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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 235 records · Page 13Linked to original sources
PubMed1990

Complete heart block in fetal lambs. I. Technique and acute physiological response.

Prenatally diagnosed complete heart block (CHB), without associated cardiac anomalies, is often refractory to attempts to increase heart rate and cardiac output by medical therapy, and results in fetal death. We developed a model of CHB in fetal lambs in order to evaluate the acute physiological consequences of CHB and to assess the feasibility of fetal cardiac ventricular (V) and atrioventricular (AV) pacing. After hysterotomy and fetal sternotomy AV-sequential pacing leads were placed on the right atrium and ventricle (RV). Electromagnetic flow transducers were placed around the pulmonary artery and the ascending aorta to measure combined ventricular output (CVO) in normal sinus rhythm (NSR), CHB, AV, and V pacing. CHB block was successfully induced in 19 of 21 (90%) fetal lambs at 100 to 110 days' gestation by injection of formalin into the interventricular septum. Two fetuses were refractory to CHB despite multiple injections. The mean ventricular escape rate was 52 +/- 3 (+/- SEM) beats/min (range, 45 to 60 beats/min). CHB lasted for the period of study (1 to 8 hours), and spontaneously reverted to NSR in one fetus after 3 hours. Combined ventricular output in NSR was 470 +/- 31 mL/min (+/- SEM), which fell to 213 +/- 13 mL/min in CHB, 45% of normal CVO (P less than .0001). CVO during AV-sequential and V pacing was 77% (P = .02) and 62% (P less than .001), respectively, of combined ventricular output in NSR. Both RV (27%) and left ventricles (LV) (37%) showed compensatory increase in stroke volume during CHB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Nephron-sparing approach to bilateral Wilms' tumor: in situ or ex vivo surgery and radiation therapy.

Bilateral Wilms' tumor patients, who experience local recurrence after maximal multimodality therapy, present a difficult surgical problem. The role of surgery in the management of these patients has changed from ablation to preservation of renal tissue, with bilateral nephrectomy as a last resort. Two children who had recurrent tumors in the remaining kidney underwent nephron-sparing surgery and focal intraoperative radiation therapy. In one case, this nephron-sparing surgery and intraoperative radiation therapy were performed in situ, in the other kidney was removed and reimplanted (ex vivo bench surgery and irradiation). These techniques may allow complete obliteration of gross and microscopic disease, while maximizing residual renal function.

Child↗
PubMed1990

Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid.

Fetal wound healing occurs rapidly and without inflammation, fibrosis, or scar formation. It is a process fundamentally different from adult wound healing. The mechanisms that underlie such unique healing properties are unknown. However, hyaluronic acid, a glycosaminoglycan component of the extracellular matrix, is prominent throughout the course of fetal wound healing, and is thought to play a major role in the healing process. Amniotic fluid contains high levels of hyaluronic acid. Amniotic fluid also contains a number of potent growth factors that are critical for fetal development. In this report, a new factor in amniotic fluid that stimulates deposition of hyaluronic acid is described. This activity is measured in an in vitro assay system in which cultured fibrosarcoma cells are used as indicator cells. Amniotic fluid thus provides two separate mechanisms for the deposition of hyaluronic acid. One is by exogenous application directly onto fetal skin wounds; the second is by providing a factor to increase the production of hyaluronic acid endogenously, by stimulating cells around the wound site. The resulting hyaluronic acid-rich area may support the ability of the fetal wound to heal with its unique properties.

Amniotic Fluid↗
PubMed1990

Death due to high-output cardiac failure in fetal sacrococcygeal teratoma.

Fetal sacrococcygeal teratoma (SCT) is being recognized with increasing frequency. Placentomegaly and hydrops fetalis are preterminal events, and it has been suggested that fetal death may be due to high-output cardiac failure from arteriovenous shunting through the tumor. We had a chance to examine this hypothesis when a 21-week fetus presented with a huge sacrococcygeal teratoma. There were marked placentomegaly, cardiomegaly, hyperdynamic ventricles, and a pericardial effusion. Doppler studies showed tremendous flow through the SCT with extreme enlargement of the inferior vena cava, consistent with congestive heart failure from increased flow through the tumor. Hydrops developed, and the fetus was delivered because of placental abruption. This case provides supportive evidence that the teratoma acts as a large arteriovenous shunt, causing high-output cardiac failure. We have now collected 18 more cases of sacrococcygeal teratoma diagnosed in utero. Of the total 45 cases of fetal SCT, 9 had placentomegaly and/or fetal hydrops and all 9 fetuses died in utero or shortly after birth. We conclude that the only hope for survival in these severely affected fetuses is to reduce blood flow to the tumor before birth.

Cardiac Output↗
PubMed1990

Etiology of intestinal damage in gastroschisis, II. Timing and reversibility of histological changes, mucosal function, and contractility.

Previous work in the fetal lamb examined the relative effects of amniotic fluid and bowel constriction in the etiology of bowel damage in gastroschisis. The present study used the same model to assess the timing and reversibility of these changes during gestation. Gastroschisis was created at 80 days' gestation, and a tape was placed around the bowel to cause gradual constriction with growth. Lambs were killed at 100 days, 120 days, and term. Bowel damage was assessed using histology, mucosal enzyme activity, and in vitro motility. In an additional "repaired" group, the constrictor was removed at 120 days, a silastic pouch placed over the bowel, and bowel damage assessed at term. Normal fetuses at each gestational age were used as controls. A fibrous peel was observed at all gestational ages. Mucosal villous atrophy and mesenteric venous and lymphatic dilation were mild at 100 and 120 days, but severe at term. These changes were present but mild in repaired animals at term. Mucosal enzyme activity decreased gradually with gestational age; inhibition of maltase activity was maximal at term, and was significantly reversed by repair, whereas inhibition of aminooligopeptidase activity was maximal at 120 days, and was not affected by repair. Protein/DNA, DNA/weight, and protein/weight ratios showed that repaired mucosal cells were significantly more proliferative, smaller, and less mature than control or gastroschisis cells. In vitro motility studies demonstrated a mild decrease in contractility at 100 and 120 days, and a large decrease at term. This deleterious effect at the end of gestation was only partially reversed by repair in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1990

Influence of alterations in loading produced by lower body negative pressure on aortic blood flow acceleration.

The objectives of this study were to evaluate the effects of alterations in loading induced by lower body negative pressure on aortic blood flow velocity and acceleration. Twenty-seven normal men were studied during various levels of lower body negative pressure (0 to -60 mm Hg) during which echocardiographic, Doppler and hormonal measurements were obtained. Lower body negative pressure induced a decrease in left ventricular diastolic diameter from 5.18 +/- 0.08 to 4.41 +/- 0.1 cm (p less than 0.0001) and in left ventricular systolic diameter from 3.33 +/- 0.09 to 2.84 +/- 0.1 cm (p less than 0.0001). Shortening fraction remained unchanged. The decrease in diastolic diameter resulted in a reduction in flow velocity integral from 13.8 +/- 0.8 to 7.5 +/- 0.4 cm (p less than 0.0001) and, therefore, in stroke volume from 89.6 +/- 4.7 to 49.5 +/- 2.8 ml (p less than 0.0001). Heart rate reflexly increased from 62.5 +/- 1.9 to 82.2 +/- 2.3 beats/min (p less than 0.0001) as did systemic vascular resistance from 1,280.8 +/- 69.5 to 1,863.4 +/- 121.4 dyne.s.cm-5 (p less than 0.0001). The increase in heart rate was insufficient to maintain cardiac output, which decreased from 5.53 +/- 0.29 to 3.99 +/- 0.21 liters/min (p less than 0.0001). Systolic, diastolic and mean arterial blood pressure was maintained. The negative pressure resulted in a concomitant significant increase in norepinephrine levels from 1.46 +/- 0.09 to 2.056 +/- 0.2 nmol/liter (p = 0.0019) but no change in plasma epinephrine: 0.845 +/- 0.22 to 0.78 +/- 0.11 nmol/liter (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Relation of echocardiographic morphology of the mitral apparatus to mitral regurgitation in mitral valve prolapse: assessment by Doppler color flow imaging.

Few data exist regarding the relationship of valvular anatomy and coaptation to the presence of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP). Therefore this study was undertaken to assess the ability of two-dimensional echocardiographic features of mitral valve morphology to predict the presence, direction, and magnitude of MR as assessed by color Doppler flow imaging. MR was present in 21 of 46 patients with MVP on two-dimensional echocardiography. Echocardiograms were specifically evaluated for leaflet apposition, leaflet morphology, and mitral anulus diameter. Color flow images were analyzed for presence of MR, direction of the regurgitant jet, and area encompassing the largest jet visible in any view. Abnormal mitral leaflet coaptation on two-dimensional echocardiography was strongly associated with the presence of MR (p = 0.003), being present in 15 of 21 patients with as compared with 5 of 25 patients without MR. Similarly, mitral leaflet thickness and MR were closely associated (p = 0.0035), with the latter being present in 9 of 30 patients with normal and 12 of 16 patients with excessive leaflet thickness. MR jet direction tended to be anterior to central with posterior leaflet prolapse and posterior or central with anterior leaflet prolapse (p = 0.02). Maximal jet area of MR tended to be larger in patients with compared with those without mitral annular dilatation (5.4 +/- 2.3 versus 2.1 +/- 1.9 cm2, p = 0.001), and in those with abnormal rather than normal leaflet thickness (4.5 +/- 2.7 versus 2.0 +/- 1.6 cm2, p = 0.009). Thus the presence, direction, and size of MR jets in MVP are related to structural abnormality of the mitral apparatus on echocardiography.

Adolescent↗
PubMed1990

Fetal trauma: relation to maternal injury.

Conventional surgical wisdom is that fetal death is a predictable consequence of severe maternal injury. In order to define the natural history of maternal-fetal trauma and better formulate management strategies, we reviewed our recent experience with 32 cases of maternal trauma at a major trauma center. There were three cases of fetal death; two were associated with severe maternal injury, but one had no significant injury to the mother. All cases had placental injury. Conversely, there were five cases of severe maternal trauma but only two unsuccessful pregnancy outcomes. We conclude that the extent of maternal injury does not necessarily correlate with the degree of fetal injury. Lethal placental or direct fetal injury can occur even in the absence of significant maternal injury. In selected cases, fetal salvage after maternal-fetal trauma may be achieved by early delivery and prompt pediatric surgical intervention.

Adult↗
PubMed1990

The modified Puestow procedure for chronic relapsing pancreatitis in children.

Chronic relapsing pancreatitis in children is an unusual condition that often goes undiagnosed and untreated for years. In light of recent reports in adults that endocrine and exocrine function may be preserved by early pancreaticojejunostomy, we reviewed our experience with this procedure (one Duval, 10 Puestows) in 10 children between 1969 and 1989. The underlying etiology was familial pancreatitis in four patients, one case of unknown etiology, congenital ductal anomalies in four (one pancreas divisum, one annular pancreas, one choledochal cyst, and one ductal stenosis), and posttraumatic in one. All 10 had intractable recurrent abdominal pain. Preoperatively, only three patients evidenced exocrine insufficiency and none had endocrine insufficiency. There was complete resolution of pain in eight patients and improvement in two during a mean observation period of 4 years (range, 7 months to 19.75 years). Exocrine insufficiency resolved in two patients but has persisted in the third patient now on Viokase. Endocrine insufficiency has developed during follow-up in one patient. Pancreaticojejunostomy provides excellent relief of recurrent pain in chronic relapsing pancreatitis in children. Endoscopic retrograde cholangiopancreatography (ERCP) is indicated when the diagnosis of chronic relapsing pancreatitis is suspected to define the ductal anatomy. Pancreaticojejunostomy may prevent the progression of exocrine and endocrine insufficiency if performed early in the course of the disease.

Abdominal Pain↗
PubMed1990

Testing the limits of neonatal tracheal resection.

Obstructive lesions of the trachea in infants can be life-threatening because secretions or mucosal inflammation can easily obstruct the tiny compromised airway, and distal obstruction cannot be relieved by an endotracheal or tracheostomy tube. The principles of tracheal resection in adults are well established. The limits of tracheal resection in neonates are unknown. We present a case in which at least two-thirds of the trachea was resected successfully in a neonate.

Anastomosis, Surgical↗
PubMed1990

Pulmonary lobar transplantation in neonatal swine: a model for treatment of congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Lung transplantation is a potential treatment for these otherwise doomed infants using ECMO as a bridge to transplantation. Cadaveric, or living related donation of a more mature reduced size lung (pulmonary lobe or segment) may help solve the critical donor shortage problem. We evaluated the physiological response of mature left lower lobe (LLL) transplants in neonatal swine with the hemodynamic conditions of CDH simulated by occlusion of the right pulmonary artery (PA), and also studied the pulmonary function of the mature lobar graft compared with the neonatal lung. LLL transplantation was well tolerated and resulted in minimal alteration in hemodynamic parameters. The response to right PA occlusion was similar pre- and posttransplantation with a fall in cardiac output and a significant rise in pulmonary vascular resistance. Compared with the contralateral native lung, the lobar graft was preferentially ventilated with resultant higher pH (7.65 +/- 0.17 v 7.41 +/- 0.08, P less than .01) and lower pCO2 (17 +/- 6 v 36 +/- 5, P less than .001). The more mature lobar graft was preferentially ventilated due to the increased compliance compared with the neonatal right lung (8.16 +/- 1.28 v 5.48 +/- 0.82 mL/cm, P less than .0001). Reduced size lung transplantation is technically feasible and may help solve the donor problem for severe CDH neonates for whom no effective therapy is currently available.

Animals↗
PubMed1990

Correction of congenital diaphragmatic hernia in utero, V. Initial clinical experience.

Review of our experience with 45 cases of prenatally diagnosed congenital diaphragmatic hernia (CDH) confirms that most fetuses (77%) will not survive despite optimal pre- and postnatal care. Polyhydramnios, associated anomalies, early diagnosis, and a large volume of herniated viscera (including liver) are associated with a particularly dismal prognosis. After extensive experimental work demonstrated the efficacy, feasibility, and safety of repair in utero, we attempted to salvage six highly selected fetuses with severe CDH by open fetal surgery. Five had liver incarcerated in the chest: three died at operation because attempts to reduce the liver compromised umbilical venous return. In one, a Goretex diaphragm was constructed around the liver, but the baby died after birth. The last two fetuses, one with incarcerated liver, were successfully repaired. Both demonstrated rapid growth of the lung in utero, had surprisingly good lung function after birth despite prematurity, had the abdominal patch removed at 2 weeks, and subsequently died of nonpulmonary problems (an unrelated nursery accident in one and intestinal complications in the other). The only maternal complication was amniotic fluid leak and preterm labor. All six women are well and four have had subsequent normal children. From this phase I experience, we conclude that fetal surgery appears safe for the mother and her reproductive potential, that fetal CDH repair is feasible in selected cases, and that the fetal lung responds quickly after decompression. However, fetal repair remains a formidable technical challenge.

Adolescent↗
PubMed1990

Cervical cystic hygroma in the fetus: clinical spectrum and outcome.

Cervical cystic hygroma is thought by most pediatric surgeons to be an isolated, usually resectable lesion with an excellent prognosis. However, prenatal sonography has revealed a high "hidden mortality" among fetuses with this condition, and most perinatologists consider it to be uniformly fatal. In an attempt to resolve these two differing perspectives, we analyzed 29 cases seen at two centers over 4 years. Of 27 fetuses diagnosed before 30 weeks' gestation, only one survived. Twenty-five of the 27 were aborted; severe hydrops was present in 21 of these 25. Two of the 27, both with stigmata of Noonan's syndrome, underwent spontaneous regression during the second trimester: one died at 2 weeks of age, and the other survived. Successful karyotypes were obtained on 17 fetuses: nine were normal, seven were 45X, and one was trisomy 21. Fetuses with abnormal karyotypes had a lower incidence of polyhydramnios (0% v 67%), additional anomalies (12% v 67%), and consanguinity or a history of abnormal pregnancies (0% v 89%). Two fetuses were diagnosed after 30 weeks' gestation. Neither had hydrops, polyhydramnios, associated anomalies, or an abnormal karyotype. One had a completely normal sonogram at 17 weeks' gestation. Both were operated on within the first 4 days of life; one did well without complications, and the other required a permanent tracheostomy because of extensive hypopharyngeal involvement. A cystic hygroma presenting in the fetus has a different natural history and prognosis from one presenting postnatally. The vast majority of fetal cases are diagnosed before 30 weeks' gestation, and present with hydrops or diffuse lymphangiomatosis. The dismal outlook in this group justifies elective termination in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Studies in fetal wound healing, VI. Second and early third trimester fetal wounds demonstrate rapid collagen deposition without scar formation.

The mechanisms that underlie the lack of scarring in fetal wounds are unknown, but probably relate to the control of collagen fibrillogenesis. The role of collagen in the fetal wound matrix is controversial, and several wound implant models have been used to evaluate collagen deposition in fetal wounds. Unfortunately, these models create an artificial wound environment and may thereby affect the results. In order to study fetal wound collagen deposition in linear wounds without artificially altering the wound environment, we applied a highly sensitive immunohistochemical technique that uses antibodies to collagen types I, III, IV, and VI. We found that collagen was deposited in fetal wounds much more rapidly than in adult wounds. Wound collagen deposition occurred in a normal dermal and mesenchymal pattern in second and early third trimester fetal lambs. These findings are consistent with the observation that the fetus heals rapidly and without scar formation. In contrast, wounds in late gestation fetal lambs showed some evidence of scar formation. Further studies may suggest ways to alter the adult wound so that it heals in a fetal manner.

Animals↗
PubMed1990

Pharmacodynamics of propranolol on left ventricular function: assessment by Doppler echocardiography.

The relationship of left ventricular systolic function and heart rate to serum l-propranolol concentrations was determined in 10 healthy male volunteers during maximal exercise treadmill testing. Peak aortic blood flow acceleration (ACL), measured by Doppler ultrasonography, was used to evaluate left ventricular systolic function. Repeated exercise testing was performed on two separate days after long-term oral administration of 40 mg propranolol or placebo every 6 hours in a randomized, double-blind, crossover fashion. Pharmacodynamic relationships were determined by fitting percent change in ACL and heart rate at maximal exertion with 1-propranolol with the Emax model (maximal effect) and nonlinear regression. Reductions in systolic function and heart rate during exercise were related directly to 1-propranolol. Propranolol was significantly (p less than 0.05) more potent in reducing heart rate (EC50, 10.6 +/- 9.2 ng/ml) compared with ACL (EC50, 19.2 +/- 8.9 ng/ml). However, Emax of propranolol for reducing ACL was significantly greater than that for reducing heart rate (-46.7% +/- 6.9% versus -29.5% +/- 15.9%; p less than 0.05). These data indicate that the concentration-effect relationship for 1-propranolol and its negative inotropic effect differ from its negative chronotropic effect.

Adult↗
PubMed1990

Tracheobronchial obstructions in infants and children. Experience with 45 cases.

Forty-five infants and children with intrathoracic tracheobronchial obstructions requiring surgical treatment are reported. Segmental stenosis of the trachea is defined as involvement of less than one half the length of the airway, which affected six infants. Elongated stenosis involving more than one half the length of the trachea was seen in 12 infants, and complete annular cartilage rings, along the entire length of the trachea, were present in 11. Severe tracheomalacia occurred in six infants associated with aortic arch anomalies and in nine infants with esophageal atresia. Segmental tracheal resection was performed in 17 cases (two after failure of a rib cartilage graft), and anastomotic stricture developed in three. These three anastomotic strictures were resected, resulting in an excellent airway in two and restricture in one. Rib cartilage grafts were used in five patients: two of three with elongated stenosis with complete tracheal rings required subsequent resection, and one of two infants with tracheomalacia had excellent outcome. Approximately 50% of an infant's trachea can be resected, but rib cartilage grafts should be used for elongated stenosis. Resection of bronchial stenosis in two patients resulted in a widely patent bronchus. From this experience primary segmental tracheobronchial resection and re-resection of recurrent stenosis are highly successful. Anastomotic stricture is due to tension at the suture line and suture material inciting a fibrotic reaction. Rib cartilage grafts amounting to 25% or less of the circumference of the airway readily resurfaces with adjacent epithelium, but when 30% or more of the circumference is rib graft, epithelialization may be impaired.

Bronchial Diseases↗
PubMed1990

Operative techniques in the fetal rabbit.

The development of fetal surgical techniques has made the antenatal correction of congenital defects possible. These techniques have evolved from trials with animal models, permitting increasingly sophisticated operations with low morbidity and mortality. Experimental models range from large animals offering longer gestations but with single pregnancies and high cost, to smaller animals offering multiple pregnancies at reduced cost but with shorter gestations. This paper describes operative techniques in the fetal rabbit and its advantages as a fetal surgical model. Experience with the pregnant rabbit has shown it to be a suitable surgical model for several reasons. Pregnancies are multiple, increasing cost effectiveness and permitting operation on up to eight fetuses per litter without fetal loss. Techniques that promote fetal survival include local housing of does several days prior to operation and preoperative sedation. Spontaneous mask ventilation provides ease of anesthetic administration and titration. Overall surgery is well tolerated with a low incidence of intraoperative complications. Rabbit models have been used in the study of transamniotic fetal feeding, abdominal wall defects, and wound healing. These techniques have resulted in postoperative fetal viability approaching 90%, with negligible maternal mortality in over 4000 fetal operations, thereby making the rabbit a manageable cost-effective model of fetal surgery.

Animals↗