Investigation of Mechanical Properties of Polymer-Infiltrated Tetrapodal Zinc Oxide in Different Variants.

The aim of this study was to evaluate the influence of weight ratio, the shape of the precursor particles, and the application of a phosphate-monomer-containing primer on the mechanical properties of polymer infiltrated ceramic networks (PICNs) using zinc oxide. Two different types of zinc oxide particles were used as precursors to produce zinc oxide networks by sintering, each with two different densities resulting in two different weight ratios of the PICNs. For each of these different networks, two subgroups were built: one involving the application of a phosphate-monomer-containing primer prior to the infiltration of Bis-GMA/TEGDMA and one without. Elastic modulus and flexural strength were determined by using the three-point bending test. Vertical substance loss determined by the chewing simulation was evaluated with a laser scanning microscope. There was a statistically significant influence of the type of precursor particles on the flexural strength and in some cases on the elastic modulus. The application of a primer lead to a significant increase in the flexural strength and in most cases also in the elastic modulus. A higher weight ratio of zinc oxide led to a significantly higher elastic modulus. Few statistically significant differences were found for the vertical substance loss. By varying the shape of the particles and the weight fraction of zinc oxide, the mechanical properties of the investigated PICN can be controlled. The use of a phosphate-monomer-containing primer strengthens the bond between the infiltrated polymer and the zinc oxide, thus increasing the strength of the composite.

Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation.

Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disease caused by mutations in the RMRP gene. Beside dwarfism, CHH has a wide spectrum of clinical manifestations including variable grades of combined immunodeficiency, autoimmune complications, and malignancies. Previous reports in single CHH patients with significant immunodeficiencies have demonstrated that allogeneic hematopoietic stem cell transplantation (HSCT) is an effective treatment for the severe immunodeficiency, while growth failure remains unaffected. Because long-term experience in larger cohorts of CHH patients after HSCT is currently unreported, we performed a European collaborative survey reporting on 16 patients with CHH and immunodeficiency who underwent HSCT. Immune dysregulation, lymphoid malignancy, and autoimmunity were important features in this cohort. Thirteen patients were transplanted in early childhood ( approximately 2.5 years). The other 3 patients were transplanted at adolescent age. Of 16 patients, 10 (62.5%) were long-term survivors, with a median follow-up of 7 years. T-lymphocyte numbers and function have normalized, and autoimmunity has resolved in all survivors. HSCT should be considered in CHH patients with severe immunodeficiency/autoimmunity, before the development of severe infections, major organ damage, or malignancy might jeopardize the outcome of HSCT and the quality of life in these patients.

First successful bone marrow transplantation for X-linked chronic granulomatous disease by using preimplantation female gender typing and HLA matching.

Allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen (HLA)-identical donor is currently the only proven curative treatment for chronic granulomatous disease. Hematopoietic stem cell transplantation with alternative donors is associated with higher morbidity and mortality. Therefore, we performed in vitro fertilization and preimplantation HLA matching combined with female sexing for hematopoietic stem cell transplantation in chronic granulomatous disease. Ethical and psychological issues were considered carefully. We used in vitro fertilization with X-enriched spermatozoa followed by preimplantation genetic diagnosis to identify female HLA-genoidentical embryos in a family in need of a suitable donor for their boy affected with severe X-linked chronic granulomatous disease. Two preimplantation genetic diagnosis cycles were performed in the family. In the second cycle, 2 HLA-genoidentical female embryos were transferred and a singleton pregnancy was obtained, resulting in the birth of an unaffected girl at term. Because of insufficient cell numbers in the cord-blood source, conventional hematopoietic stem cell transplantation had to be performed at 12 months of age of the donor and 5 years of age of the recipient and resulted in complete stable donor chimerism and immunologic reconstitution up to 25 months post-hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation after in vitro fertilization and combined female sexing and HLA matching offers a new and relatively rapid therapeutic option for patients with X-linked primary immunodeficiency such as chronic granulomatous disease who need hematopoietic stem cell transplantation but lack an HLA-genoidentical donor.

Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children.

CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.

Psychological distress in primary care patients with heart failure: a longitudinal study.

BACKGROUND: Psychological distress is a common phenomenon in patients with heart failure. Depressive symptoms are often under-diagnosed or inadequately treated in primary care. AIM: To analyse anxiety and/or depression in primary care patients with heart failure according to psychosocial factors, and to identify protective factors for the resolution of psychological distress. DESIGN OF STUDY: Longitudinal observation study. SETTING: Primary care practices in lower Saxony, Germany. METHOD: In 291 primary care patients with heart failure the following factors were measured using validated questionnaires at baseline and 9 months later: anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), quality of life (Minnesota Living with Heart Failure Questionnaire), coping with illness (Freiburg questionnaire for coping with illness), and social support (social support questionnaire). Severity of heart failure (New York Heart Association [NYHA] classification and Goldman's Specific Activity Scale), and sociodemographic characteristics were documented using self-report instruments. RESULTS: Twenty-six (32.5%) of the 80 patients who were distressed at baseline had normal HADS scores 9 months later, while the remainder stayed distressed. In logistic regression, baseline distress (odds ratios [OR] 5.51; 95% confidence intervals [CI] = 2.56 to 11.62), emotional problems (OR = 1.08; 95% CI = 1.00 to 1.17), social support (OR = 0.54; 95% CI = 0.35 to 0.83), and NYHA classification (OR = 1.70; 95% CI = 1.05 to 2.77) independently predicted distress at follow up. High social support contributed to a resolution of anxiety or depression, while partnership and low levels of emotional problems protected patients who began the study in a good emotional state from psychological distress. CONCLUSION: In everyday practice it is important to consider that a high NYHA classification and emotional problems may contribute to anxiety or depression, while high social support and living in a relationship may positively influence the psychological health of patients with heart failure.

Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.

BACKGROUND AND OBJECTIVES: Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. DESIGN AND METHODS: This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (< or =70%). If VOD was diagnosed clinically (according to modified Seattle criteria), high dose defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. RESULTS: The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. INTERPRETATION AND CONCLUSIONS: Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.