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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 127 records · Page 7Linked to original sources
PubMed1995

Prenatal diagnosis of esophageal atresia.

The prenatal sonographic detection of esophageal atresia (EA) has been possible for more than a decade and relies on the finding of a small or absent fetal stomach bubble associated with maternal polyhydramnios. The aims of this study were to assess the accuracy of this technique and to determine whether the outcome of prenatally diagnosed EA differs from its postnatal counterpart. All fetal sonograms performed between January 1989 and October 1993 demonstrating a small or absent fetal gastric bubble were reviewed together with all neonates with EA treated during the same period. Eighty-seven fetuses with a small (n = 53) or absent stomach bubble (n = 34) were identified, representing 1.4% of all fetal sonographic surveys. Esophageal atresia was present in 15; in 13 of these, the maternal amniotic fluid volume was increased. The positive predictive value of an absent stomach bubble and polyhydramnios was 56%, and the sensitivity of prenatal sonography in the diagnosis of EA was 42%. One neonate with EA had the prenatal diagnosis established at another institution, yielding a total of 16 cases of prenatally diagnosed EA for analysis. Seven (44%) of these had trisomy 18. Of the remaining nine, two had isolated EA, two had laryngeal atresia and EA, and there were two late-gestational unexplained fetal deaths. Only four (25%) survived through the neonatal period. The prognosis of the fetus with EA is radically different from that of the neonate with EA.

Esophageal Atresia↗
PubMed1995

Fetal diaphragmatic hernia without visceral herniation.

Many cases of congenital diaphragmatic hernia (CDH) are currently detected before birth. The authors hypothesized that there is a subgroup of patients with CDH who have no evidence of visceral herniation in utero and who would be expected to have less pulmonary hypoplasia and a good prognosis. Among 41 neonates with left-sided CDH treated between January 1990 and October 1993, 17 cases were diagnosed after birth. Ten of the 17 had undergone detailed fetal sonographic imaging at or after 20 weeks' gestation. After independent review of the prenatal scans of these 10 patients, one was found to have evidence of a diaphragmatic hernia and was excluded from further analysis. The other nine fetuses survived, and prosthetic repair of the diaphragmatic defect and extracorporeal membrane oxygenation (ECMO) were each required in only one patient. This contrasted with the outcome for 18 control patients with prenatally diagnosed CDH: 4 (22%) died, 13 (72%) required prosthetic repair, 9 (50%) were supported with ECMO and the duration of ventilatory support and hospital stay were significantly longer. There is a spectrum of severity among both pre and postnatally diagnosed cases of CDH. In the neonate with an isolated left-sided diaphragmatic hernia, a good prognosis is to be expected if the condition was not detectable by detailed prenatal sonography in the second half of pregnancy.

Female↗
PubMed1995

Cost per anomaly: what does a diaphragmatic hernia cost?

The cost of medical care in the United States is under close scrutiny. Birth defects have surpassed prematurity as the leading cause of infant mortality in the United States and contribute significantly to infant morbidity. Few estimates have been made of the costs of individual birth defects. The authors sought to determine the cost of initial hospitalization for an infant with a congenital diaphragmatic hernia (CDH). They analyzed hospital bills and professional fees from all 35 cases of infants who underwent postnatal CDH repair at their institution between January 1990 and December 1993. The cost averaged $137,000 per patient, and ECMO dramatically increased the cost. The cost per survivor was $98,000 in the non-ECMO group and $365,000 in the ECMO group. The estimated cost of CDH per year in the United States is more than $230 million. This study suggests several strategies for cost reduction, provides data for future cost comparisons, and serves as a cost comparison for evaluating new therapeutic strategies for CDH.

Birth Weight↗
PubMed1995

The 'PLUG' odyssey: adventures in experimental fetal tracheal occlusion.

In animal experiments, it has been shown that tracheal occlusion counteracts the pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH). Successful clinical implementation requires a reliable, reversible, and atraumatic technique of occluding the fetal trachea. With this clinical goal in mind, the authors evaluated the following three methods of tracheal occlusion in a fetal lamb CDH model: (1) an occluded foam-cuffed endotracheal tube, (2) a foam-cuffed endotracheal tube with a magnetically controlled flow valve, and (3) a tracheal insert constructed of a water-impermeable, expandable, polymeric foam, which is placed by a translaryngeal approach. The foam-cuffed endotracheal tube did not provide consistently reliable fetal tracheal occlusion. Although the magnetically triggered flow valve functioned well, it was not necessary to open the valve in utero (to prevent overdistension of the lungs), and the presence of the valve contributed to several occlusive failures. In contrast, the foam insert was easy to position and to remove from the trachea, while providing reliable tracheal occlusion for several weeks with consequent enlarged fetal lungs, increased lung fluid volumes, complete reduction of abdominal viscera, and improved pulmonary gas exchange after birth. Bronchoscopic evaluation of the foam-occluded neonatal tracheas showed little or no tracheal damage, which was confirmed during necropsy by gross and histological examination. Translaryngeal placement of a compressible, water-impermeable polymeric foam appears to be a simple and safe technique to achieve fetal tracheal occlusion.

Animals↗
PubMed1995

Before the horse is out of the barn: fetal surgery for hydrops.

Hydrops fetalis, a condition characterized by abnormal accumulation of fluid and edema in the fetus, is the final common pathway in a number of pathological conditions. The diagnosis of hydrops is based on ultrasonographic findings of generalized edema along with a serous effusion (ascites, pleural effusion, or pericardial effusion). Polyhydramnios and placentomegaly may also be present. Historically, hydrops fetalis has been described in cases of Rh alloimmunization and severe erythroblastosis (immune hydrops). Hydrops is considered "nonimmune" if there is no evidence of fetal-maternal blood group incompatibility. Over the past few decades, nonimmune hydrops has been recognized more frequently. In a number of series, 80% to 90% of hydropic fetuses were considered nonimmune. Incidence ranges from 1 in 1,500 to 1 in 3,800 births. Etiology is diverse and associated conditions include cardiovascular malformations, chromosomal abnormalities, thoracic lesions, infections, metabolic disorders, fetal anemia and twinning. Overall prognosis is poor, with mortality between 50% and 98%. Advances in obstetric ultrasound and prenatal diagnosis have made it possible to diagnose a number of congenital anomalies early in gestation. In some cases, anatomic anomalies diagnosed in utero progress to nonimmune hydrops and almost certain fetal demise. It is these conditions that can be considered for fetal surgical intervention. This article reviews the pathophysiology and rationale behind surgical correction of two conditions that lead to hydrops: fetal thoracic lesions (congenital cystic adenomatoid malformation, pulmonary sequestration, and fetal pleural effusions) and sacrococcygeal teratoma (SCT).

Bronchopulmonary Sequestration↗
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

A prospective study of the outcome for fetuses with diaphragmatic hernia.

OBJECTIVE: To establish the natural history and outcome of isolated congenital diaphragmatic hernia (CDH) diagnosed before birth. The mortality of CDH with currently available postnatal care, including extracorporeal membrane oxygenation (ECMO), reported in retrospective studies ranges from less than 25% to greater than 75%. This variation is attributable to a "hidden mortality" (infants who die with CDH that is not recognized) of unknown magnitude. DESIGN: Prospectively followed case series. SETTING: Patients were referred from practitioners in 18 states and evaluated and followed up by the University of California, San Francisco, Fetal Treatment Center. Arrangements were made for planned delivery at tertiary perinatal centers with ECMO capability. PATIENTS: All 83 fetuses with isolated, potentially correctable CDH diagnosed prior to 24 weeks' gestation referred to the University of California, San Francisco, Fetal Treatment Center between January 1989 and October 1993. MAIN OUTCOME MEASURES: Survival beyond 2 months after optimal postnatal care. RESULTS: Fifty-eight percent (48 of 83) died despite optimal postnatal care (95% confidence interval, 41% to 75%). Of the 48 nonsurvivors, seven suffered intrauterine fetal demise, four were too premature for ECMO, 16 died before ECMO could be started, and 21 died despite ECMO therapy. Twenty-two of the 35 survivors received ECMO, and nine of these have severe chronic illness attributable to the intensive management. CONCLUSIONS: In this study, the mortality for potentially correctable CDH diagnosed before 24 weeks' gestation is 58%, despite optimal care presently available after birth. Infants who die in utero and soon after birth constitute a substantial hidden mortality.

Extracorporeal Membrane Oxygenation↗
PubMed1994

Vascular changes with in utero correction of diaphragmatic hernia.

In utero surgical correction of fetal diaphragmatic hernia is a new therapeutic alternative for selected prenatally diagnosed patients. With increasing experience, the authors have found that fetuses with herniation of the liver through the diaphragmatic defect have a high incidence of perioperative death. The hypothesis was that reduction of the liver during fetal diaphragmatic hernia repair caused distortion of fetal vascular anatomy resulting in fetal demise. To study this, the authors performed angiograms through the umbilical vein in fetal and neonatal cadavers, with and without diaphragmatic hernias, and simulated in utero repair. Large fetal congenital diaphragmatic hernias can be associated with dramatic changes in the vascular anatomy of the liver. The liver does not simply rotate up into the chest through a diaphragmatic defect; instead, the liver more likely develops in the chest, with its vascular anatomy situated accordingly. Attempts to reduce a herniated liver can result in significant distortion of the fetal vasculature, leading to fetal death. Techniques to prevent vascular compromise during hepatic manipulation may improve the outcome for fetuses during in utero repair of diaphragmatic hernias.

Angiography, Digital Subtraction↗
PubMed1994

Amniotic fluid phospholipid analysis in the fetus with congenital diaphragmatic hernia.

The substantial morbidity and mortality of congenital diaphragmatic hernia (CDH) is attributed to the pulmonary hypoplasia caused by the presence of abdominal viscera in the chest during intrauterine life. Recent experimental studies suggest that surfactant deficiency may also contribute to CDH pathophysiology. Clinically, the amniocentesis-derived lecithin to sphingomyelin (L/S) ratio and phosphatidylglycerol (PG) data are used to assess fetal lung maturity. We have performed amniotic fluid phospholipid analyses at 33 to 38 weeks' gestation in 18 fetuses with prenatally diagnosed CDH to assess fetal lung maturity, plan optimal timing for delivery, and selectively employ prenatal glucocorticoid or postnatal surfactant therapy. Compared with published control values from uncomplicated pregnancies, there was no difference in the L/S ratio or PG in the CDH fetus. Based on amniotic fluid phospholipid data, the human CDH fetus is not surfactant-deficient.

Amniotic Fluid↗
PubMed1994

Effect of nitric oxide on the colonic smooth muscle of patients with Hirschsprung's disease.

Hirschsprung's disease results in bowel obstruction because of a failure of smooth muscle relaxation in both the aganglionic segment of bowel and the internal anal sphincter (IAS). Nonadrenergic noncholinergic (NANC) nerves, which use nitric oxide (NO) as their chemical messenger, are responsible for relaxing smooth muscle in normal bowel and the IAS. Previous work indicates that the cause of the aganglionic colon's inability to relax may be a lack of NANC nerves. To test this hypothesis, the authors compared the effect of an exogenous source of NO, S-nitroso-N-acetylpenicillamine (SNAP), on the isometric tension of smooth muscle strips taken from the ganglionic colon, aganglionic colon, and IAS of patients with Hirschsprung's disease. Exposure of ganglionic and aganglionic colon specimens to SNAP (10(-3) to 10(-5) mol/L) resulted in up to 70% reduction of resting tension. This relaxation occurred in a dose-dependent fashion and could be promptly reversed by the addition of the NO antagonist methylene blue. However, SNAP had no demonstrable effect on the smooth muscle strips taken from the IAS of patients with Hirschsprung's disease. This finding suggests that, in the aganglionic colon, a deficiency of NANC nerves contributes to the development of bowel obstruction. However, the failure of the IAS to relax in Hirschsprung's disease appears to be unrelated to NO and the NANC nervous system.

Colon↗
PubMed1994

Congenital high airway obstruction syndrome (CHAOS): a potential for perinatal intervention.

Congenital high airway obstruction syndrome (CHAOS) results in a predictable constellation of findings: large echogenic lungs, flattened or inverted diaphragms, dilated airways distal to the obstruction, and fetal ascites and/or hydrops. The authors report on four fetuses referred for evaluation. None of them survived. Postmortem evaluation showed that three fetuses had laryngeal atresia, and one had tracheal stenosis. Coexistent fetal anomalies were accurately diagnosed by ultrasound in three of the four patients. The finding of CHAOS on prenatal ultrasound examination is diagnostic of complete or near-complete obstruction of the fetal upper airway, most likely caused by laryngeal atresia. A greater understanding of the natural history of CHAOS may permit improved prenatal and perinatal management.

Adult↗
PubMed1994

Plug the lung until it grows (PLUG): a new method to treat congenital diaphragmatic hernia in utero.

Fetal lungs normally produce fluid that flows through the upper airway into the amniotic fluid. In fetuses with congenital diaphragmatic hernia (CDH), obstructing the flow of lung fluid may expand the lungs and propel the viscera from the chest, alleviating the pulmonary hypoplasia associated with CDH. To test this hypothesis, left-sided diaphragmatic hernias were created in sixteen 75-day-gestation fetal lambs (full-term, 145 days). At 120 days, the trachea was ligated in eight lambs; it was left unligated in the other eight. At 135 to 140 days, the fetuses were delivered, and a tracheostomy performed. Newborns were ventilated for 1 hour and then killed. Blood gas analysis was performed at 0,5,20,40, and 60 minutes. Lung dry weight, DNA, protein, and lipid analyses, as well as plasma cortisol measurements were performed. At autopsy, in the ligated lambs, the abdominal viscera was reduced from the thorax; however, the unligated lambs had viscera completely occupying the left chest. The lungs of the ligated lambs had a higher dry weight (4.22 +/- 1.37 g/kg v 1.95 +/- 0.59 g/kg; P =.001), DNA (193.8 +/- 90.5 mg/kg v 91.5 +/- 66.4 mg/kg; P = .02), and protein (1798 +/- 691.6 mg/kg v 766.6 +/- 201 mg/kg; P = .004). Lung saturated phosphatidyl choline (SPC) levels, DNA:protein ratio, and plasma cortisol were not different between the groups. Neonatal Po2 at 60 minutes was higher in the ligated group (179.4 +/- 127.0 mm Hg v 60.9 +/- 62.4 mm Hg; P < .05), and Pco2 was lower (44.1 +/- 21.4 v 83.9 +/- 23.5; P < .05) in the ligated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗