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Sample records for agranulocytosis

  1. Pentazocine-induced agranulocytosis.

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    Sheehan, Meg; Hyland, Robert H; Norman, Conolly

    1984-01-01

    A 46-year-old man with pentazocine-induced agranulocytosis is described. In previously reported cases of a complete absence of mature neutrophils in the peripheral blood and bone marrow the patients had undergone marrow-depressing treatment with radiation and antineoplastic drugs. This case is unique in that the patient had complete agranulocytosis without predisposing factors.

  2. Late onset clozapine induced agranulocytosis

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    Rajmohan Velayudhan

    2014-01-01

    Full Text Available Agranulocytosis is defined as an absolute neutrophil count less than 100/mm 3 in association with infectious disease. The risk of agranulocytosis is 0.38% of all clozapine treated cases and there is a relatively lesser incidence in Indian population. The risk of clozapine-induced agranulocytosis and neutropenia is highest in the first 6 months and higher in the initial 18 months after the onset of treatment. There have been very few reports of neutropenia and agranulocytosis after this period. There have so far been no reports of late onset clozapine induced agranulocytosis has been reported from India. A case of late onset clozapine induced agranulocytosis with possible mechanism of the same is reported.

  3. Carbimazole-induced agranulocytosis

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    Anisha Mohan

    2015-01-01

    Full Text Available A 47 year old lady with hyperthyroidism for past 1½ years was initially on Carbimazole 20 mg orally then changed to 30 mg (during Hysterectomy but was taking 10 mg for last 1 year. She had intermittent fever with severe B/L bifrontal headache since 3 weeks. Routine investigations showed anaemia, neutropenia, leucopenia and CRP elevation. Peripheral smear showed normocytic normochromic anaemia with Rouleaux formation, leucopenia with 2% atypical cells and mild thrombocytosis. Widal test, RA factor (Rheumatoid factor test, Ig M (Immunoglobulin M dengue, Ig M Lepto, TORCH infections (Toxoplasmosis, Other (Syphilis, varicella-zoster, parvovirus B19, Cytomegalovirus and Herpes infections, ANA (Antinuclear antibody screen cANCA (Cytoplasmic antineutrophil cytoplasmic antibodies and pANCA (Perinuclear Anti-Neutrophil Cytoplasmic Antibodies tests were negative. Bone marrow aspiration showed normo to hypercellular marrow with 15% atypical cells and plasma cells. Multiple myeloma workup was done. Carbimazole was withheld. Conclusion: Drug induced agranulocytosis occurs with in 1-2 months of taking the antithyroid medication but onset delayed by 1½ year. De-challenge resulted normalization of blood parameters.

  4. [Case of agranulocytosis associated with thymoma].

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    Sato, Keita; Nojiri, Satoko; Numata, Takanori; Kinoshita, Akira; Sakaguchi, Shinji; Homma, Sakae

    2008-02-01

    A 75-year-old-woman had undergone extended thymectomy, right upper and middle lobe resection, and radiation therapy (40 Gy) for thymoma at the age of 63. She visited our hospital complaining of low grade fever, cough, anorexia and a sore throat. Peripheral blood count revealed agranulocytosis. Agranulocytosis associated with thymoma was diagnosed, because there were no other possible causes of agranulocytosis such as drugs, infection, recent radiation therapy, or bone marrow invasion. In spite of giving G-CSF, steroid therapy and immunosuppressants, she died of pneumonia caused by agranulocytosis. We consider that agranulocytosis is a very rare complication of thymoma. PMID:18318251

  5. Agranulocytosis after Metamizole Sodium Use

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    Eren Cagan

    2015-09-01

    Full Text Available Metamizole sodium (Novalgine is commonly used as an antipyretic, analgesic, and spasmolytic agent in some parts of the world and our country; however, it is banned in developed countries because of severe side effects. Here we present a case of a three-years- four- months-old girl who developed life-threatening agranulocytosis in his bone marrow after metamizole sodium use for fever, which resolved with granulocyte colony-stimulating factor therapy. [Cukurova Med J 2015; 40(3.000: 580-583

  6. Non-chemotherapy drug-induced agranulocytosis.

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    Garbe, Edeltraut

    2007-05-01

    Acute agranulocytosis is a rare, potentially life-threatening condition, which is attributable to drugs in > 70% of cases. Agranulocytosis is characterised by a peripheral neutrophil count clozapine, ticlopidine, sulfasalazine, dipyrone, trimethoprim/sulfamethoxazole, carbamazepine and probably rituximab. Suspect drugs should be stopped immediately. In febrile patients, blood cultures and, where indicated, site-specific cultures should be obtained and treatment with empirical broad spectrum antibiotics started. Haematopoietic growth factors should be considered in patients with poor prognostic factors (e.g., a neutrophil count < 0.1 x 10(9)/l), severe clinical infection or severe underlying disease or comorbidity. Case fatality has decreased to ~ 5% in recent years, probably owing to improved intensive care treatment and increased alertness of physicians to this severe adverse reaction. PMID:17480181

  7. Drug-induced immune neutropenia/agranulocytosis.

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    Curtis, Brian R

    2014-01-01

    Neutrophils are the most abundant white blood cell in blood and play a critical role in preventing infections as part of the innate immune system. Reduction in neutrophils below an absolute count of 500 cells/pL is termed severe neutropenia or agranulocytosis. Drug-induced immune neutropenia (DIIN) occurs when drug-dependent antibodies form against neutrophil membrane glycoproteins and cause neutrophil destruction. Affected patients have fever, chills, and infections; severe infections left untreated can result in death. Treatment with granulocyte colony-stimulating factor can hasten neutrophil recovery. Cumulative data show that severe neutropenia or agranulocytosis associated with exposure to nonchemotherapy drugs ranges from approximately 1.6 to 15.4 cases per million population per year. Drugs most often associated with neutropenia or agranulocytosis include dipyrone, diclofenac, ticlopidine, calcium dobesilate, spironolactone, antithyroid drugs (e.g., propylthiouracil), carbamazepine, sulfamethoxazole- trimethoprim, [3-lactam antibiotics, clozapine, levamisole, and vancomycin. Assays used for detection of neutrophil drug-dependent antibodies (DDAbs) include flow cytometry, monoclonal antibody immobilization of granulocyte antigens, enzyme-linked immunosorbent assay, immunoblotting, granulocyte agglutination, and granulocytotoxicity. However, testing for neutrophil DDAbs is rarely performed owing to its complexity and lack of availability. Mechanisms proposed for DIIN have not been rigorously studied, but those that have been studied include drug- or hapten-induced antibody formation and autoantibody production against drug metabolite or protein adducts covalently attached to neutrophil membrane proteins. This review will address acute, severe neutropenia caused by neutrophil-reactive antibodies induced by nonchemotherapy drugs-DIIN PMID:25247619

  8. [Acute airway obstruction during chemotherapy-induced agranulocytosis with fever].

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    Vandenbos, F; Deswardt, Ph; Hyvernat, H; Burel-Vandenbos, F; Bernardin, G

    2006-02-01

    Acute airway obstruction caused by mucoid impaction can cause sometimes life-threatening respiratory distress. Bronchial plugging is usually observed in subjects with chronic diseases such as asthma, allergic bronchopulmonary aspergillosis, or cystic fibrosis. In children, it can be related to heart failure. Acute airway obstruction in a patient without a chronic respiratory disease is exceptional. We report the case of a patient who developed bronchial plugs obstructing the bronchi during a period of agranulocytosis induced by chemotherapy. The patient experienced acute respiratory distress with asphyxia. The plugs were composed of fibrin and required several fibroscopic procedures for clearance. To our knowledge, this is the first case report of acute airway obstruction by plugging during a period of agranulocytosis. PMID:16604039

  9. Antithyroid Drug-induced Agranulocytosis: Report of 13 Cases

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    Jyuhn-Huarng Juang

    2007-06-01

    Full Text Available Background: Antithyroid drug (ATD-induced agranulocytosis is rare but may cause fatalcomplications in patients with thyrotoxicosis during treatment with thionamide-derived drugs. From our previous experience, we note that 2 of 11such patients died in a 10-year retrospective study.Methods: We reviewed thirteen patients who developed agranulocytosis from 7,466patients with hyperthyroidism while they were being treated with ATD fromJuly 1989 to November 2003.Results: The incidence of ATD-induced agranulocytosis (absolute neutrophil counts< 500/mm3 was 0.17%. The age of the 13 patients (female: male = 10:3 was28 to 61 years (mean SD: 39.6 10.0 years. The most common clinicalmanifestations were fever (100%, sore throat (76.9% and chills (46.1%. Atthe time of agranulocytosis attack, ATD had been administered for 12 to 66days (mean SD: 36.4 18.7 days and the duration of symptoms was 1 to14 days (mean SD: 4.6 3.7 days. Intravenous infusion of 300 μg granulocytecolony-stimulating factor (G-CSF per day was administered to 3patients simultaneously with intravenous empirical broad-spectrum antibiotics.After intensive and supportive treatment in hospital, all the patientsrecovered with absolute neutrophil counts of more than 500/mm3 in 2 to 13days (mean SD: 7.6 3.4 days.Conclusions: In our 25-year clinical experience, the most cost-effective method of managingagranulocytosis induced by thionamide-derived ATD is that all patientswith thyrotoxicosis must be warned that their white blood cells and differentialcounts should be checked immediately whenever the “common cold”symptoms occur during treatment, especially within the first 3 months ofmedication.

  10. Toxic epidermal necrolysis and agranulocytosis: Rare adverse effects of ciprofloxacin

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    Upadya Gatha; Ruxana K

    2009-01-01

    Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis....

  11. Agranulocytosis and hepatic toxicity with ticlopidine therapy: a case report

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    Previtera Antonino M; Pagani Rossella

    2010-01-01

    Abstract Introduction Ticlopidine is a platelet inhibitor used to prevent thrombosis in patients with cerebrovascular or coronary artery disease. The most common side effects are mild and transitory: diarrhea, dyspepsia, nausea and rashes. More serious, but less frequent, adverse effects are hematological dyscrasia and cholestatic hepatitis. We report a rare case of agranulocytosis associated with hepatic toxicity, probably related to the use of ticlopidine. Case presentation A 70-year-old Ca...

  12. Toxic epidermal necrolysis and agranulocytosis: Rare adverse effects of ciprofloxacin

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    Upadya Gatha

    2009-10-01

    Full Text Available Ciprofloxacin is one of the most commonly used antibacterial agents with relatively few side effects. Serious adverse reactions reported with ciprofloxacin are rare with an incidence of 0.6%. Recently we came across two rare adverse effects of ciprofloxacin, viz. toxic epidermal necrolysis and agranulocytosis. To our knowledge, a total of seven cases have been reported in the literature documenting an association between oral ciprofloxacin administration and toxic epidermal necrolysis. One case of granulocytopenia, four of pancytopenia and fifteen of leucopenia worldwide have been reported. With the use of ciprofloxacin becoming more and more widespread, these two rare but fatal complications of ciprofloxacin should be borne in mind.

  13. Agranulocytosis and hepatic toxicity with ticlopidine therapy: a case report

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    Previtera Antonino M

    2010-08-01

    Full Text Available Abstract Introduction Ticlopidine is a platelet inhibitor used to prevent thrombosis in patients with cerebrovascular or coronary artery disease. The most common side effects are mild and transitory: diarrhea, dyspepsia, nausea and rashes. More serious, but less frequent, adverse effects are hematological dyscrasia and cholestatic hepatitis. We report a rare case of agranulocytosis associated with hepatic toxicity, probably related to the use of ticlopidine. Case presentation A 70-year-old Caucasian woman, with no previous history of hematological or liver diseases, was treated with ticlopidine 250 mg twice daily immediately after a vertebrobasilar stroke. Upon admission, her blood tests were normal. About four weeks later she developed agranulocytosis and hepatic toxicity. Ticlopidine was discontinued immediately, and aspirin 25 mg and dipyridamole 200 mg were given twice daily. She was treated with hematopoietic growth factors (granulocyte colony stimulating factor, with a rapidly increased white blood count and progressive normalization of liver tests as a result. Conclusion In the first three months following initiation of ticlopidine therapy, regular monitoring of complete blood cell count and of liver function tests is essential for the early detection of serious and unpredictable side effects.

  14. Failure of filgrastim to prevent severe clozapine-induced agranulocytosis.

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    Majczenko, Tricia G; Stewart, Jonathan T

    2008-06-01

    Although a highly effective medication, the usage of clozapine is limited mostly by its 2.7% incidence of neutropenia. It is often a treatment of last resort for patients with severe psychiatric illnesses, and therefore often the only medication to which a patient has responded. There has thus been a great deal of interest in ways to continue the medication in spite of emergent blood dyscrasias. There have been several reports documenting the successful continuation of clozapine in spite of neutropenia by adding granulocyte colony-stimulating factors such as filgrastim. This strategy was unsuccessful for a 63-year-old man, resulting in severe, prolonged agranulocytosis. Although a promising strategy for such refractory patients, its inherent dangers should not be underestimated. PMID:18475227

  15. THE APPLICATION OF HEMATOPOIETIC GROWTH-FACTORS IN DRUG-INDUCED AGRANULOCYTOSIS - A REVIEW OF 70 CASES

    NARCIS (Netherlands)

    SPRIKKELMAN, A; DEWOLF, JTM; VELLENGA, E

    1994-01-01

    Since 1989, granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF, G-CSF) have been increasingly applied in the treatment of drug-induced agranulocytosis. In order to evaluate the effectiveness of GM-CSF and G-CSF in the treatment of drug-induced agranulocytosis, we have studied

  16. Agranulocytosis and acute coronary syndrom in apathetic hyperthyreoidism

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    Ivović Miomira

    2003-01-01

    Full Text Available INTRODUCTION Tissue expose to excessive levels of circulating thyroid hormones results in thyrotoxicosis. In most cases, thyrotoxicosis is due to hyper-activity of the thyroid gland. Cardiovascular and myopathic manifestations are predominant clinical features in most hyperthyroid patients, aged 60 years and older. Some of patients have apathetic hyperthyreoidism which presents with weight loss, small goiter, severe depression and without clinical features of increased sympathetic activity [3, 6]. About 50% of patients with cardiovascular manifestations have no evidence of underlying heart disease. Cardiac problems resolve when euthyreoid state is established [3]. Three treatment modalities are available in hyperthyreodism, namely medicament therapy, surgery and radioactive iodine. Antithyroid drug therapy complications, can be mild such as rash, which is managed without cessation of therapy by antihistamines administration. On the other hand, very serious complications such as agranulocytosis, necessitate immediate discontinuation of the medication and appropriate treatment. Although extremely rear, it is life-threatening with highly variable recovery time. CASE REPORT A 62-year-old woman with recurrent hyperthyroidism was admitted after treatment of agranu locytosis due to antithyroid drugs in another institution with G-CSF. The patient presented with clinical features of apathetic hyperthyroidism with extremely elevated thyroid hormone levels (total and free T4 and suppressed TSH. Radioactive iodine (5 mCi was administered after increased thyroid uptake was confirmed. Echocardiography on admission was normal. ECG revealed moderately inverted T waves in standard and V1, V2 precordial leads. Laboratory analysis revealed mild normocytic anemia with normal white blood cell count, hypokaliemia and normal concentration of creatine phosphokinase lactic dehidrogenase and mildly elevated aspartate transaminase in sera. Chest X-ray was consistent with

  17. Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis

    DEFF Research Database (Denmark)

    Nielsen, H

    1993-01-01

    After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease...

  18. Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

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    Singh, Aakanksha; Grover, Sandeep; Malhotra, Pankaj; Varma, Subhash C.

    2016-01-01

    Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozapine and this has very rarely been linked to human leukocyte-antigen haplotypes vulnerability. In this report we review the existing data on late onset agranulocytosis with clozapine and describe the case of a young man, who developed agranulocytosis with clozapine after 35 months of treatment and was found to have genetic vulnerability in form of being positive for HLA DR4. This case highlights underlying autoimmune immune mechanism in clozapine-induced agranulocytosis and the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with genetic vulnerability to develop this condition. PMID:27121434

  19. Relation of the Allelic Variants of Multidrug Resistance Gene to Agranulocytosis Associated With Clozapine.

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    Anil Yağcioğlu, A Elif; Yoca, Gökhan; Ayhan, Yavuz; Karaca, R Özgür; Çevik, Lokman; Müderrisoğlu, Ahmet; Göktaş, Mustafa T; Eni, Nurhayat; Yazici, M Kâzim; Bozkurt, Atilla; Babaoğlu, Melih O

    2016-06-01

    Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA). Ten patients with a history of CAA and 91 control patients without a history of CAA, despite 10 years of continuous clozapine use, were included. Patient recruitment and blood sample collection were conducted at the Hacettepe University Faculty of Medicine, Department of Psychiatry, in collaboration with the members of the Schizophrenia and Other Psychotic Disorders Section of the Psychiatric Association of Turkey, working in various psychiatry clinics. After DNA extraction from peripheral blood lymphocytes, genotyping was performed using polymerase chain reaction and endonuclease digestion. Patients with CAA had shorter duration of clozapine use but did not show any significant difference in other clinical, sociodemographic characteristics and in genotypic or allelic distributions of ABCB1 variants and haplotypes compared with control patients. Among the 10 patients with CAA, none carried the ABCB1 all-variant haplotype (TT-TT-TT), whereas the frequency of this haplotype was approximately 12% among the controls. Larger sample size studies and thorough genetic analyses may reveal both genetic risk and protective factors for this serious adverse event. PMID:27043126

  20. Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

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    Goldstein, Jacqueline I; Jarskog, L Fredrik; Hilliard, Chris; Alfirevic, Ana; Duncan, Laramie; Fourches, Denis; Huang, Hailiang; Lek, Monkol; Neale, Benjamin M; Ripke, Stephan; Shianna, Kevin; Szatkiewicz, Jin P; Tropsha, Alexander; van den Oord, Edwin JCG; Cascorbi, Ingolf; Dettling, Michael; Gazit, Ephraim; Goff, Donald C; Holden, Arthur L; Kelly, Deanna L; Malhotra, Anil K; Nielsen, Jimmi; Pirmohamed, Munir; Rujescu, Dan; Werge, Thomas; Levy, Deborah L; Josiassen, Richard C; Kennedy, James L; Lieberman, Jeffrey A; Daly, Mark J; Sullivan, Patrick F

    2014-01-01

    Clozapine is a particularly effective antipsychotic medication but its use is curtailed by the risk of clozapine-induced agranulocytosis/granulocytopenia (CIAG), a severe adverse drug reaction occurring in up to 1% of treated individuals. Identifying genetic risk factors for CIAG could enable safer and more widespread use of clozapine. Here we perform the largest and most comprehensive genetic study of CIAG to date by interrogating 163 cases using genome-wide genotyping and whole-exome sequencing. We find that two loci in the major histocompatibility complex are independently associated with CIAG: a single amino acid in HLA-DQB1 (126Q) (P=4.7×10−14, odds ratio, OR=0.19, 95% CI 0.12–0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P=6.4×10−10, OR=3.3, 95% CI 2.3–4.9). These associations dovetail with the roles of these genes in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG. PMID:25187353

  1. Carbimazole-induced agranulocytosis

    OpenAIRE

    Anisha Mohan; Siby Joseph; Neeraj Sidharthan; Dhanya Murali

    2015-01-01

    A 47 year old lady with hyperthyroidism for past 1½ years was initially on Carbimazole 20 mg orally then changed to 30 mg (during Hysterectomy) but was taking 10 mg for last 1 year. She had intermittent fever with severe B/L bifrontal headache since 3 weeks. Routine investigations showed anaemia, neutropenia, leucopenia and CRP elevation. Peripheral smear showed normocytic normochromic anaemia with Rouleaux formation, leucopenia with 2% atypical cells and mild thrombocytosis. Widal test, RA f...

  2. 弥漫性毒性甲状腺肿患者白细胞减少/缺乏的机制及治疗%Pathogenesis and treatment of patients with Graves disease presenting with leucopenia or agranulocytosis

    Institute of Scientific and Technical Information of China (English)

    张荣金; 郝咏梅

    2016-01-01

    ABSTRACT:Graves disease is one of the most common endocrine diseases.Leucopenia or agranulocytosis can be coexistent with Graves'disease in some patients.It can be seen in patients before treatment and after anti-thyroid medication.This phenomenon is often delayed in clinical diagnosis and treatment,which sometimes causes serious infections and makes the disease worse.According to the research progress in the recent years,including the diagnosis, pathogenesis and treatment about the desease,the authors aim to show early discovery and timely treatment in patients with Graves’disease presenting with leucopenia or agranulocytosis.%弥漫性毒性甲状腺肿(Graves 病)是内分泌常见疾病,白细胞减少/缺乏是 Graves 病常见的合并症之一,可以发生在治疗之前和抗甲状腺药物治疗之后,在临床上经常被延误诊断和治疗,有时导致严重感染而使病情加重。本文就近几年来的研究进展,主要对其诊断、发病机制和治疗方面进行综述,着重论述临床如何早期发现与及时治疗。

  3. A clinical analysis of 361 cases of Graves disease combined with neutropenia or agranulocytosis%Graves 病合并粒细胞减少或缺乏361例临床分析

    Institute of Scientific and Technical Information of China (English)

    闫文博; 秦贵军

    2016-01-01

    Objective To explore the prevalence and the correlation factors of neutropenia or agranulocytosis in patients with Graves disease.Methods The clinical data of 361 patients diagnosed as Graves disease in General Hospital of Pingmei Shenma Medical Group from February of 201 0 to February of 201 5 were analyzed retrospectively.Results Among 361 patients,there were altogether 1 27 patients with neutropenia or agranulocytosis(35.1 8%),1 23 with neutropenia(34.07%),4 with agranulocy-tosis(1 .1 1 %).Among the 1 27 cases,72 (56.69%)were caused by Graves disease,and 55 were caused by antithyroid drugs (ATD)(43.31 %).Among neutropenia or agranulocytosis caused by Graves disease itself,the neutrophil count were negatively correlated with age,free triiodothyronine (FT3 ),free thyroxine(FT4 )and TSH receptor stimulation antibody(TSAb).Conclu-sion The incidence of neutropenia was relatively high in patients with Graves disease,and the neutropenia induced by Graves disease itself may be related with the degree of hyperthyroidism.%目的:探讨 Graves 病患者合并粒细胞减少或缺乏的发生率及相关因素。方法对平煤神马医疗集团总医院2010年2月至2015年2月收治的361例 Graves 患者的临床资料进行回顾性分析。结果361例 Graves 患者中,粒细胞减少或缺乏127例(35.18%):粒细胞减少123例(34.07%),粒细胞缺乏4例(1.11%)。其中 Graves 疾病本身导致者72例(56.69%),抗甲状腺药物(ATD)导致者55例(43.31%)。在 Graves 疾病本身所致的粒细胞减少或缺乏中,粒细胞计数与年龄、FT3、FT4、TSH 受体刺激性抗体(TSAb)呈负相关。结论Graves 病患者合并粒细胞减少的发生率较高,其疾病本身所导致的粒细胞减少可能与甲亢的病情程度相关。

  4. Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles

    DEFF Research Database (Denmark)

    Goldstein, Jacqueline I; Fredrik Jarskog, L; Hilliard, Chris;

    2014-01-01

    CIAG: a single amino acid in HLA-DQB1 (126Q) (P=4.7 × 10(-14), odds ratio (OR)=0.19, 95% confidence interval (CI)=0.12-0.29) and an amino acid change in the extracellular binding pocket of HLA-B (158T) (P=6.4 × 10(-10), OR=3.3, 95% CI=2.3-4.9). These associations dovetail with the roles of these genes...

  5. Case Report. Prevention of Clozapine-Induced Granulocytopenia/Agranulocytosis with Granulocyte-Colony Stimulating Factor (G-CSF) in an Intellectually Disabled Patient with Schizophrenia

    Science.gov (United States)

    Rajagopal, G.; Graham, J. G.; Haut, F. F. A.

    2007-01-01

    Background: While clozapine is an effective treatment for refractory schizophrenia, its use is limited by haematological side effects. Treatment options that allow continued prescription of clozapine by tackling these side effects will greatly aid patients for whom this medication is all too often their only hope of recovery. Method: In this case…

  6. Itraconazole for secondary prophylaxis of invasive fungal infection in patients undergoing chemotherapy and stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    施继敏

    2013-01-01

    Objective To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.

  7. Omeprazole-induced Blood Dyscrasia in a Clozapine-treated Patient

    OpenAIRE

    Philipps, Robert J.; Lee Demler, Tammie; Lee, Claudia

    2012-01-01

    Proton pump inhibitors are among the world’s most widely used therapeutic classes. Much of their use is attributed to their documented efficacy and apparent safety. For the most part, proton pump inhibitors are well tolerated with very few serious adverse events reported in the literature. Only a few previously identified case reports of severe neutropenia or agranulocytosis attributed to proton pump inhibitors use have been identified in the literature. However, agranulocytosis, neutropenia,...

  8. Haematological toxicity of drugs used in psychiatry.

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    Flanagan, Robert J; Dunk, Louisa

    2008-01-01

    Almost all classes of psychotropic agents have been reported to cause blood dyscrasias. Mechanisms include direct toxic effects upon the bone marrow, the formation of antibodies against haematopoietic precursors or involve peripheral destruction of cells. Agranulocytosis is probably the most important drug-related blood dyscrasia. The mortality from drug-induced agranulocytosis is 5-10% in Western countries. The manifestations of agranulocytosis are secondary to infection. Aggressive treatment with intravenous broad-spectrum antimicrobials and bone marrow stimulants may be required. Of drugs encountered in psychiatry, antipsychotics including clozapine (risk of agranulocytosis approximately 0.8%, predominantly in the first year of treatment) and phenothiazines (chlorpromazine agranulocytosis risk approximately 0.13%), and antiepileptics (notably carbamazepine, neutropenia risk approximately 0.5%) are the most common causes of drug-related neutropenia/agranulocytosis. Drugs known to cause neutropenia should not be used concomitantly with other drugs known to cause this problem. High temperature and other indicators of possible infection should be looked for routinely during treatment. Clozapine is well known as a drug that can cause blood dyscrasias, but olanzapine and other atypicals may also cause similar problems. In addition to genetic factors, there are likely to be dose-related and immunological components to these phenomena. Important lessons have been learnt from the haematological monitoring that is necessary with clozapine and the monitoring has been very successful in preventing deaths related to clozapine-induced agranulocytosis. Continuing research into the mechanisms of drug-induced neutropenia and agranulocytosis may serve to further enhance the safe use not only of clozapine, but also of other agents. PMID:18098216

  9. Respiratory failure caused by intrathoracic amoebiasis

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    Toshinobu Yokoyama

    2010-03-01

    Full Text Available Toshinobu Yokoyama1, Masashi Hirokawa1, Yutaka Imamura2, Hisamichi Aizawa11Division of Respirology, Neurology and Rheumatology, Department of Internal Medicine, Kurume University, Japan; 2Department of Hematology, St. Mary’s Hospital, Kurume, JapanAbstract: A 41-year-old male was admitted to the hospital with symptoms of diarrhea, fever and rapidly progressive respiratory distress. A chest radiograph and computed tomography (CT of the chest and the abdomen showed a large amount of right pleural effusion and a large liver abscess. The patient was thus diagnosed to have amoebic colitis, amoebic liver abscess and amoebic empyema complicated with an HIV infection. The patient demonstrated agranulocytosis caused by the administration of trimethoprim-sulfamethoxazole. However, the administration of granulocyte colony-stimulating factor made it possible for the patient to successfully recover from agranulocytosis, and he thereafter demonstrated a good clinical course.Keywords: amebiasis, amoebic empyema, HIV, agranulocytosis, trimethoprim-sulfamethoxazole

  10. Antithyroid Drug Side Effects in the Population and in Pregnancy

    DEFF Research Database (Denmark)

    Andersen, Stine Linding; Olsen, Jørn; Laurberg, Peter

    2016-01-01

    OBJECTIVE: Methimazole (MMI) and Propylthiouracil (PTU) are both associated with birth defects, and may also rarely be associated with agranulocytosis and liver failure. The frequency of these side effects when antithyroid drugs (ATD) are used in the population in general or in pregnancy remains to...... be elucidated. DESIGN: All individuals registered as the parent of a live-born child in Denmark, 1973-2008, were identified (n=2,299,952) and studied from 1995-2010 for the use of ATD. Outcomes were agranulocytosis, liver failure and birth defects in their offspring. To evaluate the frequency of......: 0.03% vs. PTU: 0.05%, p=0.4)). The majority (83%) developed the side effect within 3 months of ATD treatment, and 25% during hyperthyroidism relapse. The use of ATD in pregnancy was associated with birth defects in 3.4% of exposed children (44 cases/5 million inhabitants/10 years), and the frequency...

  11. Recombinant TSH and Lithium Overcomes Amiodarone-Induced Low Radioiodine Uptake in a Thyrotoxic Female

    OpenAIRE

    Laplano, Nestor Eric R.; Mercado-Asis, Leilani B.

    2012-01-01

    Introduction: Recombinant human thyroid-stimulating hormone(rhTSH) increases radioactive iodine uptake(RAIU) in selected populations, while lithium is used as an adjunct to radioactive iodine (RAI) therapy in Graves’ disease with low RAIU. In this report, both drugs used in combination, overcame low iodine-131 uptake in a Graves’ patient. Clinical Case: A 39-year old female with Graves’ disease, acquired thionamide-induced agranulocytosis, and severe hypokalemia, subsequently went into cardio...

  12. Development and Evaluation of a Generic HPLC-Tandem MS Screening Method for the Detection of Potential Biomarkers for Reactive Intermediates

    OpenAIRE

    Simon, Karoline

    2007-01-01

    Conjugation of reactive intermediates of drugs with proteins or DNA may result in toxic effects such as hepatotoxicity, agranulocytosis, allergies, tumors, etc. From 1975 to 1999, 2.9% of drugs were withdrawn from the market due to such severe adverse drug reactions. Thus, formation of chemically reactive intermediates is a widely discussed problem in drug development processes. Early detection of potentially toxic compounds is required for drug discovery and drug development. Conjugation of ...

  13. A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine

    OpenAIRE

    Rath Srikanta; Singh Prabhat; Mishra Shrawan

    2011-01-01

    Abstract Background Amodiaquine (AQ) along with sulphadoxine-pyrimethamine (SP) offers effective and cheaper treatment against chloroquine-resistant falciparum malaria in many parts of sub-Saharan Africa. Considering the previous history of hepatitis, agranulocytosis and neutrocytopenia associated with AQ monotherapy, it becomes imperative to study the toxicity of co-administration of AQ and SP. In this study, toxicity and resulting global differential gene expression was analyzed following e...

  14. Are Clozapine Blood Dyscrasias Associated with Concomitant Medications?

    OpenAIRE

    Demler, Tammie Lee; Trigoboff, Eileen

    2011-01-01

    Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carb...

  15. Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania

    DEFF Research Database (Denmark)

    Massaga, J J; Lusingu, J P; Makunde, R; Malebo, H M; Chile, M M; Akida, J A; Lemnge, M M; Rønn, A M; Theander, T G; Bygbjerg, I C; Kitua, A Y

    2008-01-01

    Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi-immune hea......Amodiaquine (AQ), an effective antimalarial drug for uncomplicated malaria, has been greatly restricted after cases of life-threatening agranulocytosis and hepatic toxicity during prophylactic use. We conducted a hospital based open-label randomised clinical trial in 40 indigenous semi......-immune healthy adult male volunteers with and without malaria parasites. The objective was to collect data on biological and haematological safety, tolerability, and parasitological efficacy to serve as baseline in the evaluation of the effectiveness of AQ preventive intermittent treatment against malaria......-treated volunteers. The findings indicate that there was no agranulocytosis or hepatic toxicity suggesting that AQ may pose no public health risk in its wide therapeutic dosage uses. Larger studies are needed to exclude rare adverse effects....

  16. Carbamazepine-induced Stevens Johnson syndrome: a case series of three case reports

    Directory of Open Access Journals (Sweden)

    Arvind Kumar

    2015-08-01

    Full Text Available Carbamazepine is an iminostilbene derivative that was initially used as an antiepileptic but has been used with increased frequency for different indications including chronic pain, trigeminal neuralgia, and herpetic neuralgias. This has resulted in increased incidence of carbamazepine related adverse effects such as nausea, vomiting, and serious hematological toxicities such as aplastic anemia, agranulocytosis, eosinophilia, lymphadenopathy, and splenomegaly. Life-threatening hypersensitivity reactions such as Steven Johnson syndrome (SJS and toxic epidermal necrolysis can also occur. We hereby present a series of three cases that were prescribed carbamazepine for different indications and presented with SJS. [Int J Basic Clin Pharmacol 2015; 4(4.000: 797-801

  17. Techniques for induction of neutropenia and granulocytosis in rats.

    Science.gov (United States)

    Popovic, V; Schaffer, R; Popovic, P

    1976-09-01

    After a single administration of vinblastine, rats develop profound neutropenia. The agranulocytosis lasts 3 days, and it is observed on the third, fourth and fifth day after vinblastine administration. The granulocytosis that develops on days 7-14 after vinblastine administration was significantly increased when androgenic steroids were administered. Deca-Durabolin induced greater granulocytosis than testosterone. The peak values were observed 10 and 12 days, respectively, after drug administration. All values of WBC's, granulocytes and hematocrit ratios were obtained in unanesthetized, unrestrained rats from an aortic cannula implanted at least 10 days prior to the experiment. PMID:976388

  18. [Rare side effects in management of hyperthyroidism. Case report].

    Science.gov (United States)

    Sohár, Gábor; Kovács, Mónika; Györkös, Andrea; Gasztonyi, Beáta

    2016-05-01

    The authors present the case history of a patient suffering from hyperthyroidism. The diagnostic procedures revealed the presence of propylthiouracyl induced vasculitis with renal involvement, that recovered completely after the withdrawal of propylthiouracyl and corticosteroid treatment. Thereafter, the patient was treated with thiamasol, that caused agranulocytosis with fever. After transient litium carbonate therapy a succesful thyreoidectomy was performed. Cumulative serious side effects of antithyroid drugs are rare. This case highlights some of the challenges and complications encountered in the management of hyperthyroidism. Orv. Hetil., 2016, 157(22), 869-872. PMID:27211356

  19. Proportion of drug-related serious rare blood dyscrasias: estimates from the Berlin Case-Control Surveillance Study.

    Science.gov (United States)

    Andersohn, Frank; Bronder, Elisabeth; Klimpel, Andreas; Garbe, Edeltraut

    2004-11-01

    Drugs are an important cause of serious rare blood dyscrasias. To estimate the proportion of drug-related cases, we used data from the ongoing Berlin Case-Control Surveillance Study. The analysis included a total of 171 cases. The number of cases in which a drug etiology was assessed as at least "possible" was n = 29 (97%) for acute agranulocytosis, n = 4 (0.21%) for aplastic anemia, n = 8 (26%) for immune hemolytic anemia, n = 20 (25%) for immune thrombocytopenia, and n = 2 (20%) for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Our analysis suggests that a substantial fraction of blood dyscrasias may be attributable to drug therapy. PMID:15495238

  20. [Haematological adverse effects caused by psychiatric drugs].

    Science.gov (United States)

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  1. Antipsychotic drug-induced hematologic disorders

    Directory of Open Access Journals (Sweden)

    Theocharis Kyziridis

    2014-01-01

    Full Text Available Over half a century after the discovery of chlorpromazine and haloperidol, antipsychotic drugs showed a true evolutionary revolution. The knowledge of their adverse effects is of outmost importance as it may contribute to the prevention of unwanted sequelae, to the decrease of the duration and cost of hospitalization, it may improve the quality of life of patients, minimize the problems and maximize the therapeutic gain. Aim: The aim of this review was the presentation of the hematologic side-effects of antipsychotic drugs, and most particularly their frequency and association with the different classes of these drugs, their clinical picture and their pathophysiologic mechanisms. Material-method: This paper is a review of the literature (mainly articles from journals, PubMed, as well as books and monographs of the period 1978-2012. Key-words used included antipsychotics, hematologic adverse effects, drug-induced adverse effects. Results: Antipsychotic-drug induced hematologic side-effects are not particularly highly prevalent, while many of them are found in case reports. For this reason they have not drawn much of attention. These hematologic dyscrasias may concern all the blood cell series as well as the coagulation mechanism. Excluded from this rule is the case of clozapine-induced agranulocytosis, which demands increased clinical vigilance. In fact, agranulocytosis was the reason why the drug was drawn away from circulation approximately 35 years ago. Conclusions: In any case the appearance of a hematologic disorder in a patient receiving antipsychotic medications should prompt careful evaluation.

  2. Beneficial Effects of Lithium and Radioiodine Therapy in the Treatment of Hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Wojciech Barud

    2014-09-01

    Full Text Available Intravenous contrast media used for coronary angiography are iodine-based and could induce thyroid gland dysfunction. We present the case of a 58-year-old woman with coronary artery disease who developed hyperthyroidism after percutaneus coronary intervention. Treatment with thiamazole induced agranulocytosis, complicated with severe tonsillitis. During recurrence of hyperthyroidism, after careful assessment of available methods of treatment, she was recommended to undergo radioiodine therapy (131I. The patient received lithium carbonate as pre-treatment. After 13 days of pre-treatment, patient received the therapeutic dose of 131I. Neither thyrotoxicosis progression nor acute coronary syndrome occurred. After 3 weeks, her thyroid hormones were found to be within normal ranges. Lithium therapy could be used as an effective treatment in patients who developed serious side-effects due to previous treatment with thionamides. Turk Jem 2014; 18: 92-94

  3. Low back pain after a dental procedure: a case of Streptococcus viridans vertebral osteomyelitis.

    Science.gov (United States)

    Nazir, Salik; Lohani, Saroj; Tachamo, Niranjan; Rajagopalan, Priya

    2016-01-01

    Vertebral osteomyelitis due to Streptococcus viridans following a dental procedure is a rarely reported phenomenon. We discuss the case of a 67-year-old immunocompetent woman who presented with low back pain of 3 weeks duration associated with subjective fever and chills. On admission, the MRI of the lumbar spine showed L5-S1 vertebral osteomyelitis with associated paravertebral and epidural abscesses. Subsequently, detailed history was retaken and the patient reported having had a maxillary tooth extraction followed by a dental implant 2 months prior to the onset of her symptoms. Blood and abscess fluid cultures grew S. viridans Transthoracic echocardiogram showed no evidence of endocarditis. The patient was started on intravenous ceftriaxone but her treatment course was complicated by agranulocytosis requiring a switch to vancomycin. She required a total of 9 weeks of intravenous antibiotics for complete clinical cure. PMID:27268493

  4. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  5. [Cutaneous and mucosal manifestations associated with cocaine use].

    Science.gov (United States)

    Imbernón-Moya, Adrián; Chico, Ricardo; Aguilar-Martínez, Antonio

    2016-06-17

    Complications due to cocaine are a public health problem. The typical cutaneous disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting mainly the ears. No intense systemic involvement is usually present, but there may be several cutaneous, mucosal and systemic manifestations. Other findings associated as arthralgia, neutropaenia or agranulocytosis, low titer positive antinuclear antibodies, antiphospholipid antibody positivity and neutrophil cytoplasmic antibodies against multiple antigens help the diagnosis. This disease requires a clinical suspicion with a clinical history, a complete physical examination and a broad differential diagnosis for an early and correct diagnosis. The course is usually self-limited. In most cases the only treatment is to discontinue the use of cocaine associated with symptomatic treatment, no proven benefit of systemic corticosteroids. PMID:27033438

  6. Frequency of neutropenia among Turkish and Syrian pediatric thalassemia patients under deferiprone monotherapy.

    Science.gov (United States)

    Belen, Burcu Fatma; Polat, Meltem; Özsevik, Sevinç Nursev; Soylu, Esma

    2016-02-01

    Weekly monitoring of absolute neutrophil count (ANC) under deferiprone therapy in thalassemia patients is recommended to avoid agranulocytosis adverse event. Actually, this recommendation may not be applicable in clinical setting. Our study aimed to establish incidence of neutropenia under deferiprone (DFP) monotherapy when it was monitored bimonthly due to socioeconomic conditions effecting local and refugee thalassemic patients including Syrian origin (SYR; n = 26) and Turkish origin (TR; n = 26) groups. Patients on DFP were followed up for 12 months. Fifteen neutropenic episodes were seen in 5 patients. All 5 patients (4 from SYR group and 1 from TR group) had splenomegaly and hypersplenism, and neutropenia ceased in 4 patients after splenectomy despite continuation of deferiprone. In the TR group, the frequency of patients who have neutropenia (absolute neutrophil count [ANC] studies. Other causes of neutropenia in DFP-treated patients should also be kept in mind. PMID:26918459

  7. Diagnosis of bone marrow lesions in the MR tomogram in children suffering from diseases of the haematopoietic system with special reference to post-therapy changes

    International Nuclear Information System (INIS)

    119 MR-examinations of both tibiae, knees and the lower part of both femura were performed in 41 children suffering from bone marrow disease (27 ALL, 4 AML, 3 NHL, 1 agranulocytosis, 6 anaemia). T1- and T2-spinecho sequences and a T2-gradientecho sequence were used. Bone marrow changes in leukaemia were diffuse before therapy and patchy after therapy. Due to their different signal in T2-weighted images, differentitation of the post-therapeutic patchy findings into infiltrations, fibrosis, necrosis and siderosis seems to be possible. In future, MRI will be the method of choice for screening and controlling bone marrow disease if the examination time is shortened by using only a T1-spinecho sequence and a T2-gradient-echo sequence. (orig.)

  8. Invasive aspergillosis: results of multicenter study

    Directory of Open Access Journals (Sweden)

    N. N. Klimko

    2014-01-01

    Full Text Available We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008. Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %, main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %, cytostatic chemotherapy (57 %, corticosteroid treatment (45 %, and allogeneic hematopoietic stem cells transplantation (29 %. The pathogens – A. fumigatus (42 %, A. niger (33 %, and A. flavus (21 %. The main site of infection were lungs (86 %. 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01, adequatetherapy with voriconazole (p = 0.002 and secondary antifungal prophylaxis (p = 0.0003 were positive prognostic factors for survival of patients with invasive aspergillosis.

  9. Invasive aspergillosis: results of multicenter study

    Directory of Open Access Journals (Sweden)

    N. N. Klimko

    2014-09-01

    Full Text Available We present the results of a multicenter study of 445 patients with “proven” and “probable” invasive aspergillosis (EORTC/MSG, 2008. Invasive aspergillosis usually occurs in patients with hematological malignancies (88 %, main underlying diseases were acute myeloid and acute lymphoblastic leukemia. The risk factors: prolonged agranulocytosis (64 %, cytostatic chemotherapy (57 %, corticosteroid treatment (45 %, and allogeneic hematopoietic stem cells transplantation (29 %. The pathogens – A. fumigatus (42 %, A. niger (33 %, and A. flavus (21 %. The main site of infection were lungs (86 %. 12 week overall survival was 83 %. Bronchoscopy use for the early diagnosis (p = 0.01, adequatetherapy with voriconazole (p = 0.002 and secondary antifungal prophylaxis (p = 0.0003 were positive prognostic factors for survival of patients with invasive aspergillosis.

  10. [Fungemia caused by Scedosporium prolificans in myelodysplastic syndrome].

    Science.gov (United States)

    Nishio, Hisaaki; Utsumi, Takahiko; Nakamura, Yukiko; Suzuki, Takayo; Kamei, Katsuhiko; Saitoh, Takashi

    2012-01-01

    We report a case of fungemia caused by Scedosporium prolificans, an emerging pathogen. An 83-year-old man with myelodysplastic syndrome (MDS) and agranulocytosis was admitted for pneumonia in January 2009. He was treated with meropenem, minocycline, and gamma-globulin for pneumonia and G-CSF and platelet transfusion for MDS. Although he recovered from pneumonia as neutrophil count increased, intermittent fever continued. On hospital day 17, blood culture yielded fungal colonies indicating S. prolificans. Voriconazole was started immediately, but the man's general condition deteriorated with cerebral infarction and he died of cerebral hemorrhage on hospital day 65. Attention must therefore be paid to the increasing scedosporiosis incidence in Japan. PMID:22416481

  11. Systematic comparison of the mono-, dimethyl- and trimethyl 3-hydroxy-4(1H)-pyridones - Attempted optimization of the orally active iron chelator, deferiprone.

    Science.gov (United States)

    Xie, Yuan-Yuan; Lu, Zidong; Kong, Xiao-Le; Zhou, Tao; Bansal, Sukhi; Hider, Robert

    2016-06-10

    A range of close analogues of deferiprone have been synthesised. The group includes mono-, di- and tri-methyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe(3+) values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NH-containing hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis. PMID:27014847

  12. Psychotropic medications and leukopenia.

    Science.gov (United States)

    Sedky, Karim; Lippmann, Steven

    2006-09-01

    Neutropenia and/or agranulocytosis are among the medicinal side-effects induced by many psychotropic drugs. Clozapine and carbamazepine cause the highest incidence of this side-effect and require long-term blood cell monitoring. Bone marrow suppression can have an allergic, hypersensitivity etiology (e.g., clozapine), which mandates the causative drug discontinuation. It can also be a direct, toxic effect (e.g., carbamazepine), which calls for dosage reduction or a medication change. Other treatment options may include filgrastim, sargramostim, or lithium. Blood cell count monitoring is encouraged on patients receiving clozapine as long as the drug is continued. Such evaluation is also advised on those medicated with other psychotropics, especially carbamazepine. PMID:17017894

  13. A Questionnaire-based Study of the Views of Schizophrenia Patients and Psychiatric Healthcare Professionals in Japan about the Side Effects of Clozapine

    Science.gov (United States)

    Takeuchi, Ippei; Hanya, Manako; Uno, Junji; Amano, Yuhei; Fukai, Keiko; Fujita, Kiyoshi; Kamei, Hiroyuki

    2016-01-01

    Objective It is well documented that clozapine treatment causes agranulocytosis, but it can also induce drowsiness, constipation, and hypersalivation; however, these symptoms are usually less severe. It has been reported that clozapine-treated patients with schizophrenia and psychiatric healthcare professionals consider different side effects to be important. The aim of this study was to assess current practice related to the side effects of clozapine in clozapine-treated patients with schizophrenia and psychiatric healthcare professionals in Japan. Methods Data were collected from January 2014 to August 2015 in Okehazama Hospital, Kakamigahara Hospital, and Numazu Chuo Hospital. Clozapine-treated patients with schizophrenia and psychiatric healthcare professionals (psychiatrists and pharmacists) were enrolled in this study. Results Of the 106 patients and 120 psychiatric healthcare professionals screened, 100 patients and 104 healthcare professionals were included in this study. We asked the patients what side effects caused them trouble and we asked psychiatric healthcare professionals what side effects caused them concern. The patients and psychiatrists held similarly positive views regarding the efficacy of clozapine. The healthcare professionals were concerned about agranulocytosis (92.4%), blood routines (61.3%). On the other hand, the patients experienced hypersalivation (76.0%), sleepiness (51.0%). A positive correlation (R=0.696) was found between patient satisfaction and DAI-10 score. Conclusion Patients experienced more problems than healthcare professionals expected. However, usage experience of clozapine healthcare professionals tended to have similar results to patients. It is necessary that all healthcare professionals fully understand the efficacy and potential side effects of clozapine. This is very important for promoting clozapine treatment in Japan. PMID:27489383

  14. Hematological Side Effects of Atypical Antipsychotic Drugs

    Directory of Open Access Journals (Sweden)

    Serap Erdogan

    2009-10-01

    Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or

  15. Research of Procalcitonin in Early Diagnosis of Infection in Breast Cancer Patients with Neutropenia after Chemotherapy%降钙素原早期诊断乳腺癌化疗后粒细胞减少伴感染的研究

    Institute of Scientific and Technical Information of China (English)

    郭满; 张浩; 李伟汉; 刘平贤; 杜新峰; 翟晓健

    2014-01-01

    目的:探讨降钙素原在乳腺癌化疗后粒细胞减少伴发热患者中的临床应用价值。方法:回顾性分析2008年3月-2012年9月本院收治的118例乳腺癌化疗后中性粒细胞减少伴发热患者临床资料,根据患者临床症状、体征、病原及影像学资料,将患者分为感染组和发热原因不详组,分析两组血清降钙素原水平差异及血清降钙素原水平与患者年龄、化疗方案、发热程度和粒细胞缺乏的关系。结果:感染组血清降钙素原水平明显高于发热原因不详组(P0.05)。结论:血清降钙素原水平对于乳腺癌化疗后中性粒细胞减少伴感染的早期诊断具有重要意义,且不受患者的年龄、化疗方案、发热程度和粒细胞水平影响。%Objective:To explore clinical value of procalcitonin in breast cancer patients with neutropenia associated with fever after chemotherapy. Method:The clinical data of 118 hospitalized patients with breast cancer associated with fever after chemotherapy from March 2008 to September 2012 were analyzed. The patients were divided into the infected group and the fever reasons unknown group according to clinical symptoms,signs,etiology. The relationship of serum procalcitonin levels were comparative analyzed between the two groups. The relationship of serum procalcitonin levels with age,chemotherapy scheme,heating degree and agranulocytosis levels were analyzed. Result:Serum procalcitonin levels in the infected group was significantly higher than the fever reasons unknown group(P0.05). Conclusion:Serum procalcitonin levels has a great significance for early diagnosis of infection in breast cancer patients with neutropenia associated with fever after chemotherapy,and it did not infected by patients age,chemotherapy scheme, heating degree and agranulocytosis levels.

  16. Vasculitis por Propiltiouracilo: reporte de un caso

    Directory of Open Access Journals (Sweden)

    Donato A. Salas-Segura

    2002-06-01

    Full Text Available Se reporta el caso clínico de una paciente femenina de 43 años que presentó dos complicaciones secundarias al uso de propiltiouracilo: vasculitis y agranulocitosis.La vasculitis asociada con el tratamiento antitiroideo es una entidad clínica bien documentada, pero rara, y de un mecanismo patogénico no claro aún. Hay pocos casos reportados de asociación entre la ingesta de propiltiouracilo, la aparición de anticuerpos anticitoplasmáticos antineutrófilos y vasculitis ANCA positiva. Este es probablemente uno de ellos.We report a case of 43-year-old woman who developed two complications associated with the use of propylthiouracil: vasculitis and agranulocytosis. Vasculitis associated with antithyroid therapy is a rare well-documented clinical entity with a pathogenic mechanism not clear yet. There a few published reports of an association between treatment with propylthiouracil, and the occurrence of ANCA positivity and ANCA-associated vasculitis. This is probably one more.

  17. Spontaneous hematologic recovery from bone marrow aplasia after accidental tenfold overdosage with radiophosphorus

    Energy Technology Data Exchange (ETDEWEB)

    Gmuer, J.; Bischof, B.; Coninx, S.; Bucher, U.; Poretti, G.; Henrichs, K.; Kaul, A.; Roedler, H.D.; Buettner, K.; Frick, P.G.

    1983-04-01

    Two patients with polycythemia vera received intravenously an accidental tenfold overdosage of radiophosphorus therapy (60 and 50 mCi 32P, respectively). In both patients, the occurrence of hemorrhagic complications 3 wk after the 32P medication led to detection of the error and referral to our hospital. Upon admission they showed an agranulocytosis, severe thrombocytopenia, and bone marrow aplasia. In both cases, spontaneous recovery of the hematopoiesis was observed from day 40 posttreatment onward. In one patient, a slow but ultimately complete normalization of blood counts and marrow morphology took place, whereas in the other, a mild thrombocytopenia persists. Nearly 5 yr after the accidental overdosage, both patients are clinically well. Symptoms of polycythemia vera have not reappeared up to now. Attempts were made to evaluate the radiation dose absorbed by the bone marrow. In the first patient, the daily 32P excretion was determined from day 22 to day 60, whereas in the other patient a whole body count was performed on day 78 after administration. From these results, an approximate cumulative bone marrow dose of 10 Sv (1000 rem) could be calculated.

  18. Antiepileptic drug hypersensitivity syndrome.

    Science.gov (United States)

    Schlienger, R G; Shear, N H

    1998-01-01

    The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%. PMID:9798755

  19. Drug hypersensitivity syndrome.

    Science.gov (United States)

    Kumari, Rashmi; Timshina, Dependra K; Thappa, Devinder Mohan

    2011-01-01

    Drug hypersensitivity syndrome (DHS) is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs), viz., phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins. PMID:21220873

  20. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Directory of Open Access Journals (Sweden)

    Claudia Gregoriano

    Full Text Available Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5. Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8 times the usual dose in adults. Twelve cases (30% had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

  1. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013.

    Science.gov (United States)

    Gregoriano, Claudia; Ceschi, Alessandro; Rauber-Lüthy, Christine; Kupferschmidt, Hugo; Banner, Nicholas R; Krähenbühl, Stephan; Taegtmeyer, Anne B

    2014-01-01

    Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion. PMID:24489721

  2. Drug hypersensitivity syndrome

    Directory of Open Access Journals (Sweden)

    Rashmi Kumari

    2011-01-01

    Full Text Available Drug hypersensitivity syndrome (DHS is an adverse drug reaction commonly associated with the aromatic antiepileptic drugs (AEDs, viz., phenytoin (PHT, carbamazepine (CBZ, phenobarbital (PB, lamotrigine, primidone, etc. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, gold derivatives, cyclosporine, captopril, diltiazem, terbinafine, azathioprine and allopurinol. Diagnosis of DHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic or collagen vascular disorders. The risk for developing hypersensitivity within 60 days of the first or second prescription in new users of PHT or CBZ was estimated to be 2.3-4.5 per 10,000 and 1-4.1 per 10,000, respectively. The syndrome is defined by the fever, skin rash, lymphadenopathy and internal organ involvement within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis and myositis. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Cross-reactivity among PHT, CBZ and PB is as high as 70%-80%. Management mainly includes immediate withdrawal of the culprit drug, symptomatic treatment and systemic steroids or immunoglobulins.

  3. Early diagnosis and successful treatment of disseminated toxoplasmosis after cord blood transplantation.

    Science.gov (United States)

    Kurihara, Taro; Sumi, Masahiko; Kaiume, Hiroko; Takeda, Wataru; Kirihara, Takehiko; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Ueno, Mayumi; Ichikawa, Naoaki; Kaneko, Yumi; Hikosaka, Kenji; Norose, Kazumi; Kobayashi, Hikaru

    2016-06-01

    A 66-year-old woman with refractory angioimmunoblastic T-cell lymphoma underwent cord blood transplantation. Prior to transplantation, a serological test for Toxoplasma gondii-specific IgG antibodies was positive. On day 96, she exhibited fever and dry cough. Chest CT showed diffuse centrilobular ground glass opacities in both lungs. The reactivation of T. gondii was identified by the presence of parasite DNA in peripheral blood and bronchoalveolar lavage fluid. Moreover, brain MRI revealed a space occupying lesion in the right occipital lobe. Therefore, disseminated toxoplasmosis was diagnosed. She received pyrimethamine and sulfadiazine from day 99. The lung and brain lesions both showed improvement but the PCR assay for T. gondii DNA in peripheral blood was positive on day 133. On day 146, she developed blurred vision and reduced visual acuity, and a tentative diagnosis of toxoplasmic retinochoroiditis was made based on ophthalmic examination results. As agranulocytosis developed on day 158, we decided to discontinue pyrimethamine and sulfadiazine and the treatment was thus switched to atovaquone. Moreover, we added spiramycin to atovaquone therapy from day 174, and her ocular condition gradually improved. In general, the prognosis of disseminated toxoplasmosis after hematopoietic stem cell transplantation (HSCT) is extremely poor. However, early diagnosis and treatment may contribute to improvement of the fundamentally dismal prognosis of disseminated toxoplasmosis after HSCT. PMID:27384853

  4. Blue gods, blue oil, and blue people.

    Science.gov (United States)

    Fairbanks, V F

    1994-09-01

    Studies of the composition of coal tar, which began in Prussia in 1834, profoundly affected the economies of Germany, Great Britain, India, and the rest of the world, as well as medicine and surgery. Such effects include the collapse of the profits of the British indigo monopoly, the growth in economic power of Germany based on coal tar chemistry, and an economic crisis in India that led to more humane tax laws and, ultimately, the independence of India and the end of the British Empire. Additional consequences were the development of antiseptic surgery and the synthesis of a wide variety of useful drugs that have eradicated infections and alleviated pain. Many of these drugs, particularly the commonly used analgesics, sulfonamides, sulfones, and local anesthetics, are derivatives of aniline, originally called "blue oil" or "kyanol." Some of these aniline derivatives, however, have also caused aplastic anemia, agranulocytosis, and methemoglobinemia (that is, "blue people"). Exposure to aniline drugs, particularly when two or three aniline drugs are taken concurrently, seems to be the commonest cause of methemoglobinemia today. PMID:8065194

  5. Chest x-ray findings of opportunistic infections

    International Nuclear Information System (INIS)

    The chest x-ray findings of 20 cases of pulmonary opportunistic infection were analyzed according to causative agents. The results were as follows: 1. Final diagnoses of 20 cases of opportunistic infections were tuberculosis in 6 cases, pneumocystis carinii pneumonia in 5 cases, bacterial infection in 7 cases, and fungal infection in 2 cases. 2. The underlying diseases were leukemia in 6 cases, kidney transplantation in 6 cases, lymphoma in 3 cases, nephrotic syndrome in 1 case, nasopharyngeal cancer in 1 case, multiple myeloma in 1 case, agranulocytosis in 1 case, and hypogammaglobulinemia in 1 case. 3. In tuberculosis, all the 6 cases showed severe manifestations such as military tuberculosis, tuberculous pneumonia, moderately advanced tuberculosis and tuberculous pericarditis. 4. In pneumocystis carinii pneumonia, the most frequent findings were bilateral alveolar densities and peripheral field of the lung was saved in most cases. 5. In 2 cases of fungal infections bilateral multiple cavity nodules were noted. 6. In cases of bacterial infection there was more cases of gram negative infection than gram positive and 2 cases of pseudomonas revealed bilateral multiple cavitary nodules

  6. [Infection after dental intervention. Iatrogenic or general medical cause? Case report].

    Science.gov (United States)

    Gander, Thomas; Bingoel, Alperen Sabri; Mascolo, Luana; Grätz, Klaus W; Lübbers, Heinz-Theo

    2013-01-01

    Whenever a dentist is dealing with abscess formation in the oral and maxillofacial region, it is mostly from dental origins. However, sometimes uncommon (co-)factors are present and responsible for major complications. Many general conditions or medications can significantly influence the course of an inflammation. It might spread faster and wider and also be resistant to "correct" therapy. This case report should raise awareness about general conditions supporting inflammation and demonstrate the importance of interdisciplinary treatment in these situations. A 76-year-old patient was referred to the maxillofacial surgery clinic after extraction of two teeth resulted in therapy-resistant painful swelling. Her dentist already had initiated "standard" therapy including Ponstan® (mefenamic acid) and Clamoxyl® (amoxicillin) without success. Initial blood testing came back with severe agranulocytosis. Immediately all potentially myelosuppressing drugs were stopped while myelosupporting drugs were prescribed. Under close interdisciplinary treatment conditions, healing was then uneventful without the necessity of surgical intervention. The challenge in inflammation treatment is to identify patients with uncommonly severe, fast-progressing, or therapy-resistant disease as early as possible. Further examination including blood workup for several medical parameters is indispensable in those patients. PMID:23426587

  7. Risks and benefits of rapid clozapine titration

    Directory of Open Access Journals (Sweden)

    Jeannie D. Lochhead

    2016-05-01

    Full Text Available Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  8. Discovery and SAR of 6-alkyl-2,4-diaminopyrimidines as histamine H₄ receptor antagonists.

    Science.gov (United States)

    Savall, Brad M; Chavez, Frank; Tays, Kevin; Dunford, Paul J; Cowden, Jeffery M; Hack, Michael D; Wolin, Ronald L; Thurmond, Robin L; Edwards, James P

    2014-03-27

    This report discloses the discovery and SAR of a series of 6-alkyl-2-aminopyrimidine derived histamine H4 antagonists that led to the development of JNJ 39758979, which has been studied in phase II clinical trials in asthma and atopic dermatitis. Building on our SAR studies of saturated derivatives from the indole carboxamide series, typified by JNJ 7777120, and incorporating knowledge from the tricyclic pyrimidines led us to the 6-alkyl-2,4-diaminopyrimidine series. A focused medicinal chemistry effort delivered several 6-alkyl-2,4-diaminopyrimidines that behaved as antagonists at both the human and rodent H4 receptor. Further optimization led to a panel of antagonists that were profiled in animal models of inflammatory disease. On the basis of the preclinical profile and efficacy in several animal models, JNJ 39758979 was selected as a clinical candidate; however, further development was halted during phase II because of the observation of drug-induced agranulocytosis (DIAG) in two subjects. PMID:24495018

  9. Clozapine-induced interstitial nephritis - a rare but important complication: a case report

    Directory of Open Access Journals (Sweden)

    Hunter Robert

    2009-08-01

    Full Text Available Abstract Introduction Given the limited range of effective drug treatments for patients with schizophrenia, increasing numbers of patients, often termed 'treatment-resistant' are prescribed clozapine. While the induction of neutropenia or agranulocytosis by clozapine is well appreciated, other rare potentially fatal adverse reactions may also occur including acute interstitial nephritis as reported in this case. Case presentation A 57-year-old Caucasian woman with treatment-resistant chronic schizophrenia developed acute renal failure following initiation of treatment with clozapine. The adverse reaction occurred after only four doses of the drug had been administered (titrated from 12.5 to 25 mg per day. After clozapine had been withdrawn, the patient's renal function returned to normal with no other changes to medication. The patient had been exposed to clozapine about 4 years previously when she had developed a similar reaction. Conclusion Renal reactions to clozapine are extremely rare but, if not recognized promptly, may prove fatal. Psychiatrists need to be aware of this possible complication when clozapine is initiated.

  10. Chest x-ray findings of opportunistic infections

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yul; Jeon, Suk Chul; Lim, Jeong Ki; Park, Jae Hyung; Kim, Chu Wan [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1983-06-15

    The chest x-ray findings of 20 cases of pulmonary opportunistic infection were analyzed according to causative agents. The results were as follows: 1. Final diagnoses of 20 cases of opportunistic infections were tuberculosis in 6 cases, pneumocystis carinii pneumonia in 5 cases, bacterial infection in 7 cases, and fungal infection in 2 cases. 2. The underlying diseases were leukemia in 6 cases, kidney transplantation in 6 cases, lymphoma in 3 cases, nephrotic syndrome in 1 case, nasopharyngeal cancer in 1 case, multiple myeloma in 1 case, agranulocytosis in 1 case, and hypogammaglobulinemia in 1 case. 3. In tuberculosis, all the 6 cases showed severe manifestations such as military tuberculosis, tuberculous pneumonia, moderately advanced tuberculosis and tuberculous pericarditis. 4. In pneumocystis carinii pneumonia, the most frequent findings were bilateral alveolar densities and peripheral field of the lung was saved in most cases. 5. In 2 cases of fungal infections bilateral multiple cavity nodules were noted. 6. In cases of bacterial infection there was more cases of gram negative infection than gram positive and 2 cases of pseudomonas revealed bilateral multiple cavitary nodules.

  11. Graves' Disease Pharmacotherapy in Women of Reproductive Age.

    Science.gov (United States)

    Prunty, Jeremy J; Heise, Crystal D; Chaffin, David G

    2016-01-01

    Graves' disease is an autoimmune disorder in which inappropriate stimulation of the thyroid gland results in unregulated secretion of thyroid hormones resulting in hyperthyroidism. Graves' disease is the most common cause of autoimmune hyperthyroidism during pregnancy. Treatment options for Graves' disease include thioamide therapy, partial or total thyroidectomy, and radioactive iodine. In this article, we review guideline recommendations for Graves' disease treatment in women of reproductive age including the recent guideline from the American College of Obstetricians and Gynecologists. Controversy regarding appropriate thioamide therapy before, during, and after pregnancy is reviewed. Surgical and radioactive iodine therapy considerations in this patient population are also reviewed. In patients who may find themselves pregnant during therapy or develop Graves' disease during their pregnancy, consideration should be given to the most appropriate treatment course for the mother and fetus. Thioamide therapy should be used with either propylthiouracil or methimazole at appropriate doses that target the upper range of normal to slightly hyperthyroid to avoid creating hypothyroidism in the fetus. Consideration should also be given to the adverse effects of thioamide, such as agranulocytosis and hepatotoxicity, with appropriate patient consultation regarding signs and symptoms. Individuals who wish to breastfeed their infants while taking thioamide should receive the lowest effective dose. Surgery should be reserved for extreme cases and limited to the second trimester, if possible. Radioactive iodine therapy may be used in nonpregnant individuals, with limited harm to future fertility. Radioactive iodine therapy should be withheld in pregnant women and those who are actively breastfeeding. Clinicians should keep abreast of developments in clinical trials and evidence-based recommendations regarding Graves' disease in reproductive-age women for any changes in evidence

  12. Exploring an animal model of amodiaquine-induced liver injury in rats and mice.

    Science.gov (United States)

    Liu, Feng; Cai, Ping; Metushi, Imir; Li, Jinze; Nakayawa, Tetsuya; Vega, Libia; Uetrecht, Jack

    2016-09-01

    Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4(+) T-cells, IL-17 secreting cells and TH17/Treg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance. PMID:27416278

  13. Experience of Nursing During the Treatment of Aplastic Anemia Patients to Prevent Infection%再生障碍性贫血患者治疗期间预防感染的护理体会

    Institute of Scientific and Technical Information of China (English)

    王芳

    2014-01-01

    目的浅析再生障碍性贫血患者治疗期间预防感染的护理体会。方法我院对60例再障患者予以有效的预防感染和护理。结果60例患者中,基本治愈13例,好转38例,无变化9例,总有效率85%。结论再障患者住院期间如发生粒细胞减少或缺乏,应及时采取隔离措施。同时,要做好相应基础及心理护理,并予以升白细胞类及抗感染药物治疗,以使患者快速、安全地渡过感染期,避免致命感染,促进疾病及早康复。%Objective Nursing experience of regeneration in the treatment of aplastic anemia patients during infection prevention. Methods Our hospital to prevent infection and ef ective nursing care of 60 cases of aplastic anemia patients. Results The 60 patients, 13 patients were cured, 38 cases improved, no change in 9 cases, the total ef iciency of 85%. Conclusion During such as the occurrence of neutropenia or agranulocytosis in aplastic anemia patients, should take timely measures. At the same time, to do a good job in the basic nursing and psychological nursing, and to increase white blood cell and anti infection therapy, to enable the patients quickly, safely through the period of infection, avoid fatal infection disease, promote early rehabilitation.

  14. A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine

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    Rath Srikanta

    2011-05-01

    Full Text Available Abstract Background Amodiaquine (AQ along with sulphadoxine-pyrimethamine (SP offers effective and cheaper treatment against chloroquine-resistant falciparum malaria in many parts of sub-Saharan Africa. Considering the previous history of hepatitis, agranulocytosis and neutrocytopenia associated with AQ monotherapy, it becomes imperative to study the toxicity of co-administration of AQ and SP. In this study, toxicity and resulting global differential gene expression was analyzed following exposure to these drugs in experimental Swiss mice. Methods The conventional markers of toxicity in serum, oxidative stress parameters in tissue homogenates, histology of liver and alterations in global transcriptomic expression were evaluated to study the toxic effects of AQ and SP in isolation and in combination. Results The combination therapy of AQ and SP results in more pronounced hepatotoxicity as revealed by elevated level of serum ALT, AST with respect to their individual drug exposure regimen. Furthermore, alterations in the activity of major antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, indicating the development of oxidative stress, was more significant in AQ+SP combination therapy. cDNA microarray results too showed considerably more perturbed gene expression following combination therapy of AQ and SP as compared to their individual drug treatment. Moreover, a set of genes were identified whose expression pattern can be further investigated for identifying a good biomarker for potential anti-malarial hepatotoxicity. Conclusion These observations clearly indicate AQ+SP combination therapy is hepatotoxic in experimental Swiss mice. Microarray results provide a considerable number of potential biomarkers of anti-malarial drug toxicity. These findings hence will be useful for future drug toxicity studies, albeit implications of this study in clinical conditions need to be monitored with cautions.

  15. Are clozapine blood dyscrasias associated with concomitant medications?

    Science.gov (United States)

    Demler, Tammie Lee; Trigoboff, Eileen

    2011-04-01

    Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carbamazepine, and sulfonamide antibiotics, such as sulfamethoxazole. There were no studies at the writing of this article examining the effect of concomitant medications on clozapine blood dyscrasias, and few published reports describing enhanced bone marrow suppression in those taking clozapine. The primary objective of this study was to evaluate the effect of concomitant medications used in a state psychiatric hospital on clozapine-induced blood dyscrasias. This was a retrospective record review of adverse drug reactions reported at an adult inpatient state psychiatric center. The records for a pilot sample of 26 patients with reported clozapine-related adverse drug reactions between January 1, 2007, and June 30, 2009, were reviewed. Fundamental to this study were reported adverse drug reactions defined as 1) substantial drops in white blood cell or absolute neutrophil count (a substantial drop in white blood cell is >3,000 or absolute neutrophil count is >1,500 over a 3-week period); 2) mild leukopenia/granulocytopenia; and 3) moderate-severe leukopenia/granulocytopenia. Concomitant medications were examined for contributions to an increased potential for clozapine-induced blood dyscrasias. Other data collected included demographic information (age, gender, ethnicity), medical and psychiatric diagnoses, dose and duration of medications, and changes in medications. Medications that had a statistically significant impact on the incidence of clozapine-induced blood dyscrasias are

  16. Use of psychotropic medications in treating mood disorders during lactation : practical recommendations.

    Science.gov (United States)

    Eberhard-Gran, Malin; Eskild, Anne; Opjordsmoen, Stein

    2006-01-01

    Many new mothers who need antidepressant or mood-stabilising drug treatment may wish to breastfeed their infants, but are hesitant to do so because of possible harmful effects of the medication on the infant. This article reviews current data on drug excretion into breast milk and the effects on the breast-fed child, and provides recommendations for the use of the different psychotropic drugs in lactating women. Relevant literature was identified through systematic searches of MEDLINE, EMBASE and the Science Citation Index Expanded (ISI) from 1966 to February 2005. The present knowledge is based on the accumulation of case studies. No randomised controlled trials in breast-fed infants have been performed and there is a lack of long-term follow-up studies. Use of SSRIs and TCAs (except doxepin) is compatible with breastfeeding. However, if treatment with an SSRI is started in the postpartum period, fluoxetine and citalopram may not be drugs of first choice. With regard to other antidepressants, such as venlafaxine, trazodone, mirtazapine, reboxetine, moclobemide and other MAOIs, very little knowledge exists. Breastfeeding should be avoided while using lithium. Carbamazepine and sodium valproate (valproic acid) are generally better tolerated by the breast-fed infant than lithium. Data on lamotrigine are still sparse. Knowledge is also scarce on the novel antipsychotics and thus recommendations in lactating women cannot be made for these agents. It is unwise to expose infants unnecessarily to drugs that may have severe adverse effects. As such, clozapine should probably be avoided because of the risk of agranulocytosis. Our knowledge of the impact of drug exposure through breast milk is still limited. Infant drug exposure is, however, generally higher during pregnancy through placental passage than through breast milk. Despite the low dosage transferred to the infant through breast milk, premature infants and infants with neonatal diseases or inherited disturbances in

  17. Blood dyscrasias induced by psychotropic drugs.

    Science.gov (United States)

    Stübner, S; Grohmann, R; Engel, R; Bandelow, B; Ludwig, W-D; Wagner, G; Müller-Oerlinghausen, B; Möller, H-J; Hippius, H; Rüther, E

    2004-03-01

    Drugs can cause a variety of blood dyscrasias, e. g., by interfering with hematopoiesis in the bone marrow or damaging mature blood cells by antibodies. Although numerous reports on the risks of adverse hematological effects associated with psychotropic drugs have led to stringent monitoring requirements for some compounds, particularly neuroleptics, it is still difficult to estimate the true prevalence of such risks. Sixteen episodes of thrombocytopenia, 63 of neutropenia, 22 of agranulocytosis, 4 episodes of severe neutro- and thrombocytopenia, and 2 of pancytopenia were documented by the drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) in a population of 122,562 patients between 1993 and 2000. All cases were related to the epidemiological data provided for this population and systematically analyzed as regards history of medication, co-medication, and the clinical course. Putative risk rates for the main groups of medications and a number of drugs could be estimated with this database. Most changes in the white blood cell counts, which were rated as probably or definitely drug-induced, were attributed to clozapine (0.18 % of patients exposed), carbamazepine (0.14 %) and perazine (0.09 %). In patients on newer atypical neuroleptics, we documented neutropenia assumed to be probably or definitely drug-related in five patients during treatment with olanzapine and in one case with risperidone. In all five olanzapine-related cases, the drugs were the sole cause of the adverse drug reactions. All surveyed patients who received clozapine showed no difference in age and gender distribution from those who developed hematological changes. Incidences of hematological changes for antidepressants were much lower (about 0.01 %). Although the methodological accuracy of these findings has to be critically discussed these data could be of considerable clinical relevance and should be helpful in making clinical treatment decisions. PMID:15052517

  18. Qualidade de medicamentos isentos de prescrição: um estudo com marcas de dipirona comercializadas em uma drogaria de Cascavel (PR, Brasil Quality of over-the-counter medicines: a study with dipyrone brands commercialized in a drugstore in Cascavel city (Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    André Leandro Knappmann

    2010-11-01

    Full Text Available A dipirona é um fármaco muito utilizado pela população brasileira. É considerado seguro mesmo em gestantes, lactentes e crianças, mas é proibido em alguns países do mundo pelo suposto papel de causar agranulocitose e anemia aplástica. Em 2001, a Agência Nacional de Vigilância Sanitária (Anvisa considerou que os medicamentos com esse fármaco apresentavam bom risco-benefício em relação a outros de indicação semelhante. Porém, de nada adianta segurança no uso de um medicamento se este é de baixa qualidade. É comum encontrar no mercado brasileiro medicamentos fora dos padrões, o que se constitui em um risco para a população em geral. Dessa forma, foram analisadas sete amostras de marcas diferentes de dipirona solução oral comercializados em uma farmácia de Cascavel (PR. Os resultados demonstram que a fiscalização quanto à qualidade de medicamentos similares precisa ser aprimorada, pois eles foram os que mais apresentaram desvios de qualidade.Dipyrone is an antipyretic and analgesic medicine very used by the Brazilian population. The administration is considered safe even in pregnant women, nurseling and children, but is forbidden in some countries, as supposedly causes agranulocytosis and aplastic anemia. In 2001, National Health Surveillance Agency (Anvisa approved the commercialization of this medicine in Brazil. However, it does not matter the safeness in the use of a medicine advances, if it does not have quality. Based on this quality, this work was elaborated, that analyzes seven samples of commercialized different marks of dipyrone oral solution in pharmaceutical establishment in the Cascavel city, Paraná, Brazil. The results demonstrate that the quality control of similar drugs must be improved as were the ones that presented quality deviations.

  19. [Occupational diseases caused by exposure to sensitizing metals].

    Science.gov (United States)

    Kusaka, Y

    1993-03-01

    Diseases caused by occupational exposure to sensitizing metals including platinum (Pt), rhodium (Rh), nickel (Ni), chromium (Cr), cobalt (Co), gold (Au), mercury (Hg), zirconium (Zr) and beryllium (Be) are reviewed. Allergic reactions induced by the metals are described according to the classification by Coombs and Gell. Metals with unproven sensitizing potential are not discussed if reports on these are either very rare or devoid of convincing evidence for allergic involvement. The sensitizing metals are haptens which are not themselves able to act as antigens. There is evidence that combination of the metals with circulating or tissue protein gives rise to new antigens. An alternative hypothesis is that these metals interfere with the antigen recognition step of the immune response. Immunomodulatory effects or immunotoxicity of the metals may be also involved in metal-induced hypersensitivity. Occupational exposure to Pt, Rh, Ni, Cr, and Co causes allergic asthma via type I allergic reaction in which serum from affected individuals shows specific IgE antibodies against mental-human serum albumin conjugates. Some rheumatoid arthritis patients treated with gold salt therapy develop glomerulonephritis, thrombocytopenia, or agranulocytosis, which arise from type II and/or type III allergic reactions. Occupational exposure to mercury causes glomerulonephritis in which involvement of type III reaction is suggested. Type IV hypersensitivity reaction of the skin also takes place following exposure to the metals: allergic contact dermatitis is evoked by exposure to Ni, Cr, Co, Rh, and Hg; cutaneous granuloma is formed by contact with Zr and Be. Be is also a sensitizer of the lungs, resulting in granulomatous disease. Diagnosis of metal-induced allergic diseases is made on the basis of allergological tests with metal antigens including skin tests, radioallergosorbent test for specific antibody, lymphocyte transformation test, macrophage migration inhibition test, and

  20. Clozapine reinitiation following a "red result" secondary to chemotherapy

    Directory of Open Access Journals (Sweden)

    Munshi T

    2013-08-01

    mg. The decision to reinitiate clozapine following a red result is not to be taken lightly, but needs to be considered in terms of the risks versus benefits. More literature surrounding this issue would be of great benefit to clinicians, patients, and their families.Keywords: clozapine agranulocytosis, clozapine discontinuation, red result, clozapine rechallenge, R-CHOP chemotherapy

  1. Single dose dipyrone for acute postoperative pain

    Science.gov (United States)

    Derry, Sheena; Faura, Clara; Edwards, Jayne; McQuay, Henry J; Moore, R Andrew

    2014-01-01

    Background Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. Objectives To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. Search methods The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Selection criteria Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Data collection and analysis Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Main results Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls. Over 70% of participants

  2. Combination of deferasirox and deferoxamine in clinical practice: an alternative scheme of chelation in thalassemia major patients.

    Science.gov (United States)

    Cassinerio, E; Orofino, N; Roghi, A; Duca, L; Poggiali, E; Fraquelli, M; Zanaboni, L; Cappellini, M D

    2014-09-01

    The availability of three iron chelators improved the scenario of chelation therapy for transfusion-dependent thalassemia (TDT) patients, allowing tailoring of drugs according to the goals expected for each patient. The use of Deferiprone/Deferoxamine (DFP/DFO) combined in different schemes has been reported since many years. Only recently data from combination of Deferasirox/Deferoxamine (DFX/DFO) have been reported showing that it can be safe and efficacious to remove iron overload, particularly in patients who do not respond adequately to a single chelating agent. We investigated the efficacy, tolerability and safety of combined DFX/DFO in thalassemia major patients. Ten TDT patients have started DFX/DFO for different reasons: 1) lack of efficacy in removing liver/cardiac iron with monotherapy; 2) agranulocytosis on DFP; and 3) adverse events with elevated doses of monotherapies. The study design included: cardiac and hepatic T2* magnetic resonance (CMR), transient elastography evaluation (Fibroscan), biochemical evaluation, and audiometric and ocular examinations. The drugs' starting doses were: DFO 32 ± 4 mg/kg/day for 3-4 days a week and DFX 20 ± 2 mg/kg/day. Seven patients completed the one-year follow-up period. At baseline the mean pre-transfusional Hb level was 9.4 ± 0.4 g/dl, the mean iron intake was 0.40 ± 0.10mg/kg/day, the median ferritin level was 2254 ng/ml (range 644-17,681 ng/ml). Data available at 1 year showed no alteration of renal/hepatic function and no adverse events. A marked reduction in LIC (6.54 vs 11.44 mg/g dw at baseline) and in median ferritin (1346 vs 2254 ng/ml at baseline) was achieved. A concomitant reduction of non-transferrin-bound iron (NTBI) at six months was observed (2.1 ± 1.0 vs 1.7 ± 1.2 μM). An improvement in cardiac T2* values was detected (26.34 ± 15.85 vs 19.85 ± 12.06 at baseline). At 1 year an increased dose of DFX was administered (27 ± 6 mg/kg/day vs 20 ± 2 mg/kg/day at baseline, p=0.01) with a stable

  3. Organization of Aid in Emergency Situations

    International Nuclear Information System (INIS)

    The concentration of patients in a single highly-specialized centre makes it possible to obtain comparable data from the study of various cases of injury. A specialized medical establishment should be able to undertake the necessary work in order to develop a rational course of treatment, to determine the dose received, by both physical methods and biological methods (especially those which quantitatively give the best correlation with physical tests, i.e. determination of the number and form of chromosome breakages in the bone marrow and the peripheral blood culture), and to maintain cytological, karyological and immunological observation to ascertain whether transplanted bone marrow has taken or been rejected. Under normal circumstances (where there is no accident) the centre should perform the function of a haematological and surgical clinic. A singular, though not fully adequate model for acute injury is toxic agranulocytosis, which occurs when patients with tumours of the blood system are treated, with large doses of cytostatic preparations and with whole-body irradiation. This model is used for day-to-day studies aimed at the proper evaluation and treatment of accident cases. Analysis of damage to chromosomes in bone marrow cells during local gamma therapy for patients with a variety of tumours and during whole-body irradiation of two persons suffering from acute leucosis have shown that karyological investigation may be an important link in biological dosimetry and may indicate the degree of non-uniformity of the injury; local gamma irradiation of the ilium and sternum with 220 rads shows up about 60 per cent of the mitoses with chromosome disturbances (0.005 breaks per cell per röntgen); the same proportion of chromosome aberrations can also be detected by whole-body irradiation at the same dose. Casualties should be brought to the centre immediately after the accident and at the same time be given medical attention to alleviate their initial reaction

  4. Pharmacological interventions for clozapine-induced hypersalivation

    Science.gov (United States)

    Syed, Rebecca; Au, Katie; Cahill, Caroline; Duggan, Lorna; He, Yanling; Udu, Victor; Xia, Jun

    2014-01-01

    Background Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%). Objectives To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials. Selection criteria We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation. Data collection and analysis We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data. Main results Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of ‘no clinically important improvement’ astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both

  5. Tratamento de suporte e quelação de ferro em pacientes com síndromes mielodisplásicas Supportive care, tranfusion and chelation therapy for patients with myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elizabeth X. Souto

    2006-09-01

    survival to develop clinically relevant iron overload. Chelation therapy presents with some limitations in particular the long time required for deferoxamine infusion and the difficulties of patients to comply with treatment and to acquire an infusion pump. The clinical use of deferiprone, an oral chelator, is not indicated for MDS patients because of the risk of neutropenia and agranulocytosis. Deferasirox is a new oral chelator currently under clinical development that will probably be, in the future, an adequate option for MDS patients with iron overload. Additional studies in MDS patients are necessary to establish better diagnostic and chelation therapy criteria.

  6. 急性淋巴细胞白血病患儿诱导缓解期合并可逆性后部白质脑病临床特征%Reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia after remission induction chemotherapy

    Institute of Scientific and Technical Information of China (English)

    林巍; 谢静; 郑胡镛; 程华; 张元元; 张瑞东

    2014-01-01

    Objective To investigate the etiology,clinical manifestations,imaging characteristics and treatment of reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia after remission induction chemotherapy.Methods Analysize the clinico-radiological features、central nervous system symptoms and associated symptoms、treatment and prognosis of reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia receiving induction chemotherapy in hematology center of Beijing children′s hospita from June 201 1 to March 2012.Results Eight children (3 males and 5 females)with a mean age of 5 years were identified.Presenting symptoms included seizures (8/8 ),disturbance of consciousness (3/8 ),and visual disturbance (2/8 ).High blood pressure,agranulocytosis,and coagulation disorders,electrolyte disturbance were existed,and they all used granulocyte colony-stimulating factor.All children had typical radiological features of reversible posterior leukoencephalopathy syndrome.Six cases of children with head magnetic resonance imaging results suggest that vasogenic edema,the prognosis is good.Two cases of cytotoxic edema,in one case of recurrence,the prognosis is bad.Conclusion reversible posterior leukoencephalopathy syndrome is an underappreciated complication in cancer children receiving remission induction chemotherapy.Head magnetic resonance imaging is an important means of diagnosis and assessment of reversible posterior leukoencephalopathy syndrome prognosis. During chemotherapy require close monitoring of blood pressure,electrolyte,blood coagulation,actively is needed.%目的:探讨急性淋巴细胞白血病(acute lymphoblastic leukemiu,ALL)患儿,在诱导缓解化疗期间发生可逆性后部白质性脑病综合征(reversible posterior leukoencephalopathy sysdrome,RPLS)的病因、临床表现、影像学特征及治疗。方法2011年6月至2012年3月,北京儿童医院血液病中

  7. 老年恶性血液病患者化疗后急性心力衰竭的危险因素%Risk factors of acute heart failure in elderly patients with hematologic malignancies after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    李皓亮; 袁义燕

    2013-01-01

    Objective:Study of risk factors in elderly patients with malignant hematological diseases occur in acute heart failure after chemotherapy.Methods:From 2012 March to 2013 March in our hospital in patients with hematologic malignancies therapy in 230 cases, a retrospective analysis of 230 cases with sex , fluid balance weight , hemoglobin , septic shock and sepsis , total course of chemotherapy , renal failure, respiratory failure, neutropenia, and heart disease index.Results:gender, total course of chemotherapy, renal insufficiency and respiratory failure in the two groups, the difference was not statistically significant (P >0.05); agranulocytosis and heart disease between the two groups, significant differences were statistically significant (P <0.05); liquid balance weight,hemoglobin values and infection shock and sepsis in two groups , significant differences were statistically significant (P <0.001).Conclusion:the risk of aged malignant hematonosis patients with acute heart failure after chemotherapy in the complicated factors , early diagnosis , intervention therapy is crucial to the early .%目的:研究观察老年恶性血液病患者在化疗后发生急性心力衰竭的危险因素。方法:选取2012年3月~2013年3月期间在我院住院治疗的恶性血液病患者230例,回顾性分析本组230例患者的性别、液体平衡量、血红蛋白值、感染性休克/脓毒血症、化疗总疗程、肾功能不全、呼吸衰竭、粒细胞缺乏、以及心脏病史等指标。结果:性别、化疗总疗程、肾功能不全以及呼吸衰竭2组比较,差异均无统计学意义(P均>0.05);粒细胞缺乏以及心脏病史2组比较,差异显著均有统计学意义(P均<0.05);液体平衡量、血红蛋白值以及感染性休克/脓毒血症2组比较,差异显著均有统计学意义(P均<0.001)。结论:老年恶性血液病患者在化疗后发生急性心力衰竭的危险因素复杂多样,

  8. Clozapine and Fever: A Case of Continued Therapy With Clozapine.

    Science.gov (United States)

    Bruno, Valentina; Valiente-Gómez, Alicia; Alcoverro, Oscar

    2015-01-01

    Clozapine is a major atypical antipsychotic drug used in treatment-resistant schizophrenia (Patel and Allin. Ther Adv Psychopharmacol 2011;1:25-29). It interferes with dopamine binding to D1, D2, D3, and D5 receptors but has high affinity to D4. It also has an anticholinergic effect and antagonizes α-adrenergic, histaminergic, and serotoninergic receptors (Oerther and Ahlenius. J Pharmacol Exp Ther 2000;292:731-736). Clozapine has proved effective in treating positive and negative symptoms in patients with refractory schizophrenia, thus accounting for its frequent use. Despite its effectiveness, this drug is not without its adverse effects. The most well known is agranulocytosis. There are, however, many others, such as myocarditis, aspiration pneumonia, ileus, fever, hyperglycemia, hyperlipidemia, hypertriglycemia, tachycardia, and weight gain, among others (Bruijnzeel et al. Asian J Psychiatr 2014;11:3-7). Fever induced by clozapine is a common phenomenon (Lowe et al. Ann Pharmacother 2007;41:1700-1704), which usually occurs in the first 4 weeks of treatment, and its prevalence oscillates from 0.5% and 55%, depending on the study (Jeong et al. Schizophr Res 2002;56:191-193; Young et al. Schizophr Bull 1998;24:381-390). The fever lasts for 2.5 days on average, and unless the treatment is discontinued, it generally abates between day 8 and 16 of treatment (Kohen et al. Ann Pharmacother 2009;43:143-146). There are several different theories about the physiopathological mechanism; it could be a variation of malignant neuroleptic syndrome, an infection secondary to neutropenia, and allergic reaction or the emergence of the immunomodulating effect of clozapine. Some case reports in the bibliography have shown that patients in treatment with clozapine can develop a mild leukocytosis, but the presence of other concurrent symptoms, which indicate infection, is not common (Tham and Dickson. J Clin Psychiatry 2002;63:880-884). The theory of an allergic reaction is

  9. Pathogenic features and risk factors of invasive fungal infection in patients with hematopathy%血液病合并侵袭性真菌感染病原学及危险因素

    Institute of Scientific and Technical Information of China (English)

    王凡; 韩志海; 孟激光; 李泳群; 陈韦; 赵春亭

    2015-01-01

    Objective To investigate the status of invasive fungal infection(IFI)associated with hematopathy,and evaluate drug resistance and risk factors of fungal infection.Methods 1 246 cases of infection occurred in patients in a hospital from 2006 to 2010 were analyzed retrospectively,pathogenic features and risk factors of IFI were ana-lyzed.Results There were 281 cases of fungal infection,and 162 fungal isolates were isolated,the main infection site was respiratory tract(134 isolates,82.72%).Four major Candida were Candida albicans ,Candida tropicalis , Candida glabrata ,and Candida krusei ;in 2006-2009,the main fungi were Candida albicans ,while in 2010,the majority were non-Candida albicans .The resistant rates of four isolated Candida to fluconazole and itraconazole were 5.15% and 4.41 % respectively,6 isolated Candida krusei strains were all resistant to both fluconazole and itraconazole,voriconazole-resistant strain was not found.The independent risk factors for fungal infection were dia-betes and duration time of agranulocytosis>14 days.Conclusion The proportion of infection caused by non-Candi-da albicans increased obviously,fluconazole-and itraconazole-resistant non-Candida albicans strains have emerged, comprehensive measures should be adopted to prevent IFI actively and treat patients early.%目的:了解血液病合并侵袭性真菌感染(IFI)的现状,分析真菌耐药情况及感染的危险因素。方法回顾性分析2006—2010年某院血液病科合并感染的患者1246例次,对 IFI 患者病原学特点及危险因素进行分析。结果真菌感染281例次,分离真菌162株,感染部位以呼吸道(134株,占82.72%)为主。4种主要酵母菌为白假丝酵母菌、热带假丝酵母菌、光滑假丝酵母菌和克柔假丝酵母菌;2006—2009年均以白假丝酵母菌为主,2010年非白假丝酵母菌超过白假丝酵母菌。4种主要酵母菌对氟康唑和伊曲康唑的总耐药率分别为5.15%和4

  10. 儿童期急性白血病合并水痘的特点及其高危预后因素的临床分析%Clinical features of chickenpox and high risk factors of prognosis in childhood cases with acute lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    曾慧慧; 程澄; 陈志海; 李兴旺

    2015-01-01

    were compared. Results There were 5 (31.25%) childhood patients with ALL had varicella virus exposure. Except one patient’s temperature was normal, the other 13 (81.25%) cases patients had higher fever and fever duration lasted for (7.38 ± 3.32) days, which signiifcantly longer than ordinary chickenpox patients (t=5.575, P<0.05). Skin rash scabby time were (10.92 ± 2.50) days, which signiifcantly longer than normal patients (t=4.928, P<0.05). All the patients (16 cases) had bone marrow suppression including agranulocytosis 10 (62.5%) cases and thrombocytopenia 7 (43.75%) cases. Patients with abnormal liver function were 8 (50.00%) cases, Skin infections in ALL patients were less than in ordinary patients. After antiviral treatment and active support treatment just like immunoglobulin, 11 patients cured, 4 cases were critically illed and discharged without and one case were died. The features of critically illed or dead cases were taking intravenous chemotherapy, onseting chickenpox during chemotherapy or just finish chemotherapy within a weeks. Granulocyte deficiency and granulocyte deficiency lasted for longer time than mild cases (10.08 ± 2.77 days). Conclusions Longer duration of symptoms as high fever or rash and higher complication ratio of bone marrow suppression manifestated granulocytopenia were the features of chickenpox in childhood cases with ALL. Good prognosis were achieved in childhood ALL patients when proper antiviral treatment and support treatment were implemented. Taking intravenous chemotherapy, onseting chickenpox during chemotherapy or just ifnish chemotherapy within a weeks and persistent granulocyte deifciency were associated with adverse clinical prognosis in childhood cases with ALL.

  11. Relato do uso de clozapina em 56 pacientes atendidos pelo Programa de Atenção à Esquizofrenia Refratária da Secretaria da Saúde e do Meio Ambiente do Estado do Rio Grande do Sul El relato del uso de clozapina en 56 pacientes atendidos por el Programa de Atención a la Esquizofrenia Refractaria de la Secretaria de Salud y Medio Ambiente del Estado de Rio Grande do Sul Clozapine use report in 56 patients seen by Clerkship of Health and Environment of the State of Rio Grande do Sul's Program of Attention to the Refractory Schizophrenia

    Directory of Open Access Journals (Sweden)

    Clarissa Severino Gama

    2004-04-01

    treating 30-61% of the psychotic symptoms with minimal adverse effects. METHODS: Clinical experience of 56 patients with refractory schizophrenia under treatment at the Psychiatry Service of the Hospital de Clínicas de Porto Alegre, included in the program to supply clozapine free of charge, promoted by the Department of Health and the Environment of the State of Rio Grande do Sul. RESULTS: The mean score for the Brief Psychiatric Rating Scale (BPRS was initially 77.9 (SD=16.1 and, at the end, 41.1 (SD=16.2. Two patients left the program and one was excluded because he developed agranulocytosis. There were 4 hospitalizations. DISCUSSION: Despite its well-established efficacy and applicability, clozapine is not free from adverse effects: postural hypotension, tachycardia, cloudy vision, dry eyes, hypersalivation, constipation and sedation frequently occur. Hematological alterations occur in 0.05-2.8%. CONCLUSIONS: There was a significant and lasting improvement of the symptoms in the patients enrolled. Diseases with a longer evolution had worse responses, probably related to neurochemical and neurophysiological damage. The importance of early treatment and the need for State intervention, offering psychosocial and financial support to optimize the treatment of this population should be highlighted.

  12. A clinical analysis on invasive pulmonary aspergillosis in patients with hepatic failure%肝衰竭患者合并侵袭性肺曲霉菌病临床分析

    Institute of Scientific and Technical Information of China (English)

    邓西龙; 陈志敏; 黄煌; 潘越峻; 李粤平

    2012-01-01

    Objective To explore the risk factors,clinical characteristics,and proguosis ofinvasive pulmonary aspergillosis ( IPA ) in patients with hepatic failure.Methods The clinical data of 15 patients with hepatic failure complicated with IPA were analyzed retrospectively.Results All the patients had an underlying disorder that was chronic hepatitis B,but had no granulocytopenia or agranulocytosis.The MELD score was ( 37.13 ± 11.03 )46.7% ( 7/15 ) of the patients had history of hormone uses ; 60% ( 9/15 ) had history of broad-spectrum antibiotic uses ( single or mulitple ) 60% ( 9/15 )of patients received previous blood purification.33.3% ( 5/15 )had a reduction in CD4+ T cells or ratio imbalance.Clinical manifestations lacked of obvious specificity.Roentgenographic examination of the lungs showed changes in all the patients; GM test was positive in 73.3% ( 11/15 )of the patients.20% ( 3/15 )of the patients improved after treatment; 80% ( 12/15 ) did not repond to therapies; and 40% ( 6/15 ) were dead within 7 days after diagnosis.Conclusions Patients with hepatic failure have multiple risk factors of invasive pulmonary aspergillosis.IPA is one of the reasons for deterioration in patients with hepatic failure.Early CT examination combined with GM tests can increase the early diagnostic rate.Early effective antifungal therapy can improve the prognosis of the disease.%目的 了解肝衰竭患者合并侵袭性肺曲霉菌病的危险因素、临床特征和预后,提高对肝衰竭合并侵袭性肺曲霉菌病的认识.方法 对15例肝衰竭合并侵袭性肺曲霉菌病患者的临床资料,包括基础疾病、住院时间、ICU住院时间、激素和抗生素使用情况、临床表现、诊断分层、治疗情况以及预后等进行回顾性分析.结果 全部患者存在慢性乙型肝炎基础疾病,均无粒细胞减少或缺乏.患者MELD评分(37.13±11.03)分.其中46.7%( 7/15)的患者有激素使用史;60%( 9/15)

  13. [Antipsychotics in bipolar disorders].

    Science.gov (United States)

    Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L

    2004-01-01

    and antidepressive effects, both as monotherapy and as add-on maintenance therapy with lithium or valproate. They also have a favorable side effect profile and a positive effect on overall functioning. Similarly, valproate combined with antipsychotics provides greater improvement in mania than antipsychotic medication alone and results in lower dosage of the antipsychotic medication. There is currently no double-blind study regarding the use of clozapine for bipolar disorders. However, based on the results of a number of open-label studies, clozapine appears to be effective in relation to schizo-affective and bipolar patients including those with rapid cycling or those who respond inadequately to mood stabilizers, carbamazepine, valproate or conventional antipsychotics. Clozapine seems to be more appropriate for bipolar and schizo-affective patients than schizophrenics. In particular, studies show that patients with manic and mixed-psychotic state of illness are better responders than patients with major depressive syndromes. Four open studies suggest the efficacy of clozapine in the maintenance treatment of bipolar disorder and three prospective, open-label studies show the efficacy of clozapine in the manic state of the illness. However, the number of patients in the studies was not important and these studies are not controlled. Clozapine has also adverse side affects, one of which consisting of a major risk of agranulocytosis and, potentially, death. In addition, clozapine has been shown to produce significant weight gain and sialorrhea as well as significant anticholinergic effects. As a result, clozapine should not be prescribed in the first place. As opposed to clozapine, there are open-label reports and controlled studies in respect of risperidone and olanzapine. Two recent double-blind studies of acute mania found olanzapine to be more effective than placebo. Based on these two studies, olanzapine has recently been approved for the indication of mania. The