Current and emerging imaging techniques in the diagnosis and assessment of pulmonary hypertension

Introduction: Pulmonary hypertension (PH) is a challenging condition to diagnose and treat. Over the last two decades, there have been significant advances in therapeutic approaches and imaging technologies. Current guidelines emphasize the importance of cardiac catheterization; however, the increasing availability of non-invasive imaging has the potential to improve diagnostic rates, whilst providing additional information on patient phenotypes. Areas covered: This review discusses the role of imaging in the diagnosis, prognostic assessment and follow-up of patients with PH. Imaging methods, ranging from established investigations (chest radiography, echocardiography, nuclear medicine and computerized tomography (CT)), to emerging modalities (dual energy CT, magnetic resonance imaging (MRI), optical coherence tomography and positron emission tomography (PET)) are reviewed. The value and limitations of the clinical utility of these imaging modalities and their potential clinical application are reviewed. Expert commentary: Imaging plays a key role in the diagnosis and classification of pulmonary hypertension. It also provides valuable prognostic information and emerging evidence supports a role for serial assessments. The authors anticipate an increasing role for imaging in the pulmonary hypertension clinic. This will reduce the need for invasive investigations, whilst providing valuable insights that will improve our understanding of disease facilitate a more targeted approach to treatment

Pathways for outpatient management of venous thromboembolism in a UK centre.

It has become widely recognised that outpatient treatment may be suitable for many patients with venous thromboembolism. In addition, non-vitamin K antagonist oral anticoagulants that have been approved over the last few years have the potential to be an integral component of the outpatient care pathway, owing to their oral route of administration, lack of requirement for routine anticoagulation monitoring and simple dosing regimens. A robust pathway for outpatient care is also vital; one such pathway has been developed at Sheffield Teaching Hospitals in the UK. This paper describes the pathway and the arguments in its favour as an example of best practice and value offered to patients with venous thromboembolism. The pathway has two branches (one for deep vein thrombosis and one for pulmonary embolism), each with the same five-step process for outpatient treatment. Both begin from the point that the patient presents (in the Emergency Department, Thrombosis Clinic or general practitioner's office), followed by diagnosis, risk stratification, treatment choice and, finally, follow-up. The advantages of these pathways are that they offer clear, evidence-based guidance for the identification, diagnosis and treatment of patients who can safely be treated in the outpatient setting, and provide a detailed, stepwise process that can be easily adapted to suit the needs of other institutions. The approach is likely to result in both healthcare and economic benefits, including increased patient satisfaction and shorter hospital stays

Diffusion-weighted imaging with calculated apparent diffusion coefficient of enhancing extra-axial masses.

BACKGROUND AND PURPOSE: Sometimes intracranial contrast-enhancing tumors like meningiomas, metastases, lymphomas, and schwannomas can mimic each other. It was the aim of the present study to investigate if intracranial contrast-enhancing lesions can be reliably differentiated with the help of diffusion-weighted imaging with calculated apparent diffusion coefficients (ADCs). METHODS: 29 patients (ages ranging from 22 to 82 years, mean age of 58.6 years) were included. Nine meningiomas, 7 metastases, 6 lymphomas, and 7 schwannomas were investigated. The ADC value in the lesions and in the perifocal edema was analyzed. RESULTS: For the lymphomas, the authors measured the lowest ADC values in the contrast-enhancing part (0.59 +/- 0.09 . 10(-3) mm2/sec). The meningiomas showed a mean ADC value of 0.98 +/- 0.18 . 10(-3) mm2/sec. The schwannomas and metastases showed higher ADC values of 1.33 +/- 0.28 . 10(-3) mm2/sec and 1.05 +/- 0.20 . 10(-3) mm2/sec. The authors saw a statistically significant difference between lymphomas, meningiomas, and metastases concerning the ADC values in the contrast-enhancing part. CONCLUSIONS: In spite of a small sample size and partly a wide range of values, the authors found statistically significant differences between meningiomas, metastases, and lymphomas concerning ADC values. Nevertheless, a differentiation of these lesions only with the help of ADC values seems questionable

The 3-D conformational shape of N-naphthyl-cyclopenta[d]pyrimidines affects their potency as microtubule targeting agents and their antitumor activity

A series of methoxy naphthyl substituted cyclopenta[d]pyrimidine compounds, 4-10, were designed and synthesized to study the influence of the 3-D conformation on microtubule depolymerizing and antiproliferative activities. NOESY studies with the N,2-dimethyl-N-(6\u27-methoxynaphthyl-1\u27-amino)-cyclopenta[d]pyrimidin-4-amine (4) showed hindered rotation of the naphthyl ring around the cyclopenta[d]pyrimidine scaffold. In contrast, NOESY studies with N,2-dimethyl-N-(5\u27-methoxynaphthyl-2\u27-amino)-cyclopenta[d]pyrimidin-4-amine (5) showed free rotation of the naphthyl ring around the cyclopenta[d]pyrimidine scaffold. The rotational flexibility and conformational dissimilarity between 4 and 5 led to a significant difference in biological activities. Compound 4 is inactive while 5 is the most potent in this series with potent microtubule depolymerizing effects and low nanomolar IC values in vitro against a variety of cancer cell lines. The ability of 5 to inhibit tumor growth in vivo was investigated in a U251 glioma xenograft model. The results show that 5 had better antitumor effects than the positive control temozolomide and have identified 5 as a potential preclinical candidate for further studies. The influence of conformation on the microtubule depolymerizing and antitumor activity forms the basis for the development of conformation-activity relationships for the cyclopenta[d]pyrimidine class of microtubule targeting agents

Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents

A series of eleven 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines were designed and synthesized and their biological activities were evaluated. Synthesis involved the Gewald reaction to synthesize ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ring, and SNAr reactions. Compound 4 was 1.6-and ~7-fold more potent than the lead compound 1 in cell proliferation and microtubule depolymerization assays, respectively. Compounds 4, 5 and 7 showed the most potent antiproliferative effects (IC50 values \u3c 40 nM), while compounds 6, 8, 10, 12 and 13 had lower antiproliferative potencies (IC50 values of 53–125 nM). Additionally, compounds 4–8, 10 and 12–13 circumvented Pgp and βIII-tubulin mediated drug resistance, mechanisms that diminish the clinical efficacy of paclitaxel (PTX). In the NCI-60 cell line panel, compound 4 exhibited an average GI50 of ~10 nM in the 40 most sensitive cell lines. Compound 4 demonstrated statistically significant antitumor effects in a murine MDA-MB-435 xenograft model