Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow

Human mesenchymal stem/progenitor cells (MSCs) have been identified in adult bone marrow, but little is known about their presence during fetal life. MSCs were isolated and characterized in first-trimester fetal blood, liver, and bone marrow. When 10(6) fetal blood nucleated cells (median gestational age, 10(+2) weeks [10 weeks, 2 days]) were cultured in 10% fetal bovine serum, the mean number (+/- SEM) of adherent fibroblastlike colonies was 8.2 +/- 0.6/10(6) nucleated cells (69.6 +/- 10/microL fetal blood). Frequency declined with advancing gestation. Fetal blood MSCs could be expanded for at least 20 passages with a mean cumulative population doubling of 50.3 +/- 4.5. In their undifferentiated state, fetal blood MSCs were CD29(+), CD44(+), SH2(+), SH3(+), and SH4(+); produced prolyl-4-hydroxylase, alpha-smooth muscle actin, fibronectin, laminin, and vimentin; and were CD45(-), CD34(-), CD14(-), CD68(-), vWF(-), and HLA-DR(-). Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes. Fetal blood MSCs supported the proliferation and differentiation of cord blood CD34(+) cells in long-term culture. MSCs were also detected in first-trimester fetal liver (11.3 +/- 2.0/10(6) nucleated cells) and bone marrow (12.6 +/- 3.6/10(6) nucleated cells). Their morphology, growth kinetics, and immunophenotype were comparable to those of fetal blood-derived MSCs and similarly differentiated along adipogenic, osteogenic, and chondrogenic lineages, even after sorting and expansion of a single mesenchymal cell. MSCs similar to those derived from adult bone marrow, fetal liver, and fetal bone marrow circulate in first-trimester human blood and may provide novel targets for in utero cellular and gene therapy.     

Navigating the ethics of cross‐cultural health promotion research

Health promotion researchers must consider the ethics of their research, and are usually required to abide by a set of ethical requirements stipulated by governing bodies (such as the Australian National Health and Medical Research Council) and human research ethics committees (HRECs). These requirements address both deontological (rule‐based) and consequence‐based issues. However, at times there can be a disconnect between the requirements of deontological issues and the cultural sensitivity required when research is set in cultural contexts and settings etic to the HREC. This poses a challenge for health promotion researchers who must negotiate between meeting both the requirements of the HREC and the needs of the community with whom the research is being conducted. Drawing on two case studies, this paper discusses examples from cross‐cultural health promotion research in Australian and international settings where disconnect arose and negotiation was required to appropriately meet the needs of all parties. The examples relate to issues of participant recruitment and informed consent, participants under the Australian legal age of consent, participant withdrawal when this seemingly occurs in an ad hoc rather than a formal manner and reciprocity. Although these approaches are context specific, they highlight issues for consideration to advance more culturally appropriate practice in research ethics and suggest ways a stronger anthropological lens can be applied to research ethics to overcome these challenges.     

Perimount® Bovine Pericardial Valve to Restore Pulmonary Valve Competence Late after Right Ventricular Outflow Tract Repair

Objective. No ideal option exists for restoring pulmonary valve competence late after repair of the congenitally abnormal right ventricular outflow tract (RVOT). This has driven a continued search for new alternatives. Texas Children’s Hospital has recently used the Carpentier‐Edwards Perimount RSR Pericardial Aortic Prosthesis (Edwards Lifesciences, Irvine, Calif, USA) for this indication and reports the initial experience. Design. Retrospective chart review. Setting. Academically affiliated tertiary‐care pediatric hospital. Patients. Twenty‐six patients who underwent pulmonary valve replacement with the Perimount^® valve late after RVOT reconstruction between June 2002 and November 2005. Interventions. No prospective interventions. Outcomes Measures. Hospital morbidity and mortality. Valve function assessed by follow‐up visits and echocardiograms. Results. Mean age and weight of the patients were 20.3 ± 9.8 years (range 7.0–45.1 years) and 56.2 ± 18.1 kg (range 35.8–109 kg). Twenty‐two patients (85%) had severe pulmonary insufficiency (PI), 23 (89%) had symptomatic right heart failure, and 14 (54%) had moderate to severe right ventricular dysfunction. Average prosthetic valve size was 23 mm (range 19–27 mm). Twenty‐one (88%) patients were extubated within 24 hours. There was no hospital mortality. Median length of stay for all patients from day of surgery was 6 days (range 3–56 days). Median length of last echocardiography follow‐up was 12.4 months (range 0.1–37.6 months). At that time, 16 of the 26 (62%) patients had improved right ventricular function, no patient demonstrated significant RVOT obstruction, and 24 patients (92%) have no PI or mild PI. Freedom from death, reintervention, or reoperation on the pulmonary valve is 100% at 2.5 years. Conclusion. Initial results with the Perimount^® bovine pericardial tissue prosthesis for pulmonary valve replacement are encouraging. Further follow‐up is required to define long‐term function and durability.     

Heyde's syndrome

We describe a patient with Heyde's syndrome in whom upper gastrointestinal angiodysplasias were demonstrated and who was successfully treated by bioprosthetic aortic valve replacement.     

Differential effects of G-CSF mobilisation on dendritic cell subsets in normal allogeneic donors and patients undergoing autologous transplantation

It has been suggested that the immunological properties of cytokine primed PBSC may reflect the presence of altered levels of cellular components. In this study the changes induced in blood dendritic cell (DC) subsets following G-CSF mobilisation are analysed. Analysis of normal donors (n = 64) demonstrated considerable individual variation in the absolute numbers (x10(6)/l) of resting blood CD11c(-) DC (1.2-26.2) and CD11c(+) DC (0.9-34.7) as well as in the CD11c(-)/CD11c(+) DC ratio (0.29-4.13). G-CSF therapy increased CD11c(-) DC numbers to above the normal range in all normal donors analysed (n = 6) and the CD11c(-)/CD11c(+) ratio was also increased to >2.0 in all donors. Patients undergoing autologous PBSCT showed a heterogeneous response to mobilisation and although total DC and CD11c(-) DC numbers were increased in the majority (8/14), they remained within the normal range post mobilisation. The CD11c(-)/CD11c(+) ratio decreased in 5/15 patients and only three patients had ratios >2.0 post mobilisation. Post G-CSF the DC from all normal donors and 13/14 patients had an immature phenotype. These results demonstrate that G-CSF mobilisation induces relatively consistent changes in the number and ratio of DC subsets in normal donors, but considerable variation is seen in the response of patients undergoing mobilisation for autologous PBSCT.     

Superior vena cava syndrome: Case report: A complication of permanent transvenous endocardial cardiac pacing requiring surgical correction

Superior vena cava syndrome developed in a patient in whom an endocardial transvenous pacemaker had been inserted five years previously. Venography demonstrated an obstructing lesion at the junction of the superior vena cava and right atrium. Balloon catheter dilatation failed to afford any relief from her progressive symptoms. Exploration of the area revealed a benign fibrotic lesion encircling the pacemaker lead within the right atrium. Excision of the lesion, removal of the lead, and patching the right atrium with pericardium resulted in rapid cure.