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Biomedical subjects

G Pappas

Publications and source records attributed to G Pappas.

At least 19 recordsLinked to original sources
PubMed2006

Doxycycline-rifampicin: physicians' inferior choice in brucellosis or how convenience reigns over science.

OBJECTIVES: Brucellosis treatment is based on sub-optimal, not universally implemented regimens (doxycycline-rifampicin and doxycycline-streptomycin). The authors sought to evaluate specialists' and physicians' attitude towards regimens used, non-medical aspects, and future trends in human brucellosis treatment. METHODS: A questionnaire-based survey of multi-national specialists, physicians, and trainees, was conducted, questionnaire answered following lectures outlining major scientific facts about existing regimens. Responders indicated preference between the two regimens, their opinion on protracted monotherapy or triple regimens of shorter duration, awareness of disease notification and hospitalization practices. Results were evaluated in relation with professional status and experience with the disease. RESULTS: Although scientifically inferior to doxycycline-streptomycin, doxycycline-rifampicin is the choice regimen for 64.6% of the participants. A shorter triple regimen, but not protracted monotherapy, would be desirable (60.2% and 10.4%, respectively). Low awareness of disease-notifying status and related procedures were recorded in 53.9%. CONCLUSION: When choosing between currently acceptable brucellosis regimens, medical personnel prefer convenience, even at the cost of a slightly higher relapse percentage. Future trials should evaluate shorter triple regimens. Enhancement of awareness on the disease and its principles may increase therapeutic cost effectiveness.

Anti-Bacterial Agents↗
PubMed2006

Brucella as a biological weapon.

Brucella has traditionally been considered a biological weapon. It was the subject of extensive offensive research in the past, and still belongs to category B pathogens on most lists. Its propensity for airborne transmission and induction of chronic debilitating disease requiring combined antibiotic regimens for treatment, its abundance around the world and its vague clinical characteristics defying rapid clinical diagnosis are some of the characteristics that apply to the pathogen's weapons potential. Yet minimal mortality, availability of treatment options, protracted inoculation period and the emergence of new, more virulent potential weapons means that its inclusion among agents of bioterrorism is nowadays mainly of historical significance. Nevertheless, in the interest of literacy and of avoiding panic, physicians and the public both should be aware of the most common zoonosis worldwide.

Animals↗
PubMed2006

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↗
PubMed2006

Quinolones for brucellosis: treating old diseases with new drugs.

Although quinolones are theoretically interesting candidates for the treatment of brucellosis, the existing data concerning their efficacy are limited and conflicting. A number of small clinical studies with combination regimens that include quinolones have shown adequacy, but not superiority, although cost-effectiveness, excluding certain disease complications, is an important issue. The emergence of quinolone resistance and its implications is another drawback. Experimental data have yielded contradictory results, although most studies do not indicate a bactericidal effect for quinolones. However, in-vitro studies contrast repeatedly with the clinical response, both in terms of clinical failure, despite in-vitro success, and vice versa.

Anti-Infective Agents↗
PubMed2006

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↗
PubMed2005

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↗
PubMed2005

Anti-cyclic citrullinated peptide antibodies in type 1 autoimmune hepatitis.

BACKGROUND: Besides the autoantibodies included in the diagnostic criteria of type 1 autoimmune hepatitis, many other autoantibodies have been described in this condition. Recently, antibodies against cyclic citrullinated peptide have been validated as specific diagnostic and prognostic markers of rheumatoid arthritis. AIM: To assess whether these antibodies are part of the autoantibody repertoire of type 1 autoimmune hepatitis and correlate with rheumatological manifestations. METHODS: Antibodies against cyclic citrullinated peptide were tested by a commercially available enzyme-linked immunosorbent assay. RESULTS: The antibodies were found in 12 of 133 (9%) type 1 autoimmune hepatitis, two of 49 (4%) with primary biliary cirrhosis, one of 80 (1%) with hepatitis C virus-related chronic liver disease and 53 of 89 (60%) with rheumatoid arthritis serum samples. High titres were found only in rheumatoid arthritis and type 1 autoimmune hepatitis. No clinical (in particular rheumatological manifestations), biochemical or immunoserological differences were detectable between antibodies against cyclic citrullinated peptide positive and negative type 1 autoimmune hepatitis sera, with the exception of rheumatoid factor, always negative in the positive ones. CONCLUSIONS: Antibodies against cyclic citrullinated peptide can be detected in a subgroup of patients with type 1 autoimmune hepatitis. They might be part of the wide range of autoantibody production characteristic of this condition and/or, less probably, be predictive of future rheumatoid arthritis development.

Adolescent↗
PubMed2005

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↗
PubMed2004

ConSSeq: a web-based application for analysis of amino acid conservation based on HSSP database and within context of structure.

SUMMARY: A web-based application to analyze protein amino acids conservation-Consensus Sequence (ConSSeq) is presented. ConSSeq graphically represents information about amino acid conservation based on sequence alignments reported in homology-derived structures of proteins. Beyond the relative entropy for each position in the alignment, ConSSeq also presents the consensus sequence and information about the amino acids, which are predominant at each position of the alignment. ConSSeq is part of the STING Millennium Suite and is implemented as a Java Applet. AVAILABILITY: http://sms.cbi.cnptia.embrapa.br/SMS/STINGm/consseq/, http://trantor.bioc.columbia.edu/SMS/STINGm/consseq/, http://mirrors.rcsb.org//SMS/STINGm/consseq/, http://www.es.embnet.org/SMS/STINGm/consseq/ and http://www.ar.embnet.org/SMS/STINGm/consseq/

Amino Acids↗
PubMed2004

Immune thrombocytopenia attributed to brucellosis and other mechanisms of Brucella-induced thrombocytopenia.

Thrombocytopenia often complicates the course of acute brucellosis, mainly due to bone marrow suppression or hypersplenism. Immune thrombocytopenia is also reported in brucellosis, resulting usually in massive thrombocytopenia, purpura, and spontaneous hemorrhage. We describe a case of acute brucellosis in an 85-year old woman, who presented with fever, purpuric skin lesions, anemia, and rhinorrhagia. The absolute platelet count was 1000/microL. Direct and indirect Coombs tests were positive, and a cold-agglutinin was detected. The patient was diagnosed as suffering from brucellosis on the basis of a strongly positive serologic reaction and was treated with doxycycline, streptomycin, and a short course of corticosteroids, with a rapid rise in platelet number.

Acute Disease↗
PubMed2004

Enterococcus casseliflavus bacteremia. Case report and literature review.

Motile Enterococci are rare causes of enterococcal bacteremia, usually in immunocompromised patients. We describe a case of polymicrobial bacteremia, including Enterococcus casseliflavus, Escherichia coli, and Morganella morganii, in an 80-year old woman, shortly after a liver biopsy performed to exclude cholangiocarcinoma. We further discuss the unique genetic characteristics and the clinical significance of such isolates, such as their intrinsic resistance to vancomycin, and the low virulence exhibited clinically. Further workup on the mechanisms of motile Enterococci resistance to vancomycin could probably yield useful information in achieving new ways of facing resistance attributed to the more usual, and malignant Enterococci.

Aged↗
PubMed2004

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↗
PubMed2004

'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↗
PubMed2004

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↗
PubMed2003

A large scale analysis of resistance gene homologues in Arachis.

Arachis hypogaea L., commonly known as the peanut or groundnut, is an important and widespread food legume. Because the crop has a narrow genetic base, genetic diversity in A. hypogaea is low and it lacks sources of resistance to many pests and diseases. In contrast, wild diploid Arachis species are genetically diverse and are rich sources of disease resistance genes. The majority of known plant disease resistance genes encode proteins with a nucleotide binding site domain (NBS). In this study, degenerate PCR primers designed to bind to DNA regions encoding conserved motifs within this domain were used to amplify NBS-encoding regions from Arachis spp. The Arachis spp. used were A. hypogaea var. Tatu and wild species that are known to be sources of disease resistance: A. cardenasii, A. duranensis, A. stenosperma and A. simpsonii. A total of 78 complete NBS-encoding regions were isolated, of which 63 had uninterrupted ORFs. Phylogenetic analysis of the Arachis NBS sequences derived in this study and other NBS sequences from Arabidopsis thaliana, Medicago trunculata, Glycine max, Lotus japonicus and Phaseolus vulgaris that are available in public databases This analysis indicates that most Arachis NBS sequences fall within legume-specific clades, some of which appear to have undergone extensive copy number expansions in the legumes. In addition, NBS motifs from A. thaliana and legumes were characterized. Differences in the TIR and non-TIR motifs were identified. The likely effect of these differences on the amplification of NBS-encoding sequences by PCR is discussed.

Arabidopsis↗
PubMed2003

Unusual causes of reactive arthritis: Leptospira and Coxiella burnetii.

Reactive arthritis is a well-defined clinical syndrome occurring after various infections, although most cases are usually associated with Chlamydiae and gastrointestinal pathogens. Its immunologic background has been extensively studied, as has its relationship with HLA-B27. We describe two cases of reactive arthritis arising after infections with two pathogens not so far related to the occurrence of reactive arthritis: one patient exhibited migratory oligoarthritis shortly after the course of acute Q fever, and another patient developed monoarthritis during recovery from leptospirosis. Arthritis was transient and did not exhibit a chronic course in either patient. We further discuss the context of pathophysiology of the arthritis in these patients, with an emphasis on the immunomodulatory properties of these two pathogens.

Adult↗