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A receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 (HMGB1) protein has been linked to several chronic diseases, and acts as a trigger for inflammation signaling. Here, we study RAGE and HMGB1 expression in chronic, recalcitrant rhinosinusitis with nasal polyps (CRSwNP) to determine its potential clinical significance, i.e., disease recurrence and severity. RAGE and HMGB1 expression in CRSwNP was evaluated by immunohistochemistry in epithelial cells of fresh sinonasal mucosa samples obtained from the patients diagnosed with recalcitrant CRSwNP (n = 25) and normal control mucosa (NC) (n = 26). RAGE and HMGB1 expression levels in tissues were correlated with disease severity assessed by nasal endoscopy, CT scan, number of previous sinus surgeries, allergy status and nasosinusal microbiology. RAGE and HMGB1 were moderately or strongly expressed in CRSwNP tissue. No or weak RAGE expression was found in NC. HMGB1 was equally strongly expressed in NC. We observed a strong correlation between RAGE and disease severity, recurrence, undergone operations, asthma and aspirin exacerbated respiratory disease (AERD). Elevated RAGE expression is associated with increased disease severity, as well as allergy and AERD in patients with recalcitrant CRSwNP. It is possible that the explanation for recurrent CRSwNP pathogenesis might be related to RAGE overexpression with subsequent sinus mucosa hyperproliferation, necessitating several operations.

The determinants of right ventricular (RV) performance with damaged RV free wall, such as occurs with RV infarction, are still unclear. Using 20-MHz Doppler ultrasound equipment, we investigated the changes in pulmonary blood flow velocity profiles before and after ligation of the right coronary artery. RV dp/dt, stroke volume, RV stroke work, aortic pressure and cardiac output decreased and central venous pressure rose after the ligation. The RV stroke work-end-diastolic pressure relationship indicated impaired RV function following ligation. We observed shortened acceleration time (65.0 +/- 15.1 vs 54.4 +/- 6.2 ms, P0.05) and reduced maximum velocity of forward flow (59.0 +/- 5.9 vs 52.5 +/- 7.6 cm/s, P0.05) after the ligation. Acceleration was interrupted earlier after ligation than before ligation. These alterations in flow are thought to be a consequence of the altered movement of the RV free wall and ventricular septum induced by RV infarction.

We performed a randomized, double-blind, placebo-controlled, multicenter, parallel-group, dose-response study of the efficacy and safety of the oral administration of PG-116800, a matrix metalloproteinase (MMP) inhibitor, in patients with mild to moderate knee osteoarthritis. The primary efficacy endpoints included the progression of joint space narrowing in the osteoarthritic knee, as measured by microfocal radiography with fluoroscopic positioning, and the reduction of symptoms (pain and stiffness) and/or the improvement of function, as measured by the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Four hundred and one patients were randomly assigned to either placebo (n = 80) or one of fourdoses of PG-116800: 25 mg (n = 81), 50 mg (n = 80), 100 mg (n = 80), or 200 mg (n = 80) taken twice daily for 12 months. During the study, the 200-mg dose was discontinued based on an increased frequency of musculoskeletal adverse effects. After 1 year of treatment, no statistically significant difference was observed between placebo and PG-116800 with regard to mean changes in minimum joint space width of the knee or to WOMAC scores. The most frequent adverse effect was arthralgia (35%). Twenty-three percent of evaluable patients had at least a 30% decrease from baseline of at least onerangeof-motion measurement of either shoulder at a follow-up visit. The percentage of patients with reduction in range of motion was significantly greater in the twohighest dose groups relative to placebo. Thirteen percent of patients, half of whom were in the 200-mg group, reported hand adverse events (oedema, palmar fibrosis, Dupuytren contracture, or persistent tendon thickness or nodules). The threemost frequent shoulder adverse events were reversible arthralgia, stiffness, and myalgia, which mostly affected the twohighest dose groups. The unfavorable risk-benefit balance of the MMP inhibitor PG-116800 in patients with knee osteoarthritis precludes further development of the compound for this indication. This study adds to the weight of evidence suggesting that side effect profiles of MMP inhibitors in general make them unsuitable for use in osteoarthritis. Trial Registration ClinicalTrials.gov NCT00041756.

Ureter bifidus may be a cause of abdominal pain. If urography reveals the presence of partial ureteral reduplication, pyelography should be performed to detect the uretero-ureteral outflow. The authors present a case of a female patient hospitalized because of uretero-ureteral outflow and recurrent pains in the lumbar region.

By analysing 1472 prostatectomies, the authors have stated a coexistence of tumour of the bladder in 31 cases (2.11%). In 11 patients (0.75%) the tumours were accidentally diagnosed, as late as during the operation itself. Eight patients were operated transvesically. The tumour was diagnosed immediately after opening the bladder. The tumour was removed first and then the adenoma. Three patients were operated on according to Millin's method, their tumours having been detected only after enucleation of adenoma of the prostate. In five cases cancer of the bladder was diagnosed and in six papillary tumour of the bladder was found. The bladder cancers were treated by partial excision of the bladder or by deep electrocoagulation. The authors maintain that the small percentage of accidentally diagnosed tumours is no indication for a routine performance of cystoscopy in every case of adenoma of the prostate before intended prostatectomy.