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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 109 records · Page 6Linked to original sources
PubMed1996

Fetal endoscopic ('Fetendo') tracheal clip.

Fetal surgery can correct several life-threatening malformations before birth. Despite recent advances in fetal surgery, preterm labor remains a major problem directly related to the large uterine incision required for fetal exposure. Fetal endoscopic surgery ("Fetendo") obviates the need for a large uterine incision and may reduce the overall risks of fetal surgery by causing less uterine trauma and ultimately less preterm labor. Temporary tracheal occlusion is a promising strategy to enlarge the lungs in fetuses with congenital diaphragmatic hernia. Using the technology developed for laparoscopic surgery and for temporary tracheal occlusion, we have developed an endoscopic technique for tracheal occlusion with an endoscopic clip in a fetal sheep model. The evolution of this technique may allow temporary tracheal occlusion without incisional hysterotomy or maternal laparotomy.

Animals↗
PubMed1996

Immediate reconstruction for penile agenesis.

The goal of treatment for penile agenesis is early female gender assignment and feminizing reconstruction of the perineum. Historically, this required multiple operations including both vesicostomy and colostomy. The present case demonstrates the feasibility of early total reconstruction through a posterior sagittal approach that avoids diversion of stool and urine.

Congenital Abnormalities↗
PubMed1996

Challenging the embryogenesis of cloacal exstrophy.

As presently understood, cloacal exstrophy results from a migration failure of the lateral mesodermal folds of the infraumbilical anterior abdominal wall, and rupture of the resulting enlarged, persistent cloacal membrane before the eighth week of gestation. The authors present ultrasonographic evidence that disputes this embryological theory. Routine ultrasonography of a twin gestation at 18 weeks showed that one twin had a dilated cloacal abnormality, bilateral hydronephrosis, and oligohydramnios. Repeat ultrasonography at 24 weeks demonstrated rupture of the cloacal anomaly, with resolution of both the hydronephrosis and oligohydramnios. This twin was born with classic cloacal exstrophy. This striking ultrasound evidence of an intact cloacal membrane at 18 weeks, which ruptured before 24 weeks, relieving the urinary tract outlet obstruction, forces us to rethink how this surgically correctable anomaly develops.

Abnormalities, Multiple↗
PubMed1996

Sonographic predictors of survival in fetal diaphragmatic hernia.

The authors studied the predictive value of detailed fetal sonographic parameters on outcome for 55 patients with prenatally diagnosed congenital diaphragmatic hernia managed at an ECMO center. Their sonographic assessment included gestational age at time of diagnosis, polyhydramnios (largest amniotic fluid pocket diameter), presence of liver and/or stomach herniation, and abdominal circumference at the level of the umbilical cord. They measured the right lung two-dimensional area at the level of the atria as an estimate of lung size and mediastinal shift. The ratio of right lung area to head circumference (LHR) was calculated to minimize lung size differences owing to gestational age. The principal outcome variable was survival. The overall survival rate was 65%. If the diagnosis was made after 25 weeks' gestation, the survival rate was 100% (12 of 12); the rate was 56% if the diagnosis was made at or before 25 weeks (P < .005). All five neonates with an LHR of less than 0.6 died; the survival rate was 100% for those whose LHR was greater than 1.35; and those with an LHR between 0.6 and 1.35 had a 61% survival rate (P < .001). The survival rate for those whose liver was not herniated was 100% (10 of 10); herniation of the liver decreased the survival rate to 56% (P < .05). Stomach position, polyhydramos, and abdominal circumference were not found to be useful survival predictors. No prenatal sonographic parameter was absolutely predictive of postnatal death except very small right lung size, which was present in only 5 of the 55 patients. Survival is highly likely if the liver is not herniated into the thorax and/or the right lung is large.

Female↗
PubMed1996

In utero repair of experimental myelomeningocele saves neurological function at birth.

In a previous series of fetal sheep experiments, the authors demonstrated that midgestational exposure of the normal spinal cord to the amniotic space leads to a myelomeningocele (MMC) at birth that closely resembles human MMC phenotypes in terms of morphology and functional deficit. The present study tested whether delayed in utero repair of such evolving experimental MMC lesions spares neurological function. In 12 sheep fetuses, a spina bifida-type lesion with exposure of the lumbar spinal cord was created at 75 days' gestation (full term, 150 days). Four weeks later, the developing MMC lesions were repaired in utero for seven fetuses (five fetuses died before this time). Of those that had repair, three were delivered near term by cesarean section, and four died in utero or were aborted. All survivors had healed skin wounds and near-normal neurological function. Despite mild paraparesis, they were able to stand, walk, and perform demanding motor tests. Sensory function of the hindlimbs was present clinically and confirmed electrophysiologically. No signs of incontinence were detected. Histologically, the exposed and then covered spinal cord showed significant deformation, but the anatomic hallmarks as well as the cytoarchitecture of the spinal cord essentially were preserved. These findings show that timely in utero repair of developing experimental MMC stops the otherwise ongoing process of spinal cord destruction and "rescues" neurological function by the time of birth. Because there is evidence that a similar secondary damage to the exposed neural tissue also occurs in human MMC, we propose that in utero repair of selected human fetuses might reduce the neurological disaster commonly encountered after birth.

Animals↗
PubMed1996

Fetal endoscopic tracheal occlusion ('Fetendo-PLUG') for congenital diaphragmatic hernia.

Despite recent advances in surgical technique, posthysterotomy preterm labor remains a major determinant of postoperative fetal morbidity and mortality after in utero repair of congenital diaphragmatic hernia (CDH). Temporary fetal tracheal occlusion, or "PLUG" (Plug the Lung Until it Grows), reverses the pulmonary hypoplasia seen in experimental models of CDH and provides an alternative treatment strategy for some fetuses with CDH. Adaptation of current, minimally invasive surgical technology to the PLUG technique allows treatment of CDH without opening the uterus. In this report the authors describe a video-fetoscopic, intrauterine technique of tracheal occlusion (called Fetendo-PLUG) that could be used in human fetuses with CDH. The technique was developed in four fetal lambs that underwent video-fetoscopic intervention at 110 days' gestation (full term, 145 days), having undergone open creation of diaphragmatic hernias at 75 days. After maternal laparotomy and uterine exposure, the fetal head was located and a 5-mm curved, balloon-cuffed trocar was introduced through a uterine puncture directly into the fetal oral cavity. A steerable "bronchoscope" (with an instrument channel) was used to endoscopically intubate the trachea through the trocar, and the trocar was advanced over the bronchoscope and its balloon inflated to provide secure tracheal access below the vocal cords. Next, a 10-mm trocar was placed directly over the fetal neck, and the amniotic space was expanded with warm saline. A 5-mm laparoscope was introduced, and under simultaneous, dual video-fetoscopic (endotracheal and endoamniotic) visualization, a 1-mm nephrostomy puncture wire was advanced along the instrument channel of the bronchoscope, through the anterior wall of the trachea and fetal neck, into the amniotic space, then through the uterine wall to the outside. Withdrawal of the bronchoscope over the wire left a 5-mm endotracheal "trocar channel" along which a compressed, gelatin-encapsulated, polymeric foam insert (outer diameter, 4.8 mm) could be delivered by suture attachment to the guide wire. Once the foam was in its final endotracheal position, dissolution of the gelatin membrane allowed expansion of the foam to produce a water impervious tracheal occlusion. This two-trocar video-fetoscopic PLUG technique was performed successfully in all four fetuses, with a sequential decrease in operating time (median, 3.5 hours). Although two fetuses aborted postoperatively, the other two were carried successfully to term and demonstrated the anticipated physiological effects of adequate tracheal occlusion at the time of delivery.

Animals↗
PubMed1996

Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion.

Most fetuses with congenital diaphragmatic hernia (CDH) diagnosed before 24 weeks' gestation die despite optimal postnatal care. In fetuses with liver herniation into the chest, prenatal repair has not been successful. In the course of exploring the pathophysiology of CDH and its repair in fetal lambs, the authors found that obstructing the normal egress of fetal lung fluid enlarges developing fetal lungs, reduces the herniated viscera, and accelerates lung growth, resulting in improved pulmonary function after birth. They developed and tested experimentally a variety of methods to temporarily occlude the fetal trachea, allow fetal lung growth, and reverse the obstruction at birth. The authors applied this strategy of temporary tracheal occlusion in eight human fetuses with CDH and liver herniation at 25 to 28 weeks' gestation. With ongoing experimental and clinical experience, the technique of tracheal occlusion evolved from an internal plug (two patients) to an external clip (six patients), and a technique was developed for unplugging the trachea at the time of birth (Ex Utero Intrapartum Tracheoplasty [EXIT]). Two fetuses had a foam plug placed inside the trachea. The first showed dramatic lung growth in utero and survived; the second (who had a smaller plug to avoid tracheomalacia) showed no demonstrable lung growth and died at birth. Two fetuses had external spring-loaded aneurysm clips placed on the trachea; one was aborted due to tocolytic failure, and the other showed no lung growth (presumed leak) and died 3 months after birth. Four fetuses had metal clips placed on the trachea. All showed dramatic lung growth in utero, with reversal of pulmonary hypoplasia documented after birth. However, all died of nonpulmonary causes. Temporary occlusion of the fetal trachea accelerates fetal lung growth and ameliorates the often fatal pulmonary hypoplasia associated with severe CDH. Although the strategy is physiologically sound and technically feasible, complications encountered during the evolution of these techniques have limited the survival rate. Further evolution of this technique is required before it can be recommended as therapy for fetal pulmonary hypoplasia.

Animals↗
PubMed1996

The fetal spinal cord does not regenerate after in utero transection in a large mammalian model.

OBJECTIVE: Regeneration and functional recovery after spinal cord transection do not occur in mammalian animals and humans postnatally. The goal of this study was to test whether in utero transection of the fetal spinal cord is succeeded by anatomic healing and functional recovery. METHODS: In five sheep fetuses, at 60 days of gestation and 75 days of gestation (term = 150 d), the spinal cord was completely transected at T10. The animals were delivered near term by cesarean section for clinical evaluation, measurement of cortical somatosensory evoked potentials, and morphological assessment. RESULTS: The newborn lambs demonstrated sensory-motor paraplegia, were incontinent of urine and stool, and exhibited a spinally generated, ambulatory pattern of the hindlimbs. No cortical somatosensory evoked potentials could be recorded in response to posterior tibial nerve stimulation, although potentials from the ulnar nerve, which enters the cord rostral to the lesion, were normal in all animals. Histologically, no neuronal connections across the transection site were identified. The cord proximal to the lesion was grossly normal, whereas distal to the transection, it appeared slightly smaller but with the cytoarchitecture preserved. CONCLUSIONS: Unlike in lower vertebrate and avian species, the fetal ovine spinal cord has no detectable spontaneous regenerative capabilities when transected during midgestation. Gap formation after transection, secondary posttraumatic cell death, and missing guiding channels for sprouting axons may be factors involved in the absence of any regenerative response.

Animals↗
PubMed1996

Percutaneous access to the uterus for fetal surgery.

In utero repair of selected life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery continues to pose significant risks to both the mother and the unborn child. Preterm labor is a major problem directly related to the large uterine incision required for fetal exposure. Using technology developed for laparoscopic surgery, we have devised instruments and techniques to perform fetal endoscopic surgery. We now report a percutaneous technique for direct endoscopic access to the uterus. Minimally invasive fetoscopic surgery may expand the indications for fetal surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. This technique was developed in 4 fetal lambs who underwent endoscopic intervention at 105-110 days gestation (term = 145 days). Under ultrasound guidance, a 20-gauge spinal needle was advanced through the maternal abdomen, uterus, and directly into the amniotic cavity. Warmed saline was infused through the needle to expand the amniotic cavity. Next, a 5-mm balloon-tipped trocar was placed percutaneously with ultrasound guidance into the amniotic cavity. A 5-mm laparoscope was introduced and under endoamniotic vision two more 5-mm trocars were percutaneously placed. In all four sheep a 5-mm trocar was placed percutaneously into the gravid uterus. The most difficult step was puncturing through the amniotic membranes, but the sharp tip of the trocar facilitated getting into the amniotic cavity. Excellent visualization of the fetus was obtained with minimal uterine trauma. We have developed a fetoscopic technique in sheep for percutaneous placement of trocars into the uterus using ultrasound guidance. This approach allowed excellent visualization of the fetus with significantly less uterine trauma than open fetal surgery and is an essential prerequisite for future fetal endoscopic interventions.

Animals↗
PubMed1996

In utero management of congenital diaphragmatic hernia.

Fetal surgery offers the possibility of prenatal treatment of congenital diaphragmatic hernia (CDH). The in utero management of CDH has evolved with continued experimental and clinical experience. Topics covered include the experimental rationale and techniques of in utero repair of CDH, methods of accurate diagnosis, criteria for patient selection, approaches to ethical concerns, operative techniques, and a review of the clinical experience.

Female↗
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

Etiology of intestinal damage in gastroschisis. III: Morphometric analysis of the smooth muscle and submucosa.

The response of intestinal smooth muscle to injury may explain some of the motility derangement observed in infants with gastroschisis. An experimental model of gastroschisis was created and a detailed analysis of the intestinal muscle layer was undertaken to study this response. An abdominal wall defect and evisceration of the bowel were carried out in fetal lambs at 80 days' gestation (full term, 145 days), with delivery at 100 days or 135 days. Smooth muscle cell size and number were determined by detailed morphometric analysis, proliferative rate was determined using proliferating cell nuclear antigen staining, and collagen content was determined by morphometry after Verhoeff van Gieson staining. Compared with controls, there was a significant increase in cell number (hyperplasia) in the gastroschisis animals at 100 days and an increase in size (hypertrophy) at 135 days. The proliferation rate of smooth muscle was significantly lower and the submucosal collagen thickness was significantly greater in the gastroschisis animals during both periods. These data suggest that gastroschisis is characterised by initial hyperplasia, with subsequent diminution in smooth muscle proliferation. The hypertrophy may reflect a response to injury in which cell growth instead of proliferation occurs. The persistent elevation in collagen throughout gestation in animals with gastroschisis may be a reflection of this hyperplastic response in the smooth muscle cells and an important factor in the bowel-wall thickening. This deranged pattern of growth may lead to the clinical problems observed in human infants with this disease.

Abdominal Muscles↗
PubMed1995

Scar formation in the fetal alimentary tract.

The aim of this study was to determine whether the fetal alimentary tract shares the unique scarless healing properties of fetal skin. Full-thickness incisional gastric wounds were created and sutured closed in fetal lambs at 60, 75, and 120 days' gestation (full term, 145 days), and in adult control sheep. At the time of harvest, 14 days postwounding, dense fibrous adhesions were found intraperitoneally in all fetal and adult animals. Histologically, all fetal and adult gastric wounds healed with pronounced scar formation. In contrast to the adult wound, there was no significant inflammatory response in the fetal wounds. Because scar formed in the absence of inflammation in fetal gastric wounds, there is no obvious relation between scarring and the inflammatory response at this location. This study shows that not all fetal tissues exhibit scarless repair properties.

Animals↗
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↗