More than just crushing: a prospective pre-post intervention study to reduce drug preparation errors in patients with feeding tubes.

WHAT IS KNOWN AND OBJECTIVES: Incorrect drug preparation for patients with feeding tubes can result in harm for the patient and the preparing person. Combined intervention programs are effective tools to reduce such preparation errors. However, to date, intervention programs have been mostly tested in hospitals with computerized physician order entry (CPOE), unit-dose systems, or ward-based clinical pharmacists. Hence, the primary objective of this study was to develop and evaluate an intervention program tailored to hospitals without such preconditions. METHODS: We conducted a prospective pre-/post-intervention study on a gastroenterological intensive care unit (ICU) and a surgical ward for oral, dental and maxillofacial diseases (surgical ward). During the study periods, observers documented and evaluated drug preparation processes of all peroral drugs for patients with feeding tubes. The primary endpoint was the rate of inappropriately crushed and/or suspended solid peroral drugs in regards to all solid peroral drugs. RESULTS AND DISCUSSION: Altogether, we evaluated 775 drug preparation processes of solid peroral drugs on the ICU and 975 on the surgical ward. The intervention program significantly reduced incorrect crushing and/or suspending of solid peroral drugs for administration to patients with feeding tubes from 9·8% to 4·2% (P < 0·01) on the ICU and from 5·7% to 1·4% (P < 0·01) on the surgical ward. WHAT IS NEW AND CONCLUSION: The implementation of the newly developed intervention program significantly reduced the rate of inappropriately prepared solid peroral drugs, suggesting that it is an effective measure to enable safe drug administration for inpatients with feeding tubes.

[Inhalative application devices for patients suffering from asthma bronchiale]. / Inhalative Applikationsformen bei Asthma bronchiale und COPD.

Asthma is a chronic inflammatory disorder of the airways. It is caused by infiltration of eosinophils, mast cells, and CD4+ -T-lymphocytes which leads to variable airway obstruction. The core element of therapy is to control inflammation, which is best possible with inhaled steroids, the so-called controller drugs. Cromones are only second line therapeutic agents because they are not powerful enough for optimal inflammation control. Reliever drugs like beta2-agonists or anticholinergic agents serve as a symptomatic medication because they only lead to bronchial dilatation. The inflammation in COPD is caused by neutrophils, macrophages and CD8+ -T-lymphocytes. This kind of inflammation causes an irreversible airway obstruction accompanied by destruction of the lung parenchyma. By the majority, only symptomatic medication is effective for COPD, like anticholinergic agents and beta2-agonists. About 10-20% of patients with COPD are showing improvement when treated with inhaled steroids. However, the best treatment result is only guaranteed by optimal application of the medication. The most important barrier is an insufficient coordination between manual use of the inhaling system and inhalation. Various attempts are made to solve this problem, thus leading to a huge variety of application systems. However this also leads to confusion of patients and doctors because it is difficult to choose the optimal system and to use it in the most efficient way. This article provides an overview of the different application systems and compiles important details to facilitate the optimal application of inhalation therapy by the patient.

Differential changes of cAMP-dependent protein kinase activity and 3H-cAMP binding sites in rat hippocampus during maturation and aging.

The cyclic AMP-dependent protein kinase (PKA) has been involved in the brain aging process and recent papers have reported age-associated changes in enzyme activity in rat brain. The present study was undertaken to assess simultaneously PKA activity and regulatory (R) subunit levels during maturation and aging. Five cohorts of rats of different ages were used, namely pups of 1 week and 3 weeks old, mature rats (2 months), postmature rats (1 year) and old rats (2 years or more). PKA activity and 3H-cAMP binding sites were determined in cytosolic fractions of hippocampus. Results showed a low PKA activity in newborn rats which increased in mature and postmature rats and finally declined in old rats (ANOVA, P<0.001). The maximum binding sites (Bmax) of 3H-cAMP which measure the PKA R subunit levels were elevated in newborn rats and declined in mature and old rats (ANOVA; P<0.001). It is suggested the changes in PKA R subunit levels reflect an adaptative role in maturing process, a role which is lost in aging phase.

A non-radioactive assay for the cAMP-dependent protein kinase activity in rat brain homogenates and age-related changes in hippocampus and cortex.

Cyclic AMP-dependent protein kinase (PKA) activity was involved in a number of brain functions such as cognitive process or aging. The measurement of PKA activity is traditionally based on the use of [(32)P]ATP in phosphorylation of specific protein. Recently non-isotopic PKA assays have been developed, but none has been tested on brain homogenates. This work aimed to adapt a fluorimetric method of PKA activity into a novel assay never applied before in brain homogenate, and to characterize the enzyme activity and ratio in hippocampus and cortex from rats of different ages. Optimal conditions of homogenization and enzyme protection were determined. The method was sensitive and reproducible (intra-assay and interassay variation was 5.0% and 9.0%, respectively). In hippocampal cytosol, PKA activity was 27+/-8 and 80+/-9 nmol/min per mg protein in basal and cAMP-stimulated activity, respectively, and accounted for 80% of total cell PKA activity. The non-PKA activity, assessed by the use of the PKA specific inhibitor (PKI) accounted for 49.0% and 65.0% of endogenous levels in cytosol and membrane, respectively. cAMP-augmenting drugs effects were measured and increase of 53%, 273% and 118% over basal by 10 microM isoproterenol, 100 microM forskolin, 1 microM Sp-AMP, respectively, was observed. With respect to the changes in animal age, PKA activity increased from newborn to the mature rats but decreased in older rats. The PKA ratio was higher in cytosol than in particulate fraction, and was decreased in hippocampal sample from old rats (P<0.05). This last result was interpreted as related to the loss of cognitive capacities in old animals.

Lithium and haloperidol treatments differently affect the mononuclear leukocyte Galphas protein levels in bipolar affective disorder.

Despite numerous suggestions of the involvement of GTP-binding proteins in the mechanisms of action of psychoactive drugs in bipolar affective disorder, few studies have been conducted during the drug treatment of patients. The aim of the present study was to investigate the effects of a mood stabilizer and an antipsychotic drug on Galphas proteins. Patients with bipolar affective disorder under lithium treatment with or without haloperidol were assessed with respect to their mononuclear leukocyte (MNL) Galphas subunit protein. Galphas-45 protein subunit levels were analyzed by the Western immunoblot method. The subjects consisted of a group of 20 patients, all diagnosed as euthymic bipolars, and a comparison group of 15 drug-free healthy subjects. Results showed that Galphas levels were significantly decreased in the bipolar patients (BP) compared to drug-free healthy subjects (Mann-Whitney U test, p < 0.002). The drug effect was evaluated by a factorial analysis of variance and showed significant differences between groups (Kruskal-Wallis H test, p < 0.02). Lithium-treated patients displayed the most decreased Galphas levels (normalized mean values 53.2 +/- 31 vs. 122 +/- 45% for BP and controls, respectively, p < 0.001), while no change was observed in Galphas levels of haloperidol-treated patients compared to controls (mean values: 124.9 +/- 37%; NS). The data indicate that lithium and haloperidol affect the mechanism of Galphas protein signal transduction differently, consistent with previous animal studies.

Cyclosporine A-induced decrease in calbindin-D 28 kDa in rat kidney but not in cerebral cortex and cerebellum.

Recently, we reported that in rat, cyclosporine A (CsA) markedly decreases the levels of calbindin-D (CABP-D) 28 kDa in kidney. CABP-D 28 kDa is a calcium-binding protein which is highly expressed in calcium-transporting tissues such as kidney or brain. In this study, we investigated whether, in addition to the kidney, CsA also has an effect on CABP-D 28 kDa in rat brain. Three groups of male Wistar rats received 15 mg/kg/day or 50 mg/kg/day of CsA orally for 12 days, whereas controls received vehicle solution for the same period. CABP-D 28-kDa protein and CsA were quantified in homogenates of kidney, cerebral cortex and cerebellum, and the localization of CABP-D 28 kDa was assessed in the different tissue sections by immunohistochemistry. In kidney, CABP-D 28 kDa was strongly and dose dependently decreased, and was located in tubular epithelial cells. In brain, CABP-D 28 kDa was not changed and was mainly located in pyramidal cells of the cortex and in cerebellum exclusively in Purkinje cells. High CsA concentrations were measured in kidney, more than 17-fold greater than those found in cortex. In cerebellum, CsA was below the limit of detection. These data suggest that at clinically relevant doses, CsA may not affect CABP-D 28-kDa levels in brain.