Changes in cIAP2, survivin and BimEL expression characterize the switch from autophagy to apoptosis in prolonged starvation.

BACKGROUND: Autophagy is a catabolic process involving the engulfment of cytoplasmic content within autophagosomes followed by their delivery to lysosomes. This process is a survival mechanism, enabling cells to cope with nutrient deprivation by degradation and recycling of macromolecules. Yet during continued stress such as prolonged starvation, a switch from autophagy to apoptosis is often detected. OBJECTIVE: In this work, we characterized the temporal dynamics of the transition from autophagy towards apoptosis with the aim of elucidating the molecular mechanism regulating the switch from survival autophagy to apoptotic cell death. RESULTS AND CONCLUSIONS: We defined an inverse relationship between apoptosis and autophagy spanning a period of 72 h, manifested by the sequential reduction in LC3 lipidation and the activation of caspase-3. The transition to apoptosis correlated with a selective decline in the mRNA and protein levels of two anti-apoptotic IAP family proteins, survivin and cIAP2 and a selective increase in the BH3-only protein, BimEL. This 'molecular signature' was common to several cell lines undergoing the switch from autophagy to apoptosis during prolonged starvation. Mechanistically, the increased BimEL protein levels resulted from its reduced binding to its specific E3 ligase, ßTrCP, leading to protein stabilization. Consistent with this, BimEL showed decreased phosphorylation at critical sites previously reported to be essential for binding to the E3 ligase. The decrease in the anti-apoptotic IAPs and the increase in the pro-apoptotic BimEL may thus constitute a molecular switch from autophagy to apoptosis during prolonged starvation.

[Long-term results of a phase III multicentre trial of the adjustable male sling for treating urinary incontinence after prostatectomy: minimum 3 years]. / Resultados a largo plazo del estudio multicéntrico fase III del tratamiento de la incontinencia de orina post prostatectomía con un sling masculino ajustable: seguimiento mínimo 3 años.

OBJECTIVE: To communicate long-term results of the multicentre phase III trial post-prostatectomy urinary incontinence (PPI) treated with an adjustable male sling. PATIENTS AND METHODS: 48 PPI patients were included in this trial from April 2003 to September 2004. 39 post radical prostatectomy and 9 post adenomectomy. 19 wore 5 pads per day (3-8) each weight 83 gr (17-198). 29 wore condom catheter or penile clamp The Argus was implanted through perineal approach. Using needles, the sling was transferred to the abdominal wall where it was adjusted by washers. The adjustment was done with retrograde urethral pressure from 45 to 55 cm water. Clinical data were updated till September 2007. The mean follow-up was 45 months (36-54) and median age was 67 years (52-77). The evaluation was: the ICIQ-SF score and qualification as Dry: no pads, Improved: 1 pad and Failed: 2 or more pads in 24 hr, including those with slings removed. RESULTS: 47 were evaluated, resulting: 31 (66%) Dry, 6 (12.8%) Improved and 10 (21%) Failed. The ICIQ-SF score changed from 19.5 to 6. Of the 31 dry pts, 5 required one adjustment. 10 pts failed, 9 after sling removal, 6 due to erosion and 3 for infection. One patient failed with the sling in place, 6 erosions were registered: 4 in the urethra, 1 into the bladder and 1 through the abdominal wall. Perineal pain persisted in 2. One patient was excluded, died in September 2006. CONCLUSIONS: Argus has demonstrated its efficacy in long- term follow-up. The social continence rate was about 80%. The important complication was erosion or infection.

Resultados a largo plazo del estudio multicéntrico fase III del tratamiento de la incontinencia de orina post prostatectomía con un sling masculino ajustable: seguimiento mínimo 3 años / Long term results of a phase III multicentre trial of the adjustable male sling for treating urinary incontinence after prostatectomy: minimum 3 years

Objetivo: Comunicar los resultados a largo plazo del estudio multicéntrico fase III del tratamiento de la incontinencia post- prostatectomía (IPP) con un Sling masculino ajustable (Argus®) 1.Pacientes y métodos: 48 pacientes con IPP, 39 post radical y 9 post adenomectomía, ingresaron entre abril de 2003 y septiembre de 2004. 19 usaban 5 paños por día (3-8) pesando 83 gr. (17-198) por paño. 29 usaban clamp peniano o colector externo. El seguimiento promedio fue de 45 meses (36 -54). La edad fue de 67años (52-77). Fueron evaluados con el cuestionario ICIQ-SF y la calificación de seco (sin paños), mejora (1 paño) y falla (2 o más paños en 24 hs), incluyéndose a los slings extraídos. El Argus se implantó por vía perineal, transfiriéndolo con agujas al abdomen para ser ajustado y fijado con arandelas. El ajuste se realizó por presión uretral retrograda (PUR) entre 45 y 55cm de agua. Resultados: Evaluamos 47 de 48 pacientes (1, falleció antes de 3 años) resultando secos, mejorados y fallados, 31(66%), 6 (12.8%)y 10 (21%) respectivamente. ICIQ-SF cambió de 19,5 a 6 (1-21). 5 de 31 secos, debieron reajustarse una vez. Fallaron 10 pacientes: 9 Argus retirados: 6 (12,8%) por erosión, 3 (6,2%) por infección y 1 usa 3 paños diarios. Hubieron 6 erosiones: 4 uretrales, 1 vesical y 1 parietal abdominal. El dolor persistió en 2 casos. Las complicaciones menores se resolvieron espontáneamente antes de2 meses. Conclusiones: El Argus® demostró ser eficaz en el control de la IPP en el largo plazo en casi el 80% de los pacientes evaluados. La infección y la erosión fueron las complicaciones más importantes y los desafíos a resolver (AU)

Objective: To communicate long- term results of the multicentre phase III trial post-prostatectomy urinary incontinence (PPI) treated with an adjustable male sling1.Patients and Methods: 48 PPI patients were included in this trial from april 2003 to september 2004. 39 post radical prostatectomy and 9 post adenomectomy. 19 wore 5 pads per day (3-8) each weight 83gr (17-198). 29 wore condom catheter or penile clamp. The Argus was implanted through perineal approach. Using needles, the sling was transferred to the abdominal wall where it was adjusted by washers. The adjustment was done with retrograde urethral pressure from 45 to 55 cm water. Clinical data were updated till September 2007. The mean follow-up was 45 months (36-54) and median age was 67 years (52-77). The evaluation was: the ICIQ-SF score and qualification as Dry: no pads, Improved: 1 pad and Failed: 2 or more pads in 24 hr, including those with slings removed. Results: 47 were evaluated, resulting: 31 (66%) Dry, 6 (12.8%) Improved and 10 (21%) Failed. The ICIQ-SF score changed from 19.5to 6. Of the 31 dry pts, 5 required one adjustment. 10 pts failed, 9 after sling removal, 6 due to erosion and 3 for infection. One patientfailed with the sling in place, 6 erosions were registered: 4 in the urethra, 1 into the bladder and 1 through the abdominal wall. Perineal pain persisted in 2. One patient was excluded, died in September 2006.Conclusions: Argus® has demonstrated its efficacy in long- term follow-up. The social continence rate was about 80%. The important complication was erosion or infection (AU)

Painless inter epididymal testicular torsion of the spermatic cord.

Inter epididymal testicular torsion of the spermatic cord is extremely rare and usually diagnosed at surgery. We present an unusual case of spermatic cord torsion in a 14-year-old male patient. It is important to highlight that the torsion occurred only on the distal half of the epididymis leaving the head untwisted and edematous. In addition, the fact that this condition was painless made this case extremely rare and motivated our presentation.

Painless inter epididymal testicular torsion of the spermatic cord

Inter epididymal testicular torsion of the spermatic cord is extremely rare and usually diagnosed at surgery. We present an unusual case of spermatic cord torsion in a 14-year-old male patient. It is important to highlight that the torsion occurred only on the distal half of the epididymis leaving the head untwisted and edematous. In addition, the fact that this condition was painless made this case extremely rare and motivated our presentation.

Resultados significativamente superiores en continencia y micción con la neovejiga colónica derecha parcialmente destubulizada. Trece años de experiencia / Results in continence and micturition remarkably superior with a right colonic neobladder with partial detubulization. Thirteen years of experience

Objetivos: Mostrar luego de 13 años de experiencia contínua, los resultados en lo que a continencia y micción se refiere de la neovejiga colónica derecha, como así también los fundamentos fisiológicos y urodinámicos de los mismos. Materiales y Métodos: Entre febrero de 1993 y marzo de 2006 a 43 pacientes cistectomizados, por presentar cáncer de vejiga, se les reconstruyo el tracto urinario inferior utilizando un reservorio construido con colon derecho destubulizado y reconfigurado y ciego intacto. A todos los pacientes se les realizo cistografías al retirar el catéter uretral, a 32 estudios urodinámicos y a 5 videourodinámicos. Resultados: Cuarenta y un pacientes (95,4 porciento) orinan con un flujo máximo de más de 25 ml/seg. La continencia diurna y nocturna fue completa e inmediata en el 97 porciento y 93 porciento respectivamente, un paciente requiere cateterismo intermitente, otro permanece incontinente y los dos restantes lograron continencia nocturna satisfactoria. Se define como continencia completa e inmediata al control de la orina sin necesidad de usar paño protector desde el momento en que se retira el catéter uretral, satisfactoria al uso de no mas de un pañal por día y micción espontánea y efectiva a la evacuación del reservorio con un flujo medio de 10 ml/seg. sin residuo postmiccional. Conclusión: Los resultados con esta nueva neovejiga colónica derecha, en lo que a continencia y micción se refiere, son significativamente superiores a los logrados con otros procedimientos descriptos en la literatura(AU)

Resultados significativamente superiores en continencia y micción con la neovejiga colónica derecha parcialmente destubulizada. Trece años de experiencia / Results in continence and micturition remarkably superior with a right colonic neobladder with partial detubulization. Thirteen years of experience

Objetivos: Mostrar luego de 13 años de experiencia contínua, los resultados en lo que a continencia y micción se refiere de la neovejiga colónica derecha, como así también los fundamentos fisiológicos y urodinámicos de los mismos. Materiales y Métodos: Entre febrero de 1993 y marzo de 2006 a 43 pacientes cistectomizados, por presentar cáncer de vejiga, se les reconstruyo el tracto urinario inferior utilizando un reservorio construido con colon derecho destubulizado y reconfigurado y ciego intacto. A todos los pacientes se les realizo cistografías al retirar el catéter uretral, a 32 estudios urodinámicos y a 5 videourodinámicos. Resultados: Cuarenta y un pacientes (95,4 porciento) orinan con un flujo máximo de más de 25 ml/seg. La continencia diurna y nocturna fue completa e inmediata en el 97 porciento y 93 porciento respectivamente, un paciente requiere cateterismo intermitente, otro permanece incontinente y los dos restantes lograron continencia nocturna satisfactoria. Se define como continencia completa e inmediata al control de la orina sin necesidad de usar paño protector desde el momento en que se retira el catéter uretral, satisfactoria al uso de no mas de un pañal por día y micción espontánea y efectiva a la evacuación del reservorio con un flujo medio de 10 ml/seg. sin residuo postmiccional. Conclusión: Los resultados con esta nueva neovejiga colónica derecha, en lo que a continencia y micción se refiere, son significativamente superiores a los logrados con otros procedimientos descriptos en la literatura

An adjustable male sling for treating urinary incontinence after prostatectomy: a phase III multicentre trial.

OBJECTIVE: To evaluate the efficacy and safety of a new adjustable bulbourethral sling (Argus, Promedon SA, Cordoba, Argentina) in the treatment of male stress urinary incontinence (SUI) after prostate surgery. PATIENTS AND METHODS: In all, 48 patients with SUI because of prostatic surgery for prostate cancer (39) or benign prostatic hyperplasia (nine) had a new sling implanted in a multicentre trial at six institutions between April 2003 and September 2004. All patients were fully evaluated, including a questionnaire (International Consultation on Incontinence Questionnaire-Short Form, ICIQ-SF, range 0-21), endoscopy, and urodynamic evaluation. The Argus system comprises a 4.2 x 2.6 x 0.9 cm thick silicone foam pad for soft bulbar urethral compression. The pad is attached to the silicone cone columns that, after being passed with needles from the perineum to the abdominal wall, are adjusted with silicone washers to regulate and keep the desired tension against the urethra. The pad and washers are radio-opaque, which allows their position to be assessed during follow-up. The surgical technique was one described previously, with some modifications. RESULTS: At a mean (range) follow-up of 7.5 (1-17.5) months, 35 (73%) of the 48 patients were dry, five (10%) were improved, and eight (17%) were incontinent, including four (8%) who needed sling adjustment. The mean (range) ICIQ-SF improved from 19.2 (12-21) to 4 (0-21). There were three (6%) urethral perforations during surgery that were resolved by re-passing the needle. The sling was removed in three men (6%) due to erosion and in two (4%) due to infection. Seven (15%) cases of acute urinary retention resolved spontaneously, except for one that needed the sling loosening. No cases of chronic retention were reported. There was perineal discomfort and mild dysuria soon after surgery that resolved spontaneously after a few weeks. CONCLUSION: This new adjustable male sling safely and effectively controls sphincter incontinence in men after prostate surgery, with an acceptably low complication rate. The early results are encouraging; the Argus is a valid alternative to the artificial urinary sphincter, the standard therapy for this condition.

Total and immediate daytime and nighttime continence with a right colonic neobladder--What makes it possible? An 11-year followup.

PURPOSE: We report the long-term functional results of the colonic neobladder and provide the physiological and urodynamic foundations for them. MATERIALS AND METHODS: From March 1993 to February 2004, 38 patients with cystectomy received a neobladder constructed from detubularized, remodeled right colon and intact cecum following our design at the urology service at our institution. Most patients underwent urodynamics and videourodynamics as postoperative followup. We defined total continence as not using any protection whatsoever (neither pads nor a night alarm), which was immediate upon removing the urethral catheter. RESULTS: A total of 37 patients achieved total daytime continence immediately and the remaining 1 was totally continent after 30 days (100%). Nighttime continence was total and immediate in 36 patients (92%) and satisfactory in 2. Micturition was immediate, satisfactory and total in 37 patients with an average maximum flow of more than 26 ml per second. The patient who did not achieve micturition required clean intermittent catheterization. Videourodynamic studies revealed that continence resulted from the low pressure developed in the large capacity reservoir (more than 600 ml) and from intact intestine haustral contractions, which ejected urine toward the detubularized and remodeled area. In turn, micturition was attained through a combination of abdominal wall tension and mass contractions of the nondetubularized segment, which generated a pressure of more than 100 cm. CONCLUSIONS: The functional results of this new neobladder are significantly greater than those achieved with other procedures already described in the literature because of the different way in which it functions.

[Regulatory aspects of disinfection of endoscopes]. / Aspects réglementaires de la désinfection des endoscopes.

The circular on the sterilization and the law of july 1, 1998 enact clearly that the medical devices that support steam sterilization must be sterilized with an organization of sterilization that ensure quality. Endoscope that enter normally sterile tissues should be subjected to a sterilization procedure before each use; if this is not feasible, they should receive high-level disinfection to destroy bacterial spores. The endoscope must be immersed for at least one hour in aqueous solution of 2% glutaraldehyde. This lengthened duration of processing must be integrate in the organization of medical department. The endoscopes not penetrating in a sterile cavity are disinfected with manual processing according to the protocol of the circular of april 1996, or with automated endoscope reprocessing machine. The different types of automated machine used to wash and disinfect endoscope must now answer to criterion concerning their design described in the circular of july 15, 1998. A significant work has to be made in hospitals to conform automated machine and procedure, to control the risk dependent with their use.

Introduction to special section on client-therapy interaction research.

The gap between intuition and research concerning the differential effectiveness of therapies is addressed in the current set of articles. Conceptual and methodological problems common to interactional research are discussed, and alternative research strategies are offered.

Client-treatment interaction in the study of differential change processes.

Research that combines correlational and experimental approaches in a search for aptitude-treatment interactions (ATI) is both inescapable and of potential benefit to the field. A number of epistemological and methodological issues regarding ATI research are discussed, ranging from the meaning of interaction to questions regarding the number of aptitudes and their types and the nature of interacting treatments. Despite the less than encouraging record of ATI research, it should not be abandoned, rather its purposes should be expanded. Instead of focusing on the pragmatic but hard-to-achieve goal of finding an optimal match between individual clients and specific therapies. ATI research should serve heuristic purposes. Theoretically derived and empirically tested interactions can clarify the change processes and mechanisms that make therapies differentially effective. Exploration of another type of interaction is recommended also: aptitude-outcome interaction (AOI), in which ostensibly identical therapies yield different outcomes through different mechanisms for different clients. The emphasis of AOI research is also more heuristic than pragmatic.

Identification of patients at risk for nonresponse and negative outcome in psychotherapy.

This study evaluated the use of pretherapy patient variables as correlates of 3 categorical types of outcome: negative response (negative change of more than 1 normative SEest on depression measure); nonresponse (change within +/- 1 SEest on depression measure); and positive response (positive change of more than 1 SEest on depression measure) to psychotherapy among 62 patients with major depressive disorder. By using 4 scales from the Brief Symptom Inventory, the Inventory of Interpersonal Problems, age, and sex, 75.8% of the Ss were correctly classified into the 3 groups. Negative responders were characterized by high levels of interpersonal difficulty and low levels of subjective distress. Nonresponders displayed moderate levels of both interpersonal difficulties and subjective distress. Positive responders displayed high levels of both interpersonal difficulties and subjective distress.

Interrelating research processes of process research.

Given the contextual boundedness of process variables, 3 assumptions implicit in present process research are questioned: Process variables (a) have fixed meanings, (b) discretely contribute to outcomes, and (c) have a decontextualized net worth, evaluated by their correlations with outcomes. From a systemic perspective, a conceptual framework is suggested that integrates both theory-driven and discovery-oriented strategies into a cyclical, ecologically oriented model. Experiments, observations of change events, and detailed descriptions partake in this cyclical model, informing and enriching each other. The core of this integration is a transactional conception that sees change processes as mutually defining rather than interacting with each other, thus leading to holistic examinations of changes of pattern in addition to patterns of change. The transactional core serves as the point of departure and home base for both theory-driven and discovery-oriented research strategies.

Pharmacokinetics of triamcinolone acetonide and its phosphate ester.

Triamcinolone acetonide in the form of its phosphate ester was given intravenously in two different doses (10 mg/kg and 80 mg). Plasma levels of the ester and triamcinolone acetonide were measured and pharmacokinetic parameters were calculated. The pharmacokinetics both of the phosphate and the free alcohol were dose-dependent. No unchanged ester was found in the urine, indicating complete conversion of the pro-drug. Triamcinolone was not a major metabolite of triamcinolone acetonide in humans. Renal clearance was low and independent of the dose. Only about 1% of the dose was found in the urine as triamcinolone acetonide.