Integration of cardiac energetics, function and histology from isolated rat hearts perfused with doxorubicin and doxorubicin-ol; a model for use in drug safety evaluations.

The isolated rat heart (Langendorff) assay combined with NMR spectroscopy and histology were used to elucidate functional, metabolic, and histological signs of cardiotoxicity resulting from acute exposure to clinically relevant concentrations of doxorubicin and its metabolite dox-ol. Doxorubicin blood concentrations and pharmacokinetic parameters were assessed following a clinically relevant dose of 2 mg/kg in order to select concentrations for isolated heart perfusions. Isolated rat hearts were exposed to 1 or 10 μM of doxorubicin or 0.

Effects of tyrosine kinase inhibitors on rat isolated heart function and protein biomarkers indicative of toxicity.

Introduction: Cardiac toxicity, manifested as diminished contractility, ischemic heart disease, and heart failure is a major issue in drug safety. Concerns revolve around targeted drugs (TKIs) where contractility effects were not anticipated. The ability to predict cardiac toxicity early would help to de-risk drugs in development and prepare physicians to manage risk in the clinic.

Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy.

The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor.

Computed tomography of corpus luteal cysts.

Objective: To describe the computed tomography (CT) features of corpus luteal cysts.

Methods: We retrospectively identified 10 patients with a diagnosis of corpus luteal cysts established by ultrasound who had also undergone contemporaneous CT. A single attending radiologist, without knowledge of other clinical or radiologic findings, recorded the morphologic features of the cysts based on the CT images.

High-resolution CT using MDCT: comparison of degree of motion artifact between volumetric and axial methods.

Objective: The purpose of this study was to compare the degree of motion artifact on high-resolution CT images obtained using volumetric and axial (nonvolumetric) CT methods.

Conclusion: Volumetric high-resolution CT is associated with significantly greater motion artifact compared with axial noncontiguous high-resolution imaging.

Developmental regulation of the A-type potassium-channel current in hippocampal neurons: role of the Kvbeta 1.1 subunit.

The rapidly inactivating A-type K+ current (IA) is prominent in hippocampal neurons; and the speed of its inactivation may regulate electrical excitability. The auxiliary K+ channel subunit Kvbeta 1.1 confers fast inactivation to Shaker-related channels and is postulated to affect IA.

Location, size, and distribution of mediastinal lymph node enlargement in chronic congestive heart failure.

Purpose: The purpose of this study is to identify the prevalence, location, and size of enlarged mediastinal lymph nodes in patients with chronic congestive heart failure and to correlate the presence of lymph node enlargement with cardiac ejection fraction.

Methods: Sixty-six consecutive, retrospectively identified patients underwent computer tomography (CT) imaging of the thorax as part of a routine work-up prior to cardiac transplantation from 1993 to 1996. CT images of 44 of these patients were independently examined by 3 radiologists for evidence of pulmonary edema, pleural effusions, and the presence, size, and location of lymph nodes >1 cm in short axis.

A herpes simplex viral vector expressing green fluorescent protein can be used to visualize morphological changes in high-density neuronal culture.

High-density cultures of mammalian neurons offer a model system for studies of brain development, but the morphological features of individual neurons is difficult to ascertain. We show that a herpes virus vector expressing a bioluminescent protein allows detailed morphometric analyses of living neurons in complex culture environments. Expression of enhanced green fluorescent protein (eGFP) was constitutively driven in neurons using the herpes simplex virus amplicon system.

Development and validation of personal monitoring methods for low levels of acrylonitrile in workplace atmosphere: II. Thermal desorption and field validation.

Thermal desorption is a more sensitive alternative to solvent desorption for the determination of acrylonitrile in air. A dual-bed collection tube (Tenax GC and Carbosieve B) was developed for collecting and concentrating low levels of acrylonitrile. Two thermal desorption techniques were evaluated for the recovery of acrylonitrile collected on the dual-bed tubes over a concentration range from 0.

Development and validation of personal monitoring methods for low levels of acrylonitrile in workplace atmosphere: I. Test atmosphere generation and solvent desorption methods.

The purpose of this study was to optimize monitoring methods and to investigate new technology for the determination of low levels of acrylonitrile (0.05 to 5 ppm) in workplace atmospheres. In the first phase of the study, a dynamic atmosphere generation system was developed to produce low levels of acrylonitrile in simulated workplace atmospheres.

Improved methodology for field validation of industrial hygiene monitoring methods.

During the development and validation of industrial hygiene monitoring methods in the laboratory, various parameters of collection, storage, and analysis are studied. It is not feasible, however, to study all the environmental variables in the laboratory, so field validation is necessary to detect problems which are specific to the actual work site. A statistical procedure to evaluate the field validation experiment is described together with the methodology necessary to perform these experiments and the equipment to facilitate these experiments.