Modulation of hepatocyte function in an immortalized human hepatocyte cell line following exposure to liver-failure plasma.

For hepatocytes to function effectively in a bioartificial liver device, maintained function in the milieu of plasma from patients with liver failure will be required. We have investigated the effect of plasma obtained at plasmapheresis from patients with acute liver failure on the performance of the human hepatocyte cell line HHY41 in liver-failure plasma, normal plasma, and culture medium. Cytotoxicity of plasma, DNA synthesis by thymidine incorporation, oxidative status, and cytochrome P450 functions were assayed after a 16 h culture with normal plasma, liver-failure plasma, or culture medium.

Monitoring extracellular concentrations of lactate, glutamate, and glycerol by in vivo microdialysis in the brain during liver transplantation in acute liver failure.

Swelling of cerebral glial cells is a characteristic complication in patients with acute liver failure (ALF). This astrocyte edema may result in high intracranial pressure (ICP) and brain herniation before or during liver transplantation. Metabolic alterations responsible for the development of high ICP in patients with ALF are not fully understood.

Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure.

The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant hepatic failure (FHF). Sixteen patients with FHF were studied and compared to six patients with cirrhosis of the liver. CBF was measured by the (133)Xe wash-out technique.

Hemodynamic changes during a single treatment with the molecular adsorbents recirculating system in patients with acute-on-chronic liver failure.

The aim of this pilot study is to evaluate the circulatory safety of treatment with the molecular adsorbents recirculating system (MARS) by determining the effect on systemic hemodynamics of a single MARS treatment in patients with acute-on-chronic liver failure (AOCLF). In eight patients admitted with AOCLF, a single 10-hour MARS treatment was performed. Systemic hemodynamic variables were determined before and during treatment.

S-100b and neuron-specific enolase in patients with fulminant hepatic failure.

Patients with fulminant hepatic failure (FHF) frequently develop cerebral edema and intracranial hypertension. The aim of this study was to evaluate circulating S-100b and neuron-specific enolase (NSE) levels as markers of neurological outcome in patients with FHF. In a subgroup of patients, the cerebral flux of S-100b and NSE was measured.

Cerebral blood flow in patients with chronic heart failure before and after heart transplantation.

Background And Purpose: Arterial blood pressure and cardiac output are often reduced in patients with chronic heart failure (CHF). Counterregulatory mechanisms with increased neurohormonal activation and changes in the distribution of cardiac output are assumed to secure vital organ perfusion. However, clinical examination of patients with CHF frequently reveals neurological symptoms with dizziness and memory problems, suggesting altered brain perfusion.

Pyrite oxidation in unsaturated aquifer sediments. Reaction stoichiometry and rate of oxidation.

The oxidation of pyrite (FeS2) contained in unsaturated aquifer sediment was studied by sediment incubation in gas impermeable polymer laminate bags. Reaction progress was followed over a period of nearly 2 months by monitoring the gas composition within the laminate bag. The gas phase in the incubation bags became depleted in O2 and enriched in CO2 and N2 and was interpreted as due to pyrite oxidation in combination with calcite dissolution.

Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure.

Background & Aims: High circulating levels of ammonia have been suggested to be involved in the development of cerebral edema and herniation in fulminant hepatic failure (FHF). The aim of this study was to measure cerebral metabolism of ammonia and amino acids, with special emphasis on glutamine metabolism.

Methods: The study consisted of patients with FHF (n = 16) or cirrhosis (n = 5), and healthy subjects (n = 8).

Multitemperature Resonance-Diffraction and Structural Study of the Mixed-Valence Complex [Fe(3)O(OOCC(CH(3))(3))(6)(C(5)H(5)N)(3)].

The Fe-O and Fe-N bond lengths at two iron sites of the mixed-valence complex [Fe(3)O(OOCC(CH(3))(3))(6)(C(5)H(5)N)(3)] show a pronounced temperature dependence; the bonds from two of the Fe atoms to the central oxygen atoms vary by more than 0.10 Å on cooling to 10 K whereas the bond from the third iron atom is essentially invariant. The variation is such that the longest Fe-O bonds at ambient temperature are the shorter ones at 10 K, with the crossover occurring at about 90 K.

Characterization of Actinide Bonding in Th(S(2)PMe(2))(4) by Synchrotron X-ray Diffraction.

Extensive synchrotron (28 K) and conventional sealed-tube (9 K) X-ray diffraction data have been collected on Th(S(2)PMe(2))(4). Modeling of the electron density of the complex shows the bonding is quite ionic with little diffuse f or d type bonding density. Furthermore a large polarization of the Th core is observed revealing some 5d-like involvement in the bonding.

Structural asymmetry as a dermatoscopic indicator of malignant melanoma--a latent class analysis of sensitivity and classification errors.

Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other algorithms. However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed objectively and no golden standard of asymmetry diagnosis exists.

Lack of effect of citalopram on the steady-state pharmacokinetics of carbamazepine in healthy male subjects.

Carbamazepine, a drug used in the treatment of seizure disorders, and citalopram, a highly selective serotonin reuptake inhibitor used for the treatment of depression and other psychiatric disorders, are both metabolized predominantly by the cytochrome P4503A4 isozyme. In this study, the effect of subchronic administration of citalopram on the steady-state pharmacokinetics of carbamazepine was evaluated in 12 healthy male subjects. Carbamazepine was administered orally twice daily as a 100-mg dose from days 1 to 3, as a 200-mg dose twice a day from days 4 to 6, and as a 400-mg dose once a day from days 7 to 35.

ECG-abnormalities in Japanese and Swedish patients with sarcoidosis. A comparison.

Background And Aim Of The Work: ECG abnormalities are more common in patients with sarcoidosis than in controls. The incidence of cardiac sarcoid granulomas in the Japanese population has been found to be higher than that seen in Caucasians. We compared the prevalence of ECG abnormalities in Japanese and Swedish patients with sarcoidosis.

The charge density distribution in a model compound of the catalytic triad in serine proteases.

Combined low temperature (28(1) K) X-ray and neutron diffraction measurements were carried out on the co-crystallised complex of betaine, imidazole, and picric acid (1). The experimental charge density was determined and compared with ab initio theoretical calculations at the B3LYP/6-311G(d,p) level of theory. The complex serves as a model for the active site in, for example, the serine protease class of enzymes, the so-called catalytic triad.

Cerebral blood flow velocity increases during a single treatment with the molecular adsorbents recirculating system in patients with acute on chronic liver failure.

The aim of this uncontrolled pilot study is to determine the effect of treatment with the molecular adsorbents recirculating system (MARS) on cerebral perfusion in patients with acute on chronic liver failure (AOCLF). In 8 patients (median age, 44 years; range, 35 to 52 years) admitted with AOCLF, a single 10-hour MARS treatment was performed. Hepatic encephalopathy (HE) was graded according to the Fogarty criteria.

Death related to coronary artery fistula after rupture of an aneurysm to the coronary sinus.

Large coronary fistulas are considered to cause myocardial ischemia due to diversion of the coronary blood flow. In this case the authors report the reverse effect--the spontaneous closure of a large fistulation between the left circumflex artery and the coronary sinus evoked angina pectoris in a middle aged man, who died several years later. Postmortem examination revealed a coronary aneurysm that had ruptured and dissected into the coronary sinus and finally thrombosed.

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist.

Background And Aims: The main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to determine if endogenous GRP is a physiological regulator of gastric acid secretion and gastrin release.

Methods: Our study consisted of three parts. In part I, subjects received saline or BIM26226 followed by graded doses of intravenous human GRP in a four period crossover design.

Dermatoscopic prediction of melanoma thickness using latent trait analysis and likelihood ratios.

Breslow thickness and Clark level can be used to determine surgical procedures for cutaneous malignant melanoma and patient eligibility for experimental adjuvant therapy. Efforts to predict the thickness of melanomas using dermatoscopy have focused on differences between single dermatoscopic findings. The aim of this study was to develop a method for preoperative identification of melanomas of > or = 1 mm Breslow thickness using the entire range of dermatoscopic findings.

The reproducibility and sample size requirements of exercise-induced bronchoconstriction measurements.

Dry air exercise challenges are frequently used to screen medications that have potential utility in the management of exercise-induced bronchoconstriction (EIB). The purpose of this study was to determine the reproducibility of three outcome measurements made using such challenges, and sample size requirements for drug evaluation studies based on these outcomes. Forty adult subjects with asthma, who tested positively on a screening exercise challenge, were subjected to two further identical challenges, separated by 1 to >35 days.

Cerebral hyperemia and nitric oxide synthase in rats with ammonia-induced brain edema.

Background/aim: Brain edema is a common fatal complication in acute liver failure. It is related to an acute change in brain osmolarity secondary to the glial accumulation of glutamine. Since high cerebral blood flow (CBF) precedes cerebral herniation in fulminant hepatic failure we first determined if an increase in brain water and glutamine are prerequisite to a rise in CBF in a model of ammonia-induced brain edema.

Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure.

Objective: In acute liver failure (ALF), urea production is severely impaired, and detoxification of ammonia by glutamine synthesis plays an important protective role. The aim of this study was to examine the effects of therapeutic high-volume plasmapheresis (HVP) on arterial concentrations and splanchnic exchange rates of ammonia, urea, and amino acids-in particular, glutamine.

Methods: A quantity of 8 L of plasma was exchanged over the course of 7 h in 11 patients with ALF after development of hepatic encephalopathy grade III-IV.

Transcranial Doppler sonography and internal jugular bulb saturation during hyperventilation in patients with fulminant hepatic failure.

Mechanical hyperventilation is often used to postpone or ameliorate intracranial hypertension in patients with fulminant hepatic failure (FHF). Because such treatment may critically reduce cerebral blood flow (CBF), bedside techniques to monitor CBF are warranted. In this study, we evaluated the efficacy of transcranial Doppler (TCD) sonography of the middle cerebral artery (MCA) and internal jugular bulb saturation (svJO(2)) to determine relative changes in CBF during mechanical hyperventilation in 8 patients with FHF (median age, 40 years; range, 20 to 54 years).

Lack of citalopram effect on oral digoxin pharmacokinetics.

The effect of chronic administration of citalopram on the single oral dose pharmacokinetics of digoxin was evaluated in 11 healthy adult subjects in an open, one-way crossover study. Subjects received 1 mg digoxin on day 1. Serial blood samples and total urine were collected over 192 hours, followed by an 11-day washout period.