Larry C. Ford

Estrogen and progesterone receptor sites in malignancies of the uterine cervix, vagina, and vulva.

Cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in uterine cervical, vaginal, and vulvar carcinomas by the dextran-coated charcoal (DCC) technique. Tissues from 30 patients with cervical carcinoma were examined. Thirteen percent (2 of 16) of well-differentiated squamous carcinomas had positive ER, and 19% (3 of 19) had positive PR. None of the three patients with moderately well-differentiated disease have positive ER or PR, while two of five patients with poorly differentiated lesions contained measurable ER and PR. In contrast, all four of the well-differentiated adenocarcinomas of the cervix had detectable ER, and three of four for PR. Neither of the two patients with poorly differentiated adenocarcinoma had either ER or PR. None of the five vulvar and seven vaginal epidermoid carcinomas studied had ER or PR activity. Hormonal therapies may be useful in the treatment of adenocarcinoma of the cervix.

Determination of estrogen and androgen receptors in Trichomonas vaginalis and the effects of antihormones

Trichomonas vaginalis, a common genital pathogen, was found to possess both specific estrogen and specific androgen receptors. These 4.3 S macromolecules were proteinaceous in nature. Both metronidazole-resistant and metronidazole-sensitive strains possessed both types of sex hormone-binding proteins. The estrogen receptor binding was competitively inhibited by the antiestrogen tamoxifen citrate, and the androgen binding was competitively inhibited by the antiandrogen cyoctol. The presence of these specific receptors may allow the use of hormonal and antihormonal manipulation in the treatment of infections caused by these organisms.

Estrogen and progesterone receptors in ovarian neoplasms

The cytoplasmic receptors for 17 beta-estradiol (ER) and progesterone (PR) were measured in 39 malignant and 15 benign ovarian neoplasms. All eight endometroid carcinomas had positive ER sites, one-half contained PR. The number of ER binding sites decreased as tumor grade increased. Conversely, none of the 11 mucinous tumors contained either ER or PR receptors. One-half of the well-differentiated serous tumors had ER (57 +/- 23 fmole/mg protein) while none of the poorly differentiated tumors had measurable binding. In serous carcinomas, PR was only detected in well-differentiated lesions (447 +/- 240 fmole/mg protein). Only one of 15 benign neoplasms contained ER and PR receptors. Correlation of tumor grade and type may help to plan hormonal therapies in advanced ovarian malignancies.

The metabolism of cis-dichlorodiammineplatinum (II): Distribution, clearance, and toxicity

The distribution and toxicity of 195mPt-labeled cis-platinum were studied in two groups of dogs. Serum and tissue levels, renal and marrow toxicities, and urinary excretion were compared in dogs given cis-platinum, 3 mg/kg, intravenously with a group treated by intraperitoneal administration. Peak serum levels occurred immediately after intravenous administration and 8 hours after intraperitoneal instillation, at which time the two were identical and declined at similar rates. Mean levels of cis-platinum measured in peritoneal tissues on day 4 were higher in the intraperitoneal group. Blood urea nitrogen, creatinine, and white blood cell and platelet counts were similar in both groups. Bloody ascites and adhesion formation occurred in 37.5% of dogs treated by intraperitoneal administration. The intraperitoneal route of chemotherapy administration results in higher drug levels in target peritoneal tissues without a corresponding increase in systemic toxicity.

Polysiloxane vaginal rings and cylinders for physiologic endometrial priming in functionally agonadal women

17 beta-estradiol (E2)-and/or crystalline progesterone (P)-impregnated polysiloxane vaginal rings and cylinders were tested as a system for endometrial priming in functionally agonadal women awaiting donor embryo transfer. Endometrial tissue was obtained by a transcervical biopsy procedure on simulated cycle day 26. The adequacy of the replacement regimen was judged by endometrial histologic dating, scanning electron micrographs, receptor content, and circulating E2 and P serum concentrations. Endometrial dating was consistent with cycle day 26. Electron micrographs showed normal surface characteristics. E2 and P receptor concentrations were within the normal range. Serum E2 levels were midfollicular, 105 +/- 12.8 pg/ml (mean +/- SEM), and midcycle, 254 +/- 28.6 pg/ml. P levels during the simulated follicular phase were undetectable (less than 0.2 ng/ml) but rose to a mean peak level of 17.3 +/- 1.8 ng/ml. The steroid-impregnated polysiloxane vaginal ring and cylinder system provided continuous and sustained hormone release, morphologically and endocrinologically normal endometrium, serum levels of E2 and P within the normal range for the entire menstrual cycle, and a convenient and physiologic therapeutic alternative to oral, vaginal, or intramuscular steroid replacement.

Cost-effective use of antibiotic prophylaxis for cesarean section

Clinical experience has indicated that the prophylactic use of antibiotics reduces infectious morbidity in patients undergoing cesarean section. Several factors must be considered (for instance, in vivo and in vitro efficacy, patient allergies, side effect profiles, status of host defenses, the total cost of therapy, and the risk of selecting resistant organisms that cause superinfections) before prescribing prophylactic antibiotic drugs for this indication. Moreover, medical-legal consequences associated with potential postpartum infections must be considered in assessing the costs and impact of a prophylactic regimen. Results of comparative antibiotic trials in indigent patients undergoing cesarean section demonstrated differing rates of successful antibiotic prophylaxis: piperacillin, 98%; cefoxitin, 91%; cephalothin and ceftazidime, 82%; cefotaxime, 80%; and ampicillin, 77%. Although the acquisition costs of antibiotics vary greatly, these costs are dwarfed by the substantial cost savings that can be realized by use of broad-spectrum antibiotics, which, in our hands, have resulted in reduced laboratory and pharmacy expenses and decreased hospital stays for both mother and neonate. Controlled studies designed to investigate microbiologic as well as clinical efficacy of antibiotics are indicated. Further refinements in individualizing antibiotic regimens according to patient population should be sought.

cis-Platinum in advanced gynecologic malignancy

Abstract Eighteen patients with advanced gynecologic malignancies received cis -diamminedichloroplatinum (NSC 119875), an inorganic heavy metal compound with antineoplastic properties. Twelve patients had carcinoma of the ovary resistant to other chemotherapeutic agents. Three patients had previously irradiated carcinoma of the cervix; two, disseminated pelvic sarcoma; and one, metastatic carcinoma of the vulva. Objective responses were achieved in four patients (25%) with carcinoma of the ovary. Three patients with other tumors also responded. Mild to severe myelosuppression, nephrotoxicity, and ototoxicity occurred.

Candida albicans Vaginitis: The Problem Is Diagnosis, the Enigma Is Treatment

At the UCLA Vulvovaginitis Clinic, 63 patients were diagnosed as having symptomatic Candida albicans vaginal infections. In a random select manner 3-day treatment with 200-mg clotrimazole suppositories was compared with 7-day treatment using 100-mg clotrimazole suppositories. 7- and 35-day follow-up of all patients entered revealed no statistical difference between the two groups, suggesting that short-term treatment is most efficacious and can be expected to work better since patient compliance is primarily a function of duration of treatment. In 50 cases of C. albicans patients treated with miconazole or clotrimazole in a random manner, the recurrence rate was 8 or 16. All patients in the study received perianal cultures for C. albicans before treatment and 7 and 35 days after treatment. 5 of the 8 patients with recurrence had perianal positive cultures at the 7- and 35-day check suggesting this as a source of recurrence. It is suggested that patients with persistently high perianal cultures after treatment be given an oral fungicide or fungistat to lower chronic recurrent C. albicans.

Evaluation of postpartum culture techniques

SummaryA ‘tube within a tube’ technique for obtaining postpartum endometrial cultures was compared to the usual transcervical method of collection of material for culture in a total of 603 patients. The patients were randomly assigned to one of the methods of collection. The double tube method markedly decreased contamination from the vagina and enhanced the recovery of anaerobic organisms.

Identification of leukin in amniotic fluid

SummaryLeukin, a cationic bactericidal protein of low molecular weight that is derived primarily from the polymorphonuclear leucocyte, was found to be present in amniotic fluid from 450 normal obstetric patients at teim. The concentration in the amniotic fluid was very similar to that found in circulating maternal plasma, probably indicating simple diffusion of leukin. Neutralisation of amniotic fluid leukin with specific antisera did not change the in vitro bactericidal activity of whole amniotic fluid. The role of leukin as a nonspecific host defence agent in amniotic fluid is thought to be minimal