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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

411 records · Page 23Linked to original sources

Reliability of blood pressure, heart rate, and Doppler-derived hemodynamic measurements during exercise.

Doppler echocardiography of aortic blood flow, heart rate, and blood pressure represent noninvasive methods for evaluation of the hemodynamic effects of pharmacologic agents or other stimuli during rest and exercise. In this study the reliability of continuous-wave Doppler echocardiography for detecting the effects of various interventions on left ventricular systolic function during exercise was assessed. The reliability of Doppler measurements was compared with that found for measurements of simultaneously obtained heart rate and blood pressure. Exercise treadmill testing was performed at 0, 2, 4, 6, and 8 hours in 18 healthy male subjects. All measurements were performed at rest and during the last half of each exercise stage. Reliability of peak modal velocity, peak aortic blood flow acceleration, heart rate, and blood pressure was measured by the intraclass correlation coefficient (ICC) at each stage. ICC reliability of greater than 0.75 is considered excellent, 0.4 to 0.75 fair to good, and less than 0.4 poor. The reliability of all Doppler-derived parameters, heart rate, and blood pressure improved with increasing stage of exercise. Peak modal velocity, peak acceleration, heart rate, and manually obtained systolic blood pressure had ICCs of 0.75 or greater by stage 3. The reliability of Doppler-derived aortic blood flow parameters was good or excellent at rest and advanced stages of exercise. Continuous-wave Doppler echocardiography is a reliable method for performing studies to assess the effects of interventions on cardiovascular function during exercise.

Adult↗

Ultrasound beam orientation during standard two-dimensional imaging: assessment by three-dimensional echocardiography.

Standard two-dimensional echocardiographic image planes are defined by anatomic landmarks and assumptions regarding their orientation when these landmarks are visualized. However, variations of anatomy and technique may invalidate these assumptions and thus limit reproducibility and accuracy of cardiac dimensions recorded from these views. To overcome this problem, we have developed a three-dimensional echocardiograph consisting of a real-time scanner, three-dimensional spatial locater, and personal computer. This system displays the line of intersection of a real-time image and an orthogonal reference image and may be used to assess actual image orientation during standardized two-dimensional imaging when the line-of-intersection display is not observed by the operator. Three hundred forty standard images were assessed from 85 examinations by 11 echocardiographers. Twenty-four percent of the unguided standard images were optimally positioned within +/- 5 mm and +/- 15 degrees of the standard. Of the optimal images, two thirds were parasternal long-axis views. A subsequent study with three-dimensional echocardiography and line-of-intersection guidance of image positioning showed 80% of the guided images to be optimally positioned, a threefold improvement (p < 0.001). Two-dimensional echocardiography does not achieve reasonably consistent optimal positioning of standard imaging views, suggesting that measurements taken from these views are likely to be suboptimal. Three-dimensional echocardiography that uses line-of-intersection guidance improves image positioning threefold and should therefore improve the accuracy and reproducibility of quantitative echocardiographic measurements derived from these images.

Adolescent↗

Wound healing in the fetus. Possible role for inflammatory macrophages and transforming growth factor-beta isoforms.

Macrophages are believed to play a crucial role in wound healing by synthesizing and secreting numerous cytokines. Some of these cytokines, such as transforming growth factor-beta and tumor necrosis factor-alpha, promote fibrosis and repair. We have shown that macrophages are recruited to sterile fetal wounds and have the potential to regulate repair by synthesizing transforming growth factor-beta(1), transforming growth factor-beta(2), and tumor necrosis factor-alpha. Transforming growth factor-beta was present in fetal lamb wounds in higher amounts than in adult sheep wounds. Furthermore, the concentrations and ratios of the transforming growth factor-beta isoforms in wounds that healed without scarring were different from those in wounds that scarred; transforming growth factor-beta(2) was highest in fetal wounds that did not scar and lowest in adult wounds. These data suggest that concentrations of transforming growth factor-beta isoforms rather than total transforming growth factor-beta concentration may be important in the regulation of fibrosis in prenatal and postnatal wound healing.

Journal Article↗

[Fetal surgery for severe congenital abnormalities].

BACKGROUND: Over the past two decades the diagnosis of life threatening congenital malformations has evolved rapidly. Sophisticated and powerful new imaging and sampling techniques have stripped the veil of mystery from the once secretive fetus. Early detection and close follow-up of the fetus with congenital malformations have allowed us to define their natural history, determine the clinical features that affect clinical outcome, and plan management approaches to improve prognosis. Fetal surgical intervention is the logical culmination of the progress in fetal diagnosis. The purpose of this article is to describe the current techniques and recent advances in prenatal diagnosis and fetal intervention of severe congenital malformation. MATERIAL AND METHODS: A complete review of the literature and our own experience concerning fetal surgery was performed. RESULTS: Although most prenatally diagnosed malformations are best managed by appropriate medical and surgical therapy after maternal transport and planned delivery at a tertiary care center, an expanding number of simple anatomical abnormalities with predictable, lethal consequences have been successfully corrected before birth. A malformation amenable to prenatal surgical intervention must fulfill a number of conditions. It must be severe enough to warrant the risks associated with in utero treatment and must be reliably detectable before birth. Additionally, the pathophysiology must be reversible by fetal surgery, significantly improving the prognosis over post-natal treatment. Many technical intricacies of open fetal surgery have been solved, but pre-term labor and premature rupture of membranes remain a omnipresent risks to both the mother and the fetus. To reduce maternal morbidity and the risk of prematurity we developed minimally invasive techniques to treat the fetus prenatally. Current indications of fetal surgery include the treatment of congenital diaphragmatic hernia, cystic adenomatoid malformation of the lung, sacrococcygeal teratoma, obstructive uropathy, twin-to-twin-transfusion-syndrome and myelomeningocele. Minimally invasive surgical techniques (FETENDO) have significantly lessened the incidence of preterm labor and promise to extend the indications for fetal surgical intervention. CONCLUSIONS: Fetal surgical therapy for severe congenital malformations may improve the outcome of selected patients. The development of FETENDO will in all probability reduce the importance of open fetal surgery in the future.

Congenital Abnormalities↗

Maternal fertility is not affected by fetal surgery.

The purpose of this report is to assess the impact of fetal surgery on future maternal fertility, subsequent pregnancy outcome, and the incidence of pregnancy complications. Retrospective data were collected on 70 mothers who underwent fetal surgery between April 1981 and June 1996. Indications for open hysterotomy fetal surgery included congenital diaphragmatic hernia (n = 44), congenital cystic adenomatoid malformation of the lung (n = 11), urinary obstruction (n = 9), sacrococcygeal teratoma (n = 4), heart block (n = 1), and acardiac-acephalic twin reduction (n = 1). The following data were obtained: number of pregnancy attempts, number of successful pregnancies, pregnancy outcome including obstetrical and neonatal complications, and infertility after fetal surgery. There were 45 respondents, of whom 35 attempted subsequent pregnancies. Thirty-two were successful, resulting in 31 livebirths. Two women had a strong prefetal surgery history of infertility, 1 has only attempted to conceive for 3 months. We report this experience because the effect of open fetal surgery on futrue fertility is such an important question for our patients and referring physicians. This analysis suggests that hysterotomy and open fetal surgery has a negligible impact on maternal fertility.

Adolescent↗

Are bilateral fetal lung masses double trouble?

OBJECTIVES: To examine the perinatal natural history of bilateral fetal cystic lung masses. METHODS: The records of a tertiary medical center over a 3-year period were reviewed for cases of fetal bilateral pulmonary masses. RESULTS: Three of 98 fetuses referred for evaluation over a 3-year period from September of 1995 to August of 1998 had bilateral lung lesions. Two of these cases resulted in live births, while one, associated with hydrops, resulted in death after preterm delivery. CONCLUSIONS: Similar to prenatally diagnosed unilateral lung lesions, hydropic fetuses with bilateral cystic lung lesions have a poor prognosis. Nonhydropic fetuses, however, may be asymptomatic despite persistent lesions on postnatal CT scan. These observation may prove helpful for prenatal counseling for these rare lesions.

Adult↗

Cord ultrasonic transection procedure for selective termination of a monochorionic twin.

Placental vascular communications can present a life-threatening problem in monochorionic twins when one fetus has a lethal anomaly. Although selective feticide is the best option for salvaging the normal twin, techniques normally employed (i.e. intracardiac potassium, air embolism) are not prudent given the common circulatory system. Furthermore, in monoamniotic, monochorionic twin gestations it is important to transect the umbilical cord completely to prevent entanglement of the dead fetus around the cord of the normal twin. We present two cases of monochorionic twins in which the cords were transected with a harmonic scalpel under ultrasonic guidance via one trocar. The harmonic scalpel is an instrument which can simultaneously coagulate and cut blood vessels or tissues. The cord ultrasonic transection procedure is a novel, minimally invasive technique which offers several advantages over the methods currently used for selective feticide in discordant monochorionic twin gestations.

Abortion, Eugenic↗

In utero repair of rectal atresia after complete resection of a sacrococcygeal teratoma.

PURPOSE: A case of a fetus with a prenatally diagnosed sacrococcygeal teratoma that produced high-output cardiac failure, hydrops, rectal atresia, and urinary tract obstruction is presented. The unique prenatal surgical management along with the embryogenesis of tumor-related rectal atresia is discussed. CASE REPORT: A large fetal sacrococcygeal teratoma with a significant intrapelvic component was detected at routine ultrasound in a 35-year-old gravida 3 para 2. Fetal hydrops developed rapidly due to high-output cardiac failure from the vascular 'steal' by the growing tumor. The urinary tract was obstructed due to the intrapelvic tumors mass. At 27 weeks' gestation, the female fetus underwent hysterotomy, resection of the entire mass and urinary diversion via bilateral flank ureterostomies. The rectum was found to be completely atretic due to apparent encasement by the tumor. Pull-through anorectoplasty was carried out concurrently. At 30 weeks' gestation, the mother developed preterm labor and a 1.8-kg was delivered by cesarean section. The baby did very well for 3 days but had a cardiac arrest and died due to an atrial perforation by a transfemoral venous catheter. CONCLUSIONS: To our knowledge this is the first report of a complete prenatal resection of a sacrococcygeal teratoma with concomitant pull-through anorectoplasty for rectal atresia.

Adult↗

Twin-twin transfusion syndrome: the 'Select' procedure.

OBJECTIVES: Twin-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal morbidity and mortality. The condition results from intertwin vascular connections in the shared placenta. We report here a case of early, severe TTTS that failed to respond to serial amniocenteses and that was successfully treated by means of superselective laser coagulation. METHODS: A causative arteriovenous anastomosis was identified by means of prenatal obstetrical sonography, using color and spectral Doppler techniques. At fetoscopy, performed at 23 weeks' gestation, laser occlusion of only this connection was achieved. RESULTS: This therapeutic intervention resulted in rapid resolution of all evidence of TTTS and a successful pregnancy outcome, with subsequent delivery of 2 healthy infants at 33 weeks' gestation. CONCLUSIONS: The potentially fatal pathophysiology of TTTS was reversed by interruption of a single arteriovenous connection. We have termed this the sonographically evaluated, laser-endoscopic coagulation for twins ('Select') procedure.

Adult↗

Creation of myelomeningocele in the fetal rabbit.

OBJECTIVE: Myelomeningocele is a neural tube defect resulting in an exposed spinal cord, which leads to irreversible neurologic damage at birth. We proposed development of a fetal rabbit model of myelomeningocele to study in utero spinal cord injury and repair strategies. METHODS: New Zealand white rabbits (n = 10) at 22 days of gestation (term = 31 days) underwent laparotomy to expose the gravid uterus; a hysterotomy exposed the fetal hindlimbs and back. A three to four level lumbar laminectomy was performed, and the dura over the posterior spinal cord was removed. At 30 days of gestation, the does underwent C-section for fetal harvest, and total fetal number, length, weight, and the presence or absence of a spinal defect were recorded for all viable fetuses. RESULTS: All injured fetuses were smaller and weighed less than the nonoperated littermate controls, and histologic examination confirmed a spina bifida-like lesion of their spinal cords. CONCLUSIONS: We successfully created an exposed spinal cord defect in the fetal rabbit model similar to the lesion found in humans. Advantageous because of low animal cost, relatively large fetal size, multiple fetuses per pregnancy, and short total gestation, this model will allow us to study the mechanism of injury to the exposed spinal cord, and perhaps develop strategies to repair human myelomeningoceles.

Animals↗

Safety of chronic fetal vascular access in the sheep model.

OBJECTIVE: Long-term access to the fetal circulation has the potential to open up new perspectives in the treatment of numerous fetal anomalies. The purpose of this study was to investigate the safety of long-term catheterization of fetal placental vessels. METHODS: A midline laparotomy was performed in 4 time-mated pregnant ewes at 125 days' gestation (term 145 days). Placental vessels were exposed by a small uterine incision. A specially designed catheter was inserted into a placental vessel over a length of 3 cm, the distal end of the catheter was tunneled underneath the maternal skin and attached to a subcutaneous port implanted in the maternal flank. All pregnancies were allowed to go to term. RESULTS: Ewes and fetuses tolerated the placement of the catheter and port without complications. The catheter remained patent in all cases. All lambs were delivered vaginally at term and did not require resuscitation after birth. No fetal anomalies or growth restriction were noted. CONCLUSION: The ovine placental vessel can be accessed long term without complication.

Animals↗

High-efficiency retroviral transduction of fetal liver CD38-CD34++ cells: implications for in utero and ex utero gene therapy.

OBJECTIVES: Defining methods for the efficient transduction of fetal stem cells could lead to novel fetal therapies for blood cell disorders and other birth defects. In this study, we analyzed the effects of various parameters on the retroviral transduction of primitive hematopoietic progenitors/stem cells isolated from fetal liver. METHODS: Candidate stem cells were isolated by fluorescence-activated cell sorting from midtrimester human livers based on the phenotype CD38-CD34++lineage- (lineage = glycophorin A, CD3, CD14, CD19, CD20 and CD56). A murine retroviral vector with a truncated human low-affinity nerve growth factor receptor (Delta NGFR) gene was used to transduce the candidate stem cells. Marker gene expression was monitored by flow cytometry using an anti-NGFR mAb. Candidate stem cells were transduced immediately after isolation or after up to 4 days of culture in serum-deprived medium containing the growth factors kit ligand and granulocyte-macrophage colony-stimulating factor. The effects on transduction efficiency of the addition of 4 microg/ml protamine sulfate and/or centrifugation to concentrate the candidate stem cells and virus were tested. After transduction, the cells were expanded for 10-21 days before determining the frequency of NGFR+ cells among the different hematopoietic progeny. RESULTS: Efficient transduction of candidate stem cells, at an average rate of 46%, was achieved after 3 days of culture with a single exposure to virus. Longer than 3 days of culture or repeated exposure to viral supernatant did not significantly improve the rate of transduction. The use of centrifugation at 1,200 g for 1 h and the addition of protamine sulfate during the transduction procedure were critical to achieving a high rate of transduction. Marker gene expression was observed on the progeny of the transduced cells in conjunction with CD34 (progenitors), glycophorin A (erythrocytes), CD14 (monocytes), CD15 (granulocytes) and CD41 (megakaryocytes). CONCLUSIONS: This study demonstrates that the efficient transduction of fetal candidate stem cells can be achieved under defined culture conditions using a retroviral vector. These results encourage further examination of in utero and ex utero gene therapy as a means of treating birth defects.

ADP-ribosyl Cyclase↗

Bacterial and fungal contamination of human fetal liver collected transvaginally for hematopoietic stem cell transplantation.

Transplantation of fetal hematopoietic stem cells is a new therapy for fetuses diagnosed in utero with inherited disorders. However, prior to transplantation of fetal stem cells, the cells must be free of microbial contamination. In order to investigate the contamination of human fetal liver tissue, we determined the rate and types of bacterial and fungal contamination of human fetal liver tissue collected transvaginally for use in stem cell transplantation by using the US Pharmacopoiea Assay. We found a high rate of contamination with bacteria or fungi (12 of the 14 fetal livers, or 85%). Non-fermenting gram-negative rods were the predominant contaminants. The high rate of microbial contamination of fetal tissue suggests that techniques for tissue collection need to be improved before fetal stem cells are used for clinical transplantation.

Abortion, Induced↗

Chorioamniotic membrane separation: a potentially lethal finding.

Sonographic detection of chorioamniotic membrane separation (CMS) has been considered a benign incidental finding. We now report 6 cases of CMS identified by prenatal ultrasound; 1 in an otherwise normal pregnancy and 5 following fetal surgery. Following membrane separation, amniotic bands formed and compromised the umbilical cord in 4 cases leading to 2 fetal deaths. In the first case, CMS was detected by ultrasound at 22 weeks' gestation in an otherwise uncomplicated pregnancy. Because CMS was considered benign and umbilical cord blood flow was ample, the mother was followed by intermittent sonographic examinations. Fetal demise occurred 2 weeks later, clearly due to umbilical cord strangulation by an amniotic band. Surprised by this unexpected outcome, we reviewed our experience with CMS after hysterotomy for fetal surgery. Out of more than 40 fetal surgical cases, we have 5 cases in which CMS was recognized after hysterotomy. Three of these fetuses had umbilical cord compromise by a band of amniotic membrane leading to 1 fetal death. This experience demonstrates that membrane separation may be associated with amniotic band formation which can lead to cord strangulation and fetal compromise. Following fetal surgery, serial ultrasound evaluation and close fetal monitoring are indicated. In otherwise unremarkable pregnancies, clinician awareness of the possibility of amniotic band formation following CMS should be heightened. In either situation, knowledge of this potential life-threatening complication may identify cases in which cord compromise requires emergent delivery or fetoscopic release of the strangulating amniotic band.

Adult↗

The length-time correlate in appendicitis.

A propsective study of 60 children with appendicitis suggested a correlation between the length of symptoms prior to perforation and the level of appendiceal obstruction. These observations support the concept that obstruction of the appendiceal lumen near its tip leads to early perforation, while obstruction near the base leads to late perforation.

Adolescent↗