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Biomedical subjects

G Mazzucco

Publications and source records attributed to G Mazzucco.

At least 19 recordsLinked to original sources
PubMed2006

Karyomegalic interstitial nephritis: report of 3 new cases and review of the literature.

Karyomegalic interstitial nephritis is a rare, but perhaps an "underdiagnosed" condition. Peculiar nuclear changes characterize it, involving mainly tubular cells along with glomeruli and blood vessels. Herein, 3 bioptically proven new cases of patients with chronic renal failure are discussed. The first case had a recently diagnosed karyomegalic nephritis which, to date, still does not require dialysis. The other 2 (brother and sister) required dialysis 4 and 1 years after diagnosis. Karyomegalic changes were found not only in the skin and duodenal biopsies of the male, in skin and liver biopsies of the female and in the urine cells of both patients, but also in several organs (brain, thyroid, lung, esophagus, arteries) as shown at the autopsy of the female. There was a fatal outcome for both patients. The data reported in this study emphasize the usefulness of pathologic investigation of both tissue and urine samples in the identification of this disease. Moreover, as karyomegalic interstitial nephritis is strongly suspected to have a genetic background, its identification may well not only be of clinical relevance, due to its ominous outcome, but may also bear eugenetic value.

Adult↗
PubMed2001

Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient.

The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and decoy cells identified by means of urinalysis positively stained for anti-SV40 antibody. Polymerase chain reaction performed on the DNA extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few decoy cells, which were found to be infected by JC but not BK virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.

BK Virus↗
PubMed2001

Distribution of alpha-chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome.

BACKGROUND: In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS. METHODS: GBM distribution of col IV alpha1-, alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3). RESULTS: Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving. CONCLUSIONS: Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.

Adolescent↗
PubMed2001

Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney allograft recipients.

We retrospectively examined 29 renal allograft biopsy specimens from 42 kidney transplant recipients by means of molecular biologic techniques (nested polymerase chain reaction), immunohistochemical analysis (anti-SV40 antibody), and histologic examination to evaluate the presence of polyomaviruses (PVs), viral genotypes, genomic mutations, and their pathologic significance. PV genomes were found in six cases (21%); restriction fragment length polymorphism analysis characterized 4 as JC virus (JCV) and 2 as BK virus (BKV). The latter also were positively stained immunohistochemically and showed histologically typical intranuclear viral inclusions; JCV cases were negative. DNA sequence analysis revealed only minor changes in the 4 JCV cases (3 archetypes and 1 JCV type 3, not associated with a known pathogenic genotype) but identified 2 specific variants in the BKV isolates (AS and WW strains). Given the different histologic findings (mixed inflammatory infiltration in the AS and no inflammation in the WW strain), we speculate that different BKV strains may cause differential damage in transplanted kidneys. Finally, the negative histologic and immunohistochemical JCV results, as well as the absence of viral mutations, indicate that JCV renal infection is latent in transplant recipients.

BK Virus↗
PubMed2001

[Biopsy experience at the G. Bosco Hospital from 1996 to 1999].

BACKGROUND: Aim of this study was a retrospective analysis of the renal biopsies performed in our Division. METHODS: Since January 1, 1996 to September 30, 1999 289 biopsies were performed on native kidneys, 90 patients were older than 65. RESULTS: The most frequent nephropathy was IgA glomerulonephritis (IgAGN) (28%), followed by membranous glomerulonephritis (MGN) (11%). In patients older than 65, the most frequent was MGN (20%), followed by IgAGN (12.2%). The total complications were 84 (29.1%) (hematomas >3 cm 1%; blood transfusion: 1.4%). Complications were not related to age, blood pressure, renal function, clinical presentation, number of shots. In 217 patients, the results obtained with two different modalities were compared: manual system (needle size=15 gauge) and automatic system (18 gauge). No statistically significant differences were found as regards the number of shots for single biopsy, number of glomeruli and major complications (1.6% vs 1.3%), while minor complications were more frequent in the second group. CONCLUSIONS: In conclusion, the number of renal biopsies performed in our Division has been increasing year after year. This trend can be partially explained by our wider indications to renal biopsy in elderly population (the data related to resident population showed the greatest prevalence of biopsies in patients 70 to 79 years old). Renal biopsy actually represents a safe examination even in elderly patients. From a technical point of view, on the basis of personal experience, 18 gauge acecut automatic needles seem to be preferred to other kind of devices.

Adolescent↗
PubMed1999

The concept of 'glomerulonephritis'. the fascinating history of evolution and emergence of a specialist's nosology focus on Italy and Torino.

Though the term 'nephritis' first appeared in the 19th century, this word did not bear the same meaning as it does today; indeed, for many years it was used to indicate 'renal diseases' (in the sense of Bright's disease) in a larger sense. This review summarizes the long gestation of the concept of 'glomerulonephritis' from the prehistory of medicine up to the beginning of the second half of the 20th century with emphasis on Italy and, in particular, on Torino, which was the capital of the Kingdom of Italy from 1861 to 1865. To the best of our kowledge, this is the first study reporting an epidemiology survey of Bright's disease in Italy from 1880 up to 1960. Towards the end of the 19th century, Bright's disease accounted for 26 deaths/year/10(5) population (in comparison with more than 200 from tuberculosis) in Italy, roughly paralleling that reported in the USA. At the beginning of the 20th century, Bright's disease was the seventh cause of death (almost 1% of total deaths) in Italy. Furthermore, in Italy, as elsewhere, autopsy studies showed a higher percentage of deaths attributed to Bright's disease (5-7%) in comparison with those obtained from vital statistics. In 1960, just before the beginning of renal replacement therapy, Bright's disease accounted for 15.7 deaths/year/10(5) population (= 1.46% of all deaths), roughly paralleling that reported in the United Kingdom (13.8/10(5) population = 1.25% of deaths). Probably, it was difficult to recognize the real incidence of chronic renal diseases leading to death in the 1960s, and vital statistics were able to furnish only approximate estimates. However, noteworthy is the fact that these values were very close to those estimated as being the annual need for renal replacement therapy (10-20 cases/year/10(5) population).

Glomerulonephritis↗
PubMed1998

Renal Encephalitozoon (Septata) intestinalis infection in a patient with AIDS. Post-mortem identification by means of transmission electron microscopy and PCR.

We describe the occurrence of renal Encephalitozoon (Septata) intestinalis infection in a 35-year-old AIDS patient who died with disseminated tuberculosis. The patient did not complain of specific symptoms involving the kidney or lower urinary tract during life, but at autopsy, light microscopic examination of the kidney revealed numerous small round or oval bodies in the tubules and tubular cell cytoplasm that were interpreted as intracellular protozoa. Transmission electron microscopy of tissue retrieved from paraffin-embedded samples identified these organisms as microsporidia belonging to the Encephalitozoonidae family, but did not allow definitive identification of the species of infecting parasite. This was made possible only by means of Southern blot hybridization after the polymerase chain reaction, which recognized the micro-organism as E. intestinalis.

AIDS-Related Opportunistic Infections↗
PubMed1998

Ultrastructural and immunohistochemical findings in Alport's syndrome: a study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations.

A total of 108 patients affected by Alport's syndrome, taken from 97 families, were enrolled in a genetic and ultrastructural study. Sixty-four families (75 patients) were X-linked, seven autosomal recessive, two autosomal dominant, five uninterpretable, and 19 sporadic. The ultrastructural features were consistent with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's syndrome in 22 patients in the X-linked, sporadic, and genetically uninterpretable groups (without significant differences), as well as in the autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the first three groups, without significant differences. More severe mutations were more frequently present in patients with an ultrastructural pattern consistent with Alport's syndrome. Nevertheless, there seems to be no strict correlation between mutation and ultrastructure, because a major rearrangement was found in a patient with no significant lesions, and different morphologic patterns were detected in patients Belonging to the same family. Immunohistochemical investigation into 24 patients for alpha (IV) chains showed that both alpha 3(IV) and alpha 5(IV) were lacking in the glomerular basement membrane of 13 patients (five with mutations) and were expressed in another six (three with mutations and one in the autosomal group). On the contrary, in this study the retained expression of alpha 3(IV) chain was found, despite the lack of alpha 5(IV) in the glomerular basement membrane of five patients (two with mutation). These different patterns could be related to both the type and severity of the COL4A5 mutations. All of the ultrastructural patterns were identified in all three immunohistochemical groups. Ultrastructural features and alpha 5(IV) chain production, even if an expression of a genetic mutation, do not strictly correlate. The combined use of analysis of collagen expression and electron microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort, and therefore this approach is advisable. A multidisciplinary approach is recommended in the study of Alport's syndrome in an attempt to achieve a better diagnostic definition of and insight into the pathogenetic mechanisms.

Adolescent↗
PubMed1997

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↗
PubMed1997

Long-term prognosis of Henoch-Schönlein nephritis in adults and children. Italian Group of Renal Immunopathology Collaborative Study on Henoch-Schönlein purpura.

BACKGROUND: The aim of this multicentre collaborative study was to compare the progression of renal disease in children and adults with Henoch-Schönlein purpura (HPS) nephritis selected on the basis of IgA-dominant renal deposits and biopsy material available for review. METHODS: The analysis was performed in 152 patients (95 adults and 57 children < 16 years old at diagnosis) with a follow-up (> or = 1 year up to 20 years (4.9 +/- 3.4 years in adults and 4.8 +/- 3.9 years in children). RESULTS: Renal histology and clinical presentation were similar in both age groups: crescents were found in 36% of adults and 34.6% of children (in only 2.7% of adults and 1.9% of children involving > 50% of glomeruli), nephrotic-range proteinuria in 29.5% of adults and 28.1% of children and functional impairment in 24.1% of adults and 36.9% of children. The outcome was similar for both age groups (remission, 32.5% of adults and 31.6% of children; renal function impairment, 31.6% of adults and 24.5% of children). Endstage renal disease was observed in 15.8% of adults and in 7% of children. Renal function survival at 5 years was not significantly different in the two groups (85% in adults and 95% in children) and at 10 years it was approximately 75% in both groups. None of the children died and adult survival was 97% at 5 years. In adults at presentation, renal function impairment (P < 0.02) as well as proteinuria higher than 1.5 g/day (P < 0.02) and hypertension (P < 0.001) were negative prognostic factors. Multivariate analysis stressed the main statistical relevance of proteinuria (relative risk 2.37, P < 0.02). Conversely, in children no definite level of proteinuria, hypertension or other data were found to be associated with poor prognosis. CONCLUSIONS: Among patients with a clinical presentation which warrants renal biopsy, HSP nephritis has a similar prognosis in children and adults. The evolution is more predictable in adults than in children.

Adult↗
PubMed1997

Renal changes in patients with acquired immunodeficiency syndrome: a post-mortem study on an unselected population in northwestern Italy.

The renal pathologic features of 120 consecutively autopsied patients affected by acquired immunodeficiency syndrome was investigated by light microscopic analysis. Variously associated renal changes were found in 82 patients (68.3%). Glomerular changes were present in 25. The following diagnoses were made: mesangial glomerulonephritis (16 patients), defined by the presence of deposits in the mesangium and/or mesangial cell proliferation; membranous glomerulonephritis (4 patients), cirrhotic glomerulosclerosis (2 patients); and lupuslike glomerulonephritis (3 patients). Glomerular diseases seemed to be significantly associated with chronic hepatitis or liver cirrhosis. Interstitial inflammation was present in 19 cases: chronic pyelonephritis (2 patients), focal nephritis (5 patients), multiple cortical abscesses (7 patients), granulomatous nephritis (5 patients). Cryptococci were found in one and undetermined microorganisms in two cases of multiple cortical abscesses. Atypical mycobacteria were found in two cases of granulomatous nephritis. Mycotic infections were identified in another 6 patients, in whom they did not elicit any inflammatory response. It is worth stressing that, although various generalized infections are common in patients with acquired immunodeficiency syndrome, only cryptococci and atypical mycobacteria also frequently involve the kidney. Focal tubular necrosis was observed in 15 patients. Benign nephrosclerosis was the most common vascular change (27 patients). Changes recalling hemolyticuremic and localized intravascular coagulation were found in three and six patients, respectively. Our data, dealing with a European Caucasian population, considerably differ from those reported in North American literature, in as much as we found no cases of human immunodeficiency virus nephropathy. Conversely, immune-mediated glomerular diseases were frequent, in agreement with recent studies on renal biopsy specimens from AIDS patients with acquired immunodeficiency syndrome. This type of infections, supplies multiple sources of antigens that may stimulate immune complex formation and, therefore, glomerular diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas.

To investigate the molecular mechanisms of tuberous sclerosis (TSC) histopathologic lesions, we have tested for loss of heterozygosity the two TSC loci (TSC1 and TSC2) and seven tumor suppressor gene-containing regions (TP53, NF1, NF2, BRCA1, APC, VHL, and MLM) in 20 hamartomas from 18 TSC patients. Overall, eight angiomyolipomas, eight giant cell astrocytomas, one cortical tuber, and three rhabdomyomas were analyzed. Loss of heterozygosity at either TSC locus was found in a large fraction of the informative patients, both sporadic (7/14) and familial (1/4). Interestingly, a statistically significant preponderance of loss of heterozygosity at TSC2 was observed in the sporadic group (P < 0.01). Among the possible explanations considered, the bias in the selection for TSC patients with the most severe organ impairment seems particularly appealing. According to this view, a TSC2 defect might confer a greater risk for early kidney failure or, possibly, a more rapid growth of a giant cell astrocytoma. None of the seven antioncogenes tested showed loss of heterozygosity, indicating that the loss of either TSC gene product may be sufficient to promote hamartomatous cell growth. Finally, the observation of loss of heterozygosity at different markers in an astrocytoma and in an angiomyolipoma from the same patient might suggest the multifocal origin of the second-hit mutation.

Chromosome Deletion↗
PubMed1996

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↗
PubMed1996

Intracellular protozoan infection in small intestinal biopsies of patients with AIDS. Light and electron microscopic evaluation.

Small intestinal biopsies of 21 patients with acquired immunodeficiency syndrome (AIDS) with light microscopic findings diagnostic or suspicious for parasite infection were investigated by transmission electron microscopy (TEM). TEM allowed us to identify and specify the genus and species of involved parasites in 16 out of the 21 cases: 7 Cryptosporidium parvum, 5 Enterocytozoon bieneusi and 4 Isospora belli. Cryptosporidium was easily identified on light microscopy (LM), and only slightly influenced by parasite burden in all the 7 cases; TEM confirmed LM diagnosis and made it possible to characterize the parasites as C. parvum. The identification of Microsporidium on LM in our cases was related to the burden of parasite; its presence was certainty identified in 2 cases and suspected in 3. TEM allowed to identify these parasites as E. bieneusi. Intracytoplasmic coccidia could be detected with certainly in semithin sections in all 4 cases, but TEM was always needed to specify the infectious agent as I. belli. In 5 cases the suspicious of protozoan infection on LM (3 microsporidia, 1 intracytoplasmic coccidia and 1 Cryptosporidium) was not confirmed by TEM. Our data suggest that TEM is an appropriate diagnostic tool in this field of pathology and necessary in most of the cases.

Acquired Immunodeficiency Syndrome↗