Neoadjuvant hormonal ablative therapy before radical prostatectomy: a review. Is it indicated?

PURPOSE: Neoadjuvant hormonal ablation therapy has been used to decrease the rate of positive surgical margins in patients treated with radical prostatectomy. We reviewed the available literature to determine whether this therapy is indicated and beneficial. MATERIALS AND METHODS: We performed a MEDLINE key word search and assessed randomized prospective articles. Data were analyzed for the rate of positive surgical margins, seminal vesicle invasion and lymph node metastasis as well as surgical characteristics, including operative time, blood loss, hospital stay, rate of complications and difficulty of surgical dissection. In addition, these data were evaluated for prostate specific antigen-free survival. RESULTS: Neoadjuvant hormonal therapy decreased the rate of positive margins in 6 of the 7 randomized prospective studies. In none of 4 randomized prospective series was there an improved rate of seminal vesicle invasion with neoadjuvant hormonal therapy. Of 4 studies 3 showed no improvement in the rate of lymph node metastasis after neoadjuvant hormonal therapy compared with that in controls. Similarly there was no improvement in prostate specific antigen-free survival and no significant difference in operative time, operative blood loss, transfusion or hospital stay in patients treated with neoadjuvant hormonal therapy and controls. In addition, in 2 of 3 studies there was no difference in the complication rate. CONCLUSIONS: Analysis of the available literature revealed no significant improvement in outcome to support the routine administration of neoadjuvant hormonal therapy before prostatectomy.     

Symptomatic hypertrophic pubic ramus nonunion treated with a retrograde medullary screw

Pubic ramus fracture nonunion is an unusual problem. Percutaneous retrograde superior pubic ramus medullary screw fixation was successfully used in two patients with prolonged symptomatic nonunions of the superior pubic ramus.     

Nanoparticle Generation in Glowing Wire Generator: Insight into Nucleation Peculiarities

The paper studies nanoparticle formation in a glowing wire generator (GWG), in which the gas carrier flows around heated metal wire, producing aerosols from a vapor released from the surface. The device has been customized, enabling the use of a double-wire in different orientations in regard to the gas flow. Such alterations provided different effective distances between wires enabling investigation of their mutual influence. Concentration of particles produced in the GWG at different parameters (applied voltage and a gas flow) was carefully measured and analysed. Different regimes of a nanoparticle nucleation were identified that resulted from the applied voltage variation and the gas flow direction. In particular, independent nucleation of nanoparticles on both parts of the wire occurred in the wire plane’s configuration perpendicular to the gas flow, whilst dependent nucleation of nanoparticles was observed at a certain specific set of parameters in the configuration, in which the wire plane was parallel to the gas flow. Two corresponding functions were introduced in order to quantify those nucleation regimes and they tend to zero when either independent or dependent nucleation occur. The peculiarities found ought to be considered when designing the multi-wire GWGs in order to further extend the device’s range for industrial applications.     

The outcome of advanced chronic nephropathy in type 1 and type 2 diabetic and non-diabetic patients: a prospective study.

To compare end-stage progression of nephropathy in type 1 and type 2 diabetic patients and non-diabetic subjects, we prospectively studied 92 patients with advanced uraemia not yet on dialysis (mean age 57.2 +/- 15.0 years), with a serum creatinine level above 200 mumol/L. The study included monthly serum creatinine (SC) measurements and quarterly outpatient follow-up (mean 10.8 +/- 7.1 months, range 1-21). Sixty subjects (65.2%) were diabetic (28 type 1 and 32 type 2). At inclusion, 95.6% of patients had anti-hypertensive medications. Drug category, dosage and combination were similar for both groups. Blood pressure (< or = 130/85 mmHg) and glucose level targets (fasting < or = 7.5 mmol/L and postprandial < or = 10 mmol/L) were obtained in all patients. Initial SC was not significantly different between diabetic and non-diabetic patients (426.5 +/- 189.4 mumol/L vs. 405.1 +/- 201.9 mumol/L). SC increased significantly faster in diabetic than non-diabetic patients (respectively 3.9 +/- 6.1% and 1.5 +/- 4.6% monthly, p < 0.05), with no difference between type 1 and type 2 diabetes. One-third (33.7%) of all patients started dialysis during follow-up (40% diabetic and 22% non-diabetic). Their weight, body mass index, age, sex ratio, treatment and aetiology were similar. During follow-up, the patients (29.4%) who sustained a major vascular event differed only in age (62.1 years vs. 55.2 years; p < 0.001). In this study, diabetic renal disease worsened significantly faster than other nephropathies, in spite of proper normalisation of blood pressure and glucose level. Therefore, it is essential to diagnose and manage Type 2 diabetes early to avoid encumbering dialysis centres with older patients.     

High-Energy Pulsed Light Source Hair Removal Device Used to Evaluate the Onset of Action of a New Topical Anesthetic

BACKGROUND: Topical anesthetic agents are widely used to mitigate the pain associated with laser and high-energy pulsed light source hair removal. OBJECTIVE: To evaluate the relative efficacy and onset of action of a new topical anesthetic agent, ELA-Max cream (lidocaine 4%), relative to a widely used agent, EMLA cream (lidocaine 2.5%/prilocaine 2.5%). METHODS: ELA-Max and EMLA were applied to the forearms of 10 unblinded test subjects. The EMLA-treated sites were occluded for 1.5 hours prior to testing. The ELA-Max-treated sites were unoccluded and the cream was applied immediately prior to testing. Pulses from an Epilight high-energy pulsed light source were then administered 1.5 hours after occlusion with EMLA and in 5-minute intervals after application of ELA-Max. Pain scores were recorded on a visual analog scale (VAS). RESULTS: Six of 10 patients reported some anesthetic effect from ELA-Max after 5 minutes of unoccluded skin contact. Seven of 10 subjects reported maximal pain control 20 minutes after application of unoccluded ELA-Max, roughly equivalent to EMLA after 1.5 hours of occlusion. CONCLUSION: ELA-Max is an effective topical anesthetic agent comparable to EMLA under occlusion. It appears to be faster acting than EMLA, and along with its effectiveness without occlusion, may be an easier agent to use.     

Heterogeneity of magnitude,allergen immunodominance,and cytokine polarization of cockroach allergen‐specific T cell responses in allergic sensitized children

BackgroundCharacterization of allergic responses to cockroach (CR), a common aeroallergen associated with asthma, has focused mainly on IgE reactivity, but little is known about T cell responses, particularly in children. We conducted a functional evaluation of CR allergen‐specific T cell reactivity in a cohort of CR allergic children with asthma.MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from 71 children, with mild‐to‐moderate asthma who were enrolled in a CR immunotherapy (IT) clinical trial, prior to treatment initiation. PBMC were stimulated with peptide pools derived from 11 CR allergens, and CD4+ T cell responses assessed by intracellular cytokine staining.ResultsHighly heterogeneous responses in T cell reactivity were observed among participants, both in terms of the magnitude of cytokine response and allergen immunodominance. Reactivity against Bla g 9 and Bla g 5 was most frequent. The phenotype of the T cell response was dominated by IL‐4 production and a Th2 polarized profile in 54.9% of participants, but IFNγ production and Th1 polarization was observed in 25.3% of the participants. The numbers of regulatory CD4+ T cells were also highly variable and the magnitude of effector responses and Th2 polarization were positively correlated with serum IgE levels specific to a clinical CR extract.ConclusionsOur results demonstrate that in children with mild‐to‐moderate asthma, CR‐specific T cell responses display a wide range of magnitude, allergen dominance, and polarization. These results will enable examination of whether any of the variables measured are affected by IT and/or are predictive of clinical outcomes.     

Inhibition of insulin‐like growth factor binding protein 5 proteolysis in articular cartilage and joint fluid results in enhanced concentrations of insulin‐like growth factor 1 and is associated with improved osteoarthritis

Objective

The complement component C1s is present in dog joint fluid in an activated state. Since C1s degrades insulin‐like growth factor binding protein 5 (IGFBP‐5), we undertook to determine whether inhibiting C1s in joint fluid would result in an increase in the amount of intact IGFBP‐5 and IGF‐1 in cartilage and joint fluid, and whether C1s inhibition would be associated with a reduction in cartilage destruction during the development of osteoarthritis (OA).

Methods

Twenty‐two dogs were randomized to 3 treatment groups. All dogs underwent anterior cruciate ligament transection and were exercised. Dogs received 1 of 3 treatments: buffer alone (controls; n = 6); PB‐145, a peptide derived from the sequence of antithrombin III (n = 9); and pentosan polysulfate (PPS; n = 7). PB‐145 or saline was injected into the joint space 3 times per week for 3 weeks. PPS was injected intramuscularly weekly for 3 weeks.

Results

Joint histology showed preservation of chondrocytes and a smooth joint surface in the animals treated with PB‐145 and PPS. Mankin scoring showed statistically significant reductions in joint destruction with PB‐145 and PPS treatments (P < 0.01) compared with buffer control. Mean active collagenase concentrations were decreased by these two treatments. Immunoblotting of joint fluid showed that both treatments increased concentrations of intact IGFBP‐5. Direct analysis of IGFBP‐3 and IGFBP‐5 protease activity showed that IGFBP‐5 was degraded more rapidly and that PB‐145 and PPS inhibited the degradation of both proteins. Total IGF‐1 concentrations in joint fluid were increased 5.6–5.8‐fold by these two treatments. Analysis showed that C1s was being activated in joint fluid and that its activation was inhibited by the addition of PB‐145 or PPS.

Conclusion

The findings suggest that direct inhibition of the serine protease C1s results in increased concentrations of intact IGFBP‐5 and that proteolysis of IGFBP‐3 is also inhibited, probably by the inhibition of some other protease. This increase in concentrations of intact IGFBP‐3 and IGFBP‐5 leads to an increase in IGF‐1 which is associated with an improvement in joint architecture during the development of OA.