Disseminated tuberculosis associated with deficient interleukin-23/tyrosine kinase 2 signalling.

Tuberculosis (TB) remains a significant cause of morbidity and mortality globally. The disseminated form of the disease has a worse prognosis and is commonly associated with primary and acquired immunodeficiency states such as HIV/AIDS, post-organ transplant and malnutrition. However, disseminated TB in the context of isolated impaired cellular responses to interleukin (IL)-23 due to tyrosine kinase 2 (TYK2) deficiency has been rarely reported.

BTS clinical statement for the diagnosis and management of ocular tuberculosis.

The BTS clinical statement for the diagnosis and management of ocular tuberculosis (TB) draws on the expertise of both TB and and ophthalmic specialists to outline the current understanding of disease pathogenesis, diagnosis and management in adults. Published literature lacks high-quality evidence to inform clinical practice and there is also a paucity of data from animal models to elucidate mechanisms of disease. However, in order to improve and standardise patient care, this statement provides consensus points with the currently available data and agreed best practice.

Endothelin ETA receptors predominate in chronic thromboembolic pulmonary hypertension.

Aims: Endothelin-1 levels are raised in chronic thromboembolic pulmonary hypertension. Our aim in this study was to identify the presence of endothelin receptors in patients with CTEPH by analysing tissue removed at pulmonary endarterectomy.

Main Methods: Pulmonary endarterectomy tissue cross-sections were analysed using autoradiography with [(125)I]-ET-1 using ligands selective for ETA or ETB to determine sub-type distribution.

Maximal cardiac output determines 6 minutes walking distance in pulmonary hypertension.

Purpose: The 6 minutes walk test (6MWT) is often shown to be the best predictor of mortality in pulmonary hypertension (PH) probably because it challenges the failing heart to deliver adequate cardiac output. We hypothesised that the 6MWT elicits maximal cardiac output as measured during a maximal cardiopulmonary exercise testing (CPET).

Methods: 18 patients with chronic thromboembolic pulmonary hypertension (n = 12) or pulmonary arterial hypertension (n = 6) and 10 healthy subjects performed a 6MWT and CPET with measurements of cardiac output (non invasive rebreathing device) before and directly after exercise.

Evidence for the involvement of type I interferon in pulmonary arterial hypertension.

Rationale: Evidence is increasing of a link between interferon (IFN) and pulmonary arterial hypertension (PAH). Conditions with chronically elevated endogenous IFNs such as systemic sclerosis are strongly associated with PAH. Furthermore, therapeutic use of type I IFN is associated with PAH.

Clinical review: tuberculosis on the intensive care unit.

Rates of tuberculosis (TB) are increasing in most west European nations. Patients with TB can be admitted to an ICU for a variety of reasons, including respiratory failure, multiorgan failure and decreased consciousness associated with central nervous system disease. TB is a treatable disease but the mortality for patients admitted with TB to an ICU remains high.

A ''not so superficial" skin infection in a patient with diabetes.

A woman in her 60s with type 2 diabetes presented with a 4-week history of a rash on her chest wall, flu-like symptoms and a red right eye. On examination, there was a cellulitic rash over the right chest wall, breast and neck and a hypopyon in the right eye. Chest x-ray demonstrated right upper lobe opacification, with subsequent CT and MRI revealing bilateral collections at the lung apices, and a possible permeative bone destruction of the manubrium, respectively.

(18)FDG PET imaging can quantify increased cellular metabolism in pulmonary arterial hypertension: A proof-of-principle study.

The past decade has seen increased application of 18-flurodeoxyglucose positron emission tomography ((18)FDG-PET) imaging to help diagnose and monitor disease, particularly in oncology, vasculitis and atherosclerosis. Disordered glycolytic metabolism and infiltration of plexiform lesions by inflammatory cells has been described in idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that increased (18)FDG uptake may be present in the lungs, large pulmonary arteries and right ventricle of patients with pulmonary hypertension, and that this uptake would be related to markers of immune activation.

Isolated large vessel pulmonary vasculitis as a cause of chronic obstruction of the pulmonary arteries.

Isolated pulmonary artery involvement by large vessel vasculitis is rare. This case report describes two patients with large vessel pulmonary vasculitis initially thought to have chronic thromboembolic pulmonary hypertension who had their diagnosis revised following pulmonary endarterectomy surgery. Advances in imaging techniques such as positron emission tomography and magnetic resonance imaging have permitted complementary radiological methods of diagnosis and follow up of large vessel disease and these are discussed in conjunction with the immunosuppressive and operative management of these patients.

Pulmonary hypertension, nitric oxide and nitric oxide-releasing compounds.

Nitric oxide (NO) is an important molecule in the mammalian cardiovascular system and the elucidation of its biological role has led to the awarding of a Nobel prize in medicine. There have been many significant discoveries in NO biology over the past two decades and translation of these developments from bench to bedside has allowed an explosion of therapies for pulmonary hypertension. This article provides an overview of the NO pathway in the pulmonary circulation in maintenance of normal vascular tone as well as its dysregulation in pulmonary hypertension, and a discussion of therapies based on inhaled NO or manipulation of its downstream signaling pathways.