Alexandra M. Nanzer

Regulatory T cells, inflammation and the allergic response-The role of glucocorticoids and Vitamin D.

Regulatory T cells (TRegs) play a central role in the maintenance of peripheral tolerance. They prevent inappropriate immune responses to ubiquitous allergens in healthy individuals, and contribute to the maintenance of immune homeostasis in the airways. Both Foxp3+ and IL-10+ TReg have been implicated in these functions. Glucocorticoids represent the mainstay of treatment for asthma and other allergic conditions, and evidence that steroids influence TReg function will be reviewed. Growing bodies of epidemiological and immunological data suggest a role for endogenous Vitamin D in immune regulation. This review will discuss the role of glucocorticoids and Vitamin D, and their potential interactions in promoting tolerance in the context of allergic disease and asthma.

PPAR-gamma expression in pituitary tumours and the functional activity of the glitazones: evidence that any anti-proliferative effect of the glitazones is independent of the PPAR-gamma receptor

Objectiveu2002 u2002It has been reported that both normal pituitary and pituitary tumours express PPAR‐γ, a nuclear hormone receptor, the expression being more abundant in pituitary tumours, and that this is the basis for the reported antiproliferative effects of the thiazolidinedione, rosiglitazone, in animal models. However, the mechanisms for the responsivity to rosiglitazone have remained unclear.

Role of Regulatory Factors in Pituitary Tumour Formation

The molecular basis of pituitary tumorigenesis remains controversial, but there are two major theories which have been subject to most investigation: hormonal (usually hypothalamic factors) and/or growth factor overstimulation, or a molecular defect within the pituitary itself. It has been shown, for example, that excessive regulatory hormone stimulation can lead to an increased number of cells in the pituitary in various physiological or pathological states such as pregnancy (lactotrophs), untreated primary hypothyroidism (thyrotrophs and lactotrophs),primary hypoadrenalism (corticotrophs) and ectopic GHRH-secreting tumours (somatotrophs). Animal models also provide data that in the presence of excessive hypothalamic hormone stimulation, adenoma formation can occur. However, evidence in favour of the monoclonal nature of pituitary tumours argues for an intrinsic molecular defect as the primary initiating event in tumour formation. We review the various hormonal factors and their receptors effecting the different types of pituitary cells, such as CRH, AVP and cortisol feedback on corticotrophs; GHRH, Galpha PKA, somatostatin and GH and IGF feedback on somatotrophs; GnRH, LH/FSH, activin and oestrogen feedback on gonadotrophs; dopamine, oestrogen and prolactin feedback on lactotrophs; and TRH, TSH and thyroid hormone feedback on thyrotrophs. The monoclonal origin of adenomas makes it unlikely that hypothalamic factors could initiate pituitary transformation, but they could still create an environment where there is a higher chance that a possible causative tumorigenic mutation may occur in one (or several) of the overstimulated pituitary cells, or enhance the proliferation of an already-mutated cell.

Defining severe asthma – an approach to find new therapies

Asthma is a chronic inflammatory disease that has reached epidemic proportions worldwide. It is treatable in the majority of patients, but there is no cure. Moreover, a proportion of patients suffer from severe, difficult-to-control disease with daily symptoms and high morbidity, making it imperative that we continue to improve our understanding of the underlying mechanisms of this disease. Severe asthma is a heterogeneous condition. A systematic approach to identify specific asthma phenotypes, including clinical characteristics and inflammatory processes, is the first step toward individualized, logical therapy. This review focuses on the need to characterize severe asthma phenotypes and on novel, targeted molecular treatment options currently under development.

A deadly web

An 18-year-old patient with metabolic myopathy due to long-chain fatty acid coenzyme A dehydrogenase-deficiency1 ,2 presented with worsening positional dyspnoea. He had required invasive ventilation via tracheostomy 6u2005months earlier. Examination revealed respiratory distress, a prolonged inspiratory phase and …

Steps to better understand severe asthma in adults

Primary care plays an essential role in identifying and supporting a patient with undertreated or difficult to treat asthma.

Sniffing out a hidden cause of breathlessness.

A 78-year-old man presented with severe exertional dyspnoea. He suffered from mild chronic obstructive pulmonary disease, congestive cardiac failure and seropositive myasthaenia gravis. Clinical examination of his chest and heart were unremarkable but he had speech dyspnoea and was unable to count to 20 in a single breath. Consecutive sniff nasal inspiratory measurements (SNIP) fell from 55 to 33u2005cmu2005H2O and forced vital capacity (FVC) fell from 3.4 to 2.4u2005L. A diagnosis of myasthenic crisis was carried out and treatment with non-invasive ventilation, intravenous immunoglobulis and high-dose oral prednisolone was initiated. The patient responded well and was discharged following a short period of rehabilitation. A high index of suspicion and a careful clinical examination with the help of two simple bedside tests, FVC and SNIP, allowed correct and timely treatment of his condition.