Antibiotic resistance in clinical bacterial isolates remains an ongoing problem requiring continuous monitoring to effect some form of control. Comparative studies have not been previously reported for the Eastern Cape Region, South Africa and this study was undertaken to monitor resistance patterns in clinical isolates from Provincial Hospital, Port Elizabeth. Over the three year period 1989 to 1991, 9888 susceptibility results from isolates examined in the SAIMR pathology laboratory were analysed and collated using a stand-alone computer program. Resistance patterns for a range of nineteen antibiotics were collated for isolates from various sampling points within the hospital. Results were reported as resistance patterns in individually isolated species. Levels of resistance in each species were compared to those reported from South Africa and abroad, and changing patterns of resistance were noted within the three year period at the Provincial Hospital, Port Elizabeth.

Elderly people, or those over 65 years of age, are known to comprise 10% of the United States population today and are projected to reach nearly 12% by the year 2000. Further, 5% of this population is reported to be institutionalized resulting in approximately 1.1 million chronic care patients or 0.5% of the population. The use of drugs in this population comprises approximately 25% of the prescription drug market in the United States which is directly related to the greater occurrence of pathological problems associated with the aging process. While it is evident that the beneficial outcome of drug therapies is partially related to the increased longevity observed in these elderly people, this population is also well-known to be the most prone to adverse drug reactions. Factors complicating drug use in the elderly include high usage, chronic therapy, long-term hospitalization, inappropriate and multiple prescribing of drugs, inadequate monitoring of adverse drug effects, susceptibility to physical deterioration and senility. Therefore, the objective of this project is to test the hypothesis that the quality and cost of drug therapy in SNF patients can be significantly improved by implementing measures to improve the utilization of drugs.

tudies in teaching and non-teaching hospitals have shown that one- quarter to one-third of all patients receive an antimicrobial (AMC) drug during their hospital stay." 1-30 Many of these patients (ranging from 30 to 60%), particularly those on the surgical services, have no definite evidence of infection. Inquiry regarding the use of AMC drugs can be traced back more than two decades. In 1961, the Commission on Professional and Hospital Activities in its Professional Activity Study (CPHA-PAS) surveyed 24 hospitals." They found that approximately 27% of all patients were given an AMC drug; however, it was estimated by PAS that only about 12% of these patients should have received AMC therapy under the most conservative medical practice.

No description available.

No description available.

<p>Delivery of drugs to the brain requires passage across the blood-brain barrier (BBB). Both for drugs already on the market and for new drugs under development, it is important to know to what extent a drug enters the CNS. Many drugs used clinically are racemic mixtures, <i>i.e.</i> equal parts of the (<i>S</i>)- and (<i>R</i>)-enantiomers. </p><p>The present studies focus on the enantiomers and racemates of a number of 5-HT_1A receptor agonists and antagonists (pindolol, propranolol, 8-OH-DPAT and other 8-substituted-2-(di-<i>n</i>-propylamino)tetralin derivatives) and BBB transport <i>in vitro</i> and distribution to the brain <i>in vivo.</i> Assays (HPLC-based) were set up or developed for determination of the racemates and the pure enantiomers (chiral column) of drugs in plasma and brain tissue. BBB transport was assessed <i>in vitro</i> using bovine brain endothelial cells cocultured with rat astrocytes. The physicochemical constants (log P, pKa) and plasma protein binding were determined. Pindolol, propranolol and several tetralines accumulated over time in brain tissue. For pindolol and propranolol, but not for most tetralins, the distribution to the brain was stereoselective, (<i>S</i>)>(<i>R</i>). Pretreatment with verapamil, an inhibitor of drug efflux <i>via</i> P-glycoprotein, differentially decreased the brain/plasma ratios of the enantiomers of pindolol and propranolol, indicating that verapamil may also inhibit an influx transport mechanism. <i>In vitro</i> results with racemic pindolol, propranolol and tetralins showed no differences in BBB transport between the enantiomers. A more rapid apical to basolateral transport (influx) <i>vs</i>. the basolateral to apical (efflux) transport of propranolol (not pindolol) and most tetralins <i>in vitro</i> indicated active transport across the BBB. </p><p>In conclusion, the combined <i>in vivo</i> and <i>in vitro</i> results are consistent with active transport of the studied compounds across the BBB rather than passive diffusion due to their lipophilicity. Some, but not all, chiral drugs are stereoselectively distributed to the brain. Stereoselective plasma protein binding or stereoselective transport across brain endothelial cells does not seem to explain the stereoselective accumulation of pindolol and propranolol. The stereochemical configuration of compounds contributes to their pharmacokinetic as well as their pharmacodynamic uniqueness. The characteristics of the enantiomers of chiral compounds need to be determined empirically rather than based on generalizations from structural or physicochemical information.</p>

Delivery of drugs to the brain requires passage across the blood-brain barrier (BBB). Both for drugs already on the market and for new drugs under development, it is important to know to what extent a drug enters the CNS. Many drugs used clinically are racemic mixtures, i.e. equal parts of the (S)- and (R)-enantiomers. The present studies focus on the enantiomers and racemates of a number of 5-HT1A receptor agonists and antagonists (pindolol, propranolol, 8-OH-DPAT and other 8-substituted-2-(di-n-propylamino)tetralin derivatives) and BBB transport in vitro and distribution to the brain in vivo. Assays (HPLC-based) were set up or developed for determination of the racemates and the pure enantiomers (chiral column) of drugs in plasma and brain tissue. BBB transport was assessed in vitro using bovine brain endothelial cells cocultured with rat astrocytes. The physicochemical constants (log P, pKa) and plasma protein binding were determined. Pindolol, propranolol and several tetralines accumulated over time in brain tissue. For pindolol and propranolol, but not for most tetralins, the distribution to the brain was stereoselective, (S)&gt;(R). Pretreatment with verapamil, an inhibitor of drug efflux via P-glycoprotein, differentially decreased the brain/plasma ratios of the enantiomers of pindolol and propranolol, indicating that verapamil may also inhibit an influx transport mechanism. In vitro results with racemic pindolol, propranolol and tetralins showed no differences in BBB transport between the enantiomers. A more rapid apical to basolateral transport (influx) vs. the basolateral to apical (efflux) transport of propranolol (not pindolol) and most tetralins in vitro indicated active transport across the BBB. In conclusion, the combined in vivo and in vitro results are consistent with active transport of the studied compounds across the BBB rather than passive diffusion due to their lipophilicity. Some, but not all, chiral drugs are stereoselectively distributed to the brain. Stereoselective plasma protein binding or stereoselective transport across brain endothelial cells does not seem to explain the stereoselective accumulation of pindolol and propranolol. The stereochemical configuration of compounds contributes to their pharmacokinetic as well as their pharmacodynamic uniqueness. The characteristics of the enantiomers of chiral compounds need to be determined empirically rather than based on generalizations from structural or physicochemical information.

This study examines the performance outcomes of interorganizational trust using both qualitative and quantitative methods. Using qualitative data from four informants and drawing on the literature on trust, we define interorganizational trust and derive a model of its outcomes. Regression analysis results indicate that trust is negatively related to transaction costs and positively related to cooperation, conflict resolution, satisfaction, and risk taking tendency. Dependence has a moderating effect on trust while predicting satisfaction. Confirmatory factor analysis revealed four trust components: goodwill trust, competence trust, contractual trust, and distrust. Further exploratory analyses between trust components and trust outcomes indicate that distrust is not a mere opposite of trust, but is a distinct component of it. Goodwill trust, by itself, is not sufficient for the reduction in transaction costs / it must be supplemented by the reliability and ability of the other party in the exchange relationship to fulfill obligations. Competence trust alone is not sufficient for better conflict resolution due to the divergence in the expectations of the exchange partners. Only goodwill trust affects the tendency towards risk taking, since it reduces the perceived potential for opportunistic behavior. As a result of this study, the concept of trust and its outcomes were investigated in the Turkish context, different components of trust were identified, and these components were linked to the outcomes of trust. In addition, risk taking tendency was tested as an outcome of trust, which is an important contribution to the research in this field.

Il existe une littérature abondante sur les mécanismes cellulaires de résistance à la chimiothérapie, décrivant notamment les pompes d’efflux, les modifications des cibles (comme les topoisomérases) ou les altérations de l’apoptose. Peu de publications s’intéressent aux mécanismes de chimiorésistance liée au microenvironnement tumoral. Les agents anticancéreux doivent traverser l’interstitium tumoral pour atteindre toutes les cellules (dont les cellules hypoxiques éloignées des vaisseaux sanguins) à des concentrations suffisantes pour être létales. Les modèles de culture cellulaire en couches multiples ont permis de montrer la faible pénétration des molécules de chimiothérapie. Les techniques d’immunohistochimie permettent une mesure quantitative de la distribution de ces molécules à partir des vaisseaux sanguins. Nous avons évalué la pénétration de plusieurs inhibiteurs de topoisomérases : topotécan, doxorubicine, mitoxantrone et banoxantrone. Nous avons comparé la distribution de ces molécules à travers des tissus sains et des tissus tumoraux, démontrant la pénétration limitée des molécules de chimiothérapie dans les tumeurs. Par contre, nous avons montré que la banoxantrone pénètre rapidement et de façon uniforme. Cette pro-drogue est convertit en AQ4 (un inhibiteur de topoisomérase II ressemblant à la mitoxantrone) en condition d’hypoxie. La mitoxantrone cible les cellules bien oxygénées et AQ4 cible les cellules hypoxiques. Cette combinaison de traitement aboutit à une distribution intratumorale complémentaire et à une amélioration de l’activité antitumorale. Ainsi, optimiser la pénétration des chimiothérapies et/ou cibler spécifiquement les cellules hypoxiques peut contourner la chimiorésistance liée au microenvironnement tumoral. / There is a vast literature about mechanisms that lead to drug resistance of individual cancer cells, including drug export pumps, changes in expression of targets (such as topoisomerases) or alterations in apoptosis. A smaller number of publications has drawn attention to causes of drug resistance that depend on the solid tumour microenvironment. Drugs must penetrate the extra-vascular space to reach all of the cancer cells (including cells far from blood vessels in hypoxic condition) in sufficient concentration to cause lethal toxicity. Model systems such as multilayered cell cultures provide direct evidence of poor drug penetration through tumour tissue. In vivo techniques using quantitative immunohistochemistry allow studying drug distribution as a function of distance from the nearest blood vessel. We have evaluated the penetration of several topoisomerase inhibitors: topotecan, doxorubicine, mitoxantrone and banoxantrone (AQ4N). We have compared the distribution of these drugs through normal and tumour tissue, demonstrating the limited perivascular distribution of conventional chemotherapies in tumour. We have also showed the rapid and uniform penetration of banoxantrone. This pro-drug is reduced to AQ4 (a topoisomérase II inhibitor of similar structure to mitoxantrone) under hypoxic condition. The targeting of mitoxantrone to oxygenated regions and AQ4 to hypoxic tumour regions resulted in effective drug exposure over the entire tumour and increased tumour growth delay compared with either drug alone. Improving drug penetration and/or targeting hypoxic tumour cells may overcome chemoresistance due to the tumour microenvironment.

Objetivos: Conhecer a satisfação e a percepção da equipe de enfermagem usuária dos dispensários eletrônicos com relação a estes equipamentos e adaptar transculturalmente o instrumento ISMP Medication Safety Self Assessment® for Automated Dispensing Cabinets para a realidade brasileira. Métodos: O estudo foi realizado em duas etapas. A primeira etapa consistiu de um estudo qualitativo, do tipo exploratório, através da realização de grupos focais com os técnicos de enfermagem e enfermeiros das unidades que possuem dispensários eletrônicos. Na segunda etapa foi realizado um estudo metodológico para tradução e validação do instrumento ISMP Medication Safety Self Assessment® for Automated Dispensing Cabinets através da realização das etapas de tradução por dois tradutores independentes, síntese das traduções, retrotradução, síntese da retrotradução, avaliação por especialistas e pré-teste. Resultados: Durante a realização dos grupos focais a equipe de enfermagem demonstrou estar satisfeita com o uso dos dispensários eletrônicos, necessitando de algumas adequações e melhorias no processo. As etapas de adaptação transcultural do instrumento foram realizadas obtendo-se um instrumento adaptado para a realidade brasileira que pode auxiliar no planejamento da implantação de dispensários eletrônicos. Faz-se necessária a realização de validação externa deste instrumento para utilização na realidade nacional. Conclusões: Neste estudo ficou evidente a satisfação dos usuários dos dispensários eletrônicos com o uso destes equipamentos e a importância de um planejamento adequado para a implantação de novas tecnologias. Demonstra-se a importância de um trabalho conjunto entre as equipes de farmácia e enfermagem na implantação e utilização de dispensários eletrônicos com foco na segurança do paciente. / Objectives: To know the satisfaction and perception of the user nursing staff of automated dispensing cabinets about this equipment and cross-culturally adapt the instrument ISMP Medication Safety Self Assessment® for Automated Dispensing Cabinets for the Brazilian reality. Methods: The study was conducted in two stages. The first stage consisted of a qualitative study, exploratory, by conducting focus groups with nursing technicians and nurses of the units that use automated dispensing cabinets. In the second stage it was carried out a methodological study for the translation and validation of the instrument ISMP Medication Safety Self Assessment® for Automated Dispensing Cabinets by performing the translation stages by two independent translators, synthesis of translations, back translation, synthesis of back translation, evaluation by experts and pretest. Results: During the course of the focus groups the nursing staff proved to be satisfied with the use of automated dispensing cabinets, requiring some adjustments and improvements in the process. The steps of cross-cultural adaptation of the instrument were carried out obtaining a tool that can assist in planning the implementation of automated dispensing cabinets adapted to the Brazilian reality. Conducting external validation of this instrument for use at the national reality is necessary. Conclusions: In this study it was evident the satisfaction of users of automated dispensing cabinets with the use of this equipment and the importance of proper planning for the deployment of new technologies. It demonstrates the importance of joint work between the pharmacy and nursing staff in the implementation and use of automated dispensing cabinets with a focus on patient safety.