Adverse drug event detection in a community hospital utilising computerised medication and laboratory data.

OBJECTIVE: Computerised monitors can detect and, with clinical intervention, often prevent or ameliorate adverse drug events (ADEs). We evaluated whether a computer-based alerting system was useful in a community hospital setting. METHODS: We evaluated 6 months of retrospectively collected medication and laboratory data from a 140-bed community hospital, and applied the rules from a computerised knowledge base to determine if the resulting alerts might have allowed a clinician to prevent or lessen harm related to medication toxicity. We randomly selected 11% (n = 58, of which 56 were available) of charts deemed to be high- or critical-priority alerts, based on the likelihood of the alerts being associated with injury, to determine the frequencies of ADEs and preventable ADEs. RESULTS: In 6 months, there were 8829 activations of the rule set, generating a total of 3547 alerts. Of these, 528 were of high or critical priority, 664 were of medium priority and 2355 were of low priority. Chart review among the sample (56 charts) of high- or critical-priority alerts found five non-preventable and two preventable ADEs, suggesting that among the total high- or critical-priority alerts alone, there would be approximately 94 non-preventable ADEs and 37 preventable ADEs annually in this hospital that could be detected using this method. CONCLUSIONS: Computer-based rules engines have the potential to identify and, with clinical intervention, mitigate preventable ADEs, and implementation is feasible in community hospitals without an advanced information technology application.     

A comparison of neuropsychological tests for the assessment of chronic toxic encephalopathy

BACKGROUND: From the viewpoint of the clinical neuropsychologist, it is not evident if the detection of solvent induced toxic encephalopathy (TE) could be optimized by a modification of the traditional test batteries, adding tests covering new dimensions or monitoring further functional domains. METHODS: To clarify this issue, TE patients were re-examined with (a) the tests traditionally used in screening for TE and (b) some tests hitherto less utilized within neurotoxicology, involving complex attention and frontal lobe functioning. RESULTS: The results do not indicate that tests of the latter category would be more sensitive to TE than the tests traditionally used. Using an optimized core battery, compiled of tests from both categories, the sensitivity and specificity levels reached a maximum of around 0.7 when using as criterion the reproduction of a subnormal test profile (TE type 2B). CONCLUSIONS: A combination of several traditional and a few newer tests is suggested to optimize the detection of TE. Repeated assessments over time are also recommended.     

Oral hairy leukoplakia in vertically and horizontally acquired HIV infection

Two boys aged 7 and 8 years, respectively, with oral hairy leukoplakia as the sole clinical sign indicative for HIV infection are reported.     

Atypical Kawasaki disease with peripheral gangrene and myocardial infarction: Therapeutic implications

We describe a 2-month-old girl with atypical Kawasaki disease (KD) complicated by peripheral gangrene and myocardial infarction. Peripheral ischaemia leading to gangrene is a rare but serious complication of KD in infants younger than 7 months of age. Treatment has been targeted at reducing arterial inflammation, arteriospasm and thrombosis. We report the first patient with incomplete KD and peripheral ischaemia in whom therapy with prostaglandin E1 (PGE1) as vasodilating and antithrombotic agent appeared successful, restoring hand and foot perfusion without significant long-term sequelae. However, PGE1 could have supported development of myocardial infarction by shunting blood away from ischaemic areas distal to a giant coronary artery aneurysm with beginning thrombosis.Conclusion Atypical KD with peripheral gangrene appears to react favourably to treatment with PGE1, but needs careful monitoring to detect early signs of cardiac ischaemia.     

Congenital acatalasemia: a study of neutrophil functions after provocation with hydrogen peroxide

Five Swiss subjects with hereditary acatalasemia (4 homo-, 1 heterozygous) were studied by a series of neutrophil function tests. H2O2 was added to a polymorphonuclear neutrophil leukocyte-suspension to produce a metabolic stress; neutrophil functions related to membrane deformation were subsequently found to be depressed, i.e., chemotaxis, membrane potential, and chemiluminescence. This mechanism might be one pathogenetic factor in the formation of mucosal ulcers in acatalasemic individuals.     

Clonidine toxicity revisited

The incidence of clonidine overdose is increasing, yet there is a paucity of new information regarding treatment options for clonidine toxicity. Reported treatment approaches vary widely, demonstrating the lack of science on which current treatment is based. Available research needs to be reassessed. Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy following clonidine overdose. This article reviews aspects of clonidine toxicity that need to be further investigated. Multicenter research trials will be required to evaluate new treatment options.     

Regulation of p53: intricate loops and delicate balances

The p53 tumor suppressor protein provides a major anti-cancer defense mechanism, as underscored by the fact that the p53 gene is the most frequent target for genetic alterations in human cancer. Recent work has led to the realization that p53 lies at the hub of a very complex network of signaling pathways, which integrate a variety of intracellular and extracellular inputs. Part of this network consists of an array of autoregulatory feedback loops, where p53 exhibits very intricate interactions with other proteins known to play important roles in the determination of cell fate. We discuss two such loops, one involving the beta catenin protein and the other centering on the Akt/protein kinase B. In both cases, the central module is the interplay between p53 and the murine double minute 2 (Mdm2) protein, which inactivates p53 and targets it for rapid proteolysis. Whereas deregulated beta catenin can lead to Mdm2 inactivation and p53 accumulation, active p53 can promote the degradation and downregulation of beta catenin. Similarly, Akt can block p53 activation by potentiating Mdm2, whereas activated p53 can tune down Akt in several different ways. In each case, the actual output of the loop is determined by the delicate balance between the opposing effects of its different components. Often, this balance is dictated by additional signaling processes that occur simultaneously within the same cell. Genetic alterations characteristic of cancer are capable of severely distorting this balance, thereby overriding the tumor suppressor effects of p53 in a manner that facilitates neoplastic conversion.     

Mechanisms of gonadotropin desensitization

The gonadotropic hormones, FSH and LH exert a major effect on ovarian and testicular function through interaction with specific seven-transmembrane domain glycoprotein receptors. Desensitization to the hormones, which can occur both in vivo and in vitro, is essential for prevention of overstimulation of the gonadal cells. The long-term process of desensitization to the gonadotropic hormones is probably mediated, in part, by extensive clustering and internalization of the hormone-receptor complex. Short-term desensitization may occur as a result of phosphorylation of serine or threonine residues on the receptor molecules, although a specific receptor kinase has not yet been identified. Recently, we have discovered a novel mechanism of gonadotropin desensitization, which is exerted by down-regulation of StAR expression and steroidogenesis mediated by MAPK activation as a result of hormone-receptor interaction, cAMP accumulation and PKA activation. Thus, PKA not only mediates gonadotropin-induced steroidogenesis, it also activates the down-regulation mechanism that can silence steroidogenesis under certain conditions. Moreover, our findings raise the possibility that activation or inhibition of ERK by other pathways could be an important mechanism for diminution or amplification of gonadotropin-stimulated steroidogenesis. This could contribute to functional luteolysis, a process in which luteinized granulosa cells show reduced sensitivity to LH despite maintenance of LH receptors, or to up-regulation of the steroidogenic machinery during luteinization of granulosa cells.     

贴报-P2临床毒理学、药理学和疗效研究

5-Flourouracil（5-FU） is one of well known anti-cancer drugs, but its toxicity in normal lymphocytes remains a major problem in chemotherapy. The eastern traditional drug, Bupleuri radix（BR）, has been used for the treatment of liver diseases and contains series of triterpene saponins.