Leon I. Mann

Brain damage after intermittent partial cord occlusion in the chronically instrumented fetal lamb

The relationship between intermittent partial occlusion of the umbilical circulation and fetal acid base status, brain function, and neuropathologic outcome was assessed in nine control and nine experimental singleton fetal lambs to determine if transient episodes of partial cord occlusion play a role in antenatal brain damage in this species. Intermittent partial occlusion of the umbilical circulation for 1 minute of every 3 minutes for 2 hours was associated with a 89% incidence of histologically confirmed damage confined to the cerebral white matter. This occurred without systemic evidence of progressive acidosis, but both fetal heart rate patterns and electrocortical activity were altered. We conclude that in the late gestation fetal lamb, umbilical cord compromise plays a causal role in a specific type of antenatal central nervous system injury.

Umbilical blood flow response to embolization of the uterine circulation

The uterine and umbilical blood flow response to uteroplacental insufficiency, produced by microsphere embolization of the uteroplacental circulation, was examined by means of electromagnetic flow transducers in 12 pregnant ewes. No acute changes were observed in either circulation immediately after embolization of the uterine vasculature. Significant morphometric fetal growth retardation, in terms of weight, length, and ponderal index, was not associated with early changes in fetal pH, PO2, or PCO2. However, the incremental increases in both flows that were observed in control animals did not occur either during or after embolization because of an increase in vascular resistance. During and after embolization the incremental increase in uterine blood flow was blunted or decreased in most, but not all, animals. A rapid, progressive, and persistent decrease in umbilical flow occurred in the growth-retarded group. The significance of these findings relative to intrauterine growth is discussed.

The uterine hemodynamic response to repetitive unilateral vascular embolization in the pregnant ewe

The longitudinal hemodynamic response of the uterine circulation to pregnancy and to repetitive embolic insult was assessed in 23 singleton ewe pregnancies by means of electromagnetic flow transducers and radionuclide-labeled microspheres. The data indicate that the longitudinal hemodynamic changes observed in the uterine circulation were directly related to the growth rate of the tissue which it supplied. The hemodynamic impact of embolization appears to be secondary to its impact on tissue growth. Embolization simply blunts the normal incremental increases in uterine perfusion and the cross-sectional area of the uterine vascular bed. It alters actual tissue perfusion only within a portion of the cotyledonary circulation. Finally, the data support the presence of functional arterial anastomoses between the two sides of the uterine circulation in this species.

Modern management of the breech delivery

Retrospective review of 457 breech deliveries failed to reveal a significant improvement in neonatal mortality and morbidity rates for those delivered by cesarean section vs. vaginal delivery. A slight but insignificant improvement in salvage was found for the 1,000 to 1,500 gram weight category when delivery was by cesarean section. Most of the deaths in the less than 1,500 gram breech presentation were associated with hyaline membrane disease or congenital defects incompatible with life and sepsis rather than directly related to the manner of breech delivery.

Fetal metabolic response to experimental placental vascular damage

The fetal metabolic response to repetitive placental damage, produced by microsphere embolization of the uteroplacental circulation, was examined longitudinally in eight singleton fetal lambs and compared with similar data from seven controls. Significant morphometric fetal growth retardation was associated with an abrupt cessation of the normal increases in oxygen, glucose, and lactate uptake observed in the control animals. However, fetal blood levels and umbilical substrate quotients did not change. At the time of sacrifice, fetal oxidative metabolic rate was reduced significantly. The significance of these findings relative to intact fetal survival is discussed.

Physiologic variability and fetal electrocortical activity

The relationship between fetal electrocortical activity and multiple fetal parameters was examined in chronically instrumented fetal lambs. Consistent small but significant changes in fetal heart rate, mean arterial pressure, umbilical blood flow, and the cerebral uptake of glucose relative to oxygen were observed as fetal electrocortical activity cyclically shifted between high-voltage slow activity and low-voltage fast activity. Cardiovascular parameters were higher and the cerebral uptake of glucose relative to oxygen was lower during high-voltage slow activity than during low-voltage fast activity. The implication of these observations is discussed.

The in utero ultrasonographic appearance of Klippel-Trenaunay-Weber syndrome

chemotherapy is not specific with regard to original histology, sex, or chemotherapeutic regimen. The present case demonstrates that redifferentiation also is not specific with respect to final histology. ‘Three hypotheses, not mutually exclusive, have been proposed for this phenomenon’: The first is that chemotherapy destroys some cell lines selectively, leaving others to proliferate; the second is that chemotherapy induces differentiation; the third is that there is a natural tendency for germ cell tumors to undergo benign differentiation. The natural history of malignant germ cell tumors untreated with chemotherapy makes the last hypothesis unlikely. No aspect of’this case compels acceptance of one of the first two theories to the exclusion of the other. However, it is attractive to hypothesize that the chetnotherapy destroyed all of the cell lines except the dysgerminomatous elements, allowing these to proliferate.

Modern indications for cesarean section.

Total cesarean section rates and rates of various indications for primary cesarean section were reviewed for four yearly periods during the past decade. The time periods studied were chosen to follow the introduction of new obstetric practices and technologic advances in monitoring fetal condition. The total cesarean section rate increased from 6.8% to 17.1% during this time. The most common indication for primary cesarean section was cephalopelvic disproportion, which represented approximately 40% of cases during each study period. Primary cesarean section for fetal distress increased to 28.2% but has decreased over the past 2 years to a present rate of 11.7%. Primary cesarean section for breech presentation increased from 12.3% to 21%. From the perspective of this review a total cesarean section rate of 15% is predicted for the future.

Disposition of methadone in the ovine maternal-fetal unit.

Abstract The distribution of methadone between mother and fetus after a single dose and at steady state was determined using the chronic pregnant ewe preparation. Chronic indwelling catheters were placed in the maternal aorta and vena cava, umbilical vein and fetal aorta. Following a single i.v. dose (0.5 mg/kg) to the mother, methadone was rapidly distributed to the fetus, with peak concentration in the umbilical vein occurring within two min. An umbilical venous-arterial gradient existed for 10–15 min after drug administration, indicating uptake of methadone by fetal tissues. Methadone concentration in the fetus was 2–5 times lower than those in the mother even in the post-distribution phase. The terminal half-life of methadone in 4 animals was 57±7.6 (S.E.) min in the mother, and 58.5±10.0 (S.E.) min in the fetus. When methadone was infused at a constant rate to the mother (0.01 mg/kg/min), steady state was achieved in both mother and fetus by 4–5 hrs. In 5 animals, maternal steady state was found to be 203±18.8 (S.E.) ng/ml, and fetal steady state was found to be 29.7±2.9 (S.E.) ng/ml. These studies show that methadone is rapidly distributed to the fetus, but fetal concentration remain lower than maternal concentration at all times.

The ovine fetoplacental endocrine response to placental damage.

In the chronic pregnant ewe preparation, daily blood samples, for the determination of plasma cortisol and progesterone levels by specific radioimmunoassay, were obtained from the fetal distal aorta, uterine vein, and uterine artery prior to, during, and after repetitive embolization of the uterine circulation with 15 mu microspheres. A significant increase in fetal cortisol was observed in all animals during the first 3 days of embolization. In those which subsequently entered premature labor, this increase was progressive and was associated with a fall in the uterine venous progesterone level but was unrelated to changes in either the maternal cortisol level or fetal physiologic parameters. In animals which did not enter premature labor, progesterone levels in the uterine vein and estimated progesterone release rates were elevated with an accentuated peak-trough pattern during the postembolization period. In these animals fetal cortisol returned to control levels. The data suggest that cortisol and progesterone biosynthesis within the fetoplacental unit is altered by microembolic placental damage.