Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 19 recordsLinked to original sources

PubMed1995

The incidence and spectrum of neurological injury after open fetal surgery.

A preterm infant's immature brain is susceptible to both anoxic and hemorrhagic injury during periods of physiological stress. The advent of in utero surgery has created a new population of premature patients at risk for central nervous system (CNS) injury. The aim of this study was to evaluate the frequency and nature of CNS injuries in fetal surgical patients. Of 33 fetuses with known neurological outcome after fetal surgery, CNS injuries were identified in seven (21%). Of the seven, four had significant episodes of fetal bradycardia (3) or neonatal hypotension (1), which suggests that asphyxia contributed to the neurological injury. The CNS injuries in the other three patients occurred unexpectedly and without associated signs of fetal distress. The authors speculate that these injuries may have been caused by sudden fluxes in cerebral blood flow, induced by maternal hypoxia (1) or by maternally administered tocolytic drugs (2) used to treat postoperative preterm labor.

Bradycardia↗

PubMed1995

Fetal endoscopic ('Fetendo') surgery: the relationship between insufflating pressure and the fetoplacental circulation.

Application of video-endoscopic surgery to the gravid uterus provides a new treatment option for the fetus with a correctable congenital anomaly. "Fetendo" surgery requires temporary enlargement of the uterine cavity to create a working space. Volume expansion of the amniotic space raises intrauterine pressure, which could increase placental vascular resistance and thereby reduce placental blood flow. To test this hypothesis, the authors developed a fetal sheep model to examine the relationship between insufflating pressure and flow in the placental circulation. Fetoplacental blood flow was measured via ultrasonic flow probes placed around the fetal common umbilical artery and the maternal uterine artery in five anesthetized 120-day-gestation ewes. Invasive feto-maternal monitoring permitted synchronous measurement of fetal mean arterial pressure, fetal central venous pressure, maternal mean arterial pressure, amniotic pressure, and fetal oxygen saturation, with calculated values for fetal and maternal placental vascular resistance. Amniotic pressure was raised from 10 mm Hg to 40 mm Hg in 5-mm Hg increments by a combination of saline amnioinfusion and external uterine compression. At amniotic pressures of 20 mm Hg or less, placental blood flow was preserved; however, elevation of amniotic pressure above 20 mm Hg resulted in a significant decrease in placental flow, with concomitant fetal hypoxia. The authors conclude that the relationship between intrauterine pressure, flow in the placental circulation, and fetal oxygen delivery must be considered when selecting intrauterine insufflation pressures for hysteroscopic intervention.

Amnion↗

PubMed1995

Cyclic GMP relaxes the internal anal sphincter in Hirschsprung's disease.

In Hirschsprung's disease (HD), the aganglionic colon and internal anal sphincter (IAS) fail to relax. Aganglionic colon of HD patients relaxes in response to exogenous nitric oxide (NO), whereas the IAS from HD patients does not relax. The authors hypothesized that the failure of IAS relaxation is caused by a local deficiency of cyclic guanosine monophosphate (cGMP), the final metabolite in NO-mediated smooth muscle relaxation. To test this hypothesis, the authors measured the isometric tension of smooth muscle strips taken from the IAS and aganglionic colon of patients with HD before and after exposure to cGMP and compared this with ganglionic colon and IAS from normal controls. In HD patients both the IAS and aganglionic colon relaxed in response to cGMP (P < .05). The amount of relaxation observed in both the aganglionic colon and IAS was comparable to that measured in the normal controls. The observation that exogenous cGMP relaxes the IAS, whereas exogenous NO does not, suggests that mechanisms for relaxation may be different than those in the aganglionic colon and may explain persistent IAS dysfunction after resection of aganglionic colon. The defect of the IAS in HD may be the inability of the NO/cGMP pathway to induce smooth muscle cell relaxation rather than a defect in the smooth muscle cell.

1-Methyl-3-isobutylxanthine↗

PubMed1995

Creation of myelomeningocele in utero: a model of functional damage from spinal cord exposure in fetal sheep.

A recent study in human fetuses with myelomeningocele (MMC) suggested that the primary malformation is not neural but a failed closure of the posterior vertebral column and paraspinal soft tissue, which leads to exposure and secondary destruction of the spinal cord. The goal of this study was to test whether chronic exposure of the normal spinal cord to the amniotic space produces a lesion similar to human MMC. In fetal sheep at 75 days' gestation (group A) and 60 days' gestation (group B) (term = 150 days), the lumbar spinal cord was exposed to the amniotic cavity by excising skin and paraspinal soft tissues, and by performing a laminectomy. Some animals from both groups were fetectomized and assessed morphologically at 100 days' gestation. The remainder were delivered near term and assessed clinically, electrophysiologically, and morphologically. In group A, all animals showed MMC-type pathology. The exposed spinal cord was herniated out of the spinal canal and rested on the dorsal membranes of a cystic sac. The neural tissue was stretched and flattened out. Histologically, the hallmarks of the spinal cord were not discernable and the cytoarchitecture was lost. These changes were less severe at 100 days than at term. The three survivors in group A were paraplegic. In group B, the two survivors and two fetuses harvested at 100 days had healed skin wounds and near normal spinal cord histology. The other animal harvested at 100 days had a MMC-type lesion with less severe histological changes. The two survivors had a mild paraparesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnion↗

PubMed1995

In utero surgery rescues neurological function at birth in sheep with spina bifida.

We hypothesize that the neurologic deficit associated with open spina bifida is not directly caused by the primary defect but rather is due to chronic mechanical and chemical trauma since the unprotected neural tissue is exposed to the intrauterine environment. We report here that exposure of the normal spinal cord to the amniotic cavity in midgestational sheep fetuses leads to a human-like open spina bifida with paraplegia at birth, indicating that the exposed neural tissue is progressively destroyed during pregnancy. When open spina bifida was repaired in utero at an intermediate stage, the animals had near-normal neurologic function. The spinal cord was deformed but largely preserved. These findings suggest that secondary neural tissue destruction during pregnancy is primarily responsible for the functional loss and that timely in utero repair of open spina bifida might rescue neurologic function.

Animals↗

PubMed1995

Fetal surgery.

Fetal surgery, as defined for the purpose of this chapter, is the act of opening the gravid uterus, surgically correcting a fetal abnormality, and returning the fetus to the uterus for postoperative recovery and continued gestational development. By this definition, human fetal surgery has now been performed for more than a decade, primarily at a single center (1). Tremendous progress has been made in our understanding of the natural history and pathophysiology of fetal disease, in solving the technical challenges of fetal surgery, and in intra- and postoperative care and monitoring of the maternal-fetal unit. However, success and general application of fetal surgery continue to be limited by a number of unsolved and formidable problems. The most important of these is the control of preterm labor, which is the Achilles heel of fetal surgery. Preterm labor is to the infantile field of fetal surgery what rejection was to the field of transplantation. The discovery of effective tocolysis would be analogous to the development of effective immunosuppression and would allow fetal surgery to achieve its full potential. In addition, less invasive methods of operating on the fetus are emerging that will further reduce the maternal and fetal risk of this currently highly invasive treatment.

Adolescent↗

PubMed1995

Prenatal sonographic predictors of liver herniation in congenital diaphragmatic hernia.

We conducted a retrospective review of prenatal sonograms of all fetuses (n = 25) with left sided congenital diaphragmatic hernia undergoing in utero surgical repair of the defect at the University of California, San Francisco, Fetal Treatment Center. Sixteen candidates were selected for analysis to determine reliable predictors of liver herniation. Bowing of the umbilical segment of the portal vein (portal sinus) to the left of midline and coursing of portal branches to the lateral segment of the left hepatic lobe toward or above the diaphragmatic ridge were the best predictors for liver herniation into the fetal thorax (positive predictive values of 85% and 100%, respectively). The stomach position was a good predictor if observed in a posterior or midthoracic location (positive predictive value = 100%). However, this occurred in only 7 of 16 (44%) cases. Visibility of the right lung was less informative (positive predictive value = 63%). We do not recommend in utero primary closure of congenital diaphragmatic hernia when there is sonographic evidence of liver herniation into the fetal thorax.

Female↗

PubMed1995

Fetal reconstructive surgery: experimental use of the latissimus dorsi flap to correct myelomeningocele in utero.

A recent study in human fetuses with myelomeningocele produced evidence that nonclosure of the spine leads to progressive damage of the exposed spinal cord during pregnancy. Thus in utero coverage might spare function. We tested the use of the latissimus dorsi flap for fetal myelomeningocele repair. In seven sheep fetuses, a lumbar myelomeningocele type of lesion was created at 75 days' gestation and was covered with a "reversed" latissimus dorsi flap at 100 days. At term, the three survivors had healed cutaneous wounds and normal hindlimb function. The vascular pedicle of the latissimus dorsi flap was patent, the viable flap covered the entire lesion, and the underlying spinal cord was grossly intact. We conclude that the latissimus dorsi flap repair is suitable for fetal surgery and provides efficient coverage of the lesion. These results have clinical implications, since fetal myelomeningocele repair may be a compelling way to reduce the severe neurologic deficit in humans.

Animals↗

PubMed1994

Nitric oxide synthase is deficient in the aganglionic colon of patients with Hirschsprung's disease.

OBJECTIVES: The cause of Hirschsprung's disease is unknown but defects in nonadrenergic, non-cholinergic innervation could prevent relaxation of aganglionic colon in patients with this disease. Nonadrenergic, noncholinergic nerves induce relaxation by using nitric oxide synthase to produce the smooth muscle relaxant nitric oxide (NO). In this study we asked whether aganglionic colon in patients with Hirschsprung's disease is deficient in NO synthase-containing nerves. METHODOLOGY: Using the tetrazolium blue dye method of demonstrating nicotinamide adenine dinucleotide phosphate-diaphorase enzymes, we examined eight colon specimens (four aganglionic and four ganglionic) from patients with Hirschsprung's disease for the presence of NO synthase. We further quantified NO synthase enzyme activity in these eight specimens by using the [3H]arginine-to-[3H]citrulline conversion assay. RESULTS: The nicotinamide adenine dinucleotide phosphate-diaphorase staining showed that aganglionic colon contained less NO synthase than ganglionic colon. This NO synthase deficiency was located primarily in the nerves of the circular muscle layer of the colon. In addition, there was a striking difference in the NO synthase enzyme activity between aganglionic and ganglionic colon as measured by the [3H]arginine-to-[3H]citrulline conversion assay. Total NO synthase activity, as measured by this assay, was found to be less in aganglionic than in ganglionic colon. When the total activity was divided into its four known isoforms, aganglionic colon was noted to be striking deficient in the isoform derived primarily from nerves. CONCLUSION: We conclude that aganglionic colon is deficient in NO synthase-containing nerves. This deficiency could prevent smooth muscle relaxation in the aganglionic colon of patients with Hirschsprung's disease.

Amino Acid Oxidoreductases↗

PubMed1994

An effective strategy for decontamination, ex vivo expansion, and storage of human fetal liver hematopoietic stem cells.

The transplantation of human fetal tissue has the potential to cure a variety of life-threatening diseases. The strategy for procurement, quality control, and functional assessment of human fetal liver HSC may prove useful for the transplantation of other fetal tissues. In addition to technical limitations, there are ethical and legal issues which need to be resolved before widespread use of fetal tissue. Further development of regulatory standards for the acquisition and distribution of fetal tissues will foster the application of this novel technology.

Abortion, Induced↗

PubMed1992

Improved reproducibility of left atrial and left ventricular measurements by guided three-dimensional echocardiography.

OBJECTIVES: The objective of this study was to determine whether guided three-dimensional echocardiography could improve the reproducibility of left atrial and left ventricular anteroposterior measurements over that of standard unguided two-dimensional echocardiography. BACKGROUND: Although these measurements are standard indexes for evaluating chamber size, their use is limited by significant interobserver variability largely due to variable image plane positioning. To improve measurement accuracy and reproducibility, we have developed a three-dimensional echocardiograph that displays the line of intersection of the real-time image with a previously saved orthogonal reference image. This display shows the relation of the real-time image to anatomic landmarks in its third, nonvisualized dimension and may be used to guide image positioning. METHODS: Three pairs of operators independently performed unguided two-dimensional and guided three-dimensional examinations on three groups of 10 patients each. The left atrium was measured in a plane through the inferior surface of the aortic cusps and the left ventricle in a plane perpendicular to its long axis 1 cm below the mitral leaflet tips. Interobserver variability of these measurements on unguided parasternal long-axis images and on guided short-axis images was assessed. RESULTS: The standard unguided two-dimensional examination was associated with an interobserver variability of 14.6% and 9.1% for atrial and ventricular measurements, respectively. Guided three-dimensional echocardiography significantly reduced interobserver variability to 5.0% and 3.1%, respectively, for the same measurements (p < 0.005 by McNemar's test). CONCLUSIONS: Significant interobserver variability occurs with standard unguided two-dimensional echocardiographic measurement of left atrial and left ventricular dimensions. Guided three-dimensional echocardiography achieves a nearly threefold improvement of reproducibility of these measurements and provides the basis for improved serial evaluation and comparison of atrial and ventricular size by different operators.

Adult↗

PubMed1992

Ex vivo incubation with growth factors enhances the engraftment of fetal hematopoietic cells transplanted in sheep fetuses.

Hematopoietic stem cells (HSC) transplanted in utero are in competition with endogenous HSC; thus, ultimately the graft constitutes a relatively small fraction of total HSC pool. To enhance the engraftment of donor cells in sheep fetuses, we preincubated these cells, ex vivo, for 16 hours at 37 degrees C with the conditioned medium from phytohemagglutinin-stimulated lymphocytes (PHA-LCM) before in utero transplantation. PHA-LCM is a rich source of hematopoietic growth factors in sheep. Subsequent engraftment was significantly higher in cells preincubated with PHA-LCM compared with fresh cells or those incubated with control medium only. This was reflected in all markers of the donor cells (hemoglobin type, karyotype, and progenitor cell assays). Brief ex vivo incubation with PHA-LCM also increased viability of all marrow cells as well as total numbers of progenitors. Similar enhancement of engraftment was also noted in monkeys after a brief preincubation of donor cells with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We conclude that brief (16 hours) ex vivo incubation of donor cells with a source of such growth factors as IL-3 and GM-CSF enhances the subsequent engraftment of transplanted cells.

Animals↗

PubMed1992

Adult-to-neonate lung transplantation: anatomic considerations.

Babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Using ECMO as a bridge to transplantation, reduced-size lung grafts (pulmonary lobe or segment) could expand the pool of cadaver donors and may allow for HLA-matched living-related transplants. We tested this concept first in the piglet model and developed the technical maneuvers necessary to perform lobar and segmental lung transplants from adult pigs into neonatal piglets. Prior to clinical application, a systematic evaluation of anatomic considerations for reduced-size human lung transplantation was needed. A series of human adult and neonatal cadaver thoracic dissections were performed to determine the adult pulmonary lobe or segment with the proper size, orientation, and vascular and bronchial anatomy for use as a neonatal lung transplant. The adult right middle lobe (RML) is the best candidate for neonatal left lung replacement. The adult RML, once removed, can be rotated 180 degrees around its superior-inferior axis and the vessels and bronchus align well in the left chest of the neonate. The RML may require further reduction to fit into the neonatal left chest. Selective arterial perfusion of the RML showed the anterior segment to be a near-perfect match for fit and anatomy. This technique may eventually permit living-related lung transplantation.

Adult↗

PubMed1992

New techniques in fetal surgery.

Optimal fetal management during and after fetal surgery has been limited by an inability to reliably monitor the fetal heart rate and temperature, and by a lack of access to the fetal circulation. In order to solve these problems, we used early third trimester fetal sheep to develop: (1) an implantable radiotelemetry device that transmits the fetal electrocardiogram and temperature, and (2) an intraosseous access technique. A miniaturized radiotelemeter was implanted subcutaneously in the axilla of four fetal sheep. Safe implantation of the radiotelemeter was technically feasible and the device reliably recorded the fetal electrocardiogram and temperature both intraoperatively and postoperatively. Although many possible routes for access to the fetal circulation have been tried experimentally and clinically for both resuscitation and blood sampling, none have proven satisfactory. We assessed the use of intraosseous access in fetal sheep (n = 6) for both infusion and blood sampling. Access with an intraosseous needle was obtained in both sheep fetuses and human fetal cadavers. Blood gas values (pH, PCO2, and PO2) obtained from the medullary cavity of fetal sheep accurately reflected peripheral venous values. Resuscitation drugs reached the fetal circulation via the intraosseous route: sodium bicarbonate elevated venous bicarbonate levels from 28.4 +/- 1.7 to 31.8 +/- 2.1 mEq/dL (P < .05); injected glucose increased venous glucose levels by 520 +/- 108 mg/dL (P < .01); and injection of calcium chloride elevated venous calcium levels from 11.8 +/- 0.7 to 15.2 +/- 2.2 mEq/dL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Tracheostomy in children with emphasis on home care.

Tracheostomy in children is not a benign procedure. Tracheostomy-related mortality rates among children have been previously reported to be as high as 10% to 27%. Children with tracheostomies are especially vulnerable after home discharge with mortality rates of 0.5 to 2 deaths per 100 months at home. In order to assess the impact of extensive parental education and home nursing care on tracheostomy-related mortality, we report our experience over 9 years with 44 children receiving tracheostomies. Each child was maintained at home with a tracheostomy for an average of 19 months for a total of 635 months of home tracheostomy care. Indications for tracheostomy were tracheomalacia (32%), obstructive airway lesions (23%), central nervous system lesions (16%), vocal cord paralysis (9%), Pierre Robin syndrome (9%), and a list of miscellaneous conditions (11%). Our tracheostomy care regimen begins with intensive parental training in tracheostomy management for a minimum of 10 days prior to discharge. Home nursing was arranged for 77% of these children for an average of 11 hours per day at the time of discharge. Eighty-three percent had home apnea monitors. Discharge of these children was delayed or transfer to a secondary hospital was made when parents failed to show adequate proficiency in tracheostomy management with existing home nursing. Eight percent were ventilator dependent at discharge. As of January 1, 1989, 34% of these children have been decannulated. There were six deaths, all due to underlying disease. There were no tracheostomy-related deaths in hospital or after discharge home.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗

PubMed1992

Necrotizing fasciitis in two children with acute lymphoblastic leukemia.

Necrotizing fasciitis is a severe, soft tissue infection, and is an unusual condition in children. The cornerstone of therapy is prompt, aggressive surgical treatment. Despite vigorous treatment, mortality rates are high. We report the occurrence of necrotizing fasciitis in two children during the granulocytopenic phase of induction chemotherapy for acute lymphoblastic leukemia. The diagnosis and treatment of necrotizing fasciitis in these two children was made more difficult by their underlying disease and its chemotherapy. The successful treatment of their infections relied on a multimodality approach. Aggressive surgical debridement was the mainstay of therapy. Adjuvant therapy was vital to the successful outcomes and included meticulous wound care, intravenous hyperalimentation, appropriate antibiotics, and granulocyte transfusions.

Agranulocytosis↗

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↗

PubMed1992

Value and limitations of transesophageal echocardiography in determination of left ventricular volumes and ejection fraction.

Several formulas exist for estimating left ventricular volumes and ejection fraction using conventional two-dimensional echocardiography from transthoracic views. Transesophageal imaging provides superior resolution of endocardial borders but employs slightly different scan planes. The estimation of left ventricular volumes by transesophageal echocardiography has not been validated in human patients. Therefore, the purpose of this study was to compare left ventricular volumes and ejection fraction derived from transesophageal short-axis and four-chamber images with similar variables obtained from ventriculography. End-diastolic and end-systolic volumes and ejection fraction were calculated using modified Simpson's rule, area-length and diameter-length models in 36 patients undergoing left ventriculography. Measurements of left ventricular length were obtained from the transesophageal four-chamber view and areas and diameters were taken from short-axis scans at the mitral valve, papillary muscle and apex levels. Data from transesophageal echocardiographic calculations were compared with end-diastolic volume (mean 172 +/- 90 ml), end-systolic volume (mean 91 +/- 74 ml) and ejection fraction (mean 52 +/- 15%) from cineventriculography using linear regression analysis. The area-length method (r = 0.88) resulted in a slightly better correlation with left ventricular end-diastolic volume than did Simpson's rule (r = 0.85) or area-length (r = 0.84) formulas. For end-systolic volume, the three models yielded similar correlations: Simpson's rule (r = 0.94), area-length (r = 0.93) and diameter-length (r = 0.95). Each of the methods resulted in significant underestimation of diastolic and systolic volumes compared with values assessed with angiography (p less than 0.003). Ejection fraction was best predicted by using the Simpson's rule formula (r = 0.85) in comparison with area-length (r = 0.80) or diameter-length (r = 0.73) formulas. Measurements of left ventricular length by transesophageal echocardiography were smaller for systole (mean 5.7 +/- 1.6 cm) and diastole (mean 7.7 +/- 1.2 cm) than values by ventriculography (mean 9.2 +/- 1.4 and 8.1 +/- 1.6 cm, respectively; p less than 0.0001), suggesting that underestimation of the ventricular length is a major factor contributing to the smaller volumes obtained by transesophageal echocardiography. In conclusion, currently existing formulas can be applied to transesophageal images for predicting left ventricular volumes and ejection fraction. However, volumes obtained by these models are significantly smaller than those obtained with angiography, possibly because of foreshortening in the transesophageal four-chamber view.

Adult↗