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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1999

Mid-trimester fetal livers are a rich source of CD34+/++ cells for transplantation.

Human fetal livers (FL), between 16 and 24 weeks of gestation, were studied for their potential as a source of hematopoietic stem cells for prenatal and postnatal transplantation. In this report we give a quantitative evaluation of human FL as a source of candidate stem cells, and develop a protocol for the isolation of these cells free of microbial contaminants and almost free of mature T cells. Human FLs contained a median 1.9 x 10(9) viable cells and a mean of 1.3 x 10(8) CD34+/++ cells (range 1.1 x 10(7) to 4.7 x 10(8)). Regardless of gestational age, no significant differences were apparent in the numbers of total progenitors or in the numbers of candidate stem cells (CD34++ CD38- and CD34++CD4+), suggesting that the expansion in the liver of the early compartments of hematopoietic progenitors reaches a plateau after the sixteenth week of gestation. Colony-forming units culture (CFU-C) were found to range from 4.1 x 10(6) to 2.5 x 10(7) per FL. Positive selection of FL CD34++ cells was achieved using the Baxter Isolex 50 device. An average purity of 74% and yield of 29% of CD34+/++ cells was achieved. T cells were depleted by 99.95%, resulting in a mean of 6.5 x 10(3) T cells per processed liver. Analysis of candidate stem cell populations and primitive colony-forming cells (CFC) suggested a preferential enrichment of these cells over the total population of CD34+/++ cells. Processed CD34+/++cells were found to be sterile. In conclusion, purification of FL progenitors between 16 and 24 weeks of gestation results in a large number of early progenitors suitable for in utero and possibly post-natal transplantation.

Antigens, CD34↗
PubMed1999

Optimizing femorotibial alignment in high tibial osteotomy.

OBJECTIVE: To study factors that affect femorotibial (F-T) alignment after valgus closing wedge tibial osteotomy. STUDY DESIGN: A review of standardized standing radiographs. Femorotibial alignment was measured 1 year postoperatively for over- and under-correction. Changes in F-T alignment and in tibial plateau angle were measured. SETTING: An urban hospital and orthopedic clinic. PATIENTS: Eighty-two patients with osteoarthritis and varus femorotibial alignment underwent valgus closing wedge tibial osteotomy. Patients having a diagnosis of inflammatory arthritis or a prior osteotomy about the knee were excluded. RESULTS: A 1 degree wedge removed from the tibia resulted in an average correction F-T alignment of 1.2 degrees. A knee that had increased valgus orientation of the distal femur had a greater degree of correction, averaging 1.46 degrees in F-T alignment per degree of tibial wedge. This resulted in excessive postoperative valgus alignment for some patients who had increased valgus tilt of the distal femur. Optimal F-T alignment of 6 degrees to 14 degrees valgus occurred when the postoperative tibial inclination was 4 degrees to 8 degrees of valgus. CONCLUSIONS: There was a trend for knees with increased valgus orientation of the distal femur to have greater correction in F-T alignment after tibial osteotomy, likely because of a greater opening up of the medial joint space during stance. Surgeons need to account for this in their preoperative planning.

Anthropometry↗
PubMed1998

Growth factor protection against cytokine-induced apoptosis in neonatal rat islets of Langerhans: role of Fas.

Treatment of neonatal rat islets of Langerhans with combined cytokines (interleukin-1beta 10(-10) M, tumour necrosis factor-alpha 10(-10) M, interferon-gamma 5 U/ml) led to extensive cell death, which was potentiated by Fas activation with the anti-Fas cytolytic antibody JO2. Pre-treatment with insulin (25 ng/ml) or insulin-like growth factor-1 (10(-8)M) gave only partial protection against cell killing, but prevented the Fas-mediated component. In the absence of cytokine treatment, Fas-mediated killing was not observed.

Animals↗
PubMed1998

Pulmonary edema in obstetric patients is rapidly resolved except in the presence of infection or of nitroglycerin tocolysis after open fetal surgery.

OBJECTIVES: This study was designed to determine the etiology, course, and severity of pulmonary edema in obstetric patients in a tertiary care center. STUDY DESIGN: A retrospective study was carried out on 16,810 deliveries from University of California, San Francisco, 1985-1995. Diagnosis and severity of lung injury were defined by a 4-point system that was based on the chest radiograph, oxygenation, positive end-expiratory pressure, and lung compliance. Resolution of pulmonary edema was defined by improvement in the chest radiograph and hypoxemia (ratio of arterial oxygen tension to inspired oxygen concentration) scores or by extubation. RESULTS: Pulmonary edema developed in 86 patients, or 0.5% of all obstetric cases. It usually showed extensive air space consolidation on the chest radiograph and arterial hypoxemia. Although 43% of the patients had severe pulmonary dysfunction, the average time to resolution of pulmonary edema was 2.4 days. Only 45% of patients required admission to the intensive care unit and only 15% required intubation and positive-pressure ventilation. Patients with infection (mean of 7.2 days) or fetal surgery (mean of 3.8 days) had the most severe, protracted course. CONCLUSION: Although obstetric pulmonary edema is associated with extensive radiographic infiltrates and severe hypoxemia, resolution occurs rapidly in most patients, limiting the need for intensive care support.

Critical Care↗
PubMed1998

Alpha 2 adrenergic agonists. Neurochemistry, efficacy, and clinical guidelines for use in children.

The alpha 2 adrenergic agonists are used to treat a variety of psychiatric disorders and their usage has been increasing. This article presents the rationale and neurochemical basis for treatment of psychiatric disorders with alpha 2 agents, reviews studies examining clinical efficacy, and develops guidelines for usage. Case vignettes are presented to illustrate how the alpha 2 agents can successfully be used in practice.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1998

Response and cosmetic outcome of two fractionation regimens for AIDS-related Kaposi's sarcoma.

PURPOSE: A prospective study of the response and cosmetic effect of two short duration radiotherapy regimens in the treatment of epidemic cutaneous Kaposi's sarcoma. MATERIALS AND METHODS: Between June 1990 and May 1994, 57 patients were recruited into a prospective study of radiotherapy for cutaneous epidemic Kaposi's sarcoma. Patients were offered treatment of either 16 Gy in four fractions over 4 days or 8 Gy as a single fraction. In total 596 lesions were treated in a prospective fashion. Response was assessed in 590 and pigmentation in 573 lesions. A reproducible scale for assessing response and normal cutaneous damage was developed and used to grade the results of treatment. RESULTS: There was an overall response rate of 78.8% (465/590) for complete responses and pigmented complete responses. Patients receiving 8 Gy as a single fraction had an overall response rate of 77.6% (305/393) and those treated with 16 Gy in four fractions had a response rate of 80.8% (160/198). There was no statistical difference in terms of response between the two groups. There appeared to be a significant variation in response and normal skin pigmentation according to the site irradiated with facial lesions responding best. CONCLUSIONS: Radiotherapy is a quick and effective treatment for cutaneous epidemic Kaposi's sarcoma. A single fraction of 8 Gy is an appropriate treatment for acceptable response and normal skin pigmentation within a group of patients in whom the median life expectancy is limited.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Gingival fibromatosis with prune-belly syndrome.

A case is described in which a child appeared for evaluation with marked gingival overgrowth, facial dysmorphism, and abdominal defects consistent with prune-belly syndrome. The relationship between this case and other reports of gingival enlargement are discussed. Coincidence of the oral, facial, and abdominal abnormalities has not been previously reported.

Child, Preschool↗
PubMed1998

HOX homeobox genes exhibit spatial and temporal changes in expression during human skin development.

The spatial and temporal deployment of HOX homeobox genes along the spinal axis and in limb buds during fetal development is a key program in embryonic pattern formation. Although we have previously reported that several of the HOX homeobox genes are expressed during murine skin development, there is no information about developmental expression of HOX genes in human skin. We have now used reverse transcriptase polymerase chain reaction, in conjunction with a set of degenerate oligonucleotide primers, to identify a subset of HOX genes that are expressed during human fetal skin development. In situ hybridization analyses demonstrated that there were temporal and spatial shifts in expression of these genes. Strong HOXA4 expression was detected in the basal cell layers of 10 wk fetal epidermis and throughout the epidermis and dermis of 17 wk skin, whereas weak signal was present in the granular layer of newborn and adult skin. The expression patterns of HOXA5 and HOXA7 were similar, but their expression was weaker. In situ hybridization analysis also revealed strong HOXC4 and weaker HOXB7 expression throughout fetal development, whereas HOXB4 was expressed at barely detectable levels. Differential HOX gene expression was also observed in developing hair follicles, and sebaceous and sweat glands. None of the HOX genes examined were detected in the adult dermis.

Adult↗
PubMed1998

Modulation of the human homeobox genes PRX-2 and HOXB13 in scarless fetal wounds.

Scarless healing of cutaneous wounds occurs in humans during the first two trimesters of development, but by birth all wounds are repaired with scar formation. To search for transcriptional regulatory genes that might mediate fetal tissue regeneration, we surveyed homeobox gene expression in proliferating fetal fibroblasts and in wounded and unwounded skin. Two novel human homeobox genes, PRX-2 and HOXB13, were identified that were differentially expressed during fetal versus adult wound healing. Both genes were predominantly expressed in proliferating fetal fibroblasts and developing dermis, and PRX-2 was downregulated in adult skin. In a model of scarless fetal skin regeneration, PRX-2 expression was strongly increased compared with unwounded skin and the signal was localized to the wounded dermis, the site of scarless repair. Conversely, in adult skin weak epidermal PRX-2 expression was observed, mRNA levels were not increased by wounding, and no dermal expression was detected. HOXB13 expression was decreased in wounded fetal tissue relative to unwounded fetal controls or wounded adult skin. Thus both HOXB13 and PRX-2 are expressed in patterns consistent with roles in fetal skin development and cutaneous regeneration.

Cells, Cultured↗
PubMed1998

Endogenous insulin and insulin sensitivity. An important determinant of skeletal muscle blood flow in chronic heart failure?

AIM: Patients with heart failure have a reduced sensitivity to insulin's actions on glucose metabolism and a compensatory increase in endogenous plasma insulin levels. As insulin has a selective vasodilatory action in skeletal muscle, we have studied the association between insulin sensitivity and central and regional haemodynamics in patients with heart failure. METHODS: Ten patients with stable symptomatic heart failure were studied. We used non-invasive techniques to measure cardiac output, forearm blood flow, superior mesenteric artery blood flow and right renal artery blood flow. Blood samples were assayed for noradrenaline, renin and atrial natriuretic peptide levels. Insulin sensitivity was assessed using the low dose short insulin tolerance test. RESULTS: There was a significant inverse correlation between forearm blood flow and insulin sensitivity (r = -0.67, P = 0.03), patients with lesser degrees of insulin sensitivity having the greater forearm blood flows. There was no correlation with the other haemodynamic or neurohumoral parameters. Patients with greater insulin resistance tended to have higher circulating endogenous insulin levels, although this relationship did not reach statistical significance (r = -0.53, P = 0.12). CONCLUSIONS: Insulin sensitivity appears to be an important determinant of skeletal muscle blood flow in heart failure. We speculate that this is secondary to the increased circulating endogenous insulin levels, and suggest that the therapeutic potential of exogenous insulin merits further investigation.

Aged↗
PubMed1998

Total quality management in the delivery of public health services: a focus on North Carolina WIC programs.

Principles of quality improvement have been successfully implemented in the for-profit sector of the United States economy. The purpose of this study is to test the use of quality improvement strategies including development of leadership skills, a focus on internal quality, ongoing training and staff development, and efficient use of resources in the delivery of services in the public sector. The emphasis of this study is strategies for improving the delivery of nutrition education and supplemental foods to high-risk women, infants, and children through a federally funded program called WIC.

Child Health Services↗
PubMed1998

"Value" of improved treadmill exercise capacity: lessons from a study of rate responsive pacing.

OBJECTIVES: To compare the value of a series of cardiovascular measurements in patients with symptomatic disease receiving an effective treatment (rate responsive pacing). PATIENTS: 12 pacemaker dependent patients with VVIR units. INTERVENTIONS: Single blind crossover between VVI and VVIR. OUTCOME MEASURES: Exercise capacity was assessed by treadmill tests (modified Bruce protocol and a fixed workload protocol) with respiratory gas analysis. Self paced corridor walk tests were also undertaken. Quality of life (QOL) was assessed by questionnaire. Daily activity was measured in the patients' homes using shoe and belt pedometers. RESULTS: Treadmill tests and QOL questionnaires correctly identified the clinical benefit associated with VVIR. The modified Bruce protocol was superior to the fixed workload protocol as it was better tailored to the fairly well preserved exercise capacity of the patients. Symptom scores, but not walking times, were improved with VVIR during corridor walk tests. VVIR did not improve daily activity measured using either the belt or shoe pedometers. CONCLUSIONS: VVIR pacing improved some but not all measures of exercise capacity. This finding illustrates the difficulty of selecting an instrument to measure symptomatic improvement in clinical research; and raises the question, what is the best way of measuring exercise capacity?

Activities of Daily Living↗