Glucose degradation products (GDP) retard remesothelialization independently of D-glucose concentration.

BACKGROUND: Glucose degradation products (GDP) present in heat-sterilized dialysis fluids are thought to contribute to cellular dysfunction and membrane damage during peritoneal dialysis. To examine the effects of specific GDP on the remesothelialization process, the impact of conventional and low GDP peritoneal dialysis solutions, D-glucose, and individual GDP in a scratch-wounding model was assessed. METHODS: Scratch (0.5 to 0.6 mm)-wounded human peritoneal mesothelial cells (HPMC) were treated, at pH 7.4, with either (1) control medium (M199), (2) laboratory-prepared heat or filter-sterilized solutions, (3) 10% to 80% vol/vol solution of Gambrosol or Gambrosol-trio (1.5% and 4.0% glucose), (4) D-glucose (5 to 80 mmol/L), or (5) individual or combined GDP [acetaldehyde, formaldehyde, glyoxal, methylglyoxal, 3-deoxyglucosone (3-DG), 5-hydroxy methylfufural (5-HMF), or 3,4-di-deoxyglucosone-3-ene (3,4-DGE)]. Wound closure was recorded by time-lapse photomicroscopy. RESULTS: In untreated HPMC, the rate of wound closure was linear and the process was complete by 18.4 +/- 3.6 hours (N = 16). In wounded HPMC exposed to dilutions of heat-sterilized but not filtered laboratory solutions (1.5% or 4.0% glucose, pH 7.4), remesothelialization was significantly retarded (P = 0.04 and P = 0.009 vs. M199, respectively). In Gambrosol, remesothelialization was significantly retarded in both 1.5% and 4.0% solutions. In contrast in Gambrosol-trio-treated HPMC, this rate was not significantly reduced in either 1.5% or 4.0% glucose peritoneal dialysis fluids. Remesothelialization was dose-dependently retarded in HPMC exposed to 3,4-DGE (>10 microl/L), formaldehyde (>5 micromol/L) but not by exposure to the other GDP tested even at 5 times the concentration present in low glucose solutions. The rate of remesothelialization was not significantly altered by exposure to D-glucose concentrations up to 80 mmol/L. CONCLUSION: These data identify that the formaldehyde and 3,4-DGE present in heat-sterilized peritoneal dialysis solutions are important in reducing mesothelial cell regeneration. Specifically targeting their removal may have major benefits in preserving the mesothelium during long-term peritoneal dialysis.

Acute sinusitis. Who should we be treating?

BACKGROUND: The diagnosis of acute sinusitis has been regarded as a serious condition that requires the use of antibiotics. However the increasing incidence of resistant organisms means antibiotics need to be used carefully. OBJECTIVE: To look at the evidence available regarding antibiotic use for sinusitis, and to discuss its application to general practice. DISCUSSION: There have been surprisingly few randomised double blind placebo controlled trials for sinusitis, and fewer still have been based in a representative population of primary care patients. This article discusses studies relevant to general practice. Several practical clinical symptoms and signs have been shown to increase the likelihood of a patient having acute bacterial sinusitis, and therefore benefit from antibiotics. When antibiotics are used, comparative data suggest that amoxycillin should be used first line. The issue of patient experience, expectations and satisfaction is also raised.

Evaluation of a cancer pain education program for general practitioners.

OBJECTIVE: To evaluate a cancer pain education program. METHOD: Participants in the program completed an evaluation form covering various aspects of the program's design. RESULTS: All participants who completed the program were glad that they had done so. The most and least useful aspects are included in the article. Participants were satisfied with the program and eager to participate in similar ones. CONCLUSION: The education program was both successful at improving participants' knowledge of cancer pain management and provided in a manner acceptable to the participants. Ideas for future similar projects are included.

Cancer pain management. Improving knowledge and patient care.

OBJECTIVE: A pain management project was designed to assess the effectiveness of a multifaceted intervention for improving GPs' knowledge of cancer pain management. Two hypotheses were tested: that the intervention would influence GPs' knowledge in the area of cancer pain management; that information would be gathered to assist in the production of educational material. METHOD: The project involved assessment of GP knowledge, feedback and discussion at project officer visits, mailings and participation in developing guidelines. RESULTS: All participants who completed the second round of visits were glad they had participated in the program. A discussion of the information topics covered is included. CONCLUSION: Increasing GPs' knowledge of the management of symptoms is only one of many factors that influence their prescribing patterns. In cancer pain management lack of knowledge is a significant contributor to unnecessary patient suffering. We have been able to demonstrate the success of a multifaceted intervention in improving the knowledge of cancer pain management by GPs. Although not measured directly, it is hoped that this will lead to improved quality of life for patients cared for by these practitioners.

Human peritoneal fibroblast proliferation in 3-dimensional culture: modulation by cytokines, growth factors and peritoneal dialysis effluent.

Structural and functional alterations of the peritoneal membrane are a significant problem in long-term peritoneal dialysis patients. The present study has established a 3-dimensional (3D) cell culture system to study the human peritoneal fibroblast (HPFB) and to examine its proliferative responses to cytokines and growth factors as well as dialysis effluent obtained from patients during peritoneal infection. PDGF-AB, basic FGF and IL-1 beta induced a time and dose dependent increase in 3D-HPFB proliferation. At day 9 proliferation, as assessed by MTT uptake, was increased by 2.4-, 2.3- and 1.5-fold above control by PDGF-AB (50 ng/ml), bFGF (50 ng/ml) and IL-1 beta (10 ng/ml), respectively (N = 5, P = 0.04 for all). These effects could be inhibited by co-incubation with anti-PDGF-AB antibody, anti-bFGF or IL-1ra, respectively. Exposure of 3D-HPFB to TGF-beta 1 did not result in an increase in cell proliferation. Incubation of 3D-HPFB with peritoneal macrophage (PMø) or human peritoneal mesothelial cell (HPMC) conditioned medium also resulted in a time and dose dependent increase in proliferation. At day 9, proliferation was maximally increase 1.65- and 1.92-fold by peritoneal macrophage- and mesothelial cell-conditioned medium, respectively. Cell free PDE, obtained from CAPD patients during episodes of peritonitis, induced 3D-HPFB proliferation above control values (2- to 6.5-fold increases, N = 5, P < 0.05 for all). This mitogenic potential of PDE was reduced following dilution, and with time following peritonitis there was a gradual decrease in the mitogenic effect of PDE. The proliferative potential of PDE was significantly reduced following co-incubation with IL-1ra (45.7% inhibition), anti-bFGF (34.9% inhibition) and anti PDGF-AB (27.4% inhibition). These data indicate that infected PDE causes fibroblast hyperplasia which might potentially contribute to pro-fibrotic processes during CAPD.

In vitro testing of a potentially biocompatible continuous ambulatory peritoneal dialysis fluid.

In the present study a newly formulated dialysis solution (HDF) was tested for its effects on phagocyte viability and function as well as its ability to support bacterial growth. This solution differs from standard CAPD solution (NPD) by the inclusion of histidine to buffer the fluid to pH 6.7. Low-dextrose HDF (1.36% w/v dextrose) did not significantly decrease the viability or inhibit any of the PMN functional parameters measured (phagocytosis, LTB4 release or respiratory burst activation) when compared to control buffer. NPD (1.36% w/v dextrose) at low pH as well as all high-dextrose dialysis solutions (NPD and HDF) significantly inhibited most PMN functions independently of reduced viability. Peritoneal mesothelial cell viability was unaffected by either low- or high-dextrose HDF but was significantly reduced by NPD (1.36 and 3.86% dextrose) at pH 5.2. The inhibitory effects of low dextrose dialysis solutions were confirmed as being partly related to their low initial pH. High-dextrose dialysis fluids, however, inhibit PMN function by a mechanism which, in addition to initial pH, appears to be directly related to their dextrose content but not their osmolality.