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Chronic Myeloproliferative Disorders Treatment (PDQ®): Treatment - Health Professional Information [NCI]
General Information About Chronic Myeloproliferative Disorders
The chronic myeloproliferative disorders consist of chronic myelogenous leukemia, polycythemia vera (p. vera), primary myelofibrosis, essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. All of these disorders involve dysregulation at the multipotent hematopoietic stem cell (CD34), with one or more of the following shared features:
- Overproduction of one or several blood elements with dominance of a transformed clone.
- Hypercellular marrow/marrow fibrosis.
- Cytogenetic abnormalities.
- Thrombotic and/or hemorrhagic diatheses.
- Extramedullary hematopoiesis (liver/spleen).
- Transformation to acute leukemia.
- Overlapping clinical features.
Patients with p. vera and essential thrombocythemia have marked increases of red blood cell and platelet production, respectively. Treatment is directed at reducing the excessive numbers of blood cells. Both p. vera and essential thrombocythemia can develop a spent phase late in their courses that resembles primary myelofibrosis with cytopenias and marrow hypoplasia and fibrosis.[1,2,3] A specific point mutation in one copy of the Janus kinase 2 gene (JAK2), a cytoplasmic tyrosine kinase, on chromosome 9, which causes increased proliferation and survival of hematopoietic precursors in vitro, has been identified in most patients with p. vera, essential thrombocythemia, and idiopathic myelofibrosis.[4,5,6,7,8,9] Researchers are pursuing specific targeting of this aberrant protein.
- Schafer AI: Bleeding and thrombosis in the myeloproliferative disorders. Blood 64 (1): 1-12, 1984.
- Barosi G: Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol 17 (9): 2954-70, 1999.
- Tefferi A: Myelofibrosis with myeloid metaplasia. N Engl J Med 342 (17): 1255-65, 2000.
- Kralovics R, Passamonti F, Buser AS, et al.: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352 (17): 1779-90, 2005.
- Baxter EJ, Scott LM, Campbell PJ, et al.: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365 (9464): 1054-61, 2005 Mar 19-25.
- James C, Ugo V, Le Couédic JP, et al.: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434 (7037): 1144-8, 2005.
- Levine RL, Wadleigh M, Cools J, et al.: Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7 (4): 387-97, 2005.
- Scott LM, Tong W, Levine RL, et al.: JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356 (5): 459-68, 2007.
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006.
Chronic Myelogenous Leukemia
Refer to the PDQ summary on Chronic Myelogenous Leukemia Treatment for more information.
Polycythemia Vera
Disease Overview
The proposed revised World Health Organization criteria for the diagnosis of polycythemia vera (p. vera) requires two major criteria and one minor criterion or the first major criterion together with two minor criteria.[1]
Major Criteria
- Hemoglobin of more than 18.5 g/dL in men, 16.5 g/dL in women, or elevated red cell mass greater than 25% above mean normal predicted value.
- Presence of JAK2 617V greater than F or other functionally similar mutations, such as the exon 12 mutation of JAK2.
Minor Criteria
- Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic, and megakaryocytic proliferation.
- Serum erythropoietin level below normal range.
- Endogenous erythroid colony formation in vitro.
Other confirmatory findings no longer required for diagnosis include:[2,3,4]
- Oxygen saturation with arterial blood gas greater than 92%.
- Splenomegaly.
- Thrombocytosis (>400,000 platelets/mm3).
- Leukocytosis (>12,000/mm3).
- Leukocyte alkaline phosphatase (>100 units in the absence of fever or infection).
There is no staging system for this disease.
Patients have an increased risk of cardiovascular and thrombotic events and transformation to acute myelogenous leukemia or primary myelofibrosis.[5,6,7] Age older than 65 years and a history of vascular events are independent predictors of thrombosis.[5,8]
Treatment Overview
Therapy for p. vera includes intermittent, chronic phlebotomy to maintain the hematocrit below 45% in men.[9] The target level for women may need to be lower (e.g., hematocrit <40%), but there are no empiric data to confirm this recommendation.[10]
Complications of phlebotomy include:
- Progressive and sometimes extreme thrombocytosis and symptomatology related to chronic iron deficiency, including pica, angular stomatitis, and glossitis.
- Dysphagia that is the result of esophageal webs (very rare).
- Possibly muscle weakness.
(Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information.)
In addition, progressive splenomegaly or pruritus not controllable by antihistamines may persist despite control of the hematocrit by phlebotomy. (Refer to the PDQ summary on Pruritus for more information.) If phlebotomy becomes impractical, hydroxyurea or interferon-alpha can be added to control the disease.
The Polycythemia Vera Study Group randomly assigned more than 400 patients to phlebotomy (target hematocrit <45), radioisotope phosphorous-32 (2.7 mg/m2 administered intravenously every 12 weeks as needed), or chlorambucil (10 mg administered by mouth daily for 6 weeks, then given daily on alternate months).[11] The median survival for the phlebotomy group (13.9 years) and the radioisotope phosphorous-32 group (11.8 years) was significantly better than that of the chlorambucil group (8.9 years), primarily because of excessive late deaths from leukemia or other hematologic malignancies.[11][Level of evidence: 1iiA] Because of these concerns, many clinicians use hydroxyurea for patients who require cytoreductive therapy that is caused by massive splenomegaly, a high phlebotomy requirement, or excessive thrombocytosis.[11]
In a pooled analysis of 16 different trials, interferon-alpha therapy resulted in avoidance of phlebotomy in 50% of patients, with 80% of patients experiencing marked reduction of splenomegaly.[12][Level of evidence: 3iiiDiv] Interferon posed problems of cost, side effects, and parenteral route of administration, but no cases of acute leukemia were seen in this analysis. When patients are poorly compliant with phlebotomy or issues of massive splenomegaly, leukocytosis, or thrombocytosis supervene, treatment with interferon or pegylated interferon is considered for patients younger than 50 years (who are more likely to tolerate the side effects and benefit from a lack of transformation to leukemia), while hydroxyurea is considered for patients older than 50 years.[2,13]
A phase II study (PVN1) provided evidence that V617F JAK2 mutation is a reliable molecular marker of p. vera and is potentially useful in monitoring treatment effect.
In a Cochrane review of two randomized studies of 630 patients with no clear indication or contraindication for aspirin, those receiving 100 mg of aspirin versus placebo had reduction of fatal thrombotic events, but this benefit was not statistically significant (OR = 0.20; 95% CI, .03–1.14).[14] A retrospective review of 105 patients who underwent surgery documented 8% thromboembolism and 7% major hemorrhage with prior cytoreduction by phlebotomy and postoperative subcutaneous heparin in one half of the patients.[15]
Guidelines based on anecdotal reports have been developed for the management of pregnant patients with p. vera.[3]
Treatment options:
- Phlebotomy.[9]
- Hydroxyurea (alone or with phlebotomy).[10,11]
- Interferon-alpha [12,16,17] and pegylated interferon-alpha.[18]
- Rarely, chlorambucil or busulfan may be required, especially if interferon or hydroxyurea are not tolerated, as is often seen in patients older than 70 years.[2]
- Low-dose aspirin (≤100 mg) daily, unless contraindicated by major bleeding or gastric intolerance.[8,14]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with polycythemia vera. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Tefferi A, Thiele J, Vardiman JW: The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer 115 (17): 3842-7, 2009.
- Streiff MB, Smith B, Spivak JL: The diagnosis and management of polycythemia vera in the era since the Polycythemia Vera Study Group: a survey of American Society of Hematology members' practice patterns. Blood 99 (4): 1144-9, 2002.
- McMullin MF, Bareford D, Campbell P, et al.: Guidelines for the diagnosis, investigation and management of polycythaemia/erythrocytosis. Br J Haematol 130 (2): 174-95, 2005.
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006.
- Marchioli R, Finazzi G, Landolfi R, et al.: Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23 (10): 2224-32, 2005.
- Elliott MA, Tefferi A: Thrombosis and haemorrhage in polycythaemia vera and essential thrombocythaemia. Br J Haematol 128 (3): 275-90, 2005.
- Chait Y, Condat B, Cazals-Hatem D, et al.: Relevance of the criteria commonly used to diagnose myeloproliferative disorder in patients with splanchnic vein thrombosis. Br J Haematol 129 (4): 553-60, 2005.
- Finazzi G, Barbui T: How I treat patients with polycythemia vera. Blood 109 (12): 5104-11, 2007.
- Berk PD, Goldberg JD, Donovan PB, et al.: Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols. Semin Hematol 23 (2): 132-43, 1986.
- Lamy T, Devillers A, Bernard M, et al.: Inapparent polycythemia vera: an unrecognized diagnosis. Am J Med 102 (1): 14-20, 1997.
- Kaplan ME, Mack K, Goldberg JD, et al.: Long-term management of polycythemia vera with hydroxyurea: a progress report. Semin Hematol 23 (3): 167-71, 1986.
- Lengfelder E, Berger U, Hehlmann R: Interferon alpha in the treatment of polycythemia vera. Ann Hematol 79 (3): 103-9, 2000.
- Kiladjian JJ, Cassinat B, Chevret S, et al.: Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 112 (8): 3065-72, 2008.
- Squizzato A, Romualdi E, Middeldorp S: Antiplatelet drugs for polycythaemia vera and essential thrombocythaemia. Cochrane Database Syst Rev (2): CD006503, 2008.
- Ruggeri M, Rodeghiero F, Tosetto A, et al.: Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 111 (2): 666-71, 2008.
- Silver RT: Long-term effects of the treatment of polycythemia vera with recombinant interferon-alpha. Cancer 107 (3): 451-8, 2006.
- Quintás-Cardama A, Kantarjian HM, Giles F, et al.: Pegylated interferon therapy for patients with Philadelphia chromosome-negative myeloproliferative disorders. Semin Thromb Hemost 32 (4 Pt 2): 409-16, 2006.
- Quintás-Cardama A, Kantarjian H, Manshouri T, et al.: Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 27 (32): 5418-24, 2009.
Primary Myelofibrosis
Disease Overview
Primary myelofibrosis (also known as agnogenic myeloid metaplasia, chronic idiopathic myelofibrosis, myelosclerosis with myeloid metaplasia, and idiopathic myelofibrosis) is characterized by splenomegaly, immature peripheral blood granulocytes and erythrocytes, and teardrop-shaped red blood cells.[1] In its early phase, the disease is characterized by elevated numbers of CD34-positive cells in the marrow, while the later phases involve marrow fibrosis with decreasing CD34 cells in the marrow and a corresponding increase in splenic and liver engorgement with CD34 cells.
As distinguished from chronic myelogenous leukemia (CML), primary myelofibrosis usually presents as follows:[2]
- A white blood cell count smaller than 30,000/mm3.
- Prominent teardrops on peripheral smear.
- Normocellular or hypocellular marrow with moderate to marked fibrosis.
- An absence of the Philadelphia chromosome or the BCR/ABL translocation.
- Frequent positivity for the JAK2 mutation.
In addition to the clonal proliferation of a multipotent hematopoietic progenitor cell, an event common to all chronic myeloproliferative disorders, myeloid metaplasia is characterized by colonization of extramedullary sites such as the spleen or liver.[3,4]
Most patients are older than 60 years at diagnosis, and 33% of patients are asymptomatic at presentation. Splenomegaly, sometimes massive, is a characteristic finding.
Symptoms include:
- Splenic pain.
- Early satiety.
- Anemia.
- Bone pain.
- Fatigue.
- Fever.
- Night sweats.
- Weight loss.
(Refer to the PDQ summaries on Pain; Fatigue; Fever, Sweats, and Hot Flashes; and Nutrition for information on many of the symptoms listed above.)
The proposed World Health Organization criteria for the diagnosis of primary myelofibrosis requires all three major criteria and two minor criteria.[5]
Major Criteria
- Presence of megakaryocyte proliferation and atypia, usually accompanied by either reticulin and/or collagen fibrosis; or, in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (so-called prefibrotic cellular-phase disease).
- Not meeting criteria for polycythemia vera, chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm.
- Demonstration of JAK2 617V greater than F or other clonal marker; or, in the absence of a clonal marker, no evidence of bone marrow fibrosis caused by an underlying inflammatory disease or another neoplastic disease.
Minor Criteria
- Leukoerythroblastosis.
- Increased serum level of lactate dehydrogenase.
- Anemia.
- Palpable splenomegaly.
Distinguishing prefibrotic myelofibrosis from essential thrombocythemia can be difficult because of substantial interobserver variability and because of no difference in clinical outcome.[6]
The median survival is 3.5 years to 5.5 years, but patients younger than 55 years have a median survival of 11 years.[3,4] The major causes of death include:[7]
- Progressive marrow failure.
- Transformation to acute nonlymphoblastic leukemia.
- Infection.
- Thrombohemorrhagic events.
- Heart failure.
- Portal hypertension.
Fatal and nonfatal thrombosis was associated with age more than 60 years and JAK2 positivity in a multivariable analysis of 707 patients followed from 1973 to 2008.[8] Bone marrow examination including cytogenetic testing may exclude other causes of myelophthisis, such as CML, myelodysplastic syndrome, metastatic cancer, lymphomas, and plasma cell disorders.[4] In acute myelofibrosis, patients present with pancytopenia but no splenomegaly or peripheral blood myelophthisis. Peripheral blood or marrow monocytosis is suggestive for myelodysplasia in this setting.
There is no staging system for this disease.
Prognostic factors include:[9,10,11,12,13]
- Age 65 years or older.
- Anemia (hemoglobin <10 g/dL).
- Constitutional symptoms: fever, night sweats, or weight loss.
- Leukocytosis (WBC >25 × 109 /L).
- Circulating blasts of at least 1%.
Patients without any of these adverse features, excluding age, have a median survival of more than 10 years, while the presence of any two of these adverse features lowers the median survival to less than 3 years.[14] An international prognostic scoring system has been proposed by the Working Group for Myelofibrosis Research and Treatment.[14]
Karyotype abnormalities can also affect prognosis. In a retrospective series of 200 patients, 13q and 20q deletions and trisomy 9 correlated with improved survival and no leukemia transformation in comparison to the trisomy 8 or a complex karyotype.[8]
Treatment Overview
The profound anemia that develops in this disease usually requires red blood cell transfusion. Red blood cell survival is markedly decreased in some patients; this can sometimes be treated with glucocorticoids. Disease-associated anemia may occasionally respond to the following:[4,15,16,17]
- Erythropoietic growth factors.
- Hydroxyurea.
- Cladribine.
- Thalidomide.
- Lenalidomide.
- Interferon.
JAK2 inhibitors are being evaluated in randomized trials, and patients may be eligible even in the absence of a JAK2 mutation.(COMFORT-I trial [NCT00952289])
Painful splenomegaly can be treated temporarily with chemotherapy (hydroxyurea), interferon, thalidomide, lenalidomide, or radiation therapy, but often requires splenectomy.[17,18] The decision to perform splenectomy represents a weighing of the benefits (i.e., reduction of symptoms, decreased portal hypertension, and less need for red blood cell transfusions) versus the debits (i.e., postoperative mortality of 10% and morbidity of 30% caused by infection, bleeding, or thrombosis; no benefit for thrombocytopenia; and accelerated progression to blast crisis that was seen by some investigators but not others).[4,18]
Hydroxyurea is useful in patients with this disease but may have a potential leukemogenic effect.[4] In patients with thrombocytosis and hepatomegaly after splenectomy, cladribine has shown responses as an alternative to hydroxyurea.[19] The use of interferon-alpha can result in hematologic responses, including reduction in spleen size in 30% to 50% of patients, though many patients do not tolerate this medication.[20,21] Favorable responses to thalidomide and lenalidomide have been reported in about 20% to 60% of patients.[15,16,17,22,23][Level of evidence: 3iiiDiv]
A response defined as 50% reduction of splenomegaly or development of transfusion independence was attained by one-third of 34 symptomatic patients using tipifarnib.[24][Level of evidence: 3iiiDiv] A more aggressive approach involves allogeneic peripheral stem cell or bone marrow transplantation when a suitable sibling donor is available.[25,26,27] Detection of the JAK2 mutation after transplantation is feasible, but there are no data to confirm that a change in therapy based on persistence of this marker would have an effect on outcome.[28] A retrospective review of 150 patients who underwent surgery documented 8% thromboembolism and 7% major hemorrhage with prior cytoreduction and postoperative subcutaneous heparin in one-half of the patients.[29]
Treatment options:
- Clinical trials involving JAK2 inhibitors.(COMFORT-I trial [NCT00952289])
- Interferon-alpha.[20,21]
- Splenectomy.[18,30]
- Splenic radiation therapy.[4]
- Hydroxyurea.[3,4]
- Allogeneic peripheral stem cell or bone marrow transplantation.[26,27,31,32]
- Thalidomide.[15,22,23,25]
- Lenalidomide.[17,33]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with primary myelofibrosis. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Hennessy BT, Thomas DA, Giles FJ, et al.: New approaches in the treatment of myelofibrosis. Cancer 103 (1): 32-43, 2005.
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006.
- Barosi G: Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol 17 (9): 2954-70, 1999.
- Tefferi A: Myelofibrosis with myeloid metaplasia. N Engl J Med 342 (17): 1255-65, 2000.
- Tefferi A, Thiele J, Vardiman JW: The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer 115 (17): 3842-7, 2009.
- Wilkins BS, Erber WN, Bareford D, et al.: Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 111 (1): 60-70, 2008.
- Chim CS, Kwong YL, Lie AK, et al.: Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med 165 (22): 2651-8, 2005 Dec 12-26.
- Hussein K, Pardanani AD, Van Dyke DL, et al.: International Prognostic Scoring System-independent cytogenetic risk categorization in primary myelofibrosis. Blood 115 (3): 496-9, 2010.
- Cervantes F, Barosi G, Demory JL, et al.: Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups. Br J Haematol 102 (3): 684-90, 1998.
- Strasser-Weippl K, Steurer M, Kees M, et al.: Age and hemoglobin level emerge as most important clinical prognostic parameters in patients with osteomyelofibrosis: introduction of a simplified prognostic score. Leuk Lymphoma 47 (3): 441-50, 2006.
- Tefferi A: Survivorship and prognosis in myelofibrosis with myeloid metaplasia. Leuk Lymphoma 47 (3): 379-80, 2006.
- Tam CS, Kantarjian H, Cortes J, et al.: Dynamic model for predicting death within 12 months in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. J Clin Oncol 27 (33): 5587-93, 2009.
- Morel P, Duhamel A, Hivert B, et al.: Identification during the follow-up of time-dependent prognostic factors for the competing risks of death and blast phase in primary myelofibrosis: a study of 172 patients. Blood 115 (22): 4350-5, 2010.
- Cervantes F, Dupriez B, Pereira A, et al.: New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113 (13): 2895-901, 2009.
- Giovanni B, Michelle E, Letizia C, et al.: Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies. Leuk Lymphoma 43 (12): 2301-7, 2002.
- Marchetti M, Barosi G, Balestri F, et al.: Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial. J Clin Oncol 22 (3): 424-31, 2004.
- Tefferi A, Cortes J, Verstovsek S, et al.: Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 108 (4): 1158-64, 2006.
- Barosi G, Ambrosetti A, Centra A, et al.: Splenectomy and risk of blast transformation in myelofibrosis with myeloid metaplasia. Italian Cooperative Study Group on Myeloid with Myeloid Metaplasia. Blood 91 (10): 3630-6, 1998.
- Tefferi A, Mesa RA, Nagorney DM, et al.: Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 95 (7): 2226-33, 2000.
- Sacchi S: The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update. Leuk Lymphoma 19 (1-2): 13-20, 1995.
- Gilbert HS: Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer 83 (6): 1205-13, 1998.
- Strupp C, Germing U, Scherer A, et al.: Thalidomide for the treatment of idiopathic myelofibrosis. Eur J Haematol 72 (1): 52-7, 2004.
- Mesa RA, Elliott MA, Schroeder G, et al.: Durable responses to thalidomide-based drug therapy for myelofibrosis with myeloid metaplasia. Mayo Clin Proc 79 (7): 883-9, 2004.
- Mesa RA, Camoriano JK, Geyer SM, et al.: A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Leukemia 21 (9): 1964-70, 2007.
- Guardiola P, Anderson JE, Bandini G, et al.: Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Société Française de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood 93 (9): 2831-8, 1999.
- Deeg HJ, Gooley TA, Flowers ME, et al.: Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood 102 (12): 3912-8, 2003.
- Daly A, Song K, Nevill T, et al.: Stem cell transplantation for myelofibrosis: a report from two Canadian centers. Bone Marrow Transplant 32 (1): 35-40, 2003.
- Kröger N, Badbaran A, Holler E, et al.: Monitoring of the JAK2-V617F mutation by highly sensitive quantitative real-time PCR after allogeneic stem cell transplantation in patients with myelofibrosis. Blood 109 (3): 1316-21, 2007.
- Ruggeri M, Rodeghiero F, Tosetto A, et al.: Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey. Blood 111 (2): 666-71, 2008.
- Tefferi A, Silverstein MN, Li CY: 2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia. Br J Haematol 99 (2): 352-7, 1997.
- Deeg HJ, Appelbaum FR: Stem-cell transplantation for myelofibrosis. N Engl J Med 344 (10): 775-6, 2001.
- Kröger N, Holler E, Kobbe G, et al.: Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, multicenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 114 (26): 5264-70, 2009.
- Quintás-Cardama A, Kantarjian HM, Manshouri T, et al.: Lenalidomide plus prednisone results in durable clinical, histopathologic, and molecular responses in patients with myelofibrosis. J Clin Oncol 27 (28): 4760-6, 2009.
Essential Thrombocythemia
Disease Overview
The proposed revised World Health Organization criteria for the diagnosis of essential thrombocythemia requires all four criteria.[1]
- Sustained platelet count of at least 450 × 109 /L.
- Bone marrow biopsy showing predominant proliferation of enlarged mature megakaryocytes; no significant increase of granulocytic or erythroid precursors.
- Not meeting criteria for polycythemia vera (p. vera), primary myelofibrosis, chronic myelogenous leukemia, myelodysplastic syndrome, or other myeloid neoplasm.
- Demonstration of JAK2 617V greater than F or other clonal marker.[2] In the absence of a clonal marker, there must be no evidence for reactive thrombocytosis. In particular, with a decreased serum ferritin, there must be no increase in hemoglobin level to p. vera range with iron replacement therapy.
Patients older than 60 years or those with a prior thrombotic episode have as much as a 25% chance of developing cerebral, cardiac, or peripheral arterial thromboses and, less often, a chance of developing a pulmonary embolism or deep venous thrombosis.[3] Similar to the other myeloproliferative syndromes, conversion to acute leukemia is found in a small percentage of patients (<10%) with long-term follow-up.
There is no staging system for this disease.
Untreated essential thrombocythemia means that a patient is newly diagnosed and has had no prior treatment except supportive care.
Treatment Overview
Controversy is considerable regarding whether asymptomatic patients with essential thrombocythemia require treatment. A randomized trial of patients with essential thrombocythemia and a high risk of thrombosis compared treatment with hydroxyurea titrated to attain a platelet count below 600,000/mm3 with a control group that received no therapy. Hydroxyurea was found to be effective in preventing thrombotic episodes (4% vs. 24%).[3][Level of evidence: 1iiDiv] A retrospective analysis of this trial found that antiplatelet drugs had no significant influence on the outcome. Resistance to hydroxyurea is defined as a platelet count of greater than 600,000/mcL after 3 months of at least 2 g per day of hydroxyurea or a platelet count greater than 400,000/µL and a white blood count of less than 2,500/µL or a hemoglobin less than 10 g/dL at any dose of hydroxyurea.[4]
In a case-controlled observational study of 65 low-risk patients (<60 years of age, platelet count <1,500 × 109 /L, and no history of thrombosis or hemorrhage) with a median follow-up of 4.1 years, the thrombotic risk of 1.91 cases per 100 patient years and hemorrhagic risk of 1.12 cases per 100 patient years was not increased over the normal controls.[5] A prospective randomized trial of 809 patients compared hydroxyurea plus aspirin versus anagrelide plus aspirin.[6] Although the platelet-lowering effect was equivalent, the anagrelide group had significantly more thrombotic and hemorrhagic events (hazard ratio [HR] = 1.57; P = .03) and more myelofibrosis (HR = 2.92; P = .01). No differences were seen for myelodysplasia or acute leukemia.[7][Level of evidence: 1iiA] Many clinicians use hydroxyurea or platelet apheresis prior to elective surgery to reduce the platelet count and to prevent postoperative thromboembolism. No prospective or randomized trials document the value of this approach.
Among low-risk patients (defined as age 60 years or younger with no prior thrombotic episodes), a retrospective review of 300 patients showed benefit for antiplatelet agents in reducing venous thrombosis in JAK2-positive cases and in reducing arterial thrombosis in patients with cardiovascular risk factors.[8]
Treatment options:
- No treatment, unless complications develop, if patients are asymptomatic, younger than 60 years, and have a platelet count of less than 1,500 × 109 /L.
- Hydroxyurea.[3]
- Interferon-alpha [9,10] or pegylated interferon-alpha.[11]
- Anagrelide.[7,12]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with essential thrombocythemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Tefferi A, Thiele J, Vardiman JW: The 2008 World Health Organization classification system for myeloproliferative neoplasms: order out of chaos. Cancer 115 (17): 3842-7, 2009.
- Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006.
- Cortelazzo S, Finazzi G, Ruggeri M, et al.: Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332 (17): 1132-6, 1995.
- Barosi G, Besses C, Birgegard G, et al.: A unified definition of clinical resistance/intolerance to hydroxyurea in essential thrombocythemia: results of a consensus process by an international working group. Leukemia 21 (2): 277-80, 2007.
- Ruggeri M, Finazzi G, Tosetto A, et al.: No treatment for low-risk thrombocythaemia: results from a prospective study. Br J Haematol 103 (3): 772-7, 1998.
- Harrison CN, Campbell PJ, Buck G, et al.: Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353 (1): 33-45, 2005.
- Green A, Campbell P, Buck G: The Medical Research Council PT1 trial in essential thrombocythemia. [Abstract] Blood 104 (11): A-6, 2004.
- Alvarez-Larrán A, Cervantes F, Pereira A, et al.: Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116 (8): 1205-10; quiz 1387, 2010.
- Sacchi S: The role of alpha-interferon in essential thrombocythaemia, polycythaemia vera and myelofibrosis with myeloid metaplasia (MMM): a concise update. Leuk Lymphoma 19 (1-2): 13-20, 1995.
- Gilbert HS: Long term treatment of myeloproliferative disease with interferon-alpha-2b: feasibility and efficacy. Cancer 83 (6): 1205-13, 1998.
- Quintás-Cardama A, Kantarjian H, Manshouri T, et al.: Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 27 (32): 5418-24, 2009.
- Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Anagrelide Study Group. Am J Med 92 (1): 69-76, 1992.
Chronic Neutrophilic Leukemia
Disease Overview
Chronic neutrophilic leukemia (CNL) is a rare chronic myeloproliferative disorder of unknown etiology, characterized by sustained peripheral blood neutrophilia (>25 × 109 /L) and hepatosplenomegaly.[1,2] The bone marrow is hypercellular. No significant dysplasia is in any of the cell lineages, and bone marrow fibrosis is uncommon.[1,2] Cytogenetic studies are normal in nearly 90% of the patients. In the remaining patients, clonal karyotypic abnormalities may include +8, +9, del (20q) and del (11q).[1,3,4,5] There is no Philadelphia chromosome or BCR/ABL fusion gene. CNL is a slowly progressive disorder, and the survival of patients is variable, ranging from 6 months to more than 20 years.
Treatment Overview
Until the last few years, the treatment of CNL focused on disease control rather than cure. Once the disease progressed to a more aggressive leukemia, there was typically little chance of obtaining a long-lasting remission because of the older age of most patients as well as the acquisition of multiple poor prognostic cytogenetic abnormalities. Allogeneic bone marrow transplantation represents a potentially curative treatment modality in the management of this disorder.[6,7,8] Varying success has been reported with the use of traditional chemotherapies including hydroxyurea and interferon.[9]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with chronic neutrophilic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Imbert M, Bain B, Pierre R, et al.: Chronic neutrophilic leukemia. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 27-8.
- Zittoun R, Réa D, Ngoc LH, et al.: Chronic neutrophilic leukemia. A study of four cases. Ann Hematol 68 (2): 55-60, 1994.
- Froberg MK, Brunning RD, Dorion P, et al.: Demonstration of clonality in neutrophils using FISH in a case of chronic neutrophilic leukemia. Leukemia 12 (4): 623-6, 1998.
- Yanagisawa K, Ohminami H, Sato M, et al.: Neoplastic involvement of granulocytic lineage, not granulocytic-monocytic, monocytic, or erythrocytic lineage, in a patient with chronic neutrophilic leukemia. Am J Hematol 57 (3): 221-4, 1998.
- Matano S, Nakamura S, Kobayashi K, et al.: Deletion of the long arm of chromosome 20 in a patient with chronic neutrophilic leukemia: cytogenetic findings in chronic neutrophilic leukemia. Am J Hematol 54 (1): 72-5, 1997.
- Piliotis E, Kutas G, Lipton JH: Allogeneic bone marrow transplantation in the management of chronic neutrophilic leukemia. Leuk Lymphoma 43 (10): 2051-4, 2002.
- Hasle H, Olesen G, Kerndrup G, et al.: Chronic neutrophil leukaemia in adolescence and young adulthood. Br J Haematol 94 (4): 628-30, 1996.
- Böhm J, Schaefer HE: Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease. J Clin Pathol 55 (11): 862-4, 2002.
- Elliott MA, Dewald GW, Tefferi A, et al.: Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study. Leukemia 15 (1): 35-40, 2001.
Chronic Eosinophilic Leukemia
Disease Overview
Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative disorder of unknown etiology in which a clonal proliferation of eosinophilic precursors results in persistently increased numbers of eosinophils in the blood, bone marrow, and peripheral tissues. In CEL, the eosinophil count is greater than or equal to 1.5 × 109 /L in the blood.[1] To make a diagnosis of CEL, there should be evidence for clonality of the eosinophils or an increase in blasts in the blood or bone marrow. In many cases, however, it is impossible to prove clonality of the eosinophils, in which case, if there is no increase in blast cells, the diagnosis of idiopathic hypereosinophilic syndrome (HES) is preferred. Because of the difficulty in distinguishing CEL from HES, the true incidence of these diseases is unknown, though they are rare. In about 10% of patients, eosinophilia is detected incidentally. In others, the constitutional symptoms found include:[1,2]
- Fever.
- Fatigue.
- Cough.
- Angioedema.
- Muscle pains.
- Pruritus.
- Diarrhea.
No single or specific cytogenetic or molecular genetic abnormality has been identified in CEL.
(Refer to the PDQ summaries on Fever, Sweats, and Hot Flashes; Fatigue; Cardiopulmonary Syndromes; Pain; Pruritus; and Gastrointestinal Complications for information on many of the symptoms listed above.)
Treatment Overview
The optimal treatment of CEL remains uncertain, partially on account of the rare incidence of this chronic myeloproliferative disorder and the variable clinical course, which can range from cases with decades of stable disease to cases with rapid progression to acute leukemia. Case reports suggest that treatment options include bone marrow transplantation and interferon-alpha.[3,4]
Treatment of HES has included the following:[5,6]
- Corticosteroids.
- Chemotherapeutic agents such as hydroxyurea, cyclophosphamide, and vincristine.
- Interferon-alpha.
Case reports suggest symptomatic responses to imatinib mesylate for patients with HES who have not responded to conventional options.[6,7,8][Level of evidence: 3iiiDiv] Imatinib mesylate acts as an inhibitor of a novel fusion tyrosine kinase, FIP1L1-PDGFR alpha fusion tyrosine kinase, which results as a consequence of interstitial chromosomal deletion.[6,9][Level of evidence: 3iiiDiv] HES with the FIP1L1-PDGFR alpha fusion tyrosine kinase translocation has been shown to respond to low-dose imatinib mesylate.[9]
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with chronic eosinophilic leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
- Bain B, Pierre P, Imbert M, et al.: Chronic eosinophillic leukaemia and the hypereosinophillic syndrome. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 29-31.
- Weller PF, Bubley GJ: The idiopathic hypereosinophilic syndrome. Blood 83 (10): 2759-79, 1994.
- Basara N, Markova J, Schmetzer B, et al.: Chronic eosinophilic leukemia: successful treatment with an unrelated bone marrow transplantation. Leuk Lymphoma 32 (1-2): 189-93, 1998.
- Yamada O, Kitahara K, Imamura K, et al.: Clinical and cytogenetic remission induced by interferon-alpha in a patient with chronic eosinophilic leukemia associated with a unique t(3;9;5) translocation. Am J Hematol 58 (2): 137-41, 1998.
- Butterfield JH, Gleich GJ: Interferon-alpha treatment of six patients with the idiopathic hypereosinophilic syndrome. Ann Intern Med 121 (9): 648-53, 1994.
- Gotlib J, Cools J, Malone JM 3rd, et al.: The FIP1L1-PDGFRalpha fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management. Blood 103 (8): 2879-91, 2004.
- Gleich GJ, Leiferman KM, Pardanani A, et al.: Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet 359 (9317): 1577-8, 2002.
- Ault P, Cortes J, Koller C, et al.: Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylate. Leuk Res 26 (9): 881-4, 2002.
- Cools J, DeAngelo DJ, Gotlib J, et al.: A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348 (13): 1201-14, 2003.
Changes to This Summary (07 / 13 / 2012)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
About This PDQ Summary
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of chronic myeloproliferative disorders. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
- be discussed at a meeting,
- be cited with text, or
- replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Chronic Myeloproliferative Disorders Treatment are:
- Steven D. Gore, MD (Johns Hopkins University)
- Mark J. Levis, MD, PhD (Johns Hopkins University)
- Eric J. Seifter, MD (Johns Hopkins University)
- Mikkael A. Sekeres, MD, MS (Cleveland Clinic Taussig Cancer Institute)
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Chronic Myeloproliferative Disorders Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/myeloproliferative/HealthProfessional. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.
Contact Us
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.
Get More Information From NCI
Call 1-800-4-CANCER
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
Chat online
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
Write to us
For more information from the NCI, please write to this address:
NCI Public Inquiries Office |
Suite 3036A |
6116 Executive Boulevard, MSC8322 |
Bethesda, MD 20892-8322 |
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
Find Publications
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Last Revised: 2012-07-13
This information does not replace the advice of a doctor. Healthwise disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions. |
Topic Contents
- General Information About Chronic Myeloproliferative Disorders
- Chronic Myelogenous Leukemia
- Polycythemia Vera
- Primary Myelofibrosis
- Essential Thrombocythemia
- Chronic Neutrophilic Leukemia
- Chronic Eosinophilic Leukemia
- Changes to This Summary (07 / 13 / 2012)
- About This PDQ Summary
- Get More Information From NCI


text:
Remember this ad? The ad where Microsoft attempts to position the iPad as a chopstick-playing toy and the Surface as a PowerPoint-editing machine?
Yeah, that's why we can't have nice things. → Read More
Being behind in a market sucks, and it's understandable to want to lash out at the top dog, as Microsoft has shown it's willing to do with Google in search and email, and now with Apple in tablet computers. A brand new Windows 8 ad pits the iPad against Microsoft's Windows 8 tablet, in an attempt to show how much more versatile the Asus VivoTab is vs. the iOS device. → Read More
The iPad mini is quickly becoming a key component of Apple's product lineup, and according to some sources, might even be the best-selling tablet Apple makes at this point. The smaller tablet hit shelves in early November last year, and likely had a huge impact on Apple's record tablet sales last quarter, which topped 19.5 million devices. It's impossible not to see a Retina update in the mini's… → Read More
BlackBerry CEO Thorsten Heins seems to be among the most transparent executives in tech in terms of showing his hand regarding future product plans, which may be partly because he doesn't have much to lose at this point. In an interview yesterday, he downplayed tablet computing in what looks to be an indicator that BlackBerry will drop the PlayBook, its own lame duck tablet and the first of its… → Read More
San Francisco-based virtual meeting player FuzeBox has had some impressive success to kick-off 2013, posting a 200 percent rise in demand for its product in the initial quarter of the year, with 50,000 new subscribers added in just a few short months. The company also now counts 30 percent of the Fortune 500 among its clients, and is debuting new features for its iPad client to help continue its… → Read More
Keyboard cases for iPad are many and multiplying, but at this point it's a question of refining the best concepts, not creating dramatically different devices. The Belkin Ultimate Keyboard Case for iPad is a great example, taking a lot of cues from the massively popular Logitech Ultrathin Keyboard Cover for iPad and folio style designs to create a solution that might be as near as perfect as… → Read More
A group of MIT students created an app at a PennApps Hackathon that can do amazing things, connecting multiple iOS devices into a single, interactive screen. The app itself, which doesn't require any kind of jailbreaking or special access and is currently available in the App Store for free, is impressive enough, but Mosaic has much bigger plans: They've also created an SDK to let other developers… → Read More
Swiss mobile development and design firm Clever & Son bills itself as a "maker of premium apps," and judging by Couch Player, its latest creation, the startup lives up to its name. Couch Player is essentially a replacement for the built-in Apple Music app on the iPad, but it manages to be much more with just a few simple tweaks. → Read More
Apple has been working on the iPhone since long before it hit the market in 2007, and today a new prototype has come to light that shows how it might have looked if they'd rushed it to market earlier. The 2005 internal prototype is pictured in photos obtained by Ars Technica, from an unnamed former Apple employee. → Read More
Seattle, WA
San Diego, CA
Menlo Park, CA
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subset: commoncrawl


text:
By: Big 2 News Staff
Updated: March 1, 2013
The Obama administration has formally expressed support for same-sex marriage in California.
The Justice Department filed a legal brief with the U-S Supreme Court Thursday challenging California's same-sex marriage ban.
The brief states gay and lesbian couples have the same "equal protection" rights to wed and that voters in California didn't have the power to take those rights away.
An appeal in the California Proposition 8 case was submitted after-hours with the Supreme Court, which is expected to hear the issue in March.


text:
Phone: 901-755-6777
Email: Send Email
Street Address Is:
Maxwell Driving School
7777 Walnut Grove Rd.
Memphis, TN 38120
Mailing address is:
Maxwell Driving School
7777 Walnut Grove Rd., Ste. 49
Memphis, TN 38120-2121
The driving school office is open Monday-Friday 10am to 5pm, and is located in the Agricenter International in the second story of Building C. If calling after hours or on weekends, please leave a message and your call will be returned during business hours.


text:
MAKE A DIFFERENCEInvest in McCombs
MAKE A DIFFERENCEInvest in Texas BHP
MAKE A DIFFERENCEInvest in Texas BBA
Home · Giving to McCombs · How to Give
Your support helps educate business leaders who create value for society. Every gift matters, no matter the size. Your contribution, for the purpose you choose, plays a crucial role in advancing the prominence of the McCombs School. Your contribution enhances the entire McCombs experience by supporting faculty excellence, innovative programs, student scholarships and world-class educational facilities.
There are several convenient methods to facilitate your generosity.
You may make a gift or pledge online with a credit card via our secure gift page.
Mail checks (payable to The University of Texas at Austin) to: The University of Texas at Austin McCombs School of Business ATTN: Development and External Relations 2110 Speedway, Mail Stop B6006 Austin, TX 78712-1270
FedEx and UPS deliveries may be sent to: 21st & Speedway, GSB 2.104 Austin, TX 78712
Are you a UT employee? If so, visit the university's "How to Give" page to learn how to contribute via payroll deduction (information is located toward the bottom of the page).
Please contact Development and External Relations at 512-475-8179.
Areas for Support
Providing student assistance in the form of scholarships is a McCombs School priority. Our impressive and diverse student body excels academically and is active in numerous organizations.
Student success is our success, and the school supports their efforts in every way possible. With your help, students will have the opportunity to reach their full potential.
Endowments supporting the 40 Acres Scholarship program are a top initiative for Dean Gilligan. They are unique because they provide four years of tuition and supplemental educational support to exceptional students, which helps us attract the best and brightest scholars to the McCombs School.
Contact Director of Major Gifts, Dianne Bangle at email@example.com or (512) 475-8177.
Faculty Chairs, Professorships, and Fellowships build the reputation of the school and show a strong commitment to academic achievement. They foster a sense of tradition, and reward our best faculty with the tools to become more productive. They provide year-round salary incentives for our most productive faculty, but Chairs and Fellowships also provide for support staff, research assistance, conference travel, and continuing education allowances. To support the efforts of faculty and help us recruit, retain, and reward the faculty excellence that increases our standing and benefits our constituents, consider supporting one of the following options:
Faculty Excellence Funds are flexible funds dedicated to promoting faculty research, teaching, and continuing education. They can be used to respond quickly to sudden opportunities that may arise, and are a key asset in a rapidly-changing business world. In conjunction with visionary leadership, Excellence Funds ensure we can fulfill our mandate to take the McCombs School to the next level of greatness.
Alumni Endowed Excellence Funds Support BBA, BHP, MBA and Accounting student programs and initiatives. Department of Accounting Support faculty, students and curriculum in the number-one accounting program in the nation. Department of Finance Support the department or invest in one of the five centers in the McCombs Department of Finance.
Program Excellence Endowments are unrestricted endowments that support particular programs at the McCombs School.
We are establishing two new centers focusing on our strengths in Entrepreneurship, Technology and Globalization to complement, unify, and strengthen our many research centers. These Centers will attract great students and top scholars, foster relationship-based corporate partnerships, and produce research that garners national attention. The new centers are:
Facility Endowments assure that students and researchers always have access to the latest business technology. These endowments also provide for repair and replacement of damaged furnishings, ensuring appropriately maintained surroundings for our students. These funds support the "behind the scenes" work of the McCombs School, providing for technology infrastructure upgrades as well as enhancements to the public face of the school.
Contributions that materially improve the McCombs School of Business are often honored by a naming designation. There are many naming opportunities available, including interview rooms in the Ford Career Center Interview suite and student study facilities. Plus, naming opportunities are available at the AT&T Executive Education and Conference Center where we hold our continuing education and working professional and executive MBA programs.
For information on McCombs School Facility Excellence Endowments, contact Dianne Bangle at email@example.com or (512) 475-8177.


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3. | pecker checker | ||
A U.S. Army medic or hospital personnel assigned to inspect soldierss' genitals for signs of sexually transmitted diseases, a process otherwise known as a short arm inspection. After the actor Robert Mitchum was drafted into the Army in 1945, he spent his year in the service as a pecker checker at a Tarzana induction center.
1. | Pecker Checker | ||
Prison slang for a guy who looks at other guy's dicks while they are in the shower.
AKA Shower Shark or Peter Gazer Gary didn't like to go into the shower with the other guys because there were too many pecker checkers in jail.
2. | pecker checker | ||
A US Navy Hospital Corpsman who is assigned to the STD clinic, to conduct a short arm inspection or otherwise inspect scores of human genitalia for signs of sexually transmited disease. Corpsman: Dude, they just made me the new pecker checker at Balboa.
Shipmate: It's easy, just tell 'em to drop their skivvies, pretend to look interested, and tell 'em not to wave that thing so close to your cigar. |
4. | pecker checker | ||
A man, regardless of sexual orientation, who has a habit of glancing (or checking out) at other men's penises. John makes me feel uncomfortable. Have you noticed how he looks at everyone's dick? I think he's a pecker checker.
5. | pecker checker | ||
To grab a man's crotch in order to check for male genitals. That dude was talking like a female so I had to pull a pecker checker.
6. | pecker checker | ||
A sort-of synonym for size queen, this is a chick who checks out dudes' packages like men check out tits. She's not always very subtle, either, and there are more of them than you think. She will befriend a male of average to less-than-average penis size, but she only dates/fucks well endowed men. The girl I just talked to at school glanced more than once at my crotch- I think she's a pecker checker.
7. | Pecker Checker | ||
What you call a Guy who you trick into looking at your junk. hey look dude i got a new phone, reach to pocket, other guy looks down, then you say: ay pecker checker stop lookin at my junk!!


text:
Welcome. We may listen to a whole range of personal comments on life during the course of a week at different venues and events, whether it be the breakfast table, a lunch time snack or an evening gathering. By the end of the week most of the discussions are forgotten with a smile, but often somebody said one thing that has taken root. Maybe we would want to ask more about it if we took the opportunity and the time. Social reflection is borne out of such exchanges and unplanned-for experiences in life. Social reflection is most frequently engaged in through opinion columns that allow us draw a deeper perspective than is assumed by general media and the wisdom of mass communication today. Behind social reflection there is a framework and method. For social analysis that is open to a faith experience it may be deepened with theological reflection. ESSC is an organization that works in many difficult contexts where the general social norms frequently do not apply and there is a constant need to be attune to what is really happening with people and how effectively to work with critical knowledge and empowering implementation. A number of events this year have been occasion for various group engagements and reflection. The effort here is to share these experiences amongst such like-minded groups and draw further reflective response rather than simply reaction. There is a greater truth to be found in our experiences and in what is shared and there is a value in taking it deeper into our own lives and broader in relating with society. A number of reflections are shared here. This is not a directly open web page as it is initially focused on those who have participated in the different events and how we want to continue our reflection. If there are other personal friends you feel might benefit from the site, you can share the link. The invitation is for those who join to share their experience and as others from different groups or experiences may want to read they too may want to comment. |
Social Reflections


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By: Web Staff
SULLIVAN COUNTY, N.Y. -- Police arrested a man they say burglarized a convenience store in the Village of Monticello.
Police say it happened on December 2nd around 12:30 p.m. at the Veo Express Lanes store on Forestburg Road. They say Bazeley Burns, 50, pried open a door and stole cash from a register before fleeing the store.
Police say officers found Burns on Tuesday and say they had to use a taser on him when he resisted arrest.
Burns has been charged with burglary, grand larceny, criminal mischief, resisting arrest and possession of burglar's tools. He is being held in the Sullivan County Jail without bail.


text:
Things to Do in Maryland
Things to Do Deals
Fisherman's Wharf
- Lewes
Captains supply rods and reels as they lead vessels out to capture deep-sea fish
Press Play Entertainment
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Players play full versions of games at stations outfitted with surround sound, flat screen 3D TVs, and Xbox 360, Wii, and PlayStation 3
Talbot Run Equestrian Center, LLC
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Group lessons at a 147-acre equestrian center focus on proper, safe technique in the disciplines of English riding, jumping, and dressage
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Local museum explores the area's history as a Quaker community and historic hub of Maryland with rotating and permanent exhibits
Recommended Things to Do by Groupon Customers
At Adventure Park USA, visitors amble, shriek, and laugh through a sprawling 17.5 acres replete with Old West–themed rides and attractions such as the Wildcat roller coaster, which dips and curves around a track in order to elicit screams of joy akin to Steven Tyler on Christmas morning. Outdoor diversions such as bumper boats and go-karts stoke competitive fires, and a collection of little tykes rides invite pintsize riders to spin in teacups or gallop on carousel horseback. Open year-round, a 22,000-square-foot indoor playzone thumbs its nose at inclement weather with laser tag, an arcade, a ropes course, and a climbing wall. Owner Larry Stottlemeyer continues to expand this already extensive list of family-friendly diversions.
Arundel challenges Mother Nature herself with its covered and heated driving range. At night, swingers can stay in the game thanks to extended hours (until 8:30 every night except Sundays) and lit facilities. With four rounds of mini golf, perfect putting skills or rustle up friends for a round on Arudel's well-manicured little greens. The golf park also boasts batting cages, allowing visitors the chance to hone their hitting skills. A staff of PGA gurus keeps the facilities all-age friendly.
Newlyweds can't stop praising the staff at Flowers & Fancies. In several glowing reviews posted on the business's website, satisfied customers praise their bridal bouquets and aisle-side blooms, with some even hand-scrawling their thank-you notes to the florist. While the shop's employees boast a special knack for creating wedding-day arrangements, their artistic bouquets express a wide spectrum of sentiments so flower givers don't ever have to change facial expressions. On anniversaries, 12 long-stem roses commemorate years of devotion, while sprays of pink flowers make a friend's day. The floral artists also indulge a whimsical streak with pup-shaped arrangements and a line of cocktail-inspired bouquets that only cause intoxication if soaked in vodka and eaten as a snack.
The wellness exam includes a basic physical of your beast's body, during which his or her weight and blood pressure will be measured and noted, as well as an exam of the all-around level of wellness (Heartowrm/Lyme Snap Test and fecal exam for intestinal parasites not included). If the dog doc recommends additional tests for your feral friend, you'll receive 25% off a blood profile (usually between $105 and $150) as well as 25% off dental procedures (usually $493). An additional $25 credit toward any other Maltese-mending or Siamese-soothing service is also included.
The story follows military man Don Jose, who falls helmet over boots for a gypsy girl named Carmen. As he spirals into an obsessive jealous spell, his world begins to crumble faster than Sid's first cookie. Don Jose's consuming passion for Carmen leads to disgraceful acts that can only be described operatically. The production is sung in French, with English supertitles and English dialogue.
Drivers rev their engines across three separate raceways at The Go-Kart Track, where thrill seekers can split their time between high-speed chases and rounds of mini golf. The family-oriented entertainment center's three distinct go-kart tracks cater to drivers young and old. The junior track safeguards youngsters with an automatic braking system every time they release the gas pedal, and the family track lets people ride shotgun in double-seater cars. Finally, the drift track—coated in a special powder—allows drivers 54 inches and taller to slip and slide around turns, drifting like their favorite racecar driver or continent. Aside from its automotive pursuits, The Go-Kart track features a mini-golf course with nine professionally designed holes peppered with obstacles such as cacti and tires.


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Windows Phone apps to help you keep that New Year's Resolution
Windows Phone Central's Roundup: Exercise Apps
With the new year comes New Year's Resolutions and what may be the most popular resolution is to get into shape or lose weight. There are several Windows Phone fitness apps and we thought that if you are trying to stick with a resolution for better health, we'd roundup a few fitness apps to help you along the way.
Included are a few freebies and a few structured for men or women. As always, with as many apps in the Windows Phone Store, we can't touch on them all. If we've missed your favorite fitness app, feel free to sound off in the comments.
Men's Health Workouts (free trial/$1.99): Men's Health Workouts is brought to you by the popular Men's Health publication. The app features a variety of exercises that are sorted alphabetically, by body part or preference. Each exercise includes detailed, step by step instructions.
The app features a circuit training interface that is designed for maximum results in minimum time. Men's Health Workouts also includes a training log to track your progress and an exercise/rest timer to pace your workouts.
There is a free trial version for Men's Health Workouts that includes five workouts. The full version will run you $1.99 and you can find it all here at the Windows Phone Store.
Gym Assistant (free): Gym Assistant is designed to help you track and schedule your gym workouts. Gym Assistant is more or less a free form app that lets you plan and monitor your exercises throughout the week.
You can view Today's schedule, the week's schedule and plan your week. You name the targeted muscle group, name the exercise and set the sets, reps and weights used. As you complete the exercise, you can check off on it as complete.
Gym Assistant is a fairly basic, free exercise app for your Windows Phone. You can find Gym Assistant here at the Windows Phone Store.
Women's Health Workouts (free trial/$1.99): Similar to Men's Health Workouts, Women's Health Workouts focus on exercise routines designed for a women's physique.
The app is laid out in the same manner as the men's app with workouts sorted alphabetically, by muscle focus and fitness goal. Each exercise is detailed with step by step instructions and visual demos to help you get things right.
Women's Health Workouts also features a training log to track your progress and a workout/rest timer to pace your routines.
There is a free trial version for Women's Health Workouts with the full version running $1.99. You can find Women's Health Workouts here at the Windows Phone Store.
Sports Tracker (free): Sports Tracker is a Windows Phone fitness app that is designed more for those who prefer the more mobile fitness routines (running, cycling, etc.) over the gym workouts. Along with mapping out your routes, Sports Tracker will track and analyze your exercise performance that includes duration, distance, pace, energy, and other stats.
The Sports Tracker Windows Phone app will also connect and sync workouts with your Sports Tracker account (free) to allow you to view your workouts online at Sports-Tracker.com.
Sports Tracker is a free app for your Windows Phone and you can find it here at the Windows Phone.
Nike+Kinect Training (free): Nike+ Kinect Training is a supplemental Windows Phone app for Nike+ Kinect Training for Xbox 360.
The app allows you to access your Xbox 360 activity, track your program progress, explore your workouts, get Challenge reminders, connect and cheer on your friends and prepare for upcoming workout sessions.
If you need to keep track of your Nike+ Kinect workouts while on the go, the Nike+ Kinect Training app will come in handy. It is a free app and you can find Nike+ Kinect Training here at the Windows Phone Store.
If fitness is an every day event or a New Year's Resolution, these Windows Phone apps can help you monitor and plan your exercise activities. You can find the full listing of fitness apps in the Windows Phone Store under the Health and Fitness Category in the App Section of the Store.
Again, if we've miss your favorite Windows Phone fitness app, chime in below in the comments with your favorite fitness app. And for those who have resolved to stay fit this new year, good luck!
There are 12 comments. Sign in to commentSiah1214 says:
A good alternative to Gym Assistant would be Deekfit Gym. I've been using it for a year, fairly well supported and a lot of features. Developer never seems to advertise it though.
manzanotti says:
For cycling, I'm really enjoying Marathon: http://www.windowsphone.com/en-us/store/app/marathon/325015cf-2ad9-df11-...
Version 4 is in beta testing at the moment, and uses a WinPho 8 background task, but it seems to work fine for me on my Lumia, so it will hopefully be released by the developer soon. You can apply to get the beta from the developer here: http://www.jmd-software.net/
I've nothing to do with it, by the way, I've been using the app for a couple of months now, and I like it a lot.
MrSean490 says:
For running I highly recommend Total C25K (couch to 5km). Excellent app that properly guides you along for 8 weeks from couch potato to running 5ks in 30 minutes. My new years resolution is to follow through with this app, hopefully that happens lol
Free(ads) & paid (no ads) available.
There's another app C210K but I haven't tried it and it's by a different author so I can't vouch for its quality
Mark Roffey says:
Great tip. Need this. Thanks.
branedge says:
i've been using Endomondo Sports it's free, happy with it so far (but always looking)
Heath Cates says:
Runtastic Pro!
I used the free version for a while and it works just as well. To get the Pro app is just $5 and it adds voice feedback and media player functions in the app itself. I'm a walk/runner and I love this app because it keeps track of everything for me. I don't even pay attention to mile markers on tracks anymore as the app does it.
Some of my favorite features. (I now realize I may sound like an employee but in reality I just love this app)
- Automatically tracks: Distance, Temp & Weather, Split Times (in 1/2 mile increments), Maps (via GPS), Duration, Pace, Elevation
- You can also add things like: Trail/Track type, How you feel at the end of a workout.
welshandy86 says:
I've been using Endomondo Sports Tracker and MyFitnessPal for tracking sports and calories recently. Both great apps and sync with their respective websites.
Gazlar says:
Try My Run, currenty has
- a learn to run program which is basically a couch to 5k in 9 weeks program
- Free run where you just run untill you want to stop
- Timed mode so you tell it how long you want to run for it will tell you when to finish.
- It gives you a 7 day weather forecast so you can check running conditions for later in the week,
- Tracks all the usual stats such as GPS, distance, speed, calories burnt.
- Show stats of previous runs and graphs and maps.
Version 2 is under development with bug fixes and lost of new features. Best of all its free!
mango.lover says:
I can't believe you skipped Livescape™
ZuNuKoo says:
Exactly my thoughts. I think that has a bit of everything all the other apps offer but in one app.
PhoebeRogers says:
One of the best app I've tried. Very useful to me almost everyday. - Rich Von Alvensleben


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Varaluz 116B01 Single Light Bathroom Wall Sconce from the Modisty Collection
Item #:
Originally $158.00
We still have product details, accessories, and reviews below, scroll down to see them!
Compare Our Prices
Technical Specs
ADA | No |
Bulb Base | Medium (E26) |
Bulb Type | Incandescent or Fluorescent |
Bulbs Included | No |
Collection | Modisty |
Energy Star | No |
Finish | Bakersfield |
Glass Type | Hand-Made Frosted |
Height | 8.75 |
Light Direction | Down Lighting |
Number of Bulbs | 1 |
Shade | Hand-Made Frosted |
Suggested Room Fit | Entry / Foyer, Living Room, Office |
Theme | Traditional / Classic |
Wattage | 100 |
Watts Per Bulb | 100 |
Width | 10.5 |
Single Light Bathroom Wall Sconce from the Modisty Collection
Modisty One Light bath/sconce with recycled steel and hand-made frosted glass. Arts & Crafts, Asian and Mid-Century Modern influences combine to pay homage to Frank Floyd Wright. Each piece of glass is acid-etched, hand-made artisan ice glass. It is characterized by pits, bubbles and cooling lines. These rougher, hand-made details are an intentional contrast with the more linear metalwork.
- Glass:Hand-Made Frosted Glass
- Bulb Type:Medium Base
- Number of Bulbs:one
- Wattage:100W
- Installation Location:Interior
- Voltage:120V
- Made From Recycled Steel
Additional Varaluz Links
- Shop All Varaluz Products
- Shop All Varaluz Modisty Collection Products
Our SKU: 116B01
This product is listed under the following manufacturer number(s):
Bakersfield With Hand-Made Frosted Glass Shade
*Denotes a finish or option that has been discontinued
Varaluz challenges their customers to find a more distinct and unique design. With all of their fixtures being constructed almost entirely (and some 100%) from recycled materials there is a story behind every piece. If you're looking for something you have never seen before, something striking and so beautiful the first thing you want to do is show it off, Varaluz delivers. Sustainability, quality and elegance shine through in every fixture that Varaluz produces. Browse the entire Varaluz line to discover lighting you've never imagined and buy a Varaluz fixture to own lighting that you'll never forget.
Varaluz Modisty Collection
Arts & Crafts, organic, and Mid-Century Modern influences unite in our homage to Frank Lloyd Wright. While the lines and floating planes certainly are hallmarks of his designs, the use of recycled materials and our own unique hand crafting make this very much ours. Each piece of glass is hand crafted artisan ice glass. The glass is made all the more interesting by the visible tool marks and individual accents, so that no two pieces are alike.
Other Products In The Varaluz Modisty Collection
Varaluz 116P03
3 Light Chandelier from the Modisty Collection
$1,726.34$1,449.00 -
Varaluz 116P01
Single Light Mini Pendant from the Modisty Collection
$662.34$559.00 -
Varaluz 116P02
2 Light Island / Billard Fixture With Hand-Made Shades from the Modisty Collection
$1,194.34$999.00 -
Varaluz 116S01
Bakersfield Semi-Flush Ceiling Fixture from the Modisty Collection


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The Hanley Award for Vision and Leadership in Sustainable Housing honors individuals who have demonstrated extraordinary, lasting, and far-reaching contributions to the advancement of sustainable housing in the United States. The Hanley Award is a $50,000 cash prize, the largest annual prize ever established for advancing sustainable housing. The Hanley Award is the industry's premier award recognizing achievements in environmental building and is sponsored by The Hanley Foundation, Hanley Wood, and BUILDER and EcoHome magazines. The goal of the award is to address critical environmental challenges, and to acknowledge and encourage the housing industry's response. Learn more about The Hanley Award.
The AIA COTE Top Ten Green Project Awards are awarded annually by the AIA's Committee on the Environment (COTE) and recognizes ecological design thinking. With an emphasis on holistic thinking, the program recognizes 10 projects for their successful integration of exemplary aesthetics, performance, community connection, social responsibility, and stewardship of the natural environment. In addition, in 2013, AIA COTE launched the AIA COTE Top Ten Plus award, designed to recognize a past AIA COTE Top Ten Green Project for its on-going high-performance.
While no longer in operation, the ECOHOME Design Awards presented by ECOHOME magazine honored the best sustainable homes for outstanding design, high-performance features, environmental performance, and site and community integration. Winners each year were chosen from an open call for entries and reviewed by a panel of industry experts. The awards were discontinued in 2013.
From 2008-2012, the Evergreen Awards, presented by ECOSTRUCTURE magazine, recognized outstanding design and environmental performance in the commercial building realm. Winners were chosen each year in categories representing new construction, existing buildings, commercial interiors on-the-boards work. In addition, the competition included a residential category and a Perspective category, which recognized a green-building professional for his or her work moving the green-building industry forward. The awards were discontinued in 2013.
Eight outstanding green-building professionals are under consideration for the 2013 award, which includes a $50,000 prize, from The Hanley Foundation, ECOHOME, and BUILDER.
ECOHOME May 02, 2013
DOE's Sam Rashkin receives The 2012 Hanley Award for Vision and Leadership in Sustainable Housing.
ECOHOME May 07, 2012
Learn more about this prestigious award and all of its winners.
ECOHOME April 16, 2012
A past COTE Top Ten Green Project outperforms expectations and earns more recognition.
eco-structure May 06, 2013
Designed by Ross Barney Architects, a Midwest educational facility serves as a living laboratory for high-performance building techniques.
eco-structure May 03, 2013
Brooks + Scarpa sets a new standard for the home office with a light-filled, comfortable live–work space.
eco-structure May 02, 2013
Along with Gensler, this firm is the other half of the design team behind the new Tower at PNC Plaza in Pittsburgh, Pa., scheduled to be completed in 2015. In this Q&A, they discuss the project and their philosophy.
eco-structure October 24, 2012
PNC's ambitious new headquarters under construction in Pittsburgh wins the 2012 Evergreen Awards On the Boards category.
The a Q&A with the firm behind the dormitory at Unity College in Unity, Maine, winner of the 2012 Evergreen Award in the Residential category.
eco-structure October 23, 2012
Palo Alto, Calif., Passive House touts greywater system and urine-diverting toilets.
ECOHOME July 19, 2012
Portland, Ore., infill project for both market-rate and low-income buyers promotes low-income affordable housing along light-rail line.
This Santa Fe, N.M., house shows how production housing and net-zero energy can go hand in hand.
Follow our extensive coverage of this year's winners.


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Why The Video Looks Shaky (Don Ward)
Updated: 06/18/2013 - We did a quick helicopter tour of the Black Forest burn area. Someone asked why the video looks shaky.
SUMMIT COUNTY, COLORADO - A Jack Russell terrier was reunited with his owners after some tense moments when the dog ended up stuck on the partially frozen Tiger Road dredge pond. The Vargas family from Frisco was on their way back from a hike when their dog Jonah slipped his leash and chased after ducks that were out on the pond.
"He was running around and all of a sudden he just froze," said Rod Vargas. "I think he looked down and realized where he was."
When Jonah refused to move, the family called 911.
Animal Control Officer Ian Andrews was the first on scene, and did his best to keep the family calm until Special Operations Sergeant Cale Osborn from the Sheriff's Office arrived with a dry suit. Osborn used a log to help coach Jonah towards him, then carefully slid them both back towards shore.
Vargas had nothing but praise for Jonah's rescuers.
"We told all our friends. It was so touching what they did," said Vargas. "I know for them it was probably something they deal with daily,
but for us it was a big deal."
Jonah doesn't appear to have suffered any ill effects from his time on the ice; however, the incident should serve as a warning to other pet owners.
"This time of year, you should assume that no ice is safe," said Sheriff John Minor. "Keep your pet on a leash, and don't go out on the
ice after your pet. Hypothermia can render you unconscious in less than 15 minutes."
Updated: 06/18/2013 - We did a quick helicopter tour of the Black Forest burn area. Someone asked why the video looks shaky.
Updated: 05/20/2013 - Two weekends left to catch one great show!
Updated: 05/14/2013 - I'm still focused on meeting my goal of doing a pull-up. And I'm almost there! But I'm always getting this question:
Updated: 04/17/2013 - Crossing the finish line is such an awesome moment. It's hard to imagine what it has been like for the runners in Boston.
Updated: 04/09/2013 - Admittedly, there are days that I just don't feel like working out. But then I met Viola. And if she can make working out a priority at 99, then none of us have any excuses! Here's how she's living a FIT LIFE:


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What is your favorite occupation?
Probably gardening. Also dressmaking.
Love. Her!
To see Ann's latest projects, tips, how-tos and giveaways, change your links to: http://blog.gorgeousfabrics.com/
What is your favorite occupation?
Probably gardening. Also dressmaking.
I've always liked her and to find out that she shares my love of dressmaking - simply amazing!
Do you remember when she won the Oscar and she was on the Oprah special? She brought the dress she wore and showed how the inside was constructed. I thought that was so kewl! And yes, I really like her too...a classy lady!
Isn't that wonderful? Can I really like her even more?
Any woman who campaigns for sleeves in formalwear is on my list of proto-saints.
I adore her! No, I worship her! She is everything I want to be as I age: elegant, classy, beautiful. And she can still rock a bikini!
As if her talent and class were not reason enough to admire her – I love the fact that she sews!
That is so awesome! I jsut love her, too.
Nicole Richie said in "In Style" a few months ago that many of her friends sew, and so she took up the hobby, and then began designing her own line. I was impressed that she took up sewing before getting a design gig. I mean, she definitely got it b/c of her celebrity status but still... her esteem grew in my eyes.
Wow, already love her as an icon of how to age well but she sews too? Pretty cool.
Way cool...She is just the classiest lady (and a fabulous actress!)
I think it's fabulous she wants to come back as you, Ann: A businesswoman athlete (hey zumba counts, right?) who can sing!
Loved the interview, thanks for posting the link!
Yes, What a LADY
I hope to age as gracefully and beautifully as her!
I adore Helen Mirren - she is a consumate actor, a dignified beauty and very intellent. When I was very young she also had that whiff of scandal about her for appearing nude in the Australian film Age of Consent.
Yeah, she's just too cool.
She is just fabulous . . . luv her!
Besides all the positives mentioned already I love that she still gets important work even as she ages (not hiding the advance of years, but incorporating the changes to best flatter herself). She was, as usual, brilliant in "The Last Station" as Countess Tolstoy; her costumes were lovely.
Yup, this just adds to my high regard for her.
I love that comment!
She recently did a movie here in New Mexico and visited one of our local vintage stores. The owner said she was a great customer! She came in by herself without an entourage and didn't act like a diva (even though she is one in the best sense of the word).
Loved her since I first saw her in Prime Suspect!
I love her clothes and would like to help dress her. Because of her age, she is an encouragement to me.


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photo credit: dSeneste.dk
How do you get more done in less time? Business Insider recently presented the results of a study by Dr. K. Anders Ericcson in which the musicians were evaluated to see what the best performers did differently from the rest. The four significant practices of top performers:
- Work for shorter periods of time: 4 hours of deliberate, hard work is more effective than 7 hours of steady work. By working for shorter periods of time, you are motivated to optimize each working session since you know it is limited in length.
- Set goals for each work session: Leo Babauta at Zen Habits describes this as having three Most Important Tasks for each day - the goals that must be accomplished that day. Before starting any work session, know what you want to accomplish.
- Take Breaks: In Dr. Ericcson's study, they found the best performers took significant breaks between their intense work sessions. I'm much more productive in the afternoons if I take a long break for lunch and hit the gym. Enlightened work environments even encourage afternoon naps.
- Rest and Recuperate: I've mentioned this before - when we put our work aside it percolates in our subconscious. Our minds have a great way of working things out in the background. There are countless stories of scientists and inventors literally solving big problems in their sleep! They immerse themselves in the problem, and then when they put is aside and sleep, they wake up with the solution. There is a good reason the advice to "sleep on it" is given out so often: it works!
Read More: Why Successful People Leave Work Early.
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And More
Feather - Imitation Red-Tailed Hawk
Replica of a red-tailed hawk tail feather. Approximately 11 inches long. For use in ceremony, decoration or in making special ceremonial clothing. USA made. Learn More$9.00 -
Feather - Imitation Red-tailed Hawk - Wing
Replica of a Red-tailed hawk wing feather. Approximately 11 inches long and 2 inches wide. Learn More$9.00 -
Llama Doll - 4.5 inches
These adorable llamas are made from real and very soft alpaca fur. They feature red and white yarn bridles & ear tassels and have a cloth blanket on their fluffy backs. Peru. Learn More$9.75 -
Pendulum - Gold Plated Spriral Vortex
This gold plated spiral pendulum creates a vortex that can amplify whatever energy it contacts. It is very precise and so is used by map dowsers, distance dowsers and astrologers. Learn More$8.00 -
Worry Dolls 2 inch - set of 12
Worry dolls or trouble dolls, are very small and colorful dolls traditionally made in Guatemala. A person (usually a child) who cannot sleep due to worrying can express their worries to a doll and place it under their pillow before going to sleep.
According to folklore, the doll is thought to worry in the person's place, thereby permitting the person to sleep peacefully. The person will wake up without their worries, which have been taken away by the dolls during the night. Parents may remove the doll during the night, reinforcing the child's belief that the worry is gone. They are also commonly stuck to computer monitors and office desks!
Learn More$12.95


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Currently viewing the tag: "celebration"
- "You're pretty much down to ritual suicide, lambie-toes." - Wash
Upcoming Events
- NMB Outfitters @ Supanova Sydney on June 22, 2013
- NMB Outfitters @ Supanova Sydney on June 23, 2013
- NMB Outfitters @ Oz Comic-Con Melbourne on July 6, 2013
- NMB Outfitters @ Oz Comic-Con Melbourne on July 7, 2013
- Can't Stop The Serenity 2013 on August 24, 2013 11:30 am
A charity event for Equality Now.
Get ready for some geekery!
Watch Serenity on the big screen!
Plus prizes, auctions and more!
Pre-order Merch (ends 5 May)
Australian Events:
Melbourne, VIC - 24 Aug (Tix on sale)
Nowra, NSW - 21 Sept
Perth, WA - 30 May (Quiz Night)Sponsors & Supporters
Dark Horse Comics
Jason Palmer
Mad Zombie Collectables
Ninja Monkey
Oz Comic-Con
Stewart McKenny
You can support New Melbourne Browncoats by purchasing via our Amazon links! There are so many shiny goodies!
- The Much Ado screening at @cinemanova is already sold out! If you missed out, follow us for a very cool announcement in the next few days. posted 13 hours ago
- RT @drhorrible: JossActual is now all grown up and he has become @JossWhedon. He has flown the nest. He's away, flying free! #sobs posted 17 hours ago
- RT @DendySydney: Joss Whedon's MUCH ADO ABOUT NOTHING has a special preview screening at Dendy Newtown on May 30. Tickets on sale now! http… posted 17 hours ago
- See Joss's Much Ado About Nothing on 30 May in Sydney thanks to @sharmillfilms & @DendySydney! Tickets on sale now at bit.ly/16HySeV posted 17 hours ago
- See Joss's Much Ado About Nothing on 30 May in Melbourne thanks to @sharmillfilms & @cinemanova! Details at tinyurl.com/nh5jhuh posted 17 hours ago


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A collection of news and information related to Robert N. Levine published by this site and its partners.
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Mary Tyler Moore's taboo-breaking shows seen in new light
In recent months the name Mary Tyler Moore has been bandied about with unexpected regularity bordering on reckless abandon. This is not just because she recently made her first TV appearance in many moons on pal Betty White's show "Hot in Cleveland" or...Tags: Unions, Ken Howard, The Good Wife (tv program), Betty White, Chelsea Handler
Why Google and music labels don't get along
Company TownGoogle has been unsuccessfully courting major music companies for the past year and a half. Robert Levine, former executive editor of Billboard magazine and author of a new book entitled "Free Ride," talks about why he thinks Google rubs labels the... -
Update: Catasauqua Area School Board race
Valley 610Catasauqua Area School Board candidate Dawn M. Berrigan, who served on the board from 2003-07, is looking to re-join the board. In May, she was among the top vote-getters for both the 2- and 4-year term but decided to withdraw from the 2-year position... -
Yale Bioethicist Testifies For Defense In St. Francis Case
The Hartford CourantWATERBURY — A medical ethicist testified Tuesday that St. Francis Hospital could not have been expected — under widely accepted scientific guidelines — to monitor Dr. George Reardon's fictitious growth study because the so-called study...Tags: Sex, Medical Research, Lawyers, Yale University, Colleges and Universities
Mary Tyler Moore recovering after 4-hour surgery to remove benign tumor
Ministry of GossipMary Tyler Moore is "recovering nicely" after a four-hour surgery to remove a benign tumor, a meningioma, from the membrane lining her brain, the actress's rep said Friday. Mary Tyler Moore had known of the meningioma for years and recently decided to...
Jan 29, 2012
|Story| Los Angeles Times
Nov 7, 2011
| Los Angeles Times
Aug 1, 2011
| Allentown Morning Call
May 3, 2011
|Story| Hartford Courant
May 13, 2011
| Zap2It


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Heat Shoot Down the Hawks
After the 1st half ended, it was over. The only thing Miami needed to do was play strongly with a lead, and sure enough, they did. LeBron James and Dwyane Wade didn't even have to play in the fourth…Read More
Heat vs. Hawks Preview
Tonight, the 20-7 Miami Heat go to Atlanta to take on the 18-9 Hawks in a big showdown in the Southeast Division. This is the Heat's 3rd game of their 6 game road trip. On the season, Miami is 8-5 on…Read More


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Goonies are coming April 28th. They say Jita will burn. A resistance has been formed. Either way its all gonna burn.
This is our one opportunity to show some guts and participate in an eve-wide event. I want us to participate that night and join the fleet.
We'll have to wardec Goonfleet on the 26th-27th, sure, and to watch our back for the rest of the week, but I assure you it'll be a night to remember.
Heck, even if you're a total carebear, you can always fit a frigate and join the fray.
We're expecting a full army of gank-fit tornados. They're fast, strong, have superb range, but they've got three weaknesses we can exploit.
1) A fleet full of Tornado is vulnerable to racial ECM. We'll be able to lock down several of them with the red jam modules.
2) Artillery-fitted Tornado cannot defend themselves at anything under 10km. That means HAM and Blasterboats will rip them to shreds.
3) Being minmatar, they're extra vulnerable to webs and scrambles, preventing them from escaping.
But first, a vote: Do you want the whole corporation to participate and help save Jita?