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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 361 records · Page 20Linked to original sources

Intrauterine cardiothoracic surgery: the fetal lamb model.

We have developed fetal lamb models of congenital cardiothoracic lesions that have been allowed to progress through birth for physiological study. Simulated lesions, simulated repairs, actual lesions, and actual repairs have been performed in this model. Sixty-two fetal lambs comprised the study group, including 48 in which models were created and 14 controls. Models included pulmonary stenosis, aortic stenosis, and diaphragmatic hernia. Gestational age ranged from 90 to 120 days (0.6 of normal gestation). In each pregnant ewe, laparotomy and hysterotomy were performed under general anesthesia, with care taken to avoid placental vessels. The foreleg was exposed, the appropriate anterior chest wall was isolated, and a thoracotomy was done. Thoracic or cardiac procedures then were performed under controlled transplacental anesthesia and perfusion. Following completion of the procedure, the fetal thoracotomy was closed, sterile antibiotic solution was placed in the amniotic sac, and the hysterotomy and laparotomy were closed. Subsequently the fetus either was allowed to progress to birth and infant study or underwent subsequent intrauterine repair and then was allowed to progress to birth and neonatal study. This fetal lamb model provides reproducible anatomical and pathophysiological lesions to facilitate the development of techniques for repair of such lesions in early infancy. Further, it offers the potential for developing methods of intrauterine cardiothoracic surgical repair.

Animals↗

Fetal surgery in the primate I. Anesthetic, surgical, and tocolytic management to maximize fetal-neonatal survival.

There are compelling physiologic arguments for correcting certain malformations before birth. Although fetal surgery has been successful in sheep and lower animals, it has proven difficult in primates because the gravid uterus is exquisitely sensitive to induction of preterm labor and abortion. Because the feasibility of fetal intervention can be determined only in a primate model, we have investigated the variables affecting fetal-neonatal survival after fetal surgery in 25 monkeys. As we improved our anesthetic and surgical techniques and refined our tocolytic therapy, mortality fell from 73.3% (11/15) to 20% (2/10). Since spontaneous perinatal loss in 56 controls was 21.4% we can now operate on the late second and early third trimester fetal monkey without increasing maternal or fetal-neonatal mortality. Success in this rigorous model is a requisite for attempted correction of human malformations in utero.

Anesthetics↗

Management of the fetus with congenital hydronephrosis.

Twenty-six fetuses with dilated urinary tracts were studied with serial sonograms. Eight fetuses with unilateral hydronephrosis were followed without intervention; all are well after postnatal surgical correction. Three cases of bilateral hydronephrosis resolved spontaneously before birth. Eight fetuses with bilateral hydronephrosis had evidence of poor function: Three were not treated and died shortly after birth with small lungs and dysplastic kidneys; three others had diagnostic intervention that demonstrated irreversible disease and allowed termination of the pregnancy; two had obstruction successfully corrected in utero, but renal damage proved irreversible and precluded survival at birth. Seven fetuses with bilateral hydronephrosis and equivocal function underwent early decompression. Four were delivered early and corrected ex utero; 1 has renal failure and the other 3 are well. Three had obstruction relieved in utero by a catheter shunt placed percutaneously; 1 had multiple anomalies and died; the other 2 are well. Serial sonographic observation improves perinatal management of the fetus with a dilated urinary tract. The need for diagnostic or therapeutic intervention depends on the type and severity of obstruction and the time in gestation when it is discovered. Most fetuses do not require treatment before birth; a few may benefit from early decompression in or ex utero.

Drainage↗

Reconstructive surgery for obstructing lesions of the intrathoracic trachea in infants and small children.

This is a report of ten infants and small children with congenital obstructive lesions of the distal trachea and main bronchi. Four were successfully resected. One with a distal segment stenosis required tracheal resection at age 6 wk, another with stenosis of the distal half of the trachea at age 18 mo, and 2 (1 with distal stenosis and 1 with tracheal hamartoma) at age 4 yr. All 4 are presently free of symptoms and their anastomoses have grown without stricture. A child with coil-spring mucosal stenosis of the left main bronchus developed an excellent airway following bronchoscopic removal of the folds, and a baby with tracheomalacia was successfully treated with a rib splint on a segment of distal tracheomalacia, but she died later of associated cyanotic congenital heart disease. Four babies died with airway obstruction in the newborn period. Two with critical distal stenoses died before tracheal reconstruction could be performed. Two died following emergency resections in which all of the congenital stenosis could not be removed. In both, stenotic trachea remained despite operation. All of these infants had complete cartilage rings the entire length of the trachea. Congenital lesions of the distal trachea may become suddenly life-threatening at birth or during the onset of a respiratory infection. An abrupt or insidious onset of airway symptoms requires an expeditious diagnostic evaluation to define the tracheobronchial anatomy, and the operating team has to be prepared for emergency tracheal reconstruction.

Abnormalities, Multiple↗

Correction of congenital hydronephrosis in utero II. Decompression reverses the effects of obstruction on the fetal lung and urinary tract.

Urethral obstruction and urachal ligation at 93-107 days gestation produced severe hydronephrosis, hydroureter, megacystis, and urinary ascites as well as significant pulmonary hypoplasia in 17 fetal lambs. Obstructions in 9 fetuses subsequently were relieved in utero by suprapubic cutaneous cystostomy. At birth, all 4 liveborn obstructed lambs had respiratory insufficiency, and only 1 survived. Four others were stillborn. The lungs were significantly hypoplastic by weight and volume (p less than 0.025). All 8 had advanced megacystis, hydroureter, and hydronephrosis but no cystic or dysplastic renal changes. In contrast, 7 liveborn lambs diverted in utero had far less respiratory difficulty and all survived (p = 0.002). Two were stillborn. The lung weight was significantly increased (p less than 0.05). All lambs undergoing in utero decompression showed significant resolution of the severe urinary tract dilatation seen in the obstructed lambs. In utero decompression of the obstructed fetal urinary tract allows the abnormally small lungs to grow and develop and hydronephrosis to resolve.

Animals↗

Management of the fetus with a urinary tract malformation.

Obstetric sonography revealed urinary tract malformations in 13 fetuses. Six had severe dysplastic lesions incompatible with postnatal life; in all six, oligohydramnios and inability to detect normal kidney or bladder allowed appropriate counseling and management. Four fetuses had unilateral lesions (three hydronephrotic, one multicystic); all had evidence of adequate contralateral function and were successfully treated after delivery near term. Three fetuses had bilateral hydronephrosis secondary to urethral obstruction. The two who were born near term died of hypoplastic lungs, end-stage hydronephrosis, and facial and skeletal deformities. The other, electively delivered at 32 weeks, had none of the stigmata of Potter's syndrome, and early decompression salvaged sufficient renal function for survival. Prenatal sonographic assessment of urinary tract anatomy and function can improve perinatal management. The fetus with hydronephrosis may benefit from early decompression.

Abnormalities, Multiple↗

Correction of congenital diaphragmatic hernia in utero. III. Development of a successful surgical technique using abdominoplasty to avoid compromise of umbilical blood flow.

Infants born with congenital diaphragmatic hernia (CDH) die because their lungs are hypoplastic. In the fetal lamb, the lung made hypoplastic by compression with an intrathoracic balloon can, if decompressed in utero, grow and develop enough to permit survival at term. To study the efficacy and feasibility of in utero repair of CDH, we created diaphragmatic hernias in fetal lambs at approximately 100 days gestation and corrected them surgically at approximately 120 days. Repair of the diaphragm with closure of the abdomen resulted in postoperative fetal death in six lambs. Acute studies demonstrated that increased intraabdominal pressure compromises blood flow in the umbilical vein and produces severe fetal distress. When a silastic patch was used to enlarge the abdomen after reduction of the viscera and repair of the diaphragm, six of nine lambs were viable after term delivery. In sacrificed lambs, the lungs were well expanded, mature histologically, and greatly increased in size. Correction of CDH in utero appears physiologically sound and technically feasible.

Animals↗

Congenital diaphragmatic hernia.

Surgical intervention for congenital diaphragmatic hernia is urgent, but success depends more on preoperative and postoperative management of the associated physiologic derangements. Survival seems to depend on the condition of the lungs at birth. In the future, correction of congenital diaphragmatic hernia in utero may be possible.

Abnormalities, Multiple↗

White liver disease in lambs.

An outbreak of white liver disease in lambs in Western Australia is described. The disease affected 2- to 3-month-old lambs and was characterised by liver damage, severe ill-thrift, depression, serous ocular discharge, photosensitization, and a high mortality rate. Transient central nervous system signs occurred. A positive response to vitamin B12 therapy was demonstrated.

Animals↗

Breath hydrogen reflects canine intestinal ischemia.

The relationship between breath hydrogen excretion and intestinal ischemia was investigated in nine mechanically ventilated dogs under pentobarbital anesthesia. An ileal segment was isolated in situ, ligated at each end, and insufflated with hydrogen. Expired air was collected at intervals. Blood volume was reduced 30% by three successive equivalent hemorrhages 10 min apart. Local bowel ischemia was produced by clamping the blood supply to the isolated segment for 10 min. Graded hemorrhage produced step-wise reductions in breath hydrogen concentration, to 77 +/- 13, 66 +/- 15, and 35 +/- 8% (mean +/- S.E.) of baseline after the first, second, and third hemorrhages, respectively. These reductions correlated highly (r = 0.84; P less than 0.01) with declines in mean aortic blood pressure. Occlusion of blood supply caused a significant (P less than 0.025) decrease in breath hydrogen concentration and excretion to 39 +/- 14% of baseline. Termination of occlusion was followed within 2 min by a 7-fold increase in breath H2 concentration above the original baseline, probably reflecting reactive hyperemia. Breath hydrogen measurements appear to reflect functional (hemorrhagic shock-induced) and mechanical (vascular occlusion induced) enteric ischemia in dogs.

Animals↗

Surgical treatment of tumors in the newborn.

With the exception of hemangiomas, neoplasms occur in newborn infants once per 15,000 births. These tumors are mostly derived from embryonic mesenchymal or neural crest tissues and consists of teratomas, neuroblastomas, and tumors of the kidneys and soft tissues. Many of these neoplasms are very malignant in older children, while the same tumor type in the newborn is generally well circumscribed and has a benign biological behavior. Therefore, the surgical treatment should be conservative. The operative is conducted with attention to the minute details that support the metabolic needs of the infant. The management of specific tumors encountered in the neonate are described.

Anesthesia, Endotracheal↗