Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 50-year-old man was admitted to our hospital because of intracranial hemorrhage and thrombocytopenia (platelet count: 3,000/microliter). Low levels of IgG (76 mg/dl) and IgA (30 mg/dl) and a normal pattern of peripheral blood T and B cell subsets yielded a diagnosis of common variable immunodeficiency (CVID). The number of megakaryocytes in bone marrow was within normal limits (64/microliter), and a diagnosis of idiopathic thrombocytopenic purpura was made. Both high-dose intravenous gamma-globulin and prednisolone were ineffective. Because of the coexistence of CVID, splenic irradiation (total 15 Gy) was performed instead of splenectomy. The platelet number began to increase 5 days after the initiation of irradiation, had increased to 8.7 x 10(4)/microliter at the end of irradiation, and was 22.9 x 10(4)/microliter 2 weeks later.
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PMID:[Successful treatment with splenic irradiation for idiopathic thrombocytopenic purpura associated with primary immunodeficiency syndrome]. 1062 29

Since the purification of thrombopoietin 6 years ago, c-Mpl ligands such as recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) have undergone extensive clinical investigation. Both recombinant forms have been shown to reduce the thrombocytopenia associated with nonmyeloablative chemotherapy. Several areas of research have been identified for further clinical development of c-Mpl ligands. One future direction is to continue to explore the intravenous route of administration of rhTPO and PEG-rHuMGDF, as well as fusion proteins of interleukin-3-thrombopoietin and thrombopoietin peptide mimetics, which may be as potent as thrombopoietin, but may lack antigenicity. Another focus would be on the use of these molecules in treating non-chemotherapy-induced thrombocytopenia associated with myelodysplastic syndrome (MDS), idiopathic thrombocytopenic purpura (ITP), human immunodeficiency virus (HIV)-related ITP, and liver disease. Additionally, c-Mpl ligands may have a role in improving apheresis yields when administered to normal platelet donors. Considerable data demonstrate the effectiveness of PEG-rHuMGDF in raising the platelet yields in apheresis donors. In the past few years, investigation into the use of thrombopoietin for ex vivo expansion of pluripotent stem cells has been extensive. Last, thrombopoietin may serve as a radioprotectant by preventing radiation-induced apoptosis of pluripotent stem cells. In the coming years, the clinical role of rhTPO, PEG-rHuMGDF, and related molecules such as the thrombopoietin peptide mimetics will probably be established for both chemotherapeutic and nonchemotherapeutic indications.
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PMID:Future directions with platelet growth factors. 1083 Dec 88

Patients with human immunodeficiency virus 1-associated immunological thrombocytopenia (HIV-1-ITP) have markedly elevated platelet-bound immunoglobulin (Ig)G, IgM, and C3C4, as well as serum circulating immune complexes (CICs) composed of the same. Affinity purification of IgGs from their CICs with fixed platelets reveals high-affinity antibody (Ab) against platelet glycoprotein (GP)IIIa 49-66, which correlates inversely with their platelet count. However, sera from these patients have little to no anti-GPIIIa activity. To investigate this, we assayed serum, purified serum IgG, and CIC-Ig from these patients. This revealed approximately 150-fold greater Ab activity in purified serum IgG, and approximately 4,000-fold greater reactivity in CIC-IgG. This was shown to be associated with the presence of antiidiotype Ab2 (both IgG and IgM) sequestered in the CIC-IgG. The IgM antiidiotype was predominantly blocking Ab, as demonstrated by specificity for F(ab')(2) fragments of anti-GPIIIa 49-66 of HIV-1-ITP patients and inhibition of reactivity with peptide GPIIIa 49-66, not with a control peptide. The IgM antiidiotype was not polyreactive. Similar measurements were made in nonthrombocytopenic HIV-1-infected patients. Their serum reactivity was not measurable, but serum Ig and CIC-IgG against platelet GPIIIa 49-66 was present, although considerably lower than that found in HIV-1-ITP patients (26- and 35-fold lower, respectively). In addition, their IgM antiidiotype reactivity was 12-fold greater than that found in HIV-1-ITP patients. The IgM antiidiotype Ab titer of both cohorts correlated with in vivo platelet count (r = 0.7, P = 0. 0001, n = 32). To test the in vivo effectiveness of the IgM antiidiotype, thrombocytopenia was induced in mice with 25 microgram of affinity-purified anti-GPIIIa 49-66 (mouse GPIIIa has 83% homology with human GPIIIa and Fc receptors for human IgG1). Maximum effect was obtained at 4-6 h after intraperitoneal injection into Balb/c mice with a platelet count of approximately 30% baseline value. Preincubation of the anti-GPIIIa Ab with control IgM at molar ratios of IgM/IgG of 1:7 before intraperitoneal injection had no effect on the in vivo platelet count, whereas preincubation with patient IgM antiidiotype improved the platelet count to 50-80% of normal. Thrombocytopenia could be reversed after addition of IgM antiidiotype 4 h after induction of thrombocytopenia. Thus, CICs of HIV-1-infected patients contain IgM antiidiotype Ab against anti-GPIIIa, which appears to regulate their serum reactivity in vitro and their level of thrombocytopenia in vivo.
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PMID:Antiidiotype antibody against platelet anti-GPIIIa contributes to the regulation of thrombocytopenia in HIV-1-ITP patients. 1085 34

Anemia, thrombocytopenia, and neutropenia are common manifestations in patients with human immunodeficiency virus infection that become more frequent and severe with progression from the asymptomatic state to acquired immunodeficiency syndrome (AIDS). Causes of anemia in AIDS include nutritional deficiencies, infection, and marrow suppression by antiretroviral drugs and by the disease itself. Autoimmune hemolysis and blood loss from gastrointestinal lymphoma or Kaposi sarcoma may also contribute. Granulocytopenia may be due to infection, autoimmunity, or bone marrow suppression by drugs or the immunodeficiency virus. Lymphopenia, the classic hallmark of the disease, typically affects T-helper cells first and worsens as the disease advances. Lymphopenia is a result of the direct cytopathic effects of the virus. Thrombocytopenia can occur from antibodies causing an idiopathic thrombocytopenic purpura-like state from bone marrow suppression or from thrombotic thrombocytopenic purpura. A prolonged partial thromboplastin time due to a coagulopathy caused by lupus anticoagulant causing has been described. A variety of malignancies occurs.
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PMID:Hematological Effects of Human Immunodeficiency Virus Infection. 1088 19

Common variable immunodeficiency (CVI) is a primary immunodeficiency characterized by deficient antibody production. The cause of this immunodeficiency is unknown; several in vitro studies have revealed a significant number of alterations that could explain the hypogammaglobulinemia present in this syndrome. Among those described are primary B cell alterations, numerical and functional T cell abnormalities, and defects in the interaction between accessory cells. The alteration typical of CVI is the failure of B lymphocytes to differentiate from antibody-producing cells, resulting in deficient immunoglobulin secretion. Among the T cell abnormalities described are a diminished proliferative response to mitogens and antigens, alterations in the level of production of several cytokines, especially reduction in the production of IL-2, diminished antigen-specific T cells and increase basal apoptosis after stimulation. Antigen presenting cells, monocytes and dendritic cells can also present alterations and contribute to deficient antigen response. The clinical manifestations of these patients is variable; most present recurrent bacterial infections due to encapsulated bacteria, especially sinusitis, otitis, bronchitis, and pneumonias. A few patients can present mycobacterial or fungal infection and occasionally Pneumocystis carinii. Viral infection is uncommon in these patients although some suffer recurrent herpes zoster infection. Clinical features of septicemia and central nervous system infections are less frequent. The incidence of digestive tract infections in these patients is high. The most common cause of diarrhea is Giardia lamblia; Salmonella, Shigella and Campylobacter are also common pathogens. Autoimmune disease is also more prevalent in these patients than in the general population. The most frequently associated diseases are hemolytic anemia, idiopathic thrombocytopenic purpura and autoimmune neutropenia. Cancer is also frequently associated with CVI, the most common forms being lymphoproliferative syndromes, especially non-Hodgkin's lymphoma. Granulomas are a unusual manifestation in some patients with CVI; their localization varies but the most commonly affected organs are the spleen and lungs. Some authors have compared these granulomas with those characterizing sarcoidosis, especially when appearing in the lung. Diagnosis of CVI is usually by exclusion of other diseases, such as cystic fibrosis, immotile cilia syndrome or allergic processes. CVI should be suspected in all patients with recurrent bacterial infections especially those localized in the respiratory tract. Other primary immunodeficiencies which present clinical findings similar to CVI and which should be ruled out are selective IgG subclass deficiency, IgA deficiency and selective deficiency in the response to polysaccharide antigens with normal immunoglobulin levels. The serum hypogammaglobulinemia present in all patients with CVI provides the diagnostic key. The age at which clinical manifestations appear, the absence of familial antecedents and the presence of circulating B lymphocytes form the basis of the differential diagnosis between X-linked agammaglobulinemia and autosomal recessive forms. The treatment of choice of patients with CVI is treatment with human gamma-globulin. Currently, the most common route of administration is intravenous; these molecules have a half-life of approximately 21 days and a high degree of safety concerning the possible transmission of viral infections. Adverse reactions are generally few and clinically unimportant. The most frequently used doses oscillate between 200 and 400 mg/kg body weight every 2-4 weeks. Both the dose and its frequency should be personalized for each patient. Early diagnosis of patients with CVI, application of treatment with appropriate antibiotics for infections and treatment with gamma-globulins prevent long-term complications of this disease and dramatically improve the quality of life and life expectancy of these patients.
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PMID:[Common variable immunodeficiency. Review]. 1143 84

Combined immunodeficiency disorders are characterized by abnormalities in cellular and humoral immunity. This classification includes common variable immunodeficiency (CVI), a primary immunodeficiency disorder characterized by hypogammaglobulinemia, recurrent bacterial infections, and significant T-cell abnormalities. Associated autoimmune diseases include rheumatoid arthritis, pernicious anemia, idiopathic thrombocytopenic purpura, and systemic lupus erythematous. Granulomatous lesions in lymphoid tissues, solid organs, and skin have been reported. We describe a patient with CVI who developed cutaneous granulomas with perineural invasion; to our knowledge, this is a previously undescribed feature.
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PMID:Cutaneous granulomas masquerading as tuberculoid leprosy in a patient with congenital combined immunodeficiency. 1151 20

Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura (TTP) are each well recognized clinical syndromes which may appear as single episodes or may have chronic relapsing courses. We present four patients negative for human immunodeficiency virus (HIV) infection who appear to have both diagnoses with either concomitant or intermingled episodes, and we review seven additional patients reported in the literature with similar features. All four of our patients are female, two have underlying connective tissue disorders, and their ATP processes came to our attention because of incomplete response of the platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and 2) or development of thrombocytopenia in the absence of microangiopathy on the background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in platelet count followed treatment for ATP. Based upon this experience, we conclude that some individuals may have a mixed immune thrombocytopenia syndrome; careful analysis of the mechanism of thrombocytopenia, especially in recurrent episodes and in patients who respond incompletely to PEX for TTP, is important when deciding whether to initiate or continue PEX, or to consider therapies appropriate for other mechanisms of thrombocytopenia.
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PMID:Four patients with both thrombotic thrombocytopenic purpura and autoimmune thrombocytopenic purpura: the concept of a mixed immune thrombocytopenia syndrome and indications for plasma exchange. 1183 14

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELlSA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.
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PMID:Virus-associated immune thrombocytopenic purpura in childhood. 1218 67

To combat the spread of human immunodeficiency virus (HIV) in Africa, IDRC is supporting collaborative research of the University of Manitoba and the University of Nairobi which targets prostitutes, children, and long-distance truck drivers. The team of 70 researchers (African, Canadian, and European) is led by Dr. J.O. Ndinya-Achola (University of Nairobi) and Dr. Frank Plummer (University of Manitoba). A study of 1700 Nairobi sex workers has shown that 95% are infected with HIV or have acquired immunodeficiency syndrome (AIDS); the remaining 5% of the cohort have not acquired the disease, even though their behavior appears to be the same. Plummer believes their apparent resistance to the disease may hold the answer for a vaccine or a cure. Another area of research concerns the transmission of HIV in breast milk. In a study of 500 children whose mothers were HIV-positive, 47% were infected. Of these, 50% had acquired the virus through breast feeding, a common and necessary practice in Africa because it nourishes the child and prevents disease. The researchers believe that a 3-6 month period of breast feeding, rather than 2 years, among HIV-positive mothers will lower the rate of transmission to infants while providing immunity to other diseases. Dr. J.J. Bwayo leads the research effort which focuses on truck drivers. 30% of 800 tested drivers were positive for HIV; the percentage increases approximately 4% annually. 350 drivers were interviewed in 1990; in spite of adequate knowledge concerning AIDS and other sexually transmitted diseases, 80% reported having unprotected sex with a prostitute within the last year, and 25% reported weekly sex with sex workers. Only 10% reported they had ever used a condom. Dr. Bwayo's group has established a roadside clinic near a police checkpoint. The truck drivers are offered HIV tests, condoms, education, and counseling while they wait for police to check their rigs. Plummer believes this mobile population is important in the spread of HIV geographically.
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PMID:A critical mass of AIDS research. 1234 97

Thrombocytopenia is a common medical problem for which the main treatment is platelet transfusion. Given the increasing use of platelets and the declining donor population, identification of a safe and effective platelet growth factor could improve the management of thrombocytopenia. Thrombopoietin (TPO), the c-Mpl ligand, is the primary physiologic regulator of megakaryocyte and platelet development. Since the purification of TPO in 1994, 2 recombinant forms of the c-Mpl ligand--recombinant human thrombopoietin (rhTPO) and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF)--have undergone extensive clinical investigation. Both have been shown to be potent stimulators of megakaryocyte growth and platelet production and are biologically active in reducing the thrombocytopenia of nonmyeloablative chemotherapy. However, neither TPO has demonstrated benefit in stem cell transplantation or leukemia chemotherapy. Other clinical studies have investigated the use of TPO in treating chronic nonchemotherapy-induced thrombocytopenia associated with myelodysplastic syndromes, idiopathic thrombocytopenic purpura, thrombocytopenia due to human immunodeficiency virus, and liver disease. Based solely on animal studies, TPO may be effective in reducing surgical thrombocytopenia and bleeding, ex vivo expansion of pluripotent stem cells, and as a radioprotectant. Ongoing and future studies will help define the clinical role of recombinant TPO and TPO mimetics in the treatment of chemotherapy- and nonchemotherapy-induced thrombocytopenia.
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PMID:Recombinant human thrombopoietin: basic biology and evaluation of clinical studies. 1241 15


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