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2002; 100: 3063-3067 Schey SA, Fields P, Bartlett JB, Clarke IA, Ashan G, Knight RD, Streetly M, Dalgleish AG. Phase I study of an immunomodulatory thalidomide analog, CC4047, in relapsed or refractory multiple myeloma. J Clin Oncol. 2004; 22: 32693276 Cushman M, He HM, Katzenellenbogen JA, Lin CM, Hamel E. Synthesis, antitubulin and antimitotic activity, and cytotoxicity of analogs of 2.
This study was supported in part by grant HL-42370 from the National Institutes of Health, grant 91015190 from the American Heart Association, Dallas, Tex, by the Veterans Administration, Washington, DC, and by the Herman C. Krannert Fund. M.R. was a recipient of a postdoctoral fellowship grant from the Max-Kade Foundation, New York, NY. The authors wish to thank Dr Gregory Ayres for his development of software for analysis of in vivo recordings, Dr Naomi Fineberg for assistance with statistical analysis, and Pfizer Central Research, Kent, UK, for their generous gift of dofetilide.
The literature review presented in chapters 1 and 4 demonstrates the limited and partial information available on unwanted pregnancy and abortion for Burmese women. In Burma elective induced abortion is highly restricted, abortion is a common cause of maternal morbidity and mortality, and there is a documented unmet need for contraceptive services and falling fertility rate. The censored literature from Burma suggests a `culture of abortion' where there is limited health education, a faltering health system, marginalised and displaced populations who find access to health services difficult. Traditional midwives provide basic maternal health care and fertility limiting services. Burmese migrants bring their culture with them as they migrate into Thailand, where the reproductive culture is different. In Thailand fertility rates are low, modern contraceptive use high, maternal and infant mortality low and there is good access to public health services. Many informants in this study reported hearing about contraception and purchasing it for the first time after their arrival in Thailand but despite this Burmese men and women have low levels of sexual health knowledge and limited experience with modern methods of contraception even when in Thailand. In chapter 5, approximately one third of patients with post-abortion complications had attempted to end their own pregnancy. Married women who already had children were the most typical patient to present for post-abortion care and they were working.
Ventricle of Lorraine's heart, has only two leafs. This deformity results in a severe constriction of the valve that connects the heart to the main artery through which blood flows to the rest of the body. As a child, Lorraine was diagnosed with this defect. She had her first treatment at age 12, when the blood vessel was "stretched" through an open chest procedure, allowing for a greater flow of blood. But this widening of the vessel is not permanent. One year prior to becoming pregnant, Lorraine went to her cardiologist who reported that the artery measured .7 centimeters. But time and the stress of the three-month pregnancy had narrowed the vessel down to .4 centimeters. A normal diameter is 3 - 4 centimeters.
Thalidomide multiple myeloma 2006
This activity has been planned and implemented in accordance with the Essentials Areas and Policies of the Accreditation Council for Continuing Medical Education through the sponsorship of University of Kentucky College of Medicine. The University of Kentucky College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. The University of Kentucky College of Medicine designates this educational activity for a maximum of 1 Category 1 credits towards the AMA Physician's Recognition Award. Each physician should claim only those hours of credit actually spent in the educational activity. The University of Kentucky College of Medicine presents this activity for educational purposes only. Participants are expected to utilize their own expertise and judgment while engaged in the practice of medicine. The content of the presentations is provided solely by presenters who have been selected for presentations because of recognized expertise in their field
With the integration of Famous Players now complete, the fund will shift its focus to growing the business through non-traditional measures. We believe this positive shift is not fully reflected in current price levels. Over the next three years, we expect CGX's DCPU growth to outperform our universe of coverage 7% vs. 3% group average ; driven by: 1 ; a full year's contribution from the Famous Players acquisition and related synergies, 2 ; three new theatre openings, 3 ; our expectation that the Canadian box office will grow 3% in 2007 as a result of a strong summer film slate and market share gains via the company's new loyalty program with Scotiabank, and 4 ; 10% growth in the high-margin other ancillary business segment including cinema advertising and alternative content programming and thalomid.
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Brands with generic substitutions BWGS ; not selected for the sample because the quantities dispensed were few. * Drugs that have only a brand-name version on the market, usually because the drug's patent prevents generic versions from being sold. * Consists mostly of medical supplies and durable medical equipment DME ; . Note: Individual drug-prescription figures are rounded to the nearest ten, individual drug payment figures and aggregate prescription and payment figures are rounded to the nearest hundred; figures and percents may not add to totals, due to rounding and thiabendazole.
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Lidomide also acts as a costimulatory signal to T cells, inducing increased T-cell proliferation and enhanced gamma interferon and IL-2 production 5, 14 ; . The new thalidomide analogs, and IMiD3 in particular, have been shown to be even more-potent inhibitors of monocyte TNF- , IL-1 , and IL-6 production and to be more-effective inducers of Th1-type cytokines 6 ; . In addition, a recent report has shown that thalidomide and IMiD3 augment the number of NK cells in vivo and NK cell cytotoxic activity in vitro 9 ; . In the present study, it appears that IMiD3 inhibits TNF, and this is associated with reduced pathology in the brain. Whether IMiD3 also induces increased Th1 T-cell responses in this experimental system is yet to be established. In humans, adjunctive thalidomide therapy of a tuberculous abscess and of stage II childhood TBM was initially reported to be safe and well tolerated 26, 27 ; . However, a subsequent randomized, placebo-controlled trial of thalidomide therapy, administered for 1 month in addition to standard antituberculosis therapy and steroids in children with severe TBM stages II and III ; , was terminated because thalidomide therapy was associated with a worse neurological outcome after 1 month than placebo therapy 25 ; . This was noted particularly in children with the most severe disease stage III ; . No difference in clinical outcome between thalidomide- and placebo-treated patients was noted at 6 months 25 ; . This patient-based study underscored the importance of developing better drugs, which may be safer for clinical use. Indeed, our experiments indicate that a combination of antituberculous drugs plus the thalidomide analog IMiD3 reduces the inflammatory response and markedly improves the clinical outcome and survival of rabbits with TBM, despite the lower delivery dose and lower levels of drug in CSF. In addition, IMiD3 appears to not be teratogenic in the pregnant rabbit model D. Stirling, unpublished observations ; . Together, these results suggest a potential role for IMiD3 in the treatment of human TBM and thioguanine.
Aim: We present data on all patients receiving tandem HDM NMAT SCT for multiple myeloma at a single centre in NZ. Results: The tandem HDM NMAT SCT approach was offered to all patients with myeloma and an HLA identical sibling donor who were considered suitable for the procedure from 2000 onwards n 12 ; . Following induction, most patients received high dose melphalan 200mg m2 ; with autologous stem cell rescue except for three who received 140mg m2 melphalan without stem cell rescue. Patients then proceeded directly to NMAT SCT conditioned with fludarabine 3x30mg m2 + TBI 200cGy. Median age at NMAT was 50 years range 34-63 years ; and median follow up post NMAT was 22 months range 2-56 months ; . All patients engrafted but one case initially showing poor and decreasing donor T-cell chimerism was rescued using pentostatin and donor lymphocyte infusion. Of 10 patients evaluable for disease response and GVHD, 5 subsequently achieved complete remission CR ; , one of these patients achieving CR after being treated for progressive disease with thalidomide and withdrawal of immunosuppression. Two patients achieved partial response and 3 have shown progressive disease, one of whom died at day + 120 post NMAT. Seven of the 10 patients developed grade II-IV acute and or extensive chronic graft versus host disease GVHD ; . Overall 11 12 patients remain alive. Conclusions: The use of tandem HDM NMAT SCT in multiple myeloma remains investigational and the outcomes of comparative trials are awaited. Our data shows a low 1 year TRM 10% ; with acceptable outcomes in terms of disease control CR + PR 70% ; and incidence of manageable GVHD 70.
Thalidomide defects pictures
Activity was minimally altered by FMLP. An exposure to complement C5a 5.0 x 10 g also decreased ecto5'-nucleotidase activity, whereas it did not decrease cytosolic 5'-nucleotidase activity Fig 3 ; . Fig 4 shows the dose-response relation between complement CSa 5.0x 10-9 to 5.0x 10-6 g mL ; and 5'-nucleotidase activities. Ecto-5'-nucleotidase activity of polymorphonuclear leukocytes was dose-dependently decreased by complement C5a. However, cytosolic 5'-nucleotidase activity was not altered by administration of complement C5a. To test the idea that superoxide anions generated from activated polymorphonuclear leukocytes are responsible for the attenuation of their ecto-5'-nucleotidase activity due to FMLP and complement C5a, ecto5'-nucleotidase and cytosolic 5'-nucleotidase activities were observed in the presence of SOD. Interestingly, as shown in Fig 5, SOD blunted the decreases in ecto-5'nucleotidase activity caused by FMLP. Fig 6 shows the dose-response relations between 10`8 to 10-5 M FMLP and 5'-nucleotidase activity under SOD treatment. The decreases in ecto-5'-nucleotidase activity caused by FMLP were completely abolished by SOD. Fig 7 shows the dose-response relations between complement C5a 5.0x 10-9 to 5.0x10-6 g mL ; and 5'-nucleotidase activities under SOD treatment. The decreases in ecto-5'nucleotidase activity caused by complement C5a were also abolished by SOD treatment. However, the decreases in ecto-5'-nucleotidase activities caused by FMLP were not altered by desferrioxamine treatment Fig 8 ; . These results indicate that the reduction of ecto-5'-nucleotidase activity in activated polymorphonuclear leukocytes is not attributable to hydrogen peroxide but to the superoxide anion. Fig 9 shows adenosine concentration of the effluent of polymorphonuclear leukocytes with and without a 30minute exposure to 10-6 M FMLP. Adenosine release and thiotepa.
[22] Damaj G., Lefrere F., Delarue R., Varet B., Furman R., Hermine O.: Thalidomide therapy induces response in relapsed mantle cell lymphoma. Leukemia, 2003; 17: 19141915 [23] Davies F.E., Raje N., Hideshima T., Lentzsch S., Young G., Tai Y.T., Lin B., Podar K., Gupta D., Chauhan D., Treon S.P., Richardson P.G., . Schlossman R.L., Morgan G.J., . Muller G.W., . Stirling D.I., . Anderson K.C.: Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood, 2001; 98: 210216 [24] Davis T.A., Kaminski M.S., Leonard J.P., Gregory S.A., Wahl R., Hsu F.Y., Wilkinson M., Zelenetz A., Wahl R.L., Kroll S., Coleman M., Goris M., Levy R., Knox S.J.: Results of randomized trial of Bexxar tositumomab and iodine I 131 tositumomab ; vs unlabeled tositumomab in patients with relapse and refractory low-grade or transformed non-Hodgkin's lymphoma. Blood, 2001; 98: 843a, abstract 3503 [25] de Boer C.J, Schuuring E., Dreef E., Peters G., Bartek J., Kluin P.M., van Krieken J.H.: Cyclin D1 protein analysis in the diagnosis of mantle cell lymphoma. Blood, 1995; 86: 27152723 [26] Dillman R.O.: Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies. Clin. Exp. Med., 2006; 6: 112 [27] Duan H., Heckman C.A., Boxer L.M.: Histone deacetylase inhibitors down-regulate bcl-2 expression and induce apoptosis in t 14; 18 ; lymphomas. Mol. Cell. Biol. 2005; 25: 16081619 [28] Dunleavy KM, Janik J, Grant N., White T., Pittaluga S., Jaffe E.S., Staudt L.: Phase I II study of bortezomib combined with dose adjusted EPOCH chemotherapy in relapsed or refractory diffuse large B-cell lymphomas. Blood, 2003; 102: supl., 636a637a, abstract 2349 ASH Annual Meeting Abstracts ; [29] Engel P., Nojima Y., Rothstein D., Zhou L.J., Wilson G.L., Kehrl J.H., Tedder T.F.: The same epitope on CD22 of B lymphocytes mediates the adhesion of erythrocytes, T and B lymphocytes, neutrophils, and monocytes. J. Immunol., 1993; 150: 47194732 [30] Fung H., Forman S., Nademanee A.: A new preparative regimen for older patients with aggressive CD20-positive B-cell lymphoma utilizing standard-dose yttrium-90 ibritumomab tiuxetan Zevalin ; radioimmunotherapy RIT ; combined with high-dose BEAM followed by autologous hematopoietic cell transplantation AHCT ; : targeted intensification without increased transplant related toxicity. Blood, 2003; 102: supl., 248a, abstract 870 ASH Annual Meeting Abstracts ; [31] Gandhi A., Kang J., Schafer P., Stirling D.: Combination studies on lenalidomide and limphoproliferative agents on the proliferation on the chromosome 5 deleted Burkitts lymphoma Namalwa CSN.70 cell lines. Haematologica, 2006; 91 Suppl.1 ; : abstract 1390 11th Congress of the EHA ; [32] Gordon L.I., Molina A., Witzig T., Emmanouilides C., Raubtischek A., Darif M., Schilder R.J., Wiseman G., White C.A: Durable responses after ibritumomab-tiuxetan radioimmunotherapy for CD20 + B-cell lymphoma: long term follow-upof phase 1 2 study. Blood, 2004; 103: 44294431 [33] Goy A., De Vos S., Dakhil S., McLaughlin P., Saleh M., Belt R, Flowers C., Knapp M., Hart L., Patel-Donnelly D., Glenn M., Gregory S., Holladay C., Boral A., Zhang T.: Bortezomib plus rituximab in patients with indolent non-Hodgkin's lymphoma NHL ; , a phase 2 study. Haematologica, 2006; 91 Suppl.1 ; : abstract 0187, 11th Congress of the EHA ; [34] Goy A., Younes A., McLaughlin P., Pro B., Romaguera J.E., Hagemeister F., Fayad L., Dang N.H., Samaniego F., Wang M., Broglio K., Samuels B., Gilles F., Sarris A.H., Hart S., Trehu E., Schenkein D., Cabanillas F., Rodriguez A.M.: Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J. Clin. Oncol., 2005; 23: 667675 [35] Guedez L., Quintanilla-Martinez L., Lahusen T.: Flavopiridol-induced apoptosis is associated with decrease in cyclin D1 in mantle lymphoma cell lines. Presented at Am. Assoc. Cancer Res. Annual Meeting, Philadelphia, PA, 1999 [36] Heckman C.A., Mehew J.W., Boxer L.M.: NF-kappaB activates Bcl-2 expression in t 14; 18 ; lymphoma cells. Oncogene, 2002; 21: 38983908 [37] Heider U., Kaiser M., Sterz J., Zavrski I., Jakob C., Fleissner C., Eucker J., Possinger K., Sezer O.: Histone deacetylase inhibitors reduce VEGF production and induce growth suppression and apoptosis in human mantle cell lymphoma. Eur. J. Haematol. 2006; 76: 4250 [38] Hernandez-Ilizaliturri F.J., Reddy N., Holkova B., Ottman E., Czuczman M.S.: Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin. Cancer Res., 2005; 11: 59845992 [39] Hipp S., Ringshausen I., Oelsner M., Bogner C., Peschel C., Decker T.: Inhibition of the mammalian target of rapamycin and the induction of cell cycle arrest in mantle cell lymphoma cells. Haematologica, 2005; 90: 14331434 [40] Johnstone R.W.: Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat. Rev. Drug Discov. 2002; 1: 287299 [41] Jurczak W., Giza A., . Krochmalczyk D., Wegrzyn J., HubalewskaDydejczyk A., Sowa-Staszczak A., Knopinska-Posluszny W., Zdziarska B., Krycz-Krzemien S., Boguradzki P., Poplawska L., Skotnicki A.: Consolidation of chemotherapy response in mantle cell lymphoma MCL ; patients with 90Y-ibritumomab tiuxetan 90Y-Zevalin ; radioimmunotherapy RIT ; . Blood, 2005; 105: abstract 2453 ASH Annual Meeting Abstracts ; [42] Kaufmann H., Raderer M., Wohrer S., Puspok A., Bankier A., Zielinski C., Chott A., Drach J.: Antitumor activity of rituximab plus thalidomide in patients with relapsed refractory mantle cell lymphoma. Blood, 2004; 104: 22692271 [43] Keifer J.A., Guttridge D.C., Ashburner B.P., Baldwin A.S. Jr: Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J. Biol. Chem.: 2001; 276: 2238222387 [44] Kelly W.K., O'Connor O.A., Krug L.M., Chiao J.H., Heaney M., Curley T., MacGregore-Cortelli B., Tong W., Secrist J.P., Schwartz L., Richardson S., Chu E., Olgac S., Marks P.A., Scher H., Richon V.M.: Phase I study of an oral histone deacetylase inhibitor, suberoylanilide hydroxamic acid, in patients with advanced cancer. J. Clin. Oncol., 2005; 23: 39233931 [45] Kelly W.K., Richon V.M., O'Connor O., Curley T., MacGregor-Curtelli B., Tong W., Klang M., Schwartz L., Richardson S., Rosa E., Drobnjak M., Cordon-Cordo C., Chiao J.H., Rifkind R., Marks P.A., Scher H.: Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously. Clin. Cancer Res., 2003; 9: 35783588 [46] Kitada S., Zapata J.M., Andreeff M., Reed J.C.: Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia. Blood, 2000; 96: 393397 [47] Kouroukis C.T., Belch A., Crump M., Eisenhauer E., Gascoyne R.D., Meyer R., Lohmann R., Lopez P., Powers J., Turner R., Connors J.M., National Cancer Institute of Canada Clinical Trials Group: Flavopiridol in untreated or relapsed mantle-cell lymphoma: results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol., 2003; 21: 17401745 [48] Kumar S., Witzig T.E., Rajkumar S.V.: Thalidomid: current role in the treatment of non-plasma cell malignancies J. Clin. Oncol., 2004; 22: 24772488 [49] Kuo S.H., Hsu C.H., Yeh P.Y., Hsu H.C., Gao M., Cheng H.J., Cheng A.: RAD001 everolimus ; down-regulates cyclin D3 and c-Myc and is particularly effective in the treatment of aggressive B-cell lymphomas. J. Clin. Oncol., 2006; 24: abstract 17573 ASCO Meeting Abstracts ; [50] Leonard J.P., Coleman M., Ketas J., Ashe M., Fiore J.M., Furman R.R., Niesvizky R., Shore T., Chadburn A., Horne H., Kovacs J., Ding C.L., Wegener W.A., Horak I.D., Goldenberg D.M.: Combination of antibody therapy with epratuzumab and rituximab in relapsed or refractory non-Hodgkin's lymphoma. J. Clin. Oncol., 2005; 23: 50445051 [51] Leonard J.P., Coleman M, Ketas J., Chadburn A., Ely S., Furmann R.R., Wegener W.A., Hansen H.J., Ziccardi H., Eschenberg M., Gayko U., Cesano A., Goldenberg D.M.: Phase I II trial of Epratuzumab humanized anti-CD22 antibody ; in indolent non-Hodgkin's lymphoma. J. Clin. Oncol., 2003; 21: 30513059 [52] Leonard J.P., Coleman M., Ketas J., Chadburn A., Furman R., Schuster M.W., Feldman E.J., Ashe M., Schuster S.J., Wegener W.A., Hansen H.J., Ziccardi H., Eschenberg M., Gayko U., Fields S.Z., Cesano A., Goldenberg D.M.: Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin's lymphoma: phase I II clinical trial results. Clin. Cancer Res., 2004; 10: 53275334 [53] Leonard J.P., Coleman M., Matthews J.C.: Phase I II trial of epratuzumab humanized anti-CD22 antibody ; in non-Hodgkin's lymphoma NHL ; . Blood, 2002; 100: supl., 358a ASH Annual Meeting Abstracts ; [54] Leonard P., Friedberg J., Younes A., Fisher D., Gordon L., Moore J., Czuczman M., Miller T., Stiff P., Cheson B., Forero-Torres A., McKinney B., Molina A.: Galiximab anty-CD80 antibody ; in combination with rituximab in relapsed or refractory follicular NHL: results of a phase II study. Haematologica, 2006; 91 Suppl.1 ; : abstract 502 11th Congres of the EHA.
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In july 2005, we announced the completion of the scientific advice procedure with the emea regarding the clinical data needed to support a marketing authorization for thalidomide in relapsed refractory multiple myeloma and thalidomide.
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