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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

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

Successful stable xenograft of human fetal hemopoietic cells in preimmune fetal sheep.

Human fetal liver hemopoietic stem cells were transplanted into preimmune fetal sheep. Significant numbers of recipient fetuses showed evidence of engraftment of human stem cells which responded in vivo to human-specific hemopoietic growth factors. The chimerism has persisted now for > 2 years without significant graft loss. No evidence of GVHD has been noted. Successful engraftment was associated with the expression of human erythroid, myeloid, and lymphoid differentiation. This xenograft model offers useful possibilities for the study of the biology of human hemopoiesis in vivo.

Animals↗
PubMed1991

Doppler echocardiographic evaluation of diastolic dysfunction.

Recently, considerable effort has been directed toward the application of Doppler methods for detecting diastolic dysfunction. Recordings of transmitral filling velocity as obtained from pulsed-wave Doppler have been extensively investigated as a noninvasive method for determining left ventricular diastolic filling properties. Although Doppler parameters appear to reflect volumetric transmitral flow, close correlations with invasive descriptors of diastolic performance have not been found. Furthermore, Doppler transmitral velocities are sensitive to changes in ventricular preload, afterload, and heart rate. However, at least two distinct Doppler spectral patterns have been identified that are associated with impaired ventricular relaxation and restrictive physiology. Thus, Doppler recordings have proven to be of value in identifying the presence and type of diastolic dysfunction, and in the future they may be helpful in following the response to therapeutic interventions. The purpose of this paper is to review the available information relating Doppler transmitral recordings with catheterization and clinical descriptors of diastolic function. Additionally, the aim is to provide an understanding of the value and limitations of these noninvasive measurements in identifying and treating patients with diastolic abnormalities.

Amyloidosis↗
PubMed1990

Antenatal intervention for congenital cystic adenomatoid malformation.

In 2 fetuses with congenital cystic adenomatoid malformation (CCAM) with hydrops, in-utero resection of the enlarged pulmonary lobe reduced mediastinal shift and allowed expansion of normal lung tissue in both cases. In case 1, the 27-week-gestation fetus died from severe hydrops after premature delivery. In case 2, fetal CCAM resection was completed at 23 weeks' gestation. At 30 weeks a girl was delivered with no evidence of pulmonary hypoplasia. Fetal surgery can now be entertained for otherwise fatal space-occupying intrathoracic lesions.

Adult↗
PubMed1990

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↗
PubMed1990

Retroviral vector-mediated transfer of the bacterial neomycin resistance gene into fetal and adult sheep and human hematopoietic progenitors in vitro.

We compared the efficiency of retroviral vector (N2)-mediated transfer of the bacterial neomycin resistance gene (NeoR) into adult and fetal hematopoietic progenitors of sheep and humans by assessing their ability to form colonies in the presence of lethal doses of the neomycin analogue G418 in vitro. Fetal cells from both sheep and humans exhibited a higher degree of NeoR transfer than adult cells. The overall level of NeoR expression was significantly higher for sheep than human cells. The transfer/expression of NeoR into adult human bone marrow hematopoietic progenitors was not affected by the presence or absence of T cells and monocyte/macrophages. The efficiency of NeoR transfer into both adult and fetal human cells, however, was improved when transduction was carried out in the presence of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor. These results demonstrate the greater efficiency of NeoR gene transfer into fetal hematopoietic progenitors, which may provide a basis for the relatively higher efficiency of the in utero approach to gene therapy.

Animals↗
PubMed1990

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↗
PubMed1990

Influence of beta-adrenergic blockade upon hemodynamic response to exercise assessed by Doppler echocardiography.

Peak aortic blood flow acceleration and velocity measured by Doppler echocardiography have been documented to be accurate descriptors of left ventricular systolic function. Both acceleration and velocity are reduced in the presence of beta-blockade at rest and during exercise. Whether and to what extent the simultaneous alterations in heart rate (HR) due to beta-blockade affect these parameters has received little study. In order to determine the influence of alterations in HR on Doppler measurements of velocity and acceleration, 10 healthy men were studied during upright exercise under control conditions, following propranolol administration, and following propranolol plus transesophageal atrial pacing. In addition, we assessed the response of stroke volume (measured as flow velocity integral) during beta-blocked and control exercise. Propranolol significantly reduced acceleration and velocity during all stages of exercise compared with control values (p less than 0.05). Increasing the HR during exercise via pacing had no effect on acceleration or velocity compared with propranolol administration alone, thus demonstrating that during upright exercise, changes in acceleration and velocity are independent of alterations in HR. At low levels of exercise, propranolol significantly reduced flow velocity integral (FVI) compared with control (-1.14 cm, p less than 0.05.). At high levels of exertion, however, FVI exceeded values obtained during control conditions (1.2 cm at stage 4). Pacing during beta-blockade reduced FVI at high levels of exercise but had no effect at lower levels. Our results suggest that during low levels of exercise stroke volume is increased as a consequence of both increased contractility and augmented left ventricular filling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

In utero transplantation of hematopoietic stem cells in sheep: the role of T cells in engraftment and graft-versus-host disease.

Transplantation of hematopoietic stem cells (HSC) from adult sheep into fetal lambs results in hematopoietic chimerism and graft-versus-host disease (GVHD). To evaluate the role of T cells in HSC engraftment and GVHD we depleted adult marrow HSC of T cells and observed the incidence of chimerism and GVHD in the fetal recipients. Using a naturally occurring polymorphism of the beta-globin locus to detect engraftment, bone marrow obtained from homozygous type A hemoglobin adult sheep were transplanted (2 x 10(9) cells/kg fetal weight) into 90 days' gestation fetal lambs homozygous for type B hemoglobin. Donor HSC were T-cell depleted by treatment with antisera (raised in rabbits against sheep thymocytes) in the presence of complement. T-cell depletion resulted in significant decrease in hematopoietic colony formation by donor HSC in vitro (305 +/- 49 v 134 +/- 21 colonies/10(5) cells) that normalized by the addition of autologous T cells (433 +/- 32 colonies/10(5) cells). Marrow depleted of T cells exhibited reduced engraftment in the recipient fetuses. When T cells were added back to donor HSC (depleted of T cells) at near-normal concentrations, engraftment improved but the lambs also developed GVHD. The addition of T cells to donor HSC (depleted of T cells) at concentrations below that present in unprocessed bone marrow resulted in significant engraftment but not GVHD. T cells play an important role in both the engraftment of adult HSC in fetal recipients and the development of GVHD in chimeric newborns. The elimination of T cells prevents GVHD but markedly reduces engraftment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

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↗