Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials of recombinant biologic agents have resulted in new treatment options for hematologic, oncologic, and cardiologic disorders. These agents include the interferons, recombinant human erythropoietin (r-HuEPO), colony-stimulating factors (CSFs), interleukins (ILs), and tissue plasminogen activator (t-PA). Interferon alfa has proven efficacious in treating certain hematologic malignancies and solid tumors and has recently been indicated for acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma. Treatment with r-HuEPO has relieved the chronic anemia of hemodialysis patients. Recombinant human granulocyte CSF (G-CSF) or human granulocyte macrophage CSF (GM-CSF) has been used to treat patients after autologous bone marrow transplantation for lymphoid or solid malignancies, resulting in increased production of granulocytes and platelets. G-CSF and GM-CSF have been used to treat aplastic anemia, myelodysplastic syndromes, chemotherapy-induced neutropenia, and neutropenia associated with AIDS. In patients with evolving myocardial infarction, the recombinant agent t-PA has proved more efficacious than streptokinase in terms of average coronary artery patency rates and survival rates in patients with evolving myocardial infarction. While these agents all offer promising therapeutic advances, the expenses associated with developing and testing biotherapeutic substances have resulted in high treatment costs. Since in many instances investigational therapy is the best treatment option available, physicians, patients, the pharmaceutical industry, the government, and insurance carriers must work together to ensure that these therapies are financially available to those in need.
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PMID:New directions in hematologic biotherapy. 247 3

The characteristics and clinical uses of recombinant colony-stimulating factors (CSFs) are described, and the pharmacist's role as a consultant and educator on biotherapeutic substances is discussed. CSFs stimulate the formation and differentiation of the erythrocytes, neutrophils, eosinophils, basophils, monocytes, and platelets that compose the blood cell population. Recombinant CSFs represent a means by which the numbers of hematopoietic cells can be modulated, thus making these agents potentially useful in treating hematologic and immunologic deficiencies. CSFs also can increase the ability of neutrophils and monocyte-macrophages to protect the body against foreign invasion. Granulocyte macrophage colony-stimulating factor (GM-CSF) has increased host defenses in acquired immunodeficiency syndrome patients with Kaposi's sarcoma; increased neutrophil, platelet, and erythrocyte counts in preleukemic patients; and increased neutrophil counts in patients with aplastic anemia. GM-CSF and granulocyte colony-stimulating factor (G-CSF) have appeared to alleviate the drastic decrease in neutrophil counts associated with cytotoxic chemotherapy. G-CSF also has shown promise in stimulating neutrophil production in patients with transitional cell carcinoma, congenital agranulocytosis, and hairy-cell leukemia. Mild adverse effects such as fever, chills, rash, fatigue, myalgia, and bone pain are associated with GM-CSF therapy; G-CSF therapy is associated mostly with mild to moderate bone pain. Areas of education for pharmacists working with biotherapeutic substances include stability, storage temperature, drug interactions, novel drug-delivery systems such as monoclonal antibodies or liposomes, variations in biologic activity, and the evolving nature of the information about these investigational drugs. The pharmacist can anticipate an increasing role as a consultant on the use of CSFs and other biotherapeutic substances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Colony-stimulating factors and tomorrow's pharmacy: why we must be ready. 269 Jun 7

Kaposi's sarcoma of the skin and an aplastic syndrome occurred together in a 51-year-old patient. Macroscopically livid papules and nodules were observed. Histomorphologically endotheliomatous cell proliferation with signs of infiltrative growth was found. Because of the aplastic pancytopenia cytostatic treatment of the Kaposi sarcoma was contraindicated. The patient finally died of vascular failure with haemorrhagic diathesis being manifest. Syntropy of Kaposi's sarcoma with malignant haematological diseases is known. However, association with aplastic anaemia has not been observed so far. The pathogenesis of Kaposi's sarcoma is unknown.
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PMID:[Kaposi's sarcoma (author's transl)]. 737 53

The authors report one case of AIDS-related-like Kaposi's sarcoma (KS) in a 59-year-old bisexual man without HIV-1 and HIV-2 infection. KS developed while the patient was receiving both androgen and steroid therapy for aplastic anemia, and regressed after their simultaneous interruption, despite the persistence of aplastic anemia. The authors discuss the etiology of KS in the patient, with a special regard to a putative role of the androgen therapy. The authors examine the arguments of the literature, probably underestimated, that may suggest a role of sex hormones in the pathogenesis of KS.
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PMID:[Kaposi disease and sex hormones: apropos of a case, review of the literature]. 805 33

We have recently demonstrated the presence of Kaposi's sarcoma-associated herpesvirus (KSHV) in cultured bone marrow (BM) stromal dendritic cells from all patients with myeloma studied. To show that these findings were not an artifact of tissue culture, we performed in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect KSHV in BM core biopsies. Using ISH to open reading frame-72 (ORF 72), we localized KSHV to BM dendritic cells in 17 of 20 patients with myeloma, 2 patients with plasmacytosis associated with the acquired immunodeficiency syndrome, and 1 case of aplastic anemia. In contrast, BM from normal subjects (n = 4) and patients with lymphoma and leukemia (n = 21) did not contain KSHV. PCR amplification with KSHV primers demonstrated product in fresh BM biopsy samples from 6 of 7 myeloma patients, whereas three normal marrows contained no amplified product. These findings suggest that KSHV, possibly through alterations in the BM microenvironment and production of viral interleukin-6 (vIL-6), may stimulate and maintain abnormal plasma cell proliferation in myeloma and related disorders.
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PMID:Localization of Kaposi's sarcoma-associated herpesvirus in bone marrow biopsy samples from patients with multiple myeloma. 978 98

Human herpesvirus 8 (HHV8) has been consistently linked to Kaposi's sarcoma and many hematological diseases such as pleural effusion lymphoma, multicentric Castleman's disease, some lymphoproliferative diseases and posttransplantation bone marrow failure. However, whether patients with hematological disorders are at a higher risk of HHV8 infection has not been determined. In this study, indirect immunofluorescence was used to detect antibodies against lytic antigens of HHV8 in 265 patients with hematological disorders. Our data showed that 24.5% of patients (65/265) were seropositive for HHV8 IgG antibody, which was significantly higher than in our general population (p < 0.001). A significantly higher seropositive rate can be found in patients with lymphoma, leukemia, autoimmune cytopenias and myeloproliferative disorders, but not in patients with myeloma or aplastic anemia. No difference in the seropositive rate is associated with gender or age. We conclude that some patients with hematological disorders are at a higher risk of HHV8 infection.
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PMID:Increased seroprevalence of human herpesvirus 8 in patients with hematological disorders. 1610 32

We report a 2.5-year-old boy with an X-linked lymphoproliferative disease (XLP) phenotype who presented with human herpes virus-8 (HHV-8)-related hemophagocytic lymphohistiocytosis (HLH). XLP is a rare primary immunodeficiency characterized by extreme susceptibility to herpes viruses, mainly Epstein-Barr virus (EBV). Approximately 60% of patients with XLP present with fulminant mononucleosis associated with HLH, whereas remaining patients present with hypogammaglobulinemia or lymphoproliferative disease. Most commonly, one of the XLP phenotypes appears after exposure to EBV, but at least 12% of affected individuals developed symptoms without an evidence of EBV infection. Rarely, patients with XLP may present with central nervous system vasculitis or aplastic anemia. HHV-8 is lymphotrophic and it is associated with lymphoproliferative disorders and Kaposi sarcoma in immunodeficient hosts. Kaposi sarcoma rarely occurs in children with well-defined primary immunodeficiency. Also, HHV-8-related HLH was previously reported in 2 siblings with a perforin gene deficiency. Recently, it became evident that besides EBV, other viruses may trigger the symptoms in XLP. We report for the first time HHV-8-related HLH in EBV-negative pediatric patient with an XLP phenotype.
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PMID:HHV-8-related hemophagocytic lymphohistiocytosis in a boy with XLP phenotype. 2225 54

A 33-year-old Chinese male patient with severe aplastic anemia received matched sibling allogeneic hematopoietic stem cell transplantation using antithymocyte globulin containing conditioning regimen after 4 months of unsuccessful treatment with cyclosporine A. Following transplantation, the patient was immunosuppressed demonstrated by intermittent infections, including a varicella 3 months after transplantation. Although DNA-STR results on day +30 confirmed complete donor engraftment, repeat DNA-STR analysis performed more than 3 months after transplantation showed a mosaic phenotype. Cyclosporine tapering commenced early, but the last DNA-STR result confirmed complete graft rejection. On day +198, the patient presented with fever, skin boil in the right temporal region, severe pancytopenia, intrabodominal lymphadenopathy and hepatosplenomegaly. Within 1 month, superficial lymphadenopathy and right exophthalmos developed. Excisional lymph node biopsy pathology confirmed Kaposi's sarcoma (KS). The patient succumbed due to intracranial bleeding as a result of thrombocytopenia. This is the first study of KS that developed following stem cell transplantation for severe aplastic anemia. The precipitating factors underlying KS development in this case and its differentiation from post-transplant lymphoproliferative disorders are analyzed.
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PMID:Kaposi's sarcoma developed after allogeneic hematopoietic stem cell transplantation. 2286 13

Several exanthems including Gianotti-Crosti syndrome, pityriasis rosea, asymmetrical periflexural exanthem, eruptive pseudoangiomatosis, and papular-purpuric gloves and socks syndrome are suspected to be caused by viruses. These viruses are potentially dangerous. Gianotti-Crosti syndrome is related to hepatitis B virus infection which is the commonest cause of hepatocellular carcinoma, and Epstein-Barr virus infection which is related to nasopharyngeal carcinoma. Pityriasis rosea has been suspected to be related to human herpesvirus 7 and 8 infections, with the significance of the former still largely unknown, and the latter being a known cause of Kaposi's sarcoma. Papular-purpuric gloves and socks syndrome is significantly associated with human B19 erythrovirus infection which can lead to aplastic anemia in individuals with congenital hemoglobinopathies, and when transmitted to pregnant women, can cause spontaneous abortions and congenital anomalies. With viral DNA sequence detection technologies, false positive results are common. We can no longer apply Koch's postulates to establish cause-effect relationships. Biological properties of some viruses including lifelong latent infection, asymptomatic shedding, and endogenous reactivation render virological results on various body tissues difficult to interpret. We might not be able to confirm or refute viral causes for these rashes in the near future. Owing to the relatively small number of patients, virological and epidemiology studies, and treatment trials usually recruit few study and control subjects. This leads to low statistical powers and thus results have little clinical significance. Moreover, studies with few patients are less likely to be accepted by mainstream dermatology journals, leading to publication bias. Aggregation of data by meta-analyses on many studies each with a small number of patients can theoretically elevate the power of the results. Techniques are also in place to compensate for publication bias. However, these are not currently feasible owing to different inclusion and exclusion criteria in clinical studies and treatment trials. The diagnoses of these rashes are based on clinical assessment. Investigations only serve to exclude important differential diagnoses. A wide spectrum of clinical features is seen, and clinical features can vary across different populations. The terminologies used to define these rashes are confusing, and even more so are the atypical forms and variants. Previously reported virological and epidemiological results for these rashes are conflicting in many aspects. The cause of such incongruence is unknown, but low homogeneity during diagnosis and subject recruitment might be one of the factors leading to these incongruent results. The establishment and proper validation of diagnostic criteria will facilitate clinical diagnosis, hasten recruitment into clinical studies, and allow results of different studies to be directly compared with each another. Meta-analyses and systematic reviews would be more valid. Diagnostic criteria also streamline clinical audits and surveillance of these diseases from community perspectives. However, over-dependence on diagnostic criteria in the face of conflicting clinical features is a potential pitfall. Clinical acumen and the experience of the clinicians cannot be replaced by diagnostic criteria. Diagnostic criteria should be validated and re-validated in response to the ever-changing manifestations of these intriguing rashes. We advocate the establishment and validation of diagnostic criteria of these rashes. We also encourage the ongoing conduction of studies with a small number of patients. However, for a wider purpose, these studies should recruit homogenous patient groups with a view towards future data aggregation.
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PMID:Gianotti-Crosti syndrome, pityriasis rosea, asymmetrical periflexural exanthem, unilateral mediothoracic exanthem, eruptive pseudoangiomatosis, and papular-purpuric gloves and socks syndrome: a brief review and arguments for diagnostic criteria. 2447 Sep 19

Kaposi sarcoma (KS) is an angioproliferative disease associated with human herpesvirus 8 (HHV-8). We report the case of a 10-year-old male from a high HHV-8 prevalence area, diagnosed with severe aplastic anemia who underwent an upfront hematopoietic stem cell transplantation (HSCT). Five months after transplant, the patient was diagnosed with KS with skin, mucosae, lymph nodes and lung involvement. After withdrawal of immunosuppression the patient achieved complete remission without requiring further treatments. KS may occur after HSCT in patients from high HHV-8 prevalence areas. Considering that, we propose that screening of HHV-8 by antibody testing could be considered in HSCT donors/recipients from these areas.
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PMID:Kaposi sarcoma in a child after hematopoietic stem cell transplantation: Should pre-transplant HHV-8 screening be considered in recipients from high prevalence areas? 3323 1


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