Cystoscopically Guided Repair of a Posterior Perforation of Augmented Bladder.

Background: Augmentation cystoplasty for the management of neurogenic bladder is one of the mainstays of pediatric urology. This procedure has multiple well-known complications. The most dangerous of these complications is bladder perforation, which has a mortality rate of 23% to 25% in large part caused by delayed presentation and sepsis. This case report discusses a novel method for identifying the perforation using endourologic techniques to allow for easier repair. Case Presentation: A 24-year-old woman with a history of spina bifida s/p augmentation cystoplasty with appendicovesicostomy and rectus fascia bladder neck sling 5 years ago presented to the emergency department with a 2-day history of decreased oral intake, nausea, vomiting, fevers, diffuse abdominal pain, and distention. She was found on CT cystogram to have a contrast extravasation from the posterior-dependent portion of the bladder and a large retrovesical fluid collection. On exploratory laparotomy, a leak from the posterior portion of the bladder was confirmed. Owing to the conditions in the abdomen and the patient's obese body habitus, the perforation was very difficult to view. A 17F rigid cystoscope was utilized and the perforation was identified on the posterior inferior portion of the bladder at the anastomotic line. A wire was passed through the perforation into the abdomen where it was seen and an 18F council catheter was then placed in an antegrade manner from the abdomen. Placement of the catheter and inflation of the balloon did not cause any additional apparent damage to the bladder mucosa. With the catheter on traction, the dependent bladder could be pulled back into the operative field, allowing complete observation of the defect for water-tight two-layer closure. Conclusion: Bladder perforation after augmentation cystoplasty is a potentially life-threatening complication that can be difficult to repair. This article serves to present a novel way to identify and facilitate repair of the defect intraoperatively using endourologic principles for a posterior defect.

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

BACKGROUND: The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells. A different protein profile in transport-specialized caveolae may induce pathological changes affecting the integrity of the blood labyrinth barrier and ultimately contributing to hearing loss. METHOD: Caveolae isolation from treated and untreated cells is achieved through ultracentrifugation of the lysates in discontinuous gradients. Mass spectrometry (LC-MS/MS) analysis identifies the proteins in the two groups. Proteins segregating with caveolae isolated from untreated SL pericytes are then compared to caveolae isolated from SL pericytes treated with the gentamicin for 24 h. Data are analyzed using bioinformatic tools. RESULTS: The caveolae proteome in gentamicin treated cells shows that 40% of total proteins are uniquely associated with caveolae during the treatment, and 15% of the proteins normally associated with caveolae in untreated cell are suppressed. Bioinformatic analysis of the data shows a decreased expression of proteins involved in genetic information processing, and an increase in proteins involved in metabolism, vesicular transport and signal transduction in gentamicin treated cells. Several Rab GTPases proteins, ubiquitous transporters, uniquely segregate with caveolae and are significantly enriched in gentamicin treated cells. CONCLUSION: We report that gentamicin exposure modifies protein profile of caveolae from SL pericytes. We identified a pool of proteins which are uniquely segregating with caveolae during the treatment, mainly participating in metabolic and biosynthetic pathways, in transport pathways and in genetic information processing. Finally, we show for the first time proteins associated with caveolae SL pericytes linked to nonsyndromic hearing loss.

Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study

Abstract Background l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2-4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study.

BACKGROUND: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. METHODS: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. RESULTS: Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value=0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2-4), compared to none of the nine children who relapsed who had positive skin tests (p-value<0.001). CONCLUSION: Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

Increased oxidative phosphorylation in response to acute and chronic DNA damage.

Accumulation of DNA damage is intricately linked to aging, aging-related diseases and progeroid syndromes such as Cockayne syndrome (CS). Free radicals from endogenous oxidative energy metabolism can damage DNA, however the potential of acute or chronic DNA damage to modulate cellular and/or organismal energy metabolism remains largely unexplored. We modeled chronic endogenous genotoxic stress using a DNA repair-deficient Csa-/-|Xpa-/- mouse model of CS. Exogenous genotoxic stress was modeled in mice in vivo and primary cells in vitro treated with different genotoxins giving rise to diverse spectrums of lesions, including ultraviolet radiation, intrastrand crosslinking agents and ionizing radiation. Both chronic endogenous and acute exogenous genotoxic stress increased mitochondrial fatty acid oxidation (FAO) on the organismal level, manifested by increased oxygen consumption, reduced respiratory exchange ratio, progressive adipose loss and increased FAO in tissues ex vivo. In multiple primary cell types, the metabolic response to different genotoxins manifested as a cell-autonomous increase in oxidative phosphorylation (OXPHOS) subsequent to a transient decline in steady-state NAD+ and ATP levels, and required the DNA damage sensor PARP-1 and energy-sensing kinase AMPK. We conclude that increased FAO/OXPHOS is a general, beneficial, adaptive response to DNA damage on cellular and organismal levels, illustrating a fundamental link between genotoxic stress and energy metabolism driven by the energetic cost of DNA damage. Our study points to therapeutic opportunities to mitigate detrimental effects of DNA damage on primary cells in the context of radio/chemotherapy or progeroid syndromes.

A patient with a unique frameshift mutation in GPC3, causing Simpson-Golabi-Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle.

We present a Hispanic male with the clinical and molecular diagnosis of Simpson-Golabi-Behmel syndrome (SGBS). The patient was born with multiple anomalies not entirely typical of SGBS patients, including penoscrotal hypospadias, a large prostatic utricle, and left coronal craniosynostosis. In addition, he demonstrated endocrine anomalies including a low random cortisol level suspicious for adrenal insufficiency and low testosterone level. To our knowledge, this is the first report of a prostatic utricle in SGBS and the second report of craniosynostosis. The unique disease-causing mutation likely arose de novo in the mother. It is a deletion-insertion that leads to a frameshift at the p.p. S359 [corrected] residue of GPC3 and a premature stop codon after five more amino acids. p. S359 [corrected] is the same residue that is normally cleaved by the Furin convertase, although the significance of this novel mutation with respect to the patient's multiple anomalies is unknown. We present this case as the perinatal course of a patient with unique features of SGBS and a confirmed molecular diagnosis.

Outcomes of and satisfaction with the inflatable penile prosthesis in the elderly male.

Objective. To determine the outcomes of and satisfaction with the multi-component inflatable penile prosthesis (IPP) in the elderly male (age >71). Methods. Using a chart review and telephone survey, we retrospectively assessed patients who underwent IPP or combined IPP/artificial urinary sphincter (AUS) from 2004-2006. Results. We identified 56 patients that underwent IPP (48) or IPP/AUS (8). The age range was 71-86 (mean 74.3) at the time of surgery, with a follow-up range of 0.5-2.4 years (mean 1.5). The overall complication rate was 3.8% (2 of 56) with one device removed for infection and a second patient requiring exploration for a postoperative hematoma. The telephone interview was conducted with 35 of 56 patients. Patients rated ease of use (a scale from 1-5, 5 meaning very easy) and overall satisfaction (a scale of 1-5, 5 meaning very satisfied) at an average of 4.1 and 4.3, respectively. IPP usage varied from 0-7 times per month (mean 3.3). 32 of 35 patients (91%) said they would undergo the procedure again. Conclusion. Our review demonstrates that the IPP is well tolerated in the elderly male population, who report a high degree of satisfaction and ease of use with this device.

Effect of combining anti-epidermal growth factor receptor antibody C225 and radiation on DU145 prostate cancer.

The epidermal growth factor receptor (EGFR) network has rich targets for prostate cancer killing. Herein we evaluated the effects of combining the EGFR inhibition and radiation on DU145 prostate cancer. We treated DU145 prostate cancer cells with various doses of anti-EGFR antibody (C225) and gamma-irradiation (RAD). The effects of the treatment on cell viability and growth were assessed with cell counting, XTT and clonogenic assays. In vivo treatment effects were assessed using a subcutaneous tumor xenograft in mice. Cell cycle distribution and progression were assessed with flow cytometry. The apoptotic components of cell death were quantified using Annexin-V binding assays. The results demonstrated that when combined with radiation, C225 augmented the inhibition of cell viability and growth in the DU145 cell line and EGFR inhibition appeared to have some interaction with RAD. C225 inhibited the growth of implanted DU145 tumors and increased the efficacy of radiation treatment. Flow cytometric analysis suggested that mostly necrotic cell death resulted from the EGFR inhibition or irradiation, although there may be some apoptosis. We drew the conclusion that the inhibition of EGFR augments the radiation killing of DU145 prostate cancer via a combination of cytostatic, necrotic and apoptotic mechanisms.

Effect of temperature on lipids, proteins, and carbohydrates levels during development from egg extrusion to juvenile stage of Cherax quadricarinatus (Decapoda: Parastacidae).

The influence of temperature on biochemical composition, survival and duration of development of Cherax quadricarinatus from egg extrusion to juvenile was analyzed. Berried females were individually subjected to each of 22, 25, 28 and 31 degrees C (n=5 per temperature). Egg samples were obtained every 3 days from egg extrusion to juvenile stage for biochemical analysis. Duration of development and survival decreased with increasing temperature. At 22 and 25 degrees C half of the initial lipid content was consumed during development. At 28 and 31 degrees C, 80% of the initial amount of lipids was consumed. For proteins, depletion rate was significantly lower at 25 degrees C (36% of the initial amount) than at 22, 28 and 31 degrees C (61-65% of the initial amount). For carbohydrates, a significant consumption was observed only at 22 degrees C. Total energy consumption was lower at 22 and 25 degrees C than at 28 and 31 degrees C. We conclude that 22-25 degrees C is the optimal temperature range for C. quadricarinatus egg incubation, although 25 degrees C might be better in terms of development duration in terms of survival, energy cost and protein consumption.