The Use of Systemically Absorbed Drugs to Explore An In Vitro Bioequivalence Approach For Comparing Non-Systemically Absorbed Active Pharmaceutical Ingredients in Drug Products For Use in Dogs.

Purpose: Currently, for veterinary oral formulations containing one or more active pharmaceutical ingredient (API) that are not systemically absorbed and act locally within the gastrointestinal (GI) tract, the use of terminal clinical endpoint bioequivalence (BE) studies is the only option for evaluating product BE. This investigation explored the use of a totality of evidence approach as an alternative to these terminal studies.

Methods: Three formulations of tablets containing ivermectin plus praziquantel were manufactured to exhibit distinctly different in vitro release characteristics.

A method for the tribological assessment of oral pharmaceutical liquids.

Objective: Patient acceptance of pediatric formulations is critical to compliance and consequently therapeutic outcomes; thus, having an method to evaluate sensory perception of pharmaceutical products would be beneficial. The objective of this research is to develop a sensitive and reproducible tribological method to characterize pharmaceutical suspensions at low force and sliding speeds.

Methods: The discriminating potential of the method was examined using tribology profiles (coefficient of friction (COF) vs.

Utility of Films to Anticipate Effect of Drug Load and Polymer on Dissolution Performance from Tablets of Amorphous Itraconazole Spray-Dried Dispersions.

Because spray-dried dispersion (SDD) performance depends on polymer selection and drug load, time- and resource-sparing methods to screen drug/polymer combinations before spray drying are desirable. The primary objective was to assess the utility of films to anticipate the effects of drug load and polymer grade on dissolution performance of tablets containing SDDs of itraconazole (ITZ). A secondary objective was to characterize the solid-state attributes of films and SDDs to explain drug load and polymer effects on dissolution performance.

Delirium in Survivors of Cardiac Arrest Treated With Mild Therapeutic Hypothermia.

Background: Mild therapeutic hypothermia is recommended for comatose patients resuscitated from cardiac arrest. However, the prevalence of delirium and its associated risk factors have not been assessed in survivors of cardiac arrest treated with therapeutic hypothermia.

Objective: To determine the prevalence of and risk factors for delirium among survivors of cardiac arrest who were treated with therapeutic hypothermia.

Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.

Objectives: The aim of this study was to compare outcomes and coronary angiographic findings in post-cardiac arrest patients with and without ST-segment elevation myocardial infarction (STEMI).

Background: The 2013 STEMI guidelines recommend performing immediate angiography in resuscitated patients whose initial electrocardiogram shows STEMI. The optimal approach for those without STEMI post-cardiac arrest is less clear.

Higher achieved mean arterial pressure during therapeutic hypothermia is not associated with neurologically intact survival following cardiac arrest.

Introduction: To determine if higher achieved mean arterial blood pressure (MAP) during treatment with therapeutic hypothermia (TH) is associated with neurologically intact survival following cardiac arrest.

Methods: Retrospective analysis of a prospectively collected cohort of 188 consecutive patients treated with TH in the cardiovascular intensive care unit of an academic tertiary care hospital.

Results: Neurologically intact survival was observed in 73/188 (38.

Effectiveness of mild therapeutic hypothermia following cardiac arrest in adult patients with congenital heart disease.

Mild therapeutic hypothermia (TH) is an established therapy to improve survival and reduce neurologic injury after cardiac arrest. Adult patients with congenital heart disease (ACHD) are at increased risk of sudden cardiac death. The use of TH in this population has not been extensively studied.

Early bispectral index and sedation requirements during therapeutic hypothermia predict neurologic recovery following cardiac arrest.

Objectives: To test the hypothesis that low bispectral index scores and low sedative requirements during therapeutic hypothermia predict poor neurologic outcome.

Design: Observational study of a prospectively collected cohort.

Setting: Cardiovascular ICU.

Hereditary hemochromatosis: missed diagnosis or misdiagnosis?

Background: Hereditary hemochromatosis is a disorder that can cause iron overload and organ damage. Hereditary hemochromatosis is characterized by mutations in the HFE gene. HFE C282Y homozygotes and compound heterozygotes (C282Y/H63D) are at risk of developing manifestations of hemochromatosis.

Sequential moderate coronary artery fistula and moderate coronary artery stenosis causing ischemia demonstrated by fractional flow reserve and relieved following percutaneous coronary intervention.

Coronary artery fistulae are rare anomalous connections arising from the coronary circulation. We report a case of anterior wall myocardial ischemia caused by the combination of sequential coronary-to-pulmonary artery fistula and moderate (50-60%) stenosis of the left anterior descending coronary artery. Ischemia was demonstrated by myocardial stress perfusion imaging as well as fractional flow reserve.

A history of smoking is associated with improved survival in patients treated with mild therapeutic hypothermia following cardiac arrest.

Objectives: To assess the association between smoking and survival with a good neurologic outcome in patients following cardiac arrest treated with mild therapeutic hypothermia (TH).

Methods: We conducted a retrospective observational study of a prospectively collected cohort of 188 consecutive patients following cardiac arrest treated with TH between May 2007 and January 2012. Smoking status was retrospectively collected via chart review and was classified as "ever" or "never".

Early cardiac catheterization is associated with improved survival in comatose survivors of cardiac arrest without STEMI.

Aim: To determine if early cardiac catheterization (CC) is associated with improved survival in comatose patients who are resuscitated after cardiac arrest when electrocardiographic evidence of ST-elevation myocardial infarction (STEMI) is absent.

Methods: We conducted a retrospective observational study of a prospective cohort of 754 consecutive comatose patients treated with therapeutic hypothermia (TH) following cardiac arrest.

Results: A total of 269 (35.

Hyperoxia is associated with increased mortality in patients treated with mild therapeutic hypothermia after sudden cardiac arrest.

Objective: To determine whether higher levels of PaO2 are associated with in-hospital mortality and poor neurological status at hospital discharge in patients treated with mild therapeutic hypothermia after sudden cardiac arrest.

Design: Retrospective analysis of a prospective cohort.

Patients: A total of 170 consecutive patients treated with therapeutic hypothermia in the cardiovascular care unit of an academic tertiary care hospital.

Implementation of a standardized pathway for the treatment of cardiac arrest patients using therapeutic hypothermia: "CODE ICE".

Out-of-hospital cardiac arrest is common and is associated with high mortality. The majority of in-hospital deaths from resuscitated victims of cardiac arrest are due to neurologic injury. Therapeutic hypothermia (TH) is now recommended for the management of comatose survivors of cardiac arrest.

Long-term treatment with rituximab of autoimmune autonomic ganglionopathy in a patient with lymphoma.

Objective: To report on the response to therapy in a patient with autoimmune autonomic ganglionopathy with a high titer of an autoantibody directed against the α-3 subunit of the nicotinic acetylcholine receptor (nAChR) of the autonomic ganglia.

Design: Case report.

Setting: University-based referral center for autonomic dysfunction.

Dissolution test development for complex veterinary dosage forms: oral boluses.

Fundamental aspects of electrolyte chemistry were used to design an appropriate dissolution medium with the capacity to maintain sink conditions throughout the test. Dissolution of various bolus dosage forms was studied using USP Apparatus II at various stirring speeds. Complete dissolution of each drug in the designed medium was achieved, and there is evidence that such a dissolution test could be discriminating.

Stability of bioreductive drug delivery systems containing melphalan is influenced by conformational constraint and electronic properties of substituents.

The stability of bioreductive drug delivery systems (TDDS) was monitored at various pH values and in the presence of glutathione (GSH). Results suggest that steric hindrance due to conformational constraint in TDDS led to an increase in stability of TDDS toward nucleophilic degradation under aqueous conditions. The electronic properties of substituents influenced TDDS stability at different pH values and in the presence of GSH.

Design and manufacture of a zero-order sustained-release pellet dosage form through nonuniform drug distribution in a diffusional matrix.

A theoretical basis is presented for the design of dosage forms containing a drug which is initially distributed throughout a noneroding diffusional matrix in a nonuniform manner, for the purpose of achieving zero-order release. Modeling of these dosage forms is based on Higuchi's square root of time diffusional model. Derivations of theoretical drug release profiles for both flat slab and spherical geometry are included.

Absorption and disposition of colloidal drug delivery systems. I. High-performance liquid chromatographic (HPLC) analysis of a cyclosporin emulsion.

The amount of cyclosporin A in an oil-in-water emulsion drug delivery system was determined by HPLC. The direct extraction and analysis of an intact emulsion were compared to the analysis of a cracked emulsion and an olive oil solution of the drug. The intra- and interday variability for the intact emulsion was less than 10% from 35 to 150 micrograms/ml, with recovery of 94%.

Physicochemical characteristics of ferric adriamycin complexes.

Ferric ions and adriamycin in solution interact to form complexes that can yield colloidal and flocculant mixtures. At high concentrations (Fe3+ greater than or equal to 10(-4) M, adriamycin greater than or equal to 10(-5) M) an absorption appears at 600 nm, indicating colloid formation, which is directly responsive to concentrations of the reactants. Evidence from dilution experiments by spectral analysis, ultracentrifugation, titration, and filtration indicate that phase transition that is sensitive to pH and time occurs with iron-adriamycin complexes to yield flocculated drug.

Translocation of cytosol protein kinase into nuclei and the induction of tyrosine hydroxylase in NBD-2 neuroblastoma cells.

Exposure of neuroblastoma cells (NBD-2) to 8-bromo-adenosine 3',5'-cyclic monophosphate (0.2-1.0 mM) (8-Br-cAMP) for 15 min caused a long term increase in the Vmax of tyrosine-3-monooxygenase activity (TH) beginning about 1 day after 8-Br-cAMP application.

Soluble and membrane-bound protein kinases in newborn and mature rat brain.

We studied the developmental changes of soluble and membrane-bound protein kinases (EC 2.7.1.

Application of immersional calorimetry to investigation of solid-liquid interactions: microcrystalline cellulose-water system.

A comprehensive characterization of the specific solid-liquid interaction for microcrystalline cellulose and water is presented. The procedure consisted of a conjoint vapor adsorption and immersional wetting experiment. The following information was obtained with respect to the solid.