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Biomedical subjects

R Selgas

Publications and source records attributed to R Selgas.

At least 127 records · Page 7Linked to original sources

Respiratory muscle weakness in uremic patients under continuous ambulatory peritoneal dialysis.

The increasingly frequent use of continuous ambulatory peritoneal dialysis (CAPD) as substitutive therapy in terminal renal failure has induced the investigation of the advantages and disadvantages of this therapeutic modality. The effects of CAPD on pulmonary function are one of the aspects currently under study. Based on previous data suggesting the existence of extrapulmonary ventilatory restriction in uremic patients under CAPD, we have studied in these patients the respiratory muscle function as expressed in the maximal inspiratory pressure (MIP) and assessed the impact of the infusion of 2 liters of dialysis fluid into the peritoneal cavity on both MIP and the pulmonary volumes. Uremic patients evidenced significantly lower MIP values as compared with healthy controls. The filling of the peritoneal cavity induced, both in the supine and in the sitting position, a restrictive effect and an increase in the inspiratory capacity. We conclude that uremic patients under CAPD evidence a respiratory muscle dysfunction of as yet unclear cause. Our findings further suggest that the infusion of 2 liters of dialysis fluid into the peritoneal cavity induces not only a restrictive effect, but also an increase in the strength of the respiratory muscles, the latter effect being probably due to increased diaphragmatic contractility.

Adult↗

Characteristics of the peritoneal mass transfer of parathormone in patients under continuous ambulatory peritoneal dialysis therapy.

Recent studies have shown that the mass transfer coefficients (MTC) for low- and middle-molecular-weight substances are maintained at medium terms in patients under continuous ambulatory peritoneal dialysis (CAPD) therapy. We have studied the MTC for parathormone (MW 5,500-6,000) in 29 patients under CAPD. 11 patients were assessed once, 9 patients were assessed twice, and 9 were assessed three times, with 6-month intervals between assessments; in 15 cases nitroprusside (4.5 mg/l) was added to the dialysate, and in 2 cases the assessment was carried out during an episode of peritonitis. A bicompartmental model with exponential ultrafiltration was used, and the generation rates were calculated by mass balance. The MTC was calculated by minimization of the quadratic error, following the procedure of Runge and Kutta. The mean MTC values were 21.2 +/- 5.9 for urea, 10.26 +/- 5.9 for creatinine 2.8 +/- 1.8 for inulin and 1.0 +/- 0.8 for parathormone (PTH), with significant correlation between the MTC values for PTH and inulin (r = 0.5, p less than 0.01). There is a direct correlation between MTCPTH and peritoneal PTH clearance, and an inverse one between MTCPTH and serum PTH, with r = 0.8 and 0.51, respectively. No correlation was found between the MTC for inulin or PTH and the duration of the CAPD therapy, nor with the number of episodes of peritonitis. No significant medium-term variations were detected in the MTC values for PTH and inulin. Both peritonitis and the intraperitoneal administration of nitroprusside induce significant increases in the MTCPTH.

Creatinine↗

Plasma calcitonin concentration in patients treated with chronic dialysis: differences between hemodialysis and CAPD.

We have determined plasma calcitonin levels in 72 chronic dialysis patients and investigated their possible correlations with other parameters of calcium and phosphorus metabolism, including plasma levels of calcium, phosphorus, alkaline phosphatase and parathormone, as well as with the duration of treatment. Forty-one of the patients were being treated with hemodialysis (HD) and thirty-one with continuous ambulatory peritoneal dialysis (CAPD). Increased calcitonin levels were detected in 83% of the HD patients and in 79% of the CAPD group. In the former there was a positive correlation between the levels of calcitonin and the calcium, corrected calcium, alkaline phosphatase and parathormone levels and with the duration of treatment, whereas in the latter the calcitonin levels only correlated with the serum calcium. The patients receiving CAPD also showed significantly lower calcium and calcitonin levels than the HD patients. Our conclusion is that, apart from accumulation due to renal failure, the main factor determining the calcitonin level is the blood calcium level, and that the observed increase might play a role in the physiological protection of bone against the action of parathyroid hormone.

Calcitonin↗

[Polycystic renal disease in the adult associated with an incomplete form of Marfan's syndrome (author's transl)].

A case of polycystic renal disease of the adult associated to dissecting aneurysm of the ascending aorta with histological findings compatible with Marfan's syndrome is reported. A review of the literature discloses only one case of this association, although without cardiovascular abnormalities. Polycystic renal disease of the adult is associated with some frequency to aneurysms of the cerebral arteries and, occasionally, to aneurysms of systemic arteries (splenic and renal). On the other hand, the Marfan's syndrome presents the well known dysmorphic manifestations associated to cystic degeneration of certain organs (congenital pulmonary cystic disease and congenital renal cysts, amongst others), constituting the so-called secondary abnormalities. The association herein reported might be considered as casual, but could also represent simultaneous mutations due to a single mutagenic factor. This explanation is supported by the identical hereditary pattern and the fact that both diseases share some secondary abnormalities.

Adult↗

Prevalence of TT virus in serum and peripheral mononuclear cells from a CAPD population.

BACKGROUND: A novel virus named TT virus (TTV) has been isolated recently from patients with posttransfusional hepatitis of unknown etiology. The prevalence of TTV in several groups at risk has been reported, however, there is no information about the prevalence of TTV in patients on continuous ambulatory peritoneal dialysis (CAPD) without blood transfusions or hemodialysis antecedents. OBJECTIVE: To study the incidence of TTV in serum and peripheral blood mononuclear cells (PBMC) of CAPD patients. DESIGN: TTV DNA was detected by polymerase chain reaction, using primers from the open reading frames (ORF) 1 and 2, in serum and PBMC from 22 CAPD patients who had not received blood transfusions or hemodialysis therapy prior to CAPD. As controls, sera from 20 patients with chronic viral hepatitis (10 with HBV and 10 with HCV) and 20 healthy donors were included in the study. RESULTS: TTV DNA was detected in the serum of 5 of 22 (22.7%) CAPD patients with both sets of primers. Four of the 5 (80%) patients with TTV DNA in their serum were TTV positive in their PBMC with primers from ORF1 and ORF2. Five of 20 (25%) patients with chronic viral hepatitis (2 patients with HBV and 3 with HCV) and 4 of 20 (20%) healthy donors were TTV DNA positive in serum. No relation was found between TTV infection and the underlying kidney disease, previous surgery, and abnormal alanine aminotransferase levels. CONCLUSION: We have found a relatively high prevalence of TTV that is similar to that found in healthy donors and in patients with chronic viral hepatitis.

Adult↗

Protein-losing enteropathy is associated with peritoneal functional abnormalities in peritoneal dialysis patients.

OBJECTIVE: To evaluate the relationship between acquired peritoneal transport disorders and the presence of protein-losing enteropathy (PLE), and their contribution to the protein malnutrition in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: We studied 31 clinically stable PD patients that received a fat overload diet for 3 days. We measured intestinal absorption of fecal fat (normal < 6 g/24-hour stool) and nitrogen (normal < 2 g/24-hr stool), intestinal protein permeability [fecal clearance of alpha1-antitrypsin (Calpha1AT) (normal < 12 mL/24-hr stool)], and nutritional markers [normalized protein nitrogen appearance (nPNA), half-life medium-term proteins, and body mass index]. Peritoneal solute transport was measured by mass transfer coefficient (MTC), and water transport by peritoneal ultrafiltration (UF) capacity. To define protein maldigestion it was necessary to find high fecal nitrogen values with normal Calpha1AT; PLE was defined when both values were elevated. RESULTS: High fecal nitrogen (mean 2.1+/-1 g/24-hr stool) and fat (mean 5.8+/-3.6 g/24-hr stool) were found in 15 patients; 6 patients had high Calpha1AT levels (PLE). These 6 patients showed a worse nutritional status: lower albumin (3.57+/-0.57 g/dL vs 3.98+/-0.38 g/dL, p < 0.05) and transferrin (243+/-70 mg/dL vs 272+/-44.3 mg/dL, p < 0.05), as well as lower triglycerides (131.3+/-31.7 mg/dL vs 187+/-116 mg/dL, p< 0.05). Higher urea MTCs were found in 10 patients, normal in 7, and lower in 14. Higher creatinine MTCs were found in 8 patients, normal in 15, and lower in 8. Normal peritoneal UF capacity was found in 25 and lower in 6 patients. These 6 patients showed higher urea and creatinine MTCs and Calpha1AT. A positive linear correlation between Calpha1AT, urea MTC (r = 0.56, p < 0.01), and creatinine MTC (r = 0.46, p < 0.01) was found. A similar situation occurred between Calpha1AT, fecal fat (r = 0.45, p < 0.05), and fecal nitrogen (r = 0.43, p < 0.05). Thirteen patients with previous history of peritonitis showed higher Calpha1AT than those without peritonitis (10.2+/-8 mL/24-hr stool vs 5.2+/-4.4 mL/24-hr stool, p < 0.05). CONCLUSIONS: We confirm that protein and fat malabsorption, maldigestion, and PLE are present in some PD patients. Higher fecal Calpha1AT is associated with malnutrition and poorer showings of the viability markers of peritoneal membrane function.

Adult↗

[Methods to assess the ex vivo growth capacity of mesothelial cells obtained directly from peritoneal effluent].

The anatomical and functional integrity of mesothelial cells (MC) is necessary for peritoneal membrane stability. At present, there is no satisfactory method to assess MC function and regenerative capacity in individual peritoneal dialysis (PD) patients. MC may be cultured from peritoneal biopsy specimens, but peritoneal biopsy is an invasive procedure that cannot be performed serially. The aim of this study is to explore the feasibility of serial culture of MC from the peritoneal effluent of PD patients. Fifty-two randomly selected PD patients were studied. MC were obtained from the peritoneal effluent of nocturnal 2.27% glucose exchanges and cultured in T25 tissue culture flasks. Subconfluent MC cultures were obtained in 80.7% of patients. At this stage, the percentage of cells in the tissue cultured flask characterized as MC by morphology and immunostaining had increased to 95.5%. MC were then subcultured in multi-well culture plates, where they showed exponential cell growth until day 16. Nine (17%) patients released low numbers of MC into the effluent and MC could not be cultured to subconfluence. One additional patient released and apparently adequate number of MC that repeatedly failed to reach confluence. Patients showed the same behavior in several cultures performed. In conclusion, peritoneal MC released into peritoneal effluent are accessible for profound analysis by a culture technique. This technique opens the possibility of serial follow-up of the biology of MC individual PD patients.

Cell Division↗

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis.

OBJECTIVE: To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). DESIGN: Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. SETTING: A tertiary-care public university hospital. PATIENTS: Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. MAIN OUTCOME MEASURES: Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). RESULTS: None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 +/- 0.5% in the LUFF group, but as high as 25.5 +/- 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group (p = 0.016). CONCLUSIONS: Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms.

Hemodiafiltration↗

Icodextrin effluent leads to a greater proliferation than glucose effluent of human mesothelial cells studied ex vivo.

OBJECTIVE: To compare the effect of glucose (Glu) and icodextrin (Ico) dialysate on in vitro culture of mesothelial cells (MC) from peritoneal dialysis (PD) patients. DESIGN: Prospective, controlled comparative study on the effects of two PD solutions. SETTING: A tertiary-care public university hospital. PATIENTS: Sixteen PD patients regularly using Glu dialysate were asked to collect an 8-hour dwell peritoneal effluent on 2 different days, with an interval shorter than 7 days. In the first collection, 2.27% Glu solution and in the last, 7.5% Ico solution was infused. Human MC were isolated from the nocturnal peritoneal effluent bags and grown ex vivo. MAIN OUTCOME MEASURES: Mesothelial cell proliferative capacity ex vivo. RESULTS: Mesothelial cells were present in all patient dialysates except that of a single patient's Glu dialysate. The number of MC drained was similar with both solutions. After the initial culture reached confluence, MC were identified in 14 and 12 patients receiving Ico and Glu, respectively. However, in 1 patient using Ico and in 2 using Glu, the MC count at this stage was so low that further subculture could not be performed. Cells from Ico-derived solutions exhibited a higher degree of proliferation than cells from Glu-derived solutions. The morphology of MC was also different. Cells from drained effluent were typical in 11 patients using Glu solution in contrast with 14 patients using Ico. At confluence, the percentages of typical appearance were 50% and 92.9% (p < 0.05) in Glu and Ico respectively. CONCLUSIONS: Mesothelial cells taken from icodextrin effluent show a greater proliferation ex vivo than those taken from glucose effluent.

Cell Division↗

Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

Amino Acids↗

Vascular endothelial growth factor (VEGF) levels in peritoneal dialysis effluent.

BACKGROUND: Long-term peritoneal dialysis (PD) patients who develop peritoneal ultrafiltration failure have an abnormally large number of capillaries and sclerotic changes in peritoneal biopsy. Peritoneal vascular endothelial growth factor (VEGF) production has been suggested to explain the higher levels in peritoneal effluent than in plasma. The high effluent VEGF levels have been related to peritoneal changes consisting of increased permeability to small molecules. To further analyze the relationship between peritoneal neoangiogenesis induced by VEGF and peritoneal transport, we studied peritoneal effluent VEGF levels in active PD patients. METHODS: VEGF levels were determined in serum and plasma, and in peritoneal effluent (PE) after 4, 8 and 15 h dwell times. RESULTS: PE VEGF levels were 58.6+/-33.7 pg/mL, with a mean VEGF D/P ratio of 0.45+/-0.29 (range 0.06-0.93). In low-transport patients (n = 7) this ratio did not differ from high-average ones (n=5) (0.48+/-0.3 and 0.41+/-0.1, NS). In multivariate analysis, the VEGF D/P ratio showed no correlation with the independent variables included in this study. VEGF levels were higher in 15 h than in 8 h effluent; so the VEGF D/P ratios were higher as well. Regression analysis showed a direct correlation between PEVEGF levels and dwell time (r: 0.57, p = 0.03), but not between VEGF D/P ratio and dwell time. PEVEGF levels directly correlated with effluent protein content. Regression analysis showed no correlation between PEVEGF levels and age, time on PD, days of peritonitis, urea and creatinine-mass transfer coefficients, ultrafiltration capacity, and accumulated glucose dose. Multivariate regression analysis showed correlation only between PEVEGF levels and dwell time, but not with the other independent variables. CONCLUSIONS: This study confirms that VEGF is present in fresh PE from PD patients at levels that suggest local production and filtration from plasma. Peritoneal effluent VEGF levels are not significantly associated with peritoneal functional parameters and background, and seem to be influenced by ultrafiltration in a dilution process. We believe that the role of VEGF in peritoneal pathophysiology is part of a complex relationship involving multiple peritoneal structures and other growth factors, including local counteracting factors for VEGF that regulate neoangiogenesis.

Dialysis Solutions↗

Diverticular disease and treatment with gastric acid inhibitors do not predispose to peritonitis of enteric origin in peritoneal dialysis patients.

OBJECTIVE: Enteric peritonitis (EP) is an infrequent complication of peritoneal dialysis (PD), with severe consequences for peritoneal membrane viability and patient outcome. Factors such as diverticular disease and gastric acid inhibitors have been implicated in its appearance. We investigated several risk factors, including those mentioned below, that can influence the development of EP. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary-care public university hospital. PATIENTS: Fifty-seven PD patients treated in our PD unit during August 1998. MAIN OUTCOME MEASURES: A barium enema was performed on 50 of the 57 patients (the remaining 7 patients refused it) in order to exclude the presence of diverticulosis. All episodes of peritonitis occurring in those patients, including EP, were registered. Enteric peritonitis was defined as that caused by gram-positive, gram-negative, or fungus micro-organisms that colonized the intestinal tract, excluding episodes secondary to genitourinary tract or peritoneal catheter exit-site infections. RESULTS: Twenty-four patients showed diverticular disease in the barium enema, but only 5 of them (21%) had any EP episode. Five of the 26 patients with no diverticula (19%) had EP. Fifty-five episodes of peritonitis were reported in 21 patients; 15 episodes of EP (27.3% of all) developed in 11 patients. Seven of the 11 patients (64%) required peritoneal catheter removal and 3 of them (27%) finally were transferred to hemodialysis due to consequences of the EP episode. Logistic regression analysis did not find any of the independent variables analyzed (age, sex, time on PD, type of PD, peritoneal transport parameters, presence of polycystic kidney disease, constipation or diverticulosis, or treatment with gastric acid inhibitors, or phosphate-binding agents) to be risk factors for developing EP. CONCLUSIONS: Neither diverticulosis nor treatment with gastric acid inhibitors seem to be risk factors for developing peritonitis of enteric origin in PD patients. This type of peritonitis has to be promptly identified and treated in order to diminish the high frequency of peritoneal catheter removal and PD dropout due to such episodes.

Adolescent↗