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Interferon beta for MS experience in the UK Title: Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre. Authors: BD Dubois, E Keenan, BE Porter, R Kapoor, P Rudg, AJ Thompson, DH Miller, G Giovanni. Place of Report: London, UK. Journal Reference: Journal of Neurology, Neurosurgery and Psychiatry, 2003. Vol. 74, pages 946-949. Research Summary Interferon beta IFN beta ; has been proven to reduce the relapse rate in people who have relapsing remitting MS RRMS ; . This therapy is also thought to slow the rate of disability progression. However, long-term effects and side effects are largely unknown, and there are problems with compliance and cost. An additional problem is the development of "neutralising antibodies" NABs ; , which occurs over time with this therapy. Development of these antibodies has recently been demonstrated to make the drugs less effective. This audit describes the implementation of IFN beta therapy for the treatment of people with MS in one London hospital. This review reported relapse rate, the number of disabling relapses requiring steroid treatment ; and mobility before and after treatment, in order to determine the benefit of IFN beta therapy in 101 people with MS. The proportion of people with NABs after treatment onset was also assessed, as was the proportion of people fulfilling the current "stopping criteria" of the therapy. The three beta interferon types Avonex, Betaferon, Rebif ; were found to reduce relapse rate to a similar extent, during an average treatment period of 26 months. None of the participants receiving Avonex were relapse free, 25% developed secondary progressive MS SPMS ; , but none developed NABs. 19% of participants receiving Betaferon were relapse free, 21% developed SPMS, and 38% developed NABs.
Author for correspondence : Jeffrey Cohen. Fax j1 301 496 7383. e-mail jcohen!niaid.nih.gov.
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The synthetic prostaglandin E1 analogue misoprostol has become an important drug in obstetric and gynaecological practice because of its uterotonic and cervical priming actions. A better understanding of the impact of the route of administration on pharmacokinetics, uterine contractility and cervical softening would help to further improve misoprostol regimens for several indications. The aims of this thesis were therefore to investigate the following effects of misoprostol in the first trimester of pregnancy.
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The complexity of the in utero effects of smoke exposure on the developing lung is further suggested by the fact that even though direct nicotine exposure might induce lipoto-myofibroblast transdifferentiation, in utero fetal smoke exposure is also accompanied by relative fetal hypoxia, which may prevent lipo-to-myofibroblast transdifferentiation. As we have previously demonstrated that exposure to hyperoxia augments the spontaneously occurring pulmonary lipo-to-myofibroblast transdifferentiation, it is tempting to speculate that the relative fetal hypoxia occurring with in utero smoke exposure may in fact have a protective effect on nicotine-induced lipo-to-myofibroblast transdifferentiation. The exact mechanism s ; by which nicotine induces lipo-to and refresh.
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Welcome and Introductions Keynote Address Mary Lou Clements-Mann Memorial Lecture Coffee Break Poster Session Charles Mrieux Award Luncheon Lunch on your own ; Lunch on your own ; Symposium 1: Conjugate Vaccine Issues Symposium 4: Concrete Proposals for Ensuring a Secure Supply of Vaccines in the U.S. Coffee Break Symposium 2: Update on Vaccines Against Enteric and Oral Infections Adjournment Poster Reception Coffee Break Exhibits Symposium 5: Vaccinology of Neglected Diseases: Malaria Adjournment Albert B. Sabin Vaccine Institute Reception Registration Presentation of the Albert B. Sabin Gold Medal Coffee Break Exhibits Symposium 8: Multi-Agent and Chimeric Vaccines Adjournment Participant Evaluation Symposium 7: Vaccinology Impact of Recent Advances in Immunology Coffee Break Exhibits Submitted Presentations 1&2 Coffee Break Exhibits Submitted Presentations 3&4 and relenza.
Researchers at ECTRIMS called for physicians and clinicians to recognise neutralising antibodies NAbs ; as a primary consideration when starting interferonbeta treatment for MS. Evidence confirms that high levels of therapyinduced NAbs may reduce or abolish the efficacy of beta-interferon IFN beta ; . Various studies presented at ECTRIMS demonstrate that the type of Interferon, dosage, dose frequency and route of administration may each influence the rate of NAb development. For example, IFN-beta 1a Avonex ; is administered once a week by intra-muscular injection and the incidence of NAb formation ranges from 2-8%. IFN-beta-1a Rebif ; is administered three times a week by subcutaneous injection and generates levels of Nabs from 15-30%. Finally, over 40% of patients receiving IFNbeta-1b Betaferon ; administered sub-cutaneously every other day will develop NAbs. A clinical consensus also suggests that NAbs caused by any of these products are cross-reactive, so switching a patient to a less antigenic Interferon after NAbs have been generated may not overcome their negative effects. Clinical trials demonstrate that IFN-beta-1a Avonex ; is associated with the lowest incidence of NAbs and is the least immunogenic. Physicians and clinicians should therefore consider the long-term immunogenicity of NAbs as major criteria when initiating MS treatment to ensure continued therapeutic efficacy. Many ECTRIMS speakers also emphasised a vital need for standardised IFN-antibody measurements and ongoing NAb monitoring during treatment. "The clinical impact of NAbs is not generally seen in the short-term since MS is a long-term chronic disease. Patients need to be followed up regularly for at least a year for the effects to be reliably detected, " noted Dr Jeffrey Greenstein of the Temple University School of Medicine, Philadelphia, USA. For further information contact Biogen on Tel. 01628 501000. Modern concepts of motor learning favour a task-specific, repetitive approach, ie. if someone wants to re-learn walking, they have to walk. So far, conventional therapy requires the strenuous effort of up to three therapists to assist the gait of severely disabled subjects resulting in a non-sufficient seldom more than 100 steps ; and non-optimal practice. This is the reason for the design of the gait trainer: the harnesssecured patient is positioned on two footplates, whose movements simulate stance and swing in a physiological manner, a drive supports the patient according to his abilities, and the highly relevant trunk movements are controlled phase-dependently. By themselves or with only a little help, wheelchair-bound subjects can thus practice up to 1000 almost natural steps per session. The gait trainer operates successfully in several European countries, improving gait ability in stroke, TBI, paraparetic, MS, CP and orthopaedic patients. For more information contact Reha-Stim, Kastanienallee 32, 14050 Berlin, Germany, or use the reader enquiry service enclosed with this magazine.
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Creases the oxygen partial pressure from 51514 mm Hg n 4019 mm Hg n 10, p 0.001 ; in the bathing medium, thereby producing hypoxic effects on the preparations; and 2 ; tension development recovers gradually over a long period of time usually for 2 hours ; in the presence of 15% CO2, which was not suitable for this study. A pH, of 6.4 was chosen for acidosis because it mimics the pH value in ischemia.29, 30 For converting aequorin light signals into quantitative intracellular calcium concentrations [Ca2 + ]i ; , the following equation31 was used: [Ca2 + ]i [L LS]13 [131.0]- 1 ; 4.5 x 106[1 - L L , a1 ; 3] ; the particular light signal averaged during twitches and L, is the maximal light emission that would be obtained if all the aequorin in the cells were exposed to a saturating concentration of Ca2 + . To obtain this Lma, 1 ; the volume of the organ bath was reduced from 55 ml to enough volume to just cover the muscle ; , and the temperature of the solution in the organ bath was maintained at 30C; 2 ; warmed physiological salt solution containing Triton X-100 and high [Ca 2 + ] was rapidly flushed into the organ bath 2.5% Triton X-100, 20 mM [Ca2`]0 ; to lyse the preparation and discharge the remaining aequorin; 3 ; the emitted light during lysis was integrated until complete discharge of the aequorin; and 4 ; the time integral of this light signal was then corrected by the rate constant for aequorin consumption 2.11 sec ; determined in vitro.31 Complete discharge of aequorin was assumed when no further light emission was detected during a 10-minute period, and the background had fallen to the level of the dark current. It is conceivable that endothelin-1 or its metabolites might diffuse into myocardial cells and interact directly with the loaded aequorin to alter the luminescent reaction or the responsiveness of aequorin to Ca2 + .32 Therefore, endothelin-1 was tested in vitro using the basic method and calibration device described by Blinks et al.33 These tests showed that neither the Ca2 + dependent light emission nor the Ca2 + -independent light emission were affected by endothelin-1, indicating that endothelin-1 does not interact directly with aequorin in a way that would alter the experimental results. In vitro results show that a fall in pH causes a slight reduction in the light emission from aequorin.25, 3233 This indicates that the detected aequorin light at pHo 6.4 may provide a slight underestimate of quantitative [Ca 2 + ]i. However, because this study is concerned principally with the effects of endothelin-1 on intracellular Ca 2 + and contraction under steady-state acidosis pHO 6.4 ; , the slight effect of changing pH on aequorin light emission would not alter the experimental results; therefore, we have not made any corrections for this effect. Data are expressed as mean + SEM. Student's t test was used for paired data from the same muscle or unpaired data from different muscles. Number of experiments is indicated by n and remicade.
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Are the search engines provided by Internet Service Providers such as Tiscali and other sites such as the BBC site bbc ; . In addition to the search engines that index the whole web, there are also medical sites with search facilities, which act almost like mini-search engines, but cover only medical topics or even a particular area of medicine. Again, it is wise to look at who is responsible for compiling the information offered to ensure that it is impartial and medically accurate. The NHS Direct site nhsdirect. nhs ; is an example of a searchable medical site. Links to many British medical charities can be found at the Association of Medical Research Charities' website amrc ; and at Charity Choice charitychoice ; . Search phrases Be specific when entering a search phrase. Searching for information on `cancer' will return results for many different types of cancer as well as on cancer in general. You may even find sites offering astrological information. More useful results will be returned by using search phrases such as `lung cancer' and `treatments for lung cancer'. Both Google and Yahoo! offer an advanced search option that includes the ability to search for the exact phrase; enclosing the search phrase in quotes, that is, `treatments for lung cancer', will have the same effect. Limiting a search to an exact phrase reduces the number of results returned but it is best to refine a search to an exact match only if you are not getting useful results with a normal search. Adding `UK' to your search term will bring up mainly British sites, so a good phrase might be `lung cancer' UK don't include UK within the quotes ; . 104 Understanding Thyroid Disorders, Family Doctor Publications Ltd.
Vicki Oakley - answerphone checked regularly ext. 7318 If answerphone message states Vicki on annual leave for more than 3 days, please ring secretary on 6337 ; Drug Information Service Interface Pharmacist 01922-656610 and remodulin.
Medical research no specific medical research has been undertaken since the previous scar conference, although dr gary steel continues with his psychological research!
Those terms it was easier to catch grayling on artificial fly because more available food is present in the river and the grayling are consuming food in bigger amount. This is because they are preparing for the upcoming spawning season in March. The average value of CPUE parameter is 2.251.01. Beside our CPUE result of 2.25 fish per hour, only [4] in the Una river presents such data, where 11 fishermen caught 270 fish in 120 hours. From this data we have calculated CPUE for the Una river, and it was the same as ours: 2.25. The result of total catch in period 1991-1994 years shows that grayling was the dominant species 41%-82% ; , while in later years total catch of grayling have declined 48%39% ; and catches of brown trout prevailed [14]. Data of our research 55%-77% show that grayling population slightly increases there share in total catch. High angling intensity, especially for grayling, has disordered the natural balance in the Kupa river ecosystem. The decrease of grayling population in the Una and Drina rivers is the result of exceeded fishing and poaching [4, 9]. Beside injuries from fish eating birds we noticed many mouth and renagel.
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27. Bradley KK, Jaggar JH, Bonev AD, Heppner TJ, Flynn ER, Nelson MT, Horowitz B. Kir2.1 encodes the inward rectifier potassium channel in rat arterial smooth muscle cells. J Physiol. 1999; 515: 639 Faraci FM, Sobey CG. Role of potassium channels in regulation of cerebral vascular tone. J Cereb Blood Flow Metab. 1998; 18: 10471063. Dimitropoulou C, Han G, Miller AW, Molero M, Fuchs LC, White RE, Carrier GO. Potassium BK Ca currents are reduced in microvascular smooth muscle cells from insulin-resistant rats. J Physiol Heart Circ Physiol. 2002; 282: H908 H917. 30. Ciorba MA, Heinemann SH, Weissbach H, Brot N, Hoshi T. Modulation of potassium channel function by methionine oxidation and reduction. Proc Natl Acad Sci U S A. 1997; 94: 99329937. Marrelli SP, Johnson TD, Khorovets A, Childres WF, Bryan RM Jr. Altered function of inward rectifier potassium channels in cerebrovascular smooth muscle after ischemia reperfusion. Stroke. 1998; 29: 1469 Bastide M, Bordet R, Pu Q, Robin E, Puisieux F, Dupuis B. Relationship between inward rectifier potassium current impairment and brain injury after cerebral ischemia reperfusion. J Cereb Blood Flow Metab. 1999; 19: 1309.
Similar results in terms of relative decrease in the rate of disease progression or absolute decrease have also been shown in published literature and have been accepted by the CPMP as of a clinical relevance. Risk benefit comparison between Rebif 22 and Rebif 44 mcg. The main clinical study was designed as a three-armed, dose-comparative trial with a prespecified analysis plan with respect to the 44-mcg dose. A reasonable way to handle the situation appears to be to give some priority to analyses related to the higher dose in the overall benefit risk assessment, but to accept results derived from the low-dose arm as valid for this comparative analysis. Clinical safety comparison between Rebif 22 and Rebif 44 mcg. Serious adverse events were reported in 34, and 27 patients, placebo, 6, and 12 MIU, respectively. Events classified as "probably related" were, respectively, 1, 2 and 4 groups as previously ; . As possibly related were 2, 6 and 6 events reported groups as previously ; . As expected AEs known to, or and renova.
First Published Online September 21, 2006 Abbreviations: COX-2, Cyclooxygenase 2; DOC, deoxycorticosterone; EPL, eplerenone; GR, glucocorticoid receptor s MR, mineralocorticoid receptor s NAD , nicotinamide adenine dinucleotide; NADH, reduced NAD; NAD P ; H, reduced NAD phosphate; TBS, Tris-buffered saline; VSMC, vascular smooth muscle cell s ; . Endocrinology is published monthly by The Endocrine Society : endo-society ; , the foremost professional society serving the endocrine community and rebif.
A total of five patients died of treatment-related toxicity: three in IP cerebral hemorrhage, interstitial pneumonia, acute circulatory failure disseminated intravascular coagulation: 2.0% ; , one in TC acute renal failure: 0.7% ; , and one in NP pulmonary embolism: 0.7 and reserpine.
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Golod DA, Van Ginneken AC, Wagner MB, and Goolsby WN. Modulating L-type calcium current affects discontinuous cardiac action potential conduction. Biophys J 71: 237245, 1996. Joyner RW and van Capelle FJ. Propagation through electrically coupled cells. How a small SA node drives a large atrium. Biophys J 50: 11571164, 1986. Joyner RW, Veenstra R, Rawling D, and Chorro A. Propagation through electrically coupled cells. Effects of a resistive barrier. Biophys J 45: 10171025, 1984. Kaab S, Dixon J, Duc J, Ashen D, Nabauer M, Beuckelmann DJ, Steinbeck G, McKinnon D, and Tomaselli GF. Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density. Circulation 98: 13831393, 1998. Kadish A, Shinnar M, Moore EN, Levine JH, Balke CW, and Spear JF. Interaction of fiber orientation and direction of impulse propagation with anatomic barriers in anisotropic canine myocardium. Circulation 78: 1478 1494, Kagiyama Y, Hill JL, and Gettes LS. Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. Circ Res 51: 614 623, Kanter H, Saffitz J, and Beyer E. Cardiac myocytes express multiple gap junction proteins. Circ Res 70: 438 444, Karma A. Spiral breakup in model equations of action potential propagation in cardiac tissue. Phys Rev Lett 71: 11031106, 1993. Kass RS and Sanguinetti MC. Inactivation of calcium channel current in the calf cardiac Purkinje fiber. Evidence for voltage- and calcium-mediated mechanisms. J Gen Physiol 84: 705726, 1984. Keating MT and Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell 104: 569 580, Ken Knight BH, Bayly PV, Gerstle RJ, Rollins DL, Wolf PD, Smith WM, and Ideker RE. Regional capture of fibrillating ventricular myocardium. Evidence of an excitable gap. Circ Res 77: 849 855, Kimura J, Miyamae S, and Noma A. Identification of sodiumcalcium exchange current in single ventricular cells of guinea-pig. J Physiol 384: 199 222, Kirchhof C, Chorro F, Scheffer GJ, Brugada J, Konings K, Zetelaki Z, and Allessie M. Regional entrainment of atrial fibrillation studied by high-resolution mapping in open-chest dogs. Circulation 88: 736 749, Kirchhof C, Wijffels M, Brugada J, Planellas J, and Allessie M. Mode of action of a new class IC drug ORG 7797 ; against atrial fibrillation in conscious dogs. J Cardiovasc Pharmacol 17: 116 124, Kleber AG. Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts. Circ Res 52: 442 450, Kleber AG. Extracellular potassium accumulation in acute myo cardial ischemia. J Mol Cell Cardiol 16: 389 394, Kleber AG, Janse MJ, and Fast VG. Normal and abnomal con duction in the heart. In: The Handbook of Physiology. The Cardiovascular System. The Heart. Bethesda, MD: Am. Physiol. Soc., 2002, sect. 2, vol. I, p. 455530. Kleber AG, Janse MJ, Wilms-Schopmann FJG, Wilde AAM, and Coronel R. Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart. Circ Res 73: 189 198, Kleber AG and Riegger CB. Electrical constants of arterially perfused rabbit papillary muscle. J Physiol 385: 307324, 1987. Kleber AG, Riegger CB, and Janse MJ. Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. Circ Res 61: 271279, 1987. Knisley SB and Hill BC. Effects of bipolar point and line stimulation in anisotropic rabbit epicardium: assessment of the critical radius of curvature for longitudinal block. IEEE Trans Biomed Eng 42: 957966, 1995. Kodama I, Wilde A, Janse MJ, Durrer D, and Yamada K. Combined effects of hypoxia, hyperkalemia and acidosis on mem prv.
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Again this year, Downers Grove Grade School District 58 has been awarded both state and national honors for its communication publications. District 58 Coordinator of Community Relations, Kristine Liptrot, received Awards of Merit for both the 2005-06 issues of The Loop, the district's staff newsletter, and the 2005 Summer Report from the National School Public Relations Association NSPRA ; . In addition, the Illinois Chapter of NSPRA recognized Liptrot with awards for the new District 58 brochure as well as the 2005 Summer Report in its statewide competition and restasis.
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