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Biomedical subjects

L Muratori

Publications and source records attributed to L Muratori.

At least 19 recordsLinked to original sources

Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.

BACKGROUND: Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. AIM: To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. METHODS: Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. RESULTS: Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. CONCLUSIONS: Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.

Adult↗

Antibodies to filamentous actin (F-actin) in type 1 autoimmune hepatitis.

AIMS: To evaluate the diagnostic significance of anti-filamentous actin antibodies (A-FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti-smooth muscle antibodies (SMA); and to correlate A-FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH-1). METHODS: We studied 78 consecutive untreated AIH-1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH-2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A-FAA with a modified commercial ELISA. RESULTS: SMA was detected by IIF in 61 (78%) of 78 AIH-1 patients, of whom 47 (60%) had the SMA-T/G and 14 (18%) the SMA-V pattern. Of the pathological controls, 32 (20%) had the SMA-V pattern (25 with hepatitis C, 2 with AIH-2, 2 with PBC, 3 with CD). A-FAA were present in 55 AIH-1 patients (70.5%; 46 with SMA-T/G, 7 with SMA-V, and 2 SMA-negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH-2, two PBC and one CD. The association between A-FAA and the SMA-T/G pattern was statistically significant (p<0.0001). A-FAA levels were higher in SMA-T/G positive than SMA-V positive AIH-1 patients and controls (p<0.0001). A-FAA positivity was significantly associated with higher gamma-globulin and IgG levels, but did not correlate with other considered parameters. CONCLUSION: The modified A-FAA ELISA strictly correlates with the SMA-T/G pattern and is a reliable and operator independent assay for AIH-1. Detection of A-FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise.

Actins↗

Hepatic steatosis in chronic hepatitis C: impact on response to anti-viral treatment with peg-interferon and ribavirin.

BACKGROUND: There is increasing evidence that hepatic steatosis contributes to the progression of liver fibrosis, whereas its impact on the efficacy of anti-viral treatment is still under investigation. AIM: To evaluate the effect of steatosis on the outcome of combined anti-viral treatment. METHODS: We studied 102 consecutive naive patients with chronic hepatitis C receiving combined anti-viral therapy (peg-interferon alpha-2b and ribavirin). RESULTS: Fifty (49%) of 102 patients had evidence of hepatic steatosis (29 grade 1, 16 grade 2 and 5 grade 3). Sustained virological response was similar in patients with and without steatosis (58% vs. 56%); moreover, the grade of steatosis did not affect the rate of sustained virological response (grade 1: 58%, grade 2: 56% and grade 3: 60%). Patients with steatosis had significantly higher serum levels of aspartate transaminase, alanine transaminase and gamma-glutamyltransferase (P = 0.007, 0.004 and 0.03, respectively), higher histological activity (P = 0.03), more advanced stage of fibrosis (P = 0.0394) and more often hepatitis C virus genotype 3 (P = 0.04). CONCLUSIONS: Our findings suggest that hepatic steatosis in chronic hepatitis C, irrespective of its grade, is not a negative prognostic factor of response to combined anti-viral therapy, even when the histological and biochemical profile of the disease is more aggressive.

Adult↗

Clinical features of type 1 autoimmune hepatitis in elderly Italian patients.

BACKGROUND: The usual onset of type 1 autoimmune hepatitis occurs at puberty or around menopause, whereas disease presentation in the advanced age is less often reported. AIM: To assess the clinical, immunological and histological features of Type 1 autoimmune hepatitis in elderly Italian patients. METHODS: We assessed, at diagnosis, the clinical and immunological features of 76 consecutive Italian patients with type 1 autoimmune hepatitis, focusing particularly on a subgroup of 20 patients presenting at > or = 65 years (females 95%, median age 72 years, range 65-82). RESULTS: In comparison with the younger group, at the time of autoimmune hepatitis diagnosis, elderly Italian patients are more often asymptomatic (25% vs. 7%; P = 0.04), are more frequently positive for antinuclear autoantibodies (95% vs. 52%; P = 0.0004) and HLA-DR4 (45% vs. 18%; P = 0.03); among the extra-hepatic manifestations, autoimmune thyroid disorders are prevalent in the elderly group (25% vs. 5%; P = 0.02). However, no difference was observed in the histological/biochemical expression of the liver disease and response to immunosuppression. CONCLUSIONS: In elderly Italian patients, autoimmune hepatitis has typical serological and genetic characteristics, is more frequently asymptomatic, although prognosis and response to therapy is similar to that of younger patients. As a concomitant autoimmune thyroid disorder is common, autoimmune hepatitis should be suspected and investigated in elderly patients with autoimmune thyroid disorder and abnormal liver function tests.

Adult↗

Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic antibodies in coeliac disease before and after gluten-free diet.

BACKGROUND: Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. AIM: To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. METHODS: One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. RESULTS: In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. CONCLUSION: More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.

Adolescent↗

The Western immunoblotting pattern of anti-mitochondrial antibodies is independent of the clinical expression of primary biliary cirrhosis.

Anti-mitochondrial antibodies are the serological markers of primary biliary cirrhosis. We analysed the detailed anti-mitochondrial antibodies patterns to see whether the immunological specificities detected at the time of the diagnosis correlate with the histological, clinical and immunological expression of the disease. One hundred and thirty primary biliary cirrhosis patients were studied at the time of presentation/diagnosis. Anti-mitochondrial antibodies reactivity was dissected and evaluated by Western immunoblotting with bovine heart submitochondrial particles as antigenic source. Six different Western immunoblotting patterns have been identified with the following hierarchy: pattern A (anti-PDC-E2+anti-E3BP, 38.5%), pattern B (anti-PDC-E2+anti-E3BP+anti-OGDC-E2, 20.8%), pattern C (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2+anti-OGDC-E2, 13.1%), pattern D (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2, 6.9%), pattern E (anti-BCOADC-E, 6.1%) and pattern F (anti-mitochondrial antibodies negative primary biliary cirrhosis, 14.6%). The different patterns were neither associated with peculiar clinical, biochemical, histological and immunological features nor with the Mayo Risk Score. The anti-mitochondrial antibodies pattern at presentation is independent of the stage of the liver disease; therefore, the Western immunoblotting characterisation of anti-mitochondrial antibodies does not seem to be helpful in identifying the clinical, biochemical or histological expression of primary biliary cirrhosis at the time of the diagnosis.

Adult↗

Type 1 autoimmune hepatitis: patterns of clinical presentation and differential diagnosis of the 'acute' type.

BACKGROUND: Autoimmune hepatitis (AIH) has three different presentations: chronic, acute and asymptomatic. AIM: To evaluate AIH presentation in Italian patients and investigate criteria that differentiate between acute-type AIH and acute viral hepatitis. DESIGN: Prospective observational study. METHODS: Eighty-six consecutive patients with type 1 AIH and 41 with acute viral hepatitis (controls) were studied. 'Acute' AIH was defined as recent-onset (<30 days) symptoms (jaundice and/or fatigue and/or fever) with marked alterations in serum liver tests; the 'asymptomatic' pattern as the occasional detection of liver abnormalities, and the 'chronic' pattern as the presence of signs and/or symptoms of long-lasting liver disease. RESULTS: Of 86 AIH patients, 59 (68%) presented with the chronic pattern, 22 (26%) with the acute pattern, and 5 (6%) were asymptomatic. 'Acute' patients had higher AST, ALT and bilirubin serum levels (p < 0.0001). No differences were detected with respect to age and serum levels of alkaline phosphatase, gamma-GT, albumin or gamma-globulin. All three groups had similar prevalences of moderate/severe (vs. mild) histological findings and liver cirrhosis. When compared with controls with acute viral hepatitis, 'acute' AIH patients were more often female (82% vs. 24%, p < 0.0001) and had higher serum gamma-globulin levels (26.9 vs. 13.4 g/l, p < 0.0001) and AST/ALT ratio (1.20 vs. 0.61, p < 0.0001). DISCUSSION: Although in Italy type 1 AIH patients usually present with a chronic pattern, some 25% have an acute presentation resembling that of viral hepatitis. 'Acute' AIH and viral hepatitis can be reliably differentiated by simple parameters such as gender, gamma-globulin serum levels and AST/ALT ratio.

Acute Disease↗

'True' antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both?

Anti-mitochondrial antibody (AMA) is considered the serological hallmark of primary biliary cirrhosis (PBC), but may be missing in a proportion of these patients. We assessed sensitivity and specificity of the currently available techniques for AMA detection in a large series of PBC patients and controls, and analysed their clinical and immunological features according to the AMA status. By indirect immunofluorescence on rat tissue sections and HEp-2 cells, Western immunoblot with bovine submitochondrial particles, and two ELISAs with AMA-specific recombinant proteins, we evaluated the presence of AMA in 127 PBC patients, 166 patients with type 1 autoimmune hepatitis and 100 with non alcoholic fatty liver disease. In PBC patients Western immunoblot detects AMA significantly more often than indirect immunofluorescence on HEp-2 cells (85%versus 72%, P = 0.02) or rodent tissue sections (71%, P = 0.01); both ELISAs are only slightly less sensitive than Western immunoblot (81% and 78%). Ten patients with non alcoholic fatty liver disease were AMA-positive by indirect immunofluorescence, but none recognized AMA-specific epitopes in Western immunoblot or in ELISAs. Twelve patients with type 1 autoimmune hepatitis were AMA-positive by indirect immunofluorescence, but only 6 (3.6%) reacted by Western immunoblot and ELISAs. Western immunoblot or ELISA should be regarded as first-line assay for the detection of AMA. Up to 15% of PBC patients are consistently AMA-negative, yet they share the same clinical, biochemical and histological features of AMA-positive PBC. Detection of AMA in type 1 autoimmune hepatitis might identify a subset of patients at risk of developing a hepatitic/cholestatic syndrome.

Adult↗

Anti-actin IgA antibodies in severe coeliac disease.

Anti-actin IgA antibodies have been found in sera of coeliacs. Our aim was to define the prevalence and clinical significance of anti-actin IgA in coeliacs before and after gluten withdrawal. One hundred and two biopsy-proven coeliacs, 95 disease controls and 50 blood donors were studied. Anti-actin IgA were evaluated by different methods: (a) antimicrofilament positivity on HEp-2 cells and on cultured fibroblasts by immunofluorescence; (b) anti-actin positivity by enzyme-linked immuosorbent assay (ELISA); and (c) presence of the tubular/glomerular pattern of anti-smooth muscle antibodies on rat kidney sections by immunofluorescence. Antimicrofilament IgA were present in 27% of coeliacs and in none of the controls. Antimicrofilament antibodies were found in 25 of 54 (46%) coeliacs with severe villous atrophy and in three of 48 (6%) with mild damage (P < 0.0001). In the 20 patients tested, antimicrofilaments IgA disappeared after gluten withdrawal in accordance with histological recovery. Our study shows a significant correlation between antimicrofilament IgA and the severity of intestinal damage in untreated coeliacs. The disappearance of antimicrofilament IgA after gluten withdrawal predicts the normalization of intestinal mucosa and could be considered a useful tool in the follow-up of severe coeliac disease.

Actins↗

Prevalence of non-organ specific autoantibodies in HCV-infected subjects in the general population.

The significance of non-organ specific antibodies (NOSAs) in HCV-related chronic hepatitis is largely unclear. In this study we evaluated the prevalence of NOSAs in a non-selected population of HCV-infected subjects. One hundred and seventy anti-HCV positive and 192 anti-HCV negative sex and age-matched subjects (median age 64 years, range 7-91 years, female 68%) enrolled from the general population of a small Italian town were evaluated for NOSAs by indirect immunofluorescence on rat tissue sections and HEp-2 cells, and by counterimmunoelectrophoresis with thymus and spleen extracts as the antigen source. One hundred and sixty-three (96%) HCV-infected subjects had normal ALT serum levels and no evidence of liver disease. NOSAs were found in 31 out of 170 (18%) anti-HCV positive subjects and in 20 out of 192 (10%) controls (P = NS), with similar median titre (1:40) and range (1:40 to 1:160). Neither liver/kidney microsomal antibody type 1 nor antiactin reactivity were detected. No significant association between NOSAs and HCV genotypes was observed. In the general population, HCV-infected subjects and healthy controls have a similar prevalence of NOSAs. Without continuous liver damage HCV infection is unlikely to induce the appearance of NOSAs.

Adolescent↗

Anti-Saccharomyces cerevisiae antibodies (ASCA) and autoimmune liver diseases.

Antibodies to the baker's yeast Saccharomyces cerevisiae (ASCA), recently proposed as a serological marker of Crohn's disease, have also been detected in other autoimmune disorders. The aim of this study was to determine prevalence and clinical significance of ASCA in autoimmune liver disease. The presence of IgG and IgA ASCA was evaluated using a commercially available immunoassay in 215 patients with autoimmune liver disease (primary biliary cirrhosis, PBC, 123 cases; autoimmune hepatitis, AIH, 67 cases; primary sclerosing cholangitis, PSC, 25 cases), 48 with inflammatory bowel disease and 19 healthy blood donors. Anti neutrophil cytoplasmic antibodies with the perinuclear pattern (p-ANCA) were assessed by indirect immunofluorescence in PSC patients. The main clinical and biochemical parameters between ASCA-positive and negative patients were analysed and compared. ASCA are predominant in Crohn's disease (70%); among liver patients, PSC and AMA-negative PBC show the highest ASCA prevalence (53% and 44%). In PBC ASCA correlate with higher levels of circulating IgA (P < 0.05). In PSC the detection of either ASCA or p-ANCA is neither associated with any clinical or biochemical feature, nor with an underlying inflammatory bowel disease. ASCA can not be considered an additional serological marker of autoimmune liver disease, but the possibility of detecting such a reactivity in autoimmune liver disorders should be considered; their correlation with elevated IgA in PBC suggests that ASCA may be an indirect sign of enhanced mucosal immunity; in PSC patients neither ASCA nor p-ANCA predict the occurrence of a concomitant inflammatory bowel disease.

Antibodies, Antineutrophil Cytoplasmic↗

Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders.

Multiple nuclear dots pattern has been described in primary biliary cirrhosis and, less often, in rheumatological disorders. Sp100 is the major antigen of multiple nuclear dots. We evaluated prevalence and diagnostic significance of multiple nuclear dots and anti-Sp100 reactivity both in hepatic and rheumatological diseases. A series of 283 consecutive liver patients (89 primary biliary cirrhosis, 12 primary sclerosing cholangitis, 85 autoimmune hepatitis, 97 hepatitis C virus-related chronic liver disease) and of 89 consecutive rheumatological cases were evaluated. Presence of multiple nuclear dots was assessed by indirect immunofluorescence on HEp-2 cells, anti-Sp100 reactivity by ELISA with recombinant protein. Multiple nuclear dots were detected in 20 patients (7%) with liver disease (of whom 15 with primary biliary cirrhosis), and in eight patients (9%) with rheumatological disorders. Anti-Sp100 was detected in 45 liver patients (16%), of whom 30 with primary biliary cirrhosis, but in only two with rheumatological disorders (2%) (P =0.0004). The concordance between multiple nuclear dots and anti-Sp100 in liver and rheumatological patients was 90% and 25% (P=0.0018), respectively. Among 89 consecutive patients with primary biliary cirrhosis, multiple nuclear dots and anti-Sp100 were present in 17% and 34%, respectively (P=0.0152). Anti-Sp100 positivity was associated with older age and higher gamma-globulin levels. Multiple nuclear dots are similarly observed in liver and rheumatological patients. In contrast, anti-Sp100 is more frequent in liver patients and is significantly more often detected in primary biliary cirrhosis, of which it can be regarded as a highly specific serological marker. The antigenic target of multiple nuclear dots in most rheumatological patients is other than Sp100.

Antibodies, Antinuclear↗

Mammary implants: laboratory simulation of recreational diving conditions.

To ascertain whether mammary implants are prone to changes in conformation or structure if they are submitted to recreational dives, eight mammary implants were submitted to 40 simulated dives to imitate an average recreational diving schedule. Matching implants were used as a control group. Photographs were taken before and after completion of the protocol. All implants were observed for changes in volume and checked for integrity. Variations in density were evaluated using a Tc scan. No changes in volume occurred after each dive. None of the implants showed ruptures, and Tc scanning failed to reveal any differences in density between tested and control implants. Cohesive-gel implants submitted to the simulated dives showed some morphological alterations. This study indicates that the mammary implants tested could be implanted in a sports diver, but raises concern about whether the increased exposure to stress could negatively affect their durability.

Breast Implants↗