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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 73 records · Page 4Linked to original sources
PubMed1998

Correction of congenital diaphragmatic hernia in utero IX: fetuses with poor prognosis (liver herniation and low lung-to-head ratio) can be saved by fetoscopic temporary tracheal occlusion.

BACKGROUND/PURPOSE: Fetuses with congenital diaphragmatic hernia (CDH) who have a "poor prognosis" with postnatal treatment now can be identified on the basis of liver herniation, early diagnosis (before 25 weeks' gestation) and a low lung-to-head ratio (LHR). Because complete in utero repair proved unsuccessful for this group, the strategy of temporary tracheal occlusion was developed to gradually enlarge the hypoplastic fetal lung. The purpose of this study is to compare the outcome of patients in the poor-prognosis group treated by one of three methods: (1) standard postnatal care, (2) fetal tracheal occlusion via open hysterotomy, and (3) the recently developed video-fetoscopic (Fetendo) technique of tracheal occlusion without hysterotomy. METHODS: In the past 3 years, 34 of 86 fetuses with an isolated left CDH met criteria for the poor-prognosis group. Thirteen families chose postnatal treatment at an extracorporeal membrane oxygenation (ECMO) center, 13 underwent open fetal tracheal occlusion, and eight underwent fetoscopic tracheal occlusion. RESULTS: The survival rate was 38% in the group treated by standard postnatal therapy, 15% in the open tracheal occlusion group, and 75% in the Fetendo group. There were less postoperative pulmonary complications noted in mothers who underwent the Fetendo procedure versus the open tracheal occlusion. All but one Fetendo clip patient had a striking physiological response demonstrated by sonographic enlargement of the small left lung that was documented postnatally by plain radiographs and its subjective appearance during repair of the CDH. In contrast, only 5 of the 13 open tracheal occlusion patients demonstrated lung growth. CONCLUSION: Fetuses with a left CDH who have liver herniation and a low LHR are at high risk of neonatal demise and appear to benefit from temporary tracheal occlusion when performed fetoscopically, but not when performed by open fetal surgery.

Adult↗
PubMed1998

Successful treatment of liver hemorrhage in the premature infant.

Intraoperative neonatal liver hemorrhage usually results in exsanguination and death. The parenchyma of a neonatal liver is fragile, and the capsule is very thin, unlike that in the pediatric and adult patient. This renders the treatment of a neonatal liver fracture almost universally unsuccessful. The current report describes two cases of successful management of intraoperative neonatal liver hemorrhage during surgery for necrotizing enterocolitis (NEC).

Enterocolitis, Pseudomembranous↗
PubMed1998

Fetal urinary tract abnormalities. Natural history, pathophysiology, and treatment.

Urologic abnormalities are commonly detected on routine obstetric sonographic examinations. The progressive nature and potential reversibility of obstructive urologic anomalies have led to interest in in utero treatment of these lesions. Over 90% of obstructive urologic lesions do not need treatment until after birth. For a select group of patients, antenatal treatment may improve postnatal renal and pulmonary function. When indicated, minimally invasive nephroamniotic or vesicoamniotic stenting is the preferred method of treatment.

Animals↗
PubMed1998

Initial studies of holmium:YAG laser creation of spinal defects in fetal rabbits: model for urologic effects of myelomeningocele.

Myelomeningocele (MMC) is characterized by paraplegia and incontinence, often necessitating surgery. Current models of MMC in sheep and primates create a spinal defect long after anomalous neural tube closure ordinarily occurs. An ideal model of MMC would allow creation of the defect at the earliest age in a low-cost species with a short gestation. We present a method utilizing the holmium laser to create spinal defects in rabbits in utero for the study of the pathophysiology and repair of MMC. Pregnant rabbits of 22 to 23 days' gestational age were prepared and draped in sterile fashion for laparotomy under general anesthesia. The abdomen was opened, and both uterine horns were inspected. Double opposing pursestring sutures were placed to secure the chorioamniotic membranes over the fetal lumbar spine. Amniotic fluid was removed with a needle and saved. Electrocautery was used to open the uterus within the pursestring suture, exposing the fetal dorsum. The spine was exposed by laser dissection of the fetal dorsal musculature. Posterior laminectomy was accomplished with laser incisions of each side of the spinous process, leaving the underlying dura and cord exposed. The pursestring was then cinched, amniotic fluid was returned, and the uterus and trocar sites were closed. Cesarian section was performed at 30 to 31 gestational days, and the pups were examined and then humanely sacrificed for histologic evaluation of the lesion. The rabbit is an inexpensive species with a short gestation (33-35 days), and four or more fetuses may be operated on per litter, with the remainder serving as controls. Utilization of minimally invasive techniques including holmium:YAG laser dissection facilitates creation of spinal defects at an early age in this small-animal model.

Animals↗
PubMed1998

Bone morphogenetic protein-2 induces scar formation and skin maturation in the second trimester fetus.

Fetal mammals heal skin wounds through the second trimester of development without evidence of scar. We have investigated the role of bone morphogenetic protein 2 (BMP-2), which is a member of the TGF-beta superfamily, in normal skin development and fetal wound healing. We first used RNA in situ hybridization to demonstrate that BMP-2 was expressed at low levels in the developing hair follicles and in the epidermis of normal human fetal skin. We then created an in vivo model to test how exogenous BMP-2 would affect fetal skin development and wound healing. Fifty micrograms of BMP-2 was implanted into the subcutis of five 70-day-old fetal lambs through a full-thickness linear incision. The BMP-2 was placed beneath the right half of the wound, whereas the left half served as an untreated control. In two of the five animals 1 microgram of TGF-beta was placed into the same position in addition to the 50 micrograms of BMP-2. Twenty days later (90 days gestation, term = 140 days) all the fetal wounds were examined for evidence of cellular hyperproliferation and scar formation. BMP-2 induced massive dermal and epidermal growth when compared with controls. This finding was characterized by marked epidermal thickening and keratinization, a dramatic increase in the number of hair follicles, and more than 50 percent thickening of the dermis. The dermal thickening was the result of both increased cellularity and deposition of large irregular collagen bundles. Wounds treated with both BMP-2 and TGF-beta healed also with an adult-like pattern of scar formation. Surprisingly, the wounds with BMP-2 alone healed with an equal pattern of scar, indicating that there was not an additive effect of combining BMP-2 and TGF-beta. We conclude that BMP-2 is a pleomorphic growth factor that induces cellular growth, maturation, and fibroplasia in both the dermis and epidermis. Further analysis of this growth factor in both fetal and adult wound healing may lead to important discoveries regarding the control of scar formation and fibrosis in many adult tissues.

Adult↗
PubMed1998

A new in utero sheep model for unilateral coronal craniosynostosis.

Several animal models have been designed in the past to analyze the pathophysiology and management of craniosynostosis, very few of which were intrauterine. Those that were interuterine had problems with either a short gestation or limited availability that prevented most researchers from using them in treatment analysis. We desired to create a biologically sound intrauterine model of craniosynostosis, using an animal with a long gestation and an early calvarial bone formation, which was easy to manipulate in utero, that could be created by any researcher studying this disorder. Using biologic data available regarding growth factors thought to be involved in bone growth and cranial suture closure, we developed a new in utero fetal lamb model for the study of craniosynostosis. Ten 70-day gestation fetal lambs (term gestation 140 days) received a midline coronal incision to expose both coronal sutures. The entire right coronal suture was then excised along with a 4-mm bony margin. In each animal, the site was packed with 25 mg of demineralized sheep bone powder augmented with 50 microg of bone morphogenetic protein-2 (BMP-2) and 1 microg of poly-transforming growth factor-beta. The scalp was closed, and the sheep were returned to the uterus until either 90 or 140 days of gestation. Complete fusion of the right coronal suture occurred in all fetuses by 90 days gestation. In every animal, right-sided frontal bone flattening and supraorbital rim elevation were evident. Histologic analysis showed bony synostosis at the suture site without evidence of suture regeneration. By 140 days, this isolated suture fusion led to marked craniofacial abnormalities including right supraorbital rim elevation, significant frontal bone flattening, a decrease in the anterior-posterior length of the cranial vault, and flattening of the cranial base. In conclusion, we have developed a new model for the study of the secondary effects induced by the process of cranial suture fusion, which produces abnormalities seen in naturally occurring cases of isolated right coronal suture synostosis. In addition, this model confirms that isolated coronal suture fusion alone can lead to the multiple cranial and facial abnormalities seen with this disorder, even in the absence of associated cranial base suture fusions.

Animals↗
PubMed1998

The in utero correction of unilateral coronal craniosynostosis.

We performed the first in utero correction of a unilateral right coronal craniosynostosis using 70-day gestation fetal lambs. The craniosynostosis was created in eight fetuses by excising their right coronal sutures, and then placing demineralized bone powder, transforming growth factor-beta, and bone morphogenetic protein-2 into the defect. Twenty-one days later, after suture fusion had occurred, four of the eight sheep were treated with a 4 mm x 12 mm strip craniectomy to open the entire synostosed right coronal suture. The edges of the excision were wrapped with 100-microm-thick Gore-Tex (W. L. Gore & Associates, Flagstaff, Ariz.) sheets to prevent bony refusion. All eight lambs then progressed to term (140 days). The skulls of four normal, unoperated, term lambs were used as controls. At 140 days, all four treated lambs had a widely patent strip craniectomy site without any evidence of bone regeneration. This in utero correction led to a marked improvement in craniofacial morphology of three of four animals when compared with the uncorrected controls with significant (p < 0.01) correction in orbital position, skull length, and shape of the frontal bone. This was in sharp contrast to the uncorrected animals, which had marked orbital elevation, compression of the anteroposterior length of the cranial vault, frontal bone flattening, and shortening of the cranial base. The fourth corrected animal also showed evidence of improvement but had some abnormal calvarial changes secondary to the development of horns, which displaced the calvaria in a downward vector. We conclude that the in utero correction of craniosynostosis is feasible and provides a significant benefit by decreasing the severity of many of the associated deformities seen with this disorder.

Animals↗
PubMed1998

Adverse outcomes following endoscopic repair of a fetal cleft lip using an ovine model.

OBJECTIVE: The purpose of this study was to determine if endoscopic techniques could be used to repair an epithelialized lip cleft with accuracy and with an outcome comparable to fetuses treated through an open hysterotomy. INTERVENTIONS AND RESULTS: In contrast to previous open fetal cleft lip repairs in the same model, none of the five fetuses reported here had a good aesthetic result. Although there was no evidence of scar histologically, the edges of the lip were poorly approximated. The epithelial lining and underlying dermis of the wound margins were notably inverted. The orbicularis oris muscle, which had been reapproximated, appeared thin and hypoplastic. Most of the vermilion elements were poorly aligned, and in one animal, there was a complete dehiscence of the repair. CONCLUSIONS: In a more representative model of cleft lip that is not an acute lip wound, in utero endoscopic suture repair of the ovine lip gave a poor result using current technology. Only a meticulously performed, multilayered, open repair of a cleft appears to give a good cosmetic and functional outcome. Further studies to improve the endoscopic repair as our technology advances are therefore warranted.

Animals↗
PubMed1997

Fetoscopic and open transumbilical fetal cardiac catheterization in sheep. Potential approaches for human fetal cardiac intervention.

BACKGROUND: Shortening the prenatal disease course of severe aortic and pulmonary stenoses by balloon valvuloplasty may diminish their postnatal expression. The purpose of this study in fetal sheep was to assess the feasibility of fetoscopic and open transumbilical fetal cardiac catheterization guided by fetal transesophageal echocardiography to provide alternative approaches for human fetal cardiac intervention. METHODS AND RESULTS: We studied a total of nine fetal sheep (95 to 103 days of gestation; term = 145 to 150 days) and performed transumbilical fetal cardiac catheterization by a minimally invasive fetoscopic (n = 6) or an open fetal surgical approach (n = 3). Monitored by fetal transesophageal echocardiography, with an 8F or 10F, 10-MHz intravascular ultrasound catheter we placed guidewires and interventional catheters via the umbilical arterial route into the fetal heart. In three of the fetuses, we created supravalvar pulmonary artery stenosis by open fetal cardiac surgery After fetal and maternal recovery, we exteriorized these fetuses and performed open transumbilical fetal cardiac catheterization with successful pulmonary arterial angioplasty in two. Three fetuses survived fetoscopic transumbilical catheterization for 1 or 2 days and died most likely of blood loss after sheath dislodgment (n = 1) or removal (n = 2). By securing the sheath insertion site with a suture, we prevented sheath dislodgment and minimized bleeding during sheath removal in three fetuses. These fetuses then survived fetoscopic transumbilical fetal cardiac catheterization for 1 to 2 weeks before being killed. CONCLUSIONS: This study in fetal sheep demonstrates that fetoscopic and open transumbilical fetal cardiac catheterization are feasible and, guided by fetal transesophageal echocardiography, provide potential alternative approaches for human fetal cardiac intervention.

Angioplasty, Balloon↗
PubMed1997

Percutaneous fetal access and uterine closure for fetoscopic surgery. Lessons learned from 16 consecutive procedures in pregnant sheep.

BACKGROUND: Maternal morbidity and preterm labor from fetal surgery might be minimized by a percutaneous technique for fetal access and uterine closure. METHODS: In each of 16 ewes, we inserted three trocars percutaneously into the amniotic cavity using ultrasound and fetoscopic guidance. In six ewes, percutaneous uterine closure after the procedure was attempted. We assessed feasibility and acute complications of our technique during surgery and at autopsy. RESULTS: We achieved percutaneous fetal access in 14 ewes and closed the uterus percutaneously in all six ewes attempted. Fetal injury was related to amnioinfusion or fixation of chorioamniotic membranes. Other complications were trocar dislodgment and damage to uterine wall and chorioamniotic membranes. The latter complication was prevented using balloon-tipped trocars. CONCLUSIONS: Percutaneous intraamniotic access and uterine closure for fetoscopic surgery can be achieved reliably with little maternal and fetal morbidity in sheep. Minor modifications are desired to apply this approach in humans.

Amnion↗
PubMed1997

A mediastinal window approach to aortopexy.

Between 1989 and 1994 six infants underwent aortopexy for symptomatic tracheomalacia via an anterior mediastinal window. This approach avoids a thoracotomy by using a small transverse incision over the second and third intercostal spaces followed by subchondral excision of these costal cartilages to expose the mediastinum. All patients had stridor and significant respiratory difficulty preoperatively; all experienced significant improvement in symptoms after aortopexy. There were no significant complications attributable to the procedure. The authors recommend this approach for aortopexy.

Airway Obstruction↗
PubMed1997

Tracheal ligation increases cell proliferation but decreases surfactant protein in fetal murine lungs in vitro.

Tracheal occlusion affects both fetal lung growth and maturation. The authors used a murine in vitro whole organ culture model to investigate these effects. The authors hypothesized that tracheal ligation would increase lung growth by increasing cell proliferation and would change surfactant protein synthesis in this system. Lungs were removed from day 14 gestation murine fetuses (term, 21 days). Tracheas were ligated and explants cultured in chemically defined, serum-free media for 1, 3, 4, 5, 7, or 14 days. DNA synthesis and cell division were assessed using a 5-bromo-2'-deoxy-uridine (BrdU) incorporation assay. Surfactant proteins A and B, markers of lung maturity, were detected using immunohistochemistry. Ligated lungs showed more BrdU-labeled cells per 1,000 x field (cells/hpf) at every time point. Ligated lungs on day 1 showed 27% more cells/hpf than unligated, on day 3, 21% more, on day 5, 54% more, on day 7, 60% more, and on day 14, 123% more (P < .05). In contrast, ligated lungs showed significantly less staining for surfactant proteins A and B than did unligated lungs. The authors conclude that tracheal ligation increases cell division but decreases surfactant protein in fetal murine lungs in vitro. These data suggest that although tracheal occlusion increases lung growth, it may decrease or delay lung maturation. This model provides a powerful tool for investigating the mechanisms underlying fetal lung development and tracheal occlusion-induced pulmonary hyperplasia.

Animals↗
PubMed1997

Fetal hydrops after in utero tracheal occlusion.

In utero tracheal occlusion accelerates fetal lung growth in experimental animals. Following tracheal occlusion, animals with an intact diaphragm can develop hydrops; presumably the enlarged lungs increase intrathoracic pressure, compress the fetal heart, and occlude venous return. In contrast, in animals with a diaphragmatic hernia, even excessive lung expansion has not led to hydrops because the lung can expand through the diaphragmatic defect into the abdomen. The authors had assumed that the diaphragmatic defect in human fetuses with congenital diaphragmatic hernia would provide a similar "release valve" if excessive lung growth occurred. A recent case proved this assumption wrong. At 26 weeks' gestation, an in utero fetal tracheal occlusion was performed on a human fetus with a diaphragmatic hernia. Over the next 9 days there was rapid lung expansion and overdistention, compression of the fetal heart, and hydrops. These findings mimic those seen in fetuses with congenital high airway obstruction syndrome and has implications for in utero treatment of congenital diaphragmatic hernia.

Adult↗
PubMed1997

Fetal diaphragmatic hernia: echocardiography and clinical outcome.

It is difficult to predict survival of fetuses diagnosed prenatally with congenital diaphragmatic hernia. Some studies suggest that left heart underdevelopment is associated with poor outcome, but fetal echocardiographic variables have not been conclusively proven to be good predictors of postnatal survival. The authors reviewed detailed fetal echocardiographic studies in twelve fetuses with congenital diaphragmatic hernia. Ten echocardiographic variables, including left and right ventricular width, left ventricular volume, and left ventricular mass, were examined from a four-chamber view, corrected for gestational age, and compared with normal data. The results of this study showed no significant differences between survivors and nonsurvivors in the ten variables analyzed. Although left heart dimensions and left ventricular volume in fetuses with congenital diaphragmatic hernia were below the expected normal range, these results did not predict postnatal outcome.

Echocardiography↗
PubMed1997

Operating on placental support: the ex utero intrapartum treatment procedure.

While treating eight fetuses with predictable airway obstruction, the authors developed a systematic approach, the ex utero intrapartum treatment procedure, to secure the airway during delivery. Six patients had their trachea plugged or clipped in utero for treatment of congenital diaphragmatic hernia, and two patients had prenatally diagnosed cystic hygroma of the neck and oropharynx. The ex utero intrapartum treatment procedure was performed by using high doses of inhaled halogenated agents to facilitate uterine relaxation during cesarean section, securing the fetal airway while feto-placental circulation remained intact, and then dividing the umbilical cord. A variety of procedures were performed during the ex utero intrapartum treatment procedure including bronchoscopy, orotracheal intubation, tracheostomy, tracheostomy with retrograde orotracheal intubation, tracheoplasty, removal of internal tracheal plug, removal of external tracheal clip, central line placement, and instillation of surfactant. There were minimal maternal or fetal complications during the procedure. This approach requires the coordinated efforts of pediatric surgeons, obstetricians, anesthesiologists, sonographers, and neonatologists. The combination of intensive maternal-fetal monitoring, cesarean section with maximal uterine relaxation, and maintenance of intact feto-placental circulation provides a controlled environment for securing the airway in babies with prenatally diagnosed airway obstruction.

Airway Obstruction↗
PubMed1997

Nitroglycerin attenuates the bowel damage of necrotizing enterocolitis in a rabbit model.

Endogenous enteric nitric oxide has multiple functions. Enteric nitric oxide may be diminished in the premature infant and may therefore predispose the immature intestine to injury. The aim of this study was to determine if the infusion of a nitric oxide donor (nitroglycerin) would attenuate intestinal damage in a rabbit model of necrotizing enterocolitis. Transmural injection of rabbit intestinal loops with an acidified solution of casein and calcium gluconate simulates certain aspects of necrotizing enterocolitis. After injection of acidified casein solution into rabbit intestinal loops, twelve rabbits were randomly divided into two groups: six received maintenance fluids only and six received maintenance fluids and a nitroglycerin infusion adjusted to maintain mean arterial pressure 10 mm Hg below baseline (range, 2 to 12 micrograms/kg/min). After 3 hours, the rabbits were killed, and the intestinal tissue graded histologically. Intestinal damage in the nitroglycerin-treated rabbits was significantly less than that of untreated controls (mean histological grade of 0.39 v 1.48, P < .001). In this rabbit model of necrotizing enterocolitis, infusion of the nitric oxide donor nitroglycerin significantly attenuates intestinal damage. We speculate that enteric nitric oxide deficiency, as may exist in the preterm infant, predisposes the intestine to necrotizing enterocolitis.

Animals↗
PubMed1997

Familial diaphragmatic agenesis: an autosomal-recessive syndrome with a poor prognosis.

Diaphragmatic agenesis is a severe form of congenital diaphragmatic hernia for which an autosomal recessive form of inheritance has been proposed. The authors report six families with 13 pregnancies with diaphragmatic agenesis in which inheritance followed an autosomal recessive pattern, including the first reported case of bilateral diaphragmatic agenesis in twins. None of the thirteen affected fetuses survived. Familial diaphragmatic agenesis appears to be a distinct clinical entity with a worse prognosis than posterolateral diaphragmatic hernia.

Adult↗