PubMed Health⌕ Search

Biomedical subjects

F Ferrario

Publications and source records attributed to F Ferrario.

At least 19 recordsLinked to original sources
PubMed2006

Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans.

Mechanisms for human membranous glomerulonephritis (MGN) remain elusive. Most up-to-date concepts still rely on the rat model of Passive Heymann Nephritis that derives from an autoimmune response to glomerular megalin, with complement activation and membrane attack complex assembly. Clusterin has been reported as a megalin ligand in immunodeposits, although its role has not been clarified. We studied renal biopsies of 60 MGN patients by immunohistochemistry utilizing antibodies against clusterin, C5b-9, and phosphorylated-protien kinase C (PKC) isoforms (pPKC). In vitro experiments were performed to investigate the role of clusterin during podocyte damage by MGN serum and define clusterin binding to human podocytes, where megalin is known to be absent. Clusterin, C5b-9, and pPKC-alpha/beta showed highly variable glomerular staining, where high clusterin profiles were inversely correlated to C5b-9 and PKC-alpha/beta expression (P=0.029), and co-localized with the low-density lipoprotein receptor (LDL-R). Glomerular clusterin emerged as the single factor influencing proteinuria at multivariate analysis and was associated with a reduction of proteinuria after a follow-up of 1.5 years (-88.1%, P=0.027). Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment. Preliminary in vitro experiments showed podocyte binding of biotinilated clusterin, co-localization with LDL-R and specific binding inhibition with anti-LDL-R antibodies and with specific ligands. These data suggest a central role for glomerular clusterin in MGN as a modulator of inflammation that potentially influences the clinical outcome. Binding of clusterin to the LDL-R might offer an interpretative key for the pathogenesis of MGN in humans.

Adult↗
PubMed2001

Idiopathic IgA nephropathy with segmental necrotizing lesions of the capillary wall.

BACKGROUND: Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for the clinical outcome is still unknown. METHODS: Thirty-five out of 340 patients (10.3%) biopsied in our division at the San Carlo Hospital since 1974 showed active segmental necrotizing lesions. The morphological features and the natural history of this group of patients were compared with those of a control group of 229 patients who had comparable serum creatinine and extent of glomerular sclerosis, but who lacked active segmental necrosis. RESULTS: Patients with the necrotic variant showed a significantly more marked extracapillary proliferation and interstitial accumulation of monocytes and T lymphocytes and, in the segmental areas of necrotizing and extracapillary lesions, infiltration of monocytes, deposition of fibrinogen, and expression of the adhesion molecule vascular cell adhesion molecule-1. No difference was found in the presenting clinical syndrome. The clinical course was frequently characterized by acute flare ups, and the progression to end-stage renal failure was more frequent, although actuarial renal survival was not significantly worse (P = 0.07). The aggressive treatment with steroids and cyclophosphamide, carried out in 20 of the 35 patients, has probably been beneficial, justifying the multicenter controlled trial that recently has been initiated. CONCLUSIONS: Vasculitic lesions of the glomerular capillaries, with histologic and immunohistological features similar to those of Henoch-Schönlein purpura and antineutrophil cytoplasmic antibody-positive renal vasculitis, were found in 10% of patients with idiopathic IgAN. Clinical features at presentation did not differ from those of the other patients with IgAN, and despite of the more frequent occurrences of recurrent acute flare ups, rapid progression to end-stage renal failure was a rare phenomenon, even in untreated patients.

Adult↗
PubMed1999

Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis.

BACKGROUND: In kidney biopsies of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis, a variety of histopathological lesions occur, and their relationship to renal outcome is virtually unknown. This multicenter European study reports a clinicopathological analysis of biopsies from 157 patients with systemic vasculitis. METHODS: The biopsies were evaluated according to a previously standardized scoring protocol. Serum creatinine values were measured at the time of biopsy and one year later. In addition, the lowest creatinine level during follow-up was taken into account as the optimum level of renal function recovery. The clinical prognostic value of the histopathological parameters was analyzed with the Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U-test. RESULTS: The percentage of normal glomeruli correlated most significantly with renal outcome at all points of measurement (all P < 0.001). Other lesions predicting for renal function were glomerular sclerosis (P < 0.0005 at one year after the biopsy), diffuse interstitial infiltrates (P < 0.0001 at entry, P < 0.0003 at one year), tubular necrosis (P < 0.0025 at entry), and tubular atrophy (P < 0.002 at entry, P < 0.0002 at one year). CONCLUSION: Traditionally, attention is focused on the extent of active lesions in the renal biopsy in order to determine the severity of renal disease and its implication for renal outcome. Because of their significant impact on renal function, combined with their easy recognition, we recommend the use of the percentage of normal glomeruli in an adequate biopsy in predicting renal function of patients with systemic vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

Reconstruction of major orbital-maxillary defects with free latissimus dorsi myocutaneous flap.

Reconstruction following excision of tumors of the orbital-maxillary region represents a challenge to the head and neck surgeons. Microvascular techniques have significantly improved the possibilities of an adequate three-dimensional repair. Among the different available options, the latissimus dorsi myocutaneous flap (LDMF) has been considered, as it seems to fulfill the requirements for a functional obliterations of the orbital-maxillary cavity and to restore the facial contour. Two cases of large orbital-maxillary defects repaired with a LDMF are reported; in one of them the intraoral palatal competence and lining were achieved through a temporalis muscle flap. Technical remarks are presented and discussed as well as the indications and possibilities for more sophisticated reconstructions, aimed at a better cosmetic outcome.

Basal Cell Carcinoma↗
PubMed1999

[Radiation treatment of early stage supraglottic cancer].

The management of early-stage squamous cell carcinoma (SCC) of the supraglottic larynx is still controversial. Supraglottic laryngectomy as well as irradiation alone is correlated with good oncological and functional results. In order to evaluate the results and prognostic factors influencing the successful using radiotherapy (RT), the authors performed a retrospective study of 100 consecutive T1-T2 N0 M0 cases of SCC of the supraglottic larynx, treated at a single institution between 1983 and 1992. RT was delivered with 60Co or 6 MeV photons through two lateral parallel opposed portals encompassing the primary laryngeal tumor and the upper and mid-neck nodes (Robbins' levels II, III and V). Supraclavicular nodes (level IV) were electively irradiated in 54 patients with T2 N0 tumors only, using an anterior field with midline block. Sixty-three patients received conventional fractionation (2 Gy/fraction, once-a-day, five times a week), while 37 patients were irradiated according to a twice-a-day fractionation regimen (1.5 Gy/fraction, twice a day with six-hour interval, five days a week). The median total tumor dose delivered was 67 Gy. A multivariate analysis showed that performance status, tumor grade and fractionation modality were the only statistically significant variables influencing disease-free survival. Acute and late radiation reactions were relatively low. This retrospective study confirms that conservative management of T1-T2 N0 supraglottic cancer using RT can achieve good cure rates with the possibility of larynx preservation for the majority of the patients. The decision between different conservative treatment modalities may be influenced by several factors correlated to the patient's conditions, tumor characteristics, but especially treatment modalities.

Adult↗
PubMed1999

Morphological features in IgA nephropathy.

The hallmark of Berger's disease is the mesangial and/or mesangioparietal deposition of IgA as the predominant or sole immunoglobulin. Despite similar appearance to the immunohistological pattern, morphological glomerular lesions differ in that they are wide ranging and variable, making precise and uniform classificatory approaches extremely difficult. The most characteristic and frequent abnormality is mesangial enlargement, which is produced by various combinations of excess of matrix and of hypercellularity, ranging from minimal to very extensive. In some cases the mesangial lesions are more severe giving a pattern of membrano-proliferative glomerulonephritis. The concomitant presence of necrotizing alterations of glomerular tuft with segmental extracapillary proliferation, similar to capillaritis of Henoch-Schönlein purpura and ANCA associated vasculitis, is now well documented and recognized by researchers. This similarity with vasculitic lesions is confirmed by the strong positivity of fibrinogen, of VCAM-1, and of the accumulation of monocytes within the same areas of segmental necrotic glomerular lesions. These active lesions appear to play a crucial role in the progression of the disease due to repeat formations of necrotizing/extracapillary alterations with subsequent glomerular sclerosis and fibrous adhesions. In the last decade, many groups of investigators have focused their attention on tubulo-interstitial lesions in IgA nephropathy, in particular, on leukocyte infiltration and intersitial fibrosis, demonstrating that the impairment of the glomerular filtration rate and the progression of the disease correlate better with tubulo-interstitial damage than with the degree of glomerular damage. This has also been confirmed by studies with repeat biopsies. Moreover, the recent availability of immunohistochemical and in situ hybridation methods that allow more precise evaluations of infiltrating cells and of numerous factors secreted by these cells (chemokines, cytokines, adhesion molecules etc ...) offers us incredible opportunities to expand our knowledge on mechanisms involved in the inflammatory process and in the progression of the disease.

Biopsy↗
PubMed1998

DNA/protein flow cytometry as a predictive marker of malignancy in dysplasia-free Barrett's esophagus: thirteen-year follow-up study on a cohort of patients.

Intestinal metaplasia identifies Barrett's esophagus (BE) and is associated with an increased risk for esophageal adenocarcinoma. Dysplasia occurs as an intermediate step. However, progression from metaplasia to neoplasia without the demonstration of dysplasia has been described. The role of dual-parameter flow cytometry (FC) as a predictor of neoplastic risk in dysplasia-free cases was evaluated. DNA/protein FC and histology were performed on 362 samples from 30 dysplasia-free BE patients, followed up since 1985 once every 1-2 years. Nine cases were aneuploid, five of which (group IV) were frankly aneuploid; in the other four cases (group III), aneuploidy was detectable by dual-parameter analysis only. Twenty-one patients were diploid. Twelve (group II) also had an abnormally high G1-phase protein content compared to group I (nine patients), which were diploid with a low-moderate protein content. In three patients of group IV an adenocarcinoma in situ was diagnosed, after 5, 6, and 10 years, respectively. In two patients of group III, a low- and a high-grade dysplasia were observed at 3 and 6 years follow-up, respectively. One patient of group I first acquired a high protein content, then an aneuploid DNA content, and then progressed to adenocarcinoma (12 years). None of the still diploid patients (17 cases) have progressed to dysplasia or cancer compared with 6 of 13 presently aneuploid patients (P < 0.01). In conclusion, DNA/protein FC is a marker of increased malignant potential and thus may be used to detect patients at higher risk in dysplasia-free BE and assist in understanding the various stages of malignant transformation in long-term follow-up studies.

Adult↗
PubMed1998

Transforming growth factor-beta, endothelin-1, and c-fos expression in necrotizing/crescentic IgA glomerulonephritis.

BACKGROUND: Among our cases of IgA glomerulonephritis (IgAGN), 10% show necrotizing/extracapillary lesions involving a small percentage of glomeruli and associated with a certain degree of inflammation in absence of glomerular and interstitial scarring. In our experience, also in repeat biopsies, these cases of IgAGN have a worse prognosis probably because necrotizing/extracapillary lesions can repeat and accumulate, leading to the progression of damage. As it is well known that transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) are key-factors in the progression of glomerulonephritis, aim of the study was to examine their expression in renal biopsies of primary IgAGN with necrotizing/crescentic lesions in complete absence of interstitial fibrosis. To obtain information about the mitogenic effect of ET-1, the expression of c-fos, whose upregulation by ET-1 has been established in culture, was also studied. METHODS: Eighteen renal biopsies of patients with necrotizing/crescentic IgAGN were examined by immunohistochemistry with antibodies against TGF-beta, ET-1 and c-fos. The results were compared with those obtained on 22 cases of IgAGN characterized only by pure mesangial proliferation and 25 IgAGN biopsies with advanced, not active, glomerulointerstitial lesions. RESULTS: In necrotizing/crescentic IgAGN glomerular TGF-beta appeared more positive than in cases characterized only by pure mesangial proliferation and was especially expressed on cellular crescents. In the interstitium, TGF-beta, ET-1 and c-fos were expressed by infiltrating leukocytes, tubules, and small vessels. This positivity, although similar as localization, was less diffuse than in biopsies with advanced interstitial damage, but significantly greater than in cases with pure mesangial proliferation. CONCLUSIONS: Positivity of TGF-beta on cellular crescents is similar to that observed from other authors in different types of necrotizing/crescentic human glomerulonephritis and supports our hypothesis that this is a peculiar type of IgAGN. Moreover, interstitial expression of TGF-beta, ET-1 and c-fos in biopsies with glomerular active lesions but complete absence of interstitial fibrosis may potentially represent a signal of activation of mechanisms that induce and amplify the damage leading to further progression of the disease.

Adolescent↗
PubMed1998

Fibrillary and immunotactoid glomerulopathies.

There is sufficient clinical and morphological evidence to suggest that Fibrillary Glomerulonephritis (FGN) and Immunotactoid (IT) Glomerulopathy are two different diseases. Is still open to debate if IT glomerulopathy is a distinct entity or is strictly associated with a spectrum of systemic syndromes ("forme fruste" of Cryoglobulin and paraprotein associated diseases). Further studies about pathogenetic mechanisms of fibril or microtubule formation may allow a better understanding of these diseases.

Glomerulonephritis↗
PubMed1998

[Basaloid-squamous cell carcinoma of the larynx: a new morphologic entity. Case report].

Basaloid-Squamous Cell Carcinoma (BSCC) is considered a biologically aggressive variation of squamous cell carcinoma (SCC). Wain et al. first reported BSCC as an independent neoplasm in 1986. In the past, it was most likely misinterpreted as atypical SCC. To date approximately one hundred cases have been reported in the literature. The pathognomonic characteristic of BSCC is an intimate association between basaloid and squamous patterns: for this reason a small biopsy specimen may be insufficient for correct diagnosis. In such cases, knowledge of the biological behavior of these tumors (i.e. local aggressiveness and tendency to spread both regionally and at a distance) may prove useful. Prognosis and survival rates are certainly worse than in SCC. Within the upper aero-digestive tract, BSCC is most likely to arise in the supraglottic larynx, the pyriform sinus and the base of the tongue. Treatment should include surgery of the primary tumor and of the neck lymph nodes, followed by radiotherapy. The authors present a new case report indicating the typical feature of this tumor (aggressiveness, synchronous basaloid and squamous histology, supraglottic involvement.

Aged↗
PubMed1997

A new rational hypothesis for the pharmacophore of the active metabolite of leflunomide, a potent immunosuppressive drug.

Leflunomide is one of the most promising disease-modifying antirheumatic drug now in clinical trials for the treatment of rheumatoid arthritis. Metabolic studies have indicated that leflunomide is rapidly processed in vivo to an active metabolite, A771726 (2). To identify the chemical characteristics necessary for the immunosuppressive activity of 2, configurational and conformational studies were carried out on the latter and its inactive analogues (ethyl 3-hydroxy-2-((4-(trifluoromethyl)phenyl)carbamoyl)but-2-enoate, 3a, and 3-hydroxy-2-nitro-N-(4-(trifluoromethyl)phenyl)but-2-enamide, 3b). These studies suggested that the pharmacophore responsible for the immunosuppressive activity of 2 is a beta-keto amide with the enolic hydroxy group cis to the amidic moiety. To verify this hypothesis, a new class of immunosuppressive agents was designed and synthesized. Their testing in vitro and in vivo identified compounds which were more potent than both leflunomide and 2 and above all confirmed our hypothesis as to the key structural and chemical determinants for the immunosuppressive properties of 2 and our compounds.

Aniline Compounds↗
PubMed1997

Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.

Adult↗
PubMed1997

[Solitary fibrous tumor of the nasopharynx. Apropos of a case].

Solitary fibrous tumor (SFT) is a rare neoplasm, arising in the adult and more commonly in the pleura. For many years it has been referred to the serous surfaces of the body, namely pleura, peritoneum and pericardium; recently cases arising in mesenchymal organs such as lung, mediastinum, liver and paranasal sinuses were reported. We present a SFT of the nasopharynx, observed in a 41 year-old patient complaining a 6 months history of aural fullness at the right ear. Clinical examination revealed the presence of secretory otitis media and swelling of the lateral wall of the nasopharynx. CT scan and MR showed the presence of a solid mass, with scarce vascularization, extending from the right side of the nasopharynx to the infratemporal and pterigoid fossae. The surgical approach consisted in a facial translocation by the rotation of a maxillary-check flap through different osteotomies; a firm whitish mass not invading the surrounding tissues was identified and enucleated. A definitive diagnosis cannot be made at frozen sections, requiring more accurate processing and immunohistochemical staining. Literature reports fourteen cases of SFT of the upper aero-digestive tracts (nasopharynx, paranasal sinuses, larynx) and some 8 more cases in the head and neck area (thyroid, salivary glands and parapharyngeal spaces). This case report adds a further contribution to support the mesenchymal origin of the SFT.

Adult↗
PubMed1997

[Idiopathic thrombosis of the internal jugular vein].

The venous thrombosis represents a vascular disorder usually involving the low limbs. The manifestation at the level of the upper limbs and the neck is much more rare, particularly as a consequence of a central venous catheterization of an infectious disease or of a trauma. The authors report an unusual case of spontaneous thrombosis of the internal jugular vein and analyze the most salient nosologic, diagnostic and therapeutic aspects.

Anticoagulants↗
PubMed1997

[A free radial forearm flap in oral cavity reconstruction].

A relatively recent method for reconstruction of the oral cavity after tumor removal employs the use of revascularized free flaps. In particular, the Radial Forearm Flap has gained significant international recognition. After a review of the history of this procedure, the authors describe the essential aspects of the technique including what is involved in removal as well as in microanastomosis and reconstruction. In addition, the paper also deals with operative patient monitoring, prevention and treatment of any complications. Finally, a series of 10 cases is presented all of which underwent surgery at the E.N.T. Division of the Varese Hospital. The case study presents the oncological and functional results and emphasizes the technical details of the entire sampling. The purpose of this work has been to demonstrate that this procedure can be used by an E.N.T. surgical staff without requiring input from an outside team of specialists. Although this technique is difficult and somewhat limited, it must be considered one of the most innovative proposals in the field of plastic, reconstructive surgery of the head and neck.

Adult↗