Axisymmetric ridges and circumferential buckling of indented shells of revolution.

When poking a thin shell-like structure, like a plastic water bottle, experience shows that an initial axisymmetric dimple forms around the indentation point. The ridge of this dimple, with increasing indentation, eventually buckles into a polygonal shape. The polygon order generally continues to increase with further indentation. In the case of spherical shells, both the underlying axisymmetric deformation and the buckling evolution have been studied in detail. However, little is known about the behavior of general geometries. In this work we describe the geometrical and mechanical features of the axisymmetric ridge that forms in indented general shells of revolution with non-negative Gaussian curvature and the conditions for circumferential buckling of this ridge. We show that under the assumption of "mirror buckling," a single unified description of this ridge can be written if the problem is nondimensionalized using the local slope of the undeformed shell midprofile at the ridge radial location. However, in dimensional form the ridge properties evolve in quite different ways for different midprofiles. Focusing on the indentation of shallow shells of revolution with constant Gaussian curvature, we use our theoretical framework to study the properties of the ridge at the circumferential buckling threshold and evaluate the validity of the mirror buckling assumption against a linear stability analysis on the shallow shell equations, showing very good agreement. Our results highlight that circumferential buckling in indented thin shells is controlled by a complex interplay between the geometry and the stress state in the ridge. The results of our study will provide greater insight into the mechanics of thin shells. This could enable indentation to be used as a means to measure the mechanical properties of a wide range of shell geometries or used to design shells with specific mechanical behaviors.

Mechanics of generically creased disks.

Folded structures are often idealized as a series of rigid faces connected by creases acting as revolute hinges. However, real folded structures can deform between creases. An example of particular interest is a disk decorated by multiple radial creases. Such disks are bistable, snapping between a "natural" and "inverted" shape. We investigate the mechanical behavior of these creased disks and propose a new analytical approach to describe their mechanics. Detailed experiments are performed which show that, when indented at the center, a localized dimple forms, precluding the conical shape assumed in previous studies. As the indentation depth increases this dimple expands radially until reaching the disk edge when it snaps to the inverted shape, which has a conical form. We develop an analytical model which approximates each face as a series of rigid facets connected by hinges that can both rotate and stretch. Energy expressions are derived relating hinge rotation and stretching to compatible shell deformations of the facets and equilibrium enforced by minimizing the total strain energy. By increasing the number of facets, the mechanics of the continuum shell is approached asymptotically. The analysis shows that membrane stretching of the faces is required when a conical form of deformation is enforced. However, in the limit of zero thickness, the forming and propagation of a localized dimple is inextensional. This new approach relates the kinematic analysis of rigid origami to the mechanics of thin shells, offering an efficient method to predict the behavior of folded structures.

Factors predictive of survival and estimated years of life lost in the decade following nontraumatic and traumatic spinal cord injury.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To identify factors predictive of survival after spinal cord injury (SCI). SETTING: Tertiary care institution. METHODS: Multiple-variable Cox proportional hazards regression analysis for 759 patients with SCI (535 nontraumatic and 221 traumatic) included age, sex, completeness of injury, level of injury, functional independence measure (FIM) scores, rehabilitation length of stay and SCI cause. Estimated years of life lost in the decade after injury was calculated for patients vs uninjured controls. RESULTS: Median follow-up was 11.4 years. Population characteristics included paraplegia, 58%; complete injury, 11%; male sex, 64%; and median rehabilitation length of stay, 16 days. Factors independently predictive of decreased survival were increased age (+10 years; hazard ratio (HR (95% CI)), 1.6 (1.4-1.7)), male sex (1.3 (1.0-1.6)), lower dismissal FIM score (-10 points; 1.3 (1.2-1.3)) and all nontraumatic causes. Metastatic cancer had the largest decrease in survival (HR (95% CI), 13.3 (8.7-20.2)). Primary tumors (HR (95% CI), 2.5 (1.7-3.8)), vascular (2.5 (1.6-3.8)), musculoskeletal/stenosis (1.7 (1.2-2.5)) and other nontraumatic SCI (2.3 (1.5-3.6)) were associated with decreased survival. Ten-year survival was decreased in nontraumatic SCI (mean (s.d.), 1.8 (0.3) years lost), with largest decreases in survival for metastatic cancer and spinal cord ischemia. CONCLUSIONS: Age, male sex and lower dismissal FIM score were associated with decreased survival, but neither injury severity nor level was associated with it. Survival after SCI varies depending on SCI cause, with survival better after traumatic SCI than after nontraumatic SCI. Metastatic cancer and vascular ischemia were associated with the greatest survival reduction.

Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery.

OBJECTIVES: Since pregnancies with a male fetus have higher perinatal complications attributed to placental dysfunction, including severe pre-eclampsia and intrauterine growth restriction, the objective of our study was to formally evaluate placental pathology for a placental origin of these sex-specific differences. DESIGN: Retrospective study at Mount Sinai Hospital in Toronto, Canada. Identification of 262 singleton pregnancies affected by severe pre-eclampsia and/or intrauterine growth restriction who delivered between 22 and 32 weeks' gestation from 2000 to 2010. Detailed placental pathology was reviewed, and data from 140 pregnancies with male fetuses were compared with 122 pregnancies with female fetuses. A comparison group of 40 unaffected pregnancies who delivered in the same gestational range was used to determine baseline rates of placental pathology. MAIN OUTCOME MEASURED: Detailed placental pathology, including placental development/differentiation, velamentous umbilical cord insertion, maternal-fetal interface pathology, villous infarction, hemorrhagic lesions, villous development, and fetal vascular under-perfusion. RESULTS: Impaired placental development and differentiation was equally common amongst males (73/140, 52.1%) and females (69/122, 56.6%). Male placentas exhibited significantly higher rates of chronic deciduitis (17.9% vs. 9.0%; relative risk [RR] 1.98, 95% confidence interval [CI] 1.02-3.86) and velamentous umbilical cord insertion (9.5% vs. 1.7%; RR 5.66, 95% CI 1.30-24.6), and a significantly lower frequency of villous infarction (55.4% vs. 73.7%; RR 0.75, 95% CI 0.62-0.90) than female placentas. No significant differences were noted for other lesions. CONCLUSIONS: Fetal sex exerts a differential effect on the placental pathology that mediates severe pre-eclampsia and/or IUGR. Placental pathology at birth may provide insight into the mechanisms linking adverse in utero events with long-term adult disease since, for example, a male tendency to an inflammatory pathology at the maternal-fetal interface may be linked to the excess risk of coronary artery disease.

A systematic review of open versus endovascular repair of inflammatory abdominal aortic aneurysms.

INTRODUCTION: Inflammatory abdominal aortic aneurysms (IAAAs) have traditionally been treated by open surgical repair (OSR). Over the last decade, endovascular aneurysm repair (EVAR) has been increasingly employed. The optimal treatment option for IAAA remains unclear. This article aims to evaluate and compare outcomes of OSR and EVAR in IAAA repair. METHODS: All publications in the English language relating to IAAA were sought electronically using OVID and MEDLINE (1972-2008). Studies identifying 30-day mortality were considered. Periaortic inflammation (PAI), hydronephrosis and 1-year mortality were obtained from studies with at least 1-year computed tomography (CT) follow-up. Outcomes of OSR and EVAR were compared and analysed for statistical significance using Fisher's exact test. RESULTS: The results were obtained from 35 studies comprising 999 patients and 21 studies with 121 patients who underwent OSR and EVAR, respectively. One-year CT follow-up was available for 124 and 52 patients from the two groups, respectively. Thirty-day mortality after OSR was 6% (95% confidence interval (CI); 6-13) and 2% (95% CI; 0-7) after EVAR (p=0.1). At 1 year, PAI regressed in 73% (95% CI; 64-80) in the OSR group compared to 65% (95% CI; 49-77) of the EVAR group (p=0.7). Conversely, inflammation progressed in 1% and 4%, respectively (p=0.1). Forty-five patients undergoing OSR and 29 EVAR were found to have preoperative hydronephrosis. This regressed postoperatively in 69% (95% CI; 53.3-81.8) and 38% (95% CI; 20.6-57.7), respectively (p=0.01). Hydronephrosis progressed in 9% of patients after OSR and in 21% after EVAR (p=0.1). New-onset hydronephrosis developed in 6% undergoing OSR compared to 2% with EVAR (p=0.2). One-year all-cause mortality after OSR was 14% (95% CI; 6-18) compared to 2% (95% CI; 0-13) after EVAR (p=0.02). CONCLUSION: Either OSR or EVAR may be considered based on patient suitability. EVAR is associated with lower 1-year mortality compared to OSR. However, OSR may be preferred in those patients who have hydronephrosis and are deemed low risk.

Immobilizing live bacteria for AFM imaging of cellular processes.

Coccoid cells of the bacterial species Staphylococcus aureus have been mechanically trapped in lithographically patterned substrates and imaged under growth media using atomic force microscopy (AFM) in order to follow cellular processes. The cells are not perturbed as there is no chemical linkage to the surface. Confinement effects are minimized compared to trapping the cells in porous membranes or soft gels. S. aureus cells have been imaged undergoing cell division whilst trapped in the patterned substrates. Entrapment in lithographically patterned substrates provides a novel way for anchoring bacterial cells so that the AFM tip will not push the cells off during imaging, whilst allowing the bacteria to continue with cellular processes.

Contemporary management of aorto-iliac aneurysms in the endovascular era.

Up to 40% of abdominal aortic aneurysms have co-existing unilateral or bilateral iliac artery ectasia or aneurysm. These are associated with an increased risk of endoleak, morbidity and mortality following endoluminal repair. To reduce the adverse sequelae of internal iliac artery (IIA) occlusion, various open, endovascular and hybrid measures have been described to maintain perfusion to the pelvis. This review discusses the contemporary management of aorto-iliac aneurysm in the endovascular era with reference to the sequelae of IIA occlusion and the strategies to preserve IIA perfusion. Particular consideration is given to iliac bifurcation devices.

The natural history of stenoses within lower limb arterial bypass grafts using a graft surveillance program.

Graft surveillance aims to identify those grafts that are at risk of failure as intervention in a patent but failing graft results in improved long-term patency and limb salvage rates compared to rescue of an occluded graft. Controversy exists as to which types of graft benefit the most from surveillance and whether patient factors such as diabetes and smoking status have an effect on graft survival. Our aims were (1) to clarify the natural history of midterm graft failure as a consequence of myointimal hyperplasia and (2) to identify which patients and grafts are at a higher risk of failure and at what time points this is most prevalent. Serial vascular laboratory and clinical data of 212 infrainguinal lower limb grafts in 197 patients were analyzed. Follow-up within the surveillance program was by focused examination with color flow duplex ultrasound at 0, 1, 3, 6, 12, and 18 months with respect to surgery. Outcomes were correlated with retrospectively collected data regarding patient demographics, smoking status, concurrent medication, comorbidity, and operative factors such as distal target vessel and conduit. During the program, 21.6% of grafts occluded. Overall, 16% of grafts underwent a salvage procedure, 40.5% of which were carried out at the 6-month time point. There were 56.6% of occlusions preceded by a stenotic lesion. Primary occlusions accounted for 95.9% in the prosthetic group and 66.5% in the femorocrural group. As a group, vein grafts were more likely to develop a progressive stenosis prior to occlusion, with 58.3% in this group predated by a stenotic lesion. Fewer than 75% of stenoses were common and had a variable natural history, with over 40% resolving or failing to progress. Throughout the study period, 56.2% of grafts remained stenosis-free. Stenoses were more common at the proximal anastomosis in the vein graft cohort. There were low rates of significant stenoses within the prosthetic group. These lesions were more likely to occur at the distal anastomosis but were poor predictors of occlusion. Statin use postoperatively was protective against the development of significant stenosis and occlusions, particularly in the above-knee grafts (p = 0.03). Surprisingly, preoperative smoking status was predictive of neither occlusion nor development of significant stenosis. The presence of diabetes was not predictive of poor outcome. Our findings suggest that graft surveillance is a valid method for detecting the presence of significant stenoses in vein grafts at high risk of failure without intervention. Despite the intensive follow-up, the program failed to detect lesions prior to occlusion in a large percentage of prosthetic and femorocrural grafts, so perhaps this group is poorly served by graft surveillance.

Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype.

OBJECTIVES: We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. METHODS: We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. RESULTS: SLE patients <55 years old had more plaque (21% vs 3% P < 0.01) and more SLE patients had plaque in the internal carotid artery (11% vs 4%; P < 0.05). Traditional risk factor models performed less well in SLE compared with controls [area under Receiver Operator Characteristic curves (AUC ROC) = 0.76 vs 0.90; P < 0.01]. A multivariable model using SLE factors only, performed significantly better (AUC ROC = 0.87; P < 0.01). The final model in SLE included age and cigarette pack-years smoking as well as azathioprine exposure ever, antiphospholipid antibodies (APLA) and previous arterial events (AUC ROC = 0.88). CONCLUSIONS: SLE patients have a higher prevalence and different distribution of carotid plaque than controls. SLE factors perform significantly better than traditional risk factors in their association with atherosclerosis in SLE and these factors add to the influence of traditional risk factors rather than sensitizing lupus patients to traditional factors. The SLE phenotype helps identify patients at increased risk of atherosclerosis.

Intimal neovascularisation is a prominent feature of atherosclerotic plaques in diabetic patients with critical limb ischaemia.

INTRODUCTION: Neovascularisation of atherosclerotic plaques correlates with increased plaque instability and subsequent risk of vascular complications. Diabetics have widespread atherosclerotic involvement of the arterial tree and a more aggressive form of the disease culminating in increased plaque instability. This results in a greater incidence of ischaemic sequelae than in non-diabetics. Previous studies have examined neovascularisation as a marker of plaque instability in both the carotid and coronary territories and revealed a greater degree in both symptomatic and diabetic patients. This is the first study to examine intimal neovascularisation in lower limb peripheral arterial disease. METHODS: Arterial specimens were taken from 20 patients, ten of whom were type 2 diabetics, undergoing major lower limb amputation for unreconstructable critical ischaemia. Sections were stained with H&E for morphological assessment and inflammatory cell characterisation. Additional sections underwent immunohistochemical staining for CD31 and von-Willebrand Factor (vWF) and the number of intimal vessels per four 40x magnification fields assessed. RESULTS: There was a more prominent inflammatory infiltrate in diabetic subjects compared to non-diabetic controls. Diabetic patients had a greater degree of intimal neovascularisation compared to controls with a median of 11.5 and 2.0 vessels per field respectively (P<0.05). Sub-group analysis revealed that diabetic patients medicating with HMG-CoA Reductase inhibitors (Statins) had a greater degree of neovascularisation compared to those not taking this class of medication. CONCLUSION: Diabetic patients with critical limb ischaemia requiring amputation demonstrate a greater degree of plaque intimal neovascularisation and inflammatory infiltrate compared to their non-diabetic counterparts. This may explain the greater plaque instability and subsequent cardiovascular complications seen in these patients.

Tissue engineering of blood vessels.

BACKGROUND: Tissue engineering techniques have been employed successfully in the management of wounds, burns and cartilage repair. Current prosthetic alternatives to autologous vascular bypass grafts remain poor in terms of patency and infection risk. Growing biological blood vessels has been proposed as an alternative. METHODS: This review is based on a literature search using Medline, PubMed, ISIS and CAS of original articles and reviews, and unpublished material and abstracts. RESULTS AND CONCLUSIONS: Complete incorporation into host tissues and the maintenance of a viable and self-renewing endothelial layer are the fundamental goals to be achieved when developing a tissue-engineered blood vessel. Sourcing of cells and modulating their interaction with extracellular matrix and supporting scaffold have been the focus of intense research. Although the use of tissue-engineered blood vessels in humans is so far limited, advances in our knowledge of stem cell precursors and the development of new biomaterials should enable this technology to reach routine clinical practice within a decade.

Expression of growth factors and growth factor receptor in non-healing and healing ischaemic ulceration.

OBJECTIVES: To characterise the histological and cytokinetic characteristics of purely ischaemic ulcers and the processes that underpin healing following successful revascularisation. DESIGN: Prospective observational study. MATERIALS AND METHODS: Biopsies were taken immediately pre- and 6 weeks following successful revascularisation of solely ischaemic ulceration. They were evaluated for morphological differences using H&E staining for the platelet derived growth factor receptor (PDGFR), epidermal growth factor receptor (EGFR), TGFbeta receptorIII (TGFbetaRIII), transforming growth factor beta 1 and 3 (TGFbeta1 and TGFbeta3) and von Willebrand factor (vWF) expression using immunohistochemistry. Localisation and quantification of these growth factors and receptors was assessed systematically by three independent investigators who were blinded to the timing of biopsy. RESULTS: Pre-operatively, small vessel vasculitis, necrosis and infection with a profuse neutrophil and macrophage infiltrate was observed in all samples. Post-operative biopsies revealed a proliferation of new capillaries in and around the ulcer edge and base. vWF staining confirmed an endothelial layer within these new vessels. Following successful revascularisation there was less infection and inflammation with minimal vasculitis. These newly formed capillaries had increased staining for TGFbeta3, PDGFR and TGFbetaRIII with staining for PDGFR also localised to dermal fibroblasts which were larger and more numerous. Accelerated epithelial cell proliferation was observed with detachment from the underlying dermis. CONCLUSIONS: Healing of purely ischaemic ulcers is characterised by vasculogenesis associated with increased presence of the proangiogenic cytokines PDGF and TGFbeta3. These findings show promise for the use of growth factor manipulation to aid healing in ischaemic ulcers.

Colonic epithelial apoptosis during conventional and endoluminal aortic surgery.

BACKGROUND: This study characterized the initial modes of colonic mucosal injury during aneurysm surgery and correlated these with proinflammatory cytokine release into the colonic and systemic circulations. METHODS: Twenty-four patients undergoing conventional open aortic aneurysm repair and ten who had endovascular aneurysm repair (EVAR) were recruited. Mucosal biopsies were taken from the sigmoid colon immediately before and after surgery, for histological examination. Inferior mesenteric vein (IMV) and peripheral blood from patients who had conventional surgery was assayed for interleukin (IL) 1 beta, IL-6 and tumour necrosis factor (TNF) alpha. Only peripheral blood from patients who had EVAR was assayed. RESULTS: Conventional aneurysm repair resulted in a threefold increase in columnar epithelial apoptosis. There was a 26-fold increase in IL-6 in IMV blood within 5 min of reperfusion, with an equivalent rise in peripheral blood after 30 min. A 20-fold rise in peripheral blood TNF-alpha was observed after surgery. Splanchnic IL-6 correlated positively with cross-clamp time and increased apoptosis. No histological changes were seen after EVAR. There were no intraoperative cytokine changes during EVAR, although a postoperative increase in IL-6 and TNF-alpha was observed. CONCLUSION: The lack of columnar epithelial apoptosis following EVAR reflects the relatively minor ischaemic injury incurred during this procedure.

The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.

OBJECTIVES: Controversy exists regarding the optimal management of patients with coexisting coronary and extracranial carotid artery disease. This study investigates the incidence of death, cerebrovascular events and myocardial infarction (MI) in patients with asymptomatic significant carotid artery disease undergoing coronary artery bypass graft (CABG) surgery. DESIGN: Prospective cohort. METHODS: Fifty patients with asymptomatic carotid stenoses > or =70% associated with cervical bruits undergoing CABG without prophylactic carotid endarterectomy (CEA) were followed up over a median period of 68 months following surgery cerebrovascular events, MI and mortality were recorded. All patients received optimal secondary prevention for cardiovascular disease unless contraindicated. RESULTS: No cerebrovascular events occurred within 30 days of surgery. One patient suffered an ipsilateral transient ischaemic attack (TIA) 14 months after CABG. Two patients died within 30 days; one from an MI, the other from pancreatitis. Three deaths occurred after 30 days; one from MI, one from primary lung cancer and one following rupture of an abdominal aortic aneurysm. No non-fatal MIs occurred. CONCLUSIONS: In this patient group the overall risk of death, cerebrovascular events and MI was 4% during the first 30 days postoperatively and 8% thereafter. This compares favourably with published series for staged or combined CEA-CABG procedures. For asymptomatic significant carotid disease, prophylactic CEA prior to CABG does not appear to confer any advantage over CABG alone.

Outcome of transaxillary rib resection for thoracic outlet syndrome--a 10 year experience.

BACKGROUND: This study assessed the outcome of transaxillary first and/or cervical rib resection in a unit, which has a policy of combined assessment by a neurologist and vascular surgeon. METHODS: 61 patients underwent 83 transaxillary rib resections for thoracic outlet syndrome. A retrospective case note review of these patients was undertaken. All patients completed a telephone questionnaire regarding long-term outcome. RESULTS: Post-operative outpatient assessment at a median of 6 months recorded 91.5% improved, of whom 61.5% were symptom-free. 61% were available for the telephone questionnaire at a median follow-up of 4 yr. 74% reported an improvement, with complete resolution in 58%. Six described temporary improvement following surgery. CONCLUSION: Transaxillary rib resection is a safe and effective procedure, allowing almost two thirds of patients a return to normal activity. Combined assessment by vascular and neurological teams may help in patient selection for surgery, as well as the accurate long-term assessment of outcome.

A randomized study to evaluate the effect of a perioperative infusion of dopexamine on colonic mucosal ischemia after aortic surgery.

PURPOSE: Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates. This study was conducted as a single-center side arm to a multicenter, randomized, placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence. METHODS: Thirty patients, mean age 65.1 years (range, 46-84), undergoing elective infrarenal aortic surgery were entered. Preoperative hemodynamic and respiratory parameters were optimized. Patients were then randomly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute (n = 12) or 0.9% saline placebo (n = 18). All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively. Specimens were assessed for evidence of mucosal ischemia, presence of mast cell tryptase, myeloperoxidase activity, and both the inducible and endothelial isoforms of nitric oxide synthase. RESULTS: There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups. However, there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients (n = 1) compared with placebo (n = 8) (P =.049). Furthermore, when preoperative biopsies were compared with those performed 1 week postoperatively, nine (50%) patients in the placebo group and two (16.7%) in the dopexamine group scored worse. Although there was no significant difference in inflammatory markers between the two groups, both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia (P <.05). Furthermore, inducible nitric oxide synthase staining within the vascular (P =.001) and lamina propria (P <.05) components of the mucosa was also significantly greater. CONCLUSION: A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery.

A comparison of para-anastomotic compliance profiles after vascular anastomosis: nonpenetrating clips versus standard sutures.

PURPOSE: Anastomotic compliance is an important predictive factor for long-term patency of small diameter vascular reconstruction. In this experimental study we compare the compliance of continuous and interrupted sutured vascular anastomoses with those using nonpenetrating clips. METHODS: Both common carotid arteries in nine goats (average weight, 57 +/- 5.7 kg) were transected, and end-to-end anastomoses were constructed with nonpenetrating clips or polypropylene sutures. The latter were applied with both interrupted and continuous techniques. Intraluminal pressure was measured with a Millar Mikro-tip transducer, and vessel wall motion was determined with duplex ultrasound equipped with an echo-locked wall-tracking system. Diametrical compliance was determined. Environmental scanning electron microscopy was performed on explanted anastomoses. RESULTS: There was a reduction in anastomotic compliance and associated proximal and distal para-anastomotic hypercompliant zones with the use of all techniques. However, compliance loss was significantly less in those anastomoses with clips and interrupted sutures when compared with continuous suture (P <.001). Furthermore, the total compliance mismatch across anastomoses with continuous sutures was significantly greater than those with clips or interrupted sutures (P <.05). The mean time for constructing clipped anastomoses was 5.7 +/- 1.4 minutes, which was significantly less than either continuous (P <.0001) or interrupted sutures (P <.0001). Furthermore, environmental scanning electron microscopy demonstrated minimal intimal damage with good intimal apposition in the clip group. CONCLUSION: Anastomoses performed with nonpenetrating clips resulted in improved para-anastomotic compliance profiles and reduced intimal damage when compared with those with polypropylene sutures. These benefits may enhance long-term graft patency by reducing the risk of anastomotic intimal hyperplasia.

Pharmaceutical target identification by gene expression analysis.

The majority of newly-identified genes in the human genome show no significant sequence similarity to genes whose function is known, so they are not easily recognized as potential drug targets. Expression analysis is an alternative method to suggest possible functions of genes. We review statistical methods for gene expression analysis to identify potential pharmaceutical targets. Specifically, we illustrate the analysis of differential gene expression (using discriminant analysis, t-tests, and analysis of variance) and co-expression (using correlation, clustering, and chi-square). We present an example of the use of expression analysis to identify co-expressed cardiomyopathy-associated genes.

Drug target discovery by gene expression analysis: cell cycle genes.

Gene expression microarrays and gene expression databases provide new opportunities for the discovery of drug targets and for determination of a drug's mode of action. We review gene expression analysis methods and describe studies that have identified cell cycle genes using differential expression analysis and co-expression analysis. We present an example of the identification of previously-unrecognized human cell cycle genes, CDCA1 through CDCA8, that are co-expressed with known cell cycle genes including CDC2, CDC7, CDC23, cyclin, MCAK, mki67a, topoisomerase II, and others.

The significance of CD105, TGFbeta and CD105/TGFbeta complexes in coronary artery disease.

We have quantified levels of CD105, its ligand TGFbeta and receptor-ligand complexes in sera from healthy individuals (n=31), patients with triple vessel disease documented by coronary angiography (TVD; n=36) and patients with chest pain and a positive exercise electrocardiogram but with normal coronary angiogram (NCA; n=30). Both active TGFbeta1 and active plus acid-activatable TGFbeta1 [(a+l)TGFbeta1] were significantly depressed in patients with TVD compared with the other two groups (P