Contrast enhanced computed tomography characterization of fluorodeoxygluocose-avid regional and non-regional lymph nodes in patients with suspicion of metastatic bladder cancer.

Objective: The objective of this study is to assess if size alone can predict the presence of metastatic disease within lymph nodes seen on contrast enhanced-computed tomography (CE-CT) in patients with suspicion of metastatic bladder cancer and also to evaluate the nodal distribution and morphological characteristics of fluorodeoxygluocose (FDG) avid lymph nodes on CE-CT.

Materials And Methods: A retrospective analysis from 2002 to 2009 was performed on patients with suspicion of recurrent disease undergoing restaging FDG-positron emission tomography (PET)/CT. Standardized uptake value (SUVmax) adjusted for lean body mass was recorded in abnormal lymph nodes in the abdominopelvic region.

Cellular bioenergetics is an important determinant of the molecular imaging signal derived from luciferase and the sodium-iodide symporter.

Rationale: Molecular imaging is useful for longitudinal assessment of engraftment. However, it is not known which factors, other than cell number, can influence the molecular imaging signal obtained from reporter genes.

Objective: The effects of cell dissociation/suspension on cellular bioenergetics and the signal obtained by firefly luciferase and human sodium-iodide symporter labeling of cardiosphere-derived cells were investigated.

Study of the impact of tissue density heterogeneities on 3-dimensional abdominal dosimetry: comparison between dose kernel convolution and direct Monte Carlo methods.

Unlabelled: Dose kernel convolution (DK) methods have been proposed to speed up absorbed dose calculations in molecular radionuclide therapy. Our aim was to evaluate the impact of tissue density heterogeneities (TDH) on dosimetry when using a DK method and to propose a simple density-correction method.

Methods: This study has been conducted on 3 clinical cases: case 1, non-Hodgkin lymphoma treated with (131)I-tositumomab; case 2, a neuroendocrine tumor treatment simulated with (177)Lu-peptides; and case 3, hepatocellular carcinoma treated with (90)Y-microspheres.

The evaluation of FDG-PET imaging for epileptogenic focus localization in patients with MRI positive and MRI negative temporal lobe epilepsy.

Introduction: We studied the contribution of interictal FDG-PET ([18 F] fluorodeoxyglucose-positron emission tomography) in epileptic focus identification in temporal lobe epilepsy patients with positive, equivocal and negative magnetic resonance imaging (MRI).

Methods: Ninety-eight patients who underwent surgical treatment for drug resistant temporal lobe epilepsy after neuropsychological evaluation, scalp video EEG monitoring, FDG-PET, MRI and/or long-term intracranial EEG and with >12 months clinical follow-up were included in this study. FDG-PET findings were compared to MRI, histopathology, scalp video EEG and long-term intracranial EEG monitoring.

A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of β-Secretase.

β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid.

Cardiac PET/CT misregistration causes significant changes in estimated myocardial blood flow.

Unlabelled: Misregistration of cardiac PET/CT data can lead to misinterpretation of regional myocardial perfusion. However, the effect of misregistration on the quantification of myocardial blood flow (MBF) has not been studied.

Methods: Cardiac (82)Rb-PET/CT scans of 10 patients with normal regional myocardial perfusion were analyzed.

Structure- and property-based design of aminooxazoline xanthenes as selective, orally efficacious, and CNS penetrable BACE inhibitors for the treatment of Alzheimer's disease.

A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human β-secretase inhibitors. These compounds exhibited good isolated enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy.

Promise and pitfalls of quantitative imaging in oncology clinical trials.

Quantitative imaging using computed tomography, magnetic resonance imaging and positron emission tomography modalities will play an increasingly important role in the design of oncology trials addressing molecularly targeted, personalized therapies. The advent of molecularly targeted therapies, exemplified by antiangiogenic drugs, creates new complexities in the assessment of response. The Quantitative Imaging Network addresses the need for imaging modalities which can accurately and reproducibly measure not just change in tumor size but changes in relevant metabolic parameters, modulation of relevant signaling pathways, drug delivery to tumor and differentiation of apoptotic cell death from other changes in tumor volume.

Hyaluronic acid-human blood hydrogels for stem cell transplantation.

Tissue engineering-based approaches have the potential to improve stem cell engraftment by increasing cell delivery to the myocardium. Our objective was to develop and characterize a naturally-derived, autologous, biodegradable hydrogel in order to improve acute stem cell retention in the myocardium. HA-blood hydrogels (HA-BL) were synthesized by mixing in a 1:1(v/v) ratio, lysed whole blood and hyaluronic acid (HA), whose carboxyl groups were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS).

Comparison and effectiveness of regadenoson versus dipyridamole on stress electrocardiographic changes during positron emission tomography evaluation of patients with hypertrophic cardiomyopathy.

Dipyridamole is the most common vasodilator used with positron emission tomography for the evaluation of patients with hypertrophic cardiomyopathy (HC). The aim of this study was to evaluate whether positron emission tomographic quantification of regional myocardial perfusion (rMP), myocardial blood flow (MBF), and coronary flow reserve are comparable between dipyridamole and the newer vasodilator regadenoson in HC. An additional aim was to evaluate the association between vasodilator-induced ST-segment depression on electrocardiography and myocardial flow in HC.

Noise considerations for PET quantification using maximum and peak standardized uptake value.

Unlabelled: In tumor response monitoring studies with (18)F-FDG PET, maximum standardized uptake value (SUV(max)) is commonly applied as a quantitative metric. Although it has several advantages due to its simplicity of determination, concerns about the influence of image noise on single-pixel SUV(max) persist. In this study, we measured aspects of bias and reproducibility associated with SUV(max) and the closely related peak SUV (SUV(peak)) using real patient data to provide a realistic noise context.

Interspecies differences in membrane-associated protease activities of thyrocytes and their relevance for thyroid cancer studies.

Background: To understand the role of proteases involved in human thyroid cancer progression and tissue invasion, thyrocytes from other species could potentially be used provided their characteristics are similar. It is not known whether dipeptidyl peptidase IV and aminopeptidase N activities, which are overexpressed in human thyroid cancer, are, as in human, also absent in normal thyrocytes of other species, making them suitable models for studies on the regulation of these proteases.

Methods: To assess the role of these proteases, activity was measured in thyroid tissue of human, mouse, rat, porcine, bovine and ovine origin.

Reviewing responsibilities and renewing relationships: an intervention with men on violence against women in India.

Violence against women is increasingly seen as a key women's rights issue in India. Some efforts to address it have started to engage men. The current study focuses on the impacts of Men's Action to Stop Violence Against Women (MASVAW), a network of men working on gender-based violence in the state of Uttar Pradesh, in India.

Design and synthesis of potent, orally efficacious hydroxyethylamine derived β-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.

We have previously shown that hydroxyethylamines can be potent inhibitors of the BACE1 enzyme and that the generation of BACE1 inhibitors with CYP 3A4 inhibitory activities in this scaffold affords compounds (e.g., 1) with sufficient bioavailability and pharmacokinetic profiles to reduce central amyloid-β peptide (Aβ) levels in wild-type rats following oral dosing.

Design and preparation of a potent series of hydroxyethylamine containing β-secretase inhibitors that demonstrate robust reduction of central β-amyloid.

A series of potent hydroxyethyl amine (HEA) derived inhibitors of β-site APP cleaving enzyme (BACE1) was optimized to address suboptimal pharmacokinetics and poor CNS partitioning. This work identified a series of benzodioxolane analogues that possessed improved metabolic stability and increased oral bioavailability. Subsequent efforts focused on improving CNS exposure by limiting susceptibility to Pgp-mediated efflux and identified an inhibitor which demonstrated robust and sustained reduction of CNS β-amyloid (Aβ) in Sprague-Dawley rats following oral administration.

Quantification of the spatial distribution of rectally applied surrogates for microbicide and semen in colon with SPECT and magnetic resonance imaging.

Aims: We sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection.

Methods: Eight subjects were dosed rectally with radiolabelled and gadolinium-labelled gels to simulate microbicide gel and seminal fluid.

PET/CT assessment of symptomatic individuals with obstructive and nonobstructive hypertrophic cardiomyopathy.

Unlabelled: Patients with obstructive hypertrophic cardiomyopathy (HCM) exhibit elevated left ventricular outflow tract gradients (LVOTGs) and appear to have a worse prognosis than those with nonobstructive HCM. The aim of this study was to evaluate whether patients with obstruction, compared with nonobstructive HCM, demonstrate significant differences in PET parameters of microvascular function.

Methods: PET was performed in 33 symptomatic HCM patients at rest and during dipyridamole stress (peak) for the assessment of regional myocardial perfusion (rMP), left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), and myocardial flow reserve (MFR).

Air pollutant exposure and preterm and term small-for-gestational-age births in Detroit, Michigan: long-term trends and associations.

Studies in a number of countries have reported associations between exposure to ambient air pollutants and adverse birth outcomes, including low birth weight, preterm birth (PTB) and, less commonly, small for gestational age (SGA). Despite their growing number, the available studies have significant limitations, e.g.

Distribution of cell-free and cell-associated HIV surrogates in the female genital tract after simulated vaginal intercourse.

Background: Rational development of drugs to prevent human immunodeficiency virus (HIV) transmission benefits from an understanding HIV distribution in the female genital tract after intercourse. This study describes HIV distribution using surrogates of cell-free and cell-associated HIV and semen.

Methods: Apheresis-derived, autologous, lymphocyte-rich cells radiolabeled with 3.

A phase I trial of erlotinib and concurrent chemoradiotherapy for stage III and IV (M0) squamous cell carcinoma of the head and neck.

Purpose: Erlotinib, an orally active selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has synergistic activity with radiation and with cisplatin. The EGFR is overexpressed in the majority of head and neck cancers. The primary objective of this phase I study was to determine the maximum-tolerated dose (MTD) of erlotinib in combination with low-dose daily cisplatin and radiotherapy.

Tumor dosimetry and response for 153Sm-ethylenediamine tetramethylene phosphonic acid therapy of high-risk osteosarcoma.

Unlabelled: (153)Sm-ethylenediamine tetramethylene phosphonic acid ((153)Sm-EDTMP) therapy for osteosarcoma is being investigated. In this study, we analyzed the influence of (153)Sm-EDTMP administered activity (AA), osteosarcoma tumor density, mass, and the shape of the tumor on absorbed dose (AD). We also studied the biologic implication of the nonuniform tumor AD distribution using radiobiologic modeling and examined the relationship between tumor AD and response.

Systemic administration of 3-bromopyruvate in treating disseminated aggressive lymphoma.

The Warburg hypothesis states that aggressive cancers obtain much of their adenosine triphosphate (ATP) by metabolizing glucose directly to lactic acid. As a result of its high tumor selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism, has been proposed as a specific anticancer agent. We investigated the effect of 3-BrPA in a mouse model of aggressive metastatic lymphoma.

Effect of patient arm motion in whole-body PET/CT.

Unlabelled: Arm motion during whole-body PET/CT acquisition is not uncommon and can give rise to striking cold artifacts on PET images. We investigated the mechanisms that underlie these artifacts and proposed a potential solution.

Methods: A phantom experiment based on 5 clinical cases of suspected arm motion was designed.

[Perioperative anaphylaxis caused by rocuronium allergy in a child].

During the induction of anesthesia for strabismus correction, a six-year-old boy suffered anaphylaxis with hypotension. Midazolam, propofol, sufentanil, rocuronium, dexamethasone and ibuprofen had been administered. The boy's history failed to reveal any drug allergies.

Poly(ADP-ribose) polymerase inhibitors combined with external beam and radioimmunotherapy to treat aggressive lymphoma.

Purpose: To assess the possible radiosensitizing capabilities of two different poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam and I-tositumomab in a non-Hodgkin's lymphoma cell line.

Methods And Materials: Epstein-Barr virus-infected human Raji lymphoma cells with lentivirally transfected green fluorescent protein and luciferase in log-phase growth were incubated with various doses of AZD-2281 and ABT-888 24 h before external beam radiation exposure. A 500 nmol/l concentration of AZD-2281 and ABT-888 was used to assess the growth curve of Raji lymphoma cells over 5 days.