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[ { "id": "15376", "type": "title", "text": [ "Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome." ], "offsets": [ [ 0, 111 ] ] }, { "id": "15377", "type": "abstract", "text": [ "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures." ], "offsets": [ [ 112, 1149 ] ] } ]

[ { "id": "15378", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 7, 23 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "15379", "type": "Disease", "text": [ "haemolytic anaemia" ], "offsets": [ [ 28, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000743" } ] }, { "id": "15380", "type": "Chemical", "text": [ "ciprofloxacin" ], "offsets": [ [ 63, 76 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002939" } ] }, { "id": "15381", "type": "Chemical", "text": [ "ciprofloxacin" ], "offsets": [ [ 206, 219 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002939" } ] }, { "id": "15382", "type": "Disease", "text": [ "abdominal pain" ], "offsets": [ [ 263, 277 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015746" } ] }, { "id": "15383", "type": "Disease", "text": [ "jaundice" ], "offsets": [ [ 282, 290 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "15384", "type": "Chemical", "text": [ "ciprofloxacin" ], "offsets": [ [ 326, 339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002939" } ] }, { "id": "15385", "type": "Disease", "text": [ "urinary tract infection" ], "offsets": [ [ 357, 380 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014552" } ] }, { "id": "15386", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 444, 460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "15387", "type": "Disease", "text": [ "haemolysis" ], "offsets": [ [ 465, 475 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006461" } ] }, { "id": "15388", "type": "Disease", "text": [ "petechiae" ], "offsets": [ [ 513, 522 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011693" } ] }, { "id": "15389", "type": "Disease", "text": [ "purpura" ], "offsets": [ [ 527, 534 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011693" } ] }, { "id": "15390", "type": "Disease", "text": [ "haemorrhages" ], "offsets": [ [ 758, 770 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006470" } ] }, { "id": "15391", "type": "Disease", "text": [ "bone marrow depression" ], "offsets": [ [ 784, 806 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001855" } ] }, { "id": "15392", "type": "Disease", "text": [ "thrombi" ], "offsets": [ [ 822, 829 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013927" } ] }, { "id": "15393", "type": "Disease", "text": [ "microangiopathies" ], "offsets": [ [ 842, 859 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014652" } ] }, { "id": "15394", "type": "Chemical", "text": [ "ciprofloxacin" ], "offsets": [ [ 983, 996 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002939" } ] }, { "id": "15395", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 1030, 1046 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "15396", "type": "Disease", "text": [ "haemolytic anaemia" ], "offsets": [ [ 1051, 1069 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000743" } ] } ]

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[ { "id": "15397", "type": "CID", "arg1_id": "15380", "arg2_id": "15388", "normalized": [] }, { "id": "15398", "type": "CID", "arg1_id": "15380", "arg2_id": "15389", "normalized": [] }, { "id": "15399", "type": "CID", "arg1_id": "15381", "arg2_id": "15388", "normalized": [] }, { "id": "15400", "type": "CID", "arg1_id": "15381", "arg2_id": "15389", "normalized": [] }, { "id": "15401", "type": "CID", "arg1_id": "15384", "arg2_id": "15388", "normalized": [] }, { "id": "15402", "type": "CID", "arg1_id": "15384", "arg2_id": "15389", "normalized": [] }, { "id": "15403", "type": "CID", "arg1_id": "15394", "arg2_id": "15388", "normalized": [] }, { "id": "15404", "type": "CID", "arg1_id": "15394", "arg2_id": "15389", "normalized": [] }, { "id": "15405", "type": "CID", "arg1_id": "15380", "arg2_id": "15383", "normalized": [] }, { "id": "15406", "type": "CID", "arg1_id": "15381", "arg2_id": "15383", "normalized": [] }, { "id": "15407", "type": "CID", "arg1_id": "15384", "arg2_id": "15383", "normalized": [] }, { "id": "15408", "type": "CID", "arg1_id": "15394", "arg2_id": "15383", "normalized": [] }, { "id": "15409", "type": "CID", "arg1_id": "15380", "arg2_id": "15378", "normalized": [] }, { "id": "15410", "type": "CID", "arg1_id": "15380", "arg2_id": "15386", "normalized": [] }, { "id": "15411", "type": "CID", "arg1_id": "15380", "arg2_id": "15395", "normalized": [] }, { "id": "15412", "type": "CID", "arg1_id": "15381", "arg2_id": "15378", "normalized": [] }, { "id": "15413", "type": "CID", "arg1_id": "15381", "arg2_id": "15386", "normalized": [] }, { "id": "15414", "type": "CID", "arg1_id": "15381", "arg2_id": "15395", "normalized": [] }, { "id": "15415", "type": "CID", "arg1_id": "15384", "arg2_id": "15378", "normalized": [] }, { "id": "15416", "type": "CID", "arg1_id": "15384", "arg2_id": "15386", "normalized": [] }, { "id": "15417", "type": "CID", "arg1_id": "15384", "arg2_id": "15395", "normalized": [] }, { "id": "15418", "type": "CID", "arg1_id": "15394", "arg2_id": "15378", "normalized": [] }, { "id": "15419", "type": "CID", "arg1_id": "15394", "arg2_id": "15386", "normalized": [] }, { "id": "15420", "type": "CID", "arg1_id": "15394", "arg2_id": "15395", "normalized": [] }, { "id": "15421", "type": "CID", "arg1_id": "15380", "arg2_id": "15379", "normalized": [] }, { "id": "15422", "type": "CID", "arg1_id": "15380", "arg2_id": "15396", "normalized": [] }, { "id": "15423", "type": "CID", "arg1_id": "15381", "arg2_id": "15379", "normalized": [] }, { "id": "15424", "type": "CID", "arg1_id": "15381", "arg2_id": "15396", "normalized": [] }, { "id": "15425", "type": "CID", "arg1_id": "15384", "arg2_id": "15379", "normalized": [] }, { "id": "15426", "type": "CID", "arg1_id": "15384", "arg2_id": "15396", "normalized": [] }, { "id": "15427", "type": "CID", "arg1_id": "15394", "arg2_id": "15379", "normalized": [] }, { "id": "15428", "type": "CID", "arg1_id": "15394", "arg2_id": "15396", "normalized": [] }, { "id": "15429", "type": "CID", "arg1_id": "15380", "arg2_id": "15382", "normalized": [] }, { "id": "15430", "type": "CID", "arg1_id": "15381", "arg2_id": "15382", "normalized": [] }, { "id": "15431", "type": "CID", "arg1_id": "15384", "arg2_id": "15382", "normalized": [] }, { "id": "15432", "type": "CID", "arg1_id": "15394", "arg2_id": "15382", "normalized": [] } ]

[ { "id": "15434", "type": "title", "text": [ "Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism." ], "offsets": [ [ 0, 102 ] ] }, { "id": "15435", "type": "abstract", "text": [ "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients." ], "offsets": [ [ 103, 503 ] ] } ]

[ { "id": "15436", "type": "Chemical", "text": [ "Simvastatin" ], "offsets": [ [ 0, 11 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "15437", "type": "Disease", "text": [ "compartment syndrome" ], "offsets": [ [ 34, 54 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003161" } ] }, { "id": "15438", "type": "Disease", "text": [ "myonecrosis" ], "offsets": [ [ 59, 70 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "15439", "type": "Disease", "text": [ "hypothyroidism" ], "offsets": [ [ 87, 101 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007037" } ] }, { "id": "15440", "type": "Disease", "text": [ "hypothyroid" ], "offsets": [ [ 117, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007037" } ] }, { "id": "15441", "type": "Chemical", "text": [ "thyroxine" ], "offsets": [ [ 141, 150 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013974" } ] }, { "id": "15442", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 155, 166 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "15443", "type": "Disease", "text": [ "compartment syndrome" ], "offsets": [ [ 196, 216 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003161" } ] }, { "id": "15444", "type": "Disease", "text": [ "myonecrosis" ], "offsets": [ [ 221, 232 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "15445", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 336, 347 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "15446", "type": "Disease", "text": [ "arteriopathic" ], "offsets": [ [ 480, 493 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014652" } ] } ]

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[ { "id": "15447", "type": "CID", "arg1_id": "15436", "arg2_id": "15437", "normalized": [] }, { "id": "15448", "type": "CID", "arg1_id": "15436", "arg2_id": "15443", "normalized": [] }, { "id": "15449", "type": "CID", "arg1_id": "15442", "arg2_id": "15437", "normalized": [] }, { "id": "15450", "type": "CID", "arg1_id": "15442", "arg2_id": "15443", "normalized": [] }, { "id": "15451", "type": "CID", "arg1_id": "15445", "arg2_id": "15437", "normalized": [] }, { "id": "15452", "type": "CID", "arg1_id": "15445", "arg2_id": "15443", "normalized": [] } ]

[ { "id": "15454", "type": "title", "text": [ "Bile duct hamartoma occurring in association with long-term treatment with danazol." ], "offsets": [ [ 0, 83 ] ] }, { "id": "15455", "type": "abstract", "text": [ "We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis." ], "offsets": [ [ 84, 473 ] ] } ]

[ { "id": "15456", "type": "Disease", "text": [ "Bile duct hamartoma" ], "offsets": [ [ 0, 19 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001650" }, { "db_name": "MESH", "db_id": "D006222" } ] }, { "id": "15457", "type": "Disease", "text": [ "Bile duct hamartoma" ], "offsets": [ [ 0, 19 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001650" } ] }, { "id": "15458", "type": "Disease", "text": [ "hamartoma" ], "offsets": [ [ 10, 19 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006222" } ] }, { "id": "15459", "type": "Chemical", "text": [ "danazol" ], "offsets": [ [ 75, 82 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003613" } ] }, { "id": "15460", "type": "Disease", "text": [ "bile duct hamartoma" ], "offsets": [ [ 104, 123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001650" }, { "db_name": "MESH", "db_id": "D006222" } ] }, { "id": "15461", "type": "Disease", "text": [ "bile duct hamartoma" ], "offsets": [ [ 104, 123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001650" } ] }, { "id": "15462", "type": "Disease", "text": [ "hamartoma" ], "offsets": [ [ 114, 123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006222" } ] }, { "id": "15463", "type": "Chemical", "text": [ "danazol" ], "offsets": [ [ 179, 186 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003613" } ] }, { "id": "15464", "type": "Disease", "text": [ "liver mass" ], "offsets": [ [ 333, 343 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] } ]

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[ { "id": "15465", "type": "CID", "arg1_id": "15459", "arg2_id": "15456", "normalized": [] }, { "id": "15466", "type": "CID", "arg1_id": "15459", "arg2_id": "15457", "normalized": [] }, { "id": "15467", "type": "CID", "arg1_id": "15459", "arg2_id": "15460", "normalized": [] }, { "id": "15468", "type": "CID", "arg1_id": "15459", "arg2_id": "15461", "normalized": [] }, { "id": "15469", "type": "CID", "arg1_id": "15463", "arg2_id": "15456", "normalized": [] }, { "id": "15470", "type": "CID", "arg1_id": "15463", "arg2_id": "15457", "normalized": [] }, { "id": "15471", "type": "CID", "arg1_id": "15463", "arg2_id": "15460", "normalized": [] }, { "id": "15472", "type": "CID", "arg1_id": "15463", "arg2_id": "15461", "normalized": [] }, { "id": "15473", "type": "CID", "arg1_id": "15459", "arg2_id": "15456", "normalized": [] }, { "id": "15474", "type": "CID", "arg1_id": "15459", "arg2_id": "15458", "normalized": [] }, { "id": "15475", "type": "CID", "arg1_id": "15459", "arg2_id": "15460", "normalized": [] }, { "id": "15476", "type": "CID", "arg1_id": "15459", "arg2_id": "15462", "normalized": [] }, { "id": "15477", "type": "CID", "arg1_id": "15463", "arg2_id": "15456", "normalized": [] }, { "id": "15478", "type": "CID", "arg1_id": "15463", "arg2_id": "15458", "normalized": [] }, { "id": "15479", "type": "CID", "arg1_id": "15463", "arg2_id": "15460", "normalized": [] }, { "id": "15480", "type": "CID", "arg1_id": "15463", "arg2_id": "15462", "normalized": [] } ]

[ { "id": "15482", "type": "title", "text": [ "Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid." ], "offsets": [ [ 0, 78 ] ] }, { "id": "15483", "type": "abstract", "text": [ "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role." ], "offsets": [ [ 79, 622 ] ] } ]

[ { "id": "15484", "type": "Disease", "text": [ "Granulomatous hepatitis" ], "offsets": [ [ 0, 23 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006099" }, { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15485", "type": "Disease", "text": [ "Granulomatous" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006099" } ] }, { "id": "15486", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 14, 23 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15487", "type": "Chemical", "text": [ "combination of amoxicillin and clavulanic acid" ], "offsets": [ [ 31, 77 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019980" } ] }, { "id": "15488", "type": "Chemical", "text": [ "amoxicillin-clavulanic acid" ], "offsets": [ [ 116, 143 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019980" } ] }, { "id": "15489", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 152, 161 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15490", "type": "Disease", "text": [ "granulomas" ], "offsets": [ [ 187, 197 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006099" } ] }, { "id": "15491", "type": "Disease", "text": [ "liver injury" ], "offsets": [ [ 244, 256 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15492", "type": "Disease", "text": [ "cholestatic syndrome" ], "offsets": [ [ 318, 338 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "15493", "type": "Disease", "text": [ "granulomas" ], "offsets": [ [ 359, 369 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006099" } ] }, { "id": "15494", "type": "Disease", "text": [ "eosinophilia" ], "offsets": [ [ 374, 386 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004802" } ] }, { "id": "15495", "type": "Chemical", "text": [ "penicillin" ], "offsets": [ [ 425, 435 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010406" } ] }, { "id": "15496", "type": "Chemical", "text": [ "amoxicillin" ], "offsets": [ [ 452, 463 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000658" } ] }, { "id": "15497", "type": "Chemical", "text": [ "amoxicillin" ], "offsets": [ [ 517, 528 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000658" } ] }, { "id": "15498", "type": "Chemical", "text": [ "clavulanic acid" ], "offsets": [ [ 581, 596 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019818" } ] } ]

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[ { "id": "15499", "type": "CID", "arg1_id": "15487", "arg2_id": "15484", "normalized": [] }, { "id": "15500", "type": "CID", "arg1_id": "15487", "arg2_id": "15486", "normalized": [] }, { "id": "15501", "type": "CID", "arg1_id": "15487", "arg2_id": "15489", "normalized": [] }, { "id": "15502", "type": "CID", "arg1_id": "15487", "arg2_id": "15491", "normalized": [] }, { "id": "15503", "type": "CID", "arg1_id": "15488", "arg2_id": "15484", "normalized": [] }, { "id": "15504", "type": "CID", "arg1_id": "15488", "arg2_id": "15486", "normalized": [] }, { "id": "15505", "type": "CID", "arg1_id": "15488", "arg2_id": "15489", "normalized": [] }, { "id": "15506", "type": "CID", "arg1_id": "15488", "arg2_id": "15491", "normalized": [] }, { "id": "15507", "type": "CID", "arg1_id": "15487", "arg2_id": "15484", "normalized": [] }, { "id": "15508", "type": "CID", "arg1_id": "15487", "arg2_id": "15485", "normalized": [] }, { "id": "15509", "type": "CID", "arg1_id": "15487", "arg2_id": "15490", "normalized": [] }, { "id": "15510", "type": "CID", "arg1_id": "15487", "arg2_id": "15493", "normalized": [] }, { "id": "15511", "type": "CID", "arg1_id": "15488", "arg2_id": "15484", "normalized": [] }, { "id": "15512", "type": "CID", "arg1_id": "15488", "arg2_id": "15485", "normalized": [] }, { "id": "15513", "type": "CID", "arg1_id": "15488", "arg2_id": "15490", "normalized": [] }, { "id": "15514", "type": "CID", "arg1_id": "15488", "arg2_id": "15493", "normalized": [] }, { "id": "15515", "type": "CID", "arg1_id": "15487", "arg2_id": "15492", "normalized": [] }, { "id": "15516", "type": "CID", "arg1_id": "15488", "arg2_id": "15492", "normalized": [] } ]

[ { "id": "15518", "type": "title", "text": [ "Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators." ], "offsets": [ [ 0, 76 ] ] }, { "id": "15519", "type": "abstract", "text": [ "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management." ], "offsets": [ [ 77, 1521 ] ] } ]

[ { "id": "15520", "type": "Disease", "text": [ "Intracranial aneurysms" ], "offsets": [ [ 0, 22 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002532" } ] }, { "id": "15521", "type": "Disease", "text": [ "cocaine abuse" ], "offsets": [ [ 27, 40 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019970" } ] }, { "id": "15522", "type": "Disease", "text": [ "subarachnoid hemorrhage" ], "offsets": [ [ 103, 126 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013345" } ] }, { "id": "15523", "type": "Disease", "text": [ "cocaine abuse" ], "offsets": [ [ 143, 156 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019970" } ] }, { "id": "15524", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 387, 394 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "15525", "type": "Disease", "text": [ "aneurysms" ], "offsets": [ [ 403, 412 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15526", "type": "Disease", "text": [ "ruptured aneurysms" ], "offsets": [ [ 480, 498 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017542" } ] }, { "id": "15527", "type": "Disease", "text": [ "cocaine abuse" ], "offsets": [ [ 517, 530 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019970" } ] }, { "id": "15528", "type": "Disease", "text": [ "subarachnoid hemorrhage" ], "offsets": [ [ 610, 633 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013345" } ] }, { "id": "15529", "type": "Disease", "text": [ "aneurysm" ], "offsets": [ [ 647, 655 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15530", "type": "Disease", "text": [ "aneurysm" ], "offsets": [ [ 673, 681 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15531", "type": "Disease", "text": [ "aneurysms" ], "offsets": [ [ 903, 912 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15532", "type": "Disease", "text": [ "aneurysms" ], "offsets": [ [ 977, 986 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15533", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 1281, 1288 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "15534", "type": "Disease", "text": [ "aneurysms" ], "offsets": [ [ 1297, 1306 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] }, { "id": "15535", "type": "Chemical", "text": [ "Cocaine" ], "offsets": [ [ 1320, 1327 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "15536", "type": "Disease", "text": [ "aneurysmal rupture" ], "offsets": [ [ 1344, 1362 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017542" } ] }, { "id": "15537", "type": "Disease", "text": [ "aneurysms" ], "offsets": [ [ 1414, 1423 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000783" } ] } ]

[]

[]

[ { "id": "15538", "type": "CID", "arg1_id": "15524", "arg2_id": "15526", "normalized": [] }, { "id": "15539", "type": "CID", "arg1_id": "15524", "arg2_id": "15536", "normalized": [] }, { "id": "15540", "type": "CID", "arg1_id": "15533", "arg2_id": "15526", "normalized": [] }, { "id": "15541", "type": "CID", "arg1_id": "15533", "arg2_id": "15536", "normalized": [] }, { "id": "15542", "type": "CID", "arg1_id": "15535", "arg2_id": "15526", "normalized": [] }, { "id": "15543", "type": "CID", "arg1_id": "15535", "arg2_id": "15536", "normalized": [] } ]

[ { "id": "15545", "type": "title", "text": [ "Anti-epileptic drugs-induced de novo absence seizures." ], "offsets": [ [ 0, 54 ] ] }, { "id": "15546", "type": "abstract", "text": [ "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures." ], "offsets": [ [ 55, 1142 ] ] } ]

[ { "id": "15547", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 5, 14 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "15548", "type": "Disease", "text": [ "absence seizures" ], "offsets": [ [ 37, 53 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15549", "type": "Disease", "text": [ "absence epilepsy" ], "offsets": [ [ 103, 119 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15550", "type": "Chemical", "text": [ "carbamazepine" ], "offsets": [ [ 144, 157 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002220" } ] }, { "id": "15551", "type": "Chemical", "text": [ "vigabatrin" ], "offsets": [ [ 162, 172 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020888" } ] }, { "id": "15552", "type": "Disease", "text": [ "absence seizure" ], "offsets": [ [ 246, 261 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15553", "type": "Chemical", "text": [ "gamma-aminobutyric acid" ], "offsets": [ [ 354, 377 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "15554", "type": "Disease", "text": [ "absence epilepsy" ], "offsets": [ [ 483, 499 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15555", "type": "Disease", "text": [ "absence seizure" ], "offsets": [ [ 530, 545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15556", "type": "Disease", "text": [ "absence seizure" ], "offsets": [ [ 752, 767 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15557", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 869, 876 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "15558", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 898, 905 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "15559", "type": "Disease", "text": [ "absence epilepsy" ], "offsets": [ [ 1002, 1018 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] }, { "id": "15560", "type": "Disease", "text": [ "epilepsy" ], "offsets": [ [ 1091, 1099 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "15561", "type": "Disease", "text": [ "absence seizures" ], "offsets": [ [ 1125, 1141 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004832" } ] } ]

[]

[]

[ { "id": "15562", "type": "CID", "arg1_id": "15551", "arg2_id": "15548", "normalized": [] }, { "id": "15563", "type": "CID", "arg1_id": "15551", "arg2_id": "15549", "normalized": [] }, { "id": "15564", "type": "CID", "arg1_id": "15551", "arg2_id": "15552", "normalized": [] }, { "id": "15565", "type": "CID", "arg1_id": "15551", "arg2_id": "15554", "normalized": [] }, { "id": "15566", "type": "CID", "arg1_id": "15551", "arg2_id": "15555", "normalized": [] }, { "id": "15567", "type": "CID", "arg1_id": "15551", "arg2_id": "15556", "normalized": [] }, { "id": "15568", "type": "CID", "arg1_id": "15551", "arg2_id": "15559", "normalized": [] }, { "id": "15569", "type": "CID", "arg1_id": "15551", "arg2_id": "15561", "normalized": [] }, { "id": "15570", "type": "CID", "arg1_id": "15550", "arg2_id": "15548", "normalized": [] }, { "id": "15571", "type": "CID", "arg1_id": "15550", "arg2_id": "15549", "normalized": [] }, { "id": "15572", "type": "CID", "arg1_id": "15550", "arg2_id": "15552", "normalized": [] }, { "id": "15573", "type": "CID", "arg1_id": "15550", "arg2_id": "15554", "normalized": [] }, { "id": "15574", "type": "CID", "arg1_id": "15550", "arg2_id": "15555", "normalized": [] }, { "id": "15575", "type": "CID", "arg1_id": "15550", "arg2_id": "15556", "normalized": [] }, { "id": "15576", "type": "CID", "arg1_id": "15550", "arg2_id": "15559", "normalized": [] }, { "id": "15577", "type": "CID", "arg1_id": "15550", "arg2_id": "15561", "normalized": [] } ]

[ { "id": "15579", "type": "title", "text": [ "Procainamide-induced polymorphous ventricular tachycardia." ], "offsets": [ [ 0, 58 ] ] }, { "id": "15580", "type": "abstract", "text": [ "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia." ], "offsets": [ [ 59, 1134 ] ] } ]

[ { "id": "15581", "type": "Chemical", "text": [ "Procainamide" ], "offsets": [ [ 0, 12 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15582", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 34, 57 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15583", "type": "Chemical", "text": [ "procainamide" ], "offsets": [ [ 74, 86 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15584", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 108, 131 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15585", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 178, 201 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15586", "type": "Chemical", "text": [ "procainamide" ], "offsets": [ [ 264, 276 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15587", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 308, 331 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15588", "type": "Chemical", "text": [ "procainamide" ], "offsets": [ [ 366, 378 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15589", "type": "Disease", "text": [ "premature ventricular contractions" ], "offsets": [ [ 428, 462 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018879" } ] }, { "id": "15590", "type": "Disease", "text": [ "atrial flutter" ], "offsets": [ [ 466, 480 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001282" } ] }, { "id": "15591", "type": "Disease", "text": [ "Q-T prolongation" ], "offsets": [ [ 501, 517 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008133" } ] }, { "id": "15592", "type": "Disease", "text": [ "syncope" ], "offsets": [ [ 532, 539 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013575" } ] }, { "id": "15593", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 560, 583 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15594", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 607, 617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] }, { "id": "15595", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 698, 708 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] }, { "id": "15596", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 731, 741 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] }, { "id": "15597", "type": "Disease", "text": [ "ventricular fibrillation" ], "offsets": [ [ 772, 796 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014693" } ] }, { "id": "15598", "type": "Chemical", "text": [ "procainamide" ], "offsets": [ [ 921, 933 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15599", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 956, 979 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] }, { "id": "15600", "type": "Chemical", "text": [ "procainamide" ], "offsets": [ [ 1032, 1044 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011342" } ] }, { "id": "15601", "type": "Disease", "text": [ "prolonged Q-T syndrome" ], "offsets": [ [ 1069, 1091 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008133" } ] }, { "id": "15602", "type": "Disease", "text": [ "ventricular tachycardia" ], "offsets": [ [ 1110, 1133 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017180" } ] } ]

[]

[]

[ { "id": "15603", "type": "CID", "arg1_id": "15581", "arg2_id": "15582", "normalized": [] }, { "id": "15604", "type": "CID", "arg1_id": "15581", "arg2_id": "15584", "normalized": [] }, { "id": "15605", "type": "CID", "arg1_id": "15581", "arg2_id": "15585", "normalized": [] }, { "id": "15606", "type": "CID", "arg1_id": "15581", "arg2_id": "15587", "normalized": [] }, { "id": "15607", "type": "CID", "arg1_id": "15581", "arg2_id": "15593", "normalized": [] }, { "id": "15608", "type": "CID", "arg1_id": "15581", "arg2_id": "15599", "normalized": [] }, { "id": "15609", "type": "CID", "arg1_id": "15581", "arg2_id": "15602", "normalized": [] }, { "id": "15610", "type": "CID", "arg1_id": "15583", "arg2_id": "15582", "normalized": [] }, { "id": "15611", "type": "CID", "arg1_id": "15583", "arg2_id": "15584", "normalized": [] }, { "id": "15612", "type": "CID", "arg1_id": "15583", "arg2_id": "15585", "normalized": [] }, { "id": "15613", "type": "CID", "arg1_id": "15583", "arg2_id": "15587", "normalized": [] }, { "id": "15614", "type": "CID", "arg1_id": "15583", "arg2_id": "15593", "normalized": [] }, { "id": "15615", "type": "CID", "arg1_id": "15583", "arg2_id": "15599", "normalized": [] }, { "id": "15616", "type": "CID", "arg1_id": "15583", "arg2_id": "15602", "normalized": [] }, { "id": "15617", "type": "CID", "arg1_id": "15586", "arg2_id": "15582", "normalized": [] }, { "id": "15618", "type": "CID", "arg1_id": "15586", "arg2_id": "15584", "normalized": [] }, { "id": "15619", "type": "CID", "arg1_id": "15586", "arg2_id": "15585", "normalized": [] }, { "id": "15620", "type": "CID", "arg1_id": "15586", "arg2_id": "15587", "normalized": [] }, { "id": "15621", "type": "CID", "arg1_id": "15586", "arg2_id": "15593", "normalized": [] }, { "id": "15622", "type": "CID", "arg1_id": "15586", "arg2_id": "15599", "normalized": [] }, { "id": "15623", "type": "CID", "arg1_id": "15586", "arg2_id": "15602", "normalized": [] }, { "id": "15624", "type": "CID", "arg1_id": "15588", "arg2_id": "15582", "normalized": [] }, { "id": "15625", "type": "CID", "arg1_id": "15588", "arg2_id": "15584", "normalized": [] }, { "id": "15626", "type": "CID", "arg1_id": "15588", "arg2_id": "15585", "normalized": [] }, { "id": "15627", "type": "CID", "arg1_id": "15588", "arg2_id": "15587", "normalized": [] }, { "id": "15628", "type": "CID", "arg1_id": "15588", "arg2_id": "15593", "normalized": [] }, { "id": "15629", "type": "CID", "arg1_id": "15588", "arg2_id": "15599", "normalized": [] }, { "id": "15630", "type": "CID", "arg1_id": "15588", "arg2_id": "15602", "normalized": [] }, { "id": "15631", "type": "CID", "arg1_id": "15598", "arg2_id": "15582", "normalized": [] }, { "id": "15632", "type": "CID", "arg1_id": "15598", "arg2_id": "15584", "normalized": [] }, { "id": "15633", "type": "CID", "arg1_id": "15598", "arg2_id": "15585", "normalized": [] }, { "id": "15634", "type": "CID", "arg1_id": "15598", "arg2_id": "15587", "normalized": [] }, { "id": "15635", "type": "CID", "arg1_id": "15598", "arg2_id": "15593", "normalized": [] }, { "id": "15636", "type": "CID", "arg1_id": "15598", "arg2_id": "15599", "normalized": [] }, { "id": "15637", "type": "CID", "arg1_id": "15598", "arg2_id": "15602", "normalized": [] }, { "id": "15638", "type": "CID", "arg1_id": "15600", "arg2_id": "15582", "normalized": [] }, { "id": "15639", "type": "CID", "arg1_id": "15600", "arg2_id": "15584", "normalized": [] }, { "id": "15640", "type": "CID", "arg1_id": "15600", "arg2_id": "15585", "normalized": [] }, { "id": "15641", "type": "CID", "arg1_id": "15600", "arg2_id": "15587", "normalized": [] }, { "id": "15642", "type": "CID", "arg1_id": "15600", "arg2_id": "15593", "normalized": [] }, { "id": "15643", "type": "CID", "arg1_id": "15600", "arg2_id": "15599", "normalized": [] }, { "id": "15644", "type": "CID", "arg1_id": "15600", "arg2_id": "15602", "normalized": [] } ]

[ { "id": "15646", "type": "title", "text": [ "Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension." ], "offsets": [ [ 0, 113 ] ] }, { "id": "15647", "type": "abstract", "text": [ "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors." ], "offsets": [ [ 114, 938 ] ] } ]

[ { "id": "15648", "type": "Chemical", "text": [ "bradykinin" ], "offsets": [ [ 22, 32 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001920" } ] }, { "id": "15649", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 100, 112 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15650", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 200, 212 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15651", "type": "Chemical", "text": [ "bradykinin" ], "offsets": [ [ 301, 311 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001920" } ] }, { "id": "15652", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 391, 403 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15653", "type": "Chemical", "text": [ "dextran" ], "offsets": [ [ 497, 504 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003911" } ] }, { "id": "15654", "type": "Chemical", "text": [ "phenylephrine" ], "offsets": [ [ 523, 536 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010656" } ] }, { "id": "15655", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 551, 563 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15656", "type": "Chemical", "text": [ "Hoe-140" ], "offsets": [ [ 597, 604 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065679" } ] }, { "id": "15657", "type": "Chemical", "text": [ "Phenylephrine" ], "offsets": [ [ 619, 632 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010656" } ] }, { "id": "15658", "type": "Chemical", "text": [ "dextran" ], "offsets": [ [ 720, 727 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003911" } ] }, { "id": "15659", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 846, 858 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15660", "type": "Chemical", "text": [ "bradykinin" ], "offsets": [ [ 902, 912 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001920" } ] } ]

[]

[]

[ { "id": "15661", "type": "CID", "arg1_id": "15654", "arg2_id": "15649", "normalized": [] }, { "id": "15662", "type": "CID", "arg1_id": "15654", "arg2_id": "15650", "normalized": [] }, { "id": "15663", "type": "CID", "arg1_id": "15654", "arg2_id": "15652", "normalized": [] }, { "id": "15664", "type": "CID", "arg1_id": "15654", "arg2_id": "15655", "normalized": [] }, { "id": "15665", "type": "CID", "arg1_id": "15654", "arg2_id": "15659", "normalized": [] }, { "id": "15666", "type": "CID", "arg1_id": "15657", "arg2_id": "15649", "normalized": [] }, { "id": "15667", "type": "CID", "arg1_id": "15657", "arg2_id": "15650", "normalized": [] }, { "id": "15668", "type": "CID", "arg1_id": "15657", "arg2_id": "15652", "normalized": [] }, { "id": "15669", "type": "CID", "arg1_id": "15657", "arg2_id": "15655", "normalized": [] }, { "id": "15670", "type": "CID", "arg1_id": "15657", "arg2_id": "15659", "normalized": [] } ]

[ { "id": "15672", "type": "title", "text": [ "5-azacytidine potentiates initiation induced by carcinogens in rat liver." ], "offsets": [ [ 0, 73 ] ] }, { "id": "15673", "type": "abstract", "text": [ "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA." ], "offsets": [ [ 74, 1665 ] ] } ]

[ { "id": "15674", "type": "Chemical", "text": [ "5-azacytidine" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15675", "type": "Disease", "text": [ "initiation induced by carcinogens" ], "offsets": [ [ 26, 59 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011230" } ] }, { "id": "15676", "type": "Disease", "text": [ "initiation of carcinogenic process" ], "offsets": [ [ 172, 206 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011230" } ] }, { "id": "15677", "type": "Chemical", "text": [ "5-azacytidine" ], "offsets": [ [ 208, 221 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15678", "type": "Chemical", "text": [ "5-AzC" ], "offsets": [ [ 223, 228 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15679", "type": "Chemical", "text": [ "benzo[a]-pyrene" ], "offsets": [ [ 364, 379 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001564" } ] }, { "id": "15680", "type": "Chemical", "text": [ "N-methyl-N-nitrosourea" ], "offsets": [ [ 393, 415 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008770" } ] }, { "id": "15681", "type": "Chemical", "text": [ "1,2-dimethylhydrazine" ], "offsets": [ [ 431, 452 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019813" } ] }, { "id": "15682", "type": "Chemical", "text": [ "1,2-DMH" ], "offsets": [ [ 454, 461 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019813" } ] }, { "id": "15683", "type": "Chemical", "text": [ "2-acetylaminofluorene" ], "offsets": [ [ 658, 679 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015073" } ] }, { "id": "15684", "type": "Chemical", "text": [ "CCl4" ], "offsets": [ [ 714, 718 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002251" } ] }, { "id": "15685", "type": "Chemical", "text": [ "5-AzC" ], "offsets": [ [ 801, 806 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15686", "type": "Chemical", "text": [ "5-AzC" ], "offsets": [ [ 911, 916 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15687", "type": "Chemical", "text": [ "[3H]-5-azadeoxycytidine" ], "offsets": [ [ 1028, 1051 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C014347" } ] }, { "id": "15688", "type": "Chemical", "text": [ "1,2-DMH" ], "offsets": [ [ 1091, 1098 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019813" } ] }, { "id": "15689", "type": "Chemical", "text": [ "cytosine" ], "offsets": [ [ 1134, 1142 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003596" } ] }, { "id": "15690", "type": "Chemical", "text": [ "5-AzC" ], "offsets": [ [ 1226, 1231 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] }, { "id": "15691", "type": "Chemical", "text": [ "5-AzC" ], "offsets": [ [ 1298, 1303 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001374" } ] } ]

[]

[]

[ { "id": "15692", "type": "CID", "arg1_id": "15683", "arg2_id": "15675", "normalized": [] }, { "id": "15693", "type": "CID", "arg1_id": "15683", "arg2_id": "15676", "normalized": [] }, { "id": "15694", "type": "CID", "arg1_id": "15679", "arg2_id": "15675", "normalized": [] }, { "id": "15695", "type": "CID", "arg1_id": "15679", "arg2_id": "15676", "normalized": [] }, { "id": "15696", "type": "CID", "arg1_id": "15684", "arg2_id": "15675", "normalized": [] }, { "id": "15697", "type": "CID", "arg1_id": "15684", "arg2_id": "15676", "normalized": [] }, { "id": "15698", "type": "CID", "arg1_id": "15674", "arg2_id": "15675", "normalized": [] }, { "id": "15699", "type": "CID", "arg1_id": "15674", "arg2_id": "15676", "normalized": [] }, { "id": "15700", "type": "CID", "arg1_id": "15677", "arg2_id": "15675", "normalized": [] }, { "id": "15701", "type": "CID", "arg1_id": "15677", "arg2_id": "15676", "normalized": [] }, { "id": "15702", "type": "CID", "arg1_id": "15678", "arg2_id": "15675", "normalized": [] }, { "id": "15703", "type": "CID", "arg1_id": "15678", "arg2_id": "15676", "normalized": [] }, { "id": "15704", "type": "CID", "arg1_id": "15685", "arg2_id": "15675", "normalized": [] }, { "id": "15705", "type": "CID", "arg1_id": "15685", "arg2_id": "15676", "normalized": [] }, { "id": "15706", "type": "CID", "arg1_id": "15686", "arg2_id": "15675", "normalized": [] }, { "id": "15707", "type": "CID", "arg1_id": "15686", "arg2_id": "15676", "normalized": [] }, { "id": "15708", "type": "CID", "arg1_id": "15690", "arg2_id": "15675", "normalized": [] }, { "id": "15709", "type": "CID", "arg1_id": "15690", "arg2_id": "15676", "normalized": [] }, { "id": "15710", "type": "CID", "arg1_id": "15691", "arg2_id": "15675", "normalized": [] }, { "id": "15711", "type": "CID", "arg1_id": "15691", "arg2_id": "15676", "normalized": [] }, { "id": "15712", "type": "CID", "arg1_id": "15681", "arg2_id": "15675", "normalized": [] }, { "id": "15713", "type": "CID", "arg1_id": "15681", "arg2_id": "15676", "normalized": [] }, { "id": "15714", "type": "CID", "arg1_id": "15682", "arg2_id": "15675", "normalized": [] }, { "id": "15715", "type": "CID", "arg1_id": "15682", "arg2_id": "15676", "normalized": [] }, { "id": "15716", "type": "CID", "arg1_id": "15688", "arg2_id": "15675", "normalized": [] }, { "id": "15717", "type": "CID", "arg1_id": "15688", "arg2_id": "15676", "normalized": [] }, { "id": "15718", "type": "CID", "arg1_id": "15680", "arg2_id": "15675", "normalized": [] }, { "id": "15719", "type": "CID", "arg1_id": "15680", "arg2_id": "15676", "normalized": [] } ]

[ { "id": "15721", "type": "title", "text": [ "Withdrawal-emergent rabbit syndrome during dose reduction of risperidone." ], "offsets": [ [ 0, 73 ] ] }, { "id": "15722", "type": "abstract", "text": [ "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS." ], "offsets": [ [ 74, 683 ] ] } ]

[ { "id": "15723", "type": "Disease", "text": [ "Withdrawal-emergent rabbit syndrome" ], "offsets": [ [ 0, 35 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" }, { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15724", "type": "Disease", "text": [ "Withdrawal", "syndrome" ], "offsets": [ [ 0, 10 ], [ 27, 35 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" } ] }, { "id": "15725", "type": "Disease", "text": [ "emergent rabbit syndrome" ], "offsets": [ [ 11, 35 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15726", "type": "Chemical", "text": [ "risperidone" ], "offsets": [ [ 61, 72 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018967" } ] }, { "id": "15727", "type": "Disease", "text": [ "Rabbit syndrome" ], "offsets": [ [ 74, 89 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15728", "type": "Disease", "text": [ "RS" ], "offsets": [ [ 91, 93 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15729", "type": "Disease", "text": [ "withdrawal-emergent RS" ], "offsets": [ [ 202, 224 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" }, { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15730", "type": "Disease", "text": [ "withdrawal", "RS" ], "offsets": [ [ 202, 212 ], [ 222, 224 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" } ] }, { "id": "15731", "type": "Disease", "text": [ "emergent RS" ], "offsets": [ [ 213, 224 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15732", "type": "Disease", "text": [ "RS" ], "offsets": [ [ 295, 297 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15733", "type": "Chemical", "text": [ "risperidone" ], "offsets": [ [ 323, 334 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018967" } ] }, { "id": "15734", "type": "Chemical", "text": [ "trihexyphenidyl" ], "offsets": [ [ 378, 393 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014282" } ] }, { "id": "15735", "type": "Disease", "text": [ "withdrawal-emergent RS" ], "offsets": [ [ 447, 469 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" }, { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15736", "type": "Disease", "text": [ "withdrawal", "RS" ], "offsets": [ [ 447, 457 ], [ 467, 469 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" } ] }, { "id": "15737", "type": "Disease", "text": [ "emergent RS" ], "offsets": [ [ 458, 469 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "15738", "type": "Chemical", "text": [ "risperidone" ], "offsets": [ [ 546, 557 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018967" } ] }, { "id": "15739", "type": "Chemical", "text": [ "serotonin" ], "offsets": [ [ 561, 570 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "15740", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 571, 579 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "15741", "type": "Chemical", "text": [ "serotonin" ], "offsets": [ [ 641, 650 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "15742", "type": "Disease", "text": [ "RS" ], "offsets": [ [ 680, 682 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] } ]

[]

[]

[ { "id": "15743", "type": "CID", "arg1_id": "15726", "arg2_id": "15723", "normalized": [] }, { "id": "15744", "type": "CID", "arg1_id": "15726", "arg2_id": "15725", "normalized": [] }, { "id": "15745", "type": "CID", "arg1_id": "15726", "arg2_id": "15727", "normalized": [] }, { "id": "15746", "type": "CID", "arg1_id": "15726", "arg2_id": "15728", "normalized": [] }, { "id": "15747", "type": "CID", "arg1_id": "15726", "arg2_id": "15729", "normalized": [] }, { "id": "15748", "type": "CID", "arg1_id": "15726", "arg2_id": "15731", "normalized": [] }, { "id": "15749", "type": "CID", "arg1_id": "15726", "arg2_id": "15732", "normalized": [] }, { "id": "15750", "type": "CID", "arg1_id": "15726", "arg2_id": "15735", "normalized": [] }, { "id": "15751", "type": "CID", "arg1_id": "15726", "arg2_id": "15737", "normalized": [] }, { "id": "15752", "type": "CID", "arg1_id": "15726", "arg2_id": "15742", "normalized": [] }, { "id": "15753", "type": "CID", "arg1_id": "15733", "arg2_id": "15723", "normalized": [] }, { "id": "15754", "type": "CID", "arg1_id": "15733", "arg2_id": "15725", "normalized": [] }, { "id": "15755", "type": "CID", "arg1_id": "15733", "arg2_id": "15727", "normalized": [] }, { "id": "15756", "type": "CID", "arg1_id": "15733", "arg2_id": "15728", "normalized": [] }, { "id": "15757", "type": "CID", "arg1_id": "15733", "arg2_id": "15729", "normalized": [] }, { "id": "15758", "type": "CID", "arg1_id": "15733", "arg2_id": "15731", "normalized": [] }, { "id": "15759", "type": "CID", "arg1_id": "15733", "arg2_id": "15732", "normalized": [] }, { "id": "15760", "type": "CID", "arg1_id": "15733", "arg2_id": "15735", "normalized": [] }, { "id": "15761", "type": "CID", "arg1_id": "15733", "arg2_id": "15737", "normalized": [] }, { "id": "15762", "type": "CID", "arg1_id": "15733", "arg2_id": "15742", "normalized": [] }, { "id": "15763", "type": "CID", "arg1_id": "15738", "arg2_id": "15723", "normalized": [] }, { "id": "15764", "type": "CID", "arg1_id": "15738", "arg2_id": "15725", "normalized": [] }, { "id": "15765", "type": "CID", "arg1_id": "15738", "arg2_id": "15727", "normalized": [] }, { "id": "15766", "type": "CID", "arg1_id": "15738", "arg2_id": "15728", "normalized": [] }, { "id": "15767", "type": "CID", "arg1_id": "15738", "arg2_id": "15729", "normalized": [] }, { "id": "15768", "type": "CID", "arg1_id": "15738", "arg2_id": "15731", "normalized": [] }, { "id": "15769", "type": "CID", "arg1_id": "15738", "arg2_id": "15732", "normalized": [] }, { "id": "15770", "type": "CID", "arg1_id": "15738", "arg2_id": "15735", "normalized": [] }, { "id": "15771", "type": "CID", "arg1_id": "15738", "arg2_id": "15737", "normalized": [] }, { "id": "15772", "type": "CID", "arg1_id": "15738", "arg2_id": "15742", "normalized": [] }, { "id": "15773", "type": "CID", "arg1_id": "15726", "arg2_id": "15723", "normalized": [] }, { "id": "15774", "type": "CID", "arg1_id": "15726", "arg2_id": "15724", "normalized": [] }, { "id": "15775", "type": "CID", "arg1_id": "15726", "arg2_id": "15729", "normalized": [] }, { "id": "15776", "type": "CID", "arg1_id": "15726", "arg2_id": "15730", "normalized": [] }, { "id": "15777", "type": "CID", "arg1_id": "15726", "arg2_id": "15735", "normalized": [] }, { "id": "15778", "type": "CID", "arg1_id": "15726", "arg2_id": "15736", "normalized": [] }, { "id": "15779", "type": "CID", "arg1_id": "15733", "arg2_id": "15723", "normalized": [] }, { "id": "15780", "type": "CID", "arg1_id": "15733", "arg2_id": "15724", "normalized": [] }, { "id": "15781", "type": "CID", "arg1_id": "15733", "arg2_id": "15729", "normalized": [] }, { "id": "15782", "type": "CID", "arg1_id": "15733", "arg2_id": "15730", "normalized": [] }, { "id": "15783", "type": "CID", "arg1_id": "15733", "arg2_id": "15735", "normalized": [] }, { "id": "15784", "type": "CID", "arg1_id": "15733", "arg2_id": "15736", "normalized": [] }, { "id": "15785", "type": "CID", "arg1_id": "15738", "arg2_id": "15723", "normalized": [] }, { "id": "15786", "type": "CID", "arg1_id": "15738", "arg2_id": "15724", "normalized": [] }, { "id": "15787", "type": "CID", "arg1_id": "15738", "arg2_id": "15729", "normalized": [] }, { "id": "15788", "type": "CID", "arg1_id": "15738", "arg2_id": "15730", "normalized": [] }, { "id": "15789", "type": "CID", "arg1_id": "15738", "arg2_id": "15735", "normalized": [] }, { "id": "15790", "type": "CID", "arg1_id": "15738", "arg2_id": "15736", "normalized": [] } ]

[ { "id": "15792", "type": "title", "text": [ "Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram." ], "offsets": [ [ 0, 123 ] ] }, { "id": "15793", "type": "abstract", "text": [ "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed." ], "offsets": [ [ 124, 723 ] ] } ]

[ { "id": "15794", "type": "Chemical", "text": [ "Verapamil" ], "offsets": [ [ 0, 9 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "15795", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 44, 65 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "15796", "type": "Disease", "text": [ "hypertensive" ], "offsets": [ [ 71, 83 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15797", "type": "Chemical", "text": [ "Verapamil" ], "offsets": [ [ 124, 133 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "15798", "type": "Disease", "text": [ "depression" ], "offsets": [ [ 266, 276 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003866" } ] }, { "id": "15799", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 408, 429 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "15800", "type": "Chemical", "text": [ "captopril" ], "offsets": [ [ 465, 474 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002216" } ] }, { "id": "15801", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 497, 506 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "15802", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 554, 566 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "15803", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 603, 612 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "15804", "type": "Chemical", "text": [ "catecholamines" ], "offsets": [ [ 694, 708 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002395" } ] } ]

[]

[]

[ { "id": "15805", "type": "CID", "arg1_id": "15794", "arg2_id": "15795", "normalized": [] }, { "id": "15806", "type": "CID", "arg1_id": "15794", "arg2_id": "15799", "normalized": [] }, { "id": "15807", "type": "CID", "arg1_id": "15797", "arg2_id": "15795", "normalized": [] }, { "id": "15808", "type": "CID", "arg1_id": "15797", "arg2_id": "15799", "normalized": [] }, { "id": "15809", "type": "CID", "arg1_id": "15801", "arg2_id": "15795", "normalized": [] }, { "id": "15810", "type": "CID", "arg1_id": "15801", "arg2_id": "15799", "normalized": [] }, { "id": "15811", "type": "CID", "arg1_id": "15803", "arg2_id": "15795", "normalized": [] }, { "id": "15812", "type": "CID", "arg1_id": "15803", "arg2_id": "15799", "normalized": [] } ]

[ { "id": "15814", "type": "title", "text": [ "Remission induction of meningeal leukemia with high-dose intravenous methotrexate." ], "offsets": [ [ 0, 82 ] ] }, { "id": "15815", "type": "abstract", "text": [ "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia." ], "offsets": [ [ 83, 1395 ] ] } ]

[ { "id": "15816", "type": "Disease", "text": [ "meningeal leukemia" ], "offsets": [ [ 23, 41 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008577" } ] }, { "id": "15817", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 69, 81 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15818", "type": "Disease", "text": [ "acute lymphoblastic leukemia" ], "offsets": [ [ 104, 132 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D054198" } ] }, { "id": "15819", "type": "Disease", "text": [ "meningeal disease" ], "offsets": [ [ 147, 164 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002493" } ] }, { "id": "15820", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 207, 219 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15821", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 274, 286 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15822", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 375, 387 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15823", "type": "Chemical", "text": [ "Leucovorin" ], "offsets": [ [ 518, 528 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002955" } ] }, { "id": "15824", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 717, 729 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15825", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 814, 826 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15826", "type": "Disease", "text": [ "toxicities" ], "offsets": [ [ 1053, 1063 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "15827", "type": "Chemical", "text": [ "bilirubin" ], "offsets": [ [ 1114, 1123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001663" } ] }, { "id": "15828", "type": "Disease", "text": [ "neutropenia" ], "offsets": [ [ 1136, 1147 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009503" } ] }, { "id": "15829", "type": "Disease", "text": [ "mucositis" ], "offsets": [ [ 1153, 1162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D052016" } ] }, { "id": "15830", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1186, 1194 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "15831", "type": "Disease", "text": [ "transient hemiparesis" ], "offsets": [ [ 1199, 1220 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010291" } ] }, { "id": "15832", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 1269, 1281 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "15833", "type": "Disease", "text": [ "acute lymphoblastic leukemia" ], "offsets": [ [ 1366, 1394 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D054198" } ] } ]

[]

[]

[ { "id": "15834", "type": "CID", "arg1_id": "15817", "arg2_id": "15831", "normalized": [] }, { "id": "15835", "type": "CID", "arg1_id": "15820", "arg2_id": "15831", "normalized": [] }, { "id": "15836", "type": "CID", "arg1_id": "15821", "arg2_id": "15831", "normalized": [] }, { "id": "15837", "type": "CID", "arg1_id": "15822", "arg2_id": "15831", "normalized": [] }, { "id": "15838", "type": "CID", "arg1_id": "15824", "arg2_id": "15831", "normalized": [] }, { "id": "15839", "type": "CID", "arg1_id": "15825", "arg2_id": "15831", "normalized": [] }, { "id": "15840", "type": "CID", "arg1_id": "15832", "arg2_id": "15831", "normalized": [] }, { "id": "15841", "type": "CID", "arg1_id": "15817", "arg2_id": "15828", "normalized": [] }, { "id": "15842", "type": "CID", "arg1_id": "15820", "arg2_id": "15828", "normalized": [] }, { "id": "15843", "type": "CID", "arg1_id": "15821", "arg2_id": "15828", "normalized": [] }, { "id": "15844", "type": "CID", "arg1_id": "15822", "arg2_id": "15828", "normalized": [] }, { "id": "15845", "type": "CID", "arg1_id": "15824", "arg2_id": "15828", "normalized": [] }, { "id": "15846", "type": "CID", "arg1_id": "15825", "arg2_id": "15828", "normalized": [] }, { "id": "15847", "type": "CID", "arg1_id": "15832", "arg2_id": "15828", "normalized": [] }, { "id": "15848", "type": "CID", "arg1_id": "15817", "arg2_id": "15830", "normalized": [] }, { "id": "15849", "type": "CID", "arg1_id": "15820", "arg2_id": "15830", "normalized": [] }, { "id": "15850", "type": "CID", "arg1_id": "15821", "arg2_id": "15830", "normalized": [] }, { "id": "15851", "type": "CID", "arg1_id": "15822", "arg2_id": "15830", "normalized": [] }, { "id": "15852", "type": "CID", "arg1_id": "15824", "arg2_id": "15830", "normalized": [] }, { "id": "15853", "type": "CID", "arg1_id": "15825", "arg2_id": "15830", "normalized": [] }, { "id": "15854", "type": "CID", "arg1_id": "15832", "arg2_id": "15830", "normalized": [] }, { "id": "15855", "type": "CID", "arg1_id": "15817", "arg2_id": "15829", "normalized": [] }, { "id": "15856", "type": "CID", "arg1_id": "15820", "arg2_id": "15829", "normalized": [] }, { "id": "15857", "type": "CID", "arg1_id": "15821", "arg2_id": "15829", "normalized": [] }, { "id": "15858", "type": "CID", "arg1_id": "15822", "arg2_id": "15829", "normalized": [] }, { "id": "15859", "type": "CID", "arg1_id": "15824", "arg2_id": "15829", "normalized": [] }, { "id": "15860", "type": "CID", "arg1_id": "15825", "arg2_id": "15829", "normalized": [] }, { "id": "15861", "type": "CID", "arg1_id": "15832", "arg2_id": "15829", "normalized": [] } ]

[ { "id": "15863", "type": "title", "text": [ "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure." ], "offsets": [ [ 0, 118 ] ] }, { "id": "15864", "type": "abstract", "text": [ "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine." ], "offsets": [ [ 119, 368 ] ] } ]

[ { "id": "15865", "type": "Disease", "text": [ "Hypersensitivity" ], "offsets": [ [ 0, 16 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "15866", "type": "Chemical", "text": [ "carbamazepine" ], "offsets": [ [ 20, 33 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002220" } ] }, { "id": "15867", "type": "Disease", "text": [ "leukemoid reaction" ], "offsets": [ [ 52, 70 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007955" } ] }, { "id": "15868", "type": "Disease", "text": [ "eosinophilia" ], "offsets": [ [ 72, 84 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004802" } ] }, { "id": "15869", "type": "Disease", "text": [ "erythroderma" ], "offsets": [ [ 86, 98 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003873" } ] }, { "id": "15870", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 104, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "15871", "type": "Disease", "text": [ "hypersensitivity" ], "offsets": [ [ 147, 163 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "15872", "type": "Chemical", "text": [ "carbamazepine" ], "offsets": [ [ 167, 180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002220" } ] }, { "id": "15873", "type": "Disease", "text": [ "erythroderma" ], "offsets": [ [ 208, 220 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003873" } ] }, { "id": "15874", "type": "Disease", "text": [ "leukemoid reaction" ], "offsets": [ [ 231, 249 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007955" } ] }, { "id": "15875", "type": "Disease", "text": [ "eosinophilia" ], "offsets": [ [ 251, 263 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004802" } ] }, { "id": "15876", "type": "Disease", "text": [ "hyponatremia" ], "offsets": [ [ 265, 277 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007010" } ] }, { "id": "15877", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 283, 296 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "15878", "type": "Chemical", "text": [ "carbamazepine" ], "offsets": [ [ 354, 367 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002220" } ] } ]

[]

[]

[ { "id": "15879", "type": "CID", "arg1_id": "15866", "arg2_id": "15870", "normalized": [] }, { "id": "15880", "type": "CID", "arg1_id": "15866", "arg2_id": "15877", "normalized": [] }, { "id": "15881", "type": "CID", "arg1_id": "15872", "arg2_id": "15870", "normalized": [] }, { "id": "15882", "type": "CID", "arg1_id": "15872", "arg2_id": "15877", "normalized": [] }, { "id": "15883", "type": "CID", "arg1_id": "15878", "arg2_id": "15870", "normalized": [] }, { "id": "15884", "type": "CID", "arg1_id": "15878", "arg2_id": "15877", "normalized": [] }, { "id": "15885", "type": "CID", "arg1_id": "15866", "arg2_id": "15869", "normalized": [] }, { "id": "15886", "type": "CID", "arg1_id": "15866", "arg2_id": "15873", "normalized": [] }, { "id": "15887", "type": "CID", "arg1_id": "15872", "arg2_id": "15869", "normalized": [] }, { "id": "15888", "type": "CID", "arg1_id": "15872", "arg2_id": "15873", "normalized": [] }, { "id": "15889", "type": "CID", "arg1_id": "15878", "arg2_id": "15869", "normalized": [] }, { "id": "15890", "type": "CID", "arg1_id": "15878", "arg2_id": "15873", "normalized": [] }, { "id": "15891", "type": "CID", "arg1_id": "15866", "arg2_id": "15867", "normalized": [] }, { "id": "15892", "type": "CID", "arg1_id": "15866", "arg2_id": "15874", "normalized": [] }, { "id": "15893", "type": "CID", "arg1_id": "15872", "arg2_id": "15867", "normalized": [] }, { "id": "15894", "type": "CID", "arg1_id": "15872", "arg2_id": "15874", "normalized": [] }, { "id": "15895", "type": "CID", "arg1_id": "15878", "arg2_id": "15867", "normalized": [] }, { "id": "15896", "type": "CID", "arg1_id": "15878", "arg2_id": "15874", "normalized": [] }, { "id": "15897", "type": "CID", "arg1_id": "15866", "arg2_id": "15865", "normalized": [] }, { "id": "15898", "type": "CID", "arg1_id": "15866", "arg2_id": "15871", "normalized": [] }, { "id": "15899", "type": "CID", "arg1_id": "15872", "arg2_id": "15865", "normalized": [] }, { "id": "15900", "type": "CID", "arg1_id": "15872", "arg2_id": "15871", "normalized": [] }, { "id": "15901", "type": "CID", "arg1_id": "15878", "arg2_id": "15865", "normalized": [] }, { "id": "15902", "type": "CID", "arg1_id": "15878", "arg2_id": "15871", "normalized": [] }, { "id": "15903", "type": "CID", "arg1_id": "15866", "arg2_id": "15876", "normalized": [] }, { "id": "15904", "type": "CID", "arg1_id": "15872", "arg2_id": "15876", "normalized": [] }, { "id": "15905", "type": "CID", "arg1_id": "15878", "arg2_id": "15876", "normalized": [] } ]

[ { "id": "15907", "type": "title", "text": [ "The interpeduncular nucleus regulates nicotine's effects on free-field activity." ], "offsets": [ [ 0, 80 ] ] }, { "id": "15908", "type": "abstract", "text": [ "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain." ], "offsets": [ [ 81, 855 ] ] } ]

[ { "id": "15909", "type": "Chemical", "text": [ "nicotine" ], "offsets": [ [ 38, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009538" } ] }, { "id": "15910", "type": "Chemical", "text": [ "kainic acid" ], "offsets": [ [ 112, 123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007608" } ] }, { "id": "15911", "type": "Disease", "text": [ "locomotor hypoactivity" ], "offsets": [ [ 301, 323 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009069" } ] }, { "id": "15912", "type": "Chemical", "text": [ "nicotine" ], "offsets": [ [ 334, 342 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009538" } ] }, { "id": "15913", "type": "Chemical", "text": [ "nicotine" ], "offsets": [ [ 398, 406 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009538" } ] }, { "id": "15914", "type": "Disease", "text": [ "hyperactivity" ], "offsets": [ [ 415, 428 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "15915", "type": "Chemical", "text": [ "choline" ], "offsets": [ [ 535, 542 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002794" } ] }, { "id": "15916", "type": "Chemical", "text": [ "tyrosine" ], "offsets": [ [ 616, 624 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014443" } ] }, { "id": "15917", "type": "Disease", "text": [ "depression" ], "offsets": [ [ 750, 760 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003866" } ] } ]

[]

[]

[ { "id": "15918", "type": "CID", "arg1_id": "15909", "arg2_id": "15914", "normalized": [] }, { "id": "15919", "type": "CID", "arg1_id": "15912", "arg2_id": "15914", "normalized": [] }, { "id": "15920", "type": "CID", "arg1_id": "15913", "arg2_id": "15914", "normalized": [] } ]

[ { "id": "15922", "type": "title", "text": [ "Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia." ], "offsets": [ [ 0, 118 ] ] }, { "id": "15923", "type": "abstract", "text": [ "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise." ], "offsets": [ [ 119, 1625 ] ] } ]

[ { "id": "15924", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 79, 89 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15925", "type": "Disease", "text": [ "myocardial ischemia" ], "offsets": [ [ 98, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] }, { "id": "15926", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 191, 201 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15927", "type": "Disease", "text": [ "myocardial ischemia" ], "offsets": [ [ 210, 229 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] }, { "id": "15928", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 429, 439 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15929", "type": "Disease", "text": [ "myocardial ischemia" ], "offsets": [ [ 448, 467 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] }, { "id": "15930", "type": "Chemical", "text": [ "Tc99m-Sestamibi" ], "offsets": [ [ 475, 490 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017256" } ] }, { "id": "15931", "type": "Disease", "text": [ "ischemia" ], "offsets": [ [ 606, 614 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007511" } ] }, { "id": "15932", "type": "Chemical", "text": [ "Sestamibi" ], "offsets": [ [ 674, 683 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017256" } ] }, { "id": "15933", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 690, 700 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15934", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 799, 809 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15935", "type": "Disease", "text": [ "ischemia" ], "offsets": [ [ 876, 884 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007511" } ] }, { "id": "15936", "type": "Chemical", "text": [ "dobutamine" ], "offsets": [ [ 953, 963 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004280" } ] }, { "id": "15937", "type": "Disease", "text": [ "myocardial ischemia" ], "offsets": [ [ 1562, 1581 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] } ]

[]

[]

[ { "id": "15938", "type": "CID", "arg1_id": "15924", "arg2_id": "15925", "normalized": [] }, { "id": "15939", "type": "CID", "arg1_id": "15924", "arg2_id": "15927", "normalized": [] }, { "id": "15940", "type": "CID", "arg1_id": "15924", "arg2_id": "15929", "normalized": [] }, { "id": "15941", "type": "CID", "arg1_id": "15924", "arg2_id": "15937", "normalized": [] }, { "id": "15942", "type": "CID", "arg1_id": "15926", "arg2_id": "15925", "normalized": [] }, { "id": "15943", "type": "CID", "arg1_id": "15926", "arg2_id": "15927", "normalized": [] }, { "id": "15944", "type": "CID", "arg1_id": "15926", "arg2_id": "15929", "normalized": [] }, { "id": "15945", "type": "CID", "arg1_id": "15926", "arg2_id": "15937", "normalized": [] }, { "id": "15946", "type": "CID", "arg1_id": "15928", "arg2_id": "15925", "normalized": [] }, { "id": "15947", "type": "CID", "arg1_id": "15928", "arg2_id": "15927", "normalized": [] }, { "id": "15948", "type": "CID", "arg1_id": "15928", "arg2_id": "15929", "normalized": [] }, { "id": "15949", "type": "CID", "arg1_id": "15928", "arg2_id": "15937", "normalized": [] }, { "id": "15950", "type": "CID", "arg1_id": "15933", "arg2_id": "15925", "normalized": [] }, { "id": "15951", "type": "CID", "arg1_id": "15933", "arg2_id": "15927", "normalized": [] }, { "id": "15952", "type": "CID", "arg1_id": "15933", "arg2_id": "15929", "normalized": [] }, { "id": "15953", "type": "CID", "arg1_id": "15933", "arg2_id": "15937", "normalized": [] }, { "id": "15954", "type": "CID", "arg1_id": "15934", "arg2_id": "15925", "normalized": [] }, { "id": "15955", "type": "CID", "arg1_id": "15934", "arg2_id": "15927", "normalized": [] }, { "id": "15956", "type": "CID", "arg1_id": "15934", "arg2_id": "15929", "normalized": [] }, { "id": "15957", "type": "CID", "arg1_id": "15934", "arg2_id": "15937", "normalized": [] }, { "id": "15958", "type": "CID", "arg1_id": "15936", "arg2_id": "15925", "normalized": [] }, { "id": "15959", "type": "CID", "arg1_id": "15936", "arg2_id": "15927", "normalized": [] }, { "id": "15960", "type": "CID", "arg1_id": "15936", "arg2_id": "15929", "normalized": [] }, { "id": "15961", "type": "CID", "arg1_id": "15936", "arg2_id": "15937", "normalized": [] } ]

[ { "id": "15963", "type": "title", "text": [ "Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage." ], "offsets": [ [ 0, 113 ] ] }, { "id": "15964", "type": "abstract", "text": [ "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol." ], "offsets": [ [ 114, 1041 ] ] } ]

[ { "id": "15965", "type": "Disease", "text": [ "Acute liver failure" ], "offsets": [ [ 0, 19 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017114" } ] }, { "id": "15966", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 49, 56 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "15967", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 79, 90 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15968", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 147, 154 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "15969", "type": "Disease", "text": [ "hepatotoxicity" ], "offsets": [ [ 177, 191 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15970", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 229, 240 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15971", "type": "Chemical", "text": [ "acetaminophen" ], "offsets": [ [ 242, 255 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15972", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 345, 352 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "15973", "type": "Disease", "text": [ "liver failure" ], "offsets": [ [ 371, 384 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017093" } ] }, { "id": "15974", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 436, 443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "15975", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 485, 496 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15976", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 504, 515 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15977", "type": "Disease", "text": [ "hepatotoxicity" ], "offsets": [ [ 635, 649 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "15978", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 696, 707 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15979", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 794, 801 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "15980", "type": "Disease", "text": [ "liver failure" ], "offsets": [ [ 803, 816 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017093" } ] }, { "id": "15981", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 886, 897 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "15982", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 1029, 1040 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] } ]

[]

[]

[ { "id": "15983", "type": "CID", "arg1_id": "15967", "arg2_id": "15969", "normalized": [] }, { "id": "15984", "type": "CID", "arg1_id": "15967", "arg2_id": "15977", "normalized": [] }, { "id": "15985", "type": "CID", "arg1_id": "15970", "arg2_id": "15969", "normalized": [] }, { "id": "15986", "type": "CID", "arg1_id": "15970", "arg2_id": "15977", "normalized": [] }, { "id": "15987", "type": "CID", "arg1_id": "15971", "arg2_id": "15969", "normalized": [] }, { "id": "15988", "type": "CID", "arg1_id": "15971", "arg2_id": "15977", "normalized": [] }, { "id": "15989", "type": "CID", "arg1_id": "15975", "arg2_id": "15969", "normalized": [] }, { "id": "15990", "type": "CID", "arg1_id": "15975", "arg2_id": "15977", "normalized": [] }, { "id": "15991", "type": "CID", "arg1_id": "15976", "arg2_id": "15969", "normalized": [] }, { "id": "15992", "type": "CID", "arg1_id": "15976", "arg2_id": "15977", "normalized": [] }, { "id": "15993", "type": "CID", "arg1_id": "15978", "arg2_id": "15969", "normalized": [] }, { "id": "15994", "type": "CID", "arg1_id": "15978", "arg2_id": "15977", "normalized": [] }, { "id": "15995", "type": "CID", "arg1_id": "15981", "arg2_id": "15969", "normalized": [] }, { "id": "15996", "type": "CID", "arg1_id": "15981", "arg2_id": "15977", "normalized": [] }, { "id": "15997", "type": "CID", "arg1_id": "15982", "arg2_id": "15969", "normalized": [] }, { "id": "15998", "type": "CID", "arg1_id": "15982", "arg2_id": "15977", "normalized": [] }, { "id": "15999", "type": "CID", "arg1_id": "15967", "arg2_id": "15973", "normalized": [] }, { "id": "16000", "type": "CID", "arg1_id": "15967", "arg2_id": "15980", "normalized": [] }, { "id": "16001", "type": "CID", "arg1_id": "15970", "arg2_id": "15973", "normalized": [] }, { "id": "16002", "type": "CID", "arg1_id": "15970", "arg2_id": "15980", "normalized": [] }, { "id": "16003", "type": "CID", "arg1_id": "15971", "arg2_id": "15973", "normalized": [] }, { "id": "16004", "type": "CID", "arg1_id": "15971", "arg2_id": "15980", "normalized": [] }, { "id": "16005", "type": "CID", "arg1_id": "15975", "arg2_id": "15973", "normalized": [] }, { "id": "16006", "type": "CID", "arg1_id": "15975", "arg2_id": "15980", "normalized": [] }, { "id": "16007", "type": "CID", "arg1_id": "15976", "arg2_id": "15973", "normalized": [] }, { "id": "16008", "type": "CID", "arg1_id": "15976", "arg2_id": "15980", "normalized": [] }, { "id": "16009", "type": "CID", "arg1_id": "15978", "arg2_id": "15973", "normalized": [] }, { "id": "16010", "type": "CID", "arg1_id": "15978", "arg2_id": "15980", "normalized": [] }, { "id": "16011", "type": "CID", "arg1_id": "15981", "arg2_id": "15973", "normalized": [] }, { "id": "16012", "type": "CID", "arg1_id": "15981", "arg2_id": "15980", "normalized": [] }, { "id": "16013", "type": "CID", "arg1_id": "15982", "arg2_id": "15973", "normalized": [] }, { "id": "16014", "type": "CID", "arg1_id": "15982", "arg2_id": "15980", "normalized": [] } ]

[ { "id": "16016", "type": "title", "text": [ "Cocaine related chest pain: are we seeing the tip of an iceberg?" ], "offsets": [ [ 0, 64 ] ] }, { "id": "16017", "type": "abstract", "text": [ "The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed." ], "offsets": [ [ 65, 595 ] ] } ]

[ { "id": "16018", "type": "Chemical", "text": [ "Cocaine" ], "offsets": [ [ 0, 7 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "16019", "type": "Disease", "text": [ "chest pain" ], "offsets": [ [ 16, 26 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002637" } ] }, { "id": "16020", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 89, 96 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "16021", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 206, 213 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "16022", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 250, 257 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "16023", "type": "Disease", "text": [ "chest pain" ], "offsets": [ [ 269, 279 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002637" } ] }, { "id": "16024", "type": "Disease", "text": [ "chest pain" ], "offsets": [ [ 361, 371 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002637" } ] }, { "id": "16025", "type": "Disease", "text": [ "chest pain" ], "offsets": [ [ 419, 429 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002637" } ] }, { "id": "16026", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 441, 448 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "16027", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 563, 570 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] } ]

[]

[]

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[ { "id": "16053", "type": "title", "text": [ "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir." ], "offsets": [ [ 0, 118 ] ] }, { "id": "16054", "type": "abstract", "text": [ "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors." ], "offsets": [ [ 119, 2018 ] ] } ]

[ { "id": "16055", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 7, 21 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16056", "type": "Disease", "text": [ "acute renal failure" ], "offsets": [ [ 26, 45 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" } ] }, { "id": "16057", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 78, 89 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16058", "type": "Chemical", "text": [ "amiodarone" ], "offsets": [ [ 91, 101 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "16059", "type": "Chemical", "text": [ "atazanavir" ], "offsets": [ [ 107, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C413408" } ] }, { "id": "16060", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 179, 190 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16061", "type": "Chemical", "text": [ "amiodarone" ], "offsets": [ [ 192, 202 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "16062", "type": "Chemical", "text": [ "atazanavir" ], "offsets": [ [ 208, 218 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C413408" } ] }, { "id": "16063", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 232, 246 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16064", "type": "Disease", "text": [ "acute renal failure" ], "offsets": [ [ 251, 270 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" } ] }, { "id": "16065", "type": "Disease", "text": [ "human immunodeficiency virus" ], "offsets": [ [ 324, 352 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015658" } ] }, { "id": "16066", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 354, 373 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "16067", "type": "Disease", "text": [ "coronary artery disease" ], "offsets": [ [ 375, 398 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003324" } ] }, { "id": "16068", "type": "Disease", "text": [ "hyperlipidemia" ], "offsets": [ [ 404, 418 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006949" } ] }, { "id": "16069", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 446, 450 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "16070", "type": "Disease", "text": [ "fatigue" ], "offsets": [ [ 452, 459 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005221" } ] }, { "id": "16071", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 524, 535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16072", "type": "Chemical", "text": [ "amiodarone" ], "offsets": [ [ 576, 586 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "16073", "type": "Chemical", "text": [ "atazanavir" ], "offsets": [ [ 683, 693 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C413408" } ] }, { "id": "16074", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 783, 791 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "16075", "type": "Chemical", "text": [ "blood urea nitrogen" ], "offsets": [ [ 809, 828 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001806" } ] }, { "id": "16076", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 840, 850 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "16077", "type": "Chemical", "text": [ "aspartate" ], "offsets": [ [ 861, 870 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001224" } ] }, { "id": "16078", "type": "Chemical", "text": [ "alanine" ], "offsets": [ [ 901, 908 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000409" } ] }, { "id": "16079", "type": "Chemical", "text": [ "Simvastatin" ], "offsets": [ [ 927, 938 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16080", "type": "Chemical", "text": [ "amiodarone" ], "offsets": [ [ 940, 950 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "16081", "type": "Disease", "text": [ "human immunodeficiency virus" ], "offsets": [ [ 970, 998 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015658" } ] }, { "id": "16082", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 1151, 1159 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "16083", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 1195, 1205 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "16084", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 1354, 1368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16085", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 1432, 1443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16086", "type": "Chemical", "text": [ "Simvastatin" ], "offsets": [ [ 1456, 1467 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16087", "type": "Chemical", "text": [ "Amiodarone" ], "offsets": [ [ 1494, 1504 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "16088", "type": "Chemical", "text": [ "atazanavir" ], "offsets": [ [ 1509, 1519 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C413408" } ] }, { "id": "16089", "type": "Chemical", "text": [ "statins" ], "offsets": [ [ 1598, 1605 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16090", "type": "Chemical", "text": [ "statins" ], "offsets": [ [ 1736, 1743 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16091", "type": "Chemical", "text": [ "pravastatin" ], "offsets": [ [ 1767, 1778 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017035" } ] }, { "id": "16092", "type": "Chemical", "text": [ "fluvastatin" ], "offsets": [ [ 1780, 1791 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065180" } ] }, { "id": "16093", "type": "Chemical", "text": [ "rosuvastatin" ], "offsets": [ [ 1797, 1809 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C422923" } ] }, { "id": "16094", "type": "Chemical", "text": [ "atorvastatin" ], "offsets": [ [ 1854, 1866 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16095", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 1898, 1909 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "16096", "type": "Chemical", "text": [ "lovastatin" ], "offsets": [ [ 1914, 1924 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] } ]

[]

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"arg2_id": "16055", "normalized": [] }, { "id": "16173", "type": "CID", "arg1_id": "16087", "arg2_id": "16063", "normalized": [] }, { "id": "16174", "type": "CID", "arg1_id": "16087", "arg2_id": "16084", "normalized": [] }, { "id": "16175", "type": "CID", "arg1_id": "16059", "arg2_id": "16055", "normalized": [] }, { "id": "16176", "type": "CID", "arg1_id": "16059", "arg2_id": "16063", "normalized": [] }, { "id": "16177", "type": "CID", "arg1_id": "16059", "arg2_id": "16084", "normalized": [] }, { "id": "16178", "type": "CID", "arg1_id": "16062", "arg2_id": "16055", "normalized": [] }, { "id": "16179", "type": "CID", "arg1_id": "16062", "arg2_id": "16063", "normalized": [] }, { "id": "16180", "type": "CID", "arg1_id": "16062", "arg2_id": "16084", "normalized": [] }, { "id": "16181", "type": "CID", "arg1_id": "16073", "arg2_id": "16055", "normalized": [] }, { "id": "16182", "type": "CID", "arg1_id": "16073", "arg2_id": "16063", "normalized": [] }, { "id": "16183", "type": "CID", "arg1_id": "16073", "arg2_id": "16084", "normalized": [] }, { "id": "16184", "type": "CID", "arg1_id": "16088", "arg2_id": "16055", "normalized": [] }, { "id": "16185", "type": "CID", "arg1_id": "16088", "arg2_id": "16063", "normalized": [] }, { "id": "16186", "type": "CID", "arg1_id": "16088", "arg2_id": "16084", "normalized": [] } ]

[ { "id": "16188", "type": "title", "text": [ "Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group." ], "offsets": [ [ 0, 187 ] ] }, { "id": "16189", "type": "abstract", "text": [ "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted." ], "offsets": [ [ 188, 1764 ] ] } ]

[ { "id": "16190", "type": "Chemical", "text": [ "vinorelbine" ], "offsets": [ [ 18, 29 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16191", "type": "Disease", "text": [ "squamous cell esophageal carcinoma" ], "offsets": [ [ 44, 78 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C562729" } ] }, { "id": "16192", "type": "Disease", "text": [ "Cancer" ], "offsets": [ [ 132, 138 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "16193", "type": "Disease", "text": [ "Cancer" ], "offsets": [ [ 162, 168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "16194", "type": "Chemical", "text": [ "vinorelbine" ], "offsets": [ [ 248, 259 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16195", "type": "Chemical", "text": [ "VNB" ], "offsets": [ [ 261, 264 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16196", "type": "Disease", "text": [ "squamous cell esophageal carcinoma" ], "offsets": [ [ 311, 345 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C562729" } ] }, { "id": "16197", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 557, 566 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16198", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 606, 614 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16199", "type": "Chemical", "text": [ "VNB" ], "offsets": [ [ 629, 632 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16200", "type": "Chemical", "text": [ "VNB" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16201", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1261, 1269 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16202", "type": "Disease", "text": [ "granulocytopenia" ], "offsets": [ [ 1317, 1333 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000380" } ] }, { "id": "16203", "type": "Disease", "text": [ "infection" ], "offsets": [ [ 1378, 1387 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007239" } ] }, { "id": "16204", "type": "Disease", "text": [ "deaths" ], "offsets": [ [ 1430, 1436 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "16205", "type": "Disease", "text": [ "peripheral neurotoxicity" ], "offsets": [ [ 1481, 1505 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] }, { "id": "16206", "type": "Chemical", "text": [ "VNB" ], "offsets": [ [ 1573, 1576 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] }, { "id": "16207", "type": "Disease", "text": [ "esophageal squamous cell carcinoma" ], "offsets": [ [ 1610, 1644 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C562729" } ] }, { "id": "16208", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1692, 1700 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16209", "type": "Chemical", "text": [ "VNB" ], "offsets": [ [ 1724, 1727 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C030852" } ] } ]

[]

[]

[ { "id": "16210", "type": "CID", "arg1_id": "16190", "arg2_id": "16202", "normalized": [] }, { "id": "16211", "type": "CID", "arg1_id": "16194", "arg2_id": "16202", "normalized": [] }, { "id": "16212", "type": "CID", "arg1_id": "16195", "arg2_id": "16202", "normalized": [] }, { "id": "16213", "type": "CID", "arg1_id": "16199", "arg2_id": "16202", "normalized": [] }, { "id": "16214", "type": "CID", "arg1_id": "16200", "arg2_id": "16202", "normalized": [] }, { "id": "16215", "type": "CID", "arg1_id": "16206", "arg2_id": "16202", "normalized": [] }, { "id": "16216", "type": "CID", "arg1_id": "16209", "arg2_id": "16202", "normalized": [] }, { "id": "16217", "type": "CID", "arg1_id": "16190", "arg2_id": "16205", "normalized": [] }, { "id": "16218", "type": "CID", "arg1_id": "16194", "arg2_id": "16205", "normalized": [] }, { "id": "16219", "type": "CID", "arg1_id": "16195", "arg2_id": "16205", "normalized": [] }, { "id": "16220", "type": "CID", "arg1_id": "16199", "arg2_id": "16205", "normalized": [] }, { "id": "16221", "type": "CID", "arg1_id": "16200", "arg2_id": "16205", "normalized": [] }, { "id": "16222", "type": "CID", "arg1_id": "16206", "arg2_id": "16205", "normalized": [] }, { "id": "16223", "type": "CID", "arg1_id": "16209", "arg2_id": "16205", "normalized": [] } ]

[ { "id": "16225", "type": "title", "text": [ "Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma." ], "offsets": [ [ 0, 155 ] ] }, { "id": "16226", "type": "abstract", "text": [ "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens." ], "offsets": [ [ 156, 2298 ] ] } ]

[ { "id": "16227", "type": "Chemical", "text": [ "Paclitaxel" ], "offsets": [ [ 0, 10 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "16228", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 12, 21 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16229", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 27, 38 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C056507" } ] }, { "id": "16230", "type": "Disease", "text": [ "nonsmall cell lung carcinoma" ], "offsets": [ [ 126, 154 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16231", "type": "Chemical", "text": [ "Cisplatin" ], "offsets": [ [ 168, 177 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16232", "type": "Disease", "text": [ "nonsmall cell lung carcinoma" ], "offsets": [ [ 259, 287 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16233", "type": "Disease", "text": [ "NSCLC" ], "offsets": [ [ 289, 294 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16234", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 501, 509 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16235", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 515, 525 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "16236", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 527, 536 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16237", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 542, 553 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C056507" } ] }, { "id": "16238", "type": "Disease", "text": [ "NSCLC" ], "offsets": [ [ 586, 591 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16239", "type": "Disease", "text": [ "NSCLC" ], "offsets": [ [ 659, 664 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16240", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 768, 778 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "16241", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 834, 843 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16242", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 903, 914 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C056507" } ] }, { "id": "16243", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1182, 1190 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16244", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1296, 1304 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16245", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 1651, 1661 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "16246", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1687, 1696 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16247", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 1727, 1738 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C056507" } ] }, { "id": "16248", "type": "Disease", "text": [ "neutropenia" ], "offsets": [ [ 1784, 1795 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009503" } ] }, { "id": "16249", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 1800, 1816 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "16250", "type": "Disease", "text": [ "death" ], "offsets": [ [ 1904, 1909 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "16251", "type": "Disease", "text": [ "toxicities" ], "offsets": [ [ 1926, 1936 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16252", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 2119, 2129 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "16253", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 2131, 2140 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "16254", "type": "Chemical", "text": [ "gemcitabine" ], "offsets": [ [ 2146, 2157 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C056507" } ] }, { "id": "16255", "type": "Disease", "text": [ "NSCLC" ], "offsets": [ [ 2214, 2219 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "16256", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 2273, 2282 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] } ]

[]

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[ { "id": "16257", "type": "CID", "arg1_id": "16228", "arg2_id": "16248", "normalized": [] }, { "id": "16258", "type": "CID", "arg1_id": "16231", "arg2_id": "16248", "normalized": [] }, { "id": "16259", "type": "CID", "arg1_id": "16236", "arg2_id": "16248", "normalized": [] }, { "id": "16260", "type": "CID", "arg1_id": "16241", "arg2_id": "16248", "normalized": [] }, { "id": "16261", "type": "CID", "arg1_id": "16246", "arg2_id": "16248", "normalized": [] }, { "id": "16262", "type": "CID", "arg1_id": "16253", "arg2_id": "16248", "normalized": [] }, { "id": "16263", "type": "CID", "arg1_id": "16256", "arg2_id": "16248", "normalized": [] }, { "id": "16264", "type": "CID", "arg1_id": "16227", "arg2_id": "16249", "normalized": [] }, { "id": "16265", "type": "CID", "arg1_id": "16235", "arg2_id": "16249", "normalized": [] }, { "id": "16266", "type": "CID", "arg1_id": "16240", "arg2_id": "16249", "normalized": [] }, { "id": "16267", "type": "CID", "arg1_id": "16245", "arg2_id": "16249", "normalized": [] }, { "id": "16268", "type": "CID", "arg1_id": "16252", "arg2_id": "16249", "normalized": [] }, { "id": "16269", "type": "CID", "arg1_id": "16229", "arg2_id": "16248", "normalized": [] }, { "id": "16270", "type": "CID", "arg1_id": "16237", "arg2_id": "16248", "normalized": [] }, { "id": "16271", "type": "CID", "arg1_id": "16242", "arg2_id": "16248", "normalized": [] }, { "id": "16272", "type": "CID", "arg1_id": "16247", "arg2_id": "16248", "normalized": [] }, { "id": "16273", "type": "CID", "arg1_id": "16254", "arg2_id": "16248", "normalized": [] }, { "id": "16274", "type": "CID", "arg1_id": "16227", "arg2_id": "16248", "normalized": [] }, { "id": "16275", "type": "CID", "arg1_id": "16235", "arg2_id": "16248", "normalized": [] }, { "id": "16276", "type": "CID", "arg1_id": "16240", "arg2_id": "16248", "normalized": [] }, { "id": "16277", "type": "CID", "arg1_id": "16245", "arg2_id": "16248", "normalized": [] }, { "id": "16278", "type": "CID", "arg1_id": "16252", "arg2_id": "16248", "normalized": [] }, { "id": "16279", "type": "CID", "arg1_id": "16229", "arg2_id": "16249", "normalized": [] }, { "id": "16280", "type": "CID", "arg1_id": "16237", "arg2_id": "16249", "normalized": [] }, { "id": "16281", "type": "CID", "arg1_id": "16242", "arg2_id": "16249", "normalized": [] }, { "id": "16282", "type": "CID", "arg1_id": "16247", "arg2_id": "16249", "normalized": [] }, { "id": "16283", "type": "CID", "arg1_id": "16254", "arg2_id": "16249", "normalized": [] }, { "id": "16284", "type": "CID", "arg1_id": "16228", "arg2_id": "16249", "normalized": [] }, { "id": "16285", "type": "CID", "arg1_id": "16231", "arg2_id": "16249", "normalized": [] }, { "id": "16286", "type": "CID", "arg1_id": "16236", "arg2_id": "16249", "normalized": [] }, { "id": "16287", "type": "CID", "arg1_id": "16241", "arg2_id": "16249", "normalized": [] }, { "id": "16288", "type": "CID", "arg1_id": "16246", "arg2_id": "16249", "normalized": [] }, { "id": "16289", "type": "CID", "arg1_id": "16253", "arg2_id": "16249", "normalized": [] }, { "id": "16290", "type": "CID", "arg1_id": "16256", "arg2_id": "16249", "normalized": [] } ]

[ { "id": "16292", "type": "title", "text": [ "Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution." ], "offsets": [ [ 0, 79 ] ] }, { "id": "16293", "type": "abstract", "text": [ "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people." ], "offsets": [ [ 80, 1369 ] ] } ]

[ { "id": "16294", "type": "Chemical", "text": [ "aponidine hydrochloride" ], "offsets": [ [ 35, 58 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016986" } ] }, { "id": "16295", "type": "Chemical", "text": [ "apraclonidine" ], "offsets": [ [ 132, 145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016986" } ] }, { "id": "16296", "type": "Chemical", "text": [ "apraclonidine" ], "offsets": [ [ 204, 217 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016986" } ] }, { "id": "16297", "type": "Disease", "text": [ "ocular hypotensive" ], "offsets": [ [ 521, 539 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015814" } ] }, { "id": "16298", "type": "Chemical", "text": [ "apraclonidine" ], "offsets": [ [ 583, 596 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016986" } ] }, { "id": "16299", "type": "Chemical", "text": [ "apraclonidine" ], "offsets": [ [ 741, 754 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016986" } ] }, { "id": "16300", "type": "Disease", "text": [ "Decreases in systolic blood pressure" ], "offsets": [ [ 756, 792 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "16301", "type": "Disease", "text": [ "Conjunctival blanching" ], "offsets": [ [ 946, 968 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003229" } ] }, { "id": "16302", "type": "Disease", "text": [ "mydriasis" ], "offsets": [ [ 973, 982 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015878" } ] }, { "id": "16303", "type": "Disease", "text": [ "entropion" ], "offsets": [ [ 1221, 1230 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004774" } ] }, { "id": "16304", "type": "Disease", "text": [ "corneal abrasion" ], "offsets": [ [ 1242, 1258 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003316" } ] } ]

[]

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[ { "id": "16305", "type": "CID", "arg1_id": "16294", "arg2_id": "16297", "normalized": [] }, { "id": "16306", "type": "CID", "arg1_id": "16295", "arg2_id": "16297", "normalized": [] }, { "id": "16307", "type": "CID", "arg1_id": "16296", "arg2_id": "16297", "normalized": [] }, { "id": "16308", "type": "CID", "arg1_id": "16298", "arg2_id": "16297", "normalized": [] }, { "id": "16309", "type": "CID", "arg1_id": "16299", "arg2_id": "16297", "normalized": [] }, { "id": "16310", "type": "CID", "arg1_id": "16294", "arg2_id": "16302", "normalized": [] }, { "id": "16311", "type": "CID", "arg1_id": "16295", "arg2_id": "16302", "normalized": [] }, { "id": "16312", "type": "CID", "arg1_id": "16296", "arg2_id": "16302", "normalized": [] }, { "id": "16313", "type": "CID", "arg1_id": "16298", "arg2_id": "16302", "normalized": [] }, { "id": "16314", "type": "CID", "arg1_id": "16299", "arg2_id": "16302", "normalized": [] }, { "id": "16315", "type": "CID", "arg1_id": "16294", "arg2_id": "16303", "normalized": [] }, { "id": "16316", "type": "CID", "arg1_id": "16295", "arg2_id": "16303", "normalized": [] }, { "id": "16317", "type": "CID", "arg1_id": "16296", "arg2_id": "16303", "normalized": [] }, { "id": "16318", "type": "CID", "arg1_id": "16298", "arg2_id": "16303", "normalized": [] }, { "id": "16319", "type": "CID", "arg1_id": "16299", "arg2_id": "16303", "normalized": [] }, { "id": "16320", "type": "CID", "arg1_id": "16294", "arg2_id": "16304", "normalized": [] }, { "id": "16321", "type": "CID", "arg1_id": "16295", "arg2_id": "16304", "normalized": [] }, { "id": "16322", "type": "CID", "arg1_id": "16296", "arg2_id": "16304", "normalized": [] }, { "id": "16323", "type": "CID", "arg1_id": "16298", "arg2_id": "16304", "normalized": [] }, { "id": "16324", "type": "CID", "arg1_id": "16299", "arg2_id": "16304", "normalized": [] }, { "id": "16325", "type": "CID", "arg1_id": "16294", "arg2_id": "16301", "normalized": [] }, { "id": "16326", "type": "CID", "arg1_id": "16295", "arg2_id": "16301", "normalized": [] }, { "id": "16327", "type": "CID", "arg1_id": "16296", "arg2_id": "16301", "normalized": [] }, { "id": "16328", "type": "CID", "arg1_id": "16298", "arg2_id": "16301", "normalized": [] }, { "id": "16329", "type": "CID", "arg1_id": "16299", "arg2_id": "16301", "normalized": [] } ]

[ { "id": "16331", "type": "title", "text": [ "Carmofur-induced organic mental disorders." ], "offsets": [ [ 0, 42 ] ] }, { "id": "16332", "type": "abstract", "text": [ "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe." ], "offsets": [ [ 43, 788 ] ] } ]

[ { "id": "16333", "type": "Chemical", "text": [ "Carmofur" ], "offsets": [ [ 0, 8 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C017367" } ] }, { "id": "16334", "type": "Disease", "text": [ "organic mental disorders" ], "offsets": [ [ 17, 41 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019965" } ] }, { "id": "16335", "type": "Disease", "text": [ "Organic mental disorder" ], "offsets": [ [ 43, 66 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019965" } ] }, { "id": "16336", "type": "Chemical", "text": [ "carmofur" ], "offsets": [ [ 148, 156 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C017367" } ] }, { "id": "16337", "type": "Disease", "text": [ "leukoencephalopathy" ], "offsets": [ [ 165, 184 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056784" } ] }, { "id": "16338", "type": "Disease", "text": [ "organic personality syndrome" ], "offsets": [ [ 292, 320 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010554" } ] }, { "id": "16339", "type": "Disease", "text": [ "frontal lobe syndrome" ], "offsets": [ [ 396, 417 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "16340", "type": "Chemical", "text": [ "carmofur" ], "offsets": [ [ 608, 616 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C017367" } ] }, { "id": "16341", "type": "Disease", "text": [ "leukoencephalopathy" ], "offsets": [ [ 625, 644 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056784" } ] }, { "id": "16342", "type": "Disease", "text": [ "organic personality syndrome" ], "offsets": [ [ 670, 698 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010554" } ] }, { "id": "16343", "type": "Disease", "text": [ "structural damage to the frontal lobe" ], "offsets": [ [ 750, 787 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] } ]

[]

[]

[ { "id": "16344", "type": "CID", "arg1_id": "16333", "arg2_id": "16337", "normalized": [] }, { "id": "16345", "type": "CID", "arg1_id": "16333", "arg2_id": "16341", "normalized": [] }, { "id": "16346", "type": "CID", "arg1_id": "16336", "arg2_id": "16337", "normalized": [] }, { "id": "16347", "type": "CID", "arg1_id": "16336", "arg2_id": "16341", "normalized": [] }, { "id": "16348", "type": "CID", "arg1_id": "16340", "arg2_id": "16337", "normalized": [] }, { "id": "16349", "type": "CID", "arg1_id": "16340", "arg2_id": "16341", "normalized": [] }, { "id": "16350", "type": "CID", "arg1_id": "16333", "arg2_id": "16334", "normalized": [] }, { "id": "16351", "type": "CID", "arg1_id": "16333", "arg2_id": "16335", "normalized": [] }, { "id": "16352", "type": "CID", "arg1_id": "16336", "arg2_id": "16334", "normalized": [] }, { "id": "16353", "type": "CID", "arg1_id": "16336", "arg2_id": "16335", "normalized": [] }, { "id": "16354", "type": "CID", "arg1_id": "16340", "arg2_id": "16334", "normalized": [] }, { "id": "16355", "type": "CID", "arg1_id": "16340", "arg2_id": "16335", "normalized": [] } ]

[ { "id": "16357", "type": "title", "text": [ "International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group." ], "offsets": [ [ 0, 134 ] ] }, { "id": "16358", "type": "abstract", "text": [ "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group." ], "offsets": [ [ 135, 1435 ] ] } ]

[ { "id": "16359", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 14, 24 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16360", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 81, 91 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] }, { "id": "16361", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 195, 205 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16362", "type": "Chemical", "text": [ "Mexitil-Perlongets" ], "offsets": [ [ 207, 225 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16363", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 313, 334 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "16364", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 767, 777 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16365", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 942, 952 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16366", "type": "Disease", "text": [ "deaths" ], "offsets": [ [ 1096, 1102 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "16367", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 1110, 1120 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] }, { "id": "16368", "type": "Disease", "text": [ "tremor" ], "offsets": [ [ 1328, 1334 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014202" } ] }, { "id": "16369", "type": "Disease", "text": [ "gastrointestinal problems" ], "offsets": [ [ 1339, 1364 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012817" } ] }, { "id": "16370", "type": "Chemical", "text": [ "mexiletine" ], "offsets": [ [ 1392, 1402 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008801" } ] } ]

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[ { "id": "16371", "type": "CID", "arg1_id": "16359", "arg2_id": "16368", "normalized": [] }, { "id": "16372", "type": "CID", "arg1_id": "16361", "arg2_id": "16368", "normalized": [] }, { "id": "16373", "type": "CID", "arg1_id": "16362", "arg2_id": "16368", "normalized": [] }, { "id": "16374", "type": "CID", "arg1_id": "16364", "arg2_id": "16368", "normalized": [] }, { "id": "16375", "type": "CID", "arg1_id": "16365", "arg2_id": "16368", "normalized": [] }, { "id": "16376", "type": "CID", "arg1_id": "16367", "arg2_id": "16368", "normalized": [] }, { "id": "16377", "type": "CID", "arg1_id": "16370", "arg2_id": "16368", "normalized": [] }, { "id": "16378", "type": "CID", "arg1_id": "16359", "arg2_id": "16369", "normalized": [] }, { "id": "16379", "type": "CID", "arg1_id": "16361", "arg2_id": "16369", "normalized": [] }, { "id": "16380", "type": "CID", "arg1_id": "16362", "arg2_id": "16369", "normalized": [] }, { "id": "16381", "type": "CID", "arg1_id": "16364", "arg2_id": "16369", "normalized": [] }, { "id": "16382", "type": "CID", "arg1_id": "16365", "arg2_id": "16369", "normalized": [] }, { "id": "16383", "type": "CID", "arg1_id": "16367", "arg2_id": "16369", "normalized": [] }, { "id": "16384", "type": "CID", "arg1_id": "16370", "arg2_id": "16369", "normalized": [] } ]

[ { "id": "16386", "type": "title", "text": [ "Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections." ], "offsets": [ [ 0, 116 ] ] }, { "id": "16387", "type": "abstract", "text": [ "Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity." ], "offsets": [ [ 117, 929 ] ] } ]

[ { "id": "16388", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 43, 54 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "16389", "type": "Disease", "text": [ "hyperactivity" ], "offsets": [ [ 63, 76 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "16390", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 94, 104 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16391", "type": "Chemical", "text": [ "Calcitonin" ], "offsets": [ [ 117, 127 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16392", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 193, 203 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16393", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 313, 324 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "16394", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 456, 466 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16395", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 557, 567 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16396", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 687, 697 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16397", "type": "Chemical", "text": [ "calcitonin" ], "offsets": [ [ 865, 875 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002116" } ] }, { "id": "16398", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 890, 901 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] } ]

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[ { "id": "16399", "type": "CID", "arg1_id": "16388", "arg2_id": "16389", "normalized": [] }, { "id": "16400", "type": "CID", "arg1_id": "16393", "arg2_id": "16389", "normalized": [] }, { "id": "16401", "type": "CID", "arg1_id": "16398", "arg2_id": "16389", "normalized": [] } ]

[ { "id": "16403", "type": "title", "text": [ "Fatal intracranial bleeding associated with prehospital use of epinephrine." ], "offsets": [ [ 0, 75 ] ] }, { "id": "16404", "type": "abstract", "text": [ "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution." ], "offsets": [ [ 76, 663 ] ] } ]

[ { "id": "16405", "type": "Disease", "text": [ "intracranial bleeding" ], "offsets": [ [ 6, 27 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013345" } ] }, { "id": "16406", "type": "Chemical", "text": [ "epinephrine" ], "offsets": [ [ 63, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004837" } ] }, { "id": "16407", "type": "Disease", "text": [ "allergic reaction" ], "offsets": [ [ 171, 188 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "16408", "type": "Disease", "text": [ "pulmonary edema" ], "offsets": [ [ 202, 217 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011654" } ] }, { "id": "16409", "type": "Disease", "text": [ "wheezing" ], "offsets": [ [ 223, 231 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012135" } ] }, { "id": "16410", "type": "Disease", "text": [ "respiratory distress" ], "offsets": [ [ 253, 273 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012128" } ] }, { "id": "16411", "type": "Disease", "text": [ "rash" ], "offsets": [ [ 275, 279 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005076" } ] }, { "id": "16412", "type": "Chemical", "text": [ "epinephrine" ], "offsets": [ [ 376, 387 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004837" } ] }, { "id": "16413", "type": "Disease", "text": [ "cardiac arrest" ], "offsets": [ [ 409, 423 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006323" } ] }, { "id": "16414", "type": "Disease", "text": [ "subarachnoid hemorrhage" ], "offsets": [ [ 434, 457 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013345" } ] }, { "id": "16415", "type": "Chemical", "text": [ "Epinephrine" ], "offsets": [ [ 468, 479 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004837" } ] }, { "id": "16416", "type": "Disease", "text": [ "cardiac arrest" ], "offsets": [ [ 501, 515 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006323" } ] }, { "id": "16417", "type": "Disease", "text": [ "allergic reaction" ], "offsets": [ [ 591, 608 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "16418", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 620, 632 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] } ]

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[ { "id": "16419", "type": "CID", "arg1_id": "16406", "arg2_id": "16405", "normalized": [] }, { "id": "16420", "type": "CID", "arg1_id": "16406", "arg2_id": "16414", "normalized": [] }, { "id": "16421", "type": "CID", "arg1_id": "16412", "arg2_id": "16405", "normalized": [] }, { "id": "16422", "type": "CID", "arg1_id": "16412", "arg2_id": "16414", "normalized": [] }, { "id": "16423", "type": "CID", "arg1_id": "16415", "arg2_id": "16405", "normalized": [] }, { "id": "16424", "type": "CID", "arg1_id": "16415", "arg2_id": "16414", "normalized": [] }, { "id": "16425", "type": "CID", "arg1_id": "16406", "arg2_id": "16413", "normalized": [] }, { "id": "16426", "type": "CID", "arg1_id": "16406", "arg2_id": "16416", "normalized": [] }, { "id": "16427", "type": "CID", "arg1_id": "16412", "arg2_id": "16413", "normalized": [] }, { "id": "16428", "type": "CID", "arg1_id": "16412", "arg2_id": "16416", "normalized": [] }, { "id": "16429", "type": "CID", "arg1_id": "16415", "arg2_id": "16413", "normalized": [] }, { "id": "16430", "type": "CID", "arg1_id": "16415", "arg2_id": "16416", "normalized": [] } ]

[ { "id": "16432", "type": "title", "text": [ "A case of massive rhabdomyolysis following molindone administration." ], "offsets": [ [ 0, 68 ] ] }, { "id": "16433", "type": "abstract", "text": [ "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction." ], "offsets": [ [ 69, 509 ] ] } ]

[ { "id": "16434", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 18, 32 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16435", "type": "Chemical", "text": [ "molindone" ], "offsets": [ [ 43, 52 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008972" } ] }, { "id": "16436", "type": "Disease", "text": [ "Rhabdomyolysis" ], "offsets": [ [ 69, 83 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16437", "type": "Disease", "text": [ "psychiatric" ], "offsets": [ [ 122, 133 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001523" } ] }, { "id": "16438", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 255, 269 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16439", "type": "Disease", "text": [ "schizophrenic" ], "offsets": [ [ 299, 312 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012559" } ] }, { "id": "16440", "type": "Disease", "text": [ "rhabdomyolysis" ], "offsets": [ [ 355, 369 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012206" } ] }, { "id": "16441", "type": "Disease", "text": [ "acute renal failure" ], "offsets": [ [ 385, 404 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" } ] }, { "id": "16442", "type": "Chemical", "text": [ "molindone" ], "offsets": [ [ 415, 424 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008972" } ] }, { "id": "16443", "type": "Chemical", "text": [ "molindone" ], "offsets": [ [ 466, 475 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008972" } ] } ]

[]

[]

[ { "id": "16444", "type": "CID", "arg1_id": "16435", "arg2_id": "16434", "normalized": [] }, { "id": "16445", "type": "CID", "arg1_id": "16435", "arg2_id": "16436", "normalized": [] }, { "id": "16446", "type": "CID", "arg1_id": "16435", "arg2_id": "16438", "normalized": [] }, { "id": "16447", "type": "CID", "arg1_id": "16435", "arg2_id": "16440", "normalized": [] }, { "id": "16448", "type": "CID", "arg1_id": "16442", "arg2_id": "16434", "normalized": [] }, { "id": "16449", "type": "CID", "arg1_id": "16442", "arg2_id": "16436", "normalized": [] }, { "id": "16450", "type": "CID", "arg1_id": "16442", "arg2_id": "16438", "normalized": [] }, { "id": "16451", "type": "CID", "arg1_id": "16442", "arg2_id": "16440", "normalized": [] }, { "id": "16452", "type": "CID", "arg1_id": "16443", "arg2_id": "16434", "normalized": [] }, { "id": "16453", "type": "CID", "arg1_id": "16443", "arg2_id": "16436", "normalized": [] }, { "id": "16454", "type": "CID", "arg1_id": "16443", "arg2_id": "16438", "normalized": [] }, { "id": "16455", "type": "CID", "arg1_id": "16443", "arg2_id": "16440", "normalized": [] }, { "id": "16456", "type": "CID", "arg1_id": "16435", "arg2_id": "16441", "normalized": [] }, { "id": "16457", "type": "CID", "arg1_id": "16442", "arg2_id": "16441", "normalized": [] }, { "id": "16458", "type": "CID", "arg1_id": "16443", "arg2_id": "16441", "normalized": [] } ]

[ { "id": "16460", "type": "title", "text": [ "Cardiovascular alterations in rat fetuses exposed to calcium channel blockers." ], "offsets": [ [ 0, 78 ] ] }, { "id": "16461", "type": "abstract", "text": [ "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil." ], "offsets": [ [ 79, 1117 ] ] } ]

[ { "id": "16462", "type": "Disease", "text": [ "Cardiovascular alterations" ], "offsets": [ [ 0, 26 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018376" } ] }, { "id": "16463", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 53, 60 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16464", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 138, 145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16465", "type": "Chemical", "text": [ "Ro 40-5967" ], "offsets": [ [ 163, 173 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020748" } ] }, { "id": "16466", "type": "Disease", "text": [ "cardiovascular alterations" ], "offsets": [ [ 183, 209 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018376" } ] }, { "id": "16467", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 335, 342 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16468", "type": "Disease", "text": [ "cardiovascular malformations" ], "offsets": [ [ 378, 406 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018376" } ] }, { "id": "16469", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 465, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16470", "type": "Chemical", "text": [ "nifedipine" ], "offsets": [ [ 514, 524 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009543" } ] }, { "id": "16471", "type": "Chemical", "text": [ "diltiazem" ], "offsets": [ [ 526, 535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004110" } ] }, { "id": "16472", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 541, 550 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "16473", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 623, 630 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16474", "type": "Disease", "text": [ "cardiovascular malformations" ], "offsets": [ [ 745, 773 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018376" } ] }, { "id": "16475", "type": "Disease", "text": [ "cardiovascular malformations" ], "offsets": [ [ 794, 822 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018376" } ] }, { "id": "16476", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 871, 878 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16477", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 955, 964 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "16478", "type": "Chemical", "text": [ "nifedipine" ], "offsets": [ [ 969, 979 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009543" } ] }, { "id": "16479", "type": "Chemical", "text": [ "Ro 40-5967" ], "offsets": [ [ 1092, 1102 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020748" } ] }, { "id": "16480", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 1107, 1116 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] } ]

[]

[]

[ { "id": "16481", "type": "CID", "arg1_id": "16472", "arg2_id": "16462", "normalized": [] }, { "id": "16482", "type": "CID", "arg1_id": "16472", "arg2_id": "16466", "normalized": [] }, { "id": "16483", "type": "CID", "arg1_id": "16472", "arg2_id": "16468", "normalized": [] }, { "id": "16484", "type": "CID", "arg1_id": "16472", "arg2_id": "16474", "normalized": [] }, { "id": "16485", "type": "CID", "arg1_id": "16472", "arg2_id": "16475", "normalized": [] }, { "id": "16486", "type": "CID", "arg1_id": "16477", "arg2_id": "16462", "normalized": [] }, { "id": "16487", "type": "CID", "arg1_id": "16477", "arg2_id": "16466", "normalized": [] }, { "id": "16488", "type": "CID", "arg1_id": "16477", "arg2_id": "16468", "normalized": [] }, { "id": "16489", "type": "CID", "arg1_id": "16477", "arg2_id": "16474", "normalized": [] }, { "id": "16490", "type": "CID", "arg1_id": "16477", "arg2_id": "16475", "normalized": [] }, { "id": "16491", "type": "CID", "arg1_id": "16480", "arg2_id": "16462", "normalized": [] }, { "id": "16492", "type": "CID", "arg1_id": "16480", "arg2_id": "16466", "normalized": [] }, { "id": "16493", "type": "CID", "arg1_id": "16480", "arg2_id": "16468", "normalized": [] }, { "id": "16494", "type": "CID", "arg1_id": "16480", "arg2_id": "16474", "normalized": [] }, { "id": "16495", "type": "CID", "arg1_id": "16480", "arg2_id": "16475", "normalized": [] }, { "id": "16496", "type": "CID", "arg1_id": "16470", "arg2_id": "16462", "normalized": [] }, { "id": "16497", "type": "CID", "arg1_id": "16470", "arg2_id": "16466", "normalized": [] }, { "id": "16498", "type": "CID", "arg1_id": "16470", "arg2_id": "16468", "normalized": [] }, { "id": "16499", "type": "CID", "arg1_id": "16470", "arg2_id": "16474", "normalized": [] }, { "id": "16500", "type": "CID", "arg1_id": "16470", "arg2_id": "16475", "normalized": [] }, { "id": "16501", "type": "CID", "arg1_id": "16478", "arg2_id": "16462", "normalized": [] }, { "id": "16502", "type": "CID", "arg1_id": "16478", "arg2_id": "16466", "normalized": [] }, { "id": "16503", "type": "CID", "arg1_id": "16478", "arg2_id": "16468", "normalized": [] }, { "id": "16504", "type": "CID", "arg1_id": "16478", "arg2_id": "16474", "normalized": [] }, { "id": "16505", "type": "CID", "arg1_id": "16478", "arg2_id": "16475", "normalized": [] }, { "id": "16506", "type": "CID", "arg1_id": "16465", "arg2_id": "16462", "normalized": [] }, { "id": "16507", "type": "CID", "arg1_id": "16465", "arg2_id": "16466", "normalized": [] }, { "id": "16508", "type": "CID", "arg1_id": "16465", "arg2_id": "16468", "normalized": [] }, { "id": "16509", "type": "CID", "arg1_id": "16465", "arg2_id": "16474", "normalized": [] }, { "id": "16510", "type": "CID", "arg1_id": "16465", "arg2_id": "16475", "normalized": [] }, { "id": "16511", "type": "CID", "arg1_id": "16479", "arg2_id": "16462", "normalized": [] }, { "id": "16512", "type": "CID", "arg1_id": "16479", "arg2_id": "16466", "normalized": [] }, { "id": "16513", "type": "CID", "arg1_id": "16479", "arg2_id": "16468", "normalized": [] }, { "id": "16514", "type": "CID", "arg1_id": "16479", "arg2_id": "16474", "normalized": [] }, { "id": "16515", "type": "CID", "arg1_id": "16479", "arg2_id": "16475", "normalized": [] } ]

[ { "id": "16517", "type": "title", "text": [ "Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains." ], "offsets": [ [ 0, 165 ] ] }, { "id": "16518", "type": "abstract", "text": [ "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns." ], "offsets": [ [ 166, 2009 ] ] } ]

[ { "id": "16519", "type": "Chemical", "text": [ "lamivudine" ], "offsets": [ [ 85, 95 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16520", "type": "Chemical", "text": [ "hepatitis B virus e antigen" ], "offsets": [ [ 106, 133 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006513" } ] }, { "id": "16521", "type": "Disease", "text": [ "hepatitis B" ], "offsets": [ [ 196, 207 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006509" } ] }, { "id": "16522", "type": "Chemical", "text": [ "lamivudine" ], "offsets": [ [ 774, 784 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16523", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 786, 789 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16524", "type": "Chemical", "text": [ "HBeAg" ], "offsets": [ [ 798, 803 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006513" } ] }, { "id": "16525", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 876, 879 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16526", "type": "Chemical", "text": [ "HBeAg" ], "offsets": [ [ 941, 946 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006513" } ] }, { "id": "16527", "type": "Chemical", "text": [ "HBeAg" ], "offsets": [ [ 963, 968 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006513" } ] }, { "id": "16528", "type": "Chemical", "text": [ "HBsAg" ], "offsets": [ [ 1083, 1088 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006514" } ] }, { "id": "16529", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 1154, 1157 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16530", "type": "Chemical", "text": [ "HBsAg" ], "offsets": [ [ 1319, 1324 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006514" } ] }, { "id": "16531", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 1374, 1377 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16532", "type": "Chemical", "text": [ "HBeAg" ], "offsets": [ [ 1435, 1440 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006513" } ] }, { "id": "16533", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 1474, 1477 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16534", "type": "Chemical", "text": [ "LAM" ], "offsets": [ [ 1606, 1609 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "16535", "type": "Chemical", "text": [ "nucleotide" ], "offsets": [ [ 1636, 1646 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009711" } ] }, { "id": "16536", "type": "Chemical", "text": [ "adefovir" ], "offsets": [ [ 1657, 1665 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C053001" } ] }, { "id": "16537", "type": "Chemical", "text": [ "tenofovir" ], "offsets": [ [ 1670, 1679 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C096918" } ] } ]

[]

[]

[ { "id": "16538", "type": "CID", "arg1_id": "16528", "arg2_id": "16521", "normalized": [] }, { "id": "16539", "type": "CID", "arg1_id": "16530", "arg2_id": "16521", "normalized": [] }, { "id": "16540", "type": "CID", "arg1_id": "16520", "arg2_id": "16521", "normalized": [] }, { "id": "16541", "type": "CID", "arg1_id": "16524", "arg2_id": "16521", "normalized": [] }, { "id": "16542", "type": "CID", "arg1_id": "16526", "arg2_id": "16521", "normalized": [] }, { "id": "16543", "type": "CID", "arg1_id": "16527", "arg2_id": "16521", "normalized": [] }, { "id": "16544", "type": "CID", "arg1_id": "16532", "arg2_id": "16521", "normalized": [] } ]

[ { "id": "16546", "type": "title", "text": [ "The effects of sevoflurane on lidocaine-induced convulsions." ], "offsets": [ [ 0, 60 ] ] }, { "id": "16547", "type": "abstract", "text": [ "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression." ], "offsets": [ [ 61, 1495 ] ] } ]

[ { "id": "16548", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 15, 26 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16549", "type": "Chemical", "text": [ "lidocaine" ], "offsets": [ [ 30, 39 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008012" } ] }, { "id": "16550", "type": "Disease", "text": [ "convulsions" ], "offsets": [ [ 48, 59 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16551", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 78, 89 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16552", "type": "Chemical", "text": [ "lidocaine" ], "offsets": [ [ 93, 102 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008012" } ] }, { "id": "16553", "type": "Disease", "text": [ "convulsions" ], "offsets": [ [ 111, 122 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16554", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 148, 158 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16555", "type": "Chemical", "text": [ "lidocaine" ], "offsets": [ [ 215, 224 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008012" } ] }, { "id": "16556", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 345, 356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16557", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 427, 438 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16558", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 481, 492 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16559", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 566, 576 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16560", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 595, 606 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16561", "type": "Chemical", "text": [ "enflurane" ], "offsets": [ [ 611, 620 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004737" } ] }, { "id": "16562", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 698, 709 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16563", "type": "Chemical", "text": [ "enflurane" ], "offsets": [ [ 713, 722 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004737" } ] }, { "id": "16564", "type": "Disease", "text": [ "convulsions" ], "offsets": [ [ 767, 778 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16565", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 811, 822 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16566", "type": "Chemical", "text": [ "enflurane" ], "offsets": [ [ 845, 854 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004737" } ] }, { "id": "16567", "type": "Chemical", "text": [ "lidocaine" ], "offsets": [ [ 908, 917 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008012" } ] }, { "id": "16568", "type": "Chemical", "text": [ "Apamin" ], "offsets": [ [ 991, 997 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001030" } ] }, { "id": "16569", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 1022, 1029 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "16570", "type": "Chemical", "text": [ "potassium" ], "offsets": [ [ 1040, 1049 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011188" } ] }, { "id": "16571", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 1134, 1145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16572", "type": "Chemical", "text": [ "Apamin" ], "offsets": [ [ 1206, 1212 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001030" } ] }, { "id": "16573", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 1252, 1262 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16574", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 1379, 1390 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "16575", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 1403, 1413 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "16576", "type": "Chemical", "text": [ "lidocaine" ], "offsets": [ [ 1424, 1433 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008012" } ] }, { "id": "16577", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1434, 1442 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16578", "type": "Disease", "text": [ "depression" ], "offsets": [ [ 1484, 1494 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003866" } ] } ]

[]

[]

[ { "id": "16579", "type": "CID", "arg1_id": "16549", "arg2_id": "16550", "normalized": [] }, { "id": "16580", "type": "CID", "arg1_id": "16549", "arg2_id": "16553", "normalized": [] }, { "id": "16581", "type": "CID", "arg1_id": "16549", "arg2_id": "16554", "normalized": [] }, { "id": "16582", "type": "CID", "arg1_id": "16549", "arg2_id": "16559", "normalized": [] }, { "id": "16583", "type": "CID", "arg1_id": "16549", "arg2_id": "16564", "normalized": [] }, { "id": "16584", "type": "CID", "arg1_id": "16549", "arg2_id": "16573", "normalized": [] }, { "id": "16585", "type": "CID", "arg1_id": "16549", "arg2_id": "16575", "normalized": [] }, { "id": "16586", "type": "CID", "arg1_id": "16552", "arg2_id": "16550", "normalized": [] }, { "id": "16587", "type": "CID", "arg1_id": "16552", "arg2_id": "16553", "normalized": [] }, { "id": "16588", "type": "CID", "arg1_id": "16552", "arg2_id": "16554", "normalized": [] }, { "id": "16589", "type": "CID", "arg1_id": "16552", "arg2_id": "16559", "normalized": [] }, { "id": "16590", "type": "CID", "arg1_id": "16552", "arg2_id": "16564", "normalized": [] }, { "id": "16591", "type": "CID", "arg1_id": "16552", "arg2_id": "16573", "normalized": [] }, { "id": "16592", "type": "CID", "arg1_id": "16552", "arg2_id": "16575", "normalized": [] }, { "id": "16593", "type": "CID", "arg1_id": "16555", "arg2_id": "16550", "normalized": [] }, { "id": "16594", "type": "CID", "arg1_id": "16555", "arg2_id": "16553", "normalized": [] }, { "id": "16595", "type": "CID", "arg1_id": "16555", "arg2_id": "16554", "normalized": [] }, { "id": "16596", "type": "CID", "arg1_id": "16555", "arg2_id": "16559", "normalized": [] }, { "id": "16597", "type": "CID", "arg1_id": "16555", "arg2_id": "16564", "normalized": [] }, { "id": "16598", "type": "CID", "arg1_id": "16555", "arg2_id": "16573", "normalized": [] }, { "id": "16599", "type": "CID", "arg1_id": "16555", "arg2_id": "16575", "normalized": [] }, { "id": "16600", "type": "CID", "arg1_id": "16567", "arg2_id": "16550", "normalized": [] }, { "id": "16601", "type": "CID", "arg1_id": "16567", "arg2_id": "16553", "normalized": [] }, { "id": "16602", "type": "CID", "arg1_id": "16567", "arg2_id": "16554", "normalized": [] }, { "id": "16603", "type": "CID", "arg1_id": "16567", "arg2_id": "16559", "normalized": [] }, { "id": "16604", "type": "CID", "arg1_id": "16567", "arg2_id": "16564", "normalized": [] }, { "id": "16605", "type": "CID", "arg1_id": "16567", "arg2_id": "16573", "normalized": [] }, { "id": "16606", "type": "CID", "arg1_id": "16567", "arg2_id": "16575", "normalized": [] }, { "id": "16607", "type": "CID", "arg1_id": "16576", "arg2_id": "16550", "normalized": [] }, { "id": "16608", "type": "CID", "arg1_id": "16576", "arg2_id": "16553", "normalized": [] }, { "id": "16609", "type": "CID", "arg1_id": "16576", "arg2_id": "16554", "normalized": [] }, { "id": "16610", "type": "CID", "arg1_id": "16576", "arg2_id": "16559", "normalized": [] }, { "id": "16611", "type": "CID", "arg1_id": "16576", "arg2_id": "16564", "normalized": [] }, { "id": "16612", "type": "CID", "arg1_id": "16576", "arg2_id": "16573", "normalized": [] }, { "id": "16613", "type": "CID", "arg1_id": "16576", "arg2_id": "16575", "normalized": [] } ]

[ { "id": "16615", "type": "title", "text": [ "Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat." ], "offsets": [ [ 0, 86 ] ] }, { "id": "16616", "type": "abstract", "text": [ "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats." ], "offsets": [ [ 87, 2015 ] ] } ]

[ { "id": "16617", "type": "Chemical", "text": [ "atorvastatin" ], "offsets": [ [ 24, 36 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16618", "type": "Chemical", "text": [ "dexamethasone" ], "offsets": [ [ 40, 53 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16619", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 62, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "16620", "type": "Chemical", "text": [ "Dexamethasone" ], "offsets": [ [ 90, 103 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16621", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 105, 108 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16622", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 118, 130 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "16623", "type": "Chemical", "text": [ "nitric oxide" ], "offsets": [ [ 191, 203 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009569" } ] }, { "id": "16624", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 205, 207 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009569" } ] }, { "id": "16625", "type": "Chemical", "text": [ "superoxide" ], "offsets": [ [ 234, 244 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16626", "type": "Chemical", "text": [ "O2-" ], "offsets": [ [ 246, 249 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16627", "type": "Chemical", "text": [ "Atorvastatin" ], "offsets": [ [ 263, 275 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16628", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 277, 280 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16629", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 405, 407 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009569" } ] }, { "id": "16630", "type": "Chemical", "text": [ "O2-" ], "offsets": [ [ 420, 423 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16631", "type": "Disease", "text": [ "hypertension" ], "offsets": [ [ 455, 467 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006973" } ] }, { "id": "16632", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 539, 542 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16633", "type": "Chemical", "text": [ "NO" ], "offsets": [ [ 569, 571 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009569" } ] }, { "id": "16634", "type": "Chemical", "text": [ "O2-" ], "offsets": [ [ 623, 626 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16635", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 732, 735 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16636", "type": "Chemical", "text": [ "Dexamethasone" ], "offsets": [ [ 799, 812 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16637", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 880, 883 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16638", "type": "Chemical", "text": [ "acetylcholine" ], "offsets": [ [ 1069, 1082 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000109" } ] }, { "id": "16639", "type": "Chemical", "text": [ "phenylephrine" ], "offsets": [ [ 1110, 1123 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010656" } ] }, { "id": "16640", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1295, 1298 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16641", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 1412, 1415 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16642", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1418, 1421 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16643", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1586, 1589 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16644", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1686, 1689 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16645", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 1692, 1695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16646", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1714, 1717 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16647", "type": "Chemical", "text": [ "superoxide" ], "offsets": [ [ 1777, 1787 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16648", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1816, 1819 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16649", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 1822, 1825 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16650", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1869, 1872 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "16651", "type": "Chemical", "text": [ "Ato" ], "offsets": [ [ 1911, 1914 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C065179" } ] }, { "id": "16652", "type": "Chemical", "text": [ "superoxide" ], "offsets": [ [ 1954, 1964 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "16653", "type": "Chemical", "text": [ "Dex" ], "offsets": [ [ 1995, 1998 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] } ]

[]

[]

[ { "id": "16654", "type": "CID", "arg1_id": "16618", "arg2_id": "16619", "normalized": [] }, { "id": "16655", "type": "CID", "arg1_id": "16618", "arg2_id": "16622", "normalized": [] }, { "id": "16656", "type": "CID", "arg1_id": "16618", "arg2_id": "16631", "normalized": [] }, { "id": "16657", "type": "CID", "arg1_id": "16620", "arg2_id": "16619", "normalized": [] }, { "id": "16658", "type": "CID", "arg1_id": "16620", "arg2_id": "16622", "normalized": [] }, { "id": "16659", "type": "CID", "arg1_id": "16620", "arg2_id": "16631", "normalized": [] }, { "id": "16660", "type": "CID", "arg1_id": "16621", "arg2_id": "16619", "normalized": [] }, { "id": "16661", "type": "CID", "arg1_id": "16621", "arg2_id": "16622", "normalized": [] }, { "id": "16662", "type": "CID", "arg1_id": "16621", "arg2_id": "16631", "normalized": [] }, { "id": "16663", "type": "CID", "arg1_id": "16636", "arg2_id": "16619", "normalized": [] }, { "id": "16664", "type": "CID", "arg1_id": "16636", "arg2_id": "16622", "normalized": [] }, { "id": "16665", "type": "CID", "arg1_id": "16636", "arg2_id": "16631", "normalized": [] }, { "id": "16666", "type": "CID", "arg1_id": "16640", "arg2_id": "16619", "normalized": [] }, { "id": "16667", "type": "CID", "arg1_id": "16640", "arg2_id": "16622", "normalized": [] }, { "id": "16668", "type": "CID", "arg1_id": "16640", "arg2_id": "16631", "normalized": [] }, { "id": "16669", "type": "CID", "arg1_id": "16642", "arg2_id": "16619", "normalized": [] }, { "id": "16670", "type": "CID", "arg1_id": "16642", "arg2_id": "16622", "normalized": [] }, { "id": "16671", "type": "CID", "arg1_id": "16642", "arg2_id": "16631", "normalized": [] }, { "id": "16672", "type": "CID", "arg1_id": "16643", "arg2_id": "16619", "normalized": [] }, { "id": "16673", "type": "CID", "arg1_id": "16643", "arg2_id": "16622", "normalized": [] }, { "id": "16674", "type": "CID", "arg1_id": "16643", "arg2_id": "16631", "normalized": [] }, { "id": "16675", "type": "CID", "arg1_id": "16644", "arg2_id": "16619", "normalized": [] }, { "id": "16676", "type": "CID", "arg1_id": "16644", "arg2_id": "16622", "normalized": [] }, { "id": "16677", "type": "CID", "arg1_id": "16644", "arg2_id": "16631", "normalized": [] }, { "id": "16678", "type": "CID", "arg1_id": "16646", "arg2_id": "16619", "normalized": [] }, { "id": "16679", "type": "CID", "arg1_id": "16646", "arg2_id": "16622", "normalized": [] }, { "id": "16680", "type": "CID", "arg1_id": "16646", "arg2_id": "16631", "normalized": [] }, { "id": "16681", "type": "CID", "arg1_id": "16648", "arg2_id": "16619", "normalized": [] }, { "id": "16682", "type": "CID", "arg1_id": "16648", "arg2_id": "16622", "normalized": [] }, { "id": "16683", "type": "CID", "arg1_id": "16648", "arg2_id": "16631", "normalized": [] }, { "id": "16684", "type": "CID", "arg1_id": "16650", "arg2_id": "16619", "normalized": [] }, { "id": "16685", "type": "CID", "arg1_id": "16650", "arg2_id": "16622", "normalized": [] }, { "id": "16686", "type": "CID", "arg1_id": "16650", "arg2_id": "16631", "normalized": [] }, { "id": "16687", "type": "CID", "arg1_id": "16653", "arg2_id": "16619", "normalized": [] }, { "id": "16688", "type": "CID", "arg1_id": "16653", "arg2_id": "16622", "normalized": [] }, { "id": "16689", "type": "CID", "arg1_id": "16653", "arg2_id": "16631", "normalized": [] } ]

[ { "id": "16691", "type": "title", "text": [ "99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats." ], "offsets": [ [ 0, 85 ] ] }, { "id": "16692", "type": "abstract", "text": [ "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction." ], "offsets": [ [ 86, 1215 ] ] } ]

[ { "id": "16693", "type": "Chemical", "text": [ "99mTc-glucarate" ], "offsets": [ [ 0, 15 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C067171" } ] }, { "id": "16694", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 33, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "16695", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 55, 76 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "16696", "type": "Disease", "text": [ "Infarct" ], "offsets": [ [ 86, 93 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007238" } ] }, { "id": "16697", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 174, 195 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "16698", "type": "Disease", "text": [ "infarction" ], "offsets": [ [ 230, 240 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007238" } ] }, { "id": "16699", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 316, 329 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "16700", "type": "Disease", "text": [ "infarct" ], "offsets": [ [ 337, 344 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007238" } ] }, { "id": "16701", "type": "Chemical", "text": [ "glucaric acid" ], "offsets": [ [ 379, 392 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005937" } ] }, { "id": "16702", "type": "Chemical", "text": [ "99mTc-glucarate" ], "offsets": [ [ 452, 467 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C067171" } ] }, { "id": "16703", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 560, 573 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "16704", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 588, 609 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "16705", "type": "Disease", "text": [ "infarct" ], "offsets": [ [ 672, 679 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007238" } ] }, { "id": "16706", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 691, 704 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "16707", "type": "Chemical", "text": [ "99mTc-glucarate" ], "offsets": [ [ 822, 837 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C067171" } ] }, { "id": "16708", "type": "Disease", "text": [ "cardiac infarction" ], "offsets": [ [ 1196, 1214 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] } ]

[]

[]

[ { "id": "16709", "type": "CID", "arg1_id": "16694", "arg2_id": "16695", "normalized": [] }, { "id": "16710", "type": "CID", "arg1_id": "16694", "arg2_id": "16697", "normalized": [] }, { "id": "16711", "type": "CID", "arg1_id": "16694", "arg2_id": "16704", "normalized": [] }, { "id": "16712", "type": "CID", "arg1_id": "16694", "arg2_id": "16708", "normalized": [] }, { "id": "16713", "type": "CID", "arg1_id": "16699", "arg2_id": "16695", "normalized": [] }, { "id": "16714", "type": "CID", "arg1_id": "16699", "arg2_id": "16697", "normalized": [] }, { "id": "16715", "type": "CID", "arg1_id": "16699", "arg2_id": "16704", "normalized": [] }, { "id": "16716", "type": "CID", "arg1_id": "16699", "arg2_id": "16708", "normalized": [] }, { "id": "16717", "type": "CID", "arg1_id": "16703", "arg2_id": "16695", "normalized": [] }, { "id": "16718", "type": "CID", "arg1_id": "16703", "arg2_id": "16697", "normalized": [] }, { "id": "16719", "type": "CID", "arg1_id": "16703", "arg2_id": "16704", "normalized": [] }, { "id": "16720", "type": "CID", "arg1_id": "16703", "arg2_id": "16708", "normalized": [] }, { "id": "16721", "type": "CID", "arg1_id": "16706", "arg2_id": "16695", "normalized": [] }, { "id": "16722", "type": "CID", "arg1_id": "16706", "arg2_id": "16697", "normalized": [] }, { "id": "16723", "type": "CID", "arg1_id": "16706", "arg2_id": "16704", "normalized": [] }, { "id": "16724", "type": "CID", "arg1_id": "16706", "arg2_id": "16708", "normalized": [] } ]

[ { "id": "16726", "type": "title", "text": [ "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease." ], "offsets": [ [ 0, 132 ] ] }, { "id": "16727", "type": "abstract", "text": [ "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors." ], "offsets": [ [ 133, 1984 ] ] } ]

[ { "id": "16728", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 58, 69 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16729", "type": "Disease", "text": [ "psychosis" ], "offsets": [ [ 74, 83 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011618" } ] }, { "id": "16730", "type": "Disease", "text": [ "disruptive behaviors" ], "offsets": [ [ 88, 108 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019958" } ] }, { "id": "16731", "type": "Disease", "text": [ "Alzheimer's disease" ], "offsets": [ [ 112, 131 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000544" } ] }, { "id": "16732", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 228, 239 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16733", "type": "Disease", "text": [ "psychosis" ], "offsets": [ [ 272, 281 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011618" } ] }, { "id": "16734", "type": "Disease", "text": [ "disruptive behaviors" ], "offsets": [ [ 286, 306 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019958" } ] }, { "id": "16735", "type": "Disease", "text": [ "Alzheimer's disease" ], "offsets": [ [ 324, 343 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000544" } ] }, { "id": "16736", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 434, 445 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16737", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 479, 490 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16738", "type": "Disease", "text": [ "Alzheimer's disease" ], "offsets": [ [ 558, 577 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000544" } ] }, { "id": "16739", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 683, 694 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16740", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 797, 808 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16741", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 876, 887 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16742", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 934, 945 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16743", "type": "Disease", "text": [ "psychosis" ], "offsets": [ [ 1007, 1016 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011618" } ] }, { "id": "16744", "type": "Disease", "text": [ "psychomotor agitation" ], "offsets": [ [ 1031, 1052 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011595" } ] }, { "id": "16745", "type": "Disease", "text": [ "extrapyramidal signs" ], "offsets": [ [ 1286, 1306 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "16746", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 1472, 1483 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16747", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 1627, 1638 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16748", "type": "Disease", "text": [ "extrapyramidal signs" ], "offsets": [ [ 1712, 1732 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "16749", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 1858, 1869 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "16750", "type": "Disease", "text": [ "Alzheimer's disease" ], "offsets": [ [ 1915, 1934 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000544" } ] }, { "id": "16751", "type": "Disease", "text": [ "psychosis" ], "offsets": [ [ 1949, 1958 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011618" } ] }, { "id": "16752", "type": "Disease", "text": [ "disruptive behaviors" ], "offsets": [ [ 1963, 1983 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019958" } ] } ]

[]

[]

[ { "id": "16753", "type": "CID", "arg1_id": "16728", "arg2_id": "16745", "normalized": [] }, { "id": "16754", "type": "CID", "arg1_id": "16728", "arg2_id": "16748", "normalized": [] }, { "id": "16755", "type": "CID", "arg1_id": "16732", "arg2_id": "16745", "normalized": [] }, { "id": "16756", "type": "CID", "arg1_id": "16732", "arg2_id": "16748", "normalized": [] }, { "id": "16757", "type": "CID", "arg1_id": "16736", "arg2_id": "16745", "normalized": [] }, { "id": "16758", "type": "CID", "arg1_id": "16736", "arg2_id": "16748", "normalized": [] }, { "id": "16759", "type": "CID", "arg1_id": "16737", "arg2_id": "16745", "normalized": [] }, { "id": "16760", "type": "CID", "arg1_id": "16737", "arg2_id": "16748", "normalized": [] }, { "id": "16761", "type": "CID", "arg1_id": "16739", "arg2_id": "16745", "normalized": [] }, { "id": "16762", "type": "CID", "arg1_id": "16739", "arg2_id": "16748", "normalized": [] }, { "id": "16763", "type": "CID", "arg1_id": "16740", "arg2_id": "16745", "normalized": [] }, { "id": "16764", "type": "CID", "arg1_id": "16740", "arg2_id": "16748", "normalized": [] }, { "id": "16765", "type": "CID", "arg1_id": "16741", "arg2_id": "16745", "normalized": [] }, { "id": "16766", "type": "CID", "arg1_id": "16741", "arg2_id": "16748", "normalized": [] }, { "id": "16767", "type": "CID", "arg1_id": "16742", "arg2_id": "16745", "normalized": [] }, { "id": "16768", "type": "CID", "arg1_id": "16742", "arg2_id": "16748", "normalized": [] }, { "id": "16769", "type": "CID", "arg1_id": "16746", "arg2_id": "16745", "normalized": [] }, { "id": "16770", "type": "CID", "arg1_id": "16746", "arg2_id": "16748", "normalized": [] }, { "id": "16771", "type": "CID", "arg1_id": "16747", "arg2_id": "16745", "normalized": [] }, { "id": "16772", "type": "CID", "arg1_id": "16747", "arg2_id": "16748", "normalized": [] }, { "id": "16773", "type": "CID", "arg1_id": "16749", "arg2_id": "16745", "normalized": [] }, { "id": "16774", "type": "CID", "arg1_id": "16749", "arg2_id": "16748", "normalized": [] } ]

[ { "id": "16776", "type": "title", "text": [ "Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage." ], "offsets": [ [ 0, 119 ] ] }, { "id": "16777", "type": "abstract", "text": [ "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage." ], "offsets": [ [ 120, 1858 ] ] } ]

[ { "id": "16778", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 87, 97 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16779", "type": "Disease", "text": [ "renal damage" ], "offsets": [ [ 106, 118 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16780", "type": "Chemical", "text": [ "angiotensin" ], "offsets": [ [ 155, 166 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000809" } ] }, { "id": "16781", "type": "Disease", "text": [ "renal damage" ], "offsets": [ [ 488, 500 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16782", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 534, 544 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16783", "type": "Chemical", "text": [ "Hip-His-Leu" ], "offsets": [ [ 583, 594 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C010980" } ] }, { "id": "16784", "type": "Disease", "text": [ "proteinuria" ], "offsets": [ [ 716, 727 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011507" } ] }, { "id": "16785", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 743, 753 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16786", "type": "Disease", "text": [ "Proteinuria" ], "offsets": [ [ 824, 835 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011507" } ] }, { "id": "16787", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 955, 965 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16788", "type": "Disease", "text": [ "nephrotic" ], "offsets": [ [ 975, 984 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009404" } ] }, { "id": "16789", "type": "Disease", "text": [ "proteinuria" ], "offsets": [ [ 991, 1002 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011507" } ] }, { "id": "16790", "type": "Disease", "text": [ "renal interstitial damage" ], "offsets": [ [ 1004, 1029 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16791", "type": "Disease", "text": [ "focal glomerulosclerosis" ], "offsets": [ [ 1039, 1063 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005923" } ] }, { "id": "16792", "type": "Disease", "text": [ "proteinuria" ], "offsets": [ [ 1132, 1143 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011507" } ] }, { "id": "16793", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 1150, 1160 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16794", "type": "Disease", "text": [ "focal glomerulosclerosis" ], "offsets": [ [ 1483, 1507 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005923" } ] }, { "id": "16795", "type": "Chemical", "text": [ "adriamycin" ], "offsets": [ [ 1675, 1685 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "16796", "type": "Disease", "text": [ "renal damage" ], "offsets": [ [ 1694, 1706 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16797", "type": "Disease", "text": [ "renal damage" ], "offsets": [ [ 1845, 1857 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] } ]

[]

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[ { "id": "16798", "type": "CID", "arg1_id": "16778", "arg2_id": "16784", "normalized": [] }, { "id": "16799", "type": "CID", "arg1_id": "16778", "arg2_id": "16786", "normalized": [] }, { "id": "16800", "type": "CID", "arg1_id": "16778", "arg2_id": "16789", "normalized": [] }, { "id": "16801", "type": "CID", "arg1_id": "16778", "arg2_id": "16792", "normalized": [] }, { "id": "16802", "type": "CID", "arg1_id": "16782", "arg2_id": "16784", "normalized": [] }, { "id": "16803", "type": "CID", "arg1_id": "16782", "arg2_id": "16786", "normalized": [] }, { "id": "16804", "type": "CID", "arg1_id": "16782", "arg2_id": "16789", "normalized": [] }, { "id": "16805", "type": "CID", "arg1_id": "16782", "arg2_id": "16792", "normalized": [] }, { "id": "16806", "type": "CID", "arg1_id": "16785", "arg2_id": "16784", "normalized": [] }, { "id": "16807", "type": "CID", "arg1_id": "16785", "arg2_id": "16786", "normalized": [] }, { "id": "16808", "type": "CID", "arg1_id": "16785", "arg2_id": "16789", "normalized": [] }, { "id": "16809", "type": "CID", "arg1_id": "16785", "arg2_id": "16792", "normalized": [] }, { "id": "16810", "type": "CID", "arg1_id": "16787", "arg2_id": "16784", "normalized": [] }, { "id": "16811", "type": "CID", "arg1_id": "16787", "arg2_id": "16786", "normalized": [] }, { "id": "16812", "type": "CID", "arg1_id": "16787", "arg2_id": "16789", "normalized": [] }, { "id": "16813", "type": "CID", "arg1_id": "16787", "arg2_id": "16792", "normalized": [] }, { "id": "16814", "type": "CID", "arg1_id": "16793", "arg2_id": "16784", "normalized": [] }, { "id": "16815", "type": "CID", "arg1_id": "16793", "arg2_id": "16786", "normalized": [] }, { "id": "16816", "type": "CID", "arg1_id": "16793", "arg2_id": "16789", "normalized": [] }, { "id": "16817", "type": "CID", "arg1_id": "16793", "arg2_id": "16792", "normalized": [] }, { "id": "16818", "type": "CID", "arg1_id": "16795", "arg2_id": "16784", "normalized": [] }, { "id": "16819", "type": "CID", "arg1_id": "16795", "arg2_id": "16786", "normalized": [] }, { "id": "16820", "type": "CID", "arg1_id": "16795", "arg2_id": "16789", "normalized": [] }, { "id": "16821", "type": "CID", "arg1_id": "16795", "arg2_id": "16792", "normalized": [] } ]

[ { "id": "16823", "type": "title", "text": [ "Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study." ], "offsets": [ [ 0, 74 ] ] }, { "id": "16824", "type": "abstract", "text": [ "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin." ], "offsets": [ [ 75, 931 ] ] } ]

[ { "id": "16825", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 9, 23 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16826", "type": "Chemical", "text": [ "tobramycin" ], "offsets": [ [ 27, 37 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014031" } ] }, { "id": "16827", "type": "Chemical", "text": [ "gentamicin" ], "offsets": [ [ 42, 52 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "16828", "type": "Chemical", "text": [ "aminoglycoside" ], "offsets": [ [ 125, 139 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000617" } ] }, { "id": "16829", "type": "Chemical", "text": [ "Gentamicin sulfate" ], "offsets": [ [ 162, 180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "16830", "type": "Chemical", "text": [ "tobramycin sulfate" ], "offsets": [ [ 185, 203 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014031" } ] }, { "id": "16831", "type": "Disease", "text": [ "ototoxicity" ], "offsets": [ [ 228, 239 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "16832", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 244, 258 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "16833", "type": "Chemical", "text": [ "gentamicin sulfate" ], "offsets": [ [ 405, 423 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "16834", "type": "Chemical", "text": [ "tobramycin sulfate" ], "offsets": [ [ 427, 445 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014031" } ] }, { "id": "16835", "type": "Chemical", "text": [ "aminoglycoside" ], "offsets": [ [ 528, 542 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000617" } ] }, { "id": "16836", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 551, 564 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "16837", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 669, 682 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "16838", "type": "Chemical", "text": [ "tobramycin" ], "offsets": [ [ 728, 738 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014031" } ] }, { "id": "16839", "type": "Chemical", "text": [ "gentamicin" ], "offsets": [ [ 784, 794 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "16840", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 816, 829 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "16841", "type": "Chemical", "text": [ "gentamicin" ], "offsets": [ [ 837, 847 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "16842", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 868, 881 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "16843", "type": "Chemical", "text": [ "tobramycin" ], "offsets": [ [ 920, 930 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014031" } ] } ]

[]

[]

[ { "id": "16844", "type": "CID", "arg1_id": "16827", "arg2_id": "16836", "normalized": [] }, { "id": "16845", "type": "CID", "arg1_id": "16827", "arg2_id": "16837", "normalized": [] }, { "id": "16846", "type": "CID", "arg1_id": "16827", "arg2_id": "16840", "normalized": [] }, { "id": "16847", "type": "CID", "arg1_id": "16827", "arg2_id": "16842", "normalized": [] }, { "id": "16848", "type": "CID", "arg1_id": "16829", "arg2_id": "16836", "normalized": [] }, { "id": "16849", "type": "CID", "arg1_id": "16829", "arg2_id": "16837", "normalized": [] }, { "id": "16850", "type": "CID", "arg1_id": "16829", "arg2_id": "16840", "normalized": [] }, { "id": "16851", "type": "CID", "arg1_id": "16829", "arg2_id": "16842", "normalized": [] }, { "id": "16852", "type": "CID", "arg1_id": "16833", "arg2_id": "16836", "normalized": [] }, { "id": "16853", "type": "CID", "arg1_id": "16833", "arg2_id": "16837", "normalized": [] }, { "id": "16854", "type": "CID", "arg1_id": "16833", "arg2_id": "16840", "normalized": [] }, { "id": "16855", "type": "CID", "arg1_id": "16833", "arg2_id": "16842", "normalized": [] }, { "id": "16856", "type": "CID", "arg1_id": "16839", "arg2_id": "16836", "normalized": [] }, { "id": "16857", "type": "CID", "arg1_id": "16839", "arg2_id": "16837", "normalized": [] }, { "id": "16858", "type": "CID", "arg1_id": "16839", "arg2_id": "16840", "normalized": [] }, { "id": "16859", "type": "CID", "arg1_id": "16839", "arg2_id": "16842", "normalized": [] }, { "id": "16860", "type": "CID", "arg1_id": "16841", "arg2_id": "16836", "normalized": [] }, { "id": "16861", "type": "CID", "arg1_id": "16841", "arg2_id": "16837", "normalized": [] }, { "id": "16862", "type": "CID", "arg1_id": "16841", "arg2_id": "16840", "normalized": [] }, { "id": "16863", "type": "CID", "arg1_id": "16841", "arg2_id": "16842", "normalized": [] }, { "id": "16864", "type": "CID", "arg1_id": "16826", "arg2_id": "16836", "normalized": [] }, { "id": "16865", "type": "CID", "arg1_id": "16826", "arg2_id": "16837", "normalized": [] }, { "id": "16866", "type": "CID", "arg1_id": "16826", "arg2_id": "16840", "normalized": [] }, { "id": "16867", "type": "CID", "arg1_id": "16826", "arg2_id": "16842", "normalized": [] }, { "id": "16868", "type": "CID", "arg1_id": "16830", "arg2_id": "16836", "normalized": [] }, { "id": "16869", "type": "CID", "arg1_id": "16830", "arg2_id": "16837", "normalized": [] }, { "id": "16870", "type": "CID", "arg1_id": "16830", "arg2_id": "16840", "normalized": [] }, { "id": "16871", "type": "CID", "arg1_id": "16830", "arg2_id": "16842", "normalized": [] }, { "id": "16872", "type": "CID", "arg1_id": "16834", "arg2_id": "16836", "normalized": [] }, { "id": "16873", "type": "CID", "arg1_id": "16834", "arg2_id": "16837", "normalized": [] }, { "id": "16874", "type": "CID", "arg1_id": "16834", "arg2_id": "16840", "normalized": [] }, { "id": "16875", "type": "CID", "arg1_id": "16834", "arg2_id": "16842", "normalized": [] }, { "id": "16876", "type": "CID", "arg1_id": "16838", "arg2_id": "16836", "normalized": [] }, { "id": "16877", "type": "CID", "arg1_id": "16838", "arg2_id": "16837", "normalized": [] }, { "id": "16878", "type": "CID", "arg1_id": "16838", "arg2_id": "16840", "normalized": [] }, { "id": "16879", "type": "CID", "arg1_id": "16838", "arg2_id": "16842", "normalized": [] }, { "id": "16880", "type": "CID", "arg1_id": "16843", "arg2_id": "16836", "normalized": [] }, { "id": "16881", "type": "CID", "arg1_id": "16843", "arg2_id": "16837", "normalized": [] }, { "id": "16882", "type": "CID", "arg1_id": "16843", "arg2_id": "16840", "normalized": [] }, { "id": "16883", "type": "CID", "arg1_id": "16843", "arg2_id": "16842", "normalized": [] } ]

[ { "id": "16885", "type": "title", "text": [ "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats." ], "offsets": [ [ 0, 206 ] ] }, { "id": "16886", "type": "abstract", "text": [ "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia." ], "offsets": [ [ 207, 1676 ] ] } ]

[ { "id": "16887", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 26, 30 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16888", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 66, 81 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16889", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 103, 116 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "16890", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 150, 158 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16891", "type": "Disease", "text": [ "hyperthermia" ], "offsets": [ [ 185, 197 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005334" } ] }, { "id": "16892", "type": "Chemical", "text": [ "glutamate" ], "offsets": [ [ 269, 278 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018698" } ] }, { "id": "16893", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 322, 337 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16894", "type": "Chemical", "text": [ "Methamphetamine" ], "offsets": [ [ 372, 387 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16895", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 450, 458 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16896", "type": "Chemical", "text": [ "2-methyl-6-(phenylethynyl)pyridine" ], "offsets": [ [ 577, 611 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16897", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 613, 617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16898", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 685, 700 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16899", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 740, 755 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16900", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 774, 778 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16901", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 834, 842 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16902", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 877, 885 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16903", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 915, 930 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16904", "type": "Chemical", "text": [ "veratridine" ], "offsets": [ [ 980, 991 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014701" } ] }, { "id": "16905", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 1046, 1061 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16906", "type": "Disease", "text": [ "hyperthermia" ], "offsets": [ [ 1084, 1096 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005334" } ] }, { "id": "16907", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 1133, 1137 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16908", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 1229, 1237 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16909", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 1381, 1385 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16910", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 1428, 1443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16911", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1452, 1460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "16912", "type": "Chemical", "text": [ "MPEP" ], "offsets": [ [ 1490, 1494 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121465" } ] }, { "id": "16913", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 1539, 1554 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "16914", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 1563, 1571 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "16915", "type": "Disease", "text": [ "hyperthermia" ], "offsets": [ [ 1663, 1675 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005334" } ] } ]

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[ { "id": "16916", "type": "CID", "arg1_id": "16888", "arg2_id": "16891", "normalized": [] }, { "id": "16917", "type": "CID", "arg1_id": "16888", "arg2_id": "16906", "normalized": [] }, { "id": "16918", "type": "CID", "arg1_id": "16888", "arg2_id": "16915", "normalized": [] }, { "id": "16919", "type": "CID", "arg1_id": "16893", "arg2_id": "16891", "normalized": [] }, { "id": "16920", "type": "CID", "arg1_id": "16893", "arg2_id": "16906", "normalized": [] }, { "id": "16921", "type": "CID", "arg1_id": "16893", "arg2_id": "16915", "normalized": [] }, { "id": "16922", "type": "CID", "arg1_id": "16894", "arg2_id": "16891", "normalized": [] }, { "id": "16923", "type": "CID", "arg1_id": "16894", "arg2_id": "16906", "normalized": [] }, { "id": "16924", "type": "CID", "arg1_id": "16894", "arg2_id": "16915", "normalized": [] }, { "id": "16925", "type": "CID", "arg1_id": "16898", "arg2_id": "16891", "normalized": [] }, { "id": "16926", "type": "CID", "arg1_id": "16898", "arg2_id": "16906", "normalized": [] }, { "id": "16927", "type": "CID", "arg1_id": "16898", "arg2_id": "16915", "normalized": [] }, { "id": "16928", "type": "CID", "arg1_id": "16899", "arg2_id": "16891", "normalized": [] }, { "id": "16929", "type": "CID", "arg1_id": "16899", "arg2_id": "16906", "normalized": [] }, { "id": "16930", "type": "CID", "arg1_id": "16899", "arg2_id": "16915", "normalized": [] }, { "id": "16931", "type": "CID", "arg1_id": "16903", "arg2_id": "16891", "normalized": [] }, { "id": "16932", "type": "CID", "arg1_id": "16903", "arg2_id": "16906", "normalized": [] }, { "id": "16933", "type": "CID", "arg1_id": "16903", "arg2_id": "16915", "normalized": [] }, { "id": "16934", "type": "CID", "arg1_id": "16905", "arg2_id": "16891", "normalized": [] }, { "id": "16935", "type": "CID", "arg1_id": "16905", "arg2_id": "16906", "normalized": [] }, { "id": "16936", "type": "CID", "arg1_id": "16905", "arg2_id": "16915", "normalized": [] }, { "id": "16937", "type": "CID", "arg1_id": "16910", "arg2_id": "16891", "normalized": [] }, { "id": "16938", "type": "CID", "arg1_id": "16910", "arg2_id": "16906", "normalized": [] }, { "id": "16939", "type": "CID", "arg1_id": "16910", "arg2_id": "16915", "normalized": [] }, { "id": "16940", "type": "CID", "arg1_id": "16913", "arg2_id": "16891", "normalized": [] }, { "id": "16941", "type": "CID", "arg1_id": "16913", "arg2_id": "16906", "normalized": [] }, { "id": "16942", "type": "CID", "arg1_id": "16913", "arg2_id": "16915", "normalized": [] } ]

[ { "id": "16944", "type": "title", "text": [ "Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl." ], "offsets": [ [ 0, 74 ] ] }, { "id": "16945", "type": "abstract", "text": [ "OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6." ], "offsets": [ [ 75, 1598 ] ] } ]

[ { "id": "16946", "type": "Chemical", "text": [ "desipramine HCl" ], "offsets": [ [ 20, 35 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16947", "type": "Chemical", "text": [ "cinacalcet HCl" ], "offsets": [ [ 59, 73 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16948", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 122, 132 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16949", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 251, 261 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16950", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 288, 299 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16951", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 518, 529 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16952", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 609, 619 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16953", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 771, 782 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16954", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 813, 824 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16955", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 878, 888 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16956", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 907, 918 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16957", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 935, 946 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16958", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 971, 981 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16959", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 1115, 1126 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16960", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 1153, 1164 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16961", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 1170, 1180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16962", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 1226, 1232 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "16963", "type": "Disease", "text": [ "headache" ], "offsets": [ [ 1237, 1245 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006261" } ] }, { "id": "16964", "type": "Chemical", "text": [ "desipramine" ], "offsets": [ [ 1299, 1310 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003891" } ] }, { "id": "16965", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 1314, 1324 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16966", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 1367, 1377 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] }, { "id": "16967", "type": "Chemical", "text": [ "cinacalcet" ], "offsets": [ [ 1469, 1479 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C476217" } ] } ]

[]

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[ { "id": "16968", "type": "CID", "arg1_id": "16946", "arg2_id": "16962", "normalized": [] }, { "id": "16969", "type": "CID", "arg1_id": "16950", "arg2_id": "16962", "normalized": [] }, { "id": "16970", "type": "CID", "arg1_id": "16951", "arg2_id": "16962", "normalized": [] }, { "id": "16971", "type": "CID", "arg1_id": "16953", "arg2_id": "16962", "normalized": [] }, { "id": "16972", "type": "CID", "arg1_id": "16954", "arg2_id": "16962", "normalized": [] }, { "id": "16973", "type": "CID", "arg1_id": "16956", "arg2_id": "16962", "normalized": [] }, { "id": "16974", "type": "CID", "arg1_id": "16957", "arg2_id": "16962", "normalized": [] }, { "id": "16975", "type": "CID", "arg1_id": "16959", "arg2_id": "16962", "normalized": [] }, { "id": "16976", "type": "CID", "arg1_id": "16960", "arg2_id": "16962", "normalized": [] }, { "id": "16977", "type": "CID", "arg1_id": "16964", "arg2_id": "16962", "normalized": [] }, { "id": "16978", "type": "CID", "arg1_id": "16947", "arg2_id": "16963", "normalized": [] }, { "id": "16979", "type": "CID", "arg1_id": "16948", "arg2_id": "16963", "normalized": [] }, { "id": "16980", "type": "CID", "arg1_id": "16949", "arg2_id": "16963", "normalized": [] }, { "id": "16981", "type": "CID", "arg1_id": "16952", "arg2_id": "16963", "normalized": [] }, { "id": "16982", "type": "CID", "arg1_id": "16955", "arg2_id": "16963", "normalized": [] }, { "id": "16983", "type": "CID", "arg1_id": "16958", "arg2_id": "16963", "normalized": [] }, { "id": "16984", "type": "CID", "arg1_id": "16961", "arg2_id": "16963", "normalized": [] }, { "id": "16985", "type": "CID", "arg1_id": "16965", "arg2_id": "16963", "normalized": [] }, { "id": "16986", "type": "CID", "arg1_id": "16966", "arg2_id": "16963", "normalized": [] }, { "id": "16987", "type": "CID", "arg1_id": "16967", "arg2_id": "16963", "normalized": [] }, { "id": "16988", "type": "CID", "arg1_id": "16946", "arg2_id": "16963", "normalized": [] }, { "id": "16989", "type": "CID", "arg1_id": "16950", "arg2_id": "16963", "normalized": [] }, { "id": "16990", "type": "CID", "arg1_id": "16951", "arg2_id": "16963", "normalized": [] }, { "id": "16991", "type": "CID", "arg1_id": "16953", "arg2_id": "16963", "normalized": [] }, { "id": "16992", "type": "CID", "arg1_id": "16954", "arg2_id": "16963", "normalized": [] }, { "id": "16993", "type": "CID", "arg1_id": "16956", "arg2_id": "16963", "normalized": [] }, { "id": "16994", "type": "CID", "arg1_id": "16957", "arg2_id": "16963", "normalized": [] }, { "id": "16995", "type": "CID", "arg1_id": "16959", "arg2_id": "16963", "normalized": [] }, { "id": "16996", "type": "CID", "arg1_id": "16960", "arg2_id": "16963", "normalized": [] }, { "id": "16997", "type": "CID", "arg1_id": "16964", "arg2_id": "16963", "normalized": [] }, { "id": "16998", "type": "CID", "arg1_id": "16947", "arg2_id": "16962", "normalized": [] }, { "id": "16999", "type": "CID", "arg1_id": "16948", "arg2_id": "16962", "normalized": [] }, { "id": "17000", "type": "CID", "arg1_id": "16949", "arg2_id": "16962", "normalized": [] }, { "id": "17001", "type": "CID", "arg1_id": "16952", "arg2_id": "16962", "normalized": [] }, { "id": "17002", "type": "CID", "arg1_id": "16955", "arg2_id": "16962", "normalized": [] }, { "id": "17003", "type": "CID", "arg1_id": "16958", "arg2_id": "16962", "normalized": [] }, { "id": "17004", "type": "CID", "arg1_id": "16961", "arg2_id": "16962", "normalized": [] }, { "id": "17005", "type": "CID", "arg1_id": "16965", "arg2_id": "16962", "normalized": [] }, { "id": "17006", "type": "CID", "arg1_id": "16966", "arg2_id": "16962", "normalized": [] }, { "id": "17007", "type": "CID", "arg1_id": "16967", "arg2_id": "16962", "normalized": [] } ]

[ { "id": "17009", "type": "title", "text": [ "Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia." ], "offsets": [ [ 0, 86 ] ] }, { "id": "17010", "type": "abstract", "text": [ "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID." ], "offsets": [ [ 87, 1566 ] ] } ]

[ { "id": "17011", "type": "Chemical", "text": [ "L-DOPA" ], "offsets": [ [ 60, 66 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "17012", "type": "Disease", "text": [ "dyskinesia" ], "offsets": [ [ 75, 85 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17013", "type": "Chemical", "text": [ "L-DOPA" ], "offsets": [ [ 87, 93 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "17014", "type": "Disease", "text": [ "dyskinesia" ], "offsets": [ [ 102, 112 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17015", "type": "Disease", "text": [ "LID" ], "offsets": [ [ 114, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17016", "type": "Disease", "text": [ "Parkinson's disease" ], "offsets": [ [ 166, 185 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "17017", "type": "Disease", "text": [ "PD" ], "offsets": [ [ 187, 189 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "17018", "type": "Chemical", "text": [ "L-DOPA" ], "offsets": [ [ 233, 239 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "17019", "type": "Disease", "text": [ "LID" ], "offsets": [ [ 314, 317 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17020", "type": "Chemical", "text": [ "6-hydroxydopamine" ], "offsets": [ [ 541, 558 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016627" } ] }, { "id": "17021", "type": "Disease", "text": [ "PD" ], "offsets": [ [ 579, 581 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "17022", "type": "Chemical", "text": [ "L-DOPA" ], "offsets": [ [ 603, 609 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "17023", "type": "Chemical", "text": [ "bromocriptine" ], "offsets": [ [ 613, 626 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001971" } ] }, { "id": "17024", "type": "Chemical", "text": [ "L-DOPA" ], "offsets": [ [ 726, 732 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "17025", "type": "Disease", "text": [ "LID" ], "offsets": [ [ 798, 801 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17026", "type": "Disease", "text": [ "LID" ], "offsets": [ [ 1124, 1127 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "17027", "type": "Disease", "text": [ "LID" ], "offsets": [ [ 1562, 1565 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] } ]

[]

[]

[ { "id": "17028", "type": "CID", "arg1_id": "17011", "arg2_id": "17012", "normalized": [] }, { "id": "17029", "type": "CID", "arg1_id": "17011", "arg2_id": "17014", "normalized": [] }, { "id": "17030", "type": "CID", "arg1_id": "17011", "arg2_id": "17015", "normalized": [] }, { "id": "17031", "type": "CID", "arg1_id": "17011", "arg2_id": "17019", "normalized": [] }, { "id": "17032", "type": "CID", "arg1_id": "17011", "arg2_id": "17025", "normalized": [] }, { "id": "17033", "type": "CID", "arg1_id": "17011", "arg2_id": "17026", "normalized": [] }, { "id": "17034", "type": "CID", "arg1_id": "17011", "arg2_id": "17027", "normalized": [] }, { "id": "17035", "type": "CID", "arg1_id": "17013", "arg2_id": "17012", "normalized": [] }, { "id": "17036", "type": "CID", "arg1_id": "17013", "arg2_id": "17014", "normalized": [] }, { "id": "17037", "type": "CID", "arg1_id": "17013", "arg2_id": "17015", "normalized": [] }, { "id": "17038", "type": "CID", "arg1_id": "17013", "arg2_id": "17019", "normalized": [] }, { "id": "17039", "type": "CID", "arg1_id": "17013", "arg2_id": "17025", "normalized": [] }, { "id": "17040", "type": "CID", "arg1_id": "17013", "arg2_id": "17026", "normalized": [] }, { "id": "17041", "type": "CID", "arg1_id": "17013", "arg2_id": "17027", "normalized": [] }, { "id": "17042", "type": "CID", "arg1_id": "17018", "arg2_id": "17012", "normalized": [] }, { "id": "17043", "type": "CID", "arg1_id": "17018", "arg2_id": "17014", "normalized": [] }, { "id": "17044", "type": "CID", "arg1_id": "17018", "arg2_id": "17015", "normalized": [] }, { "id": "17045", "type": "CID", "arg1_id": "17018", "arg2_id": "17019", "normalized": [] }, { "id": "17046", "type": "CID", "arg1_id": "17018", "arg2_id": "17025", "normalized": [] }, { "id": "17047", "type": "CID", "arg1_id": "17018", "arg2_id": "17026", "normalized": [] }, { "id": "17048", "type": "CID", "arg1_id": "17018", "arg2_id": "17027", "normalized": [] }, { "id": "17049", "type": "CID", "arg1_id": "17022", "arg2_id": "17012", "normalized": [] }, { "id": "17050", "type": "CID", "arg1_id": "17022", "arg2_id": "17014", "normalized": [] }, { "id": "17051", "type": "CID", "arg1_id": "17022", "arg2_id": "17015", "normalized": [] }, { "id": "17052", "type": "CID", "arg1_id": "17022", "arg2_id": "17019", "normalized": [] }, { "id": "17053", "type": "CID", "arg1_id": "17022", "arg2_id": "17025", "normalized": [] }, { "id": "17054", "type": "CID", "arg1_id": "17022", "arg2_id": "17026", "normalized": [] }, { "id": "17055", "type": "CID", "arg1_id": "17022", "arg2_id": "17027", "normalized": [] }, { "id": "17056", "type": "CID", "arg1_id": "17024", "arg2_id": "17012", "normalized": [] }, { "id": "17057", "type": "CID", "arg1_id": "17024", "arg2_id": "17014", "normalized": [] }, { "id": "17058", "type": "CID", "arg1_id": "17024", "arg2_id": "17015", "normalized": [] }, { "id": "17059", "type": "CID", "arg1_id": "17024", "arg2_id": "17019", "normalized": [] }, { "id": "17060", "type": "CID", "arg1_id": "17024", "arg2_id": "17025", "normalized": [] }, { "id": "17061", "type": "CID", "arg1_id": "17024", "arg2_id": "17026", "normalized": [] }, { "id": "17062", "type": "CID", "arg1_id": "17024", "arg2_id": "17027", "normalized": [] } ]

[ { "id": "17064", "type": "title", "text": [ "Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives." ], "offsets": [ [ 0, 73 ] ] }, { "id": "17065", "type": "abstract", "text": [ "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone." ], "offsets": [ [ 74, 1419 ] ] } ]

[ { "id": "17066", "type": "Disease", "text": [ "allergic reactions" ], "offsets": [ [ 7, 25 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "17067", "type": "Chemical", "text": [ "corticosteroids" ], "offsets": [ [ 29, 44 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000305" } ] }, { "id": "17068", "type": "Chemical", "text": [ "paramethasone" ], "offsets": [ [ 111, 124 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010248" } ] }, { "id": "17069", "type": "Chemical", "text": [ "dexamethasone" ], "offsets": [ [ 139, 152 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "17070", "type": "Disease", "text": [ "urticaria" ], "offsets": [ [ 244, 253 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014581" } ] }, { "id": "17071", "type": "Disease", "text": [ "conjunctivitis" ], "offsets": [ [ 277, 291 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003231" } ] }, { "id": "17072", "type": "Chemical", "text": [ "corticosteroids" ], "offsets": [ [ 577, 592 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000305" } ] }, { "id": "17073", "type": "Chemical", "text": [ "paramethasone" ], "offsets": [ [ 672, 685 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010248" } ] }, { "id": "17074", "type": "Chemical", "text": [ "corticosteroids" ], "offsets": [ [ 973, 988 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000305" } ] }, { "id": "17075", "type": "Chemical", "text": [ "paramethasone" ], "offsets": [ [ 1055, 1068 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010248" } ] }, { "id": "17076", "type": "Chemical", "text": [ "paramethasone" ], "offsets": [ [ 1149, 1162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010248" } ] }, { "id": "17077", "type": "Disease", "text": [ "hypersensitivity" ], "offsets": [ [ 1177, 1193 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "17078", "type": "Disease", "text": [ "allergy" ], "offsets": [ [ 1387, 1394 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004342" } ] }, { "id": "17079", "type": "Chemical", "text": [ "paramethasone" ], "offsets": [ [ 1405, 1418 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010248" } ] } ]

[]

[]

[ { "id": "17080", "type": "CID", "arg1_id": "17068", "arg2_id": "17070", "normalized": [] }, { "id": "17081", "type": "CID", "arg1_id": "17073", "arg2_id": "17070", "normalized": [] }, { "id": "17082", "type": "CID", "arg1_id": "17075", "arg2_id": "17070", "normalized": [] }, { "id": "17083", "type": "CID", "arg1_id": "17076", "arg2_id": "17070", "normalized": [] }, { "id": "17084", "type": "CID", "arg1_id": "17079", "arg2_id": "17070", "normalized": [] }, { "id": "17085", "type": "CID", "arg1_id": "17069", "arg2_id": "17071", "normalized": [] }, { "id": "17086", "type": "CID", "arg1_id": "17069", "arg2_id": "17070", "normalized": [] }, { "id": "17087", "type": "CID", "arg1_id": "17068", "arg2_id": "17071", "normalized": [] }, { "id": "17088", "type": "CID", "arg1_id": "17073", "arg2_id": "17071", "normalized": [] }, { "id": "17089", "type": "CID", "arg1_id": "17075", "arg2_id": "17071", "normalized": [] }, { "id": "17090", "type": "CID", "arg1_id": "17076", "arg2_id": "17071", "normalized": [] }, { "id": "17091", "type": "CID", "arg1_id": "17079", "arg2_id": "17071", "normalized": [] } ]

[ { "id": "17093", "type": "title", "text": [ "Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children." ], "offsets": [ [ 0, 148 ] ] }, { "id": "17094", "type": "abstract", "text": [ "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously." ], "offsets": [ [ 149, 877 ] ] } ]

[ { "id": "17095", "type": "Chemical", "text": [ "Valproic acid" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17096", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 22, 36 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17097", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 109, 112 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17098", "type": "Chemical", "text": [ "Valproic acid" ], "offsets": [ [ 149, 162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17099", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 164, 167 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17100", "type": "Disease", "text": [ "pancreatitis" ], "offsets": [ [ 317, 329 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010195" } ] }, { "id": "17101", "type": "Disease", "text": [ "bone marrow suppression" ], "offsets": [ [ 331, 354 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001855" } ] }, { "id": "17102", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 356, 359 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17103", "type": "Disease", "text": [ "hepatotoxicity" ], "offsets": [ [ 368, 382 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "17104", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 387, 390 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17105", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 399, 413 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17106", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 436, 439 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17107", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 448, 462 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17108", "type": "Disease", "text": [ "impaired consciousness" ], "offsets": [ [ 467, 489 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003244" } ] }, { "id": "17109", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 542, 549 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17110", "type": "Disease", "text": [ "hyperammonemia" ], "offsets": [ [ 577, 591 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D022124" } ] }, { "id": "17111", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 640, 643 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17112", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 661, 675 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17113", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 764, 767 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "17114", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 779, 793 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] } ]

[]

[]

[ { "id": "17115", "type": "CID", "arg1_id": "17095", "arg2_id": "17101", "normalized": [] }, { "id": "17116", "type": "CID", "arg1_id": "17097", "arg2_id": "17101", "normalized": [] }, { "id": "17117", "type": "CID", "arg1_id": "17098", "arg2_id": "17101", "normalized": [] }, { "id": "17118", "type": "CID", "arg1_id": "17099", "arg2_id": "17101", "normalized": [] }, { "id": "17119", "type": "CID", "arg1_id": "17102", "arg2_id": "17101", "normalized": [] }, { "id": "17120", "type": "CID", "arg1_id": "17104", "arg2_id": "17101", "normalized": [] }, { "id": "17121", "type": "CID", "arg1_id": "17106", "arg2_id": "17101", "normalized": [] }, { "id": "17122", "type": "CID", "arg1_id": "17111", "arg2_id": "17101", "normalized": [] }, { "id": "17123", "type": "CID", "arg1_id": "17113", "arg2_id": "17101", "normalized": [] }, { "id": "17124", "type": "CID", "arg1_id": "17095", "arg2_id": "17100", "normalized": [] }, { "id": "17125", "type": "CID", "arg1_id": "17097", "arg2_id": "17100", "normalized": [] }, { "id": "17126", "type": "CID", "arg1_id": "17098", "arg2_id": "17100", "normalized": [] }, { "id": "17127", "type": "CID", "arg1_id": "17099", "arg2_id": "17100", "normalized": [] }, { "id": "17128", "type": "CID", "arg1_id": "17102", "arg2_id": "17100", "normalized": [] }, { "id": "17129", "type": "CID", "arg1_id": "17104", "arg2_id": "17100", "normalized": [] }, { "id": "17130", "type": "CID", "arg1_id": "17106", "arg2_id": "17100", "normalized": [] }, { "id": "17131", "type": "CID", "arg1_id": "17111", "arg2_id": "17100", "normalized": [] }, { "id": "17132", "type": "CID", "arg1_id": "17113", "arg2_id": "17100", "normalized": [] }, { "id": "17133", "type": "CID", "arg1_id": "17095", "arg2_id": "17096", "normalized": [] }, { "id": "17134", "type": "CID", "arg1_id": "17095", "arg2_id": "17105", "normalized": [] }, { "id": "17135", "type": "CID", "arg1_id": "17095", "arg2_id": "17107", "normalized": [] }, { "id": "17136", "type": "CID", "arg1_id": "17095", "arg2_id": "17112", "normalized": [] }, { "id": "17137", "type": "CID", "arg1_id": "17095", "arg2_id": "17114", "normalized": [] }, { "id": "17138", "type": "CID", "arg1_id": "17097", "arg2_id": "17096", "normalized": [] }, { "id": "17139", "type": "CID", "arg1_id": "17097", "arg2_id": "17105", "normalized": [] }, { "id": "17140", "type": "CID", "arg1_id": "17097", "arg2_id": "17107", "normalized": [] }, { "id": "17141", "type": "CID", "arg1_id": "17097", "arg2_id": "17112", "normalized": [] }, { "id": "17142", "type": "CID", "arg1_id": "17097", "arg2_id": "17114", "normalized": [] }, { "id": "17143", "type": "CID", "arg1_id": "17098", "arg2_id": "17096", "normalized": [] }, { "id": "17144", "type": "CID", "arg1_id": "17098", "arg2_id": "17105", "normalized": [] }, { "id": "17145", "type": "CID", "arg1_id": "17098", "arg2_id": "17107", "normalized": [] }, { "id": "17146", "type": "CID", "arg1_id": "17098", "arg2_id": "17112", "normalized": [] }, { "id": "17147", "type": "CID", "arg1_id": "17098", "arg2_id": "17114", "normalized": [] }, { "id": "17148", "type": "CID", "arg1_id": "17099", "arg2_id": "17096", "normalized": [] }, { "id": "17149", "type": "CID", "arg1_id": "17099", "arg2_id": "17105", "normalized": [] }, { "id": "17150", "type": "CID", "arg1_id": "17099", "arg2_id": "17107", "normalized": [] }, { "id": "17151", "type": "CID", "arg1_id": "17099", "arg2_id": "17112", "normalized": [] }, { "id": "17152", "type": "CID", "arg1_id": "17099", "arg2_id": "17114", "normalized": [] }, { "id": "17153", "type": "CID", "arg1_id": "17102", "arg2_id": "17096", "normalized": [] }, { "id": "17154", "type": "CID", "arg1_id": "17102", "arg2_id": "17105", "normalized": [] }, { "id": "17155", "type": "CID", "arg1_id": "17102", "arg2_id": "17107", "normalized": [] }, { "id": "17156", "type": "CID", "arg1_id": "17102", "arg2_id": "17112", "normalized": [] }, { "id": "17157", "type": "CID", "arg1_id": "17102", "arg2_id": "17114", "normalized": [] }, { "id": "17158", "type": "CID", "arg1_id": "17104", "arg2_id": "17096", "normalized": [] }, { "id": "17159", "type": "CID", "arg1_id": "17104", "arg2_id": "17105", "normalized": [] }, { "id": "17160", "type": "CID", "arg1_id": "17104", "arg2_id": "17107", "normalized": [] }, { "id": "17161", "type": "CID", "arg1_id": "17104", "arg2_id": "17112", "normalized": [] }, { "id": "17162", "type": "CID", "arg1_id": "17104", "arg2_id": "17114", "normalized": [] }, { "id": "17163", "type": "CID", "arg1_id": "17106", "arg2_id": "17096", "normalized": [] }, { "id": "17164", "type": "CID", "arg1_id": "17106", "arg2_id": "17105", "normalized": [] }, { "id": "17165", "type": "CID", "arg1_id": "17106", "arg2_id": "17107", "normalized": [] }, { "id": "17166", "type": "CID", "arg1_id": "17106", "arg2_id": "17112", "normalized": [] }, { "id": "17167", "type": "CID", "arg1_id": "17106", "arg2_id": "17114", "normalized": [] }, { "id": "17168", "type": "CID", "arg1_id": "17111", "arg2_id": "17096", "normalized": [] }, { "id": "17169", "type": "CID", "arg1_id": "17111", "arg2_id": "17105", "normalized": [] }, { "id": "17170", "type": "CID", "arg1_id": "17111", "arg2_id": "17107", "normalized": [] }, { "id": "17171", "type": "CID", "arg1_id": "17111", "arg2_id": "17112", "normalized": [] }, { "id": "17172", "type": "CID", "arg1_id": "17111", "arg2_id": "17114", "normalized": [] }, { "id": "17173", "type": "CID", "arg1_id": "17113", "arg2_id": "17096", "normalized": [] }, { "id": "17174", "type": "CID", "arg1_id": "17113", "arg2_id": "17105", "normalized": [] }, { "id": "17175", "type": "CID", "arg1_id": "17113", "arg2_id": "17107", "normalized": [] }, { "id": "17176", "type": "CID", "arg1_id": "17113", "arg2_id": "17112", "normalized": [] }, { "id": "17177", "type": "CID", "arg1_id": "17113", "arg2_id": "17114", "normalized": [] }, { "id": "17178", "type": "CID", "arg1_id": "17095", "arg2_id": "17103", "normalized": [] }, { "id": "17179", "type": "CID", "arg1_id": "17097", "arg2_id": "17103", "normalized": [] }, { "id": "17180", "type": "CID", "arg1_id": "17098", "arg2_id": "17103", "normalized": [] }, { "id": "17181", "type": "CID", "arg1_id": "17099", "arg2_id": "17103", "normalized": [] }, { "id": "17182", "type": "CID", "arg1_id": "17102", "arg2_id": "17103", "normalized": [] }, { "id": "17183", "type": "CID", "arg1_id": "17104", "arg2_id": "17103", "normalized": [] }, { "id": "17184", "type": "CID", "arg1_id": "17106", "arg2_id": "17103", "normalized": [] }, { "id": "17185", "type": "CID", "arg1_id": "17111", "arg2_id": "17103", "normalized": [] }, { "id": "17186", "type": "CID", "arg1_id": "17113", "arg2_id": "17103", "normalized": [] }, { "id": "17187", "type": "CID", "arg1_id": "17095", "arg2_id": "17108", "normalized": [] }, { "id": "17188", "type": "CID", "arg1_id": "17097", "arg2_id": "17108", "normalized": [] }, { "id": "17189", "type": "CID", "arg1_id": "17098", "arg2_id": "17108", "normalized": [] }, { "id": "17190", "type": "CID", "arg1_id": "17099", "arg2_id": "17108", "normalized": [] }, { "id": "17191", "type": "CID", "arg1_id": "17102", "arg2_id": "17108", "normalized": [] }, { "id": "17192", "type": "CID", "arg1_id": "17104", "arg2_id": "17108", "normalized": [] }, { "id": "17193", "type": "CID", "arg1_id": "17106", "arg2_id": "17108", "normalized": [] }, { "id": "17194", "type": "CID", "arg1_id": "17111", "arg2_id": "17108", "normalized": [] }, { "id": "17195", "type": "CID", "arg1_id": "17113", "arg2_id": "17108", "normalized": [] } ]

[ { "id": "17197", "type": "title", "text": [ "Haemolytic-uraemic syndrome after treatment with metronidazole." ], "offsets": [ [ 0, 63 ] ] }, { "id": "17198", "type": "abstract", "text": [ "This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome." ], "offsets": [ [ 64, 709 ] ] } ]

[ { "id": "17199", "type": "Disease", "text": [ "Haemolytic-uraemic syndrome" ], "offsets": [ [ 0, 27 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006463" } ] }, { "id": "17200", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 49, 62 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17201", "type": "Disease", "text": [ "haemolytic-uraemic syndrome" ], "offsets": [ [ 141, 168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006463" } ] }, { "id": "17202", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 190, 203 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17203", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 361, 374 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17204", "type": "Disease", "text": [ "haemolytic-uraemic syndrome" ], "offsets": [ [ 399, 426 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006463" } ] }, { "id": "17205", "type": "Disease", "text": [ "haemolytic-uraemic syndrome" ], "offsets": [ [ 575, 602 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006463" } ] }, { "id": "17206", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 635, 648 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17207", "type": "Disease", "text": [ "haemolytic-uraemic syndrome" ], "offsets": [ [ 681, 708 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006463" } ] } ]

[]

[]

[ { "id": "17208", "type": "CID", "arg1_id": "17200", "arg2_id": "17199", "normalized": [] }, { "id": "17209", "type": "CID", "arg1_id": "17200", "arg2_id": "17201", "normalized": [] }, { "id": "17210", "type": "CID", "arg1_id": "17200", "arg2_id": "17204", "normalized": [] }, { "id": "17211", "type": "CID", "arg1_id": "17200", "arg2_id": "17205", "normalized": [] }, { "id": "17212", "type": "CID", "arg1_id": "17200", "arg2_id": "17207", "normalized": [] }, { "id": "17213", "type": "CID", "arg1_id": "17202", "arg2_id": "17199", "normalized": [] }, { "id": "17214", "type": "CID", "arg1_id": "17202", "arg2_id": "17201", "normalized": [] }, { "id": "17215", "type": "CID", "arg1_id": "17202", "arg2_id": "17204", "normalized": [] }, { "id": "17216", "type": "CID", "arg1_id": "17202", "arg2_id": "17205", "normalized": [] }, { "id": "17217", "type": "CID", "arg1_id": "17202", "arg2_id": "17207", "normalized": [] }, { "id": "17218", "type": "CID", "arg1_id": "17203", "arg2_id": "17199", "normalized": [] }, { "id": "17219", "type": "CID", "arg1_id": "17203", "arg2_id": "17201", "normalized": [] }, { "id": "17220", "type": "CID", "arg1_id": "17203", "arg2_id": "17204", "normalized": [] }, { "id": "17221", "type": "CID", "arg1_id": "17203", "arg2_id": "17205", "normalized": [] }, { "id": "17222", "type": "CID", "arg1_id": "17203", "arg2_id": "17207", "normalized": [] }, { "id": "17223", "type": "CID", "arg1_id": "17206", "arg2_id": "17199", "normalized": [] }, { "id": "17224", "type": "CID", "arg1_id": "17206", "arg2_id": "17201", "normalized": [] }, { "id": "17225", "type": "CID", "arg1_id": "17206", "arg2_id": "17204", "normalized": [] }, { "id": "17226", "type": "CID", "arg1_id": "17206", "arg2_id": "17205", "normalized": [] }, { "id": "17227", "type": "CID", "arg1_id": "17206", "arg2_id": "17207", "normalized": [] } ]

[ { "id": "17229", "type": "title", "text": [ "Risk factors of sensorineural hearing loss in preterm infants." ], "offsets": [ [ 0, 62 ] ] }, { "id": "17230", "type": "abstract", "text": [ "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe." ], "offsets": [ [ 63, 865 ] ] } ]

[ { "id": "17231", "type": "Disease", "text": [ "sensorineural hearing loss" ], "offsets": [ [ 16, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17232", "type": "Disease", "text": [ "sensorineural hearing loss" ], "offsets": [ [ 208, 234 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17233", "type": "Disease", "text": [ "hearing loss" ], "offsets": [ [ 275, 287 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] }, { "id": "17234", "type": "Disease", "text": [ "hearing loss" ], "offsets": [ [ 455, 467 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] }, { "id": "17235", "type": "Disease", "text": [ "Ototoxicity" ], "offsets": [ [ 520, 531 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "17236", "type": "Disease", "text": [ "ototoxic" ], "offsets": [ [ 612, 620 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "17237", "type": "Chemical", "text": [ "aminoglycosides" ], "offsets": [ [ 641, 656 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000617" } ] }, { "id": "17238", "type": "Chemical", "text": [ "furosemide" ], "offsets": [ [ 661, 671 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005665" } ] }, { "id": "17239", "type": "Disease", "text": [ "hearing loss" ], "offsets": [ [ 793, 805 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] } ]

[]

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[ { "id": "17240", "type": "CID", "arg1_id": "17237", "arg2_id": "17231", "normalized": [] }, { "id": "17241", "type": "CID", "arg1_id": "17237", "arg2_id": "17232", "normalized": [] }, { "id": "17242", "type": "CID", "arg1_id": "17238", "arg2_id": "17231", "normalized": [] }, { "id": "17243", "type": "CID", "arg1_id": "17238", "arg2_id": "17232", "normalized": [] } ]

[ { "id": "17245", "type": "title", "text": [ "Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion." ], "offsets": [ [ 0, 93 ] ] }, { "id": "17246", "type": "abstract", "text": [ "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine." ], "offsets": [ [ 94, 1172 ] ] } ]

[ { "id": "17247", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 54, 64 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17248", "type": "Disease", "text": [ "confusion" ], "offsets": [ [ 83, 92 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003221" } ] }, { "id": "17249", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 106, 116 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17250", "type": "Disease", "text": [ "confusion" ], "offsets": [ [ 135, 144 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003221" } ] }, { "id": "17251", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 370, 380 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17252", "type": "Disease", "text": [ "renal and liver dysfunction" ], "offsets": [ [ 445, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" }, { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "17253", "type": "Disease", "text": [ "renal", "dysfunction" ], "offsets": [ [ 445, 450 ], [ 461, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "17254", "type": "Disease", "text": [ "liver dysfunction" ], "offsets": [ [ 455, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "17255", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 504, 514 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17256", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 730, 740 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17257", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 786, 796 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] }, { "id": "17258", "type": "Chemical", "text": [ "histamine" ], "offsets": [ [ 901, 910 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006632" } ] }, { "id": "17259", "type": "Disease", "text": [ "confusion" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003221" } ] }, { "id": "17260", "type": "Disease", "text": [ "renal and hepatic dysfunction" ], "offsets": [ [ 1061, 1090 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" }, { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "17261", "type": "Disease", "text": [ "renal", "dysfunction" ], "offsets": [ [ 1061, 1066 ], [ 1079, 1090 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "17262", "type": "Disease", "text": [ "hepatic dysfunction" ], "offsets": [ [ 1071, 1090 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "17263", "type": "Chemical", "text": [ "cimetidine" ], "offsets": [ [ 1161, 1171 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002927" } ] } ]

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[ { "id": "17264", "type": "CID", "arg1_id": "17247", "arg2_id": "17248", "normalized": [] }, { "id": "17265", "type": "CID", "arg1_id": "17247", "arg2_id": "17250", "normalized": [] }, { "id": "17266", "type": "CID", "arg1_id": "17247", "arg2_id": "17259", "normalized": [] }, { "id": "17267", "type": "CID", "arg1_id": "17249", "arg2_id": "17248", "normalized": [] }, { "id": "17268", "type": "CID", "arg1_id": "17249", "arg2_id": "17250", "normalized": [] }, { "id": "17269", "type": "CID", "arg1_id": "17249", "arg2_id": "17259", "normalized": [] }, { "id": "17270", "type": "CID", "arg1_id": "17251", "arg2_id": "17248", "normalized": [] }, { "id": "17271", "type": "CID", "arg1_id": "17251", "arg2_id": "17250", "normalized": [] }, { "id": "17272", "type": "CID", "arg1_id": "17251", "arg2_id": "17259", "normalized": [] }, { "id": "17273", "type": "CID", "arg1_id": "17255", "arg2_id": "17248", "normalized": [] }, { "id": "17274", "type": "CID", "arg1_id": "17255", "arg2_id": "17250", "normalized": [] }, { "id": "17275", "type": "CID", "arg1_id": "17255", "arg2_id": "17259", "normalized": [] }, { "id": "17276", "type": "CID", "arg1_id": "17256", "arg2_id": "17248", "normalized": [] }, { "id": "17277", "type": "CID", "arg1_id": "17256", "arg2_id": "17250", "normalized": [] }, { "id": "17278", "type": "CID", "arg1_id": "17256", "arg2_id": "17259", "normalized": [] }, { "id": "17279", "type": "CID", "arg1_id": "17257", "arg2_id": "17248", "normalized": [] }, { "id": "17280", "type": "CID", "arg1_id": "17257", "arg2_id": "17250", "normalized": [] }, { "id": "17281", "type": "CID", "arg1_id": "17257", "arg2_id": "17259", "normalized": [] }, { "id": "17282", "type": "CID", "arg1_id": "17263", "arg2_id": "17248", "normalized": [] }, { "id": "17283", "type": "CID", "arg1_id": "17263", "arg2_id": "17250", "normalized": [] }, { "id": "17284", "type": "CID", "arg1_id": "17263", "arg2_id": "17259", "normalized": [] } ]

[ { "id": "17286", "type": "title", "text": [ "Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis." ], "offsets": [ [ 0, 129 ] ] }, { "id": "17287", "type": "abstract", "text": [ "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability." ], "offsets": [ [ 130, 1775 ] ] } ]

[ { "id": "17288", "type": "Disease", "text": [ "intrahepatic and extrahepatic cholestasis" ], "offsets": [ [ 87, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002780" }, { "db_name": "MESH", "db_id": "D001651" } ] }, { "id": "17289", "type": "Disease", "text": [ "intrahepatic", "cholestasis" ], "offsets": [ [ 87, 99 ], [ 117, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002780" } ] }, { "id": "17290", "type": "Disease", "text": [ "extrahepatic cholestasis" ], "offsets": [ [ 104, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001651" } ] }, { "id": "17291", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 321, 332 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "17292", "type": "Disease", "text": [ "intrahepatic cholestasis" ], "offsets": [ [ 678, 702 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002780" } ] }, { "id": "17293", "type": "Chemical", "text": [ "ethinyl estradiol" ], "offsets": [ [ 706, 723 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004997" } ] }, { "id": "17294", "type": "Chemical", "text": [ "EE" ], "offsets": [ [ 725, 727 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004997" } ] }, { "id": "17295", "type": "Disease", "text": [ "extrahepatic cholestasis" ], "offsets": [ [ 743, 767 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001651" } ] }, { "id": "17296", "type": "Chemical", "text": [ "EE" ], "offsets": [ [ 1356, 1358 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004997" } ] }, { "id": "17297", "type": "Chemical", "text": [ "EE" ], "offsets": [ [ 1682, 1684 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004997" } ] } ]

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[ { "id": "17298", "type": "CID", "arg1_id": "17293", "arg2_id": "17288", "normalized": [] }, { "id": "17299", "type": "CID", "arg1_id": "17293", "arg2_id": "17289", "normalized": [] }, { "id": "17300", "type": "CID", "arg1_id": "17293", "arg2_id": "17292", "normalized": [] }, { "id": "17301", "type": "CID", "arg1_id": "17294", "arg2_id": "17288", "normalized": [] }, { "id": "17302", "type": "CID", "arg1_id": "17294", "arg2_id": "17289", "normalized": [] }, { "id": "17303", "type": "CID", "arg1_id": "17294", "arg2_id": "17292", "normalized": [] }, { "id": "17304", "type": "CID", "arg1_id": "17296", "arg2_id": "17288", "normalized": [] }, { "id": "17305", "type": "CID", "arg1_id": "17296", "arg2_id": "17289", "normalized": [] }, { "id": "17306", "type": "CID", "arg1_id": "17296", "arg2_id": "17292", "normalized": [] }, { "id": "17307", "type": "CID", "arg1_id": "17297", "arg2_id": "17288", "normalized": [] }, { "id": "17308", "type": "CID", "arg1_id": "17297", "arg2_id": "17289", "normalized": [] }, { "id": "17309", "type": "CID", "arg1_id": "17297", "arg2_id": "17292", "normalized": [] } ]

[ { "id": "17311", "type": "title", "text": [ "Long term audiological evaluation of beta-thalassemic patients." ], "offsets": [ [ 0, 63 ] ] }, { "id": "17312", "type": "abstract", "text": [ "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment." ], "offsets": [ [ 64, 1616 ] ] } ]

[ { "id": "17313", "type": "Disease", "text": [ "beta-thalassemic" ], "offsets": [ [ 37, 53 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017086" } ] }, { "id": "17314", "type": "Disease", "text": [ "hearing loss" ], "offsets": [ [ 167, 179 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] }, { "id": "17315", "type": "Disease", "text": [ "beta-thalassemia" ], "offsets": [ [ 214, 230 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017086" } ] }, { "id": "17316", "type": "Chemical", "text": [ "desferrioxamine" ], "offsets": [ [ 479, 494 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003676" } ] }, { "id": "17317", "type": "Chemical", "text": [ "DFO" ], "offsets": [ [ 496, 499 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003676" } ] }, { "id": "17318", "type": "Disease", "text": [ "sensorineural hearing loss" ], "offsets": [ [ 804, 830 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17319", "type": "Disease", "text": [ "SNHL" ], "offsets": [ [ 832, 836 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17320", "type": "Disease", "text": [ "ototoxic" ], "offsets": [ [ 874, 882 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "17321", "type": "Chemical", "text": [ "DFO" ], "offsets": [ [ 902, 905 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003676" } ] }, { "id": "17322", "type": "Disease", "text": [ "SNHL" ], "offsets": [ [ 957, 961 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17323", "type": "Disease", "text": [ "SNHL" ], "offsets": [ [ 1125, 1129 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006319" } ] }, { "id": "17324", "type": "Chemical", "text": [ "DFO" ], "offsets": [ [ 1148, 1151 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003676" } ] }, { "id": "17325", "type": "Chemical", "text": [ "DFO" ], "offsets": [ [ 1346, 1349 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003676" } ] }, { "id": "17326", "type": "Disease", "text": [ "hearing impairment" ], "offsets": [ [ 1392, 1410 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] }, { "id": "17327", "type": "Disease", "text": [ "thalassemic" ], "offsets": [ [ 1463, 1474 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013789" } ] }, { "id": "17328", "type": "Disease", "text": [ "hearing impairment" ], "offsets": [ [ 1597, 1615 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D034381" } ] } ]

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[ { "id": "17329", "type": "CID", "arg1_id": "17316", "arg2_id": "17318", "normalized": [] }, { "id": "17330", "type": "CID", "arg1_id": "17316", "arg2_id": "17319", "normalized": [] }, { "id": "17331", "type": "CID", "arg1_id": "17316", "arg2_id": "17322", "normalized": [] }, { "id": "17332", "type": "CID", "arg1_id": "17316", "arg2_id": "17323", "normalized": [] }, { "id": "17333", "type": "CID", "arg1_id": "17317", "arg2_id": "17318", "normalized": [] }, { "id": "17334", "type": "CID", "arg1_id": "17317", "arg2_id": "17319", "normalized": [] }, { "id": "17335", "type": "CID", "arg1_id": "17317", "arg2_id": "17322", "normalized": [] }, { "id": "17336", "type": "CID", "arg1_id": "17317", "arg2_id": "17323", "normalized": [] }, { "id": "17337", "type": "CID", "arg1_id": "17321", "arg2_id": "17318", "normalized": [] }, { "id": "17338", "type": "CID", "arg1_id": "17321", "arg2_id": "17319", "normalized": [] }, { "id": "17339", "type": "CID", "arg1_id": "17321", "arg2_id": "17322", "normalized": [] }, { "id": "17340", "type": "CID", "arg1_id": "17321", "arg2_id": "17323", "normalized": [] }, { "id": "17341", "type": "CID", "arg1_id": "17324", "arg2_id": "17318", "normalized": [] }, { "id": "17342", "type": "CID", "arg1_id": "17324", "arg2_id": "17319", "normalized": [] }, { "id": "17343", "type": "CID", "arg1_id": "17324", "arg2_id": "17322", "normalized": [] }, { "id": "17344", "type": "CID", "arg1_id": "17324", "arg2_id": "17323", "normalized": [] }, { "id": "17345", "type": "CID", "arg1_id": "17325", "arg2_id": "17318", "normalized": [] }, { "id": "17346", "type": "CID", "arg1_id": "17325", "arg2_id": "17319", "normalized": [] }, { "id": "17347", "type": "CID", "arg1_id": "17325", "arg2_id": "17322", "normalized": [] }, { "id": "17348", "type": "CID", "arg1_id": "17325", "arg2_id": "17323", "normalized": [] } ]

[ { "id": "17350", "type": "title", "text": [ "Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure." ], "offsets": [ [ 0, 147 ] ] }, { "id": "17351", "type": "abstract", "text": [ "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients." ], "offsets": [ [ 148, 1134 ] ] } ]

[ { "id": "17352", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 51, 60 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] }, { "id": "17353", "type": "Chemical", "text": [ "prazosin" ], "offsets": [ [ 65, 73 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011224" } ] }, { "id": "17354", "type": "Disease", "text": [ "congestive heart failure" ], "offsets": [ [ 122, 146 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "17355", "type": "Chemical", "text": [ "angiotensin converting enzyme (ACE) inhibitors" ], "offsets": [ [ 174, 220 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000806" } ] }, { "id": "17356", "type": "Disease", "text": [ "congestive heart failure" ], "offsets": [ [ 268, 292 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "17357", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 310, 321 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "17358", "type": "Chemical", "text": [ "ACE inhibitor" ], "offsets": [ [ 426, 439 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000806" } ] }, { "id": "17359", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 440, 449 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] }, { "id": "17360", "type": "Chemical", "text": [ "prazosin" ], "offsets": [ [ 477, 485 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011224" } ] }, { "id": "17361", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 572, 583 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "17362", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 643, 652 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] }, { "id": "17363", "type": "Chemical", "text": [ "prazosin" ], "offsets": [ [ 660, 668 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011224" } ] }, { "id": "17364", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 790, 799 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] }, { "id": "17365", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 872, 883 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "17366", "type": "Chemical", "text": [ "prazosin" ], "offsets": [ [ 922, 930 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011224" } ] }, { "id": "17367", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 1001, 1010 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] }, { "id": "17368", "type": "Chemical", "text": [ "enalapril" ], "offsets": [ [ 1110, 1119 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004656" } ] } ]

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[ { "id": "17369", "type": "CID", "arg1_id": "17355", "arg2_id": "17357", "normalized": [] }, { "id": "17370", "type": "CID", "arg1_id": "17355", "arg2_id": "17361", "normalized": [] }, { "id": "17371", "type": "CID", "arg1_id": "17355", "arg2_id": "17365", "normalized": [] }, { "id": "17372", "type": "CID", "arg1_id": "17358", "arg2_id": "17357", "normalized": [] }, { "id": "17373", "type": "CID", "arg1_id": "17358", "arg2_id": "17361", "normalized": [] }, { "id": "17374", "type": "CID", "arg1_id": "17358", "arg2_id": "17365", "normalized": [] }, { "id": "17375", "type": "CID", "arg1_id": "17353", "arg2_id": "17357", "normalized": [] }, { "id": "17376", "type": "CID", "arg1_id": "17353", "arg2_id": "17361", "normalized": [] }, { "id": "17377", "type": "CID", "arg1_id": "17353", "arg2_id": "17365", "normalized": [] }, { "id": "17378", "type": "CID", "arg1_id": "17360", "arg2_id": "17357", "normalized": [] }, { "id": "17379", "type": "CID", "arg1_id": "17360", "arg2_id": "17361", "normalized": [] }, { "id": "17380", "type": "CID", "arg1_id": "17360", "arg2_id": "17365", "normalized": [] }, { "id": "17381", "type": "CID", "arg1_id": "17363", "arg2_id": "17357", "normalized": [] }, { "id": "17382", "type": "CID", "arg1_id": "17363", "arg2_id": "17361", "normalized": [] }, { "id": "17383", "type": "CID", "arg1_id": "17363", "arg2_id": "17365", "normalized": [] }, { "id": "17384", "type": "CID", "arg1_id": "17366", "arg2_id": "17357", "normalized": [] }, { "id": "17385", "type": "CID", "arg1_id": "17366", "arg2_id": "17361", "normalized": [] }, { "id": "17386", "type": "CID", "arg1_id": "17366", "arg2_id": "17365", "normalized": [] } ]

[ { "id": "17388", "type": "title", "text": [ "Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells." ], "offsets": [ [ 0, 132 ] ] }, { "id": "17389", "type": "abstract", "text": [ "Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production." ], "offsets": [ [ 133, 1463 ] ] } ]

[ { "id": "17390", "type": "Chemical", "text": [ "azidothymidine" ], "offsets": [ [ 65, 79 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015215" } ] }, { "id": "17391", "type": "Disease", "text": [ "anemia" ], "offsets": [ [ 88, 94 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000740" } ] }, { "id": "17392", "type": "Chemical", "text": [ "Azidothymidine" ], "offsets": [ [ 133, 147 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015215" } ] }, { "id": "17393", "type": "Chemical", "text": [ "AZT" ], "offsets": [ [ 149, 152 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015215" } ] }, { "id": "17394", "type": "Disease", "text": [ "anemia" ], "offsets": [ [ 162, 168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000740" } ] }, { "id": "17395", "type": "Chemical", "text": [ "AZT" ], "offsets": [ [ 472, 475 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015215" } ] }, { "id": "17396", "type": "Chemical", "text": [ "thymidine" ], "offsets": [ [ 924, 933 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013936" } ] }, { "id": "17397", "type": "Chemical", "text": [ "thymidine" ], "offsets": [ [ 1187, 1196 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013936" } ] } ]

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[ { "id": "17398", "type": "CID", "arg1_id": "17390", "arg2_id": "17391", "normalized": [] }, { "id": "17399", "type": "CID", "arg1_id": "17390", "arg2_id": "17394", "normalized": [] }, { "id": "17400", "type": "CID", "arg1_id": "17392", "arg2_id": "17391", "normalized": [] }, { "id": "17401", "type": "CID", "arg1_id": "17392", "arg2_id": "17394", "normalized": [] }, { "id": "17402", "type": "CID", "arg1_id": "17393", "arg2_id": "17391", "normalized": [] }, { "id": "17403", "type": "CID", "arg1_id": "17393", "arg2_id": "17394", "normalized": [] }, { "id": "17404", "type": "CID", "arg1_id": "17395", "arg2_id": "17391", "normalized": [] }, { "id": "17405", "type": "CID", "arg1_id": "17395", "arg2_id": "17394", "normalized": [] } ]

[ { "id": "17407", "type": "title", "text": [ "Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency." ], "offsets": [ [ 0, 89 ] ] }, { "id": "17408", "type": "abstract", "text": [ "The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)" ], "offsets": [ [ 90, 1642 ] ] } ]

[ { "id": "17409", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 38, 40 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17410", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 48, 50 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17411", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 149, 151 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17412", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 156, 158 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17413", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 161, 163 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17414", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 171, 173 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17415", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 250, 259 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "17416", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 422, 424 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17417", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 437, 439 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17418", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 484, 486 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17419", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 543, 545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17420", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 562, 564 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17421", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 616, 618 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17422", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 647, 649 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17423", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 684, 686 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17424", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 735, 737 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17425", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 805, 807 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17426", "type": "Disease", "text": [ "bradycardia" ], "offsets": [ [ 920, 931 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001919" } ] }, { "id": "17427", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 943, 952 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "17428", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 1031, 1033 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17429", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 1038, 1040 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17430", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 1082, 1091 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "17431", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 1236, 1245 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] }, { "id": "17432", "type": "Chemical", "text": [ "Na" ], "offsets": [ [ 1438, 1440 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17433", "type": "Chemical", "text": [ "Ca" ], "offsets": [ [ 1452, 1454 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17434", "type": "Chemical", "text": [ "verapamil" ], "offsets": [ [ 1534, 1543 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014700" } ] } ]

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[ { "id": "17435", "type": "CID", "arg1_id": "17415", "arg2_id": "17426", "normalized": [] }, { "id": "17436", "type": "CID", "arg1_id": "17427", "arg2_id": "17426", "normalized": [] }, { "id": "17437", "type": "CID", "arg1_id": "17430", "arg2_id": "17426", "normalized": [] }, { "id": "17438", "type": "CID", "arg1_id": "17431", "arg2_id": "17426", "normalized": [] }, { "id": "17439", "type": "CID", "arg1_id": "17434", "arg2_id": "17426", "normalized": [] } ]

[ { "id": "17441", "type": "title", "text": [ "Sodium status influences chronic amphotericin B nephrotoxicity in rats." ], "offsets": [ [ 0, 71 ] ] }, { "id": "17442", "type": "abstract", "text": [ "The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats." ], "offsets": [ [ 72, 1380 ] ] } ]

[ { "id": "17443", "type": "Chemical", "text": [ "Sodium" ], "offsets": [ [ 0, 6 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17444", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 33, 47 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17445", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 48, 62 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "17446", "type": "Disease", "text": [ "nephrotoxic" ], "offsets": [ [ 76, 87 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "17447", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 101, 115 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17448", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 262, 276 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17449", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 287, 297 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "17450", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 394, 404 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "17451", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 493, 503 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "17452", "type": "Chemical", "text": [ "sodium" ], "offsets": [ [ 593, 599 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] }, { "id": "17453", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 779, 793 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17454", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 922, 936 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17455", "type": "Chemical", "text": [ "creatinine" ], "offsets": [ [ 1204, 1214 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003404" } ] }, { "id": "17456", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 1235, 1249 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17457", "type": "Chemical", "text": [ "amphotericin B" ], "offsets": [ [ 1277, 1291 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000666" } ] }, { "id": "17458", "type": "Chemical", "text": [ "sodium" ], "offsets": [ [ 1357, 1363 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012964" } ] } ]

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[ { "id": "17459", "type": "CID", "arg1_id": "17444", "arg2_id": "17445", "normalized": [] }, { "id": "17460", "type": "CID", "arg1_id": "17444", "arg2_id": "17446", "normalized": [] }, { "id": "17461", "type": "CID", "arg1_id": "17447", "arg2_id": "17445", "normalized": [] }, { "id": "17462", "type": "CID", "arg1_id": "17447", "arg2_id": "17446", "normalized": [] }, { "id": "17463", "type": "CID", "arg1_id": "17448", "arg2_id": "17445", "normalized": [] }, { "id": "17464", "type": "CID", "arg1_id": "17448", "arg2_id": "17446", "normalized": [] }, { "id": "17465", "type": "CID", "arg1_id": "17453", "arg2_id": "17445", "normalized": [] }, { "id": "17466", "type": "CID", "arg1_id": "17453", "arg2_id": "17446", "normalized": [] }, { "id": "17467", "type": "CID", "arg1_id": "17454", "arg2_id": "17445", "normalized": [] }, { "id": "17468", "type": "CID", "arg1_id": "17454", "arg2_id": "17446", "normalized": [] }, { "id": "17469", "type": "CID", "arg1_id": "17456", "arg2_id": "17445", "normalized": [] }, { "id": "17470", "type": "CID", "arg1_id": "17456", "arg2_id": "17446", "normalized": [] }, { "id": "17471", "type": "CID", "arg1_id": "17457", "arg2_id": "17445", "normalized": [] }, { "id": "17472", "type": "CID", "arg1_id": "17457", "arg2_id": "17446", "normalized": [] } ]

[ { "id": "17474", "type": "title", "text": [ "Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging." ], "offsets": [ [ 0, 177 ] ] }, { "id": "17475", "type": "abstract", "text": [ "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement." ], "offsets": [ [ 178, 2072 ] ] } ]

[ { "id": "17476", "type": "Disease", "text": [ "inferior colliculus lesion" ], "offsets": [ [ 11, 37 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17477", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 41, 54 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17478", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 63, 77 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17479", "type": "Disease", "text": [ "inferior colliculus lesions" ], "offsets": [ [ 219, 246 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17480", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 250, 263 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17481", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 272, 286 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17482", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 511, 524 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17483", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 533, 547 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17484", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 595, 608 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17485", "type": "Disease", "text": [ "infection" ], "offsets": [ [ 678, 687 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007239" } ] }, { "id": "17486", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 999, 1012 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17487", "type": "Disease", "text": [ "callosal lesion" ], "offsets": [ [ 1869, 1884 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17488", "type": "Disease", "text": [ "inferior colliculus lesions" ], "offsets": [ [ 1920, 1947 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17489", "type": "Chemical", "text": [ "metronidazole" ], "offsets": [ [ 1994, 2007 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008795" } ] }, { "id": "17490", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 2016, 2030 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] } ]

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[ { "id": "17491", "type": "CID", "arg1_id": "17477", "arg2_id": "17476", "normalized": [] }, { "id": "17492", "type": "CID", "arg1_id": "17477", "arg2_id": "17478", "normalized": [] }, { "id": "17493", "type": "CID", "arg1_id": "17477", "arg2_id": "17479", "normalized": [] }, { "id": "17494", "type": "CID", "arg1_id": "17477", "arg2_id": "17481", "normalized": [] }, { "id": "17495", "type": "CID", "arg1_id": "17477", "arg2_id": "17483", "normalized": [] }, { "id": "17496", "type": "CID", "arg1_id": "17477", "arg2_id": "17487", "normalized": [] }, { "id": "17497", "type": "CID", "arg1_id": "17477", "arg2_id": "17488", "normalized": [] }, { "id": "17498", "type": "CID", "arg1_id": "17477", "arg2_id": "17490", "normalized": [] }, { "id": "17499", "type": "CID", "arg1_id": "17480", "arg2_id": "17476", "normalized": [] }, { "id": "17500", "type": "CID", "arg1_id": "17480", "arg2_id": "17478", "normalized": [] }, { "id": "17501", "type": "CID", "arg1_id": "17480", "arg2_id": "17479", "normalized": [] }, { "id": "17502", "type": "CID", "arg1_id": "17480", "arg2_id": "17481", "normalized": [] }, { "id": "17503", "type": "CID", "arg1_id": "17480", "arg2_id": "17483", "normalized": [] }, { "id": "17504", "type": "CID", "arg1_id": "17480", "arg2_id": "17487", "normalized": [] }, { "id": "17505", "type": "CID", "arg1_id": "17480", "arg2_id": "17488", "normalized": [] }, { "id": "17506", "type": "CID", "arg1_id": "17480", "arg2_id": "17490", "normalized": [] }, { "id": "17507", "type": "CID", "arg1_id": "17482", "arg2_id": "17476", "normalized": [] }, { "id": "17508", "type": "CID", "arg1_id": "17482", "arg2_id": "17478", "normalized": [] }, { "id": "17509", "type": "CID", "arg1_id": "17482", "arg2_id": "17479", "normalized": [] }, { "id": "17510", "type": "CID", "arg1_id": "17482", "arg2_id": "17481", "normalized": [] }, { "id": "17511", "type": "CID", "arg1_id": "17482", "arg2_id": "17483", "normalized": [] }, { "id": "17512", "type": "CID", "arg1_id": "17482", "arg2_id": "17487", "normalized": [] }, { "id": "17513", "type": "CID", "arg1_id": "17482", "arg2_id": "17488", "normalized": [] }, { "id": "17514", "type": "CID", "arg1_id": "17482", "arg2_id": "17490", "normalized": [] }, { "id": "17515", "type": "CID", "arg1_id": "17484", "arg2_id": "17476", "normalized": [] }, { "id": "17516", "type": "CID", "arg1_id": "17484", "arg2_id": "17478", "normalized": [] }, { "id": "17517", "type": "CID", "arg1_id": "17484", "arg2_id": "17479", "normalized": [] }, { "id": "17518", "type": "CID", "arg1_id": "17484", "arg2_id": "17481", "normalized": [] }, { "id": "17519", "type": "CID", "arg1_id": "17484", "arg2_id": "17483", "normalized": [] }, { "id": "17520", "type": "CID", "arg1_id": "17484", "arg2_id": "17487", "normalized": [] }, { "id": "17521", "type": "CID", "arg1_id": "17484", "arg2_id": "17488", "normalized": [] }, { "id": "17522", "type": "CID", "arg1_id": "17484", "arg2_id": "17490", "normalized": [] }, { "id": "17523", "type": "CID", "arg1_id": "17486", "arg2_id": "17476", "normalized": [] }, { "id": "17524", "type": "CID", "arg1_id": "17486", "arg2_id": "17478", "normalized": [] }, { "id": "17525", "type": "CID", "arg1_id": "17486", "arg2_id": "17479", "normalized": [] }, { "id": "17526", "type": "CID", "arg1_id": "17486", "arg2_id": "17481", "normalized": [] }, { "id": "17527", "type": "CID", "arg1_id": "17486", "arg2_id": "17483", "normalized": [] }, { "id": "17528", "type": "CID", "arg1_id": "17486", "arg2_id": "17487", "normalized": [] }, { "id": "17529", "type": "CID", "arg1_id": "17486", "arg2_id": "17488", "normalized": [] }, { "id": "17530", "type": "CID", "arg1_id": "17486", "arg2_id": "17490", "normalized": [] }, { "id": "17531", "type": "CID", "arg1_id": "17489", "arg2_id": "17476", "normalized": [] }, { "id": "17532", "type": "CID", "arg1_id": "17489", "arg2_id": "17478", "normalized": [] }, { "id": "17533", "type": "CID", "arg1_id": "17489", "arg2_id": "17479", "normalized": [] }, { "id": "17534", "type": "CID", "arg1_id": "17489", "arg2_id": "17481", "normalized": [] }, { "id": "17535", "type": "CID", "arg1_id": "17489", "arg2_id": "17483", "normalized": [] }, { "id": "17536", "type": "CID", "arg1_id": "17489", "arg2_id": "17487", "normalized": [] }, { "id": "17537", "type": "CID", "arg1_id": "17489", "arg2_id": "17488", "normalized": [] }, { "id": "17538", "type": "CID", "arg1_id": "17489", "arg2_id": "17490", "normalized": [] } ]

[ { "id": "17540", "type": "title", "text": [ "Comparison of the respiratory effects of i.v. infusions of morphine and regional analgesia by extradural block." ], "offsets": [ [ 0, 111 ] ] }, { "id": "17541", "type": "abstract", "text": [ "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group." ], "offsets": [ [ 112, 905 ] ] } ]

[ { "id": "17542", "type": "Chemical", "text": [ "morphine" ], "offsets": [ [ 59, 67 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009020" } ] }, { "id": "17543", "type": "Disease", "text": [ "apnoea" ], "offsets": [ [ 155, 161 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001049" } ] }, { "id": "17544", "type": "Chemical", "text": [ "morphine" ], "offsets": [ [ 237, 245 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009020" } ] }, { "id": "17545", "type": "Chemical", "text": [ "bupivacaine" ], "offsets": [ [ 331, 342 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002045" } ] }, { "id": "17546", "type": "Chemical", "text": [ "carbon dioxide" ], "offsets": [ [ 458, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002245" } ] }, { "id": "17547", "type": "Disease", "text": [ "obstructive (P less than 0.05) and central apnoea" ], "offsets": [ [ 617, 666 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020181" }, { "db_name": "MESH", "db_id": "D020182" } ] }, { "id": "17548", "type": "Disease", "text": [ "obstructive (P less than 0.05)", "apnoea" ], "offsets": [ [ 617, 647 ], [ 660, 666 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020181" } ] }, { "id": "17549", "type": "Disease", "text": [ "central apnoea" ], "offsets": [ [ 652, 666 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020182" } ] }, { "id": "17550", "type": "Chemical", "text": [ "morphine" ], "offsets": [ [ 733, 741 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009020" } ] }, { "id": "17551", "type": "Disease", "text": [ "tachyarrhythmias" ], "offsets": [ [ 789, 805 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013610" } ] }, { "id": "17552", "type": "Disease", "text": [ "ventricular ectopic beats" ], "offsets": [ [ 829, 854 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018879" } ] }, { "id": "17553", "type": "Chemical", "text": [ "morphine" ], "offsets": [ [ 881, 889 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009020" } ] } ]

[]

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[ { "id": "17554", "type": "CID", "arg1_id": "17542", "arg2_id": "17547", "normalized": [] }, { "id": "17555", "type": "CID", "arg1_id": "17542", "arg2_id": "17549", "normalized": [] }, { "id": "17556", "type": "CID", "arg1_id": "17544", "arg2_id": "17547", "normalized": [] }, { "id": "17557", "type": "CID", "arg1_id": "17544", "arg2_id": "17549", "normalized": [] }, { "id": "17558", "type": "CID", "arg1_id": "17550", "arg2_id": "17547", "normalized": [] }, { "id": "17559", "type": "CID", "arg1_id": "17550", "arg2_id": "17549", "normalized": [] }, { "id": "17560", "type": "CID", "arg1_id": "17553", "arg2_id": "17547", "normalized": [] }, { "id": "17561", "type": "CID", "arg1_id": "17553", "arg2_id": "17549", "normalized": [] }, { "id": "17562", "type": "CID", "arg1_id": "17542", "arg2_id": "17547", "normalized": [] }, { "id": "17563", "type": "CID", "arg1_id": "17542", "arg2_id": "17548", "normalized": [] }, { "id": "17564", "type": "CID", "arg1_id": "17544", "arg2_id": "17547", "normalized": [] }, { "id": "17565", "type": "CID", "arg1_id": "17544", "arg2_id": "17548", "normalized": [] }, { "id": "17566", "type": "CID", "arg1_id": "17550", "arg2_id": "17547", "normalized": [] }, { "id": "17567", "type": "CID", "arg1_id": "17550", "arg2_id": "17548", "normalized": [] }, { "id": "17568", "type": "CID", "arg1_id": "17553", "arg2_id": "17547", "normalized": [] }, { "id": "17569", "type": "CID", "arg1_id": "17553", "arg2_id": "17548", "normalized": [] }, { "id": "17570", "type": "CID", "arg1_id": "17542", "arg2_id": "17552", "normalized": [] }, { "id": "17571", "type": "CID", "arg1_id": "17544", "arg2_id": "17552", "normalized": [] }, { "id": "17572", "type": "CID", "arg1_id": "17550", "arg2_id": "17552", "normalized": [] }, { "id": "17573", "type": "CID", "arg1_id": "17553", "arg2_id": "17552", "normalized": [] } ]

[ { "id": "17575", "type": "title", "text": [ "Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages." ], "offsets": [ [ 0, 97 ] ] }, { "id": "17576", "type": "abstract", "text": [ "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders." ], "offsets": [ [ 98, 1530 ] ] } ]

[ { "id": "17577", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 50, 59 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "17578", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 75, 84 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17579", "type": "Disease", "text": [ "overdosages" ], "offsets": [ [ 85, 96 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "17580", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 161, 170 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17581", "type": "Disease", "text": [ "cerebellar atrophy" ], "offsets": [ [ 186, 204 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002526" } ] }, { "id": "17582", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 979, 986 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17583", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 1010, 1019 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17584", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 1119, 1128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17585", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 1222, 1231 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17586", "type": "Disease", "text": [ "overdosage" ], "offsets": [ [ 1232, 1242 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "17587", "type": "Disease", "text": [ "cerebellar atrophy" ], "offsets": [ [ 1274, 1292 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002526" } ] }, { "id": "17588", "type": "Chemical", "text": [ "phenytoin" ], "offsets": [ [ 1317, 1326 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010672" } ] }, { "id": "17589", "type": "Disease", "text": [ "cerebellar atrophy" ], "offsets": [ [ 1360, 1378 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002526" } ] }, { "id": "17590", "type": "Disease", "text": [ "cerebellar disorders" ], "offsets": [ [ 1509, 1529 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002526" } ] } ]

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[ { "id": "17591", "type": "CID", "arg1_id": "17578", "arg2_id": "17579", "normalized": [] }, { "id": "17592", "type": "CID", "arg1_id": "17578", "arg2_id": "17586", "normalized": [] }, { "id": "17593", "type": "CID", "arg1_id": "17580", "arg2_id": "17579", "normalized": [] }, { "id": "17594", "type": "CID", "arg1_id": "17580", "arg2_id": "17586", "normalized": [] }, { "id": "17595", "type": "CID", "arg1_id": "17583", "arg2_id": "17579", "normalized": [] }, { "id": "17596", "type": "CID", "arg1_id": "17583", "arg2_id": "17586", "normalized": [] }, { "id": "17597", "type": "CID", "arg1_id": "17584", "arg2_id": "17579", "normalized": [] }, { "id": "17598", "type": "CID", "arg1_id": "17584", "arg2_id": "17586", "normalized": [] }, { "id": "17599", "type": "CID", "arg1_id": "17585", "arg2_id": "17579", "normalized": [] }, { "id": "17600", "type": "CID", "arg1_id": "17585", "arg2_id": "17586", "normalized": [] }, { "id": "17601", "type": "CID", "arg1_id": "17588", "arg2_id": "17579", "normalized": [] }, { "id": "17602", "type": "CID", "arg1_id": "17588", "arg2_id": "17586", "normalized": [] } ]

[ { "id": "17604", "type": "title", "text": [ "Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings." ], "offsets": [ [ 0, 194 ] ] }, { "id": "17605", "type": "abstract", "text": [ "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments." ], "offsets": [ [ 195, 3282 ] ] } ]

[ { "id": "17606", "type": "Disease", "text": [ "myocardial damage" ], "offsets": [ [ 60, 77 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17607", "type": "Chemical", "text": [ "doxorubicin" ], "offsets": [ [ 81, 92 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17608", "type": "Disease", "text": [ "cardiomyopathy" ], "offsets": [ [ 101, 115 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17609", "type": "Disease", "text": [ "myocardial cell injury" ], "offsets": [ [ 310, 332 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17610", "type": "Disease", "text": [ "myocardial damage" ], "offsets": [ [ 409, 426 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17611", "type": "Chemical", "text": [ "doxorubicin" ], "offsets": [ [ 445, 456 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17612", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 458, 461 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17613", "type": "Disease", "text": [ "cardiomyopathy" ], "offsets": [ [ 471, 485 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17614", "type": "Disease", "text": [ "cardiac disorders" ], "offsets": [ [ 573, 590 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006331" } ] }, { "id": "17615", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 720, 723 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17616", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1125, 1128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17617", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1227, 1230 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17618", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1268, 1271 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17619", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1323, 1326 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17620", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1360, 1368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "17621", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1526, 1529 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17622", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1650, 1653 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17623", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1723, 1731 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "17624", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1878, 1886 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "17625", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 1928, 1931 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17626", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 2111, 2114 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17627", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 2185, 2188 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17628", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 2289, 2292 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17629", "type": "Disease", "text": [ "ischemic injury" ], "offsets": [ [ 2693, 2708 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] }, { "id": "17630", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 2715, 2718 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17631", "type": "Disease", "text": [ "myocardial damage" ], "offsets": [ [ 2771, 2788 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "17632", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 2930, 2933 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17633", "type": "Chemical", "text": [ "DOX" ], "offsets": [ [ 3064, 3067 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "17634", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 3221, 3235 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] } ]

[]

[]

[ { "id": "17635", "type": "CID", "arg1_id": "17607", "arg2_id": "17606", "normalized": [] }, { "id": "17636", "type": "CID", "arg1_id": "17607", "arg2_id": "17608", "normalized": [] }, { "id": "17637", "type": "CID", "arg1_id": "17607", "arg2_id": "17609", "normalized": [] }, { "id": "17638", "type": "CID", "arg1_id": "17607", "arg2_id": "17610", "normalized": [] }, { "id": "17639", "type": "CID", "arg1_id": "17607", "arg2_id": "17613", "normalized": [] }, { "id": "17640", "type": "CID", "arg1_id": "17607", "arg2_id": "17631", "normalized": [] }, { "id": "17641", "type": "CID", "arg1_id": "17611", "arg2_id": "17606", "normalized": [] }, { "id": "17642", "type": "CID", "arg1_id": "17611", "arg2_id": "17608", "normalized": [] }, { "id": "17643", "type": "CID", "arg1_id": "17611", "arg2_id": "17609", "normalized": [] }, { "id": "17644", "type": "CID", "arg1_id": "17611", "arg2_id": "17610", "normalized": [] }, { "id": "17645", "type": "CID", "arg1_id": "17611", "arg2_id": "17613", "normalized": [] }, { "id": "17646", "type": "CID", "arg1_id": "17611", "arg2_id": "17631", "normalized": [] }, { "id": "17647", "type": "CID", "arg1_id": "17612", "arg2_id": "17606", "normalized": [] }, { "id": "17648", "type": "CID", "arg1_id": "17612", "arg2_id": "17608", "normalized": [] }, { "id": "17649", "type": "CID", "arg1_id": "17612", "arg2_id": "17609", "normalized": [] }, { "id": "17650", "type": "CID", "arg1_id": "17612", "arg2_id": "17610", "normalized": [] }, { "id": "17651", "type": "CID", "arg1_id": "17612", "arg2_id": "17613", "normalized": [] }, { "id": "17652", "type": "CID", "arg1_id": "17612", "arg2_id": "17631", "normalized": [] }, { "id": "17653", "type": "CID", "arg1_id": "17615", "arg2_id": "17606", "normalized": [] }, { "id": "17654", "type": "CID", "arg1_id": "17615", "arg2_id": "17608", "normalized": [] }, { "id": "17655", "type": "CID", "arg1_id": "17615", "arg2_id": "17609", "normalized": [] }, { "id": "17656", "type": "CID", "arg1_id": "17615", "arg2_id": "17610", "normalized": [] }, { "id": "17657", "type": "CID", "arg1_id": "17615", "arg2_id": "17613", "normalized": [] }, { "id": "17658", "type": "CID", "arg1_id": "17615", "arg2_id": "17631", "normalized": [] }, { "id": "17659", "type": "CID", "arg1_id": "17616", "arg2_id": "17606", "normalized": [] }, { "id": "17660", "type": "CID", "arg1_id": "17616", "arg2_id": "17608", "normalized": [] }, { "id": "17661", "type": "CID", "arg1_id": "17616", "arg2_id": "17609", "normalized": [] }, { "id": "17662", "type": "CID", "arg1_id": "17616", "arg2_id": "17610", "normalized": [] }, { "id": "17663", "type": "CID", "arg1_id": "17616", "arg2_id": "17613", "normalized": [] }, { "id": "17664", "type": "CID", "arg1_id": "17616", "arg2_id": "17631", "normalized": [] }, { "id": "17665", "type": "CID", "arg1_id": "17617", "arg2_id": "17606", "normalized": [] }, { "id": "17666", "type": "CID", "arg1_id": "17617", "arg2_id": "17608", "normalized": [] }, { "id": "17667", "type": "CID", "arg1_id": "17617", "arg2_id": "17609", "normalized": [] }, { "id": "17668", "type": "CID", "arg1_id": "17617", "arg2_id": "17610", "normalized": [] }, { "id": "17669", "type": "CID", "arg1_id": "17617", "arg2_id": "17613", "normalized": [] }, { "id": "17670", "type": "CID", "arg1_id": "17617", "arg2_id": "17631", "normalized": [] }, { "id": "17671", "type": "CID", "arg1_id": "17618", "arg2_id": "17606", "normalized": [] }, { "id": "17672", "type": "CID", "arg1_id": "17618", "arg2_id": "17608", "normalized": [] }, { "id": "17673", "type": "CID", "arg1_id": "17618", "arg2_id": "17609", "normalized": [] }, { "id": "17674", "type": "CID", "arg1_id": "17618", "arg2_id": "17610", "normalized": [] }, { "id": "17675", "type": "CID", "arg1_id": "17618", "arg2_id": "17613", "normalized": [] }, { "id": "17676", "type": "CID", "arg1_id": "17618", "arg2_id": "17631", "normalized": [] }, { "id": "17677", "type": "CID", "arg1_id": "17619", "arg2_id": "17606", "normalized": [] }, { "id": "17678", "type": "CID", "arg1_id": "17619", "arg2_id": "17608", "normalized": [] }, { "id": "17679", "type": "CID", "arg1_id": "17619", "arg2_id": "17609", "normalized": [] }, { "id": "17680", "type": "CID", "arg1_id": "17619", "arg2_id": "17610", "normalized": [] }, { "id": "17681", "type": "CID", "arg1_id": "17619", "arg2_id": "17613", "normalized": [] }, { "id": "17682", "type": "CID", "arg1_id": "17619", "arg2_id": "17631", "normalized": [] }, { "id": "17683", "type": "CID", "arg1_id": "17621", "arg2_id": "17606", "normalized": [] }, { "id": "17684", "type": "CID", "arg1_id": "17621", "arg2_id": "17608", "normalized": [] }, { "id": "17685", "type": "CID", "arg1_id": "17621", "arg2_id": "17609", "normalized": [] }, { "id": "17686", "type": "CID", "arg1_id": "17621", "arg2_id": "17610", "normalized": [] }, { "id": "17687", "type": "CID", "arg1_id": "17621", "arg2_id": "17613", "normalized": [] }, { "id": "17688", "type": "CID", "arg1_id": "17621", "arg2_id": "17631", "normalized": [] }, { "id": "17689", "type": "CID", "arg1_id": "17622", "arg2_id": "17606", "normalized": [] }, { "id": "17690", "type": "CID", "arg1_id": "17622", "arg2_id": "17608", "normalized": [] }, { "id": "17691", "type": "CID", "arg1_id": "17622", "arg2_id": "17609", "normalized": [] }, { "id": "17692", "type": "CID", "arg1_id": "17622", "arg2_id": "17610", "normalized": [] }, { "id": "17693", "type": "CID", "arg1_id": "17622", "arg2_id": "17613", "normalized": [] }, { "id": "17694", "type": "CID", "arg1_id": "17622", "arg2_id": "17631", "normalized": [] }, { "id": "17695", "type": "CID", "arg1_id": "17625", "arg2_id": "17606", "normalized": [] }, { "id": "17696", "type": "CID", "arg1_id": "17625", "arg2_id": "17608", "normalized": [] }, { "id": "17697", "type": "CID", "arg1_id": "17625", "arg2_id": "17609", "normalized": [] }, { "id": "17698", "type": "CID", "arg1_id": "17625", "arg2_id": "17610", "normalized": [] }, { "id": "17699", "type": "CID", "arg1_id": "17625", "arg2_id": "17613", "normalized": [] }, { "id": "17700", "type": "CID", "arg1_id": "17625", "arg2_id": "17631", "normalized": [] }, { "id": "17701", "type": "CID", "arg1_id": "17626", "arg2_id": "17606", "normalized": [] }, { "id": "17702", "type": "CID", "arg1_id": "17626", "arg2_id": "17608", "normalized": [] }, { "id": "17703", "type": "CID", "arg1_id": "17626", "arg2_id": "17609", "normalized": [] }, { "id": "17704", "type": "CID", "arg1_id": "17626", "arg2_id": "17610", "normalized": [] }, { "id": "17705", "type": "CID", "arg1_id": "17626", "arg2_id": "17613", "normalized": [] }, { "id": "17706", "type": "CID", "arg1_id": "17626", "arg2_id": "17631", "normalized": [] }, { "id": "17707", "type": "CID", "arg1_id": "17627", "arg2_id": "17606", "normalized": [] }, { "id": "17708", "type": "CID", "arg1_id": "17627", "arg2_id": "17608", "normalized": [] }, { "id": "17709", "type": "CID", "arg1_id": "17627", "arg2_id": "17609", "normalized": [] }, { "id": "17710", "type": "CID", "arg1_id": "17627", "arg2_id": "17610", "normalized": [] }, { "id": "17711", "type": "CID", "arg1_id": "17627", "arg2_id": "17613", "normalized": [] }, { "id": "17712", "type": "CID", "arg1_id": "17627", "arg2_id": "17631", "normalized": [] }, { "id": "17713", "type": "CID", "arg1_id": "17628", "arg2_id": "17606", "normalized": [] }, { "id": "17714", "type": "CID", "arg1_id": "17628", "arg2_id": "17608", "normalized": [] }, { "id": "17715", "type": "CID", "arg1_id": "17628", "arg2_id": "17609", "normalized": [] }, { "id": "17716", "type": "CID", "arg1_id": "17628", "arg2_id": "17610", "normalized": [] }, { "id": "17717", "type": "CID", "arg1_id": "17628", "arg2_id": "17613", "normalized": [] }, { "id": "17718", "type": "CID", "arg1_id": "17628", "arg2_id": "17631", "normalized": [] }, { "id": "17719", "type": "CID", "arg1_id": "17630", "arg2_id": "17606", "normalized": [] }, { "id": "17720", "type": "CID", "arg1_id": "17630", "arg2_id": "17608", "normalized": [] }, { "id": "17721", "type": "CID", "arg1_id": "17630", "arg2_id": "17609", "normalized": [] }, { "id": "17722", "type": "CID", "arg1_id": "17630", "arg2_id": "17610", "normalized": [] }, { "id": "17723", "type": "CID", "arg1_id": "17630", "arg2_id": "17613", "normalized": [] }, { "id": "17724", "type": "CID", "arg1_id": "17630", "arg2_id": "17631", "normalized": [] }, { "id": "17725", "type": "CID", "arg1_id": "17632", "arg2_id": "17606", "normalized": [] }, { "id": "17726", "type": "CID", "arg1_id": "17632", "arg2_id": "17608", "normalized": [] }, { "id": "17727", "type": "CID", "arg1_id": "17632", "arg2_id": "17609", "normalized": [] }, { "id": "17728", "type": "CID", "arg1_id": "17632", "arg2_id": "17610", "normalized": [] }, { "id": "17729", "type": "CID", "arg1_id": "17632", "arg2_id": "17613", "normalized": [] }, { "id": "17730", "type": "CID", "arg1_id": "17632", "arg2_id": "17631", "normalized": [] }, { "id": "17731", "type": "CID", "arg1_id": "17633", "arg2_id": "17606", "normalized": [] }, { "id": "17732", "type": "CID", "arg1_id": "17633", "arg2_id": "17608", "normalized": [] }, { "id": "17733", "type": "CID", "arg1_id": "17633", "arg2_id": "17609", "normalized": [] }, { "id": "17734", "type": "CID", "arg1_id": "17633", "arg2_id": "17610", "normalized": [] }, { "id": "17735", "type": "CID", "arg1_id": "17633", "arg2_id": "17613", "normalized": [] }, { "id": "17736", "type": "CID", "arg1_id": "17633", "arg2_id": "17631", "normalized": [] } ]

[ { "id": "17738", "type": "title", "text": [ "Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation." ], "offsets": [ [ 0, 112 ] ] }, { "id": "17739", "type": "abstract", "text": [ "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS." ], "offsets": [ [ 113, 1275 ] ] } ]

[ { "id": "17740", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 30, 34 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17741", "type": "Disease", "text": [ "CIPS" ], "offsets": [ [ 45, 49 ] ], "normalized": [] }, { "id": "17742", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 118, 122 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17743", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 272, 276 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17744", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 304, 308 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17745", "type": "Disease", "text": [ "bone marrow oedema" ], "offsets": [ [ 491, 509 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001855" }, { "db_name": "MESH", "db_id": "D004487" } ] }, { "id": "17746", "type": "Disease", "text": [ "bone marrow" ], "offsets": [ [ 491, 502 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001855" } ] }, { "id": "17747", "type": "Disease", "text": [ "oedema" ], "offsets": [ [ 503, 509 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004487" } ] }, { "id": "17748", "type": "Disease", "text": [ "Pain" ], "offsets": [ [ 532, 536 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17749", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 586, 590 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17750", "type": "Disease", "text": [ "reflex sympathetic dystrophy" ], "offsets": [ [ 597, 625 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012019" } ] }, { "id": "17751", "type": "Disease", "text": [ "polyneuropathy" ], "offsets": [ [ 627, 641 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011115" } ] }, { "id": "17752", "type": "Disease", "text": [ "Morton's neuralgia" ], "offsets": [ [ 643, 661 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009437" } ] }, { "id": "17753", "type": "Disease", "text": [ "gout" ], "offsets": [ [ 663, 667 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006073" } ] }, { "id": "17754", "type": "Disease", "text": [ "osteoporosis" ], "offsets": [ [ 669, 681 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010024" } ] }, { "id": "17755", "type": "Disease", "text": [ "avascular necrosis" ], "offsets": [ [ 683, 701 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010020" } ] }, { "id": "17756", "type": "Disease", "text": [ "intermittent claudication" ], "offsets": [ [ 703, 728 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007383" } ] }, { "id": "17757", "type": "Disease", "text": [ "foot deformities" ], "offsets": [ [ 742, 758 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005530" } ] }, { "id": "17758", "type": "Disease", "text": [ "stress fractures" ], "offsets": [ [ 760, 776 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015775" } ] }, { "id": "17759", "type": "Disease", "text": [ "hyperparathyroidism" ], "offsets": [ [ 782, 801 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006961" } ] }, { "id": "17760", "type": "Chemical", "text": [ "cyclosporine" ], "offsets": [ [ 820, 832 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "17761", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 837, 847 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "17762", "type": "Chemical", "text": [ "calcium" ], "offsets": [ [ 888, 895 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002118" } ] }, { "id": "17763", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 930, 934 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17764", "type": "Disease", "text": [ "Pain" ], "offsets": [ [ 970, 974 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "17765", "type": "Disease", "text": [ "CIPS" ], "offsets": [ [ 985, 989 ] ], "normalized": [] }, { "id": "17766", "type": "Chemical", "text": [ "cyclosporine" ], "offsets": [ [ 1027, 1039 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "17767", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 1043, 1053 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "17768", "type": "Disease", "text": [ "CIPS" ], "offsets": [ [ 1270, 1274 ] ], "normalized": [] } ]

[]

[]

[ { "id": "17769", "type": "CID", "arg1_id": "17761", "arg2_id": "17740", "normalized": [] }, { "id": "17770", "type": "CID", "arg1_id": "17761", "arg2_id": "17742", "normalized": [] }, { "id": "17771", "type": "CID", "arg1_id": "17761", "arg2_id": "17743", "normalized": [] }, { "id": "17772", "type": "CID", "arg1_id": "17761", "arg2_id": "17744", "normalized": [] }, { "id": "17773", "type": "CID", "arg1_id": "17761", "arg2_id": "17748", "normalized": [] }, { "id": "17774", "type": "CID", "arg1_id": "17761", "arg2_id": "17749", "normalized": [] }, { "id": "17775", "type": "CID", "arg1_id": "17761", "arg2_id": "17763", "normalized": [] }, { "id": "17776", "type": "CID", "arg1_id": "17761", "arg2_id": "17764", "normalized": [] }, { "id": "17777", "type": "CID", "arg1_id": "17767", "arg2_id": "17740", "normalized": [] }, { "id": "17778", "type": "CID", "arg1_id": "17767", "arg2_id": "17742", "normalized": [] }, { "id": "17779", "type": "CID", "arg1_id": "17767", "arg2_id": "17743", "normalized": [] }, { "id": "17780", "type": "CID", "arg1_id": "17767", "arg2_id": "17744", "normalized": [] }, { "id": "17781", "type": "CID", "arg1_id": "17767", "arg2_id": "17748", "normalized": [] }, { "id": "17782", "type": "CID", "arg1_id": "17767", "arg2_id": "17749", "normalized": [] }, { "id": "17783", "type": "CID", "arg1_id": "17767", "arg2_id": "17763", "normalized": [] }, { "id": "17784", "type": "CID", "arg1_id": "17767", "arg2_id": "17764", "normalized": [] }, { "id": "17785", "type": "CID", "arg1_id": "17761", "arg2_id": "17745", "normalized": [] }, { "id": "17786", "type": "CID", "arg1_id": "17761", "arg2_id": "17747", "normalized": [] }, { "id": "17787", "type": "CID", "arg1_id": "17767", "arg2_id": "17745", "normalized": [] }, { "id": "17788", "type": "CID", "arg1_id": "17767", "arg2_id": "17747", "normalized": [] }, { "id": "17789", "type": "CID", "arg1_id": "17761", "arg2_id": "17745", "normalized": [] }, { "id": "17790", "type": "CID", "arg1_id": "17761", "arg2_id": "17746", "normalized": [] }, { "id": "17791", "type": "CID", "arg1_id": "17767", "arg2_id": "17745", "normalized": [] }, { "id": "17792", "type": "CID", "arg1_id": "17767", "arg2_id": "17746", "normalized": [] }, { "id": "17793", "type": "CID", "arg1_id": "17760", "arg2_id": "17745", "normalized": [] }, { "id": "17794", "type": "CID", "arg1_id": "17760", "arg2_id": "17746", "normalized": [] }, { "id": "17795", "type": "CID", "arg1_id": "17766", "arg2_id": "17745", "normalized": [] }, { "id": "17796", "type": "CID", "arg1_id": "17766", "arg2_id": "17746", "normalized": [] }, { "id": "17797", "type": "CID", "arg1_id": "17760", "arg2_id": "17745", "normalized": [] }, { "id": "17798", "type": "CID", "arg1_id": "17760", "arg2_id": "17747", "normalized": [] }, { "id": "17799", "type": "CID", "arg1_id": "17766", "arg2_id": "17745", "normalized": [] }, { "id": "17800", "type": "CID", "arg1_id": "17766", "arg2_id": "17747", "normalized": [] }, { "id": "17801", "type": "CID", "arg1_id": "17760", "arg2_id": "17740", "normalized": [] }, { "id": "17802", "type": "CID", "arg1_id": "17760", "arg2_id": "17742", "normalized": [] }, { "id": "17803", "type": "CID", "arg1_id": "17760", "arg2_id": "17743", "normalized": [] }, { "id": "17804", "type": "CID", "arg1_id": "17760", "arg2_id": "17744", "normalized": [] }, { "id": "17805", "type": "CID", "arg1_id": "17760", "arg2_id": "17748", "normalized": [] }, { "id": "17806", "type": "CID", "arg1_id": "17760", "arg2_id": "17749", "normalized": [] }, { "id": "17807", "type": "CID", "arg1_id": "17760", "arg2_id": "17763", "normalized": [] }, { "id": "17808", "type": "CID", "arg1_id": "17760", "arg2_id": "17764", "normalized": [] }, { "id": "17809", "type": "CID", "arg1_id": "17766", "arg2_id": "17740", "normalized": [] }, { "id": "17810", "type": "CID", "arg1_id": "17766", "arg2_id": "17742", "normalized": [] }, { "id": "17811", "type": "CID", "arg1_id": "17766", "arg2_id": "17743", "normalized": [] }, { "id": "17812", "type": "CID", "arg1_id": "17766", "arg2_id": "17744", "normalized": [] }, { "id": "17813", "type": "CID", "arg1_id": "17766", "arg2_id": "17748", "normalized": [] }, { "id": "17814", "type": "CID", "arg1_id": "17766", "arg2_id": "17749", "normalized": [] }, { "id": "17815", "type": "CID", "arg1_id": "17766", "arg2_id": "17763", "normalized": [] }, { "id": "17816", "type": "CID", "arg1_id": "17766", "arg2_id": "17764", "normalized": [] } ]

[ { "id": "17818", "type": "title", "text": [ "The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4)." ], "offsets": [ [ 0, 108 ] ] }, { "id": "17819", "type": "abstract", "text": [ "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied." ], "offsets": [ [ 109, 1055 ] ] } ]

[ { "id": "17820", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 28, 36 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17821", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 57, 66 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17822", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 166, 174 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17823", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 289, 298 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17824", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 302, 310 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17825", "type": "Disease", "text": [ "hypotensive" ], "offsets": [ [ 334, 345 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "17826", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 410, 419 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17827", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 433, 441 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17828", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 559, 568 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17829", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 572, 580 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17830", "type": "Disease", "text": [ "hypotensive" ], "offsets": [ [ 632, 643 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "17831", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 656, 664 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17832", "type": "Disease", "text": [ "tachycardia" ], "offsets": [ [ 714, 725 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013610" } ] }, { "id": "17833", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 753, 762 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17834", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 783, 791 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] }, { "id": "17835", "type": "Disease", "text": [ "tachycardia" ], "offsets": [ [ 912, 923 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013610" } ] }, { "id": "17836", "type": "Disease", "text": [ "myocardial ischemia" ], "offsets": [ [ 933, 952 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017202" } ] }, { "id": "17837", "type": "Chemical", "text": [ "ephedrine" ], "offsets": [ [ 1019, 1028 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004809" } ] }, { "id": "17838", "type": "Chemical", "text": [ "propofol" ], "offsets": [ [ 1029, 1037 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015742" } ] } ]

[]

[]

[ { "id": "17839", "type": "CID", "arg1_id": "17820", "arg2_id": "17825", "normalized": [] }, { "id": "17840", "type": "CID", "arg1_id": "17820", "arg2_id": "17830", "normalized": [] }, { "id": "17841", "type": "CID", "arg1_id": "17822", "arg2_id": "17825", "normalized": [] }, { "id": "17842", "type": "CID", "arg1_id": "17822", "arg2_id": "17830", "normalized": [] }, { "id": "17843", "type": "CID", "arg1_id": "17824", "arg2_id": "17825", "normalized": [] }, { "id": "17844", "type": "CID", "arg1_id": "17824", "arg2_id": "17830", "normalized": [] }, { "id": "17845", "type": "CID", "arg1_id": "17827", "arg2_id": "17825", "normalized": [] }, { "id": "17846", "type": "CID", "arg1_id": "17827", "arg2_id": "17830", "normalized": [] }, { "id": "17847", "type": "CID", "arg1_id": "17829", "arg2_id": "17825", "normalized": [] }, { "id": "17848", "type": "CID", "arg1_id": "17829", "arg2_id": "17830", "normalized": [] }, { "id": "17849", "type": "CID", "arg1_id": "17831", "arg2_id": "17825", "normalized": [] }, { "id": "17850", "type": "CID", "arg1_id": "17831", "arg2_id": "17830", "normalized": [] }, { "id": "17851", "type": "CID", "arg1_id": "17834", "arg2_id": "17825", "normalized": [] }, { "id": "17852", "type": "CID", "arg1_id": "17834", "arg2_id": "17830", "normalized": [] }, { "id": "17853", "type": "CID", "arg1_id": "17838", "arg2_id": "17825", "normalized": [] }, { "id": "17854", "type": "CID", "arg1_id": "17838", "arg2_id": "17830", "normalized": [] }, { "id": "17855", "type": "CID", "arg1_id": "17820", "arg2_id": "17832", "normalized": [] }, { "id": "17856", "type": "CID", "arg1_id": "17820", "arg2_id": "17835", "normalized": [] }, { "id": "17857", "type": "CID", "arg1_id": "17822", "arg2_id": "17832", "normalized": [] }, { "id": "17858", "type": "CID", "arg1_id": "17822", "arg2_id": "17835", "normalized": [] }, { "id": "17859", "type": "CID", "arg1_id": "17824", "arg2_id": "17832", "normalized": [] }, { "id": "17860", "type": "CID", "arg1_id": "17824", "arg2_id": "17835", "normalized": [] }, { "id": "17861", "type": "CID", "arg1_id": "17827", "arg2_id": "17832", "normalized": [] }, { "id": "17862", "type": "CID", "arg1_id": "17827", "arg2_id": "17835", "normalized": [] }, { "id": "17863", "type": "CID", "arg1_id": "17829", "arg2_id": "17832", "normalized": [] }, { "id": "17864", "type": "CID", "arg1_id": "17829", "arg2_id": "17835", "normalized": [] }, { "id": "17865", "type": "CID", "arg1_id": "17831", "arg2_id": "17832", "normalized": [] }, { "id": "17866", "type": "CID", "arg1_id": "17831", "arg2_id": "17835", "normalized": [] }, { "id": "17867", "type": "CID", "arg1_id": "17834", "arg2_id": "17832", "normalized": [] }, { "id": "17868", "type": "CID", "arg1_id": "17834", "arg2_id": "17835", "normalized": [] }, { "id": "17869", "type": "CID", "arg1_id": "17838", "arg2_id": "17832", "normalized": [] }, { "id": "17870", "type": "CID", "arg1_id": "17838", "arg2_id": "17835", "normalized": [] }, { "id": "17871", "type": "CID", "arg1_id": "17821", "arg2_id": "17832", "normalized": [] }, { "id": "17872", "type": "CID", "arg1_id": "17821", "arg2_id": "17835", "normalized": [] }, { "id": "17873", "type": "CID", "arg1_id": "17823", "arg2_id": "17832", "normalized": [] }, { "id": "17874", "type": "CID", "arg1_id": "17823", "arg2_id": "17835", "normalized": [] }, { "id": "17875", "type": "CID", "arg1_id": "17826", "arg2_id": "17832", "normalized": [] }, { "id": "17876", "type": "CID", "arg1_id": "17826", "arg2_id": "17835", "normalized": [] }, { "id": "17877", "type": "CID", "arg1_id": "17828", "arg2_id": "17832", "normalized": [] }, { "id": "17878", "type": "CID", "arg1_id": "17828", "arg2_id": "17835", "normalized": [] }, { "id": "17879", "type": "CID", "arg1_id": "17833", "arg2_id": "17832", "normalized": [] }, { "id": "17880", "type": "CID", "arg1_id": "17833", "arg2_id": "17835", "normalized": [] }, { "id": "17881", "type": "CID", "arg1_id": "17837", "arg2_id": "17832", "normalized": [] }, { "id": "17882", "type": "CID", "arg1_id": "17837", "arg2_id": "17835", "normalized": [] } ]

[ { "id": "17884", "type": "title", "text": [ "Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan." ], "offsets": [ [ 0, 98 ] ] }, { "id": "17885", "type": "abstract", "text": [ "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug." ], "offsets": [ [ 99, 1446 ] ] } ]

[ { "id": "17886", "type": "Disease", "text": [ "Neurotoxicity" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "17887", "type": "Chemical", "text": [ "halogenated hydroxyquinolines" ], "offsets": [ [ 17, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006912" } ] }, { "id": "17888", "type": "Disease", "text": [ "neurotoxic" ], "offsets": [ [ 149, 159 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "17889", "type": "Chemical", "text": [ "halogenated hydroxyquinolines" ], "offsets": [ [ 173, 202 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006912" } ] }, { "id": "17890", "type": "Chemical", "text": [ "clioquinol" ], "offsets": [ [ 354, 364 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007464" } ] }, { "id": "17891", "type": "Chemical", "text": [ "clioquinol" ], "offsets": [ [ 420, 430 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007464" } ] }, { "id": "17892", "type": "Disease", "text": [ "neurological disturbance" ], "offsets": [ [ 520, 544 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" } ] }, { "id": "17893", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 578, 592 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17894", "type": "Chemical", "text": [ "clioquinol" ], "offsets": [ [ 644, 654 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007464" } ] }, { "id": "17895", "type": "Disease", "text": [ "optic atrophy" ], "offsets": [ [ 750, 763 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009896" } ] }, { "id": "17896", "type": "Chemical", "text": [ "clioquinol" ], "offsets": [ [ 835, 845 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007464" } ] }, { "id": "17897", "type": "Disease", "text": [ "acrodermatitis enteropathica" ], "offsets": [ [ 863, 891 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C538178" } ] }, { "id": "17898", "type": "Disease", "text": [ "myelopathy" ], "offsets": [ [ 934, 944 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013118" } ] }, { "id": "17899", "type": "Disease", "text": [ "visual disturbance" ], "offsets": [ [ 946, 964 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014786" } ] }, { "id": "17900", "type": "Disease", "text": [ "peripheral neuropathy" ], "offsets": [ [ 970, 991 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] }, { "id": "17901", "type": "Disease", "text": [ "myelopathy" ], "offsets": [ [ 1036, 1046 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013118" } ] }, { "id": "17902", "type": "Disease", "text": [ "peripheral neuropathy" ], "offsets": [ [ 1050, 1071 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] }, { "id": "17903", "type": "Disease", "text": [ "encephalopathy" ], "offsets": [ [ 1180, 1194 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001927" } ] }, { "id": "17904", "type": "Disease", "text": [ "myelo-optic neuropathy" ], "offsets": [ [ 1334, 1356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013118" }, { "db_name": "MESH", "db_id": "D009901" } ] }, { "id": "17905", "type": "Disease", "text": [ "myelo", "neuropathy" ], "offsets": [ [ 1334, 1339 ], [ 1346, 1356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013118" } ] }, { "id": "17906", "type": "Disease", "text": [ "optic neuropathy" ], "offsets": [ [ 1340, 1356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009901" } ] } ]

[]

[]

[ { "id": "17907", "type": "CID", "arg1_id": "17890", "arg2_id": "17893", "normalized": [] }, { "id": "17908", "type": "CID", "arg1_id": "17890", "arg2_id": "17903", "normalized": [] }, { "id": "17909", "type": "CID", "arg1_id": "17891", "arg2_id": "17893", "normalized": [] }, { "id": "17910", "type": "CID", "arg1_id": "17891", "arg2_id": "17903", "normalized": [] }, { "id": "17911", "type": "CID", "arg1_id": "17894", "arg2_id": "17893", "normalized": [] }, { "id": "17912", "type": "CID", "arg1_id": "17894", "arg2_id": "17903", "normalized": [] }, { "id": "17913", "type": "CID", "arg1_id": "17896", "arg2_id": "17893", "normalized": [] }, { "id": "17914", "type": "CID", "arg1_id": "17896", "arg2_id": "17903", "normalized": [] }, { "id": "17915", "type": "CID", "arg1_id": "17890", "arg2_id": "17899", "normalized": [] }, { "id": "17916", "type": "CID", "arg1_id": "17891", "arg2_id": "17899", "normalized": [] }, { "id": "17917", "type": "CID", "arg1_id": "17894", "arg2_id": "17899", "normalized": [] }, { "id": "17918", "type": "CID", "arg1_id": "17896", "arg2_id": "17899", "normalized": [] }, { "id": "17919", "type": "CID", "arg1_id": "17890", "arg2_id": "17900", "normalized": [] }, { "id": "17920", "type": "CID", "arg1_id": "17890", "arg2_id": "17902", "normalized": [] }, { "id": "17921", "type": "CID", "arg1_id": "17891", "arg2_id": "17900", "normalized": [] }, { "id": "17922", "type": "CID", "arg1_id": "17891", "arg2_id": "17902", "normalized": [] }, { "id": "17923", "type": "CID", "arg1_id": "17894", "arg2_id": "17900", "normalized": [] }, { "id": "17924", "type": "CID", "arg1_id": "17894", "arg2_id": "17902", "normalized": [] }, { "id": "17925", "type": "CID", "arg1_id": "17896", "arg2_id": "17900", "normalized": [] }, { "id": "17926", "type": "CID", "arg1_id": "17896", "arg2_id": "17902", "normalized": [] }, { "id": "17927", "type": "CID", "arg1_id": "17890", "arg2_id": "17895", "normalized": [] }, { "id": "17928", "type": "CID", "arg1_id": "17891", "arg2_id": "17895", "normalized": [] }, { "id": "17929", "type": "CID", "arg1_id": "17894", "arg2_id": "17895", "normalized": [] }, { "id": "17930", "type": "CID", "arg1_id": "17896", "arg2_id": "17895", "normalized": [] }, { "id": "17931", "type": "CID", "arg1_id": "17890", "arg2_id": "17898", "normalized": [] }, { "id": "17932", "type": "CID", "arg1_id": "17890", "arg2_id": "17901", "normalized": [] }, { "id": "17933", "type": "CID", "arg1_id": "17890", "arg2_id": "17904", "normalized": [] }, { "id": "17934", "type": "CID", "arg1_id": "17890", "arg2_id": "17905", "normalized": [] }, { "id": "17935", "type": "CID", "arg1_id": "17891", "arg2_id": "17898", "normalized": [] }, { "id": "17936", "type": "CID", "arg1_id": "17891", "arg2_id": "17901", "normalized": [] }, { "id": "17937", "type": "CID", "arg1_id": "17891", "arg2_id": "17904", "normalized": [] }, { "id": "17938", "type": "CID", "arg1_id": "17891", "arg2_id": "17905", "normalized": [] }, { "id": "17939", "type": "CID", "arg1_id": "17894", "arg2_id": "17898", "normalized": [] }, { "id": "17940", "type": "CID", "arg1_id": "17894", "arg2_id": "17901", "normalized": [] }, { "id": "17941", "type": "CID", "arg1_id": "17894", "arg2_id": "17904", "normalized": [] }, { "id": "17942", "type": "CID", "arg1_id": "17894", "arg2_id": "17905", "normalized": [] }, { "id": "17943", "type": "CID", "arg1_id": "17896", "arg2_id": "17898", "normalized": [] }, { "id": "17944", "type": "CID", "arg1_id": "17896", "arg2_id": "17901", "normalized": [] }, { "id": "17945", "type": "CID", "arg1_id": "17896", "arg2_id": "17904", "normalized": [] }, { "id": "17946", "type": "CID", "arg1_id": "17896", "arg2_id": "17905", "normalized": [] } ]

[ { "id": "17948", "type": "title", "text": [ "Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats." ], "offsets": [ [ 0, 104 ] ] }, { "id": "17949", "type": "abstract", "text": [ "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient." ], "offsets": [ [ 105, 1582 ] ] } ]

[ { "id": "17950", "type": "Disease", "text": [ "Epileptic seizures" ], "offsets": [ [ 0, 18 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "17951", "type": "Chemical", "text": [ "tranexamic acid" ], "offsets": [ [ 80, 95 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17952", "type": "Chemical", "text": [ "tranexamic acid" ], "offsets": [ [ 356, 371 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17953", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 373, 378 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17954", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 440, 445 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17955", "type": "Disease", "text": [ "epileptic seizures" ], "offsets": [ [ 470, 488 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "17956", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 517, 522 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17957", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 535, 545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17958", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 643, 648 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17959", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 916, 921 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17960", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 990, 1000 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17961", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1033, 1041 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17962", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 1085, 1090 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17963", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 1123, 1128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17964", "type": "Disease", "text": [ "generalized seizures" ], "offsets": [ [ 1136, 1156 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17965", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 1216, 1221 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17966", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 1280, 1290 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17967", "type": "Chemical", "text": [ "Tranexamic acid" ], "offsets": [ [ 1410, 1425 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] }, { "id": "17968", "type": "Disease", "text": [ "convulsive" ], "offsets": [ [ 1438, 1448 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "17969", "type": "Chemical", "text": [ "tAMCA" ], "offsets": [ [ 1494, 1499 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014148" } ] } ]

[]

[]

[ { "id": "17970", "type": "CID", "arg1_id": "17951", "arg2_id": "17957", "normalized": [] }, { "id": "17971", "type": "CID", "arg1_id": "17951", "arg2_id": "17960", "normalized": [] }, { "id": "17972", "type": "CID", "arg1_id": "17951", "arg2_id": "17961", "normalized": [] }, { "id": "17973", "type": "CID", "arg1_id": "17951", "arg2_id": "17964", "normalized": [] }, { "id": "17974", "type": "CID", "arg1_id": "17951", "arg2_id": "17966", "normalized": [] }, { "id": "17975", "type": "CID", "arg1_id": "17951", "arg2_id": "17968", "normalized": [] }, { "id": "17976", "type": "CID", "arg1_id": "17952", "arg2_id": "17957", "normalized": [] }, { "id": "17977", "type": "CID", "arg1_id": "17952", "arg2_id": "17960", "normalized": [] }, { "id": "17978", "type": "CID", "arg1_id": "17952", "arg2_id": "17961", "normalized": [] }, { "id": "17979", "type": "CID", "arg1_id": "17952", "arg2_id": "17964", "normalized": [] }, { "id": "17980", "type": "CID", "arg1_id": "17952", "arg2_id": "17966", "normalized": [] }, { "id": "17981", "type": "CID", "arg1_id": "17952", "arg2_id": "17968", "normalized": [] }, { "id": "17982", "type": "CID", "arg1_id": "17953", "arg2_id": "17957", "normalized": [] }, { "id": "17983", "type": "CID", "arg1_id": "17953", "arg2_id": "17960", "normalized": [] }, { "id": "17984", "type": "CID", "arg1_id": "17953", "arg2_id": "17961", "normalized": [] }, { "id": "17985", "type": "CID", "arg1_id": "17953", "arg2_id": "17964", "normalized": [] }, { "id": "17986", "type": "CID", "arg1_id": "17953", "arg2_id": "17966", "normalized": [] }, { "id": "17987", "type": "CID", "arg1_id": "17953", "arg2_id": "17968", "normalized": [] }, { "id": "17988", "type": "CID", "arg1_id": "17954", "arg2_id": "17957", "normalized": [] }, { "id": "17989", "type": "CID", "arg1_id": "17954", "arg2_id": "17960", "normalized": [] }, { "id": "17990", "type": "CID", "arg1_id": "17954", "arg2_id": "17961", "normalized": [] }, { "id": "17991", "type": "CID", "arg1_id": "17954", "arg2_id": "17964", "normalized": [] }, { "id": "17992", "type": "CID", "arg1_id": "17954", "arg2_id": "17966", "normalized": [] }, { "id": "17993", "type": "CID", "arg1_id": "17954", "arg2_id": "17968", "normalized": [] }, { "id": "17994", "type": "CID", "arg1_id": "17956", "arg2_id": "17957", "normalized": [] }, { "id": "17995", "type": "CID", "arg1_id": "17956", "arg2_id": "17960", "normalized": [] }, { "id": "17996", "type": "CID", "arg1_id": "17956", "arg2_id": "17961", "normalized": [] }, { "id": "17997", "type": "CID", "arg1_id": "17956", "arg2_id": "17964", "normalized": [] }, { "id": "17998", "type": "CID", "arg1_id": "17956", "arg2_id": "17966", "normalized": [] }, { "id": "17999", "type": "CID", "arg1_id": "17956", "arg2_id": "17968", "normalized": [] }, { "id": "18000", "type": "CID", "arg1_id": "17958", "arg2_id": "17957", "normalized": [] }, { "id": "18001", "type": "CID", "arg1_id": "17958", "arg2_id": "17960", "normalized": [] }, { "id": "18002", "type": "CID", "arg1_id": "17958", "arg2_id": "17961", "normalized": [] }, { "id": "18003", "type": "CID", "arg1_id": "17958", "arg2_id": "17964", "normalized": [] }, { "id": "18004", "type": "CID", "arg1_id": "17958", "arg2_id": "17966", "normalized": [] }, { "id": "18005", "type": "CID", "arg1_id": "17958", "arg2_id": "17968", "normalized": [] }, { "id": "18006", "type": "CID", "arg1_id": "17959", "arg2_id": "17957", "normalized": [] }, { "id": "18007", "type": "CID", "arg1_id": "17959", "arg2_id": "17960", "normalized": [] }, { "id": "18008", "type": "CID", "arg1_id": "17959", "arg2_id": "17961", "normalized": [] }, { "id": "18009", "type": "CID", "arg1_id": "17959", "arg2_id": "17964", "normalized": [] }, { "id": "18010", "type": "CID", "arg1_id": "17959", "arg2_id": "17966", "normalized": [] }, { "id": "18011", "type": "CID", "arg1_id": "17959", "arg2_id": "17968", "normalized": [] }, { "id": "18012", "type": "CID", "arg1_id": "17962", "arg2_id": "17957", "normalized": [] }, { "id": "18013", "type": "CID", "arg1_id": "17962", "arg2_id": "17960", "normalized": [] }, { "id": "18014", "type": "CID", "arg1_id": "17962", "arg2_id": "17961", "normalized": [] }, { "id": "18015", "type": "CID", "arg1_id": "17962", "arg2_id": "17964", "normalized": [] }, { "id": "18016", "type": "CID", "arg1_id": "17962", "arg2_id": "17966", "normalized": [] }, { "id": "18017", "type": "CID", "arg1_id": "17962", "arg2_id": "17968", "normalized": [] }, { "id": "18018", "type": "CID", "arg1_id": "17963", "arg2_id": "17957", "normalized": [] }, { "id": "18019", "type": "CID", "arg1_id": "17963", "arg2_id": "17960", "normalized": [] }, { "id": "18020", "type": "CID", "arg1_id": "17963", "arg2_id": "17961", "normalized": [] }, { "id": "18021", "type": "CID", "arg1_id": "17963", "arg2_id": "17964", "normalized": [] }, { "id": "18022", "type": "CID", "arg1_id": "17963", "arg2_id": "17966", "normalized": [] }, { "id": "18023", "type": "CID", "arg1_id": "17963", "arg2_id": "17968", "normalized": [] }, { "id": "18024", "type": "CID", "arg1_id": "17965", "arg2_id": "17957", "normalized": [] }, { "id": "18025", "type": "CID", "arg1_id": "17965", "arg2_id": "17960", "normalized": [] }, { "id": "18026", "type": "CID", "arg1_id": "17965", "arg2_id": "17961", "normalized": [] }, { "id": "18027", "type": "CID", "arg1_id": "17965", "arg2_id": "17964", "normalized": [] }, { "id": "18028", "type": "CID", "arg1_id": "17965", "arg2_id": "17966", "normalized": [] }, { "id": "18029", "type": "CID", "arg1_id": "17965", "arg2_id": "17968", "normalized": [] }, { "id": "18030", "type": "CID", "arg1_id": "17967", "arg2_id": "17957", "normalized": [] }, { "id": "18031", "type": "CID", "arg1_id": "17967", "arg2_id": "17960", "normalized": [] }, { "id": "18032", "type": "CID", "arg1_id": "17967", "arg2_id": "17961", "normalized": [] }, { "id": "18033", "type": "CID", "arg1_id": "17967", "arg2_id": "17964", "normalized": [] }, { "id": "18034", "type": "CID", "arg1_id": "17967", "arg2_id": "17966", "normalized": [] }, { "id": "18035", "type": "CID", "arg1_id": "17967", "arg2_id": "17968", "normalized": [] }, { "id": "18036", "type": "CID", "arg1_id": "17969", "arg2_id": "17957", "normalized": [] }, { "id": "18037", "type": "CID", "arg1_id": "17969", "arg2_id": "17960", "normalized": [] }, { "id": "18038", "type": "CID", "arg1_id": "17969", "arg2_id": "17961", "normalized": [] }, { "id": "18039", "type": "CID", "arg1_id": "17969", "arg2_id": "17964", "normalized": [] }, { "id": "18040", "type": "CID", "arg1_id": "17969", "arg2_id": "17966", "normalized": [] }, { "id": "18041", "type": "CID", "arg1_id": "17969", "arg2_id": "17968", "normalized": [] } ]

[ { "id": "18043", "type": "title", "text": [ "A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine." ], "offsets": [ [ 0, 101 ] ] }, { "id": "18044", "type": "abstract", "text": [ "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system." ], "offsets": [ [ 102, 1594 ] ] } ]

[ { "id": "18045", "type": "Disease", "text": [ "sugar dependency" ], "offsets": [ [ 17, 33 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019966" } ] }, { "id": "18046", "type": "Disease", "text": [ "behavioral cross-sensitization" ], "offsets": [ [ 41, 71 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "18047", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 89, 100 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18048", "type": "Disease", "text": [ "drug dependency" ], "offsets": [ [ 272, 287 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019966" } ] }, { "id": "18049", "type": "Disease", "text": [ "behavioral cross-sensitization" ], "offsets": [ [ 383, 413 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "18050", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 431, 442 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18051", "type": "Chemical", "text": [ "sucrose" ], "offsets": [ [ 599, 606 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013395" } ] }, { "id": "18052", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 954, 965 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18053", "type": "Chemical", "text": [ "sucrose" ], "offsets": [ [ 1019, 1026 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013395" } ] }, { "id": "18054", "type": "Disease", "text": [ "hyperactive" ], "offsets": [ [ 1041, 1052 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "18055", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1068, 1079 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18056", "type": "Chemical", "text": [ "sucrose" ], "offsets": [ [ 1130, 1137 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013395" } ] }, { "id": "18057", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1159, 1170 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18058", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1206, 1217 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18059", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1250, 1261 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18060", "type": "Chemical", "text": [ "sucrose" ], "offsets": [ [ 1277, 1284 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013395" } ] }, { "id": "18061", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1521, 1532 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "18062", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 1578, 1586 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] } ]

[]

[]

[ { "id": "18063", "type": "CID", "arg1_id": "18051", "arg2_id": "18046", "normalized": [] }, { "id": "18064", "type": "CID", "arg1_id": "18051", "arg2_id": "18049", "normalized": [] }, { "id": "18065", "type": "CID", "arg1_id": "18051", "arg2_id": "18054", "normalized": [] }, { "id": "18066", "type": "CID", "arg1_id": "18053", "arg2_id": "18046", "normalized": [] }, { "id": "18067", "type": "CID", "arg1_id": "18053", "arg2_id": "18049", "normalized": [] }, { "id": "18068", "type": "CID", "arg1_id": "18053", "arg2_id": "18054", "normalized": [] }, { "id": "18069", "type": "CID", "arg1_id": "18056", "arg2_id": "18046", "normalized": [] }, { "id": "18070", "type": "CID", "arg1_id": "18056", "arg2_id": "18049", "normalized": [] }, { "id": "18071", "type": "CID", "arg1_id": "18056", "arg2_id": "18054", "normalized": [] }, { "id": "18072", "type": "CID", "arg1_id": "18060", "arg2_id": "18046", "normalized": [] }, { "id": "18073", "type": "CID", "arg1_id": "18060", "arg2_id": "18049", "normalized": [] }, { "id": "18074", "type": "CID", "arg1_id": "18060", "arg2_id": "18054", "normalized": [] }, { "id": "18075", "type": "CID", "arg1_id": "18047", "arg2_id": "18046", "normalized": [] }, { "id": "18076", "type": "CID", "arg1_id": "18047", "arg2_id": "18049", "normalized": [] }, { "id": "18077", "type": "CID", "arg1_id": "18047", "arg2_id": "18054", "normalized": [] }, { "id": "18078", "type": "CID", "arg1_id": "18050", "arg2_id": "18046", "normalized": [] }, { "id": "18079", "type": "CID", "arg1_id": "18050", "arg2_id": "18049", "normalized": [] }, { "id": "18080", "type": "CID", "arg1_id": "18050", "arg2_id": "18054", "normalized": [] }, { "id": "18081", "type": "CID", "arg1_id": "18052", "arg2_id": "18046", "normalized": [] }, { "id": "18082", "type": "CID", "arg1_id": "18052", "arg2_id": "18049", "normalized": [] }, { "id": "18083", "type": "CID", "arg1_id": "18052", "arg2_id": "18054", "normalized": [] }, { "id": "18084", "type": "CID", "arg1_id": "18055", "arg2_id": "18046", "normalized": [] }, { "id": "18085", "type": "CID", "arg1_id": "18055", "arg2_id": "18049", "normalized": [] }, { "id": "18086", "type": "CID", "arg1_id": "18055", "arg2_id": "18054", "normalized": [] }, { "id": "18087", "type": "CID", "arg1_id": "18057", "arg2_id": "18046", "normalized": [] }, { "id": "18088", "type": "CID", "arg1_id": "18057", "arg2_id": "18049", "normalized": [] }, { "id": "18089", "type": "CID", "arg1_id": "18057", "arg2_id": "18054", "normalized": [] }, { "id": "18090", "type": "CID", "arg1_id": "18058", "arg2_id": "18046", "normalized": [] }, { "id": "18091", "type": "CID", "arg1_id": "18058", "arg2_id": "18049", "normalized": [] }, { "id": "18092", "type": "CID", "arg1_id": "18058", "arg2_id": "18054", "normalized": [] }, { "id": "18093", "type": "CID", "arg1_id": "18059", "arg2_id": "18046", "normalized": [] }, { "id": "18094", "type": "CID", "arg1_id": "18059", "arg2_id": "18049", "normalized": [] }, { "id": "18095", "type": "CID", "arg1_id": "18059", "arg2_id": "18054", "normalized": [] }, { "id": "18096", "type": "CID", "arg1_id": "18061", "arg2_id": "18046", "normalized": [] }, { "id": "18097", "type": "CID", "arg1_id": "18061", "arg2_id": "18049", "normalized": [] }, { "id": "18098", "type": "CID", "arg1_id": "18061", "arg2_id": "18054", "normalized": [] } ]

[ { "id": "18100", "type": "title", "text": [ "D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel." ], "offsets": [ [ 0, 168 ] ] }, { "id": "18101", "type": "abstract", "text": [ "Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin." ], "offsets": [ [ 169, 1793 ] ] } ]

[ { "id": "18102", "type": "Chemical", "text": [ "D-penicillamine" ], "offsets": [ [ 0, 15 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18103", "type": "Disease", "text": [ "angiopathy" ], "offsets": [ [ 24, 34 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001018" } ] }, { "id": "18104", "type": "Chemical", "text": [ "D-penicillamine" ], "offsets": [ [ 68, 83 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18105", "type": "Chemical", "text": [ "D-penicillamine" ], "offsets": [ [ 212, 227 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18106", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 229, 234 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18107", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 659, 664 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18108", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 1103, 1108 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18109", "type": "Chemical", "text": [ "hyaluronate" ], "offsets": [ [ 1236, 1247 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006820" } ] }, { "id": "18110", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 1298, 1303 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18111", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 1561, 1566 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "18112", "type": "Chemical", "text": [ "D-pen" ], "offsets": [ [ 1654, 1659 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] } ]

[]

[]

[ { "id": "18113", "type": "CID", "arg1_id": "18102", "arg2_id": "18103", "normalized": [] }, { "id": "18114", "type": "CID", "arg1_id": "18104", "arg2_id": "18103", "normalized": [] }, { "id": "18115", "type": "CID", "arg1_id": "18105", "arg2_id": "18103", "normalized": [] }, { "id": "18116", "type": "CID", "arg1_id": "18106", "arg2_id": "18103", "normalized": [] }, { "id": "18117", "type": "CID", "arg1_id": "18107", "arg2_id": "18103", "normalized": [] }, { "id": "18118", "type": "CID", "arg1_id": "18108", "arg2_id": "18103", "normalized": [] }, { "id": "18119", "type": "CID", "arg1_id": "18110", "arg2_id": "18103", "normalized": [] }, { "id": "18120", "type": "CID", "arg1_id": "18111", "arg2_id": "18103", "normalized": [] }, { "id": "18121", "type": "CID", "arg1_id": "18112", "arg2_id": "18103", "normalized": [] } ]

[ { "id": "18123", "type": "title", "text": [ "Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity." ], "offsets": [ [ 0, 81 ] ] }, { "id": "18124", "type": "abstract", "text": [ "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity." ], "offsets": [ [ 82, 1684 ] ] } ]

[ { "id": "18125", "type": "Chemical", "text": [ "anthracycline" ], "offsets": [ [ 44, 57 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018943" } ] }, { "id": "18126", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 66, 80 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] }, { "id": "18127", "type": "Chemical", "text": [ "Anthracyclines" ], "offsets": [ [ 82, 96 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018943" } ] }, { "id": "18128", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 172, 186 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] }, { "id": "18129", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 192, 206 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] }, { "id": "18130", "type": "Chemical", "text": [ "anthracycline" ], "offsets": [ [ 223, 236 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018943" } ] }, { "id": "18131", "type": "Disease", "text": [ "cardiac dysfunction" ], "offsets": [ [ 337, 356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006331" } ] }, { "id": "18132", "type": "Chemical", "text": [ "anthracycline" ], "offsets": [ [ 495, 508 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018943" } ] }, { "id": "18133", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 517, 531 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] }, { "id": "18134", "type": "Disease", "text": [ "acute leukemia" ], "offsets": [ [ 549, 563 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015470" } ] }, { "id": "18135", "type": "Chemical", "text": [ "daunorubicin" ], "offsets": [ [ 579, 591 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003630" } ] }, { "id": "18136", "type": "Chemical", "text": [ "DNR" ], "offsets": [ [ 593, 596 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003630" } ] }, { "id": "18137", "type": "Disease", "text": [ "acute leukemia" ], "offsets": [ [ 641, 655 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015470" } ] }, { "id": "18138", "type": "Chemical", "text": [ "DNR" ], "offsets": [ [ 676, 679 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003630" } ] }, { "id": "18139", "type": "Disease", "text": [ "congestive heart failure" ], "offsets": [ [ 928, 952 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18140", "type": "Disease", "text": [ "heart failure" ], "offsets": [ [ 1042, 1055 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18141", "type": "Disease", "text": [ "heart failure" ], "offsets": [ [ 1169, 1182 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18142", "type": "Disease", "text": [ "heart failure" ], "offsets": [ [ 1275, 1288 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18143", "type": "Disease", "text": [ "heart failure" ], "offsets": [ [ 1382, 1395 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18144", "type": "Chemical", "text": [ "DNR" ], "offsets": [ [ 1402, 1405 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003630" } ] }, { "id": "18145", "type": "Disease", "text": [ "heart failure" ], "offsets": [ [ 1536, 1549 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006333" } ] }, { "id": "18146", "type": "Chemical", "text": [ "anthracycline" ], "offsets": [ [ 1647, 1660 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018943" } ] }, { "id": "18147", "type": "Disease", "text": [ "cardiotoxicity" ], "offsets": [ [ 1669, 1683 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D066126" } ] } ]

[]

[]

[ { "id": "18148", "type": "CID", "arg1_id": "18135", "arg2_id": "18139", "normalized": [] }, { "id": "18149", "type": "CID", "arg1_id": "18135", "arg2_id": "18140", "normalized": [] }, { "id": "18150", "type": "CID", "arg1_id": "18135", "arg2_id": "18141", "normalized": [] }, { "id": "18151", "type": "CID", "arg1_id": "18135", "arg2_id": "18142", "normalized": [] }, { "id": "18152", "type": "CID", "arg1_id": "18135", "arg2_id": "18143", "normalized": [] }, { "id": "18153", "type": "CID", "arg1_id": "18135", "arg2_id": "18145", "normalized": [] }, { "id": "18154", "type": "CID", "arg1_id": "18136", "arg2_id": "18139", "normalized": [] }, { "id": "18155", "type": "CID", "arg1_id": "18136", "arg2_id": "18140", "normalized": [] }, { "id": "18156", "type": "CID", "arg1_id": "18136", "arg2_id": "18141", "normalized": [] }, { "id": "18157", "type": "CID", "arg1_id": "18136", "arg2_id": "18142", "normalized": [] }, { "id": "18158", "type": "CID", "arg1_id": "18136", "arg2_id": "18143", "normalized": [] }, { "id": "18159", "type": "CID", "arg1_id": "18136", "arg2_id": "18145", "normalized": [] }, { "id": "18160", "type": "CID", "arg1_id": "18138", "arg2_id": "18139", "normalized": [] }, { "id": "18161", "type": "CID", "arg1_id": "18138", "arg2_id": "18140", "normalized": [] }, { "id": "18162", "type": "CID", "arg1_id": "18138", "arg2_id": "18141", "normalized": [] }, { "id": "18163", "type": "CID", "arg1_id": "18138", "arg2_id": "18142", "normalized": [] }, { "id": "18164", "type": "CID", "arg1_id": "18138", "arg2_id": "18143", "normalized": [] }, { "id": "18165", "type": "CID", "arg1_id": "18138", "arg2_id": "18145", "normalized": [] }, { "id": "18166", "type": "CID", "arg1_id": "18144", "arg2_id": "18139", "normalized": [] }, { "id": "18167", "type": "CID", "arg1_id": "18144", "arg2_id": "18140", "normalized": [] }, { "id": "18168", "type": "CID", "arg1_id": "18144", "arg2_id": "18141", "normalized": [] }, { "id": "18169", "type": "CID", "arg1_id": "18144", "arg2_id": "18142", "normalized": [] }, { "id": "18170", "type": "CID", "arg1_id": "18144", "arg2_id": "18143", "normalized": [] }, { "id": "18171", "type": "CID", "arg1_id": "18144", "arg2_id": "18145", "normalized": [] } ]

[ { "id": "18173", "type": "title", "text": [ "Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study." ], "offsets": [ [ 0, 113 ] ] }, { "id": "18174", "type": "abstract", "text": [ "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny." ], "offsets": [ [ 114, 2036 ] ] } ]

[ { "id": "18175", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 58, 71 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18176", "type": "Disease", "text": [ "Birth Defects" ], "offsets": [ [ 82, 95 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18177", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 200, 213 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18178", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 372, 385 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18179", "type": "Disease", "text": [ "birth defect" ], "offsets": [ [ 401, 413 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18180", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 772, 785 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18181", "type": "Chemical", "text": [ "Sulfonamides" ], "offsets": [ [ 926, 938 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013449" } ] }, { "id": "18182", "type": "Disease", "text": [ "anencephaly" ], "offsets": [ [ 960, 971 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000757" } ] }, { "id": "18183", "type": "Disease", "text": [ "hypoplastic left heart syndrome" ], "offsets": [ [ 1038, 1069 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018636" } ] }, { "id": "18184", "type": "Disease", "text": [ "coarctation of the aorta" ], "offsets": [ [ 1100, 1124 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001017" } ] }, { "id": "18185", "type": "Disease", "text": [ "choanal atresia" ], "offsets": [ [ 1155, 1170 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002754" } ] }, { "id": "18186", "type": "Disease", "text": [ "transverse limb deficiency" ], "offsets": [ [ 1202, 1228 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017880" } ] }, { "id": "18187", "type": "Disease", "text": [ "diaphragmatic hernia" ], "offsets": [ [ 1263, 1283 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006548" } ] }, { "id": "18188", "type": "Chemical", "text": [ "Nitrofurantoins" ], "offsets": [ [ 1314, 1329 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009582" } ] }, { "id": "18189", "type": "Disease", "text": [ "anophthalmia" ], "offsets": [ [ 1351, 1363 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000853" } ] }, { "id": "18190", "type": "Disease", "text": [ "microphthalmos" ], "offsets": [ [ 1367, 1381 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008850" } ] }, { "id": "18191", "type": "Disease", "text": [ "hypoplastic left heart syndrome" ], "offsets": [ [ 1413, 1444 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018636" } ] }, { "id": "18192", "type": "Disease", "text": [ "atrial septal defects" ], "offsets": [ [ 1475, 1496 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006344" } ] }, { "id": "18193", "type": "Disease", "text": [ "cleft lip" ], "offsets": [ [ 1531, 1540 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002971" } ] }, { "id": "18194", "type": "Disease", "text": [ "cleft palate" ], "offsets": [ [ 1546, 1558 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002972" } ] }, { "id": "18195", "type": "Chemical", "text": [ "erythromycins" ], "offsets": [ [ 1650, 1663 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004917" } ] }, { "id": "18196", "type": "Chemical", "text": [ "penicillins" ], "offsets": [ [ 1677, 1688 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010406" } ] }, { "id": "18197", "type": "Chemical", "text": [ "cephalosporins" ], "offsets": [ [ 1701, 1715 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "18198", "type": "Chemical", "text": [ "quinolones" ], "offsets": [ [ 1732, 1742 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015363" } ] }, { "id": "18199", "type": "Chemical", "text": [ "penicillins" ], "offsets": [ [ 1782, 1793 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010406" } ] }, { "id": "18200", "type": "Chemical", "text": [ "erythromycins" ], "offsets": [ [ 1795, 1808 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004917" } ] }, { "id": "18201", "type": "Chemical", "text": [ "cephalosporins" ], "offsets": [ [ 1814, 1828 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "18202", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 1902, 1915 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] }, { "id": "18203", "type": "Chemical", "text": [ "Sulfonamides" ], "offsets": [ [ 1917, 1929 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013449" } ] }, { "id": "18204", "type": "Chemical", "text": [ "nitrofurantoins" ], "offsets": [ [ 1934, 1949 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009582" } ] }, { "id": "18205", "type": "Disease", "text": [ "birth defects" ], "offsets": [ [ 1979, 1992 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000014" } ] } ]

[]

[]

[ { "id": "18206", "type": "CID", "arg1_id": "18181", "arg2_id": "18187", "normalized": [] }, { "id": "18207", "type": "CID", "arg1_id": "18203", "arg2_id": "18187", "normalized": [] }, { "id": "18208", "type": "CID", "arg1_id": "18181", "arg2_id": "18183", "normalized": [] }, { "id": "18209", "type": "CID", "arg1_id": "18181", "arg2_id": "18191", "normalized": [] }, { "id": "18210", "type": "CID", "arg1_id": "18203", "arg2_id": "18183", "normalized": [] }, { "id": "18211", "type": "CID", "arg1_id": "18203", "arg2_id": "18191", "normalized": [] }, { "id": "18212", "type": "CID", "arg1_id": "18181", "arg2_id": "18186", "normalized": [] }, { "id": "18213", "type": "CID", "arg1_id": "18203", "arg2_id": "18186", "normalized": [] }, { "id": "18214", "type": "CID", "arg1_id": "18188", "arg2_id": "18192", "normalized": [] }, { "id": "18215", "type": "CID", "arg1_id": "18204", "arg2_id": "18192", "normalized": [] }, { "id": "18216", "type": "CID", "arg1_id": "18188", "arg2_id": "18183", "normalized": [] }, { "id": "18217", "type": "CID", "arg1_id": "18188", "arg2_id": "18191", "normalized": [] }, { "id": "18218", "type": "CID", "arg1_id": "18204", "arg2_id": "18183", "normalized": [] }, { "id": "18219", "type": "CID", "arg1_id": "18204", "arg2_id": "18191", "normalized": [] }, { "id": "18220", "type": "CID", "arg1_id": "18188", "arg2_id": "18194", "normalized": [] }, { "id": "18221", "type": "CID", "arg1_id": "18204", "arg2_id": "18194", "normalized": [] }, { "id": "18222", "type": "CID", "arg1_id": "18188", "arg2_id": "18189", "normalized": [] }, { "id": "18223", "type": "CID", "arg1_id": "18204", "arg2_id": "18189", "normalized": [] }, { "id": "18224", "type": "CID", "arg1_id": "18181", "arg2_id": "18184", "normalized": [] }, { "id": "18225", "type": "CID", "arg1_id": "18203", "arg2_id": "18184", "normalized": [] }, { "id": "18226", "type": "CID", "arg1_id": "18181", "arg2_id": "18175", "normalized": [] }, { "id": "18227", "type": "CID", "arg1_id": "18181", "arg2_id": "18176", "normalized": [] }, { "id": "18228", "type": "CID", "arg1_id": "18181", "arg2_id": "18177", "normalized": [] }, { "id": "18229", "type": "CID", "arg1_id": "18181", "arg2_id": "18178", "normalized": [] }, { "id": "18230", "type": "CID", "arg1_id": "18181", "arg2_id": "18179", "normalized": [] }, { "id": "18231", "type": "CID", "arg1_id": "18181", "arg2_id": "18180", "normalized": [] }, { "id": "18232", "type": "CID", "arg1_id": "18181", "arg2_id": "18202", "normalized": [] }, { "id": "18233", "type": "CID", "arg1_id": "18181", "arg2_id": "18205", "normalized": [] }, { "id": "18234", "type": "CID", "arg1_id": "18203", "arg2_id": "18175", "normalized": [] }, { "id": "18235", "type": "CID", "arg1_id": "18203", "arg2_id": "18176", "normalized": [] }, { "id": "18236", "type": "CID", "arg1_id": "18203", "arg2_id": "18177", "normalized": [] }, { "id": "18237", "type": "CID", "arg1_id": "18203", "arg2_id": "18178", "normalized": [] }, { "id": "18238", "type": "CID", "arg1_id": "18203", "arg2_id": "18179", "normalized": [] }, { "id": "18239", "type": "CID", "arg1_id": "18203", "arg2_id": "18180", "normalized": [] }, { "id": "18240", "type": "CID", "arg1_id": "18203", "arg2_id": "18202", "normalized": [] }, { "id": "18241", "type": "CID", "arg1_id": "18203", "arg2_id": "18205", "normalized": [] }, { "id": "18242", "type": "CID", "arg1_id": "18181", "arg2_id": "18185", "normalized": [] }, { "id": "18243", "type": "CID", "arg1_id": "18203", "arg2_id": "18185", "normalized": [] }, { "id": "18244", "type": "CID", "arg1_id": "18188", "arg2_id": "18190", "normalized": [] }, { "id": "18245", "type": "CID", "arg1_id": "18204", "arg2_id": "18190", "normalized": [] }, { "id": "18246", "type": "CID", "arg1_id": "18188", "arg2_id": "18193", "normalized": [] }, { "id": "18247", "type": "CID", "arg1_id": "18204", "arg2_id": "18193", "normalized": [] }, { "id": "18248", "type": "CID", "arg1_id": "18181", "arg2_id": "18182", "normalized": [] }, { "id": "18249", "type": "CID", "arg1_id": "18203", "arg2_id": "18182", "normalized": [] }, { "id": "18250", "type": "CID", "arg1_id": "18188", "arg2_id": "18175", "normalized": [] }, { "id": "18251", "type": "CID", "arg1_id": "18188", "arg2_id": "18176", "normalized": [] }, { "id": "18252", "type": "CID", "arg1_id": "18188", "arg2_id": "18177", "normalized": [] }, { "id": "18253", "type": "CID", "arg1_id": "18188", "arg2_id": "18178", "normalized": [] }, { "id": "18254", "type": "CID", "arg1_id": "18188", "arg2_id": "18179", "normalized": [] }, { "id": "18255", "type": "CID", "arg1_id": "18188", "arg2_id": "18180", "normalized": [] }, { "id": "18256", "type": "CID", "arg1_id": "18188", "arg2_id": "18202", "normalized": [] }, { "id": "18257", "type": "CID", "arg1_id": "18188", "arg2_id": "18205", "normalized": [] }, { "id": "18258", "type": "CID", "arg1_id": "18204", "arg2_id": "18175", "normalized": [] }, { "id": "18259", "type": "CID", "arg1_id": "18204", "arg2_id": "18176", "normalized": [] }, { "id": "18260", "type": "CID", "arg1_id": "18204", "arg2_id": "18177", "normalized": [] }, { "id": "18261", "type": "CID", "arg1_id": "18204", "arg2_id": "18178", "normalized": [] }, { "id": "18262", "type": "CID", "arg1_id": "18204", "arg2_id": "18179", "normalized": [] }, { "id": "18263", "type": "CID", "arg1_id": "18204", "arg2_id": "18180", "normalized": [] }, { "id": "18264", "type": "CID", "arg1_id": "18204", "arg2_id": "18202", "normalized": [] }, { "id": "18265", "type": "CID", "arg1_id": "18204", "arg2_id": "18205", "normalized": [] } ]

[ { "id": "18267", "type": "title", "text": [ "Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens." ], "offsets": [ [ 0, 101 ] ] }, { "id": "18268", "type": "abstract", "text": [ "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications." ], "offsets": [ [ 102, 1642 ] ] } ]

[ { "id": "18269", "type": "Disease", "text": [ "neoplasms" ], "offsets": [ [ 13, 22 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18270", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 40, 60 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "18271", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 203, 223 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "18272", "type": "Chemical", "text": [ "cyclophosphamide" ], "offsets": [ [ 253, 269 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003520" } ] }, { "id": "18273", "type": "Chemical", "text": [ "chlorambucil" ], "offsets": [ [ 274, 286 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002699" } ] }, { "id": "18274", "type": "Chemical", "text": [ "alkylating agents" ], "offsets": [ [ 288, 305 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000477" } ] }, { "id": "18275", "type": "Chemical", "text": [ "azathioprine" ], "offsets": [ [ 308, 320 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001379" } ] }, { "id": "18276", "type": "Chemical", "text": [ "purine" ], "offsets": [ [ 322, 328 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011687" } ] }, { "id": "18277", "type": "Chemical", "text": [ "methotrexate" ], "offsets": [ [ 344, 356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008727" } ] }, { "id": "18278", "type": "Chemical", "text": [ "folic acid" ], "offsets": [ [ 358, 368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005492" } ] }, { "id": "18279", "type": "Disease", "text": [ "synovitis" ], "offsets": [ [ 447, 456 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013585" } ] }, { "id": "18280", "type": "Chemical", "text": [ "alkylating agents" ], "offsets": [ [ 827, 844 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000477" } ] }, { "id": "18281", "type": "Disease", "text": [ "acute nonlymphocytic leukemia" ], "offsets": [ [ 886, 915 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015470" } ] }, { "id": "18282", "type": "Chemical", "text": [ "alkylating agents" ], "offsets": [ [ 926, 943 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000477" } ] }, { "id": "18283", "type": "Chemical", "text": [ "azathioprine" ], "offsets": [ [ 948, 960 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001379" } ] }, { "id": "18284", "type": "Disease", "text": [ "non-Hodgkin's lymphoma" ], "offsets": [ [ 1000, 1022 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008228" } ] }, { "id": "18285", "type": "Chemical", "text": [ "Cyclophosphamide" ], "offsets": [ [ 1024, 1040 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003520" } ] }, { "id": "18286", "type": "Disease", "text": [ "carcinoma of the bladder" ], "offsets": [ [ 1071, 1095 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001749" }, { "db_name": "MESH", "db_id": "D002277" } ] }, { "id": "18287", "type": "Disease", "text": [ "carcinoma of the bladder" ], "offsets": [ [ 1071, 1095 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001749" } ] }, { "id": "18288", "type": "Disease", "text": [ "carcinoma" ], "offsets": [ [ 1071, 1080 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002277" } ] }, { "id": "18289", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 1156, 1176 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "18290", "type": "Chemical", "text": [ "azathioprine" ], "offsets": [ [ 1190, 1202 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001379" } ] }, { "id": "18291", "type": "Chemical", "text": [ "cyclophosphamide" ], "offsets": [ [ 1207, 1223 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003520" } ] }, { "id": "18292", "type": "Disease", "text": [ "cancers" ], "offsets": [ [ 1264, 1271 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18293", "type": "Disease", "text": [ "malignancy" ], "offsets": [ [ 1329, 1339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18294", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 1343, 1363 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "18295", "type": "Chemical", "text": [ "alkylating agents" ], "offsets": [ [ 1484, 1501 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000477" } ] }, { "id": "18296", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 1523, 1543 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] } ]

[]

[]

[ { "id": "18297", "type": "CID", "arg1_id": "18274", "arg2_id": "18281", "normalized": [] }, { "id": "18298", "type": "CID", "arg1_id": "18280", "arg2_id": "18281", "normalized": [] }, { "id": "18299", "type": "CID", "arg1_id": "18282", "arg2_id": "18281", "normalized": [] }, { "id": "18300", "type": "CID", "arg1_id": "18295", "arg2_id": "18281", "normalized": [] }, { "id": "18301", "type": "CID", "arg1_id": "18272", "arg2_id": "18286", "normalized": [] }, { "id": "18302", "type": "CID", "arg1_id": "18272", "arg2_id": "18287", "normalized": [] }, { "id": "18303", "type": "CID", "arg1_id": "18285", "arg2_id": "18286", "normalized": [] }, { "id": "18304", "type": "CID", "arg1_id": "18285", "arg2_id": "18287", "normalized": [] }, { "id": "18305", "type": "CID", "arg1_id": "18291", "arg2_id": "18286", "normalized": [] }, { "id": "18306", "type": "CID", "arg1_id": "18291", "arg2_id": "18287", "normalized": [] }, { "id": "18307", "type": "CID", "arg1_id": "18274", "arg2_id": "18284", "normalized": [] }, { "id": "18308", "type": "CID", "arg1_id": "18280", "arg2_id": "18284", "normalized": [] }, { "id": "18309", "type": "CID", "arg1_id": "18282", "arg2_id": "18284", "normalized": [] }, { "id": "18310", "type": "CID", "arg1_id": "18295", "arg2_id": "18284", "normalized": [] }, { "id": "18311", "type": "CID", "arg1_id": "18275", "arg2_id": "18284", "normalized": [] }, { "id": "18312", "type": "CID", "arg1_id": "18283", "arg2_id": "18284", "normalized": [] }, { "id": "18313", "type": "CID", "arg1_id": "18290", "arg2_id": "18284", "normalized": [] }, { "id": "18314", "type": "CID", "arg1_id": "18272", "arg2_id": "18286", "normalized": [] }, { "id": "18315", "type": "CID", "arg1_id": "18272", "arg2_id": "18288", "normalized": [] }, { "id": "18316", "type": "CID", "arg1_id": "18285", "arg2_id": "18286", "normalized": [] }, { "id": "18317", "type": "CID", "arg1_id": "18285", "arg2_id": "18288", "normalized": [] }, { "id": "18318", "type": "CID", "arg1_id": "18291", "arg2_id": "18286", "normalized": [] }, { "id": "18319", "type": "CID", "arg1_id": "18291", "arg2_id": "18288", "normalized": [] } ]

[ { "id": "18321", "type": "title", "text": [ "Patterns of hepatic injury induced by methyldopa." ], "offsets": [ [ 0, 49 ] ] }, { "id": "18322", "type": "abstract", "text": [ "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug." ], "offsets": [ [ 50, 1547 ] ] } ]

[ { "id": "18323", "type": "Disease", "text": [ "hepatic injury" ], "offsets": [ [ 12, 26 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "18324", "type": "Chemical", "text": [ "methyldopa" ], "offsets": [ [ 38, 48 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008750" } ] }, { "id": "18325", "type": "Disease", "text": [ "liver disease" ], "offsets": [ [ 71, 84 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "18326", "type": "Chemical", "text": [ "methyldopa" ], "offsets": [ [ 96, 106 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008750" } ] }, { "id": "18327", "type": "Disease", "text": [ "Jaundice" ], "offsets": [ [ 334, 342 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "18328", "type": "Disease", "text": [ "hepatomegaly" ], "offsets": [ [ 355, 367 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006529" } ] }, { "id": "18329", "type": "Disease", "text": [ "anorexia" ], "offsets": [ [ 410, 418 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000855" } ] }, { "id": "18330", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 420, 426 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "18331", "type": "Disease", "text": [ "vomiting" ], "offsets": [ [ 431, 439 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014839" } ] }, { "id": "18332", "type": "Disease", "text": [ "abdominal pain" ], "offsets": [ [ 467, 481 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015746" } ] }, { "id": "18333", "type": "Disease", "text": [ "necrosis" ], "offsets": [ [ 584, 592 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009336" } ] }, { "id": "18334", "type": "Disease", "text": [ "hepatic injury" ], "offsets": [ [ 643, 657 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "18335", "type": "Disease", "text": [ "fatty change" ], "offsets": [ [ 693, 705 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005234" } ] }, { "id": "18336", "type": "Disease", "text": [ "necrosis" ], "offsets": [ [ 731, 739 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009336" } ] }, { "id": "18337", "type": "Disease", "text": [ "massive hepatic necrosis" ], "offsets": [ [ 743, 767 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D047508" } ] }, { "id": "18338", "type": "Disease", "text": [ "acute hepatitis" ], "offsets": [ [ 809, 824 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017114" } ] }, { "id": "18339", "type": "Disease", "text": [ "chronic active hepatitis" ], "offsets": [ [ 828, 852 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006521" } ] }, { "id": "18340", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 869, 880 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "18341", "type": "Disease", "text": [ "hepatic failure" ], "offsets": [ [ 1025, 1040 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017093" } ] }, { "id": "18342", "type": "Chemical", "text": [ "methyldopa" ], "offsets": [ [ 1075, 1085 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008750" } ] }, { "id": "18343", "type": "Disease", "text": [ "fulminant hepatitis" ], "offsets": [ [ 1228, 1247 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017114" } ] }, { "id": "18344", "type": "Chemical", "text": [ "methyldopa" ], "offsets": [ [ 1323, 1333 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008750" } ] }, { "id": "18345", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 1342, 1351 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "18346", "type": "Chemical", "text": [ "methyldopa" ], "offsets": [ [ 1426, 1436 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008750" } ] }, { "id": "18347", "type": "Disease", "text": [ "hepatic dysfunction" ], "offsets": [ [ 1441, 1460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "18348", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 1495, 1504 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] } ]

[]

[]

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"normalized": [] }, { "id": "18360", "type": "CID", "arg1_id": "18326", "arg2_id": "18328", "normalized": [] }, { "id": "18361", "type": "CID", "arg1_id": "18342", "arg2_id": "18328", "normalized": [] }, { "id": "18362", "type": "CID", "arg1_id": "18344", "arg2_id": "18328", "normalized": [] }, { "id": "18363", "type": "CID", "arg1_id": "18346", "arg2_id": "18328", "normalized": [] }, { "id": "18364", "type": "CID", "arg1_id": "18324", "arg2_id": "18330", "normalized": [] }, { "id": "18365", "type": "CID", "arg1_id": "18326", "arg2_id": "18330", "normalized": [] }, { "id": "18366", "type": "CID", "arg1_id": "18342", "arg2_id": "18330", "normalized": [] }, { "id": "18367", "type": "CID", "arg1_id": "18344", "arg2_id": "18330", "normalized": [] }, { "id": "18368", "type": "CID", "arg1_id": "18346", "arg2_id": "18330", "normalized": [] }, { "id": "18369", "type": "CID", "arg1_id": "18324", "arg2_id": "18335", "normalized": [] }, { "id": "18370", "type": "CID", "arg1_id": "18326", 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"type": "CID", "arg1_id": "18344", "arg2_id": "18327", "normalized": [] }, { "id": "18393", "type": "CID", "arg1_id": "18346", "arg2_id": "18327", "normalized": [] }, { "id": "18394", "type": "CID", "arg1_id": "18324", "arg2_id": "18323", "normalized": [] }, { "id": "18395", "type": "CID", "arg1_id": "18324", "arg2_id": "18334", "normalized": [] }, { "id": "18396", "type": "CID", "arg1_id": "18324", "arg2_id": "18345", "normalized": [] }, { "id": "18397", "type": "CID", "arg1_id": "18324", "arg2_id": "18348", "normalized": [] }, { "id": "18398", "type": "CID", "arg1_id": "18326", "arg2_id": "18323", "normalized": [] }, { "id": "18399", "type": "CID", "arg1_id": "18326", "arg2_id": "18334", "normalized": [] }, { "id": "18400", "type": "CID", "arg1_id": "18326", "arg2_id": "18345", "normalized": [] }, { "id": "18401", "type": "CID", "arg1_id": "18326", "arg2_id": "18348", "normalized": [] }, { "id": "18402", "type": "CID", "arg1_id": "18342", "arg2_id": "18323", "normalized": [] }, { "id": "18403", "type": "CID", "arg1_id": "18342", "arg2_id": "18334", "normalized": [] }, { "id": "18404", "type": "CID", "arg1_id": "18342", "arg2_id": "18345", "normalized": [] }, { "id": "18405", "type": "CID", "arg1_id": "18342", "arg2_id": "18348", "normalized": [] }, { "id": "18406", "type": "CID", "arg1_id": "18344", "arg2_id": "18323", "normalized": [] }, { "id": "18407", "type": "CID", "arg1_id": "18344", "arg2_id": "18334", "normalized": [] }, { "id": "18408", "type": "CID", "arg1_id": "18344", "arg2_id": "18345", "normalized": [] }, { "id": "18409", "type": "CID", "arg1_id": "18344", "arg2_id": "18348", "normalized": [] }, { "id": "18410", "type": "CID", "arg1_id": "18346", "arg2_id": "18323", "normalized": [] }, { "id": "18411", "type": "CID", "arg1_id": "18346", "arg2_id": "18334", "normalized": [] }, { "id": "18412", "type": "CID", "arg1_id": "18346", "arg2_id": "18345", "normalized": [] }, { "id": "18413", "type": "CID", "arg1_id": "18346", "arg2_id": "18348", "normalized": [] }, { "id": "18414", "type": "CID", "arg1_id": "18324", "arg2_id": "18329", "normalized": [] }, { "id": "18415", "type": "CID", "arg1_id": "18326", "arg2_id": "18329", "normalized": [] }, { "id": "18416", "type": "CID", "arg1_id": "18342", "arg2_id": "18329", "normalized": [] }, { "id": "18417", "type": "CID", "arg1_id": "18344", "arg2_id": "18329", "normalized": [] }, { "id": "18418", "type": "CID", "arg1_id": "18346", "arg2_id": "18329", "normalized": [] } ]

[ { "id": "18420", "type": "title", "text": [ "A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results." ], "offsets": [ [ 0, 117 ] ] }, { "id": "18421", "type": "abstract", "text": [ "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2." ], "offsets": [ [ 118, 2648 ] ] } ]

[ { "id": "18422", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 22, 32 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18423", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 38, 47 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18424", "type": "Disease", "text": [ "head and neck cancers" ], "offsets": [ [ 74, 95 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006258" } ] }, { "id": "18425", "type": "Disease", "text": [ "head and neck carcinomas" ], "offsets": [ [ 156, 180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006258" } ] }, { "id": "18426", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 323, 333 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18427", "type": "Chemical", "text": [ "Taxol" ], "offsets": [ [ 335, 340 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18428", "type": "Disease", "text": [ "head and neck cancer" ], "offsets": [ [ 433, 453 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006258" } ] }, { "id": "18429", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 463, 473 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18430", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 474, 483 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18431", "type": "Disease", "text": [ "ovarian cancer" ], "offsets": [ [ 582, 596 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010051" } ] }, { "id": "18432", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 669, 677 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "18433", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 692, 702 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18434", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 734, 743 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18435", "type": "Disease", "text": [ "head and neck carcinoma" ], "offsets": [ [ 850, 873 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006258" } ] }, { "id": "18436", "type": "Disease", "text": [ "tumor" ], "offsets": [ [ 981, 986 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18437", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1172, 1180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "18438", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 1305, 1315 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18439", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1376, 1385 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18440", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 1437, 1447 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18441", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1527, 1535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "18442", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 1684, 1694 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18443", "type": "Disease", "text": [ "Alopecia" ], "offsets": [ [ 2223, 2231 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000505" } ] }, { "id": "18444", "type": "Disease", "text": [ "paresthesias" ], "offsets": [ [ 2233, 2245 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010292" } ] }, { "id": "18445", "type": "Disease", "text": [ "arthralgias" ], "offsets": [ [ 2251, 2262 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018771" } ] }, { "id": "18446", "type": "Disease", "text": [ "myalgias" ], "offsets": [ [ 2263, 2271 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D063806" } ] }, { "id": "18447", "type": "Disease", "text": [ "myalgia" ], "offsets": [ [ 2332, 2339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D063806" } ] }, { "id": "18448", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 2399, 2407 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "18449", "type": "Chemical", "text": [ "Paclitaxel" ], "offsets": [ [ 2423, 2433 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18450", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 2434, 2443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18451", "type": "Disease", "text": [ "head and neck cancer" ], "offsets": [ [ 2507, 2527 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006258" } ] }, { "id": "18452", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 2615, 2625 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] } ]

[]

[]

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[ { "id": "18499", "type": "title", "text": [ "A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics." ], "offsets": [ [ 0, 96 ] ] }, { "id": "18500", "type": "abstract", "text": [ "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks." ], "offsets": [ [ 97, 1658 ] ] } ]

[ { "id": "18501", "type": "Chemical", "text": [ "4'-0-tetrahydropyranyladriamycin" ], "offsets": [ [ 19, 51 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18502", "type": "Chemical", "text": [ "4'-0-tetrahydropyranyladriamycin" ], "offsets": [ [ 139, 171 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18503", "type": "Chemical", "text": [ "Pirarubicin" ], "offsets": [ [ 173, 184 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18504", "type": "Disease", "text": [ "tumors" ], "offsets": [ [ 253, 259 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18505", "type": "Disease", "text": [ "renal and/or hepatic dysfunction" ], "offsets": [ [ 367, 399 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" }, { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "18506", "type": "Disease", "text": [ "renal", "dysfunction" ], "offsets": [ [ 367, 372 ], [ 388, 399 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "18507", "type": "Disease", "text": [ "hepatic dysfunction" ], "offsets": [ [ 380, 399 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "18508", "type": "Disease", "text": [ "granulocytopenia" ], "offsets": [ [ 622, 638 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000380" } ] }, { "id": "18509", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 724, 740 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "18510", "type": "Disease", "text": [ "anemia" ], "offsets": [ [ 742, 748 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000740" } ] }, { "id": "18511", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 750, 756 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "18512", "type": "Disease", "text": [ "alopecia" ], "offsets": [ [ 763, 771 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000505" } ] }, { "id": "18513", "type": "Disease", "text": [ "phlebitis" ], "offsets": [ [ 773, 782 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010689" } ] }, { "id": "18514", "type": "Disease", "text": [ "mucositis" ], "offsets": [ [ 788, 797 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D052016" } ] }, { "id": "18515", "type": "Disease", "text": [ "Myelosuppression" ], "offsets": [ [ 799, 815 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001855" } ] }, { "id": "18516", "type": "Disease", "text": [ "hepatic dysfunction" ], "offsets": [ [ 842, 861 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] }, { "id": "18517", "type": "Chemical", "text": [ "Pirarubicin" ], "offsets": [ [ 912, 923 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18518", "type": "Chemical", "text": [ "Adriamycinol" ], "offsets": [ [ 1207, 1219 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C010013" } ] }, { "id": "18519", "type": "Chemical", "text": [ "doxorubicin" ], "offsets": [ [ 1221, 1232 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "18520", "type": "Chemical", "text": [ "adriamycinone" ], "offsets": [ [ 1234, 1247 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C010012" } ] }, { "id": "18521", "type": "Chemical", "text": [ "tetrahydropyranyladriamycinol" ], "offsets": [ [ 1253, 1282 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18522", "type": "Chemical", "text": [ "doxorubicin" ], "offsets": [ [ 1341, 1352 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004317" } ] }, { "id": "18523", "type": "Chemical", "text": [ "Pirarubicin" ], "offsets": [ [ 1430, 1441 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C027260" } ] }, { "id": "18524", "type": "Disease", "text": [ "mesothelioma" ], "offsets": [ [ 1517, 1529 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008654" } ] }, { "id": "18525", "type": "Disease", "text": [ "leiomyosarcoma" ], "offsets": [ [ 1531, 1545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007890" } ] }, { "id": "18526", "type": "Disease", "text": [ "basal cell carcinoma" ], "offsets": [ [ 1551, 1571 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002280" } ] } ]

[]

[]

[ { "id": "18527", "type": "CID", "arg1_id": "18519", "arg2_id": "18513", "normalized": [] }, { "id": "18528", "type": "CID", "arg1_id": "18522", "arg2_id": "18513", "normalized": [] }, { "id": "18529", "type": "CID", "arg1_id": "18519", "arg2_id": "18508", "normalized": [] }, { "id": "18530", "type": "CID", "arg1_id": "18522", "arg2_id": "18508", "normalized": [] }, { "id": "18531", "type": "CID", "arg1_id": "18519", "arg2_id": "18514", "normalized": [] }, { "id": "18532", "type": "CID", "arg1_id": "18522", "arg2_id": "18514", "normalized": [] }, { "id": "18533", "type": "CID", "arg1_id": "18519", "arg2_id": "18512", "normalized": [] }, { "id": "18534", "type": "CID", "arg1_id": "18522", "arg2_id": "18512", "normalized": [] }, { "id": "18535", "type": "CID", "arg1_id": "18519", "arg2_id": "18509", "normalized": [] }, { "id": "18536", "type": "CID", "arg1_id": "18522", "arg2_id": "18509", "normalized": [] }, { "id": "18537", "type": "CID", "arg1_id": "18519", "arg2_id": "18510", "normalized": [] }, { "id": "18538", "type": "CID", "arg1_id": "18522", "arg2_id": "18510", "normalized": [] }, { "id": "18539", "type": "CID", "arg1_id": "18519", "arg2_id": "18511", "normalized": [] }, { "id": "18540", "type": "CID", "arg1_id": "18522", "arg2_id": "18511", "normalized": [] } ]

[ { "id": "18542", "type": "title", "text": [ "Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures." ], "offsets": [ [ 0, 100 ] ] }, { "id": "18543", "type": "abstract", "text": [ "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel." ], "offsets": [ [ 101, 1718 ] ] } ]

[ { "id": "18544", "type": "Chemical", "text": [ "gamma-hexachlorocyclohexane" ], "offsets": [ [ 24, 51 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18545", "type": "Chemical", "text": [ "lindane" ], "offsets": [ [ 53, 60 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18546", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 91, 99 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18547", "type": "Chemical", "text": [ "Gamma-hexachlorocyclohexane" ], "offsets": [ [ 101, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18548", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 130, 139 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18549", "type": "Chemical", "text": [ "lindane" ], "offsets": [ [ 183, 190 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18550", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 219, 226 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18551", "type": "Chemical", "text": [ "PTZ" ], "offsets": [ [ 257, 260 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010433" } ] }, { "id": "18552", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 284, 293 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18553", "type": "Chemical", "text": [ "PTZ" ], "offsets": [ [ 331, 334 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010433" } ] }, { "id": "18554", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 343, 351 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18555", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 375, 384 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18556", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 457, 464 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18557", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 560, 569 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18558", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 608, 617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18559", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 635, 642 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18560", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 722, 731 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18561", "type": "Disease", "text": [ "Seizure" ], "offsets": [ [ 770, 777 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18562", "type": "Chemical", "text": [ "PTZ" ], "offsets": [ [ 794, 797 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010433" } ] }, { "id": "18563", "type": "Chemical", "text": [ "picrotoxin" ], "offsets": [ [ 802, 812 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010852" } ] }, { "id": "18564", "type": "Chemical", "text": [ "PTX" ], "offsets": [ [ 814, 817 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010852" } ] }, { "id": "18565", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 857, 864 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18566", "type": "Chemical", "text": [ "3-mercaptopropionic acid" ], "offsets": [ [ 881, 905 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015097" } ] }, { "id": "18567", "type": "Chemical", "text": [ "MPA" ], "offsets": [ [ 907, 910 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015097" } ] }, { "id": "18568", "type": "Chemical", "text": [ "bicuculline" ], "offsets": [ [ 913, 924 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001640" } ] }, { "id": "18569", "type": "Chemical", "text": [ "BCC" ], "offsets": [ [ 926, 929 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001640" } ] }, { "id": "18570", "type": "Chemical", "text": [ "methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate" ], "offsets": [ [ 932, 986 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C034818" } ] }, { "id": "18571", "type": "Chemical", "text": [ "DMCM" ], "offsets": [ [ 988, 992 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C034818" } ] }, { "id": "18572", "type": "Chemical", "text": [ "strychnine" ], "offsets": [ [ 998, 1008 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013331" } ] }, { "id": "18573", "type": "Chemical", "text": [ "STR" ], "offsets": [ [ 1010, 1013 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013331" } ] }, { "id": "18574", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 1057, 1066 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18575", "type": "Chemical", "text": [ "pentylenetetrazol" ], "offsets": [ [ 1068, 1085 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010433" } ] }, { "id": "18576", "type": "Chemical", "text": [ "picrotoxin" ], "offsets": [ [ 1090, 1100 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010852" } ] }, { "id": "18577", "type": "Chemical", "text": [ "3H-TBOB" ], "offsets": [ [ 1123, 1130 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C046308" } ] }, { "id": "18578", "type": "Chemical", "text": [ "MPA" ], "offsets": [ [ 1220, 1223 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015097" } ] }, { "id": "18579", "type": "Chemical", "text": [ "BCC" ], "offsets": [ [ 1225, 1228 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001640" } ] }, { "id": "18580", "type": "Chemical", "text": [ "DMCM" ], "offsets": [ [ 1230, 1234 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C034818" } ] }, { "id": "18581", "type": "Chemical", "text": [ "STR" ], "offsets": [ [ 1240, 1243 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013331" } ] }, { "id": "18582", "type": "Chemical", "text": [ "3H-TBOB" ], "offsets": [ [ 1268, 1275 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C046308" } ] }, { "id": "18583", "type": "Chemical", "text": [ "t-butyl bicyclo-orthobenzoate" ], "offsets": [ [ 1277, 1306 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C046308" } ] }, { "id": "18584", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 1420, 1427 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18585", "type": "Chemical", "text": [ "PTZ" ], "offsets": [ [ 1448, 1451 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010433" } ] }, { "id": "18586", "type": "Chemical", "text": [ "PTX" ], "offsets": [ [ 1456, 1459 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010852" } ] }, { "id": "18587", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 1471, 1480 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18588", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 1519, 1526 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18589", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 1629, 1636 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18590", "type": "Chemical", "text": [ "gamma-HCH" ], "offsets": [ [ 1657, 1666 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001556" } ] }, { "id": "18591", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 1678, 1682 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] } ]

[]

[]

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"normalized": [] }, { "id": "18765", "type": "CID", "arg1_id": "18586", "arg2_id": "18556", "normalized": [] }, { "id": "18766", "type": "CID", "arg1_id": "18586", "arg2_id": "18559", "normalized": [] }, { "id": "18767", "type": "CID", "arg1_id": "18586", "arg2_id": "18561", "normalized": [] }, { "id": "18768", "type": "CID", "arg1_id": "18586", "arg2_id": "18565", "normalized": [] }, { "id": "18769", "type": "CID", "arg1_id": "18586", "arg2_id": "18584", "normalized": [] }, { "id": "18770", "type": "CID", "arg1_id": "18586", "arg2_id": "18588", "normalized": [] }, { "id": "18771", "type": "CID", "arg1_id": "18586", "arg2_id": "18589", "normalized": [] }, { "id": "18772", "type": "CID", "arg1_id": "18566", "arg2_id": "18546", "normalized": [] }, { "id": "18773", "type": "CID", "arg1_id": "18566", "arg2_id": "18550", "normalized": [] }, { "id": "18774", "type": "CID", "arg1_id": "18566", "arg2_id": "18554", "normalized": [] }, { "id": "18775", "type": "CID", "arg1_id": "18566", "arg2_id": "18556", "normalized": [] }, { "id": "18776", "type": "CID", "arg1_id": "18566", "arg2_id": "18559", "normalized": [] }, { "id": "18777", "type": "CID", "arg1_id": "18566", "arg2_id": "18561", "normalized": [] }, { "id": "18778", "type": "CID", "arg1_id": "18566", "arg2_id": "18565", "normalized": [] }, { "id": "18779", "type": "CID", "arg1_id": "18566", "arg2_id": "18584", "normalized": [] }, { "id": "18780", "type": "CID", "arg1_id": "18566", "arg2_id": "18588", "normalized": [] }, { "id": "18781", "type": "CID", "arg1_id": "18566", "arg2_id": "18589", "normalized": [] }, { "id": "18782", "type": "CID", "arg1_id": "18567", "arg2_id": "18546", "normalized": [] }, { "id": "18783", "type": "CID", "arg1_id": "18567", "arg2_id": "18550", "normalized": [] }, { "id": "18784", "type": "CID", "arg1_id": "18567", "arg2_id": "18554", "normalized": [] }, { "id": "18785", "type": "CID", "arg1_id": "18567", "arg2_id": "18556", "normalized": [] }, { "id": "18786", "type": "CID", "arg1_id": "18567", "arg2_id": "18559", "normalized": [] }, { "id": "18787", "type": "CID", "arg1_id": "18567", "arg2_id": "18561", "normalized": [] }, { "id": "18788", "type": "CID", "arg1_id": "18567", "arg2_id": "18565", "normalized": [] }, { "id": "18789", "type": "CID", "arg1_id": "18567", "arg2_id": "18584", "normalized": [] }, { "id": "18790", "type": "CID", "arg1_id": "18567", "arg2_id": "18588", "normalized": [] }, { "id": "18791", "type": "CID", "arg1_id": "18567", "arg2_id": "18589", "normalized": [] }, { "id": "18792", "type": "CID", "arg1_id": "18578", "arg2_id": "18546", "normalized": [] }, { "id": "18793", "type": "CID", "arg1_id": "18578", "arg2_id": "18550", "normalized": [] }, { "id": "18794", "type": "CID", "arg1_id": "18578", "arg2_id": "18554", "normalized": [] }, { "id": "18795", "type": "CID", "arg1_id": "18578", "arg2_id": "18556", "normalized": [] }, { "id": "18796", "type": "CID", "arg1_id": "18578", "arg2_id": "18559", "normalized": [] }, { "id": "18797", "type": "CID", "arg1_id": "18578", "arg2_id": "18561", "normalized": [] }, { "id": "18798", "type": "CID", "arg1_id": "18578", "arg2_id": "18565", "normalized": [] }, { "id": "18799", "type": "CID", "arg1_id": "18578", "arg2_id": "18584", "normalized": [] }, { "id": "18800", "type": "CID", "arg1_id": "18578", "arg2_id": "18588", "normalized": [] }, { "id": "18801", "type": "CID", "arg1_id": "18578", "arg2_id": "18589", "normalized": [] } ]

[ { "id": "18803", "type": "title", "text": [ "Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas." ], "offsets": [ [ 0, 107 ] ] }, { "id": "18804", "type": "abstract", "text": [ "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects." ], "offsets": [ [ 108, 1773 ] ] } ]

[ { "id": "18805", "type": "Disease", "text": [ "ocular and orbital toxicity" ], "offsets": [ [ 7, 34 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" }, { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18806", "type": "Disease", "text": [ "ocular", "toxicity" ], "offsets": [ [ 7, 13 ], [ 26, 34 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" } ] }, { "id": "18807", "type": "Disease", "text": [ "orbital toxicity" ], "offsets": [ [ 18, 34 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18808", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 67, 78 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18809", "type": "Disease", "text": [ "glioblastomas" ], "offsets": [ [ 93, 106 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005909" } ] }, { "id": "18810", "type": "Disease", "text": [ "Glioblastoma" ], "offsets": [ [ 120, 132 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005909" } ] }, { "id": "18811", "type": "Disease", "text": [ "malignant tumor" ], "offsets": [ [ 138, 153 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "18812", "type": "Disease", "text": [ "glioblastoma" ], "offsets": [ [ 393, 405 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005909" } ] }, { "id": "18813", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 505, 516 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18814", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 558, 567 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18815", "type": "Disease", "text": [ "ocular and orbital toxicity" ], "offsets": [ [ 575, 602 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" }, { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18816", "type": "Disease", "text": [ "ocular", "toxicity" ], "offsets": [ [ 575, 581 ], [ 594, 602 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" } ] }, { "id": "18817", "type": "Disease", "text": [ "orbital toxicity" ], "offsets": [ [ 586, 602 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18818", "type": "Disease", "text": [ "ocular and orbital toxicity" ], "offsets": [ [ 660, 687 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" }, { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18819", "type": "Disease", "text": [ "ocular", "toxicity" ], "offsets": [ [ 660, 666 ], [ 679, 687 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" } ] }, { "id": "18820", "type": "Disease", "text": [ "orbital toxicity" ], "offsets": [ [ 671, 687 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009916" } ] }, { "id": "18821", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 720, 731 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18822", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 827, 838 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18823", "type": "Disease", "text": [ "glioblastomas" ], "offsets": [ [ 853, 866 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005909" } ] }, { "id": "18824", "type": "Disease", "text": [ "pain and visual disturbance in the ipsilateral eye" ], "offsets": [ [ 911, 961 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058447" }, { "db_name": "MESH", "db_id": "D014786" } ] }, { "id": "18825", "type": "Disease", "text": [ "pain", "in the ipsilateral eye" ], "offsets": [ [ 911, 915 ], [ 939, 961 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058447" } ] }, { "id": "18826", "type": "Disease", "text": [ "visual disturbance in the ipsilateral eye" ], "offsets": [ [ 920, 961 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014786" } ] }, { "id": "18827", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 1035, 1046 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18828", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1047, 1055 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "18829", "type": "Chemical", "text": [ "glycerin" ], "offsets": [ [ 1146, 1154 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005990" } ] }, { "id": "18830", "type": "Disease", "text": [ "glaucoma" ], "offsets": [ [ 1271, 1279 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005901" } ] }, { "id": "18831", "type": "Disease", "text": [ "ocular pain" ], "offsets": [ [ 1294, 1305 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058447" } ] }, { "id": "18832", "type": "Disease", "text": [ "papilledema" ], "offsets": [ [ 1329, 1340 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010211" } ] }, { "id": "18833", "type": "Disease", "text": [ "retinal detachment" ], "offsets": [ [ 1355, 1373 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012163" } ] }, { "id": "18834", "type": "Disease", "text": [ "chorioretinal atrophy" ], "offsets": [ [ 1429, 1450 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C566236" } ] }, { "id": "18835", "type": "Disease", "text": [ "optic atrophy" ], "offsets": [ [ 1456, 1469 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009896" } ] }, { "id": "18836", "type": "Chemical", "text": [ "carboplatin" ], "offsets": [ [ 1574, 1585 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016190" } ] }, { "id": "18837", "type": "Disease", "text": [ "ocular toxicity" ], "offsets": [ [ 1632, 1647 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005128" } ] } ]

[]

[]

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"normalized": [] }, { "id": "18849", "type": "CID", "arg1_id": "18836", "arg2_id": "18832", "normalized": [] }, { "id": "18850", "type": "CID", "arg1_id": "18808", "arg2_id": "18833", "normalized": [] }, { "id": "18851", "type": "CID", "arg1_id": "18813", "arg2_id": "18833", "normalized": [] }, { "id": "18852", "type": "CID", "arg1_id": "18821", "arg2_id": "18833", "normalized": [] }, { "id": "18853", "type": "CID", "arg1_id": "18822", "arg2_id": "18833", "normalized": [] }, { "id": "18854", "type": "CID", "arg1_id": "18827", "arg2_id": "18833", "normalized": [] }, { "id": "18855", "type": "CID", "arg1_id": "18836", "arg2_id": "18833", "normalized": [] }, { "id": "18856", "type": "CID", "arg1_id": "18808", "arg2_id": "18824", "normalized": [] }, { "id": "18857", "type": "CID", "arg1_id": "18808", "arg2_id": "18825", "normalized": [] }, { "id": "18858", "type": "CID", "arg1_id": "18808", "arg2_id": "18831", "normalized": [] }, { "id": "18859", "type": "CID", "arg1_id": "18813", "arg2_id": "18824", "normalized": [] }, { "id": "18860", "type": "CID", "arg1_id": "18813", "arg2_id": "18825", "normalized": [] }, { "id": "18861", "type": "CID", "arg1_id": "18813", "arg2_id": "18831", "normalized": [] }, { "id": "18862", "type": "CID", "arg1_id": "18821", "arg2_id": "18824", "normalized": [] }, { "id": "18863", "type": "CID", "arg1_id": "18821", "arg2_id": "18825", "normalized": [] }, { "id": "18864", "type": "CID", "arg1_id": "18821", "arg2_id": "18831", "normalized": [] }, { "id": "18865", "type": "CID", "arg1_id": "18822", "arg2_id": "18824", "normalized": [] }, { "id": "18866", "type": "CID", "arg1_id": "18822", "arg2_id": "18825", "normalized": [] }, { "id": "18867", "type": "CID", "arg1_id": "18822", "arg2_id": "18831", "normalized": [] }, { "id": "18868", "type": "CID", "arg1_id": "18827", "arg2_id": "18824", "normalized": [] }, { "id": "18869", "type": "CID", "arg1_id": "18827", "arg2_id": "18825", "normalized": [] }, { "id": "18870", "type": "CID", "arg1_id": "18827", "arg2_id": "18831", "normalized": [] }, { "id": "18871", "type": "CID", "arg1_id": "18836", "arg2_id": "18824", "normalized": [] }, { "id": "18872", "type": "CID", "arg1_id": "18836", "arg2_id": "18825", "normalized": [] }, { "id": "18873", "type": "CID", "arg1_id": "18836", "arg2_id": "18831", "normalized": [] }, { "id": "18874", "type": "CID", "arg1_id": "18808", "arg2_id": "18824", "normalized": [] }, { "id": "18875", "type": "CID", "arg1_id": "18808", "arg2_id": "18826", "normalized": [] }, { "id": "18876", "type": "CID", "arg1_id": "18813", "arg2_id": "18824", "normalized": [] }, { "id": "18877", "type": "CID", "arg1_id": "18813", "arg2_id": "18826", "normalized": [] }, { "id": "18878", "type": "CID", "arg1_id": "18821", "arg2_id": "18824", "normalized": [] }, { "id": "18879", "type": "CID", "arg1_id": "18821", "arg2_id": "18826", "normalized": [] }, { "id": "18880", "type": "CID", "arg1_id": "18822", "arg2_id": "18824", "normalized": [] }, { "id": "18881", "type": "CID", "arg1_id": "18822", "arg2_id": "18826", "normalized": [] }, { "id": "18882", "type": "CID", "arg1_id": "18827", "arg2_id": "18824", "normalized": [] }, { "id": "18883", "type": "CID", "arg1_id": "18827", "arg2_id": "18826", "normalized": [] }, { "id": "18884", "type": "CID", "arg1_id": "18836", "arg2_id": "18824", "normalized": [] }, { "id": "18885", "type": "CID", "arg1_id": "18836", "arg2_id": "18826", "normalized": [] }, { "id": "18886", "type": "CID", "arg1_id": "18808", "arg2_id": "18805", "normalized": [] }, { "id": "18887", "type": "CID", "arg1_id": "18808", "arg2_id": "18807", "normalized": [] }, { "id": "18888", "type": "CID", "arg1_id": "18808", "arg2_id": "18815", "normalized": [] }, { "id": "18889", "type": "CID", "arg1_id": "18808", "arg2_id": "18817", "normalized": [] }, { "id": "18890", "type": "CID", "arg1_id": "18808", "arg2_id": "18818", "normalized": [] }, { "id": "18891", "type": "CID", "arg1_id": "18808", "arg2_id": "18820", "normalized": [] }, { "id": "18892", "type": "CID", "arg1_id": "18813", "arg2_id": "18805", "normalized": [] }, { "id": "18893", "type": "CID", "arg1_id": "18813", "arg2_id": "18807", "normalized": [] }, { "id": "18894", "type": "CID", "arg1_id": "18813", "arg2_id": "18815", "normalized": [] }, { "id": "18895", "type": "CID", "arg1_id": "18813", "arg2_id": "18817", "normalized": [] }, { "id": "18896", "type": "CID", "arg1_id": "18813", "arg2_id": "18818", "normalized": [] }, { "id": "18897", "type": "CID", "arg1_id": "18813", "arg2_id": "18820", "normalized": [] }, { "id": "18898", "type": "CID", "arg1_id": "18821", "arg2_id": "18805", "normalized": [] }, { "id": "18899", "type": "CID", "arg1_id": "18821", "arg2_id": "18807", "normalized": [] }, { "id": "18900", "type": "CID", "arg1_id": "18821", "arg2_id": "18815", "normalized": [] }, { "id": "18901", "type": "CID", "arg1_id": "18821", "arg2_id": "18817", "normalized": [] }, { "id": "18902", "type": "CID", "arg1_id": "18821", "arg2_id": "18818", "normalized": [] }, { "id": "18903", "type": "CID", "arg1_id": "18821", "arg2_id": "18820", "normalized": [] }, { "id": "18904", "type": "CID", "arg1_id": "18822", "arg2_id": "18805", "normalized": [] }, { "id": "18905", "type": "CID", "arg1_id": "18822", "arg2_id": "18807", "normalized": [] }, { "id": "18906", "type": "CID", "arg1_id": "18822", "arg2_id": "18815", "normalized": [] }, { "id": "18907", "type": "CID", "arg1_id": "18822", "arg2_id": "18817", "normalized": [] }, { "id": "18908", "type": "CID", "arg1_id": "18822", "arg2_id": "18818", "normalized": [] }, { "id": "18909", "type": "CID", "arg1_id": "18822", "arg2_id": "18820", "normalized": [] }, { "id": "18910", "type": "CID", "arg1_id": "18827", "arg2_id": "18805", "normalized": [] }, { "id": "18911", "type": "CID", "arg1_id": "18827", "arg2_id": "18807", "normalized": [] }, { "id": "18912", "type": "CID", "arg1_id": "18827", "arg2_id": "18815", "normalized": [] }, { "id": "18913", "type": "CID", "arg1_id": "18827", "arg2_id": "18817", "normalized": [] }, { "id": "18914", "type": "CID", "arg1_id": "18827", "arg2_id": "18818", "normalized": [] }, { "id": "18915", "type": "CID", "arg1_id": "18827", "arg2_id": "18820", "normalized": [] }, { "id": "18916", "type": "CID", "arg1_id": "18836", "arg2_id": "18805", "normalized": [] }, { "id": "18917", "type": "CID", "arg1_id": "18836", "arg2_id": "18807", "normalized": [] }, { "id": "18918", "type": "CID", "arg1_id": "18836", "arg2_id": "18815", "normalized": [] }, { "id": "18919", "type": "CID", "arg1_id": "18836", "arg2_id": "18817", "normalized": [] }, { "id": "18920", "type": "CID", "arg1_id": "18836", "arg2_id": "18818", "normalized": [] }, { "id": "18921", "type": "CID", "arg1_id": "18836", "arg2_id": "18820", "normalized": [] } ]

[ { "id": "18923", "type": "title", "text": [ "Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer." ], "offsets": [ [ 0, 91 ] ] }, { "id": "18924", "type": "abstract", "text": [ "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted." ], "offsets": [ [ 92, 1238 ] ] } ]

[ { "id": "18925", "type": "Chemical", "text": [ "amsacrine" ], "offsets": [ [ 22, 31 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000677" } ] }, { "id": "18926", "type": "Chemical", "text": [ "CI-921" ], "offsets": [ [ 41, 47 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C042315" } ] }, { "id": "18927", "type": "Chemical", "text": [ "NSC 343499" ], "offsets": [ [ 49, 59 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C042315" } ] }, { "id": "18928", "type": "Disease", "text": [ "non-small cell lung cancer" ], "offsets": [ [ 64, 90 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "18929", "type": "Chemical", "text": [ "CI-921" ], "offsets": [ [ 92, 98 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C042315" } ] }, { "id": "18930", "type": "Chemical", "text": [ "NSC 343499" ], "offsets": [ [ 100, 110 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C042315" } ] }, { "id": "18931", "type": "Chemical", "text": [ "9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide" ], "offsets": [ [ 112, 202 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C042315" } ] }, { "id": "18932", "type": "Disease", "text": [ "non-small cell lung cancer" ], "offsets": [ [ 346, 372 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "18933", "type": "Disease", "text": [ "NSCLC" ], "offsets": [ [ 374, 379 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002289" } ] }, { "id": "18934", "type": "Disease", "text": [ "squamous carcinoma" ], "offsets": [ [ 663, 681 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002294" } ] }, { "id": "18935", "type": "Disease", "text": [ "adenocarcinoma" ], "offsets": [ [ 688, 702 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000230" } ] }, { "id": "18936", "type": "Disease", "text": [ "bronchio-alveolar carcinoma" ], "offsets": [ [ 729, 756 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002282" } ] }, { "id": "18937", "type": "Disease", "text": [ "undifferentiated carcinoma" ], "offsets": [ [ 776, 802 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002277" } ] }, { "id": "18938", "type": "Disease", "text": [ "Neutropenia" ], "offsets": [ [ 808, 819 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009503" } ] }, { "id": "18939", "type": "Disease", "text": [ "infections" ], "offsets": [ [ 878, 888 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007239" } ] }, { "id": "18940", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 923, 931 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "18941", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 976, 982 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "18942", "type": "Disease", "text": [ "vomiting" ], "offsets": [ [ 987, 995 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014839" } ] }, { "id": "18943", "type": "Disease", "text": [ "phlebitis" ], "offsets": [ [ 1024, 1033 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010689" } ] }, { "id": "18944", "type": "Disease", "text": [ "squamous cell carcinoma" ], "offsets": [ [ 1077, 1100 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002294" } ] }, { "id": "18945", "type": "Disease", "text": [ "tumour" ], "offsets": [ [ 1181, 1187 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] } ]

[]

[]

[ { "id": "18946", "type": "CID", "arg1_id": "18926", "arg2_id": "18939", "normalized": [] }, { "id": "18947", "type": "CID", "arg1_id": "18927", "arg2_id": "18939", "normalized": [] }, { "id": "18948", "type": "CID", "arg1_id": "18929", "arg2_id": "18939", "normalized": [] }, { "id": "18949", "type": "CID", "arg1_id": "18930", "arg2_id": "18939", "normalized": [] }, { "id": "18950", "type": "CID", "arg1_id": "18931", "arg2_id": "18939", "normalized": [] }, { "id": "18951", "type": "CID", "arg1_id": "18926", "arg2_id": "18940", "normalized": [] }, { "id": "18952", "type": "CID", "arg1_id": "18927", "arg2_id": "18940", "normalized": [] }, { "id": "18953", "type": "CID", "arg1_id": "18929", "arg2_id": "18940", "normalized": [] }, { "id": "18954", "type": "CID", "arg1_id": "18930", "arg2_id": "18940", "normalized": [] }, { "id": "18955", "type": "CID", "arg1_id": "18931", "arg2_id": "18940", "normalized": [] }, { "id": "18956", "type": "CID", "arg1_id": "18926", "arg2_id": "18938", "normalized": [] }, { "id": "18957", "type": "CID", "arg1_id": "18927", "arg2_id": "18938", "normalized": [] }, { "id": "18958", "type": "CID", "arg1_id": "18929", "arg2_id": "18938", "normalized": [] }, { "id": "18959", "type": "CID", "arg1_id": "18930", "arg2_id": "18938", "normalized": [] }, { "id": "18960", "type": "CID", "arg1_id": "18931", "arg2_id": "18938", "normalized": [] }, { "id": "18961", "type": "CID", "arg1_id": "18926", "arg2_id": "18941", "normalized": [] }, { "id": "18962", "type": "CID", "arg1_id": "18927", "arg2_id": "18941", "normalized": [] }, { "id": "18963", "type": "CID", "arg1_id": "18929", "arg2_id": "18941", "normalized": [] }, { "id": "18964", "type": "CID", "arg1_id": "18930", "arg2_id": "18941", "normalized": [] }, { "id": "18965", "type": "CID", "arg1_id": "18931", "arg2_id": "18941", "normalized": [] }, { "id": "18966", "type": "CID", "arg1_id": "18926", "arg2_id": "18943", "normalized": [] }, { "id": "18967", "type": "CID", "arg1_id": "18927", "arg2_id": "18943", "normalized": [] }, { "id": "18968", "type": "CID", "arg1_id": "18929", "arg2_id": "18943", "normalized": [] }, { "id": "18969", "type": "CID", "arg1_id": "18930", "arg2_id": "18943", "normalized": [] }, { "id": "18970", "type": "CID", "arg1_id": "18931", "arg2_id": "18943", "normalized": [] }, { "id": "18971", "type": "CID", "arg1_id": "18926", "arg2_id": "18942", "normalized": [] }, { "id": "18972", "type": "CID", "arg1_id": "18927", "arg2_id": "18942", "normalized": [] }, { "id": "18973", "type": "CID", "arg1_id": "18929", "arg2_id": "18942", "normalized": [] }, { "id": "18974", "type": "CID", "arg1_id": "18930", "arg2_id": "18942", "normalized": [] }, { "id": "18975", "type": "CID", "arg1_id": "18931", "arg2_id": "18942", "normalized": [] } ]

[ { "id": "18977", "type": "title", "text": [ "Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy." ], "offsets": [ [ 0, 106 ] ] }, { "id": "18978", "type": "abstract", "text": [ "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials." ], "offsets": [ [ 107, 1804 ] ] } ]

[ { "id": "18979", "type": "Chemical", "text": [ "Alpha-lipoic acid" ], "offsets": [ [ 0, 17 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18980", "type": "Disease", "text": [ "mitochondrial damage" ], "offsets": [ [ 27, 47 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "18981", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 52, 65 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "18982", "type": "Disease", "text": [ "neuropathy" ], "offsets": [ [ 95, 105 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" } ] }, { "id": "18983", "type": "Chemical", "text": [ "alpha-lipoic acid" ], "offsets": [ [ 133, 150 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18984", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 199, 212 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "18985", "type": "Disease", "text": [ "mitochondrial damage" ], "offsets": [ [ 217, 237 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "18986", "type": "Disease", "text": [ "toxic neurodegenerative cascade" ], "offsets": [ [ 263, 294 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009410" } ] }, { "id": "18987", "type": "Chemical", "text": [ "alpha-lipoic acid" ], "offsets": [ [ 330, 347 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18988", "type": "Disease", "text": [ "peripheral neuropathy" ], "offsets": [ [ 433, 454 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] }, { "id": "18989", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 574, 584 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18990", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 589, 598 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18991", "type": "Chemical", "text": [ "alpha-lipoic acid" ], "offsets": [ [ 713, 730 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18992", "type": "Disease", "text": [ "axonal damage" ], "offsets": [ [ 745, 758 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001480" } ] }, { "id": "18993", "type": "Chemical", "text": [ "alpha-lipoic acid" ], "offsets": [ [ 872, 889 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18994", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 925, 934 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "18995", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 939, 949 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "18996", "type": "Disease", "text": [ "mitochondrial impairment" ], "offsets": [ [ 962, 986 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "18997", "type": "Chemical", "text": [ "Alpha-lipoic acid" ], "offsets": [ [ 1068, 1085 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "18998", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 1146, 1159 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "18999", "type": "Disease", "text": [ "mitochondrial toxicity" ], "offsets": [ [ 1195, 1217 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "19000", "type": "Disease", "text": [ "mitochondrial toxicity" ], "offsets": [ [ 1351, 1373 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "19001", "type": "Chemical", "text": [ "paclitaxel" ], "offsets": [ [ 1407, 1417 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017239" } ] }, { "id": "19002", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1422, 1431 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19003", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 1440, 1453 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "19004", "type": "Chemical", "text": [ "Alpha-lipoic acid" ], "offsets": [ [ 1455, 1472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "19005", "type": "Chemical", "text": [ "alpha-lipoic acid" ], "offsets": [ [ 1637, 1654 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008063" } ] }, { "id": "19006", "type": "Disease", "text": [ "peripheral nerve toxicity" ], "offsets": [ [ 1691, 1716 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] } ]

[]

[]

[ { "id": "19007", "type": "CID", "arg1_id": "18989", "arg2_id": "18986", "normalized": [] }, { "id": "19008", "type": "CID", "arg1_id": "18995", "arg2_id": "18986", "normalized": [] }, { "id": "19009", "type": "CID", "arg1_id": "19001", "arg2_id": "18986", "normalized": [] }, { "id": "19010", "type": "CID", "arg1_id": "18990", "arg2_id": "18986", "normalized": [] }, { "id": "19011", "type": "CID", "arg1_id": "18994", "arg2_id": "18986", "normalized": [] }, { "id": "19012", "type": "CID", "arg1_id": "19002", "arg2_id": "18986", "normalized": [] }, { "id": "19013", "type": "CID", "arg1_id": "18990", "arg2_id": "18988", "normalized": [] }, { "id": "19014", "type": "CID", "arg1_id": "18990", "arg2_id": "19006", "normalized": [] }, { "id": "19015", "type": "CID", "arg1_id": "18994", "arg2_id": "18988", "normalized": [] }, { "id": "19016", "type": "CID", "arg1_id": "18994", "arg2_id": "19006", "normalized": [] }, { "id": "19017", "type": "CID", "arg1_id": "19002", "arg2_id": "18988", "normalized": [] }, { "id": "19018", "type": "CID", "arg1_id": "19002", "arg2_id": "19006", "normalized": [] }, { "id": "19019", "type": "CID", "arg1_id": "18989", "arg2_id": "18988", "normalized": [] }, { "id": "19020", "type": "CID", "arg1_id": "18989", "arg2_id": "19006", "normalized": [] }, { "id": "19021", "type": "CID", "arg1_id": "18995", "arg2_id": "18988", "normalized": [] }, { "id": "19022", "type": "CID", "arg1_id": "18995", "arg2_id": "19006", "normalized": [] }, { "id": "19023", "type": "CID", "arg1_id": "19001", "arg2_id": "18988", "normalized": [] }, { "id": "19024", "type": "CID", "arg1_id": "19001", "arg2_id": "19006", "normalized": [] } ]

[ { "id": "19026", "type": "title", "text": [ "Optimising stroke prevention in non-valvular atrial fibrillation." ], "offsets": [ [ 0, 65 ] ] }, { "id": "19027", "type": "abstract", "text": [ "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients." ], "offsets": [ [ 66, 1381 ] ] } ]

[ { "id": "19028", "type": "Disease", "text": [ "stroke" ], "offsets": [ [ 11, 17 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020521" } ] }, { "id": "19029", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 45, 64 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "19030", "type": "Disease", "text": [ "Atrial fibrillation" ], "offsets": [ [ 66, 85 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "19031", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 230, 238 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19032", "type": "Disease", "text": [ "stroke" ], "offsets": [ [ 259, 265 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020521" } ] }, { "id": "19033", "type": "Chemical", "text": [ "aspirin" ], "offsets": [ [ 283, 290 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001241" } ] }, { "id": "19034", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 354, 362 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19035", "type": "Chemical", "text": [ "aspirin" ], "offsets": [ [ 378, 385 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001241" } ] }, { "id": "19036", "type": "Disease", "text": [ "strokes" ], "offsets": [ [ 400, 407 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020521" } ] }, { "id": "19037", "type": "Chemical", "text": [ "Ximelagatran" ], "offsets": [ [ 448, 460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C426686" } ] }, { "id": "19038", "type": "Chemical", "text": [ "vitamin K" ], "offsets": [ [ 529, 538 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014812" } ] }, { "id": "19039", "type": "Disease", "text": [ "embolic events" ], "offsets": [ [ 577, 591 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004617" } ] }, { "id": "19040", "type": "Disease", "text": [ "abnormal liver function" ], "offsets": [ [ 636, 659 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "19041", "type": "Disease", "text": [ "Atrial Fibrillation" ], "offsets": [ [ 681, 700 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "19042", "type": "Chemical", "text": [ "Clopidogrel" ], "offsets": [ [ 701, 712 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C055162" } ] }, { "id": "19043", "type": "Chemical", "text": [ "Irbesartan" ], "offsets": [ [ 724, 734 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C081309" } ] }, { "id": "19044", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 798, 806 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19045", "type": "Chemical", "text": [ "clopidogrel" ], "offsets": [ [ 840, 851 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C055162" } ] }, { "id": "19046", "type": "Chemical", "text": [ "aspirin" ], "offsets": [ [ 857, 864 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001241" } ] }, { "id": "19047", "type": "Disease", "text": [ "embolic events" ], "offsets": [ [ 887, 901 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004617" } ] }, { "id": "19048", "type": "Chemical", "text": [ "Idraparinux" ], "offsets": [ [ 903, 914 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C479958" } ] }, { "id": "19049", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 975, 994 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "19050", "type": "Chemical", "text": [ "Angiotensin" ], "offsets": [ [ 996, 1007 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000809" } ] }, { "id": "19051", "type": "Chemical", "text": [ "angiotensin II" ], "offsets": [ [ 1041, 1055 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000804" } ] }, { "id": "19052", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 1096, 1115 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "19053", "type": "Disease", "text": [ "cardiac remodelling" ], "offsets": [ [ 1124, 1143 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020257" } ] }, { "id": "19054", "type": "Chemical", "text": [ "statins" ], "offsets": [ [ 1178, 1185 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] } ]

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[ { "id": "19055", "type": "CID", "arg1_id": "19037", "arg2_id": "19040", "normalized": [] } ]

[ { "id": "19057", "type": "title", "text": [ "Interaction of cyclosporin A with antineoplastic agents." ], "offsets": [ [ 0, 56 ] ] }, { "id": "19058", "type": "abstract", "text": [ "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions." ], "offsets": [ [ 57, 689 ] ] } ]

[ { "id": "19059", "type": "Chemical", "text": [ "cyclosporin A" ], "offsets": [ [ 15, 28 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "19060", "type": "Chemical", "text": [ "etoposide" ], "offsets": [ [ 81, 90 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005047" } ] }, { "id": "19061", "type": "Chemical", "text": [ "cyclosporin A" ], "offsets": [ [ 95, 108 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "19062", "type": "Disease", "text": [ "acute T-lymphocytic leukemia" ], "offsets": [ [ 140, 168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D054218" } ] }, { "id": "19063", "type": "Chemical", "text": [ "etoposide" ], "offsets": [ [ 215, 224 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005047" } ] }, { "id": "19064", "type": "Chemical", "text": [ "cyclosporin A" ], "offsets": [ [ 229, 242 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "19065", "type": "Disease", "text": [ "leukemic infiltration" ], "offsets": [ [ 290, 311 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017254" } ] }, { "id": "19066", "type": "Disease", "text": [ "confusion" ], "offsets": [ [ 367, 376 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003221" } ] }, { "id": "19067", "type": "Disease", "text": [ "hyperbilirubinemia" ], "offsets": [ [ 393, 411 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006932" } ] }, { "id": "19068", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 493, 501 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19069", "type": "Chemical", "text": [ "cyclosporin A" ], "offsets": [ [ 604, 617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] } ]

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[ { "id": "19070", "type": "CID", "arg1_id": "19059", "arg2_id": "19066", "normalized": [] }, { "id": "19071", "type": "CID", "arg1_id": "19061", "arg2_id": "19066", "normalized": [] }, { "id": "19072", "type": "CID", "arg1_id": "19064", "arg2_id": "19066", "normalized": [] }, { "id": "19073", "type": "CID", "arg1_id": "19069", "arg2_id": "19066", "normalized": [] }, { "id": "19074", "type": "CID", "arg1_id": "19060", "arg2_id": "19067", "normalized": [] }, { "id": "19075", "type": "CID", "arg1_id": "19063", "arg2_id": "19067", "normalized": [] }, { "id": "19076", "type": "CID", "arg1_id": "19060", "arg2_id": "19066", "normalized": [] }, { "id": "19077", "type": "CID", "arg1_id": "19063", "arg2_id": "19066", "normalized": [] }, { "id": "19078", "type": "CID", "arg1_id": "19059", "arg2_id": "19067", "normalized": [] }, { "id": "19079", "type": "CID", "arg1_id": "19061", "arg2_id": "19067", "normalized": [] }, { "id": "19080", "type": "CID", "arg1_id": "19064", "arg2_id": "19067", "normalized": [] }, { "id": "19081", "type": "CID", "arg1_id": "19069", "arg2_id": "19067", "normalized": [] } ]

[ { "id": "19083", "type": "title", "text": [ "The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man." ], "offsets": [ [ 0, 121 ] ] }, { "id": "19084", "type": "abstract", "text": [ "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders." ], "offsets": [ [ 122, 1803 ] ] } ]

[ { "id": "19085", "type": "Chemical", "text": [ "cefonicid" ], "offsets": [ [ 27, 36 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015790" } ] }, { "id": "19086", "type": "Chemical", "text": [ "cefazedone" ], "offsets": [ [ 41, 51 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C021341" } ] }, { "id": "19087", "type": "Chemical", "text": [ "cephalosporin" ], "offsets": [ [ 85, 98 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "19088", "type": "Disease", "text": [ "hematotoxicity" ], "offsets": [ [ 99, 113 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19089", "type": "Chemical", "text": [ "Cephalosporin" ], "offsets": [ [ 122, 135 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "19090", "type": "Disease", "text": [ "hematologic disturbances" ], "offsets": [ [ 167, 191 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19091", "type": "Disease", "text": [ "blood dyscrasias" ], "offsets": [ [ 338, 354 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19092", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 388, 396 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19093", "type": "Chemical", "text": [ "cefonicid" ], "offsets": [ [ 440, 449 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015790" } ] }, { "id": "19094", "type": "Chemical", "text": [ "cefazedone" ], "offsets": [ [ 453, 463 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C021341" } ] }, { "id": "19095", "type": "Disease", "text": [ "anemia" ], "offsets": [ [ 516, 522 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000740" } ] }, { "id": "19096", "type": "Disease", "text": [ "neutropenia" ], "offsets": [ [ 524, 535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009503" } ] }, { "id": "19097", "type": "Disease", "text": [ "thrombocytopenia" ], "offsets": [ [ 541, 557 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013921" } ] }, { "id": "19098", "type": "Disease", "text": [ "anemia" ], "offsets": [ [ 607, 613 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000740" } ] }, { "id": "19099", "type": "Disease", "text": [ "cytopenias" ], "offsets": [ [ 647, 657 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19100", "type": "Chemical", "text": [ "cefonicid" ], "offsets": [ [ 724, 733 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015790" } ] }, { "id": "19101", "type": "Chemical", "text": [ "cefazedone" ], "offsets": [ [ 751, 761 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C021341" } ] }, { "id": "19102", "type": "Disease", "text": [ "cytopenias" ], "offsets": [ [ 773, 783 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19103", "type": "Chemical", "text": [ "cephalosporin" ], "offsets": [ [ 1036, 1049 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "19104", "type": "Disease", "text": [ "hematologic syndrome" ], "offsets": [ [ 1055, 1075 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19105", "type": "Chemical", "text": [ "cefonicid" ], "offsets": [ [ 1112, 1121 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015790" } ] }, { "id": "19106", "type": "Chemical", "text": [ "cefazedone" ], "offsets": [ [ 1131, 1141 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C021341" } ] }, { "id": "19107", "type": "Disease", "text": [ "hemolytic" ], "offsets": [ [ 1406, 1415 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006461" } ] }, { "id": "19108", "type": "Disease", "text": [ "cytopenia" ], "offsets": [ [ 1530, 1539 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19109", "type": "Chemical", "text": [ "cefonicid" ], "offsets": [ [ 1594, 1603 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015790" } ] }, { "id": "19110", "type": "Chemical", "text": [ "cefazedone" ], "offsets": [ [ 1607, 1617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C021341" } ] }, { "id": "19111", "type": "Disease", "text": [ "hematotoxicity" ], "offsets": [ [ 1637, 1651 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] }, { "id": "19112", "type": "Chemical", "text": [ "cephalosporin" ], "offsets": [ [ 1667, 1680 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002511" } ] }, { "id": "19113", "type": "Disease", "text": [ "blood dyscrasias" ], "offsets": [ [ 1689, 1705 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006402" } ] } ]

[]

[]

[ { "id": "19114", "type": "CID", "arg1_id": "19086", "arg2_id": "19096", "normalized": [] }, { "id": "19115", "type": "CID", "arg1_id": "19094", "arg2_id": "19096", "normalized": [] }, { "id": "19116", "type": "CID", "arg1_id": "19101", "arg2_id": "19096", "normalized": [] }, { "id": "19117", "type": "CID", "arg1_id": "19106", "arg2_id": "19096", "normalized": [] }, { "id": "19118", "type": "CID", "arg1_id": "19110", "arg2_id": "19096", "normalized": [] }, { "id": "19119", "type": "CID", "arg1_id": "19085", "arg2_id": "19097", "normalized": [] }, { "id": "19120", "type": "CID", "arg1_id": "19093", "arg2_id": "19097", "normalized": [] }, { "id": "19121", "type": "CID", "arg1_id": "19100", "arg2_id": "19097", "normalized": [] }, { "id": "19122", "type": "CID", "arg1_id": "19105", "arg2_id": "19097", "normalized": [] }, { "id": "19123", "type": "CID", "arg1_id": "19109", "arg2_id": "19097", "normalized": [] }, { "id": "19124", "type": "CID", "arg1_id": "19085", "arg2_id": "19095", "normalized": [] }, { "id": "19125", "type": "CID", "arg1_id": "19085", "arg2_id": "19098", "normalized": [] }, { "id": "19126", "type": "CID", "arg1_id": "19093", "arg2_id": "19095", "normalized": [] }, { "id": "19127", "type": "CID", "arg1_id": "19093", "arg2_id": "19098", "normalized": [] }, { "id": "19128", "type": "CID", "arg1_id": "19100", "arg2_id": "19095", "normalized": [] }, { "id": "19129", "type": "CID", "arg1_id": "19100", "arg2_id": "19098", "normalized": [] }, { "id": "19130", "type": "CID", "arg1_id": "19105", "arg2_id": "19095", "normalized": [] }, { "id": "19131", "type": "CID", "arg1_id": "19105", "arg2_id": "19098", "normalized": [] }, { "id": "19132", "type": "CID", "arg1_id": "19109", "arg2_id": "19095", "normalized": [] }, { "id": "19133", "type": "CID", "arg1_id": "19109", "arg2_id": "19098", "normalized": [] }, { "id": "19134", "type": "CID", "arg1_id": "19086", "arg2_id": "19097", "normalized": [] }, { "id": "19135", "type": "CID", "arg1_id": "19094", "arg2_id": "19097", "normalized": [] }, { "id": "19136", "type": "CID", "arg1_id": "19101", "arg2_id": "19097", "normalized": [] }, { "id": "19137", "type": "CID", "arg1_id": "19106", "arg2_id": "19097", "normalized": [] }, { "id": "19138", "type": "CID", "arg1_id": "19110", "arg2_id": "19097", "normalized": [] }, { "id": "19139", "type": "CID", "arg1_id": "19085", "arg2_id": "19096", "normalized": [] }, { "id": "19140", "type": "CID", "arg1_id": "19093", "arg2_id": "19096", "normalized": [] }, { "id": "19141", "type": "CID", "arg1_id": "19100", "arg2_id": "19096", "normalized": [] }, { "id": "19142", "type": "CID", "arg1_id": "19105", "arg2_id": "19096", "normalized": [] }, { "id": "19143", "type": "CID", "arg1_id": "19109", "arg2_id": "19096", "normalized": [] }, { "id": "19144", "type": "CID", "arg1_id": "19086", "arg2_id": "19095", "normalized": [] }, { "id": "19145", "type": "CID", "arg1_id": "19086", "arg2_id": "19098", "normalized": [] }, { "id": "19146", "type": "CID", "arg1_id": "19094", "arg2_id": "19095", "normalized": [] }, { "id": "19147", "type": "CID", "arg1_id": "19094", "arg2_id": "19098", "normalized": [] }, { "id": "19148", "type": "CID", "arg1_id": "19101", "arg2_id": "19095", "normalized": [] }, { "id": "19149", "type": "CID", "arg1_id": "19101", "arg2_id": "19098", "normalized": [] }, { "id": "19150", "type": "CID", "arg1_id": "19106", "arg2_id": "19095", "normalized": [] }, { "id": "19151", "type": "CID", "arg1_id": "19106", "arg2_id": "19098", "normalized": [] }, { "id": "19152", "type": "CID", "arg1_id": "19110", "arg2_id": "19095", "normalized": [] }, { "id": "19153", "type": "CID", "arg1_id": "19110", "arg2_id": "19098", "normalized": [] } ]

[ { "id": "19155", "type": "title", "text": [ "A pyridoxine-dependent behavioral disorder unmasked by isoniazid." ], "offsets": [ [ 0, 65 ] ] }, { "id": "19156", "type": "abstract", "text": [ "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior." ], "offsets": [ [ 66, 883 ] ] } ]

[ { "id": "19157", "type": "Chemical", "text": [ "pyridoxine" ], "offsets": [ [ 2, 12 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] }, { "id": "19158", "type": "Disease", "text": [ "behavioral disorder" ], "offsets": [ [ 23, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002653" } ] }, { "id": "19159", "type": "Chemical", "text": [ "isoniazid" ], "offsets": [ [ 55, 64 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007538" } ] }, { "id": "19160", "type": "Disease", "text": [ "behavioral deterioration" ], "offsets": [ [ 88, 112 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002653" } ] }, { "id": "19161", "type": "Disease", "text": [ "hyperkinesis" ], "offsets": [ [ 119, 131 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "19162", "type": "Disease", "text": [ "irritability" ], "offsets": [ [ 133, 145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001523" } ] }, { "id": "19163", "type": "Disease", "text": [ "sleeping difficulties" ], "offsets": [ [ 151, 172 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012893" } ] }, { "id": "19164", "type": "Chemical", "text": [ "isoniazid" ], "offsets": [ [ 213, 222 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007538" } ] }, { "id": "19165", "type": "Chemical", "text": [ "pyridoxine hydrochloride" ], "offsets": [ [ 269, 293 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] }, { "id": "19166", "type": "Chemical", "text": [ "isoniazid" ], "offsets": [ [ 350, 359 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007538" } ] }, { "id": "19167", "type": "Chemical", "text": [ "pyridoxine" ], "offsets": [ [ 431, 441 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] }, { "id": "19168", "type": "Chemical", "text": [ "niacinamide" ], "offsets": [ [ 472, 483 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009536" } ] }, { "id": "19169", "type": "Chemical", "text": [ "pyridoxine" ], "offsets": [ [ 504, 514 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] }, { "id": "19170", "type": "Chemical", "text": [ "pyridoxine" ], "offsets": [ [ 539, 549 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] }, { "id": "19171", "type": "Disease", "text": [ "hyperkinesis" ], "offsets": [ [ 584, 596 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "19172", "type": "Chemical", "text": [ "pyridoxal" ], "offsets": [ [ 611, 620 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011730" } ] }, { "id": "19173", "type": "Chemical", "text": [ "kynurenine" ], "offsets": [ [ 719, 729 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007737" } ] }, { "id": "19174", "type": "Chemical", "text": [ "tryptophan" ], "offsets": [ [ 741, 751 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014364" } ] }, { "id": "19175", "type": "Chemical", "text": [ "pyridoxine" ], "offsets": [ [ 848, 858 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011736" } ] } ]

[]

[]

[ { "id": "19176", "type": "CID", "arg1_id": "19159", "arg2_id": "19161", "normalized": [] }, { "id": "19177", "type": "CID", "arg1_id": "19159", "arg2_id": "19171", "normalized": [] }, { "id": "19178", "type": "CID", "arg1_id": "19164", "arg2_id": "19161", "normalized": [] }, { "id": "19179", "type": "CID", "arg1_id": "19164", "arg2_id": "19171", "normalized": [] }, { "id": "19180", "type": "CID", "arg1_id": "19166", "arg2_id": "19161", "normalized": [] }, { "id": "19181", "type": "CID", "arg1_id": "19166", "arg2_id": "19171", "normalized": [] }, { "id": "19182", "type": "CID", "arg1_id": "19159", "arg2_id": "19158", "normalized": [] }, { "id": "19183", "type": "CID", "arg1_id": "19159", "arg2_id": "19160", "normalized": [] }, { "id": "19184", "type": "CID", "arg1_id": "19164", "arg2_id": "19158", "normalized": [] }, { "id": "19185", "type": "CID", "arg1_id": "19164", "arg2_id": "19160", "normalized": [] }, { "id": "19186", "type": "CID", "arg1_id": "19166", "arg2_id": "19158", "normalized": [] }, { "id": "19187", "type": "CID", "arg1_id": "19166", "arg2_id": "19160", "normalized": [] } ]

[ { "id": "19189", "type": "title", "text": [ "A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile." ], "offsets": [ [ 0, 97 ] ] }, { "id": "19190", "type": "abstract", "text": [ "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics." ], "offsets": [ [ 98, 1462 ] ] } ]

[ { "id": "19191", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 12, 20 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19192", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 45, 52 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19193", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 98, 105 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19194", "type": "Chemical", "text": [ "5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide" ], "offsets": [ [ 107, 212 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19195", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 251, 259 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19196", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 344, 351 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19197", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 390, 398 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19198", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 444, 452 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19199", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 467, 474 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19200", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 520, 528 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19201", "type": "Chemical", "text": [ "serotonin" ], "offsets": [ [ 557, 566 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "19202", "type": "Chemical", "text": [ "5-HT" ], "offsets": [ [ 568, 572 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "19203", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 639, 646 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19204", "type": "Chemical", "text": [ "clozapine" ], "offsets": [ [ 651, 660 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003024" } ] }, { "id": "19205", "type": "Disease", "text": [ "hyperactivity" ], "offsets": [ [ 683, 696 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "19206", "type": "Chemical", "text": [ "methamphetamine" ], "offsets": [ [ 708, 723 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "19207", "type": "Chemical", "text": [ "MAP" ], "offsets": [ [ 725, 728 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "19208", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 739, 746 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19209", "type": "Chemical", "text": [ "clozapine" ], "offsets": [ [ 751, 760 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003024" } ] }, { "id": "19210", "type": "Chemical", "text": [ "MAP" ], "offsets": [ [ 773, 776 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008694" } ] }, { "id": "19211", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 901, 908 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19212", "type": "Chemical", "text": [ "clozapine" ], "offsets": [ [ 913, 922 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003024" } ] }, { "id": "19213", "type": "Disease", "text": [ "catalepsy" ], "offsets": [ [ 945, 954 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19214", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 1048, 1055 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19215", "type": "Chemical", "text": [ "clozapine" ], "offsets": [ [ 1060, 1069 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003024" } ] }, { "id": "19216", "type": "Chemical", "text": [ "apomorphine" ], "offsets": [ [ 1157, 1168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001058" } ] }, { "id": "19217", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 1170, 1177 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] }, { "id": "19218", "type": "Chemical", "text": [ "clozapine" ], "offsets": [ [ 1182, 1191 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003024" } ] }, { "id": "19219", "type": "Chemical", "text": [ "phencyclidine" ], "offsets": [ [ 1220, 1233 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010622" } ] }, { "id": "19220", "type": "Chemical", "text": [ "PCP" ], "offsets": [ [ 1235, 1238 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010622" } ] }, { "id": "19221", "type": "Chemical", "text": [ "NRA0160" ], "offsets": [ [ 1333, 1340 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C121249" } ] } ]

[]

[]

[ { "id": "19222", "type": "CID", "arg1_id": "19206", "arg2_id": "19205", "normalized": [] }, { "id": "19223", "type": "CID", "arg1_id": "19207", "arg2_id": "19205", "normalized": [] }, { "id": "19224", "type": "CID", "arg1_id": "19210", "arg2_id": "19205", "normalized": [] }, { "id": "19225", "type": "CID", "arg1_id": "19204", "arg2_id": "19213", "normalized": [] }, { "id": "19226", "type": "CID", "arg1_id": "19209", "arg2_id": "19213", "normalized": [] }, { "id": "19227", "type": "CID", "arg1_id": "19212", "arg2_id": "19213", "normalized": [] }, { "id": "19228", "type": "CID", "arg1_id": "19215", "arg2_id": "19213", "normalized": [] }, { "id": "19229", "type": "CID", "arg1_id": "19218", "arg2_id": "19213", "normalized": [] }, { "id": "19230", "type": "CID", "arg1_id": "19192", "arg2_id": "19213", "normalized": [] }, { "id": "19231", "type": "CID", "arg1_id": "19193", "arg2_id": "19213", "normalized": [] }, { "id": "19232", "type": "CID", "arg1_id": "19194", "arg2_id": "19213", "normalized": [] }, { "id": "19233", "type": "CID", "arg1_id": "19196", "arg2_id": "19213", "normalized": [] }, { "id": "19234", "type": "CID", "arg1_id": "19199", "arg2_id": "19213", "normalized": [] }, { "id": "19235", "type": "CID", "arg1_id": "19203", "arg2_id": "19213", "normalized": [] }, { "id": "19236", "type": "CID", "arg1_id": "19208", "arg2_id": "19213", "normalized": [] }, { "id": "19237", "type": "CID", "arg1_id": "19211", "arg2_id": "19213", "normalized": [] }, { "id": "19238", "type": "CID", "arg1_id": "19214", "arg2_id": "19213", "normalized": [] }, { "id": "19239", "type": "CID", "arg1_id": "19217", "arg2_id": "19213", "normalized": [] }, { "id": "19240", "type": "CID", "arg1_id": "19221", "arg2_id": "19213", "normalized": [] } ]

[ { "id": "19242", "type": "title", "text": [ "Prolonged cholestasis after troleandomycin-induced acute hepatitis." ], "offsets": [ [ 0, 67 ] ] }, { "id": "19243", "type": "abstract", "text": [ "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis." ], "offsets": [ [ 68, 720 ] ] } ]

[ { "id": "19244", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 10, 21 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "19245", "type": "Chemical", "text": [ "troleandomycin" ], "offsets": [ [ 28, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014217" } ] }, { "id": "19246", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 57, 66 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "19247", "type": "Chemical", "text": [ "troleandomycin" ], "offsets": [ [ 108, 122 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014217" } ] }, { "id": "19248", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 131, 140 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "19249", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 177, 188 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "19250", "type": "Disease", "text": [ "Jaundice" ], "offsets": [ [ 190, 198 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "19251", "type": "Chemical", "text": [ "troleandomycin" ], "offsets": [ [ 232, 246 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014217" } ] }, { "id": "19252", "type": "Disease", "text": [ "hypereosinophilia" ], "offsets": [ [ 282, 299 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004802" } ] }, { "id": "19253", "type": "Disease", "text": [ "Jaundice" ], "offsets": [ [ 301, 309 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "19254", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 378, 389 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "19255", "type": "Disease", "text": [ "pruritus" ], "offsets": [ [ 400, 408 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011537" } ] }, { "id": "19256", "type": "Disease", "text": [ "pruritus" ], "offsets": [ [ 499, 507 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011537" } ] }, { "id": "19257", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 602, 611 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "19258", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 658, 669 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "19259", "type": "Chemical", "text": [ "troleandomycin" ], "offsets": [ [ 681, 695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014217" } ] }, { "id": "19260", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 710, 719 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] } ]

[]

[]

[ { "id": "19261", "type": "CID", "arg1_id": "19245", "arg2_id": "19244", "normalized": [] }, { "id": "19262", "type": "CID", "arg1_id": "19245", "arg2_id": "19249", "normalized": [] }, { "id": "19263", "type": "CID", "arg1_id": "19245", "arg2_id": "19254", "normalized": [] }, { "id": "19264", "type": "CID", "arg1_id": "19245", "arg2_id": "19258", "normalized": [] }, { "id": "19265", "type": "CID", "arg1_id": "19247", "arg2_id": "19244", "normalized": [] }, { "id": "19266", "type": "CID", "arg1_id": "19247", "arg2_id": "19249", "normalized": [] }, { "id": "19267", "type": "CID", "arg1_id": "19247", "arg2_id": "19254", "normalized": [] }, { "id": "19268", "type": "CID", "arg1_id": "19247", "arg2_id": "19258", "normalized": [] }, { "id": "19269", "type": "CID", "arg1_id": "19251", "arg2_id": "19244", "normalized": [] }, { "id": "19270", "type": "CID", "arg1_id": "19251", "arg2_id": "19249", "normalized": [] }, { "id": "19271", "type": "CID", "arg1_id": "19251", "arg2_id": "19254", "normalized": [] }, { "id": "19272", "type": "CID", "arg1_id": "19251", "arg2_id": "19258", "normalized": [] }, { "id": "19273", "type": "CID", "arg1_id": "19259", "arg2_id": "19244", "normalized": [] }, { "id": "19274", "type": "CID", "arg1_id": "19259", "arg2_id": "19249", "normalized": [] }, { "id": "19275", "type": "CID", "arg1_id": "19259", "arg2_id": "19254", "normalized": [] }, { "id": "19276", "type": "CID", "arg1_id": "19259", "arg2_id": "19258", "normalized": [] }, { "id": "19277", "type": "CID", "arg1_id": "19245", "arg2_id": "19250", "normalized": [] }, { "id": "19278", "type": "CID", "arg1_id": "19245", "arg2_id": "19253", "normalized": [] }, { "id": "19279", "type": "CID", "arg1_id": "19247", "arg2_id": "19250", "normalized": [] }, { "id": "19280", "type": "CID", "arg1_id": "19247", "arg2_id": "19253", "normalized": [] }, { "id": "19281", "type": "CID", "arg1_id": "19251", "arg2_id": "19250", "normalized": [] }, { "id": "19282", "type": "CID", "arg1_id": "19251", "arg2_id": "19253", "normalized": [] }, { "id": "19283", "type": "CID", "arg1_id": "19259", "arg2_id": "19250", "normalized": [] }, { "id": "19284", "type": "CID", "arg1_id": "19259", "arg2_id": "19253", "normalized": [] }, { "id": "19285", "type": "CID", "arg1_id": "19245", "arg2_id": "19252", "normalized": [] }, { "id": "19286", "type": "CID", "arg1_id": "19247", "arg2_id": "19252", "normalized": [] }, { "id": "19287", "type": "CID", "arg1_id": "19251", "arg2_id": "19252", "normalized": [] }, { "id": "19288", "type": "CID", "arg1_id": "19259", "arg2_id": "19252", "normalized": [] }, { "id": "19289", "type": "CID", "arg1_id": "19245", "arg2_id": "19255", "normalized": [] }, { "id": "19290", "type": "CID", "arg1_id": "19245", "arg2_id": "19256", "normalized": [] }, { "id": "19291", "type": "CID", "arg1_id": "19247", "arg2_id": "19255", "normalized": [] }, { "id": "19292", "type": "CID", "arg1_id": "19247", "arg2_id": "19256", "normalized": [] }, { "id": "19293", "type": "CID", "arg1_id": "19251", "arg2_id": "19255", "normalized": [] }, { "id": "19294", "type": "CID", "arg1_id": "19251", "arg2_id": "19256", "normalized": [] }, { "id": "19295", "type": "CID", "arg1_id": "19259", "arg2_id": "19255", "normalized": [] }, { "id": "19296", "type": "CID", "arg1_id": "19259", "arg2_id": "19256", "normalized": [] }, { "id": "19297", "type": "CID", "arg1_id": "19245", "arg2_id": "19246", "normalized": [] }, { "id": "19298", "type": "CID", "arg1_id": "19245", "arg2_id": "19248", "normalized": [] }, { "id": "19299", "type": "CID", "arg1_id": "19245", "arg2_id": "19257", "normalized": [] }, { "id": "19300", "type": "CID", "arg1_id": "19245", "arg2_id": "19260", "normalized": [] }, { "id": "19301", "type": "CID", "arg1_id": "19247", "arg2_id": "19246", "normalized": [] }, { "id": "19302", "type": "CID", "arg1_id": "19247", "arg2_id": "19248", "normalized": [] }, { "id": "19303", "type": "CID", "arg1_id": "19247", "arg2_id": "19257", "normalized": [] }, { "id": "19304", "type": "CID", "arg1_id": "19247", "arg2_id": "19260", "normalized": [] }, { "id": "19305", "type": "CID", "arg1_id": "19251", "arg2_id": "19246", "normalized": [] }, { "id": "19306", "type": "CID", "arg1_id": "19251", "arg2_id": "19248", "normalized": [] }, { "id": "19307", "type": "CID", "arg1_id": "19251", "arg2_id": "19257", "normalized": [] }, { "id": "19308", "type": "CID", "arg1_id": "19251", "arg2_id": "19260", "normalized": [] }, { "id": "19309", "type": "CID", "arg1_id": "19259", "arg2_id": "19246", "normalized": [] }, { "id": "19310", "type": "CID", "arg1_id": "19259", "arg2_id": "19248", "normalized": [] }, { "id": "19311", "type": "CID", "arg1_id": "19259", "arg2_id": "19257", "normalized": [] }, { "id": "19312", "type": "CID", "arg1_id": "19259", "arg2_id": "19260", "normalized": [] } ]

[ { "id": "19314", "type": "title", "text": [ "HMG CoA reductase inhibitors. Current clinical experience." ], "offsets": [ [ 0, 58 ] ] }, { "id": "19315", "type": "abstract", "text": [ "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences." ], "offsets": [ [ 59, 1821 ] ] } ]

[ { "id": "19316", "type": "Chemical", "text": [ "Lovastatin" ], "offsets": [ [ 59, 69 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] }, { "id": "19317", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 74, 85 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "19318", "type": "Chemical", "text": [ "lovastatin" ], "offsets": [ [ 217, 227 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] }, { "id": "19319", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 328, 339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "19320", "type": "Chemical", "text": [ "Lovastatin" ], "offsets": [ [ 422, 432 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] }, { "id": "19321", "type": "Chemical", "text": [ "cholesterol" ], "offsets": [ [ 564, 575 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002784" } ] }, { "id": "19322", "type": "Chemical", "text": [ "cholesterol" ], "offsets": [ [ 599, 610 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002784" } ] }, { "id": "19323", "type": "Chemical", "text": [ "cholesterol" ], "offsets": [ [ 663, 674 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002784" } ] }, { "id": "19324", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 1254, 1262 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "19325", "type": "Disease", "text": [ "Myopathy" ], "offsets": [ [ 1315, 1323 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19326", "type": "Disease", "text": [ "myoglobinuria" ], "offsets": [ [ 1355, 1368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009212" } ] }, { "id": "19327", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 1400, 1413 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "19328", "type": "Chemical", "text": [ "lovastatin" ], "offsets": [ [ 1445, 1455 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] }, { "id": "19329", "type": "Chemical", "text": [ "cyclosporin" ], "offsets": [ [ 1507, 1518 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "19330", "type": "Chemical", "text": [ "gemfibrozil" ], "offsets": [ [ 1520, 1531 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015248" } ] }, { "id": "19331", "type": "Chemical", "text": [ "niacin" ], "offsets": [ [ 1535, 1541 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009525" } ] }, { "id": "19332", "type": "Chemical", "text": [ "Lovastatin" ], "offsets": [ [ 1543, 1553 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008148" } ] }, { "id": "19333", "type": "Chemical", "text": [ "simvastatin" ], "offsets": [ [ 1558, 1569 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019821" } ] }, { "id": "19334", "type": "Chemical", "text": [ "cholesterol" ], "offsets": [ [ 1653, 1664 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002784" } ] }, { "id": "19335", "type": "Disease", "text": [ "hypercholesterolaemia" ], "offsets": [ [ 1778, 1799 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006937" } ] } ]

[]

[]

[ { "id": "19336", "type": "CID", "arg1_id": "19330", "arg2_id": "19325", "normalized": [] }, { "id": "19337", "type": "CID", "arg1_id": "19329", "arg2_id": "19325", "normalized": [] }, { "id": "19338", "type": "CID", "arg1_id": "19316", "arg2_id": "19327", "normalized": [] }, { "id": "19339", "type": "CID", "arg1_id": "19318", "arg2_id": "19327", "normalized": [] }, { "id": "19340", "type": "CID", "arg1_id": "19320", "arg2_id": "19327", "normalized": [] }, { "id": "19341", "type": "CID", "arg1_id": "19328", "arg2_id": "19327", "normalized": [] }, { "id": "19342", "type": "CID", "arg1_id": "19332", "arg2_id": "19327", "normalized": [] }, { "id": "19343", "type": "CID", "arg1_id": "19331", "arg2_id": "19325", "normalized": [] }, { "id": "19344", "type": "CID", "arg1_id": "19316", "arg2_id": "19326", "normalized": [] }, { "id": "19345", "type": "CID", "arg1_id": "19318", "arg2_id": "19326", "normalized": [] }, { "id": "19346", "type": "CID", "arg1_id": "19320", "arg2_id": "19326", "normalized": [] }, { "id": "19347", "type": "CID", "arg1_id": "19328", "arg2_id": "19326", "normalized": [] }, { "id": "19348", "type": "CID", "arg1_id": "19332", "arg2_id": "19326", "normalized": [] } ]

[ { "id": "19350", "type": "title", "text": [ "Sulfasalazine-induced lupus erythematosus." ], "offsets": [ [ 0, 42 ] ] }, { "id": "19351", "type": "abstract", "text": [ "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome." ], "offsets": [ [ 43, 752 ] ] } ]

[ { "id": "19352", "type": "Chemical", "text": [ "Sulfasalazine" ], "offsets": [ [ 0, 13 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19353", "type": "Disease", "text": [ "lupus erythematosus" ], "offsets": [ [ 22, 41 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008180" } ] }, { "id": "19354", "type": "Disease", "text": [ "Pneumonitis" ], "offsets": [ [ 43, 54 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011014" } ] }, { "id": "19355", "type": "Disease", "text": [ "pleural effusions" ], "offsets": [ [ 66, 83 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010996" } ] }, { "id": "19356", "type": "Disease", "text": [ "cardiac tamponade" ], "offsets": [ [ 115, 132 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002305" } ] }, { "id": "19357", "type": "Chemical", "text": [ "sulfasalazine" ], "offsets": [ [ 222, 235 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19358", "type": "Disease", "text": [ "ulcerative colitis" ], "offsets": [ [ 256, 274 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003093" } ] }, { "id": "19359", "type": "Chemical", "text": [ "sulfasalazine" ], "offsets": [ [ 299, 312 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19360", "type": "Chemical", "text": [ "sulfasalazine" ], "offsets": [ [ 467, 480 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19361", "type": "Disease", "text": [ "lupus" ], "offsets": [ [ 489, 494 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008180" } ] }, { "id": "19362", "type": "Disease", "text": [ "serositis" ], "offsets": [ [ 518, 527 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012700" } ] }, { "id": "19363", "type": "Chemical", "text": [ "sulfasalazine" ], "offsets": [ [ 619, 632 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19364", "type": "Disease", "text": [ "inflammatory bowel disease" ], "offsets": [ [ 656, 682 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015212" } ] }, { "id": "19365", "type": "Chemical", "text": [ "sulfasalazine" ], "offsets": [ [ 715, 728 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012460" } ] }, { "id": "19366", "type": "Disease", "text": [ "lupus syndrome" ], "offsets": [ [ 737, 751 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008180" } ] } ]

[]

[]

[ { "id": "19367", "type": "CID", "arg1_id": "19352", "arg2_id": "19355", "normalized": [] }, { "id": "19368", "type": "CID", "arg1_id": "19357", "arg2_id": "19355", "normalized": [] }, { "id": "19369", "type": "CID", "arg1_id": "19359", "arg2_id": "19355", "normalized": [] }, { "id": "19370", "type": "CID", "arg1_id": "19360", "arg2_id": "19355", "normalized": [] }, { "id": "19371", "type": "CID", "arg1_id": "19363", "arg2_id": "19355", "normalized": [] }, { "id": "19372", "type": "CID", "arg1_id": "19365", "arg2_id": "19355", "normalized": [] }, { "id": "19373", "type": "CID", "arg1_id": "19352", "arg2_id": "19354", "normalized": [] }, { "id": "19374", "type": "CID", "arg1_id": "19357", "arg2_id": "19354", "normalized": [] }, { "id": "19375", "type": "CID", "arg1_id": "19359", "arg2_id": "19354", "normalized": [] }, { "id": "19376", "type": "CID", "arg1_id": "19360", "arg2_id": "19354", "normalized": [] }, { "id": "19377", "type": "CID", "arg1_id": "19363", "arg2_id": "19354", "normalized": [] }, { "id": "19378", "type": "CID", "arg1_id": "19365", "arg2_id": "19354", "normalized": [] }, { "id": "19379", "type": "CID", "arg1_id": "19352", "arg2_id": "19353", "normalized": [] }, { "id": "19380", "type": "CID", "arg1_id": "19352", "arg2_id": "19361", "normalized": [] }, { "id": "19381", "type": "CID", "arg1_id": "19352", "arg2_id": "19366", "normalized": [] }, { "id": "19382", "type": "CID", "arg1_id": "19357", "arg2_id": "19353", "normalized": [] }, { "id": "19383", "type": "CID", "arg1_id": "19357", "arg2_id": "19361", "normalized": [] }, { "id": "19384", "type": "CID", "arg1_id": "19357", "arg2_id": "19366", "normalized": [] }, { "id": "19385", "type": "CID", "arg1_id": "19359", "arg2_id": "19353", "normalized": [] }, { "id": "19386", "type": "CID", "arg1_id": "19359", "arg2_id": "19361", "normalized": [] }, { "id": "19387", "type": "CID", "arg1_id": "19359", "arg2_id": "19366", "normalized": [] }, { "id": "19388", "type": "CID", "arg1_id": "19360", "arg2_id": "19353", "normalized": [] }, { "id": "19389", "type": "CID", "arg1_id": "19360", "arg2_id": "19361", "normalized": [] }, { "id": "19390", "type": "CID", "arg1_id": "19360", "arg2_id": "19366", "normalized": [] }, { "id": "19391", "type": "CID", "arg1_id": "19363", "arg2_id": "19353", "normalized": [] }, { "id": "19392", "type": "CID", "arg1_id": "19363", "arg2_id": "19361", "normalized": [] }, { "id": "19393", "type": "CID", "arg1_id": "19363", "arg2_id": "19366", "normalized": [] }, { "id": "19394", "type": "CID", "arg1_id": "19365", "arg2_id": "19353", "normalized": [] }, { "id": "19395", "type": "CID", "arg1_id": "19365", "arg2_id": "19361", "normalized": [] }, { "id": "19396", "type": "CID", "arg1_id": "19365", "arg2_id": "19366", "normalized": [] }, { "id": "19397", "type": "CID", "arg1_id": "19352", "arg2_id": "19356", "normalized": [] }, { "id": "19398", "type": "CID", "arg1_id": "19357", "arg2_id": "19356", "normalized": [] }, { "id": "19399", "type": "CID", "arg1_id": "19359", "arg2_id": "19356", "normalized": [] }, { "id": "19400", "type": "CID", "arg1_id": "19360", "arg2_id": "19356", "normalized": [] }, { "id": "19401", "type": "CID", "arg1_id": "19363", "arg2_id": "19356", "normalized": [] }, { "id": "19402", "type": "CID", "arg1_id": "19365", "arg2_id": "19356", "normalized": [] } ]

[ { "id": "19404", "type": "title", "text": [ "Optimization of levodopa therapy." ], "offsets": [ [ 0, 33 ] ] }, { "id": "19405", "type": "abstract", "text": [ "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups." ], "offsets": [ [ 34, 1067 ] ] } ]

[ { "id": "19406", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 16, 24 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "19407", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 85, 93 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "19408", "type": "Chemical", "text": [ "carbidopa" ], "offsets": [ [ 240, 249 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002230" } ] }, { "id": "19409", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 250, 258 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "19410", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 306, 314 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19411", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 627, 635 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "19412", "type": "Disease", "text": [ "gastrointestinal disorders" ], "offsets": [ [ 685, 711 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005767" } ] }, { "id": "19413", "type": "Disease", "text": [ "orthostatic hypotension" ], "offsets": [ [ 713, 736 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007024" } ] }, { "id": "19414", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 738, 746 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "19415", "type": "Disease", "text": [ "psychosis" ], "offsets": [ [ 755, 764 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011618" } ] }, { "id": "19416", "type": "Disease", "text": [ "sleep disturbances" ], "offsets": [ [ 766, 784 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012893" } ] }, { "id": "19417", "type": "Disease", "text": [ "parasomnias" ], "offsets": [ [ 788, 799 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020447" } ] }, { "id": "19418", "type": "Disease", "text": [ "Parkinson's disease" ], "offsets": [ [ 917, 936 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] } ]

[]

[]

[ { "id": "19419", "type": "CID", "arg1_id": "19406", "arg2_id": "19417", "normalized": [] }, { "id": "19420", "type": "CID", "arg1_id": "19407", "arg2_id": "19417", "normalized": [] }, { "id": "19421", "type": "CID", "arg1_id": "19409", "arg2_id": "19417", "normalized": [] }, { "id": "19422", "type": "CID", "arg1_id": "19414", "arg2_id": "19417", "normalized": [] }, { "id": "19423", "type": "CID", "arg1_id": "19406", "arg2_id": "19412", "normalized": [] }, { "id": "19424", "type": "CID", "arg1_id": "19407", "arg2_id": "19412", "normalized": [] }, { "id": "19425", "type": "CID", "arg1_id": "19409", "arg2_id": "19412", "normalized": [] }, { "id": "19426", "type": "CID", "arg1_id": "19414", "arg2_id": "19412", "normalized": [] }, { "id": "19427", "type": "CID", "arg1_id": "19406", "arg2_id": "19413", "normalized": [] }, { "id": "19428", "type": "CID", "arg1_id": "19407", "arg2_id": "19413", "normalized": [] }, { "id": "19429", "type": "CID", "arg1_id": "19409", "arg2_id": "19413", "normalized": [] }, { "id": "19430", "type": "CID", "arg1_id": "19414", "arg2_id": "19413", "normalized": [] } ]

[ { "id": "19432", "type": "title", "text": [ "Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia." ], "offsets": [ [ 0, 75 ] ] }, { "id": "19433", "type": "abstract", "text": [ "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated." ], "offsets": [ [ 76, 1261 ] ] } ]

[ { "id": "19434", "type": "Disease", "text": [ "coma" ], "offsets": [ [ 15, 19 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003128" } ] }, { "id": "19435", "type": "Disease", "text": [ "cerebral hypoxia" ], "offsets": [ [ 58, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002534" } ] }, { "id": "19436", "type": "Disease", "text": [ "comatose" ], "offsets": [ [ 108, 116 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003128" } ] }, { "id": "19437", "type": "Disease", "text": [ "stuporous" ], "offsets": [ [ 120, 129 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D053608" } ] }, { "id": "19438", "type": "Chemical", "text": [ "chlormethiazole" ], "offsets": [ [ 231, 246 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002719" } ] }, { "id": "19439", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 251, 258 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "19440", "type": "Disease", "text": [ "withdrawal symptoms" ], "offsets": [ [ 259, 278 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013375" } ] }, { "id": "19441", "type": "Disease", "text": [ "overdose" ], "offsets": [ [ 304, 312 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "19442", "type": "Chemical", "text": [ "nitrazepam" ], "offsets": [ [ 316, 326 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009567" } ] }, { "id": "19443", "type": "Chemical", "text": [ "nitrazepam" ], "offsets": [ [ 345, 355 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009567" } ] }, { "id": "19444", "type": "Disease", "text": [ "overdose" ], "offsets": [ [ 356, 364 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "19445", "type": "Chemical", "text": [ "chlormethiazole" ], "offsets": [ [ 387, 402 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002719" } ] }, { "id": "19446", "type": "Disease", "text": [ "coma" ], "offsets": [ [ 452, 456 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003128" } ] }, { "id": "19447", "type": "Chemical", "text": [ "chlormethiazole" ], "offsets": [ [ 589, 604 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002719" } ] }, { "id": "19448", "type": "Disease", "text": [ "neurological sequelae" ], "offsets": [ [ 725, 746 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" } ] }, { "id": "19449", "type": "Disease", "text": [ "depression" ], "offsets": [ [ 876, 886 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003866" } ] }, { "id": "19450", "type": "Disease", "text": [ "coma" ], "offsets": [ [ 1064, 1068 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003128" } ] }, { "id": "19451", "type": "Disease", "text": [ "hypoxaemia" ], "offsets": [ [ 1209, 1219 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000860" } ] } ]

[]

[]

[ { "id": "19452", "type": "CID", "arg1_id": "19438", "arg2_id": "19434", "normalized": [] }, { "id": "19453", "type": "CID", "arg1_id": "19438", "arg2_id": "19436", "normalized": [] }, { "id": "19454", "type": "CID", "arg1_id": "19438", "arg2_id": "19446", "normalized": [] }, { "id": "19455", "type": "CID", "arg1_id": "19438", "arg2_id": "19450", "normalized": [] }, { "id": "19456", "type": "CID", "arg1_id": "19445", "arg2_id": "19434", "normalized": [] }, { "id": "19457", "type": "CID", "arg1_id": "19445", "arg2_id": "19436", "normalized": [] }, { "id": "19458", "type": "CID", "arg1_id": "19445", "arg2_id": "19446", "normalized": [] }, { "id": "19459", "type": "CID", "arg1_id": "19445", "arg2_id": "19450", "normalized": [] }, { "id": "19460", "type": "CID", "arg1_id": "19447", "arg2_id": "19434", "normalized": [] }, { "id": "19461", "type": "CID", "arg1_id": "19447", "arg2_id": "19436", "normalized": [] }, { "id": "19462", "type": "CID", "arg1_id": "19447", "arg2_id": "19446", "normalized": [] }, { "id": "19463", "type": "CID", "arg1_id": "19447", "arg2_id": "19450", "normalized": [] }, { "id": "19464", "type": "CID", "arg1_id": "19442", "arg2_id": "19434", "normalized": [] }, { "id": "19465", "type": "CID", "arg1_id": "19442", "arg2_id": "19436", "normalized": [] }, { "id": "19466", "type": "CID", "arg1_id": "19442", "arg2_id": "19446", "normalized": [] }, { "id": "19467", "type": "CID", "arg1_id": "19442", "arg2_id": "19450", "normalized": [] }, { "id": "19468", "type": "CID", "arg1_id": "19443", "arg2_id": "19434", "normalized": [] }, { "id": "19469", "type": "CID", "arg1_id": "19443", "arg2_id": "19436", "normalized": [] }, { "id": "19470", "type": "CID", "arg1_id": "19443", "arg2_id": "19446", "normalized": [] }, { "id": "19471", "type": "CID", "arg1_id": "19443", "arg2_id": "19450", "normalized": [] }, { "id": "19472", "type": "CID", "arg1_id": "19438", "arg2_id": "19437", "normalized": [] }, { "id": "19473", "type": "CID", "arg1_id": "19445", "arg2_id": "19437", "normalized": [] }, { "id": "19474", "type": "CID", "arg1_id": "19447", "arg2_id": "19437", "normalized": [] }, { "id": "19475", "type": "CID", "arg1_id": "19442", "arg2_id": "19441", "normalized": [] }, { "id": "19476", "type": "CID", "arg1_id": "19442", "arg2_id": "19444", "normalized": [] }, { "id": "19477", "type": "CID", "arg1_id": "19443", "arg2_id": "19441", "normalized": [] }, { "id": "19478", "type": "CID", "arg1_id": "19443", "arg2_id": "19444", "normalized": [] } ]

[ { "id": "19480", "type": "title", "text": [ "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery." ], "offsets": [ [ 0, 106 ] ] }, { "id": "19481", "type": "abstract", "text": [ "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery." ], "offsets": [ [ 107, 2017 ] ] } ]

[ { "id": "19482", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 9, 17 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19483", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 26, 32 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "19484", "type": "Disease", "text": [ "vomiting" ], "offsets": [ [ 37, 45 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014839" } ] }, { "id": "19485", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 66, 70 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "19486", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 78, 89 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "19487", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 201, 212 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "19488", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 214, 247 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19489", "type": "Chemical", "text": [ "Fentanyl" ], "offsets": [ [ 267, 275 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19490", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 447, 480 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19491", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 485, 489 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "19492", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 514, 525 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "19493", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 643, 651 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19494", "type": "Chemical", "text": [ "dexamethasone" ], "offsets": [ [ 682, 695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "19495", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 711, 719 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19496", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 742, 750 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19497", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 791, 824 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19498", "type": "Disease", "text": [ "vomiting" ], "offsets": [ [ 858, 866 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014839" } ] }, { "id": "19499", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 893, 899 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "19500", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 941, 949 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19501", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 954, 962 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19502", "type": "Chemical", "text": [ "dexamethasone" ], "offsets": [ [ 963, 976 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "19503", "type": "Chemical", "text": [ "Dexamethasone" ], "offsets": [ [ 1085, 1098 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003907" } ] }, { "id": "19504", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 1157, 1190 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19505", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 1210, 1218 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19506", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 1304, 1337 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19507", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 1342, 1348 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "19508", "type": "Disease", "text": [ "nausea" ], "offsets": [ [ 1447, 1453 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009325" } ] }, { "id": "19509", "type": "Disease", "text": [ "Pain" ], "offsets": [ [ 1515, 1519 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "19510", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 1591, 1599 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19511", "type": "Chemical", "text": [ "Fentanyl" ], "offsets": [ [ 1601, 1609 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19512", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 1662, 1673 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] }, { "id": "19513", "type": "Disease", "text": [ "respiratory depression" ], "offsets": [ [ 1703, 1725 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012131" } ] }, { "id": "19514", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 1727, 1738 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "19515", "type": "Disease", "text": [ "bradycardia" ], "offsets": [ [ 1743, 1754 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001919" } ] }, { "id": "19516", "type": "Chemical", "text": [ "fentanyl" ], "offsets": [ [ 1771, 1779 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005283" } ] }, { "id": "19517", "type": "Disease", "text": [ "postoperative nausea and vomiting" ], "offsets": [ [ 1792, 1825 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020250" } ] }, { "id": "19518", "type": "Disease", "text": [ "postoperative pain" ], "offsets": [ [ 1852, 1870 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010149" } ] }, { "id": "19519", "type": "Chemical", "text": [ "sevoflurane" ], "offsets": [ [ 1990, 2001 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C009250" } ] } ]

[]

[]

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"arg1_id": "19489", "arg2_id": "19506", "normalized": [] }, { "id": "19553", "type": "CID", "arg1_id": "19489", "arg2_id": "19517", "normalized": [] }, { "id": "19554", "type": "CID", "arg1_id": "19493", "arg2_id": "19488", "normalized": [] }, { "id": "19555", "type": "CID", "arg1_id": "19493", "arg2_id": "19490", "normalized": [] }, { "id": "19556", "type": "CID", "arg1_id": "19493", "arg2_id": "19497", "normalized": [] }, { "id": "19557", "type": "CID", "arg1_id": "19493", "arg2_id": "19504", "normalized": [] }, { "id": "19558", "type": "CID", "arg1_id": "19493", "arg2_id": "19506", "normalized": [] }, { "id": "19559", "type": "CID", "arg1_id": "19493", "arg2_id": "19517", "normalized": [] }, { "id": "19560", "type": "CID", "arg1_id": "19495", "arg2_id": "19488", "normalized": [] }, { "id": "19561", "type": "CID", "arg1_id": "19495", "arg2_id": "19490", "normalized": [] }, { "id": "19562", "type": "CID", "arg1_id": "19495", "arg2_id": "19497", "normalized": [] }, { "id": "19563", 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"normalized": [] }, { "id": "19585", "type": "CID", "arg1_id": "19505", "arg2_id": "19490", "normalized": [] }, { "id": "19586", "type": "CID", "arg1_id": "19505", "arg2_id": "19497", "normalized": [] }, { "id": "19587", "type": "CID", "arg1_id": "19505", "arg2_id": "19504", "normalized": [] }, { "id": "19588", "type": "CID", "arg1_id": "19505", "arg2_id": "19506", "normalized": [] }, { "id": "19589", "type": "CID", "arg1_id": "19505", "arg2_id": "19517", "normalized": [] }, { "id": "19590", "type": "CID", "arg1_id": "19510", "arg2_id": "19488", "normalized": [] }, { "id": "19591", "type": "CID", "arg1_id": "19510", "arg2_id": "19490", "normalized": [] }, { "id": "19592", "type": "CID", "arg1_id": "19510", "arg2_id": "19497", "normalized": [] }, { "id": "19593", "type": "CID", "arg1_id": "19510", "arg2_id": "19504", "normalized": [] }, { "id": "19594", "type": "CID", "arg1_id": "19510", "arg2_id": "19506", "normalized": [] }, { "id": "19595", "type": "CID", "arg1_id": "19510", "arg2_id": "19517", "normalized": [] }, { "id": "19596", "type": "CID", "arg1_id": "19511", "arg2_id": "19488", "normalized": [] }, { "id": "19597", "type": "CID", "arg1_id": "19511", "arg2_id": "19490", "normalized": [] }, { "id": "19598", "type": "CID", "arg1_id": "19511", "arg2_id": "19497", "normalized": [] }, { "id": "19599", "type": "CID", "arg1_id": "19511", "arg2_id": "19504", "normalized": [] }, { "id": "19600", "type": "CID", "arg1_id": "19511", "arg2_id": "19506", "normalized": [] }, { "id": "19601", "type": "CID", "arg1_id": "19511", "arg2_id": "19517", "normalized": [] }, { "id": "19602", "type": "CID", "arg1_id": "19516", "arg2_id": "19488", "normalized": [] }, { "id": "19603", "type": "CID", "arg1_id": "19516", "arg2_id": "19490", "normalized": [] }, { "id": "19604", "type": "CID", "arg1_id": "19516", "arg2_id": "19497", "normalized": [] }, { "id": "19605", "type": "CID", "arg1_id": "19516", "arg2_id": "19504", "normalized": [] }, { "id": "19606", "type": "CID", "arg1_id": "19516", "arg2_id": "19506", "normalized": [] }, { "id": "19607", "type": "CID", "arg1_id": "19516", "arg2_id": "19517", "normalized": [] }, { "id": "19608", "type": "CID", "arg1_id": "19482", "arg2_id": "19515", "normalized": [] }, { "id": "19609", "type": "CID", "arg1_id": "19489", "arg2_id": "19515", "normalized": [] }, { "id": "19610", "type": "CID", "arg1_id": "19493", "arg2_id": "19515", "normalized": [] }, { "id": "19611", "type": "CID", "arg1_id": "19495", "arg2_id": "19515", "normalized": [] }, { "id": "19612", "type": "CID", "arg1_id": "19496", "arg2_id": "19515", "normalized": [] }, { "id": "19613", "type": "CID", "arg1_id": "19500", "arg2_id": "19515", "normalized": [] }, { "id": "19614", "type": "CID", "arg1_id": "19501", "arg2_id": "19515", "normalized": [] }, { "id": "19615", "type": "CID", "arg1_id": "19505", "arg2_id": "19515", "normalized": [] }, { "id": "19616", "type": "CID", "arg1_id": "19510", "arg2_id": "19515", "normalized": [] }, { "id": "19617", "type": "CID", "arg1_id": "19511", "arg2_id": "19515", "normalized": [] }, { "id": "19618", "type": "CID", "arg1_id": "19516", "arg2_id": "19515", "normalized": [] } ]

[ { "id": "19620", "type": "title", "text": [ "Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?" ], "offsets": [ [ 0, 102 ] ] }, { "id": "19621", "type": "abstract", "text": [ "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine." ], "offsets": [ [ 103, 1292 ] ] } ]

[ { "id": "19622", "type": "Disease", "text": [ "Renal Fanconi syndrome" ], "offsets": [ [ 0, 22 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005198" } ] }, { "id": "19623", "type": "Disease", "text": [ "myopathy" ], "offsets": [ [ 27, 35 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19624", "type": "Disease", "text": [ "mitochondrial cytopathy" ], "offsets": [ [ 78, 101 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C540770" } ] }, { "id": "19625", "type": "Disease", "text": [ "Wilson's disease" ], "offsets": [ [ 444, 460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006527" } ] }, { "id": "19626", "type": "Chemical", "text": [ "Tacrolimus" ], "offsets": [ [ 462, 472 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "19627", "type": "Chemical", "text": [ "MMF" ], "offsets": [ [ 474, 477 ] ], "normalized": [] }, { "id": "19628", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 483, 491 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013256" } ] }, { "id": "19629", "type": "Chemical", "text": [ "Lamivudine" ], "offsets": [ [ 525, 535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] }, { "id": "19630", "type": "Disease", "text": [ "hepatitis B infection" ], "offsets": [ [ 565, 586 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006509" } ] }, { "id": "19631", "type": "Disease", "text": [ "renal Fanconi syndrome" ], "offsets": [ [ 654, 676 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005198" } ] }, { "id": "19632", "type": "Disease", "text": [ "metabolic acidosis" ], "offsets": [ [ 689, 707 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000138" } ] }, { "id": "19633", "type": "Disease", "text": [ "hypophosphatemia" ], "offsets": [ [ 709, 725 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017674" } ] }, { "id": "19634", "type": "Disease", "text": [ "glycosuria" ], "offsets": [ [ 727, 737 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006029" } ] }, { "id": "19635", "type": "Disease", "text": [ "aminoaciduria" ], "offsets": [ [ 743, 756 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000608" } ] }, { "id": "19636", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 767, 777 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "19637", "type": "Disease", "text": [ "acidosis" ], "offsets": [ [ 838, 846 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000138" } ] }, { "id": "19638", "type": "Chemical", "text": [ "sirolimus" ], "offsets": [ [ 867, 876 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "19639", "type": "Disease", "text": [ "acidosis" ], "offsets": [ [ 878, 886 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000138" } ] }, { "id": "19640", "type": "Disease", "text": [ "muscle weakness" ], "offsets": [ [ 934, 949 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018908" } ] }, { "id": "19641", "type": "Disease", "text": [ "Fanconi syndrome" ], "offsets": [ [ 986, 1002 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005198" } ] }, { "id": "19642", "type": "Disease", "text": [ "myopathy" ], "offsets": [ [ 1015, 1023 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19643", "type": "Disease", "text": [ "mitochondrial disorders" ], "offsets": [ [ 1061, 1084 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "19644", "type": "Disease", "text": [ "tubular dysfunction" ], "offsets": [ [ 1149, 1168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005198" } ] }, { "id": "19645", "type": "Disease", "text": [ "myopathy" ], "offsets": [ [ 1173, 1181 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19646", "type": "Disease", "text": [ "mitochondrial dysfunction" ], "offsets": [ [ 1205, 1230 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D028361" } ] }, { "id": "19647", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 1253, 1263 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "19648", "type": "Chemical", "text": [ "lamivudine" ], "offsets": [ [ 1281, 1291 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019259" } ] } ]

[]

[]

[ { "id": "19649", "type": "CID", "arg1_id": "19626", "arg2_id": "19622", "normalized": [] }, { "id": "19650", "type": "CID", "arg1_id": "19626", "arg2_id": "19631", "normalized": [] }, { "id": "19651", "type": "CID", "arg1_id": "19626", "arg2_id": "19641", "normalized": [] }, { "id": "19652", "type": "CID", "arg1_id": "19626", "arg2_id": "19644", "normalized": [] }, { "id": "19653", "type": "CID", "arg1_id": "19636", "arg2_id": "19622", "normalized": [] }, { "id": "19654", "type": "CID", "arg1_id": "19636", "arg2_id": "19631", "normalized": [] }, { "id": "19655", "type": "CID", "arg1_id": "19636", "arg2_id": "19641", "normalized": [] }, { "id": "19656", "type": "CID", "arg1_id": "19636", "arg2_id": "19644", "normalized": [] }, { "id": "19657", "type": "CID", "arg1_id": "19647", "arg2_id": "19622", "normalized": [] }, { "id": "19658", "type": "CID", "arg1_id": "19647", "arg2_id": "19631", "normalized": [] }, { "id": "19659", "type": "CID", "arg1_id": "19647", "arg2_id": "19641", "normalized": [] }, { "id": "19660", "type": "CID", "arg1_id": "19647", "arg2_id": "19644", "normalized": [] }, { "id": "19661", "type": "CID", "arg1_id": "19626", "arg2_id": "19623", "normalized": [] }, { "id": "19662", "type": "CID", "arg1_id": "19626", "arg2_id": "19642", "normalized": [] }, { "id": "19663", "type": "CID", "arg1_id": "19626", "arg2_id": "19645", "normalized": [] }, { "id": "19664", "type": "CID", "arg1_id": "19636", "arg2_id": "19623", "normalized": [] }, { "id": "19665", "type": "CID", "arg1_id": "19636", "arg2_id": "19642", "normalized": [] }, { "id": "19666", "type": "CID", "arg1_id": "19636", "arg2_id": "19645", "normalized": [] }, { "id": "19667", "type": "CID", "arg1_id": "19647", "arg2_id": "19623", "normalized": [] }, { "id": "19668", "type": "CID", "arg1_id": "19647", "arg2_id": "19642", "normalized": [] }, { "id": "19669", "type": "CID", "arg1_id": "19647", "arg2_id": "19645", "normalized": [] }, { "id": "19670", "type": "CID", "arg1_id": "19629", "arg2_id": "19623", "normalized": [] }, { "id": "19671", "type": "CID", "arg1_id": "19629", "arg2_id": "19642", "normalized": [] }, { "id": "19672", "type": "CID", "arg1_id": "19629", "arg2_id": "19645", "normalized": [] }, { "id": "19673", "type": "CID", "arg1_id": "19648", "arg2_id": "19623", "normalized": [] }, { "id": "19674", "type": "CID", "arg1_id": "19648", "arg2_id": "19642", "normalized": [] }, { "id": "19675", "type": "CID", "arg1_id": "19648", "arg2_id": "19645", "normalized": [] }, { "id": "19676", "type": "CID", "arg1_id": "19629", "arg2_id": "19622", "normalized": [] }, { "id": "19677", "type": "CID", "arg1_id": "19629", "arg2_id": "19631", "normalized": [] }, { "id": "19678", "type": "CID", "arg1_id": "19629", "arg2_id": "19641", "normalized": [] }, { "id": "19679", "type": "CID", "arg1_id": "19629", "arg2_id": "19644", "normalized": [] }, { "id": "19680", "type": "CID", "arg1_id": "19648", "arg2_id": "19622", "normalized": [] }, { "id": "19681", "type": "CID", "arg1_id": "19648", "arg2_id": "19631", "normalized": [] }, { "id": "19682", "type": "CID", "arg1_id": "19648", "arg2_id": "19641", "normalized": [] }, { "id": "19683", "type": "CID", "arg1_id": "19648", "arg2_id": "19644", "normalized": [] } ]

[ { "id": "19685", "type": "title", "text": [ "Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice." ], "offsets": [ [ 0, 87 ] ] }, { "id": "19686", "type": "abstract", "text": [ "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia." ], "offsets": [ [ 88, 1929 ] ] } ]

[ { "id": "19687", "type": "Chemical", "text": [ "thioperamide" ], "offsets": [ [ 30, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19688", "type": "Disease", "text": [ "schizophrenia" ], "offsets": [ [ 195, 208 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012559" } ] }, { "id": "19689", "type": "Chemical", "text": [ "histamine" ], "offsets": [ [ 264, 273 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006632" } ] }, { "id": "19690", "type": "Disease", "text": [ "catalepsy" ], "offsets": [ [ 319, 328 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19691", "type": "Chemical", "text": [ "apomorphine" ], "offsets": [ [ 330, 341 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001058" } ] }, { "id": "19692", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 372, 383 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "19693", "type": "Disease", "text": [ "Catalepsy" ], "offsets": [ [ 422, 431 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19694", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 447, 458 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "19695", "type": "Chemical", "text": [ "apomorphine" ], "offsets": [ [ 481, 492 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001058" } ] }, { "id": "19696", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 514, 525 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "19697", "type": "Chemical", "text": [ "(R)-alpha-methylhistamine" ], "offsets": [ [ 622, 647 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19698", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 649, 653 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19699", "type": "Chemical", "text": [ "thioperamide" ], "offsets": [ [ 677, 689 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19700", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 691, 694 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19701", "type": "Disease", "text": [ "catalepsy" ], "offsets": [ [ 734, 743 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19702", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 763, 766 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19703", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 810, 821 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "19704", "type": "Disease", "text": [ "catalepsy" ], "offsets": [ [ 867, 876 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19705", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 922, 926 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19706", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 968, 971 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19707", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 989, 993 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19708", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1089, 1092 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19709", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1154, 1165 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "19710", "type": "Disease", "text": [ "hyperactivity" ], "offsets": [ [ 1174, 1187 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "19711", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1189, 1192 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19712", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 1309, 1313 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19713", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1372, 1375 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19714", "type": "Chemical", "text": [ "apomorphine" ], "offsets": [ [ 1424, 1435 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001058" } ] }, { "id": "19715", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1472, 1475 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19716", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 1530, 1534 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19717", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1536, 1539 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19718", "type": "Chemical", "text": [ "haloperidol" ], "offsets": [ [ 1596, 1607 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006220" } ] }, { "id": "19719", "type": "Disease", "text": [ "catalepsy" ], "offsets": [ [ 1616, 1625 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002375" } ] }, { "id": "19720", "type": "Chemical", "text": [ "amphetamine" ], "offsets": [ [ 1636, 1647 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000661" } ] }, { "id": "19721", "type": "Disease", "text": [ "hyperactivity" ], "offsets": [ [ 1656, 1669 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006948" } ] }, { "id": "19722", "type": "Chemical", "text": [ "apomorphine" ], "offsets": [ [ 1683, 1694 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001058" } ] }, { "id": "19723", "type": "Chemical", "text": [ "THP" ], "offsets": [ [ 1737, 1740 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C052075" } ] }, { "id": "19724", "type": "Chemical", "text": [ "RAMH" ], "offsets": [ [ 1758, 1762 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C069357" } ] }, { "id": "19725", "type": "Chemical", "text": [ "histamine" ], "offsets": [ [ 1793, 1802 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006632" } ] }, { "id": "19726", "type": "Disease", "text": [ "schizophrenia" ], "offsets": [ [ 1915, 1928 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012559" } ] } ]

[]

[]

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"normalized": [] }, { "id": "19738", "type": "CID", "arg1_id": "19694", "arg2_id": "19704", "normalized": [] }, { "id": "19739", "type": "CID", "arg1_id": "19694", "arg2_id": "19719", "normalized": [] }, { "id": "19740", "type": "CID", "arg1_id": "19703", "arg2_id": "19690", "normalized": [] }, { "id": "19741", "type": "CID", "arg1_id": "19703", "arg2_id": "19693", "normalized": [] }, { "id": "19742", "type": "CID", "arg1_id": "19703", "arg2_id": "19701", "normalized": [] }, { "id": "19743", "type": "CID", "arg1_id": "19703", "arg2_id": "19704", "normalized": [] }, { "id": "19744", "type": "CID", "arg1_id": "19703", "arg2_id": "19719", "normalized": [] }, { "id": "19745", "type": "CID", "arg1_id": "19718", "arg2_id": "19690", "normalized": [] }, { "id": "19746", "type": "CID", "arg1_id": "19718", "arg2_id": "19693", "normalized": [] }, { "id": "19747", "type": "CID", "arg1_id": "19718", "arg2_id": "19701", "normalized": [] }, { "id": "19748", "type": "CID", "arg1_id": "19718", "arg2_id": "19704", "normalized": [] }, { "id": "19749", "type": "CID", "arg1_id": "19718", "arg2_id": "19719", "normalized": [] }, { "id": "19750", "type": "CID", "arg1_id": "19687", "arg2_id": "19690", "normalized": [] }, { "id": "19751", "type": "CID", "arg1_id": "19687", "arg2_id": "19693", "normalized": [] }, { "id": "19752", "type": "CID", "arg1_id": "19687", "arg2_id": "19701", "normalized": [] }, { "id": "19753", "type": "CID", "arg1_id": "19687", "arg2_id": "19704", "normalized": [] }, { "id": "19754", "type": "CID", "arg1_id": "19687", "arg2_id": "19719", "normalized": [] }, { "id": "19755", "type": "CID", "arg1_id": "19699", "arg2_id": "19690", "normalized": [] }, { "id": "19756", "type": "CID", "arg1_id": "19699", "arg2_id": "19693", "normalized": [] }, { "id": "19757", "type": "CID", "arg1_id": "19699", "arg2_id": "19701", "normalized": [] }, { "id": "19758", "type": "CID", "arg1_id": "19699", "arg2_id": "19704", "normalized": [] }, { "id": "19759", "type": "CID", "arg1_id": "19699", "arg2_id": "19719", "normalized": [] }, { "id": "19760", "type": "CID", "arg1_id": "19700", "arg2_id": "19690", "normalized": [] }, { "id": "19761", "type": "CID", "arg1_id": "19700", "arg2_id": "19693", "normalized": [] }, { "id": "19762", "type": "CID", "arg1_id": "19700", "arg2_id": "19701", "normalized": [] }, { "id": "19763", "type": "CID", "arg1_id": "19700", "arg2_id": "19704", "normalized": [] }, { "id": "19764", "type": "CID", "arg1_id": "19700", "arg2_id": "19719", "normalized": [] }, { "id": "19765", "type": "CID", "arg1_id": "19702", "arg2_id": "19690", "normalized": [] }, { "id": "19766", "type": "CID", "arg1_id": "19702", "arg2_id": "19693", "normalized": [] }, { "id": "19767", "type": "CID", "arg1_id": "19702", "arg2_id": "19701", "normalized": [] }, { "id": "19768", "type": "CID", "arg1_id": "19702", "arg2_id": "19704", "normalized": [] }, { "id": "19769", "type": "CID", "arg1_id": "19702", "arg2_id": "19719", "normalized": [] }, { "id": "19770", "type": "CID", "arg1_id": "19706", "arg2_id": "19690", "normalized": [] }, { "id": "19771", "type": "CID", "arg1_id": "19706", "arg2_id": "19693", "normalized": [] }, { "id": "19772", "type": "CID", "arg1_id": "19706", "arg2_id": "19701", "normalized": [] }, { "id": "19773", "type": "CID", "arg1_id": "19706", "arg2_id": "19704", "normalized": [] }, { "id": "19774", "type": "CID", "arg1_id": "19706", "arg2_id": "19719", "normalized": [] }, { "id": "19775", "type": "CID", "arg1_id": "19708", "arg2_id": "19690", "normalized": [] }, { "id": "19776", "type": "CID", "arg1_id": "19708", "arg2_id": "19693", "normalized": [] }, { "id": "19777", "type": "CID", "arg1_id": "19708", "arg2_id": "19701", "normalized": [] }, { "id": "19778", "type": "CID", "arg1_id": "19708", "arg2_id": "19704", "normalized": [] }, { "id": "19779", "type": "CID", "arg1_id": "19708", "arg2_id": "19719", "normalized": [] }, { "id": "19780", "type": "CID", "arg1_id": "19711", "arg2_id": "19690", "normalized": [] }, { "id": "19781", "type": "CID", "arg1_id": "19711", "arg2_id": "19693", "normalized": [] }, { "id": "19782", "type": "CID", "arg1_id": "19711", "arg2_id": "19701", "normalized": [] }, { "id": "19783", "type": "CID", "arg1_id": "19711", "arg2_id": "19704", "normalized": [] }, { "id": "19784", "type": "CID", "arg1_id": "19711", "arg2_id": "19719", "normalized": [] }, { "id": "19785", "type": "CID", "arg1_id": "19713", "arg2_id": "19690", "normalized": [] }, { "id": "19786", "type": "CID", "arg1_id": "19713", "arg2_id": "19693", "normalized": [] }, { "id": "19787", "type": "CID", "arg1_id": "19713", "arg2_id": "19701", "normalized": [] }, { "id": "19788", "type": "CID", "arg1_id": "19713", "arg2_id": "19704", "normalized": [] }, { "id": "19789", "type": "CID", "arg1_id": "19713", "arg2_id": "19719", "normalized": [] }, { "id": "19790", "type": "CID", "arg1_id": "19715", "arg2_id": "19690", "normalized": [] }, { "id": "19791", "type": "CID", "arg1_id": "19715", "arg2_id": "19693", "normalized": [] }, { "id": "19792", "type": "CID", "arg1_id": "19715", "arg2_id": "19701", "normalized": [] }, { "id": "19793", "type": "CID", "arg1_id": "19715", "arg2_id": "19704", "normalized": [] }, { "id": "19794", "type": "CID", "arg1_id": "19715", "arg2_id": "19719", "normalized": [] }, { "id": "19795", "type": "CID", "arg1_id": "19717", "arg2_id": "19690", "normalized": [] }, { "id": "19796", "type": "CID", "arg1_id": "19717", "arg2_id": "19693", "normalized": [] }, { "id": "19797", "type": "CID", "arg1_id": "19717", "arg2_id": "19701", "normalized": [] }, { "id": "19798", "type": "CID", "arg1_id": "19717", "arg2_id": "19704", "normalized": [] }, { "id": "19799", "type": "CID", "arg1_id": "19717", "arg2_id": "19719", "normalized": [] }, { "id": "19800", "type": "CID", "arg1_id": "19723", "arg2_id": "19690", "normalized": [] }, { "id": "19801", "type": "CID", "arg1_id": "19723", "arg2_id": "19693", "normalized": [] }, { "id": "19802", "type": "CID", "arg1_id": "19723", "arg2_id": "19701", "normalized": [] }, { "id": "19803", "type": "CID", "arg1_id": "19723", "arg2_id": "19704", "normalized": [] }, { "id": "19804", "type": "CID", "arg1_id": "19723", "arg2_id": "19719", "normalized": [] } ]

[ { "id": "19806", "type": "title", "text": [ "Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly." ], "offsets": [ [ 0, 118 ] ] }, { "id": "19807", "type": "abstract", "text": [ "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography." ], "offsets": [ [ 119, 985 ] ] } ]

[ { "id": "19808", "type": "Disease", "text": [ "platypnea-orthodeoxia-like syndrome" ], "offsets": [ [ 10, 45 ] ], "normalized": [] }, { "id": "19809", "type": "Chemical", "text": [ "propafenone" ], "offsets": [ [ 57, 68 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011405" } ] }, { "id": "19810", "type": "Disease", "text": [ "overdose" ], "offsets": [ [ 69, 77 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "19811", "type": "Disease", "text": [ "Ebstein's anomaly" ], "offsets": [ [ 100, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004437" } ] }, { "id": "19812", "type": "Disease", "text": [ "Ebstein's anomaly" ], "offsets": [ [ 189, 206 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004437" } ] }, { "id": "19813", "type": "Disease", "text": [ "platypnea-orthodeoxia" ], "offsets": [ [ 245, 266 ] ], "normalized": [] }, { "id": "19814", "type": "Disease", "text": [ "hypoxia" ], "offsets": [ [ 352, 359 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000860" } ] }, { "id": "19815", "type": "Disease", "text": [ "cyanosis" ], "offsets": [ [ 364, 372 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003490" } ] }, { "id": "19816", "type": "Disease", "text": [ "patent foramen ovale" ], "offsets": [ [ 400, 420 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D054092" } ] }, { "id": "19817", "type": "Chemical", "text": [ "propafenone" ], "offsets": [ [ 520, 531 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011405" } ] }, { "id": "19818", "type": "Disease", "text": [ "overdose" ], "offsets": [ [ 532, 540 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D062787" } ] }, { "id": "19819", "type": "Disease", "text": [ "biventricular dysfunction" ], "offsets": [ [ 559, 584 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018754" } ] }, { "id": "19820", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 628, 639 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] } ]

[]

[]

[ { "id": "19821", "type": "CID", "arg1_id": "19809", "arg2_id": "19819", "normalized": [] }, { "id": "19822", "type": "CID", "arg1_id": "19817", "arg2_id": "19819", "normalized": [] }, { "id": "19823", "type": "CID", "arg1_id": "19809", "arg2_id": "19814", "normalized": [] }, { "id": "19824", "type": "CID", "arg1_id": "19817", "arg2_id": "19814", "normalized": [] }, { "id": "19825", "type": "CID", "arg1_id": "19809", "arg2_id": "19815", "normalized": [] }, { "id": "19826", "type": "CID", "arg1_id": "19817", "arg2_id": "19815", "normalized": [] } ]

[ { "id": "19828", "type": "title", "text": [ "A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188)." ], "offsets": [ [ 0, 141 ] ] }, { "id": "19829", "type": "abstract", "text": [ "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial." ], "offsets": [ [ 142, 2351 ] ] } ]

[ { "id": "19830", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 20, 29 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19831", "type": "Chemical", "text": [ "WR-2721" ], "offsets": [ [ 35, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19832", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 44, 54 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19833", "type": "Disease", "text": [ "breast carcinoma" ], "offsets": [ [ 71, 87 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001943" } ] }, { "id": "19834", "type": "Chemical", "text": [ "Cisplatin" ], "offsets": [ [ 154, 163 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19835", "type": "Disease", "text": [ "breast carcinoma" ], "offsets": [ [ 254, 270 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001943" } ] }, { "id": "19836", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 348, 357 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19837", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 446, 455 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19838", "type": "Disease", "text": [ "toxicities" ], "offsets": [ [ 475, 485 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19839", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 502, 511 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19840", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 519, 533 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "19841", "type": "Disease", "text": [ "ototoxicity" ], "offsets": [ [ 535, 546 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "19842", "type": "Disease", "text": [ "neurotoxicity" ], "offsets": [ [ 552, 565 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "19843", "type": "Disease", "text": [ "breast carcinoma" ], "offsets": [ [ 607, 623 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001943" } ] }, { "id": "19844", "type": "Chemical", "text": [ "WR-2721" ], "offsets": [ [ 625, 632 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19845", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 636, 646 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19846", "type": "Chemical", "text": [ "Amifostine" ], "offsets": [ [ 730, 740 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19847", "type": "Chemical", "text": [ "alkylating agents" ], "offsets": [ [ 816, 833 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000477" } ] }, { "id": "19848", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 838, 847 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19849", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 925, 934 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19850", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 939, 949 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19851", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1000, 1009 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19852", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 1018, 1032 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "19853", "type": "Disease", "text": [ "ototoxicity" ], "offsets": [ [ 1034, 1045 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006311" } ] }, { "id": "19854", "type": "Disease", "text": [ "neuropathy" ], "offsets": [ [ 1051, 1061 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" } ] }, { "id": "19855", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1124, 1133 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19856", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 1139, 1149 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19857", "type": "Disease", "text": [ "breast carcinoma" ], "offsets": [ [ 1204, 1220 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001943" } ] }, { "id": "19858", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 1329, 1339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19859", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 1406, 1416 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19860", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1427, 1436 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19861", "type": "Chemical", "text": [ "mannitol" ], "offsets": [ [ 1507, 1515 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008353" } ] }, { "id": "19862", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 1550, 1559 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19863", "type": "Disease", "text": [ "Neurologic toxicity" ], "offsets": [ [ 1940, 1959 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020258" } ] }, { "id": "19864", "type": "Disease", "text": [ "toxicities" ], "offsets": [ [ 2026, 2036 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19865", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 2122, 2131 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] }, { "id": "19866", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 2136, 2146 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19867", "type": "Disease", "text": [ "tumor" ], "offsets": [ [ 2216, 2221 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009369" } ] }, { "id": "19868", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 2252, 2260 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "19869", "type": "Chemical", "text": [ "amifostine" ], "offsets": [ [ 2313, 2323 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004999" } ] }, { "id": "19870", "type": "Chemical", "text": [ "cisplatin" ], "offsets": [ [ 2327, 2336 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002945" } ] } ]

[]

[]

[ { "id": "19871", "type": "CID", "arg1_id": "19830", "arg2_id": "19854", "normalized": [] }, { "id": "19872", "type": "CID", "arg1_id": "19834", "arg2_id": "19854", "normalized": [] }, { "id": "19873", "type": "CID", "arg1_id": "19836", "arg2_id": "19854", "normalized": [] }, { "id": "19874", "type": "CID", "arg1_id": "19837", "arg2_id": "19854", "normalized": [] }, { "id": "19875", "type": "CID", "arg1_id": "19839", "arg2_id": "19854", "normalized": [] }, { "id": "19876", "type": "CID", "arg1_id": "19848", "arg2_id": "19854", "normalized": [] }, { "id": "19877", "type": "CID", "arg1_id": "19849", "arg2_id": "19854", "normalized": [] }, { "id": "19878", "type": "CID", "arg1_id": "19851", "arg2_id": "19854", "normalized": [] }, { "id": "19879", "type": "CID", "arg1_id": "19855", "arg2_id": "19854", "normalized": [] }, { "id": "19880", "type": "CID", "arg1_id": "19860", "arg2_id": "19854", "normalized": [] }, { "id": "19881", "type": "CID", "arg1_id": "19862", "arg2_id": "19854", "normalized": [] }, { "id": "19882", "type": "CID", "arg1_id": "19865", "arg2_id": "19854", "normalized": [] }, { "id": "19883", "type": "CID", "arg1_id": "19870", "arg2_id": "19854", "normalized": [] }, { "id": "19884", "type": "CID", "arg1_id": "19830", "arg2_id": "19841", "normalized": [] }, { "id": "19885", "type": "CID", "arg1_id": "19830", "arg2_id": "19853", "normalized": [] }, { "id": "19886", "type": "CID", "arg1_id": "19834", "arg2_id": "19841", "normalized": [] }, { "id": "19887", "type": "CID", "arg1_id": "19834", "arg2_id": "19853", "normalized": [] }, { "id": "19888", "type": "CID", "arg1_id": "19836", "arg2_id": "19841", "normalized": [] }, { "id": "19889", "type": "CID", "arg1_id": "19836", "arg2_id": "19853", "normalized": [] }, { "id": "19890", "type": "CID", "arg1_id": "19837", "arg2_id": "19841", "normalized": [] }, { "id": "19891", "type": "CID", "arg1_id": "19837", "arg2_id": "19853", "normalized": [] }, { "id": "19892", "type": "CID", "arg1_id": "19839", "arg2_id": "19841", "normalized": [] }, { "id": "19893", "type": "CID", "arg1_id": "19839", "arg2_id": "19853", "normalized": [] }, { "id": "19894", "type": "CID", "arg1_id": "19848", "arg2_id": "19841", "normalized": [] }, { "id": "19895", "type": "CID", "arg1_id": "19848", "arg2_id": "19853", "normalized": [] }, { "id": "19896", "type": "CID", "arg1_id": "19849", "arg2_id": "19841", "normalized": [] }, { "id": "19897", "type": "CID", "arg1_id": "19849", "arg2_id": "19853", "normalized": [] }, { "id": "19898", "type": "CID", "arg1_id": "19851", "arg2_id": "19841", "normalized": [] }, { "id": "19899", "type": "CID", "arg1_id": "19851", "arg2_id": "19853", "normalized": [] }, { "id": "19900", "type": "CID", "arg1_id": "19855", "arg2_id": "19841", "normalized": [] }, { "id": "19901", "type": "CID", "arg1_id": "19855", "arg2_id": "19853", "normalized": [] }, { "id": "19902", "type": "CID", "arg1_id": "19860", "arg2_id": "19841", "normalized": [] }, { "id": "19903", "type": "CID", "arg1_id": "19860", "arg2_id": "19853", "normalized": [] }, { "id": "19904", "type": "CID", "arg1_id": "19862", "arg2_id": "19841", "normalized": [] }, { "id": "19905", "type": "CID", "arg1_id": "19862", "arg2_id": "19853", "normalized": [] }, { "id": "19906", "type": "CID", "arg1_id": "19865", "arg2_id": "19841", "normalized": [] }, { "id": "19907", "type": "CID", "arg1_id": "19865", "arg2_id": "19853", "normalized": [] }, { "id": "19908", "type": "CID", "arg1_id": "19870", "arg2_id": "19841", "normalized": [] }, { "id": "19909", "type": "CID", "arg1_id": "19870", "arg2_id": "19853", "normalized": [] }, { "id": "19910", "type": "CID", "arg1_id": "19830", "arg2_id": "19840", "normalized": [] }, { "id": "19911", "type": "CID", "arg1_id": "19830", "arg2_id": "19852", "normalized": [] }, { "id": "19912", "type": "CID", "arg1_id": "19834", "arg2_id": "19840", "normalized": [] }, { "id": "19913", "type": "CID", "arg1_id": "19834", "arg2_id": "19852", "normalized": [] }, { "id": "19914", "type": "CID", "arg1_id": "19836", "arg2_id": "19840", "normalized": [] }, { "id": "19915", "type": "CID", "arg1_id": "19836", "arg2_id": "19852", "normalized": [] }, { "id": "19916", "type": "CID", "arg1_id": "19837", "arg2_id": "19840", "normalized": [] }, { "id": "19917", "type": "CID", "arg1_id": "19837", "arg2_id": "19852", "normalized": [] }, { "id": "19918", "type": "CID", "arg1_id": "19839", "arg2_id": "19840", "normalized": [] }, { "id": "19919", "type": "CID", "arg1_id": "19839", "arg2_id": "19852", "normalized": [] }, { "id": "19920", "type": "CID", "arg1_id": "19848", "arg2_id": "19840", "normalized": [] }, { "id": "19921", "type": "CID", "arg1_id": "19848", "arg2_id": "19852", "normalized": [] }, { "id": "19922", "type": "CID", "arg1_id": "19849", "arg2_id": "19840", "normalized": [] }, { "id": "19923", "type": "CID", "arg1_id": "19849", "arg2_id": "19852", "normalized": [] }, { "id": "19924", "type": "CID", "arg1_id": "19851", "arg2_id": "19840", "normalized": [] }, { "id": "19925", "type": "CID", "arg1_id": "19851", "arg2_id": "19852", "normalized": [] }, { "id": "19926", "type": "CID", "arg1_id": "19855", "arg2_id": "19840", "normalized": [] }, { "id": "19927", "type": "CID", "arg1_id": "19855", "arg2_id": "19852", "normalized": [] }, { "id": "19928", "type": "CID", "arg1_id": "19860", "arg2_id": "19840", "normalized": [] }, { "id": "19929", "type": "CID", "arg1_id": "19860", "arg2_id": "19852", "normalized": [] }, { "id": "19930", "type": "CID", "arg1_id": "19862", "arg2_id": "19840", "normalized": [] }, { "id": "19931", "type": "CID", "arg1_id": "19862", "arg2_id": "19852", "normalized": [] }, { "id": "19932", "type": "CID", "arg1_id": "19865", "arg2_id": "19840", "normalized": [] }, { "id": "19933", "type": "CID", "arg1_id": "19865", "arg2_id": "19852", "normalized": [] }, { "id": "19934", "type": "CID", "arg1_id": "19870", "arg2_id": "19840", "normalized": [] }, { "id": "19935", "type": "CID", "arg1_id": "19870", "arg2_id": "19852", "normalized": [] } ]

[ { "id": "19937", "type": "title", "text": [ "Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy." ], "offsets": [ [ 0, 74 ] ] }, { "id": "19938", "type": "abstract", "text": [ "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity." ], "offsets": [ [ 75, 686 ] ] } ]

[ { "id": "19939", "type": "Chemical", "text": [ "Warfarin" ], "offsets": [ [ 0, 8 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19940", "type": "Disease", "text": [ "hemorrhage" ], "offsets": [ [ 27, 37 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006470" } ] }, { "id": "19941", "type": "Disease", "text": [ "femoral nerve palsy" ], "offsets": [ [ 54, 73 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020428" } ] }, { "id": "19942", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 127, 135 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19943", "type": "Disease", "text": [ "muscle tear" ], "offsets": [ [ 166, 177 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19944", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 203, 207 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "19945", "type": "Disease", "text": [ "contracture" ], "offsets": [ [ 222, 233 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003286" } ] }, { "id": "19946", "type": "Disease", "text": [ "hematoma" ], "offsets": [ [ 295, 303 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006406" } ] }, { "id": "19947", "type": "Disease", "text": [ "nerve entrapment" ], "offsets": [ [ 316, 332 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009408" } ] }, { "id": "19948", "type": "Disease", "text": [ "femoral nerve palsy" ], "offsets": [ [ 349, 368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020428" } ] }, { "id": "19949", "type": "Disease", "text": [ "partial loss of quadriceps functions" ], "offsets": [ [ 373, 409 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009135" } ] }, { "id": "19950", "type": "Disease", "text": [ "femoral nerve palsy" ], "offsets": [ [ 433, 452 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020428" } ] }, { "id": "19951", "type": "Chemical", "text": [ "warfarin" ], "offsets": [ [ 488, 496 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014859" } ] }, { "id": "19952", "type": "Disease", "text": [ "peripheral neuropathy" ], "offsets": [ [ 505, 526 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010523" } ] }, { "id": "19953", "type": "Disease", "text": [ "pain" ], "offsets": [ [ 558, 562 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010146" } ] }, { "id": "19954", "type": "Disease", "text": [ "motor and sensory impairment" ], "offsets": [ [ 606, 634 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D015417" } ] }, { "id": "19955", "type": "Disease", "text": [ "contracture" ], "offsets": [ [ 648, 659 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003286" } ] } ]

[]

[]

[ { "id": "19956", "type": "CID", "arg1_id": "19939", "arg2_id": "19941", "normalized": [] }, { "id": "19957", "type": "CID", "arg1_id": "19939", "arg2_id": "19948", "normalized": [] }, { "id": "19958", "type": "CID", "arg1_id": "19939", "arg2_id": "19950", "normalized": [] }, { "id": "19959", "type": "CID", "arg1_id": "19942", "arg2_id": "19941", "normalized": [] }, { "id": "19960", "type": "CID", "arg1_id": "19942", "arg2_id": "19948", "normalized": [] }, { "id": "19961", "type": "CID", "arg1_id": "19942", "arg2_id": "19950", "normalized": [] }, { "id": "19962", "type": "CID", "arg1_id": "19951", "arg2_id": "19941", "normalized": [] }, { "id": "19963", "type": "CID", "arg1_id": "19951", "arg2_id": "19948", "normalized": [] }, { "id": "19964", "type": "CID", "arg1_id": "19951", "arg2_id": "19950", "normalized": [] }, { "id": "19965", "type": "CID", "arg1_id": "19939", "arg2_id": "19947", "normalized": [] }, { "id": "19966", "type": "CID", "arg1_id": "19942", "arg2_id": "19947", "normalized": [] }, { "id": "19967", "type": "CID", "arg1_id": "19951", "arg2_id": "19947", "normalized": [] }, { "id": "19968", "type": "CID", "arg1_id": "19939", "arg2_id": "19943", "normalized": [] }, { "id": "19969", "type": "CID", "arg1_id": "19939", "arg2_id": "19949", "normalized": [] }, { "id": "19970", "type": "CID", "arg1_id": "19942", "arg2_id": "19943", "normalized": [] }, { "id": "19971", "type": "CID", "arg1_id": "19942", "arg2_id": "19949", "normalized": [] }, { "id": "19972", "type": "CID", "arg1_id": "19951", "arg2_id": "19943", "normalized": [] }, { "id": "19973", "type": "CID", "arg1_id": "19951", "arg2_id": "19949", "normalized": [] }, { "id": "19974", "type": "CID", "arg1_id": "19939", "arg2_id": "19946", "normalized": [] }, { "id": "19975", "type": "CID", "arg1_id": "19942", "arg2_id": "19946", "normalized": [] }, { "id": "19976", "type": "CID", "arg1_id": "19951", "arg2_id": "19946", "normalized": [] } ]

[ { "id": "19978", "type": "title", "text": [ "Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis." ], "offsets": [ [ 0, 91 ] ] }, { "id": "19979", "type": "abstract", "text": [ "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process." ], "offsets": [ [ 92, 373 ] ] } ]

[ { "id": "19980", "type": "Disease", "text": [ "Myasthenia gravis" ], "offsets": [ [ 0, 17 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009157" } ] }, { "id": "19981", "type": "Chemical", "text": [ "penicillamine" ], "offsets": [ [ 28, 41 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "19982", "type": "Chemical", "text": [ "chloroquine" ], "offsets": [ [ 46, 57 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002738" } ] }, { "id": "19983", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 70, 90 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "19984", "type": "Disease", "text": [ "myasthenia gravis" ], "offsets": [ [ 163, 180 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009157" } ] }, { "id": "19985", "type": "Chemical", "text": [ "penicillamine" ], "offsets": [ [ 187, 200 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010396" } ] }, { "id": "19986", "type": "Chemical", "text": [ "chloroquine" ], "offsets": [ [ 205, 216 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002738" } ] }, { "id": "19987", "type": "Disease", "text": [ "rheumatoid arthritis" ], "offsets": [ [ 229, 249 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001172" } ] }, { "id": "19988", "type": "Chemical", "text": [ "acetylcholine" ], "offsets": [ [ 260, 273 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000109" } ] } ]

[]

[]

[ { "id": "19989", "type": "CID", "arg1_id": "19982", "arg2_id": "19980", "normalized": [] }, { "id": "19990", "type": "CID", "arg1_id": "19982", "arg2_id": "19984", "normalized": [] }, { "id": "19991", "type": "CID", "arg1_id": "19986", "arg2_id": "19980", "normalized": [] }, { "id": "19992", "type": "CID", "arg1_id": "19986", "arg2_id": "19984", "normalized": [] }, { "id": "19993", "type": "CID", "arg1_id": "19981", "arg2_id": "19980", "normalized": [] }, { "id": "19994", "type": "CID", "arg1_id": "19981", "arg2_id": "19984", "normalized": [] }, { "id": "19995", "type": "CID", "arg1_id": "19985", "arg2_id": "19980", "normalized": [] }, { "id": "19996", "type": "CID", "arg1_id": "19985", "arg2_id": "19984", "normalized": [] } ]

[ { "id": "19998", "type": "title", "text": [ "Nephrotoxicity of combined cephalothin-gentamicin regimen." ], "offsets": [ [ 0, 58 ] ] }, { "id": "19999", "type": "abstract", "text": [ "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen." ], "offsets": [ [ 59, 527 ] ] } ]

[ { "id": "20000", "type": "Disease", "text": [ "Nephrotoxicity" ], "offsets": [ [ 0, 14 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "20001", "type": "Chemical", "text": [ "cephalothin" ], "offsets": [ [ 27, 38 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002512" } ] }, { "id": "20002", "type": "Chemical", "text": [ "gentamicin" ], "offsets": [ [ 39, 49 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "20003", "type": "Disease", "text": [ "acute tubular necrosis" ], "offsets": [ [ 82, 104 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007683" } ] }, { "id": "20004", "type": "Disease", "text": [ "oliguric renal failure" ], "offsets": [ [ 140, 162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009846" }, { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "20005", "type": "Disease", "text": [ "oliguric" ], "offsets": [ [ 140, 148 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009846" } ] }, { "id": "20006", "type": "Disease", "text": [ "renal failure" ], "offsets": [ [ 149, 162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] }, { "id": "20007", "type": "Chemical", "text": [ "cephalothin sodium" ], "offsets": [ [ 207, 225 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002512" } ] }, { "id": "20008", "type": "Chemical", "text": [ "gentamicin sulfate" ], "offsets": [ [ 230, 248 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005839" } ] }, { "id": "20009", "type": "Disease", "text": [ "nephrotoxicity" ], "offsets": [ [ 352, 366 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "20010", "type": "Disease", "text": [ "renal insufficiency" ], "offsets": [ [ 474, 493 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D051437" } ] } ]

[]

[]

[ { "id": "20011", "type": "CID", "arg1_id": "20002", "arg2_id": "20003", "normalized": [] }, { "id": "20012", "type": "CID", "arg1_id": "20008", "arg2_id": "20003", "normalized": [] }, { "id": "20013", "type": "CID", "arg1_id": "20001", "arg2_id": "20003", "normalized": [] }, { "id": "20014", "type": "CID", "arg1_id": "20007", "arg2_id": "20003", "normalized": [] }, { "id": "20015", "type": "CID", "arg1_id": "20002", "arg2_id": "20004", "normalized": [] }, { "id": "20016", "type": "CID", "arg1_id": "20002", "arg2_id": "20005", "normalized": [] }, { "id": "20017", "type": "CID", "arg1_id": "20008", "arg2_id": "20004", "normalized": [] }, { "id": "20018", "type": "CID", "arg1_id": "20008", "arg2_id": "20005", "normalized": [] }, { "id": "20019", "type": "CID", "arg1_id": "20001", "arg2_id": "20004", "normalized": [] }, { "id": "20020", "type": "CID", "arg1_id": "20001", "arg2_id": "20005", "normalized": [] }, { "id": "20021", "type": "CID", "arg1_id": "20007", "arg2_id": "20004", "normalized": [] }, { "id": "20022", "type": "CID", "arg1_id": "20007", "arg2_id": "20005", "normalized": [] } ]

[ { "id": "20024", "type": "title", "text": [ "Components of lemon essential oil attenuate dementia induced by scopolamine." ], "offsets": [ [ 0, 76 ] ] }, { "id": "20025", "type": "abstract", "text": [ "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method." ], "offsets": [ [ 77, 962 ] ] } ]

[ { "id": "20026", "type": "Disease", "text": [ "dementia" ], "offsets": [ [ 44, 52 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003704" } ] }, { "id": "20027", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 64, 75 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] }, { "id": "20028", "type": "Disease", "text": [ "dementia" ], "offsets": [ [ 86, 94 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003704" } ] }, { "id": "20029", "type": "Chemical", "text": [ "s-limonene" ], "offsets": [ [ 106, 116 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C008281" } ] }, { "id": "20030", "type": "Chemical", "text": [ "s-perillyl alcohol" ], "offsets": [ [ 121, 139 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C032208" } ] }, { "id": "20031", "type": "Disease", "text": [ "memory impaired" ], "offsets": [ [ 295, 310 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008569" } ] }, { "id": "20032", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 314, 325 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] }, { "id": "20033", "type": "Chemical", "text": [ "s-perillyl alcohol" ], "offsets": [ [ 336, 354 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C032208" } ] }, { "id": "20034", "type": "Disease", "text": [ "deficit of associative memory" ], "offsets": [ [ 368, 397 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008569" } ] }, { "id": "20035", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 568, 576 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "20036", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 606, 617 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] }, { "id": "20037", "type": "Chemical", "text": [ "s-limonene" ], "offsets": [ [ 726, 736 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C008281" } ] }, { "id": "20038", "type": "Chemical", "text": [ "s-perillyl alcohol" ], "offsets": [ [ 740, 758 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C032208" } ] }, { "id": "20039", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 801, 812 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] } ]

[]

[]

[ { "id": "20040", "type": "CID", "arg1_id": "20027", "arg2_id": "20031", "normalized": [] }, { "id": "20041", "type": "CID", "arg1_id": "20027", "arg2_id": "20034", "normalized": [] }, { "id": "20042", "type": "CID", "arg1_id": "20032", "arg2_id": "20031", "normalized": [] }, { "id": "20043", "type": "CID", "arg1_id": "20032", "arg2_id": "20034", "normalized": [] }, { "id": "20044", "type": "CID", "arg1_id": "20036", "arg2_id": "20031", "normalized": [] }, { "id": "20045", "type": "CID", "arg1_id": "20036", "arg2_id": "20034", "normalized": [] }, { "id": "20046", "type": "CID", "arg1_id": "20039", "arg2_id": "20031", "normalized": [] }, { "id": "20047", "type": "CID", "arg1_id": "20039", "arg2_id": "20034", "normalized": [] } ]

[ { "id": "20049", "type": "title", "text": [ "The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat." ], "offsets": [ [ 0, 149 ] ] }, { "id": "20050", "type": "abstract", "text": [ "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists." ], "offsets": [ [ 150, 1525 ] ] } ]

[ { "id": "20051", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 40, 49 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20052", "type": "Disease", "text": [ "memory deficiency" ], "offsets": [ [ 120, 137 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008569" } ] }, { "id": "20053", "type": "Chemical", "text": [ "serotonin" ], "offsets": [ [ 165, 174 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "20054", "type": "Chemical", "text": [ "5-HT" ], "offsets": [ [ 183, 187 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "20055", "type": "Chemical", "text": [ "acetylcholine" ], "offsets": [ [ 353, 366 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000109" } ] }, { "id": "20056", "type": "Chemical", "text": [ "ACh" ], "offsets": [ [ 368, 371 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000109" } ] }, { "id": "20057", "type": "Chemical", "text": [ "5-HT" ], "offsets": [ [ 461, 465 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] }, { "id": "20058", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 480, 489 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20059", "type": "Chemical", "text": [ "3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole" ], "offsets": [ [ 491, 545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20060", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 605, 616 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] }, { "id": "20061", "type": "Chemical", "text": [ "tryptophan" ], "offsets": [ [ 652, 662 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014364" } ] }, { "id": "20062", "type": "Chemical", "text": [ "TRP" ], "offsets": [ [ 664, 667 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014364" } ] }, { "id": "20063", "type": "Chemical", "text": [ "metrifonate" ], "offsets": [ [ 780, 791 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014236" } ] }, { "id": "20064", "type": "Chemical", "text": [ "metrifonate" ], "offsets": [ [ 909, 920 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014236" } ] }, { "id": "20065", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 985, 994 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20066", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 1015, 1024 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20067", "type": "Chemical", "text": [ "metrifonate" ], "offsets": [ [ 1072, 1083 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014236" } ] }, { "id": "20068", "type": "Disease", "text": [ "memory deficits" ], "offsets": [ [ 1124, 1139 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008569" } ] }, { "id": "20069", "type": "Chemical", "text": [ "scopolamine" ], "offsets": [ [ 1151, 1162 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012601" } ] }, { "id": "20070", "type": "Chemical", "text": [ "TRP" ], "offsets": [ [ 1167, 1170 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014364" } ] }, { "id": "20071", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 1256, 1265 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20072", "type": "Disease", "text": [ "memory deficit" ], "offsets": [ [ 1361, 1375 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008569" } ] }, { "id": "20073", "type": "Chemical", "text": [ "Ro4368554" ], "offsets": [ [ 1465, 1474 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C507242" } ] }, { "id": "20074", "type": "Chemical", "text": [ "5-HT" ], "offsets": [ [ 1496, 1500 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012701" } ] } ]

[]

[]

[ { "id": "20075", "type": "CID", "arg1_id": "20060", "arg2_id": "20052", "normalized": [] }, { "id": "20076", "type": "CID", "arg1_id": "20060", "arg2_id": "20068", "normalized": [] }, { "id": "20077", "type": "CID", "arg1_id": "20060", "arg2_id": "20072", "normalized": [] }, { "id": "20078", "type": "CID", "arg1_id": "20069", "arg2_id": "20052", "normalized": [] }, { "id": "20079", "type": "CID", "arg1_id": "20069", "arg2_id": "20068", "normalized": [] }, { "id": "20080", "type": "CID", "arg1_id": "20069", "arg2_id": "20072", "normalized": [] } ]

[ { "id": "20082", "type": "title", "text": [ "Lone atrial fibrillation associated with creatine monohydrate supplementation." ], "offsets": [ [ 0, 78 ] ] }, { "id": "20083", "type": "abstract", "text": [ "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature." ], "offsets": [ [ 79, 1887 ] ] } ]

[ { "id": "20084", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 5, 24 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "20085", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 41, 49 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20086", "type": "Disease", "text": [ "Atrial fibrillation" ], "offsets": [ [ 79, 98 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "20087", "type": "Disease", "text": [ "heart disease" ], "offsets": [ [ 136, 149 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006331" } ] }, { "id": "20088", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 179, 189 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] }, { "id": "20089", "type": "Disease", "text": [ "Thyroid disorders" ], "offsets": [ [ 272, 289 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013959" } ] }, { "id": "20090", "type": "Disease", "text": [ "acute alcohol intoxication" ], "offsets": [ [ 326, 352 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000435" } ] }, { "id": "20091", "type": "Disease", "text": [ "atrial fibrillation" ], "offsets": [ [ 467, 486 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001281" } ] }, { "id": "20092", "type": "Disease", "text": [ "fractures" ], "offsets": [ [ 575, 584 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D050723" } ] }, { "id": "20093", "type": "Chemical", "text": [ "magnesium" ], "offsets": [ [ 639, 648 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008274" } ] }, { "id": "20094", "type": "Chemical", "text": [ "potassium" ], "offsets": [ [ 654, 663 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011188" } ] }, { "id": "20095", "type": "Chemical", "text": [ "alcohol" ], "offsets": [ [ 734, 741 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000431" } ] }, { "id": "20096", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 856, 864 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20097", "type": "Chemical", "text": [ "heparin" ], "offsets": [ [ 968, 975 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006493" } ] }, { "id": "20098", "type": "Chemical", "text": [ "diltiazem" ], "offsets": [ [ 999, 1008 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004110" } ] }, { "id": "20099", "type": "Chemical", "text": [ "amiodarone" ], "offsets": [ [ 1042, 1052 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000638" } ] }, { "id": "20100", "type": "Chemical", "text": [ "metoprolol" ], "offsets": [ [ 1141, 1151 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008790" } ] }, { "id": "20101", "type": "Chemical", "text": [ "aspirin" ], "offsets": [ [ 1156, 1163 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001241" } ] }, { "id": "20102", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 1258, 1266 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20103", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 1360, 1368 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20104", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 1491, 1499 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20105", "type": "Disease", "text": [ "arrhythmia" ], "offsets": [ [ 1522, 1532 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001145" } ] } ]

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[ { "id": "20106", "type": "CID", "arg1_id": "20085", "arg2_id": "20084", "normalized": [] }, { "id": "20107", "type": "CID", "arg1_id": "20085", "arg2_id": "20086", "normalized": [] }, { "id": "20108", "type": "CID", "arg1_id": "20085", "arg2_id": "20091", "normalized": [] }, { "id": "20109", "type": "CID", "arg1_id": "20096", "arg2_id": "20084", "normalized": [] }, { "id": "20110", "type": "CID", "arg1_id": "20096", "arg2_id": "20086", "normalized": [] }, { "id": "20111", "type": "CID", "arg1_id": "20096", "arg2_id": "20091", "normalized": [] }, { "id": "20112", "type": "CID", "arg1_id": "20102", "arg2_id": "20084", "normalized": [] }, { "id": "20113", "type": "CID", "arg1_id": "20102", "arg2_id": "20086", "normalized": [] }, { "id": "20114", "type": "CID", "arg1_id": "20102", "arg2_id": "20091", "normalized": [] }, { "id": "20115", "type": "CID", "arg1_id": "20103", "arg2_id": "20084", "normalized": [] }, { "id": "20116", "type": "CID", "arg1_id": "20103", "arg2_id": "20086", "normalized": [] }, { "id": "20117", "type": "CID", "arg1_id": "20103", "arg2_id": "20091", "normalized": [] }, { "id": "20118", "type": "CID", "arg1_id": "20104", "arg2_id": "20084", "normalized": [] }, { "id": "20119", "type": "CID", "arg1_id": "20104", "arg2_id": "20086", "normalized": [] }, { "id": "20120", "type": "CID", "arg1_id": "20104", "arg2_id": "20091", "normalized": [] } ]

[ { "id": "20122", "type": "title", "text": [ "Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study." ], "offsets": [ [ 0, 149 ] ] }, { "id": "20123", "type": "abstract", "text": [ "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control." ], "offsets": [ [ 150, 2003 ] ] } ]

[ { "id": "20124", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 28, 36 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "20125", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 125, 128 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20126", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 133, 142 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20127", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 268, 276 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "20128", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 409, 417 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "20129", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 440, 449 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20130", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 466, 469 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20131", "type": "Chemical", "text": [ "5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon" ], "offsets": [ [ 471, 545 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20132", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 716, 725 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20133", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 757, 760 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20134", "type": "Disease", "text": [ "ventricular septal (VSD) and midline (MD) defects" ], "offsets": [ [ 919, 968 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006345" }, { "db_name": "MESH", "db_id": "D009436" } ] }, { "id": "20135", "type": "Disease", "text": [ "ventricular septal (VSD)", "defects" ], "offsets": [ [ 919, 943 ], [ 961, 968 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006345" } ] }, { "id": "20136", "type": "Disease", "text": [ "midline (MD) defects" ], "offsets": [ [ 946, 966 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009436" } ] }, { "id": "20137", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 1010, 1019 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20138", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1119, 1127 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "20139", "type": "Disease", "text": [ "intrauterine growth retardation" ], "offsets": [ [ 1129, 1160 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005317" } ] }, { "id": "20140", "type": "Disease", "text": [ "increase of external and skeletal variations" ], "offsets": [ [ 1166, 1210 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009139" } ] }, { "id": "20141", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 1263, 1272 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20142", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 1325, 1328 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20143", "type": "Disease", "text": [ "toxicity" ], "offsets": [ [ 1343, 1351 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D064420" } ] }, { "id": "20144", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 1443, 1452 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20145", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 1457, 1460 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20146", "type": "Chemical", "text": [ "DFU" ], "offsets": [ [ 1771, 1774 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C106876" } ] }, { "id": "20147", "type": "Chemical", "text": [ "piroxicam" ], "offsets": [ [ 1776, 1785 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010894" } ] }, { "id": "20148", "type": "Disease", "text": [ "ventricular septal and midline defects" ], "offsets": [ [ 1899, 1937 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006345" }, { "db_name": "MESH", "db_id": "D009436" } ] }, { "id": "20149", "type": "Disease", "text": [ "ventricular septal", "defects" ], "offsets": [ [ 1899, 1917 ], [ 1930, 1937 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006345" } ] }, { "id": "20150", "type": "Disease", "text": [ "midline defects" ], "offsets": [ [ 1922, 1937 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009436" } ] } ]

[]

[]

[ { "id": "20151", "type": "CID", "arg1_id": "20126", "arg2_id": "20139", "normalized": [] }, { "id": "20152", "type": "CID", "arg1_id": "20129", "arg2_id": "20139", "normalized": [] }, { "id": "20153", "type": "CID", "arg1_id": "20132", "arg2_id": "20139", "normalized": [] }, { "id": "20154", "type": "CID", "arg1_id": "20137", "arg2_id": "20139", "normalized": [] }, { "id": "20155", "type": "CID", "arg1_id": "20141", "arg2_id": "20139", "normalized": [] }, { "id": "20156", "type": "CID", "arg1_id": "20144", "arg2_id": "20139", "normalized": [] }, { "id": "20157", "type": "CID", "arg1_id": "20147", "arg2_id": "20139", "normalized": [] }, { "id": "20158", "type": "CID", "arg1_id": "20126", "arg2_id": "20140", "normalized": [] }, { "id": "20159", "type": "CID", "arg1_id": "20129", "arg2_id": "20140", "normalized": [] }, { "id": "20160", "type": "CID", "arg1_id": "20132", "arg2_id": "20140", "normalized": [] }, { "id": "20161", "type": "CID", "arg1_id": "20137", "arg2_id": "20140", "normalized": [] }, { "id": "20162", "type": "CID", "arg1_id": "20141", "arg2_id": "20140", "normalized": [] }, { "id": "20163", "type": "CID", "arg1_id": "20144", "arg2_id": "20140", "normalized": [] }, { "id": "20164", "type": "CID", "arg1_id": "20147", "arg2_id": "20140", "normalized": [] }, { "id": "20165", "type": "CID", "arg1_id": "20125", "arg2_id": "20139", "normalized": [] }, { "id": "20166", "type": "CID", "arg1_id": "20130", "arg2_id": "20139", "normalized": [] }, { "id": "20167", "type": "CID", "arg1_id": "20131", "arg2_id": "20139", "normalized": [] }, { "id": "20168", "type": "CID", "arg1_id": "20133", "arg2_id": "20139", "normalized": [] }, { "id": "20169", "type": "CID", "arg1_id": "20142", "arg2_id": "20139", "normalized": [] }, { "id": "20170", "type": "CID", "arg1_id": "20145", "arg2_id": "20139", "normalized": [] }, { "id": "20171", "type": "CID", "arg1_id": "20146", "arg2_id": "20139", "normalized": [] } ]

[ { "id": "20173", "type": "title", "text": [ "Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice." ], "offsets": [ [ 0, 85 ] ] }, { "id": "20174", "type": "abstract", "text": [ "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse." ], "offsets": [ [ 86, 1657 ] ] } ]

[ { "id": "20175", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 35, 43 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013256" } ] }, { "id": "20176", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 52, 59 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "20177", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 68, 76 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20178", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 98, 106 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013256" } ] }, { "id": "20179", "type": "Disease", "text": [ "neurological and psychiatric disorders" ], "offsets": [ [ 177, 215 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" }, { "db_name": "MESH", "db_id": "D001523" } ] }, { "id": "20180", "type": "Disease", "text": [ "neurological", "disorders" ], "offsets": [ [ 177, 189 ], [ 206, 215 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009422" } ] }, { "id": "20181", "type": "Disease", "text": [ "psychiatric disorders" ], "offsets": [ [ 194, 215 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001523" } ] }, { "id": "20182", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 247, 255 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20183", "type": "Disease", "text": [ "drug dependence" ], "offsets": [ [ 315, 330 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019966" } ] }, { "id": "20184", "type": "Chemical", "text": [ "steroid" ], "offsets": [ [ 447, 454 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013256" } ] }, { "id": "20185", "type": "Chemical", "text": [ "gamma-aminobutyric acid" ], "offsets": [ [ 484, 507 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "20186", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 509, 513 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "20187", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 592, 599 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "20188", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 623, 630 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "20189", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 647, 654 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20190", "type": "Chemical", "text": [ "Allopregnanolone" ], "offsets": [ [ 666, 682 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20191", "type": "Chemical", "text": [ "3alpha-hydroxy-5alpha-pregnan-20-one" ], "offsets": [ [ 684, 720 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20192", "type": "Chemical", "text": [ "pregnanolone" ], "offsets": [ [ 723, 735 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20193", "type": "Chemical", "text": [ "3alpha-hydroxy-5beta-pregnan-20-one" ], "offsets": [ [ 737, 772 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20194", "type": "Chemical", "text": [ "ganaxolone" ], "offsets": [ [ 778, 788 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C105051" } ] }, { "id": "20195", "type": "Chemical", "text": [ "allopregnanolone" ], "offsets": [ [ 816, 832 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20196", "type": "Chemical", "text": [ "3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one" ], "offsets": [ [ 833, 882 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C105051" } ] }, { "id": "20197", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 1011, 1018 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "20198", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1027, 1035 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20199", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1073, 1081 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20200", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 1131, 1138 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] }, { "id": "20201", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 1173, 1177 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "20202", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1229, 1237 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20203", "type": "Chemical", "text": [ "allopregnanolone" ], "offsets": [ [ 1252, 1268 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20204", "type": "Chemical", "text": [ "ganaxolone" ], "offsets": [ [ 1273, 1283 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C105051" } ] }, { "id": "20205", "type": "Chemical", "text": [ "Allopregnanolone" ], "offsets": [ [ 1323, 1339 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20206", "type": "Chemical", "text": [ "pregnanolone" ], "offsets": [ [ 1344, 1356 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D011280" } ] }, { "id": "20207", "type": "Chemical", "text": [ "ganaxolone" ], "offsets": [ [ 1366, 1376 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C105051" } ] }, { "id": "20208", "type": "Chemical", "text": [ "steroids" ], "offsets": [ [ 1487, 1495 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013256" } ] }, { "id": "20209", "type": "Chemical", "text": [ "cocaine" ], "offsets": [ [ 1547, 1554 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003042" } ] } ]

[]

[]

[ { "id": "20210", "type": "CID", "arg1_id": "20176", "arg2_id": "20177", "normalized": [] }, { "id": "20211", "type": "CID", "arg1_id": "20176", "arg2_id": "20182", "normalized": [] }, { "id": "20212", "type": "CID", "arg1_id": "20176", "arg2_id": "20189", "normalized": [] }, { "id": "20213", "type": "CID", "arg1_id": "20176", "arg2_id": "20198", "normalized": [] }, { "id": "20214", "type": "CID", "arg1_id": "20176", "arg2_id": "20199", "normalized": [] }, { "id": "20215", "type": "CID", "arg1_id": "20176", "arg2_id": "20202", "normalized": [] }, { "id": "20216", "type": "CID", "arg1_id": "20187", "arg2_id": "20177", "normalized": [] }, { "id": "20217", "type": "CID", "arg1_id": "20187", "arg2_id": "20182", "normalized": [] }, { "id": "20218", "type": "CID", "arg1_id": "20187", "arg2_id": "20189", "normalized": [] }, { "id": "20219", "type": "CID", "arg1_id": "20187", "arg2_id": "20198", "normalized": [] }, { "id": "20220", "type": "CID", "arg1_id": "20187", "arg2_id": "20199", "normalized": [] }, { "id": "20221", "type": "CID", "arg1_id": "20187", "arg2_id": "20202", "normalized": [] }, { "id": "20222", "type": "CID", "arg1_id": "20188", "arg2_id": "20177", "normalized": [] }, { "id": "20223", "type": "CID", "arg1_id": "20188", "arg2_id": "20182", "normalized": [] }, { "id": "20224", "type": "CID", "arg1_id": "20188", "arg2_id": "20189", "normalized": [] }, { "id": "20225", "type": "CID", "arg1_id": "20188", "arg2_id": "20198", "normalized": [] }, { "id": "20226", "type": "CID", "arg1_id": "20188", "arg2_id": "20199", "normalized": [] }, { "id": "20227", "type": "CID", "arg1_id": "20188", "arg2_id": "20202", "normalized": [] }, { "id": "20228", "type": "CID", "arg1_id": "20197", "arg2_id": "20177", "normalized": [] }, { "id": "20229", "type": "CID", "arg1_id": "20197", "arg2_id": "20182", "normalized": [] }, { "id": "20230", "type": "CID", "arg1_id": "20197", "arg2_id": "20189", "normalized": [] }, { "id": "20231", "type": "CID", "arg1_id": "20197", "arg2_id": "20198", "normalized": [] }, { "id": "20232", "type": "CID", "arg1_id": "20197", "arg2_id": "20199", "normalized": [] }, { "id": "20233", "type": "CID", "arg1_id": "20197", "arg2_id": "20202", "normalized": [] }, { "id": "20234", "type": "CID", "arg1_id": "20200", "arg2_id": "20177", "normalized": [] }, { "id": "20235", "type": "CID", "arg1_id": "20200", "arg2_id": "20182", "normalized": [] }, { "id": "20236", "type": "CID", "arg1_id": "20200", "arg2_id": "20189", "normalized": [] }, { "id": "20237", "type": "CID", "arg1_id": "20200", "arg2_id": "20198", "normalized": [] }, { "id": "20238", "type": "CID", "arg1_id": "20200", "arg2_id": "20199", "normalized": [] }, { "id": "20239", "type": "CID", "arg1_id": "20200", "arg2_id": "20202", "normalized": [] }, { "id": "20240", "type": "CID", "arg1_id": "20209", "arg2_id": "20177", "normalized": [] }, { "id": "20241", "type": "CID", "arg1_id": "20209", "arg2_id": "20182", "normalized": [] }, { "id": "20242", "type": "CID", "arg1_id": "20209", "arg2_id": "20189", "normalized": [] }, { "id": "20243", "type": "CID", "arg1_id": "20209", "arg2_id": "20198", "normalized": [] }, { "id": "20244", "type": "CID", "arg1_id": "20209", "arg2_id": "20199", "normalized": [] }, { "id": "20245", "type": "CID", "arg1_id": "20209", "arg2_id": "20202", "normalized": [] } ]

[ { "id": "20247", "type": "title", "text": [ "Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat." ], "offsets": [ [ 0, 125 ] ] }, { "id": "20248", "type": "abstract", "text": [ "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated." ], "offsets": [ [ 126, 2359 ] ] } ]

[ { "id": "20249", "type": "Chemical", "text": [ "cyclosporine A" ], "offsets": [ [ 73, 87 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20250", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 89, 99 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20251", "type": "Chemical", "text": [ "sirolimus" ], "offsets": [ [ 104, 113 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20252", "type": "Chemical", "text": [ "Sirolimus" ], "offsets": [ [ 138, 147 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20253", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 149, 152 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20254", "type": "Disease", "text": [ "nephrotoxic" ], "offsets": [ [ 237, 248 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "20255", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 254, 257 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20256", "type": "Disease", "text": [ "nephrotoxic" ], "offsets": [ [ 305, 316 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "20257", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 405, 408 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20258", "type": "Disease", "text": [ "nephrotoxic" ], "offsets": [ [ 480, 491 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007674" } ] }, { "id": "20259", "type": "Chemical", "text": [ "cyclosporine A" ], "offsets": [ [ 676, 690 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20260", "type": "Chemical", "text": [ "CsA" ], "offsets": [ [ 692, 695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20261", "type": "Chemical", "text": [ "tacrolimus" ], "offsets": [ [ 698, 708 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20262", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 710, 715 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20263", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 720, 723 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20264", "type": "Chemical", "text": [ "CsA" ], "offsets": [ [ 805, 808 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20265", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 838, 843 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20266", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 876, 879 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20267", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1302, 1310 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "20268", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1324, 1332 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "20269", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1435, 1443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "20270", "type": "Chemical", "text": [ "CsA" ], "offsets": [ [ 1492, 1495 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20271", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 1497, 1502 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20272", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 1507, 1510 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20273", "type": "Chemical", "text": [ "CsA" ], "offsets": [ [ 1586, 1589 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20274", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 1615, 1620 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20275", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 1624, 1627 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20276", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 1690, 1695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016559" } ] }, { "id": "20277", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 1701, 1704 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20278", "type": "Chemical", "text": [ "CsA" ], "offsets": [ [ 1904, 1907 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D016572" } ] }, { "id": "20279", "type": "Chemical", "text": [ "SRL" ], "offsets": [ [ 1913, 1916 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020123" } ] }, { "id": "20280", "type": "Disease", "text": [ "fibrosis" ], "offsets": [ [ 1989, 1997 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005355" } ] }, { "id": "20281", "type": "Chemical", "text": [ "FK506" ], "offsets": [ [ 2111, 2116 ] ], "normalized": [ { "db_name": "MESH", "db_id": 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[]

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"normalized": [] }, { "id": "20408", "type": "CID", "arg1_id": "20286", "arg2_id": "20284", "normalized": [] }, { "id": "20409", "type": "CID", "arg1_id": "20288", "arg2_id": "20254", "normalized": [] }, { "id": "20410", "type": "CID", "arg1_id": "20288", "arg2_id": "20256", "normalized": [] }, { "id": "20411", "type": "CID", "arg1_id": "20288", "arg2_id": "20258", "normalized": [] }, { "id": "20412", "type": "CID", "arg1_id": "20288", "arg2_id": "20284", "normalized": [] } ]

[ { "id": "20414", "type": "title", "text": [ "Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats." ], "offsets": [ [ 0, 85 ] ] }, { "id": "20415", "type": "abstract", "text": [ "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage." ], "offsets": [ [ 86, 1371 ] ] } ]

[ { "id": "20416", "type": "Chemical", "text": [ "fucoidan" ], "offsets": [ [ 10, 18 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C007789" } ] }, { "id": "20417", "type": "Disease", "text": [ "intracerebral hemorrhage" ], "offsets": [ [ 52, 76 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002543" } ] }, { "id": "20418", "type": "Disease", "text": [ "brain damage" ], "offsets": [ [ 143, 155 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001925" } ] }, { "id": "20419", "type": "Disease", "text": [ "ischemic stroke" ], "offsets": [ [ 166, 181 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002544" } ] }, { "id": "20420", "type": "Disease", "text": [ "Intracerebral hemorrhage" ], "offsets": [ [ 183, 207 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002543" } ] }, { "id": "20421", "type": "Disease", "text": [ "inflammation" ], "offsets": [ [ 232, 244 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007249" } ] }, { "id": "20422", "type": "Disease", "text": [ "ischemic stroke" ], "offsets": [ [ 250, 265 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002544" } ] }, { "id": "20423", "type": "Chemical", "text": [ "fucoidan" ], "offsets": [ [ 305, 313 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C007789" } ] }, { "id": "20424", "type": "Disease", "text": [ "brain damage" ], "offsets": [ [ 362, 374 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001925" } ] }, { "id": "20425", "type": "Disease", "text": [ "intracerebral hemorrhage" ], "offsets": [ [ 394, 418 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002543" } ] }, { "id": "20426", "type": "Chemical", "text": [ "fucoidan" ], "offsets": [ [ 548, 556 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C007789" } ] }, { "id": "20427", "type": "Disease", "text": [ "hematoma" ], "offsets": [ [ 593, 601 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006406" } ] }, { "id": "20428", "type": "Chemical", "text": [ "Fucoidan" ], "offsets": [ [ 757, 765 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C007789" } ] }, { "id": "20429", "type": "Disease", "text": [ "impaired blood clotting" ], "offsets": [ [ 801, 824 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20430", "type": "Disease", "text": [ "hemodilution" ], "offsets": [ [ 829, 841 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20431", "type": "Disease", "text": [ "hematomas" ], "offsets": [ [ 854, 863 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006406" } ] }, { "id": "20432", "type": "Disease", "text": [ "inflammation" ], "offsets": [ [ 889, 901 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007249" } ] }, { "id": "20433", "type": "Disease", "text": [ "hematoma" ], "offsets": [ [ 925, 933 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006406" } ] }, { "id": "20434", "type": "Disease", "text": [ "hemorrhage" ], "offsets": [ [ 1047, 1057 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006470" } ] }, { "id": "20435", "type": "Disease", "text": [ "white matter edema" ], "offsets": [ [ 1123, 1141 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001929" } ] }, { "id": "20436", "type": "Disease", "text": [ "neuronal loss" ], "offsets": [ [ 1155, 1168 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009410" } ] }, { "id": "20437", "type": "Disease", "text": [ "hematoma" ], "offsets": [ [ 1201, 1209 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006406" } ] }, { "id": "20438", "type": "Disease", "text": [ "intracerebral hemorrhage" ], "offsets": [ [ 1346, 1370 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002543" } ] } ]

[]

[]

[ { "id": "20439", "type": "CID", "arg1_id": "20416", "arg2_id": "20429", "normalized": [] }, { "id": "20440", "type": "CID", "arg1_id": "20416", "arg2_id": "20430", "normalized": [] }, { "id": "20441", "type": "CID", "arg1_id": "20423", "arg2_id": "20429", "normalized": [] }, { "id": "20442", "type": "CID", "arg1_id": "20423", "arg2_id": "20430", "normalized": [] }, { "id": "20443", "type": "CID", "arg1_id": "20426", "arg2_id": "20429", "normalized": [] }, { "id": "20444", "type": "CID", "arg1_id": "20426", "arg2_id": "20430", "normalized": [] }, { "id": "20445", "type": "CID", "arg1_id": "20428", "arg2_id": "20429", "normalized": [] }, { "id": "20446", "type": "CID", "arg1_id": "20428", "arg2_id": "20430", "normalized": [] }, { "id": "20447", "type": "CID", "arg1_id": "20416", "arg2_id": "20435", "normalized": [] }, { "id": "20448", "type": "CID", "arg1_id": "20423", "arg2_id": "20435", "normalized": [] }, { "id": "20449", "type": "CID", "arg1_id": "20426", "arg2_id": "20435", "normalized": [] }, { "id": "20450", "type": "CID", "arg1_id": "20428", "arg2_id": "20435", "normalized": [] } ]

[ { "id": "20452", "type": "title", "text": [ "Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure." ], "offsets": [ [ 0, 75 ] ] }, { "id": "20453", "type": "abstract", "text": [ "A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered." ], "offsets": [ [ 76, 383 ] ] } ]

[ { "id": "20454", "type": "Chemical", "text": [ "Paracetamol" ], "offsets": [ [ 0, 11 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] }, { "id": "20455", "type": "Disease", "text": [ "coma" ], "offsets": [ [ 23, 27 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003128" } ] }, { "id": "20456", "type": "Disease", "text": [ "metabolic acidosis" ], "offsets": [ [ 29, 47 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000138" } ] }, { "id": "20457", "type": "Disease", "text": [ "renal and hepatic failure" ], "offsets": [ [ 49, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" }, { "db_name": "MESH", "db_id": "D017093" } ] }, { "id": "20458", "type": "Disease", "text": [ "renal", "failure" ], "offsets": [ [ 49, 54 ], [ 67, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" } ] }, { "id": "20459", "type": "Disease", "text": [ "hepatic failure" ], "offsets": [ [ 59, 74 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017093" } ] }, { "id": "20460", "type": "Disease", "text": [ "metabolic acidosis" ], "offsets": [ [ 86, 104 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000138" } ] }, { "id": "20461", "type": "Disease", "text": [ "acute renal failure and hepatic failure" ], "offsets": [ [ 106, 145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" }, { "db_name": "MESH", "db_id": "D017114" } ] }, { "id": "20462", "type": "Disease", "text": [ "acute renal failure" ], "offsets": [ [ 106, 125 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D058186" } ] }, { "id": "20463", "type": "Disease", "text": [ "acute", "hepatic failure" ], "offsets": [ [ 106, 111 ], [ 130, 145 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D017114" } ] }, { "id": "20464", "type": "Chemical", "text": [ "paracetamol" ], "offsets": [ [ 156, 167 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000082" } ] } ]

[]

[]

[ { "id": "20465", "type": "CID", "arg1_id": "20454", "arg2_id": "20456", "normalized": [] }, { "id": "20466", "type": "CID", "arg1_id": "20454", "arg2_id": "20460", "normalized": [] }, { "id": "20467", "type": "CID", "arg1_id": "20464", "arg2_id": "20456", "normalized": [] }, { "id": "20468", "type": "CID", "arg1_id": "20464", "arg2_id": "20460", "normalized": [] }, { "id": "20469", "type": "CID", "arg1_id": "20454", "arg2_id": "20461", "normalized": [] }, { "id": "20470", "type": "CID", "arg1_id": "20454", "arg2_id": "20463", "normalized": [] }, { "id": "20471", "type": "CID", "arg1_id": "20464", "arg2_id": "20461", "normalized": [] }, { "id": "20472", "type": "CID", "arg1_id": "20464", "arg2_id": "20463", "normalized": [] }, { "id": "20473", "type": "CID", "arg1_id": "20454", "arg2_id": "20457", "normalized": [] }, { "id": "20474", "type": "CID", "arg1_id": "20454", "arg2_id": "20458", "normalized": [] }, { "id": "20475", "type": "CID", "arg1_id": "20454", "arg2_id": "20461", "normalized": [] }, { "id": "20476", "type": "CID", "arg1_id": "20454", "arg2_id": "20462", "normalized": [] }, { "id": "20477", "type": "CID", "arg1_id": "20464", "arg2_id": "20457", "normalized": [] }, { "id": "20478", "type": "CID", "arg1_id": "20464", "arg2_id": "20458", "normalized": [] }, { "id": "20479", "type": "CID", "arg1_id": "20464", "arg2_id": "20461", "normalized": [] }, { "id": "20480", "type": "CID", "arg1_id": "20464", "arg2_id": "20462", "normalized": [] } ]

[ { "id": "20482", "type": "title", "text": [ "Hepatic reactions associated with ketoconazole in the United Kingdom." ], "offsets": [ [ 0, 69 ] ] }, { "id": "20483", "type": "abstract", "text": [ "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury." ], "offsets": [ [ 70, 1690 ] ] } ]

[ { "id": "20484", "type": "Chemical", "text": [ "ketoconazole" ], "offsets": [ [ 34, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007654" } ] }, { "id": "20485", "type": "Chemical", "text": [ "Ketoconazole" ], "offsets": [ [ 70, 82 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007654" } ] }, { "id": "20486", "type": "Disease", "text": [ "hepatotoxicity" ], "offsets": [ [ 219, 233 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20487", "type": "Disease", "text": [ "deaths" ], "offsets": [ [ 275, 281 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "20488", "type": "Disease", "text": [ "deaths" ], "offsets": [ [ 383, 389 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "20489", "type": "Disease", "text": [ "hepatotoxicity" ], "offsets": [ [ 621, 635 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20490", "type": "Disease", "text": [ "jaundice" ], "offsets": [ [ 718, 726 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "20491", "type": "Disease", "text": [ "hepatocellular injury" ], "offsets": [ [ 878, 899 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20492", "type": "Disease", "text": [ "cholestasis" ], "offsets": [ [ 1037, 1048 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D002779" } ] }, { "id": "20493", "type": "Disease", "text": [ "rash" ], "offsets": [ [ 1157, 1161 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005076" } ] }, { "id": "20494", "type": "Disease", "text": [ "eosinophilia" ], "offsets": [ [ 1166, 1178 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004802" } ] }, { "id": "20495", "type": "Disease", "text": [ "Hepatitis" ], "offsets": [ [ 1190, 1199 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20496", "type": "Disease", "text": [ "deaths" ], "offsets": [ [ 1364, 1370 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003643" } ] }, { "id": "20497", "type": "Chemical", "text": [ "ketoconazole" ], "offsets": [ [ 1396, 1408 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007654" } ] }, { "id": "20498", "type": "Disease", "text": [ "jaundice" ], "offsets": [ [ 1466, 1474 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007565" } ] }, { "id": "20499", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 1497, 1506 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20500", "type": "Disease", "text": [ "hepatitis" ], "offsets": [ [ 1581, 1590 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] }, { "id": "20501", "type": "Chemical", "text": [ "ketoconazole" ], "offsets": [ [ 1634, 1646 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007654" } ] }, { "id": "20502", "type": "Disease", "text": [ "hepatic injury" ], "offsets": [ [ 1675, 1689 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D056486" } ] } ]

[]

[]

[ { "id": "20503", "type": "CID", "arg1_id": "20484", "arg2_id": "20490", "normalized": [] }, { "id": "20504", "type": "CID", "arg1_id": "20484", "arg2_id": "20498", "normalized": [] }, { "id": "20505", "type": "CID", "arg1_id": "20485", "arg2_id": "20490", "normalized": [] }, { "id": "20506", "type": "CID", "arg1_id": "20485", "arg2_id": "20498", "normalized": [] }, { "id": "20507", "type": "CID", "arg1_id": "20497", "arg2_id": "20490", "normalized": [] }, { "id": "20508", "type": "CID", "arg1_id": "20497", "arg2_id": "20498", "normalized": [] }, { "id": "20509", "type": "CID", "arg1_id": "20501", "arg2_id": "20490", "normalized": [] }, { "id": "20510", "type": "CID", "arg1_id": "20501", "arg2_id": "20498", "normalized": [] }, { "id": "20511", "type": "CID", "arg1_id": "20484", "arg2_id": "20492", "normalized": [] }, { "id": "20512", "type": "CID", "arg1_id": "20485", "arg2_id": "20492", "normalized": [] }, { "id": "20513", "type": "CID", "arg1_id": "20497", "arg2_id": "20492", "normalized": [] }, { "id": "20514", "type": "CID", "arg1_id": "20501", "arg2_id": "20492", "normalized": [] }, { "id": "20515", "type": "CID", "arg1_id": "20484", "arg2_id": "20486", "normalized": [] }, { "id": "20516", "type": "CID", "arg1_id": "20484", "arg2_id": "20489", "normalized": [] }, { "id": "20517", "type": "CID", "arg1_id": "20484", "arg2_id": "20491", "normalized": [] }, { "id": "20518", "type": "CID", "arg1_id": "20484", "arg2_id": "20495", "normalized": [] }, { "id": "20519", "type": "CID", "arg1_id": "20484", "arg2_id": "20499", "normalized": [] }, { "id": "20520", "type": "CID", "arg1_id": "20484", "arg2_id": "20500", "normalized": [] }, { "id": "20521", "type": "CID", "arg1_id": "20484", "arg2_id": "20502", "normalized": [] }, { "id": "20522", "type": "CID", "arg1_id": "20485", "arg2_id": "20486", "normalized": [] }, { "id": "20523", "type": "CID", "arg1_id": "20485", "arg2_id": "20489", "normalized": [] }, { "id": "20524", "type": "CID", "arg1_id": "20485", "arg2_id": "20491", "normalized": [] }, { "id": "20525", "type": "CID", "arg1_id": "20485", "arg2_id": "20495", "normalized": [] }, { "id": "20526", "type": "CID", "arg1_id": "20485", "arg2_id": "20499", "normalized": [] }, { "id": "20527", "type": "CID", "arg1_id": "20485", "arg2_id": "20500", "normalized": [] }, { "id": "20528", "type": "CID", "arg1_id": "20485", "arg2_id": "20502", "normalized": [] }, { "id": "20529", "type": "CID", "arg1_id": "20497", "arg2_id": "20486", "normalized": [] }, { "id": "20530", "type": "CID", "arg1_id": "20497", "arg2_id": "20489", "normalized": [] }, { "id": "20531", "type": "CID", "arg1_id": "20497", "arg2_id": "20491", "normalized": [] }, { "id": "20532", "type": "CID", "arg1_id": "20497", "arg2_id": "20495", "normalized": [] }, { "id": "20533", "type": "CID", "arg1_id": "20497", "arg2_id": "20499", "normalized": [] }, { "id": "20534", "type": "CID", "arg1_id": "20497", "arg2_id": "20500", "normalized": [] }, { "id": "20535", "type": "CID", "arg1_id": "20497", "arg2_id": "20502", "normalized": [] }, { "id": "20536", "type": "CID", "arg1_id": "20501", "arg2_id": "20486", "normalized": [] }, { "id": "20537", "type": "CID", "arg1_id": "20501", "arg2_id": "20489", "normalized": [] }, { "id": "20538", "type": "CID", "arg1_id": "20501", "arg2_id": "20491", "normalized": [] }, { "id": "20539", "type": "CID", "arg1_id": "20501", "arg2_id": "20495", "normalized": [] }, { "id": "20540", "type": "CID", "arg1_id": "20501", "arg2_id": "20499", "normalized": [] }, { "id": "20541", "type": "CID", "arg1_id": "20501", "arg2_id": "20500", "normalized": [] }, { "id": "20542", "type": "CID", "arg1_id": "20501", "arg2_id": "20502", "normalized": [] } ]

[ { "id": "20544", "type": "title", "text": [ "Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function." ], "offsets": [ [ 0, 111 ] ] }, { "id": "20545", "type": "abstract", "text": [ "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function." ], "offsets": [ [ 112, 1525 ] ] } ]

[ { "id": "20546", "type": "Chemical", "text": [ "prostaglandin E1" ], "offsets": [ [ 30, 46 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000527" } ] }, { "id": "20547", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 55, 66 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20548", "type": "Disease", "text": [ "haemodilution" ], "offsets": [ [ 71, 84 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20549", "type": "Chemical", "text": [ "prostaglandin E1" ], "offsets": [ [ 142, 158 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000527" } ] }, { "id": "20550", "type": "Chemical", "text": [ "PGE1" ], "offsets": [ [ 160, 164 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000527" } ] }, { "id": "20551", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 174, 185 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20552", "type": "Disease", "text": [ "haemodilution" ], "offsets": [ [ 190, 203 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20553", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 392, 403 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20554", "type": "Disease", "text": [ "haemodilution" ], "offsets": [ [ 440, 453 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20555", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 509, 520 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20556", "type": "Disease", "text": [ "haemodilution" ], "offsets": [ [ 525, 538 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20557", "type": "Disease", "text": [ "Haemodilution" ], "offsets": [ [ 540, 553 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20558", "type": "Chemical", "text": [ "dextran" ], "offsets": [ [ 672, 679 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003911" } ] }, { "id": "20559", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 746, 757 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20560", "type": "Chemical", "text": [ "PGE1" ], "offsets": [ [ 793, 797 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000527" } ] }, { "id": "20561", "type": "Chemical", "text": [ "aceto-acetate" ], "offsets": [ [ 919, 932 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C016635" } ] }, { "id": "20562", "type": "Chemical", "text": [ "3-hydroxybutyrate" ], "offsets": [ [ 933, 950 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020155" } ] }, { "id": "20563", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 1206, 1217 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20564", "type": "Chemical", "text": [ "bilirubin" ], "offsets": [ [ 1301, 1310 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001663" } ] }, { "id": "20565", "type": "Chemical", "text": [ "PGE1" ], "offsets": [ [ 1430, 1434 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000527" } ] }, { "id": "20566", "type": "Disease", "text": [ "hypotension" ], "offsets": [ [ 1443, 1454 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007022" } ] }, { "id": "20567", "type": "Disease", "text": [ "haemodilution" ], "offsets": [ [ 1468, 1481 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D020141" } ] }, { "id": "20568", "type": "Disease", "text": [ "impairment of hepatic function" ], "offsets": [ [ 1494, 1524 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008107" } ] } ]

[]

[]

[ { "id": "20569", "type": "CID", "arg1_id": "20546", "arg2_id": "20547", "normalized": [] }, { "id": "20570", "type": "CID", "arg1_id": "20546", "arg2_id": "20551", "normalized": [] }, { "id": "20571", "type": "CID", "arg1_id": "20546", "arg2_id": "20553", "normalized": [] }, { "id": "20572", "type": "CID", "arg1_id": "20546", "arg2_id": "20555", "normalized": [] }, { "id": "20573", "type": "CID", "arg1_id": "20546", "arg2_id": "20559", "normalized": [] }, { "id": "20574", "type": "CID", "arg1_id": "20546", "arg2_id": "20563", "normalized": [] }, { "id": "20575", "type": "CID", "arg1_id": "20546", "arg2_id": "20566", "normalized": [] }, { "id": "20576", "type": "CID", "arg1_id": "20549", "arg2_id": "20547", "normalized": [] }, { "id": "20577", "type": "CID", "arg1_id": "20549", "arg2_id": "20551", "normalized": [] }, { "id": "20578", "type": "CID", "arg1_id": "20549", "arg2_id": "20553", "normalized": [] }, { "id": "20579", "type": "CID", "arg1_id": "20549", "arg2_id": "20555", "normalized": [] }, { "id": "20580", "type": "CID", "arg1_id": "20549", "arg2_id": "20559", "normalized": [] }, { "id": "20581", "type": "CID", "arg1_id": "20549", "arg2_id": "20563", "normalized": [] }, { "id": "20582", "type": "CID", "arg1_id": "20549", "arg2_id": "20566", "normalized": [] }, { "id": "20583", "type": "CID", "arg1_id": "20550", "arg2_id": "20547", "normalized": [] }, { "id": "20584", "type": "CID", "arg1_id": "20550", "arg2_id": "20551", "normalized": [] }, { "id": "20585", "type": "CID", "arg1_id": "20550", "arg2_id": "20553", "normalized": [] }, { "id": "20586", "type": "CID", "arg1_id": "20550", "arg2_id": "20555", "normalized": [] }, { "id": "20587", "type": "CID", "arg1_id": "20550", "arg2_id": "20559", "normalized": [] }, { "id": "20588", "type": "CID", "arg1_id": "20550", "arg2_id": "20563", "normalized": [] }, { "id": "20589", "type": "CID", "arg1_id": "20550", "arg2_id": "20566", "normalized": [] }, { "id": "20590", "type": "CID", "arg1_id": "20560", "arg2_id": "20547", "normalized": [] }, { "id": "20591", "type": "CID", "arg1_id": "20560", "arg2_id": "20551", "normalized": [] }, { "id": "20592", "type": "CID", "arg1_id": "20560", "arg2_id": "20553", "normalized": [] }, { "id": "20593", "type": "CID", "arg1_id": "20560", "arg2_id": "20555", "normalized": [] }, { "id": "20594", "type": "CID", "arg1_id": "20560", "arg2_id": "20559", "normalized": [] }, { "id": "20595", "type": "CID", "arg1_id": "20560", "arg2_id": "20563", "normalized": [] }, { "id": "20596", "type": "CID", "arg1_id": "20560", "arg2_id": "20566", "normalized": [] }, { "id": "20597", "type": "CID", "arg1_id": "20565", "arg2_id": "20547", "normalized": [] }, { "id": "20598", "type": "CID", "arg1_id": "20565", "arg2_id": "20551", "normalized": [] }, { "id": "20599", "type": "CID", "arg1_id": "20565", "arg2_id": "20553", "normalized": [] }, { "id": "20600", "type": "CID", "arg1_id": "20565", "arg2_id": "20555", "normalized": [] }, { "id": "20601", "type": "CID", "arg1_id": "20565", "arg2_id": "20559", "normalized": [] }, { "id": "20602", "type": "CID", "arg1_id": "20565", "arg2_id": "20563", "normalized": [] }, { "id": "20603", "type": "CID", "arg1_id": "20565", "arg2_id": "20566", "normalized": [] }, { "id": "20604", "type": "CID", "arg1_id": "20546", "arg2_id": "20568", "normalized": [] }, { "id": "20605", "type": "CID", "arg1_id": "20549", "arg2_id": "20568", "normalized": [] }, { "id": "20606", "type": "CID", "arg1_id": "20550", "arg2_id": "20568", "normalized": [] }, { "id": "20607", "type": "CID", "arg1_id": "20560", "arg2_id": "20568", "normalized": [] }, { "id": "20608", "type": "CID", "arg1_id": "20565", "arg2_id": "20568", "normalized": [] } ]

[ { "id": "20610", "type": "title", "text": [ "Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap." ], "offsets": [ [ 0, 100 ] ] }, { "id": "20611", "type": "abstract", "text": [ "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias." ], "offsets": [ [ 101, 1069 ] ] } ]

[ { "id": "20612", "type": "Chemical", "text": [ "Levodopa" ], "offsets": [ [ 0, 8 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "20613", "type": "Disease", "text": [ "dyskinesias" ], "offsets": [ [ 17, 28 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "20614", "type": "Disease", "text": [ "Parkinson's disease" ], "offsets": [ [ 46, 65 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "20615", "type": "Chemical", "text": [ "Levodopa" ], "offsets": [ [ 101, 109 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "20616", "type": "Disease", "text": [ "Parkinson's disease" ], "offsets": [ [ 158, 177 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "20617", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 214, 222 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "20618", "type": "Disease", "text": [ "dyskinesias" ], "offsets": [ [ 285, 296 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "20619", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 436, 444 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "20620", "type": "Disease", "text": [ "dyskinesias" ], "offsets": [ [ 453, 464 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "20621", "type": "Disease", "text": [ "Parkinson's disease" ], "offsets": [ [ 551, 570 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010300" } ] }, { "id": "20622", "type": "Disease", "text": [ "dyskinetic movements" ], "offsets": [ [ 721, 741 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] }, { "id": "20623", "type": "Chemical", "text": [ "dopamine" ], "offsets": [ [ 891, 899 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004298" } ] }, { "id": "20624", "type": "Chemical", "text": [ "glutamate" ], "offsets": [ [ 947, 956 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018698" } ] }, { "id": "20625", "type": "Chemical", "text": [ "levodopa" ], "offsets": [ [ 1040, 1048 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007980" } ] }, { "id": "20626", "type": "Disease", "text": [ "dyskinesias" ], "offsets": [ [ 1057, 1068 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004409" } ] } ]

[]

[]

[ { "id": "20627", "type": "CID", "arg1_id": "20612", "arg2_id": "20613", "normalized": [] }, { "id": "20628", "type": "CID", "arg1_id": "20612", "arg2_id": "20618", "normalized": [] }, { "id": "20629", "type": "CID", "arg1_id": "20612", "arg2_id": "20620", "normalized": [] }, { "id": "20630", "type": "CID", "arg1_id": "20612", "arg2_id": "20622", "normalized": [] }, { "id": "20631", "type": "CID", "arg1_id": "20612", "arg2_id": "20626", "normalized": [] }, { "id": "20632", "type": "CID", "arg1_id": "20615", "arg2_id": "20613", "normalized": [] }, { "id": "20633", "type": "CID", "arg1_id": "20615", "arg2_id": "20618", "normalized": [] }, { "id": "20634", "type": "CID", "arg1_id": "20615", "arg2_id": "20620", "normalized": [] }, { "id": "20635", "type": "CID", "arg1_id": "20615", "arg2_id": "20622", "normalized": [] }, { "id": "20636", "type": "CID", "arg1_id": "20615", "arg2_id": "20626", "normalized": [] }, { "id": "20637", "type": "CID", "arg1_id": "20619", "arg2_id": "20613", "normalized": [] }, { "id": "20638", "type": "CID", "arg1_id": "20619", "arg2_id": "20618", "normalized": [] }, { "id": "20639", "type": "CID", "arg1_id": "20619", "arg2_id": "20620", "normalized": [] }, { "id": "20640", "type": "CID", "arg1_id": "20619", "arg2_id": "20622", "normalized": [] }, { "id": "20641", "type": "CID", "arg1_id": "20619", "arg2_id": "20626", "normalized": [] }, { "id": "20642", "type": "CID", "arg1_id": "20625", "arg2_id": "20613", "normalized": [] }, { "id": "20643", "type": "CID", "arg1_id": "20625", "arg2_id": "20618", "normalized": [] }, { "id": "20644", "type": "CID", "arg1_id": "20625", "arg2_id": "20620", "normalized": [] }, { "id": "20645", "type": "CID", "arg1_id": "20625", "arg2_id": "20622", "normalized": [] }, { "id": "20646", "type": "CID", "arg1_id": "20625", "arg2_id": "20626", "normalized": [] } ]

[ { "id": "20648", "type": "title", "text": [ "Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy." ], "offsets": [ [ 0, 151 ] ] }, { "id": "20649", "type": "abstract", "text": [ "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network." ], "offsets": [ [ 152, 1487 ] ] } ]

[ { "id": "20650", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 14, 22 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20651", "type": "Disease", "text": [ "epilepsy" ], "offsets": [ [ 142, 150 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20652", "type": "Disease", "text": [ "epilepsy" ], "offsets": [ [ 263, 271 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20653", "type": "Chemical", "text": [ "pilocarpine" ], "offsets": [ [ 283, 294 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010862" } ] }, { "id": "20654", "type": "Disease", "text": [ "status epilepticus" ], "offsets": [ [ 430, 448 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013226" } ] }, { "id": "20655", "type": "Disease", "text": [ "SE" ], "offsets": [ [ 450, 452 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013226" } ] }, { "id": "20656", "type": "Disease", "text": [ "Spontaneous recurrent seizures" ], "offsets": [ [ 455, 485 ] ], "normalized": [] }, { "id": "20657", "type": "Disease", "text": [ "SRS" ], "offsets": [ [ 487, 490 ] ], "normalized": [] }, { "id": "20658", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 522, 529 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20659", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 584, 593 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20660", "type": "Disease", "text": [ "SRS" ], "offsets": [ [ 618, 621 ] ], "normalized": [] }, { "id": "20661", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 655, 664 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20662", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 677, 685 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20663", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 858, 867 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20664", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 880, 888 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20665", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 946, 955 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20666", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 1197, 1206 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20667", "type": "Disease", "text": [ "epileptic" ], "offsets": [ [ 1296, 1305 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D004827" } ] }, { "id": "20668", "type": "Disease", "text": [ "seizures" ], "offsets": [ [ 1386, 1394 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20669", "type": "Disease", "text": [ "neuronal loss" ], "offsets": [ [ 1403, 1416 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009410" } ] } ]

[]

[]

[ { "id": "20670", "type": "CID", "arg1_id": "20653", "arg2_id": "20651", "normalized": [] }, { "id": "20671", "type": "CID", "arg1_id": "20653", "arg2_id": "20652", "normalized": [] }, { "id": "20672", "type": "CID", "arg1_id": "20653", "arg2_id": "20659", "normalized": [] }, { "id": "20673", "type": "CID", "arg1_id": "20653", "arg2_id": "20661", "normalized": [] }, { "id": "20674", "type": "CID", "arg1_id": "20653", "arg2_id": "20663", "normalized": [] }, { "id": "20675", "type": "CID", "arg1_id": "20653", "arg2_id": "20665", "normalized": [] }, { "id": "20676", "type": "CID", "arg1_id": "20653", "arg2_id": "20666", "normalized": [] }, { "id": "20677", "type": "CID", "arg1_id": "20653", "arg2_id": "20667", "normalized": [] }, { "id": "20678", "type": "CID", "arg1_id": "20653", "arg2_id": "20654", "normalized": [] }, { "id": "20679", "type": "CID", "arg1_id": "20653", "arg2_id": "20655", "normalized": [] } ]

[ { "id": "20681", "type": "title", "text": [ "Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats." ], "offsets": [ [ 0, 101 ] ] }, { "id": "20682", "type": "abstract", "text": [ "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction." ], "offsets": [ [ 102, 1725 ] ] } ]

[ { "id": "20683", "type": "Chemical", "text": [ "salvianolic acid A" ], "offsets": [ [ 27, 45 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C066201" } ] }, { "id": "20684", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 49, 62 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20685", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 71, 92 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "20686", "type": "Chemical", "text": [ "salvianolic acid A" ], "offsets": [ [ 179, 197 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C066201" } ] }, { "id": "20687", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 201, 214 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20688", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 223, 244 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] }, { "id": "20689", "type": "Chemical", "text": [ "Isoproterenol" ], "offsets": [ [ 556, 569 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20690", "type": "Chemical", "text": [ "lactate" ], "offsets": [ [ 629, 636 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D019344" } ] }, { "id": "20691", "type": "Chemical", "text": [ "aspartate" ], "offsets": [ [ 652, 661 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001224" } ] }, { "id": "20692", "type": "Chemical", "text": [ "creatine" ], "offsets": [ [ 676, 684 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D003401" } ] }, { "id": "20693", "type": "Chemical", "text": [ "malondialdehyde" ], "offsets": [ [ 696, 711 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D008315" } ] }, { "id": "20694", "type": "Chemical", "text": [ "superoxide" ], "offsets": [ [ 759, 769 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D013481" } ] }, { "id": "20695", "type": "Chemical", "text": [ "glutathione" ], "offsets": [ [ 794, 805 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005978" } ] }, { "id": "20696", "type": "Disease", "text": [ "respiratory dysfunction" ], "offsets": [ [ 1073, 1096 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012131" } ] }, { "id": "20697", "type": "Chemical", "text": [ "ADP" ], "offsets": [ [ 1154, 1157 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000244" } ] }, { "id": "20698", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 1176, 1189 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20699", "type": "Chemical", "text": [ "salvianolic acid A" ], "offsets": [ [ 1222, 1240 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C066201" } ] }, { "id": "20700", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 1289, 1302 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20701", "type": "Disease", "text": [ "cardiac dysfunction" ], "offsets": [ [ 1311, 1330 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D006331" } ] }, { "id": "20702", "type": "Disease", "text": [ "myocardial injury" ], "offsets": [ [ 1335, 1352 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "20703", "type": "Chemical", "text": [ "salvianolic acid A" ], "offsets": [ [ 1425, 1443 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C066201" } ] }, { "id": "20704", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 1452, 1465 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20705", "type": "Disease", "text": [ "myocardial damage" ], "offsets": [ [ 1474, 1491 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009202" } ] }, { "id": "20706", "type": "Chemical", "text": [ "salvianolic acid A" ], "offsets": [ [ 1586, 1604 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C066201" } ] }, { "id": "20707", "type": "Chemical", "text": [ "isoproterenol" ], "offsets": [ [ 1681, 1694 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D007545" } ] }, { "id": "20708", "type": "Disease", "text": [ "myocardial infarction" ], "offsets": [ [ 1703, 1724 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D009203" } ] } ]

[]

[]

[ { "id": "20709", "type": "CID", "arg1_id": "20684", "arg2_id": "20685", "normalized": [] }, { "id": "20710", "type": "CID", "arg1_id": "20684", "arg2_id": "20688", "normalized": [] }, { "id": "20711", "type": "CID", "arg1_id": "20684", "arg2_id": "20708", "normalized": [] }, { "id": "20712", "type": "CID", "arg1_id": "20687", "arg2_id": "20685", "normalized": [] }, { "id": "20713", "type": "CID", "arg1_id": "20687", "arg2_id": "20688", "normalized": [] }, { "id": "20714", "type": "CID", "arg1_id": "20687", "arg2_id": "20708", "normalized": [] }, { "id": "20715", "type": "CID", "arg1_id": "20689", "arg2_id": "20685", "normalized": [] }, { "id": "20716", "type": "CID", "arg1_id": "20689", "arg2_id": "20688", "normalized": [] }, { "id": "20717", "type": "CID", "arg1_id": "20689", "arg2_id": "20708", "normalized": [] }, { "id": "20718", "type": "CID", "arg1_id": "20698", "arg2_id": "20685", "normalized": [] }, { "id": "20719", "type": "CID", "arg1_id": "20698", "arg2_id": "20688", "normalized": [] }, { "id": "20720", "type": "CID", "arg1_id": "20698", "arg2_id": "20708", "normalized": [] }, { "id": "20721", "type": "CID", "arg1_id": "20700", "arg2_id": "20685", "normalized": [] }, { "id": "20722", "type": "CID", "arg1_id": "20700", "arg2_id": "20688", "normalized": [] }, { "id": "20723", "type": "CID", "arg1_id": "20700", "arg2_id": "20708", "normalized": [] }, { "id": "20724", "type": "CID", "arg1_id": "20704", "arg2_id": "20685", "normalized": [] }, { "id": "20725", "type": "CID", "arg1_id": "20704", "arg2_id": "20688", "normalized": [] }, { "id": "20726", "type": "CID", "arg1_id": "20704", "arg2_id": "20708", "normalized": [] }, { "id": "20727", "type": "CID", "arg1_id": "20707", "arg2_id": "20685", "normalized": [] }, { "id": "20728", "type": "CID", "arg1_id": "20707", "arg2_id": "20688", "normalized": [] }, { "id": "20729", "type": "CID", "arg1_id": "20707", "arg2_id": "20708", "normalized": [] } ]

[ { "id": "20731", "type": "title", "text": [ "Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats." ], "offsets": [ [ 0, 126 ] ] }, { "id": "20732", "type": "abstract", "text": [ "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated." ], "offsets": [ [ 127, 1786 ] ] } ]

[ { "id": "20733", "type": "Chemical", "text": [ "N-(2-propylpentanoyl)urea" ], "offsets": [ [ 17, 42 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C108761" } ] }, { "id": "20734", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 58, 68 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000596" } ] }, { "id": "20735", "type": "Chemical", "text": [ "pilocarpine" ], "offsets": [ [ 90, 101 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010862" } ] }, { "id": "20736", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 110, 117 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20737", "type": "Chemical", "text": [ "amino acid" ], "offsets": [ [ 245, 255 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D000596" } ] }, { "id": "20738", "type": "Chemical", "text": [ "glutamate" ], "offsets": [ [ 275, 284 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018698" } ] }, { "id": "20739", "type": "Chemical", "text": [ "aspartate" ], "offsets": [ [ 286, 295 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001224" } ] }, { "id": "20740", "type": "Chemical", "text": [ "glycine" ], "offsets": [ [ 297, 304 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005998" } ] }, { "id": "20741", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 309, 313 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "20742", "type": "Chemical", "text": [ "N-(2-propylpentanoyl)urea" ], "offsets": [ [ 318, 343 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C108761" } ] }, { "id": "20743", "type": "Chemical", "text": [ "VPU" ], "offsets": [ [ 345, 348 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C108761" } ] }, { "id": "20744", "type": "Chemical", "text": [ "valproic acid" ], "offsets": [ [ 388, 401 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "20745", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 403, 406 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "20746", "type": "Chemical", "text": [ "VPU" ], "offsets": [ [ 409, 412 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C108761" } ] }, { "id": "20747", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 434, 437 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "20748", "type": "Chemical", "text": [ "pilocarpine" ], "offsets": [ [ 524, 535 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010862" } ] }, { "id": "20749", "type": "Disease", "text": [ "seizure" ], "offsets": [ [ 544, 551 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D012640" } ] }, { "id": "20750", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 588, 591 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "20751", "type": "Chemical", "text": [ "pilocarpine" ], "offsets": [ [ 684, 695 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010862" } ] }, { "id": "20752", "type": "Chemical", "text": [ "glutamate" ], "offsets": [ [ 742, 751 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D018698" } ] }, { "id": "20753", "type": "Chemical", "text": [ "aspartate" ], "offsets": [ [ 756, 765 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D001224" } ] }, { "id": "20754", "type": "Chemical", "text": [ "glycine" ], "offsets": [ [ 825, 832 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005998" } ] }, { "id": "20755", "type": "Chemical", "text": [ "GABA" ], "offsets": [ [ 837, 841 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D005680" } ] }, { "id": "20756", "type": "Chemical", "text": [ "VPU" ], "offsets": [ [ 868, 871 ] ], "normalized": [ { "db_name": "MESH", "db_id": "C108761" } ] }, { "id": "20757", "type": "Chemical", "text": [ "VPA" ], "offsets": [ [ 894, 897 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D014635" } ] }, { "id": "20758", "type": "Chemical", "text": [ "pilocarpine" ], "offsets": [ [ 939, 950 ] ], "normalized": [ { "db_name": "MESH", "db_id": "D010862" } ] }, { "id": "20759", 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[]

[]

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