Surgical treatment of osteoarthritis of the shoulder

Shoulder dysfunction is unusual in osteoarthritis and usually responds to conservative treatment. The primary indication for surgery is pain unresponsive to medical management. The procedure of choice for degenerative changes in the glenohumeral joint is hemiarthroplasty or total shoulder replacement depending on the condition of the glenoid. Shoulder fusion is rarely necessary for osteoarthritis and is recommended for chronic infection, flail shoulder, and failed total shoulder replacement not amenable to revision. Joint resection is reserved for infected joints with massive bone loss. The results of shoulder arthroplasty are good to excellent in 86 to 94 per cent of all patients. The results of shoulder arthrodesis are less predictable, but are usually satisfactory in approximately 75 per cent of patients with 10-year follow-up. The treatment of AC and SC joint arthritis is conservative with rest, local heat, and medication. Pain unresponsive to this regimen is an indication for resection of the joint. Good results with this procedure directly correlate with pain relief on injection of the joint with local anesthetic.     

C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties.

We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine.     

Role of urethral reconstruction and artificial sphincter in complicated salvage radical prostatectomy

Patients undergoing radical prostatectomy following failed definitive radiation therapy for adenocarcinoma of the prostate run a substantial risk of refractory bladder neck contractures and urinary incontinence developing. A combined reconstructive technique utilizing a urethral pull-through procedure and implantation of an artificial urinary sphincter to treat these complications is described. When a patient can truly be cured by radical prostatectomy, this relatively straightforward reconstruction can salvage what otherwise would be considered a surgical failure.     

Coagulation factor deficiency as a cause of recurrent fetal loss: a red herring!

Whether severe coagulation factor deficiency can cause adverse pregnancy outcomes or recurrent fetal loss is not definitely known. We report here on five women with severe deficiency of coagulation factors (two factor X, one factor XI, one factor VII and one von Willebrand factor) who presented with history of unexplained fetal loss or with adverse pregnancy outcome. Detailed investigations of thrombophilia showed that four patients were positive for antiphospholipid antibodies, one of whom was also homozygous for the plasminogen-activator inhibitor-1 4G/4G polymorphism, and the fifth patient was deficient for protein C. Despite the concomitant presence of both coagulation factor defect and thrombophilia, fetal loss may be attributed to factor defect that in reality is a red herring, with underlying thrombophilia not being evaluated.     

Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer.

PURPOSE: The presence of similar histologic subtypes of epithelial ovarian and endometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers of the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and endometrium using the same genomic platform to determine the similarities and differences between these tumors. EXPERIMENTAL DESIGN: Gene expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial brushings were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohistochemical staining. RESULTS: Comparison across endometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian surface epithelium. CONCLUSIONS: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and endometrial cancer are largely unique to the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity in gene expression profiles across organs (including kidney) and could not be statistically distinguished.     

Synovial membrane and cartilage changes in an arthrosis model. Instability and impact stress model

Surgical instability and repetitive impulsive loading was used to generate degenerative changes in knee joints of rabbits. Light- and electronmicroscopy was carried out at synovial membrane and cartilage samples. The instabilised joints had early synovial inflammation, preceding overall cartilage changes. Synoviocytes were activated and showed more and dilatated cytoplasmatic organells. Invaded round cells--potentially cartilage degenerative--were seen. In the loading model no initial synovial inflammation could be seen. Focal cartilage changes were located at the weight bearing zone. Two different inductive pathways may be involved in cartilage breakdown comparing the two arthrosis models. Mechanical factors seemed to trigger cartilage changes in the loading model, an inflammatory synovial pathway is likely to initiate cartilage breakdown in the instability model. Clinical relevance: The synovial membrane has the key-position for the cartilage degeneration in posttraumatic joint affections. The therapeutic use of antiphlogistic substances is indicated to supreme inflammatory mediators from the synovial membrane. This therapeutic concept seemed not to be useful in primary mechanical induced osteoarthrosis.     

Activity measurements of calcium, sodium, potassium, and chloride after equilibrium dialysis used to show lack of evidence for protein interference with calcium electrodes

We measured the activity of Ca2+, Na+, K+, and Cl- with ion-selective electrodes after equilibrium dialysis of solutions with different albumin concentrations. The calculated Donnan ratio was the same for all ions in the same solution and increased with the albumin concentration, as predicted by the Donnan theory. The Donnan distribution ratio for Ca2+ was similar, as determined with instruments from three different manufacturers. For healthy subjects and patients with renal stone disease, we did not find any correlation between serum concentrations of ionized calcium and albumin. The discordance between measured ionized calcium and albumin-corrected total calcium depended on the correction algorithm we utilized. The difficulties of absolutely proving or disproving a protein error in these measurements are discussed, but our data are not consistent with protein being a source of error in measurements of ionized calcium.