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Biomedical subjects

Michael R Harrison

Publications and source records attributed to Michael R Harrison.

At least 37 records · Page 2Linked to original sources
PubMed2004

Quantitative study of pulmonary endocrine cells in fetal, postnatal and adult sheep.

Using light microscopic immunohistochemistry, neuron-specific enolase (NSE)-positive endocrine cells were quantitatively analyzed in the sheep lung during different stages of development from the canalicular stages to adulthood. In all stages, NSE-positive endocrine cells were usually located in the bronchi and bronchioles as solitary cells, although a few NSE-positive cell clusters, the so-called neuroepithelial bodies, were found in some places. The number of NSE-positive endocrine cells decreased with advanced stages of gestation. In the late alveolar stage, the number of NSE-positive endocrine cells reached its bottom during the fetal period. There was a gradual upturn after birth. The overall pattern of growth and differentiation of the endocrine cells is most likely species-related and depends on the state of airway development; the number of the endocrine cells of almost all animals, excluding the sheep, in relation to the size of the lung reaches a peak in the late fetal and early neonatal periods and decreases shortly thereafter. NSE-positive endocrine cells were also predominantly located in the large airways during the early stage of development (canalicular stage), and were found more frequently in the small peripheral airways towards the term. These results show the number of NSE-positive endocrine cells in the sheep to be different from that seen in other species.

Age Factors↗
PubMed2003

Fetal surgery for repair of myelomeningocele allows normal development of anal sphincter muscles in sheep.

One major problem for patients with myelomeningocele (MMC) is fecal incontinence. To prevent this problem, fetal surgery for repair of MMC has been recently undertaken. The strategy behind this surgery is to allow normal development of anal sphincter muscles. The purpose of this study was to determine whether fetal surgery for repair of MMC allows normal development of anal sphincter muscles. Myelomeningocele was surgically created in fetal sheep at 75 days of gestation. At 100 days of gestation, fetal surgery for repair of the MMC lesion was performed. Three repair methods were used: standard neurosurgical repair (4 fetal sheep), covering the MMC lesion with Alloderm (2 fetal sheep), and covering the MMC lesion with Gore-Tex (2 fetal sheep). After the sheep were delivered (140 days of gestation), external and internal anal sphincter muscles were analyzed histopathologically. In control fetal sheep (not repaired) anal sphincter muscles did not develop normally. In contrast, in fetal sheep that underwent repair of the MMC, the external and internal anal sphincter muscles developed normally. Histopathologically, in the external sphincter muscles, muscle fibers were dense. In the internal sphincter muscles, endomysial spaces were small, myofibrils were numerous, and fascicular units were larger than those in unrepaired fetal sheep. There was no difference in muscle development for the repair methods. Fetal surgery for repair of MMC allows normal development of anal sphincter muscles.

Anal Canal↗
PubMed2003

A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia.

BACKGROUND: Experimental and clinical data suggest that fetal endoscopic tracheal occlusion to induce lung growth may improve the outcome of severe congenital diaphragmatic hernia. We performed a randomized, controlled trial comparing fetal tracheal occlusion with standard postnatal care. METHODS: Women carrying fetuses that were between 22 and 27 weeks of gestation and that had severe, left-sided congenital diaphragmatic hernia (liver herniation and a lung-to-head ratio below 1.4), with no other detectable anomalies, were randomly assigned to fetal endoscopic tracheal occlusion or standard care. The primary outcome was survival at the age of 90 days; the secondary outcomes were measures of maternal and neonatal morbidity. RESULTS: Of 28 women who met the entry criteria, 24 agreed to randomization. Enrollment was stopped after 24 patients had been enrolled because of the unexpectedly high survival rate with standard care and the conclusion of the data safety monitoring board that further recruitment would not result in significant differences between the groups. Eight of 11 fetuses (73 percent) in the tracheal-occlusion group and 10 of 13 (77 percent) in the group that received standard care survived to 90 days of age (P=1.00). The severity of the congenital diaphragmatic hernia at randomization, as measured by the lung-to-head ratio, was inversely related to survival in both groups. Premature rupture of the membranes and preterm delivery were more common in the group receiving the intervention than in the group receiving standard care (mean [+/-SD] gestational age at delivery, 30.8+/-2.0 weeks vs. 37.0+/-1.5 weeks; P<0.001). The rates of neonatal morbidity did not differ between the groups. CONCLUSIONS: Tracheal occlusion did not improve survival or morbidity rates in this cohort of fetuses with congenital diaphragmatic hernia.

Adult↗
PubMed2003

Minimal access fetal surgery.

The development of fetal surgery has led to promising therapeutic options for a number of congenital malformations. However, preterm labor (PTL) and premature rupture of membranes continue to be ubiquitous risks for both mother and fetus. To reduce maternal morbidity and the risk of prematurity, minimal access surgical techniques were developed and are increasingly employed. Congenital diaphragmatic hernia (CDH), obstructive uropathy, twin-to-twin transfusion syndrome (TTTS), and sacrococcygeal teratoma have already been successfully treated using minimal access fetal surgical procedures. Other life-threatening diseases as well as severely disabling but not life-threatening conditions are potentially amenable to treatment. The wider application of minimal access fetal surgery depends on a continued improvement in technology and a better understanding of complications associated with fetal intervention.

Congenital Abnormalities↗
PubMed2003

Fetal surgery for repair of myelomeningocele allows normal development of the rectum in sheep.

To determine whether fetal surgery in a fetus with myelomeningocele (MMC) allows normal development of rectal muscles and nerves, we analyzed the rectum after fetal surgery in a sheep model. An MMC lesion was surgically created in 13 fetal sheep at 75 days of gestation. One fetal sheep died after the lesion was created. Eight fetal sheep were repaired at 100 days of gestation; the others were not repaired, as a control (n=4). Three methods were used for fetal surgery of MMC: standard neurosurgical repair (4 fetal sheep), covering of the MMC lesion by Alloderm (2 fetal sheep), and covering of the MMC lesion by Gore-Tex (2 fetal sheep). At 140 days of gestation, fetal sheep were harvested and histo-pathological analysis was performed on the rectum using hematoxylin and eosin staining for muscles and S-100 protein staining for nerves. One fetal sheep treated by standard neurosurgical repair died before harvesting. The four untreated fetal sheep had hypoplastic longitudinal muscles of the rectum but well developed-circular muscles. In addition, the untreated fetuses had a hypoplastic submucosal nerve plexus but a well-developed intermuscular nerve plexus. In contrast, treated fetal sheep had well-developed longitudinal and circular muscles except for one sheep treated with standard neurosurgical repair. In addition, except for the same fetal sheep, treated fetal sheep had well-developed nerve plexuses. There was no difference in muscle and nerve development of the rectum among the three repair methods. Fetal surgery for repair of MMC allows normal development of rectal muscles and nerves.

Animals↗
PubMed2003

In utero repair of myelomeningocele: experimental pathophysiology, initial clinical experience, and outcomes.

HYPOTHESIS: Experimental work raises the possibility that in utero repair of myelomeningocele (MMC) may improve lower extremity, bladder, and bowel function, ameliorate the Arnold-Chiari malformation, and decrease the need for postnatal shunting. DESIGN: We previously developed fetal lamb models to create and reverse lower extremity damage and the Arnold-Chiari malformation in utero. We then applied our extensive experience with fetal surgery, including fetal endoscopic (fetoscopic) surgical manipulation, to develop techniques for MMC repair. SETTING: A tertiary referral center. PATIENTS: All patients treated between 1998 and 2002 for a prenatally diagnosed MMC. INTERVENTIONS: Either fetoscopic MMC repair, fetoscopic patch repair, or limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair was performed. MAIN OUTCOME MEASURES: Gestational age at delivery, survival, neurologic outcome, and need for ventricular shunting at 1 year. RESULTS: Complete fetoscopic repair was accomplished in 1 fetus. Two other fetuses underwent partial fetoscopic procedures. The remaining 10 patients underwent limited maternal hysterotomy and microsurgical 3-layered fetal MMC repair. Four of 13 patients died, and the mean gestational age at delivery of 11 fetuses born alive was 31 weeks. Five of 9 required ventricular shunting by age 1 year. In 2 patients, lower extremity function improved by more than 2 vertebral levels compared with prenatal ultrasonography. Five of 10 patients who lived longer than 3 weeks required postnatal wound revision within 7 days after birth. CONCLUSIONS: Fetoscopic repair, although feasible, does not yet yield optimal surgical results. Open surgical repair before 22 weeks' gestation is physiologically sound and technically feasible. One third of patients appear to be spared the need for a shunt at age 1 year, but improvement in distal neurologic function is less clear. Additionally, fetal mortality is associated with this procedure. Our results complement the data published by groups at Children's Hospital of Philadelphia, in Pennsylvania, and Vanderbilt University, Nashville, Tenn. A National Institutes of Health-sponsored prospective randomized trial is now underway at these 3 centers to compare fetal repair with postnatal repair.

Adult↗
PubMed2003

Congenital diaphragmatic hernia: advances in prenatal therapy.

Congenital diaphragmatic hernia (CDH) is one of the most common causes of neonatal morbidity and mortality. The clinical spectrum of CDH ranges from minimally affected infants who do well with modern neonatal care to severely affected infants who die despite all interventions. Two decades of research have led to advances in the prenatal diagnosis of CDH and have better defined the natural history of CDH. Fetuses with CDH now can be stratified into "low" and "high" risk groups based on sonographic parameters. "Low risk" fetuses have an excellent chance of survival with postnatal therapy. Prenatal intervention is reserved for "high risk" fetuses. Ongoing research is focused on improving both prenatal and postnatal treatment of these severely affected infants.

Extracorporeal Membrane Oxygenation↗
PubMed2003

Prenatal therapy for thoracic and mediastinal lesions.

Most prenatally diagnosed lung lesions can be managed successfully during the neonatal period. Prenatal imaging and experimental models have provided a comprehensive understanding of the pathophysiology, natural history, and prognosis of intrathoracic and mediastinal lesions. Clinical experience has demonstrated that progression to nonimmune hydrops fetalis and pulmonary hypoplasia is a harbinger of fetal or neonatal demise. Advances in fetal anesthesia, tocolysis, and surgical techniques have made fetal surgery a viable in utero option to ameliorate life-threatening masses. Congenital cystic adenomatoid malformation, bronchopulmonary sequestration, and congenital hydrothorax are the most common abnormalities amenable to surgical intervention. The natural history, evaluation, and treatment of intrathoracic and mediastinal lesions are discussed.

Algorithms↗
PubMed2003

Comparison of drainage techniques for biliary atresia.

PURPOSE: Traditional Kasai portoenterostomy and porto-appendiceal duodenostomy have been utilized for biliary atresia. Differences in outcome between patients who underwent either Kasai portoenterostomy or porto-appendiceal duodenostomy were compared. METHODS: A review of all children who underwent a drainage procedure for biliary atresia from 1986 to 2000 (n = 30) was performed. Age at drainage procedure, subsequent liver transplantation, and outcomes were evaluated. Outcome variables included success rates (total bilirubin < 2.0 mg/dL) and survival rate. Statistical analysis was done with chi2 and Student's t test. RESULTS: Long-term follow-up was available on 28 of 30 patients. Age at biliary drainage was insignificant. Success rates between porto-appendiceal duodenostomy (31%) and Kasai portoenterostomy (82%) were statistically significant. Survival rate for patients who underwent a Kasai portoenterostomy was 10 of 11 patients. Survival rate for patients who underwent porto-appendiceal duodenostomy was 14 of 16 patients. Overall survival rate was comparable between porto-appendiceal duodenostomy (88%) and Kasai portoenterostomy (91%). CONCLUSIONS: Although overall survival rate was comparable, patients who underwent porto-appendiceal duodenostomy were less successful in alleviating hyperbilirubinemia compared with Kasai portoenterostomy. This is shown further by the greater incidence of subsequent liver transplantation in infants with prior porto-appendiceal duodenostomy. Although the appendix may serve as an alternative biliary conduit, traditional Kasai portoenterostomy appears to achieve better biliary drainage.

Adolescent↗
PubMed2003

Fetoscopic temporary tracheal occlusion for congenital diaphragmatic hernia: prelude to a randomized, controlled trial.

OBJECTIVE: As previously reported, high postnatal mortality seen in fetuses with congenital diaphragmatic hernia (CDH) with liver herniation and low lung-to-head ratio (LHR) appears to be improved in fetuses who undergo fetoscopic temporary tracheal occlusion (TO). To test whether further evolution of this technique produces results that justify a randomized controlled trial comparing prenatal intervention to postnatal care, the authors analyzed 11 additional cases and the cumulative experience with 19 cases. METHODS: The authors analyzed retrospectively the outcome of 11 new and 8 previously reported cases of fetoscopic temporary tracheal occlusion. Various factors were studied including maternal morbidity, antenatal outcome, physiologic lung response, and neonatal course. RESULTS: Temporary TO can be accomplished using 3 5-mm radially expanding uterine ports without hysterotomy. Obstetric morbidity included mild pulmonary edema in 6 cases, chorioamniotic separation and premature rupture of membranes in 12 patients, and preterm labor and delivery in all patients. Thirteen of 19 (68%) neonates survived for 90 days after delivery; one died in utero, and 5 died after birth. Late mortality included one death caused by sepsis and 2 by complications associated with tracheostomies. Morbidity from gastroesophageal reflux requiring Nissen fundoplication, tracheal injury requiring repair or tracheostomy, and recurrent hernias after diaphragmatic repair were characteristic in longterm survivors. CONCLUSIONS: Fetoscopic temporary TO may improve outcome in poor-prognosis fetuses with CDH. However, complications related to tracheal dissection, premature delivery and late morbidity are significant. This experience has led to simpler techniques for fetoscopic tracheal occlusion and to an National Institutes of Health-sponsored randomized controlled trial comparing fetoscopic tracheal occlusion with optimal postnatal care.

Fetal Diseases↗
PubMed2003

Congenital diaphragmatic hernia: advances in prenatal therapy.

Despite intensive clinical and experimental efforts, mortality from CDH remains high. More than two decades of research in multiple centers has led to a better understanding of the pathophysiology, prognosis, and treatment options for fetuses that have CDH. It now appears that fetuses that have prenatally diagnosed CDH can be stratified into high- and low-risk groups based upon sonographic parameters. Fetuses that do not have liver herniation into the chest that have a favorable LHR have an excellent chance of survival with postnatal therapy. Prenatal diagnosis allows the time and place of delivery to be planned in advance so these infants can be treated in a tertiary care nursery that has maximal medical and surgical therapy. Fetuses that have liver herniation into the chest and an unfavorable LHR have a grim prognosis. These fetuses might benefit from in utero intervention. There is no role for open fetal repair of the diaphragmatic detect; however, fetoscopic temporary tracheal occlusion might improve lung growth and development and might decrease morbidity and mortality in these infants. The FETENDO strategy appears to work, and for the first time it offers hope to the fetus that has high-risk CDH, but its efficacy must be proven in a proper randomized, controlled trial.

Animals↗
PubMed2003

The ex utero intrapartum treatment (EXIT) procedure.

The ex utero intrapartum treatment (EXIT) procedure was originally developed to reverse temporary tracheal occlusion in patients who had undergone foetal surgery for severe congenital diaphragmatic hernia (CDH). In a select group of foetuses with CDH, tracheal occlusion is used to obstruct the normal flow of foetal lung fluid and to stimulate lung expansion and growth. With the airway obstructed, airway management at birth is critical. The solution was to arrange delivery in such a way that the occlusion could be removed and the airway secured while the baby remained on placental support. If the uterus was kept relaxed and the utero-placental blood flow kept intact, the foetus could remain on a maternal 'heart-lung machine' while the airway was secured. While the technique of tracheal occlusion remains under study in clinical trials, EXIT procedures have been shown to be useful for management of other causes of foetal airway obstruction.

Airway Obstruction↗
PubMed2003

Resolution of hydrops fetalis in congenital cystic adenomatoid malformation after prenatal steroid therapy.

BACKGROUND/PURPOSE: Development of hydrops fetalis in fetuses with congenital cystic adenomatoid malformations (CCAM) is a significant risk factor for fetal or neonatal demise. In rare cases, resolution of CCAM has occurred, presumably owing to lesion maturation or involution. Steroid therapy, utilized for lung maturity, has been postulated to accelerate this process. The natural history of hydropic fetuses with CCAM after receiving steroid therapy is presented. METHODS: The authors prospectively followed up with 3 patients who had antenatally diagnosed CCAM and nonimmune hydrops fetalis with predicted mortality. All patients declined or were not candidates for fetal intervention and were treated with standard prenatal betamethasone to increase lung maturity. RESULTS: Three fetuses had CCAM and nonimmune hydrops fetalis diagnosed prenatally. After a course of prenatal steroids during the second trimester, all 3 patients had resolution of their hydrops and were delivered at term without respiratory distress. CONCLUSIONS: Nonimmune hydrops fetalis in fetuses with congenital cystic adenomatoid malformation is a harbinger for fetal demise. The resolution of hydrops in these patients after receiving steroid therapy is an interesting and compelling observation. Because the mechanism of this process is speculative, further studies are needed to elucidate the relationship between antenatal steroids and maturation of congenital cystic adenomatoid malformation.

Adult↗
PubMed2003

Tissue ablation using high-intensity focused ultrasound in the fetal sheep model: potential for fetal treatment.

OBJECTIVE: The aim of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) ablation of fetal tissue in a sheep model. HIFU can deliver large amounts of thermal energy by using ultrasonic waves to induce tissue necrosis, without damaging intervening tissues. In contrast to diagnostic ultrasound where intensity levels are below 0.1 W/cm(2), HIFU can deliver 1,000 to 10,000 W/cm(2) at the focal spot. STUDY DESIGN: A protocol for HIFU-induced tissue coagulation in the fetus was developed in the ovine model. The fetal liver, lung, kidney, muscle, and placenta were targets for ultrasound-guided tissue ablation by a HIFU beam. All lesions were assessed macroscopically and by histologic analysis. RESULTS: In all animals, a necrotic lesion, similar in size to the HIFU focus (approximately 1x9 mm), was achieved. The fetal heart rate remained stable immediately after the procedure. CONCLUSION: In conclusion, HIFU ablation seems to be an effective means to coagulate even highly vascularized tissues in the fetus. This procedure shows promise as a transcutaneous, minimally invasive technique to decrease blood flow through fetal tumors or vascular anastomoses. We are currently conducting further studies to refine the HIFU technique and assess safety for fetus and mother.

Animals↗
PubMed2002

Fetal operations in the head and neck area: current state.

BACKGROUND: Fetal surgery is defined as prenatal surgical intervention. Such intervention is currently considered in selected cases of fetal malformations that endanger the child's life prenatally or postnatally, such as death or severe impairment. METHODS: Current indications are reviewed, with special emphasis on success rates and complications, including concomitant ethical problems. Data sources are based on personal experience and medical information systems (especially MEDLINE). RESULTS AND CONCLUSIONS: In the head and neck areas, especially the upper respiratory tract, such procedures can be indicated in selected cases. They include exposure and temporary obstruction of the fetal trachea to reduce the viscera and to prevent pulmonary hypoplasia in congenital diaphragmatic hernia, prenatal tracheotomy in laryngeal atresia, and intranatal establishment of an airway in airway-obstructing embryonic tumors. The latter surgery can be performed after delivery of the fetal head and neck and before umbilical cord severance. This method ensures oxygenation of the fetus by the maternofetal circulation until completion of the surgical intervention (so called EXIT procedure = Ex-Utero Intrapartum Treatment). The relatively high surgical risk of fetal surgery, in particular postoperative preterm labor, may be reduced by the use of minimally invasive endoscopic techniques. By reducing operative risks even further, prenatal surgical interventions may even be used in nonlethal conditions. Consequently, more diseases of the head and neck area could thus be included in the spectrum of indications, such as prenatal correction of the cleft lip palate. Because fetal wound healing incurs no scarring up to a certain stage in pregnancy, such fetal surgical correction could be a perspective.

Cleft Lip↗
PubMed2002

Fetal therapy.

Over the past 40 years, a small but increasing number of fetal genetic and congenital anomalies has become amenable to in utero treatment. Successful fetal therapies have included open procedures for congenital diaphragmatic hernia, cystadenomatoid malformation of the lung and saccrococygeal teratoma, shunts for uropathies and thoracic fluids, pharmacological therapies for congenital adrenal hyperplasia and neural tube defect prevention, and the stem cell treatment of severe combined immunodeficiency disorder.

Adrenal Hyperplasia, Congenital↗