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PubMed2005

Identification of phenotypic neural stem cells in a pediatric astroblastoma.

OBJECT: The goal of this study was to illustrate the findings of a significant subpopulation of cells within a pediatric astroblastoma that have the specific cell surface phenotype found on known human neural stem cells. METHODS: Cells with a cell surface marker profile characteristic of human neural stem cells were isolated using fluorescence-activated cell sorting from a mostly nonmitotic astroblastoma removed from the brain of an 11-year-old girl. An unusually high proportion (24%) of the cells were CD133 positive and CD24, CD34, and CD45 negative (CD133(+)CD24(-)CD34(-)CD45(-) cells), the phenotypic antigenic pattern associated with neural stem cells; very few CD133-positive cells were not also CD24, CD34, and CD45 negative. Some cells (12%) were CD34 positive, indicating the presence within the tumor of hematopoietic stem cells. Cells formed cytospheres that resembled neurospheres when seeded into stem cell media and coexpressed beta-tubulin and glial fibrillary acidic protein (GFAP) but did not express the oligodendrocyte marker O4. Cell proliferation was demonstrated by incorporation of bromodeoxyuridine. The cells lost their capacity for self-renewal in vitro after four to six passages, although they continued to coexpress beta-tubulin and GFAP. The cells did not differentiate into neurons or astrocytes when placed in differentiation medium. CONCLUSIONS: Although this astroblastoma contained a high proportion of phenotypic neural stemlike cells, the cells had limited proliferative capacity and multipotency. Their role in astroblastoma formation and growth is unknown.

Antigens, CD↗
PubMed1998

Vertical latent nystagmus component and vertical saccadic asymmetries in subjects with dissociated vertical deviation.

PURPOSE: This study was conducted to quantify the vertical component of a latent nystagmus observed in subjects with dissociated vertical deviation (DVD), as well as to provide further evidence for vertical saccadic asymmetries in these individuals. METHODS: Binocular eye movements of subjects with DVD were recorded in two dimensions using a noninvasive video-based eye tracker while cover/uncover tests, alternate cover tests, and vertical saccades were performed. RESULTS: A small amplitude (1.5 degrees or less) vertical component of latent nystagmus can be observed in some subjects with DVD and is larger in the deviating eye than in the viewing eye. The frequency of the vertical nystagmus component is the same in each eye for any given fixation condition but may change depending on which eye is fixating. DVD in the presence of a vertical component of latent nystagmus can be adequately modeled by the algebraic sum of an exponentially decreasing velocity DVD and a nystagmus with an exponentially decreasing slow phase velocity. In general, the occluded eyes of DVD subjects make smaller downward saccades than the viewing eyes. CONCLUSIONS: It is possible but not obligatory that DVD subjects will have a vertical component of latent nystagmus. Algebraic summation of an exponentially decreasing velocity DVD and a vertical component of latent nystagmus provides a more parsimonious explanation of the observed saccadic eye movements than modeling the DVD itself as a combination of vergence and saccadic movements. Subjects with DVD show a range of saccadic yoking from nearly complete saccadic conjugacy to nearly complete dissociation.

Adult↗
PubMed2002

Effect of combination therapy (ribavirin and interferon) in HCV-related glomerulopathy.

BACKGROUND: Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis throughout the world. Several extrahepatic manifestations, including glomerulonephritis, have been reported to be associated with this type of infection. Cryoglobulinaemic and non-cryoglobulinaemic membranoproliferative glomerulonephritis (MPGN) and membranous nephropathy (MN) are the commonest lesions associated with HCV. Results of treatment of these patients with interferon therapy have been disappointing, since relapse of the viraemia and subsequent relapse of the renal disease are major problems. Combination of interferon with ribavirin in patients with chronic liver disease has been shown to increase the rate of sustained response. METHODS: In this work, 20 patients with HCV-associated glomerulopathy were subjected to an in-depth evaluation of their kidney lesions and HCV involvement. Laboratory, histopathological, immunohistochemical, and electron-microscopy techniques were used. The patients received interferon therapy for 12 months; in interferon-resistant subjects, interferon was combined with ribavirin. RESULTS: MPGN was the commonest kidney lesion, being reported in 85% of these cases, followed by MN and mesangioproliferative glomerulonephritis (10 and 5% respectively). Mixed cryoglobulinaemia was encountered in 60% of the cases. Twelve months' anti-viral treatment resulted in aviraemia in 25% of cases, while liver enzymes were normalized in 75%, 24-h proteinuria significantly decreased (from median 4 g to 1.10 g, P=0.001), serum albumin increased (from median 2.50 to 3.55 g/dl, P=0.012), lower viral titres (from median 1.15 to 0.53 mega-Eq/ml, P=0.049), and C3 and C4 concentrations returned to normal. Basal serum creatinine and viral titres were important determinants of response to treatment. CONCLUSION: This study supports the relationship between HCV and glomerulonephritis, especially MPGN, and the use of a combination of interferon and ribavirin in the treatment of selected cases of HCV-related glomerulopathy.

Adult↗
PubMed2006

Does preoperative ejection fraction predict operative mortality with left ventricular restoration?

BACKGROUND: Ischemic cardiomyopathy and aneurysmal disease have been treated surgically with coronary artery bypass grafting in the past. The Dor technique for left ventricular restoration has demonstrated improved outcomes in patients with ischemic, akinetic ventricles. Our hypothesis was that even marked reduction in preoperative cardiac function (ejection fraction < .25) would not correlate with worse outcomes since the ventricle would be reshaped to improve function. METHODS: A retrospective analysis was performed on all patients who had undergone ventricular restoration with the Dor procedure from January 1996 through September 2005. Patients with a preoperative ejection fraction (EF) < .25 and those with a EF > or = .25 were compared. All Society of Thoracic Surgeons database characteristics, mortality, length of stay (LOS), and need for intraaortic balloon pump (IABP) were analyzed. RESULTS: The study included 89 patients (69 men, 20 women), 28 of whom had preoperative EFs < .25 (mean, .183 +/- .035; range, .08 to .25) and 61 had an EF > or = .25 (mean, .334 +/- .074; mean, .25 to .45). Overall operative mortality was 3.4% (3/89), with no statistically significant difference between the two groups (3.6% versus 3.3%). LOS was 7.4 +/- 3.6 days versus 8.9 +/- 15.6 days (p = NS), and need for IABP was 39.2% versus 8.1% (p < 0.05). Overall 5-year survival was 82%. Five-year survival in the EF < .25 cohort was 69.6% versus 88.3% in the EF > or = .25 cohort (p = 0.066). CONCLUSIONS: Ventricular restoration with the Dor technique is a safe procedure. Marked reduction in ejection fraction is not a contraindication to left ventricular restoration; however, increased usage of IABP should be anticipated.

Adult↗
PubMed2005

Decreased recipient survival following orthotopic heart transplantation with use of hearts from donors with projectile brain injury.

BACKGROUND: Fatal gunshot injury to the brain can cause significant alterations in the neuroendocrine state and myocardial dysfunction. Therefore heart allografts from these donors may result in graft failure following orthotopic heart transplantation (OHTx). We evaluated whether receiving a heart from a donor who died from fatal gunshot wound to the brain independently affected the outcome of transplantation. METHODS: A retrospective review of 113 consecutive patients undergoing OHTx at a university hospital from 1996 to 2002 was performed. Group 1 received hearts from donors with fatal gun shot brain injury (n = 17), and Group 2 received hearts from donors who died from other causes (n = 96). RESULTS: Recipient age, gender, United Network for Organ Sharing (UNOS) status, indication for transplantation, and other co-morbid conditions were similar in both groups. Young male donors pre-dominated in Group 1, but other donor characteristics were not significantly different. The incidence of Grade 3A rejection was higher in Group 1 than Group 2 (35% vs 6.3%, p = 0.003), as was the incidence of post-operative infection (35% vs 7.2%, p = 0.004). Actuarial survival at 1 and 5 years was significantly lower in Group 1 than in Group 2 (81% and 74% vs 97% and 94%, respectively, p = 0.005). Multivariate logistic regression analysis also demonstrated that fatal gunshot brain injury, as cause of donor death, was a risk factor for recipient mortality (p = 0.01). CONCLUSION: Receiving a heart from a donor with fatal gunshot brain injury is a significant risk factor for recipient mortality following OHTx. Cautious use of heart allograft from these donors, especially in low-risk recipients, may lead to improved outcome following heart transplantation.

Adult↗
PubMed2002

Adenosine A2A receptor activation decreases reperfusion injury associated with high-flow reperfusion.

INTRODUCTION: High pulmonary artery flow rates can result in severe reperfusion injury after lung transplantation. Our hypothesis was that selective activation of the adenosine A(2A) receptor with a highly specific analog (ATL-146e) would inhibit leukocyte activation and decrease reperfusion injury after high-flow reperfusion. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, all groups (n = 8 per group) underwent lung harvest, 4 hours of cold storage, and blood reperfusion for 30 minutes. Measurements of pulmonary artery pressure (in millimeters of mercury), arterial oxygenation (in millimeters of mercury), myeloperoxidase, peak inspiratory pressure, and wet/dry weight ratio were obtained. Groups 1 (high flow) and 2 (high flow ATL-146e) underwent reperfusion at 120 mL/min for 30 minutes. Groups 3 (controlled high flow) and 4 (controlled high flow ATL-146e) underwent controlled reperfusion with an initial reperfusion of 60 mL/min for the first 5 minutes, followed by a rate of 120 mL/min for 25 minutes. During reperfusion, groups 2 and 4 received ATL-146e at 4 microg. kg(-1). min(-1). RESULTS: ATL-146e significantly improved lung physiologic measurements under both high-flow (group 1 vs group 2) and controlled high-flow (group 3 vs group 4) conditions after 30 minutes. CONCLUSIONS: The adenosine A(2A) receptor analogue ATL-146e significantly decreases the severity of reperfusion injury in the setting of both high-flow and controlled high-flow reperfusion.

Animals↗
PubMed2004

YOUTH: decisions and challenges in designing an osteoporosis prevention intervention for teen girls.

BACKGROUND: This paper describes decisions about the experimental design for the Youth, Osteoporosis, and Understanding Total Health Project (YOUTH), a trial designed to test the efficacy of a health plan-based lifestyle intervention for increasing bone mineral density among adolescent women 14 to 16 years of age. METHODS: This randomized controlled trial recruited adolescent women who were at higher risk for developing osteoporosis (body mass index 16-23) from a large HMO in the Pacific Northwest. The intervention focused on improving diet (high calcium foods, fruits, and vegetables) and increasing physical activity (high impact and spinal motion). The intervention included both group and individual activities. The primary endpoint in the study was total bone mineral density as measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Baseline data were collected on the trial cohort of 228 adolescent women and their families. This paper discusses how researchers met the following challenges in designing and implementing the trial: determining appropriate dietary and exercise targets to affect bone mineral density in adolescents; choosing suitable assessments; and developing an intervention well suited for implementation in a non-school (health plan) setting. We also discuss the rationale for the specific study population chosen (females, younger adolescents). CONCLUSIONS: The YOUTH project is one of very few preventive research interventions with adolescents conducted in a health plan setting. Many of the recruitment and intervention strategies used in this trial may be appropriate for adoption in other health plan-based prevention studies.

Adolescent↗
PubMed1994

3D MRI volume sizing of knee meniscus cartilage.

Meniscal replacement by allograft and meniscal regeneration through collagen meniscal scaffolds have been recently reported. To evaluate the effectiveness of a replaced or regrown meniscal cartilage, a method for measuring the size and function of the regenerated tissue in vivo is required. To solve this problem, we developed and evaluated a magnetic resonance imaging (MRI) technique to measure the volume of meniscal tissues. Twenty-one intact fresh cadaver knees were evaluated and scanned with MRI for meniscal volume sizing. The sizing sequence was repeated six times for each of 21 lateral and 12 medial menisci. The menisci were then excised and measured by water volume displacement. Each volume displacement measurement was repeated six times. The MRI technique employed to measure the volume of the menisci was shown to correspond to that of the standard measure of volume and was just as precise. However, the MRI technique consistently underestimated the actual volume. The average of the coefficient of variation for lateral volumes was 0.04 and 0.05 for the water and the MRI measurements, respectively. For medial measurements it was 0.04 and 0.06. The correlation for the lateral menisci was r = 0.45 (p = 0.04) and for the medial menisci it was r = 0.57 (p = 0.05). We conclude that 3D MRI is precise and repeatable but not accurate when used to measure meniscal volume in vivo and therefore may only be useful for evaluating changes in meniscal allografts and meniscal regeneration templates over time.

Analysis of Variance↗
PubMed2006

Improving albumin levels among hemodialysis patients: a community-based randomized controlled trial.

BACKGROUND: Low albumin level is a strong predictor of mortality and morbidity among hemodialysis patients, yet few interventions are available to improve albumin levels. Moreover, the relative importance of nutritional barriers versus inflammation in contributing to hypoalbuminemia is unclear. We sought to determine whether targeting specific nutritional barriers will improve albumin levels. METHODS: We conducted a randomized controlled trial involving 180 patients with baseline albumin levels less than 3.7 g/dL (<37 g/L) at 44 long-term hemodialysis facilities. Study coordinators identified and intervened on specific barriers present among intervention patients, whereas control patients continued to receive the usual care. Barriers targeted included poor nutritional knowledge, poor appetite, help needed with shopping or cooking, low fluid intake, inadequate dialysis dose, depression, difficulty chewing, difficulty swallowing, gastrointestinal symptoms, and acidosis. RESULTS: At baseline, intervention and control patients had similar albumin levels, dietary intakes, levels of inflammatory markers, and numbers of nutritional barriers. After 12 months, intervention patients had greater increases in albumin levels compared with control patients (+0.21 versus +0.06 g/dL [+2.1 versus +0.6 g/L]; P < 0.01), as well as greater increases in energy intake (+4.1 versus -0.6 Kcal/d/kg; P < 0.001) and protein intake (+0.13 versus -0.06 g/d/kg; P < 0.001). The intervention appeared most effective for barriers related to poor nutritional knowledge, help needed with shopping or cooking, and difficulty swallowing. About half the subjects had elevated levels of inflammatory markers, but there was no relationship between change in levels of albumin and inflammatory markers. CONCLUSION: A nutrition intervention tailored to patient-specific barriers resulted in modest improvements in albumin levels regardless of levels of inflammatory markers.

Appetite↗
PubMed2004

Chloramphenicol resistance in vancomycin-resistant enterococcal bacteremia: impact of prior fluoroquinolone use?

OBJECTIVE: The prevalence of vancomycin-resistant enterococci (VRE) has increased markedly during the past decade. Few data exist regarding the epidemiology of resistance of VRE to chloramphenicol, one of the few therapeutic options. DESIGN: Survey and case-control study. SETTING: A 725-bed, tertiary-care academic medical center and a 344-bed urban community hospital. PATIENTS: Hospitalized patients with blood cultures demonstrating VRE. METHODS: We examined the trends in the prevalence of chloramphenicol resistance in VRE blood isolates at our institution from 1991 through 2002 and conducted a case-control study to identify risk factors for chloramphenicol resistance among these isolates. RESULTS: From 1991 through 2002, the annual prevalence of chloramphenicol-resistant VRE increased from 0% to 12% (P < .001, chi-square test for trend). Twenty-two case-patients with chloramphenicol-resistant VRE bloodstream isolates were compared with 79 randomly selected control-patients with chloramphenicol-susceptible VRE. Independent risk factors for chloramphenicol-resistant VRE were prior chloramphenicol use (odds ratio [OR], 10.9; 95% confidence interval [CI95], 1.72-68.91; P = .01) and prior fluoroquinolone use (OR, 4.74; CI95, 1.15-19.42; P = .03). Chloramphenicol-resistant VRE isolates were more likely to be susceptible to beta-lactams and resistant to tetracycline than were chloramphenicol-susceptible VRE isolates. CONCLUSIONS: Significant increases in the prevalence of chloramphenicol-resistant VRE may limit the future utility of chloramphenicol in the treatment of VRE infections, and close monitoring of susceptibility trends should continue. The association between fluoroquinolone use and chloramphenicol-resistant VRE, reflecting possible co-selection of resistance, suggests that recent dramatic increases in fluoroquinolone use may have broader implications than previously recognized.

Bacteremia↗
PubMed2006

Comparison of unit-specific and hospital-wide antibiograms: potential implications for selection of empirical antimicrobial therapy.

OBJECTIVE: To identify differences between unit-specific and hospital-wide antibiograms and to determine the potential impact of these differences on selection of empirical antimicrobial therapy. SETTING: A 625-bed tertiary care medical center. METHODS: Antimicrobial susceptibility results were collected for all inpatient clinical bacterial isolates recovered over a 3-year period; isolates were categorized by the hospital location of the patient at the time of sampling and by the anatomic site from which the isolate was recovered. Antibiograms from each unit were compiled for the most commonly isolated organisms and were compared to the hospital-wide antibiogram. RESULTS: A total of 9,970 bacterial isolates were evaluated in this study, including 2,646 enterococcal isolates, 2,806 S. aureus isolates, 2,795 E. coli isolates, and 1,723 Pseudomonas aeruginosa isolates. The percentages of bacterial isolates resistant to antimicrobials were significantly higher in the medical ICU and surgical ICU than the hospital-wide antibiogram would have predicted, whereas the percentages of isolates susceptible to antimicrobials were significantly higher in the non-ICU units, compared with the hospital overall. However, on general medicine units, the prevalence of susceptibility to levofloxacin was significantly lower than that for the hospital overall. CONCLUSIONS: Unit-specific antibiograms are important for making informed decisions about empirical antimicrobial therapy, because the hospital-wide antibiogram may mask important differences in susceptibility rates across different units. These differences may have important implications for selecting the optimal empirical antimicrobial therapy.

Anti-Infective Agents↗
PubMed2004

Formation of platelet-leukocyte aggregates in inflammatory bowel disease.

OBJECTIVES: Formation of platelet-leukocyte aggregates (PLAs) is increased in several inflammatory and thrombotic conditions. This may result from and enhance platelet and neutrophil activation and could contribute to the inflammatory process in inflammatory bowel disease (IBD). We investigated platelet-leukocyte aggregation in patients with IBD and its relation to treatment, disease activity and platelet and neutrophil activation. METHODS: PLAs, platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression) were assessed 30 and 180 minutes after drawing blood into EDTA/citrate-theophylline-adenosine and dipyridamole, a novel anticoagulant, using fluorescent antibodies to CD45 (for leukocytes), CD42a (for platelets), CD62P (P-selectin) and CD62L (L-selectin) and flow cytometry. Platelet activation was also measured using the ADVIA 120 hematology analyser. RESULTS: Samples from 67 patients with IBD measured within 30 minutes had a higher platelet count (P < 0.001), more platelets expressing P-selectin (P = 0.01), and more PLAs (P < 0.01) than from 20 healthy controls and more PLAs (P < 0.05) than from 9 controls with inflammatory arthropathies. IBD patients on thiopurines had fewer PLAs than those not taking them (P < 0.05); corticosteroids and aminosalicylates had no such effects. Incubation for 180 minutes increased the number of platelets expressing P-selectin (P < 0.0001), and the number of PLAs (P < 0.0001). The PLAs correlated with the number of platelets expressing P-selectin before (r=+0.40, P < 0.001) and after (r=+0.66, P < 0.0001) incubation. CONCLUSIONS: The number of PLAs is higher in patients with IBD than in healthy and inflammatory controls, but their numbers are lowered by thiopurines. Increased PLA formation may in part be due to increased platelet activation and could be pathogenic in IBD.

Adolescent↗
PubMed1994

Mild dilatation of the fetal kidney: a follow-up study.

OBJECTIVE: To assess morbidity in children with mild prenatally detected pelvicalyceal dilatation and to document the natural history of this ultrasound finding in post-natal life. PATIENTS AND METHODS: A retrospective (on-going) study was carried out in 29 children (39 kidneys) with mild dilatation confined to the pelvis and/or calices confirmed on initial post-natal ultrasound scan. Re-evaluation was carried out at a mean age of 4.2 years (range 1.5-7.8). Clinically, each patient's history, height, weight and blood pressure were recorded. On ultrasound examination the renal length, collecting system appearances and dimensions were recorded. RESULTS: Vesico-ureteric reflux was demonstrated in 1 of 14 infants who underwent neonatal micturating cystourethrography. During cumulative follow-up totaling 122 years, there were only two documented episodes of urological morbidity, i.e. one episode of unexplained haematuria and one of urinary tract infection. By a mean age of 4.2 years the ultrasound appearances had reverted to normal in 69% of kidneys. In 31% dilatation persisted and was unchanged or diminished in severity. No case of increasing dilatation was seen. Renal growth was normal in 97% of kidneys. CONCLUSIONS: Mild dilatation of the fetal urinary tract is a common prenatal ultrasound finding. When confined to the renal pelvis and/or calices it is of doubtful clinical significance and is associated with a low level of morbidity in infancy and early childhood. Invasive investigation in post-natal life is not justified.

Child↗
PubMed2005

Risk-adjustment in hepatobiliary pancreatic surgery.

AIM: The present study evaluates the performance of the POSSUM, the American Society of Anesthetists (ASA), APACHE and Childs classification in predicting mortality and morbidity in hepatopancreaticobiliary (HPB) surgery. We describe especially the limitations and advantages of risk in stratifying the patients. METHODS: We investigated 177 randomly chosen patients undergoing elective complex HPB surgery in a single institution with a total of 71 pre-operative and intra-operative risk factors. Primary endpoint was in-hospital mortality and morbidity. Ordered logistic regression analysis was used to identify individual predictors of operative morbidity and mortality. RESULTS: The operative mortality in the series was 3.95%. This compared well with the p-POSSUM and APACHE predicted mortality of 4.31% and 4.29% respectively. Post-operative complications amounted to 45% with 24 (13.6%) patients having a major adverse event. On multivariate analysis the pre-operative POSSUM physiological score (OR = 1.18, P = 0.009) was superior in predicting complications compared to the ASA (P = 0.108), APACHE (P = 0.117) or Childs classification (P = 0.136). In addition, serum sodium, creatinine, international normalized ratio (INR), pulse rate, and intra-operative blood loss were independent risk factors. A combination of the POSSUM variables and INR offered the optimal combination of risk factors for risk prognostication in HPB surgery. CONCLUSION: Morbidity for elective HPB surgery can be accurately predicted and applied in everyday surgical practice as an adjunct in the process of informed consent and for effective allocation of resources for intensive and high-dependency care facilities.

Adult↗
PubMed2005

They are not stealthy in the heart: embryonic stem cells trigger cell infiltration, humoral and T-lymphocyte-based host immune response.

OBJECTIVE: The in vivo immunogenicity of Embryonic Stem Cells is controversial. At present, there is only in vitro evidence of MHC I expression by this cell population but vivid speculation about their immune-privileged state. The immunology aspect of ESC transplantation deserves thorough investigation. METHODS: We injected mouse ESC (expressing Green Fluorescent Protein, GFP) into injured myocardium of syngeneic, allogeneic and SCID recipients. Furthermore, we monitored host response for up to 4 weeks post cell transfer. We determined local response (CD 3, CD 11c expression by host cells), MHC I expression by donor cells, MHC-II expression within and around the graft, humoral response of allogeneic hosts using Flow Cytometry and evaluated the hosts' cytokine response using stimulated spleenocytes by means of ELISPOT. Cell survival was estimated by morphometry, by calculating the area of the GFP+ graft over the area of infarction at multiple sections of the harvested heart. RESULTS: There was significant cellular infiltration into and around the graft consisting of T-lymphocytes (CD3+) and dendritic cells (CD 11c). Infiltration was detectable at 1 week and progressed through 4 weeks following cell transplantation. The humoral Ab response was moderate at 2 weeks but frank at 4 weeks. ELISPOT demonstrated a Th1 pathway of donor specific T-lymphocyte response with strong IFN-gamma and Il-2 production (figure A). MHC I expression was significant within the graft and maximal in the allogeneic groups. CONCLUSIONS: An immune response against transplanted ESC was demonstrated and the future use of ESC will likely require the use of systemic immunosuppression.

Animals↗
PubMed2005

The incidence of implantable cardioverter defibrillator indications in patients admitted to all coronary care units in a single district.

AIMS: Implantable cardioverter defibrillators (ICDs) have been shown to reduce all-cause mortality in groups of patients at high risk of ventricular arrhythmias. The true incidence of ICD indications is unknown but we hypothesize that it far exceeds the number actually implanted. METHODS: In a one month observational audit, we reviewed the clinical records of all 336 patients admitted to coronary care units serving a district with a population of 471,000, to determine the additional screening tests required in myocardial infarction (MI) survivors and the number of additional ICDs which would be implanted for the primary and secondary prevention indications recommended in UK National Institute for Clinical Excellence (NICE) guidance. A further analysis was performed to determine the effect of extending the primary prevention indications to include the selection criteria used in the second multicentre automatic defibrillator trial, MADIT II. RESULTS: Using NICE criteria, we found the incidence of ICD indications to be 98.4/10(6)/year. The addition of patients fulfilling MADIT II selection criteria for primary prevention would have increased this to 453/10(6)/year. CONCLUSION: We conclude that the implementation of national guidance on the use of ICDs for arrhythmias will require the systematic screening of MI survivors, and would identify an incidence of ICD indications at least three times that anticipated by NICE, and eight times as many as were actually implanted in the UK in 2000. If the primary prevention indications were widened to include MADIT II selection criteria, the total would be nearer to 12 times that anticipated, and 47 times the number actually implanted.

Adult↗
PubMed2005

In vivo behavior of decellularized vein allograft.

BACKGROUND: We are investigating decellularized vein allograft as a scaffold to engineer a non-synthetic, small-diameter vascular graft. This study examines the in vivo behavior of this scaffolding after implantation into the arterial circulation. MATERIALS AND METHODS: Canine animals underwent bilateral carotid interposition grafting using jugular vein implanted as either: 1) fresh autograft, 2) fresh allograft, or 3) decellularized allograft. Decellularization was achieved using sodium dodecyl sulfate. Grafts were examined with duplex ultrasound biweekly to determine luminal diameter, thrombosis, stenosis, or anastomotic breakdown. After perfusion fixation at 2 or 8 weeks, grafts underwent histological, morphometric, and immunohistochemical examination. RESULTS: All animals survived without neurological or hemorrhagic complication. No deterioration of graft integrity (rupture, aneurysm) was observed in any group. Luminal narrowing was observed in both allograft groups, but secondary to different pathology. Fresh allografts had significant mononuclear cell infiltrate, intimal hyperplasia, and intramural hemorrhage consistent with rejection. Conversely, decellularized allografts had minimal evidence of rejection but instead had a compact fibrin layer formed along their lumen. This fibrin layer was absent in the peri-anastomotic regions where endothelium had migrated from the native artery. By 8 weeks, decellularized grafts had repopulated with cells staining positive for smooth muscle alpha-actin. CONCLUSIONS: After 8 weeks of arterial flow, decellularized vein allograft exhibits satisfactory strength, reduced antigenicity compared to fresh allograft, and supports cellular repopulation. These characteristics make it satisfactory for further tissue engineering; combined with luminal vascular cell seeding, it may prove useful as a small-diameter arterial bypass graft.

Animals↗
PubMed2006

Incorporation of bone marrow-derived Flk-1-expressing CD34+ cells in the endothelium of tumor vessels in the mouse brain.

OBJECTIVE: Neoangiogenesis is a prerequisite for the full phenotypic expression and growth of a malignant tumor mass. It is believed to be triggered by tissue hypoxia and involves proliferation and sprouting of the preexisting vessels and the recruitment of endothelial progenitor cells from bone marrow. METHODS: A chimeric mouse model was used to examine the contribution of these progenitor cells to the neovasculature of brain tumor. T-cell knockout (RAG/KO5.2) mice were irradiated lethally, and their bone marrow was repopulated with T-cell depleted green fluorescent protein (GFP)-expressing bone marrow cells. RAG/RT-2 glioma cells were implanted into the striatum of the animals. Neovascular formation at various times of tumor growth was monitored together with the extent of incorporation of GFP+ bone marrow-derived cells within the vascular tree, in particular, cells carrying the endothelial progenitor markers CD34 and Flk-1. RESULTS: The recruitment of GFP+ cells to the growing tumor and their incorporation into the vascular network occurred during the period of increasing vascular density and preceded the expansion of the tumor. The number of marrow-derived cells with endothelial morphology and phenotype was small but significant (4% of all endothelial cells at Day 12); 54% of all tumor vessels contained at least one GFP+ cell. CONCLUSION: Our results suggest that bone marrow cells are recruited to newly formed and remodeled tumor vessels. Their recruitment may occur in response to signals from a highly proliferating milieu, and their role is to support the neovascular complex and to promote tumor growth.

Animals↗