Evaluation of 3 Methods of Bladder Irrigation to Treat Bacteriuria in Persons With Neurogenic Bladder

Abstract

Background/Objective: We conducted a randomized, double-blind comparison of twice daily bladder irrigation using 1 of 3 different solutions in community-residing persons with neurogenic bladder who used indwelling catheters to evaluate efficacy in treatment of bacteriuria.

Methods: Eighty-nine persons with bacteriuria were randomized to irrigate their bladders twice daily for 8 weeks with 30 mL of (a) sterile saline, (b) acetic acid, or (c) neomycin-polymyxin solution. Urinalysis, cultures, and antimicrobial susceptibility tests were performed at baseline and weeks 2, 4, and 8 to determine the extent to which each of the solutions affected numbers and types of bacteria, urinary pH, urinary leukocytes, and generation of antimicrobial-resistant organisms.

Results: Bladder irrigation was well tolerated with the exception of 3 participants who had bladder spasms. None of the 3 irrigants had a detectable effect on the degree of bacteriuria or pyuria in 52 persons who completed the study protocol. A significant increase in urinary pH occurred in all 3 groups. No significant development of resistance to oral antimicrobials beyond what was observed at baseline was detected.

Conclusions: Bladder irrigation was generally well tolerated for 8 weeks. No advantages were detected for neomycin-polymyxin or acetic acid over saline in terms of reducing the urinary bacterial load and inflammation. We cannot recommend bladder irrigation as a means of treatment for bacteriuria in persons with neurogenic bladder.     

Cell Therapy for Parkinson's Disease: A Translational Approach to Assess the Role of Local and Systemic Immunosuppression

Neural transplantation is a promising therapeutic approach for neurodegenerative diseases; however, many patients receiving intracerebral fetal allografts exhibit signs of immunization to donor antigens that could compromise the graft. In this context, we intracerebrally transplanted mesencephalic pig xenografts into primates to identify a suitable strategy to enable long‐term cell survival, maturation, and differentiation. Parkinsonian primates received WT or CTLA4‐Ig transgenic porcine xenografts and different durations of peripheral immunosuppression to test whether systemic plus graft‐mediated local immunosuppression might avoid rejection. A striking recovery of spontaneous locomotion was observed in primates receiving systemic plus local immunosuppression for 6 mo. Recovery was associated with restoration of dopaminergic activity detected both by positron emission tomography imaging and histological examination. Local infiltration by T cells and CD80/86+ microglial cells expressing indoleamine 2,3‐dioxigenase were observed only in CTLA4‐Ig recipients. Results suggest that in this primate neurotransplantation model, peripheral immunosuppression is indispensable to achieve the long‐term survival of porcine neuronal xenografts that is required to study the beneficial immunomodulatory effect of local blockade of T cell costimulation.     

Quantitative analysis of estrogen receptor heterogeneity in breast cancer

Immunohistochemical analyses (IHC) of biomarkers are extensively used for tumor characterization and as prognostic and predictive measures. The current standard of single slide analysis assumes that one 5 microM section is representative of the entire tumor. We used our automated image analysis technology (AQUA) using a modified IHC technique with fluorophores to compare estrogen receptor (ER) expression in multiple blocks/slides from cases of primary breast cancer with the objective of quantifying tumor heterogeneity within sections and between blocks. To normalize our ER scores and allow slide-to-slide comparisons, 0.6 microm histospots of representative breast cancer cases with known ER scores were assembled into a 'gold standard array' (GSA) and placed adjacently to each whole section. Overall, there was excellent correlation between AQUA scores and the pathologist's scores and reproducibility of GSA scores (mean linear regression R value 0.8903). Twenty-nine slides from 11 surgical cases were then analyzed totaling over 2000 AQUA images. Using standard binary assignments of AQUA (>10) and pathologist's (>10%) scores as being positive, there was fair concordancy between AQUA and pathologist scores (73%) and between slides from different blocks from the same cases (75%). However using continuous AQUA scores, agreement between AQUA and pathologist was far lower and between slides from different blocks from the same cases only 19%. Within individual slides there was also significant heterogeneity in a scattered pattern, most notably for slides with the highest AQUA scores. In sum, using a quantitative measure of ER expression, significant block-to-block heterogeneity was found in 81% of cases. These results most likely reflect both laboratory-based variability due to lack of standardization of immunohistochemistry and true biological heterogeneity. It is also likely to be dependent on the biomarker analyzed and suggests further studies should be carried out to determine how these findings may affect clinical decision-making processes.     

Fetal alcohol exposure impairs Hedgehog cholesterol modification and signaling

Consumption of alcohol by pregnant women can cause fetal alcohol spectrum defects (FASD), a congenital disease, which is characterized by an array of developmental defects that include neurological, craniofacial, cardiac, and limb malformations, as well as generalized growth retardation. FASD remains a significant clinical challenge and an important social problem. Although there has been great progress in delineating the mechanisms contributing to alcohol-induced birth defects, gaps in our knowledge still remain; for instance, why does alcohol preferentially induce a spectrum of defects in specific organs and why is the spectrum of defects reproducible and predictable. In this study, we show that exposure of zebrafish embryos to low levels of alcohol during gastrulation blocks covalent modification of Sonic hedgehog by cholesterol. This leads to impaired Hh signal transduction and results in a dose-dependent spectrum of permanent developmental defects that closely resemble FASD. Furthermore, supplementing alcohol-exposed embryos with cholesterol rescues the loss of Shh signal transduction, and prevents embryos from developing FASD-like morphologic defects. Overall, we have shown that a simple post-translational modification defect in a key morphogen may contribute to an environmentally induced complex congenital syndrome. This insight into FASD pathogenesis may suggest novel strategies for preventing these common congenital defects.     

Health status, sociodemographic factors, and the use of prescribed psychotropic drugs

The relations among sociodemographic factors, health status, and use of prescribed sleeping pills and tranquilizers are examined. The data are from the Rand Health Insurance Experiment, which has a random sample of the nonaged, noninstitutionalized, civilian population in six U.S. sites. Information on sociodemographic factors, health status, and the use of prescribed psychotropic drugs during the previous 3 months was obtained from self-report questionnaires collected at enrollment. Mental and physical health status have large independent and significant effects on the probability of use of both prescribed tranquilizers (P less than 0.0001) and sleeping pills (P less than 0.0001), whether or not we remove the effects of sociodemographic factors. For the probability of tranquilizer use, there is no significant interaction between gender and mental health or between mental health and physical health. Age and gender have large and significant effects on the use of prescribed psychotropic drugs even after controlling for differences in health status and other demographic factors. The effects of site and socioeconomic status are modest compared with the effects of health, age, and gender.     

Management of Positive Sub‐areolar/Nipple Duct Margins in Nipple‐Sparing Mastectomies

We evaluated management of positive sub‐areolar/nipple duct margins in nipple‐sparing mastectomies (NSM) at our institution. Retrospective chart review of all NSM from January 2007 to April 2012 was performed and patient, tumor, and treatment information was collected. Sub‐areolar/nipple duct margins included ductal tissue from within the nipple. Of 438 NSM, 22 (5%) had positive sub‐areolar/nipple duct margins; 21 of 220 cancer‐bearing breasts (10%) and 1 of 218 prophylactic mastectomies (0.5%). Positive margins included four with invasive lobular carcinoma and 18 with ductal carcinoma in situ (DCIS). Management included removal of eight nipples and nine nipple areola complexes (NAC). Four of 17 nipple/NAC specimens had evidence of residual DCIS and none had residual invasive cancer. The majority of nipple/NAC specimens excised for a positive margin had no residual malignancy. Future studies are needed to determine the extent of NAC tissue removal required for positive margins.     

The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. © 1996 Wiley-Liss, Inc.