Annual Review of Medicine - Volume 40, 1989

The discovery of β protein, the major component of the amyloid fibrils of the plaques and cerebral vessels and of the paired helical filaments of the neurofibrillary tangles, has provided a means to decipher the pathogenesis of Alzheimer's disease. The same lesions in aged Down's syndrome individuals have also been shown to be composed of β protein. Gene probes localize the gene for β protein, as well as that for familial Alzheimer's disease, to chromosome 21, but these genes are not linked. A study of posttranslational modifications of the 695-amino-acid β-protein gene precursor, with specific reference to abnormal proteolysis, may provide insights into the cause of the amyloidotic lesions of Alzheimer's disease and the means of arresting them.

Traditionally perceived as a seco-steroid hormone involved in the regulation of calcium metabolism, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] is now known also to be active in tissues not directly contributing to mineral metabolism. New data show that 1α,25(OH)2D3 is produced by and interacts with hematopoietic cells. The hormone promotes myeloid differentiation and modulates the function of activated lymphocytes. Another new target tissue for 1α,25(OH)2D3 is the skin, where 1α,25(OH)2D3 enhances differentiation of epidermal cells. Therapeutic application of 1α,25(OH)2D3 or suitable analogues in differentiation disorders of hematopoietic and skin cells is currently under investigation.

Anticoagulant therapy during pregnancy is problematic because both heparin and oral anticoagulants can potentially produce adverse maternal and fetal effects. Reviewing the relevant literature makes it clear that heparin is safer for the fetus than are oral anticoagulants. For the prophylaxis and treatment of venous thromboembolic disease in pregnant patients, heparin is the preferred anticoagulant because its efficacy and safety are established. However, because the efficacy of heparin in preventing systemic embolism in patients with prosthetic heart valves is not established, either adjusted-dose heparin or a combination of heparin and oral anticoagulants can be used.

Autologous bone marrow transplantation in the acute leukemias and lymphomas offers potentially curative treatment in patients who do not have a histocompatible, allogeneic donor. Results of marrow autografting in the lymphomas are especially encouraging, with disease-free survivals of 50-60% in patients who have failed primary and secondary treatment regimens. In the acute leukemias, one may expect 20-40% relapse-free survival after autologous marrow transplantation. We feel that ex vivo treatment (“purging”) is necessary to eradicate occult tumor cells from autologous remission marrow in hematological malignancies, but this remains a controversial issue to some investigators. Preliminary studies of autologous bone marrow transplantation are promising in multiple myeloma and certain childhood tumors, and autografting is currently being explored in the treatment of other solid tumors such as adenocarcinoma of the breast.

The strong association between the Philadelphia chromosome (Ph) and chronic myelogenous leukemia (CML) suggests that the Ph translocation plays a significant role in CML pathogenesis. For this reason, Ph-positive leukemias have been well studied from the molecular, clinical, and cell biological perspective. We attempt to integrate these data in order to better our understanding of the role of the Ph chromosome in human leukemia.

Attention-deficit hyperactivity disorder, as described in the American Psychiatric Association's diagnostic manual DSM III-R (1), is a broadly defined syndrome of cognitive and behavioral problems that were originally found in children, but that have been increasingly identified in adults who had similar complaints in childhood (2). This paper briefly reviews the definition and treatment of this syndrome in children, evidence for specific neurochemical abnormalities, and effects of stimulants on neurochemistry. Finally, problems of diagnosis and treatment in adults are discussed.