Fatal high-grade skull osteosarcoma 30 years following radiotherapy for Cushing's disease

Cushing’s disease is a rare disorder characterised by excessive cortisol production as a consequence of a corticotroph pituitary tumour. While the primary treatment is surgical resection, post-operative radiation therapy may be used in cases of ongoing inadequate hormonal control or residual or progressive structural disease. Despite improved outcomes, radiotherapy for pituitary tumours is associated with hypopituitarism, visual deficits and, rarely, secondary malignancies. We describe an unusual case of a 67-year-old female with presumed Cushing’s disease diagnosed at the age of 37, treated with transsphenoidal resection of a pituitary tumour with post-operative external beam radiotherapy (EBRT), ketoconazole for steroidogenesis inhibition, and finally bilateral adrenalectomy for refractory disease. She presented 30 years after her treatment with a witnessed generalised tonic-clonic seizure. Radiological investigations confirmed an extracranial mass infiltrating through the temporal bone and into brain parenchyma. Due to recurrent generalised seizures, the patient was intubated and commenced on dexamethasone and anti-epileptic therapy. Resection of the tumour revealed a high-grade osteoblastic osteosarcoma. Unfortunately, the patient deteriorated in intensive care and suffered a fatal cardiac arrest following a likely aspiration event. We describe the risk factors, prevalence and treatment of radiation-induced osteosarcoma, an exceedingly rare and late complication of pituitary irradiation. To our knowledge, this is the longest reported latency period between pituitary irradiation and the development of an osteosarcoma of the skull

Childhood trauma, posttraumatic stress disorder symptoms, early maladaptive schemas, and schema modes : a comparison of individuals with obesity and normal weight controls

Background: Previous research on the psychological mechanisms of obesity has primarily focused on acute psychopathology. However, there is limited literature on the role of more complex and entrenched psychological processes in weight management. The current study aimed to expand previous research by examining more enduring psychological constructs, including early maladaptive schemas (EMS), schemas modes, and trauma. Methods: Participants (N=125) comprised adults with normal weight (n=40) and obesity (n=85) from community and clinical settings in Australia. Eligible participants completed a series of self-report questionnaires via Research Electronic Data Capture (REDCap). Two, separate, one-way multivariate analysis of variance (MANOVA) were conducted to examine group differences on the outcome variables. Results: Findings indicated a significant effect of group on EMS and schema modes, V=.51, F(32, 92)=2.97, p<.001, partial η2=.51. Follow-up univariate tests revealed that individuals with obesity endorsed significantly more maladaptive schemas and schema modes and significantly less healthy schema modes than individuals with normal weight. In addition, results demonstrated a significant effect of group on childhood trauma and posttraumatic stress disorder (PTSD) symptoms, V=.19, F(6, 118)=4.70, p<.001, partial η2=.19. Subsequent univariate tests and chi-square analyses indicated that individuals with obesity reported significantly more childhood trauma as well as significantly more PTSD symptoms within the last month than normal weight individuals. Conclusion: This was the first study to compare EMS and schema modes in treatment-seeking individuals with obesity and normal weight controls using the short form version 3 of the Young Schema Questionnaire and revised, 118-item, Schema Mode Inventory. Overall, findings revealed that individuals with obesity experience more complex and enduring psychological difficulties than normal weight individuals. Increased assessment and targeted treatment of these underlying mental health concerns may contribute to a more holistic conceptualisation of obesity and could improve the long-term success of weight management

The psychometric properties of the grazing questionnaire in an obesity sample with and without binge eating disorder

Background: Despite being the first validated measure of grazing, the Grazing Questionnaire (GQ) has not been investigated among individuals with obesity. Therefore, the current study aimed to examine the psychometric properties of the GQ in an obesity sample. Methods: Participants (N=259) were recruited from community and clinical settings in Australia. The sample comprised adults with normal weight (n=77) and obesity (n=182). A portion of individuals with obesity (n=102) had binge eating disorder (BED). Data from the obesity group was examined to establish the factor structure, validity, and reliability of the GQ. A one-way ANOVA with planned contrasts was conducted to compare scores on the GQ across groups. Results: Confirmatory factor analysis revealed that the 2-factor model of the GQ was the best model ft for individuals with obesity. The GQ demonstrated high internal consistency, test–retest reliability over 3 months, and convergent and divergent validity. As hypothesised, the obesity group had significantly higher scores on the GQ than the normal weight group, while the obesity with BED group had significantly higher scores than the obesity without BED group. Conclusion: This was the first study to investigate the psychometric properties of the GQ in an obesity sample. Overall, findings indicated that the GQ is a psychometrically sound measure of grazing among individuals with obesity. These findings provide further support for two distinct subtypes of grazing and highlight the importance of increased assessment and management of grazing behaviours for individuals with obesity and eating disorders. Plain English summary: Maintaining a healthy weight is one of the greatest challenges for individuals with obesity. Certain eating patterns such as grazing may contribute to difficulties in weight management. Grazing is the repetitive and unplanned eating of small amounts of food that is not related to feeling hungry. Researchers and clinicians often use self-report questionnaires to measure grazing. However, the first validated questionnaire of grazing has not been investigated among individuals with obesity. Therefore, the goal of this study was to examine and validate the Grazing Questionnaire in individuals with obesity. Overall, our results showed that the Grazing Questionnaire is a valid and reliable self-report measure of grazing in individuals with obesity. Similar to previous research, we found that there are two subtypes of grazing. The first subtype involves continuous, unplanned eating. The second subtype is associated with a sense of loss of control over eating. We also found that people with obesity and binge eating disorder graze more than people with obesity that do not have binge eating disorder, while both groups graze more than individuals with normal weight. We recommend that clinicians routinely assess and treat unhelpful grazing patterns when working with individuals with obesity and eating disorders

The ‘mighty mouse’ model in experimental cardiac transplantation

Tissue rejection remains a major problem in organ transplantation. The use of experimental animal models continues to enhance our understanding of the rejection process and offers strategies for its prevention. The popular mouse model of heterotopic cardiac transplantation has been used for over three decades to help investigators understand the pathogenesis of graft rejection and in turn, how novel drugs can attenuate the immune response to transplanted organs. Also, since the genetic blueprint of mice is well-known, specific genes can be modified to study their affect on graft acceptance and tolerance. This review briefly outlines what is known about the unique physiology, haemodynamics and dynamic morphology of the transplanted mouse heart, with particular emphasis on insights gleaned from hi-resolution ultrasound. Current applications and methods to assess rejection are also discussed

Seeing the Transplanted Mouse Heart Like Never Before: New Insights into Experimental Heart Rejection using Novel Ultrasound Applications

Heart rejection is a major problem for heart transplant patients. The best strategy for understanding and preventing organ rejection is to study experimental animal models. The popular mouse model of heterotopic cardiac transplantation has been used for over three decades to help investigators understand the pathogenesis of graft rejection and in turn, how novel drugs can attenuate the immune response to transplanted organs. Also, since the genetic blueprint of mice is well-known, specific genes can be modified to study its effect on graft acceptance and tolerance. Despite the large potential for this model, little is known about the physiology, haemodynamics, and morphology of the transplanted heart and there is no method to assess objectively graft survival. This work describes in detail the use of high-frequency ultrasound for investigating the small transplanted mouse heart. For the first time, insights are made into blood flow, the effects of graft rejection, and organ survival with never before seen high-resolution images unachievable with conventional ultrasound. This work will be of significant interest to investigators, clinicians and students in the field

Cardiac allograft vasculopathy : the silent, long-suffering enemy

Cardiac transplantation is currently the preferred choice of treatment for end-stage cardiac disease. Despite great advances in controlling rejection and infection episodes, cardiac allograft vasculopathy (CAV) remains the leading cause of death after the first year of transplantation. CAV is an accelerated form of obliterative coronary artery disease that occurs in the heart transplant recipient. Currently, retransplantation is the only definitive treatment for patients with CAV and bioethical concerns of the growing donor shortage and increasing demand have served as a major obstacle in the long-term care for these patients. This short review will discuss the various molecular etiologies of CAV, emphasizing the endothelium as a critical site of injury that is capable of inducing CAV pathogenesis. Potential preventative, existing and novel immunosuppression regimens for treating CAV will also be reviewed

Lent, lust and the libido : what patristic theology taught us about testosterone biosynthesis

Abstinence from meat and animal-based foods has been a long-held tradition of the three major world faiths. The myriad of Judeo-Christian traditions, particularly the writings of the Catholic-Orthodox Church Fathers still in extant, attests to the ubiquitous belief in this common form of observance during periods of fasting and penance. Aside from procuring practical benefits, abstaining from flesh-foods virtually eliminates consumption of dietary cholesterol. Evidence-based studies have shown that certain types of cholesterol are positively correlated with testosterone levels, the major androgen responsible for the sex drive. Writings from the Church Fathers and the Judeo-Christian tradition have made an appreciable connection between meat-eating and increased libido, though until recently, no historical-scientific approaches have been initiated to shed light on this fascinating subtlety

How to investigate weight gain in an adult : ‘I’ve put on so much weight, doc’

The global prevalence of people with a body mass index (BMI) over 30 kg/m2 has doubled, over 40 kg/m2 quadrupled, and over 50 kg/m2 increased fivefold. It is projected in Australia that if current rates of weight gain continue, normal-weight adults will constitute less than a third of the population by 2025, and the obesity prevalence will have increased by 65%

Self-empowerment and health outcomes in obese adults with type 2 diabetes following completion of a multi-disciplinary metabolic rehabilitation program

Introduction: Type 2 diabetes mellitus (T2DM) is a worldwide epidemic yet; self-empowerment remains an important yet under-utilised aspect of daily self-care in patients with T2DM. Methods: We retrospectively administered the validated Diabetes Empowerment Scale (DES) to evaluate self-empowerment in 42 obese, adult patients with T2DM who completed a minimum 1-year participation in an intensive multi-disciplinary metabolic rehabilitation program. We sought to determine correlations with clinical outcomes in nine cardiometabolic parameters collected at baseline and subsequently 6-monthly till 30-months. Results: Over 87% of patients attended > 3 sessions/week, with 95% enrolled up to 30-months. Patients indicated a moderately high level of empowerment both globally and in all three DES domains. Subscale III (setting and achieving diabetes goals) was significantly and inversely correlated with % change in waist circumference (WCC) at 12-months (R = -0.337, P = 0.03) and % reduction in diastolic blood pressure at 24-months (r = -0.381, P = 0.01). Subscale II (assessing dissatisfaction and readiness to change) was positively correlated with duration of diagnosis (R = 0.354, P = 0.02). Furthermore, the number of exercise sessions attended was correlated with decreased 12-month % change in weight (r = -0.320, P = 0.04) and glycosylated haemoglobin (HbA1c) (r = -0.344, P = 0.03). Significant reduction was achieved in as early as 6-months for weight (-4.2 + 0.9%, P < 0.001), BMI (-3.9 + 0.9%, P = 0.002) and WCC (-2.8 + 0.7%, P = 0.004) and continued to decrease at 30 months (-8.6 + 1.4%, P < 0.001; -8.4 + 1.5%, P < 0.001; -5.0 + 1.3%, P < 0.001, respectively). Concurrent with weight reduction, significant improvement in HbA1c was also observed early at 6-months (-8.5 + 1.6%, P < 0.001) with maximum benefit at 24-months (-10.1 + 2.2%, P < 0.001). High-density lipoprotein cholesterol also reached a maximal increase at 24 months (10.6 + 4.3%, P = 0.049). Conclusion: Setting and achieving goals was associated with reductions in waist circumference and blood pressure. The role of empowerment-based intervention in conjunction with intensive multi-disciplinary rehabilitation on health outcomes in these patients remains under-researched and under-utilised in clinical practice

A review of maturity onset diabetes of the young (MODY) and challenges in the management of glucokinase-MODY

Letter in reply: We thank Flack and colleagues for their detailed comments on our review (Med J Aust 2017; 207 (5): 223. doi: 10.5694/mja16.01404). The prevalence of gestational diabetes mellitus (GDM) of 5e10% was based on a prospective study by Moses and colleagues using the Australasian Diabetes in Pregnancy Society criteria, which found a prevalence in Wollongong, New South Wales, of 8.6e10.5% (9.6% overall). Using the more recently adopted International Association of Diabetes and Pregnancy Study Groups diagnostic definition in the same study, the prevalence of GDM was 13.0%