Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002; 20: 242940. Christman JK. 5-Azacytidine and 5-aza-2V -deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy. Oncogene 2002; 21: 548395. Santi DV, Norment A, Garrett CE. Covalent bond formation between a DNA-cytosine methyltransferase and DNA containing 5-azacytosine. Proc Natl Acad Sci U S A 1984; 81: 69937. Zhou L, Cheng X, Connolly BA, Dickman MJ, Hurd PJ, Hornby DP. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol 2002; 321: 5919. Juttermann R, Li E, Jaenisch R. Toxicity of 5-aza-2V deoxycytidine to mammalian cells is mediated primarily by covalent trapping of DNA methyltransferase rather than DNA demethylation. Proc Natl Acad Sci U S A 1994; 91: 11797801.
1. Raza A, Meyer P, Dutt D, et al. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood. 2001; 98: 958-965. List AF, Kurtin S, Glinsmann-Gibson B, et al. Efficacy and safety of CC5013 for treatment of anemia in patients with myelodysplastic syndromes MDS ; . Blood. 2003; 102 suppl 1 ; : 184a. 3. Karp JE, Gotlib J, Liesveld J, et al. Zarnestra R115777 ; in previously untreated poor-risk AML and MDS: preliminary results of a phase II trial. Blood. 2002; 101: 11: Lancet JE, Gojo I, Gotlib J, et al. Tipifarnib ZarnestraTM ; in previously untreated poor-risk AML and MDS: interim results of a phase 2 trial. Blood. 2003; 102 suppl 1 ; : 176a. 5. Feldman EJ, Cortes J, Holyoake TL, et al. Continuous oral lonafarnib SarasarTM ; for the treatment of patients with myelodysplastic syndrome. Blood. 2003; 102 suppl 1 ; : 421a. 6. List AF, Tache-Tallmadge C, Tate W, et al. Lonafarnib SarasarTM ; modulates integrin affinity to promote homotypic and heterotypic adhesion of chronic myelomonocytic leukemia CMMS ; cells. Proc Assoc Cancer Res. 2003; 44: 39a. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002; 20: 24292440!
The item "Financial income from securities recorded as current assets" of Euro 177 thousand relates to interest accruing on repurchase agreements. The item "Other financial income from other companies" of Euro 141 thousand relates to interest receivable on current accounts with banks and interest-bearing deposits: the significant increase is related to interest accruing on receipts banked in the course of the flotation process.
ASN enjoyed a record membership year in 2005! The Society's leadership and staff extend their thanks to all those who remained ASN members or joined as new members in 2005. During 2005, ASN launched a new clinical journal CJASN ; , entered into an arrangement with the American Board of Internal Medicine ABIM ; , under which completion of NephSAP examinations will be accepted as partial fulfillment of certain maintenance of certification requirements, added a Continuing Medical Education CME ; transcript feature to the Society's website, and provided over .3 million in grants to support basic and clinical research. ASN also stepped up efforts to garner additional National Institutes of Health NIH ; funding of kidney disease research, an increasingly important Society activity in these times of significant federal budget constraints. With your support in 2006, these programs and others can be sustained and enhanced. In December, all ASN members should have received a 2006 renewal invoice with a US postage-paid return envelope. If you have not received your membership renewal invoice for 2006, please email us at email asn-online . Please remember to renew promptly to avoid the inconvenience of having access to ASN journals or other benefits interrupted.
49 p. - RCSS policy studies ; ISBN: 955-8051-06-3 Keywords: Firearms; Armament; Politics; Government; Political Impact Assessment; Arms Trade; Weapons South Asia; Bangladesh; India; Nepal; Pakistan; Sri Lanka; Maldives Call No.: 327.174095492 HUS-P 1999 950. The regional paradox : essays in Nepali and South Asian affairs Eng ; by Baral, Lok Raj. - Delhi : Adroit Publishers, 2000 xxiii, 287 p., tables ISBN: 80-87392-10 Keywords: Foreign Relations; Foreign Policy; History; Regional Relations; Regional Cooperation; Political Parties; Democracy; Good Governance; Constitutions; Bilateral Relations; Refugees; Regional Security; Elite; SAARC Nepal; South Asia; India; Japan; Bhutan - Kathmandu Call No.: N 327.5496054 BAR-R 2000 951. Regional security in South Asia Eng ; by Khatri, Sridhar K, ed. - Kathmandu : CNAS, 1987 xxi, 295 p., tables International Seminar on Regional Security in South Asia, Kathmandu, Nepal, 3-6 Nov 1985 TU, CNAS, Kathmandu, Nepal Keywords: Regional Security; National Security; Regional Cooperation; Regional Organizations; Politics; Water Resources; Foreign Policy; Economic Aspects; Defence Expenditure; Economic Development; Political Demography; SAARC; Armament; Military Balance; Nuclear Policy; War; Foreign Intervention; Ethnic Conflicts; Crisis Management; Himalayan Rivers; River Basins; Water Politics; Sino-Indian War 1962; India-Pakistan War 1971; Sino-Indian Conflict 1962 - South Asia; Nepal; Bangladesh; Bhutan; India; Maldives; Pakistan; Sri Lanka; China; Afghanistan; USA; USSR - Indo-Soviet Treaty, 1971; Indus Basin; Ganges Basin; Brahmaputra Basin Call No.: 327.10954 KHA-R 1987 952. The Sino-Indian boundary question Eng ; . - 2nd enlg. ed. - Peking : Foreign Languages Press, 1962 134 p., maps Keywords: Sino-Indian Border Dispute 1957-; Boundaries; Foreign Relations; History; Government; Diplomatic and Consular Service; Government Documents - India; China Nehru, Jawaharlal, Prime Minister of India, 1889-1964; Chao Enlai, Prime Minister of China, 1898-1975 Call No.: 320.12051 SIN 1962 953. South Asia : vision and perspective Eng ; by.
Acute rejection episodes are uncommon but may occur after delivery. Therefore, immunosuppression should be re-adjusted immediately after delivery. 2 ; Pre-eclampsia develops in 30% of pregnant transplant patients, especially those with prior arterial hypertension. Thus blood pressure, renal function, proteinuria and weight should be monitored every 2-4 weeks, with more attention during the third trimester. Anti hypertensive agents should be changed to those tolerated during pregnancy, but ACE inhibitors and ATII receptor antagonists are absolutely contraindicated. 3 ; Immunosuppressive therapy based on cyclosporin or tacrolimus, with or without steroids and azathioprine, may be continued in renal transplant women during pregnancy. Because of drug transfer into maternal milk, breastfeeding is not recommended and bacitracin.
Integrate and synthesize material. Active involvement also improves the students' conceptualization of systems and how they function and increases the students' level of retention 8, 13 ; . The most effective means to promote problem solving, critical thinking, and cooperative learning is through active participation in laboratory experimentation and analysis 17 ; . Employment opportunities in the future will require employees to work cooperatively to solve problems and develop solutions. However, experimentation is often neglected in many curricula because of the scarcity of suitable laboratory equipment, space, and experiments. The use of laboratory animals for experimentation is another obstacle.
This review is intended to describe briefly some of the medications, techniques, and devices currently employed in equine ophthalmology. One should not assume that the products and techniques mentioned are the only ones acceptable for treating any given disease, but they will provide a foundation for the sound management of ocular disease. Some of the drugs and techniques are new, whereas others are not. Since the successful medical management of ophthalmic disease is directly related to the method of medication used and the selection of appropriate drugs, a brief review of medication techniques is necessary before drugs can be discussed. The methods of medicating the eye are topical, subconjunctival, intraocular, and systemic administration. The disease presented will determine the medication technique or combination of techniques that will be most effective. The efficacy of topical medication is determined by the chemical characteristics of the drug, the health of the cornea and conjunctiva, and the frequency of application. In the equine, it is further limited by the diluting effect of high tear production and the difficulty in administering drops or ointments to a painful eye. The use of subpalpebral delivery systems is the most common method of providing intensive topical medication. They re and baraclude.
C. Epigenetic Therapy: DNA Methyl Transferase Inhibitors Hypermethylation of specific gene promotors, resulting in suppression of gene transcription, is a frequent feature of cancer and has been implicated in the pathogenesis of MDS and the progression to AML. DNA methyltransferase inhibitors show activity in both low and high risk MDS and may alter the natural history of the disease. The two most studied agents are listed below. 5-Azacitidine 5-Aza, VidazaTM ; undergoes conversion to 5-deoxy-azacitidine before incorporation into DNA and binding to and depleting methyltransferases. In a phase III multicenter study of the CALGB , 5-AZA given subcutaneously 7 out of 28 days was studied against observation in a crossover model. The overall response rate was 60% 7% CR, 16% PR, 37% Improved ; compared with 5% in control arm. Median time to leukemic transformation was 21 months in the 5-AZA arm, versus 13 months in supportive care arm P 0.003 ; suggesting that the drug decreased the rate of transformation to AML. There was no significant difference in survival, likely because of the crossover. No difference in response rate was observed in different MDS risk groups. Quality of life was enhanced in responding patients . Based on these data, azacitidine received approval by the FDA for use in MDS patients and is in widespread use in USA and Europe. 5-Aza-2-Deoxycitidine Decitabine, DacogenTM ; Decitabine is a more DNA-specific nucleoside analog and potent hypomethylating agent. Results of a US multicenter phase III MDS trial n 170 ; were recently presented at the 2004 ASH Annual Meeting. Decitabine was effective in delaying time to AML progression or death, especially in high-risk patients. The overall response rate was significantly higher compared to the supportive care arm. Using the IWG response criteria, 9% of patients had a complete response and 8% had a partial response. 11% had hematologic improvement for an overall response rate of 28%. There was a 50% reduction in transfusion requirements and a delay until leukemia and death in higher risk MDS subtypes. The median duration of response was 8.7 months . Decitabine dosed as 20 mg m2 IV daily for 5 days 28d schedule may be associated with higher response rates  and is currently undergoing clinical testing in a multi-center phase II study. d. Low Dose Chemotherapy Low dose cytosine arabinoside Ara-C ; is the most extensively studied agent in this category. Although low dose Ara-C has been reported to induce complete or partial remissions in approximately 30% of patients with RAEB, RAEBT and MDS, the only prospective randomized phase III comparing low dose ara-C with supportive care failed to show improvement in survival [38, 39]. Responses may be as high as 55% in patients with platelet counts 150, or without ringed sideroblasts, cellularity 70%, or complex karyotype . Low dose melphalan 2 mg day ; has been studied in two small series with response rates of 38% and 40% [41, 42], but responses may not be durable and may be associated with the development of 17p deletion. e. Angiogenesis Inhibitors Angiogenesis, the process by which new blood vessels are formed, is increased in the bone marrow in MDS [18, 43-45]. Studies suggest a correlation between increased VEGF and progression to leukemia possibly via autocrine and paracrine stimulation [46-49]. This process is therefore a logical target for therapy. Anti-angiogenic agents being studied in MDS include thalidomide, thalidomide analogues CC5013 ; see below ; as well as VEGF receptor antagonists and matrix metalloproteinase inhibitors to name a few [50-52]. Combination approaches of thalidomide with other agents are being explored. SU5416, a VEGF receptor antagonist has also shown some success in MDS  and its successor S6668 and others are currently in clinical trials. f. Histone Deacetylase Inhibitors Histones are very important for chromatin architecture and gene transcription. When histones are acetylated, gene transcription is enhanced. Histone deacetylation by HDACs leads to chromatin condensation and suppression of gene transcription. In MDS, this may lead to transcriptional silencing of tumor suppressor genes. Several HDAC inhibitors are now undergoing investigation in MDS trials, including phenylbutyrate, valproic acid VPA ; and other. In one small phase II study, n 18 ; , 44% of patients responded to VPA monotherapy, including one partial remission . HDACI's may act synergistically with hypomethylating agents and this combination is under investigation.
Hepatic lesions Ultrasonography and computed tomography In AE, the liver is usually enlarged. In the US and CT, lesions are characterised by heterogenous hypodense masses, often associated with necrotic cavities. The lesion contours are irregular and there is lack of a welldefined wall Fig. 2.11. ; . Calcifications are often found and exhibit a typical pattern in regard to shape and distribution: clusters of microcalcifications or irregular plaque-like calcified foci are located in the central or peripheral parts of the lesions. There may be discrepancies between US and CT patterns, since the two methods yield identical results in only 42% of the cases 78 ; . Hyperechoic haemangioma-like nodules could represent early forms of AE lesions. Quite frequently an extension of the lesions beyond the liver is found toward diaphragm, lungs, pericardium, retroperitoneum, hepatoduodenal ligament and pancreas. Table 2.14. Staging of alveolar echinococcosis cases based on PNM classification Stage of alveolar echinococcosis Stage I Stage II Stage IIIa Stage IIIb Stage IV PNM classification P1 P2 P3 P1-3 P4 P4 Any P N0 N0 Any N M0 M0 and barberry.
Gynecologists Committee on Gynecologic Practice, 1996; Barakat, 1996, 1998 ; . Nonetheless, tamoxifen continued to be considered an `anti-oestrogen'. Concerns over potential acceleration of osteoporosis, because of its anti-oestrogenic effects, led to studies of bone mineral density in patients who were being treated with tamoxifen for breast cancer Turken et al., 1989 ; . The data were reassuring, and further studies have supported the notion that tamoxifen is a skeletal anti-resorptive agent in post-menopausal women Love et al., 1992; Grey et al., 1995b ; . Concurrent preclinical and clinical work relative to another compound, raloxifene, provided the information necessary to firmly establish the concept of SERMs. SERMs are a structurally diverse group of compounds that bind to both oestrogen ER ; and ER ; receptors and produce oestrogen agonist effects in some tissues, but oestrogen antagonist activity in others Sato et al., 1994a ; . The tissue specificity of SERMs is determined in part by the formation of oestrogen receptorSERM complexes that vary in their ability to activate genes when bound to ER or Paech et al., 1997 ; . Further discussion on the mechanism of action of SERMs is presented elsewhere in this issue. At present, a number of compounds that possess a SERM profile are in clinical use or in advanced stages of clinical development. By definition, SERMs fulfil the criteria outlined
It is well established that carbon partitioning between shoots and roots is exible and highly responsive to the environment Dalton et al., 1997; Fageria et al., 1997 and belladonna.
Clude capillary microaneurysms, hard exudates, small intraretinal hemorrhages, and cotton-wool spots swellings of the axons of the nerve fiber layer ; . More advanced or preproliferative defects are composed of capillary dropout and intraretinal microangiopathy. Finally, severe abnormalities such as extraretinal neovascularization, periretinal membrane formation with retinal traction detachment, and vitreous hemorrhages are seen in the proliferative form of the disease. Panretinal laser photocoagulation has been found to be of benefit in preventing visual loss in many patients with proliferative changes.29 As with other retinal degenerative processes, the characteristic pattern of color vision loss in diabetic retinopathy is of the tritan-like or Verriest Type III.30 This selectivity of damage for the S-cone pathway was further demonstrated by Adams et al31 who measured the spectral sensitivities for each of 3 cone pathways in patients with diabetic macular edema. They found that the blue pathway was 40 times less sensitive than normal controls compared with the L- and M-pathways that were only 2.2 times less sensitive. More recently, Greenstein et al32-34 have carefully measured S-cone pathway sensitivity using an in ARCHOPHTHALMOL.
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Azacitidine has been studied in a wide range of disease including aids, β -thalassemia, sickle cell disease, myeloid leukemias, myelodysplastic syndromes, metastatic lung cancer, hormone-refractory prostate cancer, cervical cancer, testicular cancer, colorectal and rectal cancer, melanoma, ovarian cancer, and head and neck cancer and benicar
The CSM is comprised of 13 students, representing all Medical Student Members of the ACP in its United States, Canadian, and international chapters. The CSM meets at various times throughout the year to discuss issues of particular importance to medical students. On a regional level, each Council member works hard to promote activities related to internal medicine and to gather ideas from local internal medicine interest groups. We welcome and strongly encourage your input and feedback, as we aim to enrich the quality of your medical school experience. Please consult the ACP web site acponline srf med csm ; to find the contact.
18 pancreas 7, 19, 66 ; . Further, our results show that activation of ERK-1 2 preceded the activation of JNK-1 2, a finding that is identical to that observed in freshly isolated pancreatic acini cells 17 ; . In addition to mitogenesis, we have also focused on the involvement of nicotine in the basal and CCK-stimulated secretory response in this cell line. As shown previously, AR42J rat pancreatic acinar cells retain the potential to secrete digestive enzymes, in addition to their ability to proliferate upon stimulation with CCK and other growth factors 17, 21, 29, ; . CCK can also activate MAPK in pancreatic acinar cells in a concentration- and time-dependent manner by a mechanism involving protein kinase C and tyrosine kinase activity 21 ; , via activation of MEK and Ras 17, 22 ; and p125FAK 29 ; . The dose of CCK that maximally stimulates enzyme secretion in freshly isolated normal pancreatic acini is 10 nM. While Kiehne et. al 29 ; have demonstrated that CCK induces maximal secretion and p42ERK2 activation in AR42J cells at a dose of 10 nM, different regulatory peptides, such as bombesin, cause only p42ERK2 activation but not significant enzyme secretion, suggesting that kinase activation and receptor-mediated signal transduction pathways leading to enzyme secretion might involve separate mechanisms. In our current study, nicotine maximally increased basal and CCK-stimulated enzyme secretions at 6 minutes at the same dose, while kinase activation was maximal at 3 minutes and declined steadily thereafter. Although ERK-1 2 activation by nicotine is completely inhibited with specific kinase inhibitors, these inhibitors have no influence on the basal and stimulated secretory responses induced by nicotine. Together, these results suggest that nicotine-induced proliferation of AR42J cells is correlated with ERK-1 2 activation as demonstrated by and benzphetamine.
Counter these stories with several examples told by Mr. Stephen Portela, Walton Feed's manager: He stores his long term food storage in his basement where the temperature hovers around 60 degrees F. The experts give brown rice a 6 month storage life because of all the oils in it that go rancid. Yet, Mr. Portela has been eating from a supply of brown rice that has been in his basement over 10 years. It is still wholesome! In another example, there is a family living near him who purchased a supply of food in #10 cans 30 years ago. Their basement hovers around 58 degrees F. After 28 years, Mr. Portela took a sample of many of these items to the Benson Institute at BYU to have it tested. The results can be seen at the bottom of Mr. Portela's welcome page. You will see everything tested had a `good' to `satisfactory' rating except for the eggs which had a `minimum passing' rating. After 28 years I think it is most interesting that it passed at all. Mr. Portela tells me as 30 years have now passed, their storage is still in very good condition and azacitidine.
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Pr newswire ; clinical data on vidaza r ; azacitidine for injectable suspension ; in various hematologic and solid tumor cancers presented at the american society of clinical oncology 42nd annual meeting jun 5, 2006 the seven studies investigate a variety of uses for vidaza - including alternative dosing schedules, and combination use with approved and or investigational therapies, such as thalidomide, carboplatin and the histone deacetylase hdac ; inhibitor valproic acid vpa
Physiology and prevention of disease. Her group was the first to identify a potentially protective role for ligands to the nuclear receptor, peroxisome proliferator activated receptor PPAR ; . in vascular injury and. more recently, in diabetes complications, particularly in regulation of genes that may mediate vascular complications. The PPAR class of therapeutics is emerging as an important strategy in the war against the metabolic syndrome and diabetes. Dr. Hsueh and her colleagues also demonstrated that coronary vascular damage occurs in insulin resistance in the absence of traditional cardiovascular disease risk and may be related to adipokine production and inflammatory changes, all of which are improved by PPAR ligands. Her group has also identified mechanisms of angiotensin II tissue damage in insulin resistance and diabetes and recently reported a novel effect to inhibit reverse cholesterol transport. Dr. Hsueh is a fellow of the Council for High Blood Pressure Research of the American Heart Association and presented their Arthur Corcoran Memorial Lectureship 2003 ; . She is a member of numerous other professional societies, including the American Society for Clinical Investigation and the American Association of Physicians. She served on the American Board of Internal Medicine, Endocrinology, Metabolism and Diabetes Committee. Dr. Hsueh was listed among The Best Doctors in America in Endocrinology from 1998 through 2004 and has received many awards, including a MERIT Award of the National Institute of Arthritis, Metabolism, and Digestive Diseases and the Harry Goldblatt Award for Cardiovascular Research of the American Heart Association. Robert M. Carey and bepridil.
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