Are supplementary services provided during methadone maintenance really cost-effective?

OBJECTIVE: Previous research has suggested that support services supplementing methadone maintenance programs vary in their cost-effectiveness. This study examined the cost-effectiveness of varying levels of supplementary support services to determine whether the relative cost-effectiveness of alternative levels of support is sustained over time. METHOD: A group of 100 methadone-maintained opiate users were randomly assigned to three treatment groups receiving different levels of support services during a 24-week clinical trial. One group received methadone treatment with a minimum of counseling, the second received methadone plus more intensive counseling, and the third received methadone plus enhanced counseling, medical, and psychosocial services. The results at the end of the trial period have been published elsewhere. This article reports the results of an analysis at a 6-month follow-up. RESULTS: The follow-up analysis reaffirmed the preliminary findings that the methadone plus counseling level provided the most cost-effective implementation of the treatment program. At 12 months, the annual cost per abstinent client was $16,485, $9,804, and $11,818 for the low, intermediate, and high levels of support, respectively. Abstinence rates were highest, but modestly so, for the group receiving the high-intensity, high-cost methadone with enhanced services intervention. CONCLUSIONS: This study suggests that large amounts of support to methadone-maintained clients are not cost-effective, but it also demonstrates that moderate amounts of support are better than minimal amounts. As funding for these programs is reduced, these findings suggest a floor below which supplementary support should not fall.     

Oral administration of rapamycin and cyclosporine differentially alter intestinal function in rabbits

The immunosuppressive drugs rapamycin (Rap) and cyclosporine A (CsA) are used clinically to modify or abolish immune-mediated functions. This study examined the effect of orally administered regimens of Rap, CsA, and a combination of Rap/CsA on intestinal function in male New Zealand white rabbits. Animals received oral doses of CsA (15 mg/kg/body weight/day), low-dose (LD) and high-dose (HD) Rap (0.25 or 1 mg/kg/body wt/day, respectively), or Rap/CsA (0.25 and 5 mg/kg/body wt/day, or 0.5 and 5 mg/kg/body wt/day, respectively) for 20 days. We measured in vitro uptake of nutrients and permeability, and morphometric measurements in the jejunum and ileum were made. Animals receiving HD-Rap or HD-Rap/CsA had decreased food intake, body weight, and intestinal weight, when compared with LD-Rap, LD-Rap/CsA, CsA, or controls. The maximal transport rate (Vmax) for the active jejunal uptake of D-glucose was increased in HD-Rap and CsA, but not in the HD-Rap/CsA-treated animals. The jejunal Vmax of D-glucose in the LD-Rap- or -Rap/CsA-treated animals was no different from controls. In the HD-Rap- and HD-Rap/ CsA-treated animals, jejunal rates of uptake of stearic, linoleic, and linolenic acids were reduced when compared with controls. Jejunal and ileal permeability (as assessed by the passive uptake of L-glucose, tissue conductance, and mucosal-to-serosal flux of [3H]inulin) was increased in animals treated with HD-Rap or HD-Rap/CsA, when compared with CsA or controls. These parameters of permeability were no different at lower doses of Rap or Rap/CsA. The jejunal and ileal villous surface area was increased in CsA, but decreased in HD-Rap or HD-Rap/CsA animals. Thus, HD-Rap given alone or in combination with CsA reduced body weight gain, in part due to reduced food intake and malabsorption of lipids, which was due at least in part to reduced intestinal surface area. The relevance of these findings to patients undergoing chronic immunosuppressive drug therapy needs to be established.     

Fluid catalytic cracking optimisation using factorial design and genetic algorithm techniques

Statistical techniques coupled with genetic algorithm (GA) were used to identify optimal values of key operational variables in fluid catalytic cracking (FCC) process. A Kellog Orthoflow F fluid catalytic cracking process model was considered. It is known as a highly nonlinear process with a large number of variables with strong interactions among them. A reduced process model was obtained through factorial design technique to be used as a process function in the optimisation work giving as result the operational conditions that maximise conversion without infringing operational restrictions with savings in computational burden and time. An increase of 8.71% in process conversion was achieved applying GA as optimisation technique. © 2012 Canadian Society for Chemical Engineering     

Osteopontin in chronic puromycin aminonucleoside nephrosis

Increased expression of osteopontin (OPN) associated with interstitial monocyte infiltration has been demonstrated in the early phase of a variety of experimental renal diseases. Whether these changes occur in the chronic phase of progressive glomerular disease is unknown. Chronic puromycin aminonucleoside nephrosis (PAN) was induced in 16 rats by the injection of a single bolus of PA into the internal jugular vein, which results in a triphasic disease characterized by minimal glomerular change and marked proteinuria, peaking at about 10 to 14 d and subsiding by 28 d, followed by a quiescent 4-wk period of no or minimal proteinuria and then the development of progressive focal glomerulosclerosis (FGS) and increasing proteinuria. Fifteen rats injected similarly with normal saline served as controls. At 11 d after injection, PA rats demonstrated significantly greater urinary protein excretion (P = 0.0107), cortical tubular OPN expression (P = 0.0086), and intraglomerular (P = 0.0009) and interstitial (P = 0.0212) monocyte infiltration than did the controls. At 42 d, no significant differences between the two groups with respect to the above parameters were detected. At 98 d, PA rats had FGS and showed a definite trend to increased proteinuria, cortical tubular OPN, and intraglomerular monocyte infiltration. Although the cortical interstitial monocyte count was not elevated in PA rats compared with controls, there were significantly more monocytes around OPN-positive cortical tubules than around OPN-negative ones (P = 0.0011). Cortical tubular OPN expression correlated well with urinary protein excretion (r = 0.932, P < 0.0001), cortical tubular proliferating cell nuclear antigen (r = 0.796, P < 0.0001), and intraglomerular monocyte count (r = 0.552, P = 0.0013). The results are consistent with a monocyte chemoattractant role for OPN and suggest that OPN is upregulated in the chronic phase of PAN and that this increase in expression is a result of glomerular events.     

Optimisation of a continuous flash fermentation for butanol production using the response surface methodology

Factorial design and response surface techniques were used in combination with mathematical modelling and computational simulation to optimise an innovative industrial bioprocess, the production of biobutanol employing the flash fermentation technology. A parametric analysis performed by means of a full factorial design at two levels determined the influence of operating variables on butanol yield and productivity. A second set of simulations were carried out based on the central composite rotatable design. This procedure generated simplified statistical models that describe butanol yield and productivity as functions of the significant operating variables. From these models, response surfaces were obtained and used to optimise the process. For a range of substrate concentration from 130 to 180 g/l, the optimum operating ranges ensure butanol productivity between 7.0 and 8.0 g/l h, butanol yield between 19 and 22%, substrate conversion above 90% and final butanol concentration around 25 g/l.     

Variable distributions of Ca(2+)-permeable and Ca(2+)-impermeable AMPA receptors on embryonic rat dorsal horn neurons

1. By measuring the apparent reversal potential (aErev) of kainate- and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA)-evoked currents associated with changes in extracellular Ca2+ concentration ([Ca2+]e), we have been able to identify embryonic dorsal horn neurons grown in tissue culture that express Ca(2+)-permeable non-N-methyl-D-aspartic acid (NMDA) receptors. 2. The relative expression of Ca(2+)-permeable and Ca(2+)-impermeable non-NMDA receptors varies from cell to cell. This was evident from the range of a ErevS observed for kainate-evoked currents in a 0 mM [Na+]e, 10 mM [Ca2+]e bath. Under these conditions, aErev ranged from -96 to -21 mV, suggesting that the percentage of the non-NMDA receptors on each neuron that are Ca(2+)-permeable is variable. 3. To determine the extent to which the variability in aErev is due to variable receptor expression rather than experimental variability, we compared the effects of changes in [Ca2+]e on kainate-evoked currents and NMDA-evoked currents on the same cells. Assuming that all of the NMDA receptors on each neuron have a similar Ca2+ permeability, this approach provides an index of the sensitivity of our assay system. The reversal potential of NMDA-evoked currents in 10 mM [Ca2+]e ranged from -30 to -7 mV, whereas on the same population of neurons, the aErev of kainate-evoked currents ranged from -92 to -40 mV. 4. The rectification properties of the non-NMDA currents were generally linear or outwardly rectifying in normal bath solution. When the PCa/PCs ratio in 0 mM [Na+]e, 10 mM [Ca2+]e bath solution was assessed as a function of the rectification index in standard bath, a poor correlation was found between Ca2+ permeability and the rectification index. 5. The aErev of kainate-evoked currents was similar to that of cyclothiazide-enhanced AMPA-evoked currents observed on the same cells (-66.5 +/- 18.4 and -64.0 +/- 13.9 mV, mean +/- SD, respectively). This suggests that kainate is primarily activating the AMPA receptor and that the majority of non-NMDA receptors on embryonic dorsal horn neurons in culture are high-affinity AMPA receptors. 6. Immunocytochemical evidence suggests that the AMPA receptor subunits GluR1-4 are expressed to a variable degree from cell to cell in our cultures. We found evidence for low levels of expression of the kainate receptor subunits GluR5-7. The immunocytochemical observations support the physiological data indicating that much of the kainate-evoked current recorded in our experiments can be accounted for by kainate activation of AMPA receptors.(ABSTRACT TRUNCATED AT 400 WORDS)     

Promyelocytic blast crisis of chronic myelogenous leukaemia with translocations (9;22) and (15;17)

The murine monoclonal antibody A7 (MAb A7) is reactive against most human gastric cancer cell lines. Using a nude mouse peritoneal dissemination model of human gastric cancer, we investigated targeted chemotherapy using a conjugate of neocarzinostatin (NCS) with MAb A7 (A7-NCS). After demonstrating cytotoxicity of the complex against the human gastric cancer cell line MKN45 in vitro, we intraperitoneally injected A7-NCS, NCS or saline into nude mice bearing peritoneally disseminated human gastric cancer. A7-NCS inhibited peritoneal dissemination significantly more effectively than NCS. MAb A7 may prove to be an effective carrier for antineoplastic drugs in patients with peritoneal dissemination of gastric cancer.     

Detraining from total body exercise ergometry in individuals with spinal cord injury

Fibroblast-mediated cytokine gene therapy has proven to be a promising strategy for restoring hematopoiesis following repeated chemotherapy. Interleukin 3 (IL-3) and interleukin 6 (IL-6) can synergistically promote the recovery of hematopoiesis following chemotherapy. In this investigation, combined use of fibroblast-mediated IL-3 and IL-6 gene therapy was tested for hematopoietic effects on mice with or without 5-fluorouracil administration. The results demonstrated that combined therapy with IL-3 gene-modified NIH3T3 cell (NIH3T3-IL-3) and IL-6 gene-modified fibroblast NIH3T3 cell (NIH3T3-IL-6) implantation achieves obvious stimulation of hematopoiesis in normal mice and accelerates recovery of hematopoiesis. In normal mice the quantities of platelets, neutrophils, and total white blood cells in peripheral blood increased significantly after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells. The numbers of colony-forming unit (CFU) granulocyte/macrophage (CFU-GM) and CFU megakaryocyte (CFU-MK) formed by stem cells in bone marrow was significantly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than after the implantation of NIH3T3-IL-3 alone, NIH3T3-IL-6 alone, or neomycin gene-modified NIH3T3 cells. In hematopoiesis-depressed mice induced by preinjection with 5-fluorouracil at the dose of 150 mg/kg before cell implantation, the platelets, neutrophils, and white blood cells showed accelerated recovery, and the numbers of CFU-GM and CFU-MK formed by bone marrow cells were also markedly higher after the combined implantation of NIH3T3-IL-3 and NIH3T3-IL-6 cells than in control groups. Our data show that combined use of fibroblast-mediated IL-3 and IL-6 gene therapy may be of clinical relevance for the recovery of hematopoietic depression for patients after chemotherapy.     

One-step synthesis of composite electrolytes of Eu-doped ceria and alkali metal carbonates

Europium-doped ceria (EDC, Ce_0.9Eu_0.1O_2−δ)/alkaline carbonate (LNC, (Li,Na)₂CO₃) composite ceramics prepared through a one-step citrate-based route were analyzed by powder X-ray diffraction, infrared and laser Raman spectroscopies as well as scanning and transmission electron microscopy. The electrochemical behavior of the electrolyte material was studied by impedance spectroscopy in air, CO₂ and N₂ + H₂ (90/10 vol%, respectively) gas mixtures, in the temperature range 300–600 °C. The sub micrometric and even nanosized ceramic particles appeared as merged inside the mixed carbonates, with modest grain to grain necking. The EDC/LNC composite electrolytes showed a conductivity of 0.27 S cm⁻¹ at 600 °C in air, amongst the best ever reported, exceeding the usual requirements for fuel cell applications.