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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 307 records · Page 17Linked to original sources

Fetal surgery in the primate. III. Maternal outcome after fetal surgery.

Maternal safety and future reproduction potential are paramount considerations in fetal surgery. In a series of 102 fetal surgical procedures on time-dated pregnant monkeys, we examined the maternal complications, the potential for future pregnancy, and the effects of uterine staples used for hysterotomy and uterine closure. There were significant maternal complications associated with the development of the present techniques for fetal surgery including 3 maternal deaths, 5 uterine ruptures, and 5 cases of wound infection of dehiscence. All were preventable with knowledge gained from this experience. Compared with a control unoperated breeding colony, fetal surgery did not interfere with subsequent reproductive capacity in animals that had uterine closure with absorbable sutures. However, metal staple hysterotomy resulted in a markedly decreased fertility rate probably related to exposure of the endometrial cavity to a permanent foreign body. Although serious maternal complications occurred in this series, many are avoidable as we improve both our obstetric management and our anesthetic and surgical techniques. Prenatal intervention carries considerable maternal risk and should not be attempted clinically under any but the most rigorous conditions.

Animals↗

Transamniotic fetal feeding. III. The effect of nutrient infusion on fetal growth retardation.

The small-for-gestational age (SGA) infant resulting from intrauterine growth retardation (IUGR) is at high risk for perinatal complications and chronic morbidity. Most IUGR is the result of inadequate transfer of nutrients and/or oxygen 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 used by the growth retarded fetus. To study the efficacy of TAFF in the treatment of IUGR, we have previously described a rabbit model for TAFF that takes advantage of the relationship between "natural runting" (IUGR) and position on the uterine horn. We report on a controlled study of the effects of specific nutrient infusion on fetal growth retardation in this model. The infusion of dextrose, a dextrose-amino acid mixture, or lipid did not reverse or ameliorate fetal IUGR compared with controls. In addition, the infusion of lipid emulsion resulted in chronic lipid aspiration and further growth retardation. This work does not support the use of TAFF as a prenatal treatment for IUGR and suggests that oxygen may be the growth-limiting factor in most substrate deficiency IUGR. In addition, the infusion of solutions containing lipid may be harmful to the developing fetus.

Amino Acids↗

Auxiliary transplantation of the fetal liver. I. Development of a sheep model.

Current methods of orthotopic liver transplantation are expensive, entail high morbidity and mortality, and are limited by a serious shortage of donor organs for the pediatric recipient. Auxiliary transplantation of livers from anencephalics is a potential solution to the problems of size discrepancy and organ availability for the pediatric patient. To investigate the feasibility of auxiliary fetal liver transplantation, we have developed a sheep model of auxiliary transplantation of the fetal liver into the adult neck. We report here the results of the transplantation of 32 fetal lamb livers ranging in age from 100 to 140 days gestation (term 145 days). We conclude that (1) fetal organ harvest can be effectively accomplished by surface cooling followed by umbilical cold perfusion; (2) auxiliary transplantation of the fetal lamb liver is technically feasible; (3) the fetal liver can survive on umbilical inflow alone but function is improved by hepatic arterial inflow; and (4) the fetal liver is sensitive to excessive flow or pressure and is best transplanted in a parallel vascular arrangement. Auxiliary transplantation of the fetal liver is a promising alternative to current methods of liver transplantation.

Animals↗

Fetal sacrococcygeal teratoma.

Sacrococcygeal teratoma (SCT) is being diagnosed before birth with increasing frequency. We were recently consulted about management of a 22-week fetus with SCT and reviewed our experience (6 cases) and the literature. We found that most fetal SCT present from 22 to 34 weeks gestation with a uterus enlarged by the tumor and/or associated polyhydramnios; although the American Academy of Pediatrics Surgical Section clinical classification is an important prognostic indicator in neonatal SCT, it does not appear to predict outcome in fetal SCT; associated chromosomal abnormalities or life threatening anomalies are rare; presentation after 30-weeks gestation is a relatively good prognostic sign with fetal survival, after planned cesarean delivery, in 6 of 8 cases; and hydrops and/or placentomegaly in association with fetal SCT predicts fetal demise soon after diagnosis with 7 of 7 cases dying in utero.

Female↗

Prognosis of posterior urethral valves presenting at birth.

Urethral obstruction due to posterior urethral valves (PUV) is a more lethal condition in the newborn than is commonly recognized. To study its prognosis when the diagnosis of PUV is made shortly after birth, cases of PUV presenting in the first week of life were reviewed. Eleven cases were seen at the University of California, San Francisco from 1974 to 1982. Five babies died, three within two hours of birth of respiratory insufficiency secondary to severe pulmonary hypoplasia, and two within three weeks with rapidly progressive renal failure. Of the six survivors, four exhibited respiratory difficulty (prolonged ventilatory support required in two, and bilateral pneumothoraces in two), three developed renal failure despite early urinary diversion, and one had renal tubular dysfunction. Only two infants had normal renal function after undergoing a successful series of reconstructions. Prune-belly syndrome and limb deformities were present in two surviving and two fatal cases. Although most cases of congenital hydronephrosis can be successfully treated after birth, those presenting in the newborn period represent a subset with high morbidity and mortality. With advances in prenatal diagnosis of congenital hydronephrosis, salvage of severe cases detected early in gestation may require more aggressive management in the prenatal period.

Humans↗

Primates and anencephalics as sources for pediatric organ transplants. Medical, legal, and ethical issues.

This article discusses some of the medical, legal, and ethical issues in using organs from primates and anencephalics to transplant to infants who will otherwise die. The use of primates is discouraging on ethical grounds due to scarcity of chimpanzees, the preferred species, and to the poor chance of survival. Anencephalic fetuses and newborns are promising sources of organs for pediatric transplants, provided that ethical and legal considerations are met. An argument is made, based on current practice in management of dying donors, that complies with the legal requirement to delay organ removal until after whole brain death; however, this approach requires the compensating step of gradual cooling of the body of the newly delivered anencephalic to save the organs from ischemia.

Anencephaly↗

Development of a fetal renal function test using endogenous creatinine clearance.

Selecting appropriate management for the fetus with obstructive uropathy depends on our ability to accurately assess the severity of existing renal damage and to predict the potential for recovery of renal function if the obstruction is relieved. Diagnosis and treatment would be markedly enhanced by a simple, safe, quantitative fetal renal function test. To answer the question of whether endogenous fetal creatinine clearance (CrC) is an accurate measure of glomerular filtration rate (GFR) in the obstructed fetal kidney, we compared fetal CrC to a standard test for GFR--iothalamate clearance (IC). Six fetal lambs underwent unilateral ureteral ligation at 60 to 63 days gestation (term = 145 days). The contralateral unobstructed kidneys served as a control. At a second operation at 113 to 120 days, renal function was measured by hourly split urine collections for determination of CrC, IC, and fractional sodium excretion on each side over a 4-hr study period. There was excellent correlation of CrC with IC in all kidneys (r = 0.997, P less than 0.001, y = 1.14 x). Compared to the control side, the obstructed fetal kidneys had significantly decreased GFR and abnormal tubular function with marked sodium loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Urinary extravasation in the fetus with obstructive uropathy.

Urinary extravasation resulting in either urinary ascites or an isolated perirenal urinoma is relatively common in the fetus with severe obstructive uropathy. We examined the effect of fetal urinary extravasation on the developing kidney and abdominal wall in 12 fetuses taken from a series of 44 cases of fetal urinary tract obstruction. Based on this experience, we conclude that fetal urinary extravasation has predictable pathophysiologic consequences. Fetal urinary ascites appears to ameliorate obstruction-induced renal dysplasia by decompressing the high-pressure, obstructed fetal urinary system. Conversely, contained urinomas secondary to ureteropelvic junction obstruction provide inadequate decompression and are associated with renal dysplasia. Last, the severity of abdominal wall laxity (prune belly) relates directly to the timing and degree of fetal ascites.

Abnormalities, Multiple↗

Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis.

Infants born with congenital diaphragmatic hernia (CDH) often have specific pathologic abnormalities of the pulmonary microcirculation that result in high pulmonary vascular resistance and extrapulmonary right-to-left shunting after birth. In an attempt to make an animal model with similar vascular changes, we created CDH in fetal lambs at 60 to 63 days gestation, repaired some at 100 to 113 days gestation, and subsequently performed morphometric analysis of the pulmonary vasculature. Creation of CDH at this early gestational age resulted in a high fetal mortality rate. In the unrepaired CDH lambs, the pulmonary vascular abnormalities were more severe in the left lung. Similar to human CDH, diaphragmatic hernia in the fetal lamb resulted in a decrease in the total size of the pulmonary vascular bed, a decrease in the number of vessels per unit area lung, and increased muscularization of the arterial tree. Fetal surgical repair of CDH restored the pulmonary arterial bed towards normal.

Animals↗

Comparison of fetal, newborn, and adult wound healing by histologic, enzyme-histochemical, and hydroxyproline determinations.

We compared simultaneous healing processes in fetal, newborn, and maternal rabbits using a miniaturized wound cylinder of expanded Gore-Tex tubing. The tubing was placed subcutaneously in fetal and maternal rabbits on day 23 of pregnancy (term = 31 to 32 days), and in 7-day-old newborn rabbits. At specific intervals, the tubing was removed and analyzed for hydroxyproline accumulation, histology, and cellular enzyme-histochemistry. Granulation tissue ingrowth and accumulation of hydroxyproline were each inversely related to age (fetus greater than newborn greater than maternal). The fetus showed an impressive infiltration of macrophages by day 4, fibroblasts by day 7, and a conspicuous lack of neutrophils in all specimens. Newborns and mothers had few cells until day 7, when a mixture of macrophages, neutrophils, and some fibroblasts appeared. We conclude that the fetus heals wounds rapidly by both mesenchymal cell proliferation and collagen deposition, and that these processes are more rapid in fetuses than in newborn or adult animals despite relative fetal hypoxemia.

Age Factors↗

Diaphragmatic hernia in the fetus: prenatal diagnosis and outcome in 94 cases.

Most babies born with congenital diaphragmatic hernia (CDH) die after birth. The natural course of CDH in the human fetus is not known. We found 94 cases of fetal CDH in the records of surgeons and obstetricians surveyed in the United States and Canada. We found the following: (1) prenatal diagnosis of CDH is accurate and current techniques can detect lethal nonpulmonary anomalies and prevent diagnostic errors; (2) despite optimal conventional therapy, most fetuses with detectable CDH will die in the neonatal period (80% mortality); (3) polyhydramnios is both a common prenatal marker for CDH (present in 76% of fetuses) and a predictor for poor clinical outcome (only 11% survived); (4) fetal CDH is a dynamic process--nonsurvivors have larger defects and may have more viscera displaced into the chest at an earlier stage of development. Surgical intervention before birth may be necessary to improve survival of the fetus with CDH and polyhydramnios.

Congenital Abnormalities↗

Major childhood tumor resection using normovolemic hemodilution anesthesia and hetastarch.

Acute normovolemic hemodilution is a safe technique for minimizing operative blood loss during major tumor resection in children. Based on our experience using hemodilution anesthesia in 14 successful extensive tumor resections, we conclude the following: (1) this is an effective means of reducing use of bank blood and thus avoiding the risks of multiple transfusions; (2) it facilitates surgical dissection due to increased visibility with dilute blood, and decreased bleeding due to controlled hypotension; (3) this technique is acceptable for Jehovah's Witnesses; (4) hetastarch is an effective, inexpensive colloid hemodiluent which minimized perioperative edema compared to crystalloid hemodilution.

Adolescent↗

Management of the fetus with congenital hydronephrosis II: Prognostic criteria and selection for treatment.

Selecting appropriate management for the fetus with bilateral congenital hydronephrosis depends on our ability to accurately assess the severity of existing renal damage and to predict the potential for recovery of renal and pulmonary function if the obstruction is relieved. We reviewed our experience with 20 fetuses with congenital bilateral hydronephrosis to determine the prognostic value of various criteria used to assess functional potential, including temporary catheter exteriorization to measure fetal urine output and composition. Based on autopsy, biopsy, or clinical outcome, ten fetuses were classified retrospectively as "poor function," and ten fetuses as "good function." The good function group could be distinguished from the poor function group by the following criteria: Amniotic fluid (AF) status at presentation (P less than .001), ultrasound appearance of the fetal kidneys (P less than .05), fetal urine sodium and chloride concentration and osmolarity (P less than .001), and hourly urine output (P less than .02), but not by fetal urine iothalamate excretion or potassium and creatinine concentrations (P greater than .05). Based on these results, we have identified prognostic criteria that accurately identify the fetus with "good function" from the fetus with "poor function." We also reviewed the clinical management of our last 12 unreported cases. Ten fetuses had undergone diagnostic catheter placement and in utero renal function testing. This led to placement of a therapeutic indwelling catheter-shunt in seven fetuses (three required multiple shunts) and a suprapubic vesicostomy in another. Catheter related complications, including three cases of chorioamnionitis, emphasize the need for better methods of in utero decompression in selected cases. Our ability to select appropriate management has improved markedly.

Biopsy↗