Adrenal crises: perspectives and research directions

Adrenal crises (AC) are life-threatening complications of adrenal insufficiency (AI). These events have an estimated incidence of between 5 and 10 ACs/100 patient years (PY) and are responsible for some of the increased morbidity and excess mortality experienced by patients with AI. Treatment involves urgent administration of IV/IM hydrocortisone and IV fluids. Patient education regarding preventive measures, such as increasing the dose of replacement therapy (“stress dosing”) when sick, using parenteral hydrocortisone as necessary and accessing medical assistance promptly, is still considered the best approach to averting the onset of an AC at times of physiological stress, most commonly an infection. However, recent evidence has demonstrated that patient education does not prevent many AC events and the reasons for this are not fully understood. Furthermore, there is no widely accepted definition of AC. Without a validated AC definition it is difficult to interpret variations in the incidence of AC and determine the effectiveness of preventive measures. This article aims to review the clinical aspects of AC events; to explore the epidemiology; and to offer a definition for an AC and to offer a perspective on future directions for research into AC prevention

Misleading information for consumers

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.David Torp

Can Green Walls Reduce Outdoor Ambient Particulate Matter, Noise Pollution and Temperature?

Green walls have previously demonstrated the capacity to reduce particulate matter (PM), noise pollution, and temperature conditions in manipulative experiments and computational models. There is, however, minimal evidence that green walls can influence ambient environmental conditions, especially taking into account the variable environmental conditions encountered in situ. The aim of this paper was to determine if green walls have a quantitative effect on ambient air quality in an urban environment. Ambient PM, noise, and temperature were recorded at 12 green wall and adjacent reference wall locations across a dense urban centre, over a 6-month period. The results indicated that PM levels and temperature did not significantly differ between the green wall and reference wall sites. Ambient noise at the green wall sites, however, was significantly lower than at the reference wall locations. It is suggested that mechanically assisted, or 'active' green wall systems may have a higher PM and temperature reduction capacity, and if so, they will be more valuable for installation in situ compared to standard passive systems, although this will require further research

Airborne particulate matter accumulation on common green wall plants

© 2019, © 2019 Taylor & Francis Group, LLC. In order to better design greening systems for effective particulate matter (PM) removal, it is important to understand the impact leaf traits have on PM deposition. There are however, inconsistences amongst the leaf traits that have previously been correlated with PM accumulation. The aim of this paper was to identify vegetation characteristics of green wall plants that were associated with the accumulation of particulate matter. To determine patterns associated with different leaf morphologies, eleven common ornamental plant species were sampled across 15 sites, over a 6 month duration. PM deposition was determined gravimetrically and its associated size fractions determined microscopically. Linear mixed models were used to identify statistical patterns relating to differences in PM deposition across plant species. PM deposition and the relative frequencies of particle size fractions were found to be statistically different among species, sites and months. Green wall plants were shown to be effective at PM accumulation as all of the assessed plant species had equivalent PM removal efficiency, with minimal evidence of influential leaf characteristics that could enhance PM removal

A descriptive study of adrenal crises in adults with adrenal insufficiency: increased risk with age and in those with bacterial infections

BACKGROUND: An adrenal crisis (AC) is a major cause of morbidity in hypoadrenal patients. However, there is little information available on the incidence and underlying causes of AC. METHODS: The aim of the present study was to describe the incidence of AC in New South Wales (NSW), Australia. Using a health department database, we selected de-identified data on all adults aged 20 years and over who were treated in any hospital in NSW between July1, 2000-June 30, 2011, with either a principal or secondary diagnosis of an AC. AC admission rates were calculated overall and within age categories. Frequencies of co-morbid diagnoses were analysed by age and sex groups. Poisson regression was used to assess the significance of the observed change in AC related admissions with age, while controlling for any secular trends by including year in the model. Chi sq tests were used to assess the differences in frequencies of categorical variables between groups. RESULTS: 824 patients received treatment for an AC in hospital, corresponding to 74.9 admissions/year. The majority (62.5%) of the patients were women and 52.8% were aged 60 years and over. Admission rates were significantly associated with increasing age (p < 0.0001). Patients in the 60-69, 70-79 and 80+ age groups had the highest average admission rates (24.3, 35.2 and 45.8 per million/year). A principal or secondary diagnosis of an infection was reported in 317 (38.5%) patients and infection was significantly associated with age (p < 0.0001) with older patients having the highest proportion of cases. The most frequent infections were pneumonia/lower respiratory tract infection in 85 (10.3%) cases and urinary tract infection (UTI) in 82 (10.0%) patients. Women experienced 78.0% of the reported UTIs. There were 125 patients (15.2%) with an AC and a record of gastroenteritis. Twenty-six (3.2%) patients died in hospital but, of these, only 4 deaths (0.9%) were recorded among the 467 patients with a principal diagnosis of an AC. CONCLUSIONS: The incidence of AC increases with age. Infections, especially bacterial infections, are associated with the incidence of ACs and this increases with age.R Louise Rushworth, and David J Torp

A case of Aromatase deficiency due to a novel CYP19A1 mutation

BACKGROUND Aromatase deficiency is a rare, autosomal recessive disorder of which there are approximately twenty four case reports. The aromatase enzyme is crucial in the biosynthesis of oestrogens from androgens. The phenotype of aromatase deficiency therefore is the result of androgen excess and oestrogen deficiency in the absence of normal aromatase activity. We report the first case of aromatase deficiency diagnosed in a female adult, at the age of 32 years, due to a novel duplication in the aromatase gene. CASE PRESENTATION A 32 year old Indian woman presented with a history of gender assignment difficulties at birth, lack of pubertal development, osteopaenia with fracture and tall stature. She had central obesity, impaired fasting glucose and borderline hypertension. Past examinations had revealed partial fusion of urethra and vagina, hypoplastic uterus and streak ovaries. The ovaries had been excised due to malignant risk after an initial clinical diagnosis of Turner’s syndrome with Y mosaicism. Oestrogen replacement commenced shortly after her fracture, in adulthood. After reassessment, aromatase deficiency was diagnosed. Sequencing of the coding exons of the aromatase (CYP19A1; OMIM 109710) gene revealed a novel 27-base duplication in exon 8 (p.Ala306_Ser314dup). This duplication, occurring within the aromatase α-helix, would be likely to disrupt substrate (androgen) and cofactor (protoporphyrin IX) binding, resulting in a lack of oestrogen synthesis. CONCLUSIONS We report a female with a phenotype compatible with aromatase deficiency which was unrecognised until adulthood and found she had a novel duplication in CYP19A1. Previous case reports have described polycystic ovarian morphology, especially in childhood and adolescence, but never streak ovaries. This may reflect the few adult cases reported, that aromatase deficiency in females is generally diagnosed at birth and oestrogen treatment commences decades earlier than occurred in our patient. Streak ovaries are consistent with the phenotype of the aromatase knockout mouse followed through adulthood. The observed clinical features of obesity, dysglycaemia and hypertension, are compatible with the observation that lack of a counterbalancing effect of oestrogen on tissue androgens until adulthood may lead to a metabolic syndrome phenotype. This report broadens the spectra of phenotype and genetic mutations underlying this rare disorder.Lucia Gagliardi, Hamish S Scott, Jinghua Feng, and David J Torp

Reversal of diabetes following transplantation of an insulin-secreting human liver cell line: Melligen cells

© 2015 American Society of Gene & Cell Therapy As an alternative to the transplantation of islets, a human liver cell line has been genetically engineered to reverse type 1 diabetes (TID). The initial liver cell line (Huh7ins) commenced secretion of insulin in response to a glucose concentration of 2.5 mmol/l. After transfection of the Huh7ins cells with human islet glucokinase, the resultant Melligen cells secreted insulin in response to glucose within the physiological range; commencing at 4.25 mmol/l. Melligen cells exhibited increased glucokinase enzymatic activity in response to physiological glucose concentrations, as compared with Huh7ins cells. When transplanted into diabetic immunoincompetent mice, Melligen cells restored normoglycemia. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that both cell lines expressed a range of β-cell transcription factors and pancreatic hormones. Exposure of Melligen and Huh7ins cells to proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) affected neither their viability nor their ability to secrete insulin to glucose. Gene expression (microarray and qRT-PCR) analyses indicated the survival of Melligen cells in the presence of known β-cell cytotoxins was associated with the expression of NF-κB and antiapoptotic genes (such as BIRC3). This study describes the successful generation of an artificial β-cell line, which, if encapsulated to avoid allograft rejection, may offer a clinically applicable cure for T1D

The epidemiology, healthcare and societal burden and costs of asthma in the UK and its member nations: analyses of standalone and linked national databases

Background There are a lack of reliable data on the epidemiology and associated burden and costs of asthma. We sought to provide the first UK-wide estimates of the epidemiology, healthcare utilisation and costs of asthma. Methods We obtained and analysed asthma-relevant data from 27 datasets: these comprised national health surveys for 2010–11, and routine administrative, health and social care datasets for 2011–12; 2011–12 costs were estimated in pounds sterling using economic modelling. Results The prevalence of asthma depended on the definition and data source used. The UK lifetime prevalence of patient-reported symptoms suggestive of asthma was 29.5 % (95 % CI, 27.7–31.3; n = 18.5 million (m) people) and 15.6 % (14.3–16.9, n = 9.8 m) for patient-reported clinician-diagnosed asthma. The annual prevalence of patient-reported clinician-diagnosed-and-treated asthma was 9.6 % (8.9–10.3, n = 6.0 m) and of clinician-reported, diagnosed-and-treated asthma 5.7 % (5.7–5.7; n = 3.6 m). Asthma resulted in at least 6.3 m primary care consultations, 93,000 hospital in-patient episodes, 1800 intensive-care unit episodes and 36,800 disability living allowance claims. The costs of asthma were estimated at least £1.1 billion: 74 % of these costs were for provision of primary care services (60 % prescribing, 14 % consultations), 13 % for disability claims, and 12 % for hospital care. There were 1160 asthma deaths. Conclusions Asthma is very common and is responsible for considerable morbidity, healthcare utilisation and financial costs to the UK public sector. Greater policy focus on primary care provision is needed to reduce the risk of asthma exacerbations, hospitalisations and deaths, and reduce costs

Regulation of human CD4+ T cell differentiation

Naive CD4+ T cells differentiate into specific effector subsets—Th1, Th2, Th17, and T follicular helper (Tfh)—that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4+ T cell differentiation in vitro. IL12Rβ1/TYK2 and IFN-γR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10–secreting cells. IL12Rβ1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4+ T cell effector function in the settings of infection, vaccination, or immune dysregulation