Biomedical subjects
Publications and source records attributed to M R Harrison.
Newly developed diagnostic techniques allowed us to select a fetus with potentially reversible renal damage from the usually fatal group with bilateral hydronephrosis and severe oligohydramnios early in gestation. Fetal surgery to marsupialize the fetal bladder at 24 weeks gestation restored normal amniotic fluid dynamics and allowed sufficient pulmonary and renal development to insure survival after delivery near term.
To evaluate the use of the fetal liver as an auxiliary graft, we have developed a model of intraabdominal heterotopic transplantation of late gestational fetal lamb livers into weanling lambs. Thirty-eight transplants have been performed of which 31 were technically successful. Twenty-three grafts functioned for intervals of 5 to 22 days after transplantation. Grafts were functionally evaluated by analysis of total bile acid and bilirubin excretion. To determine whether host liver excretory function would influence function of the graft, common bile duct ligated recipients were compared with recipients with normal host liver function. We found that (1) intraabdominal auxiliary transplantation of the fetal lamb liver is technically feasible; (2) the fetal liver graft is capable of rapid adaptation and can assume a significant portion of host excretory function; and (3) excretory function of the fetal liver is proportional to the functional demands of the host. Auxiliary transplantation of the fetal liver is a promising alternative to current methods of liver transplantation.
In a critically ill neonate, simple ligation of intestinal segments to be preserved for a second look procedure allows expeditious resection of intervening necrotic segments.
Two infants who required a Nissen fundoplication for severe gastroesophageal reflux developed small bowel obstruction 5 and 21 months postoperatively. Their inability to belch or vomit, coupled with inappropriate airway management during resuscitation led to massive gastric dilation, and eventual infarction of their stomach, duodenum, and small intestines. These complications are preventable with appropriate management.
Intrauterine growth retardation (IUGR) is a leading cause of perinatal morbidity and mortality. Most IUGR is the result of inadequate transfer of nutrients from mother to fetus. Transamniotic fetal feeding (TAFF) has been proposed as a method of treating IUGR in which nutrients, infused into the amniotic fluid, would be swallowed, absorbed, and utilized by the growth retarded fetus. To study this hypothesis, we have developed a rabbit model for IUGR and TAFF. We studied the effects of maternal nutritional deprivation, uterine artery ligation, and fetal position in the uterine horn on fetal body and organ growth in 96 rabbit litters. Nutritional deprivation (n = 28) and vascular interruption (n = 34) yielded inconsistent results with high fetal mortality. We were surprised to find that fetal growth was directly and consistently related to position in the uterine horn. There is a highly significant difference (P less than .0001) in weight between siblings in the no. 1 and no. 3 positions in the rabbit uterine horn at 30 days gestation that is not present at 23 days. This "natural" runting resembles human IUGR, which occurs during the last trimester of pregnancy and shows relative brain sparing. This model, in combination with our previously reported technique for TAFF, will make possible a controlled study of the efficacy of TAFF in the treatment of IUGR.
The purpose of this study was to evaluate the ability of continuous wave Doppler ultrasound recordings to reflect the magnitude and hemodynamic effects of aortic regurgitation. Forty-five patients with angiographically proved aortic regurgitation had Doppler studies performed within 24 hours of cardiac catheterization. High quality spectral recordings of the regurgitant jet were obtained in 31 patients, whereas 14 patients exhibited dropout of high velocity signals precluding measurement of maximal velocities. The slope of the peak to end-diastolic velocity decrease measured by Doppler examination was compared with the decay in the aortic to left ventricular diastolic pressure gradient by catheterization and was found to correlate well (r = 0.86). The Doppler velocity decay slope was generally higher in patients with angiographically severe rather than mild or moderate aortic regurgitation, but considerable overlap was present among groups. However, a diastolic velocity decay slope of greater than 3 m/s2 was seen only in those patients with advanced (3 or 4+) aortic regurgitation. Left ventricular end-diastolic pressure was estimated from the Doppler recordings by subtracting the end-diastolic pressure gradient obtained by the modified Bernoulli equation from the cuff diastolic blood pressure. A correlation was observed (r = 0.84) between Doppler and catheterization left ventricular end-diastolic pressure in the 31 patients with high quality spectral data, although the SEE was substantial (5.5 mm Hg). These data demonstrate that continuous wave Doppler recordings of the regurgitant jet can be useful in assessing the angiographic severity and hemodynamics of aortic regurgitation.
This study tested the hypothesis that coronary artery disease might be identified by a decrease in Doppler measurements of flow velocity and acceleration. The response of aortic blood flow velocity and acceleration to exercise was determined in 102 subjects (28 young control subjects and 74 older patients) who underwent continuous wave Doppler echocardiographic examination before, during and immediately after near maximal treadmill exercise. Patients were grouped according to the results of thallium perfusion imaging: Group I = normal, Group II = ischemia with or without prior infarction and Group III = prior infarction only. A significant decrease in the level of velocity and acceleration achieved with exercise was observed both in patients in Group I (normal thallium study) (1.2 +/- 0.3 m/s and 36.8 +/- 14 m/s per s, p less than or equal to 0.005) and in patients in Group II (ischemia) (1.1 +/- 0.3 m/s and 27.7 +/- 11 m/s per s, p less than or equal to 0.0005) compared with values in young control subjects (1.4 +/- 0.2 m/s and 52.7 +/- 16 m/s per s). When groups of patients of similar age who differed in the presence (Group II) or absence (Group I) of ischemia on thallium scintigraphy were compared, no difference was found for maximal velocity (1.1 +/- 0.3 versus 1.2 +/- 0.3 m/s, p = NS), but acceleration was significantly lower in Group II (27.7 +/- 11 versus 36.8 +/- 14 m/s per s, p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Early prenatal diagnosis of fetal sacrococcygeal teratoma (SCT) has enabled the perinatal team to institute management of this condition during the perinatal period. We report 2 additional cases to our previous 27 cases including 1 which represents the earliest diagnosis of SCT. Fetal SCT behaves in a different manner than neonatal SCT. In utero manipulation of fetal SCT may be possible if diagnosis is made during the second trimester.
A prenatal diagnosis of congenital diaphragmatic hernia (CDH) is associated with a poor prognosis, especially if diagnosed early in gestation and associated with polyhydramnios. Although uncommon, it is important to rule out associated anomalies, so that elective termination can be considered. If CDH is an isolated anomaly, the outcome is related to the degree of pulmonary hypoplasia caused by viscera displacing the lung in utero. Unfortunately, our ability to assess lung size, and thus prognosis, is limited. Most babies with CDH either die shortly after birth or survive to lead normal lives, so that continuation of the pregnancy is extremely unlikely to produce a chronically ill pulmonary cripple. The fetus should be followed with periodic ultrasounds and delivered at a perinatal center with appropriate neonatal and surgical expertise. There is no evidence that altering the timing or mode of delivery affects outcome. The only way to alter outcome and save the severely affected fetus is to remove the viscera from the chest and allow the fetal lung to develop before birth. Despite the fact that fetal repair of CDH makes sense physiologically, however, it remains a highly experimental technique. Postnatal management of CDH involves resuscitation, paralysis, and positive pressure ventilation. The practice of emergency repair is not supported by pathophysiology, and operation should be delayed until the patient has been stabilized. Mortality is often due to pulmonary hypoplasia, but in some cases, there is a period of deterioration due to pulmonary hypertension resulting in right-to-left shunting (persistent fetal circulation). Pharmacological agents are often used to decrease pulmonary vascular resistance and increase cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
The antenatal diagnosis of abdominal wall defects has allowed improved perinatal management. For fetuses with associated anomalies, the options of elective termination or minimal intervention can be offered. Our ability to predict the extent of bowel damage in gastroschisis based on the ultrasound findings enables us to offer early delivery to those fetuses who are at high risk. The data are not clear at the present time whether cesarean section offers any advantage. These fetuses should, however, be delivered at a center which is capable of providing high level medical and surgical care to these potentially ill infants. Initial resuscitation of these neonates requires early insertion of an intravenous line and a nasogastric tube, the administration of antibiotics, sterile coverage of the eviscerated bowel, and careful attention to temperature instability. Neonates with gastroschisis should be operated on as soon as they are stable, whereas infants with omphalocele can be investigated for associated anomalies prior to surgery. Primary fascial closure is performed whenever possible. Where this is not possible, a staged repair using a silastic chimney achieves closure within 3-6 days. Skin coverage alone or nonoperative management is reserved for the few cases with giant omphalocele, associated anomalies, or poor operative risk. Decisions about primary versus delayed closure, while usually dictated by clinical judgement, can be aided by indirect measurement of intraabdominal pressure. Postoperative ventilation, and consideration of long-term nutritional needs, are also important parts of the perioperative management.
A morphometric study was made of the remaining lung of term lambs that had undergone left pneumonectomy at 60, 80, 100, or 120 days gestation. All pneumonectomy lambs showed some compensatory growth since right lung volume to body weight ratio was higher in all lambs after pneumonectomy than in term controls. In 3 lambs operated at 80, 100, and 120 days, respectively, however, compensatory volume increase was more complete than in the other lamb of each age pair or the 2 lambs operated at 60 days. Despite individual variation, the potential for compensatory lung growth seems greater in the canalicular and later stages than in the pseudoglandular. Measurements indicating distal air-space size (volume density of alveoli, volume density of alveolar duct, surface density of alveolar epithelium, numerical density of alveoli, and mean linear intercept) were similar in all animals, but total alveolar surface area and number increased proportionally to lung volume. The fact that the remaining lung compensates by increasing alveolar number rather than by enlarging air spaces is a model of human developmental abnormalities in which the alveolar number at birth is greater than normal (polyalveolar). At the intraacinar level, a higher than normal proportion of muscularized arteries was found in lambs operated early in gestation and in lambs with smaller compensatory lung growth: an inverse relationship was seen--the lower the lung volume the higher the proportion of muscular arteries. The cause for this is unknown, but may result from the relatively increased flow to a vascular bed smaller than that of two normal lungs.
To gain insight into the mammalian liver to kidney erythropoietin (Ep) switch, we heterotopically transplanted livers from preswitch, switched, and postswitch fetal and newborn lambs into normal adult sheep. Recipients' serum Ep and circulating reticulocyte levels were serially determined until rejection of the graft and compared with identical samples from sham-operated control adult ewes. Transplantation of preswitch and switched fetal livers caused an impressive rise in recipients' serum Ep activity and provoked a corresponding increase in reticulocytosis. In contrast, Ep activity and reticulocyte counts did not change from preoperative levels in adult ewes transplanted with postswitch livers or in the sham-operated controls. The production of Ep by the preswitch fetal liver in the adult environment was not dependent on the presence or absence of host kidneys and was stimulated by anemic hypoxia. These results suggest that the fetal liver is capable of producing relatively large amounts of Ep activity, and the production of Ep can be maintained in the adult environment in the presence of functional adult kidneys. This argues against suppression of liver Ep production by renal Ep, or some other factor in the postnatal environment, and suggests that the liver to kidney switch of Ep production during ontogeny may represent a genetically determined event.
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Transplantation of normal, immature, fetal hematopoietic cells into a preimmune fetal recipient with a congenital hemoglobinopathy may allow partial reconstitution of normal hemoglobin production without the complications associated with postnatal bone marrow transplantation (immunosuppression and the occurrence of graft versus host disease). In order to test this hypothesis the naturally occurring polymorphism at the beta-hemoglobin locus of the sheep was used as a marker for engraftment and hematopoietic chimerism. Intraperitoneal injection of allogeneic fetal stem cells into normal fetal lambs resulted in hematopoietic chimerism in three of four surviving recipients. This chimerism has been sustained for 6 months after birth and 9 months after engraftment, without evidence of graft versus host disease, and without the use of immunosuppressive therapy.
In the period 1982 to 1985, 73 placements of catheter shunts for fetal obstructive uropathy and 44 drainage procedures for obstructive hydrocephalus were reported to a voluntary international registry. The attempts to decompress the obstructed fetal urinary tracts resulted in the survival of 30 fetuses (41 percent), with a procedure-related death rate of 4.6 percent. Pulmonary hypoplasia was the major cause of death in both untreated and treated fetuses. Although the natural history of fetal obstructive uropathy has not been well studied, the outcome of intervention for selected fetuses with posterior urethral valve syndrome was encouraging. The results of shunt procedures for obstructive hydrocephalus were less encouraging. Although 34 of 44 fetuses (83 percent) survived, the procedure-related death rate was 10.25 percent, 18 of the 34 survivors (52.9 percent) have serious neurologic handicaps, 4 (11.8 percent) have less severe handicaps, and only 12 (35.3 percent) are developing normally. Analysis of data from this registry has guided the early development of fetal surgery, but it cannot establish the efficacy of the procedures because of selection bias. A controlled trial is needed.
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Ureteropelvic junction (UPJ) obstruction is being detected with increasing frequency before birth. To clarify the natural history of fetal UPJ obstruction, we reviewed our experience managing 28 fetuses; there were 16 bilateral cases for a total of 44 renal units. None required decompression before birth. We found that fetal bilateral UPJ obstruction is associated with significant morbidity and mortality; resolution of fetal hydronephrosis secondary to UPJ obstruction is rare; antenatal diagnosis of UPJ obstruction improves clinical management by allowing early detection and appropriate treatment of otherwise clinically undetectable disease; oligohydramnios in the mature fetus with bilateral UPJ obstruction is an indication for early delivery and immediate repair; and prenatally diagnosed UPJ obstructions should be repaired as early as possible after birth.
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