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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 55 records · Page 3Linked to original sources
PubMed1999

Perineal one-stage pull-through for Hirschsprung's disease.

PURPOSE: The aim of this study was to present the strategy of a one-stage repair of Hirschsprung's Disease (HD) performed via a transanal approach. METHODS: Ten consecutive neonates and one toddler underwent transanal repair for biopsy-proven HD. A rectosigmoid transition zone was suggested by contrast enema in all patients. The mean age at operation for the neonates was 4 days. A mucosal dissection was begun 0.5 cm proximal to the dentate line. Once the correct plane was established, up to 15 cm of bowel can be resected without ligating vessels or performing a transabdominal dissection. The proximal extent of dissection was delineated by the presence of ganglion cells seen on frozen section analysis. RESULTS: The mean operating time was 105 minutes. There were no intraoperative or postoperative complications. All children had the presence of ganglion cells confirmed postoperatively on permanent sections. The mean hospital stay was 2 days. All children averaged three to six bowel movements per day without oral or enema therapy. CONCLUSIONS: The perineal one-stage operative pull-through (POOP) procedure for Hirschsprung's disease is a quick and easy adaptation of a well-described technique of transanal mucosectomy. Long-term follow-up will be required to determine whether bowel function is better that that seen after traditional staged repairs.

Child, Preschool↗
PubMed1999

Fetal pulmonary sequestration: a favorable congenital lung lesion.

OBJECTIVE: We reviewed the perinatal clinical course of prenatally diagnosed pulmonary sequestrations to determine the natural history of this anomaly. METHODS: From January 1992 to August 1998, 192 women were referred to the University of California, San Francisco, Fetal Treatment Center because obstetric ultrasound had demonstrated fetal lung lesions. In 14 fetuses, the echogenic lung masses were pulmonary sequestrations deriving arterial blood supply from clearly identifiable systemic arteries rather than the pulmonary artery. We examined records of the 14 fetuses and documented the location of the lesion, gestational age at diagnosis, need for fetal intervention, prenatal and postnatal complications, gestational age at delivery, and survival. RESULTS: There were 16 intrathoracic pulmonary sequestrations in 14 fetuses (eight left-sided, four right-sided, two bilateral). Three fetuses had histologically mixed lesions (congenital cystic adenomatoid malformation and pulmonary sequestration). The mean age at diagnosis was 23 weeks' gestation (range 19-31 weeks). Two fetuses required prenatal intervention (placement of a thoracoamniotic shunt for drainage of an ipsilateral tension hydrothorax). The mean gestational age at delivery was 37 weeks (range 32-40 weeks). The large lesions of four fetuses regressed completely prior to birth, and the lesions of the remaining ten fetuses were electively resected after birth without causing morbidity or mortality. CONCLUSION: Pulmonary sequestrations are a subgroup of congenital lung lesions with a favorable outlook; many regress prenatally, and the persistent ones are resected safely postnatally. Pulmonary sequestrations cause hydrops only because of a tension hydrothorax, which can be drained prenatally, if necessary.

Algorithms↗
PubMed1999

Role of CD95/Fas and its ligand in the regulation of the growth of human CD34(++)CD38(-) fetal liver cells.

The functional significance of CD95/Fas expressed by candidate hematopoietic stem cells (HSCs) from human fetal liver was studied by testing the effect of agonistic anti-CD95 monoclonal antibody (mAb) CH-11 and soluble CD95 ligand (sCD95L) on the growth of CD34(++)CD38(-)lineage cells in vitro. Candidate fetal HSCs exhibited a dose-dependent proliferative response to CH-11 as well as to sCD95L when combined with kit ligand (KL) + interleukin 3 (IL-3) under serum-deprived culture conditions. CH-11 mAb increased, in a synergistic fashion, the number of myeloid colony-forming unit culture (CFU-C) generated by candidate HSCs in liquid cultures with the cytokine combinations KL + IL-3, KL + granulocytemacrophage colony-stimulating factor, and KL + IL-6. CH-11 mAb and sCD95L also enhanced erythropoiesis supported by KL + IL-3 + erythropoietin (Epo). Furthermore, sCD95L was able to increase the number of megakaryocytes, granulocytes, and CD34- cells generated in the presence of KL + IL-3 + Epo + thrombopoietin. An analysis performed using Western blotting revealed that the membrane-bound CD95L (mCD95L) was expressed by both immature (total CD34+/++) and mature (CD34-) hematopoietic lin(-) FL cells. Among the CD34(++)lin(-)cells, both the freshly isolated CD38+ and CD38 subsets as well as CD95+ and CD95- cells constitutively expressed mCD95L, demonstrating that the CD95/CD95L system represents a paracrine and potentially autocrine regulator of early hematopoiesis. To study the role of the endogenously produced CD95L, we determined the effects of a neutralizing anti-CD95L NOK-1 on the growth of candidate HSCs. By blocking the endogenous CD95L with NOK-1 mAb, we observed an increase in CFU-C generated by candidate HSCs. We conclude that the endogenous CD95L has an inhibitory effect on fetal candidate HSCs, which can be blocked by sCD95L and CH-11 mAb.

ADP-ribosyl Cyclase↗
PubMed1999

Prenatal cellular transplantation.

Based on the ontogeny of fetal immunologic development, the strategy of fetal cellular transplantation may prove to be the most physiological way to achieve replacement of abnormal hemoglobin, immune cells, or enzyme defects diagnosed early prenatally. Similarly, if cellular transplantation can induce tolerance, postnatal solid organ transplantation may be performed without the need for chronic immunosuppression or with a reduced risk of graft-versus-host disease. This review presents experimental data from the late 1940s until the present for both small and large animal models; it also describes the limited clinical experience with prenatal cellular transplantation.

Animals↗
PubMed1999

Natural history of fetuses with cleft lip.

The prospect of fetal surgery for cleft lip is predicated on our ability to accurately identify fetuses with clefts and exclude those that have associated anomalies. Prenatal ultrasound is currently the most appropriate means with which to do this. We reviewed the ultrasonographic data from two large perinatal referral institutions to determine the natural history of fetuses with cleft lip who may be candidates for fetal surgery. Forty fetuses had a cleft lip diagnosed prenatally by ultrasound. In this group, severe associated anomalies were common (30 of the 40) and multiple (23 of the 40) in a majority of fetuses. Life-threatening anomalies, such as central nervous system and cardiac anomalies, were the most common defects. As a result, many fetuses were aborted therapeutically or died in the perinatal period. Out of 12 surviving fetuses, only six had isolated clefts, and two surviving fetuses, diagnosed with isolated cleft lip, had no defect identified postnatally. This information has important implications for the perinatal management of fetuses with cleft lip and the potential role of fetal intervention.

Abnormalities, Multiple↗
PubMed1999

A long-term, controlled-outcome analysis of in utero versus neonatal cleft lip repair using an ovine model.

Successful open repair of a cleft lip in utero has the advantage of scarless wound healing in the fetus. Unfortunately, no long-term outcome studies have been performed to evaluate the efficacy of these repairs. Moreover, no study to date has compared the long-term results of an in utero cleft lip repair to a similar, control-matched, newborn cleft repair. This study was performed to evaluate the 9-month outcome of in utero cleft lip surgery compared with an identical cleft lip repair performed on infant lambs. In utero epithelialized cleft lips were created through an open hysterotomy in sixteen 65-day-old fetal lambs (term = 140 days) using methods described by Longaker et al. Eight of 16 animals underwent subsequent in utero repair of these clefts at 90 days gestational age. The repair of the remaining eight animals was delayed until 1 week postpartum. At 9 months, the animals were analyzed for changes in lip contour and for the degree of scarring by hematoxylin and eosin and Masson's trichrome collagen staining. Two animals in each group died from preterm labor. Of the animals that survived to term, all repaired lips had some degree of abnormality postoperatively. One of six lips repaired in utero dehisced before delivery. Three of six neonatal repairs dehisced in the first postoperative month. In the remaining animals with intact lip repairs, the vertical lip height on the repaired side was an average of 9 to 12 mm shorter than the normal lip in both the in utero and neonatally repaired animals. Phenotypically, the postnatally repaired animals had more lip distortion and visible notching. Histologically, the in utero repair was scarless and the neonatal repairs had scar throughout the entire vertical height of the lip with an associated loss of hair in this region. Maxillary growth was also evaluated. There was no inhibition of maxillary growth in the animals that underwent in utero cleft lip repair. However, in the neonatal repair group, significant maxillary retrusion was evident. Compared with the cleft side of the maxilla, horizontal growth was decreased by 11 percent (p = 0.01). Compared with the intrauterine repair group, there was a 17-percent decrease in horizontal maxillary width (p = 0.01). Straight-line in utero repair of a cleft lip produces a better long-term result in terms of maxillary growth than a similar repair performed postnatally in the ovine model. There was no diminution in maxillary growth in the animals treated in utero. Histologically, in utero repair of clefts was indeed scarless. However, both lip repairs produced lips that were significantly shorter than their contralateral noncleft sides. This degree of lip shortening would require a secondary lip revision, thereby defeating the purpose of performing an intrauterine repair. Comparisons now need to be made between in utero and neonatal repairs using a Millard-type rotation advancement technique before intrauterine treatment can be considered to be more beneficial than our current treatment modalities.

Animals↗
PubMed1999

Complex fetal disorders: effect of MR imaging on management--preliminary clinical experience.

PURPOSE: To determine the effect of magnetic resonance (MR) imaging findings on management of complex fetal disorders. MATERIALS AND METHODS: MR imaging of the fetus was performed in 25 consecutive pregnant patients referred because of possible complex fetal disorders suspected on the basis of ultrasonographic (US) findings. Spoiled gradient-echo and single-shot rapid acquisition with relaxation enhancement MR imaging were performed in multiple planes anatomic to the fetus during maternal breath holding. RESULTS: In the fetuses in 24 of 25 women, MR studies were technically satisfactory. MR imaging directly influenced fetal care in four (17%) of 24 cases by demonstrating congenital high airway obstruction syndrome, congenital hemochromatosis, unilateral cerebellar deficiency in association with congenital diaphragmatic hernia, and severe facial disfigurement due to a giant anterior neck mass. In eight (33%) cases, MR imaging provided supplementary findings, but did not affect fetal care. In 12 (50%) cases, MR imaging results confirmed US findings. CONCLUSION: In cases of complex fetal disorders, MR imaging results can be used to supplement or confirm US findings and may directly affect management.

Abnormalities, Multiple↗
PubMed1998

Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: a retrospective study of 60 patients and literature review.

Congenital diaphragmatic defects (CDDs) may occur in malformation syndromes of varied causes. Syndromic cases of CDDs due to chromosomal defects, autosomal recessive, autosomal dominant, or X-linked inheritance have been described. In order to determine the frequency and nature of syndromes, malformations, and chromosome abnormalities associated with CDDs, we reviewed the records of all patients with CDDs evaluated over a 4-year period. During the 4-year interval, a total of 60 patients was evaluated. Of these, 29 had a therapeutic or spontaneous abortion, and 31 received postnatal care. On prenatal ultrasonography, 20 of 60 (33%) of patients with CDDs had additional anomalies. Additional anomalies, besides CDDs, were present in 15 of 31 (48%) of liveborn patients on newborn evaluation. In total, 16 patients with multiple anomalies were evaluated. Of these, 12 of 16 (75%) had additional abnormalities detected by prenatal ultrasonography. The 4 of 16 (25%) without additional anomalies on prenatal sonography had multiple anomalies found neonatally, lethal multiple pterygium syndrome being diagnosed in one case. Prenatal chromosome analysis was performed in 7 of 16 patients, and all had postnatal karyotypes. All initial karyotypes were normal. Tetrasomy 12p was documented on postnatal fibroblast analysis in one case who had percutaneous umbilical blood sampling (PUBS). Syndromes diagnosed postnatally in 7 of 16 patients (44%) include: Fryns syndrome (2), Simpson-Golabi-Behmel syndrome (2), tetrasomy 12p (1), Brachmann-de Lange syndrome (1), and lethal multiple pterygium syndrome (1). We were unable to make a specific diagnosis in 9 of 16 patients (56%) with multiple malformations. In patients with CDDs, a normal prenatal karyotype, especially if obtained by PUBS, and absence of other detected abnormalities by fetal ultrasonography, do not exclude the presence of other major anomalies, including chromosome abnormalities and severe multiple malformation syndromes.

Chromosome Aberrations↗
PubMed1998

Surgical treatment for fetal disease. The state of the art.

Sophisticated imaging and fetal sampling techniques have defined the natural history and pathophysiologic characteristics of many previously mysterious conditions of newborn. Although most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after delivery, an increasing number of simple anatomic abnormalities with predictably devastating developmental consequences have been successfully corrected before birth. Many of the technical intricacies of open fetal surgery have been solved, but preterm labor remains an omnipresent risk to the mother and fetus. The recent development of minimally invasive techniques to treat the fetus prenatally has significantly lessened preterm labor. Minimally invasive surgical techniques, in combination with new tocolytic strategies, promise to extend the indications for fetal surgical intervention.

Congenital Abnormalities↗
PubMed1998

Fetal liver position and perinatal outcome for congenital diaphragmatic hernia.

Despite advances in postnatal care, patients born with a congenital diaphragmatic hernia (CDH) suffer substantial morbidity and mortality. The present study was undertaken to determine the prognostic influence of prenatally-diagnosed liver herniation in the hemithorax in fetuses with CDH. The medical records of 48 patients evaluated for a prenatally-diagnosed left CDH were retrospectively reviewed. Patients were analysed according to the position of the liver by prenatal ultrasound; 32 fetuses had a major portion of the liver herniated into the left hemithorax ('liver up') and 16 had an intra-abdominal liver ('liver down'). Liver position was determined using colour-flow Doppler ultrasonography. There were two fetal deaths in the liver-up group and one in the liver-down group. The liver-up group more frequently required extracorporeal membrane oxygenation (ECMO) support (53 per cent) compared with the liver-down group (19 per cent). Postnatal survival was significantly less in the liver-up group (43 per cent) vs. the liver-down group (93 per cent). Fetuses with congenital diaphragmatic hernia and liver herniated into the hemithorax have a much worse prognosis than similarly afflicted fetuses without liver herniation. Prenatal ultrasonographic diagnosis of congenital diaphragmatic hernia allows for preparation for a critically ill newborn and aids in prenatal family counselling.

Adolescent↗
PubMed1998

Fetal lung lesions: management and outcome.

OBJECTIVE: Our purpose was to review our experience with fetal congenital cystic adenomatoid malformation and extralobar pulmonary sequestration emphasizing natural history, management, and outcome. STUDY DESIGN: We conducted a retrospective review of 175 fetal lung lesions diagnosed by antenatal ultrasonography at 2 fetal treatment centers. RESULTS: There were 134 congenital cystic adenomatoid malformation cases. Fourteen women underwent elective abortion, 101 women were managed expectantly, 13 women had fetal surgery, and 6 women had placement of a thoracoamniotic shunt. For the congenital cystic adenomatoid malformation lesions that were not associated with nonimmune hydrops, all babies survived. Of 25 large congenital cystic adenomatoid malformations that had associated hydrops that were followed expectantly, all fetuses died before or shortly after birth. Fetal surgical resection of the tumor (fetal lobectomy) was performed at 21 to 29 weeks' gestation in 13 hydropic fetuses with 8 fetuses continuing gestation with subsequent hydrops resolution, impressive in utero lung growth, and neonatal survival. Six fetuses with a very large solitary cyst underwent thoracoamniotic shunting and 5 survived. There were 41 extralobar pulmonary sequestration cases. Twenty-eight extralobar pulmonary sequestrations dramatically regressed on serial prenatal sonography, were asymptomatic after birth, and were only detectable by imaging studies postnatally (no resection required). Of the remaining 13 extralobar pulmonary sequestration cases, 2 underwent elective abortion, 7 symptomatic lesions were resected after birth with survival, 1 hydropic fetus died, and 3 fetuses had an associated tension hydrothorax with secondary hydrops that was successfully treated by either fetal thoracenteses or thoracoamniotic shunting followed by postnatal resection. CONCLUSIONS: The natural history of prenatally diagnosed lung masses is variable, and associated anomalies are rare. Most congenital cystic adenomatoid malformation lesions can be managed with maternal transport, planned term delivery, and postnatal resection. Many extralobar pulmonary sequestrations dramatically decrease in size before birth and may not need treatment after birth. Fetal therapy is now an option for lung lesions associated with nonimmune hydrops.

Amnion↗
PubMed1998

Neurodevelopmental outcome after open fetal surgery.

PURPOSE: This study examined the neurological and age-appropriate developmental outcomes of 11 children who underwent open fetal surgery. RESULTS: Nine children have normal neurological outcomes, and nine have normal development. CONCLUSION: Intensive postnatal care, intracranial hemorrhage, and requirement for prolonged respiratory support were associated with a worse neurological and developmental prognosis.

Central Nervous System Diseases↗
PubMed1998

Pancreas divisum and stenosis of the major and minor papillae in an 8-year-old girl: treatment by dual sphincteroplasty.

Pancreas divisum is the most common congenital anomaly of the pancreas. Its relationship to the development of pancreatitis is controversial. The authors report on an 8-year-old girl who presented with recurrent bouts of acute pancreatitis and multiple failed attempts at endoscopic retrograde cholangiopancreatography (ERCP) who was referred for surgical exploration. She was found to have marked stenoses of both major and minor papillae and an intraoperative pancreaticogram consistent with pancreas divisum. She underwent sphincteroplasty of both major and minor papillae and remains symptom-free after 22 months. It is believed that in a patient with pancreatitis and pancreas divisum, or in a patient with pancreatitis and multiple failed attempts at ERCP, transduodenal exploration and intraoperative pancreaticogram are appropriate next steps in management. If pancreas divisum in association with minor papilla stenosis is found, sphincteroplasty is appropriate therapy. If major papilla stenosis is also present, we recommend sphincteroplasty of both the major and minor papillae.

Child↗
PubMed1998

A surprising histological evolution of preterm sacrococcygeal teratoma.

In fetuses with sacrococcygeal teratomas (SCT), the development of hydrops is a harbinger of imminent fetal demise. In such instances, tumor debulking, either at fetal surgery or postnatally after urgent cesarean section, may prove lifesaving. Definitive SCT resection is carried out in the newborn period when the infant has stabilized. In five such patients, retrospective comparison of the SCT histological findings from the initial debulking procedure and later definitive resection or, in one case, autopsy results, showed a surprising change. After the initial debulking procedure, SCT histology findings from three patients were grade 3 immature teratoma without malignant elements, and in two patients grade 3 immature teratoma with nests of malignant yolk sac elements. In the three patients having grade 3 immature tumor without malignant elements, histological examination after definitive resection (two cases) and autopsy (one case) showed only fibrosis; there was no evidence of the SCT despite the fact that residual tumor had clearly been left at the initial debulking. In the patients in whom the initial histology finding was grade 3 immature with malignant elements, SCT histology results from the definitive resection showed grade 3 immature teratoma without malignancy in one case, and mature, benign tissue in the other. Preterm SCT debulking may induce tumor maturation or, alternatively, maturation of SCT that occurs naturally during gestation may be observed.

Female↗
PubMed1998

The biology and ethics of banking fetal liver hematopoietic stem cells for in utero transplantation.

BACKGROUND/PURPOSE: Transplantation of fetal liver hematopoietic stem cells (HSCs) in utero has the potential to treat a variety of hematologic, immunologic, and metabolic diseases. One prerequisite for broad clinical application is the establishment of a bank of fetal liver HSC tissue. The authors describe their methods for processing fetal liver free of known human pathogens while maximizing HSC activity after cryopreservation. METHODS: The authors developed a protocol that separates the abortion decision from the donation decision and preserves confidentiality between donor and recipient. Human fetal livers (12 to 14 weeks' gestation) were procured from aborted specimens and the light-density hematopoietic cells isolated by density centrifugation. Total viable cell count increased with gestational age and averaged from 4.36 x 10(7) cells for 12-week livers to 2.0 x 10(8) cells for 14-week livers. RESULTS: Flow cytometric analysis demonstrated the presence of early progenitors in fresh and thawed specimens and a low number of T cells in each group. The functional capacity of fetal liver progenitors was assessed with colony-forming assays before and after cryopreservation. Thawed specimens showed an average 63% recovery rate for the high-proliferative potential colony-forming cells, a primitive subset of progenitors thought to include HSC. However, the more mature fraction of low-proliferative potential colony-forming cells had a recovery rate of only 35%. These data suggest that fetal liver HSC maybe more resistant to the detrimental effects of cryopreservation than mature progenitors. The fetal liver was screened for bacterial, fungal, and viral contaminates and the serum from donor mothers was screened for human immunodeficiency virus (HIV), hepatitis A, B, and C, human T-cell lymphoma virus (HTLV I/II), rapid plasma reagent (RPR), cytomegalovirus (CMV), and toxoplasmosis IgM. The bacterial contamination rate was 14% (n = 28). The maternal serum was positive for CMV in 78% of cases, and positive for hepatitis C in 0.7% of cases (n = 28). However, all fetal liver specimens were culture negative for CMV. CONCLUSIONS: These findings demonstrate that human fetal liver HSCs can be procured ethically and processed to ensure a safe graft with a small number of T-cells, and a high yield of progenitors after cryopreservation. A bank of fetal liver HSC will prove useful in treating a variety of genetic diseases before birth by in utero HSC transplantation.

Cryopreservation↗
PubMed1998

Anterior cervical approach for repair of laryngotracheoesophageal cleft.

Laryngotracheoesophageal cleft is a very rare congenital malformation characterized by a long midline communication between the esophagus and trachea extending from the larynx down the trachea for a variable distance. The most common repair strategy involves separation of the trachea and esophagus by a lateral approach via both a thoracotomy and a neck incision. The authors report a case of complete repair (without thoracotomy) via a neck incision through the anterior wall of the trachea.

Abnormalities, Multiple↗