Drug use evaluation of ipratropium bromide at two tertiary referral hospitals in Brisbane.

Objective: To assess the appropriateness of ipratropium bromide prescribing in two tertiary referral hospitals. Method: Criteria for optimal use were developed based on current literature and modified after consultation with respiratory physicians and clinical pharmacists. A prospective review of prescribing was performed over a 2-month period to assess conformity to these criteria. Results: Information was collected from 84 patients; 5% were receiving inhalers and 96% nebuliser therapy (one patient used both). 77% of patients (n = 65) had a principal diagnosis of chronic obstructive pulmonary disease, 14% (n = 12) asthma and 8% (n = 7) had neither diagnosis. 75% of patients were using ipratropium outside the guidelines. The major areas where the guidelines were not met were a lack of therapeutic justification, use of inappropriate doses, and use of an inappropriate delivery device. Feedback and educational interventions were designed and delivered based on the data obtained. Conclusions: There was widespread use of ipratropium outside the developed guidelines. Interventions in specific areas could lead to significant improvements in the use of this high cost drug

Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

Animal model to compare the effects of suture technique on cross-sectional compliance on end-to-side anastomoses.

OBJECTIVE: An animal model has been developed to compare the effects of suture technique on the luminal dimensions and compliance of end-to-side vascular anastomoses. METHODS: Carotid and internal mammalian arteries (IMAs) were exposed in three pigs (90 kg). IMAs were sectioned distally to perform end-to-side anastomoses on carotid arteries. One anastomosis was performed with 7/0 polypropylene running suture. The other was performed with the automated suture delivery device (Perclose/Abbott Labs Inc.) that makes a 7/0 polypropylene interrupted suture. Four piezoelectric crystals were sutured on toe, heel and both lateral sides of each anastomosis to measure anastomotic axes. Anastomotic cross-sectional area (CSAA) was calculated with: CSAA = pi x mM/4 where m and M are the minor and major axes of the elliptical anastomosis. Cross-sectional anastomotic compliance (CSAC) was calculated as CSAC=Delta CSAA/Delta P where Delta P is the mean pulse pressure and Delta CSAA is the mean CSAA during cardiac cycle. RESULTS: We collected a total of 1200000 pressure-length data per animal. For running suture we had a mean systolic CSAA of 26.94+/-0.4 mm(2) and a mean CSAA in diastole of 26.30+/-0.5 mm(2) (mean Delta CSAA was 0.64 mm(2)). CSAC for running suture was 4.5 x 10(-6)m(2)/kPa. For interrupted suture we had a mean CSAA in systole of 21.98+/-0.2 mm(2) and a mean CSAA in diastole of 17.38+/-0.3 mm(2) (mean Delta CSAA was 4.6+/-0.1 mm(2)). CSAC for interrupted suture was 11 x 10(-6) m(2)/kPa. CONCLUSIONS: This model, even with some limitations, can be a reliable source of information improving the outcome of vascular anastomoses. The study demonstrates that suture technique has a substantial effect on cross-sectional anastomotic compliance of end-to-side anastomoses. Interrupted suture may maximise the anastomotic lumen and provides a considerably higher CSAC than continuous suture, that reduces flow turbulence, shear stress and intimal hyperplasia. The Heartflo anastomosis device is a reliable instrument that facilitates performance of interrupted suture anastomoses.

Electrophysiological recording from Drosophila taste sensilla.

INTRODUCTION The chemical senses smell and taste, detect and discriminate an enormous diversity of environmental stimuli and provide fascinating but challenging models to investigate how sensory cues are represented in the brain. Important stimulus-coding events occur in peripheral sensory neurons, which express specific combinations of chemosensory receptors with defined ligand-response profiles. These receptors convert ligand recognition into spatial and temporal patterns of neural activity that are transmitted to and interpreted in central brain regions. Drosophila provides an attractive model to study chemosensory coding, because it possesses relatively simple peripheral olfactory and gustatory systems that display many organizational parallels to those of vertebrates. Moreover, virtually all of the peripheral chemosensory neurons are easily accessible for physiological analysis, as they are exposed on the surface of sensory organs in specialized sensory hairs called sensilla. In recent years, improvements in microscopy and instrumentation for electrode manipulation have opened up the much smaller Drosophila system to electrophysiological techniques, powerfully complementing many years of molecular genetic studies. As with most electrophysiological methods, there is probably no substitute for learning this technique directly from a laboratory in which it is already established. This protocol describes the basics of setting up the electrophysiology rig and stimulus delivery device, sample preparation, and performing and analyzing recordings of stimulus-evoked activity from Drosophila taste sensilla.

Tuotanto- ja pakkausmateriaalien varastojen nykytila ja kehittäminen lääkeannostelijoita valmistavassa tehtaassa

Diplomityön tarkoituksena oli selvittää lääkeannostelijoita valmistavan tehtaan materiaalivarastojen nykytila. Varaston nykytila-analyysi jaettiin pääoma- ja operatiivisen tehokkuuden arviointiin. Työssä haluttiin kartoittaa toimenpide-ehdotuksia varastonohjauksen tehostamiseksi. Diplomityön tarkoituksena oli myös lisätä avainhenkilöiden ymmärrystä koskien varastojen pidon vaikutuksia yrityksen liiketoimintaan. Varastojen nykytila voitiin kiteyttää suureen pääoman sitoutumiseen, hitaisiin kiertoaikoihin sekä tehokkaan työskentelyn kannalta liian pieniin ja ahtaisiin varastoihin. Kustannuksia ei ole otettu kokonaisuudessaan huomioon tilattaessa ja varastoitaessa materiaalia. Varaston hitaita kiertonopeuksia ei ole tunnistettu vaikuttajina yrityksen tulokseen ja kannattavuuteen. Jotta varastonohjaus- ja hankintaprosesseja voitaisiin tehostaa, pitäisi ostotoimintoihin tehdä muutoksia. Tilausrytmiä ja –määriä täytyisi harkita uudelleen, jotta voitaisiin vähentää varastoihin sitoutuvan pääoman määrää. Informaationvirtaa tehtaalla sekä organisaatiorajojen yli pitäisi parantaa, jotta voitaisiin vähentää kysynnän heilahteluja sekä siihen varautumista. Varmuusvarastojen pidosta saatavien korvausten olisi katettava koko materiaalin kiertoajan aikana syntyvät varastoinnin kustannukset.

Dispositivo de no reinhalación NRMASK, pruebas de eficacia, desempeño y seguridad

Objetivo del estudio: comparar las mediciones realizadas en el dispositivo de entrega de agente halogenado, con un modelo matemático donde se encontraron los valores ideales de fracción espirada de agente halogenado para cada evento. Diseño del estudio: diseño de tecnología. Lugar de desarrollo: salas de cirugía de un Hospital Universitario, Bogotá, Colombia. Intervenciones y medidas: luego de diseñar y ensamblar un circuito anestésico semiabierto tipo mascara facial con dos válvulas unidireccionales (una inspitratoria y otra espiratoria), se procedió a tomar las medidas de Concentración inspirada de sevofluorane, y fracción inspirada de oxigeno, con volúmenes espiratorios de 70 a 170 mL con intervalos de 10 mL, y con el dial de sevoflorane a 2, 2.2, 2.4, 2.6 vol%, los resultados consignados fueron comparados con los valores matemáticamente calculados para cada evento. Resultados: las mediciones realizadas en la máscara son concordantes con los cálculos realizados en el modelo matemático. La concentración espirada de sevoflorane es ligeramente superior en cada evento con respecto a lo encontrado en el modelo matemático, no es posible asegurar la no reinhalación con las mediciones realizadas.

Development, characterization and clinical use of a biodegradable composite scaffold for bone engineering in oro-maxillo-facial surgery

We have developed a biodegradable composite scaffold for bone tissue engineering applications with a pore size and interconnecting macroporosity similar to those of human trabecular bone. The scaffold is fabricated by a process of particle leaching and phase inversion from poly(lactide-co-glycolide) (PLGA) and two calcium phosphate (CaP) phases both of which are resorbable by osteoclasts; the first a particulate within the polymer structure and the second a thin ubiquitous coating. The 3-5 mu m thick osteoconductive surface CaP abrogates the putative foreign body giant cell response to the underlying polymer, while the internal CaP phase provides dimensional stability in an otherwise highly compliant structure. The scaffold may be used as a biomaterial alone, as a carrier for cells or a three-phase drug delivery device. Due to the highly interconnected macroporosity ranging from 81% to 91%, with macropores of 0.8 similar to 1.8 mm, and an ability to wick up blood, the scaffold acts as both a clot-retention device and an osteoconductive support for host bone growth. As a cell delivery vehicle, the scaffold can be first seeded with human mesenchymal cells which can then contribute to bone formation in orthotopic implantation sites, as we show in immune-compromised animal hosts. We have also employed this scaffold in both lithomorph and particulate forms in human patients to maintain alveolar bone height following tooth extraction, and augment alveolar bone height through standard sinus lift approaches. We provide a clinical case report of both of these applications; and we show that the scaffold served to regenerate sufficient bone tissue in the wound site to provide a sound foundation for dental implant placement. At the time of writing, such implants have been in occlusal function for periods of up to 3 years in sites regenerated through the use of the scaffold.

Modeling Small Molecule Elution From a Hydrogel using a Microfluidic Technique

Drug release from a fluid-contacting biomaterial is simulated using a microfluidic device with channels defined by solute-loaded hydrogel. In order to mimic a drug delivery device, a solution of poly(ethylene glycol) diacrylate (PEG-DA), solute, and photoinitiator is cured inside a microfluidic device with a channel through the center ofthe hydrogel. As water is pumped through the channel, solute diffuses out of the hydrogel and into the water. Channel sizes within the devices range from 300 µm to 1000 µm to simulate vessels within the body. The properties of the PEG hydrogel were characterizedby the extent of crosslinking, the swelling ratio, and the mesh size of the gel. The structure of the hydrogel was related to the UV exposure dosage and the initial water and solute content in the PEG-DA solution.

A Microfluidic Method to Measure Small Molecule Diffusion in Hydrogels

Drug release from a fluid-contacting biomaterial is simulated using a microfluidic device with a channel defined by solute-loaded hydrogel; as water is pumped through the channel, solute transfers from the hydrogel into the water. Optical analysis of in-situ hydrogels, characterization of the microfluidic device effluent, and NMR methods were used to find diffusion coefficients of several dyes (model drugs) in poly( ethylene glycol) diacrylate (PEG-DA) hydrogels. Diffusion coefficients for methylene blue and sulforhodamine 101 in PEG-DA calculated using the three methods are in good agreement; both dyes are mobile in the hydrogel and elute from the hydrogel at the aqueous channel interface. However, the dye acid blue 22 deviates from typical diffusion behavior and does not release as expected from the hydrogel. Importantly, only the microfluidic method is capable of detecting this behavior. Characterizing solute diffusion with a combination of NMR, optical and effluent methods offer greater insight into molecular diffusion in hydrogels than employing each technique individually. The NMR method made precise measurements for solute diffusion in all cases. The microfluidic optical method was effective for visualizing diffusion of the optically active solutes. The optical and effluent methods show potential to be used to screen solutes to determine if they elute from a hydrogel in contact with flowing fluid. Our data suggest that when designing a drug delivery device, analyzing the diffusion from the molecular level to the device level is important to establish a complete picture of drug elution, and microfluidic methods to study such diffusion can play a key role. (C) 2013 Elsevier B.V. All rights reserved.

Closing the gap between coil and balloon in the neurointerventional armamentarium? Initial clinical experience with a nitinol vascular occlusion plug

INTRODUCTION: The use of vascular plug devices for the occlusion of high-flow lesions is a relatively new and successful procedure in peripheral and cardiopulmonary interventions. We report on the use and efficiency of the Amplatzer vascular plug in a small clinical series and discuss its potential for occlusion of large vessels and high-flow lesions in neurointerventions. METHODS: Between 2005 and 2007 four patients (mean age 38.5 years, range 16-62 years) were treated with the device, in three patients to achieve parent artery occlusion of the internal carotid artery, in one patient to occlude a high-flow arteriovenous fistula of the neck. The application, time to occlusion, and angiographic and clinical results and the follow-up were evaluated. RESULTS: Navigation, positioning and detachment of the device were satisfactory in all cases. No flow-related migration of the plug was seen. The cessation of flow was delayed by a mean of 10.5 min after deployment of the first device. In the procedures involving vessel sacrifice, two devices had to be deployed to achieve total occlusion. No patient experienced new neurological deficits; the 3-month follow-up revealed stable results. CONCLUSION: The Amplatzer vascular plug can be adapted for the treatment of high-flow lesions and parent artery occlusions in the head and neck. In this small series the use of the devices was uncomplicated and safe. The rigid and large delivery device and the delayed cessation of flow currently limit the device's use in neurointerventions.

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination

Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types.

Controlled release of heparin from poly(epsilon-caprolactone) electrospun fibers

Sustained delivery of heparin to the localized adventitial surface of grafted blood vessels has been shown to prevent the vascular smooth muscle cell (VSMC) proliferation that can lead to graft occlusion and failure. In this study heparin was incorporated into electrospun poly(epsilon-caprolactone) (PCL) fiber mats for assessment as a controlled delivery device. Fibers with smooth surfaces and no bead defects could be spun from polymer solutions with 8% w/v PCL in 7:3 dichloromethane: methanol. A significant decrease in fiber diameter was observed with increasing heparin concentration. Assessment of drug loading, and imaging of fluorescently labeled heparin showed homogenous distribution of heparin throughout the fiber mats. A total of approximately half of the encapsulated heparin was released by diffusional control from the heparin/PCL fibers after 14 days. The fibers did not induce an inflammatory response in macrophage cells in vitro and the released heparin was effective in preventing the proliferation of VSMCs in culture. These results suggest that electrospun PCL fibers are a promising candidate for delivery of heparin to the site of vascular injury. (C) 2005 Elsevier Ltd. All rights reserved.

A cardiovascular occlusion method based on the use of a smart hydrogel

Smart hydrogels for biomedical applications are highly researched materials. However, integrating them into a device for implantation is difficult. This paper investigates an integrated delivery device designed to deliver an electro-responsive hydrogel to a target location inside a blood vessel with the purpose of creating an occlusion. The paper describes the synthesis and characterization of a Pluronic/methacrylic acid sodium salt electro-responsive hydrogel. Application of an electrical bias decelerates the expansion of the hydrogel. An integrated delivery system was manufactured to deliver the hydrogel to the target location in the body. Ex vivo and in vivo experiments in the carotid artery of sheep were used to validate the concept. The hydrogel was able to completely occlude the blood vessel reducing the blood flow from 245 to 0 ml/min after implantation. Ex vivo experiments showed that the hydrogel was able to withstand physiological blood pressures of > 270 mm·Hg without dislodgement. The results showed that the electro-responsive hydrogel used in this paper can be used to create a long-term occlusion in a blood vessel without any apparent side effects. The delivery system developed is a promising device for the delivery of electro-responsive hydrogels.

Using mobile device detection approaches to augment the accuracy of web delivery content

Recent studies of mobile Web trends show a continuous explosion of mobile-friendly content. However, the increasing number and heterogeneity of mobile devices poses several challenges for Web programmers who want to automatically get the delivery context and adapt the content to mobile devices. In this process, the devices detection phase assumes an important role where an inaccurate detection could result in a poor mobile experience for the enduser. In this paper we compare the most promising approaches for mobile device detection. Based on this study, we present an architecture for a system to detect and deliver uniform m-Learning content to students in a Higher School. We focus mainly on the devices capabilities repository manageable and accessible through an API. We detail the structure of the capabilities XML Schema that formalizes the data within the devices capabilities XML repository and the REST Web Service API for selecting the correspondent devices capabilities data according to a specific request. Finally, we validate our approach by presenting the access and usage statistics of the mobile web interface of the proposed system such as hits and new visitors, mobile platforms, average time on site and rejection rate.