Sensitive assay for midazolam and its metabolite 1'-hydroxymidazolam in human plasma by capillary high-performance liquid chromatography.

A sensitive high-performance liquid chromatographic method is described for the quantification of midazolam and 1'-hydroxymidazolam in human plasma. Sample (1 ml plasma) preparation involved a simple solvent extraction step with a recovery of approximately 90% for both compounds. An aliquot of the dissolved residue was injected onto a 3 microm capillary C18 column (150 mm x 0.

Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat content in animal models of steatosis in the absence of inflammation.

Background/aim: Fatty liver has been associated with an increased risk of primary graft non-function and drug toxicity. However, these effects have been observed mainly in fatty liver with inflammation, a situation characterized by an overall reduction in cytochrome P-450 (CYP)-dependent activities as well as a contrasting increase in CYP2E1 activity. Our aim was to examine the impact of liver-fat accumulation on CYP in two animal models of fatty liver without necroinflammation.

Acute lobular hepatitis as the first manifestation of recurrent autoimmune hepatitis after orthotopic liver transplantation.

Recurrence of autoimmune hepatitis after orthotopic liver transplantation and after reduction in immunosuppressive treatment is reported in a 43-year-old man. Diagnosis was based on biological, serological and morphological data, as well as on a complete biological recovery following steroid resumption. Recurrence was observed only 4 months after transplantation, when an abrupt increase in liver function tests was observed in association with a mainly lobular hepatitis in liver biopsy.

Inflammatory pseudotumor of the liver: MRI with mangafodipir trisodium.

Inflammatory pseudotumor of the liver is a rare benign mass that is often misdiagnosed as hepatocellular carcinoma at preoperative imaging. We report a case of inflammatory pseudotumor of the liver with special emphasis on the appearance at MRI after administration of mangafodipir trisodium. On T1-weighted images the lesion was slightly hypointense relative to the liver, and on T2-weighted images it was isointense with a hyperintense capsule.

Phenytoin hydroxylation in a healthy Caucasian population: bimodal distribution of hydroxyphenytoin urinary excretion.

The phenytoin hydroxylation index was studied in 122 unrelated Caucasian volunteers. Following a 100 mg oral dose of phenytoin, phenytoin and hydroxyphenytoin were measured in urine from 0-32 hr after administration. As phenytoin was not found in all urine collections, a phenytoin hydroxylation index was expressed as follows: Phenytoin hydroxylation index = amount of phenytoin administered/0-32 hr urinary output of hydroxyphenytoin.

The monoethylglycinexylidide test does not correctly evaluate lidocaine metabolism after ischemic liver injury in the rat.

Although the monoethylglycinexylidide (MEGX) test defined as a single determination of MEGX plasma concentration after lidocaine injection has been proposed as a liver function test, some discrepancies appeared in assessing the quality of liver donor for transplantation as well as the severity of liver disease. The present study used a severe ischemia-reperfusion liver injury (IRI) in rat to evaluate the various factors able to influence the level of MEGX. The metabolism of lidocaine was studied on microsomes isolated from intact rats and from rats submitted to this liver injury.

14C-Propoxyphene demethylation in the rat. An example of differences between liver and intestinal drug-presystemic metabolism.

Presystemic metabolism is believed to occur mainly in the liver with some minor intestinal participation. The aim of this study was to investigate the respective part of each of these two organs in the metabolism of the analgesic d-propoxyphene (DP). Pharmacological doses of DP were given in the duodenum (ID), the portal vein (IP), and the femoral vein (IV) of male Wistar rats.

Hepatobiliary cystadenocarcinoma without ovarian stroma and normal CA 19-9 levels. Unusually prolonged evolution.

Hepatobiliary cystadenoma and cystadenocarcinoma are rare tumors of the liver. The differential diagnosis of cystadenoma includes other cystic neoplasms, nonneoplastic cysts, and even on some occasions parasitic liver involvement. It has been suggested that elevated serum level of the tumor marker CA 19-9 may be of value in distinguishing between cystadenoma with ovarian stroma and hydatid disease.

Severe radiation-induced liver disease following localized radiation therapy for biliopancreatic carcinoma: activation of hepatic stellate cells as an early event.

Radiation-induced liver disease is recorded as a form of veno-occlusive disease. Its pathogenesis remains unclear even if the initial injury likely occurs in the endothelial cells of central veins. The aim of our study was to investigate liver morphological features in relation to alpha-isoform of smooth muscle actin expression in hepatic stellate cells in six patients treated by localized radiotherapy on the biliopancreatic area.

Transjugular liver biopsy. An experience based on 500 procedures.

We report our experience based on 500 transjugular liver biopsies, a safe procedure even in high risk patients. Transjugular liver biopsies represents one third of all liver biopsies performed in our Hepato-Gastroenterology units. Liver specimen was adequate to evaluate liver architecture in 87.

Adult polycystic liver disease: is fenestration the most adequate operation for long-term management?

Objective: The aim of this study was to evaluate the immediate and long-term results in a retrospective series of patients with highly symptomatic adult polycystic liver disease (APLD) treated by extensive fenestration techniques. A classification of APLD was developed as a stratification scheme to help surgeons conceptualize which operation to offer to patients with APLD.

Summary Background Data: Treatment options for APLD remain controversial, with partisans of fenestration techniques or combined liver resection-fenestration.

Detection and segmental location of malignant hepatic tumors: comparison of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging.

Objective: The aim of our prospective study was to compare the values of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging for the detection and segmental location of malignant hepatic tumors.

Subjects And Methods: Eighteen patients underwent ferumoxides-enhanced T2 weighted spin-echo and steady-state gradient-echo imaging before surgery. Intraoperative sonography was used as the reference examination and showed 28 malignant tumors involving 39 of the 144 hepatic segments.

Lactulose improves psychometric testing in cirrhotic patients with subclinical encephalopathy.

Background: Therapeutic trials suggest that lactulose is an effective treatment of acute and chronic encephalopathy in cirrhotic patients.

Aim And Methods: As it is likely that portal-systemic shunting and hepatocellular dysfunction are associated with some degree of neurological dysfunction, 14 patients with cirrhosis and documented portal-systemic shunting, but without detectable encephalopathy, were randomized to treatment with either lactulose 20 g t.d.

Georges Brohee Prize 1996. Major cytochrome P-450 families: implications in health and liver diseases.

Cytochromes P-450 are a superfamily of hemoproteins which represent the main pathway for drug and chemical oxidation. This superfamily is divided into families, subfamilies and/or single enzymes. The majority of P-450s involved in drug metabolism appear to belong to three distinct families termed CYP1, CYP2 and CYP3.

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.

Double common bile duct with ectopic drainage of the left lobe into the stomach. Case report and review of the literature.

A peculiar abnormal biliary tract consisting in a double common bile duct, one with a normal drainage into the duodenum and the other providing from the left lobe with an ectopic drainage into the stomach is described. For the first time, this anomaly was discovered by endoscopic retrograde cholangiopancreatography (E.R.

Serum and cystic fluid CA 19-9 determinations as a diagnostic help in liver cysts of uncertain nature.

The distinction between hepatobiliary cystadenoma or cystadenocarcinoma and simple hepatic cyst complicated by intracystic hemorrhage may prove difficult to determine on the sole basis of clinical and radiological features because of the presence of intracystic structures and septations well-demonstrated by ultrasound examination in both situations. We investigated four patients with various types of hepatic cysts, in whom diagnostic difficulties led to further investigations. In this small group, CA 19-9 serum levels were abnormal only in the two patients with cystadenoma or cystadenocarcinoma.

Pharmacodynamic activity of lipoprotein lipase and hepatic lipase, and pharmacokinetic parameters measured in normolipidaemic subjects receiving ciprofibrate (100 or 200 mg/day) or micronised fenofibrate (200 mg/day) therapy for 23 days.

The activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were investigated after 23 days of ciprofibrate (100 mg or 200 mg) therapy or fenofibrate (200 mg) therapy. In a double-blind, double-placebo, cross-over study, three groups of six healthy volunteers received either 100 mg ciprofibrate/day followed by 200 mg fenofibrate 'high bioavailability' (HB)/day, or vice versa (group A), 200 mg ciprofibrate HB/day followed by 200 mg fenofibrate HB/day, or vice versa (group B), or 100 mg ciprofibrate/day followed by 200 mg ciprofibrate/day, or vice versa (group C). Fasting plasma lipid levels and safety parameters were evaluated before and after treatment.

Fast determination of low-level cytochrome P-450 1A1 activity by high-performance liquid chromatography with fluorescence or visible absorbance detection.

A method to determine the activity of the cytochrome P-450 1A1 enzyme, by measuring 7-ethoxyresorufin-O-deethylase (EROD) activity using high-performance liquid chromatography (HPLC) with fluorescence or with visible absorbance detection of resorufin, is described. The lowest quantifiable activity (0.2 pmol/mg min) is obtained by incubation of 0.

Fenoterol-induced hepatitis in a pregnant woman: a case report.

The case of a pregnant woman in whom hepatitis developed after administration of high-dose fenoterol during the third trimester of a second pregnancy is described.