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Biomedical subjects

M T Longaker

Publications and source records attributed to M T Longaker.

At least 217 records · Page 12Linked to original sources
PubMed1991

Hyaluronidase levels in urine from Wilms' tumor patients.

The pathophysiology of Wilms' tumor is associated with major alterations in hyaluronic acid metabolism. Elevated levels of both hyaluronic acid and a hyaluronic acid-stimulating activity occur in the urine and serum of patients with this tumor. In the current study, we describe elevated levels of urinary hyaluronidase in five patients with Wilms' tumor. Following surgical removal of the tumor, enzyme levels decreased toward normal. Characterization of enzyme activity indicates that hyaluronidase may be produced by the tumor itself. Alternatively, normal renal tissue may also be producing enzyme in a compensatory response to the elevated hyaluronic acid levels in these patients. We suggest that urinary hyaluronidase can be used as an additional marker for Wilms' tumor.

Biomarkers, Tumor↗
PubMed1991

Intraoperative radiation therapy for Wilms' tumor in situ or ex vivo.

Patients with bilateral Wilms' tumor who have local recurrence after undergoing maximum-dose multitechnique therapy are problematic. The role of surgery in the management of these patients is changing from ablation to preservation of renal tissue. Bilateral nephrectomy is reserved as a last resort. Intraoperative radiation therapy (IORT) is advantageous to conservative management, as illustrated by the current cases of two children with recurrent Wilms' tumors in their remaining kidneys. Both children underwent limited surgery and precisely directed IORT. In one patient the nephron-sparing surgery and IORT were performed in situ. In the other the kidney was removed, treated with ex vivo bench surgery and radiation surgery, and then reimplanted. The adjuvant use of IORT, either in situ or ex vivo, in nephron-sparing surgery permits complete obliteration of gross and microscopic disease while maximizing residual renal function.

Child↗
PubMed1991

Maternal outcome after open fetal surgery. A review of the first 17 human cases.

A few fetal diseases may benefit from surgical treatment before birth, but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and reproductive potential after fetal surgery, we reviewed our experience with 17 highly selected women who underwent fetal surgery. Fifteen of these procedures were performed for one of two congenital anomalies: severe bilateral hydronephrosis and congenital diaphragmatic hernia. There were no deaths or serious maternal injuries. In the 14 women who continued pregnancy after hysterotomy, uterine irritability and preterm labor were frequent complications, requiring early confinement in most cases. There has been no detectable effect on future fertility, as indicated by eight subsequent normal pregnancies. We conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother's life or her future reproductive potential. However, morbidity related to premature labor remains a serious problem, and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery.

Adolescent↗
PubMed1991

Sheep amniotic fluid has a protein factor which stimulates human fibroblast populated collagen lattice contraction.

Sutured incisional wounds made in fetal sheep and rabbits heal without scarring. Fetal sheep excisional wounds can close by contraction, but those in fetal rabbits do not. In vivo and in vitro evidence suggests that rabbit amniotic fluid inhibits wound contraction. The question arises: does sheep amniotic fluid promote wound contraction because their fetal wounds close by contraction? Sheep amniotic fluid (SAF) from 100 and 125 days gestation was tested in fibroblast populated collagen lattice (FPCL) system, an in vitro model of wound contraction. SAF stimulated FPCL contraction in a dose responsive manner. SAF from a 100 day fetus was more stimulating than a 125 day SAF. SAF enhanced FPCL contraction in the presence or absence of serum. SAF was fractionated by size, using column chromatography. It yielded a fraction with an estimated molecular weigh near 40,000 daltons, which stimulated FPCL contraction. The factor was inactivated by proteolytic digestion and heat denaturation. This protein fraction which stimulates FPCL contraction is not related to 1) actin-myosin filaments enhanced contraction by ATP-induced cell contraction, 2) promotion of fibroblast elongation on glass surface or in collagen, or 3) increased cell number by enhanced fibroblast duplication in a collagen matrix. A mechanism for SAF promotion of FPCL contraction was investigated but not identified.

Adenosine Triphosphate↗
PubMed1991

Hyaluronic acid in a cardiac myxoma: a biochemical and histological analysis.

Cardiac myxoma is the most common primary tumor of the heart. This tumor has a gelatinous stroma that is thought to be composed of glycosaminoglycans, the classical acid mucopolysaccharide ground substance. We examined both biochemically and histologically the hyaluronic acid in a case of cardiac myxoma using a newly developed hyaluronic acid-binding protein probe. We observed that hyaluronic acid was localized in the amorphous stroma and occurred at levels 30 times that found in normal atrial septum.

Heart Neoplasms↗
PubMed1991

In utero arterial embolism from renal vein thrombosis with successful postnatal thrombolytic therapy.

Thromboembolic events in the pediatric age group occur most commonly in neonates, and newborns of diabetic mothers are particularly at risk. We report a newborn with right renal vein and inferior vena cava thrombosis who apparently embolized across the foramen ovale antenatally with resultant right brachial artery occlusion. The baby was delivered by cesarean section from an insulin-dependent diabetic mother. At the time of birth, there was severe right arm ischemia with absent brachial and radial pulses. There was clinical evidence of distal embolization with a "trash" lesion of the distal right middle finger as well as a midforearm area of full-thickness skin loss. Ultrasound demonstrated a right renal vein thrombosis and a 95% occlusion of the inferior vena cava. Regional urokinase therapy was instituted through a lower extremity vein with a 5,000 U/kg bolus and then 5,000 U/kg/h continuous infusion. Twelve hours of infusion of urokinase led to clinical resolution of the right arm ischemia, with return of pulses. Follow-up ultrasound showed the right renal vein thrombosis and inferior vena cava clot to be completely resolved. The right middle finger and forearm lesions subsequently have healed primarily. We report this as a case of in utero arterial embolization with successful postnatal therapy using regional urokinase infusion.

Arm↗
PubMed1991

Ontogeny of fetal sheep polymorphonuclear leukocyte phagocytosis.

Premature infants and neonates are vulnerable to bacterial sepsis. This susceptibility may be due to the relative immaturity of their immune systems. To determine if neonates and, in particular, premature infants have decreased polymorphonuclear leukocyte (PMN) phagocytosis, we tested PMN phagocytosis of Staphylococcus aureus as a function of gestational age in the fetal lamb model. Because phagocytosis is made more efficient by the presence of opsonins in plasma, fetal and postnatal PMN phagocytosis were also measured after exposure to fetal and adult plasma. PMNs were isolated from fetal lambs at 104, 114, 124, and 141 days' gestation (term gestation for the fetal lamb is 145 days), as well as from 10-day-old neonatal sheep and adult sheep. Labeled S aureus were opsonized by incubation in either fetal or adult plasma, or left unopsonized for baseline values. Phagocytosis was measured as a percent of adult PMN phagocytosis after adult plasma opsonization. It was found that fetal PMN function is limited by two factors during the early third trimester: a primary defect in the ability of the PMN to phagocytose S aureus despite adequate opsonization, and the diminished ability of autologous fetal plasma to opsonize bacteria. The defect in PMN phagocytosis disappears late in the third trimester, but the inability of the fetal plasma to opsonize effectively continues until after birth.

Age Factors↗
PubMed1991

Midgestational excisional fetal lamb wounds contract in utero.

Clinical observations and experimental data suggest that fetal wound healing is very different from adult wound healing. An understanding of the biology of scarless fetal wound healing has tremendous clinical potential for modulating postnatal wound problems. In this study, the fetal lamb model was used to assess excisional fetal skin wound contraction in utero. Full-thickness 9-mm punch biopsy wounds were created on fetal lambs at 100 days' gestation (term, 145 days). Half of the wounds remained exposed to amniotic fluid, whereas the other half were covered by a silastic patch to exclude amniotic fluid. Wounds were harvested 3, 7, or 14 days later and wound areas were calculated. Exposure to amniotic fluid retarded wound contraction significantly at 3 days, but by 14 days all wounds had completely contracted and reepithelialized. Myofibroblasts are an important cellular element of wound contraction. The presence of wound myofibroblasts was documented by both transmission electronmicroscopy and immunocytochemistry with antimuscle actin antibody. It is concluded that fetal lamb wounds contract in utero and exposure to amniotic fluid appears to retard fetal skin wound contraction only during the early healing process.

Amniotic Fluid↗
PubMed1991

Animal models for the study of fetal tissue repair.

Recent experimental and clinical evidence suggests that the fetus responds to injury in a fashion fundamentally different from that of the adult. Acute inflammation is almost always absent, hyaluronic acid is a prominent component of the wound matrix, and collagen is deposited in a scarless manner. Using a variety of animal models and techniques, numerous investigators have begun to analyze the constituents of the fetal wound healing process in an attempt to understand the control mechanisms that endow the fetus with unique healing abilities. Since scarring and fibrosis dominate some diseases in almost every medical specialty, the ultimate clinical aim is to delineate the biological principles of fetal wound healing and then apply them to modulate adult wound healing problems.

Animals↗
PubMed1991

Fetal diaphragmatic wounds heal with scar formation.

Fetal wound healing is fundamentally different from wound healing in the adult. Although experimental work in mice, rats, rabbits, monkeys, and sheep has demonstrated that fetal healing occurs without inflammation and scarring, all of these studies have been limited to fetal skin wounds. Whether all fetal tissues heal in a regenerative-like fashion is unknown. Amniotic fluid exposure may play an important role in scarless fetal skin wound healing, but the effect of amniotic fluid on fetal mesothelial wound healing has not been characterized. To investigate these questions we created bilateral linear diaphragmatic wounds in 100-day gestation fetal lambs (term = 145 days). The right thoracotomy was closed to exclude amniotic fluid. In contrast, the left thoracotomy was fashioned into an Eloesser flap which permitted the left diaphragmatic wound to be continually bathed in amniotic fluid. Wounds were harvested after 1, 2, 7, or 14 days and analyzed by light microscopy and immunohistochemistry with antibodies to collagen types I, III, IV, and VI. Whether bathed in or excluded from amniotic fluid, the mesothelial-lined diaphragm healed with scar formation and without evidence of muscle regeneration. Interestingly, diaphragmatic wounds exposed to amniotic fluid were covered by a thick fibrous collagen peel similar to that seen in gastroschisis bowel. These findings indicate that not all fetal tissues share the unique scarless healing properties of fetal skin.

Amniotic Fluid↗
PubMed1991

Fetal cleft lip repair in rabbits: postnatal facial growth after repair.

We have previously described a model for in utero cleft lip repair in rabbits. Cleft lip and alveolus (CL) were created in fetal rabbits at 24 days gestation (term, 31 days). In this study, postnatal maxillary growth was evaluated in three groups of animals: 1) unoperated controls, 2) unrepaired CL, and 2) repaired CL. The animals were killed at 4, 12, and 26 weeks after birth. Direct cephalometry was performed on dry skulls to evaluate premaxillary width, anterior maxillary length and width, and posterior maxillary width. The results of this study indicate that rabbits that undergo an in utero CL procedure, with or without repair, exhibit no significant decrease in maxillary length and width when compared with controls.

Alveolar Process↗
PubMed1991

Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid.

Midgestation fetal wound healing is characterized by healing without fibrosis or scar formation. The mechanisms that underlie this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid. In this study a newly developed assay was used to determine the hyaluronic acid levels in fetal and adult wound fluid. Adult wound fluid had a rapid increase in hyaluronic acid, which peaked at 3 days and decreased to 0 by 7 days. In contrast levels of hyaluronic acid in fetal wound fluid increased rapidly and remained significantly elevated for 3 weeks. This prolonged presence of hyaluronic acid in the matrix of fetal wounds creates a 'permissive' wound environment that promotes fetal fibroblast movement and proliferation and inhibits cytodifferentiation. Such a matrix environment promotes healing by regeneration rather than by scarring. This observation has therapeutic implications. The prolonged application of hyaluronic acid or hyaluronate protein complexes to wounds in children or adults may modulate healing in a manner that makes the wounds more fetal-like.

Animals↗
PubMed1991

Rapid epithelialisation of fetal wounds is associated with the early deposition of tenascin.

Wound healing is a complex process involving the interaction of many cell types with the extracellular matrix (ECM). Fetal skin wound healing differs from that in the adult in that it occurs rapidly and without scar formation. The mechanisms underlying these differing processes may be related to the fetal environment, the stage of differentiation of the fetal cells or the ECM deposited in the wound. The spatial and temporal distribution of two components of the ECM, fibronectin and tenascin, were studied by immunostaining of cryosections from trunk wounds of fetal and adult sheep. Epithelialisation was complete earlier in the fetal wound than in the adult. The distribution of fibronectin was similar in fetal and adult wounds but tenascin was present earlier in the fetal wound. Fibronectin has several roles in wound healing including acting as a substratum for cell migration and as a mediator of cell adhesion through cell surface integrins. The attachment of fibroblasts to fibronectin is inhibited by tenascin and during development the appearance of tenascin in the ECM of migratory pathways correlates with the initiation of cell migration. Similarly, the appearance of tenascin in healing wounds may initiate cell migration. Tenascin was present in these wounds prior to cell migration and the rapid epithelialisation of fetal wounds may be due to the early appearance of tenascin in the wound.

Animals↗