Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation

Previous studies have indicated that the mitogenic responsiveness of human bone cells may change with age. In the present study, we examined whether aging affects the capacity of transforming growth factor beta (TGF-beta) to stimulate the colony formation of human osteoprogenitor cells. Outgrowths of bone cells from 98 iliac crest biopsies were plated at a density of 25 cells/cm2 and cultured for 3 weeks in the presence of 10% fetal calf serum. Approximately 5% of the plated cells gave rise to clonal colonies. TGF-beta (10(-11) M) significantly increased the estimated number of cells per colony. However, the stimulatory effect of TGF-beta significantly declined with donor age (r = -0.26, P = 0.01). Whereas TGF-beta raised the average number of cells per colony in cultures from donors below the age of 50 years by 136+/-50%, the average increase was only 43+/-16% in donors older than 60 years. These data raise the possibility that aging may be associated with a declining capacity of TGF-beta to enlarge the pool of bone cells that can be generated from a single human osteoblast progenitor cell.     

Retrograde Inversion Stripping as a Complication of the Clarivein? Mechanochemical Venous Ablation Procedure

The endovenous revolution has accelerated the development of new techniques and devices for the treatment of varicose veins. The ClariVein^® mechanochemical ablation device offers tumescentless treatment with a rotating ablation tip that can theoretically become stuck in tissue. We present the first report of retrograde stripping of the small saphenous vein without anaesthesia following attempted use of the ClariVein^® device, without adverse sequelae.     

Admission inflammatory markers and isolation of a causative organism in patients with spontaneous spinal infection

Introduction

The purpose of this study was to investigate the significance of the inflammatory markers on admission in the isolation of a causative pathogen in patients with spinal infection. Spinal infection is treated frequently at spinal units and can encompass a broad range of clinical entities. Its diagnosis is often delayed because of the difficulty of identifying the responsible pathogen.

Methods

Patients with spinal infection treated in our institution over a period of eight years were identified and their notes studied retrospectively. Admission C-reactive protein (CRP), white cell count (WCC) as well as co-morbidities and mode of pathogen identification were recorded. Overall, 96 patients were included in the study.

Results

The CRP levels on admission were correlated significantly with the overall potential for isolation of a pathogen (p<0.0001) and positive biopsy cultures (p=0.0016). Admission WCC levels were associated significantly with the overall potential for isolation of a pathogen (p=0.0003) and positive biopsy cultures (p=0.0023). Both CRP and WCC levels were significantly negatively correlated with the duration of the preceding symptoms (p=0.0003 and p<0.0001 respectively). Delay in presentation was significantly negatively correlated with organism isolation (p=0.0001). Multivariate analyses identified the delay in presentation as the strongest independent variable for organism isolation (p=0.014) in cases of spontaneous spinal infection when compared with the admission CRP level (p=0.031) and WCC (p=0.056).

Conclusions

In spontaneous spinal infection, delay in presentation is the strongest independent variable for organism isolation. High inflammatory marker levels on admission are a useful prognostic marker for the overall potential of isolating a causative organism either by blood cultures or by biopsy in patients with negative blood cultures. Furthermore, the admission inflammatory marker levels allow for treating surgeons to counsel their patients of the likelihood of achieving a positive microbiological yield from biopsy.     

Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

Background

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients’ bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival.

Methods

Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin–biotin complex technique.

Results

At primary surgery, 49 % of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P = 0.007) with less often affected axillary lymph nodes (P < 0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P < 0.001). This leads to a reduced disease-free survival (P < 0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P < 0.0001).

Conclusions

Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.     

13th St. Gallen International Breast Cancer Conference 2013: Primary Therapy of Early Breast Cancer Evidence,Controversies, Consensus – Opinion of a German Team of Experts (Zurich 2013)

Zusammenfassung

Alle zwei Jahre findet in St. Gallen (Schweiz) die internationale Konsensuskonferenz zur Behandlung des primären Mammakarzinoms statt. Da sich das internationale Panel in St. Gallen aus Experten unterschiedlicher Länder zusammensetzt, spiegelt der Konsensus ein internationales Meinungsbild wider. Vor diesem Hintergrund erscheint es aus deutscher Sicht sinnvoll, die Abstimmungsergebnisse für den Therapiealltag in Deutschland zu konkretisieren. Eine deutsche Arbeitsgruppe mit acht Brustkrebsexperten, von denen zwei Mitglieder des internationalen St. Gallen-Panels sind, hat daher die Abstimmungsergebnisse der St. Gallen-Konsensuskonferenz (2013) für den Klinikalltag in Deutschland kommentiert. Inhaltliche Schwerpunkte der diesjährigen St. Gallen-Konferenz waren operative Fragestellungen der Brust und der Axilla, strahlentherapeutische und systemische Therapieoptionen sowie die klinische Relevanz der Tumorbiologie. Intensiv diskutiert wurde der klinische Einsatz von Multigen-Assays, inkl. ihrer Bedeutung für die individuelle Therapieentscheidung.     

Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy

Purpose

This study demonstrates the nasal administration (NA) of nanoemulsions complexed with the plasmid encoding for IDUA protein (pIDUA) as an attempt to reach the brain aiming at MPS I gene therapy.

Methods

Formulations composed of DOPE, DOTAP, MCT (NE), and DSPE-PEG (NE-PEG) were prepared by high-pressure homogenization, and assessed in vitro on human fibroblasts from MPS I patients and in vivo on MPS I mice for IDUA production and gene expression.

Results

The physicochemical results showed that the presence of DSPE-PEG in the formulations led to smaller and more stable droplets even when submitted to dilution in simulated nasal medium (SNM). In vitro assays showed that pIDUA/NE-PEG complexes were internalized by cells, and led to a 5% significant increase in IDUA activity, besides promoting a two-fold increase in IDUA expression. The NA of pIDUA/NE-PEG complexes to MPS I mice demonstrated the ability to reach the brain, promoting increased IDUA activity and expression in this tissue, as well as in kidney and spleen tissues after treatment. An increase in serum IL-6 was observed after treatment, although with no signs of tissue inflammatory infiltrate according to histopathology and CD68 assessments.

Conclusions

These findings demonstrated that pIDUA/NE-PEG complexes could efficiently increase IDUA activity in vitro and in vivo after NA, and represent a potential treatment for the neurological impairment present in MPS I patients.

     

Dislozierte Doppelgewindeschrauben nach Densosteosynthese in Knöringer-Technik

A type III fracture of the odontoid process according to Anderson-D’Alonzo in a 92-year-old patient was stabilized anteriorly with two double-threaded screws using the technique of Knöringer. Postoperatively, cranial dislocation of the screws was evident and attempts to correct the screw position failed resulting in screw proximity to the brain stem. In a second revision the screws could be removed by an anterior approach and fusion was achieved by a posterior approach. Type III fractures of the odontoid process are usually stable and should be treated conservatively. In case of instability posterior stabilization techniques should be selected. Anterior osteosynthesis of the odontoid process with double-threaded screws in osteoporotic bone carries the risk of screw dislocation.