Exit site

Catheter malfunction, and exit site and tunnel infection. 

Pharmacologic management of infections should cover the gram-positive organisms that most frequently cause access-related infections. Patients who have positive blood cultures should receive treatment tailored to the organism isolated. Preventive measures for access-related infections include mupirocin at the exit site and povidone-iodine ointment. The recommendations of the NKF for treatment of infections associated with hemodialysis are listed in Table 23-9. 

Infection localized to catheter exit site Bacteremia with or without systemic signs or symptoms... 

Catheter adherence to peritoneal tissue Excessive movement of catheter at exit site Peritoneal Damage... 

Peritonitis Exit-site infections Tunnel infections... 

Catheter-related infections generally occur at the exit site or the portion of the catheter that is tunneled in the subcutaneous tissue. Previous infections increase the risk and incidence of catheter-related infections. 

Exit-site infections present with purulent drainage at the site. Erythema may or may not be present with an exit-site infection. Tunnel infections are generally an extension of the exit-site infection and rarely occur alone. Symptoms of a tunnel infection may include tenderness, edema, and erythema over the tunnel pathway, but are often asymptomatic. Ultrasound can be used to detect tunnel infections in asymptomatic patients. Exit-site infections caused by S. aureus and P. aeruginosa often spread to tunnel infections and are the most common causes of catheter-infection-related peritonitis. 

Treatment Exit-site infections may be treated immediately with empiric coverage, or treatment may be delayed until cultures return. Empiric treatment of catheter-related infections should cover S. aureus. Coverage for P. aeruginosa should also be included if the patient has a history of infections with this organism.49 Cultures and sensitivity testing are particularly important in tailoring antibiotic therapy for catheter-related infections to ensure eradication of the organism and prevent recurrence or related peritonitis. 

Prevention of peritonitis and catheter-related infections starts when the catheter is placed. The exit site should be properly cared for until it is well healed before it can be used for PD. Patients should receive proper instructions for care of the catheter during this time period, which can last up to 2 weeks. Patients should also be instructed on the proper techniques to use for dialysate exchanges to minimize the risk of infections during exchanges, which is the most common cause of peritonitis. 

Intranasal S. aureus increases the risk of S. aureus exit-site infections, tunnel infections, peritonitis, and subsequent catheter loss.49 Several measures have been used to decrease the risk of peritonitis caused by S. aureus, including mupirocin cream applied daily around the exit site, intranasal mupirocin cream twice daily for 5 days each month, or rifampin 300 mg orally twice daily for 5 days, repeated every 3 months.49 Mupirocin use is preferred over rifampin to prevent the development of resistance to rifampin, although mupirocin resistance has also been reported.49 Other measures that have been used to decrease both S. aureus and P. aeruginosa infections include gentamicin cream applied twice daily and ciprofloxacin otic solution applied daily to the exit site.49... 

Clinical improvement should be seen within 48 hours of initiating treatment for peritonitis or catheter-related infections. Perform daily inspections of peritoneal fluid or the exit site to determine clinical improvement. Peritoneal fluid should become clear with improvement of peritonitis and erythema and discharge should remit with improvement of catheter-related infections. If no improvement is seen within 48 hours, obtain additional cultures and cell counts to determine the appropriate alterations in therapy. 

Endoscopic and surgical feeding tubes can be complicated by erosion of the exit site caused by leakage of gastric or intestinal contents onto the skin. This complication must be... 

Moreover, efficient rhodopsin regeneration may precede enzymatic reduction of all-fran.v-retinal to all-trans-retinol in the aged retina (Figure 15.2c) (Schadel et al., 2003). Upon rhodopsin regeneration, all-trans-retinal is released from the exit site of the protein into the lipid membrane (Figure 15.2c) (Schadel et al., 2003). From here the removal of all-tnms-retinal to the outer leaflet of the disc membrane is dependent on activity of ATP-binding cassette trasporter A4 (ABCA4) present in the rim of photoreceptor disc, known also as ABCR protein. 

Within the nucleosome, addition of ubiquitin to H2A occurs near the entry and exit sites of DNA and the binding site of HI [203]. Therefore, this post-translational modification is expected to have implications for both the stability of the particle and higher order structure of chromatin [45,203]. The C-terminal end of H2B and its ubiquitination site on the other hand is located at the opposite side of the nucleosome [45]. Incorporation of an ubiquitin adduct into the nucleosome at this site may have significant implications for the trajectory of the DNA and the integrity of the particle. In this regard there have been multiple biochemical results substantiating a role of H2B ubiquitination in transcriptional activation [207-210]. 

The principles whereby a chain of nueleosomes can compact to form a 30 nm chromatin fiber are still not well understood. Nevertheless, important aspects of this process are becoming clear from imaging studies, employing both ECM and SFM. When isolated chicken erythrocyte chromatin or chromatin reconstituted onto six tandem 208 bp nucleosome positioning units were examined by ECM, a linker DNA stem-like architectural motif was observed at the entry-exit sites (Fig. 4) [30]. Particles consistent with an octamer are surrounded with 1.7 turns of DNA, a linker... 

The model of Fig. IB is taken from a review by van Holde et al. [3] which I refer to as the disruptive model. In this model the polymerase causes conditions (step A) which promote not only the displacement of the entry site H2A, H2B dimer from DNA, but also from the H3, H4 tetramer (step B). As a result of this disruption, the polymerase is free to transcribe through the tetramer alone without a general displacement from its associated DNA (step C). The H2A, H2B dimer is now free to reassociate to the vacated entry site (step D) to re-establish contacts with both the DNA and the H3, H4 tetramer. As transcription proceeds into the exit site H2A, H2B dimer, these proteins are now displaced from both the DNA and the H3, H4 tetramer in a similar manner as the entry site H2A, H2B dimer (step E). A positive feature with regard to this model is that by displacement of H2A, H2B, the polymerase is able to transcribe the DNA with half the histones displaced prior to transcription. Therefore both models, spooling and disruptive , describe mechanisms which would favorably enhance the process of transcription. Support for the disruptive model comes from the substantial in vivo information which suggests that nucleosomes undergo substantial disruption during transcription, as was described in the previous section. Of particular note are those observations which indicate that a discrete population of H2A, H2B... 

In the 70 S initiation complex, formylme-thionine tRNA is initially located at a binding site known as the peptidyl site (P). A second binding site, the acceptor site (A), is not yet occupied during this phase of translation. Sometimes, a third tRNA binding site is defined as an exit site (E), from which uncharged tRNAs leave the ribosome again (see p. 252 not shown). 

Ban et al 7 Courtesy of T. A. Steitz. The peptidyltransferase center is marked by the green image of the transition state inhibitor shown in Fig. 29-13. (F) Model of three tRNAs bound to a ribosome from Thermus thermophilus in the A (a mi noacyl), P (pepti-dyl), and E (exit) sites. These are based on 0.75-nm X-ray data and a number of difference electron density maps. The 3-CCA end of the A-site tRNA is not modeled hut is... 

Elongation factor EF-G and translocation. The third step in the elongation sequence on ribosomes (Fig. 29-12, step g) depends upon EF-G, a monomeric GTP-binding protein with a sequence homologous with that of other members of the G protein family. It apparently utilizes the Gibbs energy of hydrolysis of GTP to GDP to drive translocation of the peptidyl-tRNA from the A site to the P site (Fig. 29-12) and of the previously utilized (de-acylated) tRNA to the exit site. 

A third elongation factor, eEF3, which is an ATPase, is required by yeast and fungi.408-410 The 1044-residue yeast protein may be required for ATP-dependent release of deacylated tRNA from the exit site. 

Fig. 2. Schematic of a prokaryotic 70S ribosome showing the peptidyl-tRNA site (P site), aminoacyl-tRNA site (A site) and exit site (E site).

Peden AA, Oorschot V, Hesser BA, Austin CD, Scheller RH, et al. 2004. Localization of the AP-3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins. J Cell Biol 164 1065-1076. 

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