6 Jahre Erfahrungen mit einem Arzneimittelberatungsdienst für Patienten

Zusammenfassung : Hintergrund und Ziel: : Viele Patienten sind nur ungenügend über ihre Arzneimitteltherapie informiert. Daher besteht bei ihnen der Bedarf an zusätzlichen Informationen über Arzneimittel. Die Erfahrungen mit einem Arzneimittelberatungsdienst für Patienten werden hier berichtet. Patienten und Methodik: : Der Beratungsdienst war über Telefon, E-Mail sowie auf dem Postweg erreichbar und richtete sich zu Beginn an Patienten in Sachsen, seit 2005 an Personen aus ganz Deutschland. Sowohl demographische wie auch arzneimitteltherapiebezogene Daten der Patienten wurden erfasst und mittels einer relationalen Datenbank analysiert. Alle an den Beratungsdienst gerichteten Anfragen zwischen August 2001 und Januar 2007 wurden ausgewertet. Ergebnisse: : 5 587 Anfragen wurden registriert. 61,4% der anfragenden Personen waren weiblich und 33,8% männlich (Geschlecht unbekannt bei 4,8% aufgrund anonymer Anrufe). Allgemeiner Informationsbedarf zu Arzneimitteln und Therapie (27,5%) und Fragen zu Nebenwirkungen (24,7%) waren die am häufigsten genannten Anfragegründe. Die am meisten nachgefragte Arzneistoffgruppe stellten Arzneimittel für das kardiovaskuläre System mit 34,4% dar, gefolgt von Pharmaka für neuropsychiatrische Erkrankungen mit 15,1%. Schlussfolgerung: : Die Ergebnisse dieser Auswertung zeigen einen offensichtlichen Bedarf an einem Arzneimittelberatungsdienst für Patienten. Dieser lässt sich möglicherweise auf Zeitmangel bei den Ärzten zurückführen. Ein unabhängiger und fachkundiger Arzneimittelinformationsdienst vermag die Qualität der medizinischen Versorgung sowie die Zufriedenheit der betroffenen Patienten zu verbesser

Comparative evaluation of three clinical decision support systems: prospective screening for medication errors in 100 medical inpatients

Purpose: Clinical decision support systems (CDSS) are promoted as powerful screening tools to improve pharmacotherapy. The aim of our study was to evaluate the potential contribution of CDSS to patient management in clinical practice. Methods: We prospectively analyzed the pharmacotherapy of 100 medical inpatients through the parallel use of three CDSS, namely, Pharmavista, DrugReax, and TheraOpt. After expert discussion that also considered all patient-specific clinical information, we selected apparently relevant alerts, issued suitable recommendations to physicians, and recorded subsequent prescription changes. Results: For 100 patients with a median of eight concomitant drugs, Pharmavista, DrugReax, and TheraOpt generated a total of 53, 362, and 328 interaction alerts, respectively. Among those we identified and forwarded 33 clinically relevant alerts to the attending physician, resulting in 19 prescription changes. Four adverse drug events were associated with interactions. The proportion of clinically relevant alerts among all alerts (positive predictive value) was 5.7, 8.0, and 7.6%, and the sensitivity to detect all 33 relevant alerts was 9.1, 87.9, and 75.8% for Pharmavista, DrugReax and TheraOpt, respectively. TheraOpt recommended 31 dose adjustments, of which we considered 11 to be relevant; three of these were followed by dose reductions. Conclusions: CDSS are valuable screening tools for medication errors, but only a small fraction of their alerts appear relevant in individual patients. In order to avoid overalerting CDSS should use patient-specific information and management-oriented classifications. Comprehensive information should be displayed on-demand, whereas a limited number of computer-triggered alerts that have management implications in the majority of affected patients should be based on locally customized and supported algorithm

Lack of antigenic diversification of major outer membrane proteins during clonal waves of Neisseria meningitidis serogroup A colonization and disease

In particular in the ‘meningitis belt' of sub-Saharan Africa, epidemic meningococcal meningitis is a severe public health problem. In the past decades, serogroup A lineages have been the dominant etiologic agents, but also other serogroups have caused outbreaks. A comprehensive vaccine based on subcapsular outer membrane proteins (OMPs) is not available. Here, we have investigated whether meningococcal populations overcome herd immunity by changing antigenic properties of their OMPs. Meningococcal isolates were collected in the context of longitudinal studies in Ghana between 2002 and 2008 and in Burkina Faso between 2006 and 2007. Serogroup A strains isolated during two clonal waves of colonization and disease showed no diversification in the genes encoding their PorA, PorB, and FetA proteins. However, we detected occasional allelic exchange of opa genes, as well as wide variation in the number of intragenic tandem repeats, showing that phase variation of Opa protein expression is a frequent event. Altogether we observed a remarkable antigenic stability of the PorA, PorB and FetA proteins over years. Our results indicate that while herd immunity may be responsible for the disappearance of meningococcal clones over time, it is not a strong driving force for antigenic diversification of the major OMPs analyzed her

Antibody-Mediated Neutralization of the Exotoxin Mycolactone, the Main Virulence Factor Produced by Mycobacterium ulcerans

Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, causes extensive tissue destruction by inducing apoptosis of host cells. In this study, we aimed at the production of antibodies that could neutralize the cytotoxic activities of mycolactone.; Using the B cell hybridoma technology, we generated a series of monoclonal antibodies with specificity for mycolactone from spleen cells of mice immunized with the protein conjugate of a truncated synthetic mycolactone derivative. L929 fibroblasts were used as a model system to investigate whether these antibodies can inhibit the biological effects of mycolactone. By measuring the metabolic activity of the fibroblasts, we found that anti-mycolactone mAbs can completely neutralize the cytotoxic activity of mycolactone.; The toxin neutralizing capacity of anti-mycolactone mAbs supports the concept of evaluating the macrolide toxin as vaccine target

Cysteine-rich protein 2 is a downstream effector of cGMP-dependent protein kinase I in nociception : poster presentation

The experience of pain is mediated by a specialized sensory system, the nociceptive system. There is considerable evidence that the cGMP/cGMP kinase I (cGKI) signaling pathway modulates the nociceptive processing within the spinal cord. However, downstream targets of cGKI in this context have not been identified to date. In this study we investigated whether cysteine-rich protein 2 (CRP2) is a downstream effector of cGKI in the spinal cord and is involved in nociceptive processing. Immunohistochemistry of the mouse spinal cord revealed that CRP2 is expressed in superficial laminae of the dorsal horn. CRP2 is colocalized with cGKI and with markers of primary afferent C fibers. Importantly, the majority of CRP2 mRNA-positive dorsal root ganglion (DRG) neurons express cGKI and CRP2 is phosphorylated in a cGMP-dependent manner. To elucidate the functional role of CRP2 in nociception, we investigated the nociceptive behavior of CRP2-deficient (CRP2-/-) mice. Touch perception and acute thermal nociception were unaltered in CRP2-/- mice. However, CRP2-/- mice showed an increased nociceptive behavior in models of persistent pain as compared to wild type mice. Intrathecal administration of cGKI activating cGMP analogs increased the nociceptive behavior in wild type but not in CRP2-/- mice, indicating that the presence of CRP2 was essential for cGMP/cGKI-mediated nociception. These data indicate that CRP2 is a new downstream effector of cGKI-mediated spinal nociceptive processing and point to an inhibitory role of CRP2 in the generation of inflammatory pain

Metabolic responses to high-fat diets rich in n-3 or n-6 long-chain polyunsaturated fatty acids in mice selected for either high body weight or leanness explain different health outcomes

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.</p> <p>Methods</p> <p>The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in <it>n</it>-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in <it>n</it>-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways.</p> <p>Results</p> <p>Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue.</p> <p>Conclusions</p> <p>A diet high in <it>n</it>-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary <it>n</it>-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.</p

Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling

Mutations of NPHS1 or NPHS2, the genes encoding nephrin and podocin, as well as the targeted disruption of CD2-associated protein (CD2AP), lead to heavy proteinuria, suggesting that all three proteins are essential for the integrity of glomerular podocytes, the visceral glomerular epithelial cells of the kidney. It has been speculated that these proteins participate in common signaling pathways; however, it has remained unclear which signaling proteins are actually recruited by the slit diaphragm protein complex in vivo. We demonstrate that both nephrin and CD2AP interact with the p85 regulatory subunit of phosphoinositide 3-OH kinase (PI3K) in vivo, recruit PI3K to the plasma membrane, and, together with podocin, stimulate PI3K-dependent AKT signaling in podocytes. Using two-dimensional gel analysis in combination with a phosphoserine-specific antiserum, we demonstrate that the nephrin-induced AKT mediates phosphorylation of several target proteins in podocytes. One such target is Bad; its phosphorylation and inactivation by 14-3-3 protects podocytes against detachment-induced cell death, suggesting that the nephrin-CD2AP-mediated AKT activity can regulate complex biological programs. Our findings reveal a novel role for the slit diaphragm proteins nephrin, CD2AP, and podocin and demonstrate that these three proteins, in addition to their structural functions, initiate PI3K/AKT-dependent signal transduction in glomerular podocytes