Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 163 records · Page 9Linked to original sources

PubMed1993

Disappearing fetal lung lesions.

Cystic adenomatoid malformations and sequestrations of the lung are uncommon but potentially devastating problems of the fetus and neonate. We have followed over 50 cases of fetal lung masses from the time of prenatal diagnosis. Serial prenatal ultrasonography demonstrated that 9 large pulmonary lesions dramatically decreased in size or disappeared completely. We conclude that the natural history of prenatally diagnosed fetal lung masses is highly variable. A huge mass associated with fetal hydrops has a dismal outcome. If hydrops is not present, then the initial impression concerning prognosis may not accurately predict outcome, because there may be marked improvement during fetal life.

Adult↗

PubMed1993

Correction of congenital diaphragmatic hernia in utero: VI. Hard-earned lessons.

Extensive experimental work suggests that repair of congenital diaphragmatic hernia (CDH) in utero may salvage severely affected fetuses who otherwise have a high expected mortality despite optimal postnatal care including extracorporeal membrane oxygenation (ECMO). We have reported that repair of CDH in utero is physiologically sound and safe for the mother, but technically difficult especially when the liver is herniated into the fetal chest. In the 3 years since our last report (1989 to 1991), 61 additional patients were referred for consideration of in utero repair. Fetal repair was attempted in 14 with severe isolated left CDH diagnosed before 24 weeks gestation. Five fetuses died intraoperatively, from technical problems related to reduction of incarcerated liver and uterine contractions--problems which have subsequently been surmounted. Nine patients were successfully repaired. Four babies survived, two delivered prematurely and died, and three died in utero within 48 hours of repair. Intraoperative technical problems have been overcome; the factors limiting successful outcome are postoperative physiologic management of the maternal-fetal unit and effective tocolysis to control preterm labor.

Fetal Death↗

PubMed1993

Fetal cleft lip repair in lambs: histologic characteristics of the healing wound.

Sequential surgical procedures in cleft lip/palate (CL/P) patients result in scar formation that is believed to be associated with midface growth retardation. By use of a previously developed fetal lamb model, wound healing characteristics were investigated after in utero CL repair. It is hypothesized that scarless healing after fetal CL repair occurs without inflammation and scar formation. CL wounds were created in mid-second-trimester fetal lambs and either repaired in three layers (mucosa, muscle, and skin) or left unrepaired. Fetuses were then harvested at 7, 14, and 21 days postoperatively, and the wound site was examined microscopically. When created at 75 days' gestation (term = 145 days), fetal lamb CL wounds heal rapidly without inflammation and scar formation. By day 21 postoperatively, there was complete regeneration of skin, muscle, and mucosa, as well as epidermal appendages. With this model, it will be possible to compare the effects of scarless fetal CL repair with those of postnatal repair on midface growth.

Animals↗

PubMed1993

Detection of a male-specific sequence in nonhuman primates through use of the polymerase chain reaction.

Sex-specific DNA sequences are useful for detecting and monitoring chimerism in transplant recipients that had received sex-mismatched donor cells. Nonhuman primates are often used as experimental transplant models because of their evolutionary proximity, and the similarity of their physical characteristics, to those of humans. Unfortunately, DNA-based molecular detection strategies to monitor engraftment in sex-mismatched transplants in monkeys and baboons have not been available. We describe development of a polymerase chain reaction-based assay to detect a 174-bp male-specific sequence present in the rhesus monkey (Macaca mulatta) and olive baboon (Papio cynocephalus). The assay is sufficiently sensitive to allow detection of 10 male cells against a background of 10(4) female cells. Human sequence is not amplified under the described assay conditions. The amplified DNA sequence is 82% homologous to a sequence located near the testis-determining factor locus in the human genome, suggesting a high degree of evolutionary conservation in this region.

Animals↗

PubMed1993

Congenital diaphragmatic hernia: an unsolved problem.

Despite significant improvements in postnatal care of infants with congenital diaphragmatic hernia (CDH), mortality remains high. Delayed surgery, improved respiratory support, and extracorporeal membrane oxygenation (ECMO) have undoubtedly improved outcome for babies diagnosed after birth, but a prospective study of 52 fetuses with isolated, potentially correctable CDH diagnosed prior to 25 weeks gestation showed that 60% died despite optimal care presently available after birth. Repair of CDH before birth, although physiologically compelling, has proven exceedingly difficult especially when the fetal liver is incarcerated in the chest. Our recent experience suggests that intraoperative technical problems are surmountable, but a trial will be necessary to determine if prenatal repair can improve outcome for babies with diaphragmatic hernia.

Combined Modality Therapy↗

PubMed1993

Fetal obstructive uropathy.

Congenital obstructive uropathy is a relatively common developmental malformation, and severely affected fetuses die soon after birth from oligohydramnios-induced pulmonary hypoplasia or renal failure. Prenatal ultrasonography can reliably diagnose the specific anatomic defect, and using fetal urine sampling we can determine the extent of renal damage in utero with reasonable certainty. With these diagnostic tools and an understanding of the natural history of congenital obstructive uropathy we can now make rational decisions regarding treatment. Clinical experience has demonstrated that the selected fetus may benefit from in utero decompression, either by percutaneous shunt placement or open fetal surgery. However, each of these procedures has certain risks that must be carefully weighed against the expected benefits. Future techniques using fetoscopic surgery may provide the ideal therapeutic approach.

Animals↗

PubMed1993

Fetal surgical techniques.

Our experimental and clinical experience with open fetal surgery has provided invaluable lessons regarding optimal maternal-fetal anesthesia, hysterotomy, fetal exposure techniques, fetal monitoring, reliable steps for in utero repair of life-threatening defects, and secure methods for uterine closure. Most importantly, open fetal surgery has been performed in both nonhuman primates and in the initial series of clinical cases with acceptable maternal safety and without detectable adverse effects on later reproduction.

Congenital Abnormalities↗

PubMed1993

The Fetal Treatment Center.

Unanimity of opinion about clinical decisions will always be difficult among a variety of specialists with disparate backgrounds. The Fetal Treatment Center is a regionalized approach that utilizes the necessary specialists and facilities to provide the most accurate diagnosis and maternal-fetal patient care management recommendations to referring physicians. This model offers a systematic approach for the mother carrying a fetus with an anatomic anomaly.

Congenital Abnormalities↗

PubMed1993

The developmental pathophysiology of surgical disease.

This article reviews the pathophysiology of congenital defects and tumors that are of interest to the pediatric surgeon. Reliable information has been obtained through prenatal diagnosis of fetal anomalies and careful studies of fetal animal models. The topics covered include fetal diaphragmatic hernia, oligohydramnios-induced pulmonary hypoplasia, renal dysplasia, prune belly, gastrointestinal obstruction, biliary atresia, Wilms' tumor, and neuroblastoma. In addition, some recent experimental studies delineating the ability of the fetus to heal without scarring may have implications for all surgeons.

Adrenal Gland Neoplasms↗

PubMed1993

Fetal surgery.

While most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after birth, a few may require or benefit from correction before birth. Extensive experimental work in animals and innovative technologic developments have made fetal surgery a viable approach to perinatal care. Managing preterm labor continues to be a vexing problem. At present, only a few life-threatening malformations have been successfully corrected. Additional research into the abnormal function of some malformations, the development of less interventional techniques, and fetal stem cell transplantation should lead to successful treatment of more fetal disorders.

Female↗

PubMed1993

Open human fetal surgery.

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Cystic Adenomatoid Malformation of Lung, Congenita↗

PubMed1993

Radiotelemetric fetal monitoring during and after open fetal operation.

Diagnosis and treatment of fetal disease processes has advanced dramatically, but the ability to monitor the fetus in utero remains rudimentary. Open fetal operation provides a unique opportunity to correct life-threatening fetal abnormalities, but it also places the fetus at risk. Continuous intraoperative and post-operative fetal electrocardiographic monitoring may decrease the risk by optimizing fetal and maternal perioperative management. We tested an implantable radiotelemetry device that allowed continuous intraoperative and postoperative fetal electrocardiographic and temperature monitoring. The radiotelemetry device was placed subcutaneously in four fetal sheep at 100 to 112 days' gestation (term equals 145 days). During and after the fetal operation, the monitor reliably and continuously transmitted the analog fetal electrocardiogram and temperature. We then tested a similar device during human fetal operations on both an acute and a chronic basis. The radiotelemetry device permits continuous and reliable fetal monitoring during and after fetal operation and we now consider it essential to the operation. Its use should facilitate optimal fetal and maternal management and improve survival of the fetus.

Animals↗

PubMed1992

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

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

Adult↗

PubMed1992

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

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

Animals↗

PubMed1992

Adult-to-neonate lung transplantation: anatomic considerations.

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

Adult↗

PubMed1992

New techniques in fetal surgery.

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

Animals↗

PubMed1992

Tracheostomy in children with emphasis on home care.

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

Child, Preschool↗

PubMed1992

Necrotizing fasciitis in two children with acute lymphoblastic leukemia.

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

Agranulocytosis↗