Acute hepatic failure: the emerging role of orthotopic liver transplantation

From 1985 through 1987, we diagnosed acute hepatic failure in 13 patients. Spontaneous recovery occurred in three of these patients. Eight patients underwent liver transplantation, five of whom survived and three of whom died. In addition, two patients died before undergoing transplantation. The survival rate of 62% was better than that among our previous series of similar patients. This improvement seems to be related to the use of orthotopic liver transplantation as a therapeutic alternative among these patients. One of the three patients who died after liver transplantation had normal liver function, but respiratory failure caused by Pneumocystis carinii developed 4 months after the transplantation. The surgical procedure was less difficult in patients with acute fulminant hepatitis than in those with chronic liver disease because fewer problems arose from adhesions, venous collaterals, and ascites. The emerging role of orthotopic liver transplantation in patients with acute hepatic failure is demonstrated by the improvement of survival rates observed by various groups, including ours, when this therapeutic modality is available.     

Use of protein A immunoadsorption as a treatment for thrombocytopenia in HIV-infected homosexual men: a retrospective evaluation of 37 cases.

Thirty-seven HIV-infected homosexual men with thrombocytopenia (less than 100 x 10(9)/l) received protein A immunoadsorption treatments to remove platelet-sensitizing immunoglobulin (Ig) G and circulating immune complexes (CIC) from plasma. Patients received an average of six treatments each, consisting of 250 ml plasma over a 3-week period. Clinical improvement in hemorrhagic symptoms associated with substantial increase in platelet counts was achieved in 18 patients. These responses were maintained over a median follow-up period of more than 7 months in 14 evaluable patients who were not lost to follow-up (three patients relapsed in 2 weeks and one received another therapy). Generally, moderate transient treatment-related side-effects included fever, musculoskeletal pain, chills and nausea. A transient serum sickness-like reaction was observed in seven patients, leading to termination of treatment in two. Clinical responses were associated with significant decreases in levels of platelet-sensitizing Ig, including CIC. Stimulation of broadly cross-reactive anti-antigen-binding fragment [F(ab)2], antibodies contributed to these responses. Protein A immunoadsorption is an effective alternative treatment for HIV-associated thrombocytopenia.     

Actions of ethanol and acetate on rat cortical neurons: ethanol/adenosine interactions.

Recent studies have suggested that ethanol may exert some of its central depressant actions by increasing the extracellular levels of adenosine in the brain. Ethanol can inhibit the cellular uptake of adenosine, thus increasing its extracellular concentration. After ethanol metabolism by the liver, blood acetate levels are elevated and acetate metabolism in the brain could also lead to the production of adenosine. Rat cerebral cortical cup release experiments failed to reveal any elevation in the extracellular levels of either adenosine or inosine following the intraperitoneal (IP) administration of ethanol (1.5 g/kg) or acetate (2 g/kg). IP-administered ethanol (0.5 and 1.0 g/kg) enhanced the magnitude and duration of the inhibition by iontophoretically applied adenosine of the spontaneous firing of rat cerebrocortical neurons; an action which would be consistent with the block of adenosine uptake. Acetate, applied iontophoretically, depressed the spontaneous firing of 63% of the cerebrocortical neurons tested. 8-p-Sulphophenyltheophylline, an adenosine antagonist, was ineffective at blocking these inhibitions, indicating that adenosine generation is unlikely to have played a major role in the acetate-evoked depression of cerebral cortical neurons.     

Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids.

We investigated the antiproliferative effect of two polyhydroxylated (quercetin and taxifolin) and two polymethoxylated (nobiletin and tangeretin) flavonoids against three cell lines in tissue culture. Tangeretin and nobiletin markedly inhibited the proliferation of a squamous cell carcinoma (HTB 43) and a gliosarcoma (9L) cell line at 2-8 micrograms/ml concentrations. Quercetin displayed no effect on 9L cell growth at these concentrations, while at 8 micrograms/ml it inhibited HTB 43 cell growth. Taxifolin slightly inhibited HTB 43 cell growth at 8 micrograms/ml, while moderately inhibiting HTB 43 cell growth at 2-8 micrograms/ml. The proliferation of a human lung fibroblast-like cell line (CCL 135) was relatively insensitive to low concentrations of the above flavonoids.     

Ontogenetic Development of 5-HT1D Receptors in Human Brain: An Autoradiographic Study

The pattern of pre- and postnatal appearance of 5-HT_1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [¹²⁵I]GTI (serotonin O -carboxymethyl-glycyl-[¹²⁵I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT_1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [¹²⁵I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT_1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT_1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT_1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.     

MINERVA-a multi-modal radiation treatment planning system.

Researchers at the Idaho National Engineering and Environmental Laboratory and Montana State University have undertaken development of MINERVA, a patient-centric, multi-modal, radiation treatment planning system. This system can be used for planning and analyzing several radiotherapy modalities, either singly or combined, using common modality independent image and geometry construction and dose reporting and guiding. It employs an integrated, lightweight plugin architecture to accommodate multi-modal treatment planning using standard interface components. The MINERVA design also facilitates the future integration of improved planning technologies. The code is being developed with the Java Virtual Machine for interoperability. A full computation path has been established for molecular targeted radiotherapy treatment planning, with the associated transport plugin developed by researchers at the Lawrence Livermore National Laboratory. Development of the neutron transport plugin module is proceeding rapidly, with completion expected later this year. Future development efforts will include development of deformable registration methods, improved segmentation methods for patient model definition, and three-dimensional visualization of the patient images, geometry, and dose data. Transport and source plugins will be created for additional treatment modalities, including brachytherapy, external beam proton radiotherapy, and the EGSnrc/BEAMnrc codes for external beam photon and electron radiotherapy.     

Evaluation of the bronchodilator properties of Ro 31-6930, a novel potassium channel opener, in the guinea-pig

1. Ro 31-6930 (0.001-0.3 microM), cromakalim (0.03-3.0 microM), salbutamol (0.001-0.3 microM) and theophylline (0.3-100 microM) evoked dose-related reductions in guinea-pig spontaneous tracheal tone with IC50 values of 0.044, 0.20, 0.021 and 21.0 microM respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4), U46619 and prostaglandin D2 (PGD2). The order of potency of tracheal relaxants was always salbutamol greater than Ro 31-6930 greater than cromakalim greater than theophylline. 2. All four agents evoked dose-related reductions in 5-HT- and histamine-induced bronchoconstriction in pithed vagotomised guinea-pigs. The dose of Ro 31-6930 producing 50% inhibition of a 5-HT bronchoconstriction was 11.6 micrograms kg-1 and the dose producing 50% inhibition of a histamine bronchoconstriction was 4.4 micrograms kg-1. Salbutamol was approximately 4-5 times more potent than Ro 31-6930 whilst cromakalim was approximately 10 times less potent than Ro 31-6930 as a bronchodilator. Theophylline was markedly less potent than any of the other agents. 3. Ro 31-6930, cromakalim, salbutamol and theophylline each protected conscious guinea-pigs from histamine-induced respiratory distress. Ro 31-6930 and salbutamol were each effective at oral doses of 1.0 and 3.0 mg kg-1 whilst cromakalim was effective at oral doses of 3.0 and 10.0 mg kg-1. Theophylline showed activity only at 300 mg kg-1 p.o. 4. Ro 31-6930 is a novel potassium channel opener which is a potent relaxant of guinea-pig tracheal smooth muscle in vitro and a bronchodilator in vivo.     

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.     

Effect of smoking on fibronectin production by human amnion and placenta.

Fibronectin production from amnion and placental tissues was evaluated in pregnant woman smokers and nonsmokers in order to examine if there were alterations of fibronectin metabolism in intrauterine tissues. In both amnion and placental tissues, cycloheximide inhibited the fibronectin output indicating that it was being synthesized. Mean fibronectin output by amnion in pregnant woman smokers was significantly lower than that in pregnant woman nonsmokers. In contrast, in the placenta from pregnant woman smokers, the output was significantly higher than that in pregnant woman nonsmokers. The present observations indicate that smoking alters an important biochemical constituent in amnion and placenta, possible leading to some complications.