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Sickle cell disease, often called sickle cell anemia, is an inherited condition that affects hemoglobin within the red blood cells, causing them to change shape so that they look like sickles or crescent moons. Because of their shape, they can get lodged in blood vessels and reduce or block blood flow to parts of the body. Depending on the location, the blockage can lead to episodes of pain, organ damage or failure and various acute and chronic complications, some of which are potentially fatal. While there are treatments to help relieve the symptoms of sickle cell, including antibiotics, blood transfusions, pain management and the drug hydroxyurea, the only curative treatment is bone marrow transplant, which has reversed the disease in about 200 children. But because the procedure requires high doses of chemotherapy and radiation to destroy the patients’ defective cells and make room for the transplanted cells, this option has been generally reserved for children whose bodies have not been weakened by the disease. Now, however, U.S. researchers say they have developed a less toxic transplant technique—one that can be tolerated even by adults with severe sickle cell disease.

The new method was born when researchers observed that bone marrow transplants in children and in patients with some other diseases can be successful even when some of the patient’s defective cells survive the chemotherapy and radiation intended to eradicate them. “We thought, ‘Can we intentionally do this, partially replace bone marrow, knowing that a little bit (of healthy cells) could be enough to make sickle cell go away?’” said the study’s senior author, Dr. John F. Tisdale of the National Heart, Lung and Blood Institute. “That would allow us to use less-toxic chemotherapy and radiation.”

The researchers tested their theory in 10 patients aged 16 to 45 with severe sickle cell who did not respond to hydroxyurea. The patients were given low doses of radiation and the immunosuppressive drug sirolimus to fight rejection of the donor cells. The chemotherapy normally given to suppress the immune system was eliminated completely. The patients then received marrow donated by siblings with matched markers in their blood. The result was a mix of cells from patient and donor.

After an average of 30 months, all are still alive and nine of the patients are considered cured of sickle cell. There were no significant side effects from the procedure and none of the patients experienced graft-versus-host-disease (GVHD), one of the most common complications of bone marrow transplants in which the body rejects the new marrow. “Because sickle red blood cells only live about six or seven days and normal red blood cells live 120 days, if you can get a little bit of the donor cells in there, the donor cells take over,” Tisdale said.

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