Sodium nitroprusside for control of severe hypertensive disease of pregnancy: a case report and discussion of potential toxicity

Sodium nitroprusside has been used to alter blood pressure in severe hypertensive disease of pregnancy; however, concern exists in regard to potential lethal complications from cyanide toxicity in both mother and fetus. We recently evaluated levels of cyanide in the liver of an infant stillborn to a woman in whom sodium nitroprusside was used to control gestational hypertension secondary to mitral valve disease. The fetal liver demonstrated levels of cyanide below toxic ranges. Biologic activity, potential toxicity, and treatment of toxic symptoms of nitroprusside are discussed.     

Immunosuppressive activity of rhesus monkey pregnancy serum

Normal pregnancy serum from the rhesus monkey was found to have immunosuppressive activity. Using two-way stimulation, the mixed lymphocyte response was suppressed as much as 80%. Control serum from nonpregnant females was not suppressive. The inhibiting factor was found to have the following characteristics: (1) it was nonspecific in activity; (2) it inhibited the mixed lymphocyte response 20% at in vitro concentrations of 1%; (3) it was heat stable (56 degrees C for 30 minutes) and nondialyzable; (4) it was present in both the IgM- and IgG-containing fractions of pregnancy serum; (5) it was detected in postpartum and second and third trimester serum; and (6) it was at low levels or absent from the serum of two pregnancies which terminated in unexplained stillbirths.     

Secretion and biosynthesis of N-acetyl-beta-D-hexosaminidases by human placental tissues in vitro

Chorionic villi selectively secrete the B isoenzyme and, to a lesser extent, the A isoenzyme of lysosomal beta-hexosaminidase when incubated in vitro, suggesting that this tissue could contribute to maternal serum beta-hexosaminidase B and A activities in vivo. The results make it unlikely, however, that the placenta is the source of the I2 isoenzyme found in maternal serum. Samples of amnion and term chorion laeve secreted predominantly the B isoenzyme whereas first-trimester chorion laeve secreted the A, B and I2 isoenzymes. Amnion and chorion laeve may, therefore, be a source of the A, B and I2 activities found in amniotic fluid. Chorionic villi supported the cycloheximide-sensitive incorporation of [3H]leucine into immunoreactive beta-hexosaminidase thereby providing direct evidence for enzyme biosynthesis. Newly synthesized beta-hexosaminidase was detectable in the medium only after extended incubation and the secretion of beta-hexosaminidase activity continued at normal rates for several hours in the absence of protein synthesis. These results indicate that enzyme synthesis is not a primary factor in the regulation of enzyme secretion.     

Expanded care in obstetrics for the 1980s: preconception and early postconception counseling

This paper is an essay in which the suggestion is made to expand obstetric care during this decade to include preconception as well as early postconception counseling. The development of perinatal and neonatal medicine is traced and medical problems that might be improved by medical counseling before pregnancy occurs are tabulated. Diabetes is suggested as a prototype of a medical disorder for which preconception counseling would be helpful. The expansion of obstetric services into an area of preventive medicine might well begin in already established regional medical centers but should quickly expand to the offices of private obstetricians. In this broader interpretation of obstetric care, prevention of maternal and fetal or neonatal problems could decrease the cost of high-risk medical care.     

Long-term reversible contraception with levonorgestrel-releasing Silastic rods

Subcutaneously placed Silastic capsules containing levonorgestrel are effective for 5 years and have a higher continuation rate than other methods of reversible contraception. Six 3 cm capsules are required to achieve satisfactory circulating levels of levonorgestrel. Two 4 cm covered Silastic rods containing levonorgestrel, which are easier to manufacture, insert, and remove than the capsules, produce similar in vitro release rates. This study compared clinical and metabolic effects as well as bleeding patterns in 23 women using either six capsules (n = 11) or two covered rods (n = 12). Serum levels of levonorgestrel, lipids, and lipoproteins as well as frequency of elevated progesterone levels were compared in serum samples obtained before treatment and 1, 6, 12, 18, and 24 months after insertion with the two systems. While bleeding patterns were similar for users of the two systems, rod users had slightly higher serum levels of levonorgestrel and a lower incidence of cycles with elevated progesterone levels. Therefore, rods could replace capsules as a long-term, reversible contraceptive method.     

Acceleration of pulmonary surfactant maturation in stressed pregnancies: A study of neonatal lung effluent

To determine the maturation of pulmonary surfactant at birth, phospholipid patterns in tracheal or pharyngeal aspirates of 54 newborn infants were analyzed by two-dimensional thin-layer chromatography. The compositions of phospholipids and their surface tension-lowering abilities were assessed after gestations with various complications. Preterm infants with respiratory distress syndrome (RDS) lacked phosphatidylglycerol and had lower lecithin/sphingomyelin ratios than infants without RDS. An acceleration of both phosphatidylcholine (lecithin) and phosphatidylglycerol concentrations was observed in 21 preterm infants born after prolonged rupture of the membranes and treatment with isoxuprine. In these infants, the phospholipid pattern of lung effluent was similar to that of term infants even at gestational ages ≤30 weeks. Biochemical lung maturation was delayed in anencephalic infants, infants of diabetic mothers, and one infant of a mother with hypothyroidism.     

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.     

Fetal blood sampling in midtrimester pregnancies

Sonographically directed placental aspiration has been investigated as a method for obtaining fetal erythrocytes. The technique is generally successful and the fetal red cells are generally usable for the prenatal diagnosis of the hemoglobinopathies.     

Gonococcal lipopolysaccharide: A toxin for human fallopian tube mucosa

Gonococci damaged the mucosa of human fallopian tubes in organ culture (FTOC), producing characteristic pathologic features. Filter-sterilized supernatant fluid from donor gonococcal-infected FTOC damaged recipient FTOC in a similar fashion. Gonococcal lipopolysaccharide (LPS) was detected in these toxic donor fluids in concentrations of 1.2 to 8.3 μg/ml. Purified gonococcal LPS in concentrations as low as 0.015 μg/ml produced damage equivalent to that caused by toxic donor fluid and was neutralized by polymyxin B. Such LPS-mediated damage to ciliated cells, if it occurs in gonococcal salpingitis, may impair mucociliary flow and predispose to ectopic pregnancy and recurrent ascending infection.     

Application of cephalosporins to obstetrics and gynecology: Transfer of cefazolin and cephalothin to uterine tissue

Antibiotics should be administered so as to maintain effective therapeutic levels in target organs. In routine clinical treatment, however, doses of antibiotics are determined on the basis of their achievable concentrations in blood. To determine the optimum doses of antibiotics against obstetric and gynecologic infections, the authors gave a single intravenous dose of 2 gm of cefazolin or cephalothin to 51 patients before hysterectomy and measured the levels of the antibiotics in uterine tissues and compared them with corresponding serum levels. The maximum tissue levels of cefazolin were generally about 6 to 7 times higher than those of cephalothin: In the perimetrium, levels were 154 μg/gm for cefazolin and 24.1 μg/gm for cephalothin; in the myometrium, 109.5 μg/gm for cefazolin, and 15.5 μg/gm for cephalothin; and in the endometrium, 98.9 μg/gm for cefazolin and 10.4 μg/gm for cephalothin. In the tissues, however, cephalothin reached peak levels more rapidly than cefazolin. Comparisons of the tissue levels and MIC of cefazolin and cephalothin revealed that cefazolin was maintained at over 12.5 μg/gm for at least 150 minutes in the perimetrium, myometrium, and endometrium, whereas cephalothin was maintained at these levels for 40 to 50 minutes only in the perimetrium and myometrium. The ratio of tissue levels to serum levels was 40–70 to 100 for cefazolin and about 30 or less to 100 for cephalothin.     

Inhibition of estrogen synthesis does not inhibit luteinizing hormone-induced ovulation

In isolated, perfused rat ovaries, the addition of luteinizing hormone (LH) to the perfusion medium consistently induced follicular ruptures. These ruptures were preceded by a marked increase in the levels of estradiol in the perfusion medium. The addition of 4-hydroxyandrostene-3,17-dione (4-OH-A) to the perfusion medium blocked this increase in estradiol, but did not prevent ovulation. Levels of estradiol in follicular fluid were also reduced during perfusion with LH plus 4-OH-A, in comparison to LH alone. The conclusion drawn was that the marked rise in the production of estrogen by preovulatory follicies of the perfused rat ovary, induced by an ovulatory dose of LH, is not required for ovulation to occur.     

Alpha and beta adrenergic receptor activity in fetal sheep

Fetal circulatory responses to infusions of isoproterenol and methoxamine were measured in 16 fetal sheep with weights between 138 grams and 4.75 kilograms. During isoproterenol infusion in 9 animals, heart rate increased from a mean of 196 to 247 and mean umbilical blood flow increased from 211 to 269 ml. per kilogram per minute. Cardiac output, measured by radionuclide labeled microspheres, did not change significantly but was redistributed with preferential flow to the placenta and myocardium. During methoxamine infusion in 7 studies, mean arterial pressure increased from a mean value of 46 mm. Hg to 56 mm. Hg and mean unbilical blood flow decreased from 217 to 177 ml. per kilogram per minute. Cardiac output decreased in all animals (mean decrease, 22.5 per cent). Renal blood flow decreased out of proportion to the change in cardiac output; the proportion of cardiac output supplying the lungs increased, and in 6 animals actual flow to the lungs also increased.     

Effect of oral contraceptives on nutrients: III. Vitamins B6, B12, and folic acid

The interactions of oral contraceptive agents (OCA's) with vitamins were studied in a large population of women. In the upper socioeconomic groups, higher incidences of abnormal clinical signs related to vitamin deficiencies were seen in OCA users than in the control subjects. Plasma pyridoxal phosphate and red cell and serum folate were lower in subjects using OCA's in the upper socioeconomic group as compared to levels in the control subjects. Reduction in erythrocyte glutamic oxalacetic transaminase (EGOT) activity and elevation in the EGOT-stimulation test were observed in subjects using OCA's in both upper and lower socioeconomic groups. These observations suggest a relatively deficient state with respect to vitamins B₆ and folic acid in OCA users. No significant effect on serum vitamin B₁₂ was observed as a result of OCA administration.