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Biomedical subjects

R Selgas

Publications and source records attributed to R Selgas.

At least 91 records · Page 5Linked to original sources

The pharmacokinetics of a single dose of calcitriol administered subcutaneously in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: To evaluate the kinetics of calcitriol (1,25(OH)2D3) administered subcutaneously. STUDY DESIGN: Calcitriol kinetics and efficacy after subcutaneous administration were studied in 13 CAPD patients with varying degrees of increased plasma levels of parathyroid hormone (i-PTH). A single dose of 2 micrograms of calcitriol was administered subcutaneously, and its serum levels at baseline and after 1, 2, 6, 12, and 24 hours were determined. Plasma ionized calcium and i-PTH were also determined at these periods. RESULTS: Serum calcitriol levels reached peak levels of 60 and 70 pg/mL at 1 and 2 hours after administration, respectively. These levels decreased thereafter, but remained above baseline values during 24 hours. The mean value of the area under the curve (AUC) was 809 +/- 226 pg/mL/hour. Plasma i-PTH levels showed a slight decrease after 1 and 2 hours, returning to baseline levels after this period. Plasma ionized calcium did not show significant changes during the study. A slight pain at the site of injection was mentioned by some patients. CONCLUSIONS: The subcutaneous route for calcitriol administration achieves theoretically adequate plasma levels in continuous ambulatory peritoneal dialysis (CAPD) patients. This is important when parenteral administration of calcitriol is considered in the treatment of secondary hyperparathyroidism.

Adult↗

Prevalence of hepatitis C antibodies (HCV) in a dialysis population at one center.

Hepatitis C (HC) has been recently diagnosed by determination of specific antibodies that represent the former so-called non-A, non-B hepatitis. We studied the prevalence of plasma HCV antibodies among 61 unselected patients on hemodialysis (HD) and 43 on continuous ambulatory peritoneal dialysis (CAPD). Plasma C-antibodies were determined through the ELISA test system. Transfusion policy was the same in both groups. The prevalence of hepatitis C virus antibodies was significantly higher in hemodialysis patients than among those on CAPD. Time on dialysis, previous blood transfusions, and renal transplantation seem to increase the prevalence of C hepatitis antibodies among hemodialysis patients. The effect of these parameters on CAPD was smaller. Understanding the reasons for these differences may help prevent this disease among dialysis patients.

Blood Transfusion↗

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I) levels in plasma and peritoneal effluent in patients on CAPD.

The formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.

Adult↗

Staphylococcus aureus nasal carrier status (SANCS) in CAPD patients; is it induced or favored by subcutaneous rHu-erythropoietin?

Staphylococcus aureus nasal carriage status (SANCS) has been recognized as a risk factor for patients on CAPD, due to a higher probability of suffering peritoneal catheter infections. The use of subcutaneous drugs (insulin dependent diabetics, drug addicts, HD patients and antiallergic vaccines), has been associated with increased risk of SANCS. On CAPD, erythropoietin (EPO) is almost universally used by the subcutaneous route. The objective of this paper was to evaluate the incidence and prevalence of SANCS in 85 CAPD patients by means of nasal smear and the influence of SANCS on peritoneal and catheter infection rate. Patients were divided in four groups according to diabetic status and EPO treatment (mean dose 2000 u. twice a week). The prevalence of SANCS in control groups was 30% in non-diabetics and 23% in diabetics. EPO treated patients showed a prevalence of SANCS of 39% in non-diabetics and 45% in diabetics due to the presence of 7 and 5 carrier patients respectively. SANCS patients (29% of the population), suffered 45% of peritonitis and 42% of exit-site infections caused by S. aureus. In a prospective part of the study, there was no difference in the frequency of developing positive cultures among EPO and control (30% of patients). No male EPO treated patients developed SANCS. We conclude that it is necessary to monitor S. aureus nasal carrier status periodically in CAPD patients especially in women. Whether or not subcutaneous erythropoietin treatment is implicated pathogenetically with SANCS, is not clarified by our data because of the frequent spontaneous appearance of SANCS among CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Sectional Studies↗

Growth hormone responses to pituitary and hypothalamic stimuli in CAPD patients treated with recombinant human erythropoietin.

Several alterations of growth hormone (GH) secretion have been described in patients with chronic renal failure. The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on GH secretion in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the GH responses to both direct and hypothalamic stimuli in CAPD patients chronically treated with rHuEPO. Eight clinically stable and well-nourished patients (age 19-59 yr) treated with subcutaneous rHuEPO, 96.5 +/- 72.1 U/kg/week, during 6-25 months were tested with GH-releasing hormone (GHRH, 100 micrograms iv in bolus). Insulin-induced hypoglycemia (0.1 U/kg iv in bolus) and clonidine (0.15 mg/m2 po) were used as indirect stimuli for GH release. Baseline concentrations of insulin-like growth factor I (IGF I) concentration was also determined. Five CAPD patients matched for age and sex and not previously treated with EPO were studied as a control group. There was no statistically significant difference in baseline IGF I concentrations in EPO treated patients in comparison with control group (2.6 +/- 0.7 vs 0.9 +/- 0.3 U/ml). GHRH administration was followed by a GH release in the treated group that did not differ significantly from that obtained in controls (peak: 10.6 +/- 3.7 vs 15.2 +/- 7.8 micrograms l, area under the curve [AUC]: 16.3 +/- 5.6 vs 24.0 +/- 11.4 micrograms.h/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Adequacy of peritoneal dialysis: does kt/v have the same predictive value as in HD? A multicenter study.

Urea kinetics and the use of KT/V has become a useful tool for assessing adequacy of small solute removal in HD. Clinical data supporting the benefit of urea kinetic analysis in CAPD patients had been lacking. Using the standards of KT/V for hemodialysis, many CAPD patients would be underdialyzed but, most studies show no significant difference in morbidity or mortality between CAPD and HD patients. We studied retrospectively, 102 patients (48 M, 54 F), aged 54.6 +/- 14.8 (range 14-82), on CAPD 24.4 +/- 23.9 months (0-120) from 6 hospitals. Clinical and biochemical parameters, co-morbidity, mortality, and hospital admission rate were registered. During the follow-up (1 year), a significant decrease of residual renal function (Kr) from 1.74 +/- 1.86 to 1.31 +/- 1.67 (p < 0.01) was noticed. The KT/V also decreased from 2.00 +/- 0.47 to 1.89 +/- 0.36 (p < 0.01) without change in BUN or plasma creatinine levels. The normalized protein catabolic rate (NPCR) decreased from 0.98 +/- 0.28 to 0.93 +/- 0.30 (p < 0.05) and serum albumin from 3.7 +/- 0.5 to 3.5 +/- 0.6 (p < 0.001). There was a positive correlation between NPCR and KT/V (r = 0.44, p < 0.05) and between NPCR with serum BUN (r = 0.27, p < 0.05). There was no correlation between KT/V and NPCR neither with hospitalization rate nor clinical symptoms index. The latter, however, showed a positive correlation with the co-morbidity index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Characterisation of the mitogenic-induced capacity of peritoneal effluent on human and mice fibroblasts in culture.

During continuous ambulatory peritoneal dialysis, solutes capable of stimulating fibroblast activity could be transferred into dialysate; their significance and consequences remain to be established. Sixty-three stable non-selected patients on CAPD were included in this study. Peritoneal transport for water and small solutes was assessed. To explore the mitogenic-induced capacity of peritoneal nocturnal effluent, 50 microliters were added to culture plates of mice and human fibroblasts. Peritoneal effluent alone shows a mitogenic potency slightly greater than insulin and clearly less than bovine fetal serum. When coadjuvants are added, mitogenicity increases but in a variable manner among patients. No differences can be observed in relation to diabetes mellitus, time on CAPD, previous peritonitis, and losses of diffusion capacity. We noted significant inverse linear correlations between mitogenicity value and ultrafiltration, effluent calcium, and creatinine. Neither adrenergic nor calcium-channel blockers influenced these values. We conclude that the peritoneal effluent of CAPD patients has a variable effect on fibroblast growth. Some of the blood components seem to be implicated in this activity. Reduced peritoneal ultrafiltration capacity, probably by a concentration mechanism, is related to a greater mitogenic potency in peritoneal effluent. CAPD patients with impaired ultrafiltration may be at high risk for autoactivation of peritoneal fibroblasts, mainly in mesothelial denudate states.

Adult↗

Osteocalcin levels in uremic patients: influence of calcitriol treatment through two different routes and type of dialysis.

Osteocalcin, the most abundant non-collagen protein of bone, is synthesized by the osteoblast. Serum osteocalcin concentration depends primarily on new cellular synthesis, and is a sensitive marker of bone turnover reflecting osteoblastic function. In uremic and hemodialysis (HD) patients, a direct relationship between serum osteocalcin and histological parameters of bone formation has been observed. The modality of dialysis may influence serum osteocalcin levels though the available data are controversial. The aim of this study is to assess the acute and chronic effects of calcitriol and the influence of modality of dialysis on serum osteocalcin levels. Twelve patients on continuous ambulatory peritoneal dialysis (CAPD) were treated with calcitriol. For control purposes, 24 patients, 12 on CAPD and 12 on HD, not treated with calcitriol serum osteocalcin levels were included. In CAPD patients previously treated with calcitriol, serum osteocalcin levels were higher than in nontreated patients. The higher levels occur independent of serum levels of parathyroid hormone (PTH), Ca and P. Hemodialysis patients had osteocalcin levels similar to those of CAPD patients under calcitriol treatment. However, the levels of HD patients were higher than CAPD nontreated patients. Serum ionized Ca was similar in CAPD and HD nontreated patients; however, total Ca was significantly higher in HD than in CAPD patients, both with and without calcitriol. After the intravenous administration of calcitriol, serum osteocalcin levels increased from 9.2 + 2.5 to 13.5 + 5.4 ng/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Effects of the addition to dialysate of calcitriol H-R-erythropoietin (EPO) and interferon-alpha-2b (IFN) on mitogenic activity of peritoneal effluent.

The presence of cellular growth factors in peritoneal effluents from CAPD patients have been described. The purpose of this paper has been to evaluate the effects of mitogenic activity of peritoneal effluents of the in vivo and in vitro additions of Calcitriol, EPO and IFN. These drugs were added to nocturnal peritoneal dialysate (in vivo) and to nocturnal effluent (in vitro) and then these fluids were tested for mitogenic-induced capacity on mice and human fibroblasts in culture. Our data show that the addition of Calcitriol and Erythropoietin have little effects on peritoneal effluent behaviour. Interferon alpha-2b seem to be useful for decreasing human fibroblasts growth.

Animals↗

Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity.

Anemia of CRF has been corrected by use of H-R-EPO both in hemodialysis and CAPD patients. Long term response to subcutaneous EPO and its relationship with serum EPO levels remain to be established. Twenty-five CAPD patients treated with CAPD during 30 +/- 28 (mean +/- SD) months were included in this study. The follow-up period was 6-24 months. All patients have been on CAPD at least 6 months and their Hemoglobin (Hb) level was lower than 8.5 g/dl. Twelve patients received EPO by subcutaneous route, at doses of 20 u./Kg daily and 13 other patients at doses of 2000 units twice a week. Thereafter, these doses were adjusted to obtain a Hemoglobin level ranging 10.5-13 g/dl. In conclusion, our results suggest that the subcutaneous route for H-R-Erythropoietin can be considered as the best choice for CAPD patients. Low doses twice a week seem to improve anemia in 2 months. Later, dose adjustment should be done according to the patient's response. The improvement in nutritional status we observed suggests a new positive aspect for EPO therapy. Our data did not show changes in peritoneal function.

Adult↗

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.

Humans↗

Secondary hyperparathyroidism in CAPD patients: its suppressibility with high doses of calcitriol.

Secondary hyperparathyroidism (HP) is well known complication of long-term uremia. CAPD patients show a peculiar behaviour due to loss of vitamin D metabolites through peritoneum. Severe degrees of hyperparathyroidism may require parathyroidectomy in order to achieve appropriate control. Recently, the possibility of controlling this situation with high oral doses of calcitriol has been communicated. The purpose of this study is to evaluate the effect of this agent on hyperparathyroidism in CAPD patients. Two different groups were constituted according to the length of time on dialysis when HP was detected. All of the patients had i-PTH serum levels five times higher than the normal values (50 pg/ml). During a six month period the daily dose of oral calcitriol was increased in order to achieve a reduction in i-PTH level. The results after this period showed a significant reduction in i-PTH levels (614 +/- 378 to 241 +/- 80 pg/ml) with an average increase in oral calcitriol from 0.16 +/- 0.1 to 0.67 +/- 0.4 with no significant changes in serum calcium or phosphorus. The group with HP at start of dialysis achieved these effects easier and with lower doses of calcitriol. We conclude that moderately high doses of oral calcitriol control secondary hyperparathyroidism in CAPD patients without hypercalcemia.

Calcitriol↗

Measurement of the peritoneal platelet activity through the effluent betathromboglobulin levels in CAPD patients.

Platelet activity is closely related to endothelium and could release factors able to influence capillary wall and surrounding tissues. BTG is a protein included in platelet vesicles and a measure of its activation. Some alterations of peritoneum could be partially related to platelet activity. BTG peritoneal transport from blood is weight limited (36000) and consequently, high levels in effluent should represent local production. The aim of this study has been to characterize peritoneal effluent BTG.12 patients, on CAPD 27 +/- 15 mon., 5 diabetics were studied. Previous peritonitis was 0.3 +/- 0.4 e/year. Determinations performed: Plasma (P) (BTG, T. protein, albumin, platelet count, Hcto and Fibrinogen) and Effluent (EF) (BTG, T. protein, Fibrinopeptide A, FDP, Fibrinolytic act., Fibrinogen, Plasminogen and Mitogenic induced capacity on Swiss 3T3 mice fibroblasts). To evaluate peritoneal function we used mass transfer coefficients (MTC) and net UF.R.:BTG levels: P 118 +/- 14 EF 34 +/- 14 ng/ml P/EF (%) 31 +/- 13 (6-54%). Regression analysis: P BTG did not show significant relationship with any of the studied parameters. EF BTG showed direct significant correlation (p less than 0.05) with Creatinine-MTC (r: 0.81) and EF Fibrinogen (0.68) and in the limit of significance with EF T. prot (0.57) and EF Mitogenicity (0.62). P/EF BTF showed significant correlation with creatinine-MTC (0.77). The analysis of these values grouping patients showed: diabetes has no influence on BTG values, hypertensive patients show higher P/EF BTG values than normotensive (39 +/- 9 vs 23 +/- 11%, p less than 0.05) and no influences of peritonitis or CAPD period were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Transport↗

Treatment of the anemia with human recombinant erythropoietin in CAPD patients.

Three homogenous groups of CAPD patients, all of them with plasma hemoglobin levels lower than 8 g/dl were studied. Group 1 included 8 patients who received EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2 included 7 patients treated with EPO by subcutaneous route but at doses of 2000 units twice a week. Group 3 was constituted by 4 patients receiving EPO by intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All patients showed an increase in hematocrit and Hb levels after three months of treatment, but the mean EPO dose was quite different comparing the groups, maintaining the reached levels at the 9th month; reticulocyte count increased only during the first month. The rest of clinical and biochemical parameters did not suffer any significant modifications. Our features showed a higher profit, that is, higher increase in Hb level with lower dose of EPO in the s.c. group in respect to i.p. group. Furthermore, we have registered a marked increase in the frequency of exogenous peritonitis in these particular patients while using i.p. EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an ideal way for this treatment, resulting in a more adequate profit ratio than that described in hemodialysis patients. The intraperitoneal route is more expensive and risky for the peritoneum, probably as a consequence of the increase of manipulations.

Adult↗