Screening for alcoholism

Alcoholism is one of the largest public health problems of the nation and is a significant cofactor in such ubiquitous diseases as hypertension, developmental abnormalities, heart failure, liver failure, and many other conditions. The cost to the nation's health is immense. One strategy for reducing morbidity and cost has been to establish methods for screening in order to increase recognition rates leading to increased rates of therapeutic intervention. In this article, the rationale for two methods of alcohol screening, brief interviews and biological markers of excessive drinking, the relevant statistical issues bearing on this problem, and the current research on screening exams are reviewed and summarized. Finally, some of the newer approaches toward alcoholism screening as well as the consequences to the medical care system should alcohol screening eventuate on a large scale are briefly described.     

Transient unresponsiveness in the elderly. Report of five cases.

Five hospitalized elderly patients had one or more self-limited episodes of unresponsiveness that could not be explained by metabolic, structural, convulsive, or psychiatric disorders. They accounted for approximately 2% of cases referred to us for evaluation of coma. Despite some heterogeneity, shared clinical features in these patients suggest an age-related disorder of arousal that may be more common than is generally appreciated.     

The pharmacology of GR203040, a novel, potent and selective non-peptide tachykinin NK1 receptor antagonist.

1. The in vitro and in vivo pharmacology of GR203040 ((2S, 3S)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), a novel, highly potent and selective non-peptide tachykinin NK1 receptor antagonist, was investigated in the present study. 2. GR203040 potently inhibited [3H]-substance P binding to human NK1 receptors expressed in Chinese hamster ovary (CHO) and U373 MG astrocytoma cells, and NK1 receptors in ferret and gerbil cortex (pKi values of 10.3, 10.5, 10.1 and 10.1 respectively). GR203040 had lower affinity at rat NK1 receptors (pKi = 8.6) and little affinity for human NK2 receptors (pKi < 5.0) in CHO cells and NK3 receptors in guinea-pig cortex (pKi < 6.0). With the exception of the histamine H1 receptor (pIC50 = 7.5). GR203040 had little affinity (pIC50 < 6.0) at all non-NK1 receptors and ion channels examined. Furthermore, GR203040 produced only weak inhibition of Na+ currents in SH-SY5Y neuroblastoma and superior cervical ganglion cells (pIC50 values < 4.0). GR203040 produced only weak antagonism of Ca(2+)-evoked contractions of rat isolated portal vein (pKn = 4.1). The enantiomer of GR203040, GR205608 (2R, 3R)-2-methoxy-5-tetrazol-1-yl-benzyl-(2-phenyl-piperidin-3-y l)-amine), had 10,000 fold lower affinity at the human NK1 receptor expressed in CHO cells (pKi = 6.3). 3. In gerbil ex vivo binding experiments, GR203040 produced a dose-dependent inhibition of the binding of [3H]-substance P to cerebral cortical membranes (ED50 = 15 micrograms kg-1 s.c. and 0.42 mg kg-1 p.o.). At 10 micrograms kg-1 s.c., the inhibition of [3H]-substance P binding was maintained for > 6 h. In the rat, GR203040 was less potent (ED50 = 15.4 mg kg-1 s.c.) probably reflecting, at least in part, its lower affinity at the rat NK1 receptor. 4. In guinea-pig isolated ileum and dog isolated middle cerebral and basilar arteries, GR203040 produced a rightward displacement of the concentration-effect curves to substance P methyl ester (SPOMe) with suppression of the maximum agonist response (apparent pKB values of 11.9, 11.2 and 11.1 respectively). 5. In anaesthetized rabbits, GR203040 antagonized reductions in carotid arterial vascular resistance evoked by SPOMe, injected via the lingual artery (DR10 (i.e. the dose producing a dose-ratio of 10) = 1.1 micrograms kg-1, i.v.). At a dose 20 fold greater than its DR10 value (i.e. 22 micrograms kg-1, i.v.), significant antagonism was evident more than 2 h after GR203040 administration. 6. In anaesthetized rats, GR203040 (3 and 10 mg kg-1, i.v.) produced a dose-dependent inhibition of plasma protein extravasation in dura mater, conjunctiva, eyelid and lip in response to electrical stimulation of the trigeminal ganglion. 7. It is concluded that GR203040 is one of the most potent and selective NK1 receptor antagonists yet described, and as such, has considerable potential as a pharmacological tool to characterize the physiological and pathological roles of substance P and NK1 receptors. GR203040 may also have potential as a novel therapeutic agent for the treatment of conditions such as migraine, emesis and pain.     

Immunohistochemical analysis of the A4 and AO10 (gp110) cell-surface antigens of human astrocytoma.

The A4 and AO10 (110 kd glycoprotein) cell-surface antigens are biochemically distinct markers of cultured human astrocytomas that are expressed by only a limited number of other cultured cell types. To further characterize these two antigens, the authors used immunohistochemical methods to determine their expression in normal human tissues, astrocytomas, and over 100 tumors of other histologic types. They found that A4 is expressed 1) throughout the central (CNS), but not peripheral nervous system (PNS); 2) in smooth muscle and a small number of epithelial tissues; and 3) in reactive glia and in astrocytomas, but not in most tumors of other histologic types. In contrast, the AO10 antigen is expressed 1) in a small subset of CNS neurons, but not in astrocytes, PNS neurons, or other normal tissues; 2) in astrocytomas and reactive glia; and 3) in some additional neuroectodermal tumors, but not melanomas, carcinomas, or sarcomas. These findings show that A4 and AO10 are restricted markers for human astrocytomas in vivo. Furthermore, the antigens show distinct patterns of expression in normal human CNS but appear to be coordinately expressed in astrocytomas and astrocytoma-derived cell lines.     

Murine embryonal carcinoma cells express class I MHC-like antigens

Previous work has concluded that murine embryonal carcinoma (EC) cells, the oncogenic stem cells of teratocarcinomas, do not express class-I, H-2K or D/L gene encoded products. Experiments using cell-mediated lysis, serological and molecular biological approaches show that EC cells do express some major histocompatibility complex (MHC) class I or class I-like molecules.