Quality of life in stoma patients: appropriate and inappropriate stoma sites.

BACKGROUND: The objective of the cross-sectional study reported here was to compare the quality of life of patients with an appropriate stoma site and with that of patients with an inappropriate stoma site. MATERIALS AND METHODS: Two groups of patients with permanent intestinal stomas were assessed, 174 patients with appropriate stoma sites and 174 patients with inappropriate stoma sites. We used the EORTC QLQ-C30 and the EORTC QLQ-CR38, which evaluate 26 quality of life (QoL) scales. Data analysis was performed with SPSS software. RESULTS: From a total of 9 functional scales, 3 scales in patients with an appropriate stoma site were significantly higher than in patients with an inappropriate stoma site: sexual enjoyment (71.2% vs. 63.2%; p = 0.02), physical functioning (74.3% vs. 68.2%; p = 0.005), and role functioning (74.3% vs. 64.4%; p < 0.0001). From the total of 16 symptom scales, patients with an inappropriate stoma site had significantly more problems than patients with an appropriate stoma site in 8 scales: micturation (27% vs. 22.5%; p = 0.04), gastrointestinal problems (32.6% vs. 27%; p = 0.01), weight loss (36.5% vs. 29.2%; p = 0.03), dyspnea (25.95% vs. 12.5%; p = 0.0001), pain (39.3% vs. 29.6%; p = 0.001), fatigue (43.5% vs. 34.5%; p < 0.0001), nausea and vomiting (18.15% vs. 12.8%; p = 0.03), and insomnia (39.8% vs. 31.1%; p = 0.01). Patients with an appropriate stoma site scored global QoL significantly higher than those with an inappropriate stoma site (56.2% vs. 49.7%; p = 0.007) CONCLUSIONS: A perfectly placed intestinal stoma is strongly related to good QoL for affected patients. From the total of 26 QoL scales assessed in the study, patients with appropriate stoma sites achieved better results in at least 50% of the scales.

L-selectin shedding is independent of its subsurface structures and topographic distribution.

L-selectin (CD62L), a lectin-like adhesion molecule, mediates lymphocyte homing and leukocyte accumulation at sites of inflammation. Its transmembrane (TM) and intracellular (IC) domains confer clustering of L-selectin on microvilli of resting leukocytes, which is important for L-selectin function. Following activation of protein kinase C (PKC) or calmodulin inhibition, the wild-type (WT) protein is rapidly cleaved in its membrane-proximal ectodomain. To examine whether L-selectin topography or TM/IC domains are involved in this shedding process, we used stable transfectants expressing WT L-selectin (on microvilli) or chimeric molecules consisting of the L-selectin ectodomain linked to the TM/IC domains of CD44 (excluded from microvilli) or CD31 (randomly distributed). PKC activation by PMA altered the cells' surface morphology, but did not induce a redistribution of L-selectin ectodomains. All cell lines shed ectodomains upon PMA activation in a dose-dependent fashion and with similar kinetics. Calmodulin inhibition by trifluoperazine induced shedding in both WT and chimera transfectants. At high trifluoperazine concentrations, shedding of WT L-selectin was significantly more pronounced than that of chimeric molecules. Regardless of the activating stimulus, shedding was blocked by a hydroxamate-based metalloprotease inhibitor, suggesting that ectodomain down-regulation occurred through proteolytic cleavage by identical protease(s). These results show that the recognition site(s) for PKC-induced L-selectin shedding is exclusively contained within the ectodomain; the nature of subsurface structures and surface topography are irrelevant. Shedding induced by calmodulin inhibition has two components: one requires the L-selectin TM/IC domain, and the other is independent of it.

BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis.

Leukotriene B(4) (LTB(4)) is a potent chemoattractant active on multiple leukocytes, including neutrophils, macrophages, and eosinophils, and is implicated in the pathogenesis of a variety of inflammatory processes. A seven transmembrane-spanning, G protein-coupled receptor, called BLTR (LTB(4) receptor), has recently been identified as an LTB(4) receptor. To determine if BLTR is the sole receptor mediating LTB(4)-induced leukocyte activation and to determine the role of LTB(4) and BLTR in regulating leukocyte function in inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene disruption. This mouse reveals that BLTR alone is responsible for LTB(4)-mediated leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoattractant-receptor pairs in vitro, LTB(4) and BLTR play an important role in the recruitment and/or retention of leukocytes, particularly eosinophils, to the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key receptor that mediates LTB(4)-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB(4) in vivo.

Ultracentrifugation and concentration of a large volume of serum for HCV RNA during treatment may predict sustained and relapse response in chronic HCV infection.

The ability to predict accurately a sustained response during therapy in patients with hepatitis C virus (HCV) infection is unavailable. The aim of this study was to differentiate, during therapy, patients who would relapse from those with a sustained response by ultracentrifugation for residual serum HCV RNA. Sixty-one specimens (from 32 patients) collected during interferon therapy were assessed by ultracentrifugation. All were negative using a quantitative polymerase chain reaction (PCR) (detection limit < or = 100 copies/ml). One-milliliter aliquots were ultracentrifuged at 23,000 x g (160 min), and then the nucleic acid pellet was extracted, precipitated, and resuspended. Qualitative PCR was carried out in quadruplicate using two separate 5'UTR primer sets (8 results/specimen). A specimen was positive if > or = 1 gels was positive compared to controls. At weeks 12 and 24, 9/9 (100%) sustained response patients were negative by ultracentrifugation. In the 23 relapse patients at week 12, 7/12 specimens were positive; at week 24, 7/14 were positive. Earlier time points could not differentiate the patients' eventual response to therapy. The predictive value of a positive ultracentrifugation test for relapse at week 12 or 24 was 100%. The predictive value of a negative test for sustained response was 62% and 50% at week 12 and 24, respectively. These preliminary results indicate that patients with an eventual sustained response will have no detectable serum HCV RNA by week 12 or week 24. A positive result is 100% predictive of relapse.