A history of shoulder surgery.

Shoulder surgery has emerged from being a marginalised sub-speciality to being an area of much research and advancement within the last seventy years. This has been despite the complexity of the joint, and success majorly rests on parallel development of biomedical technology. This article looks at the past and present of shoulder surgery and discusses future directions in the speciality.

Cluster analysis of genomic ETV6-RUNX1 (TEL-AML1) fusion sites in childhood acute lymphoblastic leukemia.

Fusion between ETV6 and RUNX1 defines the largest genetic subgroup in childhood ALL. The genomic fusion site, unique to individual patients and specific for the malignant clone, represents an ideal molecular marker for quantification of minimal residual disease. Sequencing of DNA breakpoints has been difficult due to the extended size of the respective breakpoint cluster regions. We therefore evaluated a specially designed multiplex long-range PCR assay in 65 diagnostic bone marrow samples for its suitability in routine use. Resulting fusion sites and breakpoints derived from previous studies were subject to cluster analysis to identify potential sequence motifs involved in translocation initiation.

Infantile hypophosphatasia due to a new compound heterozygous TNSALP mutation - functional evidence for a hydrophobic side-chain?

BACKGROUND: Infantile hypophosphatasia (IH) is an inherited disorder characterized by defective bone mineralization and a deficiency of alkaline phosphatase activity. OBJECTIVE/DESIGN: The aim of the study was to evaluate a new compound heterozygous TNSALP mutation for its residual enzyme activity and localization of the comprised amino acid residues in a 3D-modeling. PATIENT: We report on a 4-week old girl with craniotabes, severe defects of ossification, and failure to thrive. Typical clinical features as low serum alkaline phosphatase, high serum calcium concentration, increased urinary calcium excretion, and nephrocalcinosis were observed. Vitamin D was withdrawn and the patient was started on calcitonin and hydrochlorothiazide. Nonetheless, the girl died at the age of 5 months from respiratory failure. RESULTS: Sequence analysis of the patient's TNSALP gene revealed two heterozygous mutations [c.653T>C (I201T), c.1171C>T (R374C)]. Transfection studies of the unique I201T variant in COS-7 cells yielded a mutant TNSALP protein with only a residual enzyme activity (3.7%) compared with wild-type, whereas the R374C variant was previously shown to reduce normal activity to 10.3%. 3D-modeling of the mutated enzyme showed that I201T resides in a region that does not belong to any known functional site. CONCLUSION: We note that I201, which has been conserved during evolution, is buried in a hydrophobic pocket and, therefore, the I>T-change should affect its functional properties. Residue R374C is located in the interface between monomers and it has been previously suggested that this mutation affects dimerization. These findings explain the patient's clinical picture and severe course.

[Comparison of kidney transplantation with and without regard to HLA typing]. / Vergleich der Nierentransplantation mit und ohne Berücksichtigung der HLA-Typisierung.

OBJECTIVE: To compare the functional results after transplantation of locally obtained and assigned kidneys (without taking into account HLA typing) with those after transplantation of kidneys obtained via Eurotransplant (with HLA typing as principal criterion for assignment). PATIENTS AND METHODS: Between December 1983 and December 1993 a total of 236 kidneys were transplanted into 234 patients, 40 kidneys having been obtained via Eurotransplant and 196 removed locally and transplanted directly into patients on the local waiting list according to strict criteria: same blood group; waiting time since decision on transplantation; negative current crossmatch between recipient's serum and donor lymphocytes. Transplantation results were analysed retrospectively according to: ischaemia time, HLA mismatch, postoperative renal failure, postoperative renal function, rejection rate and transplant survival. Mean observation period was 55 months for the local and 50 months for the Eurotransplant kidneys. RESULTS: The number of HLA matches was higher in Eurotransplant group (P < 0.001). However, the cold ischaemia time was greater for this group (20.2 vs 15.7 hours; P < 0.01). Acute renal failure was less common with locally assigned kidneys (33 vs 53%: P < 0.02). There were no significant differences with regard to one-year and five-year renal function (serum creatinine; percentage of normal): 90.2% local vs 88.3% Eurotransplant and 81.8% vs 62.3%, respectively). Survival rates were also similar (96.9% local vs 95% Eurotransplant after one year, 94.4% vs 90% after 5 years). CONCLUSION: Local assignment by waiting time and blood group gave results that were similar to those via Eurotransplant based on HLA typing criteria.

Acute rejection relapses posttransplant: definition of risk group and evaluation of potent therapeutic regimens.

A group of 113 patients were investigated after allogenic cadaver renal transplantation to analyse whether the small number of patients presenting acute rejection relapses could be defined by risk factors and whether there is an efficacious regimen for the safe therapy of recurrent rejection episodes. According to these results we are aware of a group of "highly reactive rejectors" especially within the younger recipients and there are further characteristics which can be identified as being associated with an elevated risk of recurrent acute rejection. By adequate antirejection therapy we can achieve a favourable transplant survival rate of 97% in the critical first year. An additional benefit may result from ALG consolidation related to suppression of the remaining CD8-positive human natural killer cells.