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Biomedical subjects

L Minetti

Publications and source records attributed to L Minetti.

At least 37 records · Page 2Linked to original sources

Predictability of low-density lipoprotein levels during apheretic treatment of hypercholesterolaemia.

The efficiency and efficacy of low-density lipoprotein (LDL) apheresis performed with a dextran sulphate cellulose (DSC) regenerating unit were tested in five familial hypercholesterolaemic patients. LDL apheresis was repeated four times at both bi-weekly and weekly intervals, processing one plasma volume each time. The efficiency of the procedure (i.e., the extent of lipoprotein removal) was nearly identical with both schedules. Efficacy parameters, i.e., decreases of plasma total and LDL cholesterol (TC and LDL-C) and apo B, were highly correlated (r greater than 0.96) with preapheresis levels, allowing an accurate prediction of the absolute lipid removal in the single individual. Plasma triglycerides, high-density lipoprotein cholesterol, apo A-I and apo A-II recovered rather rapidly, reaching 91-96% of the pre-apheresis values in 48 hours; the recovery of TC, LDL-C and apo B was much slower, with a relatively rapid early phase (80% recovery after about 7 days) followed by a successive slower rise. This pattern was highly reproducible in the single patient, allowing the definition of a simple mathematical model for an accurate (error less than 20%) prediction of the individual process. Based on this model one can design the treatment schedule necessary to maintain lipid levels within the desired range in the single individual. The hypolipidaemic efficacy of DSC apheresis appears, otherwise, not to be dependent upon the procedure per se, but on other individual factors, e.g. the amount of removable lipoproteins and the rate of lipid recovery; both can be predicted with sufficient accuracy.

Apolipoproteins↗

High-flux acetate haemodialysis: a single-centre experience.

One hundred haemodialysed patients have been treated for 4 h thrice weekly by acetate haemodialysis with high-flux dialysers (HAHD) 1.4-1.8 m2 and automated ultrafiltration control for 18.9 +/- 8.3 months. The aim of the study was to evaluate the efficacy of treatment as regards urea and beta 2-microglobulin removal, cardiovascular stability, acid-base balance and plasma Il-1 variations. Moreover medium-term observation of both lipid profile and basal beta 2-microglobulin concentrations were performed. With our current adequacy criteria (urea clearance greater than or equal to 120 l/week; KT/V greater than or equal to 1.2; beta 2-microglobulin removal greater than or equal to 150 mg/treatment), the occurrence of hypotension was 6% during 24,500 treatments. Cardiovascular stability was preserved by the increase of total peripheral resistances in response to cardiac output decrease. No disturbances of acid-base parameters were observed in spite of plasma acetate concentrations greater than 6 mmol/l. No variations of plasma Il-1 occurred during the session or 2 h later.

Acetates↗

Impaired efficacy of selective LDL-apheresis in primary biliary cirrhosis.

Low-density lipoprotein apheresis (LDL-apheresis) was done with either cascade filtration (DF) or dextran sulfate cellulose adsorption (DSC) in a patient with primary biliary cirrhosis who developed severe dyslipidemia associated with cholestasis and accumulation of lipoprotein-X (LP-X). The extracorporeal treatment was initially performed weekly, and resulted in a sharp drop in total cholesterol from 1038 to 430 mg/dl. During the next four months the patient was treated every 10-15 days, and pre-apheresis cholesterol levels were maintained between 438 and 505 mg/dl, until an orthotopic liver transplantation was successfully performed. With semi-selective DF a mean 47.1% of total cholesterol was removed per procedure compared to 30.0% with DSC, although the volume of treated plasma was 38.0 vs 49.9 ml/kg body weight. The changes in plasma cholesterol levels during DSC and DF showed that the kinetics of cholesterol removal were similar with both techniques, but the efficacy differed; DF removed both LDL and LP-X from plasma, whereas DSC selectively lowered the LDL content. Cascade filtration may therefore be considered as a first-choice treatment for patients with LP-X accumulation due to cholestasis.

Adult↗

Erythrocyte ferritin in patients on chronic hemodialysis treatment.

Serum ferritin (SF) and erythrocyte ferritin (EF) were evaluated in 35 patients on chronic hemodialysis treatment (CHD), in 45 healthy subjects and in 22 nonnephropathic females with iron deficiency anemia. Twenty-five CHD patients with basal SF less than 500 micrograms/l were treated orally with 200 mg of Fe2+ for 2 months and the positive (hemoglobin increase greater than 1 g/dl) or negative response to the therapy was correlated to the basal levels of SF and EF. Three groups of CHD patients could be defined on the basis of their basal SF levels (hypo-, normo- or hyperferritinemic). Nine patients with increased SF levels had also EF levels significantly higher than the other CHD patients and controls since they were probably iron-overloaded. In the other 2 groups of CHD patients, EF levels were significantly higher than in controls for each level of SF probably because of the reduced utilization of iron by uremic bone marrow. Among the 25 treated CHD patients, only 5 responded to the therapy: 3 were hypoferritinemic while the other 2 responders had basal SF within the normal range. Four hypoferritinemic patients did not respond to the therapy. Four out of five responders had the lowest EF levels among CHD patients. EF measurement could be an important and useful test in detecting the presence of an iron deficiency erythropoiesis in CHD patients.

Adult↗

Effects of acute administration of acetazolamide and frusemide on lithium clearance in humans.

To investigate the mechanism(s) of acute frusemide-induced increases in FELi, the effects of frusemide and acetazolamide, the carbonic anhydrase inhibiting agent, were evaluated in 19 healthy subjects either before or after pretreatment with acetazolamide or frusemide (11 subjects and eight subjects respectively). Acetazolamide pretreatment did not modify frusemide-induced increases in FELi (delta FLi 12.8 +/- 4.1% compared to 14.6 +/- 7.3%, P = NS); similarly, frusemide pretreatment did not modify acetazolamide-induced increases in FELi (delta FLi: 11.3 +/- 5.9% compared to 9.8 +/- 3.8%, P = NS). Acetazolamide-induced changes of FELi were correlated significantly with acetazolamide-induced increases of FEHCO3 (r = 0.61, P less than 0.05), FENa (r = 0.46, P less than 0.05) but not of FECl (r = 0.25, P = NS). On the other hand, frusemide-induced changes of FELi were correlated significantly with frusemide-induced increases of FENa (r = 0.62, P less than 0.005), FEC1 (r = 0.52, P less than 0.025) but not of FEHCO3 (r = 0.3, P = NS). Thus, frusemide effects on tubular lithium reabsorption are not related to carbonic anhydrase inhibition; furthermore, it appears that frusemide and acetazolamide affect lithium reabsorption by different and independent mechanism(s), possibly acting at different nephron site(s).

Acetazolamide↗

Adequacy of haemodiafiltration.

In this study we have evaluated the influence of blood and ultrafiltration flow rate on the performance of five different high-flux membrane dialysers during haemodiafiltration. On the basis of clearance data we optimised the haemodiafiltration schedule of six uraemic patients to maintain an adequate midweek blood urea nitrogen concentration, while reducing the treatment time from 285 +/- 23 min to 210 min. After a follow-up of 6 months, we observed no difference in the clinical tolerance or in the biochemical parameters, compared to those found during the preceding haemodialysis period. Our data confirm the suggestions of other authors that haemodiafiltration is an effective alternative to conventional haemodialysis.

Adult↗

Fluorocytometric analysis of anti-HLA class 2 autoantibodies in patients with lupus nephritis.

Systemic lupus erythematosus (SLE) patients are known to produce a variety of autoantibodies (AAb), some of which may be directed against immunocompetent cells. Anti-B cell autoimmunity may encompass reactivity against HLA-class 2 molecules, which are also expressed on kidney tissue. We studied 15 patients with moderate to severe renal involvement and 5 lupus patients with no clinical renal disease, in order to detect the presence of anti-HLA class 2 AAb. Flow cytometry was employed in an inhibitory assay using patient sera, autologous cells and two anti-class 2 monoclonals, to establish the specificity of anti-B cell AAb. Seven out of 15 nephritis patients had detectable anti-class 2 AAb with an epitopic heterogeneity, as demonstrated by different degrees of inhibition on the binding of non-overlapping monoclonals. The specificity of the reaction was confirmed by the lack of inhibition of non-class 2 antibody binding. The presence of such AAb was not correlated with disease activity but with the presence of a diffuse proliferative glomerulonephritis on renal biopsy. Anti-class 2 AAb may be a marker of SLE diffuse proliferative nephritis.

Adolescent↗

Alterations in the HDL system after rapid plasma cholesterol reduction by LDL-apheresis.

Changes in high density lipoprotein (HDL) subfraction structure and composition were analyzed during and after extracorporeal removal of apo B containing lipoproteins in seven familial hypercholesterolemic (FH) patients. After the apheretic procedure, carried out with dextran-sulfate-cellulose columns, the plasma levels of very low density lipoproteins (VLDL), low density lipoproteins (LDL), and HDL decreased by 72%, 50%, and 19%, respectively. The free cholesterol to esterified cholesterol ratio in plasma increased, with a 26% drop in the lecithin:cholesterol acyl transferase (LCAT) activity. In the ensuing 24 hours, VLDL, HDL, and LCAT activity approached the pretreatment levels. During this phase, possibly as a consequence of increased cholesterol esterification and exchange of cholesteryl esters for triglycerides between HDL and VLDL, HDL2a particles were detected in plasma. However, these metabolic changes did not result in clearcut modifications in the HDL2-HDL3 subfraction distribution. These findings clearly demonstrate that rapid changes in the plasma VLDL-LDL levels affect several processes involved in the HDL metabolism, but confirm that the HDL system, in spite of a considerable plasticity, displays a marked stability of the HDL2-HDL3 subfraction distribution.

Adolescent↗

The Milan clinical trial with cyclosporine in cadaveric renal transplantation. A three-year follow-up.

Between February and November 1983, 108 recipients of cadaveric renal transplants entered a randomized multicenter trial and were treated either with cyclosporine (CsA) and prednisone (n = 55) or with conventional treatment based on azathioprine (Aza) and glucocorticoids (n = 53). The graft survival probability at 3 years was 76% for CsA patients and 48% for Aza patients (P less than 0.001). The cumulative number of acute rejections was significantly lower in the CsA group (32 vs. 104, P less than 0.001). Incidence of early posttransplant anuria was similar in both groups and did not affect renal function after three years. Nephrotoxicity in CsA patients, when present, was handled by reducing the dose of CsA, but in 12/55 patients a change to conventional therapy was thought to be necessary. However, in this group of 12, one patient lost the allograft because of irreversible rejection and one patient died 14 months later because of an infection. Mean creatinine clearance after three years was significantly lower in the CsA patients (54.7 +/- 2.6 ml/min) than in Aza patients, (67.2 +/- 4.9 ml/min, P less than 0.05). Considering only patients with grafts functioning after three years and still on the original randomized therapy, the mean creatinine clearance was similarly and significantly decreased from 1 to 3 years in both groups. There were no significant differences in occurrence of severe infections. Side effects such as hypertension, hypertrichosis, tremor and gum hyperplasia were more frequent in CsA patients.

Acute Kidney Injury↗

Selective and semiselective low-density lipoprotein apheresis in familial hypercholesterolemia.

Seven patients with familial hypercholesterolemia were treated fortnightly for 3 months by selective low-density lipoprotein apheresis with dextran-sulfate cellulose column (DSC). Subsequently, 4 of them were treated with semiselective double filtration. No cholesterol-lowering drugs were given. Plasma processed ranged from 39 to 58 ml/kg body weight/procedure. Fractional removals from plasma filtrate at the secondary treatment (adsorption or fractionation) for total cholesterol, high-density lipoprotein cholesterol, and albumin, respectively, were 0.84, 0.06, and 0.03 with DSC and 0.74, 0.47 and 0.35 with double filtration. Postapheresis reductions of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were 57, 15, and 59% with DSC and 47,35, and 48% with double filtration. Both methods are suitable for clinical use, but with a 15-day treatment schedule, lowering circulating lipid fraction levels are maintained with DSC.

Adolescent↗