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J van Hattum

Publications and source records attributed to J van Hattum.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effect of liver impairment on the pharmacokinetics of tolcapone and its metabolites.

OBJECTIVE: To assess the effect of liver impairment on the pharmacokinetics of tolcapone and to derive appropriate dose recommendations for patients with this disease who are undergoing treatment for Parkinson's disease. STUDY DESIGN: In an open, two-way crossover study, 16 patients with moderate liver disease (eight with cirrhotic and eight with noncirrhotic liver disease) and eight healthy subjects received an oral dose of 200 mg tolcapone and an intravenous dose of 50 mg tolcapone on separate occasions. The concentrations of total and unbound tolcapone and its three major metabolites (tolcapone glucuronide, carboxylic acid, and 3-O-methyl metabolite) were assessed in plasma and urine. RESULTS: On the basis of total drug concentration, the differences in tolcapone pharmacokinetics between the groups were small. However, lower clearance and volume of distribution of unbound drug were found among patients with cirrhosis than among control subjects. Plasma concentration of the pharmacologically inactive glucuronide metabolite was increased among patients with cirrhosis. CONCLUSIONS: Half of the recommended dosage of tolcapone should be administered to patients with cirrhosis of the liver to maintain the target steady-state concentration of unbound drug and to avoid accumulation of tolcapone glucuronide. Our data did not indicate a requirement for dosage adjustment in the presence of moderate chronic hepatitis.

Adult↗
PubMed1998

Tolerance and antiviral effects of high-dose interferon-alpha B/D in patients with chronic hepatitis B.

A novel recombinant interferon-alpha B/D hybrid was applied to assess tolerability, antiviral effect, and biological activity in chronic hepatitis B. The study was designed as an open nonrandomized trial. Treatment comprised a two-week run-in phase with 16 MU three times a week followed by 14 weeks with 64 MU three times a week (or 48 MU if toxicity occurred with 64 MU). Total follow-up was 36 weeks. Nineteen patients were included; three discontinued treatment during the run-in with 16 MU. Fourteen of 16 patients had 14 weeks of treatment with > or = 32 MU three times a week. Fourteen dose reductions were necessary in nine patients. The adverse experience profile was similar to other interferon-alphas. HBV-DNA decreased using all doses studied. HBV-DNA became undetectable in five patients, two of whom had HBeAg seroconversion. No HBsAg seroconversion was observed. It is concluded that interferon-alpha B/D is well tolerated in high doses. The anti-viral effect starts at at least 16 MU three times a week.

Adult↗
PubMed1997

Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. Moreover, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype.

Cholestasis, Intrahepatic↗
PubMed1997

Immunogenicity of two versus three injections of inactivated hepatitis A vaccine in adults.

AIM: To investigate the immunogenicity of two versus three injections of inactivated strain CR326F-derived hepatitis A vaccine in healthy adults. METHODS: Healthy adult volunteers (n = 105) at Utrecht University Hospital, The Netherlands, were randomly assigned to receive intramuscular injections (deltoid muscle) of 25 Units (U) at 0 and 6 months (group A, n = 53), or at 0, 2 and 6 months (group B, n = 52). Blood was drawn before and at various time points after vaccination for determination of serum antibody to hepatitis A (anti-HAV). RESULTS: One month after the first injection, the seroconversion rates (> or = 10 mIU/ml, international units) were 88% for group A and 90% for group B. Only 2/ 103 (one in each group) showed IgM anti-HAV. One month after the second injection, seroconversion rates were 100% in both groups. At months 3, 6 and 7, anti-HAV geometric mean titers were significantly different because of the different vaccination schedules, but they were similar at months 1, 2 and 12. The anti-HAV geometric mean titer increase after the second injection was higher when the interval between the two doses was of longer duration. Anti-HAV titers of females were significantly higher than those of males and vaccinees < or = 30 years had higher titers than those > 30 years. CONCLUSIONS: Two 25 U doses of the vaccine investigated given at 0 and 6 months, induce adequate anti-HAV titers in all adult healthy vaccinees and are as immunogenic as three doses given at 0, 2 and 6 months.

Adolescent↗
PubMed1996

[Hepatitis C, awakening of a giant].

Cloning of the hepatitis C virus (HCV) was reported in 1989. By now, the entire viral genome has been sequence. It consists of a single-stranded positive RNA, with relationship to the Flaviviridae. The envelope region shows considerable variability. 6 major genotypes have been described. HCV is transmitted via the parenteral route, mainly blood, rarely by sexual contact. Hepatitis C occurs worldwide and is found in 0.01 to 1.5% of blood donors. The immune response is unable to clear the virus in 80% of infected subjects, probably because of the hypervariability. In the acute phase the hepatitis has only mild symptoms and the chronic hepatitis usually also runs a mild course. After many years liver cirrhosis may develop in 20% of cases; in these subjects there is a high incidence of hepatocellular carcinoma. The diagnosis can be made by detection of anti-HCV antibodies in the blood and an immunoblot confirmation test. The viral genome can be detected by the HCV-RNA (PCR) test. Immunisation against hepatitis C is not possible yet. Therapy with interferon results in an initial response in 45% and a sustained response in < 20% of the patients. Interferon therapy reduces the incidence of hepatocellular carcinoma.

Hepacivirus↗
PubMed1996

Modulation of immune response to rDNA hepatitis B vaccination by psychological stress.

In a previous study it was shown that antibody formation after vaccination with a low-dose recombinant DNA (rDNA) hepatitis B vaccine was negatively influenced by psychological stress. The present study was designed to assess whether the same inverse relation between HBs-antibody levels and psychological stress could be observed, while administering the standard, and thus higher, dose of vaccine. Volunteers (n = 68) scoring extremely low or high on a combination of questionnaires measuring daily problems and psychoneurotic symptoms were selected for participation. Antibody levels were determined 2, 6, and 7 months after the first vaccination. Questionnaires were completed before entering the study and at month 6. In contrast to the previous study, psychological stress was not found to be related to the antibody levels at any timepoint. These results suggest that, under certain conditions, stress-induced immunomodulation in vivo might be dependent on antigen dose.

Adolescent↗
PubMed1996

Single or multiple dose ursodeoxycholic acid for cholestatic liver disease: biliary enrichment and biochemical response.

BACKGROUND: Ursodeoxycholic acid (UDCA) improves liver biochemistry in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Since UDCA acts partly by reducing the intestinal absorption of hydrophobic endogenous bile salts and is poorly absorbed from the intestine, a multiple dose regimen has been advocated. Single dose treatment, on the other hand, may improve compliance. AIM: The effects of a single or multiple dose regimen on liver enzymes and serum and biliary bile salts composition were evaluated. METHODS: Twenty-seven patients (19 PSC, 8 PBC), most with early stage disease, received UDCA (10 mg kg-1 day-1) in a single dose at bed time (n = 13) or in three divided gifts with meals (n = 14) over 3 months. Five patients had both treatment regimens in random order with a 1-month wash-out period in between. RESULTS: Liver biochemistry equally improved in both groups. Biliary enrichment (% UDCA of total bile salts, mean +/- SEM) was 40.1 +/- 2.4 in the single dose group vs 40.8 +/- 2.8 in the multiple dose group (p = NS) and was positively correlated with biochemical improvement (AP: r = 0.47, p = 0.02; GGT: r = 0.58, p = 0.002; ASAT: r = 0.67, p = 0.002; ALAT: r = 0.52, p = 0.01). Biochemical improvement was not correlated with the concentration or %UDCA in serum. Patients participating in the cross-over design had comparable biochemical response and biliary %UDCA during both regimens. CONCLUSION: Single and multiple dose UDCA have similar effects on liver biochemistry and biliary enrichment in cholestatic liver disease. Biochemical improvement appears to be related to biliary (but not serum) enrichment with UDCA.

Adult↗
PubMed1995

Exogenous protoporphyrin inhibits Hep G2 cell proliferation, increases the intracellular hydrogen peroxide concentration and causes ultrastructural alterations.

Ultrastructural hepatocellular abnormalities in early stages of erythropoietic protoporphyria lead to hepatobiliary changes that cause overt liver disease in 5-10% of patients, not infrequently progressing to fulminant hepatic failure. This cannot be attributed solely to protoporphyrin crystal deposition in the liver. Hepatic redox systems have therefore been postulated as an equivalent for the photoreaction of protoporphyrin. We studied the dark effects of protoporphyrin and hematoporphyrin on HL60 and Hep G2 cells. Cell proliferation and intracellular H2O2 concentrations were assessed and related to the ultrastructural morphology. The incubation with protoporphyrin and hematoporphyrin resulted in a dose- and time-dependent inhibition of proliferation indices of Hep G2 cells. Flow cytometric analyses of intracellular H2O2 concentrations demonstrated a dose-dependent increase in both cell lines upon incubation with protoporphyrin. Hep G2 cells displayed ultrastructural alteration of the endoplasmatic reticulum and plasma membranes. Also 'cell blebbing' occurred. We conclude that exogenous protoporphyrin increases the intracellular H2O2 concentration and exerts a cytotoxic dark effect. This may contribute to the liver injury observed in erythropoietic protoporphyria.

Carcinoma, Hepatocellular↗
PubMed1995

Postprandial reversal of the portal venous flow in a patient with liver cirrhosis.

The case of a 61-year-old man with alcoholic liver cirrhosis and a hepatocellular carcinoma is presented. He was examined with duplex Doppler before and after a meal. In the fasting state a sluggish hepatopetal portal venous flow was found. After the meal a pendulating flow and then hepatofugal flow were found. The magnitude and direction of flow alternated synchronously with the action of the heart, suggesting a significant role for the hepatic artery in the postprandial reversal of portal venous flow. One year after this examination the patient died from the complications of decompensated cirrhosis and liver failure. At autopsy a large hepatocellular carcinoma was detected.

Carcinoma, Hepatocellular↗
PubMed1995

[Hepatitis B vaccine: simple and effective].

All workers in the dental office are at risk for hepatitis B infection. Hepatitis B has a chronic course in 10% of cases and may lead to liver cirrhosis, liver cancer and death. According to European law, approved in April 1994, employees have to be protected against biological agents in their working environment. The employer has to offer vaccination, free of costs, in case of risk for infection with hepatitis B. The vaccination scheme consists of three doses. Vaccination is successful if the antibody-titer (anti-HBs) is higher than 100 IU/L. Excellent immune memory is then formed, giving protection for more than 10 years. Testing of anti-HBs or revaccination is not necessary during that period of time. Up to three additional vaccinations should be given if the anti-HBs titer remains below 100 IU/L; if the anti-HBs remains lower than 10 IU/L, there is no protection against hepatitis B. Someone with a titer between 10 and 100 IU/L is protected (if the titer was measured twice), but it is still unknown how long protection will last. Revaccination is recommended if the titer falls below 10 IU/L at any time. The policy after a needle-stick accident with HBsAg positive material is determined by the question whether a person has ever had an adequate reaction to hepatitis B vaccination (i.e. anti-HBs > 100 IU/L). If this is the case, no action is needed. If not, passive-active vaccination has to be given, by hepatitis B immunoglobulin (HBIg) and hepatitis B vaccination.

Dentistry↗
PubMed1995

31P magnetic resonance spectroscopy of the liver: correlation with standardized serum, clinical, and histological changes in diffuse liver disease.

The goal of this study was to analyze the possibilities of 31P MR spectroscopy to detect abnormal hepatic histological changes in patients with diffuse liver disease. 31P MR spectroscopy was performed, on a 1.5 T whole-body spectrometer using an image guided localization technique (ISIS), on 38 patients with various diffuse liver diseases, who all underwent histological and serum analysis, and 22 healthy volunteers. Phosphomonoester expressed as a fraction of total phosphorus (PME/P) showed a correlation with abnormal serum aspartate transaminase (AST), histological intralobular degeneration/focal necrosis, portal inflammation, and piecemeal necrosis. We found a lower correlation for PME/P with fibrosis. It was not possible to differentiate between fibrosis and cirrhosis. In summary, 31P MR spectroscopy is a technique to detect intralobular degeneration, inflammation and necrosis and to a less extent fibrosis. No diagnostic value was found with respect to steatosis and cholangitis. Furthermore, 31P MR spectroscopy is a poor method for classifying patients into diagnostic categories.

Adolescent↗
PubMed1994

Copper, zinc-superoxide dismutase and hydrogen peroxide: a hydroxyl radical generating system.

Because superoxide (O2-.) is a mediator of inflammation, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) has been employed as an anti-inflammatory compound. However, Cu,Zn-SOD can increase intra- and extracellular H2O2. This may react with the Cu atom of SOD in a Fenton-type reaction producing the hydroxyl radical (.OH). With a non-physiological concentration of H2O2 (0.8 mmol/l) to stimulate chemiluminescence (CL) at a level < 2 mV, it was observed that the addition of Cu,Zn-SOD (100 micrograms/ml) yielded an increase of 204.7 +/- 78.2 mV (P < 0.05). This increase in CL depended on the concentrations of H2O2 and Cu,Zn-SOD and was only seen with luminol (reacts with O2-. and .OH) but not with lucigenin (reacts with O2-.). No CL was observed when Cu,Zn-SOD was heat inactivated, or when Mn-SOD was used. Dissipators of H2O2, copper chelators and .OH scavengers attenuated this CL. In electron paramagnetic resonance, with the use of the spin-trap dimethylpyrroline-N-oxide (DMPO), it was demonstrated that, in the reaction between H2O2 and Cu,Zn-SOD, .OH was generated. The oxidation of keto-methylthiobutyric acid (KMB) to ethylene, assessed by gas chromatography, demonstrated that H2O2/Cu,Zn-SOD-generated .OH can react with KMB and not only with the SOD molecule itself. We conclude that H2O2 reduces SOD-bound Cu2+ to Cu1+ which, in reaction with H2O2 catalyses its reduction to OH. Whether this 'pro-inflammatory' reaction occurs in vivo remains to be established.

Acridines↗
PubMed1994

Blunted postprandial reaction of portal venous flow in chronic liver disease, assessed with duplex Doppler: significance for prognosis.

To establish the effects of a meal on portal venous flow and the prognostic value of this parameter, 46 patients with chronic liver disease and 28 healthy subjects were examined with duplex Doppler before and after a meal. The measurements were completed in 40 patients and 21 healthy subjects. Postprandial portal venous diameter, blood velocity and quantitative flow were measured for 60 min. Mean baseline values were: 11.4 mm versus 10.2 mm (p = 0.019), 10.8 cm.s-1 versus 13.4 cm.s-1 (p = 0.015) and 668 ml.min-1 versus 646 ml.min-1 (p = 0.7) respectively. Spleen size was 15.0 cm versus 10.6 cm (p = 0.0001) respectively. Postprandial diameter, velocity and flow increased significantly in patients and controls (p = 0.0001 for all). Mean postprandial flow could best be described by a polynomial equation with a parabolic curve. Patients' curves were more blunted than controls', with significantly different regression constants (p = 0.025 and p = 0.029). All subjects were followed up for survival and variceal haemorrhage. The mean follow-up time was 47 months. Early maximum postprandial velocity (p = 0.041) and large spleen size (p = 0.002) were significantly related to an unfavourable prognosis for survival. Early maximum velocity was also related to increased variceal haemorrhage. This study shows that postprandial portal venous flow is blunted in patients with chronic liver disease. Postprandial portal venous flow may have prognostic significance.

Adolescent↗
PubMed1994

Portal venous flow and follow-up in patients with liver disease and healthy subjects. Assessment with duplex Doppler.

The evolution of portal venous flow in non-end-stage chronic liver disease with portal hypertension was assessed in 59 patients and compared with that in 55 control subjects and by means of duplex Doppler measurements by a single observer. All patients were prospectively followed up, and a repeated measurement was performed in a subgroup of 23 patients. The mean (+/- SD) portal venous diameter and velocity of patients versus controls were 11.2 (+/- 2.0) mm versus 10.1 (+/- 1.4) mm (p < 0.0005) and 11.0 (+/- 4.2) cm/sec versus 13.9 (+/- 4.1) cm/sec (p < 0.0005). The portal venous flow did not differ: 671 (+/- 291) ml/min versus 652 (+/- 203) ml/min. Diagnosis, Child class, and grade of varices did not influence the portal flow. Patients were followed up during a median (+/- SD) time of 47 (+/- 17) months. Nineteen (32%) patients died, and 14 (23%) had a variceal hemorrhage. Survival and hemorrhage were not correlated with the portal venous flow. Subsequent measurements in 23 patients showed a significant decrease in portal venous flow in 5 patients who died during follow-up. This was not found in the patients who survived. It is concluded that portal venous flow in chronic liver disease with portal hypertension is stable for a long time in the evolution of chronic liver disease. The existence of a 'portostat' is postulated. Only in the terminal stage of liver disease can a reduction of the portal venous flow be detected.

Adult↗