Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures

We recently established that two midgestation-derived stromal clones--UG26-1B6, urogenital ridge-derived, and EL08-1D2, embryonic liver-derived--support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC-stroma contact is required for this stem cell maintenance. Adult bone marrow ckit+ Ly-6C- side population (K6-SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08-1D2 and UG26-1B6 with four HSC-nonsupportive clones. We found that EL08-1D2 and UG26-1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor-7, insulin-like growth factor-binding proteins 3 and 4, pleiotrophin, pentaxin-related, and thrombospondin 2, whereas 11 genes, including GPX-3 and HSP27, were expressed at a lower level. In summary, we show for the first time long-term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support.     

Refracture of proximal fifth metatarsal (Jones) fracture after intramedullary screw fixation in athletes

This study details six instances of refracture of clinically and radiographically healed fractures of the base of the fifth metatarsal after intramedullary screw fixation. Four professional football players, one college basketball player, and one recreational athlete underwent intramedullary screw fixation of fifth metatarsal fractures. The athletes were released to full activities an average of 8.5 weeks (range, 5.5 to 12) after fixation, when healing was clinically and radiographically documented. Three football players developed refracture within 1 day of return to full activity. The other three athletes refractured at 2.5, 4, and 4.5 months after return to activity. Two football players underwent repeat fixation with larger screws and returned to play in the same season. The college basketball player underwent bone grafting and returned to play in subsequent seasons. The other three athletes underwent nonoperative management and healed uneventfully over 6 to 8 weeks. On the basis of this series, we recommend that 1) screw fixation using a large-diameter screw should be given careful consideration for patients with large body mass for whom early return to activity is important; 2) functional bracing, shoe modification, or an orthosis should be considered for return to play; 3) if refracture occurs, exchange to a larger screw may allow return to play in the same season; and 4) alternative imaging should be considered to help document complete healing.     

The development of autoimmune features in aging mice is closely associated with alterations of the peripheral CD4+ T‐cell compartment

Some signs of potential autoimmunity, such as the appearance of antinuclear antibodies (ANAs) become prevalent with age. In most cases, elderly people with ANAs remain healthy. Here, we investigated whether the same holds true for inbred strains of mice. Indeed, we show that most mice of the C57BL/6 (B6) strain spontaneously produced IgG ANA at 8–12 months of age, showed IgM deposition in kidneys and lymphocyte infiltrates in submandibular salivary glands. Despite all of this, the mice remained healthy. ANA production is likely CD4⁺ T‐cell dependent, since old (40–50 weeks of age) B6 mice deficient for MHC class II do not produce IgG ANAs. BM chimeras showed that ANA production was not determined by age‐related changes in radiosensitive, hematopoietic progenitor cells, and that the CD4⁺ T cells that promote ANA production were radioresistant. Thymectomy of B6 mice at 5 weeks of age led to premature alterations in T‐cell homeostasis and ANA production, by 15 weeks of age, similar to that in old mice. Our findings suggest that a disturbed T‐cell homeostasis may drive the onset of some autoimmune features.     

Dyschromatosis universalis hereditaria: familial case and ultrastructural skin investigation

We present three families with infantile myofibromatosis (IM; OMIM no. 228550) inherited in an autosomal dominant (AD) manner. These three pedigrees prompted re-assessment of pedigrees available within the genetic, oncologic, surgical, and pathologic literature, which suggest autosomal recessive (AR) inheritance. All familial IM may be interpreted as AD or, alternatively, there may be genetic heterogeneity for IM. As most nodules tend to regress spontaneously, familial history may be difficult to obtain and/or confirm. Clinical diagnosis and establishment of inheritance pattern can be important for prognosis and the recognition that other family members may be affected.     

Stabilisation of unstable trochanteric femoral fractures. Dynamic hip screw (DHS) with trochanteric stabilisation plate vs. proximal femur nail (PFN)

The dynamic hip screw (DHS) with trochanteric stabilisation plate (TSP) as the extramedullary power transmission system and the proximal femur nail (PFN) as the means of intramedullary stabilisation are both standard in the treatment of unstable trochanteric femoral fractures in the case of old people. A total of 129 patients (average age: 81,5 years) with 31 A2.2 and A2.3 as well as per-/subtrochanteric femoral fractures were treated by means of osteosynthesis with DHS and TSP (n=64) or with PFN (n=65),and the results plotted in a retro-/prospective study. At low complication rates, the radiological operation results are equally good. 6 revisions were necessary in the case of the DHS with TSP and 4 in the case of PFN. A significantly shorter operation time (44.3 vs. 57.3 min) and a considerably shorter in-patient stay (18.6 vs. 21.3 days) were common with PFN. The application of full-weightbearing immediately after the operation was possible for 97% of the PFN patients and 88% of the DHS patients. In a follow-up 6 months after the operation, the PFN patients displayed a significantly lower pain intensity in the operated leg at the same score for ambulation and the same subjective degree of satisfaction. Unstable pertrochanteric and per-/subtrochanteric femoral comminuted fractures can be treated just as well with PFN as with DHS and TSP. Our study results,however, lead us to recommend treatment with PFN.     

Arthroscopic treatment of acromioclavicular joint injuries and results

Injuries and conditions that affect the AC joint are common. Low-grade separations, degenerative conditions, and osteolysis of the distal clavicle are frequently dealt with by the treating physician. Proper assessment requires a thorough history, examination, and radiologic work-up. An injection of bupivicaine into the AC joint can be a very useful test to evaluate the source of pain about the symptomatic shoulder. Most conditions affecting the AC joint can be treated conservatively, but patients who do not respond to these treatments or athletes who do not wish to modify their activities may require resection of the distal clavicle and the AC joint. Operative intervention can be performed as an open procedure with good results. Recent advances in operative arthroscopic procedures allow us to replicate and exceed the results of the open resection. Arthroscopic resection can be undertaken via a direct approach that does not violate the subacromial space or via an indirect or bursal approach. The indirect approach allows you to assess both the subacromial space and the AC joint because impingement pathology and subacromial compromise are frequently associated with AC change. The advantage of an arthroscopic resection is its ability to be performed as an outpatient procedure with less compromise of musculotendinous structures, shorter rehabilitation, and quicker return to activity. The amount of bone resection necessary is less than with the open procedure because of the ability to preserve the stabilizing properties of the superior AC ligaments. Resection of 4 mm to 8 mm of bone is all that may be required to give uniformly good results. Arthroscopic resection of the distal clavicle is technically demanding and requires skill and familiarity with other arthroscopic shoulder procedures. Complications related to this procedure are relatively infrequent and include infection, residual pain, lack of adequate bone resection, and instability, particularly in patients with previous grade 1 and 2 separations. Less commonly noted is the symptomatic development of heterotopic bone. To the accomplished arthroscopic shoulder surgeon, arthroscopic resection of the symptomatic AC joint gives excellent clinical results that allow a compromised athlete a relatively quick return to desired sport activities.