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Biomedical subjects

V D Fiegel

Publications and source records attributed to V D Fiegel.

At least 19 recordsLinked to original sources
PubMed1996

The effect of the platelet derived wound healing formula and the nerve growth factor on the experimentally injured spinal cord.

The main purpose of this study is to investigate the effect of platelet derived wound healing formula (PDWHF) and nerve growth factor (NGF) in the treatment of experimental spinal cord injury. PDWHF is a conglomerate of growth factors which include platelet derived growth factor (PDGF), platelet derived angiogenesis factor (PDAF), transforming growth factor-beta (TGF beta) and platelet factor IV (PF4). Complete spinal cord transection was performed at T12 in rats and the treatment of the spinal cord injury was achieved by filling the dead space with type 1 collagen gel impregnated with PDWHF, or with 2.5S-NGF. Controls were treated with only type 1 collagen gel. Animals were sacrificed at 1, 2 or 3 months. Histopathologically, tissue autolysis and cavity formation by phagocytosis expanded 1-3 mm into the cord stumps and the volume of cavitation was less in the two treated groups. In the NGF group, a greater number of surviving nerve cells were observed in this region. Most of the control animals formed only thin, short axonal bundles, however, increased axonal regrowth was noted in animals treated with trophic factors, especially in the NGF group. The NGF group formed thick axonal bundles and abundant neuroma. Increased angiogenesis was observed in the collagen gel matrix and the injured spinal cord parenchyma, in the PDWHF group. Recent studies have shown that mammalian adult CNS possesses the ability for structural and/or functional plasticity following injury under appropriate circumstances. In this in vivo study, exogenous NGF appeared to induce axomal outgrowth and nerve cell survival. PDWHF produced notable angiogenesis which seemed to improve the extracellular microenvironment. This may be important for the delivery of exogenous trophic factors, nutrients and for the changes of extracellular matrices to support nerve cells and axons.

Animals↗
PubMed1993

In vivo angiogenesis by platelet-derived wound-healing formula in injured spinal cord.

In vivo angiogenesis was investigated using platelet-derived wound-healing formula (PDWHF) in the injured cat spinal cord. Twenty-two gauge teflon sheaths, which had been coated with PDWHF-Hydron or only with Hydron, were inserted into the spinal cords of cats and the injured cats were maintained for 3 weeks. Selection of PDWHF-Hydron or Hydron was double blinded. The PDWHF-Hydron group showed notable neovascularization as well as dilation around the injury site, and this was statistically significant when compared to the control group. PDWHF seems to play a role in the healing processes of spinal cord injury and may have important interactions with other growth factors and in particular neurogenic growth factor.

Animals↗
PubMed1993

Growth factors and comprehensive surgical care of diabetic wounds.

In diabetic patients, nonhealing cutaneous ulcers are a significant clinical, social, and healthcare problem. Based on more than 10 million diabetic patients in the United States and an estimated prevalence of 15% for chronic cutaneous ulcers, there are approximately 1.5 million patients with this problem. These nonhealing cutaneous ulcers result in a high rate of lower extremity amputations in the diabetic population. Patients with diabetes have many complications that cause chronic cutaneous ulcers. These include peripheral vascular disease, autonomic and sensory neuropathy, impaired host defense against infection, and delayed wound repair. To treat diabetic patients with chronic cutaneous ulcers effectively all the complicating factors must be addressed. In this review we discuss the surgical care of these patients and the use of growth factors in combination with a comprehensive treatment algorithm.

Adult↗
PubMed1993

Alloxan diabetes alters the rabbit transarterial wall oxygen gradient.

PURPOSE: Atherosclerotic vascular occlusive disease is the most common complication of diabetes mellitus and accounts for 75% of deaths in diabetic patients. Determining the initiator and continuing stimulus for the cellular events in the formation of atherosclerotic lesions in diabetic patients could lead to the prevention of this common and deadly complication. Diabetes-induced arterial wall hypoxia is proposed as an initiator and continuing stimulus for atherosclerotic vascular occlusive disease. METHODS: Transarterial wall oxygen gradient measurements were performed on the infrarenal aorta with an oxygen microelectrode 14 to 16 weeks after the induction of alloxan diabetes in rabbits. RESULTS: Both insulin-treated and untreated alloxan diabetic rabbits revealed significantly decreased oxygen tensions throughout the arterial wall compared with control rabbits. There was no significant difference in the transarterial wall oxygen gradient between the two groups of diabetic rabbits. This effect was noted despite no difference in the partial pressure of oxygen in arterial blood or visual evidence of atherosclerotic lesion formation in the three groups. CONCLUSIONS: These findings suggest that diabetes induces arterial wall hypoxia independent of insulin therapy and before the formation of atherosclerotic lesions. Diabetes-induced arterial wall hypoxia may contribute to the formation of atherosclerotic lesions.

Animals↗
PubMed1992

The effect of diabetes on the proliferation of aortic endothelial cells.

Diabetic vascular disease is more severe, diffuse, and accelerated when compared to nondiabetic vascular disease. Endothelial cell injury or alteration in endothelial cell function is hypothesized to be the initial cellular event in the pathophysiology of diabetic vascular disease. We examined the effect of insulin-treated and untreated alloxan diabetes on the proliferation of rabbit aortic endothelial cells in vitro by growing thoracic aortic endothelial cells from alloxan diabetic rabbits in serum obtained from alloxan diabetic rabbits. Diabetes adversely affected the proliferation of aortic endothelial cells; the most significant decrease in cell proliferation was noted in untreated diabetic cells. Crossover studies between endothelial cells and serum from different groups revealed that diabetes slows endothelial proliferation by not only a serum effect but also an intrinsic cellular effect. These observations suggest that diabetes adversely affects the proliferation of aortic endothelial cells by changing cell and serum functions.

Alloxan↗
PubMed1992

The effect of growth factor formula (platelet derived wound healing formula) in experimental spinal cord injuries.

The main purpose of this study was to investigate the usefulness of platelet derived wound healing formula (PDWHF) in the treatment of experimentally induced spinal cord injuries in cats. The injury model in ten adult cats consisted of the placement of three 22-gauge Teflon catheter sheaths into the spinal cord at the L2 level. Treatment consisted of coating these sheaths with PDWHF in Hydron. Three animals were used as controls. In the 7 remaining cats, treatment was double blinded. Cats were sacrificed at 3 weeks after injury and injured spinal cord segments were excised for histologic evaluation. Electrophysiologic and clinical motor function were evaluated throughout a period of observation. Evoked potentials in both the treated and control groups indicated incomplete spinal cord lesions due to insertion of the needles. There did not appear to be any significant improvement or difference in the evoked response and clinical function as a result of treatment with PDWHF. The histological findings in the PDWHF-treated group showed significant new vessel formation as well as dilation and around the injury site. This neovascularization, both qualitative and quantitative, was noted in the treatment group. This information, with a limited injury and very simple delivery system for growth factor, would suggest there is definite neovascularization occurring as a result of this treatment and this may be useful in the subsequent wound healing response such as axonal growth and scar tissue formation.

Animals↗
PubMed1992

Changes in the aortic wall oxygen tensions of hypertensive rabbits. Hypertension and aortic wall oxygen.

Hypertension is a known risk factor for atherosclerosis. We hypothesize that hypertension causes artery wall hypoxia that contributes to the formation of atherosclerotic lesions. Therefore, we examined the effect of hypertension on the transarterial wall oxygen gradient of the rabbit aorta. Hypertensive rabbits were created by unilateral nephrectomy and contralateral renal artery narrowing. Transarterial wall oxygen gradients of the infrarenal aorta were measured using an oxygen microelectrode 14-16 weeks (short-term hypertension) and 56-58 weeks (long-term hypertension) after the rabbits were made hypertensive. The transarterial wall oxygen gradients showed significant differences among the groups. Short-term hypertension caused significantly higher oxygen tensions in the outer 30% of the artery wall and significant thinning of the artery wall when compared with long-term hypertension and control groups. Long-term hypertension caused significantly lower oxygen tensions in the inner 40% of the artery wall and significant thickening of the artery wall when compared with short-term hypertension and control groups. These changes were noted despite no difference in the partial pressure of oxygen in arterial blood or visual evidence of atherosclerotic lesion formation in the three groups. These findings suggest that hypertension alters the transarterial wall oxygen gradient. This altered transarterial wall oxygen gradient may contribute to the formation of atherosclerotic lesions.

Acute Disease↗
PubMed1992

Induction of neointima formation by platelet derived angiogenesis fraction in a small diameter, wide pore, PTFE graft.

Enhancement of endothelialization and patency of a small diameter (2 mm), wide pore, PTFE graft was attempted by coating the luminal surface with a platelet derived angiogenesis fraction (PDAF) and implanting it in a rat model. PDAF was delivered to the grafts by combining it with a carrier polymer. PDAF-treated grafts were initially implanted in the retroperitoneum for 21 days followed by removal of one for histology and in situ end to side bypass to the infrarenal aorta for the other. Vascularized grafts were examined at 14 days for patency and 100 days for patency and histology. Significant differences were noted in transmural ingrowth of capillaries and tissue at 21 days post implantation in PDAF-treated versus untreated grafts. Similarly, near significance was noted in capillary ingrowth and significance was noted in tissue ingrowth at 100 days in PDAF-treated grafts. Despite favorable trends particularly early in the time course, no significant differences in graft patency, endothelialization, or hydroxyproline content was demonstrated between PDAF-treated and untreated grafts. Results of this preliminary study are encouraging for further study of PDAF-treated PTFE grafts and the potential that rapid vascularized neointima formation results improved in graft patency rates.

Animals↗
PubMed1991

Rabbit aortic endothelial cell hypoxia induces secretion of transforming growth factor beta and augments macrophage adhesion in vitro.

Hypoxic injury of vascular endothelial cells is hypothesized to be the initial cellular event in the formation of an atherosclerotic lesion. We studied the effect of various oxygen tensions on rabbit aortic endothelial cells in culture to determine macrophage adhesion and analyzed endothelial cell-conditioned media for fibroblast mitogenesis and transforming growth factor beta production. Fibroblast mitogenesis assay of endothelial cell-conditioned media revealed decreased activity at lower oxygen tensions. Further study revealed an inverse relationship between oxygen tension and aortic endothelial cell production of transforming growth factor beta despite lower total numbers of viable aortic endothelial cells at lower oxygen tensions. When rabbit aortic endothelial cells grown at various oxygen tensions were incubated with five day old bone marrow macrophages, an increase in macrophage adherence to aortic endothelial cells was noted at low oxygen tensions. Our observations suggest that aortic endothelial cell hypoxia leads to the production of transforming growth factor beta, a known monocyte chemoattractant. Monocytes may marginate and then adhere to endothelial cells, their adherence being augmented by endothelial cell hypoxia. This may contribute to the initial cellular events in the formation of an atherosclerotic lesion.

Animals↗
PubMed1991

An angiogenic extract from skeletal muscle stimulates monocyte and endothelial cell chemotaxis in vitro.

The purpose of this study was to determine whether the extraction of skeletal muscle with a combination of ethanol and hydrochloric acid yields a product capable of stimulating angiogenesis. The resulting extract stimulated inflammation in the rabbit corneal assay, which was followed by capillary formation. In order to determine whether the observed angiogenesis was stimulated by a factor(s) acting directly on the endothelial cells versus a factor(s) recruiting macrophages that in turn release factors acting on endothelial cells, the muscle extract was tested for endothelial cell and monocyte chemotaxis activity in vitro. The muscle extract stimulated significant endothelial cell chemotaxis at concentrations between 94 and 750 micrograms of protein/ml and significant monocyte chemotaxis at concentrations between 8 and 75 micrograms of protein/ml. Polyacrylamide gel electrophoresis suggests that basic fibroblast growth factor and transforming growth factor-beta may be present in this acid/ethanol extract of skeletal muscle.

Animals↗
PubMed1990

Oxygen as an antibiotic. The effect of inspired oxygen on bacterial clearance.

Previous experimentation with the guinea pig skin injection model showed that altering the fraction of inspired oxygen had a significant effect on infectious necrosis. Using the same model, we performed quantitative bacterial cultures to determine the number of viable injected bacteria 24 and 48 hours after injection. Animals were randomized to receive 12%, 21%, and 45% inspired oxygen. A significant decrease in bacterial number was seen at 45% inspired oxygen between 24 and 48 hours, and a significant decrease occurred at 48 hours between 12% and 45% inspired oxygen. These results demonstrated a prominent role for oxygen in bacterial clearance and host defense.

Administration, Inhalation↗
PubMed1990

Amputation prevention in an independently reviewed at-risk diabetic population using a comprehensive wound care protocol.

An independent review panel composed of an orthopedic surgeon, a vascular surgeon, and an endocrinologist was convened to conduct a case history review. The 71 patients reviewed had 124 wounds on 81 limbs and participated in the comprehensive wound management program of the University of Minnesota. Based on their expertise, the review panel classified the wounds by severity and identified the limb's risk for amputation. The resulting scores were then compared with the patient's actual outcome. The review panel predicted 65 (80%) of the limbs would be salvaged and 16 (20%) would be amputated. The actual outcome was that 75 (93%) of the limbs were salvaged and 6 (7%) were amputated (p less than 0.005). The university's wound management program was highly successful, compared with the predictions of the reviewers.

Amputation, Surgical↗
PubMed1990

Wound healing angiogenesis: indirect stimulation by basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) was tested for its ability to stimulate angiogenesis in vivo using the rabbit corneal assay. Basic FGF (50-1,000 ng) was incorporated into 10% Hydron, and 50-500 ng of bFGF were incorporated into 10% Elvax. Human serum albumin (HSA) (10 ng) and 50 ng of transforming growth factor-beta (TGF-beta) served as negative and positive controls. Pellets of the polymers containing test compounds were implanted in the rabbit cornea, examined daily, and after 7 days corneal angiogenesis was scored on a graded scale [(-) for no response and +4 for a maximum response]. Histologic analysis of the corneas was performed on days 2 and 7. Basic FGF (50-500 ng) in Hydron failed to stimulate significant angiogenesis, though it did induce angiogenesis accompanied by inflammation at the 1,000-ng dose. Basic FGF in Elvax elicited inflammation-associated +3 to +4 responses at all doses tested. New blood vessels did not form in response to HSA in Hydron or Elvax, while TGF-beta induced +4 angiogenesis accompanied by vigorous inflammation. In vivo release kinetics for bFGF in Hydron and Elvax were compared, and the release of bioactive bFGF from Hydron and Elvax was demonstrated in vitro. These results suggest that the bFGF and Elvax combination incites an inflammatory response which stimulates indirect angiogenesis, while the same concentrations of bFGF delivered in Hydron produced no inflammation or angiogenesis. Although bFGF alone is a potent mitogen for endothelial cells, it does not appear to directly stimulate in vivo angiogenesis.

Animals↗
PubMed1990

Stimulation of repair in chronic, nonhealing, cutaneous ulcers using platelet-derived wound healing formula.

Chronic, nonhealing, cutaneous ulcers are a serious clinical problem. The results of previous studies using platelet-derived wound healing formula (PDWHF), derived from autologous platelets, provided evidence that PDWHF actively stimulates repair of the wound. To test whether or not PDWHF accelerates repair, a prospectively randomized, blinded trial was conducted using a placebo control. A total of 32 patients with chronic, nonhealing, cutaneous wounds of the lower extremity were randomized and treated for eight weeks with PDWHF or placebo. Epithelialization of the wound was the end point of study. In the group who received treatment, 81 per cent of patients had epithelialization in eight weeks compared with 15 per cent in the control group (p less than 0.0001). After crossover to treatment with PDWHF, all of the patients in the control group had epithelialization in an average of 7.1 weeks. Regression analysis of the rates of epithelialization also showed significant differences during the initial eight week trial and showed no difference after crossover of the control group to therapy with PDWHF. Results from this study demonstrate a highly statistically significant effect of topically applied platelet-derived growth factors on the repair of chronic, nonhealing, cutaneous ulcers.

Chronic Disease↗
PubMed1989

Macrophage-derived growth factors in wound healing: regulation of growth factor production by the oxygen microenvironment.

There is a large amount of current research investigating the pathophysiologic aspects of pulmonary hypertension. Results of this research indicate the potential role of the macrophage as one possible mediator of pulmonary hypertension. The macrophage has been shown to produce numerous soluble mediators, including various growth factors, some of which may be involved in the cellular proliferation of the arterial wall. Most of the knowledge regarding oxygen microenvironments, macrophages, and growth factor production comes from research on the healing wound. A considerable amount of what has been learned about the role of the macrophage in cutaneous wound healing may have direct applicability to macrophage function in acute lung injury and repair, and pulmonary hypertension. Macrophages play a pivotal role in cutaneous wound repair. They participate in immunologic and nonspecific host defense responses and produce numerous growth factors that regulate mesenchymal cell proliferation, migration, and synthesis of extracellular matrix proteins. These same responses are probably at work during the progression of pulmonary hypertension.

Growth Substances↗