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Background CD133 is a newly developed hematopoietic stem cell marker but little is known about its function. Whether CD133+ cell selection provides any advantage over CD34+ selection for hematopoietic stem cell isolation and transplantation is unclear. The present study compared colony formation and endothelial cell differentiation of these two cell types from umbilical cord blood (UCB). Methods Mononuclear cells from the same UCB samples were used for both CD133+ and CD34+ cell selection. Cells with 97.1% purity were incubated in semi-solid culture medium containing stem cell growth factor (SCGF) and G-CSF or erythropoietin (EPO). Purified cells were also cultured in M199 containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1). Results CD34+ and CD133+ cells produced similar numbers of CFU-GM colonies (median 43.25 and 30.5, respectively; P>0.2). However, a greater than four-fold difference in BFU-E colony formation was observed from CD34+ cells compared with CD133+ cells (median 35 and 8, respectively; P<0.04). CD34+ cells gave rise to endothelial-like cells when stimulated with VEGF, bFGF and IGF-1. CD133+ cells were unable produce this cell type under the same conditions. Discussion CD133+ cells produced smaller BFU-E colonies and were unable to differentiate into mature endothelial cells. CD34+ cells contained endothelial progenitors that could differentiate into mature cells of this lineage. Based on these data, it appears that CD133 offers no distinct advantage over CD34 as a selective marker for immunoaffinity-based isolation of hematopoietic stem cells and endothelial progenitor cells. [ABSTRACT FROM AUTHOR]

The effects of chronic respiratory failure (hypoxia and hypercapnia) on the contractile properties of cardiac muscle are not established. A study was performed of the isometric contractile properties of isolated papillary muscle removed from rats exposed in a normobaric environmental chamber to 28 days of hypoxia (fractional inspired oxygen (FIO2) 10%, fractional inspired carbon dioxide (FICO2) less than 1%), hypercapnia (FIO2 21%, FICO2 5%), and hypoxia with hypercapnia (FIO2 10%, FICO2 5%). Rats exposed to both hypoxia and hypoxia with hypercapnia developed selective right ventricular hypertrophy. Exposure to hypercapnia alone did not alter right ventricular weight. No change in right ventricular papillary muscle contractility per unit muscle mass was observed as measured by maximum active tension, maximum rate of rise or fall of tension, or time to peak tension. Rat cardiac muscle adapts successfully to the altered acid-base environment and increased work load associated with prolonged exposure to hypoxia and mild hypercapnia. [ABSTRACT FROM AUTHOR]

The role of prazosin, an alpha 1 adrenoceptor blocker, was investigated in patients with chronic stable asthma who continued to have symptoms despite conventional treatment. Forty patients were entered into a double blind, placebo controlled, crossover trial to examine the effect of adding oral prazosin (2 mg twice daily) to previous medication for three weeks. Sixteen patients withdrew from the study. The remaining 24 patients showed no significant change in peak expiratory flow, FEV1, forced vital capacity (FVC), FEV1/FVC ratio, diary card symptom scores, or dose of beta sympathomimetic. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Obstructive Pulmonary Disease (COPD) frequently presents with an acute exacerbation (AECOPD). Debate exists as to whether these patients should be admitted to intensive care units (ICUs). An integrative review was performed to determine whether clinical variables available at the time of ICU admission are predictive of the intermediate-term mortality of patients with an AECOPD., Methods: An integrative review was structured to incorporate a five-stage review framework to facilitate data extraction, analysis and presentation. The quality of the studies contributing to the integrative review was assessed with a novel scoring system developed from previously published data and adapted to this setting., Results: The integrative review search strategy identified 28 studies assessing prognostic variables in this setting. Prognostic variables associated with intermediate-term mortality were low Glasgow Coma Scale (GCS) on admission to ICU, cardio-respiratory arrest prior to ICU admission, cardiac dysrhythmia prior to ICU admission, length of hospital stay prior to ICU admission and higher values of acute physiology scoring systems. Premorbid variables such as age, functional capacity, pulmonary function tests, prior hospital or ICU admissions, body mass index and long-term oxygen therapy were not found to be associated with intermediate-term mortality nor was the diagnosis attributed to the cause of the AECOPD., Discussion: Variables associated with intermediate-term mortality after AECOPD requiring ICU admission are those variables, which reflect underlying severity of acute illness. Premorbid and diagnostic data have not been shown to be predictive of outcome. A scoring system is proposed to assess studies of prognosis in AECOPD.

Background: The NSF for Renal Services stresses the importance of collaboration between renal services and critical care networks in managing patients with acute renal failure in the most clinically appropriate setting. Anecdotal evidence in our region suggested that some patients were remaining on critical care inappropriately because of a lack of capacity for step-down care in local renal units., Aim: To determine the number of extra days patients spend on critical care receiving single-organ renal support before transfer to a renal unit., Design: Prospective, multi-centre, service evaluation., Methods: Prospective data were collected over a one-year period by either daily telephone calls or bedside review. Follow-up data were retrieved from electronic and patient records., Results: Five hundred and forty-two patients received renal replacement therapy (RRT) in critical care. With 68 (12.5%) patients already receiving RRT for end-stage renal failure, this gave an incidence of new RRT on critical care of 234 per million population per year. The median duration of RRT on critical care was 4 days (range 1-30). One hundred and twenty-seven patients (23%) were discharged from critical care still requiring RRT. A period of single-organ renal support (median 2 days, range 1-8) was provided to 74 of these patients (58%) using 113 critical care bed days., Discussion: Over half of patients receiving RRT on discharge from critical care in our network received a short period of single-organ renal support before step-down. This may represent either delayed discharge from critical care or a potential opportunity for care in an alternative high-dependency facility.

Objective: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta2 integrin CD11b., Methods: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay., Results: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated., Conclusions: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptors.

Acute lung injury after oesophagectomy is well recognized but the risk factors associated with its development are poorly defined. We analysed retrospectively the effect of a number of pre-, peri- and post-operative risk factors on the development of lung injury in 168 patients after elective oesophagectomy performed at a single centre. The acute respiratory distress syndrome (ARDS) developed in 14.5% of patients and acute lung injury in 23.8%. Mortality in patients developing ARDS was 50% compared with 3.5% in the remainder. Features associated with the development of ARDS included a low pre-operative body mass index, a history of cigarette smoking, the experience of the surgeon, the duration of both the operation and of one-lung ventilation, and the occurrence of a post-operative anastomotic leak. Peri-operative cardiorespiratory instability (measured by peri-operative hypoxaemia, hypotension, fluid and blood requirements and the need for inotropic support) was also associated with ARDS. Acute lung injury after elective oesophagectomy is associated with intraoperative cardiorespiratory instability.

The vascular endothelium has a central role in the control of microvascular tone, and it has been proposed that vascular endothelial damage occurs in septic shock, producing multiorgan failure. We have developed a method of detecting circulating endothelial cells (EC) that provides direct evidence of EC shedding in human sepsis. Human umbilical vein endothelial cells (HUVEC) were seeded in whole blood and recovered by isopycnic centrifugation to validate the technique. Blood samples were subsequently taken from 11 healthy volunteers, nine ventilated intensive care unit (ICU) control patients without sepsis, eight patients with sepsis but without shock, and 15 patients with septic shock. EC were identified by indirect immunofluorescence, using antibodies to von Willebrand factor (vWf) and the vascular endothelial growth factor receptor KDR. Mean HUVEC recovery was 86% for 20 to 100 seeded cells/ml of blood. vWf-positive EC counts per milliliter were significantly higher (analysis of variance [ANOVA], p < 0.0001) in patients with sepsis (16.1 +/- 2.7 [mean +/- SEM]) and septic shock (30.1 +/- 3.3) than in healthy (1.9 +/- 0.5) or ICU controls (2.6 +/- 0.6). KDR-positive EC counts per milliliter were also significantly higher (ANOVA, p < 0.0001) in patients with sepsis (4.2 +/- 1.1/ml) and septic shock (10.4 +/- 1.2/ml) than in healthy (0.7 +/- 0.3/ml) or ICU controls (0.5 +/- 0.2/ml). Cell counts made with anti-vWf antibody were consistently higher than those made with anti KDR antibody, but correlation between the two counts was high (r(2) = 0.93). The number of circulating KDR-positive EC was significantly higher in patients who died of septic shock than in survivors (12.0 +/- 1.6/ml versus 7.1 +/- 1.2/ml, p = 0.026). An increase in circulating EC can be identified during sepsis and septic shock. This supports the hypothesis that endothelial damage occurs in human sepsis.

1. The evidence that the infusion of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), may reduce systemic blood pressure, via the generation of intracellular cyclic guanosine-3,5-monophosphate(cGMP), in normotensive volunteers is controversial. In the first part of the study we investigated the effect of an L-arginine infusion on systemic blood pressure and plasma cGMP in healthy volunteers. 2. Patients with systemic sclerosis have widespread endothelial damage which, by reducing the release of NO, could contribute to the raised pulmonary vascular resistance (PVR) often found in this condition. We hypothesised that if there were a failure of NO synthesis this might be overcome by infusing L-arginine into the pulmonary artery, thereby lowering PVR. In the second part of the study we investigated the effect of L-arginine infusion on systemic and pulmonary haemodynamics, and on plasma cGMP levels in patients with pulmonary hypertension and systemic sclerosis. 3. L-arginine (500 mg kg-1) was infused over 30 min into five normotensive volunteers and five patients with systemic sclerosis and pulmonary hypertension. Blood pressure, heart rate and skin temperature were measured non-invasively in the volunteers and systemic and pulmonary haemodynamics recorded via radial artery cannulae and balloon-tipped, flow directed, pulmonary artery catheters in the patients with systemic sclerosis. 4. L-arginine had no significant effect on blood pressure, heart rate or skin temperature in the normotensive volunteers nor on systemic or pulmonary haemodynamics in the systemic sclerotic group. Cyclic-GMP levels did not significantly change in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

The blood pressures of 394 rural Black South African children were recorded and compared with existing records on the blood pressures of Black and White American children. It was found that the blood pressures of these rural Blacks were not significantly different from those of the American Negroes, but that they were higher than those of the White children. If blood pressure readings in the children of a population are a good predictor of future hypertension among the adults of that population, then the rural South African Black population will increasingly suffer from hypertensive disease.