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The aim was to investigate normal patterns of brain metabolism determined by F-fluorodeoxyglucose positron emission tomography (FDG PET)/MRI during childhood and adolescence.A retrospective analysis was carried out on all paediatric patients who underwent FDG PET/MRI at our institution between March 2016 and August 2017. Exclusion criteria were neurological disease, central nervous system metastases, previous chemotherapy/radiotherapy, general anaesthesia/sedation and medications suspected to affect cerebral metabolism. Standardized uptake value (SUV)mean and SUVmax were calculated for 12 brain grey matter regions. Subgroup analysis of childhood (≤10 years old) and adolescence (≥11 years old) was also carried out.From 492 PET/MRI scans, 28 patients (11 children, 17 adolescents) were deemed representative of normal brain metabolism. SUVmean and SUVmax increased with age in all regions. The highest rates of increasing SUVmean were in the thalamus, basal ganglia, frontal lobes, insula and occipital lobes. Higher SUVmean was found in the right frontal, right lateral temporal, right temporal pole, right cingulate/paracingulate, right thalamus, left occipital, left basal ganglia, left insula and left cerebellum compared with the contralateral side. This SUVmean asymmetry was present in both childhood and adolescence in the majority of regions. The highest rates of increasing SUVmax with age were in the occipital lobes, frontal lobes, thalamus and central region. There was no asymmetry in SUVmax in the majority of regions.This FDG PET/MRI study shows that normal brain metabolism measured by SUVmean and SUVmax increases with age in all regions, proceeding at different rates between distinct anatomical sites. Our results suggest that there is mild asymmetry in SUVmean, but mostly symmetric SUVmax during normal development.

Increasing brown adipose tissue (BAT) activity is a possible therapeutic strategy to increase energy expenditure and glucose and lipid clearance to ameliorate obesity and associated comorbidities. The thiazolidinedione (TZD) class of glucose-lowering drugs increase BAT browning in preclinical experimental models but whether these actions extend to humans in vivo is unknown. The aim of this study was to determine the effect of pioglitazone treatment on adipocyte browning and adaptive thermogenesis in humans.We first examined whether pioglitazone treatment of cultured human primary subacromioclavicular-derived adipocytes induced browning. Then, in a blinded, placebo-controlled, parallel trial, conducted within the Baker Institute clinical research laboratories, 14 lean male participants who were free of cardiometabolic disease were randomised to receive either placebo (lactose; n = 7, age 22 ± 1 years) or pioglitazone (45 mg/day, n = 7, age 21 ± 1 years) for 28 days. Participants were allocated to treatments by Alfred Hospital staff independent from the study via electronic generation of a random number sequence. Researchers conducting trials and analysing data were blind to treatment allocation. The change in cold-stimulated BAT activity, assessed before and after the intervention by [Pioglitazone significantly increased in vitro browning and adipogenesis of adipocytes. In the clinical trial, cold-induced BAT maximum standardised uptake value was significantly reduced after pioglitazone compared with placebo (-57 ± 6% vs -12 ± 18%, respectively; p 0.05). BAT total glucose uptake followed a similar but non-significant trend (-50 ± 10% vs -6 ± 24%, respectively; p = 0.097). Pioglitazone increased total and lean body mass compared with placebo (p 0.05). No other changes between groups were detected.The disparity in the actions of pioglitazone on BAT between preclinical experimental models and our in vivo human trial highlight the imperative to conduct human proof-of-concept studies as early as possible in BAT research programmes aimed at therapeutic development. Our clinical trial findings suggest that reduced BAT activity may contribute to weight gain associated with pioglitazone and other TZDs.ClinicalTrials.gov NCT02236962 FUNDING: This work was supported by the Diabetes Australia Research Program and OIS scheme from the Victorian State Government.

Background There has been limited examination of the performance of glomerular filtration rate estimation (eGFR) equations in lung transplant populations. This study aimed to compare the performance of serum creatinine and cystatin C based eGFR equations with Tc-99m diethylenetriaminepentaacetic acid (DTPA) GFR measurements in individuals with end-stage lung disease, either prior to, or following, lung transplantation. Methods In this prospective observational study, participants underwent GFR measurements with Tc-99m Pentetate. Measured results were compared with GFR estimates derived from estimation equations [4-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine, cystatin C and creatinine-cystatin C combined equations]. Results Ninety-seven individuals were studied (77 post- and 20 wait-listed for transplantation). Median (range) radionucleotide GFR was 56.7 ml/min/1.73 m2 (22.8–109.2 ml/min/1.73 m2). In the study cohort as a whole, the CKD-EPI creatinine-cystatin C combined equation showed the highest performance, but was only slightly superior to the CKD-EPI creatinine equation. However, in individuals with cystic fibrosis, low arm muscle mass and/or low body mass index, all of the creatinine-based equations showed unacceptable performance. In these subgroups, improved GFR estimation was seen with the CKD-EPI cystatin C equation, and predictions were better still using the CKD-EPI creatinine-cystatin C combined equation. Conclusions This study shows adequate predictive ability of CKD-EPI creatinine in the cohort as a whole, but unacceptable performance in patients with cystic fibrosis, low arm muscle mass and/or low body mass index. Our findings demonstrate that cystatin C may be a preferable filtration marker in these subgroups.

Background Macrophage migration inhibitory factor ( MIF ) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia. Methods and Results Patients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty‐two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real‐time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high‐sensitivity troponin T and C‐reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart. Conclusions Our results suggest that plasma MIF is an early marker for acute myocardial ischemia.

Testosterone therapy for osteoporosis has not been studied extensively in women because of its potential to cause virilization. Female-to-male transsexuals are genetic females who suffer from gender dysphoria and thus take supra-physiologic doses of testosterone to change from the female to male phenotype. The aim of this study is to examine the effects of testosterone treatment on the genetic female skeleton.A group of 15 female-to-male transsexuals was prospectively enrolled for observation over a 2-year period. The subjects had a mean age of 37.0 +/- 3.0 years. All of the subjects self-administered testosterone esters intramuscularly at a mean dose of 70.7 +/- 4.5 mg weekly.The subjects had measurements of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) of the femoral neck and spine (L2-L4) at 12-month intervals. They had determinations of serum oestradiol, testosterone, soluble RANKL (sRANKL), osteoprotegerin (OPG) and urine N-telopeptide (NTX) at the date of enrolment and at the end of 2 years. results There was a significant positive increase in mean BMD of 7.8% at the femoral neck and a nonsignificant increase in mean BMD of 3.1% at the spine over 2 years. The levels of testosterone reached the upper normal range for males and the levels of oestradiol declined to near the postmenopausal range. sRANKL levels decreased significantly in female-to-male transsexuals who newly initiated testosterone therapy. There was no significant change in urine NTX or serum OPG during the study.We conclude that supra-physiologic testosterone therapy increases BMD at the hip while maintaining BMD at the spine in female-to-male transsexuals. The effects of testosterone may be the result of testosterone hormone directly acting on the bone or indirectly through aromatization to oestradiol. Lower RANKL levels coupled with unchanged OPG levels results in an increased OPG/RANKL ratio, which may be beneficial to the bone by inhibiting osteoclastogenesis.

Intrapancreatic accessory spleens are relatively uncommon and can be difficult to distinguish from neuroendocrine tumours on CT, MRI and somatostatin receptor scintigraphy. We present the case of a 26-year-old woman with an incidentally diagnosed pancreatic lesion confirmed to be an intrapancreatic accessory spleen on Tc-99m heat-denatured red blood cell single photon emission computed tomography/CT.

The aim of this study is to compare the results of positron emission tomography (PET)/CT with bremsstrahlung imaging following Y-90 radiation synovectomy.All patients referred to our institution for Y-90 radiation synovectomy between July 2011 and February 2012 underwent both PET/CT and bremsstrahlung planar (± single photon emission computed tomography (SPECT) or SPECT/CT) imaging at 4 or 24 h following administration of Y-90 silicate colloid. PET image acquisition was performed for between 15 and 20 min. In patients who underwent SPECT, side-by-side comparison with PET was performed and image quality/resolution scored using a five-point scale. The distribution pattern of Y-90 on PET and bremsstrahlung imaging was compared with the intra- or extra-articular location of Y-90 activity on fused PET/CT.Thirteen joints (11 knees and two ankles) were imaged with both PET/CT and planar bremsstrahlung imaging with 12 joints also imaged with bremsstrahlung SPECT. Of the 12 joints imaged with SPECT, PET image quality/resolution was superior in 11 and inferior in one. PET demonstrated a concordant distribution pattern compared with bremsstrahlung imaging in all scans, with the pattern classified as diffuse in 12 and predominantly focal in one. In all 12 diffuse scans, PET/CT confirmed the Y-90 activity to be located intra-articularly. In the one predominantly focal scan, the fused PET/CT images localised the Y-90 activity to mostly lie in the extra-articular space of the knee.PET/CT can provide superior image quality compared with bremsstrahlung imaging and may enable reliable detection of extra-articular Y-90 activity when there are focal patterns on planar bremsstrahlung imaging.

The aim of this study is to evaluate the incremental staging information, management impact, and prognostic stratification of PET/CT in the primary staging of esophageal cancer in a cohort of patients with mature survival data.Between July 2002 and June 2005, 139 consecutive patients with newly diagnosed esophageal cancer underwent conventional staging investigations (CSI), followed by PET/CT. Disease stage was classified according to the American Joint Committee on Cancer staging system (6th edition) and grouped as stage I-IIA, stage IIB-III, and stage IV reflecting broad groupings that determine therapeutic choice. Validation of results was performed when PET/CT and CSI stage groups were discordant and in those patients where PET/CT changed management. Management impact was determined by comparing prospectively recorded pre-PET/CT management plans with post-PET/CT management plans. Survival after follow-up of at least 5 y in patients was analyzed using the Kaplan-Meier product limit method and the Cox proportional hazards regression model.PET/CT changed the stage group in 56 of 139 (40%) patients and changed management in 47 of 139 (34%) patients. In 22 patients, therapy was changed from curative to palliative and in 3 from palliative to curative; in 11, treatment modality was changed without a change in treatment intent, and in 11 the delivery of therapy or diagnostic procedure was changed. Of the 47 patients with management change, imaging results could be validated in 31 patients, and PET/CT correctly changed management in 26 (84%) of these. Of the remaining 5 patients, CSI stage was also incorrect in 4 and correct in 1. Median survival was 23 mo. PET/CT stages I-IIA, IIB-III, and IV had a 5-y survival of 40%, 38%, and 6%, respectively. Post-PET/CT stage group and treatment intent were both strongly associated with survival (P0.001).PET/CT provides incremental staging information compared with CSI, changes management in one third of patients, and has powerful prognostic stratification in the primary staging of esophageal cancer.

Skin tests with 0.1 mL of intermediate-strength Mycobacterium tuberculosis purified protein derivative (PPD) and 0.1 mL of Mycobacterium avium sensitin were conducted on 484 healthy subjects from diverse geographic sites. Reactions ofor = 5 mm to one antigen that exceeded the reaction to the other byor = 3 mm were considered M. avium- or PPD-dominant. PPD-dominant reactions were more frequent at sites where routine Bacille Calmette-Guérin immunization is done or where there are high rates of tuberculosis: New Hampshire, 2%; Boston, 7%; Finland, 14%; Trinidad, 26%; and Kenya, 28%. However, rates of M. avium-dominant reactions ranged from 7% to 12% at all sites. Analysis of dominant reactions based on a more stringent 10-mm minimum reaction size showed similar trends. These data suggest that exposure to MAC is similar in developed and developing countries but that broad mycobacterial immunity is greater in developing countries and may contribute to the lower rates of disseminated MAC infections in AIDS in these areas.

A 72-year-old woman was referred for radioiodine ablation for papillary thyroid cancer in a multinodular goiter after a right hemithyroidectomy and subsequent completion thyroidectomy. Inadequate elevation of thyroid stimulating hormone after thyroid hormone withdrawal was investigated with

Study Objective: To determine if Mycobacterium gordonae is an opportunistic respiratory tract pathogen in patients infected with human immunodeficiency virus, type 1 (HIV-1). Design: Retrospective review of medical records of all patients with positive cultures for M gordonae from 1987 to 1989. Patients: Fifteen patients had positive sputum cultures for M gordonae: five patients had AIDS or had HIV-1 infections with ≤180 CD4 cells/cu mm, and ten patients had no clinical evidence of HIV-1 infection. Results: Three of the five HIV-1 infected patients had clinical, roentgenographic, and microbiologic evidence of pulmonary infection due to M gordonae that responded to antimycobacterial therapy. One of the two remaining HIV-1 infected patients had disseminated M tuberculosis and possible coinfection with M gordonae, and the other was lost to follow-up. None of the ten patients without evidence of HIV-1 infection was considered to have M gordonae respiratory tract infection. Conclusions: Sputum isolates of M gordonae should be considered potential opportunistic respiratory tract pathogens in patients with advanced HIV-1 infection and with otherwise unexplained pulmonary infection. (Chest; 100:716-20)

To review the diagnosis, therapeutic options, and potential complications of treatment of transsexualism.We summarize the appropriate initial assessment and the current guidelines for hormonal and surgical treatment of patients with transsexualism.The cardinal feature of transsexualism is the permanent feeling of gender dysphoria. As part of the treatment of this condition, patients may seek medical and surgical therapies to change their physical appearance to match their internal gender identity. Cross-sex hormone therapy is a key medical management and is often prescribed in consultation with an endocrinologist. Patients should participate in a period of psychotherapy before such hormonal therapy is initiated. Medical therapies for transsexualism are associated with potentially serious complications, such as thromboembolism related to estrogen treatment and testosterone-induced hepatotoxicity. Patients should be carefully selected for therapy with use of the current management guidelines published by the Harry Benjamin International Gender Dysphoria Association.Physicians caring for patients with transsexualism should have a general knowledge about the diagnosis, available treatment, and monitoring for complications of hormonal therapy. Ongoing research and education are necessary for improvement in the health care of these patients.

The sensitivity and specificity of dual mycobacterial skin testing were assessed in an unblinded study of 22 patients with culture-confirmed Mycobacterium avium complex (MAC) infection and 20 patients with culture-confirmed Mycobacterium tuberculosis infection. Intradermal skin tests were performed with 0.1 mL of M. avium sensitin, 0.1 mL of PPD (purified protein derivative), and two control antigens (mumps and Candida). All patients with M. tuberculosis infection reacted to the skin tests; the mean reaction size was 19.7 +/- 1.4 mm when PPD was administered and 10.3 +/- 1.5 mm when M. avium sensitin was administered. Four patients with MAC were anergic; for the remaining 18, mean reactions of 15.2 +/- 1.4 mm to M. avium sensitin and 4.3 +/- 1.3 to PPD were noted. A skin test was defined as M. avium-dominant or PPD (M. tuberculosis)-dominant if there was a minimum reaction size of > or = 5 mm to the given species, and the reaction to the given species was > or = 3 mm greater than the reaction to the heterologous species. Dominant skin test reactions were present in 18 (90%) of 20 patients with M. tuberculosis and 15 (83%) of 18 nonanergic patients with MAC. The specificity of dominant skin tests was 100% for infection with M. tuberculosis and 100% for infection with MAC. M. avium-dominant skin tests identify subjects with prior MAC infection and distinguish them from patients with M. tuberculosis infection.

A 43-year-old woman underwent sentinel lymph node localisation prior to a left mastectomy and sentinel node biopsy for recurrent multifocal left-sided breast cancer. Previous treatment included a wide local excision and left axillary nodal clearance 15 months ago. Following one peri-areolar intradermal injection of 15 MBq of Tcantimony colloid in the upper inner quadrant of the left breast, dynamic planar imaging failed to identify a sentinel node. SPECT/CT imaging demonstrated a lymphatic channel extending from the left subpectoral region through the lingula of the left lung into the mediastinum posterior to the pulmonary trunk and terminating in the subcarinal nodal station (arrow). This unusual pattern of breast lymphatic drainage via the pulmonary lymphatic system is attributed to opening of collateral lymphatic channels following the previous left axillary nodal clearance. A left internal mammary sentinel lymph node (arrowhead) was also demonstrated and confirmed intraoperatively. While it is commonly believed that spread of breast cancer beyond the regional lymph nodes is haematogenous, it is also increasingly being recognised that traditional anatomical descriptions of lymphatic anatomy do not necessarily reflect observed variations in lymphatic pathways [1, 2]. Given that breast cancer is one of the known extrathoracic malignancies that metastasise to mediastinal nodes [3–5], this finding of a direct communication of breast lymphatic drainage with the intrapulmonary lymphatic system provides a potential mechanism for this pattern of spread. This case highlights how the combination of functional and anatomical information provided by SPECT/CT in lymphoscintigraphy continues to improve our understanding of potential paths of cancer spread.