We have developed a prototype imaging system that can perform simultaneous x-ray transmission CT and SPECT phantom studies. This system employs a 23-element high-purity-germanium detector array. The detector array is coupled to a collimator with septa angled toward the focal spot of an x-ray tube. During image acquisition, the x-ray fan beam and the detector array move synchronously along an arc pivoted at the x-ray source. Multiple projections are obtained by rotating the object, which is mounted at the center of rotation of the system. The detector array and electronics can count up to 10(6) cps/element with sufficient energy-resolution to discriminate between x-rays at 100-120 kVp and gamma rays from 99mTc. We have used this device to acquire x-ray CT and SPECT images of a three-dimensional Hoffman brain phantom. The emission and transmission images may be superimposed in order to localize the emission image on the transmission map.
We aim to capture and apply 3-dimensional bone fragility features for fracture risk estimation. Using inter-subject image registration, we constructed a hip QCT atlas comprising 37 patients with hip fractures and 38 age-matched controls. In the hip atlas space, we performed principal component analysis to identify the principal components (eigen images) that showed association with hip fracture. To develop and test a hip fracture risk model based on the principal components, we randomly divided the 75 QCT scans into two groups, one serving as the training set and the other as the test set. We applied this model to estimate a fracture risk index for each test subject, and used the fracture risk indices to discriminate the fracture patients and controls. To evaluate the fracture discrimination efficacy, we performed ROC analysis and calculated the AUC (area under curve). When using the first group as the training group and the second as the test group, the AUC was 0.880, compared to conventional fracture risk estimation methods based on bone densitometry, which had AUC values ranging between 0.782 and 0.871. When using the second group as the training group, the AUC was 0.839, compared to densitometric methods with AUC values ranging between 0.767 and 0.807. Our results demonstrate that principal components derived from hip QCT atlas are associated with hip fracture. Use of such features may provide new quantitative measures of interest to osteoporosis.
Objectives Increasing evidence suggests that a genetically determined functional impairment of the hepatocellular efflux transporters bile salt export pump (BSEP, ABCB11) and multidrug resistance protein 3 (MDR3, ABCB4) play a pathophysiological role in the development of drug-induced liver injury. The aim of this study was therefore to describe the extent of genetic variability in ABCB11 and ABCB4 in patients with drug-induced liver injury and to in vitro functionally characterize newly detected ABCB11 mutations and polymorphisms. Methods ABCB11 and ABCB4 were sequenced in 23 patients with drug-induced cholestasis and 13 patients with drug-induced hepatocellular injury. Ninety-five healthy Caucasians served as the control group. Reference and mutant BSEP were expressed in Sf9 cells and ATP-dependent transport of [3H]-taurocholate was measured in a rapid filtration assay. Results Four highly conserved nonsynonymous mutations were specific for drug-induced liver injury [ABCB11: D676Y (drug-induced cholestasis) and G855R (drug-induced cholestasis); ABCB4: I764L (drug-induced cholestasis) and L1082Q (drug-induced hepatocellular injury)]. Furthermore, a polymorphism in exon 13 of ABCB11 (V444A), which is associated with decreased hepatic BSEP expression was significantly more frequent in drug-induced cholestasis patients than in drug-induced hepatocellular injury patients and healthy controls (76 versus 50 and 59% in drug-induced cholestasis patients, drug-induced hepatocellular injury patients and healthy controls, respectively; P<0.05). The in-vitro transport activity of the V444A and the D676Y BSEP constructs was similar, whereas the G855R mutation was nonfunctional. Conclusion In summary, our data support a role of ABCB11 and ABCB4 mutations and polymorphisms in drug-induced cholestasis. Genotyping of selected patients with acquired cholestasis might help to identify individuals with a genetic predisposition.
Environmental factors cause cancer in both wild animals and humans. In ecological settings, genetic variation and natural selection can sometimes produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defense mechanisms. The Baltic and North Sea are amongst the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys flesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defense mechanisms. We conducted gene expression analyses for 30 flatfishes. By comparing cancerous and healthy fishes, and non-cancerous fishes from clean and polluted sites, we suggest genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumor suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests either hormetic upregulation of tumor suppression or a stronger natural selection pressure for higher cancer resistance for flounders in polluted environment. Based on gene expression patterns seen in cancerous and healthy fish, for liver cancer to develop in flounders, genetic defense mechanisms need to be suppressed, while in dabs, analogous process is weak or absent. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defense mechanisms.
Paternostro-Sluga T, Schuhfried O, Vacariu G, Lang T, Fialka-Moser V: Chronaxie and accommodation index in the diagnosis of muscle denervation. Am J Phys Med Rehabil 2002;81:253–260. Objective To determine the sensitivity of the combined measurement of chronaxie and the accommodation index in the qualitative diagnosis of muscle denervation with needle electromyography and to compare quantitative diagnoses. Design Ninety-three neurogenic muscles diagnosed by needle electromyography were consecutively included for measurement of chronaxie and the accommodation index in this prospective study. The sensitivity of qualitative diagnosis was assessed for all muscles, separately for the acute and subacute-chronic denervation phase and for the complete and partial denervation. Results The combined measurement of chronaxie and the accommodation index showed a 90% sensitivity to needle electromyography for qualitative diagnosis of muscle denervation for all muscles. A 100% sensitivity was found for the acute denervation phase and for complete denervation. The subacute-chronic denervation phase revealed a 86% sensitivity, and partial denervation had a 88% sensitivity. The kappa coefficients did not show satisfactory agreement in quantitative diagnosis, and Bowker's test revealed a statistically significant underestimation of muscle denervation for measurement of chronaxie. Conclusion The combined measurement of chronaxie and the accommodation index can be recommended for the screening of neurogenic lesions in the acute denervation phase.
In space, rapid losses in bone mineral density (BMD) leave astronauts at an increased risk of bone fracture. Longer microgravity missions combined with the lack of efficacy of current exercise regimes in reducing this loss leads to the need of a new treatment. This study has the goal of testing a treatment in the form of a low magnitude mechanical vibration. As an analog of space flight, 18 subjects spent 90 days in continuous 6 degree head down tilt, eight of which received 10 minutes of vibration treatment a day. Measurements of bone density and balance found that there was a 30–50% nonsignificant reduction in BMD loss in the hip, as well as a significant decrease in the loss of postural control. The combined factors of stronger bones and increased balance greatly reduce the risk of bone fracture. With a proposed multi-year planetary mission to Mars being planned by NASA, the need for improved musculoskeletal health is of increasing importance, and this device may provide the needed mode of increasing astronaut safety.
