Voiding disorders after radical hysterectomy

The authors report the reaction on bladder function observed in 15 women suffering from cervical cancer in stages I and II after the Wertheim-Meigs radical hysterectomy. All the patients were given various tests before and after operation: urodynamic investigations using uroflowmetry, gas cystometry completed by a urecholine denervation test, cystosphinctermanometry with simultaneous flowmetry, simultaneous recording of bladder and urethral pressures with flowmetry, and urethral closure pressure profile with microtip transducers (Millar Instruments). On the basis of the results, the authors maintain that the damage caused by the operation affects not only the detrusor but also the normal sphincter function as suggested, in fact, by the symptoms observed in the patients (dysuria and stress incontinence). The preoperative urodynamic study was of no help in foreseeing the amount of damage caused by the operation to the normal bladder-sphincter function. On the other hand, the study proved essential postoperatively in clarifying the pathophysiology of the voiding disorders complained of by the patients and, above all, in deciding upon the best plan of management.     

The effect of cone biopsy on subsequent pregnancy outcome

One hundred and thirty-one pregnancies occurring in 97 patients following cone biopsy were reviewed. Excluding therapeutic abortions, 27.1% of the remaining pregnancies terminated in spontaneous abortions and 11.3% in labor prior to 36 weeks. However, because of other abnormal preceding factors in many of these cases, in only a few could cone biopsy be implicated as a likely etiological factor. The majority of viable pregnancies and labors were uncomplicated. Nonetheless, it would seem advisable to minimize the risk of complications with the use of colposcopy and a “shallow” cone or by the use of cryosurgery in the treatment of preclinical carcinoma of the cervix.     

Altered effect of 3% dietary cholestyramine on plasma lipids and biliary bile acid output in the pregnant rat

The effects of a diet containing 3% (w/w) cholestyramine on plasma total, free, and high-density lipoprotein cholesterol and triglycerides and on bile flow and composition were compared between pregnant rats fed the resin from before mating until the twentieth day of gestation and virgin rats fed the resin for an equivalent length of time. Pregnant and virgin rats consuming a similar diet but not receiving cholestyramine were also studied. In the nonpregnant rat the usual response to cholestyramine was observed as a significantly elevated plasma high-density lipoprotein cholesterol level and biliary bile acid secretion. Plasma cholesterol levels and bile composition were not altered by cholestyramine in the pregnant rat. The inability of resin therapy to change plasma high-density lipoprotein cholesterol and bile composition during pregnancy is likely to be causally related to a reduced efficacy of cholestyramine treatment when administered during gestation.     

Host defenses in acute pelvic inflammatory disease: I. Bacterial clearance in the murine uterus and oviduct

Bacterial clearance in the uterine horn and oviduct as a host defense in acute pelvic inflammatory disease was studied in 8- to 12-week-old virgin Balb/c mice. Quantitative cultures of organ homogenates were determined at various intervals following intrauterine injection of a standard inoculum of E. coli by micropuncture technique. The effect of uterine horn ligation and of estrus cycle of inoculated mice was evaluated also. Mean bacterial counts in the uterine horn were significantly higher than in the contiguous oviduct (p < 0.005), suggesting a barrier function of the uterotubal junction for bacterial passage into the oviduct. Our data suggest a protective role for the uterotubal junction, and demonstrate the influence of uterine obstruction and estrus cycle on bacterial clearance of the oviduct.     

The influence of recent use of an oral contraceptive on early intrauterine development

This paper presents the results of a study of 106 normal and abnormal fetuses aborted spontaneously by women who had recently been using an oral method of contraception. The incidence of abnormal development and the types of abnormality are presented and a comparison is made with 258 patients who suffered abortions but had used no oral or chemical method of contraception.     

Comparative cervical microflora shifts after cefoxitin or cefazolin prophylaxis against infection following cesarean section

The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin, cefazolin, or placebo for infectious complications of nonelective cesarean section. Floral shifts occurred post partum, with return of Escherichia coli and Bacteroides fragilis and a decrease in Candida colonization. No significant differences in flora existed preoperatively among patients receiving cefoxitin, cefazolin, or placebo, but by day 4, both antibiotic groups had greater enterococcal colonization. This difference was more marked with cefoxitin than with cefazolin. No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups. Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization. Results of this study indicate that a three-dose cephalosporin prophylactic regimen resulted in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group. There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anaerobic microflora between the cefoxitin and cefazolin groups.     

Variant postpartum toxic shock syndrome with probable intrapartum transmission to the neonate

We report a unique mother-infant pair with variant staphylococcal toxic shock syndrome and probable intrapartum transmission to the neonate. Diagnosis of probable toxic shock was supported by the finding of fever, desquamative skin rash, multi-organ system involvement, and pronounced mucocutaneous manifestations, including strawberry tongue, dermal swelling, pharyngitis, and vulvar edema, although hypotension was absent. Staphylococcus aureus was isolated from the vagina, placenta, chorioamnion, and surface swabs and gastric aspirates of the infant. The isolates produced enterotoxin C but not enterotoxin F, and illness developed in both mother and infant despite preexisting high antibody titers to enterotoxin F and enterotoxin C. This unique mother-infant pair highlights our present lack of knowledge of the precise etiology and pathogenesis of toxic shock syndrome and illustrates the consequent difficulty in clinical diagnosis and laboratory confirmation of this disease in certain patients with atypical presentations.     

Intrauterine asphyxia and respiratory movements in the fetal goat

The respiratory response to intrauterine asphyxia was tested by compressing the umbilical cord of the fetal goat. The fetus was prepared with intravascular catheters, electrodes, and a cord compression device at hysterotomy carried out at 98 to 113 days' gestation. After recovery from the procedure, the fetus was studied up to 144 days' gestation. Fetal respiratory movements were observed as transient negative deflections in continuous records of central venous pressure. During severe cord compression over a period of 10 to 15 minutes, the mean time to “last gasp” was 6.3 minutes. Respiratory movements reappeared within 1 to 8 minutes after release of the umbilical cord and continued for about 26 minutes. Mild cord compression led to a more prolonged respiratory response which disappeared when fetal arterial oxygen levels returned toward normal values. Episodes of spontaneous respiratory movement observed in one fetal goat were associated with mild acidosis.     

Plasma bradykininogen levels before and after ovulation: Studies in women and guinea pigs,with observations on oral contraceptives and menopause

In healthy women, there was a 41 per cent fall in plasma bradykininogen 48 (36 to 60) hours before ovulation. Similarly, guinea pigs showed a 79 per cent fall 24 (18 to 30) hours before ovulation; recovery of normal values occurred by the time of ovulation itself. The 59 per cent fall in rats took place 17 (15 to 20) hours before ovulation. The fall persisted in women using oral contraceptives containing norethindrone and mestranol (1.0:0.05 to 2.0:0.1 mg. per day); a 39 per cent fall occurred 48 hours before the calculated time of “ovulation”. The women using oral contraceptives showed a 38 per cent elevation in plasma bradykininogen levels throughout the rest of the cycle, as compared with normal women. The fall in kininogen could not be found in early postmenopausal women or in control male guinea pigs. The results show that the fall in plasma bradykininogen is essentially a preovulatory change; the possibilities that it is linked to early events in the mechanism of ovulation and that it is associated with a rhythmic mechanism more fundamental than the events obstructed by the oral contraceptives are discussed.     

Successful induction of ovulation and conception with pulsatile intravenous administration of human menopausal gonadotropins in anovulatory infertile women resistant to clomiphene and pulsatile gonadotropin-releasing hormone therapy

Gonadotropins are released in a pulsatile fashion at a frequency of between 1 and 2 hours in the follicular phase of the menstrual cycle. Human menopausal gonadotropins are usually administered intramuscularly. We evaluated the gonadal response to intravenous human menopausal gonadotropins administered in a pulsatile fashion over nine treatment cycles in three anovulatory infertile women. Human menopausal gonadotropin pulses in doses up to 12 IU follicle-stimulating hormone at frequencies between 2 to 3 hours over 3 to 17 days resulted in ovulation in five cycles with one pregnancy being conceived. In the ovulatory cycles (5,000 to 10,000 IU of human chorionic gonadotropin was used to induce ovulation), the 17 beta-plasma estradiol level was 961 +/- 128 versus 326 +/- 95 pg/ml (mean +/- SEM) in the anovulatory cycles (p = 0.015). The dose of human menopausal gonadotropins (in ampules of Pergonal, 75 IU of follicle-stimulating hormone and 75 IU of luteinizing hormone) in the intravenous cycles needed to induce ovulation was 12.3 +/- 1.4 versus 20.4 +/- 0.9 for intramuscular cycles (n = 80 in 23 women, p = 0.008). Treatment was well tolerated and without complications. We are continuing to explore the use of this apparently more efficient mode of administering human menopausal gonadotropins to anovulatory patients resistant to other techniques of ovulation induction therapy.     

Real-time ultrasound observation of breathing and movements in the fetal lamb

In seven pregnant ewes with catheters chronically implanted in the fetus, real-time ultrasound observations of fetal breathing and body movements were correlated with direct measurements of fetal arterial and tracheal pressures, heart rate, and intrauterine pressure. There was excellent correlation between the ultrasound record of fetal breathing and recordings of intratracheal pressure changes even when breath amplitude was low or frequently was high. Fetal body movements (stretches, rolls, kicks) were observed during both breathing and nonbreathing periods; vigorous movements were accompanied by rapid deflections of the amniotic and tracheal pressure traces. Movement was frequently accompanied by transient increases or decreases in heart rate. The results indicate that real-time ultrasound is an accurate method for observation of fetal movement in pregnant sheep and is particularly valuable when combined with direct measurements of fetal physiologic parameters.     

Clinical, endocrinologic, and intraovarian prostaglandin F responses to H-1 receptor blockade in the ovarian hyperstimulation syndrome: studies in the rabbit model

The effects of chlorpheniramine maleate, an H-1 receptor blocker, on clinical and endocrinologic features and intraovarian prostaglandin F (PGF) content were assessed in the rabbit model of the ovarian hyperstimulation syndrome. H-1 receptor blockade prevented ascites, attenuated ovarian enlargement (2.68 +/- 0.37 gm versus 4.15 +/- 0.056 gm; p less than 0.05), and augmented intraovarian PGF content (8.4 +/- 0.84 versus 3.95 +/- 1.12 pg/mg protein; p less than 0.05). Steroidogenesis was unaffected. In the control group, in which weights remained stable, animals with minimal ascites (scores less than or equal to 2; n = 4) were compared to other control animals with a greater accumulation of fluid (scores greater than or equal to 3; n = 4). The former also exhibited lower ovarian weights (2.94 +/- 0.41 versus 5.35 +/- 0.59 gm; p less than 0.05) and higher PGF ovarian content (6.05 +/- 1.56 versus 1.8 +/- 0.75 pg/mg of protein; p less than 0.05). This triad of minimal ascites, lower ovarian weights, and elevated intraovarian PGF seen both in treated animals and in inherently more resistant control animals did not appear to depend on changes in body weight. The conclusion reached was that H-1 receptor blockade prevented ascites, reduced ovarian enlargement, and augmented PGF content but did not affect steroidogenesis. This protective effect of chlorpheniramine may be mediated at least in part by prostaglandins.     

The action of clomiphene in stress-induced amenorrhea

Seven women with stress-induced amenorrhea were challenged with metoclopramide, 10 mg intravenously, before and at the end of a course of clomiphene. Initial testing with luteinizing hormone releasing hormone demonstrated that all subjects had the capacity to release luteinizing hormone (LH), but in response to metoclopramide there was no increase in the levels of LH. This lack of response did not change after 5 days of clomiphene, although basal levels of LH and estradiol increased significantly. The pattern of response of prolactin to metoclopramide did not change after clomiphene. These results suggest that there is no significant dopamine-mediated inhibition of release of luteinizing hormone releasing hormone in women with stress-induced amenorrhea. The administration of clomiphene to these women does not appear primarily to alter hypothalamic dopaminergic activity.     

Two-dimensional and M mode echocardiography in the human fetus

One hundred unselected pregnant women underwent M mode and two-dimensional fetal echocardiographic studies between 14 and 43 weeks' gestation. The following cross-sectional views were obtained: high parasternal short axis, parasternal long axis, four chamber view, and an extended long axis to assess the aorta. These views successfully identified great vessel orientation and size (90%), atrial and ventricular size and function (90%), presence of atrioventricular valves (92%) and semilunar valves (75%), and presence and continuity of ventricular and atrial septa (91%) and the aortic arch (68%). Factors that limited visualization were persistent unfavorable lie, maternal obesity, and oligohydramnios. Disturbances in cardiac rhythm were the prevalent abnormal findings (16%). In addition, several anatomic defects were detected in utero and confirmed at autopsy. These included a biventricular cardiomyopathy, atrial septal defect, pericardial effusion, and hypoplastic heart. The potential applications of our ability to detail human fetal cardiac anatomy and dimensions are discussed.     

Prolonged pregnancy: surveillance of the fetus and the neonate and the course of labor and delivery

The perinatal events in 184 term control pregnancies and 129 prolonged pregnancies were prospectively compared. Fetal surveillance consisted of weekly biophysical profile testing. Thirty-two infants were dysmature, and 10 of these had advanced dysmaturity. The incidence of advanced dysmaturity rose quickly after 44 weeks. This group was at greater risk for fetal distress, lower Apgar scores, and emergency cesarean section. The combination of oligohydramnios, a suboptimal nonstress test, and a low profile score was highly predictive of a neonate with advanced dysmaturity. In the control pregnancies, the rate of induction of labor was 13.81% compared with 39.84% in the prolonged pregnancies. The induced labor group had a 51.32% cesarean section rate. Our approach to prolonged pregnancy consists of elective induction of labor when the cervix is favorable and biweekly profile testing when it is not; however, the high incidence of advanced dysmaturity after 44 weeks warrants delivery.     

A proportional hazards analysis of the clinical characteristics of infertile couples

Evaluated were methods of ordering the many possible predictors of infertility outcome. The clinical characteristics of infertile couples were studied with respect to the occurrence of pregnancy during follow-up, by means of the methods of survival analysis. Among 1,297 couples who were infertile for 12 months or more, the cumulative pregnancy rate at 36 months with 95% confidence limits was 49% ± 4%. The proportional hazards analysis identified three independent predictors of the occurrence of pregnancy from the couple's history (with P values in brackets); a history of pregnancy in the partnership (0.0001); shorter duration of infertility (0.0001); and shorter length of marriage (0.005). The predictors arising from the diagnostic process (with P values in brackets) were: fewer infertility diagnoses (0.0001); a favorable primary clinical diagnosis (0.001); and the presence of any tubal disease, regardless of the primary clinical diagnosis (0.001). The analysis selected an economical set of significant predictor variables and demonstrated that a longer period of contraception was associated with a lower pregnancy rate among infertile couples. Also, three simple questions from the history were nearly equivalent to the entire diagnostic process as predictors of the outcome.     

A new computer technique for continuous measurement of the pre-ejection period in the human fetus: Physiologic significance of pre-ejection period patterns

A new interactive computer graphics system was developed for continuous online or offline measurement of the pre-ejection period (PEP) in the human fetus during both the antepartum and the intrapartum period. A significant feature is the system's ability to accurately measure PEP from the onset of the QRS complex to the beginning of aortic opening with a resolution of less than 2 milliseconds. Normal patterns of PEP prolongation were observed with fetal movement and occlusion of the umbilical cord, whereas progressive shortening of PEP was noticed with late decelerations associated with acute hypoxia. A pathologic pattern of PEP prolongation associated with late decelerations and poor heart rate variability was observed with chronic hypoxia and acidosis. These patterns suggest that continuous monitoring of PEP may be a useful adjunct to current monitoring methods when attempting to assess fetal cardiac performance and well-being.     

Nonimmunologic hydrops fetalis

Twenty cases of nonimmunologic hydrops fetalis were reviewed. The incidence of nonimmunologic hydrops fetalis was 1/2,029 (20 cases in 40,588 deliveries). The diverse etiologies of nonimmunologic hydrops fetalis are demonstrated. The incidence of erythroblastosis fetalis caused by Rh isoimmunization declined markedly. The perinatal mortality rate was 14/18 or 78%. Prematurity, the presence of congenital anomalies, and the severity of hydrops fetalis contribute to this poor prognosis. However, a better understanding of the pathophysiology of hydrops fetalis, along with early detection by ultrasonography, preterm delivery with the liberal use of cesarean section, and availability of high-risk perinatal units, may enable us to improve the prognosis. A precise diagnosis should be attempted by careful antenatal and postnatal evaluation, so that accurate genetic counseling can be offered.     

Use of oral VP16-213 as primary chemotherapeutic agent in treatment of gestational trophoblastic disease

Thirty-seven patients with persistent or metastatic gestational trophoblastic disease were treated with oral etoposide (VP16-213). All responded well and achieved permanent remission. The hematologic toxicity was mild. Alopecia was present in all patients. Etoposide is an effective drug against trophoblastic disease. In patients who have received chemotherapy for long periods oral etoposide would eliminate the problem of venous access.