Degeneration at the insertion weakens the tensile strength of the supraspinatus tendon: a comparative mechanical and histologic study of the bone-tendon complex

The purpose of this investigation was to determine the relationship between the degree of degeneration at the supraspinatus insertion, the tensile strength, and the site of failure of this tendon. Thirty-three fresh cadaveric shoulders (average age: 62 years; range: 39-83 years) were examined. A tensile load to failure was applied at a constant crosshead speed of 25.4 mm/min to a 10 mm wide strip of the supraspinatus tendon that remained attached to the bone. Preexisting degenerative changes at the insertion were assessed and scored histologically and compared with the ultimate tensile stress. Twenty tendons failed at the insertion (the insertion group), and 11 failed in the midsubstance (the midsubstance group). The histologic score of degeneration for the insertion group was significantly higher than that for the midsubstance group (p = 0.0026). There was a negative correlation between the ultimate tensile stress at the insertion and the degeneration score for the insertion group (r = -0.60; p = 0.013). Histologic observations revealed that disruptions of tendon fibers were located mostly in the articular half of the tendon and that they enlarged during mechanical testing in 90% of the specimens of the insertion group. It seems that degenerative changes at the supraspinatus insertion reduce the tensile strength of the tendon and constitute a primary pathogenetic factor of rotator cuff tear.     

Genomic organization of a human cystine transporter gene (SLC3A1) and identification of novel mutations causing cystinuria

Cystinuria is a common inherited aminoaciduria that leads to recurrent cystine nephrolithiasis. Mutations in a gene encoding a renal amino acid transporter (SLC3A1) have been identified in patients with cystinuria establishing one molecular cause for the disease. To facilitate systematic screening of this gene for mutations, we have delineated the complete genomic organization of the SLC3A1 coding region using polymerase chain reaction strategies. The complete coding region of the gene is contained within a single yeast artificial chromosome clone and consists of 10 exons and 9 introns. Oligonucleotide primers capable of amplifying selected exons have been made and used in mutational analysis of DNA from 24 cystinuria probands. We illustrate the usefulness of this approach by identifying two novel SLC3A1 mutations. One novel mutation causes replacement of a highly conserved arginine residue (arginine-452) with tryptophan in the cytoplasmic loop between the putative third and fourth membrane spanning segments. A second previously unreported mutation results in replacement of a highly conserved tyrosine (tyrosine-461) residue with histidine in the same region of the protein. In addition, we detected three previously reported SLC3A1 mutations, R270X, 1500 +1/G to T, and M467T, the latter being present in approximately 20% of cystinuria chromosomes examined. Our findings provide a foundation for the development of more accessible diagnostic screening assays for detecting SLC3A1 mutations using patient genomic DNA, and also contribute to the emerging spectrum of cystinuria genotypes.     

Effect of calcium carbonate on the compliance of an apatitic calcium phosphate bone cement

Clinical requirements for calcium phosphate bone cements were formulated in terms of the initial setting time, the final setting time, the cohesion time and the ultimate compressive strength. Three cement formulations were tested. The previously developed Biocement H was made of a powder containing alpha-tertiary calcium phosphate and precipitated hydroxyapatite. Biocement B2 powder was made by adding some CaCO3 to Biocement H, whereas Biocement B1 was made by adding some CaCO3 but with simultaneous adjustment of the amount of precipitated hydroxyapatite.The liquid/ powder ratio of the cement paste and the accelerator concentrations (percentage Na2HPO4) in cement liquid were varied. For Biocement H there was no combination of L/P ratio and percentage Na2HPO4 for which all clinical requirements were satisfied. However, there was an area of full compliance for Biocements B1 and B2, of which that for B1 was the largest. Therefore, Biocement B1 may be applied in clinical situations as those in orthopaedics, plastic and reconstructive surgery and oral and maxillofacial surgery, even when early contact with blood is inevitable.     

Drug treatment of prostatic carcinoma

The basis for the medical treatment of prostate cancer is inhibition of the influence of testosterone on the prostate. Surgical castration is in 1997 still the gold standard; it reduces the testosterone level by 90% and the level of dihydrotestosterone (the active metabolite) by 60%. In the eighties luteinising hormone releasing hormone (LH-RH) analogues were introduced to avoid the psychological burden of castration. After an initial stimulation (the flare-up) testosterone decreases to castrate level within 3 weeks. Recently (non-steroidal) anti-androgens, competitive inhibitors of dihydrotestosterone on receptor level were introduced. There are also drugs which inhibit the conversion of testosterone to dihydrotestosterone: 5 alpha-reductase inhibitors. Non-steroidal anti-androgens and 5 alpha-reductase inhibitors do not decrease the testosterone level and therefore cause less loss of libido and energy than castration. Combination of (chemical) castration and anti-androgens is called maximum androgen blockade. This treatment has limited additional value in proportion to the increase in side effects and costs. A new form of treatment is intermittent androgen blockade. With this strategy growth of hormone-insensitive cells in the prostate, which is considered the main determinant of the poor prognosis, might be delayed with reduction of side effects and costs. The role of imidazoles is still investigated; the role of cytotoxic drugs is mainly palliative.