"Effect of the two chelators warrants further investigation"
This is EXACTLY how they stumbled across the cure in sickle. Investigating chelators and cured the sickle patients. Coincidentally close TO thalassemia.
"C-reactive protein decreased significantly"
Published online 10 May 2008 Haematologica, Vol 93, Issue 6, 817-825
Inflammation and oxidant-stress in â-thalassemia patients treated with iron chelators deferasirox (ICL670) or deferoxamine: an ancillary study of the Novartis CICL670A0107 trial Patrick B. Walter1, Eric A. Macklin2, John Porter3, Patricia Evans3, Janet L. Kwiatkowski4, Ellis J. Neufeld5, Thomas Coates6, Patricia J. Giardina7, Elliott Vichinsky1, Nancy Olivieri8, Daniele Alberti9, Jaymes Holland9, Paul Harmatz1 for the Thalassemia Clinical Research Network 1 Children's Hospital & Research Center Oakland, Oakland, CA,USA; 2 New England Research Institutes, Watertown, MA, USA (current address: Massachusetts General Hospital, Boston, MA); 3 University College London, London, UK; 4 Children's Hospital of Philadelphia, Philadelphia, PA; 5 Children's Hospital Boston, Boston, MA, USA; 6 Children's Hospital Los Angeles, Los Angeles, CA, USA; 7 New York-Presbyterian Hospital, New York, NY, USA; 8 University Health Network, Toronto, Canada and 9 Novartis Pharmaceuticals Corp., East Hanover, NJ, USA
Correspondence: Paul Harmatz, Children's Hospital & Research Center Oakland, 747 52nd Street, Oakland, Ca, 94609, USA. E- mail:pharm...@mail.cho.org
Background: We assessed whether oxidant-stress and inflammation in â-thalassemia could be controlled by the novel oral iron chelator deferasirox as effectively as by deferoxamine.
Design and Methods: Forty-nine subjects were enrolled from seven sites and studied at baseline, and after 1, 6, and 12 months of therapy. Malondialdehyde, protein carbonyls, vitamins E and C, total non-transferrin bound iron, transferrin saturation, C-reactive protein, cytokines, serum ferritin concentration and liver iron concentration were measured.
Results: Liver iron concentration and ferritin declined significantly in both treatment groups during the study. This paralleled a significant decline in the oxidative-stress marker malondialdehyde (deferasirox -22%/year, deferoxamine -28%/year, average decline p=0.006). The rates of decline did not differ between treatment groups. Malondialdehyde was higher in both treatment groups than in a group of 30 non-thalassemic controls (p<0.001). The inflammatory marker high-sensitivity C-reactive protein decreased significantly only in the group receiving deferasirox (deferasirox - 51%/year, deferoxamine +8.5%/year, p=0.02). This result was confounded by a chance difference in the level of high- sensitivity C-reactive protein between the two groups at baseline, but analyses controlling for this difference suggested an equally large treatment effect.
Conclusions: Iron chelation therapy with deferoxamine or with deferasirox was equally effective in decreasing iron burden and malondialdehyde. The possible differential effect of the two chelators on inflammation warrants further investigation.
Key words: iron overload, thalassemia, oxidative stress, inflammation, hsCRP, C-reactive protein, malondialdehyde, lipid peroxidation, vitamin E, vitamin C.
doi:10.3324/haematol.11755 Copyright (c) 2008 by Ferrata Storti Foundation
>"Effect of the two chelators warrants further investigation"
>This is EXACTLY how they stumbled across the cure in sickle. >Investigating chelators and cured the sickle patients. >Coincidentally close TO thalassemia.
Nonsense, these are genetic conditions, there is no "cure". The sideeffects of the full version can be reduced to some extent. It would be like "curing blue eyes.
What disease are these mutations an adaptation for, what effect do they have for the course of the disease, and how does it explain the geographical distribution of them?
Jesus ate specific molecules, and nobody has ever eaten the exact same ones (in the exact same amounts).
Inflammation is not caused by iron. Iron can contribute to an existing inflammatory condition, however. A stressor leads to the cell releasing certain molecules. When a cell contains arachidonic acid instead of the natural Mead acid, "chronic inflammation" is possible, even with a minor, persistent stressor. It also seems that a vicious cycle gets started in some cases, with molecules from the diet acting as constant fuel for this kind of inflammation (evidence of macrophage involvement here is clear, as I point out on my site).
"Genetic disease" can be enhanced greatly or brought on by diet, especially, it seems, those that start during adolescence. Due to the excessive "growth," which many view as "good," certain genetic "diseases" that would have never occurred (or would have occurred during old age, which many people never reached, of course, in "the good old days") do occur because certain checkpoints are overrun by the excess stress (growth requires stress).
On Jul 4, 7:05 pm, ironjustice <ironjust...@cashette.com> wrote:"Effect of the two chelators warrants further investigation" <<
In this study they .. 'decided' .. AFTER .. everything was tried .. to use a drug to reduce red blood cells AND use phlebotomy at the same time.
Double .. phlebotomy .. cures them.
"Some children may discontinue chronic transfusions"
Blood, Vol. 94 No. 9 (November 1), 1999: pp. 3022-3026
Hydroxyurea as an Alternative to Blood Transfusions for the Prevention of Recurrent Stroke in Children With Sickle Cell Disease Russell E. Ware, Sherri A. Zimmerman, and William H. Schultz
From the Duke Pediatric Sickle Cell Program and the Division of Hematology-Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC.
Children with sickle cell disease (SCD) and stroke receive chronic transfusions to prevent stroke recurrence. Transfusion risks including infection, erythrocyte allosensitization, and iron overload suggest a need for alternative therapies. We previously used hydroxyurea (HU) and phlebotomy in two young adults with SCD and stroke as an alternative to transfusions. We have now prospectively discontinued transfusions in 16 pediatric patients with SCD and stroke. Reasons to discontinue transfusions included erythrocyte alloantibodies or autoantibodies, recurrent stroke on transfusions, iron overload, noncompliance, and deferoxamine allergy. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d based on hematologic toxicity. Patients with iron overload underwent phlebotomy. The children have been off transfusions 22 months, (range, 3 to 52 months). Their average HU dose is 24.9 ± 4.2 mg/kg/d, hemoglobin concentration is 9.4 ± 1.3 g/dL, and mean corpuscular volume (MCV) is 112 ± 9 fL. Maximum percentage fetal hemoglobin (%HbF) is 20.6% ± 8.0% and percentage HbF-containing erythrocytes (%F cells) is 79.3% ± 14.7%. Fourteen patients underwent phlebotomy with an average of 8,993 mL (267 mL/kg) removed. Serum ferritin has decreased from 2,630 to 424 ng/ mL, and 4 children have normal ferritin values. Three patients (19%) had neurological events considered recurrent stroke, each 3 to 4 months after discontinuing transfusions, but before maximal HU effects. These preliminary data suggest some children with SCD and stroke may discontinue chronic transfusions and use HU therapy to prevent stroke recurrence. Phlebotomy is well-tolerated and significantly reduces iron overload. Modifications in HU therapy to raise HbF more rapidly might increase protection against stroke recurrence.
> "Effect of the two chelators warrants further investigation"
> This is EXACTLY how they stumbled across the cure in sickle. > Investigating chelators and cured the sickle patients. > Coincidentally close TO thalassemia.
> "C-reactive protein decreased significantly"
> Published online 10 May 2008 > Haematologica, Vol 93, Issue 6, 817-825
> Inflammation and oxidant-stress in â-thalassemia patients treated with > iron chelators deferasirox (ICL670) or deferoxamine: an ancillary > study of the Novartis CICL670A0107 trial > Patrick B. Walter1, Eric A. Macklin2, John Porter3, Patricia Evans3, > Janet L. Kwiatkowski4, Ellis J. Neufeld5, Thomas Coates6, Patricia J. > Giardina7, Elliott Vichinsky1, Nancy Olivieri8, Daniele Alberti9, > Jaymes Holland9, Paul Harmatz1 for the Thalassemia Clinical Research > Network > 1 Children's Hospital & Research Center Oakland, Oakland, CA,USA; > 2 New England Research Institutes, Watertown, MA, USA (current > address: Massachusetts General Hospital, Boston, MA); > 3 University College London, London, UK; > 4 Children's Hospital of Philadelphia, Philadelphia, PA; > 5 Children's Hospital Boston, Boston, MA, USA; > 6 Children's Hospital Los Angeles, Los Angeles, CA, USA; > 7 New York-Presbyterian Hospital, New York, NY, USA; > 8 University Health Network, Toronto, Canada and > 9 Novartis Pharmaceuticals Corp., East Hanover, NJ, USA
> Correspondence: Paul Harmatz, Children's Hospital & Research Center > Oakland, 747 52nd Street, Oakland, Ca, 94609, USA. E- > mail:pharm...@mail.cho.org
> Background: > We assessed whether oxidant-stress and inflammation in â-thalassemia > could be controlled by the novel oral iron chelator deferasirox as > effectively as by deferoxamine.
> Design and Methods: > Forty-nine subjects were enrolled from seven sites and studied at > baseline, and after 1, 6, and 12 months of therapy. Malondialdehyde, > protein carbonyls, vitamins E and C, total non-transferrin bound iron, > transferrin saturation, C-reactive protein, cytokines, serum ferritin > concentration and liver iron concentration were measured.
> Results: > Liver iron concentration and ferritin declined significantly in both > treatment groups during the study. > This paralleled a significant decline in the oxidative-stress marker > malondialdehyde (deferasirox -22%/year, deferoxamine -28%/year, > average decline p=0.006). > The rates of decline did not differ between treatment groups. > Malondialdehyde was higher in both treatment groups than in a group of > 30 non-thalassemic controls (p<0.001). > The inflammatory marker high-sensitivity C-reactive protein decreased > significantly only in the group receiving deferasirox (deferasirox - > 51%/year, deferoxamine +8.5%/year, p=0.02). > This result was confounded by a chance difference in the level of high- > sensitivity C-reactive protein between the two groups at baseline, but > analyses controlling for this difference suggested an equally large > treatment effect.
> Conclusions: > Iron chelation therapy with deferoxamine or with deferasirox was > equally effective in decreasing iron burden and malondialdehyde. The > possible differential effect of the two chelators on inflammation > warrants further investigation.
> Key words: iron overload, thalassemia, oxidative stress, inflammation, > hsCRP, C-reactive protein, malondialdehyde, lipid peroxidation, > vitamin E, vitamin C.
> doi:10.3324/haematol.11755 > Copyright (c) 2008 by Ferrata Storti Foundation
"In this study they .. 'decided' .. AFTER .. everything was tried .. to time.
Double .. phlebotomy .. cures them.
"Some children may discontinue chronic transfusions""
More nonsense, sickle cell anemia is a genetic disorder related to adaptation to a specific disease. There is no cure any more then there is for blue eyes. The article claimed no cure only fewer transfusions, not even close.
The questions remain unanswered from the equally silly first post:
What is that disease, what effect does the adaptation have in its full version, and how is the geographical distribution explain?
Here is another one, why were they doing transfusions and why did they want to reduce red blood count?
Warning, gross ignorance alert for upcoming response.
Strange that a (strict) vegetarian would empower his disciples to catch so many fish. "Let them eat it and get Fe+ overload, but not me, sayeth the lord"? Also strange that he would tell parables using fatted calves as a celebratory meal in the story. Tom, you are a loose wheel CB
"Chuck" <ShorThi...@aol.com> wrote... >> Jesus Was A Vegetarian!
> Strange that a (strict) vegetarian would empower his disciples to > catch so many fish. "Let them eat it and get Fe+ overload, but not me, > sayeth the lord"? Also strange that he would tell parables using > fatted calves as a celebratory meal in the story. > Tom, you are a loose wheel
No, he is a sad and deluded obsessive. Give the guy a break!
On Jul 7, 1:48 pm, ferr...@ironcity.com wrote: More nonsense <<
Evidence based medicine .. as opposed to the opinion of someone such as ..yourself .. ?
"Some children may discontinue chronic transfusions"
"Effect of the two chelators warrants further investigation"
In this study they .. 'decided' .. AFTER .. everything was tried .. to use a drug to reduce red blood cells AND use phlebotomy at the same time.
Double .. phlebotomy .. cures them.
"Some children may discontinue chronic transfusions"
Blood, Vol. 94 No. 9 (November 1), 1999: pp. 3022-3026
Hydroxyurea as an Alternative to Blood Transfusions for the Prevention of Recurrent Stroke in Children With Sickle Cell Disease Russell E. Ware, Sherri A. Zimmerman, and William H. Schultz
From the Duke Pediatric Sickle Cell Program and the Division of Hematology-Oncology, Department of Pediatrics, Duke University Medical Center, Durham, NC.
Children with sickle cell disease (SCD) and stroke receive chronic transfusions to prevent stroke recurrence. Transfusion risks including infection, erythrocyte allosensitization, and iron overload suggest a need for alternative therapies. We previously used hydroxyurea (HU) and phlebotomy in two young adults with SCD and stroke as an alternative to transfusions. We have now prospectively discontinued transfusions in 16 pediatric patients with SCD and stroke. Reasons to discontinue transfusions included erythrocyte alloantibodies or autoantibodies, recurrent stroke on transfusions, iron overload, noncompliance, and deferoxamine allergy. HU was started at 15 mg/kg/d and escalated to 30 mg/kg/d based on hematologic toxicity. Patients with iron overload underwent phlebotomy. The children have been off transfusions 22 months, (range, 3 to 52 months). Their average HU dose is 24.9 ± 4.2 mg/kg/d, hemoglobin concentration is 9.4 ± 1.3 g/dL, and mean corpuscular volume (MCV) is 112 ± 9 fL. Maximum percentage fetal hemoglobin (%HbF) is 20.6% ± 8.0% and percentage HbF-containing erythrocytes (%F cells) is 79.3% ± 14.7%. Fourteen patients underwent phlebotomy with an average of 8,993 mL (267 mL/kg) removed. Serum ferritin has decreased from 2,630 to 424 ng/ mL, and 4 children have normal ferritin values. Three patients (19%) had neurological events considered recurrent stroke, each 3 to 4 months after discontinuing transfusions, but before maximal HU effects. These preliminary data suggest some children with SCD and stroke may discontinue chronic transfusions and use HU therapy to prevent stroke recurrence. Phlebotomy is well-tolerated and significantly reduces iron overload. Modifications in HU therapy to raise HbF more rapidly might increase protection against stroke recurrence.
We await the answers for the below, anyone really in the know about these genetic disorders could answer them in a snap. Search enjine jockies who don't understand the abstracts they post can not answer them.
"In this study they .. 'decided' .. AFTER .. everything was tried .. to time.
Double .. phlebotomy .. cures them.
"Some children may discontinue chronic transfusions""
More nonsense, sickle cell anemia is a genetic disorder related to adaptation to a specific disease. There is no cure any more then there is for blue eyes. The article claimed no cure only fewer transfusions, not even close.
The questions remain unanswered from the equally silly first post:
What is that disease, what effect does the adaptation have in its full version, and how is the geographical distribution explain?
Here is another one, why were they doing transfusions and why did they want to reduce red blood count?
Warning, gross ignorance alert for upcoming response.
Actually, Tom's response to this one was unusually intelligent. Instead of purporting a cure with a lessening of symptoms, or otherwise demonstrating his ignorance of the very literature he claims to review, he abstained from responding. Maybe he is capable of learning after all.
> We await the answers for the below, anyone really in the know about these > genetic disorders could answer them in a snap. Search enjine jockies who > don't understand the abstracts they post can not answer them.
> "In this study they .. 'decided' .. AFTER .. everything was tried .. to > time.
> Double .. phlebotomy .. cures them.
> "Some children may discontinue chronic transfusions""
> More nonsense, sickle cell anemia is a genetic disorder related to > adaptation to a specific disease. There is no cure any more then there is > for blue eyes. The article claimed no cure only fewer transfusions, not > even close.
> The questions remain unanswered from the equally silly first post:
> What is that disease, what effect does the adaptation have in its full > version, and how is the geographical distribution explain?
> Here is another one, why were they doing transfusions and why did they > want to reduce red blood count?
> Warning, gross ignorance alert for upcoming response.
