Genetic mutations in the leptin pathway can be a cause of human obesity. It is still unknown whether leptin can be effective in the treatment of fully established morbid obesity and its endocrine and metabolic consequences in adults. To test the hypothesis that leptin has a key role in metabolic and endocrine regulation in adults, we examined the effects of human leptin replacement in the only three adults identified to date who have genetically based leptin deficiency. We treated these three morbidly obese homozygous leptin-deficient adult patients with recombinant human leptin at low, physiological replacement doses in the range of 0.01-0.04 mg͞kg for 18 months. Patients were hypogonadal, and one of them also had type 2 diabetes mellitus. We chose the doses of recombinant methionyl human leptin that would achieve normal leptin concentrations and administered them daily in the evening to model the normal circadian variation in endogenous leptin. The mean body mass index dropped from 51.2 ؎ 2.5 (mean ؎ SEM) at baseline to 26.9 ؎ 2.1 kg͞m 2 after 18 months of treatment, mainly because of loss of fat mass. We document here that leptin replacement therapy in leptin-deficient adults with established morbid obesity results in profound weight loss, increased physical activity, changes in endocrine function and metabolism, including resolution of type 2 diabetes mellitus and hypogonadism, and beneficial effects on ingestive and noningestive behavior. These results highlight the role of the leptin pathway in adults with key effects on the regulation of body weight, gonadal function, and behavior.T he increasing rates of obesity and consequent morbidity represent a major epidemic worldwide and threaten to bankrupt health care systems (1-3). While prevention is of great importance, it is medically relevant to identify biological pathways with the potential to treat obesity and related disorders, particularly in adults with fully established obesity and comorbid conditions, such as type 2 diabetes mellitus. Leptin, the product of the ob gene, plays a central role in the regulation of food intake and energy expenditure (4). Mutations in the leptin pathway can be a cause of human obesity (5-7). In children with complete leptin deficiency and who are still in the process of gaining weight and developing obesity, leptin replacement therapy can lead to substantial weight reduction (8,9).It is still unknown whether the leptin pathway is relevant to the treatment of established morbid obesity and its endocrine and metabolic consequences in adults. We addressed this question by treating three homozygous leptin-deficient adults with morbid obesity. Morbid obesity had been fully established for two to four decades in those patients, and they had been at a stable (but very high) weight for Ͼ10 years. They were hypogonadal, and one of them had type 2 diabetes mellitus. We report here the results of the first 18 months of replacement therapy with recombinant human leptin, showing that leptin is highly effective in dramatically reducing...
Radiation dose and image quality for paediatric protocols in a biplane x-ray system used for interventional cardiology have been evaluated. Entrance surface air kerma (ESAK) and image quality using a test object and polymethyl methacrylate (PMMA) phantoms have been measured for the typical paediatric patient thicknesses (4-20 cm of PMMA). Images from fluoroscopy (low, medium and high) and cine modes have been archived in digital imaging and communications in medicine (DICOM) format. Signal-to-noise ratio (SNR), figure of merit (FOM), contrast (CO), contrast-to-noise ratio (CNR) and high contrast spatial resolution (HCSR) have been computed from the images. Data on dose transferred to the DICOM header have been used to test the values of the dosimetric display at the interventional reference point. ESAK for fluoroscopy modes ranges from 0.15 to 36.60 microGy/frame when moving from 4 to 20 cm PMMA. For cine, these values range from 2.80 to 161.10 microGy/frame. SNR, FOM, CO, CNR and HCSR are improved for high fluoroscopy and cine modes and maintained roughly constant for the different thicknesses. Cumulative dose at the interventional reference point resulted 25-45% higher than the skin dose for the vertical C-arm (depending of the phantom thickness). ESAK and numerical image quality parameters allow the verification of the proper setting of the x-ray system. Knowing the increases in dose per frame when increasing phantom thicknesses together with the image quality parameters will help cardiologists in the good management of patient dose and allow them to select the best imaging acquisition mode during clinical procedures.
Lahars are among the most serious and far-reaching volcanic hazards. In regions with potential interactions of lahars with populated areas and human structures the assessment of the related hazards is crucial for undertaking appropriate mitigating actions and reduce the associated risks. Modeling of lahars has become an important tool in such assessments, in particular where the geologic record of past events is insufficient. Mass-flow modeling strongly relies on digital terrain data. Availability of digital elevation models (DEMs), however, is often limited and thus an obstacle to lahar modeling. Remote-sensing technology has now opened new perspectives in generating DEMs. In this study, we evaluate the feasibility of DEMs derived from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and the Shuttle Radar Topography Mission (SRTM) for lahar modeling on Popocatépetl Volcano, Mexico. Two GIS-based models are used for lahar modeling, LAHARZ and a flow-routing-based debris-flow model (modified single-flow direction model, MSF), both predicting areas potentially affected by lahars. Results of the lahar modeling show that both the ASTER and SRTM DEMs are basically suitable for use with LAHARZ and MSF. Flow-path prediction is found to be more reliable with SRTM data, though with a coarser spatial resolution. Errors of the ASTER DEM affecting the prediction of flow paths due to the sensor geometry are associated with deeply incised gorges with north-facing slopes. LAHARZ is more sensitive to errors of the ASTER DEM than the MSF model. Lahar modeling with the ASTER DEM results in a more finely spaced predicted inundation area but does not add any significant information in comparison with the SRTM DEM. Lahars at Popocatépetl are modeled with volumes of 1 × 10 5 to 8 × 10 6 m 3 based on ice-melt scenarios of the glaciers on top of the volcano and data on recent and historical lahar events. As regards recently observed lahars, the travel distance of lahars of corresponding volume modeled with LAHARZ falls short by 2 to 4 km. An important finding is that the travel distance of potential lahar events modeled with LAHARZ may differ by about 2 km when using SRTM or ASTER data because of varying lateral flow-volume distribution. As a consequence, verification and sensitivity analysis of the DEM is fundamental to deriving hazard maps from predicted modeled inundation areas. Because of the global coverage of this type of remote-sensing data, the conclusion that both SRTM and ASTER-derived DEMs are feasible for lahar modeling opens a wide field of application in volcanic-hazards studies.
In pediatric interventional cardiology, cardiologists need to stay closer to the patient than during adult catheterization, and the use of biplane systems increases the scatter radiation. Occupational radiation risk is rather high, and estimation of lens doses becomes necessary. Deriving factors for assessing these doses from the patient doses displayed in catheterization laboratories can help in preserving staff radiation safety. A biplane X-ray system and polymethylmethacrylate plates of 4 to 20 cm to simulate pediatric patients have been used. Patient entrance dose rates, dose-area product, and doses to the eyes of the cardiologists for the typical operation modes have been measured. Correlations between patient and staff doses have been obtained. Scatter dose rates increase by a factor of 92 from low fluoroscopy to cine acquisition when phantom thickness increases from 4 to 20 cm. Scatter doses increase linearly with dose-area product for all the thicknesses. Administration of 1 Gy x cm(2) to the patient involves 7 microSv to the eyes of the cardiologist (without extra protection). In conclusion, the experimental correlation factors found between phantom and scatter doses allow a fairly good estimation of staff doses from the dosimetric patient data.
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