Androgens block interleukin-1 beta-induced promatrilysin expression in prostate carcinoma cells

BACKGROUND: We have shown previously that interleukin (IL) -1 beta- and IL-6-induced promatrilysin expression is mediated by an indirect pathway that requires NF kappa B-dependent synthesis of IL-6 and STAT3 signaling. We now demonstrate that IL-1 beta-induced but not IL-6-induced promatrilysin expression can be blocked by androgens in the prostate carcinoma cell line LNCaP (lymph node-derived carcinoma cells of the prostate). METHODS: By using enzyme-linked immunosorbent assay analyses, promatrilysin was measured in LNCaP cells stimulated with IL-1 beta or IL-6 LNCaP-treated cells pretreated with testosterone. In addition, promatrilysin message was measured by using Northern analyses after IL-6-treated cells pretreated with testosterone. RESULTS: In LNCaP treated with testosterone before IL-1 beta stimulation induced promatrilysin expression was completely abrogated. Furthermore, testosterone completely abrogated NF kappa B transactivation activity and induction of IL-6 protein expression and mRNA. Testosterone and 5 alpha-dihydrotestosterone did not have an inhibitory effect on IL-6-induced promatrilysin expression. Testosterone also had no effect on basal promatrilysin expression or basal NF kappa B transactivation activity. CONCLUSION: From these data, we conclude that testosterone blocks IL-1 beta-induced promatrilysin expression by inhibition of NF kappa B transactivation activity, which in turn, blocks IL-6 expression. These data suggest a mechanism in vivo by which invasive and metastatic prostatic carcinoma cell clones refractory to hormone ablation therapy may develop after chemical or surgical castration. Furthermore, these data suggest that, perhaps, upstream targets such as the cytokines IL-1 beta and IL-6 may provide alternative drug targets for inhibiting prostate cancer progression.     

Single upper-pole percutaneous access for treatment of > or = 5-cm complex branched staghorn calculi: is shockwave lithotripsy necessary?

BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy for staghorn calculi is reported to have a residual stone rate of 28%, while shockwave lithotripsy alone results in residual stones in approximately 50% of cases. Combination therapy, sandwich therapy, and multiple percutaneous accesses have also been advocated for staghorn stones. We believe these stones can often be removed with a staged procedure via a single upper-pole percutaneous access using flexible nephroscopy and the holmium:YAG laser. Our experience is reviewed. PATIENTS AND METHODS: The hospital records of patients having a cumulative stone burden > or =5 cm who underwent percutaneous nephrolithotripsy (PCNL) for a single complex staghorn calculus were reviewed. There were 15 male and 34 female patients having 45 complete and 7 partial staghorn calculi constituting a mean stone burden of 6.7 cm (range 5.0-10.0 cm). A calix was punctured that would provide access to the majority of the involved calices. Thirty-five renal units were approached through a single upper-pole percutaneous access, and four and six renal units were accessed through single middle or lower-pole calices, respectively. The remaining seven renal units were treated with multiple percutaneous accesses. RESULTS: In the renal units having only a single access, a mean of 1.6 (range 1-3) procedures were required to achieve stone-free status. The mean operating room time was 2.9 hours (range 2.0-3.5 hours). For the second PCNL, the mean operating room time was 63 minutes (range 30-90 minutes). Two patients (two renal units) had residual stones <1 cm in diameter. One refused additional surgery, and the other is awaiting further treatment. The mean estimated blood loss was 238 mL (range 50-800 mL), with only one procedure (2.2%) necessitating a blood transfusion. One (2.8%) hydrothorax developed among the 35 upper-pole puncture cases. Six patients had transient oral temperature readings >101 degrees F with negative blood cultures. Other early complications included single cases of leg cellulitis, atrial fibrillation, and noncardiac chest pain. There were no delayed surgical complications. Patients were discharged from the hospital a mean 2 days (range 1-10 days) after the first PCNL. CONCLUSION: Use of flexible nephroscopy with holmium:YAG laser lithotripsy and Nitinol basket stone extraction has allowed us to render staghorn-containing renal units stone free in a mean of 1.6 procedures. Of the 45 renal units treated through a single percutaneous access, 43 (95%) were rendered stone free. The holmium:YAG laser appears to be a safe lithotrite for the kidney, as no complications occurred from its use.     

Virtual reality surgical simulation for lower urinary tract endoscopy and procedures

BACKGROUND AND PURPOSE: To provide a realistic experience of lower urinary tract endoscopic procedures, we have developed and continue to expand a computer-based surgical simulator that incorporates a surgical tool interface with anatomic detail and haptic feedback. METHODS: Surface-based geometric data for the lower urinary tract were generated from the National Library of Medicine Visible Human dataset. The three-dimensional texture map of the surface geometry was developed from recorded endoscopic video procedures. Geometry and associated texture maps were rendered in real time using the Silicon Graphics Extreme Impacts program. The surgical interface device incorporated all normal ranges of motion and resistance that occur within an actual operative environment. The hands-on endoscopic device attached to the interface device was provided by Circon-ACMI, Inc. Urologic residents evaluated the program for correlation with actual endoscopic procedures. RESULTS: Texture-mapped digitized images provided a close anatomic similarity to actual videoendoscopic images. Virtual endoscopy of the lower urinary tract was reproducible and closely simulated actual visual and tactile endoscopic experience. CONCLUSIONS: Virtual reality surgical simulation is feasible for a variety of lower urinary tract procedures. This system coordinates visual perception with appropriate haptic feedback in both longitudinal and rotational axes. These types of procedures may be incorporated into future educational experiences for urologists to introduce new techniques and to provide documentation of surgical experience.     

Arteriovenous malformation mimicking a renal-cell carcinoma

We describe a renal arteriovenous malformation in a patient with a 1-month history of flank pain. Imaging studies were interpreted as being consistent with renal-cell carcinoma. However, Doppler ultrasonography demonstrated turbulent blood flow, and selective renal angiography confirmed the diagnosis of an arteriovenous malformation. Embolization relieved the pain. This case calls attention to the need to consider arteriovenous malformations in the differential diagnosis of central homogenously enhancing renal lesions.     

The dialytic management of acute renal failure in the elderly

In this article the different dialysis strategies in the management of acute renal failure (ARF) in the elderly are discussed. Although peritoneal dialysis (PD) offers some theoretical advantages, there are several medical and technical reasons why it is currently less frequently used. The choice between intermittent hemodialysis (HD) and continuous renal replacement therapy (CRRT) is determined by a number of considerations, the most important ones being hemodynamic stability, the need for hyperalimentation and/or ultrafiltration, and the local experience with one or both techniques. Some recent studies with CRRT in elderly ARF patients describe favorable results. Slow extended daily dialysis (SLEDD) modalities may be particularly indicated in elderly, critically ill ARF patients because these techniques combine the advantages of both CRRT and HD. Finally, the importance of the biocompatibility of dialysis membranes is discussed. Although there are a number of theoretical arguments to use biocompatible membranes, this opinion is not always supported by the results of recent comparative studies. It is the opinion of the authors that all dialysis strategies should be mastered and utilized for appropriate indications in elderly ARF patients.     

Effective removal of methotrexate by high-flux hemodialysis

The purpose of the present study was to examine the clearance of methotrexate (MTX) by high-flux hemodialysis (HD) in pediatric oncology patients. We present three patients who experienced nephrotoxicity and prolonged exposure to toxic MTX concentrations following high-dose infusions during treatment for osteogenic sarcomas. Each patient was successfully treated with high-flux HD, followed by carboxypeptidase G2 (CPDG2) in two cases. Minimal systemic toxicity occurred. We review the literature and discuss guidelines for early and aggressive treatment for this complication of high-dose MTX therapy. Clinically important removal of MTX depends upon prompt initiation of HD after detection of nephrotoxicity and delayed clearance of MTX. Therapy is indicated in cases where compassionate use of CPDG(2) may not be available, or while awaiting its delivery.     

Orbital presentation of posttransplantation lymphoproliferative disorder: a small case series

OBJECTIVE: To describe a small series of patients with orbital presentation of posttransplantation lymphoproliferative disorder (PTLD). DESIGN: Retrospective, interventional case series. PARTICIPANTS: Three patients with orbital presentation of histologically diagnosed PTLD. METHODS: Review of medical records. MAIN OUTCOME MEASURES: Measured parameters included vision, proptosis, and tumor extent. RESULTS: Three cases of orbital PTLD are described. In two of the cases, the tumor initially demonstrated orbital signs and symptoms, whereas in the third case, orbital and systemic signs were synchronous. Two of three patients had disseminated disease discovered at the time of presentation. One adult patient had synchronous presentation of PTLD in the orbit and prostate. One pediatric patient had tumor dissemination to the liver at the time of presentation. The PTLD tumors were classified histologically as diffuse large cell lymphoma of monomorphic or immunoblastic type in all three cases. Treatment included local irradiation, decreased immunosuppression, and antilymphocyte monoclonal antibodies. CONCLUSIONS: Orbital presentation is a rare manifestation of PTLD. However, ophthalmologists must consider this diagnosis carefully in organ transplant recipients with subtle orbital signs and symptoms at presentation. Early detection may alter prognosis. In each case presented, the diagnosis was established via lesion biopsy and subsequent histologic or flow cytometric evaluation, or both.     

Bilateral third and unilateral sixth nerve palsies as early presenting signs of metastatic prostatic carcinoma

PURPOSE: To report four cases of cranial nerve palsy, which presented to the ophthalmologist as the only or one of the earliest manifestations of prostatic carcinoma. This is an infrequent complication of metastatic prostatic carcinoma usually only occurring late in the disease process in those with a history of prostatic carcinoma. METHODS: The case records of four patients with a history of a cranial nerve palsy who attended the ophthalmology department and who had a recent or subsequent diagnosis of prostatic carcinoma were reviewed. RESULTS: Diplopia caused by lesions affecting the third and sixth nerves sometimes in association with sensory symptoms may be a manifestation of metastatic prostatic carcinoma. These findings are consistent with base of the skull metastases from the condition.Two patients are still alive 54 months and 12 months after the diagnosis. One of the patients died 13 months after the diagnosis of prostatic carcinoma was made and the other died 21 months after the diagnosis from an unrelated hypertensive brain haemorrhage. CONCLUSIONS: Any patient presenting with diplopia must have an adequate past medical history taken and in an elderly gentleman this should include symptoms of prostatic disease. If indicated urological referral and measurement of prostate specific antigen may be performed.In patients whose cranial nerve palsy is complicated by other sensory signs or those in whom no sign of recovery occurs in 2 months, a contrast CT scan asking for bone windows to be included may be helpful in delineating any pathology.Radiotherapy may be useful for the treatment of metastatic prostatic carcinoma causing cranial nerve palsies with some patients experiencing either complete or partial resolution of their symptoms. The effect of newer hormonal agents or chemotherapy on this aspect of the disease is not well documented in current literature.     

Derivation of lenticular transmittance from fluorophotometry

PURPOSE: To derive transmittance spectra for the human lens using the ratio between posterior and anterior autofluorescence of the lens as measured by fluorophotometry. METHODS: Transmittance spectra of the lens can be described with a one-parameter model to a high degree of accuracy. The parameter m of this model defines the differences between lens transmittance spectra of individuals. In fluorophotometry literature another parameter related to lens transmittance, T, has been defined as the square root of the ratio between posterior and anterior lenticular autofluorescence. T can be predicted from parameter m, given the spectra of the excitation light, of the fluorescence emitted by the lens and of the detecting device are known, and assuming that the anterior and posterior fluorescence efficiencies of the lens are equal. When this relation is inverted, parameter m can be derived from T, giving the complete transmittance spectrum on the basis of T. RESULTS: A transformation curve was calculated to determine T from m and vice versa. The light transmittance spectrum of the lens was calculated as a function of T. The validity of this approach was evaluated using an independent method for assessment of lenticular transmittance. This method consisted of making color slitlamp slides, grading the observed color of these slides with the LOCS III NC grading system, and transforming these grades into the model parameter m using published transformation curves. CONCLUSIONS: The total transmittance spectrum can be calculated reliably from a fluorophotometric scan of the human lens.