Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus.

Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects. SUBJECTS/METHODS: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (18F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects. CONCLUSIONS: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.

Comparison of estimates of body fat content in childhood-onset systemic lupus erythematosus.

Objective We aimed to compare estimates of body fat content with respect to their ability to predict the percentage of body fat, confirmed by dual-energy X-ray absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We included 64 consecutive childhood-onset systemic lupus erythematosus patients and 64 healthy age and sex-matched controls in a cross-sectional study. Anthropometric data, body mass index and body adiposity index were calculated for all subjects. Childhood-onset systemic lupus erythematosus patients were further assessed for clinical and laboratory childhood-onset systemic lupus erythematosus manifestations and fat mass, lean mass and percentage of body fat evaluated by dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed in childhood-onset systemic lupus erythematosus patients when compared to controls ( p < 0.001). We did not find differences between body mass index and body adiposity index classification in childhood-onset systemic lupus erythematosus patients and controls. Using dual-energy X-ray absorptiometry as gold standard we observed that all indirect estimates of body fat were correlated with whole body fat mass. We observed a correlation between height and cumulative corticosteroid dose adjusted by weight ( r = 0.429, p = 0.005) in childhood-onset systemic lupus erythematosus. On whole body analysis we observed a correlation between lean mass and ACR Damage Index scores ( r = -0.395; p = 0.019); percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.008), disease duration ( r = -0.370; p = 0.012). On trunk analysis we observed a correlation between lean mass and ACR Damage Index ( r = -0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus Erythematosus Disease Activity Index ( r = 0.402; p = 0.005), disease duration ( r = -0.408; p = 0.005). Conclusions This is the first study analyzing body adiposity index in childhood-onset systemic lupus erythematosus patients. We observed that all indirect estimates of body fat were correlated with whole body fat mass. This study shows that we should not replace body mass index by body adiposity index to evaluating fat levels in childhood-onset systemic lupus erythematosus. In consideration of the importance of overweight classification in cardiovascular diseases, any direct estimates of body fat can be used in an attempt to improve the prognosis of patients. Note We believe that we have presented evidence of body adiposity index accuracy in childhood-onset systemic lupus erythematosus patients but further research on the generalizability of body adiposity index to other patient groups needs to be done.

Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity.

BACKGROUND/OBJECTIVES: The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass. SUBJECTS/METHODS: We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes. RESULTS: Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls. CONCLUSIONS: In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

Quantitative coronary arterial stenosis assessment by multidetector CT and invasive coronary angiography for identifying patients with myocardial perfusion abnormalities.

BACKGROUND: Semi-quantitative stenosis assessment by coronary CT angiography only modestly predicts stress-induced myocardial perfusion abnormalities. The performance of quantitative CT angiography (QCTA) for identifying patients with myocardial perfusion defects remains unclear. METHODS: CorE-64 is a multicenter, international study to assess the accuracy of 64-slice QCTA for detecting ≥50% coronary arterial stenoses by quantitative coronary angiography (QCA). Patients referred for cardiac catheterization with suspected or known coronary artery disease were enrolled. Area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the most severe coronary artery stenosis in a subset of 63 patients assessed by QCTA and QCA for detecting myocardial perfusion abnormalities on exercise or pharmacologic stress SPECT. RESULTS: Diagnostic accuracy of QCTA for identifying patients with myocardial perfusion abnormalities by SPECT revealed an AUC of 0.71, compared to 0.72 by QCA (P = .75). AUC did not improve after excluding studies with fixed myocardial perfusion abnormalities and total coronary arterial occlusions. Optimal stenosis threshold for QCTA was 43% yielding a sensitivity of 0.81 and specificity of 0.50, respectively, compared to 0.75 and 0.69 by QCA at a threshold of 59%. Sensitivity and specificity of QCTA to identify patients with both obstructive lesions and myocardial perfusion defects were 0.94 and 0.77, respectively. CONCLUSIONS: Coronary artery stenosis assessment by QCTA or QCA only modestly predicts the presence and the absence of myocardial perfusion abnormalities by SPECT. Confounding variables affecting the relationship between coronary anatomy and myocardial perfusion likely account for some of the observed discrepancies between coronary angiography and SPECT results.

Mast cell degranulation contributes to susceptibility to Leishmania major.

Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.

Brain single-photon emission computed tomography and magnetic resonance imaging in Machado-Joseph disease.

BACKGROUND: Machado-Joseph disease (MJD) is one of the most frequently encountered spinocerebellar ataxias. However, few reports on brain single-photon emission computed tomographic (SPECT) imaging (BSI) with hexylmethylpropylene amineoxine labled with technetium Tc 99m and magnetic resonance imaging (MRI) have been performed for the evaluation of patients with MJD. OBJECTIVES: To investigate possible abnormalities with BSI and MRI in patients with MJD and to correlate these findings with the duration of symptoms; cerebellar, extrapyramidal, and pyramidal syndromes; and the molecular characteristics of the MJD mutation. PATIENTS AND METHODS: Twelve patients (8 males and 4 females [mean age, 39 years]) with genetically proven MJD were studied. The patients underwent BSI and MRI on the same day. Brain SPECT imaging was performed after an intravenous injection of 99mTc-hexylmethylpropylene amineoxine. The transaxial, coronal, and sagittal BSIs obtained were submitted to visual and semiquantitative analyses. Magnetic resonance imaging was obtained in a 2-T system with coronal, sagittal, transaxial, and 3-dimensional (volumetric) acquisitions. The volumes of the cerebellar hemispheres and vermis were calculated. Control groups for BSI (22 female and 20 male subjects [mean age, 33 years]) and MRI (13 female and 4 male subjects [mean age, 32.2 years]) were included for comparison. RESULTS: Correlation was observed between the perfusion abnormalities identified by visual analysis in the BSI with the structural abnormalities observed on MRI in the parietal lobes and vermis. Brain SPECT imaging identified (by visual analysis) more perfusion abnormalities in the inferior portion of the frontal lobes, mesial and lateral portions of the temporal lobes, basal ganglia, and cerebellar hemispheres. Magnetic resonance imaging identified more abnormalities in the pons and superior portions of the frontal lobes. Olivary atrophy was identified by MRI. Semiquantitative analysis showed a statistically significant difference of perfusion in the inferior and superior portions of the frontal lobes, lateral portion of the temporal lobes, parietal lobes, left basal ganglia, cerebellar hemispheres, and vermis when compared with the control group. A significant difference was noted between the vermis and cerebellar volumes on MRI when compared with the control group. A significant relationship was observed between the perfusion of the left parietal lobe (P =.05) and extrapyramidal syndrome. There was a tendency toward an inverse relationship between the duration of symptoms and the perfusion of the cerebellar hemispheres (rho = -0.37; P =.24) and volume of the vermis (rho = -0.30; P =.34); between the length of the expanded (CAG)n repeat and the perfusion of the left parietal lobe (rho = -0.32; P =.36), vermis (rho = -0.28; P =.43), and pons (rho = -0.28; P =.42). A direct association was observed between the length of the expanded (CAG)n repeat and the perfusion of the lateral portion of the right temporal lobe (rho = 0.67; P =.03). CONCLUSIONS: Brain SPECT imaging and MRI were capable of identifying subclinical abnormalities in individuals with MJD. These findings may be helpful for a better understanding of the pathophysiology of this disease.

Chromomycosis: a clinical and mycologic study of thirty-five cases observed in the hinterland of Rio Grande do Sul, Brazil.

Data on thirty-five patients with chromomycosis seen in the hinterland of the State of Rio Grande do Sul (Brazil) are reviewed. Atypical lesions were found in 28.5% of the patients. The lesions were localized on the upper limbs and face in 14.2% and 8.5% of the patients, respectively. The clinical aspects and mycologic diagnosis of chromomycosis are discussed, and an account is given of its regional distribution in Rio Grande do Sul.

Gallium-67 imaging in a patient with paracoccidioidomycosis: a case report.

A 26 year-old female was admitted with abdominal pain, fever and weight loss. The clinical and laboratory investigations led to the diagnosis of paracoccidioidomycosis. Gallium-67 whole body images correlated well with the clinical course of the disease and with the patient's prognosis.

Incidental focal thyroid uptake on FDG positron emission tomographic scans may represent a second primary tumor.

PURPOSE: This article discusses the value of incidental thyroid uptake of fluorodeoxyglucose (FDG) on whole-body positron emission tomography (PET) scans performed in patients with cancer. This issue has been reported diversely in the literature. MATERIALS AND METHODS: Whole-body PET scans of four patients with cancer (two of them women; age, 49 to 78 years) in whom focal thyroid uptake was visualized and subsequently correlated with thyroid carcinoma based on cytologic or histopathologic data were reviewed. The clinical outcomes of these patients were analyzed retrospectively. Maximum and average standardized uptake values (SUVs) of thyroid accumulation were recalculated in all patients. RESULTS: Two of the four patients referred for FDG PET scans had lung adenocarcinomas, one had prostate carcinoma, and one had an unknown primary tumor. Focal thyroid uptake was visualized, with maximum and average SUVs ranging from 3.7 and 2.3 to 53 and 34, respectively. These findings were correlated with cytologic (two patients) or histopathologic data (two patients) that indicated thyroid carcinoma. In two patients, their treatment was changed and total thyroidectomy was performed; in one of them the SUVs of the focal thyroid accumulation (maximum and average values of 7.9 and 4.8, respectively) were less than the cutoff values for thyroid cancer noted in the literature. The clinical condition of the other two patients did not permit additional investigation or treatment for thyroid carcinoma. CONCLUSION: Increased focal thyroid uptake on whole-body FDG PET scans should not be overlooked, even when it is not marked, and should prompt further investigation to rule out cancer.

Detection of synchronous carcinomas of the colon with F-18 fluorodeoxyglucose: a case report.

Colon and rectal carcinomas are common in North America and Northwestern Europe. In South America, the risk of this disease is not as great. Adenocarcinomas are the most common types of tumors, and they occur mainly in the descending colon, sigmoid, and rectum. A patient with a possible right colon carcinoma was examined using F-18 FDG.

Tc-99m MDP uptake in uterine leiomyoma.

A 47-year-old woman with adenocarcinoma of the right breast had bone scintigraphy with Tc-99m MDP. Bone imaging did not show any metastases. However, a large area of increased tracer uptake was seen extending from the abdomen to the pelvis. Abdominal ultrasound revealed a large solid and heterogeneous mass, measuring 18 x 11 x 14.3 cm, that originated in an empty uterus. A biopsy of the surgical specimen showed a leiomyoma of the uterus.

Brain SPECT imaging in Huntington's disease before and after therapy with olanzapine. Case report.

Olanzapine, an atypical antipsychotic drug, was administered to a patient with Huntington's disease (HD) with marked choreiform movements. Brain SPECT with 99mTc-HMPAO was performed before and after treatment. Brain SPECT imaging has been performed in patients with HD in order to determine the status of basal ganglia perfusion. The use of brain SPECT with 99mTc-HMPAO before and after treatment in patients with HD has not been yet reported. The marked hypoperfusion of the basal ganglia on brain SPECT performed before therapy with olanzapine improved significantly after treatment.

Attenuation correction effects on SPECT/CT procedures: phantoms studies.

Attenuation correction is widely used in SPECT/CT (Single Photon Emission Computed Tomography) procedures, especially for imaging of the thorax region. Different compensation methods have been developed and introduced into clinical practice. Most of them use attenuation maps obtained using transmission scanning systems. However, this gives extra dose of radiation to the patient. The purpose of this study was to identify when attenuation correction is really important during SPECT/CT procedures.For this purpose, we used Jaszczak phantom and phantom with three line sources, filled with technetium ((99m)-Tc), with scattering materials, like air, water and acrylic, in different detectors configurations. In all images acquired were applied analytic and iterative reconstruction algorithms; the last one with or without attenuation correction. We analyzed parameters such as eccentricity, contrast and spatial resolution in the images.The best reconstruction algorithm on average was iterative, for images with 128 × 128 and 64 × 64 matrixes. The analytical algorithm was effective only to improve eccentricity in 64 × 64 matrix and matrix in contrast 128 × 128 with low statistics. Turning to the clinical routine examinations, on average, for 128 × 128 matrix and low statistics counting, the best algorithm was the iterative, without attenuation correction,improving in 150% the three parameters analyzed and, for the same matrix size, but with high statistical counting, iterative algorithm with attenuation correction was 25% better than that without correction. We can conclude that using the iterative algorithm with attenuation correction in the water, and its extra dose given, is not justified for the procedures of low statistic counting, being relevant only if the intention is to prioritize contrast in acquisitions with high statistic counting.

Decrease in bone mass in women after liver transplantation: associated factors.

BACKGROUND: In the future, an increasing number of female liver transplant recipients will reach the climacteric with osteoporosis as a common complication. We evaluated the factors associated with decreased bone mass among women after liver transplantation. METHODS: A prospective, cross-sectional study of 23 outpatient transplant recipients followed from February 2009 to March 2010 included women of age ≥35 years after liver transplantations ≥1 year prior. We recorded patient histories, liver enzyme levels, as well as bone mineral densities measured at the lumbar spine and femur. Statistical analysis used Fisher's exact test, simple odds ratio (OR), and Spearman's rank correlation coefficient. RESULTS: The mean patient age was 52.5 ± 11 years with 30.4% premenopausal, and 69.6% perimenopausal or postmenopausal. Approximately 21% showed osteoporosis and 35%, a low bone mass. Postmenopausal women: OR 69.0 (95% CI 2.89-1647.18; P<.0001), aged ≥49 years: OR 13.33 (95% CI 1.78-100.15; P=.0123) and receiving a transplant after 44 years of age: OR 49.50 (95% CI 3.84-638.43; P<.0001) were associated with a lower bone mass. Having undergone transplantation for more than 5.8 years lowered the risk of bone mass change: OR 0.11 (95% CI 0.02-0.78; P=.0361). Clinical and laboratory variables, including corticosteroid use, were not associated with decreased bone mass. CONCLUSION: Understanding the prevalence and factors associated with osteoporosis among female liver transplant recipients is important to enhance the strategies to diagnose and treat these women, seeking to improve their quality of life.