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Biomedical subjects

Michael G Walker

Publications and source records attributed to Michael G Walker.

At least 19 recordsLinked to original sources
PubMed2006

Alpha2(VIII) collagen substrata enhance endothelial cell retention under acute shear stress flow via an alpha2beta1 integrin-dependent mechanism: an in vitro and in vivo study.

BACKGROUND: Essential to tissue-engineered vascular grafts is the formation of a functional endothelial monolayer capable of resisting the forces of blood flow. This study targeted alpha2(VIII) collagen, a major component of the subendothelial matrix, and examined the ability of and mechanisms by which endothelial cells attach to this collagen under static and dynamic conditions both in vitro and in vivo. METHODS AND RESULTS: Attachment of human endothelial cells to recombinant alpha2(VIII) collagen was assessed in vitro under static and shear conditions of up to 100 dyne/cm2. Alpha2(VIII) collagen supported endothelial cell attachment in a dose-dependent manner, with an 18-fold higher affinity for endothelial cells compared with fibronectin. Cell attachment was significantly inhibited by function-blocking anti-alpha2 (56%) and -beta1 (98%) integrin antibodies but was not RGD dependent. Under flow, endothelial cells were retained at significantly higher levels on alpha2(VIII) collagen (53% and 51%) than either fibronectin (23% and 16%) or glass substrata (7% and 1%) at shear rates of 30 and 60 dyne/cm2, respectively. In vivo studies, using endothelialized polyurethane grafts, demonstrated significantly higher cell retention rates to alpha2(VIII) collagen-coated than to fibronectin-coated prostheses in the midgraft area (P < 0.05) after 24 hours' implantation in the caprine carotid artery. CONCLUSIONS: These studies demonstrate that alpha2(VIII) collagen has the potential to improve both initial cell attachment and retention of endothelial cells on vascular grafts in vivo, which opens new avenues of research into the development of single-stage endothelialized prostheses and the next generation of tissue-engineered vascular grafts.

Animals↗
PubMed2006

Upper dorsal endoscopic thoracic sympathectomy: a comparison of one- and two-port ablation techniques.

OBJECTIVE: Facial blushing and hyperhidrosis, particularly in the facial, axillary or palmar distribution, are socially, professionally, and psychologically debilitating conditions. Endoscopic thoracic sympathectomy can be carried out through multiple ports or by using a single port and a modified thoracoscope with integrated electrocautery. We reviewed our own experience to compare outcomes between these methods. METHODS: One hundred and nine consecutive endoscopic thoracic sympathectomies performed on 96 patients (M:F, 30:66) were examined with respect to operative method, symptom control, and patient satisfaction. Complete follow-up was available on 144 treated sides in 77 patients (80.2%), 38 treated with two ports, 39 performed by a one-port procedure. Mean age was 32.6 years (range 18-63) with a median follow-up of 25 months (range 5-85). Pooled data showed that the mean duration hospital stay was 1.6 nights with no deaths, conversions, or neurological injuries. RESULTS: The one-port group showed superior outcomes in terms of hospital stay, rate of postoperative pneumothorax, and the need for chest drain insertion; however, there was no correlation between number of ports and patient satisfaction. The mean overall satisfaction rating out of 5 was 3.3 with 76.6% of patients rating the outcome as 3 or more. 90.9% had an initial improvement in symptoms, although 21 patients (27.3%) described a late return of symptoms. CONCLUSION: Endoscopic thoracic sympathectomy can be safely and effectively carried out using a single port with similar results to the traditional two-port procedure. The one-port procedure may allow for a shorter duration of stay and lower complication rate.

Adolescent↗
PubMed2006

Late infection of an endovascular stent graft with septic embolization, colonic perforation, and aortoduodenal fistula.

We report on a 52-year-old male who developed late stent graft infection resulting in infective aneurysm formation with systemic septic embolization and aortoduodenal fistulation 9 months following endoluminal repair of an abdominal aortic aneurysm. Although endoluminal stent graft infection and erosion into surrounding viscera is rare, we highlight the need for awareness of this potentially catastrophic complication.

Aneurysm, Infected↗
PubMed2006

Reduction of myointimal hyperplasia after arterial anastomosis by local injection of transforming growth factor beta3.

BACKGROUND: The transforming growth factor (TGF)-beta family of cytokines exerts pleiotropic actions on vascular smooth muscle cell phenotype, proliferation, and extracellular matrix synthesis. This in vivo study assessed the use of TGF-beta3 in attenuating the development of postanastomotic smooth muscle cell proliferation. METHODS: Under general anesthesia, 10 adult goats underwent transection and reanastomosis of both common carotid arteries. After reanastomosis, one artery was infiltrated with 50 ng of TGF-beta3 in 100 microL of pH buffer around the anastomosis, and the other side was infiltrated with buffer only. After surgery, each animal received 150 mg of aspirin daily. The arteries were explanted after 3 months for histologic examination. RESULTS: Vessel wall thickness surrounding the anastomosis was reduced by 30% after TGF-beta3 treatment compared with placebo (P = .003), with a 20% (P = .002) reduction in cellular content. Although total collagen content was not significantly different between TGF-beta3 and placebo, collagen type VIII content was reduced around the TGF-beta3 anastomoses (P = .011). A reduction in the total elastin content (P = .003) and number of elastic fiber lamellae (P = .042) was found surrounding TGF-beta3-treated anastomoses, but not placebo-treated anastomosis. A 29% increase in vasa vasorum (P = .044) was present around TGF-beta3-treated anastomoses. No differences in inflammatory cell infiltration were seen between sides. CONCLUSIONS: Direct subadventitial infiltration of TGF-beta3 immediately after creation of an arterial anastomosis attenuates cell proliferation, with a reduction in elastin and collagen type VIII content and vessel wall thickness.

Anastomosis, Surgical↗
PubMed2006

A comparative study of neovascularisation in atherosclerotic plaques using CD31, CD105 and TGF beta 1.

OBJECTIVES: This study aims to identify plaque neovascularisation using antibodies to CD31, CD105 and TGFbeta1, and to compare their patterns of expression. METHODS: Tissue expression of CD31, CD105 and TGFbeta1 was examined immunohistologically in atherosclerotic plaques from 53 patients who had undergone carotid endarterectomy and in 10 controls. RESULTS: CD31 was observed in a proportion of the microvessels within atheroma. The expression of CD105 was barely visible in normal arteries, but was markedly enhanced in atherosclerotic plaques. The vast majority of the microvessels in atheroma were positive for CD105 with pronounced expression around the periphery of the lipid core. In consecutive sections, microvessels showing negative staining for CD31 were positive for CD105. Although TGFbeta1 was seen in the thickened intima, it was more strongly expressed in well-formed fibrous plaques. Consecutive sections showed that some microvessels were stained by both CD105 and TGFbeta1, but in certain areas microvessels were exclusively CD105 positive. CONCLUSIONS: These observations highlight the distinctive expression patterns of CD31, CD105 and TGFbeta1, suggesting their specific roles in the development of atherosclerotic plaques. CD105 is almost universally expressed in microvessels within the atheroma and is therefore a better vascular marker than CD31 and TGFbeta1for assessing neovascularisation in atherosclerotic plaques.

Antigens, CD↗
PubMed2006

Interpreter services in an inner city teaching hospital: a 6-year experience.

INTRODUCTION: Being able to communicate effectively with patients is essential not only from a medicolegal standpoint but more importantly from clinical governance perspectives. Issues such as informed consent and patient choice within the NHS are currently being highlighted; for these to be available to patients, their language requirements are paramount. PATIENTS AND METHODS: An audit was performed by the Linkworkers office at the Central Manchester & Manchester Children's Hospital NHS (CMMC) Trust on the total number of attendances and refusals per language in the period 1998-2003. RESULTS: In the CMMC Trust, Urdu/Punjabi, Bengali, Cantonese, Somali, Arabic and French represent the majority of the workload, comprising almost 80% of cases in 2003. In the same year, an increase in demand for languages of Eastern European countries became evident. Finding interpreters for these languages even via agencies can be extremely difficult. CONCLUSIONS: If the current trend continues, requirement for these services will increase exponentially. For this demand to be met adequately these issues must be kept at the forefront of NHS planning.

Communication Barriers↗
PubMed2006

Access for endovascular aneurysm repair.

Despite advancement in stent-graft technology, access-related problems continue to occur during endovascular repair of aortic aneurysms. Various techniques have been adopted to overcome difficult access situations, however. To survey these developments in arterial access, we performed a systematic literature review from 1994 through 2005 to identify relevant articles pertaining to endovascular access techniques and complications. Excessive iliac tortuosity, circumferential vessel wall calcification, significant occlusive disease, and small caliber vessels account for the majority of access problems, most of which are readily apparent with adequate baseline imaging. Even with careful preoperative assessment, however, some access problems may not be foreseen; nonetheless, the majority can be overcome using today's array of ancillary procedures, such as an iliac conduit, a brachiofemoral wire, or arterial reconstruction. Alternatively, other approach routes, such as the common carotid artery or direct aortic access, may be used to facilitate endovascular aneurysm repair.

Angioplasty, Balloon↗
PubMed2006

In vivo attenuation of myointimal hyperplasia using transforming growth factor-beta3 in an interposition graft model.

PURPOSE: To examine if transforming growth factor-beta3 (TGFbeta3) can attenuate the development of para-anastomotic myointimal hyperplasia in an animal model of small-diameter vascular graft failure. METHODS: Under general anesthesia, 10 adult goats underwent bilateral polyurethane interposition graft insertion in the carotid position. Following completion of the anastomoses, each artery received adventitial infiltration of 50 ng of TGFbeta3 around the anastomoses; a placebo was administered to the other side. Postoperatively, each animal received 150 mg of aspirin daily. The arteries were explanted, half at 6 weeks and the remaining 5 at 3 months, for histological examination. RESULTS: Vessel wall thickness surrounding the anastomosis was reduced by 37% in TGFbeta3-treated arteries compared to placebo at 6 weeks and 3 months, principally due to reduced smooth muscle cell proliferation. There was decreased overall luminal loss on angiography. Total collagen content was not significantly different between TGFbeta3 and placebo sides. Further analysis for the subendothelial matrix component collagen type VIII showed decreased levels on the treated side. Total elastin content was reduced on the TGFbeta3-treated side. CONCLUSION: Direct single-dose subadventitial infiltration of TGFbeta3 following insertion of an interposition graft reduces SMC proliferation and elastin content. It would appear that TGFbeta3 holds promise as a prophylaxis against the development of myointimal hyperplasia, the predominant cause of graft failure in peripheral bypass surgery.

Actins↗
PubMed2005

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

PURPOSE: This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. EXPERIMENTAL DESIGN: Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). RESULTS: Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. CONCLUSION: Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Adult↗
PubMed2005

GBA server: EST-based digital gene expression profiling.

Expressed Sequence Tag-based gene expression profiling can be used to discover functionally associated genes on a large scale. Currently available web servers and tools focus on finding differentially expressed genes in different samples or tissues rather than finding co-expressed genes. To fill this gap, we have developed a web server that implements the GBA (Guilt-by-Association) co-expression algorithm, which has been successfully used in finding disease-related genes. We have also annotated UniGene clusters with links to several important databases such as GO, KEGG, OMIM, Gene, IPI and HomoloGene. The GBA server can be accessed and downloaded at http://gba.cbi.pku.edu.cn.

Algorithms↗
PubMed2005

Staged open and endovascular repair of thoracoabdominal aneurysms using the common carotid artery.

The purpose of this study was to demonstrate the feasibility of staged open and endoluminal repair of complex thoracoabdominal aneurysms. We report the management of two patients with a staged, open abdominal and endoluminal thoracic repair of Crawford extent II aneurysms, where iliofemoral access was impossible and thoracic repair effected by endograft deployment via a common carotid artery. From this experience we conclude that staged open and endovascular repair for both ruptured and elective Crawford extent II thoracoabdominal aneurysms can be performed using the common carotid artery, when anatomy is favorable.

Aged↗
PubMed2004

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

BACKGROUND: The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. METHODS: We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. RESULTS: Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. CONCLUSIONS: The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer.

Algorithms↗
PubMed2004

A novel hyaluronan-based biomaterial (Hyaff-11) as a scaffold for endothelial cells in tissue engineered vascular grafts.

Current prosthetic small diameter vascular grafts show poor long-term patency rates, leading to the pursuit of a biological alternative. Hyaff-11 is a hyaluronan-based biodegradable polymer developed for tissue-engineering applications. This study aimed to determine whether human vascular endothelial cells attach to Hyaff-11 scaffolds and produce a subendothelial matrix. Two forms of fibrous, non-woven Hyaff-11 scaffolds: unpressed and pressed felts, were analysed. Attachment of human venous endothelial cells was investigated after 1, 5, 10 and 20 days in culture using SEM and confocal microscopy. The deposition of subendothelial matrix components was investigated by immunofluorescent staining. We demonstrate that endothelial cells adhere to the individual fibres of both unpressed and pressed scaffolds: with a seeding density of 1 x 10(6) cells/cm(2), 94% of the cells attached to Hyaff-11 fibres after 24 h. The pressed material provided the best environment for cell growth, allowing the formation of a complete endothelial monolayer after 20 days. Furthermore, endothelial cells on Hyaff-11 pressed felts deposited an organised subendothelial matrix containing laminin, fibronectin, type IV and type VIII collagen. This work indicates Hyaff-11 based biopolymers as suitable scaffolds to promote endothelialisation within the next generation of vascular grafts.

Biocompatible Materials↗
PubMed2004

Mortality in diabetic and nondiabetic patients after amputations performed from 1990 to 1995: a 5-year follow-up study.

OBJECTIVE: To compare survival rates after first amputation between patients with and without diabetes. RESEARCH DESIGN AAND METHODS: We performed a retrospective study of all nontraumatic amputations performed at our center in the years 1990-1995 in patients with (n = 100) and without (n = 151) diabetes. Survival status was assessed from the first amputation until 31 December 2001. RESULTS: Altogether, 61% of the patients with and 54.3% of those without diabetes died 5.2 (4.5-5.8) and 5.3 (4.7-5.9) [mean (95% CI)] years after the first amputation, respectively (P = 0.80). Survival was not different between patients with and without diabetes after controlling for the level (major versus minor) (P = 0.67) or the cause (ischemia versus infection) of amputation (P = 0.72). No sex differences were found for survival in either study group. Independent predictors of mortality in the diabetic group were duration of diabetes (P = 0.05), history of stroke (P = 0.02), and serum creatinine level (P < 0.0001), while in the nondiabetic group independent predictors were history of stroke (P = 0.04), serum creatinine level (P = 0.005), and higher white blood cell count (P = 0.02). The peak incidence of amputations was observed in the decade of 67-76 years of age in both groups. Major amputations were more common among nondiabetic patients in all age-groups. Median hospital stay and postoperative complications were comparable between the two groups. CONCLUSIONS: All-cause mortality is high after an amputation in both diabetic and nondiabetic patients. Mortality rates, hospital stay, and postoperative complications are not different between diabetic and nondiabetic amputees. No modifiable factors, with the exception of nephropathy, were found to improve survival in amputees. Peripheral vascular disease and neuropathy are the main cause of amputations; prevention, therefore, of these complications is warranted to prevent amputations and the subsequent high mortality.

Aged↗
PubMed2003

Are gene expression microarray analyses reliable? A review of studies of retinoic acid responsive genes.

Microarray analyses of gene expression are widely used, but reports of the same analyses by different groups give widely divergent results, and raise questions regarding reproducibility and reliability. We take as an example recent published reports on microarray experiments that were designed to identify retinoic acid responsive genes. These reports show substantial differences in their results. In this article, we review the methodology, results, and potential causes of differences in these applications of microarrays. Finally, we suggest practices to improve the reliability and reproducibility of microarray experiments.

Animals↗
PubMed2003

Gene identification and expression analysis of 86,136 Expressed Sequence Tags (EST) from the rice genome.

Expressed Sequence Tag (EST) analysis has pioneered genome-wide gene discovery and expression profiling. In order to establish a gene expression index in the rice cultivar indica, we sequenced and analyzed 86,136 ESTs from nine rice cDNA libraries from the super hybrid cultivar LYP9 and its parental cultivars. We assembled these ESTs into 13,232 contigs and leave 8,976 singletons. Overall, 7,497 sequences were found similar to existing sequences in GenBank and 14,711 are novel. These sequences are classified by molecular function, biological process and pathways according to the Gene Ontology. We compared our sequenced ESTs with the publicly available 95,000 ESTs from japonica, and found little sequence variation, despite the large difference between genome sequences. We then assembled the combined 173,000 rice ESTs for further analysis. Using the pooled ESTs, we compared gene expression in metabolism pathway between rice and Arabidopsis according to KEGG. We further profiled gene expression patterns in different tissues, developmental stages, and in a conditional sterile mutant, after checking the libraries are comparable by means of sequence coverage. We also identified some possible library specific genes and a number of enzymes and transcription factors that contribute to rice development.

Arabidopsis↗
PubMed2003

Gene expression versus sequence for predicting function: Glia Maturation Factor gamma is not a glia maturation factor.

It is standard practice, whenever a researcher finds a new gene, to search databases for genes that have a similar sequence. It is not standard practice, whenever a researcher finds a new gene, to search for genes that have similar expression (co-expression). Failure to perform co-expression searches has lead to incorrect conclusions about the likely function of new genes, and has lead to wasted laboratory attempts to confirm functions incorrectly predicted. We present here the example of Glia Maturation Factor gamma (GMF-gamma). Despite its name, it has not been shown to participate in glia maturation. It is a gene of unknown function that is similar in sequence to GMF-beta. The sequence homology and chromosomal location led to an unsuccessful search for GMF-gamma mutations in glioma. We examined GMF-gamma expression in 1432 human cDNA libraries. Highest expression occurs in phagocytic, antigen-presenting and other hematopoietic cells. We found GMF-gamma mRNA in almost every tissue examined, with expression in nervous tissue no higher than in any other tissue. Our evidence indicates that GMF-gamma participates in phagocytosis in antigen presenting cells. Searches for genes with similar sequences should be supplemented with searches for genes with similar expression to avoid incorrect predictions.

Animals↗