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Biomedical subjects

C E Flowers

Publications and source records attributed to C E Flowers.

At least 19 recordsLinked to original sources

A prospective comparison of two endogenous creatinine clearance testing methods in hospitalized hypertensive gravid women.

OBJECTIVE: Although 24-hour endogenous creatinine clearance testing is common in pregnancies complicated by hypertension, inaccuracies limit its usefulness. We controlled the conditions under which 4-hour endogenous creatinine clearance testing was performed and compared the results with outcomes of 24-hour tests from the same patients. STUDY DESIGN: In 83 women hospitalized with mild hypertension in the third trimester, we measured endogenous creatinine clearance with a 4-hour urine collection during lateral recumbency and supervised oral hydration. This test was paired with a 24-hour test performed immediately thereafter. No restrictions or recommendations regarding ambulation or oral intake were imposed for the 24-hour test. RESULTS: The 4-hour endogenous creatinine clearance value exceeded the 24-hour value in 133 of the 136 paired comparisons (p < 0.0001). Results of the tests from only the 29 patients with multiple paired tests showed more similarity (p < 0.005) among the 4-hour than among the 24-hour clearances. CONCLUSION: The 4-hour endogenous creatinine clearance test, as described, provides a higher and less variable estimate of renal function in hypertensive pregnant women than does the 24-hour test.

Creatinine↗

Peripheral placental separation: a possible relationship to premature labor.

This investigation was undertaken to determine the relationship, if any, between peripheral placental separation and idiopathic premature labor. Ninety placentas from prematurely delivered patients (who had had no antepartum bleeding) were examined grossly and microscopically. Criteria for antepartum peripheral placental separation included adherent clot, with fibrin deposition and lamination, as well as polymorphonuclear infiltration and marginal decidual necrosis. Forty-nine placentas showed unequivocal evidence of previous peripheral separation. Another three placentas showed presumptive evidence of previous peripheral separation. It is suggested that this separation is of venous origin, and that it may play a role in the process of premature labor. This is not necessarily a cause and effect relationship.

Abruptio Placentae↗

Clinical evaluation of an improved injectable microcapsule contraceptive system.

Pharmacokinetics and pharmacodynamics of a long-acting injectable microcapsule, poly(DL-lactide-co-glycolide), delivery system were tested in 10 women. Two doses (75 or 100 mg of norethindrone) were administered by intramuscular injection. Treatment suppressed ovarian function and inhibited ovulation for 3 months in all subjects. Levels of norethindrone in subjects who received the 100 mg dose were proportionately higher than those in subjects who received the 75 mg dose. Subsequent to the injection, there was a rapid rise in the serum levels of norethindrone followed by a gradual decline until 8 to 10 weeks. Between 10 and 20 weeks after treatment, there was a secondary rise and fall in the serum levels of norethindrone. Treatment caused suppression of the endometrium for 3 months, and, except for spotting and irregular menstrual cycles, there were no adverse side effects. Treatment had no significant effect on serum lipids.

Adult↗

Poly(DL-lactide-co-glycolide)/norethisterone microcapsules: an injectable biodegradable contraceptive.

Microcapsules made from a biocompatible, biodegradable polymeric excipient, poly(DL-lactide-co-glycolide) (DL-PLGA) that contained 22 weight percent (wt %) norethisterone (NET), were prepared by a solvent-evaporation microencapsulation process. The effects of changing both the lactide-to-glycolide ratio of the DL-PLGA and the size of the microcapsules on the rate of NET release and the rate of excipient biodegradation were determined in vivo. NET release rates were determined in baboons after injecting the microcapsule formulations intramuscularly. Serum samples obtained at various times following treatment were analyzed for NET, progesterone, and estrogen by radioimmunoassay (RIA). Biodegradation kinetics were determined by injecting NET microcapsules made from radiolabeled DL-PLGA intramuscularly into the hind legs of rats. Residual radioactivity at the injection site was determined at various times after treatment by combustion analysis of the muscle tissue. Changing the ratio of the comonomers to include more glycolide (DL-lactide:glycolide-96:4, 92:8, 87:13, 74:26) increased the rate of NET release and accelerated the biodegradation of the copolymer excipient. Decreasing the size of the microcapsules increased the rate of NET release. On the basis of these studies a NET microcapsule formulation has been identified for clinical testing which releases NET for 3 months and biodegrades completely within 6 months.

Animals↗

Mechanisms of uterine bleeding in postmenopausal patients receiving estrogen alone or with a progestin.

The response of postmenopausal endometrium to cyclic estrogen and progestin and cyclic estrogen alone was studied in 75 biopsies and over 2000 preparations using standard histologic, histochemical, and scanning and transmission electron microscopic techniques. Estrogen and a progestin caused the atrophic endometrium to assume normal proliferative and secretory phases and to develop nucleolar channel systems. Cyclic unopposed estrogen produced unphysiologic responses in the glands, stromal cells, and vessels. The concept of a progestin or progesterone producing a "medical curettage" should be reappraised. Cyclic estrogen and progestin therapy do not cause all the endometrium to desquamate to the basalis layer. The combination therapy is associated with increased glycoprotein production in the gland and stromal cells, and an orderly regression and remodeling of the endometrium upon hormonal withdrawal. Cyclic estrogen alone causes irregular and unpredictable breakdown, which may or may not extend to the basalis. The stimulation of the endometrium by estrogen alone may allow the endometrium to use the majority of its energy for growth, which may lead to hyperplasia and neoplasia.

Adult↗

Clinical evaluation of injectable biodegradable contraceptive system.

A new long-acting injectable contraceptive system was tested in 24 women. The system consists of microspheres made of biodegradable d,l-polylactic acid in which micronized crystals of norethisterone (NET) are homogeneously dispersed. In previous animal studies we showed that NET is slowly released from the microspheres for 6 months, and after the drug is released, the microspheres biodegrade into lactic acid by the process of hydrolysis. The serum levels of NET, estrogen, and progesterone were monitored by radioimmunoassay, and the effects of treatment on ovarian function and menstrual bleeding were evaluated. The doses ranged from 29 to 370 mg of microspheres containing 7.25 to 94.5 mg of NET or 0.134 to 2.30 mg of NET/kg of body weight. The duration of the NET release was 6 months, and the serum NET profiles in women were similar to those previously described in subhuman primates. Following a small burst, there was a gradual decline in the serum levels of NET over 6 months after treatment. The serum levels of NET varied in proportion to the dose. Doses less than 0.267 mg of NET/kg had no discernible effect on either ovarian function or menstrual bleeding. Doses ranging from 0.419 to 2.30 mg had variable effects on ovarian function and menstrual bleeding. Higher doses caused suppression of ovarian function for longer periods of time, increased the interval between episodes of menstrual bleeding, and decreased the quantity of blood loss during each episode. The treatment was well tolerated by all subjects, and, with the exception of spotting and irregular menstrual cycles, there were no adverse side effects. Based on this initial study, it was determined that doses ranging from 1.33 to 3.45 mg of NET/kg are necessary to suppress ovulation for 6 months. Additional studies with the use of higher doses are currently under way.

Adult↗

Oxytocin challenge test for antepartum fetal assessment. Report of a clinical experience.

OCT's were performed 1,209 times on 533 fetuses at risk for UPI. OCT interpretation was negative for 72% of tests, and there were were no fetal deaths within a week following a negative test. Our data thus support the concept that the use of the OCT for fetal surveillance most frequently justifies a course of nonintervention. Of 69 fetuses with positive test, 47 were subjected to the stresses of labor with maternal hyperoxygenation and lateral poisoning. Twenty of these 47 (43%) tolerated labor without biophysical evidence of distress. Reactivity of the FHR, when present during a positive test, significantly increased the likelihood that a fetus would tolerate labor. The fetal and perinatal mortality rates in the patients identified as a risk for UPI and studied with OCT's were no greater than in a comparable group of pregnancies without identifiable risk for UPI and not studied with OCT's.

Female↗

New long-acting injectable microcapsule contraceptive system.

A new long-acting, injectable contraceptive which provides continuous controlled release of the steroid norethisterone (NET) for a precise period of 6 months following a single intramuscular injection is described. The prototype system consists of microcapsules made of the biodegradable polymer d, l-polylactic acid, in which micronized crystals of NET are homogeneously dispersed. NET is slowly released from the microcapsules following intramuscular injection at a rate of 0.90 microgram NET/day/mg of microcapsule by diffusion of the steroid from the polymer matrix. Three different doses of a standard preparation of microcapsules were tested in normally cycling female babbons (4 to 5 baboons/group). Following injection of either 300, 200, or 100 mg of microcapsules containing 75, 50, or 25 mg of NET, blood samples were collected at selected intervals and analyzed for NET, estrogen, and progesterone by radioimmunoassay. All three doses provided continuous NET release for 6 months following injection. The NET serum profiles for the different doses are parallel, and ovulation was inhibited in all baboons for 6 months following treatment.

Animals↗

Management of prolonged pregnancy: results of a prospective randomized trial.

Prolonged pregnancy was rigorously defined in 180 gravid women without other complications. Patients were randomly assigned to be serially followed, either by amniocenteses or by oxytocin challenge tests (OCT's). Induction of labor, based upon only (1) a finding of meconium in the amniocentesis group or (2) a positive test in the OCT group, was nearly three times more frequent in the amniocentesis group. The incidence of meconium, which overall was 22% initially and 44% at delivery, as well as the frequencies of obstetric and perinatal complications, were similar in both management groups. Although meconium was significantly associated with abnormal labor progression, intrapartum fetal distress, and low 1 and 5 minute Apgar scores, induction of labor after discovery of meconium, when compared to nonintervention, did not improve perinatal outcome. It is concluded that a search for meconium is of little value in the management of prolonged pregnancy.

Amniocentesis↗

The effects of oxytocin on fetal scalp temperature.

During a study of fetal temperature, it was found that there was a significantly higher temperature among infants whose mothers received oxytocin than among a comparable control group. These data indicate that normal-appearing oxytocin-induced contractions may reduce uterine blood flow and thereby raise the intrauterine fetal temperature.

Female↗

New observations on the physiology of menstruation.

Endometrium was studies histologically, histochemically, and ultrastructurally in a series of biopsies taken from 3 normal, ovulating patients on Days 1-9 of the cycle. The occurrence of ovulation and the adequacy of progesterone were determined by radioimmunoassay. The most striking feature of menstruating endometrium was its vigorous attempt to survive. This was manifested by lysosomal activity, lipid accumulation, expulsion of glycoproteins, and the uptake of stromal debris by epithelial cells for passage to the uterine cavity. Regression, rather than cell death, was the chief event of menstruation. While some cells of the spongiosa underwent necrosis, the vast majority remained viable and underwent remodeling to participate in the new cycle. These studies may lead to further understanding of the process of menstruation and the pathophysiology of anovulatory bleeding and irregular shedding of the endometrium.

Biopsy↗

The prediction of fetal oxygenation by an on-line computer analysis of fetal monitor output.

The deceleration delay index (DDI) is a statistical parameter computed by an on-line system which analyzes fetal monitor output for the temporal relationship between each uterine contraction and any associated deceleration of the fetal heart rate. A similar parameter describing this relationship is known to be quantitatively predictive of fetal oxygenation in the rhesus monkey, a species for which the level of fetal oxygenation is also known to be directly and progressively related to aberrations in the vital signs, to brain damage, and to fetal death. Thus, the DDI should be of significant, practical value in predicting fetal hypoxia at a time early enough to avert severe neonatal depression and/or hypoxic brain damage. A blind clinical trial of 106 parturients is presented which supports this concept by showing the DDI to be highly correlated with another oxygenation-associated parameter, the one-minute Apgar score.

Apgar Score↗

[Effects of quingestanol acetate on the histology, histochemistry and ultrastructure of the endometrium].

According to studies carried out using the optical microscope and the electron microscope quingestanol acetate, which is a powerful progestagen, modified significantly the histology and the histochemistry of the endometrium. The mechanisms of transport across the cellular membranes are not changed, but probably there is competition between the oestrogens at the binding sites as a result of which the synthesis of proteins and hydrocarbons is changed. This in turn provokes the formation of aggregations of platelets in the blood vessels and cellular degeneration starting from the onset of the cycle. The contraceptive efficiency of quingestanol acetate when it is administered by itself is due to alterations in cellular biology which it brings about at the level of the endometrium as well as due to its inhibitory effect on gonadotropins.

Endometrium↗