Biomedical subjects

E Wilson

Publications and source records attributed to E Wilson.

At least 73 records · Page 4Linked to original sources

PubMed1998

Strain-responsive regions in the platelet-derived growth factor-A gene promoter.

Proliferation of cultured neonatal vascular smooth muscle (VSM) cells is enhanced by exposure to cyclic mechanical strain, in part through autocrine action of secreted platelet-derived growth factor (PDGF). We examined transcription factors and DNA response elements that may participate in the induction of PDGF-A gene transcription by mechanical strain. PDGF-A mRNA increased gradually over 4 to 24 hours exposure to cyclic (1 Hz) strain. This was due, at least in part, to increased transcription since a full length (890 bp) PDGF-A promoter reporter construct was induced 3.5-fold in transfected VSM cells exposed to strain for 24 hours. A series of PDGF-A promoter truncation reporter constructs was used to identify potential regions of the promoter involved in regulation by strain. Strain-responsive regions were found between -262 bp and -92 bp and between -92 bp and -41 bp of the promoter. Since these regions are GC-rich and contain response elements for Egr-1 and Sp-1, we examined expression of these transcription factors in response to strain. mRNA for both factors increased over 0.5 to 4 hours of strain, while protein expression for both increased gradually over a 24 hours period. Gel shift assays with a probe specific for Egr-1 demonstrated at least 1 prominent new shifted band after 4 to 12 hours exposure to strain. An Sp-1 probe demonstrated constitutive shifted bands that did not change in response to strain. Thus, GC-rich regions in the proximal 92 bp of the PDGF-A promoter contain mechanical strain-responsive elements that bind Egr-1 and possibly Sp-1.

Animals↗

PubMed1998

Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease.

OBJECT: In recent years, fetal mesencephalic tissue transplant for the treatment of Parkinson's disease (PD) has been demonstrated to hold promise, but potential complications related to growth of allograft tissue have not been well described. This report explores the development and possible causation of a fatal cyst arising from a fetal transplant in the brain. METHODS: The authors report the case of a 52-year-old woman who underwent bilateral putamenal fetal mesencephalic allograft transplant for PD at another hospital. Twenty-three months later she presented to the authors' institution in a coma. Admission computerized tomography and magnetic resonance (MR) studies revealed a contrast-enhancing mural nodule and associated large cyst arising from the left putamen and causing brainstem compression. Despite surgical decompression of the cyst, the patient did not regain consciousness. Biopsy and autopsy specimens were obtained, along with an analysis of the cyst fluid. Genotyping of the nodule and the patient's peripheral lymphocytes by using polymerase chain reaction-based microsatellite analysis was also performed. Biopsy samples and autopsy histopathological studies showed inflammatory cells, hemosiderin-laden macrophages, and astrocytosis. Scattered neurons and multiple rests of choroid plexus were also noted. The cyst had a thin wall and contained liquid that was identical in composition to cerebrospinal fluid (CSF). Genotyping demonstrated the presence of alleles in the nodule DNA that were not present in lymphocytic DNA, indicating that the nodule contained allograft tissue. CONCLUSIONS: The authors hypothesize that the choroid plexus tissue contained in the allograft resulted in CSF production and cyst formation at the transplant site, ultimately leading to the patient's herniation syndrome. The clinical history and large size of the mural nodule indicate slow growth of this allograft site and cyst over time. This case demonstrates that unusual patterns of tissue growth can occur in the brain after fetal tissue transplant and emphasizes the need for long-term monitoring of posttransplant patients by means of MR imaging. Cell sorting should be considered to ensure transplant of pure neuronal and astroglial populations.

Alleles↗

PubMed1998

Infant nutrition program effectively prevents iron-deficiency anemia in a First Nations community.

Iron-deficiency anemia (IDA) has received relatively little attention in Canada, with no national public health initiatives even among high-risk infants. IDA has a high prevalence in First Nations children and has been shown to cause developmental delay. This study is a before/after prevalence survey studying the effect of a public health intervention, conducted on a First Nations reserve off the central coast of British Columbia (BC). We screened for IDA one cohort of infants born January 1993 to August 1994 and between the ages of 6 and 24 months. Twenty-five of a possible 37 infants were screened. We found 13 (52%) of the 25 had anemia, with a hemoglobin less than 100 g/L. The average hemoglobin was 98.9 +/- 19.2 g/L. The subsequent implementation of an infant nutrition program focused on educating parents and encouraging the use of iron-fortified formula for nonbreast-fed infants. In the year following program implementation, the cohort of infants born between September 1994 and September 1995 were screened for IDA when they were between the ages of 6 and 15 months. Twenty-four of 27 infants participated. Only one infant was anemic with a hemoglobin less than 100 g/L. The average hemoglobin was 116.6 +/- 11.6 g/L. The increase in the average hemoglobin and the decrease in the prevalence of anemia were both highly significant (p < .01). We judged our intervention to be very effective and would recommend similar programs for other First Nations communities.

Anemia, Iron-Deficiency↗

PubMed1998

Preparation, attitudes and behaviour in nonhospital cardiac emergencies: evaluating a community's readiness to act.

OBJECTIVE: To determine how people in a moderately sized Ontario city believe they will react if they witness someone colapsing. DESIGN: Telephone survey. SETTING: The cities of Kitchener and Waterloo, part of the Regional Municipality of Waterloo, Ontario, with a combined population of 378,000. PARTICIPANTS: Households were randomly contacted and a questionnaire was administered, provided the respondent was over 44 years of age and agreed to be interviewed. Of 2479 households with eligible respondents, 811 (33%) completed the questionnaire. OUTCOMES: Age, sex, educational level, cardiac risk factors and cardiopulmonary resuscitation (CPR) training of respondents were determined, as well as actions they would take if cardiac arrest occurred in a family member at home or in stranger in the street, and associated emotions and barriers to implementing actions. RESULTS: Among the first three actions that respondents who were not prompted with possible responses said they would take, 311 (72%) witnessing a collapse at home, compared with 166 (44%) witnessing a collapse on the street, would call 911, the police or an ambulance. Other 'first three actions' in home collapse were checking for breathing (120 [28%]), checking for pulse (91 [21%]) and administering CPR (34 [8%]); these actions were less commonly selected in response to a strangers collapse and when respondents were not prompted. Respondents felt they would be more likely to perform CPR on a friend than on a stranger (OR 1.38, 95% CI 1.10 to 1.58). When asked how likely they would be to perform specific acts when witnessing a collapse, 254 (69%) of respondents thought they would call their family doctor and 179 (48%) thought they were likely to begin chest compressions. Barriers to performing CPR centred around legalities and disease transmission. CONCLUSION: Older people do not know how to act effectively in a cardiac emergency. Traditional CPR and public awareness programs have been ineffective in reaching this population; alternative means are required to help the public respond more effectively to cardiac emergencies.

Accidents↗

PubMed1997

Identification of a family of low-affinity insulin-like growth factor binding proteins (IGFBPs): characterization of connective tissue growth factor as a member of the IGFBP superfamily.

The insulin-like growth factor (IGF) binding proteins (IGFBPs) modulate the actions of the insulin-like growth factors in endocrine, paracrine, and autocrine settings. Additionally, some IGFBPs appear to exhibit biological effects that are IGF independent. The six high-affinity IGFBPs that have been characterized to date exhibit 40-60% amino acid sequence identity overall, with the most conserved sequences in their NH2 and COOH termini. We have recently demonstrated that the product of the mac25/IGFBP-7 gene, which shows significant conservation in the NH2 terminus, including an "IGFBP motif' (GCGCCXXC), exhibits low-affinity IGF binding. The closely related mammalian genes connective tissue growth factor (CTGF) gene, nov, and cyr61 encode secreted proteins that also contain the conserved sequences and IGFBP motifs in their NH2 termini. To ascertain if these genes, along with mac25/IGFBP-7, encode a family of low-affinity IGFBPs, we assessed the IGF binding characteristics of recombinant human CTGF (rhCTGF). The ability of baculovirus-synthesized rhCTGF to bind IGFs was demonstrated by Western ligand blotting, affinity cross-linking, and competitive affinity binding assays using 125I-labeled IGF-I or IGF-II and unlabeled IGFs. CTGF, like mac25/IGFBP-7, specifically binds IGFs, although with relatively low affinity. On the basis of these data, we propose that CTGF represents another member of the IGFBP family (IGFBP-8) and that the CTGF gene, mac25/IGFBP-7, nov, and cyr61 are members of a family of low-affinity IGFBP genes. These genes, along with those encoding the high-affinity IGFBPs 1-6, together constitute an IGFBP superfamily whose products function in IGF-dependent or IGF-independent modes to regulate normal and neoplastic cell growth.

Amino Acid Sequence↗

PubMed1997

Characterization of an adhesion molecule that mediates leukocyte rolling on 24 h cytokine- or lipopolysaccharide-stimulated bovine endothelial cells under flow conditions.

Bovine gamma/delta T cells and neutrophils roll on 24 h cytokine- or lipopolysaccharide-stimulated bovine fetal umbilical cord endothelial cells in assays done under physiological flow. An antibody directed against E- and L-selectin has minimal blocking effect on this rolling interaction. mAbs were raised against the stimulated bovine endothelial cells and screened for inhibition of gamma/delta T cell rolling. One mAb (GR113) was identified that recognizes an antigen (GR antigen) selectively expressed by stimulated bovine endothelial cells isolated from fetal umbilical cord, mesenteric lymph nodes, and aorta. GR113 blocked bovine gamma/delta T cell as well as neutrophil rolling on the 24 h-activated endothelial cells. The GR antigen was constitutively expressed at low levels on the cell surface of platelets and its expression was not upregulated after stimulation of these cells with thrombin or phorbol myristate acetate. However, stimulated platelets released a soluble, functionally active form of the molecule that selectively bound in solution to gamma/delta T cells in a mixed lymphocyte preparation. GR113 mAb blocked the binding of the soluble platelet molecule to the gamma/delta T cells. Soluble GR antigen also bound a subset of human lymphocytes. Cutaneous lymphocyte-associated antigen (CLA) bright human lymphocytes exhibited the greatest capacity to bind the GR antigen, though CLA was not required for binding. Subsets of both human CD4 and CD8 T cells bound the GR antigen. Immunoprecipitation experiments showed the GR antigen to be 110-120 kD Mr. The binding of soluble GR antigen was inhibited by EDTA and O-sialoglycoprotease, but not neuraminidase treatment of the target cells.

Animals↗

PubMed1997

Non-capacitative calcium entry in Chinese hamster ovary cells expressing the platelet-derived growth factor receptor.

Platelet-derived growth factor (PDGF) is believed to produce intracellular calcium (Ca2+i) transients by inositol trisphosphate (InsP3)-mediated release of intracellular Ca2+ stores followed by "capacitative" Ca2+ entry due to emptying of these stores. We examined the roles for the phospholipase Cgamma-InsP3 pathway and the emptying of InsP3-dependent intracellular Ca2+ stores in PDGF-mediated Ca2+ entry. Intracellular Ca2+ release and Ca2+ entry were measured with fluorometric methods in Chinese hamster ovary cells expressing wild type or mutant PDGF receptors. Activation of the wild type PDGF receptor caused both intracellular "Ca2+ release, " measured in nominally 0 Ca2+ extracellular medium, and "Ca2+ entry, " measured upon addition of 2 mM Ca2+ medium. Both phases were absent in Chinese hamster ovary cells expressing a PDGF receptor mutant (Y977F,Y989F) that fails to bind phospholipase Cgamma. Blockade of the InsP3 receptor, by microinjection of single cells with low molecular weight heparin (5-50 mg/ml), blocked only Ca2+i release (following PDGF or flash photolysis of caged InsP3) and had no effect on PDGF-induced Ca2+ entry. In whole cell patch-clamp experiments, intracellular heparin also failed to block PDGF-evoked ion currents. Release of InsP3-dependent intracellular Ca2+ stores, by flash photolysis of caged InsP3, was apparently not sufficient to maximally activate Ca2+ entry. Intracellular InsP3 caused significantly less Ca2+ entry than PDGF alone. These data suggest that InsP3 alone is not sufficient to maximally activate Ca2+ entry by the capacitative pathway and that products of phosphatidylinositol 4,5-bisphosphate breakdown other than InsP3 probably play a role in PDGF-mediated Ca2+ entry.

Animals↗

PubMed1997

Establishing a public health nursing project.

This article, the second in our three-part series on public health, describes the development and operation of two public health projects in Stockport. The authors place these projects in the wider context of public health nursing and highlight some of the benefits of using the approach as a framework for community project work.

Community Health Nursing↗

PubMed1997

Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study.

OBJECTIVE: To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography. DESIGN: Randomisation to conventional schedule of clinic visits or to visits only after mammography. Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms. SETTING: Combined breast clinic, Chelsea and Westminster Hospital. SUBJECTS: 211 eligible outpatients with a history of breast cancer. MAIN OUTCOME MEASURES: Acceptability of randomisation, interim use of telephone and general practitioner, satisfaction with allocation to follow up. RESULTS: Of 211 eligible patients, 196 (93%) opted for randomisation in the study. Of these, 55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not participate were more likely to be under 50 years, to be two to five years after diagnosis, and to have had aggressive primary disease. Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up. No increased use of local practitioner services or telephone triage was apparent in the cohort randomised to less frequent follow up by specialists. CONCLUSIONS: Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at standard risk in this cohort. A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes.

Adult↗

PubMed1997

Neurosurgical treatment for tetanus.

Soon after the discovery of the tetanus antitoxin, animal experiments led to the conclusion that intracerebral injection of the antitoxin would be useful in the treatment of tetanus. The French surgeon Quenu carried out the first injection and gave a description of the neurosurgical technique required. The method was applied in other European countries until it was declared to be less efficient than simple subcutaneous or intravenous injections. Outside Europe, intracerebral injections of tetanus antitoxin were reported and photographed in Montevideo, Uruguay, in 1901.

Antitoxins↗

PubMed1997

Modular bifurcation endoprosthesis for treatment of abdominal aortic aneurysms.

OBJECTIVE: The authors analyzed a single group's experience treating abdominal aortic aneurysms (AAAs) with a new self-expanding, modular, bifurcated device. SUMMARY BACKGROUND DATA: Successful exclusion of AAAs by prototype devices has led to several controlled clinical trials evaluating prostheses designed and manufactured specifically for this application. METHODS: Sixteen patients (15 males, 1 female) of American Society of Anesthesiologists grade 2 through 4 and average age of 72 years had AAAs (average 57-mm diameter) treated as part of a phase I Food and Drug Administration-approved trial. RESULTS: All patients were treated successfully with no surgical conversions. No endoleaks or aneurysm enlargement was noted either predischarge by contrast computed tomography or on follow-up at 1 month by duplex ultrasound examination. At 6 months, 12 of 13 patients who were observed for this interval had no endoleaks, whereas one patient (patient 3) showed a small area of extravasation that appeared to arise from the device in an area that was traumatized at the time of deployment. One procedure-related mortality (6%) occurred in a patient who died of septic complications secondary to a gangrenous gallbladder diagnosed 1 day after the procedure. There were no device-related mortalities. Complications included two iliac artery dissections, two groin wound infections, and two transient elevations of serum creatinine. Other significant variables including median procedure length (5 hours), intensive care unit stay (1 day), hospitalization postprocedure (4.5 days), and blood loss (1100 mL) all decreased as the study progressed. Blood replacement in all but three patients was accomplished by autotransfusion or banked-autologous blood replacement. At 6-month follow-up in 13 patients, the maximum diameter of the aneurysm decreased by an average of 5.6 mm (range, 0-15 mm), and the maximal cross-sectional area decreased an average of 20.3% (range, 0-72%). CONCLUSIONS: This study suggests that endovascular prosthesis exclusion of AAAs using a self-expanding modular device may be effective in many patients who are otherwise surgical candidates for repair if further clinical studies confirm these observations.

Aged↗

PubMed1997

Intravascular ultrasound: the ultimate tool for abdominal aortic aneurysm assessment and endovascular graft delivery.

Intravascular ultrasound (IVUS) imaging is a relatively new, rapidly evolving technology that enables precise catheter-based assessment of the dimensions and morphology of vascular structures and lesions. In extensive preclinical laboratory developmental studies and in clinical cases of endograft deployment for treatment of abdominal aortic aneurysms, we have found IVUS invaluable for determining key parameters of aortic morphology before and during interventions and for assessing the accuracy of deployment after device placement. By combining the IVUS data with information obtained from angiography, magnetic resonance imaging, and computed tomography (axial and three-dimensional reconstructions), we have been able to size devices and choose optimal fixation sites to prevent endoleaks and maintain luminal patency acutely and in the long term.

Angioplasty↗

PubMed1997

Endoluminal graft exclusion of a proximal para-anastomotic pseudoaneurysm following aortobifemoral bypass.

PURPOSE: To describe a case of endoluminal graft exclusion of a proximal para-anastomotic pseudoaneurysm that occurred 17 years following aortobifemoral bypass for occlusive disease. METHODS AND RESULTS: The lesion was found on abdominal ultrasound examination as part of a work-up for acute abdominal pain and upper gastrointestinal bleeding in a 67-year-old male. A 5-cm saccular pseudoaneurysm was confirmed by preintervention aortography and spiral computed tomography (CT) scanning. Because of the patient's acute symptoms and high-risk medical condition (cardiomyopathy), he was deemed a candidate for endoluminal bypass. At the time of intervention, intravascular ultrasound (IVUS) interrogation identified a 3.5-cm-long separation of the existing aortic graft from the proximal aortic stump with a large pseudoaneurysm. The lesion was isolated and repaired by placement of an aortic-to-right iliac endoluminal bypass, ligation of the left limb of the aortofemoral graft, and femorofemoral bypass to restore blood flow to the lower extremities. Spiral CT scans at 48 hours and 3 months following the procedure confirmed complete isolation of the lesion. CONCLUSIONS: This case illustrates the feasibility of endografting for repair of aortic para-anastomotic pseudoaneurysms, and it also highlights the potential role of IVUS imaging in endoluminal graft deployment.

Aged↗

PubMed1997

Endograft repair of an aortic pseudoaneurysm following gunshot wound injury: impact of imaging on diagnosis and planning of intervention.

PURPOSE: To describe the endovascular treatment of a gunshot injury to the visceral aorta and the role of various imaging modalities in the staging and planning of the endograft procedure. METHODS AND RESULTS: The bullet entered the aorta posteriorly beneath the origin of the superior mesenteric artery and traversed the wall in a tangential manner entering the lumen proximal to the renal arteries. Intravascular ultrasound (IVUS) imaging and spiral computed tomography (CT) identified the injury that the initial angiograms failed to demonstrate. Combined use of IVUS and CT imaging enabled observation of the evolution of a pseudoaneurysm until an interval when endograft exclusion was possible. A stent-graft was customized based on precise IVUS and CT dimensional data and implanted successfully through an arteriotomy in the common femoral artery 3 weeks after the initial injury. Three-month follow-up imaging demonstrated continued exclusion of the pseudoaneurysm, and the patient remains well at 16 months. CONCLUSIONS: IVUS and spiral CT scans were instrumental in identifying an arteriographically undetected aortic injury. The combined imaging modalities also helped determine the timing for the endovascular procedure and provided the precise measurements for device fabrication and deployment.

Adult↗

PubMed1996

Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II.

The mac25 cDNA was originally cloned from leptomeningial cells and subsequently reisolated through differential display as a sequence preferentially expressed in senescent human mammary epithelial cells. The deduced amino acid sequence of the human mac25 propeptide shares a 20-25% identity to human insulin-like growth factor-binding proteins (IGFBPs), suggesting that mac25 could be another member of the IGFBP family. In the present study, we have generated recombinant human mac25 (rh-mac25) in a baculovirus expression system and assessed its affinity for IGFs and have evaluated the pattern of expression of the mac25 gene in human tissues. Binding of 125I-IGF-I and 125I-IGF-II to rh-mac25 was demonstrated by Western ligand blotting after nondenaturing polyacrylamide gel electrophoresis and by affinity cross-linking with as little as 2 nM rh-mac25. Specificity of rh-mac25 binding to 125I-IGFs was demonstrated by competition for rh-mac25 binding with unlabeled IGFs, but not with [QAYLL]IGF-II analog, which has 100-fold less affinity for IGFBPs. In comparison with IGFBP-3, rh-mac25 has at least a 5-6-fold lower affinity for IGF-I and 20-25-fold lower affinity for IGF-II. mac25 mRNA was detectable in a wide range of normal human tissues, with decreased expression in breast, prostate, colon, and lung cancer cell lines. In conclusion, mac25 specifically binds IGFs and constitutes a new member of the IGFBP family, IGFBP-7. Its wider distribution in normal tissue and lower expression in several cancer cells indicate that IGFBP-7 may function as a growth-suppressing factor, as well as an IGF-binding protein.

Gene Expression↗

PubMed1996

Comparison of the deployment and healing of thin-walled expanded PTFE stented grafts and covered stents.

This study evaluated the deployment and short-term healing of thin-walled expanded polytetrafluoroethylene (ePTFE) stented grafts and covered stents as endoluminal prostheses in normal canine aortas and in an abdominal aortic aneurysm (AAA) model. Stented grafts consisted of a 7 cm length of 3 mm internal diameter ePTFE graft (Impra, Inc., Tempe, Ariz.) with two P-188 Palmaz stents (Johnson & Johnson Interventional Systems, Warren, N.J.) deployed along the inner surface of the ends of the graft to secure the prosthesis to the arterial wall. Covered stents were fabricated by placing a 3.7 cm length of 3 mm internal diameter thin-walled ePTFE graft over a P-394 Palmaz stent. Four covered stents and four stented graft prostheses (two of each prototype in the normal canine aorta and AAA model) were implanted in eight animals. One prosthesis of each type in each model was removed at 30 days and one at 60 days. Prior to removal, prostheses were evaluated by CT scan, arteriography, and intravascular ultrasound imaging with values compared to those obtained when the prostheses were deployed. Gross inspection and microscopic evaluation were performed at scheduled explantation. In general, the stented grafts were more difficult to accurately deploy. Healing and maintenance of long-term patency without significant luminal obstruction or occlusion occurred in only one 30-day sample in a normal canine aorta. The 30-day stented graft specimen that had been implanted in an AAA and required the addition of a covered stent to seal a maldeployment of the distal segment was also patent. The 60-day stented graft in the normal canine aorta was occluded with narrowing of the graft between the stents. The 60-day stented graft in the AAA was patent with one central fold and thrombus occupying approximately 20% to 30% of the lumen at this site. In contrast, the covered stent devices were less difficult to accurately deploy. All of the covered stent devices were patent with well-incorporated surfaces. Deployment of covered stents was more accurate and less complicated compared to stented grafts. All patent endoluminal prostheses and stent surfaces were well incorporated into aortic tissues. Problems with graft narrowing, folding, and subsequent thrombosis occurred in the unstented segments of the stented grafts. These preliminary findings support the further development and use of completely supported (stented) devices as endoluminal prostheses.

Angioplasty, Balloon↗

PubMed1996

Evaluation of a modular endovascular bifurcation prosthesis in a canine aortic aneurysm model.

PURPOSE: The study evaluated the deployment and healing of a novel self-expanding modular bifurcation endovascular prosthesis in a canine abdominal aortic aneurysm model. The endoluminal prosthesis consists of self-expanding nitinol stents lined by a synthetic prosthesis. One component of the device is a bifurcated body with a 12- to 14-mm diameter aortic segment and an integral 7- to 8-mm diameter iliac limb. The bifurcated body also has a stent-reinforced opening (pant-leg) for subsequent insertion of a contralateral 7- to 8-mm diameter iliac limb component. METHODS: Seventeen bifurcated prosthesis were placed; 7 were inserted through the left common carotid artery and 10 from the femoral arteries. With either route of access the 16F or 17F aortoiliac limb and the 13F iliac limb delivery catheters enabled easy passage and secure positioning of the bifurcated prostheses. Predeployment and postdeployment inspection of the dimensions and continuity of the aortoiliac prosthetic components were evaluated by cinefluoroscopy and intravascular ultrasonography (IVUS). RESULTS: After deployment was done, interval patency was assessed with angiography, IVUS, and contrast-enhanced computed tomography with the prostheses removed for analysis at 1 week (n = 4), 1 month (n = 3), 3 months (n = 4), and 6 months (n = 6). Five of the first seven implanted prostheses had occlusion of segments of the device. In two dogs the bifurcated body and both legs were occluded. In the other three the nonoccluded leg and bifurcation body were fully patent. In the first seven animals IVUS at implantation showed compression of an iliac leg by the orifice of the contralateral iliac component. After concentric fixation of the flow divider was performed, only one additional iliac limb occlusion occurred in the next 10 animals. Cinefluoroscopy, computed tomography, IVUS imaging, and histologic analysis of retrieved specimens demonstrated healing of the aortoiliac prostheses without evidence of perigraft leaks. CONCLUSIONS: This feasibility study demonstrates the ability to deploy and maintain acceptable patency of a self-expanding endoluminal, modular bifurcation prosthesis in a canine aortic model. Clinical evaluation of the device is planned for the near future.

Alloys↗

PubMed1996

Mechanical strain increases smooth muscle and decreases nonmuscle myosin expression in rat vascular smooth muscle cells.

The effect of cyclic (1-Hz) mechanical strain on expression of myosin heavy chain isoforms was examined in neonatal rat vascular smooth muscle cells cultured on silicone elastomer plates. Myosin heavy chain isoforms were identified by immunoblot using antibodies recognizing (1) smooth muscle myosin heavy chain isoforms SM-1 and SM-2, (2) SM-1 exclusively, and (3) nonmuscle myosin heavy chains A and B. In response to 36 to 72 hours of strain, SM-1 and SM-2 increased by fourfold to sixfold, whereas nonmuscle myosin A decreased to 30% of control. Nonmuscle myosin B was unaffected by strain. SM-1 mRNA increased by twofold to threefold after 12 hours of strain but decreased toward control levels thereafter. SM-2 mRNA was only barely detectable. Nonmuscle myosin A mRNA decreased to 50% of control after 3 hours of strain and then returned to the control level. Since these cells secrete platelet-derived growth factor (PDGF) in response to strain, we assessed the effects of PDGF on myosin isoform expression. Exogenous PDGF (10 ng/mL) decreased SM-1 expression by 35% and increased nonmuscle myosin expression twofold, opposite the effect of strain. In cells exposed to strain with neutralizing antibodies to PDGF-AB, the strain-induced increase in SM-1 was enhanced 10-fold, and nonmuscle myosin A was reduced to 40% of control. Finally, the effect of extracellular matrix on transduction of the strain signal was studied. Forty-eight hours of cyclic strain increased SM-1 by twofold in cells cultured on collagen type 1 and threefold in cells cultured on laminin. In fibronectin-cultured cells, strain elicited no increase in SM-1. Thus, mechanical strain, sensed through specific interactions with the matrix, can alter myosin isoform expression toward that found in a more differentiated state.

Animals↗