Frederick P. Zuspan

Fetal stress from methadone withdrawal

A pregnant patient in the midtrimester of pregnancy was begun on a methadone detoxification program. The fetal neurobiologic response was monitored by serial amniotic fluid amines (epinephrine and norepinephrine). The detoxification program showed a marked fetal response of the adrenal gland (E) and sympathetic nervous system (NE) that was blunted when the methadone dose was increased. Detoxification during pregnancy is not recommended unless the fetus can be biochemically monitored.

Observation and treatment of neonatal narcotic withdrawal

A total of 110 infants born to mothers who were either in a methadone maintenance program, using heroin, or recently detoxified, were studied during the neonatal period. Of these infants, 93.6 per cent developed withdrawal symptoms. No significant differences were determined in therapeutic response among those infants treated with methadone, phenobarbital, and diazepam. There was a significant reduction in the frequency of withdrawal symptoms among infants born to mothers whose methadone dose at time of delivery was less than 20 mg (17.9 per cent). It is suggested that reduction of methadone dosage in late pregnancy results in reduced incidence of withdrawal but must be carefully carried out.

Levels of prostaglandins F2α and E2 in human endometrium during the menstrual cycle

Abstract A comparison between the prostaglandins found in proliferative and secretory endometrium in normal and tumor-bearing tissues is reported. The content of prostaglandins F 2α and E 2 is related to the three phases of the menstrual cycle and correlates with cyclic ovarian hormone variations. The menstrual phase is characterized by a high content of PGF 2α . High prostaglandin levels are found in tissues from patients with pathologic diseases such as adenocarcinoma of the endometrium when compared to normal tissues.

Ovulatory plasma amine (epinephrine and norepinephrine) surge in the woman

Abstract Two normally cycling women were studied through one complete menstrual cycle with daily oral basal body temperature recordings and daily 24 hour urine collections. Blood was drawn in the basal state beginning with one patient on Day 9 and with the other patient on Day 12 of the menstrual cycle. Blood determinations were for follicle-stimulating hormone, luteinizing hormone (LH), and plasma epinephrine and norepinephrine. Urinary determinations were for creatinine, epinephrine, and norepineprine. Results indicate that a gradual rise in urinary norepinephrine occurs following ovulation which is greater than the preovulatory excertion. Urinary epinephrine does not significantly vary during the stages of the menstrual cycle. One patient showed a significant plasma amine surge on the same day as the LH surge. The other patient showed a plasma amine surge on the day of the LH peak and also on the 2 preceding days. These observations of a plasma amine surge in the woman that coincide with or precede the LH surge have not been previously reported. They indicate an increased sympathetic response around the time of ovulation and are most likely associated with a central phenomenon.

Studies of human amniotic fluid phospholipids in normal, diabetic, and drug-abuse pregnancy

Abstract The lecithin/sphingomyelin (L/S) ratios correlate well with gestational age only in normal human pregnancy. The level increases dramatically near term. Good correlation is noted between the higher L/S ratio and respiratory function. There is a higher level of palmitic acid (16:0) in phosphatidyl choline at term than in earlier gestation. The palmitic acid level in phosphatidyl choline is of diagnostic value for the maturity of the fetus in normal human pregnancy. Diabetes mellitus (Classes A, B, and C) and the drug methadone delay maturation of the fetal lung; therefore, the L/S ratios correlate poorly with gestational age as compared with normal pregnancies.

Adrenal gland and sympathetic nervous system response in eclampsia

Abstract Urinary epinephrine and norepine phrine values were used as indices to evaluate the adrenal gland and sympathetic nervous system response, respectively, in 14 eclamptic patients. The study period focused on the temporal relationship of the convulsion and delivery process. Values were compared to previously established norms for the same study period. The data showed an increased adrenal gland activity as measured by epinephrine in 17 of 25 urine samples. Increased sympathetic nervous system activity, as measured by norepinephrine, was present in 18 of 25 urine samples. Elevated mean blood pressures were associated with increased amine levels in all but 2 eclamptic patients. The implications of these findings of increased adrenal gland and sympathetic nervous system activity are discussed.

Amniotic fluid lipids in normal human pregnancy

Abstract The content of total lipids of amniotic fluid increases with gestational age and reaches its maximum at term. The lipid contains relatively more phospholipids, free fatty acids, hydrocarbons, and cholesteryl esters, but smaller amounts of triglycerides. This is the well-defined characteristic of the amniotic fluid lipid. The increase in phospholipids at term could be due to a larger contribution from tracheal fluid at that time. The phospholipids, particularly lecithin, apparently act as strong surfactants. Analysis of the phospholipid L / S ratio becomes important to the diagnosis of the status of the fetus (maturity). The role of hydrocarbons and alcohols in amniotic fluid remains to be determined.

Identification of a pressor substance in amniotic fluid

Unidentified pressor material has been isolated from amniotic fluid of toxemic patients by several investigators. Other investigators have not been able to confirm these substances. This paper deals with the isolation and identification of a specific pressor agent (norepinephrine) in amniotic fluid of normal pregnancies. Details are enumerated pointing out the necessity of meticulous handling of this fluid if data are to be valid. Catecholamine values, i.e., epinephrine and norepinephrine, are altered by pH change, temperature, preservatives, interfering substances, storage in deep freeze, and an enzyme inhibitor. A specific method is outlined to overcome these problems so that valid values are obtained. Amniotic fluid represents an amount equivalent to 2 days’ output of fetal urinary catecholamines, approximately 1.0 μg per liter of epinephrine and 3.0 μg per liter of norepinephrine. A pressor agent in amniotic fluid has been identified as norepinephrine; however this probably has no effect on the maternal organism. This report is the first in the English language to identify a specific pressor agent.

Content of amniotic fluid prostaglandins in normal diabetic and drug-abuse human pregnancy.

This study attempts quantification of prostaglandins (PGs) in amniotic fluid antepartum at 24, 26-33, 34-36 weeks of gestation and in labor in 6 normal patients, 6 diabetic patients, 3 patients taking methadone, and 1 patient taking heroin. Results of measurements of PGs showed that in the different weeks of gestation, the contents of PGs were essentially unchanged. PG values increased considerably at the time of labor, with no differences in the content of PGs in labor of normal, diabetic, and drug-abuse patients. The dominant fraction was PGF2alpha either during pregnancy or during labor, and the smallest fraction was PGE2 during gestation and PGE1 during labor. Significant differences of PGF2alpha concentrations were found in the serum of women at various stages of gestation. The high PG content in the amniotic fluid in labor indicates that PGs are needed for initiation of labor, and their origin is probably of fetal and decidual origin.

Relationship between catecholamines and the periodicity of spontaneous uterine activity in a nonpregnant primate (Macaca mulatta).

Rhesus monkeys weighing 6-8 kg and demonstrating regular menstrual cycles were used to delineate the relationships between the circadian patterns in spontaneous uterine activity, the urinary excretion of 2 catecholamines, norepinephrine and epinephrine, and the alterations in adrenergic neuroreceptors. In Experiment 1 norepinephrine and epinephrine concentrations were determined by the Zuspan and Cooley method. These values were correlated with the circadian patterns of spontaneous uterine activity. In Experiment 2 the effect on the circadian pattern evidenced by spontaneous uterine activity of pharmacologic depletion of catecholamines as well as selective blocking of alpha and beta adrenergic receptors, were evaluated. Constant iv infusion of reserpine was used to suppress catecholamines as well as selective blocking of alpha and beta adrenergic receptors, were evaluated. Constant iv infusion of reserpine was used to suppress catecholamines. In Experiment 1, lowest values occurred in the secretory phase during the periods of darkness, and highest values occurred in the proliferative phase during periods of light. Intrauterine pressure and norepinephrine excretion consistently exhibited diurnal variations conforming to sine curves and were statistically correlated (r = .838, p less than .001). In Experiment 2 the continuous infusion of reserpine produced a dose-related reduction in the average values and circadian patterns of uterine activity and norepinephrine and epinephrine excretion. Baseline resting pressures were reduced by phentolamine infusion. The frequency of contractions were also reduced and the diurnal variations of uterine activity abolished. Beta blockade increased the resting pressure and the amplitude of contractions. The results suggest that adrenergic receptors and catecholamines have a causal role in the occurrence of spontaneous variations in and the establishment of the circadian pattern of uterine activity.