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Biomedical subjects

R Vranckx

Publications and source records attributed to R Vranckx.

At least 19 recordsLinked to original sources

A new European perspective of influenza pandemic planning with a particular focus on the role of mammalian cell culture vaccines.

Sixteen EU scientists and doctors were interviewed about pandemic planning using psychometric methods applied to a scientific problem for the first time. Criticism was aimed at countries which have no plan whatsoever, the majority of nations. Many such countries have not invested in scientific infrastructure and public health. Amongst the 15 or so published pandemic plans a lack of detail was identified. Of particular need was investment into avian virus vaccine stocks (H1-15), prepared licenses of vaccine and pre purchase and agreed distribution, investment into stocks of antivirals, antibiotics and masks. Most but not all members of the group predicted a global outbreak within 5 years, most probably starting in SE Asia. However it was recognised that a pandemic could start anywhere in the world which had juxtaposition of young people, chickens, ducks and pigs. Mammalian cell culture production using wild type virus with the production factory at category III levels of security was exemplified. Antivirals would be essential to ameliorate the first wave of infection although significant quantities of cell grown vaccine could be produced if, as in 1918, 1957 and 1968 there is a long period between the first virus isolation and person to person spread. The wider scientific community is more energised than previously for very serious preparations to be in place way before the outbreak begins as this is a major public health problem, completely dwarfing concerns about bioterrorism.

Animals↗

Correlation between detection of antibodies against hepatitis C virus in oral fluid and hepatitis C virus RNA in serum.

Reported here are the results of a study designed to determine the correlation between hepatitis C virus (HCV) RNA positivity in serum and the detection of antibodies against HCV in oral fluid by testing paired serum/oral fluid samples. For the 85 serum samples found positive for antibodies against HCV, using a screening assay and a confirmation assay, 70 of the corresponding oral fluid samples tested positive for HCV antibodies using a previously modified screening assay. For 52 of the 59 serum samples found positive for HCV RNA, the corresponding oral fluid samples also tested seropositive for HCV, while 18 of the 26 serum samples that were negative for HCV RNA had corresponding oral fluid samples that tested seropositive for HCV. For the control group of 54 serum samples that were negative for HCV antibodies, all of the corresponding oral fluid samples were also negative for HCV antibodies, while 53 of the serum samples tested negative for HCV RNA. These results suggest that HCV antibody detection in oral fluid has a slightly higher sensitivity when used to test patients whose serum samples are positive for HCV RNA (chi-square test, p=0.035; Mid-P exact, p=0.049).

Antibodies, Viral↗

Hepatitis B virus (HBV) genotyping in Belgian patients with chronic HBV infection.

Several studies have demonstrated that pathogenic and therapeutic differences exist among hepatitis B virus (HBV) genotypes. Therefore, this study established the prevalence of different HBV genotypes in 128 Belgian patients with chronic HBV infection. The prevalences of genotypes A and D, and mixed genotypes A and D, were 53%, 37% and 8%, respectively, for a group of blood donors, and 54%, 31% and 9%, respectively, for a group of patients from the gastroenterology units. The results indicated that genotypes A and D are the predominant genotypes in Belgian patients with chronic HBV infection.

Adult↗

Detection of HCV antibodies in oral fluid.

Although conventionally the detection of HCV antibodies is carried out on serum, the collection of oral fluid is non-invasive, safe and cost effective. In this study, the efficacy of the detection of HCV antibodies in oral fluid was assessed. 73 anti-HCV positive and 73 anti-HCV negative paired serum/oral fluid samples, drawn from patients visiting a Belgian academic hospital, were tested using the modified Ortho HCV 3.0 and LIA confirmation assay. Performing the test on oral fluid with the modified protocol, 61/73 anti-HCV positive samples were tested positive, while 73/73 anti-HCV negative samples were tested negative, giving a sensitivity and specificity of 83.6% (95% CI: 72.7-90.9%) and 100.0% (95% CI: 93.8-100.0%), respectively. Comparing S/CO of concordantly positive and negative samples, the cut-off point was lowered by 30% resulting in a sensitivity of 89.0% (95% CI: 79.0-94.8%) while the specificity remained 100.0% (95% CI: 93.8-100.0%). The confirmation assay was carried out as described by the manufacturer, diluting the oral fluid 1:10. Testing paired samples gave a concordance of 85.6% (125/146), yielding no more accurate results. These findings suggested that the modified ELISA method for anti-HCV detection in oral fluid can be used for epidemiological surveys.

Antibodies, Viral↗

Hepatitis B vaccination coverage in Belgian health care workers.

BACKGROUND: The hepatitis B virus (HBV) vaccination policy for health care workers (HCW) started in Belgium in 1983. An update of vaccination coverage and rates of seroconversion and seroprotection among HCW can give an insight into the actual status and encourage further development of vaccination programs. PATIENTS AND METHODS: 5,064 HCW were tested for anti-HBs. We considered those who had a positive anti-HBs test as seroconverted (SC) and those who had an anti-HBs titer > 10 IU/l as seroprotected (SP). RESULTS: 4,771 HCW were eligible for vaccination; 84.9% of them were effectively vaccinated. Among high-risk professions (nurses, care and laboratory workers), 94.79% were vaccinated; for other professions the vaccination coverage was 69.26%. Of the 1,015 non-vaccinated persons, 293 were anti-HBs positive. Among these 54.95% declared they had had a previous hepatitis infection that was serologicaLly proven to be HBV (anti-HBc positive). Of the remaining 132 positives, 70.45% had previously undergone surgery and/or transfusion. Among these 1,015 non-vaccinated HCW, 59.03% were anti-HBs positive. Of these, 373 were nurses, care or laboratory workers. This contrasts with the results for HCW in other sectors, where 11.49% were anti-HBs positive. CONCLUSION: In our sample, high vaccination, seroconversion and seroprotection rates were achieved, at least for higher risk HCW. The same conclusion can be drawn if we consider hospital departments which carry a higher risk of blood-borne infections.

Adult↗

The seroepidemiology of herpes simplex virus type 1 and 2 in Europe.

OBJECTIVES: To describe the seroepidemiology of herpes simplex virus (HSV) types 1 and 2 in the general populations of eight European countries to better understand recent reported changes in disease epidemiology. METHODS: Belgium, Bulgaria, Czech Republic, England and Wales, Finland, Germany, Netherlands, and Slovenia conducted national cross sectional serological surveys for HSV-1 and HSV-2 between 1989 and 2000. Survey sizes ranged from 3000 to 7166 sera. External quality control was ensured through reference panel testing. RESULTS: Large intercountry and intracountry differences in HSV-1 and HSV-2 seroprevalence were observed. Age standardised HSV-1 seroprevalence ranged from 52% in Finland, to 57% in the Netherlands, 67% in Belgium, 81% in Czech Republic, and 84% in Bulgaria. Age standardised (>12 years) HSV-2 seroprevalence ranged from 24% in Bulgaria, to 14% in Germany, 13% in Finland, 11% in Belgium, 9% in Netherlands, 6% in Czech Republic, and 4% in England and Wales. In all countries, probability of seropositivity for both infections increased with age. A large proportion of teenagers and young adults remain HSV-1 susceptible particularly in northern Europe. Women were significantly more likely to be HSV-2 seropositive in six of seven (p<0.05) countries and HSV-1 seropositive in four of seven (p<0.05) countries, particularly in northern Europe. No significant evidence of a protective role of HSV-1 for HSV-2 infection was found adjusting for age and sex (p<0.05). CONCLUSIONS: There is large variation in the seroepidemiology of HSV-1 and HSV-2 across Europe. The observation that a significant proportion of adolescents are now HSV-1 susceptible may have implications for transmission and clinical presentation of HSV-1 and HSV-2.

Adolescent↗

Serotyping and genotyping of hepatitis C virus in Belgium.

BACKGROUND: Given that both pathogenicity and the response to treatment are possibly associated with hepatitis C virus (HCV) serotype, it appeared sensible to establish the prevalence of the different HCV types in Belgium. MATERIALS AND METHODS: The HCV serotypes were determined in 68 HCV-RNA and anti-HCV-positive samples taken from Belgian patients and compared with the results of the genotyping assay. Possible associations with age and sex were investigated. RESULTS: Antibodies were identified in 55 (80.9%) of the 68 samples, with serotype 1 (58.8%) and serotype 3 (19.1%) showing the highest prevalence. 17 samples contained several serotypes with serotype 1 being detected in 82.4% of cases. Nine of the 11 samples undetermined by serotyping could be determined by genotyping. There was no significant difference in the distribution of HCV types with respect to gender. Compared with genotype 3 (p < 0.01) and genotypes 2 and 4 (p = 0.05), genotype 1 was detected among older patients. CONCLUSION: Our data showed a 96.0% correlation between the serotyping and genotyping assays. Genotypes 1 and 3 are the most prevalent types among Belgian patients. The data suggest that genotype 1 spread earlier than genotypes 2, 3 and 4. This corroborates previous European studies.

Adult↗

Non-viral gene transfer of murine spleen cells achieved by in vivo electroporation.

Gene electrotranfer is an attractive physical method to deliver genes to target tissues. The aim of this study was to evaluate in vivo gene electrotransfer into spleen, one of the most important lymphoid organ, in order to create a new tool to modulate the immuno-inflammatory system. C57Bl/6 mice were submitted either to intramuscular electrotransfer (IME) as a reference method or to intrasplenic (ISE) gene electrotransfer. In the naked injected plasmids, the CMV promoter controlled the expression of luciferase, secreted alkaline phosphatase, EGFP, or IFNgamma. The ISE optimal electrotransfer conditions were first determined and ISE was found to be an efficient gene transfer method, which can be used to express secreted or intracellular proteins transiently. Although transfected cells were still present in the spleen 30 days after ISE, transfected spleen cells could recirculate since they were detected in extrasplenic locations. Using a T-lymphocyte-specific promoter controlling the expression of EGFP, splenic T cells could be targeted. Finally, it appeared that ISE procedure does not impair by itself the immune response and does not result in a significant production of antibodies directed to the transgenic proteins in C57Bl/6 mice. This strategy constitutes a new method to manipulate the immune response that can be used in various experimental designs.

Alkaline Phosphatase↗

Cumulative inactivation of the outward potassium current: a likely mechanism underlying electrical memory in human atrial myocytes.

The influence of the mode of cell stimulation on the outward K+ current (I(o)) was studied in whole-cell patch-clamped human atrial myocytes. Acceleration of the rate of membrane depolarization at 1 Hz or during prolonged 5-s test pulses at 0.1 Hz increased the rate and extent of I(o) inactivation, resulting in enhanced inactivating (4.9+/-0.6 v 6.3+/-0.7 pA/pF) and suppressed maintained (5.9+/-1.2 v 3.2+/-0.3 pA/pF) current components. These alterations were associated with a leftward shift of the voltage-dependency of I(o), and persisted on returning to a control depolarization protocol (750-ms test pulses delivered at 0.1 Hz). The effects of increasing external K+ concentrations (40 m m) on the kinetics of I(o) were more pronounced following both rapid and prolonged depolarization (changes in I(t)/I(o)caused by 40 m m K+: 8.9+/-3.5% v 15.5+/-3.1% before and after prolonged depolarization; and 9.2+/-1.2% v 15.4+/-1.7% before and after rapid depolarization). The phosphatase inhibitor, okadaic acid, enhanced the effect of rapid and prolonged depolarization on I(o)whereas the inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMK-II) with KN-62 or KN-93, or by intracellular application of the autocamtide-2-related inhibitory peptide, suppressed it. In conclusion, rapid and prolonged membrane depolarization both cause a cumulative increase in the rate and extent of I(o)inactivation. This process involves slow potassium channel inactivation mechanisms, is regulated by CaMK-II, and may contribute to the electrical memory of the atrial myocardium.

Adult↗

Effect of the extract of Ginkgo biloba (EGb 761) on the circulating and cellular profiles of polyunsaturated fatty acids: correlation with the anti-oxidant properties of the extract.

Ginkgo biloba extract (EGb 761) has beneficial effects on cognitive functions in aging patients, and on various pathologies, including cardiovascular diseases. Although the extract is known to have antioxidant properties and improve membrane fluidity, the cellular mechanisms underlying these effects have not been determined. Here, we examined the in vivo effects of EGb 761 on circulating and cellular lipids. EGb 761 treatment induced significant increases in the levels of circulating polyunsaturated fatty acids (PUFAs), and a decrease in the saturation index SI (saturated/polyunsaturated species). Plasma triglycerides and cholesterol were not affected, while phospholipids were slightly increased at the higher dose of EGb 761. EGb 761 treatment also induced a significant increase in the levels of PUFAs in erythrocyte membranes, especially for the eicosapentaenoic acid (EPA omega 3), and a decrease in the saturation index. Moreover, the response of erythrocytes to oxidative stress was improved in EGb 761-treated animals (H(2)O(2)-induced cell lysis decreased by 50%). Considering that PUFAs are known to improve membrane fluidity and response to oxidative damage, and are precursors of signaling molecules such as prostaglandins, the effects of EGb 761 on circulating and cellular PUFAs may explain some of the pharmacological properties of Ginkgo biloba.

Animals↗

Prevalence of hepatitis C antibodies in a large sample of Belgian healthcare workers.

OBJECTIVE: To assess the risk of hepatitis C virus (HCV) infection among Belgian (Flemish) healthcare workers. DESIGN: A seroprevalence survey of HCV IgG antibodies. SETTING AND PARTICIPANTS: A systematic sample of 5,064 employees from 22 general hospitals in Flanders and Brussels, Belgium, was tested at the annual occupational medical examination. Together with demographic and occupational data, information was collected on the frequency of blood contact, needlestick injuries, and medical and surgical history. The blood samples were tested using the third-generation Abbott Screen Kit test, with confirmation by Matrix, LIA, and an in-house polymerase chain reaction and the Quantiplex-HCV b-DNA test. RESULTS: 21 persons were found to be positive for HCV markers. The overall prevalence was 0.41% (95% confidence interval [CI95], 0.24-0.59). A statistically significant association was found with a history of blood transfusion (odds ratio [OR], 4.14; CI95, 1.67-10.31) and with history of a clinically apparent hepatitis (OR, 3.98; CI95, 1.60-9.90). Although the ORs for the frequency of blood contact were slightly elevated (between 1.17 and 2.73), this association was not significant. Moreover, a history of needlestick injuries showed a nonsignificant OR of 1.28 (CI95, 0.53-3.09), and no statistically significant difference was found with a variety of duties and tasks. The ORs for potential occupational risk factors were adjusted according to age, gender, antecedents, and other confounders using a logistic regression analysis. Based on this procedure, the ORs decreased slightly. CONCLUSIONS: Flemish healthcare workers showed a lower HCV seropositivity than is seen in the general population; a history of blood transfusion and of clinically apparent hepatitis was most strongly associated with the presence of HCV markers. We concluded that employees in Flemish regional general hospitals are not at an overall increased risk for HCV infection, although occasional transmission through percutaneous injuries is possible, and prevention therefore remains imperative.

Adult↗

Occupational risk of infection by varicella zoster virus in Belgian healthcare workers: a seroprevalence study.

OBJECTIVES: To assess the prevalence of varicella zoster virus (VZV) antibodies in Flemish (Belgian) healthcare workers, to investigate the association between seronegativity and selected variables, and to assess the reliability of recall about disease as a predictor of immunity. METHODS: A seroprevalence study of VZV antibodies (IgG) was conducted among a systematic sample of 4923 employees in various professional groups, employed in 22 hospitals in Flanders and Brussels (Belgium). Information about sex, age, department, job, and years of employment, the country of origin, and history of varicella was obtained. The presence of VZV antibodies was investigated with the enzyme linked immunosorbent assay (ELISA), Enzygnost anti VZV / IgG (Dade Behring, Marburg, Germany). Statistical analysis was performed by calculating prevalences and prevalence ratios (PRs) and their 95% confidence intervals (95% CIs). Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of the recalled history were determined. RESULTS: The prevalence of VZV seropositivity in Flemish healthcare workers was 98.5% (95% CI 98.1 to 98.8). Seronegativity was significantly associated with age and job, increasing with both older and younger age. The prevalence of seronegative workers was significantly less in nursing staff than non-nursing staff. There was no significant difference for sex and years of employment. The PPV and NPV of recalled history were 98.9% and 3.4%. Sensitivity and specificity were 83% and 38.9%. CONCLUSION: The prevalence of VZV seropositivity was very high in this sample of Flemish healthcare workers. Because of this low overall susceptibility, VZV infection seems not to be an important occupational risk among healthcare workers in Flanders. The increasing seronegativity above the age of 45 is possibly due to a loss of detectable antibodies. A positive history of varicella was a good predictor of immunity, but a negative history had no value as a predictor of susceptibility in adults.

Adult↗

PCR detects HCV RNA in a plasma pool contaminated by a single preseroconversion donation of genotype 5a.

BACKGROUND AND OBJECTIVES: To determine the prevalence of HCV-RNA-positive plasma pools in Belgium, to validate our PCR method and to increase the safety of the released blood products. MATERIALS AND METHODS: Plasma pools consisting each of about 5,000 donations from Belgian unpaid volunteer blood donors were analysed by PCR for the presence of HCV RNA. Two different extraction methods were compared and validated. RESULTS: Two out of 367 plasma pools were found to be HCV RNA positive and were discarded. For one of these two pools, the look-back procedure identified an anti-HCV-negative contaminated donation. The HCV genotype of both the contaminated pool and the donation was 5a, a genotype rare in Europe. The viral load of the preseroconverted donation was 2.9 x 10(7) gEq/ml according to the bDNA method. CONCLUSION: In the case of plasma derivatives, various important steps are already included to increase safety. Nucleic acid testing of manufacturing plasma pools ensures that viral load in the starting material is as low as possible.

Belgium↗

Hepatitis B vaccination in mentally retarded: effectiveness after 11 years.

The long-term effectiveness of hepatitis B vaccination was determined in a high-risk group of 105 institutionalized mentally retarded. All individuals were vaccinated in 1986, with three (0, 1, 6 months), four (0, 1, 6 and 12 months) or more doses according to their immune response at month 7, resulting in group 1 (G1), group 2 (G2) and group 3 (G3). They were annually followed up for five years, after which they received a booster dose. Eleven years after the initial vaccination, they were again tested for the presence of hepatitis B virus (HBV) serologic markers. The decline in anti-HBs logtitre over the first five years was 51% for G1 and 45% for G2. From the booster on month 60 to year 11, the overall decline was 31%. Eleven years after the start of vaccination and six years after the booster, 92% of the individuals had protective antibody levels higher than 10 IU/L. G1 had a geometric mean titre of 2015 IU/L, for G2 this was 245 IU/L. The difference in response to vaccination between the groups did not affect their protection. Only two vaccinees seroconverted to anti-HBc positivity without becoming carrier or ill. Long-term protection against HBV by vaccination appears to be excellent.

Adult↗

Prevalence of hepatitis A antibodies in a large sample of Belgian health care workers.

Health care workers (HCW), especially women (for example, pediatric nurses and day nursery workers), have been shown to be at risk for viral hepatitis A infections. In order to obtain a more precise estimate of the risk in Belgian HCW, a seroprevalence study was undertaken. The data from this study have been compared with the age-specific seroprevalence of anti-HAV in the general population (GP) as recently estimated. During 1996-1997, a sample of 5,068 employees in 22 general hospitals, geographically distributed over the Flemish and Brussels regions of Belgium, was tested for the presence of anti-HAV. Comparison of the anti-HAV prevalences in HCW and GP shows a significantly lower prevalence in HCW for the age groups 25-34, 35-44 and 45-54 years. Within these age-groups, employees performing catering tasks have the highest prevalence. This difference could be explained by socioeconomic parameters: overrepresentation of higher social classes in better educated HCW. The number of unprotected individuals in young and older age groups (25-54 years) is greater than in the general population. In view of the changing HAV epidemiology in western Europe, the number of unprotected persons will rise in the coming years. Considering the more severe course of the disease as age increases, vaccination may become important in the occupational health strategy for HCW.

Adult↗

Hepatitis B virus vaccination and antenatal transmission of HBV markers to neonates.

The high prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in pregnant women is considered to be the most important factor contributing to the high carrier rate of HBsAg in some populations. Several factors, including the age at which infection occurs, predispose to the acquisition and frequency of the carrier state. The proportion of infected people who become chronic carriers ranges from about 80 to 95% for babies born to HBsAg/HBeAg-positive mothers. In this study of Indonesian infants receiving only active immunization against HBV, we measured the HBV markers passively acquired from their HBsAg-positive mothers. The relationship of these markers with vaccination response and with HBV infection status was studied longitudinally in the infants. In the exposed neonates from the HBsAg-positive mothers (n=61), the seroconversion rate to hepatitis B surface antibody (HBsAb) positivity was 95% after the first booster vaccination, with a geometric mean titre (GMT) of 2017 IUl-1. After 60 months, the GMT in this group decreased to 50 IUl-1. Four newborns in this group became HBsAg carriers. Of the four vaccination failures, three newborns were HBsAg/HBeAg positive at birth, suggesting that they had been infected in utero. No vaccination strategy (active alone, or passive/active) can prevent this transmission from occurring. One carrier was HBsAg negative at birth and up to month 4 but was HBsAg positive at month 12 and subsequently, suggesting a postnatal infection. Vaccination early in life can, to a large extent, prevent perinatal transmission and hepatitis B virus (HBV) infection later in infancy and childhood. In this study, the protective efficacy of the vaccination was 85% in the subcohort of neonates from HBeAg-positive mothers and 100% in the subcohort of neonates from HBeAg-negative mothers. Lack of maternal antibodies to hepatitis B core antigen (HBcAb) correlated strongly with transmission of HBV infection.

Biomarkers↗

Heme and acute inflammation role in vivo of heme in the hepatic expression of positive acute-phase reactants in rats.

Acute-phase protein synthesis in the liver during inflammation is regulated via cytokines and glucocorticoids. Using quantitative reverse transcription (RT)-PCR analysis and immunoassay, we explored, in the rat, the response of the acute-phase protein, alpha-2 macroglobulin (A2M), after systemic inflammation induced by lipopolysaccharide (LPS) or localized inflammation induced by turpentine oil (TO). The results indicate that synthesis of A2M is higher following TO-induced inflammation than LPS-induced inflammation and is not correlated with interleukin (IL)-6 or glucocorticoid levels. We studied the putative role of heme in this differential A2M expression following localized vs. systemic inflammation; addition of heme during LPS-induced inflammation can boost the expression of A2M, whereas blocking heme synthesis (by succinyl acetone) or enhancing its consumption in parallel biosynthetic pathways (cytochrome P450 induction by phenobarbital) decreases A2M expression. This decrease was abolished by exogenous heme supplementation. Finally, we demonstrate that heme supplementation is also able to increase the A2M response in female rats to a level similar to that in male rats providing a new insight into the puzzling sexual dimorphism observed previously during localized inflammation. We propose that heme should be considered a new regulatory element in controlling liver A2M expression during inflammation.

Acute-Phase Proteins↗

A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization.

Human endothelin-converting enzyme (ECE-1) has been shown to exist as three isoforms (ECE-1a, ECE-1b and ECE-1c) diverging in their N-terminal sequence and displaying different patterns of subcellular localization. We report here the cloning of ECE-1d, a novel isoform of 767 amino acids, which is generated from the same gene via the existence of an additional promoter located upstream from the third exon of the ECE-1 gene. ECE-1d converting activity is comparable to that of the other three isoenzymes. In contrast to ECE-1b, ECE-1d is expressed at the cell surface, although less strongly than ECE-1a. We have also shown, by identifying ECE-1b and ECE-1d in rat, that the ECE-1 diversity is conserved between human and rodent, suggesting its physiological relevance. The mRNA levels of the four isoforms were assessed in the two species in various cell types, revealing some differences. In particular, the ECE-1a isoform, strongly expressed at the plasma membrane, was found to be highly expressed in primary cultures of endothelial cells but absent from primary cultures of smooth muscle cells.

Amino Acid Sequence↗