Search

Chemical reduction of naltrexone is described in an attempt to synthesize 6-beta-hydroxynaltrexone. Only the epimer, 6-alpha-hydroxynaltrexone, was produced. Pilot metabolic studies on naltrexone in the dog, rat, and guinea pig were made to determine which animal produced the greatest amount of 6-beta-hydroxynaltrexone. The guinea pig was selected and used to produce the metabolite. Isolation and purification methods are described, and spectral data are presented for structural confirmation of the metabolite.

Normorphine metabolism was studied in dogs given 20 mg of normorphine hydrochloride/kg sc. Free and (onjugated normorphine excreted in the urine over 144 hr represented 32 and 32%, respectively, of the administered dose. Eighty percent of the urinary excretion of the drug occurred within 9 hr. One percent of the administered dose was excreted as free normorphine in the feces. The urine was chromatographed on a column. Evaporation of the washing and methanolic effluent yielded a residue, which was purified by crystallization from aqueous methanol. Results of UV and IR studies, elemental analysis, and determination of normorphine and glucuronic acid content established the identity of this metabolite as normorphine 3-glucuronide. Dihydronormorphine and dehydronormorphine were detected with GLC-mass spectrometry as minor metabolites.

The effect of intravenous infusion of angiotensin II (2 to 200 ng/kg/min) on uterine blood flow and cardiovascular performance was studied in the normotensive, unanesthetized pregnant ewe. With low rates of infusion (2 to 4 ng/kg/min), only a transient increase in uterine blood flow, lasting 1 to 3 minutes, was observed. Higher rates (110 to 200 ng/kg/min) of infusion caused a decrease in uterine blood flow; this decrease was significantly correlated to the dose. Angiotensin II also caused a significant decrease in the maternal heart rate and an increase in mean maternal arterial blood pressure as the rate of infusion was increased. A high rate of infusion resulted in decreased fetal heart rate and PaO2, probably due to a marked reduction in uteroplacental blood flow.

398 infants with birthweight (BW) 500-1500 g born from January 2 1982 to December 1983 were studied to determine incidence and survival rate by BW and gestational age (GA) categories and to determine causes of death and factors influencing mortality. 58% of the group survived. Factors other than those in the perinatal and postnatal period did not significantly influence survival. Infants with BW below 1000 g delivered by elective C-section had better survival than those delivered vaginally. Survival increased progressively with increasing BW and GA categories with GA more than BW being the limiting factor. Eleven (6.6%) of the deaths in the very low birth weight infants occurred during the nursery period after 28 days of age. These deaths would not have been addressed in the neonatal mortality.

Heroin and its metabolites, 6-monoacetylmorphine, morphine, and normorphine, were determined in human urine with a GLC procedure. Heroin was extracted with chloroform at pH 4.5 and chromatographed at a temperature programmed from 200-250 degrees by 8 degrees/min. 6-Monoacetylmorphine and morphine were extracted with ethylene dichloride containing 30% isopropanol at pH 8.5, and normorphine was extracted at pH 10.4 wtih the same solvent. The extract was derivatized with trimethylsilylimidazole and chromatographed at 230 degrees for the determination of 6-monoacetylmorphine and morphine and at 220 degrees for normorphine and morphine.

Correlation between Goodwin's high-risk score and Apgar score was studied in 266 pregnancies managed with the use of the information from clinical monitoring. The correlation coefficients between Goodwin's score and Apgar scores were -0.3178 for one-minute Apgar scores and -0.2668 for five-minute Apgar scores. Both are significant at the level of p less than 0.001. When the patients were divided into two groups by Goodwin's score, fetuses of the group with the higher score (greater than or equal to 4) were significantly more acidotic than those of the group with the lower score. Therefore, Goodwin's high-risk scoring system is simple and useful in the selection of potential risk patients.

Antepartum assessments of amniotic fluid volumes and their relationship to nonstress test patterns and pregnancy outcomes were retrospectively analyzed in 234 postdate pregnancies. The incidence of clinical oligohydramnios and a nonstress test revealing fetal heart rate deceleration or bradycardia was found to increase as the sonographic estimates of the amniotic fluid volume decreased. Furthermore, the postdate pregnancy with sonographic evidence of an adequate amniotic fluid volume had a significantly better perinatal outcome than the pregnancy without an adequate fluid volume. These results suggest that the postdate pregnancy with evidence of reduced amniotic fluid volume should be considered for a trial of labor with continuous electronic fetal monitoring.

Male Sprague-Dawley rats received 20 mg/kg of pyrilamine or tripelennamine intraperitoneally. The extract obtained from an enzymatically hydrolyzed urine was derivatized with or without Tri-Sil Z and analyzed by GC/MS. 2-(2-Dimethylaminoethyl)aminopyridine, 2-(4-hydroxybenzyl)aminopyridine, 2-[4-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2-methylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine were detected as metabolites of pyrilamine. 2-(2-Dimethylaminoethyl)aminopyridine, 2-(alpha-hydroxybenzyl)aminopyridine, 2-[alpha-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxybenzyl-(2-dimethylaminoethyl)amino]pyridine, 2-[4-hydroxy-3-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine, and 2-[3-hydroxy-4-methoxybenzyl-(2-dimethylaminoethyl)amino]pyridine were detected as metabolites of tripelennamine. Thus, N-debenzylation of tripelennamine and N-demethoxybenzylation of pyrilamine occurs in vivo, through an intermediate of alpha-carbon oxidation and represents a new metabolic pathway for these compounds. The identity of the metabolite was confirmed by comparison with an authentic sample of 2-(2-dimethylaminoethyl)aminopyridine. The pharmacological implication of 2-(2-dimethylaminoethyl)aminopyridine, one of the metabolites of pyrilamine and tripelennamine, is discussed.

This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%) in the density of [3H]paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of [3H]mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.

The effect of tripelennamine on pentazocine antinociception in rats was investigated utilizing a low temperature (51.5 degrees C) hot-plate technique. Tripelennamine (10 and 20 mg/kg i.p.) showed some antinociceptive activity, which was not antagonized by naloxone. Pentazocine antinociception was potentiated by simultaneous administration of a large dose (20 mg/kg) but not a small dose (5 mg/kg) of tripelennamine. Potentiation was not observed when tripelennamine was administered 2 hr before the injection of pentazocine and chronic administration of tripelennamine for 14 days did not alter pentazocine antinociceptive activity. After administration of pentazocine and tripelennamine, levels of pentazocine under concentration-time curves in the brain and plasma were slightly and significantly larger, respectively, than the levels obtained by the administration of pentazocine alone. After the administration of tripelennamine and pentazocine, the brain tripelennamine concentration at 1/4 hr was about 2.6 times that after the administration of tripelennamine alone. The results suggest that the effect of tripelennamine on pentazocine antinociception is additive; very little was through a mechanism of inhibition of pentazocine metabolism.

In 13 patients, episodes of transient fetal cardiac arrest were observed in a group of 594 extensively monitored labors during a given 3-year period. The number of episodes per patient ranged from one to six, with a maximal duration of cardiac arrest (R-R interval) being 5.2 seconds. All of the patients responded to changing maternal position or termination of pregnancy except 1. This patient received Atropine as a premedication for cesarean section. The parasympatholytic properties of Atropine minimized the severity of cardiac arrest. The effect of cardiac arrest on fetuses is not clearly shown in these preliminary observations. The prompt elimination of cardiac arrest is thought to be imperative in reducing perinatal loss. Cardiac arrest is though to be an extensive form of severe variable deceleration. The hypothesis is made that these fetuses had an unbalanced autonomic nervous system and/or an overwhelming vagal tone. If these signs are detected early by fetal monitoring, attention should be paid to the possibility of cardiac arrest.

Mitochondrial ATPase and adenylate kinase activity of hepatoma cells were inhibited by hematoporphyrin derivative (HPD) followed by photoirradiation. Inhibition of ATPase activity was a dose- and time-related event. Malonaldehyde (MDA) content of mitochondrial membranes was markedly increased by HPD plus light. The content of mouse liver microsomal cytochrome P-450 was greatly increased after intraperitoneal injection of HPD for 4 days (5 mg/kg/day). The liver weight, and levels of liver microsomal G-6-phosphatase, MDA and triglyceride (TG) showed no difference in treated vs. control animals. The data presented here demonstrate that mitochondria may be a sensitive site of action of HPD photosensitization, and inactivation of ATPase and adenylate kinase may be an important contributing factor to tumor cell damage and death.

Biotransformation of morphine to dihydromorphinone and normorphine was studied in several mammalian species. Free and total dihydromophinone, morphine, and normorphine in the urine were determined, as propionyl derivatives, with a gas-chromatographic technique. Dihydromorphinone was detected as a morphine metabolite in the acid-hydrolyzed urine of all species studied except the dog and morphine-dependent man. Normorphine in both free and conjugated forms was detected in the urine of all species studied. The degree of biotransformation of morphine to dihydromorphinone in the guinea pig did not change during chronic administration of morphine sulfate, 25 mg/kg, daily for 28 days. The small amounts of dihydromorphinone and normorphine produced as metabolites make it unlikely that they play any significant role in the modification of the pharmacologic effects of morphine.

Direct systolic, diastolic, and mean arterial blood pressure was continuously recorded during the first 64 min of life in 150 newborn infants. The data were analyzed at 4, 8, 16, 32, and 64 min. The highest blood pressure values were noted during the first few minutes of life in all newborn infants, with a rapid drop within 4 to 8 min. Decline in blood pressure was more gradual throughout the remainder of the observation period. Blood pressures of depressed newborn infants at birth (Apgar scores 6 or less at 1 and 5 min) were compared to those of normal newborn infants (Apgar scores 7 or greater at 1 and 5 min). The former demonstrated generally higher systolic pressures during the first 16 min and diastolic pressures at 4 min when infants were compared by their 1 min Apgar scores and higher diastolic pressures at 4 min when the infants were compared by their 5 min Apgar scores.

From the beginning of biophysical and biochemical monitoring of the fetus during labor, a continuing attempt has been made to determine if a reliable correlation exists between these measurements and the well-being of the fetus. If such a correlation did indeed exist, the combined use of the two approaches would permit efficient, relatively simple fetal monitoring. This preliminary report describes the use of computer processed fetal heart rate patterns to predict fetal scalp blood pH. Initial results show a 90% overall accuracy in predictions; when corrected for some of the bias of retrospective predictions, the accuracy is 91% for high pH and 72% for low pH.

Spectral analysis techniques were used to quantitate the association between respiration and heart rate variability in eight healthy and eight asphyxiated infants born at term gestation. Respiratory sinus arrhythmia was demonstrated in all healthy infants. This arrhythmia was significantly diminished in asphyxiated newborn infants. We conclude that newborn infants with low Apgar scores have a reduced respiratory sinus arrhythmia and that this reduction could account for the loss of short-term heart rate variability commonly associated with asphyxia.

A practical management protocol to handle the large volume of post-term gestations at the Los Angeles County/University of Southern California Medical Center was introduced and evaluated in 880 patients seen between March 1, 1979, and February 29, 1980. The protocol divided patients into 2 groups based on substantiated "good" or unsubstantiated "poor" obstetric dates. After clinical examinations, the primary screening test used was twice weekly plasma unconjugated estriol (E3) determinations. Antepartum fetal heart rate testing, in the form of nonstress tests, was used initially in the good obstetric dates group, and then done twice weekly only if the E3 value was abnormal (less than 18 ng/ml with good obstetric dates and less than 12 ng/ml with poor obstetric dates). Patients with good obstetric dates were delivered electively at more than 42 weeks' gestation if the cervix was favorable (Bishop score 9 or greater); otherwise, intervention occurred only with abnormal tests and a positive or suspicious contraction stress test, or with other medical indications. Only 8 perinatal losses (3 neonatal deaths and 5 stillbirths) occurred in 880 patients. Each of these patients received a follow-up evaluation: 3 had severe congenital anomalies, and 5 deaths occurred in patients who did not comply with the protocol. The cesarean section rate was 15.8%.

A gas chromatographic-mass spectrometric assay for eight opium alkaloids in human urine following opium ingestion is described. The compounds were extracted from urine with methylene chloride-isopropanol (7:3, v/v) at pH 9.5, evaporated, derivatized with Tri-Sil Z and analyzed by methane chemical ionization mass fragmentography. The method in sensitive to ca. 0.01 microgram/ml for morphine and codeine and ca. 0.05 microgram/ml for the other compounds. Adsorption problems on the gas chromatography column prevented obtaining reproducible results for the measurement of noscapine. Extraction efficiencies over the pH range of 8-11 for the eight compounds are reported. Retention times of the opium alkaloids were determined using five different liquid phases (3%) on Gas-Chrom Q (100-120 mesh) and two column lengths (36 cm and 183 cm). The 36-cm column packed with OV-210 was selected for use in the assay. Ions were selected for monitoring for each component from their methane chemical ionization spectrum to provide the needed sensitivity and specificity for analysis of a multi-component mixture. The assay was used for the analysis of an "opium eater's" urine. Morphine, codeine, nomorphine, norcodeine and noscapine were detected; however, no evidence was obtained for thebaine, papaverine or oripavine. Unconjugated morphine (0.64 microgram/ml) was present at nearly twice the concentration of codeine (0.37 microgram/ml) and normorphine and norcodeine were present in equal amounts (ca. 0.15 microgram/ml).

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.

The pharmacokinetics of single and combined doses of pentazocine HCl (40 and 80 mg) and tripelennamine HCl (50 and 100 mg) were studied in six healthy drug abusers. After intramuscular administration of 40 or 80 mg pentazocine alone, mean peak plasma concentrations at 15 minutes were 102 and 227 ng/ml, respectively, and mean plasma t1/2 values were 4.6 and 5.3 hours, respectively. After intramuscular administration of 50 or 100 mg tripelennamine, mean plasma concentrations at 30 minutes were 105 and 194 ng/ml, respectively, and mean plasma t1/2 values were 2.9 and 4.4 hours, respectively. After concurrent administration of pentazocine with tripelennamine, plasma pentazocine and tripelennamine concentrations at all time points were not significantly different from those when pentazocine or tripelennamine was administered alone. Coadministration of pentazocine and tripelennamine had no effect on the distribution, elimination, and clearance of either pentazocine or tripelennamine. In conclusion, there did not appear to be a clinically significant metabolic interaction between pentazocine and tripelennamine.

Morphine, morphine glucuronide, morphine ethereal sulfate, normorphine and total normorphine in three consecutive 24-hour urines of four morphine-dependent subjects receiving morphine sulfate 60 mg s.c. q.i.d. have been determined with thin-layer chromatography and gas-liquid chromatography. With thin-layer chromatography the mean daily excretion of free morphine was 10% of the administered dose; morphine glucuronide, 65%; total (free and acid hydrolyzable conjugate) morphine 85%; and total normorphine, 3.5%. With gas-liquid chromatography, the percentage excretion for free morphine was 10%; total morphine, 74%; free normorphine, 1%; and total normorphine, 4%. The excretion of total drug was linearly related to the volume of the daily urine output.

Postdate pregnancy presents a difficult problem in both the antepartum and intrapartum periods. Because of the various complications associated with prolonged gestation, the following precautions should be taken during intrapartum monitoring and delivery: 1. Strict criteria must be established for elective induction should it be needed. Elective induction should be limited to those postdate patients with inducible cervices. 2. Extensive intrapartum fetal heart rate and uterine activity monitoring should be done on all patients. Physicians should be alert and ready for intervention and for any possible abnormal finding. Fetal biochemical assessment should be done liberally, especially when meconium is passed. 3. For patients with thick meconium passage, close intrapartum surveillance should be done by both biophysical and biochemical means. During delivery, attention should be given to minimizing the possibility of meconium aspiration. Good neonatal resuscitation is essential. 4. When the estimated fetal weight is 4500 gm or greater, the possibility of shoulder dystocia should be considered. Unless the patient's previous obstetric history or the progress of labor suggests a possible successful vaginal delivery, cesarean section should be considered.

Four new meperidine metabolites were identified by GC-MS in the urine of rats, guinea pigs, rabbits, cats, and dogs. In addition to known meperidine metabolites, 4-ethoxycarbonyl-4-phenyl-1,2,3,4-tetrapyridine (dehydronormeperidine; IV, the N-hydroxydehydro derivative of normeperidine (X), the dihydroxy derivative of meperidine (XII), and the dihydroxy derivative of normeperidine (XIII) were identified. The possible role of the N-hydroxy derivative of normeperidine (IX) in the pharmacological interaction of meperidine (I) with MAO inhibitors, seen selectively in the rabbit (and humans), is discussed. Following the administration of the p-hydroxy derivative of meperidine (VII), the major metabolite was conjugated VII. Trace amounts of the p-hydroxy derivative of normeperidine (VIII), the methoxy hydroxy derivative of meperidine (XI), XII, and XIII also were detected as metabolites of VII. The degree of N-demethylation of VII, both in vitro and in vivo, was small.

Ligation of the hypogastric arteries has been recommended for control of obstetric hemorrhage. However, specific information regarding its effectiveness is lacking. The hospital charts of 19 patients undergoing bilateral hypogastric artery ligation for the control of otherwise intractable obstetric hemorrhage were reviewed. Indications included uterine atony (15), lateral extension of a low-transverse uterine incision (three), and placenta accreta (one). This procedure was effective in controlling bleeding in eight of 19 patients (42%). Hysterectomy was necessary in the remaining 11 patients. In these patients, blood loss, operating time, and intraoperative morbidity was increased when compared with a group of 59 patients undergoing emergency hysterectomy for obstetric hemorrhage without prior ligation of the hypogastric arteries. Surgical approaches to hypogastric artery ligation are discussed.

Baseline FHR variability has been quantitated into the mathematical indices of differential index (short-term variability) and interval index (long-term variability). Normal values have been determined. The effect that drugs used during labor have on FHR baseline variability has been evaluated. A clinically meaningful change in variability has been observed following low-dose administration of Demerol, morphine, Nisentil, Phenergan, and Vistaril. A statistically significant increase in variability has been observed following administration of magnesium sulfate.

O-Demethylation of pyrilamine with l-propanethiol and potassium tert-butoxide gave hydroxytripelennamine, one of the major metabolites of tripelennamine. The reaction of pyrilamine with other demethylating agents has been explored and the products formed have been characterized. The reaction of pyrilamine with 48% hydrobromic acid yielded 2-(2-dimethylaminoethyl)aminopyridine. When a mild, neutral demethylating agent, Me3Sil, was used, 2,3-dihydroimidazopyridinium iodide was the sole product formed.

The analgesic activity of oripavine and phi-dihydrothebaine (5, 6, 8, 14-tetrahydro-4-hydroxy-3, 6-dimethoxy-17-methylmorphinan) has been studied in the mouse and rat with the hot-plate technique after s.c. drug administration. Peak analgesic effects in the mouse and rat were observed 20 min following drug administration, and the effect lasted about 40 to 60 min. Median analgesic (AD50) and lethal (LD50) doses and 95% confidence limits are presented. Oripavine and phi-dihydrothebaine appear to have analgesic potency of the same order as morphine in these species but have low therapeutic indexes because of severe toxicity. Toxic signs of oripavine and phi-dihydrothebaine in both species were clonic-tonic convulsions followed by death. The toxicity of oripavine, phi-dihydrothebaine and morphine in the mouse did not appear to be antagonized by pretreatment with 1 mg/kg of naloxone given 10 min prior to the test drug. toxicity does not appear to be mediated at the opiate receptor; however, oripavine did show some cross tolerance with morphine, but did not appear to suppress morphine abstinence in the mouse and rat.

The effect of magnesium sulfate on fetal heart rate (FHR) variability and uterine activity is evaluated in 19 preeclamptic patients at term in active labor. Magnesium sulfate was given by intramuscular injection in nine patients and by intravenous infusion in 10 patients after an intravenous loading dose over a period of 15 minutes. No significant change was noted in FHR variability. There was only a transient, mild decrease in the frequency of uterine contractions during the magnesium sulfate loading dose, and there was no significant change in the intensity of uterine contractions. The conclusion is that, when magnesium sulfate is used for treatment of mild preeclampsia in patients at term in established labor, there is no clinically significant effect on FHR variability or uterine activity.

Morphine metabolites were isolated with column chromatography on a resin and neutral aluminum oxide and TLC from the urine of morphine-dependent subjects maintained on morphine sulfate at a dose of 240 mg/day. These metabolites were characterized as morphine 3-glucuronide, morphine 6-glucuronide, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, normorphine 6-glucuronide, and, possibly, normorphine 3-glucuronide by free phenol and glucuronide tests, enzymatic hydrolysis, GLC, TLC, UV spectroscopy, and GLC--mass spectrometry.

The purpose of this study was to investigate the kinetics of urinary excretion of heroin and its metabolites in human subjects. Heroin and its metabolites were determined with gas-liquid chromatography. Two studies were conducted, each using 10 subjects. After i.v. administration of heroin HC1, 10 mg/70 kg, urine was collected every 8 hours and ad libitum for 1 week in the first study and every 2 hours in the first 8 hours and then at less frequent intervals for 24 hours in the second study. Heroin, 6-acetylmorphine, morphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were determined in the first 24-hour urine and accounted for 0.5, 1.5, 7.2, 52 and 4%, respectively, of the administered dose. Conjugated morphine could be detected in the urine 96 hours after drug administration. Eighty-eight percent of the free morphine and 84% of the total morphine found in the urine were excreted in the first 8 hours. The half-lives of urinary excretion of free morphine, 6-acetylmorphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were 1.28, 1.31, 2.76 and 2.72 hours, respectively. It was concluded that heroin in the body was rapidly metabolized and its metabolites were rapidly excreted in the urine.

From a clinical service using the contraction stress test as an evaluator of fetal well-being, a 37-month review of the significance of the suspicious contraction stress test was performed. There were no antepartum losses in a group of 107 patients whose initial test was suspicious. Following each testing a number of patients delivered spontaneously or were delivered for other reasons. Results in 5 of 67 patients at the second testing changed from a suspicious to a positive test, 36 became negative, and 26 remained suspicious. There were no further conversions to a positive test after the second testing. There is a strong correlation between the loss of fetal heart reactivity and the repeated suspicious contraction stress test. The chief value of the suspicious test is as a marker in the high-risk pregnancy appraisal for consideration of additional fetal and maternal evaluation and possible clinical management alteration.

To test the hypothesis that spacing the injection interval by 10 minutes would reduce the incidence of post-paracervical block bradycardia, 42 healthy subjects at low risk with normal fetal heart rate (FHR) patterns were included in a randomized trial. Twenty patients were given a conventional paracervical block (ie, almost simultaneous injection of the 2 sides), whereas 22 patients were given the second injection after a 10-minute interval. All patients were laterally positioned for 30 minutes before and 60 minutes after administration of the paracervical block. There were no cases of post-paracervical block bradycardia in either group, but a decrease in the baseline FHR of 5 beats per minute or more occurred in one half of each group. Both groups experienced significant decreases in the mean FHR. The authors conclude that patient selection and perhaps lateral positioning are more important than is spacing the injection interval. Furthermore, in properly selected subjects paracervical block offers simple, effective, and safe analgesia.

The fetal biparietal diameter (BPD) was measured at the time of real-time ultrasound-directed amniocentesis in 159 cases and a phospholipid profile was obtained from the amniotic fluid. BPD measurements of 9.0, 8.7, and 9.2 cm were then compared with a lecithin/sphingomyelin (L/S) ratio greater than or equal to 2.0 for the ability to predict the presence of phosphatidylglycerol (PG) in the profile. The data from the diabetic and nondiabetic patients were analyzed separately. The results demonstrated that in the presence of a L/S ratio greater than or equal to 2.0 the BPD does not aid in the identification of amniotic fluid samples which contain PG in either the diabetic or nondiabetic groups. The data also confirmed previous findings that the BPD is not a reliable predictor of the L/S ratio. It is concluded that for the detection of PG in amniotic fluid, the use of real-time ultrasonic cephalometry cannot substitute for the performance of the phospholipid profile.

Three FHR deceleration areas of fixed durations related to the onset of the concomitant uterine contraction were evaluated automatically with a small digital computer during labor. The correlations between these areas and the fetal scalp blood pH values were studied. The deceleration occurring 80 to 140 seconds after the onset of each uterine contraction during the 20 minutes preceding the fetal blood sampling presented the best correlation (r equals minus 0.453) with fetal pH values. In addition to FHR deceleration area, baseline FHR variability should be considered in predicting fetal condition.

Fetal monitors that feature autocorrelation have recently been introduced. This paper discusses autocorrelation and describes how it extracts periodic signals from a noisy background. An example of its performance under clinical conditions demonstrating advantages and limitations is discussed.

The estimation of weight in the very low-birth weight fetus (less than 1500 gm) is becoming more important in obstetric management as neonatal nurseries are reporting better outcome in this weight category. It has become clear that assessment of weight can best be accomplished through the use of ultrasound. In many institutions, however, ultrasonography is under the control of other departments and is not readily available. This arrangement prevents rapid access and compromises the benefit of the technique. To evaluate the accuracy of scans performed in very low-birth weight infants by personnel with limited training in ultrasonography, we undertook a systematic study of weight estimates in this select group of patients. To date, 31 ultrasound examinations have been performed by staff physicians and 50 by resident physicians. Comparisons made between ultrasound examinations by staff and resident physicians showed that the absolute error between the ultrasound-predicted weight and the actual weight, though less in the case of staff physician examinations, was not statistically significant.

Two endogenous ligands which interact preferentially with the sigma opioid receptors were identified from the guinea-pig brain extract in a Sephadex G-50 fractionation. These two ligands inhibited more potently the binding of [3H]SKF-10047 to sigma opioid receptors than [3H]naloxone to mu opioid receptors, [3H]ethylketocyclazocine to kappa opioid receptors and [3H]DADLE to delta opioid receptors. In the phencyclidine receptor assay, these two ligands were almost inactive. Incubation of these ligands with trypsin destroyed at least 50% of the activities in the sigma opioid receptor assay. Both ligands inhibited the sigma binding in a dose-dependent manner. The inhibition could be eliminated when the two ligands were removed from incubation media by extensive washings. It is therefore concluded that sigma opioid receptors are not phencyclidine receptors and that endogenous ligands for sigma opioid receptors may exist in the brain.

A randomized study on the effect of terbutaline on fetal distress was carried out in 20 patients who showed evidence of ominous fetal heart rate patterns and fetal scalp blood pH values of less than 7.25. Of those, 11 received terbutaline (study group) and nine did not (control group). There was a significant improvement in the acid-base status of the fetus in the study group compared with those in the control group (p less than 0.01). No significant maternal or fetal morbidity occurred in the study group. Apgar scores at 1 minute were 7 or greater in 10 of the 11 study subjects whereas only four of the nine control subjects had a score of 7 or greater. These results suggest that terbutaline may become a useful agent in the treatment of intrauterine fetal distress.