Urokinase‐plasminogen‐activator receptor expression in disseminated tumour cells in the bone marrow and peripheral blood of patients with clinically localized prostate cancer

OBJECTIVE

To evaluate the expression of urokinase‐plasminogen‐activator receptor (uPA‐R) in disseminated tumour cells (DTC) in bone marrow (BM) and peripheral blood (PB) of patients with clinically localized prostate cancer before radical prostatectomy (RP), and to assess the associations with pathological variables and prognosis.

PATIENTS AND METHODS

In all, 52 patients (47 with clinically localized cancer and five with benign prostatic hyperplasia, BPH, as controls) were prospectively enrolled. BM and PB samples were drawn before surgery. DTC were enriched using a commercial system, cytokeratin (CK) 8/18 was used to detect DTC, and uPA‐R expression was detected by dual‐immunostaining of the DTC. The final pathology of the RP specimen was compared with the results of immunostaining. Follow‐up was initiated to detect tumour relapse (defined as a prostate‐specific antigen (PSA) level of ≥0.2 ng/mL).

RESULTS

Overall, there was expression of ‘CK + uPA‐R’ in 60% of the BM and in 19% of the PB specimens. Expression of this marker in BM was most significantly increased in those with unfavourable Gleason scores (P = 0.004), followed by high‐risk cancer (P = 0.005). The relative risk for CK + uPA‐R expression in the BM was 3.1 times higher in high‐risk than in low‐risk prostate cancer. No relevant expression rates were detected for PB. In the control group, no patient showed CK or uPA‐R expression in BM or PB. The PSA‐recurrence free survival was significantly lower in patients with CK + uPA‐R‐positive BM cells (P = 0.01).

CONCLUSION

In this pilot study, the preoperative detection rate of CK + uPAR expression in BM of patients with prostate cancer increased with Gleason score and in those with high‐risk disease. All patients with a later PSA relapse had had uPA‐R expression in their DTC from the BM. DTC with uPA‐R expression was an adverse prognostic factor for prostate cancer.     

Use of the burn intervention score to calculate the charges of the care of burns

Background

To our knowledge this is the first published estimate of the charges of the care of burns in Sweden. The Linköping Burn Interventional Score has been used to calculate the charges for each burned patient since 1993. The treatment of burns is versatile, and depends on the depth and extension of the burn. This requires a flexible system to detect the actual differences in the care provided. We aimed to describe the model of burn care that we used to calculate the charges incurred during the acute phase until discharge, so it could be reproduced and applied in other burn centres, which would facilitate a future objective comparison of the expenses in burn care.

Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis

Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60-65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.     

Prevalence, clinical features, and CPAP adherence in REM-related sleep-disordered breathing: a cross-sectional analysis of a large clinical population

Purpose  

Due to inconsistent definitions used in the literature, the prevalence of rapid eye movement (REM)-related sleep-disordered breathing (SDB) has been quite variable and its clinical significance remains unclear. This study aimed to compare the prevalence of and clinical characteristics between various criteria for defining REM-related SDB. We also investigated how frequently CPAP therapy was recommended in patients with REM-related SDB and if they had lower CPAP adherence compared to non-stage-specific SDB.     

Simulation-assisted burn disaster planning

The aim of the study was to evaluate the Swedish medical systems response to a mass casualty burn incident in a rural area with a focus on national coordination of burn care. Data were collected from two simulations of a mass casualty incident with burns in a rural area in the mid portion of Sweden close to the Norwegian border, based on a large inventory of emergency resources available in this area as well as regional hospitals, university hospitals and burn centres in Sweden and abroad. The simulation system Emergo Train System^® (ETS) was used and risk for preventable death and complications were used as outcome measures: simulation I, 18.5% (n = 13) preventable deaths and 15.5% (n = 11) preventable complications; simulation II, 11.4% (n = 8) preventable deaths and 11.4% (n = 8) preventable complications. The last T1 patient was evacuated after 7 h in simulation I, compared with 5 h in simulation II. Better national coordination of burn care and more timely distribution based on the experience from the first simulation, and possibly a learning effect, led to a better patient outcome in simulation II. The experience using a system that combines both process and outcome indicators can create important results that may support disaster planning.     

Sitting Pressure and Perfusion of Buttock Skin in Paraplegic and Tetraplegic Patients,and in Healthy Subjects: A Comparative Study

The distribution of sitting pressure and ability to respond with reactive hyperaemia were studied in a group of paraplegic and tetraplegic patients ( n = 8) with spinal cord lesions and healthy controls ( n = 10) using a pressure sensitive plate and laser Doppler perfusion imager. The results show that the mean sitting pressure of the patients was 9.9 N/cm 2 (left) and 11.7 N/cm 2 (right) compared with 3.5 N/cm 2 controls. The differences were significant on both the left ( p < 0.01) and right ( p < 0.05) sides. The maximum pressure in patients was 42.9 N/cm 2 (left) and 48.7 N/cm 2 (right), and in controls ( p < 0.01). Both groups showed a reduction in skin perfusion in the seat area during sitting compared with unloaded resting, and in the controls it was significantly increased ( p < 0.001 on both sides) during the reactive hyperaemic phase immediately after sitting. Compared with the preload values, the patients showed a similar but slightly weaker picture significant on the right side ( p < 0.05), but not on the left. The hyperaemia was not uniformly distributed, but occurred where the pressure was greater than 2 N/cm 2 . There was no correlation between the amount of reactive hyperaemia and absolute values of sitting pressures. We conclude that tetraplegic and paraplegic patients have significantly higher sitting pressures than normal controls, and that the hyperaemic response in the buttock region in the upright position after pressure load is slightly weaker in the patients, which could be of importance for the development of decubitus ulcers.     

EPZ011989, A Potent,Orally-Available EZH2 Inhibitor with Robust in Vivo Activity

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