Changing patterns in acute clinical viral hepatitis encountered by Belgian general practitioners.
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Journal Article↗
Biomedical subjects
R Vranckx
Publications and source records attributed to R Vranckx.
Diphtheria immunity in Flanders.
A serological survey to determine the immunity to diphtheria in the Flemish population was conducted according to the recommendations of the World Health Organization. Immunity to diphtheria was determined on a randomised, stratified sample (1679 serum samples) from an existing serum bank (4058 serum samples) representative of the Flemish population. All age groups between 0 and 100 years were included. A tissue (Vero cell) culture toxin neutralisation assay was used to measure serum diph-theria antitoxin concentrations. The results showed that 43% of the Flemish population was protected against diphtheria (antitoxin titre, > or = 0.1 IU/ml), while 32% was susceptible (antitoxin titre, < 0.01 IU/ml); for 25%, protection was of limited duration (antitoxin titre, > or = 0.01 IU/ml and < 0.1 IU/ml). The proportion of susceptible subjects showed a significant age-related increase, with the highest values in the 35 to 44 and 45 to 54 age groups (57.9% and 55.5%, respectively). These results emphasise the need for booster immunization of adults.
Adolescent↗
[Radiotherapy-induced cognitive dysfunction in 4-months-old male Wistar rats]].
PURPOSE: Behavioral dysfunction of memory process arising 4 months after whole brain irradiation (30 Gy/10 fractions/12 days) has been demonstrated in 16-27 month old rats, as compared with non irradiated rats. This study was therefore aimed at delivering the same irradiation in young rats and comparing results with those previously obtained in old rats. MATERIAL AND METHODS: Thirty-three 4-month old rats were included into the study. Eighteen received whole brain irradiation (30 Gy/10 fractions/12 days), and 18 were given sham irradiation. Sequential behavior studies were done before irradiation and during the 7 months following irradiation. RESULTS: Significant decrease in memory function was observed in irradiated rats 1 month (p < 0.001), 3 months (p < 0.013), and 6 months (p = 0.007) post-irradiation. This was accompanied by learning deficit 1 month (p = 0.01), 4.5 months (p = 0.03), and 7 months (p = 0.009) post-irradiation. CONCLUSION: Response to radiation therapy observed in young rats differed from that observed in old rats. Young rats showed earlier decrease in memory function than old rats, but this deficit was followed by partial recovery. Learning deficits also arised earlier in young rats than in old rats. In two cases this deficit was permanent.
Age Factors↗
Prevalence of hepatitis A, B and C in the Flemish population.
Viral hepatitis is a serious health problem throughout the world. No recent prevalence data on hepatitis A, B and C were available for the population in Flanders, Belgium. For this reason, a sero-epidemiological study was undertaken in 1993-1994 in a sample of the general population. The purpose of this study was to obtain a clear picture of the prevalence of hepatitis A, B and C. Between April 1993 and February 1994, 4,058 blood samples were drawn and collected in 10 hospitals in Flanders. The study group was representative for the Flemish population. For hepatitis A a seroprevalence of 55.1% was found. In the non-Belgian residents the HAV prevalence was significantly higher than in Belgians (62% versus 52%; chi2 = 8.05; p = 0.005). For hepatitis B. 9.9% of the study group showed serological evidence of hepatitis B markers: 6.9% of the participants was positive for anti-HBs/anti-HBc, 0.7% appeared to be HBsAg positive and 3.5% was solely anti-HBs positive. The prevalence of HBV markers in Belgians was 6.9%, significantly lower compared to the 13.4% among non-Belgians (chi 2 = 14.05; p = 0.00018). 4055 serum samples were analysed for hepatitis C serology by second generation anti-HCV tests. Anti-HCV was detected in 0.87% of the serum samples. No statistically significant difference was found in HCV prevalnece between Belgians and non-Belgians. Results of this study should help policy makers in their decisions on the most appropriate hepatitis A and B vaccination strategy and on the most effective prevention strategy for hepatitis C.
Adolescent↗
Effect of dehydroepiandrosterone on rat thyroxine binding globulin, a protein upregulated during aging.
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Aging↗
Horizontal transmission of hepatitis B virus.
In 1991-92, a cross-sectional survey in Flanders (Belgium) for hepatitis B virus (HBV) markers among 277 relatives of institutionalised mentally handicapped persons to evaluate the prevalence of hepatitis B and the risk of infection showed that relatives of an HBV positive resident were 7.6 times more likely to be infected than relatives of an HBV seronegative mentally handicapped person. HBV infection among the family members could be attributed in 83% to exposure to an HBV positive resident. This study demonstrated the importance of horizontal transmission among relatives of institutionalised mentally handicapped people, even if family contact is reduced to weekend and holiday activities. We recommend that HBV vaccination policy should be expanded to include relatives of institutionalised mentally retarded people.
Belgium↗
Plasma proteins as biomarkers of the aging process.
This study was designed to characterize the rat serum proteins as biomarkers of the normal aging process. Crossed immunoelectrophoresis or electroimmunodiffusion quantitation of proteins was performed in rats aged 6, 12, 24, and 30 mo. Selection of healthy animals was based on confrontation of crossed immunoelectrophoresis patterns with those of experimentally inflamed young adults and with individual anatomopathological data. Convergence of inflammatory patterns and severe histological lesions was the exclusion criterion. Senescence-induced decrease was demonstrated for eight proteins [negative senescence reactants (SRs-)] and increase for six proteins [positive SRs (SRs+)]. Most SRs belonged to the class of proteins responsive to acute inflammation [acute phase reactants (APRs)]. One SR+, the thyroxine-binding globulin, a high-affinity thyroid hormone binder, emerged as a particularly reliable senescence biomarker, showing the highest aging-related variation (8-fold increase from 6 to 30 mo) and not belonging to the APR class. Chronic treatment with perindopril, an angiotensin I-converting enzyme inhibitor used in heart and renal disease therapy, significantly enhanced thyroxine-binding capacity, possibly by preventing age-related alterations of serum lipids. Serum protein patterns prove valuable both as indexes for selecting aging animals free from superimposed pathologies and as parameters of senescence-induced changes in protein biosynthesis.
Acute-Phase Proteins↗
Induction of rat alpha-1-acid glycoprotein by phenobarbital is independent of a general acute-phase response.
Phenobarbital (PB) induces transcription of the alpha 1-acid glycoprotein (AGP) gene, one of the major positive acute-phase proteins, the expression of which is controlled by a specific combination of glucocorticoids and cytokines. This raises questions as to the involvement of glucocorticoids and cytokine pathways in the PB-mediated effect on AGP gene expression. We found that the pattern of whole-serum proteins in PB-treated rats differed markedly from that observed during a typical acute inflammatory response (in turpentine-treated rats): levels of some positive acute-phase proteins (APP) increased slightly (alpha 1-acid glycoprotein, haptoglobin, hemopexin and T-kininogen), while levels of alpha 2 macroglobulin, the most sensitive marker of the acute-phase reaction, decreased. Among the negative APP, neither albumin nor prealbumin decreased while CBG increased. The cytokines involved in AGP gene regulation (mainly IL1, IL6 and TNF alpha) do not therefore seem to mediate the effect of PB on acute-phase protein expression. Glucocorticoid involvement is also ruled out by the observed enhancement of the effect of PB on AGP expression in adrenalectomized animals. Our results suggest that phenobarbital acts on AGP expression by a mechanism independent of the inflammatory pathway.
Acute-Phase Reaction↗
Increased risk of hepatitis A among female day-nursery workers in Belgium.
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Adult↗
Anti-HBs kinetics after HBV vaccination in neonates.
BACKGROUND AND OBJECTIVES: We report the results of a study using a recombinant DNA HBV vaccine in newborns from an endemic area for HBV and compare the anti-HBs kinetics with observations in adults in order to make estimates about the need for booster vaccinations. STUDY DESIGN: One hundred and forty-eight neonates were vaccinated and followed for 62 months. Based on the presence or absence of hepatitis B surface antigen in the mother, cohorts of 'exposed' and of 'non-exposed' neonates were identified. RESULTS: A maximum concentration is normally observed after the booster vaccination followed by a rapid decline. According to Ambrosch et al. and Gesemann et al., titer calculations as a function of time, yielded 37 IU/1 and 47 IU/1 at month 60 respectively. The mean titer for the three groups of neonates investigated was at that time 74 IU/1. The prospective time intervals to arrive at an anti-HBs level of at least 10 IU/1 can be individually calculated from the individual titer after the booster vaccination. These calculated estimates show respectively: that 8.3% of the vaccinated neonates need a new booster vaccination within 14 months; that 26.7% will need a new booster within 50 months; and that only 65% need a new booster in 50 or more months. CONCLUSION: It can be concluded that anti-HBs kinetics in very young children and adults are comparable. The least expensive way of maintaining protection against HBV in neonates seems to be the determination of the individual titers after the first booster vaccination and calculation of the prospective time interval to arrive at a minimum titer of 10 IU/1 and the need for a new booster vaccination.
Journal Article↗
Increased risk for hepatitis A among female day nursery workers in Belgium.
To assess the risk for hepatitis A virus (HAV) infection in an occupational group potentially at risk for faeco-oral contact with very young children, a prevalence study of total anti-HAV antibodies (IgG/IgM) was conducted among 591 female employees in day nurseries in Flanders, Belgium, and in a reference group of 560 healthy female blood donors, matched for age. Analysis was also performed on formally exposed persons (n = 413) versus blood donors (n = 560). The overall prevalence of HAV markers was 48.4% (95% CI: 44.2-52.5) in exposed day nursery personnel, compared with 42.9% (95% CI: 38.7-47.0) in blood donors. The age-specific prevalence rates showed a steeper rise from the age of 30 years among the exposed employees than among the blood donors, with significantly higher prevalences between 35 and 44 years of age. The discrepancies levelled off above 60 years of age. Standardization for parenthood using logistic regression did not affect the odds ratio. These results are in line with recent findings of a higher prevalence of HAV markers among groups of workers professionally exposed to small children. Appropriate measures for the protection of these groups should be taken.
Adult↗
Regulation of rat thyroxine-binding globulin and transthyretin: studies in thyroidectomized and hypophysectomized rats given tri-iodothyronine or/and growth hormone.
We have investigated the role of the thyroid compared with the hypophysis in the regulation of the two saturable thyroid hormone carriers of rat serum, thyroxine-binding globulin (TBG) and transthyretin (TTR). We examined, at serum and hepatic mRNA level, the responses of TBG and TTR to thyroidectomy (Tx), hypophysectomy (Hx) and replacement treatments with tri-iodothyronine (T3) or/and GH, both hormones which are depleted when the thyroid or hypophysis are removed. The studies were performed on male rats at the age of 8 weeks, when the developmentally regulated TBG becomes undetectable after its transient postnatal rise, while the nondevelopmentally regulated TTR presents its normal, age-independent level of expression. Tx-induced TBG re-expression was completely reversed by T3 replacement and unresponsive to GH replacement. TTR in the serum, on the other hand, was not affected by Tx or T3 replacement, moderately reduced by Tx in terms of the amount of mRNA, and markedly reduced by GH replacement. GH treatment, moreover, inhibited the expression of TTR in euthyroid controls. Hx, like Tx, induced TBG re-expression, an effect efficiently antagonized by T3 replacement. However, TBG synthesis was higher in Hx than in Tx rats and less effectively antagonized by T3 replacement. Most unexpectedly, GH induced a dramatic further increase in TBG synthesis, and the TBG synthesized in the GH-replaced Hx rats was entirely resistant to down-regulation by T3 replacement. TTR was markedly decreased at both serum and hepatic levels by Hx, unaffected by T3 and further decreased by GH replacement.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Structural and functional microheterogeneity of rat thyroxine-binding globulin during ontogenesis.
Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human and murine sera, is in the rat a developmentally regulated protein, showing a large surge during post-natal growth followed by virtual disappearance in adults. Here we study as a function of age, from the 19-day embryo to 60 days after birth, the structural and binding characteristics of rat TBG microheterogeneity. Serum obtained throughout development, when pre-incubated with 125I-thyroxine (T4), was shown by isoelectric focusing (IEF; pH range 4-5) to contain six labelled isoforms of TBG, with isoelectric points between 4.25 and 4.55. These isoforms differ in their sialic acid content. The relative labelling densities of the isoforms show age-related changes: in neonates, the bulk of T4 is bound to the most alkaline (least sialylated) TBG isoforms; then, with advancing age, it shifts to the most acidic isoforms. To understand whether this progressive transfer of ligand reflects developmental changes in the relative abundance of isoforms, we submitted sera from rats of different ages to crossed immunoelectrofocusing analysis. We demonstrate that the relative proportions of the TBG isoforms remain fairly constant, independent of the level of total TBG. The most acidic forms always represented the majority (approximately 50%), with the most alkaline ones only representing 15% of total TBG. Experiments based on IEF of charcoal-treated sera, supplemented or not with lipidic serum extracts, further demonstrate that the paradoxical low labelling seen in the neonates for the most abundant highly sialylated isoforms is due to inhibition of their binding abilities by liposoluble components, which are particularly concentrated in the sera at the earlier post-natal ages. These studies represent the first analysis of concentration versus binding functions of rat TBG isoforms in the physiological conditions of normal ontogeny. Our results point to an important influence for the serum environment on the binding properties of TBG isoforms. The physiological significance of such interactions remains to be clarified.
Aging↗
Sero epidemiological characteristics of hepatitis C encountered in general practice in Belgium.
A study carried out between 1982 and 1984 established by exclusion diagnosis that 35% of viral hepatitis cases registered in Belgium were due to non A, non B (NANB) viruses. Recently, a new anti-hepatitis C virus (HCV) detection test was used to analyse the sera of patients in whom NANB hepatitis was diagnosed in that study. Using this new serological test for HCV, 29% of the NANB group was found to be positive for anti-HCV. In the 1982-84 study on viral hepatitis diagnosed by general practitioners, the number of clinically recognized infections was estimated at 14,700 (+/- 2,170; confidence interval at 95%) per year. By combining these data and the results of the present study, the following estimates could be calculated: HAV (7,129 +/- 1,054/year), HBV (2,426 +/- 358/year), HCV (1,470 +/- 216/year) and non-identified hepatitis viruses (3,675 +/- 543/year).
Belgium↗
Prevalence of antibodies to hepatitis viruses in blood donors with a clinical history of hepatitis.
A comparison between the 1979, 1982 and 1989 findings indicates that the number of adults susceptible to HAV infections has increased. This fact should be given attention in view of the strongly altered travelling pattern of fairly large sections of the population. It should also be kept in mind that the group of adults born between 1951 and 1960 comprises those adults who have the most frequent contacts with younger children being at the greatest risk of acquiring HAV infection.
Adult↗
Chronic infusion of TNF-alpha reduces plasma T4 binding without affecting pituitary-thyroid activity in rats.
In the present study the effects of continuous administration of tumor necrosis factor-alpha (TNF-alpha), in a dose not affecting body temperature and food intake, on pituitary-thyroid function of rats were investigated. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps that continuously delivered recombinant human TNF-alpha (8.0 micrograms/day ip) or saline for 7 days. Infusion of TNF-alpha resulted in a significant decrease of plasma total thyroxine (T4) levels during days 2-5 of infusion as compared with the levels in saline-infused rats. This suppression of plasma T4 concentrations was caused by a decreased binding of T4 in plasma, as indicated by an increased percentage of free T4. TNF-alpha infusion did not significantly affect free T4 levels in plasma nor basal and thyrotropin-releasing hormone-stimulated TSH levels. The decreased binding of T4 was, at least partially, caused by a reduction of T4-binding prealbumin (TBPA) levels in plasma, which were significantly reduced during the first 3 days of TNF-alpha infusion. Plasma levels of free fatty acids were not affected by TNF-alpha. TNF-alpha treatment did not influence the plasma 3,5,3'-triiodothyronine (T3)-to-T4 ratio nor hepatic 5'-deiodinase activity. Plasma reverse T3 levels remained undetectable both in control and TNF-alpha-treated rats. Taken together, our findings indicate that chronic infusion of rats with TNF-alpha in a subpyrogenic and subanorectic dose induces a transient decrease of plasma T4 binding without affecting pituitary-thyroid activity and peripheral thyroid hormone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Re-expression of thyroxine-binding globulin in post-weaning rats during protein or energy malnutrition.
Thyroxine-binding globulin, the highest affinity thyroid hormone binder of rat serum, was studied during 28 days of dietary protein restriction (6% protein vs 18% protein in isocaloric control diet) or energy restriction (60% intake of control diet). Studies were performed on male rats aged four weeks at the beginning of experiments: the animals had reached the ontogenic stage when the thyroxine-binding globulin had declined, after its high postnatal surge, to undetectable levels. Short-term administration (seven days) of one or the other restricted diet similarly induced resynthesis of the protein. Its serum concentrations reached 26-46% of those measured in eight-day pups (peak of the neonatal surge) and its liver mRNAs showed corresponding enhanced signals. Serum T4 binding activities were increased, although concomitantly transthyretin, second specific T4 carrier of the rat serum, decreased markedly (65-75% of controls) in response to the dietary restrictions. Longer-term diet administration (14 or 28 days) resulted in the further increase of the thyroxine-binding globulin in the protein-restricted rats, in contrast to its decline and eventual disappearance in the energy-restricted animals. Protein restriction was associated with increased total and free T3 serum concentrations, in contrast to energy restriction which little affected these parameters. These studies reveal rat thyroxine-binding globulin as a positive (increasing), highly sensitive reactant of malnutrition, able to discriminate between energy deficiency and composition dysequilibrium of diets. They suggest that up-regulation of its synthesis in the two dietary models involves differential mechanisms.
Animals↗
The pituitary control of rat thyroxine binding globulin.
Thyroxine-binding globulin (TBG) is in the rat a developmentally regulated protein, actively synthesized in postnatal developing pups and in aging animals, but undetectable in adults. Experimental depletion of thyroid hormones (TH) in adults by thyroidectomy (Tx) or by hypophysectomy (Hx) results in marked reexpression of TBG synthesis. T3 replacement in both cases antagonizes this effect, though only moderately in Hx rats. These observations point to a regulatory pathway of TBG synthesis common to TX and Hx rats, characterized by an inverse relationship between TBG and TH levels. However, along with this thyroid-dependent TBG regulation, important differences between Tx and Hx rats are evidenced, pointing to specific pituitary factors of TBG control. The most striking difference concerns the effect of growth hormone (GH) replacement: the TBG of Tx rats is not affected, in contrast to that of Hx rats which is further increased by GH administration. The TBG response of the GH-treated Hx rats, which is strongly resistant to inhibition by T3, might involve deshomeostasis of GH-controlled functions not necessarily linked to the thyroid, e.g. the pancreatic functions regulating carbohydrate or lipid metabolism. In the light of these studies, it may be envisaged that the high surge of rat TBG during postnatal development involves a transient sensitivity of the TBG gene to stimulation by endogenous GH, and that this sensitivity lasts until functional maturity of the hypothalamic-pituitary-thyroid axis has been achieved.
Animals↗