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688 USE OF BABESIA MICROTI AS A MODEL FOR LIVE HAEMOPROTOZOA VACCINES IN CRYOPRESERVATION STUDIES. Landmann JK, Finger MJ, de Vos AJ, Jackson LA. Tick Fever Research Centre, Queensland Department of Primary Industries, Wacol, Queensland, Australia. Live vaccines are used for the control of a number of haemoprotozoa in veterinary medicine and are under investigation for the control of malaria in humans. Live parasite vaccines provide the benefit of delivering a complex multiple-antigenic stimulus to the host, however a major limitation is the distribution of either a chilled vaccine with a short-shelf life or a cryopreserved product that requires storage in liquid nitrogen until use. This limitation was addressed to improve the current cryopreserved vaccine used in the control of tick fever Babesia bigemina, B. bovis and Anaplasma marginale ; in cattle. A B. microti-mouse model system was chosen to investigate the possible cryopreservatives glycerol, polyvinylpyrrolidone PVP ; , propylene glycol, dextran and dimethyl sulfoxide DMSO , additives including sorbitol, bovine serum, glucose, sucrose ; and tonicity of salt solutions. The most promising cryopreservatives, additives and salt solutions in the B. microti-mouse system will be tested using tick fever organisms in cattle. Preliminary results suggest that 3M glycerol provides the greatest survival of parasites. The relative suitability of other cryopreservatives and additive combinations will be discussed. The outcomes of this research will provide benefits to the development of live vaccines against other blood parasites, such as Plasmodium in humans.
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Enteral nutrition in acute pancreatitis. Even though there is not a reduction in mortality for acute pancreatitis, there is reduction in morbidity, including infections, line sepsis and things like that, and there is a lower cost to treat these patients enterally. So typically we feed patients enterally, but beyond the ligament of Treitz. This next abstract looks at an interesting question "What we do without any evidence?" Most of us who take care of patients with mild acute pancreatitis when they start to eat again will give them a clear liquid diet. It is one of those things in medicine that we do that is not based on evidence. It is just what you were taught. That is where this next study comes from. This is a start toward where we need to go in pancreatic disease research. Abstract 217114: "A prospective, randomized, controlled trial of clear liquids vs. low-fat solid diet as the initial meal after mild pancreatitis" This study looked at what we should do in terms of re-feeding patients when they are getting better from their mild acute pancreatitis. This was a study of 121 patients, all of whom had mild disease according to the Atlanta Criteria. They were randomized to receive either clear liquids or a low-fat solid diet and the primary outcome of this study was the length of stay after the re-feed. They measured how many more days the patients were in the hospital once they started to eat again. When they looked at the calories the patients in each of the groups consumed, patients on the low-fat solid diet had a significantly higher number of calories that they were able to consume. That makes intuitive sense. Similarly they had higher amounts of fat if they were in the low-fat solid diet, but there was no difference in symptoms. No difference in pain, nausea, or vomiting between the two groups and there was no significant difference in the length of stay. They are almost identical; 1.7 days versus 1.9 + -2. They concluded that the low-fat solid diet was well tolerated and did not increase or decrease the length of stay. For most of us, that is the critical issue because we advance their food intake and when you get to solids you send the patient home. Their question was, "If we put you on solids to begin with, will we get you out the door sooner?" That didn't happen but it also suggested that the patients tolerated solids fine. We probably don't need to give them liquids. I think the take-home message here is that we should let the patients determine what they feel they can tolerate. That actually may end up decreasing length of stay letting the patients have a choice. We are going to move ahead to chronic pancreatitis. The next abstract looks at pain. You all know that there are multiple mechanisms for pain in chronic pancreatitis and multiple ways to treat it. Most of us use narcotic medications in patients with severe pain with chronic pancreatitis although as we mentioned earlier we also use anti-inflammatories. This abstract looked at radiation treatment for chronic pancreatitis. I did a review of the literature because it was so surprising to me to see the abstract. I found two studies that would be relevant to this. The first one was a canine study published in 1979 with 12 dogs that had bile trypsin-induced pancreatitis in which the authors randomized the dogs to receive either radiation therapy 400 rads or just general supportive care. They found a 13-fold increase in survival time in the dogs that had radiation. There was a single case report from Germany in 1998 where they treated a patient with severe pain that was resistant to even narcotic medication and that patient received 7 Gy and had pain relief after one week that persisted for up to three years of follow up. To my knowledge this abstract is the first actual study of radiation therapy for chronic pancreatitis that has been done. Abstract 220748: "Novel radiotherapeutic management of painful flare ups in chronic pancreatitis" This is a study of 12 patients, seven of whom had alcohol induced chronic pancreatitis, four that were idiopathic and one that had cystic fibrosis. The patients had to meet one of two criteria to be entered in and amaryl.
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The content of this newsletter is presented in a summary manner, is general in nature, and is provided for educational purposes only. The content is not intended to be a substitute for professional medical advice. The France Foundation does not recommend or endorse any specific test, products, or procedures that may be mentioned in this newsletter. Although The France Foundation makes every effort to publish accurate information, neither it nor any of its employees assume liability for the content of this publication. 1129-03 and atenolol!
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Exelgyn. Mifegyne patient information leaflet. Furedi A 1996 ; . Unplanned pregnancy: your choices: a practical guide to accidental pregnancy. Oxford Medical Publications. Klein D and Kaufmann T 1992 ; . Unplanned pregnancy making the right choice for you. Penguin. Penney G C, Thomson M, Norman J, McKenzie H, Vale L, Smith R and Imrie M 1998 ; . A randomised comparison of strategies for reducing infective complications of induced abortion. British Journal of Obstetrics and Gynaecology. 105: 599-604 Royal College of Obstetricians & Gynaecologists. Good Medical Practice Guidelines: Induced Abortion. Available at : rcog guidelines abortion Stafford M 1993 ; . Patient Pictures: Gynaecology. Health Press.
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The reporter transgene or both the transactivator and reporter constructs. In animals with only the reporter transgene, E transcripts were not detectable in any tissue examined by S1 nuclease analysis Fig. 2 A, left ; . A complete absence of E mRNA was also seen by RT-PCR not shown ; , confirming that there was no "leaky" expression of the reporter driven by the CMV minimal promoter. When both the reporter and transactivator constructs were present, substantial E transcripts were found in the thymus Fig. 2 A, center ; . Interestingly, no E mRNA was detectable in the spleen or LNs or any other tissue examined, but it was clearly present in the thymi, spleens, and LNs of control B10 mice, as expected Fig. 2 A, right ; . This restricted pattern of E transgene expression was also seen using RT-PCR.
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Dominant co-stimulatory ligand in several experimental animal models for autoimmune disease eg, systemic lupus erythematosus, multiple sclerosis, collagen-induced arthritis ; .4 Abatacept exhibited inhibition of the onset and progression of disease in a rat collagen-induced arthritis model with reductions in inflammation, inflammatory mediators interferon gamma, IL-2, monocyte chemoattractant protein1 [MCP-1], MCP-3, IL-1alpha, and IL-6 ; , and bone and joint destruction. PHARMACOKINETICS The mean terminal half-life of abatacept was 16.7 days range, 12 to 23 days ; following administration of a single 10 mg kg IV dose in healthy subjects.1 Multiple IV doses on days 1, 15, and 30, and monthly thereafter in patients with rheumatoid arthritis produced proportional increases in peak concentration and area under the curve over the dosing range of 2 to mg kg. The mean and amaryl.
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Physician Signature: Deliver to: Physician's Office Patient's Home Patient filling at local Pharmacy Name ; Fax: Please check if request is for Nave Patient or continuation of therapy. Nave Patient or New treatment start Start and End date of therapy: to Weight: Ib. or kg Does the patient have a history of receiving treatment? YES NO If yes, please indicate medication including dates, and dosage: NON-RESPONDER TO PREVIOUS TREATMENT RELAPSER AFTER PREVIOUS TREATMENT If yes, please indicate accordingly: Continuation Therapy - Date started: YES NO Is Member Co-infected with HIV? For treatment-Nave patients or New treatment starts, please submit a current within 3 months ; HCV viral titer, and AST ALT lab results with the form or indicate below on the form. If AST ALT are within normal limits, a liver biopsy is required to document active disease. For continuation of therapy treatment beyond 12 weeks ; , repeat HCV viral load, AST, & ALT 12 weeks after the initiation of therapy and submit lab results or indicate on form and submit pre-treatment labs or indicate on form below for reauthorization before 16 weeks after starting therapy so reauthorization is done in a timely manner.
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A. Daroszewska, R.J. van 't Hof, S.H. Ralston. Medicine and Therapeutics, University of Aberdeen, Aberdeen, Aberdeenshire, United Kingdom Background: Paget's disease of bone PDB ; is a common disorder characterized by focally increased and disorganized bone turnover. Mutations of the Sequestosome 1 gene, which codes for the scaffolding protein SQSTM1 p62, involved in NFB signalling have been found to account for up to 50% of familial PDB cases and 10% of sporadic cases. The P392L mutation is the most common one, and accounts for about 20% of familial and 10% of sporadic PDB cases. All SQSTM1 mutations identified so far, affect the ubiquitin-binding domain, responsible for the degradation of the protein itself, and for binding to ubiquitinated proteins, targeted for degradation. We previously reported that the P392L mutation increases NFB signalling in vitro in cell lines. Here we studied whether the P392L mutation increases NFB signalling in primary cells from patients with PDB as compared to age and sex matched controls. Methods: Peripheral blood mononuclear cells from patients carrying the P392L mutation and normal controls were isolated and stimulated with human recombinant TNF for 0, 5, 10, 15, and 60 minutes and phosphorylation and degradation of the NFB inhibitor IB, was assessed by Western Blotting, using P-IB and IB antibodies. Likewise, protein complexes were immunoprecipitated using IB antibodies followed by Western Blot analyis using p-62 antibodies. Results: P-IB levels at baseline were higher by about 10-20% in cells carrying the mutation. Stimulation with TNF resulted in a transient up-regulation of P-IB levels in both the mutated and normal cells, returning to baseline within 15 min. After 5 minutes of TNF stimulation P-IB peaked and was up-regulated by about 100% in the mutated cells as compared to controls. IB levels were elevated at baseline by about 100% in the mutated cells as compared to controls. IB co-precipitated with p62 in normal cells, but not in the mutated cells. Conclusions: The P392L mutation leads to accumulation of IB. In contrast to wild type p62, mutant p62 does not appear to bind to IB, suggesting impaired ubiquitination-dependent degradation of IB through a novel mechanism. This could account for the increased NFB signaling due to increased availability of IB-NFB complexes for phosphorylation. The enhanced NFB signalling could account for the increased numbers and phenotypical abnormalities of osteoclasts observed in PDB.
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Veterinary Feed Directive VFD ; Drug--The VFD category of medicated feeds was created by the Animal Drug Availability Act of 1996 to provide an alternative to prescription status for certain therapeutic animal pharmaceuticals for use in feed. Any animal feed bearing or containing a VFD drug shall be fed to animals only by or upon a lawful VFD issued by a licensed veterinarian in the course of the veterinarian's professional practice. EB 11 98; EB approved SCAR revision 4 04-oversight: SCAR ; Additional position statements and guidelines for use of antimicrobials for various species of animals for specific diseases are also provided on this website.
Sixteen percent of all GP, EPN, and SNPR neurons in awake rats had significant spectral peaks with periods in the range of 0.4 2.0 s. Distinct from slower periodic activity, which is presumably generated by endogenous processes, periodic activity in the 0.4- to 2.0-s range was clearly related to an external process, namely the artificial ventilation of the immobilized rats. Firing rate oscillations in this range in the SNPR have been previously reported in artificially ventilated rats Wilson et al. 1977 however, these authors concluded that the oscillatory activity was not related to ventilation. Although it is possible that basal ganglia neurons in the present study are oscillating spontaneously in the 0.8- to 1.1-s range, the precise correspondence between ventilator period and spectral peak period strongly suggests driving or at least entraining of a spontaneous oscillation ; by some aspect of artificial ventilation. GP, EPN, and SNPR neurons can respond to sensory input of various modalities Chernyshev and Weinberger 1998; DeLong et al. 1985; Joseph and Boussaoud 1985; Rothblat and Schneider 1995; Schwarz et al. 1984 ; , and it is difficult in the preparation used here to determine which modality mediates the present influence of artificial ventilation on GP activity. Firing rate periodicities related to ventilation did not preclude the presence of significant periodicities in the slower range 2to 60-s periods ; . Simultaneous oscillatory activity in two different bands has also been reported in other structures in awake rats Chrobak and Buzsaki 1998 ; . In many cases, spectral analysis of spike trains resulted in multiple statistically significant peaks in the power spectrum in the 2- to 60-s period range. Such multiple peaks may represent multiple simultaneous oscillations with different periods, sidelobes of a particularly powerful spectral peak, or harmonics due to a nonideal sinusoidal oscillation shape. Visual inspection of smoothed spike trains, particularly from epochs after DA agonist administration Figs. 1 and 2 ; , suggests a different interpretation. Even when firing rate oscillations were particularly strong and regular, their regularity was not perfect or "clockwork, " but often demonstrated phase shifts most common ; , gradual drift in period, or skipped cycles. It is likely that these various irregularities contribute to the appearance of multiple significant spectral peaks in many cases. Notably, periodic neuronal activity related to artificial ventilation, which is extremely regular, resulted almost exclusively in single spectral peaks without significant sidelobes Fig. 6 ; . On the other hand, in baseline spike trains, in which 2- to 60-s periodic activity when present ; was typically less regular than in post-DA agonist spike trains, and in which multiple spectral peaks sometimes spanned a relatively wide range of periods e.g., Fig. 2C ; , it is not possible to rule out the presence of multiple simultaneous firing rate oscillations. Numerous lines of research have emphasized the behavioral importance of periodic neuronal activity Cohen and Wallen 1980; Engel et al. 1997; Komisaruk 1970; Llinas and Ribary 1993; Smith et al. 1991 ; . The modulation of slow periodicities in firing rate in the present study by DAergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by DA. Firing rate oscillations in the seconds-to-minutes range may act to coordinate neuronal activity responsible for motor sequences, much as faster oscillations in sensory pathways may coordinate neuronal activity underlying perceptual binding Engel et al. 1997 ; . The behavioral actions of stimulants have been theorized to be due to an.
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