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Biomedical subjects

L F Brown

Publications and source records attributed to L F Brown.

At least 55 records · Page 3Linked to original sources
PubMed1997

The reliability of reporting of contraceptive behavior in DHS calendar data: evidence from Morocco.

This report addresses the consistency of reporting in the contraceptive calendar in the 1992 and 1995 Morocco Demographic and Health Surveys. Because a panel design was used in these surveys, the same women were interviewed in both years, providing a unique opportunity to examine the reliability of responses. Measures of reliability for various aspects of contraceptive-use dynamics are computed, and the impact of reporting errors on contraceptive failure, discontinuation, and switching rates is estimated. Results suggest that reporting of contraceptive behavior in Moroccan DHS calendar data appears to be relatively reliable at the aggregate level. Individual respondents, particularly those whose contraceptive patterns have been complex, have a lower level of reliability. The observed inconsistencies do not appear to affect aggregate-level estimates of contraceptive prevalence; however, measures of contraceptive-use dynamics are less stable.

Adult↗
PubMed1997

Expression of fibronectin splicing variants in organ transplantation: a differential pattern between rat cardiac allografts and isografts.

Allograft rejection is associated with infiltration of inflammatory cells and deposition of extracellular matrix proteins. The extent to which diversity in the extracellular matrix regulates inflammatory cell function in transplants remains unclear. One group of extracellular matrix proteins, termed fibronectins (FNs), exhibits inherent diversity as a consequence of alternative splicing in three segments: EIIIA, EIIIB, or V. Although the EIIIA segment has documented functions in mesenchymal cell differentiation, neither this segment nor the EIIIB segment have been tested for effects specific to leukocyte functions. By contrast, the V region can include the CS-1 segment to which leukocytes may adhere through alpha 4 beta 1 integrins. In this study, we demonstrate that EIIIA+, EIIIB+, and V+ FN variants are synthesized, primarily by macrophages in distinct temporal and spatial patterns in two rat cardiac transplant models: either with antigenic challenge, allografts, or without challenge, isografts. The ratio of EIIIA inclusion into FN increases by day 1 in allografts and isografts and remains high until allografts are rejected (approximately 7 days) but falls to normal levels in tolerated isografts (day 6). EIIIB+ FN ratios in allografts peak later than do EIIIA+ FNs (day 4). EIIIB+ FN ratios remain relatively low in isografts. Interestingly, EIIIA+ and EIIIB+ FNs are deposited prominently in the myocardium of rejecting allografts in close association with infiltrating leukocytes, and FN expression and deposition are prominent at sites of infarction. By contrast, these FNs are largely restricted to the epicardium and to a lesser degree in the immediately adjacent myocardium in isografts. CS-1+ FNs increase in allografts and isografts at 3 hours after transplantation but are particularly prominent in allografts 1 to 3 days before rejection. Our data suggest that FN splicing variants have a differential role in the effector functions of leukocytes in allografts and isografts and provide a foundation for testing their function on leukocytes and a rationale for FN-based therapeutics to modulate allograft rejection in transplant recipients.

Alternative Splicing↗
PubMed1997

Osteopontin is strongly expressed by histiocytes in granulomas of diverse etiology.

Granulomatous inflammation is associated with a variety of important pathologic conditions. Osteopontin (OPN), a ligand for the alpha v beta 3 integrin, is a secreted glycoprotein with a glycine-arginine-glycine-aspartate-serine cell-binding domain. In this study, we examined expression of OPN in 22 cases of granulomatous inflammation including cases of sarcoidosis, granulomatous temporal arteritis, histoplasmosis, rheumatoid nodule, granuloma annulare, erythema nodosum, granulomatous gastritis, foreign body giant-cell granulomatous reactions, and lipogranulomas. Strong expression of OPN mRNA and protein was seen in the epithelioid histiocytes and multinucleate histiocytic giant cells in granulomas by in situ hybridization and immunostaining. OPN may play an important role in granulomatous inflammation through the regulation of processes such as histiocyte migration, cell adhesion, and cellular functions including phagocytosis.

Animals↗
PubMed1997

Vascular permeability factor/vascular endothelial growth factor and its receptors in oral and laryngeal squamous cell carcinoma and dysplasia.

Increased microvessel density has been described in squamous cell carcinoma of the head and neck and is related to patient prognosis. The factors responsible for the angiogenesis have not been identified. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional angiogenic cytokine expressed at high levels in many tumors. We examined 16 cases of squamous cell carcinoma, 10 cases of high-grade squamous dysplasia, and 19 cases of normal, reactive, or mildly dysplastic squamous mucosa by in situ hybridization for expression of VPF/VEGF and VPF/VEGF receptor mRNA. Strong expression of VPF/VEGF mRNA was seen in 12 of 16 squamous cell carcinomas and in 5 of 10 high-grade squamous dysplasias. In contrast, no cases of normal, reactive, or mild dysplastic squamous epithelium showed strong expression of VPF/VEGF mRNA. Furthermore, strong expression of VPF/VEGF receptor mRNA was seen in 5 of 9 cases of squamous cell carcinoma and 3 of 6 cases of high-grade squamous dysplasia but in only 2 of 14 cases of normal, reactive, or mild dysplastic squamous epithelium. Thus, expression of VPF/VEGF and its receptors is markedly increased in high-grade squamous dysplasia and invasive squamous cell carcinoma of the oral cavity and larynx and may play an important role in the angiogenesis associated with these lesions.

Bronchopulmonary Dysplasia↗
PubMed1996

Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma.

BACKGROUND: Solid tumors, including endometrial carcinomas, must induce a vascular stroma to grow beyond a minimal size. The mechanisms responsible for angiogenesis in endometrial carcinoma, however, are not well defined. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is an important regulator of tumor angiogenesis. We evaluated VPF/VEGF mRNA and protein expression, as well as VPF/VEGF receptor mRNA expression, in endometrial carcinoma. METHODS: Fourteen examples of endometrial carcinoma were evaluated by in situ hybridization; in 7 cases, benign atrophic endometrium from the same patient was also examined. Histologic sections were subjected to in situ hybridization using 35S-labeled riboprobes specific for VPF/VEGF and, in a subset of cases, riboprobes specific for the VPF/VEGF receptors flt-1 and KDR. In addition, ten examples of endometrial carcinoma were evaluated for VPE/VEGF protein expression by immunohistochemistry. RESULTS: All 14 examples of endometrial carcinoma studied by in situ hybridization exhibited focal strong VPF/VEGF mRNA expression by tumor cells. In addition, the endothelial cells of surrounding microvessels strongly expressed flt-1 and KDR mRNAs in all ten cases examined. In contrast, no strong expression of VPF/VEGF, flt-1, or KDR mRNA was observed in the seven examples of benign atrophic endometrium studied. All ten cases of endometrial carcinoma studied by immunohistochemistry exhibited strong VPF/VEGF protein expression by tumor cells. CONCLUSIONS: These observations suggest that VPF/VEGF is an important angiogenic factor in endometrial carcinoma.

Carcinoma, Endometrioid↗
PubMed1996

Social rhythm stability following late-life spousal bereavement: associations with depression and sleep impairment.

The aim of this study was to investigate changes in social rhythm stability and sleep in spousally bereaved subjects (n = 94) and in nonbereaved elderly control subjects (n = 45). Social rhythm stability and activity level were measured with a diary-like instrument, the Social Rhythm Metric (SRM). We observed that spousal bereavement, per se, was not associated with a lower social rhythm stability or activity level except in the presence of a major depressive episode. We also observed an inverse correlation between severity of depression and social rhythm stability, and a positive correlation between depression and both subjective and objective measures of sleep impairment. Higher social rhythm stability was correlated with better sleep in subjects with high activity levels, but not in subjects with low activity levels. Longitudinal data, including pre-bereavement assessment of social rhythm stability, are necessary to ascertain directional effects, i.e., whether loss of spouse occasions disruption of social rhythms or whether such disruption precedes sleep impairment and depression.

Adjustment Disorders↗
PubMed1996

Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF in tumor biology, we screened tumorigenic lines for those expressing minimal constitutive and hypoxia-inducible VPF/VEGF. Human melanoma SK-MEL-2 cells best fit these criteria and formed small, poorly vascularized tumors in immunodeficient mice. We transfected SK-MEL-2 cells stably with sense or antisense mouse VPF/VEGF cDNA or with vector alone. Cells transfected with sense VPF/VEGF (V+) expressed and secreted large amounts of mouse VPF/VEGF and formed well-vascularized tumors with hyperpermeable blood vessels and minimal necrosis in nude/SCID mice. Antisense-transfected VPF/VEGF (V-) cells expressed reduced constitutive VPF/VEGF and no detectable mouse VPF/VEGF, and formed small, minimally vascularized tumors exhibiting extensive necrosis. Vector-alone transfectants (N1 cells) behaved like parental cells. V+ cells formed numerous lung tumor colonies in SCID mice, approximately 50-fold more than N1 cells, whereas V- cells formed few or none. These experiments demonstrate that VPF/VEGF promotes melanoma growth by stimulating angiogenesis and that constitutive VPF/VEGF expression dramatically promotes tumor colonization in the lung.

Animals↗
PubMed1996

Correlation of vascular permeability factor/vascular endothelial growth factor with extraretinal neovascularization in the rat.

OBJECTIVE: To determine whether neovascularization was spatially correlated with the distribution of messenger RNA for vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). METHODS: Neonatal rats were raised 8 days in 80% oxygen with daily intervals of relative hypoxia in room air, then transferred to room air for 5, 7, or 10 additional days. In situ hybridization for VPF/VEGF expression and avascular area were examined in retinas from oxygen-exposed animals and room-air controls. Severity of neovascularization was scored. RESULTS: The inner nuclear layer of oxygen-exposed retinas exhibited a continuous intense band of VPF/VEGF messenger RNA expression across the peripheral avascular zone that dropped sharply in vascular retina. Neovascularization occurred adjacent to regions of greatest expression. Controls had much lower expression and smaller avascular regions. The VPF/VEGF messenger RNA expression was most intense in Müller cells, scattered astrocytes, and amacrine cells, strong in retinal pigment epithelium, and moderate in the remaining inner nuclear layer and ganglion cell layer. CONCLUSION: The expression of VPF/VEGF message was spatially and quantitatively correlated with the neovascularization.

Animals↗
PubMed1996

A comparison of patients attending general dental practices employing or not employing dental hygienists.

Previous studies have shown that dental practices employing dental hygienists provide a more periodontally oriented mix of dental services. Little is known about differences in the characteristics of patients who attend these practices, and whether these reflect the orientation of service delivery. In this study, a comparison was made between patients attending private general dental practices employing hygienists and patients attending practices without hygienists in Adelaide, South Australia. A questionnaire was mailed to 2391 patients, and valid responses were received from 632 patients attending 12 practices employing hygienists, and 1052 patients attending 22 practices not employing hygienists. Bivariate analysis of the responses comparing the two groups of patients was conducted using ANOVA for continuous variables and chi-square statistics for categorical variables. A multiple logistic regression model was developed to identify characteristics of patients attending practices with hygienists. Examination of significant (p < 0.05) findings revealed that patients attending practices with hygienists had a higher socio-economic status, had a more preventive pattern of use of services, had better knowledge of periodontally related topics and it was more likely that the dental profession was their main source of information of these topics. These findings indicate that patient profiles do reflect the orientation of service delivery within dental practices and raise the question of whether the dental practice alters the patient's knowledge and behaviour or whether certain patients selectively seek care from practices with hygienists.

Adult↗
PubMed1996

VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that is thought to function by interacting with two high-affinity receptors, flk-1 and flt-1. In an adult heart, angiogenesis can occur in a number of pathological conditions, including atherosclerosis, hypertrophy, and infarction. To determine the role played by VEGF, flk-1, and flt-1 in this process in vivo, we studied the expression of the growth factor and its receptors in a rat infarct model. After an acute myocardial infarction, we observed an initial rapid (1h) rise in VEGF (275%), flk-1 (375%), and flt-1 (400%) mRNA expression throughout the entire heart. Initial diffuse induction of VEGF, flk-1, and flt-1 expression in the left ventricle was later replaced by an increase predominantly limited to perimyocardial infarction area where angiogenesis was taking place. In situ hybridization showed at 6 h after infarction, viable myocytes adjacent to the infarct zone expressed markedly increased amounts of VEGF. At both 6 and 24 h, microvessels at the infarct edge overexpressed both flk-1 and flt-1 mRNAs; at 3 and 7 days new vessels infiltrating the infarct also overexpressed both receptors and continued for as late as 6 wk. In summary, acute myocardial infarction is accompanied by rapid and prolonged increase in expression of VEGF and its receptors with characteristic spatial and temporal kinetic. These findings suggest that the VEGF/VEGF receptor system plays an important role in the angiogenesis and stromal deposition associated with myocardial infarction.

Animals↗
PubMed1996

Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a potent enhancer of microvascular permeability and a selective endothelial cell growth factor. In normal human kidney, VPF/VEGF mRNA and protein are strongly expressed by visceral glomerular epithelial cells, and VPF/VEGF may be an important regulator of glomerular endothelial cell function. This study examined 47 renal biopsies from patients with a variety of glomerular diseases for expression of VPF/VEGF mRNA and protein by in situ hybridization and immunohisto-chemistry. In many glomerular diseases, VPF/VEGF-expressing cells were decreased in number or absent in areas of focal or global glomerular sclerosis. Decreased numbers of VPF/VEGF-expressing cells in glomeruli were also noted in amyloidosis, diabetes, crescentic glomerulonephritis, and diffuse endocapillary proliferative glomerulonephritis associated with systemic lupus erythematosus. Normally, release of VPF/ VEGF must be under strict control because it is some 50,000 times more potent than histamine as an inducer of microvascular permeability. Damage to visceral epithelial cells in a variety of glomerular diseases has the potential for releasing relatively large amounts of VPF/VEGF locally, leading to increased glomerular permeability. In addition, because VPF/ VEGF is also an endothelial growth factor, the loss of normal, controlled secretion of VPF/VEGF after damage to visceral epithelial cells could lead to important alterations in glomerular endothelial cell function.

Capillary Permeability↗
PubMed1996

Strong expression of kinase insert domain-containing receptor, a vascular permeability factor/vascular endothelial growth factor receptor in AIDS-associated Kaposi's sarcoma and cutaneous angiosarcoma.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), plays an important role in the angiogenesis associated with the growth of many human and animal tumors. VPF/VEGF stimulates endothelial cell growth and increases microvascular permeability by interacting with two endothelial cell tyrosine kinase receptors, KDR and flt-1. We studied 16 cases of AIDS-associated Kaposi's sarcoma (KS), 2 cases of cutaneous angiosarcoma, and 6 cases of capillary hemangioma by in situ hybridization for expression of VPF/VEGF, KDR, and flt-1 mRNAs. We also performed immunohistochemical staining for VPF/VEGF protein in 15 cases. Tumor cells in KS and angiosarcoma strongly expressed KDR but not flt-1 mRNA. Endothelial cells in small stromal vessels in and around these tumors strongly expressed both KDR and flt-1 mRNAs. Tumor cells expressed VPF/VEGF mRNA strongly in only one case of KS, adjacent to an area of necrosis. This was also the only case in which the tumor cells stained substantially for VPF/VEGF protein. VPF/VEGF mRNA and protein were, however, strongly expressed by squamous epithelium in areas of hyperplasia and near areas of ulceration overlying tumors. VPF/VEGF mRNA was also expressed focally at lower levels by infiltrating inflammatory cells, probably macrophages. The strong expression of both KDR and flt-1 in small stromal vessels in and around tumors suggests that VPF/VEGF may be an important regulator of the edema and angiogenesis seen in these tumors. The strong expression of KDR by tumor cells in KS and angiosarcoma implies that VPF/VEGF may also have a direct effect on tumor cells. Tumor cells in four of six capillary hemangiomas strongly expressed both KDR and flt-1 mRNAs in contrast to the high level expression of only KDR observed in the malignant vascular tumors studied. Neither VPF/VEGF mRNA or protein were strongly expressed in capillary hemangiomas. VPF/VEGF and its receptors may play an important but as yet incompletely understood role in the pathogenesis of both benign and malignant vascular tumors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Strong expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in ovarian borderline and malignant neoplasms.

Angiogenesis is a critical factor in the growth, progression, and metastatic spread of solid tumors. Furthermore, angiogenesis has been correlated with prognosis in patients with ovarian cancer. The pathogenesis of the angiogenic events in ovarian cancer, however, are not well defined. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a multifunctional cytokine that has been shown to be an important regulator of tumor angiogenesis. The purpose of the present study was to define the expression of VPF/VEGF and its receptors flt-1 and KDR in ovarian tumors. Four specimens of normal ovarian cortex and 41 specimens of benign (4), borderline (8), and malignant (29) ovarian tumors were studied by in situ hybridization, and in some cases by immunohistochemical analysis. VPF/VEGF protein was also determined by an immunofluorometric assay in cyst fluids obtained from 11 patients, including 7 benign, 2 borderline, and 2 malignant tumors. VPF/VEGF mRNA and protein were expressed by the neoplastic cells in all of the malignant tumors evaluated, with the majority of tumors (28 of 29) showing strong expression of mRNA. Serous borderline tumors had variable VPF/VEGF mRNA expression, with two of six cases showing focal strong expression and four showing low-level expression. No definite expression of VPF/VEGF was seen in two cases of mucinous borderline tumors. No strong expression of VPF/VEGF mRNA was observed in normal ovarian cortex, including surface epithelium, or benign tumors. Substantially higher VPF protein concentrations were detected in cyst fluids of the two malignant (60, 440 pM) and two borderline tumors (210, 590 pM) than in the seven benign serous cysts (mean, 10 +/- 3 pM). In addition, microvascular endothelial cells strongly expressed mRNA of the VPF/VEGF receptors flt-1 and KDR and immunostained for VPF/VEGF protein in the majority of malignant and borderline tumors examined. These findings suggest that VPF/VEGF plays an important role in the angiogenesis associated with ovarian neoplasms.

Adenocarcinoma↗
PubMed1995

Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in cervical neoplasia.

BACKGROUND: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in cervical neoplasia, however, are not well defined. PURPOSE: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. METHODS: Sixty-six cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIII-related antigen were evaluated quantitatively for microvessel density and for the presence of epithelial-stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. RESULTS: VPF mRNA expression, epithelial-stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with low-grade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. CONCLUSIONS: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia.

Carcinoma, Squamous Cell↗
PubMed1995

Overexpression of vascular permeability factor (VPF/VEGF) and its endothelial cell receptors in delayed hypersensitivity skin reactions.

Delayed hypersensitivity (DH) is a T cell-mediated form of immune response characterized by a predominantly perivascular, mononuclear cell infiltrate. The venules in DH reactions are hyperpermeable to plasma proteins, leading to extravasation of plasma fibrinogen and its extravascular clotting to form a fibrin gel that promotes induration and angiogenesis. The mechanisms responsible for microvascular hyperpermeability in DH are unknown. Recently, a cytokine named vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF) has been implicated in the chronic vascular hyperpermeability and angiogenesis of solid and ascites tumors, healing wounds, rheumatoid arthritis, and psoriasis. These findings suggested that VPF/VEGF might also have a role in the pathogenesis of DH. Two model systems were studied: allergic contact dermatitis to poison ivy in human volunteers and classical tuberculin hypersensitivity in rats. In both, in situ hybridization revealed that the mRNAs encoding VPF/VEGF were strikingly overexpressed in keratinocytes of the epidermis; scattered mononuclear cells infiltrating the dermis also overexpressed VPF/VEGF mRNA, to a greater extent in rat tuberculin than in human contact reactions. In contact reactions, mRNAs for two VPF/VEGF vascular endothelial cell receptors, flt-1 and KDR, were also strikingly overexpressed. Abundant fibrin deposition in both models confirmed that dermal microvessels were indeed hyperpermeable to plasma fibrinogen. These results implicate VPF/VEGF as a potentially important mediator in the pathogenesis of cell-mediated immunity and provide further evidence that products of epithelial cells may regulate the inflammatory response.

Animals↗
PubMed1995

Anti-TNF-alpha treatment down-regulates the expression of fibronectin and decreases cellular infiltration of cardiac allografts in rats.

Extracellular matrix (ECM) components provide costimulatory signals for T cell activation in vitro, and may be critical for lymphocyte migration and tissue positioning in vivo. We conducted a series of studies in rat recipients of cardiac allografts to evaluate intragraft expression of a prominent ECM protein, fibronectin (FN), and to analyze the effects of infusing a neutralizing anti-TNF-alpha serum on FN expression and lymphocyte migration into the transplants. LBNF1 cardiac allografts were rejected within 8 days in control LEW rats. A prominent immunohistochemical feature of this immune response was the dense deposition of FN at the graft site as early as 3 h, which then peaked at 4 to 6 days. The early 3-h FN deposition (likely plasma FN) was noted before cellular infiltration. Northern blot analysis established that a marked induction of FN mRNA expression occurred in rejecting cardiac allografts at day 4 after transplantation. To determine the source of FN mRNA, we conducted a series of in situ hybridization studies with probes for FN and lysozyme, a macrophage-specific marker. Indeed, the majority of graft-infiltrating cells expressed lysozyme mRNA and FN mRNA. Administration of anti-TNF-alpha serum into LEW hosts (0.5 ml i.v. at days 1 and 3 only) abrogated acute rejection and prolonged cardiac allograft survival to approximately 13 days. This was accompanied by depressed circulating and intragraft TNF-alpha levels, and markedly down-regulated FN mRNA/protein expression patterns, as compared with those in recipients given nonimmune rabbit serum. Anti-TNF-alpha treatment also markedly decreased graft infiltration by ED1+ monocytes/macrophages, OX-8+, and VLA-4+ cells, normally peaking at 4 days. Moreover, we found that the migration of 111In-labeled specifically sensitized lymph node lymphocytes to cardiac allografts in secondary rat recipients conditioned with anti-TNF-alpha serum was significantly decreased, as compared with that in controls. Thus, FN expression by intragraft macrophages occurs within the same interval as cellular infiltration, and may act as an ECM component "signal" for selective homing of recirculating lymphocytes in graft recipients. The results of this study support the notion that in vivo interactions between mononuclear cells and ECM may be vital for the ingress of alloreactive lymphocytes at the graft site, and offer potential novel sites for therapeutic intervention in the control of transplant rejection.

Animals↗
PubMed1995

Preliminary evaluation of a technique for inhibiting intimal hyperplasia: implantation of a resorbable luminal collagen membrane.

Pharmacologic control of intimal hyperplasia has been attempted through oral and intravenous administration of smooth muscle cell inhibitors. We report a more direct method of altering arterial healing using a novel bioresorbable membrane that can be applied to the lumen of an artery or anastomosis following endarterectomy or vascular reconstruction. Following a standard balloon injury, the infrarenal aortas of 3 kg female New Zealand white rabbits were opened and a thin membrane composed of collagen/chondroitin 6-sulfate copolymer was sutured to the posterior wall of each artery. Animals were killed at intervals of up to 3 months. All arteries remained patent. By 24 hours the membrane had become infiltrated with fibrin and red blood cells. An inflammatory response ensued and by 8 days the membrane was filled with mononuclear cells. At 3 months only a small remnant of the membrane remained. Intimal hyperplasia developed throughout the injured aorta. However, the hyperplastic response beneath the membrane was no greater than that observed in the adjacent injured aorta. A bioresorbable membrane can be sutured into the lumen of a small-diameter vessel without inducing thrombosis and without locally increasing intimal hyperplasia. A prosthesis of this type might be used to deliver inhibitors of smooth muscle cell proliferation and migration to the injured arterial wall.

Absorption↗