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Biomedical subjects

S Andrulli

Publications and source records attributed to S Andrulli.

At least 19 recordsLinked to original sources
PubMed2001

Long-term treatment with low doses of interleukin-2 and interferon-alpha: immunological effects in advanced renal cell cancer.

PURPOSE: We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) in patients bearing advanced renal cell carcinoma. METHODS: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFN-alpha twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients. rIL-2 (1 x 10(6) IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3-5 of each week; rIFN-alpha (1.8 x 10(6) IU/m2) was given on days 3 and 5. In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets, and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months of follow-up). RESULTS: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P = 0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+) (28%, P = 0.011). No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R (P = 0.036 and P = 0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively thereafter. CONCLUSIONS: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3-CD56+ cells.

Adult↗
PubMed2001

How to determine ionic dialysance for the online assessment of delivered dialysis dose.

BACKGROUND: Ionic dialysance may be equivalent to blood-water urea clearance corrected for recirculation (effective urea clearance); however, this is controversial. The aims of our study were (1) to verify in vivo whether the value of ionic dialysance is affected by the method of determination, given the effect of cardiopulmonary recirculation on inlet plasma water conductivity when the inlet dialysate conductivity is changed; and (2) to define the operative modalities for determining ionic dialysance to obtain an adequate estimate of effective urea clearance. METHODS: Thirty-three hemodialysis patients were studied during 186 dialysis sessions with low-flux polysulfone dialyzers using a modified Fresenius Medical Care 4008 B machine equipped with meters to measure inlet and outlet dialysate conductivities. This machine varied inlet dialysate conductivity (Cdi) according to the following pattern: starting from baseline (step 0), Cdi was increased by 8% (step 1). After Cdi had reached the target value, which took 8 to 10 minutes, it was lowered to 8% below the baseline value (step 2). After 8 to 10 minutes, when Cdi had reached the new target, it was returned to its starting value (step 3). Four values of conventional ionic dialysance (using the standard formula) and actual ionic dialysance (taking into account cardiopulmonary recirculation) were obtained for each cycle and were compared among them and with effective urea clearance (Kde). RESULTS: Mean conventional dialysance values at steps 0 to 2 and 2 to 3 (190 and 189 mL/min) were similar and higher than those at steps 0 to 1 and 1 to 2 (171 and 181 mL/min). Mean conventional ionic dialysance values underestimated Kde, particularly at steps 0 to 1 (-22.2 mL/min, P < 0.001) and 1 to 2 (-12.6 mL/min, P < 0.001). The actual dialysance values underestimated Kde by no more than 4.3 mL/min (P < 0.001). In steps 0 to 1 and 1 to 2, the underestimate of Kde by conventional dialysance increased at higher values of Kde, but this relationship did not exist when considering actual dialysance. CONCLUSIONS: The value of ionic dialysance is affected by the method of determination, given the effect of cardiopulmonary recirculation on inlet plasma water conductivity when inlet dialysate conductivity is changed. As a consequence, to provide a correct and direct estimate of effective urea clearance, ionic dialysance must be determined by changing inlet dialysate conductivity in such a way as to keep inlet plasma water conductivity constant by means of two symmetrical high and low dialysate conductivity steps.

Dialysis Solutions↗
PubMed2001

Dialysis: its role in optimizing recombinant erythropoietin treatment.

Although iron deficiency is probably the most important factor affecting response to recombinant erythropoietin (Epo, epoetin), other factors are of significance, including dialysis adequacy. Additionally, water treatment and distribution, sterilizants and the quality of the dialysate in terms of trace elements (particularly chloramine) are of importance in relation to erythropoiesis inhibition. Microbiological or pyrogenic contamination can cause or aggravate anaemia in haemodialysis patients, and the impact of enhanced production of cytokines should be taken into consideration. By removing small and (possibly) medium/large molecules, adequate dialysis is of paramount importance in correcting anaemia and optimizing epoetin therapy. The biocompatibility of dialysis membranes and flux are other important factors. As yet unknown uraemic toxins may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to hypothesize that, because anaemia improves after the start of dialysis with cellulose membranes, low molecular weight erythropoiesis inhibitors are involved, as well as medium/large molecular weight inhibitors, which are removed by more permeable membranes. However, in highly selected, adequately dialysed patients without iron or vitamin depletion, the effects of dialysis membrane type on haematological parameters and epoetin efficacy are smaller than might be expected from the results of uncontrolled studies. Improvement in anaemia has been observed using on-line haemofiltration, haemodiafiltration, and sterile dialysate. The results of prospective, randomized trials examining the impact of these factors on anaemia and the effectiveness of epoetin treatment are eagerly awaited.

Anemia↗
PubMed2000

Color doppler ultrasonography imaging to guide transluminal angioplasty of venous stenosis.

BACKGROUND: The objective of access surveillance is the early recognition of dysfunction in order to be able to correct the stenosis by angioplasty or surgery before access thrombosis occurs. The advent of color Doppler imaging has enabled studies of color Doppler ultrasonography (CDU) for the guidance of percutaneous transluminal angioplasty (PTA). The aim of the present study was to investigate whether color Doppler imaging alone can be safely and effectively used to diagnose vascular graft access stenoses and guide subsequent PTA. METHODS: Using the ultrasound velocity dilution method, we measured access blood flow (Qa) during the first hour of hemodialysis every month in patients with grafts as vascular access. When the decrease in Qa from the baseline value was 40% or more, CDU was performed and immediately followed by PTA in the presence of a stenosis of more than 50%. The Qa was then measured during the first dialysis after PTA and one month later. Repeated-measure analysis of variance was applied to evaluate the early and late (after one month) effect of PTA. RESULTS: Twelve PTAs were performed under CDU guidance in nine patients and led to the elimination of the stenosis or its reduction (two cases). The mean Qa was 809 +/- 263 mL/min at baseline, 468 +/- 153 before PTA, and 820 +/- 281 after PTA. The difference between the pre-PTA and post-PTA values was highly significant (P < 0.001), and the mean value after PTA was not different from baseline (P = 0.672). There were no relevant complications directly related to the procedure. CONCLUSIONS: The CDU procedure is effective for the diagnosis of vascular access stenosis and as a guide during the PTA procedure. It could improve stenosis screening by avoiding the risks of exposure to ionizing radiation and of adverse reactions to contrast media.

Aged↗
PubMed2000

Effect of high-flux dialysis on the anaemia of haemodialysis patients.

BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.

Aged↗
PubMed2000

Spurious estimations of sodium removal during CAPD when [Na](+) is measured by Na electrode methodology.

BACKGROUND: The aim of this study was to investigate the effect of pH and glucose concentration on sodium removal and the dialysate and plasma sodium ratio (D/PNa) as measured by means of a flame photometer (NaF) or direct ion-selective electrode (NaE) in continuous ambulatory peritoneal dialysis (CAPD). METHODS: In vitro, glucose concentration, pH, NaF, and NaE were measured in fresh peritoneal dialysis solutions (PDSs) before and after the addition of glucose or KOH. In vivo, 66 four-hour peritoneal equilibration tests were performed in 35 patients on CAPD using a low pH PDS with a glucose concentration of 3.86%. RESULTS: In vitro, NaF and NaE were significantly influenced by the glucose concentration and pH of the PDS. In vivo, in fresh PDS, there was a significant difference between the NaF and NaE results; the respective median values were 132.1 (interquartile range 129.3 to 137.5) versus 138.0 (134.4 to 141.5) mmol/L (P < 0.0001). The D/PNa ratio calculated by NaE was significantly lower than that calculated by NaF (0.88 +/- 0.03 vs. 0.91 +/- 0.04 and 0. 90 +/- 0.03 vs. 0.94 +/- 0.04 at 60 and 240 min, respectively, P < 0.0001), whereas there was no significant difference between the NaE and NaF values after correction for plasma water and a Donnan factor of 0.96 (0.88 +/- 0.03 vs. 0.88 +/- 0.04 and 0.90 +/- 0.03 vs. 0.91 +/- 0.04, P < 0.3473). Sodium removal was significantly lower when calculated as NaE than when calculated as NaF (43.9 +/- 32.7 vs. 61.0 +/- 32.2 mmol, P < 0.0001). CONCLUSIONS: The fresh PDS sodium concentration can be corrected using a glucose concentration-related factor. The D/PNa ratio calculated as NaE or NaF is not different after correction for plasma water and a Donnan factor of 0.96. Sodium removal must be measured by means of NaF rather than NaE. This could have an important clinical impact.

Adult↗
PubMed2000

The role of underlying nephropathy in the progression of renal disease.

BACKGROUND: Disease-specific pathogenic mechanisms may be major determinants of the spontaneous rate of progression of chronic renal failure (CRF). To clarify the role of different underlying renal diseases, we examined the rate of CRF progression in 886 patients with chronic nephropathies. METHODS: Secondary analysis of two multicenter, prospective randomized trials: the Northern Italian Cooperative study (NIC) and the AIPRI study (ACE-Inhibition in Progressive Renal Insufficiency). Univariate and multivariate analyses of variance were used to select the covariates possibly related to CRF progression (estimated by means of the slope of the reciprocal of SCr against time), focusing on the contributory role of primary renal diseases. RESULTS: The overall rate of CRF progression was relatively low but there was a considerable difference in the slopes relating to the underlying nephropathy (particularly evident in the patients with chronic glomerulonephritis (CGN)). The median rate of CRF progression in both studies was more rapid in patients with polycystic kidney disease (PKD) and CGN than in those with other nephropathies. Multivariate analysis showed PKD as an independent predictor of the CRF progression rate only in the NIC Study (P < 0.0015); the selected variables in both studies predicted a variation of only 15-18% in the CRF progression rate. CONCLUSION: The underlying renal disease certainly plays a role in the natural history of CRF, but the variability of the CRF progression rates related to different renal diseases and between individuals with the same diagnosis underlines the need for caution in evaluating risk factors and predicting single patient outcomes.

Adult↗
PubMed1999

Corticosteroids in IgA nephropathy: a randomised controlled trial.

BACKGROUND: IgA nephropathy is progressive in most cases and has no established therapy. In this randomised trial, we assessed the efficacy and safety of a 6-month course of steroids in this disorder. METHODS: Between July, 1987, and September, 1995, we enrolled 86 consecutive patients from seven renal units in Italy. Eligible patients had biopsy-proven IgA nephropathy, urine protein excretion of 1.0-3.5 g daily, and plasma creatinine concentrations of 133 micromol/L (1.5 mg/dL) or less. Patients were randomly assigned either supportive therapy alone or steroid treatment (intravenous methylprednisolone 1 g per day for 3 consecutive days at the beginning of months 1, 3, and 5, plus oral prednisone 0.5 mg/kg on alternate days for 6 months). The primary endpoint was deterioration in renal function defined as a 50% or 100% increase in plasma creatinine concentration from baseline. Analyses were by intention to treat. FINDINGS: Nine of 43 patients in the steroid group and 14 of 43 in the control group reached the primary endpoint (a 50% increase in plasma creatinine) by year 5 of follow-up (p<0.048). Factors influencing renal survival were vascular sclerosis (relative risk for 1-point increase in score 1.53, p=0.0347), female sex (0.22, p=0.0163), and steroid therapy (0.41, p=0.0439). All 43 patients assigned steroids completed the treatment without experiencing any important side-effects. INTERPRETATION: A 6-month course of steroid treatment protected against deterioration in renal function in IgA nephropathy with no notable adverse effects during follow-up. An increase in urinary protein excretion could be a marker indicating the need for a second course of steroid therapy.

Administration, Oral↗
PubMed1999

On-line monitoring and convective treatment modalities: short-term advantages.

BACKGROUND: Despite technological advances in dialysis equipment, the morbidity and quality of life of uraemic patients undergoing regular haemodialytic treatment are still severely affected by acute intradialytic complications possibly related to the treatment itself. Cardiovascular instability still affects >30% of dialytic sessions and, although its pathogenesis is multifactorial, dialysate sodium concentration (and, consequently, intradialytic sodium removal) is one of the main factors affecting intradialytic hypotension. Convective treatment modalities and so-called biocompatible membranes increasingly are recognized as improving acute and particularly chronic dialytic complications because a number of the pathways activated in patients during dialysis with 'bioincompatible' membranes have the potential to produce many side effects. METHODS: The main clinical studies are reviewed to highlight the advantages of on-line monitoring and convective modalities on acute intradialytic symptoms. RESULTS: The conductivity kinetic model has been shown to be a reliable and inexpensive method of matching intradialytic sodium removal and interdialytic load. By applying this model to patients prone to dialysis hypotension, a smaller reduction in intradialytic systolic blood pressure has been observed, without any change in dialysate and reinfusate sodium concentrations or dry body weight. Furthermore, a new model of haemodialysis potassium removal based on a decreasing intradialytic potassium concentration and a constant plasma-dialysate potassium gradient is capable of reducing the arrhythmogenic effect of standard haemodialysis. Despite the proven biological superiority of biocompatible membranes, there is no definitive evidence that membrane biocompatibility and/or flux lead to a decrease in acute intradialytic clinical symptoms. CONCLUSIONS: On-line monitoring of intradialytic sodium removal and the potassium gradient is capable of reducing intradialytic hypotension and the arrhythmogenic effect of haemodialysis, and thus having a considerable clinical impact on acute intradialysis complications. As far as the effects of biocompatibility and/or flux on the incidence of acute intradialytic clinical symptoms are concerned, further trials involving a sicker patient population with higher prevalence of intradialytic hypotension are needed in order to achieve statistical power.

Cardiovascular System↗
PubMed1998

On-line assessment of delivered dialysis dose.

BACKGROUND: The adequacy of the delivered dialysis dose is essential to prevent patient morbidity and mortality. The determination of effective ionic dialysance (D) is easy, non-invasive and inexpensive, and its use instead of effective urea clearance (K) in kinetically determining apparent" urea distribution volume (Vt) is likely to lead to a correct Kt/V, even though the Vt value may be incorrect. The aim of this study was to test the possibility of using the measurement of D to monitor Kt/V on-line during each dialysis treatment. METHODS: Forty-four patients were dialyzed using a monitor equipped with specially designed "Diascan Module" (COT; Hospal) that measures effective D by means of a single conductivity probe. Vt was calculated according to the SPVV three BUN method urea kinetic model using D instead of K values. One month later, Kt/V was calculated as Dt/V, using actual D and T values and the predetermined Vt values updated for the current final body wt. Both the Dt/V and Kt/V determined according to the Smye and Daugirdas methods were compared with the Kt/V determined using the SPVV kinetic model (Kt/Veq) RESULTS: The Kt/V values calculated using ionic dialysance and predetermined Vt were approximately equivalent to those of Kt/Veq (1.14 +/- 0.16 vs. 1.14 +/- 0.17, mean difference 0.00 +/- 0.07), as were those determined according to the Smye and Daugirdas methods (1.10 +/- 0.18 and 1.13 +/- 0.17, mean difference -0.03 +/- 0.06 and 0.01 +/- 0.06, respectively). CONCLUSION: Once Vt has been determined, the evaluation of ionic dialysance in stable patients makes it possible to calculate the Kt/V accurately at each dialysis session without blood or dialysate sampling, and at no additional cost.

Blood Urea Nitrogen↗