Tim H. Parmley

The ovarian mesothelioma

Abstract Neoplasms arising from the surface or lining cells of the ovary are classically referred to under such general terms as cystadenocarcinoma, papillary carcinoma, and undifferentiated cancer. Evidence is presented in this discussion to support the thesis that such lesions are mesotheliomas, and that such a thesis can be defended embryologically, histologically, and clinically.

Pharmacokinetic studies on quinacrine following intrauterine administration to cynomolgus monkeys

Recent efforts have been made to develop a chemical oviductal occluding agent. Intrauterine quinacrine has been used in certain areas of the world with moderate success in effected tubal closure. This report presents the pharmacokinetics of a quinacrine solution (30 mg) as administered to cynomolgus monkeys via the intrauterine route, compared with intravascular injection. The data show rapid transfer of the drug from the uterine to the vascular compartment and uptake by almost all tissues examined. Although plasma concentrations disappear within 24 hours, levels can be detected in most tissues for at least 1 week following intrauterine injection. After 28 days, however, tissue levels of the drug are absent or near the limit of detection.

A two-year experience with the Falope ring sterilization procedure

The use of cautery laparoscopic sterilization procedures has two major disadvantages: (1) occasional inadvertent thermal injury to organ structures other than the Fallopian tube and (2) the inability to limit the injury to the Fallopian tube in a manner that might allow subsequent reconstructive surgery. In an effort to avoid the use of thermal energy to effect female sterilization, the Falope ring laparoscope was developed. From October, 1973, through September, 1975, 4,390 sterilization procedures were completed employing this approach; 902 cases have been completed at the Womans Clinic of the Johns Hopkins Hospital, 1,741 cases were completed by gynecologists in various cities in the United States, and 1,747 procedures were completed by physicians in various locations throughout the world sponsored by the International Fertility Research Program.

Effect of intrauterine and intravascular quinacrine administration on histopathology, blood chemistry, and hematology in cynomolgus monkeys.

Histopathologic features, blood chemistry, and hematologic features were studied in cynomolgus monkeys following intravascular or intrauterine administration of a 30-mg solution of quinacrine hydrochloride. Intrauterine quinacrine administration resulted in extensive necrosis of the endometrial surface, and lesions were observed at 24 hours after treatment which obliterated the cornual areas of the uterus. Necrosis was also observed on occasion in the ampulla or isthmic portion of the tube. Evidence of repair of the reproductive tract was seen 7 and 28 days following treatment. No lesions were observed in any nonreproductive organ examined, whether quinacrine was administered by the intrauterine or intravascular route. Blood chemistry data revealed moderate and transient increases in serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and lactic dehydrogenase (LDH). No other blood chemistry or hematologic changes were noted that could be attributed to quinacrine administration. For the conditions described in these studies, intrauterine administration of quinacrine appears to be a safe procedure. However, the potential toxicity of the drug is discussed.

Ultrastructural observations on amniotic fluid cells

Abstract Amniotic fluid was obtained at cesarean section from 5 third-trimester pregnancies and the proportion of orange-staining cells in the amniotic fluid determined using Nile blue sulfate staining. In the freshly obtained fluids 25 to 75 per cent of the cells stained orange. The cells were sedimented and processed for examination in the electron microscope. Virtually all the cells appeared to be squamous epithelial cells of fetal epidermis or mucous membrane. They contained variable numbers of keratin filaments and P.A.S.-positive particles resembling glycogen. No fat-containing cells were found. The presence of the squamous cells appeared to correlate with the thickening of the stratum corneum near term. It is concluded that the orange-staining cell is a cornified fetal squamous cell coated on its exterior surface by lipid material that appears to be intracellular in the light microscope and is removed during processing for electron microscopy.

Fetal maturity and amniotic fluid analysis

Abstract The analysis of constituents of the amniotic fluid with the objective of determining fetal maturity has been of increasing interest. Reported herein are the results of our attempts to establish normal values for amniotic fluid creatinine, bilirubin, and cytologic features at various stages of gestation, and then, using these values, to judge the accuracy with which they predicted approximate delivery dates and fetal weights in a series of pregnancies of unknown duration. In general, we have found that amniotic fluid cytologic features and creatinine levels allow us to predict with good accuracy the presence of an infant of at least 2,500 grams and/or a gestational age of 35 weeks. We have been even more struck, however, with the possible insight into intrauterine physiology that may come with greater understanding of the phenomena reported here.

Obstetric features of thanatophoric dwarfism

Abstract Thanatophoric dwarfism is the result of a generalized failure of endochondral bone formation. It may be diagnosed in utero and is almost uniformly fatal. Hydramnios, prematurity, breech presentation, and cephalopelvic disproportion are clinical features frequently associated with these infants. The early induction of labor in these cases is suggested.

Effect of intrauterine administration of tetracyclines on cynomolgus monkeys

Cynomolgus monkeys were used to screen for chemicals which potentially could be used as tubal occluding agents. Intrauterine administrations of solution or pellets of tetracycline and its analogues (100 mg doses) were tested for their effects on morphologic changes in the reproductive tract of monkeys. These effects were compared to monkeys receiving intrauterine administration of quinacrine pellets (36 mg) since quinacrine has been used successfully in the clinical setting. Blood levels of drugs, blood chemistry and hematology determinations and liver and kidney pathology data were also obtained as indices for toxicity. Morphologic damage to the uterine lining and intramural section of the tube (including necrosis, inflammation or scarring) was elicited by intrauterine tetracycline and doxycycline in the same frequency and severity as quinacrine. In contrast, saline or sham control monkeys showed no morphological damage of the tube or uterus. Although all drugs could be detected in the blood 4 hours after intrauterine administration, levels were near or below the limit of detection by one week. No evidence was found for toxicity of tetracycline or its analogues for the dosage given. Because of these results and the extensive literature on tetracycline toxicity, further studies should be directed toward the use of tetracycline as a sterilizing agent in women.

Comparative effects of intrauterine instillation of analogues of quinacrine and tetracycline on uterine morphology in the rat

Currently, intrauterine instillation of quinacrine hydrochloride is used to induce closure of the uterotubal junction in women, thus constituting a chemical method of sterilization. Questions regarding the safety of this drug have been raised. The purpose of the present study is to screen other drugs for their sterilizing potential by comparing quinacrine-induced changes in uterine morphology in the rat which have previously been correlated with decreased fertility with the changes induced by other drugs. The drugs tested include quinacrine-like compounds, namely chloroquine, primaquine and trimethoprim; and tetracycline and its analogues which are known sclerosing agents. The quinacrine-like drugs were relatively ineffective in producing uterine lesions similar to those of quinacrine, but like quinacrine, chloroquine and primaquine showed some toxicity. Tetracycline and its analogues produced quinacrine-like morphologic changes in the rat uterus and showed no toxicity for the doses tested. These results prompt further testing of tetracycline and its analogues as sterilizing agents.

Intraocular endometrium in the rabbit as a model for endometriosis

The model described suggests that endometrium can be successfully transplanted to the rabbit eye and observed through a slit lamp for morphological changes such as vascularization. Sampling of aqueous humor in volumes adequate for biochemical measurements have been demonstrated. Autografts of rabbit endometrium survived for up to 181 days. Although xenografts of human endometrial and endometriotic tissue demonstrate some adherence and vascularization, there is indication of immune rejection by day 7. Other treatment regimens will be explored with the objective of prolonging the graft survival time.