Mobile workers in healthcare and their information needs: are 2-way pagers the answer?

The ability to have access to information relevant to patient care is essential within the healthcare environment. To meet the information needs of its workers, healthcare information systems must fulfill a variety of functional requirements. One of these requirements is to define how workers will interact with the system to gain the information they need. Currently, most healthcare information systems rely on users querying the system via a fixed terminal for the information they desire; a method that is inefficient because there is no guarantee the information will be available at the time of their query and it interrupts their work flow. In general, clinical event monitors--systems whose efficacy relies on the delivery of time-critical information--have used e-mail and numeric pagers as their methods to deliver information. Each of these methods, however, still requires the user to perform additional steps, i.e., log into an information system in order to attain the information about which the system is alerting them. In this paper we describe the integration and use of 2-way alphanumeric pagers in CLEM, the UPMC Health System's Clinical Event Monitor, and how the use of these pagers addresses the information needs of mobile workers in healthcare.

Preferences of interns and residents for E-mail, paging, or traditional methods for the delivery of different types of clinical information.

We elicited from medical house staff their preferences for e-mail and alphanumeric pager as communication channels for the delivery of 18 different types of clinical information about their inpatients. For each type, we calculated the proportion of users who preferred delivery by e-mail, pager, both, or neither (usual delivery). For 14/18 (78%) types, more users preferred delivery by pager than by the other options. For 2/18 (11%) types, e-mail was preferred. For 2/18 (11%) types, more users preferred redundant delivery using both channels. For no types did more users prefer neither, meaning that the information would be delivered by traditional channels, if any. We conclude that medical house staff in the inpatient setting prefer to receive many types of clinical information by pager. The reason may be that they otherwise would have to query clinical information systems for these data, which is wasteful of their time and introduces delays into the process of care. Additionally, we found significant inter-user variability, suggesting that it may be useful for the notification services of an enterprise to employ user profiles for the delivery of clinical information.

Use of CLIPS for representation and inference in a clinical event monitor.

We developed a clinical event monitor that is currently deployed in an inpatient setting. We selected CLIPS as the basis for its KB and inference engine. This paper describes the considerations that went into that decision, how we represented drug and laboratory knowledge in CLIPSs, and how we extended CLIPS to deal with temporal inferences. We also review the published literature about the use of CLIPS in medicine.

Antihuman Immunodeficiency Virus (HIV-1) Activities of Inhibitors of Polyamine Pathways.

Four inhibitors of polyamine biosynthetic pathways were tested for their effect on HIV-1 replication in phytohemagglutinin-stimulated human peripheral blood mononuclear cells. Methyl acetylenic putrescine (MAP) and alpha-monofluoromethyldehydroornithine methyl ester, irreversible inhibitors of ornithine decarboxylase, inhibited the production of p24 antigen in phytohemagglutinin-stimulated peripheral blood mononuclear cells by clinical HIV-1 strains isolated from HIV-infected patients with IC(50) values of about 1-2 &mgr;M. 5'--5'-deoxyadenosine (MDL 73811), an enzyme-activated irreversible inhibitor of S-adenosyl-L-methionine (AdoMet) decarboxylase, also inhibited the production of p24 antigen by HIV-1 strains in peripheral blood mononuclear cells with IC(50) values of 1-2 &mgr;M. The least potent was 1-aminoxyethylamine which is another inhibitor of AdoMet decarboxylase. MAP showed the best therapeutic index of 500-1,000. Copyright 1996 S. Karger AG, Basel

Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices.

Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candles), temperature (-20, 4 and 23 degrees C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were < or = 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. Shelf-life data indicate that morphine is stable for at least 6 weeks when protected from light.(ABSTRACT TRUNCATED AT 250 WORDS)

Derivatives of 1-aminooxy-3-aminopropane as polyamine antimetabolites: stability and effects on BHK21/C13 cells.

1- or 3-methylated derivatives and oximes of 1-aminooxy-3-aminopropane (APA) with pyridoxal (PL) and pyridoxal 5'-phosphate (PLP) were synthesized to examine whether the stability of the parent APA molecule could be increased without loss of its inhibitory capacity towards ornithine decarboxylase. Preformed APA-PLP was more stable than APA and was not a substrate of cellular acetylating activity. The only detectable degradation mechanism of APA-PLP was a slow dephosphorylation to APA-PL, which was a substrate for cellular acetylating activity like the methylated APA derivatives. Methylation at the 1 or 3 position of APA did not increase its stability but markedly changed its inhibitory potency towards S-adenosylmethionine decarboxylase and spermidine synthase. Supplementation of cell growth media with 1 mM aminoguanidine markedly reduced the degradation rate of 1- or 3-Me-APA and APA. All the growth-retarding effects of the drugs were reversed by addition of 10-20 microM putrescine or spermidine to the growth media containing a drug concentration of 1 mM, except with APA-PL, which had signs of emergent toxicity at concentrations above 0.5 mM. APA-PL and APA-PLP were as good as APA and two orders of magnitude more effective than alpha-difluoromethylornithine (DFMO) in inhibiting DNA synthesis by BHK21/C13 cells.

Muscarinic receptor subtype specificity of 5'-(isobutylthio)-adenosine (SIBA) and its analogs.

1. 5'(Isobutylthio)-adenosine (SIBA) and its analogs, at 100 microM, inhibited [3H]N-methyl-scopolamine binding to homogenates of whole brain and cortex (mainly M1 subtype receptors) by 11-30% and to cerebellum (mainly M2 subtype receptors) by 20-39%. 2. At 0.01-1.0 microM, stimulation of [3H]QNB and NMS-inaccessible [3H]QNB binding was observed, with the most induced by 1 microM 3-deaza-SIBA. 3. In contrast, [3H]pirenzepine ([3H]PZ) binding to whole brain and cortex was inhibited in a dose-dependent manner with Ki values in the microM range. 4. As antagonists of acetylcholine-induced contraction of guinea pig ileum (mainly M2 subtype receptors), the analogs were slightly more potent than pirenzepine, but several orders of magnitude less than atropine; the order of potency was opposite that determined for the binding of [3H]PZ to cortex. 5. Thus, SIBA and its analogs may have differential effects on muscarinic receptor subtypes and show some specificity for the M1 receptor subtype.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induced perturbation of calcium distribution in the rat.

Altered calcium homeostasis may play a central role in the liver injury produced by some toxicants. Therefore, the dose and time dependent effects of TCDD on calcium distribution in whole homogenate and subcellular fractions of liver were examined. Groups of female rats were treated with 40 micrograms TCDD/kg for 1, 2 or 3 days. Animals treated with TCDD for 1 and 2 days were killed 1 day after treatment. Rats treated for 3 days were killed on days 1, 3, 5, 7, 9 and 12 post-treatment. A 2-fold increase in calcium content in whole homogenate occurred 5 days post-treatment. Increases in mitochondrial calcium were noted 3 days post-treatment, and significant increases in microsomal calcium were observed one day post-treatment. Small increases in cytosolic calcium also occurred. Thus, TCDD produces disturbances in the content and subcellular distribution of calcium which may contribute to the promotion of toxic manifestations by this xenobiotic.

Pharmacokinetics of methyprylon following a single oral dose.

Single oral doses of 300 mg of methyprylon were administered to 10 healthy volunteers. Plasma concentrations of methyprylon and its dehydro metabolite were measured using a recently developed HPLC assay. Plasma concentration-time data were fitted to a two-compartment model with either first-order absorption, zero-order absorption, or two consecutive, discontinuous, first-order absorption rate constants. Based on the criteria of visual inspection, the correlation coefficient, standard deviations of the parameter estimates, and the residual sum of squares, it was concluded that the zero-order absorption model fit the data best. Mean (+/- SD) values for the half-life (9.2 +/- 2.2 h), apparent clearance, (11.91 +/- 4.42 mL/h/kg) and apparent steady-state volume of distribution, (0.97 +/- 0.33 L/kg) were found.

Inhibition of muscarinic receptor binding and acetylcholine-induced contraction of guinea pig ileum by analogues of 5'-(isobutylthio)adenosine.

(Isobutylthio)adenosine (SIBA, 1) and its derivatives have been shown to produce a variety of biological effects on the basis of the hypothesis that such agents act directly as inhibitors of transmethylation reactions, as inhibitors of S-adenosylhomocysteine hydrolase, or as inhibitors of polyamine biosynthesis. We report here the ability of selected analogues of SIBA to inhibit the binding of the muscarinic antagonist quinuclidinyl benzilate (QNB) to cultured N4TG1 neuroblastoma cells and to antagonize the acetylcholine-induced contraction of guinea pig ileum. The most potent inhibitors were 5'-deoxy-5'-(isobutylthio)-1-deazaadenosine (1-deaza-SIBA, 5) and 5'-deoxy-5'-(isobutylthio)-3-deazaadenosine (3-deaza SIBA, 3), while the parent nucleoside SIBA and the carbocyclic derivative 5'-(isobutylthio)-3-deazaaristeromycin were less active. The same agents had no effect on the nicotinic receptors of NG108-15 neuroblastoma X glioma hybrid cells. The acyclic derivative 9-[[2-(isobutylthio)ethoxy]methyl]adenine, 3-deazaadenosine, 5'-(isobutylthio)tubercidin, and 5'-(isobutylamino)adenosine were inactive at the 1-mM level. These results suggest that SIBA and 3-deaza-SIBA may have profound effect on membrane-mediated phenomenon, including inhibition of muscarinic receptor binding.

The effect of oral castor oil on the disposition of methyprylon in intoxicated dogs.

Clinical observations indicate that large oral doses of castor oil are effective in reducing the time of coma resulting from acute intoxication with lipophilic drugs. It has been further suggested that the rate of removal of these drugs from the body is increased by castor oil. In order to investigate the effect of castor oil on the disposition of lipophilic drugs, five dogs were given toxic doses of methyprylon by intravenous infusion. Each dog was treated with a large oral dose of castor oil in a cross-over fashion. No significant difference was observed in the sleep times of the dogs treated with castor oil, or in the methyprylon pharmacokinetics compared to controls. It was concluded that castor oil does not affect the disposition of methyprylon.

Inhibitors of polyamine biosynthesis. 9. Effects of S-adenosyl-L-methionine analogues on mammalian aminopropyltransferases in vitro and polyamine biosynthesis in transformed lymphocytes.

Seven analogues of S-adenosyl-L-methionine were studied as inhibitors or substrates for mammalian spermidine and spermine synthases. One of these, S-(5'-deoxy-5'-adenosyl)-(+/-)-1-methyl-3-(methylthio)propylamine (5), showed a unique spectrum of activities on the polyamine biosynthesis enzymes. It was an inhibitor of S-adenosyl-L-methionine decarboxylase from rat liver and spermine synthase from bovine brain and rat ventral prostate. This compound was a substrate for the spermidine synthases from bovine brain and rat ventral prostate but not a substrate for the spermine synthases from these same sources. At concentrations of 0.2 mM and higher, compound 5 blocked the increases in polyamine levels and in [3H]thymidine incorporation induced by concanavalin A in cultured mouse lymphocytes. At approximately a 0.5 mM concentration of 5, the cellular polyamine levels and the rate of thymidine incorporation were similar to those of the unstimulated lymphocytes. Lower concentrations of 5 (0.02-0.1 mM) produced a dose-dependent increase in thymidine incorporation. A dose-dependent decrease in the cellular polyamine levels was observed in the range of 0.05-0.5 mM of the inhibitor. These results suggest that the effects of 5 on transformed lymphocytes are complex and may not be solely due to the inhibition of polyamine biosynthesis by this compound.

Cardenolide analogues. 2. 22-Methylenecard-14-enolides.

22-Methylene-3beta-hydroxy-5beta,20(S)-card-14-enolide (11) and 22-methylene-3beta-hydroxy-5beta,20(R)-card-14-enolide (12) were synthesized from digitoxin (1). Attempts to prepare the 14beta-hydroxy-22-methylene analogues were unsuccessful. The 20(R) isomer (12) was found in Na+, K+-ATPase inhibition studies to be twice as active as 14-dehydrogitoxigenin (17). The 20(S) isomer (11) was significantly less active than 17. The hydrolysis of steroid 3beta-tert-butyldimethysilyl ethers was also found to be much more difficult than with nonsteroids.

Cardenolide analogues. 1. A 17beta-unsaturated aldehyde.

A 17beta-unsaturated aldehyde analogue [3beta,14beta-dihydroxy-5beta-pregn-17beta-trans-20-en-22-al (7)] of the cardenolides was synthesized and studied. In earlier studies by Rappoport, unsaturated aldehydes were found to be highly active electrophiles, more active, for example, than unsaturated nitriles or methyl esters. The synthesis followed in part a scheme previously reported by Thomas for the syntheses of the 17beta-unsaturated nitrile 9 and the 17beta-unsaturated methyl and ethyl esters 8 and 10. Both 9 and 8 are more Na+,K+-ATPase inhibiting and slightly less inotropic than digitoxigenin (1b). However, the unsaturated aldehyde 7 was less Na+,K+-ATPase inhibiting (I50 - 9.9 +/- 0.7 X 10(-7) M) and less inotropic (100% increase in contractile force at 8.5 +/- 1.0 X 10(-6) M) than 1b (I50 - 4.6 +/- 1.6 X 10(-7) M; 100% increase at 3.0 +/- 1.0 X 10(-7) M).