Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series.

BACKGROUND: Ipilimumab (Yervoy; Bristol-Myers Squibb) is a novel fully humanised monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4, an immune checkpoint molecule, to augment anti-tumour T-cell responses. It is associated with significant immune-related side-effects including hypophysitis. AIM: We reviewed the clinical and biochemical characteristics of 10 patients with ipilimumab-induced hypophysitis (IH), and developed guidelines for the early detection and management of IH based on our experiences at three major teaching hospitals in Sydney. METHODS: All patients were evaluated at the Crown Princess Mary Cancer Centre and Department of Endocrinology, Westmead Hospital, Department of Endocrinology, Royal Prince Alfred Hospital, the Melanoma Institute Australia and Macarthur Cancer Therapy Centre, Campbelltown Hospital from 2010 to 2014. Relevant data were extracted by review of medical records. Main outcome measures included clinical features, hormone profile and radiological findings associated with IH, and presence of pituitary recovery. RESULTS: Ten patients were identified with IH. In four patients who underwent monitoring of plasma cortisol, there was a fall in levels in the weeks prior to presentation. The pituitary-adrenal and pituitary-thyroid axes were affected in the majority of patients, with the need for physiological hormone replacement. Imaging abnormalities were identified in five of 10 patients, and resolved without high-dose glucocorticoid therapy. To date, all patients remain on levothyroxine and hydrocortisone replacement, where appropriate. CONCLUSIONS: There is significant morbidity associated with development of IH. We suggest guidelines to assist with early recognition and therapeutic intervention.

Implementation of a dedicated hospital subcutaneous insulin prescription chart: effect on glycaemic control.

A dedicated subcutaneous insulin prescription chart incorporating glucose monitoring results, forced functions, and management guidelines was introduced to facilitate better hospital diabetes control. Point of care capillary blood glucose monitoring charts for 99 people with diabetes from the period before the introduction of the new chart, and 106 after its introduction were reviewed. A total of 12,649 blood glucose levels (BGLs) were collected for glucometric analysis. Following the introduction of the chart, there was an increase in the number of BGLs performed daily from 4.5 ± 1.2 to 4.9 ± 1.3 (p = 0.05). There was an increase in the proportion of BGLs within the ideal range of 4-9.9 mmol/L (51.8% vs. 54.1%, p = 0.01). There was a reduction in hypoglycaemic events (proportion of BGLs <4 mmol/L in the whole population decreased from 5.2% to 3.4% (p < 0.001), proportion of BGLs <4 mmol/L for each patient decreased from 5.6 ± 9.2% to 2.9 ± 5.4% (p = 0.01), proportion of days where patient had a BGL <4 mmol/L decreased from 17.6 ± 22.6% to 11.4 ± 18.8% (p = 0.03)), despite an increase in the use of supplemental insulin (14.2 ± 35.7 vs. 29.4 ± 51.4 u nits/patient, p = 0.02). We conclude that the use of a dedicated hospital subcutaneous insulin prescription chart can reduce hypoglycaemia and improve some measures of glycaemic control.

Sliding scale insulin: will the false idol finally fall?

Despite a lack of evidence that sliding scale insulin has any clinical benefit, and some evidence that it may even be detrimental, sliding scale insulin is still commonly prescribed in hospitals today. Adopting a proactive rather than a reactive approach to managing diabetes by the use of 'supplemental insulin', given in conjunction with either considered adjustments to the patient's regular anti-diabetic therapy or the provision of basal insulin, is a more effective and safer means of improving glycaemic control in hospital. There are now randomized trial data to support this approach. These data, together with the recognition that there is no evidence base for the use of sliding scale insulin, coupled with changes to insulin prescribing charts in Australia, should lead to the demise of sliding scale insulin use in hospital.

Mother to child transmission of diabetes mellitus: does gestational diabetes program Type 2 diabetes in the next generation?

AIM: Type 2 diabetes is frequently familial. Hyperglycaemia in pregnancy might act in addition to genetic factors to cause diabetes in the children of mothers with gestational diabetes mellitus (GDM). The first manifestation of this in female offspring is likely to be GDM in their own pregnancies. We compared the incidence of GDM in daughters of diabetic mothers and diabetic fathers to determine if in utero exposure to hyperglycaemia increased the risk of a diabetes-prone phenotype in offspring. METHODS: We analysed the outcome of a GDM screening programme in women with a family history of diabetes in their mother (n = 535), father (n = 566), both parents (n = 77) or neither (n = 4672). RESULTS: GDM was twice as common in the daughters of diabetic mothers (11%) than diabetic fathers (5%, P = 0.002). Women with two diabetic parents were no more likely to have GDM than women with only a diabetic mother. CONCLUSIONS: Genetic predisposition to GDM should be equally shared by daughters of diabetic mothers and fathers. An excess of maternal transmission of diabetes is consistent with an epigenetic effect of hyperglycaemia in pregnancy acting in addition to genetic factors to produce diabetes in the next generation.

A review of the role of inhaled corticosteroids in the treatment of acute asthma.

Systemic corticosteroids (CSs) are generally accepted as treatment for acute exacerbations of asthma. In contrast, inhaled corticosteroids (ICs) have been used for the long-term management of asthma but are not widely accepted for the treatment of asthma exacerbations. The onset of action of ICs in acute asthma begins in 1 hour. In patients with mild to moderate exacerbation, administration of high-dose ICs may decrease the need for hospital admission and the number of symptomatic days.

Approach to the difficult pediatric asthmatic.

Wheezing in infants and children presents a difficult differential diagnosis contingent on the presenting symptoms and age of the child. A determination of the anatomy of the lower airway, combined with allergic, infectious, and noninfectious irritants, is requisite to a complete evaluation. The intervention strategies to decrease wheezing and bronchial hyperresponsiveness may include both nonpharmacologic and pharmacologic management. The nonpharmacologic management of asthma in children is contingent on aggressive treatment of dietary protein sensitivity and strict environmental control. The treatment of bronchial hyperresponsiveness with pharmacologic intervention in infants and children is relegated to the optimal use of sodium cromoglycate and inhaled corticosteroid.

The erythrocyte insulin receptor response to insulin induced hypoglycaemia.

The response of the erythrocyte insulin receptor to a prolonged intravenous infusion of insulin has been measured in normal individuals during hypoglycaemia and when hypoglycaemia was prevented by the concurrent infusion of glucose. When euglycaemia was maintained, mean (+/- S.D.) specific insulin binding following the 5 hour insulin infusion was unchanged (6.9 +/- 2.1 to 6.65 +/- 2.2% bound per 2.25 X 10(9) erythrocytes). In the presence of mild hypoglycaemia, mean (+/- SD) specific insulin binding rose from 6.6 +/- 2.3 to 7.6 +/- 2.5% bound per 2.25 X 10(9) erythrocytes (P less than 0.01), after 5 hours. This increase was due to increased receptor affinity. It was not correlated with the increase in the concentration of any individual counter-regulatory hormone. Initial insulin receptor binding correlated strongly with the subsequent decline in plasma glucose concentration (r = 0.9527; P less than 0.01). Thus, acute hyperinsulinaemia, when associated with hypoglycaemia, does not result in downregulation of insulin receptors on erythrocytes but rather results in increased receptor binding. Consequently, the insulin receptor may not play an active role in protecting the individual against acute hypoglycaemia.

A semi-closed loop computer-assisted insulin infusion system. Hospital use for control of diabetes in patients.

Closed loop insulin delivery systems are impractical for widespread hospital use. Thus, a semi-closed loop computer-assisted insulin infusion system (CAIIS) was developed for the intravenous delivery of insulin. In its basal program, insulin delivery is determined by blood glucose measurements at intervals of three hours, while the open-loop meal program delivers 7.5 units over three hours. Control of meal-induced hyperglycaemia was satisfactory in six subjects with diabetes tested over two to four days, as was mean glycaemic control in the four non-obese subjects (7.1 +/- 0.8 mmol/L). To allow for variations in insulin sensitivity, an adjustment incrementing or decrementing the basal insulin delivery rate was applied according to the progressive blood glucose response. Empirical use of this adjustment resulted in good control (mean blood glucose level, 4.1-7.5 mmol/L) in 10 additional subjects with diabetes. This study demonstrates the potential usefulness of a semi-closed loop insulin infusion system.

Incidence of yeasts and influence of nystatin on their control in a group of burned children.

The incidence of yeasts in the oral cavity, rectum and urine of a population of 60 children hospitalized for treatment of acute second and third degree burns was approximately the same at the time of their admission as would be expected in healthy subjects. After hospitalization, the incidence of yeasts was reduced in the intestinal tract of acute patients who received nystatin orally but increased in the oral cavity. The majority of 418 yeasts were inhibited in vitro by less than 50 units/ml nystatin and only 6 yeasts were resistant to more than 3.1 mug/ml amphotericin B. The oral cavity appeared to act as a significant reservoir from which yeasts spread to cause or contribute to the deaths of 2 of 5 patients who died during the study.

Epidemiological tracing of Pseudomonas aeruginosa: antibiogram and serotyping.

The spread of a particular strain of Pseudomonas aeruginosa through a pediatric burn unit was monitored using serological typing and antibiotic susceptibility data.

Evaluation of three media for selective isolation of gram-positive bacteria from burn wounds.

Three media, phenylethyl alcohol blood agar, esculin-mannitol agar, and Columbia CN blood agar, were studied for the selective isolation of gram-positive bacteria from swab cultures of burn wounds.

Autograft rejection in acutely burned patients: relation to colonization by Streptococcus agalactiae.

The abrupt emergence of Streptococcus agalactiae in a population of acutely burned children is described in relationship to autograft rejection and the use of antibiotics to eradicate the organism from the patients.

Recognition of Citrobacter diversus in the clinical laboratory.

Characteristics and antibiotic sensitivities of Citrobacter diversus are described, and a minimal number of diagnostic tests to identify this organism in a clinical laboratory are suggested.