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D Roccatello

Publications and source records attributed to D Roccatello.

At least 19 recordsLinked to original sources

5-Lipoxygenase gene expression in hemodialysis.

Leukotrienes (LTs), the end products of the eicosanoid pathway released during inflammation, are markers of polymorphonuclear cell and monocyte activation. The present study focused on the possibility that 5-lipoxygenase (5-LO), the key enzyme for LT synthesis, was involved in the interaction between blood and the hemodialysis (HD) membrane. 5-LO gene expression was examined by reverse transcriptase polymerase chain reaction (RT-PCR) in samples of mononuclear cells isolated from peripheral blood withdrawn at the start and at 15 min of HD from 10 chronic HD patients, 5 treated with Cuprophan and 5 with polymethylmethacrylate (PMMA) membrane. An increased 5-LO gene expression was detected at 15 min in 4 of 5 patients using the Cuprophan membrane but in none of the 5 PMMA treated patients. Our results showed for the first time that the interaction between blood and the HD membrane upregulates 5-LO messenger ribonucleic acid (mRNA).

Aged

Intradialytic cytokine gene expression.

Along with the numerous technological improvements in molecular biology, polymerase chain reaction, which permits analysis of sequences of a very small amount of biological material, enables evaluation of hemodialysis-induced gene transcription of inflammatory cytokines. Blood samples drawn from 22 hemodialysis patients, treated with cellulose-derived or synthetic membranes, were collected at 0 and 15 min of hemodialysis. Total RNA, purified from mononuclear cells, was reverse transcribed and cDNA amplified by polymerase chain reaction primed with specific oligomers in order to determine tumor necrosis factor alpha (TNF alpha), interleukin (IL) 1 beta and IL6 gene expression. Plasma samples were collected at 0 and 180 min for detection of mature cytokines by enzyme immunoassay with plates pre-coated with monoclonal antibodies to TNF alpha, IL1 beta and IL6. A significant increase in TNF alpha mRNA was detected at 15 min of hemodialysis in 12 of 22 patients: 5 of 9 treated with cuprophan; 3 of 3 with cellulose triacetate; 3 of 5 with polysulfone, and only 1 of 5 treated with polymethyl-methacrylate membranes. A parallel increase in IL1 beta or IL6 mRNA was detected, and significant relationships were found between TNF alpha and IL1 beta (p < 0.001), and IL1 beta and IL6 gene expression (p < 0.05). Increased levels of mature TNF alpha and IL1 beta molecules in plasma were detected in the majority of patients showing an increased cytokine gene expression. However, the absolute amount of cytokine mRNA transcription at 15 min did not predict the levels of mature molecules reached in plasma at 180 min. Cytokine mRNA transcription is quite common at the beginning of a dialysis run. Possibly due to intracellular degradation of critical sequences of cytokine mRNA, gene expression does not necessarily imply translation into mature protein. It is suggested that mechanisms related to cell-to-cell interaction, which may possibly involve procytokine biology, are needed to drive phenomena of cytokine activation to clinical effectiveness.

Adult

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

Adolescent

Processing of IgA aggregates in a rat model of chronic liver disease.

Heavy alcohol intake and/or lipotrope-deficient diet induced hepatocellular injury and mesangial deposition of IgA and often IgG in Lewis rats. The experimental animals showing more severe urinary abnormalities and histologic damage in the glomeruli had increased levels of IgA antibodies to dietary antigens and altered intestinal permeability. Based on human studies, the prolonged circulation of IgA-containing complexes associated with the liver disease could be envisaged as important for the development of mesangial IgA deposits. In order to verify this hypothesis, four groups (G) of Lewis rats were studied: G1 received thrice a weak an intragastric infusion of 1.5 ml/100 g body wt of whiskey; G2 rats were nourished with lipotrope-deficient diet; G3 rats were given both whiskey and LD diet; G4 rats were nourished with regular chow. After 12 weeks, heat-aggregated rat monomeric IgA was labeled with 133I and intravenously injected. Three control subgroups of rats, one given whiskey, one nourished with LD diet, and one with regular chow, were injected with radiolabeled heat-aggregated rat IgG. A large field-of-view digital gamma camera, equipped with an ultra-high-resolution collimator and interfaced to a dedicated computer, was used to analyze tracer kinetics and fate. The liver was the main organ involved in clearance of both test probes. The hepatic mean transit (MTT) was 11.4 +/- 11 min in G1 (proteinuria of 6.9 +/- 1.41 mg/day and hematuria +/+2), 221 +/- 19 min in G2 (proteinuria 9.1 +/- 0.64 mg/day and hematuria +2/+3), and 230 +/- 15 min in G3 (proteinuria 9.5 +/- 0.58 mg/day and hematuria +2/+3). In each case MTT value was found to be significantly prolonged compared to G4 (85 +/- 4 min). The multiple regression analysis showed that MTT values, proteinuria, and hematuria were significantly correlated (P < 0.01). Controls had trace amount proteinuria (0.82 +/- 0.17 mg/day, significantly lower than for each study group, P < 0.08) and undetectable hematuria. Similar results were obtained in control rats injected with aggregated IgG; i.e., MTT values were more prolonged in rats given whiskey or LD diet than normally nourished rats (P < 0.01). The lipotrope-deficient diet and the chronic alcohol abuse per se seem to lead to critical changes in hepatic uptake and catabolism of both an IgA and an IgG aggregate, which could account in turn for the reported appearance of renal immunoglobulin deposits in this experimental model. Due to the comparable delay in removal of IgA and IgG probes in equally nourished animals, additional factors are likely to be involved in the prominent deposition of IgA.

Animals

Impaired hepatosplenic elimination of circulating cryoglobulins in patients with essential mixed cryoglobulinaemia and hepatitis C virus (HCV) infection.

The pathogenic mechanisms that lead to renal deposition of the cryoprecipitable IgM rheumatoid factor-IgG complexes in essential mixed cryoglobulinaemia (EMC) are unknown. Defective removal of cryoprecipitable complexes from the circulation has been postulated in EMC-associated nephritis. To test this hypothesis, the kinetics and fate of a trace dose of 123I-radiolabelled autologous cryoglobulins were analysed in 13 patients with EMC grouped according to renal involvement. The time course of radioactivity distribution in the blood and organ uptake were measured by gamma camera scintigraphy. In blood sampled 30-300 s after injection, only a minor fraction (< 15%) of the circulating cryoglobulins bound to the erythrocytes, suggesting the elimination mechanisms are independent of binding to CR1 on erythrocytes. The overall blood disappearance curve showed a fast (< or = 1 min) and slow (> 4 h) biphasic pattern. In patients with quiescent or mild nepthritis, the liver and to a lesser extent the spleen were the major organs that mediated the rapid uptake and processing of the cryoglobulins from the circulation. In contrast, patients with active mesangiocapillary glomerulonephritis showed significantly (P < 0.001) less hepatic uptake, low liver-to-precordium ratio, and slower processing of cryoglobulins, prolonged liver mean transit time, than quiescent patients or mild nephritis patients. To elucidate the role and influence of HCV infection in the pathogenesis of EMC-nephritis, sera and cryoglobulins from all patients were assayed for HCV. None of the control group cases without nephritis showed any evidence of HCV-RNA in serum or cryoglobulin pellet. In contrast, all 10 EMC-nephritis patients' sera, and eight corresponding cryoglobulin pellets contained HCV-RNA. Collectively, these findings suggest an impaired reticuloendothelial system removal of IgM-IgG-HCV complexes may underlie their renal deposition.

Adult

Captopril-enhanced scintigraphy using the method of the expected renogram: improved detection of patients with renin-dependent hypertension due to functionally significant renal artery stenosis.

UNLABELLED: PURPOSE AND DESIGN OF STUDY: Asymmetric-induced changes of the renogram under angiotensin-converting enzyme inhibition (ACE-i), i.e. lateralization, is probably the most distinctive finding for the detection of haemodynamically significant renal artery stenosis (RAS) in compensated kidney, since bilateral and symmetric patterns are non-specific. In the Consensus statement of diagnostic criteria of renovascular hypertension with captopril renography (Am J Hypertens 1991; 4: 749-755S) ACE-i-induced asymmetry of renograms for the left and right kidney was viewed as vitally important. However, detection of change in split function is a reliable parameter only when using a glomerular tracer, i.e. 99mTc-DTPA. No indication regarding a more widely used tubular tracer such as 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) has been given. METHODS AND RESULTS: The theoretical contralateral curve, called 'expected renogram', was calculated frame by frame from renal curves obtained under ACE-i and one of two baseline curves. The expected renogram was compared with the recorded ipsilateral curve. More than +/- 2 SD difference between expected and recorded renograms was assumed as suggestive of monolateral or bilateral RAS. Twenty-nine patients with angiographically proven RAS (bilateral in 12) and 20 patients without arteriographic evidence of stenosis were evaluated by postcaptopril/baseline 99mTc-MAG3 renography. Results obtained with the expected renogram analysis were compared with those obtained by standard criteria which included: improvement of peak time under baseline conditions, wash-out (75%) time, and monolateral or bilateral residual cortical activity > 10%, but asymmetrical, i.e. with > 5% change in split function. Compared to the standard evaluation, the use of the expected renogram for the diagnosis of RAS improved the specificity from 70 to 95% (P < 0.03) without loss of sensitivity (79.3%). Follow-up data after revascularization were available in 18 scintigraphically positive and six scintigraphically negative patients with RAS. The sensitivity of the expected renogram method referring to short-term (1 month) patient outcome following revascularization was 88.8%. The beneficial effects on blood pressure response persisted in 77% of the these patients at 18 months. Notably, four of six scintigraphically negative patients with RAS did not show any short-term benefit from revascularization and the improvement in blood pressure values lasted for 18 months in only one case. CONCLUSIONS: The high specificity of the expected renogram method reduces the number of unnecessary invasive procedures. This is a critical point for a low-prevalence disease such as renovascular hypertension.

Adult

Early increase in blood nitric oxide, detected by electron paramagnetic resonance as nitrosylhaemoglobin, in haemodialysis.

The objective of this study was to determine intradialytic blood levels of nitric oxide (NO), in patients undergoing chronic haemodialysis. This was done by detection of nitrosylhaemoglobin by a sensitive technique of spin trap electron paramagnetic resonance at 0, 5, 15, 60, 180 and 240 min of a 4-h standard bicarbonate dialysis, using the same dose (6000 U) of heparin and different dialysis membranes. The study group included 12 patients treated with cellulose-derived dialysis membranes (nine with cuprophan and three with cellulose triacetate) and 10 patients treated with synthetic membranes (five with polysulfone and five with polymethylmethacrylate). Control groups included 11 normal subjects and six patients with end-stage renal failure who were receiving intermittent peritoneal dialysis. Basal blood levels of nitrosylhaemoglobin in haemodialysis patients were significantly higher than normals, but similar to peritoneal dialysis patients. A significant increase (P < 0.01) in nitrosylhaemoglobin level was detected at 15 min of haemodialysis irrespective of the membrane used. A decrease to basal levels at 180 min was observed in all but two cuprophan-treated patients who, in contrast to the others, had a symptomatic hypotension at the end of the session and a further increase in blood nitric oxide. Patients undergoing peritoneal dialysis did not show any change in blood levels of nitrosylhaemoglobin during the first 180 min of the procedure. Thus, a constant increase in nitrosylhaemoglobin levels was observed early in haemodialysis, but not in peritoneal dialysis patients. Very preliminary evidence was obtained for a role of nitric oxide in the vascular instability at the end of haemodialysis in a few patients who had hypotensive episodes.

Adult

[The complement system in kidney diseases].

The multifaceted relations between complement system and immune-mediated nephropathies are reviewed. Several conditions in which either the complement activation induces renal damage without hypocomplementemia or hypocomplementemia occurs in the absence of circulating IC are reported as well as disorders in which immune complexes promote hypocomplementemia. The complement system is involved in the clearance of immune complexes, both modifying the immune complex size and favouring the physiologic neutralization by the erythrocyte transport system. In certain pathological conditions the immune complex intrinsic characteristic or genetic abnormalities prevent efficient removal from the blood stream. The purpose of the present review is to summarize these conditions, briefly describing their pathological consequences, and indicate a simple scheme to correctly interpret the biochemical abnormalities of the complement system in nephropathology.

Complement System Proteins

Progressive multifocal leukoencephalopathy during cyclosporine treatment. A case report.

A 45-year-old patient suffering from chronic renal insufficiency developed dermatopolymyositis. Since the patient did not respond to treatment with high doses of prednisone and immunoglobulin, concomitant cyclosporine A was added. Four months later, worsening signs of bilateral pyramidal disorder and an altered state of consciousness appeared. Serial computed tomography (CT) and magnetic resonance imaging (MRI) revealed multiple alterations of the cerebral white matter. Cyclosporine was then discontinued. One month later, exitus occurred. Microscopic examination of the brain showed diffuse tumescence; histological examination revealed perivascular and diffuse lymphomonocyte infiltrations, areas of demyelination, astrocytes with bizarre nuclei, and oligodendrocytes with enlarged nuclei due to hyperchromatic inclusion. Morphological examination confirmed the presence of intranuclear icosahedral viral bodies. Progressive multifocal leukoencephalopathy was diagnosed. The literature contains only one report of an analogous case observed during a course of cyclosporine treatment for Wegener's granulomatosis.

Brain

Incidence of biopsy-proven primary glomerulonephritis in an Italian province.

Between January 1, 1970, and December 31, 1994, 1,926 cases of biopsy-proven primary glomerulonephritis (PGN) were diagnosed in an adult population (> 15 years of age) in a northwestern region of Italy with approximately 3.5 million inhabitants. The principal long-term changes were an increase in the absolute number of biopsies per year, an increase in the mean age of patients undergoing biopsy (from 29.3 +/- 12.2 years to 47.0 +/- 17.8 years), an increase in the percentage of patients older than 65 years (from 1.7% to 20.4%), and an increase in the percentage of isolated urinary abnormalities as an indication for biopsy (from 3.5% to 29.6%). In the total biopsy material, immunoglobulin A glomerulonephritis (IgA-GN) is the most frequent type (26%), followed by membranous glomerulonephritis (MGN; 20%). An incidence study was begun in 1990; this survey was restricted to the population of the province of Torino (approximately 2 million inhabitants) as only this area completely refers to the nephrologic centers that entered patients into this study. The overall incidence of PGN is 4.68 new cases/yr/10(5) population with a predominance of males (> 2:1); IgA-GN is the most common type (1.47/yr/10(5) population [34.5%]) in the overall population. In the elderly, cases of PGN are twice as high as in adults (8.19/yr/10(5) population v 4.02/yr/10(5) population in the 65 to 74 year and 45 to 54 year age groups, respectively); MGN mainly accounts for this high incidence (3.4/yr/10(5) population), while the nephrotic syndrome is the most common indication for biopsy (53.8%). A comparison with the incidence in the same area in the early 1970s is evaluable only for PGN, which was mainly registered in the age groups for which an unrestricted biopsy policy was already in place (15 to 35 years). In contrast with a misleading increase of all types of PGN, which is in reality due to the extension of the biopsy policy to older and asymptomatic patients, membranoproliferative glomerulonephritis type I shows a countercurrent decrease from 0.43 to 0.13/yr/10(5) population. Evidence of a simultaneous decrease in severe cardiac valvulopathy, due to rheumatic fever, is also provided. We feel that before epidemiologic conclusions can be reached, a clear understanding of one's own biopsy policy is essential. An apparent change in the PGN rate in our region over the last 25 years mainly depends on modifications in our biopsy policy, most probably coupled with a change in the threshold of detection of symptoms in the general population. At present, according to our experience, IgA-GN is the most common type of PGN in the total bioptic material, as demonstrated in other European countries, while the elderly show a peculiar pattern with a higher PGN incidence, mainly represented by MGN and heralded by the nephrotic syndrome. We also confirm that membranoproliferative glomerulonephritis type I is indeed decreasing in parallel with changes in the microbiologic environment.

Adolescent

Low-dosage ibopamine treatment in progressive renal failure: a long-term multicentre trial.

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Adolescent

[Glomerulonephritis in the elderly].

The authors present a clinical analysis of the literature data regarding aged patients affected with glomerulonephritis (GN) and of 115 GN patients aged more than 65 years, biopsied in their own Center. Complications of renal biopsy, including the subclinical ones, were found in 19.1% of old patients compared to 19.2% of younger patients (p = NS), major complications in 5 and 1.4% respectively (p = NS). The most frequent GN was membranous GN (MGN) (27.8%), followed by IgA-GN (12%) and rapidly progressive GN (RPGN), idiopathic (8.6%) or secondary to vasculitis (8.6%). Eighteen out of 32 old MGN patients treated with alternated courses of steroids and immunosuppressive drugs for 6 months were compared to 32 MGN patients aged < 65 years identically treated. Complete remission was observed in 27.7% of cases and partial remission in 38.8% (p = NS). Complications of treatment were similar in the two groups of patients (p = NS). Patients with RPGN were treated with steroids (17 patients) plus immunosuppressive drugs (15 patients) and plasma exchange (13 patients). Systemic symptoms disappeared in 13/14 patients; ANCA became negative in all the 5 patients in whom they were detected; a 50% reduction of serum creatinine was obtained in 12 patients. These patients were compared to a control group of 26 patients aged < 65 years. Amelioration of renal function was evidenced more frequently among old patients with vasculitis (p < 0.05). Complications of treatment were more frequent among old patients with idiopathic RPGN (p < 0.05), but severe in only 1 case. Our data and data from the literature support the opportunity to perform renal biopsy in aged people, because it is as safe as in the younger population and allows a rational basis for treatment of GN. Clinical responses are similar to those of younger patients. Complications of treatment seem to be more frequent in old patients, but can be limited by some technical precautions and careful clinical monitorization.

Age Distribution

Indium-111-labeled granulocyte head accumulation in patients with Wegener's granulomatosis.

Among the symptoms of systemic vasculitis, purulent rhinorrhea with painful sinusitis is thought to be relatively specific to Wegener's granulomatosis (WG). Sixteen patients with rapidly progressive glomerulonephritis (GN), arteritis and extensive crescents in renal biopsy were studied by head indium-111 (111In)-granulocyte scanning. They included 8 WG, 5 microscopic polyarteritis, 2 necrotizing and crescentic GN and 1 classic polyarteritis nodosa. Autologous granulocytes labeled with 12.3 MBq of 111In-oxine were administered intravenously. Scintigraphic studies were performed at 4 and 24 h post-injection. Compared to the non-WG cases, considered as a whole, significant accumulation of tracer in sinuses was observed in WG patients (Fisher's p = 0.02). Substantial scintigraphic amelioration was obtained in a WG case treated with methylprednisolone pulses and, in another WG case, after high doses of intravenous gamma-globulins. The complete disappearance of facial uptake was obtained after 2 months of intensive therapy (i.e., steroid, cyclophosphamide and plasma exchange) in another WG patient. 111In-oxine granulocyte imaging may be useful in clinical practice as an additional marker of disease activity and a tool of identification of upper respiratory tract involvement.

Adult

Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio.

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.

Adult