Euclidean distance matrix analysis of surgical changes in prepubertal craniofacial microsomia patients treated with an inverted L osteotomy.

OBJECTIVES: Correction of craniofacial microsomia (CFM) presents several challenges concerning the modality of surgical intervention. The aim of this study was to assess early and late surgical outcome, by undertaking Euclidean distance matrix analysis (EDMA) of CFM patients exhibiting an unilateral mandibular deformity that was surgically corrected by an inverted L osteotomy and autogenous bone graft. DESIGN: Longitudinal study. Preoperative, approximately =1-year postoperative and approximately 3-year postoperative assessments of 14 consecutive children (mean age 9 years) with CFM. Posteroanterior cephalographs were scanned and five homologous mandibular landmarks were digitized in triplicate (< 1% digitization error). Average mandibular geometries, scaled to an equivalent size, were generated using a generalized rotational fit program (Procrustes superimposition) and subjected to EDMA. RESULTS: The mean pre- and both postoperative mandibular configurations differed statistically (p < .01). Early postoperative improvements in mandibular form were noted; increases in length arising in the treated mandibular body (approximately =19%) and ramus (approximately =13%). Comparing early and late postoperative configurations, a decrease of approximately =22% in the late postoperative mandibular body length was evident, but the ramus maintained steady vertical growth (approximately =7%). Comparing the preoperative and late postoperative configurations, the decrease observed in the mandibular body on the treated side was reduced to approximately =8% while the ramus maintained good growth (approximately =20%) on that side. CONCLUSION: Mandibular morphology is improved significantly in CFM patients surgically treated by an inverted L osteotomy, but relapse in the mandibular body is evident after approximately =3 years. Nevertheless, ramus growth proceeds well after the surgical reconstruction.     

Delineation of erythropoiesis in normal and malignant bone marrow using monoclonal antibody AS-E1 directed against transferrin receptors (CD71)

Abstract: We have delineated the erythropoietic compartment in normal and malignant bone marrow (BM) by using the monoclonal antibody (mAb) AS-E1 directed against the transferrin receptor by flow cytometric (FCM) analysis. In normal BM we found a bimodal expression in antigen density with a minor subset (?3%) expressing AS-E1^high and a larger subset (?15%) expressing AS-E1^low. By fluorescence activated cell sorting, morphological examination of smears stained by immunocytochemistry and by BFU–E assays the AS-E1^high fraction was shown to contain cells of erythroid origin (proerythroblasts, basophilic erythroblasts and polychromatic erythroblasts), whereas the AS-E1^low fraction consisted mainly of promyelocytes and myelocytes. In patients with malignant hematological disorders we found a more pronounced heterogeneity in the density and the degree of AS-E1^low expression compared to normal BM, and to further characterize the AS-E1^low cells in patients and to exclude that this broad reactivity interfered with the identification of the AS-E1^high cells, we employed triple-color FCM assays with mAbs directed against the myeloid surface markers CD13 and CD66 in addition to AS-E1. In all patients we found that 80–90% of the AS-E1^low cells co-expressed CD13 and/or CD66 and thus were of myeloid origin. Finally, we evaluated 2 methods for determination of the AS-E1^high subset and found an assay involving forward light scatter and logAS-E1 density to be sufficient. We conclude that AS-E1^high is a valid FCM marker for the normal erythropoiesis.     

Apoptosis induced in human colorectal carcinoma by anti-fas antibody

Background: Apoptosis or programmed cell death has been shown to play an important role in the progression from polyps to carcinomas. Fas/APO-1 is a cell surface protein that can induce apoptosis in a variety of cell types upon specific antibody binding. In this study seven human colorectal carcinoma (HCRC) cell lines of varying differentiation were analyzed for cell surface Fas expression, Fas-mediated apoptosis, and correlation of apoptosis withbcl-2 expression. Methods and Results: Using flow cytometry, all seven lines expressed varying amounts of cell surface Fas antigen. Exposure to anti-Fas antibody induced cell death in all the cell lines, albeit to varying degrees. The rate of apoptosis was quantitated using flow cytometry with propidium iodide staining of nuclear DNA. The poorly differentiated cell lines had a significantly decreased (p<0.05) anti-Fas sensitivity as compared with the well-differentiated lines. Measurement ofbcl-2 expression by flow cytometry showed an inverse correlation with anti-Fas sensitivity. Conclusions: This study confirms that HCRC cell lines express Fas antigen and, more importantly, provides the first evidence that exposure to anti-Fas antibody can induce apoptosis. Fas-mediated apoptosis in HCRC cell lines may be regulated bybcl-2 and may correlate with the degree of differentiation.     

10Haematopoietic cell transplantation with non-myeloablative conditioning in Denmark: Disease-specific outcome, complications and hospitalization requirements of the first 100 transplants

We analysed the outcome and hospitalization requirements of the first 100 patients (Hodgkin's disease (HD), N=13; multiple myeloma (MM), N=14; chronic lymphocytic leukaemia (CLL), N=12; non-Hodgkin's lymphoma (NHL), N=17; myelodysplastic syndrome (MDS), N=18; acute myeloid leukaemia (SML), N=24 and chronic myeloid leukaemia (CML), N=2) treated in Denmark with haematopoietic cell transplantation after non-myeloablative conditioning with TBI 2 Gy±fludarabine. The cumulative incidence of acute GVHD grade II–IV and extensive chronic GVHD was 67 and 49 %. After a median follow-up of 534 days, the overall survival, progression free survival (PFS), relapse-related mortality and treatment-related mortality (TRM) were 59, 50, 25 and 17 %, respectively. Patients with CLL, NHL, AML and MDS with <5% blasts at any time had a favourable outcome with a PFS of 61 – 71 %. Patients with MM, HD and MDS and a history of <5% blasts had a less favourable outcome with a PFS of 19–38% ( P =0.001). The cumulative incidence of discontinuation of immunosuppression was 37%. During the first and second year post transplant, patients experienced a mean of 41 and 13 outpatient clinic visits, and 53 and 16 days of hospitalization. Sixteen patients were admitted to the intensive care unit, of whom eight are still alive. In conclusion we found that allogeneic HCT following non-myeloablative conditioning is a valuable treatment option in patients with haematological malignancies without other potentially curative treatment options. Despite low TRM, the non-myeloablative allogeneic HCT procedure is associated with considerable morbidity, requiring frequent hospitalization and outpatient visits throughout the first and second year post-transplant.     

Mobilization of human CD34+CD133+ and CD34+CD133− stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae—related to modulation of CXCR4 expression by an L-selectin ligand?

OBJECTIVE: The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin). EXPERIMENTAL APPROACH: Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34+ cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo. RESULTS: An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34+ cells by 30% and the CD62L+ CD34+ cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34(-) cell line K562. A transient, 18% increase in numbers of circulating CD34+ stem cells maximized 1 hour after consumption (P<.0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34+ cells was 25% (P<.0001). CONCLUSION: AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34+ bone marrow cells in vitro and triggers the mobilization of CD34+ CD133+ and CD34+ CD133(-) cells in vivo.     

Predictors of hearing loss self-management in older adults

Purpose: To determine the factor structure of a clinical tool for the assessment of hearing loss self-management, and to identify predictors of the total score on the assessment and the extracted factor scores.

Materials and methods: Hearing loss self-management assessments were conducted with 62 older adults. The factor structure of the assessment was determined by exploratory factor analysis. Multiple linear regression analyses identified significant contributors to the total score and to each of the extracted factors.

Results: Three factors were identified, each representing a distinct domain of hearing loss self-management: Actions, Psychosocial Behaviours, and Knowledge. The most common significant predictor was hearing health care experience, which predicted self-management overall and in the Actions and Knowledge domains. Health literacy predicted hearing loss self-management overall and in the Psychosocial Behaviours domain. Actions were additionally predicted by hearing aid self-efficacy and gender, Psychosocial Behaviours by health locus of control, and Knowledge by age.

Conclusions: The results of the factor analysis suggested that hearing loss self-management is a multidimensional construct. Each domain of hearing loss self-management was influenced by different contextual factors. Subsequent interventions to improve hearing loss self-management should therefore be domain-specific and tailored to relevant contextual factors.

• Implications for rehabilitation

• Hearing loss is a chronic health condition that requires on-going self-management of its effects on everyday life.

• Hearing loss self-management is multidimensional and encompasses the domains of Actions, Psychosocial Behaviours, and Knowledge.

• Different contextual factors influence each hearing loss self-management domain, including previous experience receiving hearing health care services, health literacy, hearing aid self-efficacy, health locus of control, age, and gender.

• Audiological rehabilitation programs should thus ensure that interventions to improve hearing loss self-management are domain- and context-specific.

     

Avoidable 30-day mortality analysis and failure to rescue in dysvascular lower extremity amputees

Background and purpose — An enhanced treatment program may decrease 30-day mortality below 20% after lower extremity amputations (LEA). The potential and limitations for further reduction are unknown. We analyzed postoperative causes of 30-day mortality, and assessed failure to rescue (FTR) rate in LEA patients who followed an enhanced treatment program.

Patients and methods — Medical charts of 195 primary LEA procedures were reviewed independently by 3 of the authors, and deaths during hospitalization following amputation were classified according to consensus.

Results — 31 patients died within 30 days after surgery. 4 deaths were classified as “definitely unavoidable,” 4 as “probably unavoidable,” and 23 as “FTR.” Patients who died had a higher incidence of sepsis, pneumonia, and acute myocardial infarction compared with those alive. A log binominal regression analysis adjusted for age, sex, ASA score, diabetes, nursing home admission, transfemoral amputation (TFA), and BMI showed that the risk of 30-day mortality was increased for TFA (RR =2.3, 95% CI 1.1–4.8) and for patients with diabetes (RR =2.7, 95% CI 1.3–5.6). The FTR rate (patients with 30-day mortality/all patients with a severe postoperative complication) was 30%. Of the FTR deaths, 20 at some point had active lifesaving care curtailed.

Interpretation — Future initiatives should be directed at enhanced sepsis and pneumonia prophylactic actions, in addition to close monitoring of hemodynamics in anemic patients, with the potential to further reduce morbidity and mortality rates.