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Biomedical subjects

F Ferrario

Publications and source records attributed to F Ferrario.

At least 73 records · Page 4Linked to original sources

Triazine herbicides and ovarian epithelial neoplasms.

The possible role of a class of herbicides, triazines, in ovarian carcinogenesis has been evaluated in a population-based case-referent study. The trade names reported by the study subjects, and the type of cultivation in which they worked, were used for the assessment of exposure. Women previously exposed to triazines showed a significant relative risk of 2.7 for ovarian neoplasms. Although none of the doses could be quantified for the study subjects, two risk trends in favor of the plausibility of the association were found: the first by duration and the second by probability of exposure. The population representativity of the study and the comparability of information between the cases and referents suggest the lack of any major bias in the results. Triazine-related risk remained consistent when the analysis was restricted to farmers and when the exposure to other herbicides and to other types of cultivation were considered. Unexposed farmers had the same risk as unexposed nonfarmers.

Adult↗

Characterization of interstitial infiltrating cells in Berger's disease.

The role of infiltrating blood-borne cells in the pathogenesis of renal damage in human glomerulonephritis is under active investigation. We have evaluated leukocyte infiltrates (number of cells/mm2) in the renal interstitium of 21 patients with Berger's disease and eight normal kidneys with monoclonal antibodies and a four-layer immunoperoxidase technique. In our population of patients, the number of infiltrating T-lymphocytes (OKT11+ cells) was significantly higher (median, 132) than in the normal kidneys (median, 60). This increase was mainly due to T-suppressor/cytotoxic lymphocytes (OKT8+ cells; median, 68), while T-helper/inducer lymphocytes (Leu 3A+ cells) and monocytes were in the normal range. T-lymphocyte infiltration was more marked in ten patients with impaired glomerular filtration rate (GFR) at the time of biopsy (median, 167) than in patients with normal GFR (median, 88). In addition, ten patients who showed deterioration of renal function during the subsequent follow-up, whatever their serum creatinine levels at the time of biopsy, had significantly more total T cells (median, 269), OKT8+ cells (median, 143), and Leu 3A+ cells (median, 105) than 11 patients with persistently stable GFR and normal controls. More data are necessary to establish whether this T-lymphocyte infiltration is the consequence of a cell-mediated mechanism acting in the interstitium, concomitant with the immune-complex-mediated mechanism acting in the glomerulus, or is a nonspecific consequence of the tubulointerstitial damage induced by the immunologically mediated glomerular disease.

Adult↗

Light chain nephropathy: histological and clinical aspects in 15 cases.

Fifteen patients aged 31-74 years (five male, ten female) on renal biopsy showed intense linear deposits of light chains along tubular basement membranes (TBM) by immunofluorescence, and/or granular dense deposits on electronmicroscopy. Multiple myeloma was diagnosed in ten patients. The onset of myeloma and nephropathy was simultaneous in six patients; nephropathy preceded or followed the diagnosis of myeloma in three and one patients respectively. The mode of onset of nephropathy was acute or rapidly progressive renal failure in five cases, chronic renal failure in seven, and heavy proteinuria in three. Only two patients had normal renal function at biopsy. Serum monoclonal component was kappa in five patients, IgG kappa in three, IgD kappa in one, IgG lambda in one, IgA lambda in one, absent in three, and not detected in one. On light microscopy eight cases had nodular glomerulosclerosis, three cast nephropathy and 14 TBM thickening. Immunofluorescence for monoclonal light chain(s) was positive in 11 of 13 cases. Electron microscopy showed finely granular deposits in the inner side of glomerular basement membranes (GBM) and the outer side of TBM in 11 of 11 tested cases. The evolution was towards chronic renal failure in 12 patients (six of whom required dialysis), death in two, unknown in one. Four patients died after a period of dialysis, from infections or cardiovascular complications.

Adult↗

Prognostic indicators in idiopathic IgA mesangial nephropathy.

Univariate survivorship analysis of a cohort of 365 patients with idiopathic IgA mesangial nephropathy and at least one year of further observation since the apparent onset (mean = 7.79 +/- 6.19 years; median = 6.16 years) has been performed. Observations for at least one year (mean = 5.05 +/- 3.66; median = 4.08 years) after biopsy was available for 292 of these. One immunohistological, four clinical, and six histological features were associated with increased risk of developing renal failure: (i) older at onset; (ii) no history of recurrent macroscopic haematuria; (iii) proteinuria of more than 1 g/day; (iv) arterial hypertension at the time of biopsy; (v) extent of glomerular obsolescence; (vi) extent of segmental glomerulosclerosis; (vii) presence of interstitial fibrosis; (vii) presence of diffuse intracapillary proliferation; (ix) presence of extracapillary proliferation; (x) presence of segmental thickening of glomerular basement membrane; (xi) extension of IgA deposits to the peripheral capillary loops shown by immunofluorescence. Only features (iii), (v), (vii) and (xi) proved to be independent prognostic indicators in the multivariate survivorship analysis (Cox regression model).

Adolescent↗

The detection of monocytes in human glomerulonephritis.

Renal biopsy specimens from 343 patients with primary or secondary glomerulonephritis (GN) were examined for monocytes by the non-specific esterase reaction. Large numbers of monocytes per glomerulus (M/G) were found in essential cryoglobulinemia GN (29 pts, M/G 30.6 +/- 22.4), in acute post-infectious GN (27 pts, M/G 9.1 +/- 8.3), in rapidly progressive crescentic GN (20 pts, M/G 5.6 +/- 2.7), in systemic lupus GN (61 pts, M/G 5.0 +/- 5.6), and in IgA-GN associated with chronic liver disease (5 pts, M/G 6.4 +/- 5.9) or Schönlein-Henoch purpura (15 pts, M/G 3.3 +/- 6.4). Clinico-histological correlation showed that monocyte infiltration was correlated with the extent of proteinuria (all groups), with the presence of endoluminal "thrombi" (cryoglobulinemia GN), of polymorphonuclear leukocyte infiltration (post-infectious GN), of cellular crescents (crescentic GN), of "active" lesions (lupus GN), and with the extension of lesions to the peripheral capillary walls (IgA-associated GN). The M/G index was negligible in renal amyloidosis (21 pts), in idiopathic membranoproliferative GN (10 pts), in idiopathic IgA mesangial GN (63 pts), in membranous GN (40 pts), in focal glomerulosclerosis (29 pts), in minimal change nephropathy (18 pts), and in diabetic glomerulosclerosis (5 pts). The results confirm the participation of cells of the monocyte-macrophage series in the genesis of proliferative lesions, both intracapillary and extracapillary, in immune-mediated human GN and suggest their direct involvement in glomerular injury.

Cryoglobulinemia↗

Morphological parameters in lupus nephritis: their relevance for classification and relationship with clinical and histological findings and outcome.

One hundred and sixty-seven renal biopsies from 147 patients with lupus nephritis were studied retrospectively to assess the contribution to morphological classification by features assessed with immunofluorescence and electron microscopy, together with pathological indices obtained by scoring specific histologic changes. The prognostic relevance of the histologic scoring was also evaluated. The biopsies were assigned to the following classes: I, absence of glomerular lesions; II, mesangial proliferation; III, focal segmental proliferation; IVa, diffuse (more than 50 per cent of the glomeruli) but segmentally distributed proliferation; IVb, diffuse and generalised proliferation; IVc, extracapillary proliferation; Va, pure membranous changes; Vb, membranous changes with slight mesangial proliferation; VI, association of class V and class III or IV. The incidence and degree of some glomerular and non-glomerular 'active' and 'sclerotic' changes as assessed by light microscopy were evaluated in the different classes. Both the activity and sclerosis indices obtained by scoring these lesions were found to be significantly higher in classes with glomerular proliferative changes. Eighteen patients had a second biopsy and two of these had a third; more severe changes were observed in nine and improvement in four. In 146 biopsies light microscopy findings were compared with immunofluorescence patterns (negative, mesangial, mesangial and peripheral, peripheral, membranous). The mesangial pattern was mainly present in class II with a few examples in classes I and III; in the last two the mesangial-peripheral pattern was most common; the peripheral pattern was by far the most common in class IV (a, b and c) and frequent in class VI; a membranous pattern was the rule in class V and occasionally found in class VI. Immunoglobulins (Igs) and complement (C) fractions were simultaneously present in most cases, IgG, C3 and C1q being the commonest in all classes. Except for IgM and fibrinogen, the differences in distribution of Igs and C fractions among the various classes were statistically significant. The deposits most commonly found by electron microscopy in all biopsies were mesangial; subendothelial deposits were mainly found in classes with active glomerular changes, frequently associated with deposits at the other sites in the most severe cases. A highly significant correlation was found between the activity index and the sclerosis index and severity of the clinical picture at biopsy. An unfavourable progress was confined mainly to classes with extensive intracapillary proliferation and correlated significantly with the highest activity and sclerosis indices.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Idiopathic IgA mesangial nephropathy. Clinical and histological study of 374 patients.

Histological features and data on the natural history after 1 to 45 years (mean 6.56 +/- 8.55) of total apparent duration and 1 to 13 years (mean 3.48 +/- 5.04) of post-biopsy follow-up, are reported in 374 patients (mean age, 33.9 +/- 11.9 yrs) with idiopathic mesangial IgA nephropathy, who presented with a history of macroscopic hematuria (56%), recurrent in two-thirds of the patients, or with persistent microscopic hematuria and no previous episodes of gross hematuria (44%). Mesangial cell proliferation ranged from minimal to diffuse. Associated varying degrees of extracapillary proliferation, segmental and global glomerular sclerosis, tubulo-interstitial damage and arteriolar hyalinosis usually correlated with each other and with the extent of mesangial proliferation (P less than 0.05). The actuarial curve of progression to renal death showed a 75% survival after 20 years from apparent onset. Progression to renal failure was more rapid in patients with: an older age at onset (P = 0.0582); male sex (P = 0.0730); no history of recurrent gross hematuria (P = 0.0406); high blood pressure (P = 0.0011); more marked global (P = 0.0007) and segmental (P = 0.0026) glomerular sclerosis; more severe interstitial sclerosis (P = 0.0147); more diffuse and global mesangial proliferation (P = 0.0820); mesangio-parietal pattern at immunofluorescence (P = 0.0778). However, all these parameters showed a poor predictive value if applied to any single patient.

Adolescent↗

Plasma exchange in the treatment of essential mixed cryoglobulinemia nephropathy. Long-term follow up.

Plasma exchange is increasingly used for management of Essential Mixed Cryoglobulinemia. However little is known about the long term effects of this treatment. Therefore we have reviewed the clinical and laboratory data of 20 patients with type II EMC who were followed for a mean of 24 months. 16 patients had renal involvement, which was characterized histologically in all of them: 9 had diffuse proliferative GN plus endoluminal "thrombi" in 6 and vasculitis in 5, 4 had lobular membranoproliferative GN and 3 had focal proliferative GN. 14 patients had renal failure and 13 had proteinuria greater than or equal to 2 g/24 hr. PE (combined with immunosuppressive drugs in 18) was performed for a mean of 18 procedures. The combined treatment induced prompt remission of extrarenal and renal involvement. Serum creatinine and proteinuria decreased significantly in all but 2 patients during the treatment (s. creatinine from 2.9 to 1.6 mg/dl; proteinuria from 3.5 to 1.6 g/24 hr). Analysis of long term follow up revealed that these effects were long lasting in all the cases. We conclude that PE should be used for EMC nephropathy whenever prompt remission is not obtained by conventional therapy especially in consideration of its long term beneficial effects.

Adult↗

Acute endocapillary glomerulonephritis in adults: a histologic and clinical comparison between patients with and without initial acute renal failure.

30 renal biopsies were performed in 20 adult patients with acute diffuse endocapillary glomerulonephritis. 11 patients who presented with acute renal failure (ARF) and 9 patients who had normal or mildly altered renal function were compared in order to look for clinical or pathologic features peculiar to each group and possible differences in outcome. All patients underwent early renal biopsy, and 8 had repeat biopsies. There were no significant differences in clinical, immunologic or histologic features between the two groups. In repeat biopsies, there were no histologic nor immunohistologic differences between patients with or without initial ARF. After a mean follow-up period of 18 months, the overall clinical outcome appeared favorable and was similar in the two groups. Thus, initial ARF in patients with acute endocapillary glomerulonephritis does not imply a bad prognosis. The recognition of pure endocapillary proliferation in patients with anuric acute glomerulonephritis by means of renal biopsy may avoid unnecessary and potentially hazardous treatment.

Acute Kidney Injury↗

Effect of intensive plasma exchange (PE) in rapidly progressive crescentic glomerulonephritis (RPCGN).

Ten adult patients with RPCGN (crescents in greater than 70% of glomeruli), primary in 6 and associated with systemic diseases in 4, were treated with PE, associated with oral steroids (P) and cyclophosphamide (C) in all cases and with intravenous methylprednisolone pulses (MP) in 7 cases. Four out of ten patients were anuric and needed dialysis treatment at the start of treatment. Therapeutic benefit, i.e. reversal of the trend to further deterioration and substantial improvement of GFR, was achieved in 8 out of 10 patients (80%), including 2 of 4 anuric patients, and in 7 of those (8) who had still active cellular crescents (87.5%). Similar therapeutic benefit had been achieved only in 10% of a comparable population of 10 patients with RPCGN treated before 1980 with P and C, without PE or MP pulses. It is difficult to establish whether the better therapeutic results in the more recently treated group were due to PE or to MP pulses of to both the new approaches, even though the clinical improvement obtained in all the 3 patients treated with PE without concomitant MP suggest a specific beneficial role for PE. RPCGN is a catastrophic illness characterized by progressive deterioration of kidney function, resulting in oliguria and uremia, usually within weeks or months. The most consistent histopathologic finding is the presence of extensive glomerular crescents resulting from proliferation of the extracapillary epithelial cell lining of Bowman's capsule. It is apparent that RPCGN is not a homogeneous entity, clinically, histologically or immunohistologically, but rather a clinicopathologic syndrome, the features of which may be seen in a variety of systemic disorders, including SLE, polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, cryoglobulinemia, and subacute bacterial endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

IgA-mesangial nephropathy (Berger's disease) with rapid decline in renal function.

End-stage renal failure requiring dialysis treatment developed within 5 years in 11 patients with IgA mesangial glomerulonephritis (out of 94 affected by this nephropathy) whose serum creatinine levels were less than 2 mg/100 ml at the time of biopsy. We compared these patients (Group 1) with 10 patients (Group 2) whose serum creatinine was comparable at the time of biopsy (1.2 +/- 0.3 vs 1.4 +/- 0.3 mg/100 ml) but remained unchanged (1.1 +/- 0.4 mg/100 ml) at the end of a minimum post-biopsy follow-up of 5 years. The analysis of clinical findings, at the time of biopsy, showed that the mean duration of disease, from apparent onset, was shorter in Group 1. Recurrent macroscopic hematuria, never reported in this group, was present in 40% of patients of Group 2, whereas minimal urinary abnormalities, discovered by chance, were the only findings in 73% of patients of Group 1 and in 30% of Group 2. No difference was present between the patients in the two groups in the amount of proteinuria and in the incidence of high IgA serum levels, whereas hypertension was more frequent (45% vs 20%) in Group 1. The analysis of histological lesions demonstrated that in Group 1 there was a greater incidence of diffuse mesangial proliferation (82% vs 30%), of extensive glomerular obsolescence (64% vs 0) and of severe interstitial fibrosis (54% vs 0). Immunofluorescence findings were similar in the two groups. Although no single clinical or morphological parameter was characteristic of the patients with subsequent rapid decline of renal function, some features were more commonly observed, or more severe, in these patients, and therefore should be considered reliable predictors of an unfavourable outcome.

Adult↗

Renal lesions in essential mixed IgG-IgM cryoglobulinemia. Study of 48 cases.

56 renal biopsies in 48 patients affected by essential mixed IgG-IgM cryoglobulinemia have been examined by light microscopy and immunofluorescence. Patients were classified in four groups: 1) minimal lesions (4 patients); 2) pure proliferative mesangial lesions (9 patients); 3) membranoproliferative glomerulonephritis (23 patients); 4)proliferative glomerulonephritis with prominent intraluminal thrombi (12 patients). In this last group large intraluminal thrombi intensely fixing anti-IgG and IgM antisera were present; unlike the preceding groups, few deposits on capillary walls were seen. These four groups differed in renal clinical syndrome at presentation: in particular, proteinuria or nephrotic syndrome was the predominant manifestation in group 3, acute nephritic syndrome in group 4. In the latter, reversal of renal failure and regression of lesions could be observed. Various morphological aspects tend to show that in this disease more than one mechanism is operating in producing renal damage, including local trapping of abnormal circulating proteins.

Cryoglobulinemia↗