Majida N. Jassani

Study of ketamine as an obstetric anesthetic agent

Abstract Ketamine [2-(o-chlorophenyl)-2-(methylamino) cyclohexanone monohydrochloride], a new short-acting anesthetic agent which does not inhibit laryngeal or pharyngeal reflexes, has been studied in 14 pregnant subjects and 18 nonpregnant controls. Approximate clearances calculated indicated a reduced clearance in pregnant subjects (48 cf. 64 ml. per minute per kilogram). Side effects included a 30 to 40 per cent increase in systolic and diastolic blood pressure, an increase in pulse and respiration, salivation, and nausea, and vivid but usually pleasant dreams. The fetal pH did fall after administration of anesthesia, but remained in the normal range along with Pco 2 and Pco 2 . Intrauterine tone increased, and there were changes in fetal heart rate, but none that might not have occurred with advancing labor. Newborn infants were not unduly depressed if the dose was kept below a priming dose of 1.5 mg. per kilogram followed by infusing 0.08 mg. per kilogram per minute. Serum bilirubin concentrations in the newborn infant were slightly increased and could not be accounted for. Mothers and babies all went home at the expected time post partum in apparent good health.

Ethinyl estradiol administration and plasma steroid concentrations in ovariectomized women

The effect of ethinyl estradiol treatment on the plasma levels of cortisol, corticosterone, deoxycorticosterone, progesterone, testosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, and estrone was studied in eight women. All the subjects had undergone ovariectomy and hysterectomy at least one year prior to this study. The systemic concentration of cortisol and the binding of cortisol were significantly increased, paralleling the increased transcortin concentration due to ethinyl estradiol treatment. Corticosterone concentration was also significantly increased after three days of estrogen administration and this level continued to be higher than normal as long as patients were treated with estrogens, but there was no change in the plasma concentration of deoxycorticosterone. The plasma levels of progesterone testosterone, dehydroepiandrosterone sulfate, delat4-androstenedione and estrone or the ratio of estrone to delta4-androstenedione did not change with ethinyl estradiol treatment. These observations suggest that the administered estrogen increased the transcortin concentration and had only a limited effect on adrenocortical steroidogenesis.

Antenatal diagnosis of sacrococcygeal teratomas: prognostic features

During a 6-year span the prenatal ultrasound diagnosis of a sacrococcygeal mass was made eight times at the High-Risk Perinatal Centers of Case Western Reserve University. The gestational age at the time of diagnosis ranged from 21 to 35 weeks. In one of the pregnancies, the affected fetus was one of a set of fraternal twins. Two patients were delivered vaginally and five were delivered by cesarean section. One fetus died in utero. In seven the diagnosis of sacrococcygeal teratoma (SCT) was confirmed histologically. In the eighth the lesion was a fungating malignant melanoma of the lower sacral region. The decision as to mode of delivery was made based on the size of the tumor relative to the biparietal diameter and fetal presentation. Four of the six remaining patients with SCT survived. In the three with fatal outcome, the ratio of infant weight to tumor weight was below 1.7. This measurement is a clear indication of the very large size of these lesions. The increased blood flow through these tumors can lead to fetal cardiac failure, hydrops, and death. With the almost routine use of ultrasound, more SCT may be identified antenatally. Included in this group and referred to tertiary care centers will be nonviable fetuses as well as very small fetuses with exceptionally large tumors; this will raise the overall mortality in this group of patients traditionally regarded by pediatric surgeons as having a good outlook.

Ultrasonographic antenatal diagnosis: Will it change the spectrum of neonatal surgery?

The outcome of 139 fetuses with anatomical abnormalities diagnosed by ultrasonography (out of 15,180 examinations) at our institution during the last 6 years was reviewed. Of these, 56 were diagnosed before 21 weeks gestational age and 83 thereafter. Fifty-four had anomalies of the central nervous system. Of these 27 were diagnosed early. Twenty-six had anomalies of the genitourinary tract, 11 diagnosed early. Four had anomalies of the musculoskeletal system diagnosed early in 3. Thirty-seven had miscellaneous anomalies and early diagnosis was made in 6. Only the early pregnancies were terminated, 38 in number. The fetal diagnosis was clearly confirmed in 33. Of particular interest were the 18 fetuses with anomalies of the gastrointestinal tract and abdominal wall. There were nine early diagnoses. The pregnancy was interrupted in seven. In all the diagnosis was confirmed. Five of these had associated anomalies. Among the 9 fetuses whose anomalies were diagnosed late, 3 had associated anomalies and died shortly after birth before corrective surgery. In all, two fetuses with abdominal wall defects had no detectable associated anomalies and were potentially correctable but the pregnancies were terminated. With earlier, accurate imaging diagnosis possible, special attention has to be directed toward multidisciplined counseling (including a pediatric surgeon) for ultimately satisfactory fetal-neonatal salvage. Otherwise the spectrum of neonatal surgical pathology could be seriously altered.

Twin pregnancy with discordancy for Down's syndrome.

&NA; A twin pregnancy is described in which discordancy for Downs syndrome was diagnosed prenatally by karyotyping amniotic fluid cell cultures from each of the 2 sacs. The advantages of ultrasonography prior to genetic amniocentesis are discussed from this perspective. The observation that parents may deal in various ways with the reality of this prenatal dilemma demands an open‐minded approach from obstetricians and genetic counselors.

Estrogen and the metabolism of progesterone in vivo

The effect of estrogen administration on the metabolism of progesterone was studied in ovariectomized, hysterectomized women. Estrogen was withheld from each subject for at least 4 weeks, then 200 mug of ethinyl estradiol were administered orally each day for 3 weeks and then no estrogen was given for 3 weeks. The subjects were studied before estrogen was started, on the third day of estrogen, after 3 weeks of daily estrogen and after the estrogen was withdrawn for 3 weeks. In 5 women plasma transcortin concentrations, measured by equilibrium dialysis, were 0.82 plus or minus 0.06, 1.5 plus or minus 0.16, 2.1 plus or minus 0.13, and 0.90 plus or minus 0.09 (S. E.) muM before starting estrogen (control), on the third day of estrogen treatment, after 3 weeks of estrogen, and after having stopped estrogen for 3 weeks, respectively. Corresponding values for the metabolic clearance rates (MCR) of cortisol (by the continuous infusion method) were 306 plus or minus 33, 172 plus or minus 18, 136 plus or minus 14, and 258 plus or minus 23 (S. E.) L. per day. Although estrogen administration caused a significant elevation of the plasma transcortin concentrations and a significant decrease in the MCR of cortisol, it had no significant effect on the MCR of progesterone or of cortisone. The estrogen administration did cause a decrease in the peripheral conversion of progesterone to 20alpha-hydroxy-pregn-4-en-3-one (20alpha-OHP) and of cortisol to cortisone but an increase in the conversion of 20alpha-OHP to progesterone and of cortisone to cortisol.

Uterine metabolism of gonadal steroids during the menstrual cycle

The metabolic clearance rate and uterine extraction of (3H)progesterone, (3H)estradiol, and (14C)estrone were studied at the time of hysterectomy in six women on or before day 12 of the menstrual cycle, in three women after day 12, and in one postmenopausal woman. The metabolic clearance rates of progesterone, estradiol, and estrone were in the same range as for normal women as previously reported by us. The uterine extraction for progesterone ranged between 12% and 37% on or before day 12 and 0% to 5% after day 12, and was 7.4% in the postmenopausal woman. The uterine extraction of estradiol was 0% to 25% on or before day 12, and 0%, 4%, and 22% after day 12 and was 18% in the postmenopausal woman. The uterine extraction of estrone was 7% to 24.5% on or before day 12 and 0% after day 12 and was 18% in the postmenopausal woman. The across-uterine interconversion of estradiol to estrone was 0% to 2.7% and of estrone to estradiol 0% to 2.6%. Both conversions appeared to be independent of the day of the menstrual cycle. The results suggest that the uterine metabolism of progesterone and estrone and perhaps estradiol is lower in the luteal phase of the cycle as compared to the follicular phase and that the conversion of estradiol to estrone may not be a major reaction of estradiol metabolism in the human uterus.