Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate. 相似文献
PURPOSE: The relationship between seizure frequency and both health care costs and quality of life (QOL) was investigated in a retrospective, cross-sectional, multicenter study in France, Germany, and the United Kingdom. METHODS: Three hundred outpatients with stable partial epilepsy were approximately evenly distributed among five seizure-frequency groups, ranging from seizure-free in the last 3 months (group 1) to daily seizures (group 5). Economic data, obtained through patient interviews and record abstraction, comprised direct medical costs, direct nonmedical costs, and indirect costs for the preceding 3 months. Total societal costs in the three countries were pooled and converted to United States dollar equivalents. QOL was assessed through a self-administered questionnaire, the Functional Status Questionnaire (FSQ). RESULTS: Mean total costs increased from $780 in group 1 to $2,171 in group 5 (p = 0.0001), with significant increases in each cost category as seizure frequency increased. Greater seizure frequency also significantly (p = 0.0270) correlated with lower employment rates, which ranged from 57% in group 1 to 30% in group 5. QOL declined as seizure frequency increased. Particularly affected were basic and intermediate activities of daily living (ADL), mental health, social activity, and feeling about health. CONCLUSIONS: The study results show that higher seizure frequencies are associated with higher direct and indirect costs and with reduced QOL for patients with epilepsy. 相似文献
Currently in vivo gene delivery by synthetic vectors is hindered by the limited diffusibility of complexes in extra-cellular fluids and matrices. Here we show that certain formulations of plasmid DNA with linear polyethylenimine (22 kDa PEI, ExGene 500) can produce complexes that are sufficiently small and stable in physiological fluids so as to provide high diffusibility. When plasmid DNA was formulated with 22 kDa PEI in 5% glucose, it produced a homogeneous population of complexes with mean diameters ranging from 30 to 100 nm according to the amount of PEI used. In contrast, formulation in physiological saline produced complexes an order of magnitude greater (> or = 1 micron). Intraventricular injection of complexes formulated in glu-cose showed the complexes to be highly diffusible in the cerebrospinal fluid of newborn and adult mice, diffusing from a single site of injection throughout the entire brain ventricular spaces. Transfection efficiency was followed by histochemistry of beta-galactosidase activity and double immunocytochemistry was used to identify the cells transfected. Transgene expression was found in both neurons and glia adjacent to ventricular spaces. Thus, this method of formulation is promising for in vivo work and may well be adaptable to other vectors and physiological models. 相似文献
Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode. 相似文献
This paper is to introduce an application of Computational Intelligence (CI) to Moving Picture Expert Group-4 (MPEG-4) video
compression over IEEE.802.15.1 wireless communication, known as Bluetooth 1.2, in order to improve picture quality. The 2.4 GHz
Industrial, Scientific and Medical frequency band is used for the IEEE.802.15.1 standard. IEEE.802.15.1 can be affected by
noise and interference due to other neighboring wireless devices sharing the same frequency carrier. The noise and interference
create difficulties in ascertaining an accurate real-time transmission rate at the receiving end. Furthermore, the MPEG-4
codec is an object-oriented compression system and demands a high bandwidth. It is therefore difficult to avoid excessive
delay, image quality degradation and/or data loss during MPEG-4 video transmission over standard systems. A new buffer entitled
‘buffer added’ has been introduced at the input of the Bluetooth 1.2 device. This buffer is controlled by a Rule-Based Fuzzy
(RBF) logic controller at the input and a neural-fuzzy controller (NFC) at the output. The two new fuzzy rules manipulate
and supervise the flow of video over the Bluetooth 1.2 standard. The computer simulation results illustrate the comparison
between a non-CI video transmission over Bluetooth 1.2 and the proposed design, confirming that the applications of RBF and
NFC do improve the image quality, reduce data loss and reduce time delay. 相似文献
This study investigates the cumulative energy demand (CED) of different systems for the management of urban wastewater, following the methodology of Life Cycle Assessment. In a hypothetical case study for an urban area (5,000 inhabitants), all relevant processes for wastewater collection and treatment and the construction of infrastructure are described in a substance flow model. The conventional system requires 1,250 MJ/(pe*a), with the operation contributing 45%, the infrastructure 7%, and the system expansion (production of mineral fertilizer and electricity) 48% to the total CED. The separation systems have a CED of 930-1,182 MJ/(pe*a) depending on their configuration. Results of the impact assessment show that recovering energy from the organic matter of toilet wastewater and household biowaste in a digestion process can decrease the cumulative energy demand by 13-26%. Energetic benefits of mineral fertilizer substitution are relatively small compared to the energy recovered from organic matter. Decisive parameters for the energy analysis are the amount of biowaste which is co-digested with toilet wastewater and the energy demand of the vacuum plant. 相似文献
Thermal loading induces modifications of the precipitation microstructure of Al–Si–Cu–Mg alloys. This study focuses on the effect of deformation on precipitation microstructure during thermomechanical loadings. Several specimens were thermomechanically cycled while others were exposed to the same thermal cycles without any mechanical loading. The nature and morphological characteristics of the precipitation microstructure of the thermomechanically cycled specimens are compared to those of the thermally aged ones, using transmission electron microscopy (TEM), in order to assess the effect of deformation on the precipitation microstructure and especially on the kinetics of precipitate growth. The absence of any significant effect of superimposed straining during thermal cycling is discussed. Implications for the prevision of yield strength degradation during service operation are briefly presented.