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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1997-11-6
|
| pubmed:abstractText |
Thrombopoietin (TPO) was evaluated for efficacy in a placebo-controlled study in rhesus monkeys with concurrent administration of either granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte CSF, (G-CSF). Rhesus monkeys were subjected to 5 Gy total-body irradiation (TBI), resulting in 3 weeks of profound pancytopenia, and received either TPO 5 microg/kg intravenously (I.V.) at day 1 (n = 4), GM-CSF 25 microg/kg subcutaneously (S.C.) for 14 days (n = 4), TPO and GM-CSF (n = 4), G-CSF 10 microg/kg/d S.C. for 14 days (n = 3), TPO and G-CSF (n = 4), or placebo (carrier, n = 4; historical controls, n = 8). Single-dose I.V. treatment with TPO 1 day after TBI effectively counteracted the need for thrombocyte transfusions (provided whenever thrombocyte levels were <40 x 10(9)/L) and accelerated platelet reconstitution to normal levels 2 weeks earlier than placebo controls. TPO/GM-CSF was more effective than single-dose TPO alone in stimulating thrombocyte regeneration, with a less profound nadir and a further accelerated recovery to normal thrombocyte counts, as well as a slight overshoot to supranormal levels of thrombocytes. Monkeys treated with TPO/GM-CSF uniformly did not require thrombocyte transfusions, whereas those treated with GM-CSF alone needed two to three transfusions, similar to the placebo-treated monkeys, which required, on average, three transfusions. Also, reticulocyte production was stimulated by TPO and further augmented in monkeys treated with TPO/GM-CSF. TPO alone did not stimulate neutrophil regeneration, whereas GM-CSF shortened the period of neutrophil counts less than 0.5 x 10(9)/L by approximately 1 week; TPO/GM-CSF treatment elevated the neutrophil nadir, but did not further accelerate recovery to normal values. TPO also augemented the neturophil response to G-CSF, resulting in similar patterns of reconstitution following TPO/G-CSF and TPO/GM-CSF treatment. TPO/GM-CSF resulted in significantly increased reconstitution of CD34+ bone marrow cells and progenitor cells such as GM-CFU and BFU-E. Adverse effects of combining TPO with the CSFs were not observed. It is concluded that (1) a single I.V. administration of TPO is sufficient to prevent severe thrombocytopenia following myelosuppression, (2) TPO/G-CSF and TPO/GM-CSF treatment result in distinct response patterns, with TPO/GM-CSF being superior to TPO/G-CSF in stimulating thrombocyte and erythrocyte recovery while being equivalent in stimulating neutrophil recovery; and (3) TPO significantly improves the performance of CSFs in alleviating severe neutropenia.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte Colony-Stimulating...,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombopoietin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
90
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2565-73
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9326222-Animals,
pubmed-meshheading:9326222-Blood Cell Count,
pubmed-meshheading:9326222-Bone Marrow,
pubmed-meshheading:9326222-Bone Marrow Diseases,
pubmed-meshheading:9326222-Combined Modality Therapy,
pubmed-meshheading:9326222-Drug Administration Schedule,
pubmed-meshheading:9326222-Drug Therapy, Combination,
pubmed-meshheading:9326222-Erythropoiesis,
pubmed-meshheading:9326222-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:9326222-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:9326222-Hematopoiesis,
pubmed-meshheading:9326222-Injections, Intravenous,
pubmed-meshheading:9326222-Macaca mulatta,
pubmed-meshheading:9326222-Male,
pubmed-meshheading:9326222-Neutropenia,
pubmed-meshheading:9326222-Neutrophils,
pubmed-meshheading:9326222-Platelet Transfusion,
pubmed-meshheading:9326222-Radiation Injuries, Experimental,
pubmed-meshheading:9326222-Recombinant Proteins,
pubmed-meshheading:9326222-Thrombopoietin,
pubmed-meshheading:9326222-Whole-Body Irradiation
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
The efficacy of single-dose administration of thrombopoietin with coadministration of either granulocyte/macrophage or granulocyte colony-stimulating factor in myelosuppressed rhesus monkeys.
|
| pubmed:affiliation |
Institute of Hematology, Erasmus University Rotterdam, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|