Search PubMed⌕ Search

Biomedical subjects

M H Hedrick

Publications and source records attributed to M H Hedrick.

25 records · Page 2Linked to original sources
PubMed1994

Congenital cystic adenomatoid malformation: a sheep model of fetal hydrops.

Congenital cystic adenomatoid malformation (CCAM) can be diagnosed in utero. Nonimmune hydrops associated with CCAM is a predictor of fetal demise. Fetuses with prenatally diagnosed large CCAM tumors and hydrops have undergone successful in utero resection. An animal model is needed to understand the pathophysiology of CCAM and hydrops. To create a model of CCAM and hydrops, the authors implanted an intrathoracic tissue expander in six fetal sheep at 120 days' gestation. The inflatable tissue expander was implanted in the right side of the chest, and arterial, venous, intrathoracic, and intraamniotic pressure catheters were placed. Each day, the expander was inflated with 25 to 50 mL of saline (maximum, 150 mL), ultrasound examination was performed, and all pressure measurements were taken. In all six fetuses, hydrops developed after expander inflation. Expander inflation correlated with an increase in central venous pressure (CVP) (4 +/- 2 mm Hg v 16 +/- 2 mm Hg [mean +/- SD]; P < .05). To simulate in utero CCAM resection, the expander was deflated in four hydropic sheep, resulting in return of the CVP to near baseline and resolution of hydrops. Silicone vascular casts of two postmortem sheep demonstrated lateral displacement and compression of the vena cavae by the expander. The authors successfully created a model of CCAM and hydrops by inflating an intrathoracic tissue expander in fetal sheep. Based on this model, hydrops associated with CCAM results from obstruction of cardiac venous return and central venous hypertension. This pathophysiology is reversed by expander deflation, which simulates in utero CCAM resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Gastroschisis: can sonography of the fetal bowel accurately predict postnatal outcome?

To determine whether prenatal sonographic features of the small bowel can accurately predict postnatal outcome in fetuses with gastroschisis, the sonograms of 24 fetuses with prenatally detected gastroschisis were retrospectively reviewed for fetal bowel features including small bowel dilatation and bowel wall thickening. To identify a relationship between the sonographic features and neonatal outcome, each feature was analyzed against eight adverse clinical outcome measures including bowel obstruction or atresia, necrosis, and need for bowel resection, using chi-square analysis and Kendall's taub correlation. When a relationship was identified, the sensitivity and specificity of the sonographic feature for predicting adverse outcome were determined. Only maximum small bowel diameter was related to postnatal bowel complications. Significantly more fetuses with a maximum small bowel diameter of greater than 11 mm (7/12) had bowel complications than did fetuses with MBD 11 mm or less (2/12) P < 0.05). Using a cutoff point of greater than 11 mm for maximum small bowel diameter, the sensitivity was 78%, specificity 66%, and positive predictive value 71% for predicting postnatal bowel complications. However, in only seven of 24 cases did the two observers make the same maximum small bowel diameter measurement, and in 14 of 24 cases their measurements differed by 2 mm or more. The observers varied sufficiently in their measurements to shift three fetuses (13%) between categories (< or = 11 mm or > 11 mm). Although a maximum small bowel diameter of 11 mm stratified our fetuses, this measurement may not be clinically meaningful.

Abdominal Muscles↗
PubMed1993

Chronic fetal vascular access.

Intensive management of the fetus is limited by our inability to achieve access to the fetal circulation. Using laparoscopic surgery, we can maintain long-term access to the fetal circulation by extra-amniotic catheterisation of chorionic vessels in third-trimester monkeys and early-gestation sheep. We can sample fetal blood, continuously measure blood pressure, and infuse drugs without complications. Safe vascular access will permit assessment of fetal status during fetal surgical procedures and improve postoperative monitoring.

Animals↗
PubMed1993

Effect of xenogeneic chimerism in a human/sheep model on natural antibody.

Xenogeneic transplantation is a potential solution to the severe shortage of donor organs for clinical transplantation. The primary limitation to xenogeneic transplantation between widely disparate species is hyperacute rejection, which is triggered by the recipient's natural antibodies reacting against the donor's endothelial cells. Natural antibodies react between widely disparate species but do not react between closely related species. Specific tolerance for xenogeneic transplantation between closely related species can be induced by creating hematopoietic chimerism between donor and recipient. However, whether specific xenograft tolerance can be induced by the creation of chimerism between widely disparate species, where natural antibody reacts, is unknown. We previously have established a model of hematopoietic chimerism between widely disparate species by the in utero transplantation of human fetal hematopoietic stem cells into early gestation fetal lambs. In the present study, we determined whether long-standing hematopoietic chimerism in this human/sheep model reduces the level of natural antibody directed against human endothelial cells. To answer this question, we measured the reactivity of serum from five chimeric sheep, five sheep controls, and five human controls in an in vitro enzyme-linked immunoabsorbance assay directed against human umbilical vein endothelial cells. Unexpectedly, we found that long-standing hematopoietic chimerism in the human/sheep model did not reduce the reactivity of serum against human endothelial cells compared to age-matched sheep controls. These results suggest that the induction of hematopoietic chimerism between widely disparate species will not control the problem of natural antibody and hyperacute rejection.

Animals↗
PubMed1992

Fetoscopic surgery for the treatment of congenital anomalies.

Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.

Animals↗
PubMedDate not supplied

Bacterial and fungal contamination of human fetal liver collected transvaginally for hematopoietic stem cell transplantation.

Transplantation of fetal hematopoietic stem cells is a new therapy for fetuses diagnosed in utero with inherited disorders. However, prior to transplantation of fetal stem cells, the cells must be free of microbial contamination. In order to investigate the contamination of human fetal liver tissue, we determined the rate and types of bacterial and fungal contamination of human fetal liver tissue collected transvaginally for use in stem cell transplantation by using the US Pharmacopoiea Assay. We found a high rate of contamination with bacteria or fungi (12 of the 14 fetal livers, or 85%). Non-fermenting gram-negative rods were the predominant contaminants. The high rate of microbial contamination of fetal tissue suggests that techniques for tissue collection need to be improved before fetal stem cells are used for clinical transplantation.

Abortion, Induced↗