ABSTRACT
BACKGROUND: Colonization by livestock-associated MRSA (LA-MRSA) has increasingly been reported in the swine population worldwide. The aim of this study was to assess the prevalence of MRSA nasal carriage in healthy pigs, including the black (Calabrese) breed, from farms in the Calabria Region (Southern Italy). Between January and March 2018, a total of 475 healthy pigs reared in 32 farms were sampled by nasal swabbing. MRSA isolates were characterized by spa, MLST and SCCmec typing, and susceptibility testing to 17 antimicrobials. RESULTS: 22 of 32 (66.8%) pig farms resulted positive for MRSA. The prevalence of MRSA was 46.1% (219 MRSA culture-positive out of 475 samples). MRSA colonization was significantly higher in intensive farms and in pigs with a recent or ongoing antimicrobial treatment. All 219 MRSA isolates were assigned to ST398. The most common spa types were t011 (37.0%), t034 (22.4%) and t899 (15.1%). A novel spa type (t18290) was detected in one isolate. An insertion of IS256 in the ST398-specific A07 fragment of the SAPIG2195 gene was detected in 10 out of 81 t011 isolates. Nearly all isolates carried the SCCmec type V element, except 11 isolates that carried the SCCmec type IVc. None of the isolates was positive for the Panton-Valentine leukocidin. All isolates were resistant to tetracycline. High resistance rates were also found for clindamycin (93.1%), trimethoprim/sulfamethoxazole (68.4%), fluoroquinolones (47.9-65.3%) and erythromycin (46.1%). None of the isolates was resistant to vancomycin and fusidic acid. Overall, a multidrug resistant phenotype was observed in 88.6% of isolates. CONCLUSIONS: We report a high prevalence of MRSA among healthy swine in Southern Italy farms, with higher isolation frequency associated with intensive farming. The epidemiological types identified in our study reflect those reported in other European countries. Our findings underscore the importance of monitoring the evolution of LA-MRSA in pig farms in order to implement control measures and reduce the risk of spread in the animal population.
Subject(s)
Anti-Bacterial Agents/pharmacology , Carrier State/veterinary , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/veterinary , Swine Diseases/epidemiology , Animals , Bacterial Typing Techniques , Carrier State/enzymology , Carrier State/microbiology , Cross-Sectional Studies , DNA, Bacterial/genetics , Drug Resistance, Bacterial , Farms , Italy/epidemiology , Livestock/microbiology , Methicillin/pharmacology , Microbial Sensitivity Tests , Multilocus Sequence Typing , Nose/microbiology , Prevalence , Staphylococcal Infections/epidemiology , Swine , Swine Diseases/microbiology , Tetracycline/pharmacologyABSTRACT
The aim of this study was to determine and evaluate the activity of paraoxonase and arylesterase enzymes in various clinical forms of hepatitis B infection and to investigate the correlation between these parameters and chronic disease course/fibrosis. Overall, 40 patients diagnosed as hepatitis B carriers (CIHBV), 40 chronic active hepatitis B (CAHBV) patients, and 40 healthy adults (control group) between 18 and 65 years of age were enrolled the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Their activities were significantly lower in patients with CAHBV compared with CIHBV patients or with control group patients (P<0.001). There was a negative correlation between alanine aminotransferase levels and the activity of paraoxonase and arylesterase (r = -0.38, P = 0.001 and r = -0.28, P = 0.002, respectively). A statistically significant negative correlation was found between arylesterase activity in the sera of CAHBV patients and HBV DNA levels (ρ = -0.33, P = 0.03). On the contrary, no correlation was found between paraoxonase levels and HBV DNA levels (P>0.05). The histology activity index of CAHBV patients did not correlate with paraoxonase and arylesterase activities (P>0.05). In light of these findings, it may be assumed that during the progression of an inactive hepatitis B carrier to being actively infected, reduced paraoxonase and arylesterase activities may be observed.
Subject(s)
Aryldialkylphosphatase/blood , Carboxylic Ester Hydrolases/blood , Carrier State/enzymology , Hepatitis B virus , Hepatitis B, Chronic/enzymology , Adolescent , Adult , Aged , Analysis of Variance , Carrier State/blood , Case-Control Studies , Chi-Square Distribution , DNA, Viral/blood , Female , Hepatitis B, Chronic/blood , Humans , Lipoproteins, HDL/blood , Male , Middle AgedABSTRACT
Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (EPE) is increasing worldwide, though less documented in low-income settings. Here we determined the prevalence of EPE infection and carriage, and patient factors associated with EPE-carriage among pediatric patients in three health care levels in Tanzania. Between January and April 2016, 350 febrile children (median age 21Ā months) seeking care at a university or a regional referral hospital, or a health centre in Moshi municipality, Tanzania, were included. Socio-demographic characteristics were collected using a questionnaire. Rectal swabs and blood cultures were collected from all children (n = 350) and urinary samples from 259 children at admission. ESBL-phenotype and antimicrobial susceptibility were determined for Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) isolates. Only one EPE case (E. coli) in blood and four in urine (one E. coli and three K. pneumoniae) were found, whereas (n = 90, 26%) of the children were colonized in feces (ESBL-E. coli; n = 76, ESBL-K. pneumoniae, n = 14). High resistance rates were seen in fecal ESBL-E. coli (n = 76) against trimethoprim-sulfamethoxazole (n = 69, 91%), gentamicin (n = 51, 67%), ciprofloxacin (n = 39, 51%) and chloramphenicol (n = 27, 35%) whereas most isolates were sensitive to amikacin (n = 71, 93%). Similar rates were seen for fecal ESBL-K. pneumoniae. Resistance to first line antibiotics were also very high in fecal E. coli not producing ESBL. No sociodemographic factor was associated with EPE-carriage. Children colonized with EPE were younger than 12Ā months (n = 43, 48%) and often treated with antibiotics (n = 40, 44%) in the previous two months. After adjustment for age children admitted to the intensive care unit had higher odds of EPE fecal carriage compared with those in the general wards (OR = 3.9, 95%CI = 1.4-10.4). Despite comparatively high rates of fecal EPE-carriage and previous antibiotic treatment, clinical EPE cases were rare in the febrile children. The very high resistant rates for the EPE and the non-ESBL producing E. coli to commonly used antibiotics are worrying and demand implementation of antibiotic stewardship programs in all levels of health care in Tanzania.
Subject(s)
Carrier State/epidemiology , Escherichia coli Infections/epidemiology , Escherichia coli/isolation & purification , Klebsiella Infections/epidemiology , Klebsiella pneumoniae/isolation & purification , beta-Lactamases/metabolism , Adolescent , Adult , Anti-Bacterial Agents/pharmacology , Carrier State/drug therapy , Carrier State/enzymology , Carrier State/microbiology , Child , Child, Preschool , Cross-Sectional Studies , Escherichia coli/drug effects , Escherichia coli/enzymology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/enzymology , Escherichia coli Infections/microbiology , Female , Humans , Klebsiella Infections/drug therapy , Klebsiella Infections/enzymology , Klebsiella Infections/microbiology , Klebsiella pneumoniae/drug effects , Klebsiella pneumoniae/enzymology , Male , Microbial Sensitivity Tests , Middle Aged , Prevalence , Tanzania/epidemiology , Young AdultABSTRACT
BACKGROUND/AIMS: Serum matrix metalloproteinase (MMP)-9/ MMP-2 ratios are highly associated with alpha-fetoprotein levels in patients with chronic hepatitis B. In this study, we evaluate the clinical usefulness of this ratio as a biomarker in hepatitis B virus-related hepatocellular carcinoma (HCC). METHODOLOGY: Serum samples from 181 chronic hepatitis B patients (52 healthy carriers, 47 chronic hepatitis patients, 50 cirrhosis patients, and 32 HCC patients) were collected. MMP-9/ MMP-2 ratio was determined by zymography. The results were analyzed using the Receiver-Operating Characteristic (ROC) curve. RESULTS: Serum MMP-9/ MMP-2 ratios in HCC patients were significantly higher than those in healthy carriers, chronic hepatitis patients, and cirrhosis patients (p = 0.004, 0.034, and < 0.001, respectively). The sensitivity and specificity at the optimal cutoff (0.97) were 69.7% and 73.4%, respectively. Significantly higher MMP-9/ MMP-2 ratios were found in advanced, inoperable HCC patients, compared to those in early stage HCC patients (p = 0.005). No significant difference was found for alpha-fetoprotein levels between these two groups (p = 0.312). CONCLUSIONS: The serum MMP-9/ MMP-2 ratio can be used as an accessory diagnostic marker in hepatitis B virus-related HCC. This ratio is useful in distinguishing between patients with early stage HCC and those with advanced HCC.
Subject(s)
Carcinoma, Hepatocellular/enzymology , Hepatitis B, Chronic/enzymology , Liver Cirrhosis/enzymology , Liver Neoplasms/enzymology , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 9/blood , Adult , Aged , Biomarkers/blood , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/virology , Carrier State/enzymology , Carrier State/pathology , Carrier State/virology , Case-Control Studies , Cohort Studies , Female , Hepatitis B, Chronic/pathology , Humans , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Male , Middle Aged , Predictive Value of TestsABSTRACT
In countries with low endemic Methicillin-resistant Staphylococcus aureus (MRSA) prevalence, identification of risk groups at hospital admission is considered more cost-effective than universal MRSA screening. Predictive statistical models support the selection of suitable stratification factors for effective screening programs. Currently, there are no universal guidelines in Germany for MRSA screening. Instead, a list of criteria is available from the Commission for Hospital Hygiene and Infection Prevention (KRINKO) based on which local strategies should be adopted. We developed and externally validated a model for individual prediction of MRSA carriage at hospital admission in the region of Southeast Lower Saxony based on two prospective studies with universal screening in Braunschweig (n = 2065) and Wolfsburg (n = 461). Logistic regression was used for model development. The final model (simplified to an unweighted score) included history of MRSA carriage, care dependency and cancer treatment. In the external validation dataset, the score showed a sensitivity of 78.4% (95% CI: 64.7-88.7%), and a specificity of 70.3% (95% CI: 65.0-75.2%). Of all admitted patients, 25.4% had to be screened if the score was applied. A model based on KRINKO criteria showed similar sensitivity but lower specificity, leading to a considerably higher proportion of patients to be screened (49.5%).
Subject(s)
Carrier State/diagnosis , Hospitals/statistics & numerical data , Mass Screening/methods , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcal Infections/diagnosis , Adult , Aged , Aged, 80 and over , Carrier State/enzymology , Carrier State/microbiology , Diagnostic Tests, Routine , Female , Germany/epidemiology , Hospitalization , Humans , Male , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Models, Statistical , Predictive Value of Tests , Prevalence , Prospective Studies , Risk Factors , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology , Young AdultABSTRACT
Approximately 30% of patients with chronic HCV infection show persistently normal alanine aminotransferase levels (PNAL). The prevalence of HCV carriers with normal liver seems to be very low (less than 15-20%). Liver disease is usually minimal/mild and fibrosis is generally absent or minimal, although the association of normal alanine aminotransferase (ALT) with cirrhosis or with liver cancer has been reported. In all studies, liver histology was, on average, significantly less severe in subjects with PNAL than with abnormal ALT. Although the majority of data seem to show that HCV carriers with normal ALT have mild and stable disease, with a favourable prognosis, several studies reported a significant progression of fibrosis in approximately 20-30% of the patients with ALT normality, and the development of HCC in some cases has been described, despite persistent ALT normality. Sudden worsening of disease with ALT increase and histological deterioration has been described after up to 15 years of follow-up, in particular in patients harboring genotype 2. As to antiviral treatment, it has been clearly stated that it no longer seems reasonable to affirm that sustained response rates for patients with normal ALT levels are any different than those for patients with elevated ALT levels when the combination of pegylated interferon (IFN) and ribavirin is used. The issue at hand is whether or not patients with mild disease should be treated. There are numerous other factors which impact on this decision, including genotype, histology, patients motivation, symptoms, co-morbid illness, and the age of the patient.
Subject(s)
Alanine Transaminase/metabolism , Antiviral Agents/therapeutic use , Carrier State/drug therapy , Carrier State/enzymology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/enzymology , Antiviral Agents/pharmacology , Carrier State/virology , Hepacivirus/drug effects , Hepacivirus/physiology , Hepatitis C, Chronic/genetics , Hepatitis C, Chronic/virology , HumansABSTRACT
BACKGROUND: Adiponectin has been linked to the metabolic syndrome and coronary artery disease in recent years. The animal and human data also suggest that adiponectin may be beneficial for liver functions. The aim of this study was to investigate the correlation between plasma adiponectin level and liver function tests in adults with or without chronic hepatitis B virus (HBV) infection. METHODS: We analysed the blood levels of liver enzymes and adiponectin in 140 apparently healthy adults, including 21 HBV carriers. RESULTS: We found that the plasma adiponectin levels were inversely correlated to aspartate aminotransferase (r = -0.314, P = 0.000) and alanine aminotransferase (ALT) (r = -0.430, P = 0.000). Among the HBV carriers, the ALT correlated with the plasma adiponectin levels (r = -0.521, P = 0.015). In linear regression models adjusting for age, sex and the other metabolic variables, the ALT was independently related to the plasma adiponectin levels (beta = -0.371 +/- 0.134, P = 0.007), even in HBV carriers (beta = -1.143 +/- 0.482, P = 0.034). The ALT was also independently correlated to the plasma adiponectin levels (beta = 0.552 +/- 0.132, P < 0.001) with adjustment for age, sex and insulin-resistance index by homeostasis model assessment, even in HBV carriers (beta = -1.202 +/- 0.562, P = 0.048). The subjects with normal ALT had a significantly higher least square mean of plasma adiponectin than those with abnormal ALT (4.01 +/- 0.19 vs 3.30 +/- 0.30, P = 0.014) with adjustment for age, sex, homeostasis model assessment insulin resistance and HBV status. CONCLUSION: ALT was inversely related to adiponectin levels, independent of the metabolic factors and HBV status. Whether there is any potential prognostic and therapeutic value of adiponectin in human liver diseases remains to be investigated.
Subject(s)
Adiponectin/blood , Alanine Transaminase/blood , Carrier State/virology , Down-Regulation/physiology , Hepatitis B/virology , Up-Regulation/physiology , Adiponectin/antagonists & inhibitors , Adult , Alanine Transaminase/biosynthesis , Biomarkers/blood , Biomarkers/metabolism , Carrier State/enzymology , Carrier State/metabolism , Cross-Sectional Studies , Female , Hepatitis B/enzymology , Hepatitis B/metabolism , Humans , Male , Middle AgedABSTRACT
The aim of this study was to follow-up the serum alanine aminotransferase (ALT) levels in inactive HBsAg carriers during one year period and investigate the association between hepatitis B virus (HBV) DNA levels detected at the end of the year. At May 2005, 61 patients with HBeAg negative/anti-HBe positive chronic HBV infection, followed in our viral hepatitis clinic were included to the study. The patients' ultrasonographic examination of the liver were normal, they had no history of taking alcohol or routine medication, were anti-HCV seronegative and had normal ALT levels during the last 6 months and at the beginning of the study. Serum ALT levels of patients were followed in the 3rd, 6th and 12th months of the study, and blood HBV-DNA levels were analysed quantitatively in 12th month. During the one year period 89% (54/61) of the patients yielded continously normal ALT levels, while 11% (7/61) showed at least one ALT value above the normal levels (ALT > 1.2x). Total HBV-DNA positivity rate was found as 59% (36/61). In inactive HBsAg carrier group,--namely HBeAg negative and serum ALT levels constantly normal--57.4% (31/54) of patients were HBV-DNA positive and 23 (42.6%) were negative. Amongst the HBV-DNA positive patients the viral load were detected as 10(4)-10(5) copies/ml in six (19.4%), and <10(4) copies/ml in 25 (80.6%) patients. In patients who had at least one ALT value above normal limits, 71.4% (5/7) of them were found HBV-DNA positive; two with HBV-DNA values of >10(5) copies/ml and three with values between 10(4)-10(5) copies/ml. In conclusion, although ALT levels may be normal, it should always be taken into consideration that more than half of inactive HBsAg carriers exhibited low level viral replication, thus HBV-DNA and liver enzyme levels should be monitored routinely in order not to miss the acute manifestations.
Subject(s)
Alanine Transaminase/blood , Carrier State/enzymology , Hepatitis B Surface Antigens/blood , Hepatitis B, Chronic/enzymology , Adult , Carrier State/blood , DNA, Viral/blood , Female , Follow-Up Studies , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/blood , Humans , Liver/diagnostic imaging , Male , Ultrasonography , Viral LoadSubject(s)
DNA, Viral/blood , Hepatitis B, Chronic/enzymology , Hepatitis B, Chronic/virology , Alanine Transaminase/blood , Carrier State/enzymology , Carrier State/virology , Female , Hepatitis B virus/isolation & purification , Humans , Liver/enzymology , Male , Middle Aged , gamma-Glutamyltransferase/bloodABSTRACT
Serum deoxythymidine kinase (TK) was measured in 15 patients with the acute type of adult T-cell leukemia (ATL), in 4 with chronic ATL, in 10 with lymphoma type ATL, in 9 with pre-ATL, in 11 with human T-cell leukemia virus type I (HTLV-I) associated with myelopathy (HAM) and in 19 HTLV-I carriers. All these patients were positive for anti-HTLV antibody. The level of TK in pretreatment serum was highest in acute ATL (15.6-1600 U/l, median 107 U/l). It was elevated in chronic ATL (5.4-55.0 U/l, median 37.6 U/l) and lymphoma ATL (6.8-316 U/l, median 16.8 U/l) but normal in pre-ATL (1.8-4.7 U/l, median 2.8 U/l), HAM (1.2-6.0 U/l, median 3.0 U/l) and HTLV-I carriers (1.1-4.6 U/l, median 2.3 U/l). Statistical examination revealed a significant difference between the levels of acute ATL and chronic ATL/lymphoma ATL. In the patients of this series, a close correlation between the level of TK and lactic dehydrogenase (LDH) was statistically present (p less than 0.01). These facts indicate that TK level is a useful indicator of the aggressiveness of ATL cells.
Subject(s)
Leukemia-Lymphoma, Adult T-Cell/enzymology , Thymidine Kinase/blood , Acute Disease , Adult , Aged , Carrier State/enzymology , Chronic Disease , Female , Humans , L-Lactate Dehydrogenase/blood , Leukemia-Lymphoma, Adult T-Cell/pathology , Male , Middle Aged , Paraparesis, Tropical Spastic/enzymology , Preleukemia/enzymology , Reference ValuesABSTRACT
This study followed 314 children who were carriers of hepatitis B virus for 2 to 4 years and compared them with noncarriers, matched for age and sex, from the same community. No confirmed carrier lost hepatitis B surface antigen. Hepatitis B e antigen (HBeAg) was lost at a rate of 10.6% per year; the rate of decay was not affected by age or gender. Liver enzymes were higher in HBeAg-positive than in HBeAg-negative carriers and loss of HBeAg was usually followed by return to values in the normal range. There was evidence, however, of persistent mild liver dysfunction in carriers even after development of antibody to HBeAg. Serum alanine aminotransferase concentrations above twice the upper limit of normal were observed in 7% of carriers on at least one occasion but persisted for more than 1 year in less than 1% and clinical manifestations were rare. The hepatitis B carrier state was uncomplicated during the course of this study. However, risks of subsequent serious disease in adult life may be significant and continued surveillance of carriers is important for individual protection and to determine adverse prognostic features.
Subject(s)
Carrier State/physiopathology , Hepatitis B/immunology , Liver/physiology , Adolescent , Age Factors , Alanine Transaminase/blood , Carrier State/enzymology , Carrier State/immunology , Child , Child, Preschool , Cohort Studies , Female , Hepatitis B e Antigens/blood , Humans , Infant , Liver/enzymology , Liver Function Tests , Male , Sex FactorsABSTRACT
Twenty-six patients, positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus (HBV)-deoxyribonucleic acid (DNA), and DNA polymerase activity, were treated with human lymphoblastoid interferon (IFN-alpha) or human fibroblast interferon (IFN-beta) after enoxolone glycoside (glycyrrhizinic acid), given for four weeks and then withdrawn. The interferons were given continuously for four weeks. Four months after the treatment, six of 12 patients treated with IFN-alpha were both HBeAg-negative and HBV-DNA-negative while three of 14 patients treated with IFN-beta were HBV-DNA-negative and one was HBeAg-negative. None of the ten untreated control patients became negative for either HBeAg or HBV-DNA. All patients studied remained HBsAg-positive. Both interferons were generally well tolerated. A persistent low-grade fever was reported by more patients in the IFN-beta group and hair and weight loss were more common in the IFN-alpha group. The results indicate that the combination of enoxolone glycoside withdrawal and IFN-alpha treatment reduces HBV replication more effectively than does interferon alone.
Subject(s)
Carrier State/drug therapy , Glycyrrhetinic Acid/therapeutic use , Hepatitis B/drug therapy , Interferon Type I/therapeutic use , Adolescent , Adult , Alanine Transaminase/blood , Carrier State/enzymology , Chronic Disease , Drug Administration Schedule , Drug Therapy, Combination , Female , Glycyrrhetinic Acid/administration & dosage , Hepatitis B/enzymology , Hepatitis B virus/physiology , Humans , Injections, Intramuscular , Injections, Intravenous , Interferon Type I/administration & dosage , Interferon Type I/adverse effects , Male , Middle Aged , Virus ReplicationABSTRACT
To determine when the precore mutation at the 83rd nucleotide occurs, leading to the formation of a stop codon in the hepatitis B virus genome in carriers, which would indicate the presence of antibody to hepatitis B e antigen (anti-HBe), we investigated this mutation by direct sequencing and subcloning in 22 young hepatitis B antigen (HBeAg) (+) carriers. These subjects were 7-17 years old and were found during a survey for hepatitis B surface antigen (HBsAg) in three elementary schools, a junior high, and a senior high school. None of these carriers had clinical manifestations, although one-third of them had elevated serum alanine aminotransferase levels. All were HBeAg-positive by radioimmunoassay (RIA), and 6 of them had preserved titers of anti-HBe at the same time. Precore mutations were found in 4 subjects (18.2%), with predominance of the wild type. Although 3 of these 4 had preserved titers of HBeAb, the other had no HBeAb titers. In an other 3 subjects with preserved titers of HBeAb, the precore mutation was not detected, even after the subcloning of viral DNA. The remaining 15 subjects with HBeAg showed no precore mutation. Subjects with ALT levels exceeding 100 IU/l were all HBeAg-positive without the mutation. It was clear that the precore mutation itself occurred in the subjects at an early age during the course of infection. However, the chronological relationship between the emergence of the precore mutation and the onset of hepatitis requires further study.
Subject(s)
Carrier State/virology , Genome, Viral , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Hepatitis B/virology , Mutation , Adolescent , Alanine Transaminase/blood , Base Sequence , Carrier State/enzymology , Carrier State/immunology , Child , Female , Hepatitis B/enzymology , Hepatitis B/immunology , Hepatitis B Surface Antigens/analysis , Hepatitis B e Antigens/genetics , Humans , Male , Molecular Sequence Data , RadioimmunoassayABSTRACT
Starch gel electrophoresis of galactose-1-phosphate uridylyl transferase has been adapted for use on dried filter paper blood specimens submitted for the purposes of routine newborn screening for galactosemia and other inborn errors of metabolism. Selected for study were those specimens with reduced transferase activity, as determined by the Beutler enzyme spot screening test. Clinically benign low activity enzyme variants were readily identified, thus reducing significantly the number of requested additional blood specimens. Transferase-deficient specimens with potential clinical significance had too little activity for transferase visualization and thus could be separated from the benign variants. This technique would facilitate routine newborn screening for galactosemia.
Subject(s)
Clinical Enzyme Tests/methods , Galactosemias/diagnosis , Nucleotidyltransferases/blood , UTP-Hexose-1-Phosphate Uridylyltransferase/blood , Carrier State/enzymology , Electrophoresis, Starch Gel , Fetal Blood/enzymology , Filtration , Humans , Infant, NewbornABSTRACT
To examine the possible involvement of MMP-9 and -2 in the development of liver diseases caused by HCV or HBV infection, serum activities of both enzymes were studied by zymograph. Eight groups of subjects (60 for each) were examined in the study: healthy control, patients with hepatoma, liver cirrhosis, chronic hepatitis B or chronic hepatitis C, and carriers positive for HBsAg, both HBsAg and HBeAg, or anti-HCV. The results showed significant changes in the MMP-9 and -2 activities in the carriers. The presence of HBeAg was accompanied by a highest activity of MMP-2 and an inversely correlated (r=-0.578, P=<0.001), lowest activity of MMP-9 among all groups. For those with active liver diseases, MMPs activities were fluctuated at each stage of pathological symptoms. Chronic hepatitis B and C patients had significant different serum MMP-2 and -9 activities. These findings imply an influence on the balance of MMPs system by the existence of virus that might influence the following progression of liver disease, and a distinction between the pathological mechanisms of HCV and HBV. Since the serum MMPs activities were significantly varied between each stage of liver disease, an individual profile of these parameters might serve as an easy accessing serum marker to monitor the progression of liver disease.
Subject(s)
Carrier State/blood , Hepatitis B, Chronic/blood , Hepatitis C, Chronic/blood , Matrix Metalloproteinase 2/blood , Matrix Metalloproteinase 9/blood , Alanine Transaminase/blood , Analysis of Variance , Aspartate Aminotransferases/blood , Biomarkers/blood , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/enzymology , Carrier State/enzymology , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B, Chronic/enzymology , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/enzymology , Liver Cirrhosis/blood , Liver Cirrhosis/enzymology , Liver Neoplasms/blood , Liver Neoplasms/enzymology , Reference ValuesABSTRACT
Since the discovery of hepatitis C virus, the availability of serological hepatitis C virus screening has led to the identification of many subjects with normal aminotransferase levels who are chronically infected by the hepatitis C virus. To date, the epidemiology and natural history of subjects with normal aminotransferase levels are far from being clarified. Further, whether subjects with persistently normal aminotransferase levels should routinely undergo liver biopsy is still extremely controversial, and benefit from interferon treatment in this group of patients is yet to be proven. On account of the consistent normality of aminotransferases, it is not easy to calculate the rate of persons with normal aminotransferase levels among chronic hepatitis C virus carriers, nor their prevalence in the general population. It has been estimated that up to 25% of patients with chronic hepatitis C virus infection have persistently normal aminotransferase levels (10% to 40%, according to different studies). Most studies showed a clear prevalence of females, ranging from 58% to 90%. Liver biopsy shows some degree of chronic liver disease in up to 80% of these subjects, although in the majority, histological damage is mild and probably does not progress to more severe liver disease, moreover, the progression to fibrosis is slower than in patients with elevated aminotransferase levels. Virological features of these subjects (hepatitis C virus genotype distribution, viral load, quasispecies diversity) do not differ with respect to patients with elevated aminotransferase levels although a higher frequency of non 1 hepatitis C virus types has been reported. To date, no biochemical or virological tools to assess the presence and severity of liver damage exist. Antiviral treatment with interferon may induce a long-term response in only a small proportion of hepatitis C virus carriers with persistently normal aminotransferase levels, and many patients develop aminotransferase-flare-up during or shortly after treatment. Thus, interferon or combination antiviral treatment of hepatitis C virus carriers with normal aminotransferase values should be avoided in clinical practice.
Subject(s)
Carrier State/enzymology , Hepatitis C, Chronic/enzymology , Transaminases/blood , Antiviral Agents/therapeutic use , Biopsy , Carrier State/diagnosis , Carrier State/drug therapy , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Humans , Interferons/therapeutic use , Liver/pathology , Liver Function Tests , Reference Values , Viral LoadABSTRACT
This paper describes the application of a biologically motivated system to the diagnosis of chronic hepatitis B. The system integrates intra- and inter-neuronal information processing so as to capture the biology-like gradual transformability of structure/function relationships. The system was applied to a clinical hepatitis B database, divided into two sets. The first set comprised 676 records, of which one half were chronic hepatitis B patients, and the other half healthy individuals. The second set included 375 records, of which one third were chronic hepatitis B patients; another third were hepatitis B carriers, and the remaining third healthy non-carriers. Each record consisted of ten examination items. Experimental results showed that the system was able to correctly differentiate 99.3 and 91.2% of the records in the first and the second sets, respectively. Differentiation means making a distinction between different categories of data in each set. After substantial learning with the first set, the system was then tested with the second set, and it was able to correctly differentiate 95. 7% of the records, suggesting a high differentiating capability in this system. This system demonstrated an effective self-organizing capability in determining significant and insignificant examination items from patterns of the clinical data. It also showed that some combinations of these items were more effective for determining whether one is infected with chronic hepatitis B than others.
Subject(s)
Databases, Factual , Diagnosis, Computer-Assisted/methods , Hepatitis B, Chronic/diagnosis , Neural Networks, Computer , Alanine Transaminase/blood , Artificial Intelligence , Aspartate Aminotransferases/blood , Carrier State/blood , Carrier State/diagnosis , Carrier State/enzymology , Expert Systems , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/enzymology , Humans , Serum Albumin/metabolism , Serum Globulins/metabolismABSTRACT
BACKGROUND/AIMS: Chronic hepatitis C virus carriers may have repeatedly normal alanine aminotransferase activity despite detectable viremia and histological hepatitis. We aimed to evaluate the effect of interferon treatment in these cases. METHODOLOGY: Twelve patients with persistently normal alanine aminotransferase levels at least 6 months before therapy were treated with recombinant interferon (IFN)alpha-2b for 6 months, totaling 840 MU in amount. Alanine aminotransferase levels were measured monthly during treatment and after treatment withdrawal, and HCV-RNA levels were measured by polymerase chain reaction before treatment, and 6 and 12 months after treatment withdrawal. RESULTS: At treatment withdrawal, HCV-RNA levels had significantly decreased and HCV-RNA disappeared in 9 of the 12 patients by polymerase chain reaction. At 6 months after treatment withdrawal, HCV-RNA reappeared in 6 of the 9 patients whose HCV-RNA was negative at treatment withdrawal. Over all, only 4 of the 12 patients (33%) were sustained virological responders (HCV-RNA is negative more than 6 months after treatment withdrawal). Pre-treatment HCV-RNA levels in a sustained virological responder was significantly lower than that of transient and non-responders (4.9 +/- 1.6 vs. 7.7 +/- 1.6 log10[copies/ml], p < 0.05). Of 8 patients who did not achieved sustained virological response, alanine aminotransferase levels had transiently increased above normal during treatment in one patient and after treatment withdrawal in 6 patients; however, in the remaining one patient abnormal values have continued from 8 months after treatment withdrawal till now for 24 months. CONCLUSIONS: In patients with chronic hepatitis C with normal alanine aminotransferase levels, the response to interferon therapy was by no means satisfactory. However, if it would be used in cases with the lower pre-treatment HCV-RNA levels with careful attention to a transient alanine aminotransferase elevation, the more a sustained virological response might be expected.
Subject(s)
Alanine Transaminase/blood , Hepatitis C, Chronic/therapy , Interferon-alpha/administration & dosage , Viremia/therapy , Adult , Aged , Biopsy , Carrier State/enzymology , Carrier State/pathology , Carrier State/therapy , Female , Hepatitis C, Chronic/enzymology , Hepatitis C, Chronic/pathology , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Liver/pathology , Liver Function Tests , Male , Middle Aged , Recombinant Proteins , Treatment Outcome , Viremia/enzymology , Viremia/pathologyABSTRACT
Four healthy calves were inoculated with Pasteurella haemolytica serotype 1 by instillation of a broth culture into the middle nasal meatus of the left nostril. Four weeks later, calves were exposed to infectious bovine rhinotracheitis virus by aerosol into both nostrils. All calves became ill, from approximately day 3 through day 10 after virus exposure, and shed increased amounts of nasal mucus. Two calves were induced to shed P haemolytica by the virus infection, and 2 calves required reinoculation with P haemolytica for nasal passages to become actively colonized. Elastase activity in nasal mucus increased about 15-fold within 3 days and peaked about 60-fold over baseline by 7 days after virus exposure. Activity of N-acetyl-beta-D-glucosaminidase, a measure of cell damage and serum leakage, increased slightly by day 3 and reached plateau on day 5, almost threefold over baseline activity. Protein and carbohydrate content increased at a rate similar to that of N-acetyl-beta-D-glucosaminidase activity with about 12-fold and sixfold increases, respectively. None of the variables returned to baseline by 19 days after virus exposure. Increased elastase activity preceded colonization by P haemolytica and decreasing elastase activity preceded decreasing P haemolytica concentration in the nasal secretions. A causal relation between elastase activity and P haemolytica colonization could be mediated by cleavage of epithelial cell surface fibronectin and exposure of receptors.
Subject(s)
Infectious Bovine Rhinotracheitis/complications , Mannheimia haemolytica/growth & development , Nasal Mucosa/enzymology , Pancreatic Elastase/analysis , Pasteurella Infections/veterinary , Acetylglucosaminidase/analysis , Acetylglucosaminidase/blood , Animals , Body Temperature , Carbohydrates/analysis , Carrier State/enzymology , Carrier State/veterinary , Cattle , Nasal Mucosa/chemistry , Nasal Mucosa/microbiology , Pancreatic Elastase/antagonists & inhibitors , Pancreatic Elastase/blood , Pasteurella Infections/complications , Pasteurella Infections/enzymology , Proteins/analysisABSTRACT
Alanine transaminase (ALT) levels in healthy hospital personnel were studied. ALT levels in pre and post vaccinated sera were compared. In this study, all sera showed normal values of ALT, lower than 36 IU/L. Hepatitis B vaccination did not cause any change.