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Biomedical subjects

Y Horsmans

Publications and source records attributed to Y Horsmans.

At least 91 records · Page 5Linked to original sources
PubMed1996

Relationship between mephenytoin, phenytoin and tolbutamide hydroxylations in healthy African subjects.

Mephenytoin, phenytoin and tolbutamide are metabolised by the cytochrome P-450 (CYP) 2C family. Recently, it has been shown that phenytoin and tolbutamide are metabolised by CYP2C9/10 whereas mephenytoin is metabolised by CYP2C19. Until now, in vivo studies were only undertaken in Caucasian subjects and showed a strong relationship between phenytoin and tolbutamide metabolism but no significant relationship between the two drug metabolisms and that of mephenytoin. The metabolism of the three drugs was investigated in eight black Africans by urinary analysis. In this ethnic group, a strong relationship was found between phenytoin and tolbutamide oxidations (rs = -0.83, P = 0.01). On the other hand, no significant relationship was found between mephentoin oxidation and phenytoin or tolbutamide oxidations (rs = 0.31 and rs = -0.33, respectively). This study suggests that, in black Africans, phenytoin and tolbutamide but not mephenytoin are also hydroxylated by similar CYP enzyme(s).

Adult↗
PubMed1996

Clinical pharmacokinetics of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of cholesterol synthesis. HMG-CoA reductase inhibitors are potent reversible inhibitors of this enzyme, which act by competing for the substrate HMG-CoA. This review is mainly devoted to the 4 main HMG-CoA reductase inhibitors used today: lovastatin, simvastatin, pravastatin and fluvastatin. Depending upon the dosage, these drugs are able to reduce plasma cholesterol levels by more than 40%. After absorption, each undergoes extensive hepatic first-pass metabolism. Up to 5 primary metabolites are formed, some of which are active inhibitors. The elimination half-lives vary from 0.5 to 3.5 hours and excretion is mainly via the faeces. A limited number of drug interactions has been reported. Increases in liver enzymes and muscle creatine kinase activity are among the most severe adverse effects. These powerful drugs should be reserved for patients with high plasma cholesterol levels and/or those with cardiovascular disease. New therapeutic approaches to atherosclerosis are currently under investigation. HMG-CoA reductase inhibitors are the cornerstone of this research.

Aged↗
PubMed1995

Eosinophilic gastroenteritis presenting with colitis and cholangitis.

Eosinophilic gastroenteritis (EG) is a rare condition that most commonly affects the stomach and intestine. Large bowel involvement has also been described. We report a case of EG presenting with colitis and cholangitis. This is the first case of associated cholangitis demonstrated radiologically and histologically. Simultaneous biliary and gastrointestinal tract involvement suggest a common link between EG and hypereosinophilic syndrome (HES). However, HES requires high peripheral hypereosinophilia and several organs including gastrointestinal tract, lung, heart, infiltrated with eosinophils. The patient's condition improved with corticosteroids.

Adult↗
PubMed1995

Liver injury related to amoxycillin-clavulanic acid: interlobular bile-duct lesions and extrahepatic manifestations.

We report eight cases of liver injury related to amoxycillin-clavulanate. Liver biopsy performed in seven patients revealed varying degrees of injury to interlobular bile ducts in all cases. Lesions included irregularity of the nuclei, vacuolization of the cytoplasm, lymphocytic infiltration, destruction and endothelialization of the bile duct epithelium. Ductopenia was not observed. In two patients liver injury was accompanied by prominent extrahepatic manifestations (acute interstitial nephritis in one and acute lacrimal gland inflammation and sialadenitis with prolonged xerostomia in the other). We conclude that interlobular bile-duct lesions of varying severity are a common feature in liver injury related to amoxycillin-clavulanate. Side effects of the drug include acute interstitial nephritis and sialadenitis.

Aged↗
PubMed1995

Precore mutant chronic hepatitis B in an autochthonous Belgian population: a study of ten patients.

The mode of contamination, presentation, clinical evolution and liver histology of 10 native Belgian patients with chronic hepatitis B likely due to a peculiar viral strain, the so called precore mutant hepatitis B virus were reviewed. This viral strain first described in Southern European regions is characterized by a mutation of a single base change at nucleotide 1896 in the preterminal codon of the precore region which creates a stop codon that prevents the production of HBeAg. In this setting, abnormal liver biochemistry and active viral replication as evidenced by HBV DNA positivity often coincides with a serological profile similar to that observed in healthy HBsAg carriers. Our data indicate that chronic hepatitis related to such a viral strain may be observed in a native Belgian population. This unusual presentation of chronic hepatitis B should thus be kept in mind when interpreting atypical sero-biochemical features, evaluating the risk of infectivity and the potential benefit of antiviral therapy.

Adolescent↗
PubMed1995

Long-term favourable outcome of portal hypertension complicating primary systemic amyloidosis.

An unusual case of systemic amyloidosis complicated by portal hypertension is reported. In this condition, portal hypertension is a rare event associated with poor prognosis. In our patient, severe presymptomatic sinusoidal portal hypertension was demonstrated by hepatic vein catheterization and coincided with abundant perisinusoidal amyloid infiltration. Despite these features and the absence of objective response to 20 courses of melphalan and prednisone, the patient was still in good clinical condition 4 years after initial diagnosis. This observation suggests that in primary amyloidosis, the incidence of sinusoidal portal hypertension might be underestimated and also that it may be associated with a relatively good prognosis.

Amyloidosis↗
PubMed1995

Microsomal function in hepatitis B surface antigen healthy carriers: assessment of cytochrome P450 1A2 activity by the 14C-caffeine breath test.

The hepatitis B surface antigen (HBsAg) carrier state is associated with changes in hepatocellular function involving the cytochrome P450 (CYP) system. Among this system, CYP1A2 enzyme plays an important role in chemical carcinogenesis and in the metabolism of several drugs. We have thus investigated CYP1A2 function using two 14C-caffeine breath tests (3-methyl-14C; C3BT and 7-methyl-14C caffeine; C7BT) in 12 HBsAg healthy carriers and 8 healthy volunteers matched for 14C-aminopyrine breath test values. HBsAg carriers exhibited lower C3- and C7BT values than normal controls. This difference, however, did not reach statistical significance except for C7BT values normalised for aminopyrine breath test values. Our data thus do not support the association between viral presence and CYP1A2 dysfunction.

Adult↗
PubMed1995

Pharmacokinetic-pharmacodynamic relationships of H1-antihistamines.

Histamine H1-receptor antagonists are reversible, competitive inhibitors of the actions of histamine, a critical mediator in the pathophysiology of the allergic response. This review is mainly devoted to second generation antihistamines that possess a low sedation potential compared with first generation compounds. The pharmacokinetic and pharmacodynamic data of 10 compounds have been updated. Some values are lacking for drugs under development, but also for older antihistamines. Thereafter, pharmacokinetic-pharmacodynamic relationships are reported from published or original documents. A linear pharmacokinetic-pharmacodynamic relationship has been found for acrivastine, astemizole, cetirizine, ebastine and terfenadine, whereas nonlinear relationships have been calculated for ebastine (in the dog), levocabastine, mizolastine, noberastine and terfenadine. It must be concluded that this type of approach for therapeutic optimisation is very fruitful and may enable large numbers of clinical studies to be avoided. Trends for the future include: (i) in vitro binding studies with the human H1-receptor obtained by molecular biology; (ii) the characterisation of the cytochromes P450 responsible for the biotransformation of antihistamine; (iii) the calculation of the pharmacokinetic-pharmacodynamic relationship in healthy individuals; and (iv) prospective effect-controlled clinical studies.

Histamine H1 Antagonists↗