Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax.
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Adult↗
Biomedical subjects
M T Longaker
Publications and source records attributed to M T Longaker.
Hyaluronic acid-stimulating activity in the pathophysiology of Wilms' tumors.
Markedly elevated levels of hyaluronic acid occur in the serum and urine of some patients with Wilms' tumor. We have recently described a glycoprotein factor in fetal serum that stimulates deposition of hyaluronic acid. In a survey of bovine fetal tissue extracts, we have identified the fetal kidney as the source of this circulating activity. Wilms' tumors arise from transformed "rests" of fetal kidney. We demonstrate here that such tumors continue to produce this fetal factor and that the hyaluronic acid-stimulating activity is found in the urine of children with Wilms' tumors. In the three patients with Wilms' tumor who were followed, elevated levels of hyaluronic acid-stimulating activity were found in their urine before treatment. By 2 months after surgical removal of their tumors, these levels had returned to baseline. We propose that hyaluronic acid-stimulating activity is the mechanism for the elevated levels of hyaluronic acid in the sera and urine of these patients. The activity is an oncofetal protein and the first for which a function has been identified. It also is a marker for this common childhood solid tumor and has the potential for identifying children at increased risk.
Animals↗
Carotid artery reconstruction following extracorporeal membrane oxygenation.
Right hemispheric brain injury has been noted in surviving infants treated with venoarterial extracorporeal membrane oxygenation (ECMO). This phenomenon may be secondary to permanent ligation of the right carotid artery. At our institution, conventional ventilatory therapy failed in five neonates with respiratory insufficiency, and they were treated successfully with ECMO. In four of the five neonates, the right carotid artery was reconstructed at the time of decannulation. At discharge, all newborns with carotid artery repair showed no signs of unilateral brain injury and had excellent antegrade flow in the right carotid artery as assessed by both duplex and transcranial Doppler ultrasound scanning. Carotid artery reconstruction after ECMO is a technically simple procedure that may reduce the incidence of right hemispheric brain injury and long-term consequences of marginal cerebral perfusion.
Anastomosis, Surgical↗
Fetal intervention in obstructive uropathy: prognostic indicators and efficacy of intervention.
Management of the fetus with bilateral hydronephrosis is controversial; ability to predict outcome and efficacy of prenatal intervention are unknown. We studied 40 fetuses referred for ultrasonography, examination of fetal urine, and possible therapy. We retrospectively assigned fetuses to a good prognosis group if fetal urine was hypotonic (sodium less than 100 mEq/L, chloride less than 90 mEq/L, osmolarity less than 210 mOsm/L) and there was no ultrasonographic evidence of dysplasia; we assigned fetuses to a poor prognosis group if even one criterion was abnormal. Survival was greater in the good prognosis group than in the poor prognosis group (81% vs 12.5%; 87% vs 30%, excluding abortions) (p less than 0.005). We then attempted to assess the efficacy of prenatal urinary decompression by comparing outcome within the good and poor prognosis groups. Survival with intervention was greater in both the good prognosis group and the poor prognosis group (89% vs 70% and 30% vs 0%). In 6 of the 8 survivors in the good prognosis group, severe oligohydramnios was reversed by decompression. We conclude the fetal urine electrolyte levels and ultrasonographic appear helpful in predicting residual fetal renal function and neonatal outcome and that prenatal decompression may prevent the development of fatal pulmonary hypoplasia.
Amniotic Fluid↗
Reduced-size lung transplantation in neonatal swine: technique and short-term physiological response.
Lung transplantation is now a clinical reality in adults but is limited by the scarcity of appropriate donors. The donor shortage is even more acute for neonatal and pediatric patients. Reduced-size lung grafts would expand the pool of appropriate cadaveric donors and allow HLA-matched living related lobar or segmental lung transplants. To evaluate this experimentally, we developed a model of pulmonary lobar transplantation in neonatal pigs and studied the acute hemodynamic response after transplanting the left lower lobe from a more mature donor to a neonatal recipient. Technical considerations included using the recipient atrial appendage for the pulmonary venous anastomosis. Nine pairs of pigs underwent left lateral thoracotomy. The recipient left atrial and pulmonary arterial pressures, cardiac output, and pulmonary vascular resistance were measured before pneumonectomy and after left lower lobe transplantation. Although the left atrial and pulmonary arterial pressures remained unchanged after transplantation, there was a 15% increase in pulmonary vascular resistance and a 23% reduction in cardiac output. Neither change was statistically significant. The distribution of blood flow through the left and right pulmonary arteries was unchanged after transplantation. We conclude that lobar transplantation is technically feasible in immature animals and that the pulmonary venous anastomosis to the left atrial appendage facilitates the procedure. This model may prove useful in studying lung transplantation in immature recipients and expedite implementation of reduced-size lung transplantation in neonatal and pediatric patients.
Anastomosis, Surgical↗
Foetal wound healing in a large animal model: the deposition of collagen is confirmed.
Foetal wound healing occurs without scarring. A scar is a collagen-rich repair tissue, and the absence of scarring in the foetus has raised questions concerning the presence and nature of collagen deposition in foetal wounds. Studies of collagen deposition in foetal wounds in small animals, performed late in gestation, have been equivocal. In this study, using a large animal with a long gestational period, the sheep, the deposition of collagen is confirmed.
Amino Acids↗
Mediastinal pancreatic pseudocysts in children.
Mediastinal pseudocyst is an unusual complication of pancreatitis, with only four cases previously reported in children. The extent of the pseudocyst can be defined by computed tomography or magnetic resonance imaging scan and preoperative aspiration of cyst fluid for amylase level can establish the diagnosis. Endoscopic retrograde cholangiopancreatography to define ductal anatomy can help plan the appropriate drainage procedure. Although exceedingly rare, the diagnosis of pseudocyst should be considered for any cystic mass in the abdomen or thorax, even in the absence of elevated amylase or history suggesting pancreatitis.
Amylases↗
Pulmonary vascular resistance in neonatal swine: response to right pulmonary artery occlusion, isoproterenol, and prostaglandin E1.
The pulmonary physiological response of adults to unilateral pulmonary artery (PA) occlusion has been well-characterized as resulting in a decrease in the pulmonary vascular resistance (PVR), in order to maintain the same PA pressure and accommodate the entire cardiac output (CO). We evaluated the response of the neonate to unilateral PA occlusion and how this response is altered by infusions of Isoproterenol (Isuprel) and prostaglandin E1 (PGE1) in the neonatal swine model. Twenty farm piglets (five at 1 day, three at 5 days, seven at 14 days, and five at 60 days as controls) underwent left lateral thoracotomy and measurement of PA and left atrial (LA) pressures, CO, and PVR with the right PA open and occluded. To determine if neonatal PVR could be influenced by a vasodilator (indicating the vascular capacity is not fixed) or by an inotrope (indicating the lung is not maximally recruited) this experiment was then repeated with infusions of PGE1 (a vasodilator) at doses of 0.1, 0.5, and 1.0 micrograms/kg/min and subsequently with Isuprel (an inotrope and vasodilator) at doses of 0.1, 0.5, 1.0 micrograms/kg/min. Control measurements taken without unilateral PA occlusion showed that PVR is high at 1 day of age but progressively decreases to a level 89% lower by 60 days of age. The vascular capacity of the neonatal lung is fixed and responds to unilateral PA occlusion with a dramatic increase in PVR. This response cannot be altered by either a vasodilator (PGE1) or an inotrope (Isuprel) thereby limiting the utility of these drugs in treating neonatal pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Alprostadil↗
Fetal wound healing: an in vitro explant model.
The ability of fetal skin wounds to heal without scar formation is remarkable. The mechanisms that endow the fetus with this unique healing ability remain unknown. We have developed an in vitro explant model using fetal sheep skin to investigate fetal wound healing. This model eliminates the complex systemic mechanisms that modulate in vivo wound healing. We demonstrated that using an enriched medium, midgestation fetal sheep skin explants following wounding reepithelialized within 4 days. By 7 days after wounding the confluent epidermis was thicker, but the dermal wound remained open. This model demonstrates that it is possible to achieve conditions in culture that maintain tissue viability and support reepithelialization. This model may allow us to resolve some of the individual components that participate in the process of scarless fetal skin healing.
Animals↗
A new tumor marker for Wilm's tumor called hyaluronic acid-stimulating activity (HASA)
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Biomarkers, Tumor↗
Complete heart block in fetal lambs. I. Technique and acute physiological response.
Prenatally diagnosed complete heart block (CHB), without associated cardiac anomalies, is often refractory to attempts to increase heart rate and cardiac output by medical therapy, and results in fetal death. We developed a model of CHB in fetal lambs in order to evaluate the acute physiological consequences of CHB and to assess the feasibility of fetal cardiac ventricular (V) and atrioventricular (AV) pacing. After hysterotomy and fetal sternotomy AV-sequential pacing leads were placed on the right atrium and ventricle (RV). Electromagnetic flow transducers were placed around the pulmonary artery and the ascending aorta to measure combined ventricular output (CVO) in normal sinus rhythm (NSR), CHB, AV, and V pacing. CHB block was successfully induced in 19 of 21 (90%) fetal lambs at 100 to 110 days' gestation by injection of formalin into the interventricular septum. Two fetuses were refractory to CHB despite multiple injections. The mean ventricular escape rate was 52 +/- 3 (+/- SEM) beats/min (range, 45 to 60 beats/min). CHB lasted for the period of study (1 to 8 hours), and spontaneously reverted to NSR in one fetus after 3 hours. Combined ventricular output in NSR was 470 +/- 31 mL/min (+/- SEM), which fell to 213 +/- 13 mL/min in CHB, 45% of normal CVO (P less than .0001). CVO during AV-sequential and V pacing was 77% (P = .02) and 62% (P less than .001), respectively, of combined ventricular output in NSR. Both RV (27%) and left ventricles (LV) (37%) showed compensatory increase in stroke volume during CHB.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Nephron-sparing approach to bilateral Wilms' tumor: in situ or ex vivo surgery and radiation therapy.
Bilateral Wilms' tumor patients, who experience local recurrence after maximal multimodality therapy, present a difficult surgical problem. The role of surgery in the management of these patients has changed from ablation to preservation of renal tissue, with bilateral nephrectomy as a last resort. Two children who had recurrent tumors in the remaining kidney underwent nephron-sparing surgery and focal intraoperative radiation therapy. In one case, this nephron-sparing surgery and intraoperative radiation therapy were performed in situ, in the other kidney was removed and reimplanted (ex vivo bench surgery and irradiation). These techniques may allow complete obliteration of gross and microscopic disease, while maximizing residual renal function.
Child↗
Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid.
Fetal wound healing occurs rapidly and without inflammation, fibrosis, or scar formation. It is a process fundamentally different from adult wound healing. The mechanisms that underlie such unique healing properties are unknown. However, hyaluronic acid, a glycosaminoglycan component of the extracellular matrix, is prominent throughout the course of fetal wound healing, and is thought to play a major role in the healing process. Amniotic fluid contains high levels of hyaluronic acid. Amniotic fluid also contains a number of potent growth factors that are critical for fetal development. In this report, a new factor in amniotic fluid that stimulates deposition of hyaluronic acid is described. This activity is measured in an in vitro assay system in which cultured fibrosarcoma cells are used as indicator cells. Amniotic fluid thus provides two separate mechanisms for the deposition of hyaluronic acid. One is by exogenous application directly onto fetal skin wounds; the second is by providing a factor to increase the production of hyaluronic acid endogenously, by stimulating cells around the wound site. The resulting hyaluronic acid-rich area may support the ability of the fetal wound to heal with its unique properties.
Amniotic Fluid↗
Etiology of intestinal damage in gastroschisis, II. Timing and reversibility of histological changes, mucosal function, and contractility.
Previous work in the fetal lamb examined the relative effects of amniotic fluid and bowel constriction in the etiology of bowel damage in gastroschisis. The present study used the same model to assess the timing and reversibility of these changes during gestation. Gastroschisis was created at 80 days' gestation, and a tape was placed around the bowel to cause gradual constriction with growth. Lambs were killed at 100 days, 120 days, and term. Bowel damage was assessed using histology, mucosal enzyme activity, and in vitro motility. In an additional "repaired" group, the constrictor was removed at 120 days, a silastic pouch placed over the bowel, and bowel damage assessed at term. Normal fetuses at each gestational age were used as controls. A fibrous peel was observed at all gestational ages. Mucosal villous atrophy and mesenteric venous and lymphatic dilation were mild at 100 and 120 days, but severe at term. These changes were present but mild in repaired animals at term. Mucosal enzyme activity decreased gradually with gestational age; inhibition of maltase activity was maximal at term, and was significantly reversed by repair, whereas inhibition of aminooligopeptidase activity was maximal at 120 days, and was not affected by repair. Protein/DNA, DNA/weight, and protein/weight ratios showed that repaired mucosal cells were significantly more proliferative, smaller, and less mature than control or gastroschisis cells. In vitro motility studies demonstrated a mild decrease in contractility at 100 and 120 days, and a large decrease at term. This deleterious effect at the end of gestation was only partially reversed by repair in utero.(ABSTRACT TRUNCATED AT 250 WORDS)
Abdominal Muscles↗
A rabbit model for fetal cleft lip repair.
Recent clinical and experimental data indicate that fetal wound healing occurs without the accompanying inflammation and scar formation typical of postnatal wounds. The lack of scar tissue may have significant implications for craniomaxillofacial surgery. This report documents the development of a model for fetal cleft lip repair in rabbits. The survival rate for the first 47 fetuses was 76.6%.
Animals↗
Fetal trauma: relation to maternal injury.
Conventional surgical wisdom is that fetal death is a predictable consequence of severe maternal injury. In order to define the natural history of maternal-fetal trauma and better formulate management strategies, we reviewed our recent experience with 32 cases of maternal trauma at a major trauma center. There were three cases of fetal death; two were associated with severe maternal injury, but one had no significant injury to the mother. All cases had placental injury. Conversely, there were five cases of severe maternal trauma but only two unsuccessful pregnancy outcomes. We conclude that the extent of maternal injury does not necessarily correlate with the degree of fetal injury. Lethal placental or direct fetal injury can occur even in the absence of significant maternal injury. In selected cases, fetal salvage after maternal-fetal trauma may be achieved by early delivery and prompt pediatric surgical intervention.
Adult↗
The modified Puestow procedure for chronic relapsing pancreatitis in children.
Chronic relapsing pancreatitis in children is an unusual condition that often goes undiagnosed and untreated for years. In light of recent reports in adults that endocrine and exocrine function may be preserved by early pancreaticojejunostomy, we reviewed our experience with this procedure (one Duval, 10 Puestows) in 10 children between 1969 and 1989. The underlying etiology was familial pancreatitis in four patients, one case of unknown etiology, congenital ductal anomalies in four (one pancreas divisum, one annular pancreas, one choledochal cyst, and one ductal stenosis), and posttraumatic in one. All 10 had intractable recurrent abdominal pain. Preoperatively, only three patients evidenced exocrine insufficiency and none had endocrine insufficiency. There was complete resolution of pain in eight patients and improvement in two during a mean observation period of 4 years (range, 7 months to 19.75 years). Exocrine insufficiency resolved in two patients but has persisted in the third patient now on Viokase. Endocrine insufficiency has developed during follow-up in one patient. Pancreaticojejunostomy provides excellent relief of recurrent pain in chronic relapsing pancreatitis in children. Endoscopic retrograde cholangiopancreatography (ERCP) is indicated when the diagnosis of chronic relapsing pancreatitis is suspected to define the ductal anatomy. Pancreaticojejunostomy may prevent the progression of exocrine and endocrine insufficiency if performed early in the course of the disease.
Abdominal Pain↗
Testing the limits of neonatal tracheal resection.
Obstructive lesions of the trachea in infants can be life-threatening because secretions or mucosal inflammation can easily obstruct the tiny compromised airway, and distal obstruction cannot be relieved by an endotracheal or tracheostomy tube. The principles of tracheal resection in adults are well established. The limits of tracheal resection in neonates are unknown. We present a case in which at least two-thirds of the trachea was resected successfully in a neonate.
Anastomosis, Surgical↗