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Biomedical subjects

M T Longaker

Publications and source records attributed to M T Longaker.

At least 253 records · Page 14Linked to original sources
PubMed1990

Pulmonary lobar transplantation in neonatal swine: a model for treatment of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Lung transplantation is a potential treatment for these otherwise doomed infants using ECMO as a bridge to transplantation. Cadaveric, or living related donation of a more mature reduced size lung (pulmonary lobe or segment) may help solve the critical donor shortage problem. We evaluated the physiological response of mature left lower lobe (LLL) transplants in neonatal swine with the hemodynamic conditions of CDH simulated by occlusion of the right pulmonary artery (PA), and also studied the pulmonary function of the mature lobar graft compared with the neonatal lung. LLL transplantation was well tolerated and resulted in minimal alteration in hemodynamic parameters. The response to right PA occlusion was similar pre- and posttransplantation with a fall in cardiac output and a significant rise in pulmonary vascular resistance. Compared with the contralateral native lung, the lobar graft was preferentially ventilated with resultant higher pH (7.65 +/- 0.17 v 7.41 +/- 0.08, P less than .01) and lower pCO2 (17 +/- 6 v 36 +/- 5, P less than .001). The more mature lobar graft was preferentially ventilated due to the increased compliance compared with the neonatal right lung (8.16 +/- 1.28 v 5.48 +/- 0.82 mL/cm, P less than .0001). Reduced size lung transplantation is technically feasible and may help solve the donor problem for severe CDH neonates for whom no effective therapy is currently available.

Animals↗
PubMed1990

Studies in fetal wound healing, VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation.

The mechanisms that underlie the lack of scarring in fetal wounds are unknown, but probably relate to the control of collagen fibrillogenesis. The role of collagen in the fetal wound matrix is controversial, and several wound implant models have been used to evaluate collagen deposition in fetal wounds. Unfortunately, these models create an artificial wound environment and may thereby affect the results. In order to study fetal wound collagen deposition in linear wounds without artificially altering the wound environment, we applied a highly sensitive immunohistochemical technique that uses antibodies to collagen types I, III, IV, and VI. We found that collagen was deposited in fetal wounds much more rapidly than in adult wounds. Wound collagen deposition occurred in a normal dermal and mesenchymal pattern in second and early third trimester fetal lambs. These findings are consistent with the observation that the fetus heals rapidly and without scar formation. In contrast, wounds in late gestation fetal lambs showed some evidence of scar formation. Further studies may suggest ways to alter the adult wound so that it heals in a fetal manner.

Animals↗
PubMed1990

Hyaluronic acid deposition in cardiac myxomas: localization using a hyaluronate-specific binding protein.

Myxomas are the most common primary tumors of the heart. These lesions contain a gelatinous, ground-substancelike material which has been described as glycosaminoglycan in nature. Using a newly developed, cartilage-derived hyaluronic acid-binding protein and a modification of the avidin-biotin immunostaining procedure, we demonstrate that hyaluronic acid is contained in the jellylike material of cardiac myxomas.

Adult↗
PubMed1989

Hyaluronic acid-stimulating activity in sera from the bovine fetus and from breast cancer patients.

The sine qua non of malignancy is the ability of tumor cells to migrate and invade surrounding tissue. There are many substances that have been described that enhance cell motility and hyaluronic acid is prominent among these. Hyaluronic acid is a high molecular weight alternating disaccharide polymer found in abundance in extracellular matrices whenever rapid cell proliferation or tissue regeneration and repair occur. It creates a permissive environment for cell motility during embryogenesis, and high levels of hyaluronic acid also correlate with increased tumor cell invasion and aggressiveness. Little is known about the regulation of hyaluronic acid production, either in normal tissue or in malignancy. In this study, we characterize a hyaluronic acid-stimulating activity in fetal calf serum and describe a similar activity in the sera of breast cancer patients. The stimulating activity was measured by placing aliquots of test substance on fibrosarcoma cells. These indicator cells, which synthesize copious quantities of hyaluronic acid, respond to stimulation in a time- and dose-dependent fashion. The fetal calf serum hyaluronic acid-stimulating activity is maximum early in gestation and then falls rapidly to essentially no activity at term. This activity was partially purified from 120-day fetal calf serum by concanavalin A-Sepharose affinity and ion exchange chromatography and is accounted for by a glycoprotein with a molecular weight of 150,000 on gel filtration under native conditions. The sera of breast cancer patients with measurable burden of disease also contained hyaluronic acid-stimulating activity, which was not present in normal serum donors or in breast cancer patients without evidence of disease. The production of this stimulating activity may contribute to the development of the malignant phenotype by inducing hyaluronic acid-rich microenvironments that are permissive to tumor cell invasion and metastases.

Animals↗
PubMed1989

Fetal hydrops and death from sacrococcygeal teratoma: rationale for fetal surgery.

Most sacrococcygeal teratomas diagnosed before birth can be managed by planned delivery and postnatal surgery. However, large tumors early in gestation may result in placentomegaly, hydrops, and fetal death and a preeclampsia-like syndrome in the mother. This chain of events may result from high output cardiac failure in the fetus caused by arteriovenous shunting through the tumor. We recently encountered this situation in a fetus at 21 weeks' gestation and performed fetal surgery in an attempt to reverse the process. Excision of the teratoma resulted in reversal of hydrops, diminution of descending aortic flow on Doppler echocardiography, and decrease in placental thickness. Despite these changes, uterine irritability after hysterotomy resulted in labor and delivery of a nonviable premature infant. This case demonstrates that when fetal sacrococcygeal teratoma becomes very large early in gestation, high output cardiac failure can endanger both fetus and mother. In the future, use of Doppler echocardiography may allow appropriate selection of high-risk fetuses. Intervention to prevent arteriovenous shunting through the tumor may offer these fetuses an improved chance for survival.

Adult↗
PubMed1989

Systemic-to-pulmonary artery shunt using the internal mammary artery.

Systemic-to-pulmonary artery shunts may be useful for palliation of cyanotic congenital heart disease. We report the case of a 5-year-old boy in whom the internal mammary artery was used to create a systemic-to-pulmonary artery shunt after failure of a previous Blalock-Taussig shunt. This technique may have distinct advantages in selected cases and should be considered as an alternative during investigation of the older child who requires a systemic-to-pulmonary artery shunt.

Anastomosis, Surgical↗
PubMed1989

Etiology of intestinal damage in gastroschisis. I: Effects of amniotic fluid exposure and bowel constriction in a fetal lamb model.

Gastroschisis is often complicated by damage to the herniated small bowel, resulting in motility and absorption disturbances and occasional intestinal necrosis and atresia. To study the pathophysiology of this process, a model of gastroschisis was developed in fetal lambs. At 80 days' gestation, the anterior abdominal wall was partially excised to create a small peritoneal cavity, and the small bowel was extruded through a Silastic ring to create a defect of uniform size. In one experimental group, a tie was placed around the herniated bowel at the level of the abdominal wall to provide gradual constriction as the fetus grew. In a second group, no tie was placed. Control animals had a simple laparotomy and no abdominal wall defect; some also had a constrictor placed around the base of the bowel. The animals were delivered near term, and the bowel was evaluated histologically and by an in-vitro bowel motility assay. Histologic examination showed normal ganglion cells in all groups and no evidence of ischemic injury. A fibrous peel was seen only in bowel exposed to amniotic fluid, with or without a constrictor. Lymphatic and venous dilation, smooth-muscle thickening, and focal mucosal blunting were seen in bowel subjected to chronic obstruction by a constrictor, regardless of whether it was exposed to amniotic fluid. Both constriction of the bowel and amniotic fluid exposure were associated with a decrease in motility; these two effects were independent and additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1989

Primary fetal hydrothorax: natural history and management.

Primary fetal hydrothorax presents a wide spectrum of severity ranging from small, harmless effusions, to life-threatening thoracic compression. To define natural history and management, we reviewed 32 cases seen at two large perinatal centers from 1980 to 1987. Spontaneous resolution of the effusions was seen in three fetuses, all of whom survived. Three fetuses were electively terminated. The overall mortality was 53%. In the 24 untreated fetuses, sex and the presence of polyhydramnios did not influence mortality, but hydrops, gestational age less than 35 weeks at delivery, and bilateral effusions were associated with a poor prognosis. Five fetuses underwent in utero decompression. In four, thoracentesis was performed, with rapid reaccumulation of the effusion. All four died from pulmonary insufficiency. In the fifth fetus, a thoracoamniotic shunt permanently decompressed the effusion, with resolution of the hydrops, and delivery of a normal viable infant. We conclude that (1) primary fetal hydrothorax may resolve or progress to hydrops, necessitating close follow-up with ultrasound; (2) pulmonary hypoplasia as a result of undrained large pleural effusions may result in neonatal mortality; (3) the gestational age at both diagnosis and delivery, the development of hydrops, and bilaterality of effusions are important prognostic predictors; and (4) the fetus with large effusions and hydrops has a poor prognosis, and thoracic decompression with a thoracoamniotic shunt may prove life saving.

Female↗
PubMed1989

Studies in fetal wound healing: I. A factor in fetal serum that stimulates deposition of hyaluronic acid.

Fetal wound healing without scar formations, fibrosis, or contracture might be accompanied by major differences in the wound extracellular matrix. The matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. Although hyaluronic acid is a critical molecule for both embryonic development and wound healing, no factor has yet been identified that modulates hyaluronic acid in a consistent manner. We describe here a substance present in fetal sheep serum that stimulates hyaluronic acid synthesis by cultured fibroblasts. This glycoprotein factor appears to be ubiquitous, present in fetal sheep and bovine serum, reaching a peak in each at 40% of the way through gestation. This factor is also present in amniotic fluid. It might control hyaluronic acid deposition. In turn, hyaluronic acid, by creating an extracellular environment permissive for cell motility and proliferation, might be critical for fetal development. We suggest that the same sequence of events underlie the unique properties observed in fetal wound healing.

Animals↗
PubMed1989

Studies in fetal wound healing: II. A fetal environment accelerates fibroblast migration in vitro.

We have used an in vitro model of wound healing using scratches made in a confluent monolayer of fibroblasts. The effects of fetal calf and postnatal calf serum on the migration of fibroblasts were compared. Differences between fetal and calf serum-incubated fibroblasts grown on coverslips were observed within 15 minutes of exposure. Cells in fetal serum began to change both shape and orientation and to move into the trough created by the scratch. The fibroblasts incubated in fetal calf serum completely filled in the trough within 16 hours while those incubated in calf serum did not do so even after 24 hours. We estimate that, at any point, there was a 50% lag time in the migration of the fibroblasts in the presence of postnatal calf serum. This difference in migration and filling was not a function of mitogenesis; the mitogenicity of the two sera were comparable. The results suggest that fibroblast migration in vitro is accelerated by the fetal serum. A similar mechanism may occur in vivo and may underlie the ability of the fetal wound to heal more rapidly.

Animals↗
PubMed1989

Studies in fetal wound healing: III. Early deposition of fibronectin distinguishes fetal from adult wound healing.

Wound healing in the fetus proceeds through a series of steps that differ in the fetus and the adult. At each phase of this complex process, there is signaling between the tissue cells and the wound microenvironment, signals that are mediated by and through the extracellular matrix. We postulate that these signals occur earlier in fetal wounds, resulting in more rapid repair. To investigate this, we compared the first 24 hours of wound healing in the rabbit fetus and adult, using antibodies against key extracellular matrix macromolecular components: laminin, fibronectin, and type-specific collagens I, III, IV, and V. Fibronectin was the first matrix component to be deposited, and was visualized as early as four hours after fetal wounding and 12 hours after adult wounding. There was no evidence of new laminin or collagen deposition in either the fetal or adult wounds at any time point examined. The early deposition of fibronectin, a matrix adhesion molecule that provides a scaffolding for epithelial migration, may underlie the rapid reepithelialization observed in fetal wounds.

Animals↗
PubMed1989

Appendicovesicostomy: a new technique for bladder diversion during reconstruction of cloacal exstrophy.

Urinary tract diversion in the reconstruction of cloacal exstrophy presents a difficult problem. Many methods have been used, but none has been found to be ideal. We describe a simple technique that incorporates the ileocecal plate in the bladder augmentation, and uses the appendix as a conduit for urinary diversion. This technique offers the advantages of primary closure, effective urinary drainage without tubes, and simplicity of bowel reconstruction with preservation of maximal absorptive surface.

Appendix↗
PubMed1989

Biliary appendico-duodenostomy: a nonrefluxing conduit for biliary reconstruction.

Biliary conduits constructed during operations for choledochal cysts or biliary atresia are frequently complicated by reflux of gastrointestinal contents, stasis, and obstruction with resulting cholangitis. We have used the appendix as a biliary conduit for cases of biliary atresia and choledochal cyst, adapting the urologic technique of a tunneled, nonrefluxing anastomosis for reconstruction of the biliary tree--biliary appendico-duodenostomy (BAD). From our preliminary experience with this technique, it appears promising.

Anastomosis, Surgical↗
PubMed1989

Studies in fetal wound healing. IV. Hyaluronic acid-stimulating activity distinguishes fetal wound fluid from adult wound fluid.

Recent clinical and experimental evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Our initial experience with human open fetal surgery reinforces experimental observations that the fetal wounds heal without the scarring, inflammation, and contraction that often accompany adult wounds. In this study we examine fetal wound fluid in an attempt to elucidate the control mechanisms that endow the fetus with unique healing properties. The extracellular matrix of fetal wounds is rich in hyaluronic acid, a glycosaminoglycan found in high concentrations whenever there is tissue proliferation, regeneration, and repair. We establish that wound fluid from the fetus contains high levels of hyaluronic acid-stimulating activity that may underlie the elevated deposition of hyaluronic acid in the fetal wound matrix. In contrast there was no hyaluronic acid-stimulating activity present in adult wound fluid. Hyaluronic acid, in turn, fosters an extracellular environment permissive for cell motility and proliferation that may account for the unique properties observed in fetal wound healing.

Age Factors↗
PubMed1988

Prenatal diagnosis and management of bilateral hydronephrosis.

This report reviews the management of the fetus with congenital hydronephrosis (CH), a challenging diagnostic and therapeutic problem. Experimental models of obstructive uropathy have produced histologic changes similar to those seen in kidneys of human neonates with congenital hydronephrosis. Relief of obstruction in utero in these models has been shown to prevent some of the dysplastic changes caused by obstruction. These studies have formed the theoretical basis for in utero decompression to restore amniotic fluid dynamics to prevent death from pulmonary hypoplasia, and reverse or arrest dysplastic morphogenesis. The development of prognostic criteria has greatly aided in selection of appropriate fetuses for intervention. These criteria include: (1) Na less than 100 mEq/l; (2) Cl less than 90 mEq/l; (3) osmolarity less than 210 mosmol; (4) sonographic appearance of the fetal kidneys; (5) amniotic fluid status; (6) urine output at fetal bladder catheterization. All fetuses should have ultrasonography to exclude other anomalies, and karyotype analysis to exclude chromosomal abnormality. If amniotic fluid volume is normal, the pregnancy is followed with serial ultrasound examinations. If oligohydramnios develops, a prognostic evaluation is performed, including fetal bladder catheterization. If the fetus has poor residual renal function, on the basis of prognostic criteria, appropriate counseling may be given. If the fetus has good residual renal function, depending on lung maturity, it can be delivered early for corrective surgery. If diagnosed prior to lung maturity in utero, decompression by either vesicoamniotic shunting or open fetal surgery may be attempted in the highly selected case.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Early experience with open fetal surgery for congenital hydronephrosis.

The fetus with severe bilateral hydronephrosis and associated oligohydramnios in the second trimester is doomed at birth by ongoing pulmonary and renal damage. Since decompression with percutaneously placed catheters anesthetic, surgical, and tocolytic techniques for open fetal anesthetic, surgical, and tocolytic techniques for open fetal urinary tract decompression in animals, and have now applied those techniques to a small group of five patients. One had bilateral ureterostomies and the subsequent four had marsupialization of the bladder. All pregnancies proceeded to cesarean delivery at 32 to 35 weeks' gestation. There was no long-term maternal morbidity, and two mothers have since experienced normal pregnancies. Three fetuses had return of normal amniotic fluid dynamics, and all three had adequate pulmonary function at birth, suggesting that fatal pulmonary hypoplasia associated with early severe oligohydramnios had been reversed. Two neonates died at birth with pulmonary hypoplasia. One had no amniotic fluid even after decompression, and the other had some amniotic fluid after decompression but a tiny chest cavity due to the long period of severe oligohydramnios before decompression. Of the three surviving infants, one had normal renal function when she died of unrelated causes at 9 months of age. One has normal renal function at 23 months and the third had failing renal function at 2 1/2 years and has grown and developed normally, but will require renal transplantation. We have now developed selection criteria that would exclude from treatment the two fetuses who died of pulmonary hypoplasia and the one who developed renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗