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Biomedical subjects

A L de Francisco

Publications and source records attributed to A L de Francisco.

At least 19 recordsLinked to original sources
PubMed2000

Removal of xenoreactive antibodies by protein-A immunoadsorption: experience in 22 patients.

The presence of naturally occurring anti-Galalpha1-3Gal (antialphaGal) Ab in human serum is believed to be a major factor in the pathogenesis of hyperacute rejection of discordant organ xenografts such as the pig-to-human combination. Galalpha1-3Gal epitopes are expressed on pig tissues and the binding of anti-Galalpha1-3Gal leads to endothelial cell activation and complement-mediated hyperacute graft rejection. Several strategies have been suggested in donor animals or in the xenograft recipient to overcome the anti-alphaGal barrier. Protein-A immunoadsorption (PAIA) was developed for the in vivo removal of circulating Ab and it has been shown to be effective in cases where pathogenic auto or alloAb are present. The aim of our study was to analyze the effect of PAIA on total and xenoreactive serum anti-alphaGal immunoglobulin levels in a group of patients treated with this technique for different diseases. After three consecutive sessions of PAIA, total and xenoreactive IgG and IgM immunoglobulin levels were decreased by more than 50% of pre-treatment levels. So we conclude that PAIA is an effective method to significantly reduce circulating Ab, including xenogeneic IgM and IgG Ab. This mode of therapy might be considered as a tool to overcome hyperacute xenograft rejection. PAIA combined with other therapeutic approaches may well protect the xenograft.

Adolescent↗
PubMed2000

Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy.

BACKGROUND: Chronic transplant nephropathy remains the major cause of graft loss after the first year post transplant, with the exception of death with functioning graft. The histological hallmark of chronic kidney rejection is progressive fibrosis in which extracellular matrix turnover plays an important role. This turnover is regulated by several systems of connective tissue proteases, the matrix metalloproteinases family being one of them. Every metalloproteinase exerts a different function over extracellular matrix proteins and can contribute to the pathogenesis of several diseases, such as rheumatoid arthritis and glomerulonephritis. The role of metalloproteinases in the pathogenesis of chronic transplant nephropathy and in kidney transplantation has not yet been addressed. METHODS: We measured the serum levels of proMMP-1, proMMP-2 and proMMP-3 by ELISA in 40 patients with chronic transplant nephropathy, 30 with acute rejection, 30 with stable graft function for a time equivalent to chronic transplant nephropathy, 30 with stable graft function for a time equivalent to acute rejection, and 30 healthy age-paired blood donors. RESULTS: Serum proMMP-2 and proMMP-3 were significantly higher in patients with chronic transplant nephropathy than in patients with acute rejection, stable graft function and healthy donors. The most striking finding was the significant positive correlation observed between serum levels of proMMP-3 and serum creatinine, and between circulating levels of proMMP-2 and proteinuria. Serum concentration of proMMP-1 was increased in patients with acute rejection compared with those with stable graft function and healthy donors. CONCLUSIONS: Serum proMMP-2 and proMMP-3 reflect the changes of glomerular and interstitial extracellular matrix in chronic transplant nephropathy, suggesting that they could play a role in the pathogenesis of this condition. Acute rejection is associated with increased levels of proMMP-1, which could be a reflection of the stimulation induced by a number of inflammatory cytokines produced in such a process.

Acute Disease↗
PubMed2000

B lymphopenia in uremia is related to an accelerated in vitro apoptosis and dysregulation of Bcl-2.

BACKGROUND: Lymphopenia has been described in patients with chronic renal failure (CRF). It is postulated that the decline in lymphocytes is due to accelerated apoptosis. We investigated whether dysregulation of programmed cell death plays a role in the immunodeficiency described in CRF. METHODS: Peripheral blood lymphocytes (PBL) from pre-dialysis uraemic patients (nHD) and haemodialysed patients (HD) were cultured with no stimulus for 96 h. Apoptosis of lymphocytes was measured by propidium iodide staining and flow cytometry. Expression of Fas and Bcl-2 was also analysed by flow cytometry. RESULTS: Peripheral blood B cells were significantly lower in pre-dialysis and haemodialysis uraemic patients compared to control. Lymphocytes from both groups of patients had a higher rate of apoptosis in vitro than those from healthy controls. This effect was more pronounced in B lymphocytes and a significant correlation between the B lymphopenia and the percentage of apoptotic B cells after 48 h of culture without stimulus was observed. The increased lymphocyte apoptosis in CRF was accompanied by a significantly lower in vitro Bcl-2 expression. However, Fas did not seem to play a role in spontaneous lymphocyte apoptosis in end-stage renal disease. CONCLUSIONS: Our data indicate that B lymphopenia in CRF may be partially attributed to an increased susceptibility to cell death by apoptosis that is associated with a decreased expression of Bcl-2.

Adolescent↗
PubMed2000

Hemodiafiltration with on-line endogenous reinfusion.

Paired filtration dialysis is a modified form of hemodiafiltration with a double-chamber hollow fiber. Convection is separated from diffusion, eliminating the potential risk of backfiltration (which can contain endotoxin or cytokine-inducing substances). The regeneration of high volumes of plasma ultrafiltrate obtained in the first filter allows a large plasma volume to be treated, and at the same time enables the return of many beneficial substances such as hormones, small peptides and many vitamins. Ultrafiltrate is regenerated with a charcoal-resin device and reinfused to the patient. Hemodiafiltration with on-line endogenous reinfusion is an easy and safe procedure. In addition, the method avoids risks associated with exogenous fluid infusion (endotoxin, pyrogens), allows exchange at no extra costs of large volumes of fluids and reduction in storage of fluid bags. Clinical advantages also include infusion of physiological fluid containing bicarbonate and calcium, good clinical tolerance and cardiovascular stability.

Adsorption↗
PubMed1998

Effect of serum phosphate on parathyroid hormone secretion during hemodialysis.

BACKGROUND: Recent studies have demonstrated that a high concentration of phosphate directly stimulates parathyroid hormone (PTH) secretion. High serum levels of phosphate are usually observed in patients with end-stage renal disease. The aim of the present study was to evaluate whether serum phosphate concentration had an acute effect on PTH secretion in hemodialysis patients. The levels of serum phosphate were manipulated during the hemodialysis session by using a phosphate free dialysate or a dialysate with a high content of phosphate. METHODS: Ten stable hemodialysis patients with PTH values above 300 pg/ml were included in the study. A PTH-calcium curve was obtained during both high phosphate and phosphate free hemodialysis. RESULTS: The serum phosphate concentration remained high (2.17 +/- 0.18 mM) throughout the high phosphate hemodialysis and decreased progressively to normal levels (1.02 +/- 0.06 mM) during the phosphate free hemodialysis. The serum PTH levels at maximal inhibition by hypercalcemia (minimal PTH) were greater during the high phosphate than the phosphate free hemodialysis (413 +/- 79 vs. 318 +/- 76 pg/ml, P < 0.003). In all patients the values of minimum PTH were greater during the high phosphorus than the phosphorus free hemodialysis. The values of maximally stimulated PTH during hypocalcemia and the set point of the PTH-calcium curve were similar during the high phosphate and the phosphate free hemodialysis. CONCLUSION: The maintenance of high serum phosphorus levels during hemodialysis prevented, in part, the inhibition of PTH secretion by calcium, which strongly suggests that in hemodialysis patients high serum phosphate contributes directly to the elevation of PTH levels despite normal or high serum calcium concentration.

Adult↗
PubMed1998

1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with renal insufficiency.

A reduced expression of the vitamin D receptor (VDR) in parathyroid glands of uremic animals and humans has been observed. Similar results have been obtained by our own group in peripheral blood mononuclear cells (PBMC) from patients with secondary hyperparathyroidism to chronic renal failure. However, the reasons for these changes are not clear. In the present study, we have investigated the specific uptake of [3H]1,25(OH)2D3 by PBMC of 11 women with advanced chronic renal failure (A-CRF), 6 women with mild-moderate renal insufficiency (M-CRF), and 23 healthy women. The mean dissociation constant (KD) was similar in both groups of patients and in healthy women (A-CRF: 0.7 +/- 0.5 x 10(-10) M; M-CRF: 1.1 +/- 0.9 x 10(-10) M; controls: 1.0 +/- 0.6 x 10(-10) M). However, VDR concentration was significantly decreased in A-CRF (0.8 +/- 0.5 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls, p < 0.001), whereas no changes were seen in M-CRF (1.7 +/- 0.7 fmol/10(7) cells vs. 2.3 +/- 0.9 fmol/10(7) cells in controls). No correlation was seen between VDR and serum calcitriol or PTH levels, when considering both groups of patients together or separately. Conversely, a significant negative correlation was found between VDR and serum creatinine values when A-CRF and M-CRF were considered altogether (r = -0.63; p < 0.01). Treatment with two different schedules of oral calcitriol (five patients with 0.5 microgram/day for 1 month and four patients with 2 micrograms/day for 7 days) did not change VDR concentrations. We conclude that the low levels of serum 1,25(OH)2D3 of uremia are not responsible for the decrease in VDR concentration found in these patients.

Adult↗
PubMed1997

Haemodiafiltration with sorbent-regenerated ultrafiltrate as replacement fluid: a multicenter study.

BACKGROUND: Uncoated adsorbent charcoal may regenerate the ultrafiltrate suggesting its use as an endogenous substitution fluid. The objective of this study was to assess the safety and the long-term clinical results. METHODS: Thirty-three chronic uraemic patients were dialysed for 1 year using two haemodialysers in series in order to separate convection from diffusion. At the outflow of the convective haemofilter, a cartridge containing 130 g of uncoated charcoal was inserted. The regenerated ultrafiltrate was then infused at the entrance of the diffusive dialyser. Ex vivo and in vitro studies were performed to analyse the adsorption characteristics and the release of aluminium, other trace elements, and microparticles. RESULTS: Passage through the charcoal left urea, phosphate, potassium, calcium, and bicarbonate concentrations unchanged. Creatinine, uric acid and beta 2-microglobulin were almost completely absorbed by the charcoal. Aluminium release was dependent upon time of storage, as inferred from studies on inter-lot variability. Washing with bicarbonate buffer (pH 7.0) allowed reduction of aluminium levels to within the pharmacopoeia requirements for intravenous fluids. No significant pre- or post-charcoal differences were observed for several trace elements such as manganese, selenium, arsenic, cadmium, mercury, lead, chromium and zinc. Copper was completely retained in the charcoal. Regenerated ultrafiltrate infused at the entrance of the diffusive dialyser was free of microparticles, bacteria, and endotoxin. Clinical tolerance was excellent and blood pressure control satisfactory. A significant decrease in serum values of beta 2-microglobulin was observed at 6 and 12 months of treatment. CONCLUSIONS: Reinfusion of ultrafiltrate through an uncoated charcoal cartridge proved to be a safe, well-tolerated and simple technique. Further potential benefits of regenerated ultrafiltrate may also include the maintenance of acid-base balance with reinfusion of endogenous bicarbonate.

Adult↗
PubMed1995

Circulating adhesion molecules during kidney allograft rejection.

Adhesion molecules appear on leukocytes and endothelial cells mediating the localization and migration of leukocytes to sites of inflammation. Rejecting kidney grafts have shown an increased expression of these molecules. Recent reports have detected in serum soluble forms of adhesion molecules that could play a role in regulating inflammation. We have measured by ELISA the circulating serum levels of ICAM-1, VCAM-1 and E-selectin in: 23 controls, 33 chronic renal failure patients (CRF), 20 hemodialysis patients (HD), 17 samples from 6 patients with stable kidney graft function (STx), 25 samples from 8 patients with steroid-responsive rejection proven by biopsy, and 28 samples from 9 patients with steroid-resistant rejection and good response to OKT3. There was not a rise in cICAM-1 or cE-selectin levels during rejection compared with the steady phase before and after rejection. In the case of cVCAM-1, only the OKT3 group showed increased rejection levels (P < 0.05) that were maintained after rejection. For ICAM-1, CRF and HD groups had higher levels than the remaining groups. cVCAM-1 levels were elevated in all groups when compared with control, furthermore, OKT3 and HD groups had higher levels than the STx, CRF, or steroid-responsive groups. For cE-selectin, we only found differences between the CRF and both rejection groups. Serum creatinine correlated significantly with c-ICAM-1 and cVCAM-1 R = 0.30 and R = 0.22), but not with cE-selectin. We conclude that soluble adhesion molecules levels are not valuable markers for rejection. Patients with chronic renal failure have increased levels of adhesion molecules, which could reflect an impaired elimination.

Antibodies, Monoclonal↗
PubMed1994

1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism.

A decreased number of calcitriol (1,25(OH)2D3) receptors has been observed in parathyroid glands of uremic animals. In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism. Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of 3H-labelled 1,25(OH)2D3 in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women. The median dissociation constant (Kd) was similar in all three groups of patients and in healthy women (mean +/- S.D. (range): PHP, 1.2 +/- 1.0 (0.2-4) x 10(-10) M; SH, 0.6 +/- 0.4 (0.2-1.2) x 10(-10) M; RT, 1.1 +/- 0.5 (0.4-1.9) x 10(-10) M; controls, 1.0 +/- 0.6 (0.3-2.6) x 10(-10) M). However, the maximal binding capacity (Nmax) was significantly enhanced in PHP (3.9 +/- 1.9 (1.3-7.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0006) and decreased in SH (0.8 +/- 0.5 (0.2-1.6) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 +/- 0.7 (1.2-3.3) fmol/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls). In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal. Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.

Adult↗
PubMed1993

Long-term outcome in renal transplantation with terminal cutaneous ureterostomy.

We have reviewed the complications and follow-up in 6 patients who underwent kidney transplantation with cutaneous ureterostomy. Four patients had tuberculosis, 1 myelomeningocele and another congenital stenosis of the posterior urethra. Cutaneous ureterostomy was performed by suturing the edges of the distal end of the ureter to the skin. The mean follow-up was 40.6 months (range 2-105). The patient and graft survival rates were 83.3% and 66.6% respectively during the 249 months of total follow-up. Significant bacteriuria and leukocyturia were constantly present and the incidence of urinary infection was 3.1 episodes/patient/year. The early complications of the stoma were partial necrosis in 1 case and haematoma in another. The most frequent late complication was stomal stenosis requiring periodic dilatation. A plasma creatinine of 61.88 to 114.92 mumol/l reflected good long-term graft function in the remaining patients. Terminal cutaneous ureterostomy is a simple technique with good long-term results.

Adolescent↗
PubMed1993

Vitamin D therapy modulates cytokine secretion in patients with renal failure.

In studies in vitro calcitriol (1,25-dihydroxyvitamin D3) inhibits lymphocyte proliferation and modulates several monocyte functions, including the secretion of prostaglandins and monokines. However its effects on monokine production in vivo are not known. Therefore we studied the secretion of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) from 7 patients on periodic hemodialysis, before and after oral treatment with calcitriol (0.5 microgram daily) for 1 month. Calcitriol therapy resulted in significant increases in the phorbol myristate acetate (PMA)-induced secretion of IL-1 and IL-6 (p = 0.04 and 0.03, respectively). This was a transient effect, observable by day 7 of therapy, but no longer evident by day 30. However, calcitriol induced a progressive reduction of TNF secretion (down to 53% of control values by day 30, p = 0.02). There were no correlations between the individual changes in calcium/PTH and cytokine release. These results show that doses of calcitriol within the therapeutic range induce marked changes in cytokine secretion by PBMC from uremic patients.

Adult↗