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Biomedical subjects

G Rifle

Publications and source records attributed to G Rifle.

At least 37 records · Page 2Linked to original sources

Must erythropoietin be injected by the subcutaneous route for every hemodialyzed patient?

A multicenter, prospective, and controlled trial was performed to evaluate the efficacy and tolerance of intravenous (i.v.) and subcutaneous (s.c.) recombinant erythropoietin (rH-EPO) administration routes in 49 long-term hemodialyzed patients on maintenance phase of treatment, to determine the usefulness of replacing i.v. route by SC route in all of them. Each of these patients had already been treated with rH-EPO by the i.v. route for at least 6 months and included in the protocol on stabilized consumption phase. We arbitrarily chose three strata according to previous needs: Stratum A (> 150 U/kg/week) for eight patients, Stratum B (100 to 150 U/kg/week) for 12 patients, and Stratum C (< 100 U/kg/week) for 29 patients. In each stratum, the further treatment route (i.v. or s.c.) was randomized. Finally, 25 patients continued with i.v. route, and the other 24 changed to the s.c. route. The objective was to maintain a stable hemoglobin level, ranging from 9 to 10 g/dL. Tolerance and consumption in each group (i.v. and s.c.) were compared 4 months later. Globally, for an identical efficacy, rH-EPO needs were lesser using s.c. route (84 U/kg/week) than i.v. route (112 U/kg/week) (P = 0.02). However, when the strata were studied, it transpires that this benefit existed only for consumers having the highest needs (Stratum A) and not for the others. With regard to tolerance, only thrombotic events might be less frequent by using s.c. route, but the significance threshold is not reached (P = 0.09). Thus, replacing i.v. route by SC route, especially in high consumers, reduces the cost of treatment by rH-EPO. This benefit might be dependent on previous needs.

Adult↗

Combined chemotherapy and radiotherapy for esophageal carcinoma in a hemodialyzed patient. Long-term survival.

The use of antimitotic chemotherapy in hemodialysis patients is not yet well codified, and each individual decision remains difficult. We report the case of a 68-year-old hemodialyzed man who developed a squamous cell carcinoma of the upper third of the esophagus. Necessarily disabling surgery was rejected, and three courses of combined radio- and chemotherapy with 5-fluorouracil and cis-platinum were performed without decreasing standard doses. The percentage of drugs removed during hemodialysis sessions was low; peak and residual platinum plasma concentrations were only slightly above those observed in normal renal function patients. The treatment was perfectly well tolerated, and tumor response was satisfactory without any relapse for 3 years. This observation suggests that hemodialysis patients could benefit from such 'full therapies', if necessary, without major adverse effects.

Aged↗

[B lymphocytes of patients with complete IgA deficiency secrete IgA in response to interleukin 10].

We have previously shown that human B lymphocytes cultured in the CD40 system, composed of an anti-CD40 mAb presented by a CD32-transfected fibroblastic cell line, proliferate but do not secrete immunoglobulins (Igs). However, the addition of particles of Staphylococcus aureus Cowan (SAC) induces B cell to secrete considerable amounts of Igs even in the absence of exogenous cytokines (CD40/SAC system). Additionally, B lymphocytes cultured in the CD40 system in the presence of human IL-10, produce high level of IgM, IgG and IgA, which are further increased by addition of SAC. Here, we have studied the capacity of peripheral blood lymphocytes from patients with IgA deficiency (IgA-D) to secrete Igs, particularly IgA after CD40 triggering. Peripheral blood mononuclear cells (PBMNC) from IgA-D patients cultured in the CD40/SAC system produced IgM and IgG, but no IgA. The addition of IL-10 to the cultures, enhanced the production of IgM and IgG and most strikingly induced the production of high amounts of IgA. The addition of IL-10 to PBMNC from IgA-D patients activated through CD40 alone resulted in the production of IgA. Thus, IL-10 can remove the block in B cell differentiation and allows B cells from IgA-D patients to differentiate into IgA secreting cells.

Adult↗

Composition and immunoreactivity of serum low density lipoproteins (LDL) before and after LDL-apheresis on dextran sulfate-cellulose columns.

The changes in low density lipoprotein (LDL) composition and immunoreactivity occurring after LDL-apheresis on dextran sulfate-cellulose columns (DSC) were investigated in 4 hypercholesterolemic patients. After apheretic treatment, serum levels of total cholesterol, triglycerides and apolipoprotein B (apo B) were decreased by 63, 80 and 65%, respectively, whereas the high density lipoprotein (HDL)-cholesterol remained unchanged. At the end of apheresis, LDL contained less triglycerides, more phospholipids and apo E and the ratio of LDL core lipid components, cholesteryl esters and triglycerides, to LDL surface lipid components, unesterified cholesterol and phospholipids was significantly lower. The post-apheretic LDL were characterized by the presence of subfractions slightly larger than those observed in the pre-apheretic LDL. The modifications of the composition and size of LDL after apheresis were accompanied by a relative increase in the immunoreactivity of 4G3 epitope, an apo B epitope located near the LDL-receptor binding site, with no change in the affinity of 1D1, an apo B epitope located in the amino-terminal region of the molecule. The changes in LDL composition, size and immunoreactivity following apheresis, suggest that postapheresis LDL could contain newly synthesized LDL, different from mature LDL. Thus, LDL-apheresis treatment could provide the opportunity to study the structural change of LDL during intravascular metabolism.

Antibodies, Monoclonal↗

Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: changes in patient hemostasis and low molecular weight heparin benefit.

Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate columns (DSC) leads to hemostasis alterations with prolonged activated partial thromboplastin time (APTT) of more than 120 seconds. In order to explain this hypocoagulability, we studied hemostasis parameters both in patients and in the extracorporeal circulation (ECC). Hemostasis changes are first related to unfractionated heparin (UFH)--needed to avoid circuit coagulation--which leads to high residual heparinemia in the patient (more than 3 times the recommended level for therapeutic use). Second, the hypocoagulability is induced by a coagulation factor decrease (primarily factors V, VIII, and X) mainly due to an adsorption mechanism on dextran sulfate. Studies on samples from column inflow, outflow, and eluate confirm this mechanism. Low molecular weight heparin (LMWH) can be used in LDL apheresis on DSC without major changes in lipid removal or coagulation factors compared to UFH. The benefit of using LMWH is to reduce residual heparinemia into the therapeutic range.

Adult↗

Piridoxilate-induced oxalate nephropathy can lead to end-stage renal failure.

A 71-year-old woman was admitted with end-stage renal failure and histological evidence of oxalosis. This case of diffuse renal tubular crystal calcium oxalate deposits seems to be induced by long-term piridoxilate therapy (10 years) or simultaneous intake of both piridoxilate and vitamin C (500 mg/day for 6 months), since no other cause of secondary oxalosis could be found. So, it seems necessary to monitor the serum creatinine level, especially in the elderly, during piridoxilate therapy and to avoid high vitamin C intakes in patients under such treatment to prevent development of renal insufficiency.

Aged↗

[Peritoneal tuberculosis and continuous ambulatory peritoneal dialysis].

Depressed immunity in uremic patients increases by ten the risk of tuberculosis. In such patients, 40% of tuberculosis manifestations are extrapulmonary, and peritoneum is involved in about 6% of the cases. Seventeen cases of peritoneal tuberculosis have been so far reported in CAPD patients, and we add a new case. The prognosis of the disease is severe since 8 patients died. Three deaths out of 8 are directly linked to tuberculosis. Indeed, peritoneal tuberculosis diagnosis is hard and often late, at least for two main reasons: at first, it can be difficult to exclude the other causes of lymphocytic peritonitis (viral, fungal, bacterial, etc.), secondly, growth of mycobacteria in dialysate effluent cultures is late and inconstant. Omental biopsy in lymphocytic peritonitis of unknown origin could be of great value for an early diagnosis. Despite the adaptation of antituberculous drugs doses, side-effects are not so rare: optical neuritis and liver toxicity in our case. In spite of ultrafiltration loss, stopping CAPD is not always necessary, as in the reported case.

Aged↗

Erythrocytosis in renal allograft recipients. Benefit of staggered venous erythropoietin measurements.

Two adult renal allograft recipients experienced erythrocytosis--one in acute form--within 3 months of grafting. Involvement of well functioning transplanted kidneys was unlikely whereas staggered erythropoietin measurements detected a high gradient in front of venous remnant kidneys. Because of these results bilateral nephrectomy was performed, which cured polycythaemia. Multiple events leading to polycythaemia after renal transplantation are reviewed and diagnosis and therapeutic schedules are proposed.

Adult↗

Anti-major histocompatibility complex antibody removal assay in a swine model.

A swine model of anti-MHC (SLA) immunization by skin grafting was established with the aim of removing preformed anti-MHC antibodies and preventing their resynthesis, in a situation close to that of hyperimmunization in humans. Plasma exchange therapy with or without associated immunosuppressive therapy was used. The feasibility of this animal model in terms of anti-MHC immunization and its therapeutic management have been proven. However, frequent early deaths of animals still mar the experimental protocol. Synchronization of plasma exchange and subsequent cyclophosphamide pulses seemed to abolish the antibody rebound phenomenon and cause marked drop of anti-MHC antibodies. Restimulation by a new skin graft is responsible for an intense polyclonal antibody stimulation, which suggests that we have to be careful in grafting patients with positive historical crossmatches and negative current ones.

Animals↗

[Extracapillary glomerulonephritis].

Extracapillary glomerulonephritis is characterized by cell proliferation within the urinary space of 50% of the glomeruli, where it covers more than 50% of the filtration chamber, associated with acute or rapidly progressive renal failure. It is a model of curable human renal failure. Extracapillary cell proliferation is an elementary lesion which may complicate any glomerulopathy and many systemic diseases, or appear to be primary. Its clinical manifestations may be extremely marked in some systemic diseases, but they may be minimal and delay a diagnosis which rests entirely on renal biopsy. An early renal biopsy commands the prognosis which depends on the finding of young cellular crescents that respond to treatment before fibrous transformation sets in. Experiments in animals and man suggest that cell proliferation results from rupture of the capillary walls and from the production of polymerized fibrin in the urinary space. This is followed by a cascade of reactions, with increased synthesis of local mediators issued from resident and invasive glomerular cells. These data constitute the basis of modern therapies, such as emboli of methylprednisolone, plasma exchange and immunodepressive drugs, aimed not only at a possible aetiological treatment but also at the cell proliferation itself. The use of such treatments, whose risks must be carefully weighted, has transformed the prognosis of extracapillary glomerulonephritis, since almost 50% of the cases the kidneys survive at 5 years.

Glomerulonephritis, Membranoproliferative↗