Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Refractory disease occurs in 25% or more of adults with idiopathic (immune) thrombocytopenic purpura (ITP). Therapy to elevate the platelet count may be required in a proportion of these patients. Immunosuppressive agents such as prednisone, azathioprine, cyclophosphamide, and cyclosporin have been shown to be effective treatments in a proportion of patients with refractory ITP. A newer immunosuppressive medication, mycophenolate mofetil (MMF), has been used successfully with acceptable toxicity in solid organ transplant patients to reduce the risk of organ rejection. The goal of this study was to determine whether MMF is an effective treatment for refractory ITP. Efficacy, defined as a sustained platelet increase to a level greater than 50 x 10(9)/L, was seen in 7 of 18 patients with refractory ITP. Three of these 7 patients have had intermittent thrombocytopenic episodes while continuing the medication. No severe toxicity was seen, although two of the 18 patients discontinued MMF within the first month of treatment because of side effects, i.e., headache. In summary, MMF may be a useful component of a combination protocol but does not appear to be highly effective as sole therapy in patients with refractory ITP. The data suggests that response rates to MMF may be higher in patients who have had a shorter duration of their ITP.
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PMID:Efficacy of mycophenolate mofetil as single-agent therapy for refractory immune thrombocytopenic purpura. 1636 79

Abstract The objective of this open label, phase 1-2, multicentre trial was to evaluate the safety of AMG 531, a novel thrombopoiesis-stimulating peptibody, and its effect on platelet counts in adults with immune thrombocytopenic purpura. Four patients were assigned to each of four unit-dose cohorts: 30, 100, 300 or 500 microg, administered subcutaneously on days 1 and 15 (or day 22 if the day 15 platelet count was >50 x 10(9)/l). Safety was assessed by adverse event (AE) monitoring, clinical laboratory studies and antibody assays. Platelet response was defined as a platelet count double the baseline value and between 50 and 450 x 10(9)/l. Sixteen patients (10 women) were enrolled. The 500-microg cohort was discontinued because the first patient's platelet count became unacceptably high. AEs were generally expected and mild or moderate; the most frequent was headache (eight of 16 patients). Two patients experienced serious AEs related to AMG 531 (severe headache and elevated serum lactic dehydrogenase; thrombocytopenia). Platelet responses occurred with all doses and with a dose equivalent to >/=1 microg/kg in eight of 11 patients. In summary, patients tolerated AMG 531 well at the doses tested. No anti-AMG or antithrombopoietin antibodies were detected. Doses equivalent to >/=1 microg/kg increased platelet counts.
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PMID:An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. 1706 81

Brain abscess with bacteremia caused by Listeria monocytogenes in a young woman with immune thrombocytopenic purpura was reported. The clinical features included fever, headache, and left-side weakness. Computed tomography and magnetic resonance imaging of the brain showed a large single abscess at the right frontoparietal area. L. monocytogenes was isolated from a blood culture. The patient promptly received a surgical drainage. Because she had a history of penicillin allergy, and the organism was resistant to ampicillin, she was treated with trimethoprim-sulfamethoxazole (TMP-SMX) alone for 12 months. During a one-year follow-up period, the patient improved and her neurological deficit gradually recovered. This is the first case of listerial brain abscess in Thailand that was successfully treated with TMP-SMX monotherapy and surgical drainage.
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PMID:Brain abscess due to Listeria monocytogenes: first case report in Thailand. 1710 Mar 94

AMG 531 is a novel thrombopoiesis-stimulating peptibody being investigated for the treatment of chronic immune thrombocytopenic purpura. This double-blind, phase I study evaluated the safety, pharmacodynamics, and pharmacokinetics of AMG 531 in healthy Japanese men. Thirty subjects were randomly assigned 4:1 (AMG 531/placebo) to receive 1 dose of AMG 531 (0.3, 1, or 2 microg/kg) or placebo by subcutaneous injection; subjects were evaluated for 6 weeks. AMG 531 was generally well tolerated, with adverse events similar to placebo. Treatment-related adverse events (headache, "feeling hot," malaise) were reported for 5 of 24 AMG 531-treated subjects. Platelets generated after exposure to AMG 531 functioned normally. Four of 8 subjects receiving 1 microg/kg and 7 of 8 receiving 2 microg/kg had platelet count increases > or =1.5-fold over baseline, an effect similar to that seen in non-Japanese subjects. Serum AMG 531 concentrations were below the lower limit of quantification in all but 2 subjects receiving 2 microg/kg.
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PMID:Pharmacodynamics and pharmacokinetics of AMG 531, a thrombopoiesis-stimulating peptibody, in healthy Japanese subjects: a randomized, placebo-controlled study. 1792 91

The role of Helicobacter pylori (HP) in some digestive diseases (gastritis, ulcer, gastric cancer, MALT lymphoma) is well known. It has been suggested relatively recently that infection with HP can be involved in various extra-digestive conditions: respiratory disorders (chronic obstructive pulmonary disease, bronchiectasis, lung cancer, pulmonary tuberculosis, bronchial asthma); vascular disorders (ischaemic heart disease, stroke, primary Raynaud phenomena, primary headache); autoimmune disorders (Sjogren syndrome, Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune thyroiditis, Parkinson's disease, idiopathic chronic urticaria, rosacea, alopecia areata); other disorders (iron deficiency anaemia, growth retardations, liver cirrhosis). Case studies, small patient series and non-randomized trials that have shown a beneficial effect of HP eradication in different conditions are not convincing. According to Mastricht III the only conditions where HP eradication is indicated are immune thrombocytopenic purpura and iron deficiency anaemia.
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PMID:Extragastric manifestations of Helicobacter pylori infection. 1829 84

Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombotic occlusions located in the microcirculation and a syndrome of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, and renal and neurologic abnormalities. Although several factors such as viral and bacterial pathogens, pancreatitis, drugs, collagen-vascular diseases, cancers, and pregnancy have been reported to be associated with TTP, brucellosis is an exceptional cause of this disorder. We represent a 19-year-old woman applying to our outpatient department with the complaints of headache, fever, sweat, malaise, and jaundice. Clinical signs and laboratory findings were consistent with TTP. Brucella agglutination was found to be 1/320 positive. After the administration of therapeutic plasma exchange, all symptoms and laboratory abnormalities improved dramatically. Antibiotic therapy directed to Brucella infection was initiated and no recurrence of TTP was seen.
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PMID:Thrombotic thrombocytopenic purpura associated with Brucella infection. 1834 98

Immunosuppressive drugs used post-transplantation are among the most common causes of thrombotic thrombocytopenic purpura (TTP). Diagnosis is often confounded not only by its myriad presentations, but also because these manifestations may be explained by the comorbidities or complications of transplantation. A 61-year-old female who had a single lung transplant for severe chronic obstructive pulmonary disease maintained on corticosteroids, tacrolimus and mycophenolate mofetil, was admitted for fever, headache with confusion and lethargy. She was mildly anemic and thrombocytopenic. Peripheral smear showed rare fragmented red cells. Muddy brown casts were present on urinalysis. She was diagnosed with TTP. Tacrolimus was discontinued and the mental status of the patient, anemia and thrombocytopenia improved significantly.
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PMID:The spectrum of thrombotic thrombocytopenic purpura: a clinicopathologic demonstration of tacrolimus-induced thrombotic thrombocytopenic purpura in a lung transplant patient. 1858 Jul 30

Intracranial hemorrhage is a devastating complication of immune thrombocytopenic purpura (ITP). Subdural hematoma (SDH) is rare and the optimal management unsettled. We report a series of seven patients of ITP who developed isolated SDH and subsequently review the literature. Three patients had acute ITP (mean duration 2.3 months) while four had chronic ITP (mean duration 8.3 years). Mean platelet count at admission was 25 x 10(9)/L (range 16 x 10(9)/L to 30 x 10(9)/L). Mean age at which SDH occurred was 38 years. Headache and bilateral papilloedema were the commonest clinical features at presentation. Diagnosis was made by CT/MR imaging and SDH was acute in two patients and chronic in five. Precipitating factors could not be identified in any patient. Neurological parameters were closely monitored including level of consciousness, pupillary size and development of new neurological deficits. Two patients with acute SDH developed worsening neurological parameters, underwent craniotomy and hematoma evacuation, and survived. Of the two patients who expired, one was brought in an advanced stage that precluded surgery and the other developed metabolic complications due to underlying lupus nephritis. Reports of isolated SDH in ITP are infrequent. Compared to those developing intracerebral hemorrhage, SDH occurs more in patients who are older, having chronic ITP and having a higher platelet count. Medical management with close monitoring of neurological parameters is a viable treatment option in patients of ITP developing SDH.
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PMID:Management of subdural hematoma in immune thrombocytopenic purpura: report of seven patients and a literature review. 1908 27

Although the thrombopoietin receptor was discovered in 1991 and thrombopoietin (TPO) was purified in 1994, the development of a clinically useful TPO was hampered by the appearance of neutralizing antibodies to some forms of recombinant TPO. However, in 2008 two new drugs that mimic the effect of TPO became available to treat thrombocytopenia. Romiplostim is a TPO peptide mimetic given by subcutaneous injection that activates the TPO receptor by binding to the distal hematopoietic receptor domain just like TPO. Eltrombopag is a TPO nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain. Both increase the platelet count in healthy humans as well as in >80% of patients with immune thrombocytopenic purpura (ITP). Although initially restricted to the second-line treatment of ITP, both agents could help treat many thrombocytopenic disorders. Both agents are well tolerated, with mild headache being the most common complaint. Potential long-term complications include thrombosis, increased bone marrow reticulin, rebound worsening of thrombocytopenia upon discontinuation, and increased blast formation. Ongoing studies should establish the incidence of these complications and determine the efficacy of these new agents in a variety of other thrombocytopenic conditions.
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PMID:Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. 1964 21

Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombotic occlusions located in the microcirculation and a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, fever, and renal and neurologic abnormalities. Thrombotic thrombocytopenic purpura is encountered in a variety of clinical situations such as viral, bacterial, and mycobacterial infections, autoimmune disorders, drug reactions, connective tissue disease, and solid tumors. In this report, we present TTP in a case of brucellosis because of rare presentation. A 7-year-old girl was admitted with the complaints of headache, fever, hematuria, malaise, jaundice, epistaxis, and purpura. Her physical examination revealed conjunctival pallor, scleral icterus, petechial-purpuric skin lesions on both legs, and confusion. Laboratory tests showed hematocrit 14%; hemoglobin 4.8 g/dL; platelet count 6000/mm(3), and reticulocytosis 6%. Peripheral blood smear revealed fragmented red blood cells and a complete absence of platelets. The clinical and laboratory findings were consistent with TTP. Serum antibrucella titration agglutination test was found to be 1/1280 positive.
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PMID:Thrombotic thrombocytopenic purpura in a case of brucellosis. 2021 21


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