Pyelonephritis in pregnancy: A prospective randomized trial to prevent recurrent disease evaluating suppressive therapy with nitrofurantoin and close surveillance

It has been advocated that if a patient develops acute pyelonephritis during pregnancy, she should receive suppressive therapy for the remainder of the gestation to prevent a recurrence of the disease. We have prospectively evaluated 200 patients following an acute episode of pyelonephritis during pregnancy. All patients were followed in a special clinic. Half the patients received nitrofurantoin as suppressive therapy. Recurrent pyelonephritis occurred in 7% of the patients receiving suppressive therapy versus 8% of those patients receiving close surveillance in the clinic. The results cast doubt upon the need for suppressive therapy and instead dramatized the beneficial effects of close surveillance with cultures. The data also suggest, at least in a high-risk population, that patients with gram-negative bacilluria of less than 10⁵ colonies/ml may have a substantial risk of developing symptomatic recurrences. Prompt treatment of even low levels of gram-negative bacilluria should be considered in patients at risk for recurrent disease.     

Pathogenesis of acute pelvic inflammatory disease: role of contraception and other risk factors.

In a case-control study of matched pairs, the risk of acute pelvic inflammatory disease (PID) was 4.4 times higher in intrauterine contraceptive device (IUD) users than in nonusers (p less than 0.001). Of approximately 500,000 cases of acute PID occurring annually in the United States, an estimated 110,000 are attributable to IUD's, costing over forty-four million dollars per year. PID was attributable to the IUD in 77 per cent of IUD users. No particular type of IUD was implicated. The relative risk of acute PID in IUD users over nonusers was higher in nulligravid women than in previously pregnant women and was directly related to socioeconomic status (SES), but the total annual risk of PID in IUD users appear inversely related to SES. IUD use significantly increased the risk of nongonococcal PID. Fever occurred in 13 (21 per cent) of 61 IUD users and 59 (41 per cent) of 143 nonusers (p less than 0.025). Among women with nongonococcal PID, and adnexal mass greater than or equal to 6 cm. was noted in 14 (40 per cent) of 35 IUD users and in only 12 (15 per cent) of 78 nonusers (p less than 0.01). An increased risk of gonococcal PID was found among non-Caucasians and women not using contraception, while the risk of nongonococcal PID was increased among women with a past history of gonorrhea. Oral contraceptive use may protect women with gonorrhea from developing PID. Menstruation precipitates the onset of symptoms of gonococcal PID.     

Chlamydia trachomatis infection in Fitz-Hugh-Curtis syndrome

We studied 23 patients with pelvic inflammatory disease associated with symptoms of pleuritic up'per abdominal pain, characteristic of Fitz-Hugh-Curtis syndrome (FHC). A fourfold or greater change in antibody titer to Chlamydia trachomatis was demonstrated by microimmunofluorescence in 14; an IgG antibody titer ≥1 : 1,024 was seen in 13; and IgM antibody was demonstrated in 11. Twenty (87%) of the 23 FHC patients, including all of the 12 with paired sera obtained at least 6 weeks apart, had serologic evidence of acute C. trachomatis infection. Neisseria gonorrhoeae was isolated from seven (30%) of the 23 FHC cases, and C. trachomatis was isolated from three of 10. Two groups of matched controls were studied; one group with PID but without FHC, and the other without PID. A larger proportion of patients with FHC had serologic evidence of acute C. trachomatis infection than either of the two control groups (p < 0.05 for each comparison). Among those with antibody to C. trachomatis, the geometric mean antibody titer for the FHC group (1 : 724) was significantly higher than that for the PID group (1 : 138) or for the non-PID group (1 : 103). Thus, FHC is not solely attributable to infection with N. gonorrhoeae; most cases are associated with acute C. trachomatis infection.     

Purification of lamellar bodies from human amniotic fluid

Lamellar bodies were purified from human amniotic fluid obtained from pregnancies at 17, 31, and 40 weeks' gestation by means of Sephacryl S-300 column chromatography. Fractions were labeled with diphenylhexatriene and two peaks of phospholipid were identified at each gestational age. The size of peak I increased relative to that of peak II with advancing gestational age. Further study of the two peaks from 40-week pregnancies showed that peak I contained lamellar bodies that could be identified by electron microscopy. The ratio of the concentration of protein to phospholipid for peak I varied from 0.2 to 1.1. There were four proteins which could be identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis (130K, 80K, 50K, and 20K), and there was 90-degree scattering of 400 nm light. Peak II also contained phospholipid. However, bilayer structures could not be visualized by electron microscopy, and there was no 90-degree scattering of 400 nm light. Peak II had a much higher ratio of protein to phospholipid (approximately 100) and two broad bands of protein on sodium dodecyl sulfate electrophoresis (80K, 50K). The anisotropy of diphenylhexatriene in both peaks decreased with advancing gestational age. The anisotropy in peak I was always lower than that in peak II, indicating that the microenvironment in peak I was more fluid. Peak I may represent mature surfactant and peak II, precursors of surfactant.     

Human fetal extremity lengths in the interval from 9 to 21 menstrual weeks of pregnancy

Fetal arm, leg, and foot lengths were freshly measured with vernier calipers on all fetuses aborted by me from 1975 to 1983. With the use of these measurements from the 575 patients with reliable menstrual or conception dates and uterine size in agreement (±2 weeks) with dates, statistical analyses were performed to determine the polynomial regressions of menstrual weeks of pregnancy for each extremity length. The data best fit the following formulas, where W represents weeks and F, L, and A are foot, leg, and arm lengths in centimeters: W = 3.03 + 17.4(F) ? 10.8 (F²) + 3.36(F³) ? 0.367(F⁴); W = 5.74 + 6.49(L) ? 1.90(L²) + 0.305(L³) ? 0.0161(L⁴); W = 5.19 + 5.65(A) ? 1.45(A²) + 0.203(A³) ? 0.00934(A⁴). Mean foot lengths at each week agreed well with those of Streeter, and when corrected for bias, all foot lengths were in near perfect agreement with his data.     

Computer-assisted analysis of the therapy of acute salpingitis

Isolation rates of microorganisms recovered by culdocentesis and/or laparoscopy in nine studies of salpingitis were multiplied by the proportions of each species which would be inhibited in vitro at peak and ½ peak serum levels of 13 antimicrobial drugs to yield a prediction of efficacy for the drugs. Efficacies of several hundred combinations of two and three of these drugs were estimated also. Some pairs of oral drugs were predicted to be as efficacious as some parenteral regimens of two or three drugs now in use. The predictions with this model parallel the results of some recently reported studies of therapy for salpingitis, and the model may prove to be a useful tool for future trials and therapy.     

Comparison of pharyngeal aspirate and amniotic fluid surfactant composition

Amniotic fluid and oropharyngeal aspirate lung maturity profiles obtained simultaneously at delivery in 16 patients are compared. The lecithin/sphingomyelin ratio was greater in oropharyngeal aspirates than in amniotic fluid (p less than 0.02). The percent phosphatidylinositol was greater in oropharyngeal aspirates than in amniotic fluid (p less than 0.03). The mean differences between percent phosphatidylglycerol were not significant. These findings were uninfluenced by the time interval between amniotic fluid and oropharyngeal sampling, gestational age, or neonatal weight. These data could explain the lack of sensitivity of the amniotic fluid lung maturity profile.     

Supine pressor (roll-over) test: An evaluation

One hundred supine pressor (roll-over) tests were reviewed and results were compared with clinical outcome and the literature. The present study revealed insignificant statistical differences, except for test sensitivity, in a comparison of all pregnancies without a prior history of hypertension, with subgroupings excluding patients with history of or potential urinary disease and patients with a recorded elevation in blood pressure occurring only in the early postpartum period. This lent support to the lowest false positive and false negative rates observed, 46% and 27%, respectively, seen in the subgroup having neither history of urinary disease nor significant potential for renal disease. For this subgroup, sensitivity of the test was 60%. Data were combined to create a hypothetical situation and reveal maximal potential in test predictability.     

Fetal pericardial fluid: a normal finding of the second half of gestation

In a series of 104 consecutive pregnancies ranging from 20 to 40 weeks' gestation which were examined with real-time ultrasound, we observed 46 fetuses with pericardial fluid. High resolution makes the detection of normal pericardial fluid now feasible.     

Concentrations of luteinizing hormone--human chorionic gonadotropin, beta subunit of human chorionic gonadotropin, follicle-stimulating hormone, estradiol, cortisol, and testosterone in cord sera and their correlations

Luteinizing hormone-human chorionic gonadotropin (LH-hCG), beta subunit of human chorionic gonadotropin (β-hCG), follicle-stimulating hormone (FSH), estradiol, cortisol, and testosterone were determined and correlated with each other in 62 samples of cord serum. Cortisol levels in male cord serum were significantly higher than those in female cord serum. Regression analysis showed a significant positive correlation between LH-hCG or β-hCG levels and testosterone levels in male cord serum. These data suggest that there are sex differences in the maturation of the fetal pituitary-gonadal axis.     

Nitroprusside-induced hemodynamic alterations in normotensive and hypertensive pregnant sheep

It has been suggested that sodium nitroprusside, a potent vasodilator, be used in the management of an acute hypertensive crisis during pregnancy. The present study was designed to evaluate the hemodynamic effects of this agent in the same group of chronically instrumented, unanesthetized pregnant sheep during two experimental periods: (a) normotension with intact kidneys, and (b) one-kidney hypertension. The results demonstrate that (1) nitroprusside is a potent vasodilator which lowers mean arterial pressure; (2) nitroprusside-induced tachycardia was greater in the hypertensive animal; (3) uterine blood flow decreased with the development of hypertension; (4) the hypertensive-induced reduction in uterine blood flow was increased by the infusion of nitroprusside.     

Antibody to type III group B Streptococcus in the rhesus monkey

Susceptibility to infection due to intra-amniotic type III group B streptococcal infection was studied in 27 rhesus monkeys. Sera from mothers and their offspring were tested to determine the concentration of antibody to the native type III group BStreptococcus antigen. Among 17 controls there was a statistically significant association between the concentration of maternal antibody prior to infection and both the neonatal survival rate and survival time (P < 0.05). Neonatal survival was decreased to ≤6 hours (P = 0.005) if the maternal antibody concentration was <0.5 μg/ml. Modified immune serum globulin was given intravenously to the mothers prior to intra-amniotic infection with (five animals) or without (five animals) neonatal modified immune serum globulin. Neither of the modified immune serum globulin groups demonstrated a significant reduction in the neonatal mortality rate; however, the addition of the modified immune serum globulin provided protection against rapid neonatal death among those animals born to mothers which had low or no detectable antibody. All maternal groups developed a significant increase in the concentration of antibody in postpartum sera. These results indicate that both naturally acquired and passive (modified immune serum globulin) antibodies to type III group BStreptococcus antigen are partially protective against intra-amniotic infection.     

Ectopic pregnancy: current clinical trends.

During the 16 year period ending in November, 1978, 191 cases of ectopic pregnancy were managed at the University of Virginia Hospital. The overall incidence was 1/126 deliveries but during the last 3 years of the study the incidence was 1/60 deliveries. Only 56 patients have had a subsequent conception. Thirteen have had a recurrent ectopic implantation. Only 36 women (23.7% of those available for follow-up) have had subsequent term pregnancies. Ectopic pregnancy continues to be a major gynecologic problem and the potential for subsequent fertility is poor.     

The wavering midline: a diagnostic sign of fetal hydrocephalus

The significance of midline wavering in the central nervous system as a diagnostic sign in hydrocephalus was evaluated prospectively in 27 hydrocephalic fetuses. No normal fetuses in a control group exhibited a wavering midline at three different times in pregnancy. Wavering along the entire length of the midline was seen in all 27 affected infants with hydrocephalus diagnosed from 12 to 42 weeks' gestation, prior to determination of an abnormal lateral ventricular width:hemispheric width ratio in one of 23 cases for which data were available and prior to an increased biparietal diameter in 25 (48%). One fetus, not included in the series, showed wavering of the midline echo and had an abnormal lateral ventricular width:hemispheric width ratio. The neonate was later shown to have trisomy 21 (47,XY,+21) and is suspected to have had a transient ventriculomegaly. Wavering along the complete length of the midline echo appears to be a constant finding in hydrocephalus in the fetus.     

Adjunctive use of magnesium sulfate with ritodrine for preterm labor tocolysis

The purpose of the study was to determine if the adjunctive administration of magnesium sulfate with ritodrine would result in decreased dosage requirements of ritodrine, and, therefore, decrease the incidence of ritodrine-associated side effects. Candidates for tocolysis were prospectively randomized so that some received a uniform tocolytic dose of magnesium sulfate in a blinded protocol. All patients received a ritodrine infusion which was titrated in the standard manner to achieve cessation of labor. Evaluations included interval cumulative ritodrine dose, maximal ritodrine infusion rate, fluid balance, and blood chemistry studies. Contrary to our hypothesis, there were significantly more cardiovascular effects in the group that received ritodrine plus magnesium sulfate (11/24) than in the group that received ritodrine alone (1/17) (p less than or equal to 0.02). The predominant side effect was chest pain, frequently associated with electrocardiogram changes indicative of myocardial ischemia. These results are consistent with the current understanding of the regulatory mechanisms of these tocolytic agents. We conclude from the results of our prospective, randomized, blinded study that the adjunctive use of magnesium sulfate with ritodrine is associated with an unacceptable increase in serious side effects and probably does not improve efficacy.     

The effects of superovulatory doses of clomiphene citrate on spontaneous luteinizing hormone peaks in regularly ovulating women

The effects of superovulatory doses of clomiphene citrate (150 mg orally every day for 5 days) on normal spontaneous menstrual cycles were studied in 16 women. Eight-eight percent of treatment cycles had clearly defined, timely luteinizing hormone (LH) peaks indistinguishable from those observed in normal cycles. Eight percent of treatment cycles did not have clearly defined LH peaks but were ovulatory. One cycle (4%) was anovulatory. Treated cycles were 2.1 days longer than previous control cycles (p less than 0.005). The follicular phase was significantly longer than control cycles (p less than 0.025) whereas the luteal phase was not (p greater than 0.05). There was a direct positive correlation between previous menstrual cycle length and follicular phase length in the treated cycle (r = 0.730, 0.01 less than p less than 0.05). The conclusion was that 96% of menstrual cycles of normally ovulating women remained ovulatory when the women were given superovulatory doses of clomiphene and that 88% of the cycles had clearly defined LH peaks.