Obesity Is Associated with Increased Prostate Growth and Attenuated Prostate Volume Reduction by Dutasteride

Background

Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors.

Objective

To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements.

Design, setting, and participants

We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy.

Intervention

Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr.

Outcome measurements and statistical analysis

Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25–29.9, and ≥30 kg/m² using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression.

Results and limitations

Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus <25 kg/m² had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p < 0.001; at 4 yr: 29.4% vs 20.1%; p = 0.001). Men on dutasteride with BMI ≥30 versus <25 kg/m² had attenuated PV reduction from baseline (at 2 yr: −14.3% vs −18.5%; p = 0.002; at 4 yr: −13.2% vs −19.3%; p = 0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08–1.93; p = 0.014; at 4 yr: OR: 1.62; 95% CI, 1.18–2.22; p = 0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed.

Conclusions

Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy.

ClinicalTrials.gov identifier

NCT00056407.     

Lymphography--current role in oncology

A review of the use of lymphography at this hospital, a major oncology centre, is presented. The advent of computed tomography has brought a dramatic reduction in the number of lymphograms currently performed for diseases such as lymphoma, testicular tumours and gynaecological malignancies. This study analyses the reasons for this decline, and concludes that valuable information can still be obtained from lymphography in certain selected groups of patients.     

Rapid method for isolation of normal human peripheral blood eosinophils on discontinuous Percoll gradients and comparison with neutrophils

Previous studies on human eosinophils often have used cells from patients with hypereosinophilia syndrome or parasitosis owing to the difficulty in isolating pure populations of eosinophils from normal individuals. In the present study, human eosinophils were isolated with a purity of 97%, with 70% recovery from normal individuals with blood eosinophil counts of less than 3%. Human eosinophils are denser than neutrophils, but the range of densities of the two cell types overlap, making purification of eosinophils by density-gradient centrifugation difficult. However, if neutrophils were exposed to the chemotactic peptide (f-Met-Leu-Phe), which did not stimulate eosinophils, the neutrophils' density decreased, shifting them away from the density of eosinophils. Whole normal blood anticoagulated with EDTA was incubated at 37 degrees C for 15 minutes with 10(-6) mol/L f-Met-Leu-Phe and then layered over a discontinuous Percoll gradient (65% and 75% in diluted phosphate-buffered saline) and centrifuged at 400 g for 25 minutes at 22 degrees C. The cell layer between the 65% and 75% Percoll was collected and washed, and hypotonic lysis was used to remove erythrocytes. This cell layer contained 97.3 +/- 0.7% eosinophils (N = 8) with a yield of 4.9 X 10(4) eosinophils per milliliter of whole blood, or 70% of the total eosinophil count. The isolated eosinophils were in a quiescent state but responded to Escherichia coli endotoxin- activated serum with shape change and chemotaxis, membrane depolarization, and reduced nitroblue tetrazolium (96.0 +/- 1.0%), when stimulated with phorbol myristate acetate. In phagocytic assays, 89.3 +/- 1.3% of the eosinophils ingested Candida albicans v 96.0% +/- 1.0% of neutrophils. In contrast, the eosinophils did not respond chemotactically, alter membrane potential, or reduce nitroblue tetrazolium when treated with f-Met-Leu-Phe, and studies with f-Met-Leu- [3H]Phe showed that normal eosinophils lacked expression of receptors for f-Met-Leu-Phe. In control studies, normal eosinophils that were not exposed to f-Met-Leu-Phe during purification also failed to respond to f-Met-Leu-Phe, indicating intrinsic differences between normal eosinophils and neutrophils. Thus, exposure of whole blood to f-Met-Leu- Phe, followed by separation on Percoll is a simple method for rapid isolation of normal human eosinophils.     

Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Clinical safety and effectiveness evaluation of a new antimicrobial wound dressing designed to manage exudate,infection and biofilm

The objective of this work was to evaluate the safety and effectiveness of a next‐generation antimicrobial wound dressing (NGAD; AQUACEL ^® Ag+ Extra™ dressing) designed to manage exudate, infection and biofilm. Clinicians were requested to evaluate the NGAD within their standard protocol of care for up to 4 weeks, or as long as deemed clinically appropriate, in challenging wounds that were considered to be impeded by suspected biofilm or infection. Baseline information and post‐evaluation dressing safety and effectiveness data were recorded using standardised evaluation forms. This data included wound exudate levels, wound bed appearance including suspected biofilm, wound progression, skin health and dressing usage. A total of 112 wounds from 111 patients were included in the evaluations, with a median duration of 12 months, and biofilm was suspected in over half of all wounds (54%). After the introduction of the NGAD, exudate levels had shifted from predominantly high or moderate to low or moderate levels, while biofilm suspicion fell from 54% to 27% of wounds. Wound bed coverage by tissue type was generally shifted from sloughy or suspected biofilm towards predominantly granulation tissue after the inclusion of the NGAD. Stagnant (65%) and deteriorating wounds (27%) were shifted to improved (65%) or healed wounds (13%), while skin health was also reported to have improved in 63% of wounds. High levels of clinician satisfaction with the dressing effectiveness and change frequency were accompanied by a low number of dressing‐related adverse events (n = 3; 2·7%) and other negative observations or comments. This clinical user evaluation supports the growing body of evidence that the anti‐biofilm technology in the NGAD results in a safe and effective dressing for the management of a variety of challenging wound types.     

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet‐derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF‐BB (rhPDGF‐BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle‐treated animals. rhPDGF‐BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF‐BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF‐BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF‐BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF‐BB may be a new therapeutic approach to treat diabetes‐impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074–1081, 2009     

Safety and performance evaluation of a next‐generation antimicrobial dressing in patients with chronic venous leg ulcers

The objective of this study was to investigate the safety and performance of AQUACEL? Ag+ dressing, a wound dressing containing a combination of anti‐biofilm and antimicrobial agents, in the management of chronic wounds. Patients (n = 42) with venous leg ulcers exhibiting signs of clinical infection were treated for 4 weeks with AQUACEL? Ag+ dressing, followed by management with AQUACEL? wound dressings for 4 weeks. Wound progression, wound size, ulcer pain and clinical evolution of the wound were assessed for up to 8 weeks. Adverse events were recorded throughout the study. AQUACEL? Ag+ dressing had an acceptable safety profile, with only one patient discontinuing from the study, because of a non‐treatment‐related adverse event. After 8 weeks, substantial wound improvements were observed: 5 patients (11·9%) had healed ulcers and 32 patients (76·2%) showed improvement in ulcer condition. The mean ulcer size had reduced by 54·5%. Patients reported less pain as the study progressed. Notable improvements were observed in patients with ulcers that were considered to require treatment with systemic antibiotics or topical antimicrobials at baseline (n = 10), with a mean 70·2% reduction in wound area. These data indicate that AQUACEL? Ag+ dressing has an acceptable safety profile in the management of venous leg ulcers that may be impeded by biofilm.