Microbial Transfer by Intermittent Catheters: An In Vitro Evaluation of Microbial Transfer in Catheter With Variable Protective Features.

PURPOSE: The purpose of this study was to evaluate the effects of various protective features (eg, catheter cap, introducer tip, and catheter sleeve) of hydrophilic intermittent catheters against contamination with urinary tract infection-associated microorganisms using an in vitro model. DESIGN: An in vitro study of microbial transfer. MATERIALS AND METHODS: Gloves were contaminated with uropathogenic microorganisms and used to simulate intermittent catheterization of male anatomical models with and without the protective features present in 5 commercially available hydrophilic catheters. Using this contaminated touch transfer method, both the meatus of the sterile male anatomical models and sterile surgical gloves of an operator were inoculated with a high level of microorganisms (107 and 109 colony-forming units [CFU], respectively). The operator then performed catheterization of the anatomical model. The most relevant segments of the catheter were sampled, and the level of microbial transfer and catheter contamination was quantified. Results from experimental and sample replicates from the 3 microbial species and 5 catheters (sleeved and unsleeved) were analyzed by pair-wise t tests and analysis of variance. RESULTS: Of the 5 commercially available sleeved intermittent catheters evaluated in this study, use of catheters with multiple protective components (ring cap, introducer tip, and catheter sleeve) resulted in significant improvement in protection against contamination with a 25- to 2500-fold lower level of microbial contamination (C1 segment) across all species as compared to catheters protected with only sleeves or un-sleeved catheters. CONCLUSIONS: The combination of a ring cap, protective introducer tip, and protective sleeve provides additional protection when compared to sleeve alone from transferring microbial contamination from the meatus to the advancing catheter. Additional research is needed to determine whether these design features result in fewer urinary tract infections among intermittent catheter users.

Evolving Evidence Supporting Use of Rectal Irrigation in the Management of Bowel Dysfunction: An Integrative Literature Review.

Disorders of bowel function are prevalent, particularly among patients with spinal cord injuries and other neurological disorders. An individual's bowel control significantly impacts quality of life, as predictable bowel function is necessary to actively and independently participate in everyday activities. For many patients with bowel dysfunction, initial lifestyle adjustments and other conservative therapeutic interventions (eg, digital stimulation, oral laxatives, suppositories) are insufficient to reestablish regular bowel function. In addition to these options, rectal irrigation (RI) is a safe and effective method of standard bowel care that has been used for several decades in adults and children suffering from bowel dysfunction associated with neurogenic or functional bowel etiologies. Rectal irrigation is an appropriate option when conservative bowel treatments are inadequate. Unlike surgical options, RI can be initiated or discontinued at any time. This report summarizes the clinical, humanistic, and economic evidence supporting the use of RI in clinical practice, noting features (eg, practical considerations, patient education) that can improve patients' success with RI treatment.

Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells.

One of the characteristic features of cells from patients with ataxia telangiectasia (A-T) is that they are in a state of continuous oxidative stress and exhibit constitutive activation of pathways that normally respond to oxidative damage. In this report, we investigated whether the oxidative stress phenotype of A-T cells might be a reflection of an intrinsic mitochondrial dysfunction. Mitotracker Red staining showed that the structural organization of mitochondria in A-T cells was abnormal compared to wild-type. Moreover, A-T cells harbored a much larger population of mitochondria with decreased membrane potential (DeltaPsi) than control cells. In addition, the basal expression levels of several nuclear DNA-encoded oxidative damage responsive genes whose proteins are targeted to the mitochondria--polymerase gamma, mitochondrial topoisomerase I, peroxiredoxin 3 and manganese superoxide dismutase--are elevated in A-T cells. Consistent with these results, we found that overall mitochondrial respiratory activity was diminished in A-T compared to wild-type cells. Treating A-T cells with the antioxidant, alpha lipoic acid (ALA), restored mitochondrial respiration rates to levels approaching those of wild-type. When wild-type cells were transfected with ATM-targeted siRNA, we observed a small but significant reduction in the respiration rates of mitochondria. Moreover, mitochondria in A-T cells induced to stably express full-length ATM, exhibited respiration rates approaching those of wild-type cells. Taken together, our results provide evidence for an intrinsic mitochondrial dysfunction in A-T cells, and implicate a requirement for ATM in the regulation of mitochondrial function.

Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.

Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is insufficient to render ATM an active kinase towards downstream substrates, including p53.