The role of adenovirus 36 as a risk factor in obesity: the first clinical study made in the fatty tissues of adults in Turkey.

Obesity which developes due to multifactorial reasons, was associated recently with human Adenovirus-36 (Ad-36). The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese adults and also to investigate the DNA of Ad-36 in their adipose tissue. In this cross-sectional and case-control based study, 49 obese adults, with BMI ≥ 30 kg/m(2), and 49 non-obese adults, with BMI ≤ 25 kg/m(2), applied for esthetic purposes and were included in this study as patient and control groups, respectively. Adipose tissue samples, obtained by the lipoaspiration method, were studied by single-step PCR and nested-PCR methods. Simultaneously, the presence of Ad-36 antibodies and serum leptin and adiponectin levels were assessed by serum neutralization assay (SNA) and ELISA, respectively. Serum samples which didn't cause a cytopathic effect at ≥ 1:8 were accepted as positive. Ad-36 antibody was detected in 6 (12.2%) of 49 patients by SNA and was statistically significant (p < 0.05). Ad-36 DNA was not detected in any of the adipose tissue samples of the patient or control groups. Mean BMI and leptin levels were higher in the Ad-36-positive group, while adiponectin levels were found to be lower in the Ad-36-positive group. Although no statistically significant difference was found in cholesterol and triglyceride levels between the two groups (p > 0.05), lower mean serum cholesterol and triglyceride levels were found in the Ad-36-positive patients. In conclusion, we couldn't detect Ad-36 DNA in adipose tissue; however, we detected significantly higher Ad-36 antibody levels in the obese group compared to the non-obese group, according to the both univariant and multivariant analyses, suggesting that Ad-36 may play a role in obesity. There is a need for new and extended serial, particularly cohort and human-based, studies in order to have a clear understanding of the Ad-36-obesity relationship.

Confirmation of high specificity of an automated enzyme immunoassay test for serological diagnosis of syphilis: retrospective evaluation versus results after implementation.

BACKGROUND: The optimal algorithm for serological syphilis screening is still a matter of debate. We have previously evaluated the performance of the Bioelisa Syphilis 3.0, using a selection of archived sera, and in this study compare these results with the Bioelisa results after clinical implementation. METHODS: All Bioelisa Syphilis 3.0 results obtained since clinical implementation were analyzed. Bioelisa-positive or borderline samples were retested using Treponema pallidum particle agglutination, rapid plasma reagin test, fluorescent treponemal antibody-absorption test, and/or immunoblot. On sera sent in together with cerebrospinal fluid, occasionally both the T. pallidum particle agglutination and Bioelisa were performed. RESULTS: The Bioelisa was performed on 14,622 sera. Bioelisa-positive samples, which were not retested by the previously described assays, were withdrawn from the database (n = 36). In 1.3% of the samples (187/14,586), the Bioelisa was positive or borderline and, ultimately, 115 sera were considered true positive (prevalence 0.8%). The specificity of the Bioelisa was 99.5%. CONCLUSIONS: Based on the results of all performed diagnostic assays, the specificity of the Bioelisa of 99.5% is very consistent with that found in the initial study (100%; 95% confidence interval was 98.0%-100%). Interpreting (positive) test results is difficult in the absence of a gold standard, especially when the disease prevalence is low. Results should be viewed in the light of the patients' characteristics.

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study.

BACKGROUND: Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored. RESULTS: Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD. CONCLUSIONS: Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.

A delay in CD4 cell response after initiation of highly active antiretroviral therapy is associated with the presence of anti-cytomegalovirus but not with anti-herpes simplex virus antibodies.

After the successful initiation of highly active antiretroviral therapy (HAART) in HIV-1-infected patients, the mean CD4 cell response was lower in cytomegalovirus (CMV)-seropositive patients than in CMV-seronegative patients (P < 0.05). The difference between the mean CD4 cell counts of CMV-seronegative and CMV-seropositive patients was maximal (163 x 10(6)/l) at 76 weeks after the start of HAART, and decreased gradually thereafter. No association was found between herpes simplex virus types 1 and 2 serostatus and CD4 cell response.

A late episode of post-transplant diabetes mellitus during active hepatitis C infection in a renal allograft recipient using tacrolimus.

BACKGROUND: An association between hepatitis C virus and (post-transplant) diabetes mellitus has been reported. METHODS: We report a patient on tacrolimus-based immunosuppression who developed an episode of post-transplant diabetes mellitus (PTDM) 2 years after renal transplantation, after contracting a hepatitis C infection. Her glucose metabolism was evaluated regularly by intravenous glucose tolerance tests before and after the PTDM episode. RESULTS: Before contracting hepatitis C, the patient's insulin resistance and insulin secretion were normal. After contracting hepatitis C, tacrolimus exposure increased, insulin resistance increased, and insulin secretion decreased markedly. Despite low tacrolimus exposure in the last 4 years, glucose metabolism did not recover completely. Although PTDM resolved and insulin resistance normalized, pancreatic beta cell secretion remained impaired by approximately 50% compared with the period before hepatitis C infection. CONCLUSION: After an initial increase in insulin resistance, insulin secretion decreased markedly in a patient who contracted hepatitis C 12 to 22 months after renal transplantation. This change resulted in an episode of PTDM. Increased tacrolimus exposure secondary to reduced cytochrome P-450 metabolism as a result of impaired hepatocellular function at the time of the development of PTDM seems a likely explanation for the marked decrease in insulin secretion. Viral toxicity to the beta cell might be an additional explanation. The latter might be suspected from several reports about an association between diabetes mellitus and hepatitis C in patients who do not use drugs that interfere with glucose metabolism.

Lack of evidence for the role of human adenovirus-36 in obesity in a European cohort.

Adenovirus infection has been shown to increase adiposity in chickens, mice, and nonhuman primates. Adenovirus type 36 (Ad-36) DNA was detected in adipose tissues in these animal trials. In the United States, Ad-36 significantly correlates with obesity as illustrated by an Ad-36 seroprevalence of 30% in obese individuals and 11% in nonobese individuals. We investigated the possibility of a similar correlation of Ad-36 in Dutch and Belgian persons. In total, 509 serum samples were analyzed for Ad-36 antibodies using a serum neutralization assay. In addition, PCR was used to detect adenoviral DNA in visceral adipose tissue of 31 severely obese surgical patients. Our results indicated an overall Ad-36 seroprevalence of 5.5% increasing with age. BMI of Ad-36 seropositive humans was not significantly different from seronegative humans. No adenoviral DNA could be found using PCR on visceral adipose tissue. In conclusion, this first Ad-36 study in the Netherlands and in Belgium indicates that Ad-36 does not play a role as a direct cause of BMI increase and obesity in humans in Western Europe.

Acute hepatitis B virus infection with simultaneous high HBsAg and high anti-HBs signals in a previously HBV vaccinated HIV-1 positive patient.

We present a case of a clinical manifest hepatitis B virus infection and a potentially misleading HBV serological profile in an HIV-1 positive patient despite previous HBV vaccination. The patient presented with an acute hepatitis B and there was no indication of chronic HBV infection or the presence of a mutation in the 'a' determinant. Remarkably, simultaneously with high HBV surface antigen and HBV viral load, high anti-HBs antibodies were present. If, due to previous HBV vaccination only anti-HBs was tested in this patient, the result of the high anti-HBs antibodies could be very misleading and offering a false sense of security. Our findings contribute to the ongoing discussion on how to assess HBV specific immunological memory and determining the role of HBV booster vaccinations in immunocompromised individuals.

CMV DNA levels and CMV gB subtypes in ART-naive HAART-treated patients: a 2-year follow-up study in The Netherlands.

OBJECTIVE: In the pre-HAART period, HIV-1 patients were greatly at risk for cytomegalovirus (CMV) disease. In HAART-treated patients, the incidence of CMV disease has decreased dramatically and the timing and presentation of CMV infection may be different. Also the relevance of different CMV genotypes is part of debate. DESIGN AND METHODS: A total of 132 antiretroviral naive patients starting HAART were selected for a 2-year follow-up study in the Netherlands. RESULTS: In 105 (80%) patients, CMV DNA were less than 100 copies/ml in all plasma samples during follow-up. In 27 (20%) patients, a detectable CMV load was found during follow-up. In seven patients, the initial decrease in HIV-1 loads during HAART was accompanied by an increase in CMV loads. Of 1348 plasma samples, only 50 (3.7%) samples were positive with a CMV load more of than 100 copies/ml plasma. CMV loads more than 1000 copies/ml were found only in samples with CD4 levels less than 250 x 10 cells/l and with detectable HIV-1 loads. CMV glycoprotein B (gB) typing was possible in 19 patients. Among these patients, including four patients with triple CMV infection and seven patients with double infection, the most prevalent genotype was gB3 (16x) followed by gB2 (9x), gB1 (5x) and gB4 (4x). CONCLUSION: CMV disease during HAART is very unlikely as soon as the HIV-1 viral load becomes undetectable (<50 copies/ml) and/or CD4 cell levels are restored to more than 250 x 10 cells/l. Within Dutch HAART treated patients, infection with CMV gB3 is most prevalent, but also double or triple infection with other CMV gB strains are common.

Chlamydia antibody testing in screening for tubal factor subfertility: the significance of IgG antibody decline over time.

BACKGROUND: Chlamydia (C.) trachomatis antibody testing in screening for tubal factor subfertility is limited by false negative results, i.e. negative Chlamydia antibody tests in patients with tubal pathology at laparoscopy. The present study was performed to determine whether decline in C. trachomatis IgG antibodies over time is responsible for those false negative results. METHODS: A total of 39 women with an initial titre of > or =64 were re-studied after 4-7 years. A new serum sample was collected from each patient. The initial and the second serum sample were tested for C. trachomatis IgG antibodies using a micro-immunofluorescence assay (MIF). A species-specific enzyme-linked immunosorbent assay (ELISA) was used to validate the MIF test results. All patients filled out a questionnaire to determine risk factors for renewed C. trachomatis infection between the initial and second serum sample. RESULTS: Seven of the 39 patients (18.0%) showed a decline (>2 titre steps) in IgG antibodies by MIF over a period of 4-7 years, but IgG antibodies never became undetectable. In the 7/39 patients who showed a decline by MIF, signal/cut-off values by ELISA did not change. CONCLUSION: A decline in IgG antibody titre is not a significant cause of false negative Chlamydia antibody test results.

Onset and duration of cytomegalovirus immediate early 1 mRNA expression in the blood of renal transplant recipients.

Human cytomegalovirus (CMV) messenger (m) RNA expression in circulating leukocytes reflects directly viral activity in the human host. In this study, sixty-nine patients were monitored prospectively for CMV infection and mRNA expression during the first year after renal transplantation. Of the 69 recipients, 58 (84%) recipients were positive for CMV immediate early 1 (IE1) mRNA as detected by nucleic acid sequence-based amplification. The median onset of IE1 expression started at day 22 after transplantation and continued for a median duration of 82 days. IE1 mRNA expression started significantly earlier in recipients who developed an active CMV infection (P = 0.001) and in mycophenolate mofetil (MMF) treated recipients (P = 0.002). The duration of IE1 mRNA expression was significantly longer in recipients that had previously an early onset of IE1 mRNA expression (P = 0.001) and in recipients with active CMV infection (P = 0.007). Remarkably, longer prednisolone intake was correlated with a significantly (P = 0.02) shorter duration of IE1 expression compared to a longer duration of IE1 expression in recipients with only a short prednisolone intake. In recipients infected with glycoprotein B (gB) type 1 CMV strains, the duration of IE1 expression was significantly (P = 0.04) shorter compared to recipients infected with non-gB type 1 CMV strains (64 days vs. 150 days). The study indicates that multiple factors play a role in the onset and/or duration of CMV IE1 mRNA expression, for example, MMF treatment, prednisolone intake, and gB type of the specific CMV strain. The clinical significance of these correlations remains to be studied in more detail.