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Simon J Davies

Publications and source records attributed to Simon J Davies.

12 recordsLinked to original sources

Measuring transport of water across the peritoneal membrane.

INTRODUCTION: Mechanisms of water flow across the peritoneal membrane include diffusion, convection, and reabsorption. OBJECTIVES: To understand these processes more clearly we have developed a method to measure transport of water across the peritoneal membrane. METHODS: An artificial gradient of deuterated water (HDO) between blood and dialysate compartments was created in five subjects who took 0.3g per kg of body weight of D2O, which was allowed to equilibrate with total body water. During a test dwell (2 L, bicarbonate:lactate buffer, 1.36% glucose to minimize convection), frequent dialysate samples were drawn to determine the abundance of deuterium and other solutes and to calculate their time constants. Dialysate deuterium abundance was measured using flowing afterglow mass spectrometry (FA-MS). The method was combined with 125iodine-labeled albumin (RISA) to enable simultaneous estimates of intraperitoneal volume and thus calculation of the mass transfer area coefficient (MTAC) for small solutes using the Garred equation. RESULTS: The appearance of HDO in dialysate in four subjects is described by a single exponential fit with residuals of <1%, similar to method precision. In a fifth subject, the resolution of this method demonstrated that the best fit was a double exponential. When compared to other solutes, the time constant for water was as predicted by its molecular weight, with a MTAC of 38.7 +/- 4.4 mL/min. Total body water could also be estimated from the equilibrated dialysate deuterium abundance, with repeat estimates within 0.5%. CONCLUSION: Transport of water across the peritoneum can be measured with remarkable accuracy and when combined with an intraperitoneal volume estimation can be used to determine mass transfer. In conditions of low convection, the relative rate of deuterium appearance and mass transfer compared to other solutes suggests that water diffuses predominantly through the intercellular small pores.

Biological Transport↗

Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.

Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.

Adult↗

Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study.

The European APD Outcome Study (EAPOS) is a 2-yr, prospective, multicenter study of the feasibility and clinical outcomes of automated peritoneal dialysis (APD) in anuric patients. A total of 177 patients were enrolled with a median age of 54 yr (range, 21 to 91 yr). Previous median total time on dialysis was 38 mo (range, 1.6 to 259 mo), and 36% of patients had previously been on hemodialysis for >90 d. Diabetes and cardiovascular disease were present in 17% and 46% of patients, respectively. The APD prescription was adjusted at physician discretion to aim for creatinine clearance (Ccrea) >/=60 L/wk per 1.73 m(2) and ultrafiltration (UF) >/=750 ml/24 h during the first 6 mo. Baseline solute transport status (D/P) was determined by peritoneal equilibration test. At 1 yr, 78% and 74% achieved Ccrea and UF targets, respectively; median drained dialysate volume was 16.2 L/24 h with 50% of patients using icodextrin. Baseline D/P was not related to UF achieved at 1 yr. At 2 yr, patient survival was 78% and technique survival was 62%. Baseline predictors of poor survival were age (>65 yr; P = 0.006), nutritional status (Subjective Global Assessment grade C; P = 0.009), diabetic status (P = 0.008), and UF (<750 ml/24 h; P = 0.047). Time-averaged analyses showed that age, Subjective Global Assessment grade C and diabetic status predicted patient survival with UF the next most significant variable (risk ratio, 0.5/L per d; P = 0.097). Baseline Ccrea, time-averaged Ccrea, and baseline D/P had no effect on patient or technique survival. This study shows that anuric patients can successfully use APD. Baseline UF, not Ccrea or membrane permeability, is associated with patient survival.

Adult↗

Perceptual completion and object-based representations in short-term visual memory.

Object-based representations in visual short-term memory (VSTM) were examined using a change detection memory task. A display comprising two rows of four differently colored elements was followed by a probe display in which only one of the rows reappeared. On same trials, the probed row was identical to the corresponding row in the memory display. On different trials, two of the elements in the probed row had their colors exchanged. In each memory display, a task-irrelevant visual element appeared between the two rows, with the potential to function as an occluder. Performance was enhanced when perceptual completion meant that four, rather than eight, objects were perceived in the memory display and when the probe display revealed that the occluded elements continued behind the occluder. It appears that several forms of representation can co-occur to support VSTM, one of which is object based.

Feedback↗

Comparative measurements of total body water in healthy volunteers by online breath deuterium measurement and other near-subject methods.

BACKGROUND: We developed a new near-subject approach, using flowing afterglow-mass spectrometry (FA-MS) and deuterium dilution, which enables the immediate measurement of total body water (TBW) from single exhalations. OBJECTIVES: The objectives were to show the efficacy of the new FA-MS method in measuring TBW in healthy subjects and to compare these measurements with values derived from multifrequency bioelectrical impedance analysis, skinfold-thickness (SFT) measurements, and both recent and historical published regression equations. DESIGN: After baseline measurement of breath deuterium abundance, 24 healthy subjects ingested 0.3 g D(2)O/kg body wt. A second breath sample was taken after 3 h to measure the increase in deuterium, from which TBW was calculated. Bioelectrical impedance analysis was carried out with a multifrequency analyzer, and SFT was measured by a single trained observer. Methods were compared with the use of Pearson's correlation coefficient and Bland-Altman analyses. RESULTS: TBW measures obtained by all methods were highly correlated (r = 0.95-0.98, P < 0.001), especially those between FA-MS, SFT measurement, and recent regression equations. The mean values obtained were within 2% of those published for age-matched control subjects and varied by 1-6% when all methods were compared. Systematic bias was greatest when FA-MS was compared with bioelectrical impedance analysis, which tended to underestimate TBW in smaller, female subjects. No bias related to subject size was observed in a comparison of FA-MS with SFT measurement or with more recent regression equations. CONCLUSIONS: FA-MS is a simple and effective new approach to TBW measurement in healthy subjects. The difficulty of using population-derived equations to estimate TBW in individual subjects is emphasized.

Adult↗

Quantifying comorbidity in peritoneal dialysis patients and its relationship to other predictors of survival.

BACKGROUND: Comorbidity is the single most important determinant of outcome in patients on renal replacement therapy. The aims of this study were to evaluate a semi-quantitative approach to comorbidity scoring in predicting survival of patients commencing peritoneal dialysis (PD), and to establish the interaction between this and other known predictors of patient outcome, in particular membrane function, residual renal function (RRF) and plasma albumin. METHODS: Comorbidity was recorded in a prospective, single centre cohort study of 303 patients commencing on PD. Using seven disease domains, chosen to reflect the dominance of cardiovascular morbidity in the end-stage renal failure population, comorbidity was graded as '0' when absent, '1' when one or two, and '2' when three or more conditions were present. The Wright comorbidity index, which includes age within the scoring method, was also evaluated. RRF, plasma albumin and peritoneal solute transport were measured every 6 months. Patients were censored at death. RESULTS: Median survival according to grade of comorbidity was 105, 42 and 29 months, respectively (P<0.0001), with good separation of the actuarial survival curves. Using Cox regression, the addition of age and the grade of comorbidity to Kt/V(urea), solute transport and plasma albumin increased the predictive power of the model. All were independent predictors of outcome with the exception of albumin. The Wright comorbidity index also enhanced the Cox model, although was not as powerful as when age and comorbidity were considered independently. At baseline, RRF was not different according to comorbidity unless diabetes was considered separately. Diabetics started with higher RRF, but after 6 months on PD this was the same as non-diabetic patients. Otherwise, initial rate of decline of RRF was similar across the comorbid grades, although the impact of higher drop-out due to earlier loss in patients with more comorbidity may have disguised earlier loss in these patients. Peritoneal solute transport tended to be higher in patients with increased comorbidity at baseline, chi(2) 13.8, P=0.032, and this was sustained with time on treatment. CONCLUSION: Comorbidity has a quantitative effect on survival that is independent of age, RRF and membrane function in PD patients. Comorbidity also appears to be associated with increased solute transport at the start of treatment, which is sustained. With the exception of diabetes, grade of comorbidity does not have a profound effect on loss of RRF.

Analysis of Variance↗

Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.

Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [+/-0.1]; at 5 yr, 0.67 [+/-0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [+/-0.08]; at 5 yr, 0.77 [+/-0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.

Adult↗

A novel treatment of postherpetic neuralgia using peppermint oil.

BACKGROUND: Postherpetic neuralgia remains a difficult problem to treat. A number of therapies have been shown to be effective, but some patients have intractable pain. PATIENT: The case of a 76-year-old woman whose pain had been resistant to standard therapies is described. The pattern of quantitative sensory testing results for this patient led the authors to believe that she had an "irritable nociceptor" type of pathophysiology. INTERVENTION: The patient was instructed to apply neat peppermint oil (containing 10% menthol) to her skin, resulting in an almost immediate improvement in her pain. This pain relief persisted for 4-6 hours after application of the oil. RESULTS: The patient was successfully treated with topical peppermint oil. During 2 months of follow-up she has had only a minor side effect, with continuing analgesia. The authors believe this is the first evidence of peppermint oil (or menthol) having a strong analgesic effect on neuropathic pain. The possible mechanisms of action of peppermint oil are discussed.

Aged↗

Selected growth factors in peritoneal dialysis: their relationship to markers of inflammation, dialysis adequacy, residual renal function, and peritoneal membrane transport.

OBJECTIVES: Markers of chronic inflammation, acute-phase reactants, and growth factors may be concomitantly involved in a number of pathologic processes in the general population and uremic patients. In addition, growth factors may influence peritoneal membrane transport characteristics. However, the association between plasma growth factors, markers of chronic inflammation, and peritoneal membrane transport remains largely unknown. The aim of this study was to evaluate the relationship between plasma levels of selected growth factors [basic fibroblast growth factor (bFGF), transforming growth factor beta1 (TGFbeta1), vascular endothelial growth factor (VEGF)] and markers of chronic inflammation [interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen] in continuous ambulatory peritoneal dialysis (CAPD) patients. The potential link between the above substances and dialysis adequacy was also explored. DESIGN: Single-center, cross-sectional study. SETTING: Peritoneal Dialysis Unit, Medical Faculty, Jagiellonian University Hospital, Kraków, Poland. PATIENTS: 32 stable end-stage renal disease patients (13 M, 19 F; mean age 53.6 +/- 13.7 years) on CAPD for a median period of 19.5 months. Patients free from signs and symptoms of any inflammatory disease (including peritonitis) for at least 3 months were included into the study. All patients underwent measurements of dialysis dose [Kt/V, weekly creatinine clearance (wCCr)] and peritoneal solute transport using a standard peritoneal equilibration test (PET). METHODS: TGFbeta1, bFGF, VEGF, and IL-6 were measured with ELISA, CRP was assayed with immunonephelometry, and fibrinogen with Multifibren U reagent (Dade Behring Marburg GmbH, Marburg, Germany). Nephron 97 for Windows software was used to assess dialysis adequacy. RESULTS: Significant positive correlations between plasma bFGF and IL-6, as well as fibrinogen concentrations (R = 0.36, p < 0.05 and R = 0.39, p < 0.05, respectively), were found. VEGF correlated significantly with IL-6 and CRP (R = 0.65, p < 0.0001 and R = 0.51, p < 0.005, respectively). An association between VEGF and bFGF was also found (R = 0.59, p < 0.0005). Serum level of TGFbeta1 revealed no relationship with any marker of acute-phase activation, remaining growth factors, or dialysis adequacy. Positive correlation between TGFbeta1 concentration and dialysate-to-plasma ratio for creatinine in PET (R = 0.35, p < 0.05) was found. In addition, patients with lower solute transport (low/low-average transporters) had lower serum levels of both bFGF and TGFbeta1 compared to patients with higher solute transport. Patients with total wCCr > 60 L/ week/m2 were characterized by lower levels of bFGF and IL-6. Serum level of IL-6 and plasma levels of bFGF and VEGF were significantly lower among subjects with residual renal function (RRF) > 2.0 mL/minute. CONCLUSIONS: Our results indicate that systemic inflammation in peritoneal dialysis patients is associated with increased plasma VEGF and bFGF but not TGFbeta1. The negative correlation with RRF suggests that either the renal clearance of these cytokines and growth factors may contribute to their elimination, or cytokines and growth factors have a negative impact on RRF. We also suggest an association between serum levels of growth factors tested and peritoneal membrane function.

Adult↗