Distribution of artifactual gas on post-mortem multidetector computed tomography (MDCT).

PURPOSE: We investigated the incidence and distribution of post-mortem gas detected with multidetector computed tomography (MDCT) to identify factors that could distinguish artifactual gas from cardiac air embolism. MATERIAL AND METHODS: MDCT data of 119 cadavers were retrospectively examined. Gas was semiquantitatively assessed in selected blood vessels, organs, and body spaces (82 total sites). RESULTS: Seventy-four of the 119 cadavers displayed gas (62.2%; CI 95% 52.8-70.9), and 56 (75.7%) displayed gas in the heart. Most gas was detected in the hepatic parenchyma (40%), right heart (38% ventricle, 35% atrium), inferior vena cava (30% infrarenally, 26% suprarenally), hepatic veins (26% left, 29% middle, 22% right), and portal spaces (29%). Male cadavers displayed gas more frequently than female cadavers. Gas was detected 5-84 hours after death; therefore, the post-mortem interval could not reliably predict gas distribution (rho = 0.719, p < 0.0001). We found that a large amount of putrefaction-generated gas in the right heart was associated with aggregated gas bubbles in the hepatic parenchyma (sensitivity = 100%, specificity = 89.7%). In contrast, gas in the left heart (sensitivity = 41.7%, specificity = 100%) or in periumbilical subcutaneous tissues (sensitivity = 50%, specificity = 96.3%) could not predict gas due to putrefaction. CONCLUSION: This study is the first to show that the appearance of post-mortem gas follows a specific distribution pattern. An association between intracardiac gas and hepatic parenchymal gas could distinguish between post-mortem-generated gas and vital air embolism. We propose that this finding provides a key for diagnosing death due to cardiac air embolism.

Peroxisome proliferator-activated receptor-alpha-null mice have increased white adipose tissue glucose utilization, GLUT4, and fat mass: Role in liver and brain.

Activation of the peroxisome proliferator-activated receptor (PPAR)-alpha increases lipid catabolism and lowers the concentration of circulating lipid, but its role in the control of glucose metabolism is not as clearly established. Here we compared PPARalpha knockout mice with wild type and confirmed that the former developed hypoglycemia during fasting. This was associated with only a slight increase in insulin sensitivity but a dramatic increase in whole-body and adipose tissue glucose use rates in the fasting state. The white sc and visceral fat depots were larger due to an increase in the size and number of adipocytes, and their level of GLUT4 expression was higher and no longer regulated by the fed-to-fast transition. To evaluate whether these adipocyte deregulations were secondary to the absence of PPARalpha from liver, we reexpresssed this transcription factor in the liver of knockout mice using recombinant adenoviruses. Whereas more than 90% of the hepatocytes were infected and PPARalpha expression was restored to normal levels, the whole-body glucose use rate remained elevated. Next, to evaluate whether brain PPARalpha could affect glucose homeostasis, we activated brain PPARalpha in wild-type mice by infusing WY14643 into the lateral ventricle and showed that whole-body glucose use was reduced. Hence, our data show that PPARalpha is involved in the regulation of glucose homeostasis, insulin sensitivity, fat accumulation, and adipose tissue glucose use by a mechanism that does not require PPARalpha expression in the liver. By contrast, activation of PPARalpha in the brain stimulates peripheral glucose use. This suggests that the alteration in adipocyte glucose metabolism in the knockout mice may result from the absence of PPARalpha in the brain.

Protocol for the modeling the epidemiologic transition study: a longitudinal observational study of energy balance and change in body weight, diabetes and cardiovascular disease risk.

ABSTRACT: BACKGROUND: The prevalence of obesity has increased in societies of all socio-cultural backgrounds. To date, guidelines set forward to prevent obesity have universally emphasized optimal levels of physical activity. However there are few empirical data to support the assertion that low levels of energy expenditure in activity is a causal factor in the current obesity epidemic are very limited. METHODS: The Modeling the Epidemiologic Transition Study (METS) is a cohort study designed to assess the association between physical activity levels and relative weight, weight gain and diabetes and cardiovascular disease risk in five population-based samples at different stages of economic development. Twenty-five hundred young adults, ages 25-45, were enrolled in the study; 500 from sites in Ghana, South Africa, Seychelles, Jamaica and the United States. At baseline, physical activity levels were assessed using accelerometry and a questionnaire in all participants and by doubly labeled water in a subsample of 75 per site. We assessed dietary intake using two separate 24-h recalls, body composition using bioelectrical impedance analysis, and health history, social and economic indicators by questionnaire. Blood pressure was measured and blood samples collected for measurement of lipids, glucose, insulin and adipokines. Full examination including physical activity using accelerometry, anthropometric data and fasting glucose will take place at 12 and 24 months. The distribution of the main variables and the associations between physical activity, independent of energy intake, glucose metabolism and anthropometric measures will be assessed using cross-section and longitudinal analysis within and between sites. DISCUSSION: METS will provide insight on the relative contribution of physical activity and diet to excess weight, age-related weight gain and incident glucose impairment in five populations' samples of young adults at different stages of economic development. These data should be useful for the development of empirically-based public health policy aimed at the prevention of obesity and associated chronic diseases.

Impact of genomic methylation on radiation sensitivity of colorectal carcinoma.

PURPOSE: To investigate the influence of demethylation with 5-aza-cytidine (AZA) on radiation sensitivity and to define the intrinsic radiation sensitivity of methylation deficient colorectal carcinoma cells. METHODS AND MATERIALS: Radiation sensitizing effects of AZA were investigated in four colorectal carcinoma cell lines (HCT116, SW480, L174 T, Co115), defining influence of AZA on proliferation, clonogenic survival, and cell cycling with or without ionizing radiation. The methylation status for cancer or DNA damage response-related genes silenced by promoter methylation was determined. The effect of deletion of the potential target genes (DNMT1, DNMT3b, and double mutants) on radiation sensitivity was analyzed. RESULTS: AZA showed radiation sensitizing properties at >or=1 micromol/l, a concentration that does not interfere with the cell cycle by itself, in all four tested cell lines with a sensitivity-enhancing ratio (SER) of 1.6 to 2.1 (confidence interval [CI] 0.9-3.3). AZA successfully demethylated promoters of p16 and hMLH1, genes associated with ionizing radiation response. Prolonged exposure to low-dose AZA resulted in sustained radiosensitivity if associated with persistent genomic hypomethylation after recovery from AZA. Compared with maternal HCT116 cells, DNMT3b-defcient deficient cells were more sensitive to radiation with a SER of 2.0 (CI 0.9-2.1; p = 0.03), and DNMT3b/DNMT1-/- double-deficient cells showed a SER of 1.6 (CI 0.5-2.7; p = 0.09). CONCLUSIONS: AZA-induced genomic hypomethylation results in enhanced radiation sensitivity in colorectal carcinoma. The mediators leading to sensitization remain unknown. Defining the specific factors associated with radiation sensitization after genomic demethylation may open the way to better targeting for the purpose of radiation sensitization.

A comparison of the spatial dependence of body mass index among adults and children in a Swiss general population.

BACKGROUND: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether BMI clusters among children and how age-specific BMI clusters are related remains unknown. We aimed to identify and compare the spatial dependence of BMI in adults and children in a Swiss general population, taking into account the area's income level. METHODS: Geo-referenced data from the Bus Santé study (adults, n=6663) and Geneva School Health Service (children, n=3601) were used. We implemented global (Moran's I) and local (local indicators of spatial association (LISA)) indices of spatial autocorrelation to investigate the spatial dependence of BMI in adults (35-74 years) and children (6-7 years). Weight and height were measured using standardized procedures. Five spatial autocorrelation classes (LISA clusters) were defined including the high-high BMI class (high BMI participant's BMI value correlated with high BMI-neighbors' mean BMI values). The spatial distributions of clusters were compared between adults and children with and without adjustment for area's income level. RESULTS: In both adults and children, BMI was clearly not distributed at random across the State of Geneva. Both adults' and children's BMIs were associated with the mean BMI of their neighborhood. We found that the clusters of higher BMI in adults and children are located in close, yet different, areas of the state. Significant clusters of high versus low BMIs were clearly identified in both adults and children. Area's income level was associated with children's BMI clusters. CONCLUSIONS: BMI clusters show a specific spatial dependence in adults and children from the general population. Using a fine-scale spatial analytic approach, we identified life course-specific clusters that could guide tailored interventions.

Crises as a disease of the body politick: a metaphor in the history of nineteenth century economics

This paper examines the use of the medical metaphor in the early theories of crises. It first considers the borrowing of medical terminology and generic references to disease which, notwithstanding their relatively trivial character, illustrate how crises were originally conceived as disturbances (often of a political nature) to a naturally healthy system. Then it shows how a more specific metaphor, the fever of speculation, shifted the emphasis by treating prosperity as the diseased phase, to which crises are a remedy. The metaphor of the epidemic spreading of the disease introduced the theme of the cumulative character of both upswing and downswing, while the similitude with intermittent fevers accounted for the recurring nature of crises. Finally, the paper examines how the medical reflections on the causality of diseases contributed to the epistemology of crises theory, and reflects on the metaphisical shift accompanying the transition from the theories of crises to the theories of cycles.

The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression.

Metformin demonstrates anorectic effects in vivo and inhibits neuropeptide Y expression in cultured hypothalamic neurons. Here we investigated the mechanisms implicated in the modulation of feeding by metformin in animals rendered obese by long-term high-fat diet (diet-induced obesity [DIO]) and in animals resistant to obesity (diet resistant [DR]). Male Long-Evans rats were kept on normal chow feeding (controls) or on high-fat diet (DIO, DR) for 6 months. Afterward, rats were treated 14 days with metformin (75 mg/kg) or isotonic sodium chloride solution and killed. Energy efficiency, metabolic parameters, and gene expression were analyzed at the end of the high-fat diet period and after 14 days of metformin treatment. At the end of the high-fat diet period, despite higher leptin levels, DIO rats had higher levels of hypothalamic neuropeptide Y expression than DR or control rats, suggesting a central leptin resistance. In DIO but also in DR rats, metformin treatment induced significant reductions of food intake accompanied by decreases in body weight. Interestingly, the weight loss achieved by metformin was correlated with pretreatment plasma leptin levels. This effect was paralleled by a stimulation of the expression of the leptin receptor gene (ObRb) in the arcuate nucleus. These data identify the hypothalamic ObRb as a gene modulated after metformin treatment and suggest that the anorectic effects of the drug are potentially mediated via an increase in the central sensitivity to leptin. Thus, they provide a rationale for novel therapeutic approaches associating leptin and metformin in the treatment of obesity.

The Effect Of Induced Intraocular Straylight (cataract Simulation) On Sensitivity Measures Of Standard Automated Perimetry, Pulsar Perimetry And Moorfields Motion Displacement Test

Purpose: To investigate the effect of incremental increases in intraocular straylight on threshold measurements made by three modern forms of perimetry: Standard Automated Perimetry (SAP) using Octopus (Dynamic, G-Pattern), Pulsar Perimetry (PP) (TOP, 66 points) and the Moorfields Motion Displacement Test (MDT) (WEBS, 32 points).Methods: Four healthy young observers were recruited (mean age 26yrs [25yrs, 28yrs]), refractive correction [+2 D, -4.25D]). Five white opacity filters (WOF), each scattering light by different amounts were used to create incremental increases in intraocular straylight (IS). Resultant IS values were measured with each WOF and at baseline (no WOF) for each subject using a C-Quant Straylight Meter (Oculus, Wetzlar, Germany). A 25 yr old has an IS value of ~0.85 log(s). An increase of 40% in IS to 1.2log(s) corresponds to the physiological value of a 70yr old. Each WOFs created an increase in IS between 10-150% from baseline, ranging from effects similar to normal aging to those found with considerable cataract. Each subject underwent 6 test sessions over a 2-week period; each session consisted of the 3 perimetric tests using one of the five WOFs and baseline (both instrument and filter were randomised).Results: The reduction in sensitivity from baseline was calculated. A two-way ANOVA on mean change in threshold (where subjects were treated as rows in the block and each increment in fog filters was treated as column) was used to examine the effect of incremental increases in straylight. Both SAP (p<0.001) and Pulsar (p<0.001) were significantly affected by increases in straylight. The MDT (p=0.35) remained comparatively robust to increases in straylight.Conclusions: The Moorfields MDT measurement of threshold is robust to effects of additional straylight as compared to SAP and PP.

Space for thought: Representation of body boundaries and intellectual efficiency in children

Aim: The psychoanalytic theories of Bion, Anzieu, Berger and Gibello postulate that the development of thinking depends upon the formation of a psychic space. This thinking space has its origin in the body and in our interpersonal relations. This study aims to validate this psychodynamic hypothesis. Method: A group of 8- to 14-year-old children participated in this research. The presence of a thinking space was operationalized by the "barrier" and "penetration" scores on the Rorschach's Fisher and Cleveland scales and intellectual efficiency was measured using a short version of the WISC-IV. Results: Results show that extreme scores on the "barrier" and "penetration" variables predict a lower intellectual level than average scores on the same variables. Conclusion: The development of thinking and personality are undoubtedly linked and the "barrier" and "penetration" variables are useful measures when evaluating the development of a space for thought.

Ambulatory monitoring of physical activities in patients with Parkinson's disease.

A new ambulatory method of monitoring physical activities in Parkinson's disease (PD) patients is proposed based on a portable data-logger with three body-fixed inertial sensors. A group of ten PD patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) and ten normal control subjects followed a protocol of typical daily activities and the whole period of the measurement was recorded by video. Walking periods were recognized using two sensors on shanks and lying periods were detected using a sensor on trunk. By calculating kinematics features of the trunk movements during the transitions between sitting and standing postures and using a statistical classifier, sit-to-stand (SiSt) and stand-to-sit (StSi) transitions were detected and separated from other body movements. Finally, a fuzzy classifier used this information to detect periods of sitting and standing. The proposed method showed a high sensitivity and specificity for the detection of basic body postures allocations: sitting, standing, lying, and walking periods, both in PD patients and healthy subjects. We found significant differences in parameters related to SiSt and StSi transitions between PD patients and controls and also between PD patients with and without STN-DBS turned on. We concluded that our method provides a simple, accurate, and effective means to objectively quantify physical activities in both normal and PD patients and may prove useful to assess the level of motor functions in the latter.