A prospective comparison of immune reconstitution in pediatric recipients of positively selected CD34+ peripheral blood stem cells from unrelated donors vs recipients of unmanipulated bone marrow from related donors

Positively selected CD34(+) hematopoietic stem cells from unrelated donors (UD-HSCT) have been successfully transplanted, but little is known about immune reconstitution in this setting. Here we report a prospective comparison of immune reconstitution in recipients of UD-HSCT and of unmanipulated bone marrow from matched sibling donors (MSD-BMT). T-cell reconstitution occurred more than 100 days later in the UD-HSCT than in the MSD-BMT group. The first T cells after UD-HSCT were almost exclusively CD45RO(+) HLA-DR(+), whereas early-emerging T cells after MSD-BMT more frequently expressed CD62L, CD28, and CD25. In both groups, numbers of CD45RA(+) naive T cells increased after 180 days. After UD-HSCT, the T-cell-receptor (TCR)-repertoire was severely skewed and showed significantly reduced diversity during the first year, but only minor abnormalities were seen after MSD-BMT. TCR-diversity increased simultaneously with the number of naive T cells. In both groups, we observed transient expansions of gammadelta T cells. B cells were reconstituted more rapidly in UD-HSCT than in MSD-BMT recipients, whereas the rapidity of NK-cell reconstitution was similar in the two groups. In summary, T-cell reconstitution was slower after UD-HSCT than after MSD-BMT because of the delayed recovery of early memory-type T cells with reduced TCR-diversity, whereas naive T-, NK-, and B cells were reconstituted similarly in the two groups.     

Familial neonatal pneumothorax associated with transient tachypnea of the newborn

We describe neonatal spontaneous pneumothorax associated with transient tachypnea of the newborn in siblings of two families. Familial spontaneous pneumothorax is extremely rare in neonates. Was our observation just an incidental finding, or is there a familial predisposition to spontaneous pneumothorax? Pediatr Pulmonol. 2003; 36:69–72. © 2003 Wiley‐Liss, Inc.     

Undifferentiated pelvic adenocarcinomas: diagnostic potential of protein profiling and multivariate analysis

Background and aims Despite improved techniques, the determination of tumor origin in poorly differentiated adenocarcinomas still remains a challenge for the pathologist. Here we report the use of protein profiling combined with principal component analysis to improve diagnostic decision-making in tumor samples, in which standard pathologic investigations cannot present reliable results. Materials and methods A poorly differentiated adenocarcinoma of unknown origin located in the pelvis, infiltrating the sigmoid colon as well as the ovary, served as a model to evaluate our proteomic approach. Firstly, we characterized the protein expression profiles from eight advanced colon and seven ovarian adenocarcinomas using two-dimensional gel electrophoresis (2-DE). Qualitative and quantitative patterns were recorded and compared to the tumor of unknown origin. Based on these protein profiles, match sets from the different tumors were created. Finally, a multivariate principal component analysis was applied to the entire 2-DE data to disclose differences in protein patterns between the different tumors. Results Over 89% of the unknown tumor sample spots could be matched with the colon standard gel, whereas only 63% of the spots could be matched with the ovarian standard. In addition, principal component analysis impressively displayed the clustering of the unknown case within the colon cancer samples, whereas this case did not cluster at all within the group of ovarian adenocarcinomas. Conclusion These results show that 2-DE protein expression profiling combined with principal component analysis is a sensitive method for diagnosing undifferentiated adenocarcinomas of unknown origin. The described approach can contribute greatly to diagnostic decision-making and, with further technical improvements and a higher throughput, become a powerful tool in the armentarium of the pathologist. UJ Roblick and FG Bader contributed equally to this work and should be recognized as first authors.     

The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Finite element analysis on the biomechanical stability of open porous titanium scaffolds for large segmental bone defects under physiological load conditions

Repairing large segmental defects in long bones caused by fracture, tumour or infection is still a challenging problem in orthopaedic surgery. Artificial materials, i.e. titanium and its alloys performed well in clinical applications, are plenary available, and can be manufactured in a wide range of scaffold designs. Although the mechanical properties are determined, studies about the biomechanical behaviour under physiological loading conditions are rare. The goal of our numerical study was to determine the suitability of open-porous titanium scaffolds to act as bone scaffolds. Hence, the mechanical stability of fourteen different scaffold designs was characterized under both axial compression and biomechanical loading within a large segmental distal femoral defect of 30 mm. This defect was stabilized with an osteosynthesis plate and physiological hip reaction forces as well as additional muscle forces were implemented to the femoral bone. Material properties of titanium scaffolds were evaluated from experimental testing. Scaffold porosity was varied between 64 and 80%. Furthermore, the amount of material was reduced up to 50%. Uniaxial compression testing revealed a structural modulus for the scaffolds between 3.5 GPa and 19.1 GPa depending on porosity and material consumption. The biomechanical testing showed defect gap alterations between 0.03 mm and 0.22 mm for the applied scaffolds and 0.09 mm for the intact bone. Our results revealed that minimizing the amount of material of the inner core has a smaller influence than increasing the porosity when the scaffolds are loaded under biomechanical loading. Furthermore, an advanced scaffold design was found acting similar as the intact bone.