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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 271 records · Page 15Linked to original sources
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↗
PubMed1989

Ontogeny of the smooth muscle response to histamine in rabbit and human small bowel.

Histamine is known to stimulate small bowel smooth muscle contraction in adults. We studied the response to histamine of small bowel from 27 day gestation fetal (term = 31 days), 4 days-old neonatal, and weanling rabbits using an isolated muscle strip technique in vitro. Sensitivity to histamine stimulation decreased with increasing age, with a six-fold difference in mean D50 between fetal and weanling bowel. A strong contractile response was also obtained in human fetal bowel between 16 and 24 weeks gestation. The response to histamine was inhibited at all ages in both rabbit and human bowel by specific histamine H1 receptor blockade with diphenhydramine, and not by H2 or cholinergic receptor blockers. We conclude that histamine stimulates rabbit and human fetal small bowel contraction; stimulation specifically occurs via the histamine H1 receptor, and is unrelated to release of acetylcholine; sensitivity to histamine decreases significantly with maturity in the rabbit.

Animals↗
PubMed1989

Neonatal model of heterotopic heart transplantation in pigs.

To investigate the long-term success of heart transplantation in newborn infants who have complex congenital heart disease, we have developed a model of heterotopic heart transplantation in immature pigs. We chose the heterotopic technique because it is simple, does not require cardiopulmonary bypass or heparin, allows for significant size disparity between the recipient and donor hearts, and allows for experimental comparisons between the two hearts. Small newborn piglet hearts are harvested, prepared, and then transplanted into the left chest of larger weanling pigs to augment or substitute for the native left ventricle. Preliminary data from transplants into 49 pigs suggest that the technique is technically possible, the pigs can be immunosuppressed over the long term, and the donor heart can contribute hemodynamically. Experimentally, the model is well designed for the investigation of issues critical for the long-term success of heart transplantation in infants and children, including growth and development, optimal long-term immunosuppression, differences in immunotolerance, and the study of coronary obliterative disease. Clinically, the model has potential applicability in congenital heart anomalies if one native functioning atrium and ventricle are present.

Animals↗
PubMed1989

Recent advances in therapy of congestive heart failure.

Approximately 3 million Americans are currently diagnosed as having congestive heart failure, and nearly 400,000 deaths occur per year in these patients. Fortunately, recent clinical investigations have made important contributions to the care of patients with congestive heart failure, allowing great improvement in the morbidity and mortality associated with this syndrome. Most patients presenting with signs and symptoms of heart failure suffer from systolic dysfunction. On objective testing, however, up to 30% of patients initially thought to have heart failure due to poor systolic function actually have abnormal diastolic performance. Since treatment that is beneficial for systolic dysfunction can be harmful if applied to patients with diastolic dysfunction, differentiation of these causes of pulmonary congestion is particularly important. Echocardiography has been shown to be particularly useful in making this distinction and is very useful in guiding therapy for patients with heart failure. Vasodilator therapy has been recently shown to both relieve symptoms and lessen long-term mortality for patients with heart failure. Additionally, vasodilators may be more effective than digitalis in relieving symptoms of heart failure for patients with mild-to-moderate symptoms. Thus it appears that vasodilators should play a prominent and early role in the treatment of most patients with heart failure due to systolic dysfunction. The value of digitalis for patients with heart failure related to uncontrolled atrial arrhythmias is well appreciated. Controversy exists, however, regarding the role of digitalis for patients who remain in normal sinus rhythm. A recent double-blind trial of digoxin, milrinone, both, or placebo has confirmed the beneficial effects of digoxin for these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗
PubMed1989

Cesarean delivery and hysterotomy using an absorbable stapling device.

The absorbable stapling device was used in 22 hysterotomies in gravid rhesus monkeys. The efficacy of the device, subsequent fertility and delivery route, fetal effects, and pathohistology were all studied. No statistically significant difference between experimental and control animals was noted.

Animals↗
PubMed1989

In utero gene transfer and expression: a sheep transplantation model.

Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU-Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use.

Adenosine Deaminase↗
PubMed1988

Pivotal role of aortic valve area calculation by the continuity equation for Doppler assessment of aortic stenosis in patients with combined aortic stenosis and regurgitation.

Aortic regurgitation (AR) may result in overestimation of the aortic pressure gradient by continuous wave Doppler in patients with mixed aortic valve disease. However, few data are available regarding the effect of AR on noninvasive estimates of aortic valve area by the continuity equation. Therefore, 25 patients with angiographically documented severe AR and peak systolic aortic velocities of greater than 2.5 m/s were studied by continuous wave Doppler to determine the accuracy of pressure gradient and aortic valve area calculations in assessing the severity of aortic stenosis (AS) in this patient population. Peak instantaneous pressure gradient showed a general correlation to but was overestimated by Doppler (r = 0.78, Doppler = 0.70 catheter + 19.9) and did not predict aortic valve area. Mean pressure gradient by Doppler correlated more closely with catheter mean gradient (r = 0.86, Doppler = 0.79 catheter + 6.1) but was a poor predictor of the severity of AS. In contrast, the continuity equation accurately predicted the aortic valve area by catheterization (r = 0.92, Doppler = 0.89 catheter -0.08). Thus, the continuity equation provides a reliable estimate of aortic valve area in patients with severe AR and should be used to evaluate the extent of AS in such patients when high systolic aortic velocities are present.

Aortic Valve↗
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

A practical application of Doppler echocardiography for the assessment of severity of aortic stenosis.

This study evaluated a strategy that makes optimal use of Doppler echocardiography for estimating the severity of valvular aortic stenosis (AS). Fifty-eight patients with no more than moderate aortic insufficiency who underwent cardiac catheterization were evaluated with two-dimensional echocardiography and Doppler velocimetry to determine the peak velocity across the stenotic valve and aortic valve area (AVA) by means of the continuity equation. All 33 peak Doppler velocities of greater than or equal to 4 m/sec had critical AS (AVA less than or equal to 0.8 cm2 at catheterization). Conversely, six of seven patients with Doppler velocities of less than or equal to 3 m/sec had noncritical AS. The patient with a falsely low peak velocity had severely depressed left ventricular function. Doppler velocity alone was inadequate in determining severity of AS for patients with velocities between 3 and 4 m/sec. The continuity equation proved accurate in estimating AVA in the 46 patients for whom catheterization and ultrasound data were sufficient to compare calculated AVA (r = 0.81), and was also accurate for those patients with peak Doppler velocities between 3 and 4 m/sec (r = 0.90). These results suggest that Doppler velocimetry alone is adequate in determining critical vs noncritical AS in many patients, while the continuity equation should be applied for patients with peak velocities between 3 and 4 m/sec as well as in patients with severely depressed cardiac function.

Adult↗
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↗
PubMed1988

Severity of intestinal damage in gastroschisis: correlation with prenatal sonographic findings.

From 1982 to 1986, 26 abdominal wall defects were detected prenatally. Seventeen pregnancies culminated in live births with ultrasound correctly distinguishing between omphalocele and gastroschisis in all cases. In the 11 cases of gastroschisis diagnosed before birth, we attempted to correlate the clinical outcome with the size of the abdominal wall defect, sonographic appearance of the eviscerated bowel, and known time of exposure to amniotic fluid (gestational age at birth to gestational age at diagnosis). Neither the time of exposure to amniotic fluid (median duration of 14 weeks) nor the defect size could be correlated with eventual clinical outcome. The presence of small bowel dilatation and mural thickening on prenatal sonography (four patients) had a high correlation with severe intestinal damage and poor clinical outcome. The absence of these two sonographic findings (seven patients) was associated with mild intestinal changes and benign clinical course with no morbidity or mortality. We conclude that obstetric ultrasound cannot only accurately detect the presence and type of abdominal wall defect, but it also gives an indication of the severity of intestinal damage and subsequent clinical course in prenatally diagnosed cases of gastroschisis. Early delivery of the fetus with prenatally diagnosed gastroschisis should no longer be performed to limit exposure to amniotic fluid. Now that reliable sonographic criteria of severe intestinal damage have been defined, the decision to deliver early can be restricted to those fetuses with bowel dilatation and mural thickening.

Abdominal Muscles↗
PubMed1988

Use of exercise Doppler echocardiography to evaluate cardiac drugs: effects of propranolol and verapamil on aortic blood flow velocity and acceleration.

This study evaluated the ability of exercise Doppler echocardiography to identify hemodynamic changes due to cardiac medication. Twenty young healthy volunteers (mean age 30 years) underwent continuous wave Doppler examination from the suprasternal notch at rest, during each stage of a standard exercise protocol and immediately after exercise. On completion of the control test, each subject received either 60 to 80 mg of propranolol or 120 mg of verapamil orally, and the same exercise protocol was repeated after 90 min. During the control test, values for modal velocity, acceleration and flow velocity integral all increased significantly from baseline (p less than 0.0002 for each). When exercise was repeated after propranolol administration, values for all Doppler measurements were significantly altered. Modal velocity at baseline was significantly lower after propranolol when compared with control (0.53 +/- 0.11 versus 0.63 +/- 0.17 m/s; p less than 0.0001). Similarly, modal velocity at maximal exercise was significantly lower after propranolol (1.11 +/- 0.2 versus 1.25 +/- 0.21 m/s; p less than 0.0001). The effect of propranolol on acceleration was even greater, with blunting of baseline (11.4 +/- 2 versus 15.4 +/- 5 m/s per s; p less than 0.0005) and exertional (33.4 +/- 10 versus 56.3 +/- 15 m/s per s; p less than 0.0001) acceleration. The flow velocity integral during exercise was greater after propranolol (14.1 +/- 3.1 versus 10.1 +/- 3.2 cm; p less than 0.0005) than during the control test. Verapamil failed to influence any Doppler-measured index of aortic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Natural history of fetal ventriculomegaly.

The natural history of in utero ventriculomegaly was defined by a retrospective review of the outcome of 47 fetuses evaluated during a 5-year period by the Fetal Treatment Program at the University of California. In 20 fetuses, a diagnosis of ventriculomegaly associated with other severe abnormalities was made early in pregnancy. Termination of pregnancy was elected in 19 of 20 cases, and no fetus survived. In five fetuses, the diagnosis was made late in pregnancy and was associated with severe abnormalities. Fetuses were handled in a routine obstetric fashion and none survived. Of the other 22 fetuses 19 had stable and two had progressive ventriculomegaly; in one case, ventriculomegaly resolved in utero. Nineteen of these fetuses have survived, 13 with normal intellectual development and six with moderately to severely delayed development. Associated abnormalities were detected with ultrasonography in 74% of fetuses; there was a 20% false-negative rate of detection. Ventriculomegaly was isolated and progressive in two fetuses. In both cases, fetuses were delivered at term, and postnatally a shunting procedure was performed. Both children are neurologically normal. From our results and a review of the literature, which supports our findings, we were unable to define a group of fetuses with in utero ventriculomegaly that would benefit from in utero shunting.

Abortion, Therapeutic↗
PubMed1987

Platelet-binding immunoglobulins in pregnancy-induced hypertension. I. Platelet-associated IgM on fetal platelets: evidence of a fetal autoimmune reaction?

Pregnancy-induced hypertension (PIH) can be complicated by maternal or fetal thrombocytopenia, or both. In order to investigate possible immunologic causes of these thrombocytopenias, platelet-associated IgG (PAIgG) and IgM (PAIgM) were measured in mothers with PIH and in their infants and compared with those from patients with autoimmune thrombocytopenic purpura (ATP), a known immunodestructive platelet disorder. Many PIH patients (33.3%) and most ATP patients (68.1%) had elevated levels of maternal PAIgG. In both diseases, the amount of PAIgG was directly proportional with the degree of thrombocytopenia (r = 0.446 in PIH and r = 0.668 for ATP). But in neither disease did the degree of maternal thrombocytopenia correlate with the degree of neonatal thrombocytopenia (r = 0.153 for PIH and r = 0.175 for ATP). Umbilical cord samples from PIH patients contained PAIgG (53.3%) and PAIgM (53.8%), whereas the umbilical cord samples from ATP patients had elevated amounts of PAIgG but not PAIgM. PAIgM in the umbilical cord blood could not be accounted for by IgM rheumatoid factors, IgM-containing immune complexes, or non-specific adsorption because of elevated total IgM levels. The umbilical cord blood PAIgM was probably not of maternal origin because it was observed even when the maternal blood contained no PAIgM and maternal IgM is not normally transported transplacentally. Therefore, the PAIgM appears to be of fetal origin. These results suggest that both maternal and fetal immunologic mechanisms may be involved in PIH-induced thrombocytopenia; if so, this is one of the first reported examples of a possible fetal autoimmune response.

Autoantibodies↗
PubMed1987

Platelet-binding immunoglobulins in pregnancy-induced hypertension. II. Origin of circulating IgG and IgM antiplatelet antibodies in the umbilical cord serum.

IgG and IgM have been identified on the surface of maternal platelets in both autoimmune thrombocytopenia (ATP) and pregnancy-induced hypertension (PIH). IgG is also found on the umbilical cord platelets of patients with ATP and PIH, whereas IgM is only found on the umbilical cord platelets of patients with PIH. The possible maternal or fetal origins of these umbilical cord blood immunoglobulins were investigated by immunoblot analysis of antibodies in paired maternal and umbilical cord blood sera of ATP and PIH patients. Maternal sera contained IgG and IgM antibodies which reacted with several platelet proteins, however, a large amount of patient-to-patient variation was observed in the specific antigens that were identified. Analysis of paired maternal and umbilical cord sera from patients with ATP or PIH showed identical patterns of antigen specificity, which suggested that the IgG antibodies in the fetal circulation were of maternal origin. Circulating IgM antibodies were not observed in the umbilical cord sera of ATP patients. The umbilical cord sera of PIH patients, however, contained IgM antibodies that reacted against a variety of platelet antigens. In addition, most umbilical cord sera from PIH patients had identical patterns and relative intensities of reactivity, which differed from the patterns observed in the paired maternal sera. Antiplatelet IgM in the umbilical cord blood of PIH patients, therefore, appears to be a product of the fetal immune system.

Autoantibodies↗
PubMed1987

Long-term percutaneous biliary drainage in an infant with hemangioendothelioma.

A 5-month-old female infant with jaundice (bilirubin = 11) and dilated intrahepatic and extrahepatic bile ducts was explored. A 3-cm mass in the head of the pancreas and portal region completely obstructed the cystic and common bile ducts. Cholecystectomy was done and biopsy of the tumor and regional nodes revealed hemangioendothelioma with no nodal involvement. After tissue diagnosis was made, the infant's biliary tract was decompressed percutaneously. External drainage was maintained for 22 months until the tumor regressed. This infant is the youngest patient ever reported to undergo percutaneous biliary drainage.

Catheters, Indwelling↗
PubMed1987

Does an expanding fetal abdominal mass produce pulmonary hypoplasia?

Fetal pulmonary hypoplasia has been related to multiple factors. In an effort to define which fetuses may benefit from prenatal intervention to prevent or reverse pulmonary hypoplasia, we studied the relative contribution of an enlarging abdominal mass in the fetus. We produced abdominal masses in fetal rabbits at 24 days gestation by two methods. In one group, a small cylindrical chip of Takasen, (a synthetic polymer that expands to 50 times its size in 1 week; Grobeast, Pop Art Co, Cleveland, OH) was inserted into the peritoneal cavity of the fetal rabbit; in another group, the bladder neck was obstructed with a surgical clip. Amniotic fluid volume was restored at the surgical procedure. Sham-operated littermates served as controls. At cesarean delivery on day 30, fetal lung, liver, and body weights were measured, and the abdominal masses were quantitated by volume displacement of the removed mass or bladder. In both groups large abdominal masses of comparable size were produced. Newborns with the synthetic abdominal mass did not have significant pulmonary hypoplasia, but often had a prune belly deformity of the abdominal wall, whereas newborns with bladder obstruction had significant pulmonary hypoplasia. Liver weight was not significantly affected. We conclude that a fetal abdominal mass does not independently produce pulmonary hypoplasia, possibly because the "mass effect" is relieved by distension of the abdominal wall rather than elevation of the diaphragm; the pulmonary hypoplasia that occurs in bladder outlet obstruction is probably due to the associated oligohydramnios rather than the mass effect of the dilated urinary tract; and prenatal decompression of an abdominal mass or dilated urinary tract is not justified to prevent pulmonary hypoplasia in the absence of oligohydramnios.

Abdomen↗