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Nonviral Gene-Transfer Therapy for Hemophilia A
Skin fibroblasts from six patients with severe hemophilia A were grown in culture and transfected with a plasmid containing part of the gene encoding factor VIII. The transfected cells were cloned, propagated, and safely implanted into the patients' omentum; in some of the recipients, the plasma levels of factor VIII activity rose and bleeding diminished for up to 10 months.
Gene therapy has made slow progress because introducing potentially therapeutic genes into patients has been difficult. These authors bundled the gene encoding human factor VIII into a plasmid, which cannot infect mammalian cells, and with an electric shock forced this genetic package into fibroblasts. The genetically engineered cells caused no clinical problems and in some patients produced factor VIII. At this time, it is too early for conclusions about the efficacy of this form of gene therapy.
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Increased Need for Thyroxine in Women with Hypothyroidism during Estrogen Therapy
This study examined the effect of estrogen therapy on pituitary-thyroid function in postmenopausal women with normal thyroid function and postmenopausal women with hypothyroidism treated with thyroxine. In the 25 women with hypothyroidism, but not the 11 women with normal thyroid function, estrogen treatment led to decreases in serum free thyroxine concentrations and increases in serum thyrotropin concentrations that were, in some instances, sufficient to warrant an increase in the dosage of thyroxine.
This study documents the time course and magnitude of the increases in serum thyroxine-binding globulin concentrations and the consequent changes in pituitary-thyroid function that occur during estrogen therapy. The magnitude of the change indicates the need for evaluation of the adequacy of thyroxine therapy whenever estrogen is given.
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Mitotic Spindles in a Cardiac Myocyte.
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Evidence That Human Cardiac Myocytes Divide after Myocardial Infarction
It has been generally accepted that myocytes in the adult heart are not capable of replication and that the heart is not capable of repairing itself after injury. In this study of the hearts of 13 patients who had died within several days after acute myocardial infarction, special myocardial staining techniques were used to demonstrate mitotic activity in cardiac myocytes, both in areas adjacent to the infarct and in areas distant from it.
This study provides evidence that cardiac myocytes can divide after acute injury to the heart. The findings challenge previous dogma regarding the inability of the heart to regenerate and leave open the possibility that the heart may be capable of self-repair to some extent.
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Duodenal-Biopsy Specimen.
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Treatment of IPEX by Allogeneic Bone Marrow Transplantation
The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is a rare, usually fatal disorder in boys that is characterized by intractable diarrhea, ichthyosiform dermatitis, insulin-dependent diabetes mellitus, thyroiditis, and hemolytic anemia. A child with the disorder received a bone marrow transplant from his HLA-identical sister and remained in remission for over two years. During this period a rapidly progressive hemophagocytic syndrome developed, and the child died 29 months after transplantation.
IPEX has attracted interest because it is associated with a mutation in FOXP3, a gene with a key role in regulating CD4+ T-helper lymphocytes. The unregulated T lymphocytes infiltrate and damage tissues and provoke the formation of autoantibodies. In this patient, the intensive preparative regimen used before transplantation probably eliminated most of the mutant T lymphocytes, allowing the sister's lymphocytes to maintain order in her brother's immune system.
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The First 20 Years of AIDS
This week marks the 20th anniversary of the first report of the disease that became known as the acquired immunodeficiency syndrome (AIDS). In 1981, no one would have believed that the report of Pneumocystis carinii pneumonia and other unusual infections in five young, previously healthy homosexual men was the harbinger of a worldwide health catastrophe. In this issue, three articles consider the first 20 years of the AIDS epidemic. In the first, Sepkowitz discusses the extraordinary achievements of the biomedical-research community. Gottlieb, who reported the five patients with P. carinii pneumonia, provides a personal view of subsequent events. Finally, Merson, a former director of the World Health Organization's Global Program on AIDS, reviews a book about the unsuccessful efforts to develop an AIDS vaccine and offers his own perspective on the pandemic.
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Medical Progress: The Hemophilias
The commonest types of hemophilia, A (caused by a deficiency of factor VIII) and B (caused by a deficiency of factor IX), were reviewed in the Journal in 1994. Since then, real progress has resulted from the availability of safer plasma-derived products, new ways of treating patients who have high titers of antibodies against factor VIII or factor IX, and recombinant factor VIII and factor IX. The ability to cure hemophilia through gene therapy lies on the horizon. Despite this remarkable technical progress, worldwide almost 80 percent of patients with hemophilia die without ever receiving any treatment.
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