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Biomedical subjects

R Selgas

Publications and source records attributed to R Selgas.

At least 19 recordsLinked to original sources
PubMed2006

[Pasteurella multocida and Candida albicans peritonitis].

Peritonitis is a well-known complication of peritoneal dialysis (PD) treatment. Repetitive episodes may induce an irreversible damage of the peritoneal membrane and are a frequent cause of PD drop-out. The great majority of the episodes are due to Staphylococci, Streptococci or gram- negative organisms. Unusual organisms have been reported, specially in immunosuppressed hosts. Few cases of Pasteurella Multocida (PM) have been described in PD patients. To our knowledge, we describe the first case preceding a Candida Albicans (CA) peritonitis. A review of the literature of PM peritonitis and the relation between these two microorganisms is discussed.

Animals↗
PubMed2006

[Treatment of acute lithium intoxication with high-flux haemodialysis membranes].

Lithium carbonate is commonly prescribed for the treatment of bipolar (manic-depressive) disorders. However, because of its narrow therapeutic index an excessive elevation of serum lithium concentration, either during chronic maintenance therapy or after an acute overdose, can result in serious toxicity. In addition to supportive care, the established treatment of severe lithium toxicity is haemodialysis. Conventional haemodialysis can reduce serum lithium rapidly, but post-dialysis rebound elevations with recurrent toxicity have been documented in old publications. High-flux membranes should be capable of removing more lithium per hour of haemodialysis, but published values are not available. We report here three patients with acute lithium intoxication who were treated successfully with bicarbonate and high-flux haemodialysis membranes. Our patients presented with a severe degree of intoxication, based on the amount of drug ingested, the initial serum lithium level, the severity of neurologic symptoms and systemic manifestations. Two patients developed acute renal failure probably as a result of volume depletion since it was rapidly reversible by haemodialysis and infusion therapy. In addition, consecutive haemodialysis sessions and improvement of renal function allowed a rapid decrease in serum lithium levels without haemodynamic instability or rebound elevations in lithium concentration. The effectiveness of the procedure in these cases can be attributed to the use of bicarbonate dialysate and high-efficiency dialysers. This is the first report describing the effect of high-efficiency dialysers on lithium pharmacokinetic. Using this technique the elimination rate of lithium was found to be greater than previously reported with haemodialysis.

Acute Disease↗
PubMed2005

Tissue models of peritoneal fibrosis.

OBJECTIVE: To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation. METHODS: Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers. RESULTS: Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as a -SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis). CONCLUSIONS: Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

Actins↗
PubMed2005

Myofibroblastic differentiation in simple peritoneal sclerosis.

OBJECTIVE: To analyze the presence of myofibroblasts in a series of peritoneal dialysis (PD) patients with simple sclerosis and non-PD, uremic patients. Since there is a close correlation between active fibrosis and myofibroblastic differentiation we wanted to test if myofibroblasts are present in uremic, non-PD peritoneal samples. To determine if there are correlations between myofibroblastic presence and other functional and morphologic peritoneal parameters. METHODS: Biopsies were collected from three patient groups: 1) Normal control samples (n = 15) of parietal and visceral peritoneum 2) non-PD uremic patients (n = 16); and 3) uremic patients on PD (n = 32). Peritoneal morphologic and functional parameters and immunohistochemical expression of alfa-smooth muscle actin was analyzed in each case. Vascular endothelial growth factor (VEGF), bcl-2 anti-apoptotic protein, and progesterone receptor was evaluated in a subset of cases. RESULTS: Myofibroblasts were present in 56.3% of the patients with PD-related simple sclerosis. In most cases they were distributed in the upper submesothelial area. None of the biopsies from normal controls and uremic, non-PD patients showed myofibroblasts. Within the group of PD patients, myofibroblasts showed no correlation with time on dialysis, urea/creatinine MTAC, episodes of peritonitis, submesothelial thickening, hyalinizing vasculopathy or mesothelial status. In a subset of PD patients VEGF expression was observed in submesothelial fibroblastic cells. No expression of progesterone receptor or bcl-2 was observed. CONCLUSIONS: Myofibroblasts are a reliable and simple indicator of fibrosis since they appear in early stages of PD treatment and in patients with minor morphologic anomalies. They are not exclusive of patients with sclerosing peritonitis, ultrafiltration loss or long standing treatment. Their absence in non-PD, uremic patients suggest that uremia-related fibrosis takes place without a significant participation of myofibroblasts.

Adult↗
PubMed2005

Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells.

The preservation of the peritoneal membrane is crucial for long-term survival in peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) is a process demonstrated in mesothelial cells (MC), responsible for negative peritoneal changes and directly related to PD. EMT enables neovascularization and fibrogenic capabilities in MC. Vascular endothelial growth factor (VEGF) is the mediator for neo-vascularization. Rapamycin is a potent immunosuppressor with antifibrotic action in renal allografts and has a demonstrated anti-VEGF effect. We performed this study with the hypothesis that rapamycin may regulate the EMT of MC. MC from human omentum were cultured. When mesothelial cells reached confluence, some of them were stimulated with r-TGF-beta (1 ng/mL) to induce EMT, co-administered with rapamycin (0.2, 2, 4, 20 and 40 nM). Other groups of cells received similar doses of rapamycin or r-TGF-beta, separately. Cells were analyzed at 6, 24, 48 hours and 7 days. As markers of EMT we included alfa -SMA, E-cadherin and snail nuclear factor by quantitative RT-PCR. EMT markers and regulators demonstrated the following changes with rapamycin: E-cadherin (a protective gene for EMT) increased 2.5-fold relative to controls under 40 nM, at 24h. Importantly, rapamycin inhibited snail expression induced by TGF-beta at 6h, whereas TGF-beta increased snail 10-fold. At day 7, rapamycin showed no anti-EMT properties. An important decrease in alfa -SMA expression by MC after rapamycin addition was observed. In conclusion, rapamycin shows a mild protective effect on EMT, as it increases E-cadherin and decreases alfa -SMA expression. Consequently, rapamycin might partially regulate the epithelial-to-mesenchymal transition of mesothelial cells.

Actins↗
PubMed2004

Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.

BACKGROUND: Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life. AIM: To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD. METHODS: Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected. RESULTS: A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed. CONCLUSIONS: The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.

Antiviral Agents↗
PubMed2003

[Evaluation of osteodystrophy parameters in a pre-dialysis unit].

A cross-sectional study was developed with 100 of the first-time pre-dialysis patients visiting the Princesa University Hospital's Advanced Chronic Kidney Disease (ACKD) unit, with the aim of analysing various parameters of osteodystrophy at this time. Parameters evaluated were: age, gender, renal function, osteodystrophy serum parameters, comorbidity index (ICED) and the patients' origin to establish correlations between these parameters. Mean iPTH levels were higher irrespective of the patients' origin, and were significantly higher in men than in women, the former also having poorer renal function and higher comorbidity score. The mean levels of calcium, phosphorous, alkaline phosphatase and CO2 did not justify this rise in iPTH. Nutritional parameters NPNA and albumin were adequate in spite of ageing. At early stages of ESRD, iPTH could be elevated and ACKD units play an important part its early detection and subsequent treatment.

Aged↗
PubMed2003

[Influence of different pharmacological agents in the ex vivo proliferation of mesothelial cells obtained from the peritoneal effluent of patients treated with peritoneal dialysis].

UNLABELLED: Mesothelial cells (MC) are the first peritoneal membrane barrier in contact with dialysate. The aim of this study was to analyze the in vitro capacity of different pharmacological agents to modify the ex vivo proliferation of MC obtained from the peritoneal effluent of patients treated with peritoneal dialysis (PD). MATERIAL AND METHODS: Thirty cultures of MC taken from nocturnal peritoneal effluent were performed. After identification, MC are subcultured in 24 multi-well plates, adding the different exogenous agents. Proliferative capacity and cell morphology were estimated on day 16th of culture. The agents evaluated were insulin, IGF-1, tamoxifen, labetalol, carvedilol, enalapril and losartan. RESULTS: Insulin shows a dose-dependent effect on MC growth, with a limit that is stimulated by the addition of fetal bovine serum (FBS). Concentrations higher than 100 micrograms/ml, are not associated with further growth, even with cell damage. In contrast, the wide range of IGF-1 dose used did not affect to MC proliferation. Tamoxifen causes negative effects on MC growth just a very high doses, not resembling doses in clinical practice. Labetalol does not modify MC proliferation used under therapeutic calculated range. However, concentrations higher than 40 micrograms/ml showed a negative influence on growth, behaving as lethal doses that over 100 micrograms/ml. The addition of FBS attenuates this effect. These effects were very similar to that caused by carvedilol addition. Enalapril and losartan act as antiproliferative agents for MC. This effect is potentiated with angiotensin II, reaching lethal concentrations increasing the dose. In conclusion, mesothelial cell growth ex vivo taken from nocturnal peritoneal effluent on PD patients is an useful tool to explore the effects of any pharmacological agent on the biology of the cell of the peritoneum. The agents used had any influence in the proliferation capacity of mesothelial cells.

Ascitic Fluid↗
PubMed2002

[Prognostic significance of programmed dialysis in patients who initiate renal substitutive treatment. Multicenter study in Spain].

BACKGROUND: The aim of our study was to analyse patient characteristics, mortality and costs, all of them in relation to whether starting dialysis was planned or unplanned. METHODS: A total of 362 patients (227 male and 135 female) from five hospitals of the National Health System, who were started on chronic renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who were started on RRT after acute renal failure were excluded. We carried out a retrospective analysis of the demographic characteristics, patients' conditions at the time of initiating dialysis and outcome and costs at six and thirty-six months of treatment. Patients were classified as planned (PL-D) or unplanned dialysis (UNPL-D), depending on whether or not the patient had a vascular or peritoneal access ready to use for initiating RRT. RESULTS: One hundred and eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176 (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis without previous nephrological follow-up. UNPL-D was associated with older age (p < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p = 0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main primary renal diseases were glomerular and polycystic disease, whereas interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005). Multivariate analysis showed that previous non nephrological follow-up, uraemic symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D was also associated with increased number of days of hospitalization at the initiation of dialysis, and during the first 6 months (p < 0.001), increase of hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%) (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006, log rank test). The costs of UNPL-D were fivefold that of the PL-D group. CONCLUSION: UNPL-D has been associated with worse overall clinical conditions at the initiation of chronic replacement therapy, choosing haemodialysis as first RRT, increased morbi-mortality and subsequent increase of costs.

Adolescent↗
PubMed2002

[Use of icodextrin for diurnal exchange in patients undergoing automatic peritoneal dialysis. Comparison with glucose solutions].

Icodextrin (IC) is an osmotic agent that produces sustained ultrafiltration (UF) during long dwell time periods in peritoneal dialysis patients. The aim of this study was to evaluate the effects of 7.5% IC for the diurnal exchange in automated peritoneal dialysis (APD) patients and to compare them with that of 2.27% glucose solutions. Seventeen patients treated on APD during 13.9 +/- 12.7 months were included. The study was divided into three eight weeks phases. During the baseline period patients used 2.27% glucose for the daytime, second, IC 7.5% was prescribed for the day-exchange, and finally 2.27% glucose solution was used for the last eight weeks. Daytime UF increased in all patients during IC use (-53 +/- 22 to 270 +/- 304 ml/day, p < 0.01). Patients with higher peritoneal permeability capacity obtained more benefits. Daytime urea KT/V and weekly creatinine clearance (WCC) augmented significantly during IC use, but the increase of weekly urea KT/V and WCC was not significant (2.18 +/- 0.45 to 2.26 +/- 0.41 and 62.7 +/- 18 to 66.6 +/- 15 l/week/1.73 m2; respectively). On IC, nightly glucose load significantly decreased (289 +/- 82 to 266 +/- 94 g, p < 0.05), returning to previous value after withdrawal. Plasma osmolality did not change, although plasma sodium levels decreased during IC use (140 +/- 3 to 136 +/- 2, p < 0.001). Serum amylase levels significantly declined during IC use (279 +/- 151 to 29 +/- 9 U/l), returning to previous values after transfer to glucose. Peritoneal function transport parameters and peritoneal protein losses did not change. IC metabolite plasma levels increased during the use of this solution, returning to previous values after withdrawal. In conclusion, IC dialysate is an excellent alternative to glucose dialysate for the day-exchange in APD patients. Daytime UF increased in all patients, but those with higher peritoneal permeability capacity obtained more benefits. The decrease of the glucose peritoneal load overnight and the reduction for more than 50% of exposure time of the peritoneal membrane to glucose solutions, probably make IC solution a more biocompatible fluid.

Adult↗