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Biomedical subjects

M R Harrison

Publications and source records attributed to M R Harrison.

At least 199 records · Page 11Linked to original sources
PubMed1991

Midventricular obstruction associated with chronic systemic hypertension and severe left ventricular hypertrophy.

Midventricular obstruction is an uncommon finding previously defined by catheterization and angiographic techniques in patients with hypertrophic cardiomyopathy. This study describes the clinical and echocardiographic findings of 10 consecutive patients (mean age 73 years) with severe concentric left ventricular (LV) hypertrophy and the unusual finding of a dynamic systolic obstruction located in the midportion of the left ventricle. All patients were known to have chronic hypertension, and none had a history or family history of hypertrophic cardiomyopathy. In each case, a well-defined, high velocity, turbulent jet was identified by Doppler color flow imaging and subsequently confirmed with conventional Doppler techniques. Septal and posterior wall thickness averaged 1.67 and 1.57 cm, respectively. Mean LV mass index was 199 g/m2 and ejection fraction averaged 78%. Peak systolic velocity obtained by continuous-wave Doppler averaged 2.7 m/s and appeared as either a "late-peaking" or a "spike and dome" configuration. Seven of 10 patients gave a history of syncope or severe presyncope at the time of echocardiographic examination. At a mean follow-up of 1 year, syncope or presyncope had resolved in 5 patients in whom medication was adjusted based on the ultrasound study, but persisted in 2 patients in whom diuretic therapy was continued. It is concluded that obstruction to systolic flow can occur at the mid-LV level in some patients with severe concentric LV hypertrophy and avoidance of medication known to lower LV volume may relieve symptoms of transient inadequate cardiac output.

Aged↗
PubMed1991

Intraoperative radiation therapy for Wilms' tumor in situ or ex vivo.

Patients with bilateral Wilms' tumor who have local recurrence after undergoing maximum-dose multitechnique therapy are problematic. The role of surgery in the management of these patients is changing from ablation to preservation of renal tissue. Bilateral nephrectomy is reserved as a last resort. Intraoperative radiation therapy (IORT) is advantageous to conservative management, as illustrated by the current cases of two children with recurrent Wilms' tumors in their remaining kidneys. Both children underwent limited surgery and precisely directed IORT. In one patient the nephron-sparing surgery and IORT were performed in situ. In the other the kidney was removed, treated with ex vivo bench surgery and radiation surgery, and then reimplanted. The adjuvant use of IORT, either in situ or ex vivo, in nephron-sparing surgery permits complete obliteration of gross and microscopic disease while maximizing residual renal function.

Child↗
PubMed1991

Effect of heart rate on left ventricular diastolic transmitral flow velocity patterns assessed by Doppler echocardiography in normal subjects.

Although a number of factors, including age and ventricular loading, are known to influence the pattern of left ventricular (LV) filling as depicted by Doppler echocardiographic transmitral flow velocities, few and conflicting data are available regarding the influence of heart rate (HR). Therefore, 20 volunteers (mean age 30 years) were evaluated with pulsed-wave Doppler echocardiography, performed with the sample volume placed at the mitral anulus level in the apical 4-chamber projection. Transmitral flow measurements comprised peak and integrated early passive (E) and late atrial (A) filling velocities and the slope of velocity decline from peak E filling. Measurements were recorded during baseline (sinus rhythm, mean 70 beats/min) and during transesophageal atrial pacing (mean 88 beats/min). LV end-diastolic dimension, mean arterial pressure and PR interval (corrected for pacing-induced delay in interatrial conduction time) were unchanged during pacing versus baseline measurements. Peak and integrated E filling velocities averaged 0.59 +/- 0.09 m/s and 6 +/- 1 cm, respectively, at baseline and were not significantly greater at the higher HR. In contrast, baseline peak and integrated A velocities averaged 0.37 +/- 0.06 m/s and 2.3 +/- 0.7 cm, respectively, but were significantly greater at the higher HR (0.5 +/- 0.07 m/s and 3.2 +/- 1.1 cm, respectively [p less than 0.003 vs baseline for each]). Further analysis of a subgroup of 9 subjects for whom Doppler measurements were available at 3 HRs (sinus 70; pacing 80 and 90) yielded strong evidence for a linear relation between HR and peak A velocity (A = 0.008 HR - 0.21, with p less than 0.0001 for significance of the linear trend).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Maternal outcome after open fetal surgery. A review of the first 17 human cases.

A few fetal diseases may benefit from surgical treatment before birth, but hysterotomy and subsequent delivery by cesarean section pose a risk to the otherwise unaffected mother. To assess maternal risk of mortality, morbidity, and reproductive potential after fetal surgery, we reviewed our experience with 17 highly selected women who underwent fetal surgery. Fifteen of these procedures were performed for one of two congenital anomalies: severe bilateral hydronephrosis and congenital diaphragmatic hernia. There were no deaths or serious maternal injuries. In the 14 women who continued pregnancy after hysterotomy, uterine irritability and preterm labor were frequent complications, requiring early confinement in most cases. There has been no detectable effect on future fertility, as indicated by eight subsequent normal pregnancies. We conclude that hysterotomy for fetal surgery can be accomplished without unduly endangering the mother's life or her future reproductive potential. However, morbidity related to premature labor remains a serious problem, and our ability to control uterine contractions after hysterotomy remains the limiting factor in human fetal surgery.

Adolescent↗
PubMed1991

Hemodynamic effects of calcium channel and beta-receptor antagonists: evaluation by Doppler echocardiography.

To evaluate the ability of Doppler echocardiography to identify hemodynamic changes due to cardiac medications, 10 volunteers underwent Doppler examination at rest and immediately following vigorous treadmill exercise. Upon completion of the control test, each subject received moderate oral doses of propranolol, verapamil, pindolol, or nifedipine, and the same exercise protocol was repeated. During four control tests, values for peak acceleration and flow velocity integral were similar for each subject at rest and exercise. Following propranolol and pindolol, resting acceleration fell by 4.5 and 2 m/sec2, respectively p less than 0.05. Resting acceleration was unchanged by verapamil and increased following nifedipine by 1.7 m/sec2 (p less than 0.0001), but neither verapamil nor nifedipine altered either Doppler parameter. Flow velocity integral was increased by nifedipine at rest and by each of the beta-blockers during exercise (p less than 0.05). We conclude that (1) rest and exercise Doppler measurements are stable and reproducible, given stable cardiovascular status; (2) pindolol produced less hemodynamic depression as measured by Doppler echocardiography at rest relative to propranolol, but showed similar potency at maximal exertion; (3) nifedipine enhanced global cardiac performance at rest, but neither calcium antagonist affected Doppler measurements during exercise; and (4) Doppler echocardiography is a useful, noninvasive technique for evaluating hemodynamic effects of medication at rest and during vigorous exercise.

Adrenergic beta-Antagonists↗
PubMed1991

Transplantation of fetal cells.

Cellular transplantation is an attractive alternative to whole-organ transplantation when only a discrete function of the organ is deficient. Early fetal donor cells have an advantage because they engraft readily and do not cause graft-versus-host disease. Similarly, the fetus is an ideal recipient of allogeneic fetal cells as it is incapable of rejecting them early in gestation. This review presents the theoretical rationale, recent research advances, and clinical implications for adults with diabetes mellitus and Parkinson's disease; we also describe in utero transplantation of fetal hematopoietic stem cells and hepatocytes for the treatment of inherited hematologic and hepatic deficiencies, as well as the use of fetal islet cells and dopamine-producing cells to treat postnatal conditions.

Animals↗
PubMed1991

Amnion inversion in the treatment of giant omphalocele.

Operative repair of giant omphaloceles remains a technical challenge to close the wide abdominal wall defect. Currently, most surgeons remove the amnion to approximate the linea alba and/or skin edges or to suture prosthetic material to the abdominal wall and cover the defect with skin flaps. In doing so, the liver commonly becomes extruded and distended with blood, compounding the problem of reducing all of the viscera within the small abdominal cavity. Furthermore, bowel obstruction from adhesions produced from opening the abdomen is a life-long threat. We describe six cases of giant omphalocele in which the amnion was left intact, and it was progressively inverted into the abdominal cavity by using the silastic silo, as it is used for gastroschisis. The birth weight of these infants ranged from 2,360 to 3,240 g. The abdominal wall defect measured 7.0 cm to 10.5 cm in width, and protruded at least 8 cm beyond the abdominal wall. The first stage of repair was to suture the silastic silo to the skin-amnion junction, and progressively reduce the bowel and liver within the abdomen. The intrabdominal pressure is monitored by nasogastric tube or by an indwelling bladder catheter to avoid pressures greater than 20 cm H2O, which might compromise intestinal and renal circulation. The second stage consisted of incising the skin/amnion junction to expose the linea alba. The linea alba was approximated while leaving the amnion intact and folding it into the abdominal cavity. This avoids entering the peritoneum or interfering with the blood flow to and from the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles↗
PubMed1991

Midgestational excisional fetal lamb wounds contract in utero.

Clinical observations and experimental data suggest that fetal wound healing is very different from adult wound healing. An understanding of the biology of scarless fetal wound healing has tremendous clinical potential for modulating postnatal wound problems. In this study, the fetal lamb model was used to assess excisional fetal skin wound contraction in utero. Full-thickness 9-mm punch biopsy wounds were created on fetal lambs at 100 days' gestation (term, 145 days). Half of the wounds remained exposed to amniotic fluid, whereas the other half were covered by a silastic patch to exclude amniotic fluid. Wounds were harvested 3, 7, or 14 days later and wound areas were calculated. Exposure to amniotic fluid retarded wound contraction significantly at 3 days, but by 14 days all wounds had completely contracted and reepithelialized. Myofibroblasts are an important cellular element of wound contraction. The presence of wound myofibroblasts was documented by both transmission electronmicroscopy and immunocytochemistry with antimuscle actin antibody. It is concluded that fetal lamb wounds contract in utero and exposure to amniotic fluid appears to retard fetal skin wound contraction only during the early healing process.

Amniotic Fluid↗
PubMed1991

Fetal diaphragmatic wounds heal with scar formation.

Fetal wound healing is fundamentally different from wound healing in the adult. Although experimental work in mice, rats, rabbits, monkeys, and sheep has demonstrated that fetal healing occurs without inflammation and scarring, all of these studies have been limited to fetal skin wounds. Whether all fetal tissues heal in a regenerative-like fashion is unknown. Amniotic fluid exposure may play an important role in scarless fetal skin wound healing, but the effect of amniotic fluid on fetal mesothelial wound healing has not been characterized. To investigate these questions we created bilateral linear diaphragmatic wounds in 100-day gestation fetal lambs (term = 145 days). The right thoracotomy was closed to exclude amniotic fluid. In contrast, the left thoracotomy was fashioned into an Eloesser flap which permitted the left diaphragmatic wound to be continually bathed in amniotic fluid. Wounds were harvested after 1, 2, 7, or 14 days and analyzed by light microscopy and immunohistochemistry with antibodies to collagen types I, III, IV, and VI. Whether bathed in or excluded from amniotic fluid, the mesothelial-lined diaphragm healed with scar formation and without evidence of muscle regeneration. Interestingly, diaphragmatic wounds exposed to amniotic fluid were covered by a thick fibrous collagen peel similar to that seen in gastroschisis bowel. These findings indicate that not all fetal tissues share the unique scarless healing properties of fetal skin.

Amniotic Fluid↗
PubMed1991

Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 delta and epsilon but not membrane CD3.

Seventeen-week human fetal liver cells cultured with a feeder cell mixture of irradiated PBL, irradiated JY cells (an EBV-transformed B cell line) and PHA contained a subpopulation of CD3- cells in addition to a major population of T cells with the mature phenotype. After 12 days in culture, CD3- CD16- cells were sorted and cloned by limiting dilution. Two representative clones, FL121 and FL125, were expanded and characterized. They shared the phenotype of CD2+CD3-CD4-CD5-CD6+CD16-CD56+. FL121 did not express CD8 whereas FL125 expressed CD8 alpha but not CD8 beta. Both clones were found to express cytoplasmic CD3 delta and CD3 epsilon Ag while CD3- NK clones isolated from PBL were negative for them. These results indicate that FL121 and FL125 were committed to the T-cell lineage. Southern blot analysis showed that the TCR beta genes and the TCR gamma genes of these clones were in the germ-line configuration. The establishment of FL121 and FL125 may provide a novel insight into the earliest stage of T-cell development in man.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1991

The fetus as a patient. Surgical considerations.

The diagnosis and treatment of human fetal defects has evolved rapidly over the past decade due to improved fetal imaging techniques and better understanding of fetal pathophysiology derived from animal models. The detection of a fetal anomaly may now lead to a change in the timing of delivery, a change in the mode of delivery, or prenatal treatment. Because most therapeutic maneuvers involve some risk to the fetus and mother, there must be a reasonable expectation that the procedure is feasible, safe, and effective before it can be attempted in humans. This requires reliable information about the pathophysiology and natural history of the disease process, the efficacy of fetal surgical intervention in ameliorating the disease, and the feasibility and safety of the proposed intervention. This paper focuses on the rationale and initial clinical experience with fetal surgery for a variety of life-threatening fetal anatomic defects.

Algorithms↗
PubMed1991

Studies in fetal wound healing. V. A prolonged presence of hyaluronic acid characterizes fetal wound fluid.

Midgestation fetal wound healing is characterized by healing without fibrosis or scar formation. The mechanisms that underlie this remarkable process are mediated in part through a fetal wound extracellular matrix rich in hyaluronic acid. In this study a newly developed assay was used to determine the hyaluronic acid levels in fetal and adult wound fluid. Adult wound fluid had a rapid increase in hyaluronic acid, which peaked at 3 days and decreased to 0 by 7 days. In contrast levels of hyaluronic acid in fetal wound fluid increased rapidly and remained significantly elevated for 3 weeks. This prolonged presence of hyaluronic acid in the matrix of fetal wounds creates a 'permissive' wound environment that promotes fetal fibroblast movement and proliferation and inhibits cytodifferentiation. Such a matrix environment promotes healing by regeneration rather than by scarring. This observation has therapeutic implications. The prolonged application of hyaluronic acid or hyaluronate protein complexes to wounds in children or adults may modulate healing in a manner that makes the wounds more fetal-like.

Animals↗
PubMed1991

Regurgitant jet size by transesophageal compared with transthoracic Doppler color flow imaging.

Combined echocardiography and Doppler color flow mapping from transthoracic imaging windows has become the standard method for the noninvasive assessment of valvular regurgitation. This study compared regurgitant jet areas by Doppler color flow imaging derived from the newer transesophageal approach with measurements obtained from conventional transthoracic apical views. Maximal regurgitant jet area determinations and an overall visual estimate of lesion severity were obtained from 42 patients who underwent color flow examination by both techniques. Seventy-three regurgitant lesions were visualized by transesophageal flow imaging: 34 mitral, 22 aortic, and 17 tricuspid jets. Transthoracic studies in the same patients revealed fewer regurgitant lesions for each valve; 20 mitral, 16 aortic, and 12 tricuspid (p = 0.0009). A comparison of maximal jet areas determined by transesophageal and transthoracic studies showed a good overall correlation (r = 0.85, SEE = 2.8 cm2) and a systematic overestimation by the transesophageal technique (TEE = 0.96 TTX + 2.7). For the subgroup with mitral insufficiency, valve lesions visualized by both techniques were larger by the transesophageal approach (n = 18, 6.0 versus 3.6 cm2, p = 0.008). Semiquantitative visual grading of individual valve lesions by two independent observers revealed a higher grade of regurgitation with more jets classified as mild (38 versus 25), moderate (18 versus 13), and severe (17 versus 10) by esophageal imaging than by transthoracic imaging. Thus, transesophageal color flow mapping techniques yield a higher prevalence of valvular regurgitation than do transthoracic techniques in the same patients. Jet area and the overall estimate of regurgitant lesion severity were also greater by transesophageal color Doppler imaging compared with standard transthoracic imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography, Doppler↗
PubMed1991

Rapid epithelialisation of fetal wounds is associated with the early deposition of tenascin.

Wound healing is a complex process involving the interaction of many cell types with the extracellular matrix (ECM). Fetal skin wound healing differs from that in the adult in that it occurs rapidly and without scar formation. The mechanisms underlying these differing processes may be related to the fetal environment, the stage of differentiation of the fetal cells or the ECM deposited in the wound. The spatial and temporal distribution of two components of the ECM, fibronectin and tenascin, were studied by immunostaining of cryosections from trunk wounds of fetal and adult sheep. Epithelialisation was complete earlier in the fetal wound than in the adult. The distribution of fibronectin was similar in fetal and adult wounds but tenascin was present earlier in the fetal wound. Fibronectin has several roles in wound healing including acting as a substratum for cell migration and as a mediator of cell adhesion through cell surface integrins. The attachment of fibroblasts to fibronectin is inhibited by tenascin and during development the appearance of tenascin in the ECM of migratory pathways correlates with the initiation of cell migration. Similarly, the appearance of tenascin in healing wounds may initiate cell migration. Tenascin was present in these wounds prior to cell migration and the rapid epithelialisation of fetal wounds may be due to the early appearance of tenascin in the wound.

Animals↗
PubMed1991

Hematopoietic chimerism in sheep and nonhuman primates by in utero transplantation of fetal hematopoietic stem cells.

Bone marrow transplantation to reconstitute defective hematopoietic cell lines in children with congenital defects is limited by donor availability, graft rejection, and graft-versus-host disease (GVHD). These problems can be eliminated by transplanting normal preimmune fetal hematopoietic stem cells (HSC) into an unrelated preimmune fetal recipient. We show here that injections of allogeneic fetal stem cells into preimmune fetal lambs and monkeys result in long-term stable hematopoietic chimerism. HSCs harvested from the livers of preimmune fetal sheep and monkeys when injected into the peritoneal cavity of young unrelated fetal sheep and monkey recipients results in stable, long-term postnatal hematopoietic chimerism involving lymphoid, erythroid, and myeloid cells of donor origin. Donor cell engraftment was achieved without the use of cytoablative procedures and without the development of GVHD.

Animals↗