ABSTRACT
Essential thrombocythemia (ET) is a chronic myeloproliferative disorder, characterized by increased proliferation of megakaryocytes and elevated platelet count that usually occurs sporadically. We report a family with seven affected individuals in three generations, including one individual with a phenotype resembling polycythemia vera, a related disorder. Megakaryocyte (CFU-MK) colony formation occurred in the absence of added cytokines in cultures of peripheral blood from affected family members. Some reports of familial ET have identified mutations in THPO and MPL, the genes for a cytokine (thrombopoietin, TPO) that regulates platelet production and its receptor (c-MPL), respectively. In this family, the MPL gene was excluded by linkage analysis. Although TPO levels were elevated in most affected family members and evidence for linkage was found between the disease and THPO (theta=0.0, Z(max)=3.0), a THPO mutation was not identified by DNA sequencing. The JAK2 V617F mutation that has been associated with 50% of sporadic cases of ET was identified as a somatic mutation, an acquired defect, in peripheral blood of the two most severely affected family members. These patients also had elevated TPO levels. Further study of familial myeloproliferative diseases will help elucidate the initiating genetic events underlying ET.
Subject(s)
Janus Kinase 2/genetics , Megakaryocytes/pathology , Mutation , Thrombocythemia, Essential/genetics , Enzyme-Linked Immunosorbent Assay , Erythropoietin/blood , Female , Humans , Male , Pedigree , Receptors, Thrombopoietin/genetics , Thrombocythemia, Essential/enzymology , Thrombopoietin/blood , Thrombopoietin/genetics , X Chromosome InactivationABSTRACT
A 75-year-old male presented with new symptoms of a bleeding diathesis associated with a decline in the functional activity of von Willebrand factor (type 2a von Willebrand's disease). Replacement therapy was ineffective and he was subsequently treated with intravenous immunoglobulin (IvIg). IvIg not only caused symptomatic improvement but was shown to transiently restore the depleted von Willebrand factor intermediate and high molecular weight multimers. Subsequent periodic IvIg infusions have been used successfully to treat bleeding complications in this patient over the past 3 years. A secondary cause for the acquired von Willebrand's disease has not been identified.
Subject(s)
von Willebrand Diseases/therapy , Aged , Cyclophosphamide/administration & dosage , Hematuria/drug therapy , Humans , Immunoglobulins, Intravenous/therapeutic use , Male , Partial Thromboplastin Time , Prednisone/administration & dosage , von Willebrand Diseases/bloodSubject(s)
Blood Viscosity , Mediastinal Neoplasms/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Skin Diseases/etiology , Telangiectasis/etiology , Adult , Hematologic Diseases/complications , Humans , Male , Skin/blood supply , Skin Diseases/pathology , Syndrome , Telangiectasis/pathologyABSTRACT
Totally implantable drug delivery systems have facilitated chemotherapy in cancer patients. The incidence of complications has been acceptable but not optimal. A series of 140 consecutive implants over a 4-year period is presented. The total follow-up was 41,185 days. Reversible obstruction was present in 12.8% of portals. The infection-erosion rate was 4.2%; only 6.3% of patients required removal of the system because of failure. In the last 111 patients only one device failed (0.9%). The reasons for these improved results are analysed, and recommendations are made to improve the current management of these devices.
Subject(s)
Infusion Pumps, Implantable , Adult , Aged , Antineoplastic Agents/administration & dosage , Equipment Design , Equipment Failure , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Although beneficial in allergic and parasitic disease, eosinophils exert nonspecific toxic effects upon host tissues, especially the central and peripheral nervous systems. Eosinophil-induced neurotoxicity is characterized by axonal neuropathy, cerebral infarction, and dementia. Eosinophil-derived cytotoxic proteins are fundamental to the pathogenesis of this disorder.
Subject(s)
Axons/ultrastructure , Cerebral Infarction/etiology , Dementia/etiology , Eosinophils/physiology , Nervous System Diseases/etiology , Adult , Eosinophilia/complications , Female , Humans , Male , Nervous System Diseases/pathologyABSTRACT
Leukopenia is an abnormal reduction of circulating white blood cells, especially the granulocytes. The term leukopenia is often used interchangeably with neutropenia. It may result from reduced production of white blood cells or increased utilization and destruction, or both. Infection, drugs, malignancy, megaloblastosis, hypersplenism and immunoneutropenia are responsible for most cases of neutropenia. Primary neutropenia is very rare. Sometimes, particularly in children, primary neutropenia is hereditary and may be associated with other developmental defects. The major danger of neutropenia is the risk of infection. Management requires identification of the cause and effective antimicrobial therapy, especially when serious systemic infection is present.
ABSTRACT
The prognosis of Hodgkin's disease (HD) has improved impressively in the past decade. Presently, no stage of disease is beyond cure or expectancy of a long disease-free survival. The extent of disease involvement governs the choice of therapy. The treatment of choice for localized disease is irradiation, although the techniques used vary considerably among different centres. Combination chemotherapy is recommended for stages 3B and 4. The management of stage 3A and some high-risk subsets of HD remains controversial. In specific situations, combined treatments are indicated. Therapy associated complications, immediate or delayed, deserve greater attention. Ironically, their impact upon the improved survivors might be morbid and devastating.
