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Biomedical subjects

L Mosconi

Publications and source records attributed to L Mosconi.

At least 37 records · Page 2Linked to original sources

Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate.

Renal clearance of inulin is the best available indicator of GFR but cannot be used routinely for clinical purposes and is also difficult to perform for clinical investigation when repeated measurements are required. The aim of this study was to find a reliable alternative to inulin clearance that would allow one to avoid the use of radioactivity and problems related to the continuous infusion of the marker. The plasma clearance of unlabeled iohexol, a nonionic contrast agent, was used. Forty-one patients (creatinine clearance 6 to 160 mL/min per 1.73 m2) underwent simultaneous measurements of renal clearance of inulin and plasma clearance of iohexol. Iohexol was given as a single iv dose, and blood samples were drawn up to 600 min after the administration. Iohexol concentrations (by HPLC) were analyzed by a two-compartment, open-model system. A highly significant correlation between the plasma clearance of iohexol and the renal clearance of inulin over a wide range of GFR values was found. By analyzing the data with a simplified method that uses a one-compartment model corrected with the Bröchner-Mortensen formula, an excellent correlation with the inulin clearance was also observed. When only patients with moderate to severe renal failure were considered, a significant correlation between the two methods was found. A further comparison between GFR determined with iohexol and iopromide, a new low-osmolarity, low-viscosity contrast medium, was also performed in a subgroup of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Long-term treatment with either enalapril or nitrendipine stabilizes albuminuria and increases glomerular filtration rate in non-insulin-dependent diabetic patients.

The effect of short- (98 days) and long-term (1 year) treatment with nitrendipine (10 to 40 mg/d) and enalapril (5 to 20 mg/d) on kidney function was studied prospectively in a parallel group design in 16 microalbuminuric non-insulin-dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. At the end of the short-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 83.5 +/- 3.5 mm Hg (P < 0.001) in the nitrendipine group and from 96.7 +/- 2.5 to 86.7 +/- 5.6 mm Hg (P < 0.001) in the enalapril group. Both overnight urinary albumin excretion rate and albumin fractional clearance tended to increase in the nitrendipine group and to decrease in the enalapril group, whereas the glomerular filtration rate and the renal plasma flow were similar to baseline in both study groups. At the end of the long-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 86.0 +/- 6 mm Hg (P < 0.005) in the nitrendipine group and from 96.7 +/- 2.1 to 90.8 +/- 4.3 mm Hg (P < 0.05) in the enalapril group. Overnight urinary albumin excretion and albumin fractional clearance were similar to baseline in both study groups. The glomerular filtration rate significantly increased from 70.2 +/- 14.2 to 96.8 +/- 20.4 (P < 0.05) in the nitrendipine group and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) in the enalapril group. The renal plasma flow also significantly increased from 456.6 +/- 165.3 to 597.2 +/- 178.9 (P < 0.01) in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Immune hemolytic anemia and acute kidney failure due to rifampicin].

A case is reported of hemolytic anemia following rifampicin administration and complicated by acute renal failure. Furthermore clotting analyses suggested a slight disseminated intravascular coagulation, very likely activated by hemolysis products. Both hemolysis and renal function impairment subsided spontaneously, after the sole withdrawal of rifampin. Direct antiglobulin test became negative within a few days, while an indirect Coomb's test was demonstrated persistently with the patient's serum using red blood cells sensitized in vitro with the drug. Otherwise from all reports in the literature, the patient developed an acute hemolytic anemia while on daily therapy and as many as twenty years after a previous treatment with rifampicin. Mechanisms of drug-induced immune hemolytic anemia and acute nephropathy are discussed (formation of drug-antibody complexes, which adhere on the red blood cells surface and are able to fix complement and induce intravascular hemolysis; tubular necrosis due to hemoglobinuria or immuno-mediated interstitial nephritis).

Acute Kidney Injury↗

Prognosis of untreated patients with idiopathic membranous nephropathy.

BACKGROUND: Defining the most appropriate treatment for patients with idiopathic membranous nephropathy is a matter of controversy. The course of the disorder is often benign, and the immunosuppressive regimens used in some patients have uncertain benefits and substantial risks. We studied the natural history of idiopathic membranous nephropathy in patients who received only symptomatic therapy. METHODS: We prospectively studied 100 consecutive patients (68 men and 32 women; mean [+/- SD] age, 51 +/- 17 years) with biopsy-proved idiopathic membranous nephropathy. The patients received diuretic or antihypertensive drugs as needed, but no glucocorticoid or immunosuppressive drugs. We examined the patients and measured their urinary protein excretion and serum creatinine concentrations every 6 months for a mean of 52 months. RESULTS: Twenty-four (65 percent) of the 37 patients followed for at least five years had complete or partial remission of proteinuria; in 6 others (16 percent), end-stage renal disease developed, and they required dialysis. As calculated by the Kaplan-Meier method, the estimated probability (+/- the standard error of the estimate) of retaining adequate kidney function was 88 +/- 5 percent after five years and 73 +/- 7 percent after eight years. The prognosis was poorer in men and in patients over 50 years of age, but not in patients with the nephrotic syndrome, hypertension, or hypercholesterolemia. CONCLUSIONS: Most untreated patients with idiopathic membranous nephropathy maintain renal function for prolonged periods and are likely to have spontaneous remission. These results do not support the use of glucocorticoids and immunosuppressive drugs in patients with idiopathic membranous nephropathy.

Adult↗

Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion.

Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular filtration rate (GFR) that results from a form of acute reversible hypoperfusion. We sought to determine whether the Ca2+ channel blocker, lacidipine, prevented CsA-associated renal hypoperfusion in these patients. Parallel studies on CsA pharmacokinetics, renal function parameters (GFR and RPF), as inulin and p-aminohippurate (PAH) clearances, respectively, and urinary excretion of the vasoconstrictor endothelin in 10 consecutive renal transplant patients given CsA as a part of their immunosuppressive therapy were performed. Patients were studied at different time intervals after CsA alone, CsA and lacidipine (4 mg/day), and again seven days after lacidipine withdrawal. In all patients basal RPF and GFR declined on average 51% (139.3 +/- 20.7 ml/min/1.73 m2) and 50% (32.5 +/- 5.8 ml/min/1.73 m2), respectively, two to four hours after maximum blood CsA concentration was reached. As blood levels of CsA returned to trough, both parameters progressively increased to baseline. Lacidipine administration completely prevented the fall in RPF (pre-CsA: 277.1 +/- 23.6; 6 hr post-CsA: 304.5 +/- 31.1 ml/min/1.73 m2) and GFR (pre-CsA: 66.6 +/- 8.1; 6 hr post-CsA: 70.1 +/- 9.8 ml/min/1.73 m2). When lacidipine treatment was discontinued the abnormal RPF and GFR response to CsA administration was again observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Daily renal hypoperfusion induced by cyclosporine in patients with renal transplantation.

A variety of side effects are associated with the use of cyclosporine, the most relevant of which remains the renal toxicity. We did parallel studies on cyclosporine pharmacokinetics and renal function in patients who had a recent kidney transplant and were given cyclosporine as a part of their immunosuppressive therapy. Seven consecutive renal transplant patients were studied at the end of a month of treatment while on different oral cyclosporine doses (5, 3.5, 2.5, or 1.5 mg/kg, twice a day, respectively). Cyclosporine pharmacokinetics profiles and renal function parameters (GFR and renal plasma flow [RPF], as inulin and p-amino hippurate clearances, respectively) were determined before and over a 12-hr period after each single dose of cyclosporine. Plasma levels and urinary excretion rate of endothelin were also studied before and after the highest cyclosporine dose (5 mg/kg). Mean trough levels, area under the curve values, and maximum concentration of blood cyclosporine were comparable after 5 and 3.5 mg/kg cyclosporine and decreased in a dose-dependent manner after the lower doses (2.5 and 1.5 mg/kg). In the same patients GFR declined on average 63%, 53%, 35%, and 18%, 2-4 hr after maximum cyclosporine concentration was reached. As blood levels of cyclosporine returned to trough, GFR progressively increased to baseline. Similar results were found for RPF; 5 mg/kg cyclosporine did not modify endothelin plasma levels. By contrast, urinary excretion of the peptide increased significantly (P less than 0.01) in the 6 hr that followed cyclosporine administration and returned within the normal range in the subsequent 6 hr. Following each oral administration of cyclosporine, 2-4 hr after peak blood concentration was reached, patients showed renal hypoperfusion, transient and rapidly reversible. This was associated with an increased urinary endothelin excretion rate that was also transient. It is speculated that an excessive renal synthesis of endothelin is the cause of the daily renal hypoperfusion observed in patients with renal transplants given cyclosporine.

Adult↗

Angiotensin converting enzyme inhibition improves glomerular size-selectivity in IgA nephropathy.

Clearances of uncharged dextrans of broad size distribution were used to evaluate the effects of a 30 day course of enalapril on glomerular barrier function in 10 patients with IgA nephropathy and proteinuria (from 1.4 to 5.6 g/day). Dextran clearance experiments were repeated three times: before enalapril therapy, after 30 days of enalapril and again 30 days after enalapril withdrawal. GFR, but not RPF, was significantly reduced by enalapril (basal 38.3 +/- 11.9, enalapril 30.2 +/- 12.6 ml/min/1.73 m2) and returned to basal values after enalapril withdrawal. Urinary protein excretion and fractional clearance of albumin were both significantly reduced by enalapril (basal 2.3 +/- 1.1 g/day and 102 +/- 90 x 10(-5), enalapril 1.2 +/- 0.6 g/day and 51 +/- 23 x 10(-5), respectively) and returned to basal values after enalapril withdrawal. Transglomerular passage of large dextrans (radii 54 to 62 A), but not of lower size (26 to 42 A) were significantly lowered by enalapril. When enalapril was withdrawn the dextran-sieving profile returned comparable to the baseline levels. A theoretical analysis of dextran-sieving profiles indicated that enalapril lowered the radius of largest membrane pores. This effect was independent from glomerular hemodynamic changes. We conclude that angiotensin converting enzyme inhibitors (CEI) in humans with IgA nephropathy reduces urinary protein excretion by a primary action on the intrinsic glomerular membrane properties enhancing barrier size-selective function. The hypofiltration associated with enalapril therapy in these patients, which was eliminated by its withdrawal, has to be taken into account as a possible undesired effect of CEI in long-term treatment.

Adult↗

Drug analysis by near-infra-red reflectance spectroscopy. Determination of the active ingredient and water content in antibiotic powders.

Near-infra-red reflectance spectroscopy is used to determine the active ingredient concentration and water content of an antibiotic powder (ceftazidime pentahydrate). The validity of predictive models for active ingredient concentrations and water content, constructed by means of the multiple linear regression technique is discussed. A procedure is devised for the analysis of production samples, which, on account of the very limited range of concentrations, prove a difficult fit to the above-mentioned model. The results obtained in testing formulation samples from 1 year's industrial production are used to illustrate the potential of the technique.

Anti-Bacterial Agents↗

A critical approach to therapeutic apheresis in the management of inflammatory dysimmune polyneuropathies.

Data concerning 37 patients with inflammatory dysimmune polyneuropathy treated by discontinuous flow centrifugation, membrane plasma separation and cascade filtration are presented. Plasmapheresis was combined with immunosuppressants in patients with chronic or relapsing neuropathy (8 patients), cryoglobulinemic (6 patients) and paraneoplastic disease (2 patients), whereas 21 patients with acute Guillain-Barré syndrome (GBS) underwent exclusively plasmapheresis. Most patients were treated during the onset or progression of their disease and excellent or satisfactory clinical results were obtained in 18 patients with GBS, 6 with cryoglobulinemia, 2 with paraneoplastic disease and 4 with chronic relapsing polyneuropathy. Prior to therapy, 34 patients had high levels of immune complexes (CIC); this level was clearly reduced by plasmapheresis and clinical results correlated well with this removal. 3 patients with chronic dysimmune polyneuropathy, without any evidence of CIC, were completely unaffected by treatment. The possible role of CIC in demyelinating polyneuropathies is discussed on the basis of information given by cascade filtration treatment of 7 patients.

Chronic Disease↗

Plasmapheresis and cytotoxic drugs for mixed cryoglobulinemia.

Fifteen patients with symptomatic cryoglobulinaemia were subjected to apheretic treatment when acute renal insufficiency, glomerulonephritis, severe generalized vasculitis and polyneuropathy unresponsive to conventional therapy or complications due to steroids, such as vertebral collapse, peptic ulcer and steroid diabetes, had appeared. Treatment was performed by discontinuous flow centrifugation or cascade filtration: when discontinuous flow centrifugation was employed, a mixture of saline, gelatin and fresh frozen plasma was used for replacement. Cytotoxic drugs were administered to patients with lymphoma (4 patients) or chronic active hepatitis (5 patients) and also to patients suffering from essential mixed cryoglobulinaemia. Exchanges were organized into courses of 3 to 5 sessions over 5 to 10 days and employed as a supportive measure. No patient underwent long-term treatment. A complete resolution of kidney damage, skin involvement and neurologic signs was observed when treatment was started early in the course of the disease, whereas unequivocal but moderate improvement was obtained in the case of long-lasting symptoms such as polyneuropathy. Relapses were seen in most patients when cytotoxic drugs had been discontinued abruptly. In 8 patients the solubility of cryoglobulins was studied by a recently developed turbidimetric assay. Following treatment the solubility increased; when solubility decreased, 2 patients of this group had a relapse. On the basis of these preliminary observations it appears that the possibility of predicting relapsing disease or the need of continuing therapy can eventually be achieved.

Acute Kidney Injury↗

Cascade filtration: clinical application in 26 patients with immune complex and IgM mediated diseases.

A new technique which allows lymphocytapheresis to be combined with cascade filtration (CF) is described in this paper. This therapeutical approach was applied for the treatment of patients affected by necrotizing vasculitis (1), inflammatory myopathies (5), Cryoglobulinemia (5), immune complex polyneuropathies (7), rheumatoid arthritis (3) and psoriasis (3 patients). Two cases of Waldenstrom's macroglobulinemia were also treated after the onset of the hyperviscosity syndrome. 78 procedures have been performed without any untoward effect. From a clinical point of view all patients had some improvement following treatment, thereby confirming not only the clinical safety of this therapeutical approach but also its effectiveness at least in the management of diseases which usually respond to plasma exchange treatment. Laboratory investigations showed that with CF it is possible to selectively remove IgM, immune complexes, fibrinogen, lipoproteins and high molecular weight plasma components, sparing most albumin and IgG globulins (85 and 71%, respectively).

Adolescent↗

A method for the study of cryoglobulin solubilization curves at 37 degrees C. Preliminary studies and application to plasma exchange in cryoglobulinemic syndromes.

A simple method for the study of kinetic solubility curves of cryoglobulins is presented. In its first application to the study of 21 patients with cryoglobulinemia, it was possible to ascertain that clinical condition roughly correlates with decreased solubility whereas no correlation is found with per cent cryocrit. In the group of patients we studied, 6 underwent plasma exchange treatment when glomerulonephritis, acute renal insufficiency, cerebritis and polyneuropathy appeared: in these patients, following 2 to 5 apheretic sessions, solubility increased showing a sort of correlation with clinical benefits determined by treatment. The preliminarity of this study is underlined.

Cryoglobulinemia↗

Plasma exchange in the management of patients with multiple sclerosis: preliminary observations.

Since humoral factors have been implicated in the pathogenesis of multiple sclerosis (MS) and previous attempts at therapeutic intervention have not met with uniform success, plasma exchange (PE) was recently proposed for the management of this disease. We are currently investigating the possible effectiveness of PE in the treatment of MS, and to date 6 patients have been entered into the study. At least 4 of our patients who did not respond to conventional therapy have shown unequivocal, moderate to marked improvement following the first session of PE. At the time of treatment, these patients had an acute exacerbation of their disease. We found no correlation between clinical improvement and the serum immune complex levels, suggesting that other poorly known mechanisms were operative. Based on our preliminary results, we feel that PE may be efficacious in treating exacerbations of MS. More evidence is needed on the effects of PE in the chronic stage of the disease.

Adult↗