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Biomedical subjects

W Droegemueller

Publications and source records attributed to W Droegemueller.

At least 37 records · Page 2Linked to original sources

Perimortem cesarean delivery.

Postmortem cesarean delivery is an operation that has been practiced since antiquity. In previous centuries low infant survival rates led to negative opinions regarding the operation's usefulness. A review of the past centuries' cases and a review of fetal physiology suggest that to obtain optimum infant survival, cesarean delivery should be initiated within four minutes of maternal cardiac arrest. The physiology of cardiopulmonary resuscitation during pregnancy is analyzed, and recent cases of maternal cardiac arrest with successful maternal resuscitation are reviewed. This data suggests that perimortem cesarean delivery initiated within four minutes of maternal cardiac arrest will yield the highest rates of maternal survival. Legal liability from the operation is minimal.

Cesarean Section↗

Collagen sponge as vaginal contraceptive barrier: critical summary of seven years of research.

Extensive testing of collagen sponge as a vaginal contraceptive (mechanical and chemical) showed that the original expectations regarding the safety, convenience, and efficacy were not met. The collagen sponge was tested both as a cylinder and as a diaphragm and used as such or impregnated with spermicidal detergent or with zinc salt. The collagen sponge must be larger than 6 cm in diameter in order to serve as a mechanical barrier that will not be dislodged during physical activity. This creates problems with the ease of insertion and with the partners' awareness of the barrier. When the collagen sponge containing ejaculate is left in the vagina greater than 48 hours, it develops an offensive odor. The original acidity of the collagen sponge (pH 3.5, 0.1 mol/L) is soon neutralized by the large volume of alkaline vaginal secretions. In vitro studies showed that up to 10 mg of nonoxynol 9 per milliliter of growth medium did not inhibit the growth of Staphylococcus aureus. These effects, as well as the large surface area of the resilient sponge, present a potential risk for growing staphylococci within the collagen sponge. The capacity of the collagen sponge to absorb a large volume of cervical and vaginal fluid produced two symptoms that were annoying to the volunteers: an awareness of either vaginal dryness during intercourse or, conversely, saturation of the sponge from the vagina. Postcoital studies showed viable spermatozoa in the cervical mucus in 25% of the tests with the nonmedicated cylindrical sponge but in only 6% of tests with the sponge containing nonoxynol 9. The results of clinical trials conducted at four centers support the view that collagen sponge as a vaginal contraceptive barrier method is inconvenient to both partners, not effective enough to compete with present methods of vaginal contraception, and possibly might be unsafe because of the capacity to grow bacteria. Despite the negative end result of this goal-oriented research, we believe that our studies have contributed to a better understanding of vaginal physiologic features, the safety and effectiveness of spermicidal detergents, and the mechanisms of vaginal malodor. Although the acceptability study showed some advantages of the collagen sponge over the rubber diaphragm, the overall acceptability of the collagen sponge diaphragm was no better than that of the rubber diaphragm. For all these reasons, including the possible risk of an increased incidence of toxic shock syndrome, we have discontinued further testing of either type of collagen sponge as a vaginal barrier method.

Collagen↗

Three-day treatment with butoconazole nitrate for vulvovaginal candidiasis.

A multicenter clinical trial of 274 patients compared the efficacy and safety of a new vaginal antifungal compound, butoconazole nitrate cream 2% (butoconazole), to clotrimazole vaginal tablets 200 mg/day (clotrimazole). Both drugs were administered for three days. The patients were randomly assigned to one or the other treatment regimen. Eight days after treatment completion, Candida albicans was absent in vaginal cultures of 95% of patients receiving butoconazole and of 91% of patients receiving clotrimazole; 30 days after treatment completion, 80% of patients receiving butoconazole were free of the fungal infection; the corresponding number for clotrimazole was 74%. Complete absence of the entrance signs and symptoms of vulvovaginal candidiasis was noted in 82% of patients receiving butoconazole and 72% of patients receiving clotrimazole. The phamacokinetic parameters were studied in three women volunteers who received one dose of radiolabeled butoconazole nitrate vaginal cream 2%. Measurable levels of radioactivity were not detected until two to eight hours after vaginal administration of the compound. Maximum plasma levels of radioactivity were achieved 24 hours after dosing and ranged from 19 to 44 ng/mL and fell to background levels after 96 to 120 hours. Total radioactivity was excreted to an equal extent in urine (2.7%) and in feces (2.8%).

Adult↗

Evaluation of topically applied trans-retinoic acid in the treatment of cervical intraepithelial lesions.

The prevention and/or suppression of preneoplastic foci in animals has been convincingly demonstrated with the use of a variety of compounds, including retinoids. We report here a phase I/II trial of beta-trans-retinoic acid delivered via a collagen sponge/diaphragm insert for neoplasia of the cervix. Eighteen patients with biopsy-proved grades 2 and 3 cervical intraepithelial neoplasia underwent four consecutive daily applications of trans-retinoic aicd to the cervix. Conization of the cervix was performed 4 weeks later. Significant vaginal toxicity in 10 of 18 (55%) patients was unrelated to the concentration or carrying media of the drug. A reduction in size of the intraepithelial lesion was noted by colposcopy in six of 18 (33%) patients with complete resolution of disease at conization in two patients. A new delivery system designed to avoid vaginal toxicity while defining the optimal concentration and dosing schedule for these patients is currently under investigation.

Administration, Topical↗

In vitro retinoid binding and release from a collagen sponge material in a simulated intravaginal environment.

Four in vitro preparations were constructed to simulate the intravaginal release of two retinoids, all-trans-retinoic acid (t-RA) and 13-cis-retinoic acid (c-RA), from a 0.7% collagen sponge diaphragm insert. Four t-RA concentrations, 0.019, 0.05, 0.1, and 0.15% in methanol were added to the sponge. The release into an artificial vaginal fluid was monitored serially over 72 h by serial analysis for t-RA and c-RA using high-pressure liquid chromatography. In each preparation, retinoid release was immediate and noncontinuous. At 37 degrees C, the retinoids were stable for at least 48 h. Trans-retinoic acid was the predominant retinoid recovered. Only trace amounts of the cis-isomer were released. Peak t-RA levels were 20 microM after 0.01%, 60-80 microM after 0.05%, 100-200 microM after 0.1%, and 320 microM after 0.15%. When the vaginal fluid bath was changed after 5 h, no further significant retinoid release occurred. There was significant loss of up to 70% of the applied t-RA into the collagen sponge. The retinoid binding was concentration dependent (higher binding with higher concentrations) and was maximal only after 24 h of co-incubation. The discontinuous release of t-RA and the high degree of binding to collagen would seem to preclude use of the diaphragm insert as a vaginal drug delivery system, at least for retinoids.

Biocompatible Materials↗

Forearm plethysmography in normotensive and hypertensive pregnant women.

Forearm plethysmography affords a simple noninvasive method of studying dynamic changes in the microcirculation. This technic was used to study the peripheral circulation of normotensive nongravid women and normotensive and untreated hypertensive pregnant women during the third trimester. The variables of forearm blood flow, vascular resistance, venous capacitance, and capillary filtration coefficient were measured in the resting state and during and after exercise. The pregnant women demonstrated an increase in forearm blood flow over the nonpregnant women. As expected, vascular resistance was higher in the hypertensive pregnant patients than in normotensive pregnant women. The possible predictive value of these findings is discussed.

Female↗

Immunologic detection of condylomata acuminata-specific antigens.

A rabbit serum fraction was prepared which contained antibody specific for unique antigen(s) found in human condylomata acuminata tissue but not in other human papillomatous or normal tissues. Indirect immunofluorescent staining of cryostat sections of human tissues demonstrated an intense nuclear fluorescence in cells of the prickle cell layer of condylomata acuminata sections. Nuclear fluorescence was not apparent in cells in the basal or dermal layers. The serum fraction did not elicit nuclear fluorescence in epithelial cells of tissue from human vulva, human foreskin, juvenile hand wart, plantar wart, or squamous cell papilloma of the cervix. This demonstration of antigens unique to epithelial cells of condylomata acuminata may prove useful in the often difficult diagnosis of cervical condylomata.

Antigens, Neoplasm↗

Studies on Nonoxynol-9. II. Intravaginal absorption, distribution, metabolism and excretion in rats and rabbits.

Some pharmacological aspects of Igepal CO-630, used by some pharmaceutical companies as the source of nonylphenoxypoly (ethyleneoxy) ethanol (Nonoxynol-9, N-9) in various spermicidal formulations, were studied. It was found that Igepal CO-630 contains at least 13 components, 70% having molecular weights near that of N-9. After intravaginal administration, the detergent is rapidly and quantitatively absorbed through the vaginal wall into the systemic circulation. The rate of vaginal absorption of N-9 depends on the vehicle in which the detergent is carried. Once in the blood, N-9 is excreted by liver-bile-feces and the kidney-urine routes, the first being more effective in rats, the latter in rabbits. Following intravaginal or intraperitoneal injection of radioactive N-9, the highest content of radioactivity was found in the liver and kidney. The detergent was detected in the milk of lactating rats and the serum of their pups within two hours after the intravaginal dose.

Absorption↗

Studies of nonoxynol-9. I. The effect on the vaginas of rabbits and rats.

A standard rabbit vaginal irritation test was used to evaluate the morphologic reaction to an aqueous solution of a nonionic spermicidal detergent, nonoxynol-9 (N-9). Various amounts of N-9, between 2.5 mg and 50 mg, were incorporated into cylindrical collagen sponges which were retained in the vagina for 10 days. Changes in the continuity of the epithelial lining, edema of the submucosal layer, and the inflammatory cell infiltrate of this layer were proportional to the amount of N-9 tested. An increase in semiquantitative score for the inflammatory changes in the vagina was noted for increasing amounts of N-9. In young adult female rats treated vaginally with 5 mg/100 gm body weight/day of aqueous N-9 for 5 to 20 days, the number of cells (DNA) was significantly increased on day 5. The collagen content in the vaginal wall (hydroxyproline) was significantly increased after 15 and 20 daily injections of the detergent. We conclude that both morphologic and chemical changes in the vagina are compatible with the inflammatory reaction induced by the detergent tested.

Animals↗

Studies on nonoxynol-9. III. Effect on fibroblasts and spermatozoa.

Seven nonionic detergents of the Igepal CO series differing in molecular size and including nonoxynol-9 and a representative anionic (SDS) and cationic (Cepacol) detergent were tested as to their relative cytotoxicity. The biologic effects of these detergents on human W1--38 fibroblasts (DNA and glycosaminoglycans synthesis) and on the motility of human spermatozoa were studied. The relative order of cytotoxicities for both fibroblasts and spermatozoa was cationic greater than nonionic greater than anionic. The concentration of nonoxynol-9-inhibiting fibroblast activity was approximately 30 times less than the amount needed to immobilize spermatozoa. It is concluded that CO-630, used as a source of nonoxynol-9, is the most effective polymer to inhibit spermatozoa and also fibroblasts.

Anions↗

Preliminary testing of the contraceptive collagen sponge.

The results of 3 years of developing the collagen sponge as an intravaginal contraceptive are presented. Postcoital tests were used to evaluate the efficacy of the sponge as a mechanical barrier. Results with the collagen sponge alone were compared to those of the sponge with spermicidal cream or spermicidal solution (acid buffer and zinc) and of spermicidal cream alone. The presence of any motile spermatozoa in the cervical mucus was considered a failure of the barrier method. The collagen sponge alone or with acid and zinc and spermicidal cream alone had failure rates of 22, 20, and 14%, respectively, whereas the collagen sponge with spermicidal cream had a 6% failure rate. The authors conclude that the combination of a mechanical and a chemical barrier is a more effective contraceptive method than a mechanical barrier or chemical agent alone.

Adolescent↗

Ultrastructural changes in the architecture of collagen in the human cervix treated with urea.

Injection of a solution of 30% urea in acetate buffer at pH 4.0 into the stroma of the uterine cervix results in a marked change in the mechanical properties of the tissue with subsequent easy dilatation. This study analyzes the changes in the collagenous matrix of the cervix by ultrastructural and biochemical methods. Collagen fibrils in urea-treated sections of the cervix are swollen and unravelled, showing spiral configuration of subunits in both cross-sections and longitudinal sections. The regular localization of ruthenium-red-positive material is absent in urea-treated tissues. Chemical analysis of incubated cervical tissues shows a reduction of the total glycosaminoglycans and of dermatan sulfate with release of the latter into the medium. It is suggested that urea dissociates intercollagen linkages by solubilizing a certain glycosaminoglycan, possibly dermatan sulfate. After this solubilization the collagen fibril is prompted to unwind, resolving the collagen microfibrils, which appear to be organized in a spiral fashion.

Cervix Uteri↗

(15S)-15 methyl prostaglandin F2 alpha levels in amniotic fluid and blood in second trimester abortions.

A single intra-amniotic injection of (15S)-15 methyl prostaglandin F2 alpha (THAM) was used to induce second trimester abortion in five patients. Serial levels of (15S)-15 methyl prostaglandin F2 alpha were subsequently measured in amniotic fluid and plasma by radioimmunoassay. The slow removal of this drug from the amniotic fluid was documented. Plasma levels of (15S)-15 methyl prostaglandin F2 alpha increased fourfold to sevenfold after clinical rupture of the membranes in three patients, supporting the fact that prostaglandins are well absorbed from the vagina. Because this analogue of prostaglandin can cause marked peripheral bronchoconstriction when administered systemically, it is best to avoid its use in patients with a history of asthma.

Abortion, Induced↗