalities were seen in glucose metabolism of adipocytes from nondiabetic pregnant women. In conclusion, both in late normal and diabetic pregnancy, insulin binding to adipocytes is significantly reduced and accompanied by decreased insulin sensitivity and reduced maximal insulin responsiveness of glucose transport and by impaired basal and maximally insulin-stimulated glucose metabolism.     

Response of Plasmodium falciparum to dihydrofolate reductase inhibitors in Malindi, Kenya

The response of Plasmodium falciparum isolates to dihydrofolate reductase inhibitors (DHFRI) was examined in Malindi, Kenya. All 20 infected children treated with pyrimethamine/sulphadoxine responded. In contrast, after treatment with pyrimethamine, parasitaemia in 9 of 14 infections failed to clear or recrudesced during the seven-day follow-up. In a 48-hour in vitro test, five of six isolates resistant to pyrimethamine in vivo had a minimal inhibitory concentration (MIC) to pyrimethamine greater than or equal to 300 nmoles/1 compared with less than or equal to 100 nmoles/1 for the four sensitive isolates; four isolates did not grow. MIC to M-B 35769, an experimental DHFRI structurally similar to pyrimethamine were the same (six isolates) or 10-fold lower (three isolates). In the laboratory four of five isolates adapted to in vitro culture had the same MICs as in the field while one isolate became less responsive to both drugs. Cycloguanil (the active metabolite of proguanil) was more active in vitro in the laboratory than pyrimethamine or M-B 35769.     

Ovarian and omental ependymomas in peritoneal washings: cytologic and immunocytochemical features

The cytologic findings in peritoneal washings of two women, one of whom had an ovarian ependymoma and the other a primary omental ependymoma, are reported. The ependymomas were characterized by the presence of numerous, isolated, spindle and stellate cells as well as groups of cells forming true rosettes. The tumor cells displayed slightly pleomorphic, round-to-oval eccentric nuclei and abundant fibrillary cytoplasm with tapering cytoplasmic processes. In addition, one of the patients had numerous papillae and cell clusters with associated psammoma bodies indistinguishable from those found in low-grade serous carcinoma. The demonstration of glial fibrillary acidic protein (GFAP) in both cases by immunocytochemical procedures indicates the usefulness of this method in cytologic preparations to confirm the diagnosis of these uncommon neoplasms.