Sample records for agranulocytosis

  1. Late onset clozapine induced agranulocytosis

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    Rajmohan Velayudhan


    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.

  2. Carbimazole-induced agranulocytosis

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    Anisha Mohan


    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.

  3. A case of recurrent agranulocytosis due to levamisole

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    Abraham M Ittyachen


    Full Text Available Agranulocytosis is a rare complication of levamisole. We report a 22-year-old female who developed agranulocytosis due to levamisole. The patient initially presented with salmonellosis and agranulocytosis, and then she recovered with treatment. However, 2 months after discharge, she again presented with tonsillitis and agranulocytosis. This time the family revealed that she had been taking levamisole. Though Salmonella infection is a recognized cause of agranulocytosis, any patient presenting with repeated agranulocytosis after an initial recovery should make the clinician suspect another cause, especially drug-induced. A case of Salmonella infection where levamisole was an unsuspecting cause of agranulocytosis has not been described in indexed literature. Recurrent agranulocytosis due to repeated exposure to levamisole has also not been described.

  4. A case of recurrent agranulocytosis due to levamisole. (United States)

    Ittyachen, Abraham M; Jose, Mohan B; Benjamin, Jobin R


    Agranulocytosis is a rare complication of levamisole. We report a 22-year-old female who developed agranulocytosis due to levamisole. The patient initially presented with salmonellosis and agranulocytosis, and then she recovered with treatment. However, 2 months after discharge, she again presented with tonsillitis and agranulocytosis. This time the family revealed that she had been taking levamisole. Though Salmonella infection is a recognized cause of agranulocytosis, any patient presenting with repeated agranulocytosis after an initial recovery should make the clinician suspect another cause, especially drug-induced. A case of Salmonella infection where levamisole was an unsuspecting cause of agranulocytosis has not been described in indexed literature. Recurrent agranulocytosis due to repeated exposure to levamisole has also not been described.

  5. Reversible agranulocytosis in association with cimetidine and hepatic failure


    Lewis, D. S.; Beck, E. R.


    A patient is described who developed agranulocytosis in the context of hepatic failure and cimetidine therapy. The close temporal relationship between discontinuation of the drug and granulopoietic recovery is considered to imply a role for cimetidine in the mechanism of the agranulocytosis.

  6. Agranulocytosis under biotherapy in rheumatoid arthritis: three cases hypothesis of parvovirus B19 involvement in agranulocytosis observed under tocilizumab and rituximab for the treatment of rheumatoid arthritis. (United States)

    Giraud, C; Tatar, Z; Soubrier, M


    Leukopenia is a considerably common complication of tocilizumab [TCZ] and rituximab [RTX] therapy. RTX-induced leukopenia typically exhibits delayed onset. While agranulocytosis has been reported linked to RTX treatment of lymphoma, this complication rarely occurs in rheumatoid arthritis (RA) treatment and, to our knowledge, has never been reported in association with TCZ therapy. We herein report four agranulocytosis cases in three patients, with the first two cases suspected to be secondary to human parvovirus B19 (PVB19) infection. Agranulocytosis manifested in the first patient 2 months following a third RTX course. Bone marrow (BM) polymerase chain reaction (PCR) was positive for PVB19. The patient relapsed after three TCZ courses, with her PCR again positive for PVB19. Both episodes resolved under granulocyte-macrophage colony-stimulating factor (GM-CSF). In the second patient, agranulocytosis manifested after the 74th TCZ course. Bone marrow PCR was positive for PVB19, and the evolution was favorable under intravenous immunoglobulin administration. The third case was a 53-year-old female patient with seropositive RA who presented agranulocytosis after the first infusion of her fourth RTX course. Unfortunately, no PCR PVB19 was made on myelogram. Evolution was favorable after 5 days of GM-CSF. PVB19 infection should be investigated in patients suffering from agranulocytosis manifesting during biotherapy. In cases manifesting from the 15th day of RTX treatment onwards, hemogram must be conducted before readministering the infusion.

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

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    Upadya Gatha


    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.

  8. Clozapine-associated neutropenia and agranulocytosis in Argentina (2007-2012). (United States)

    Balda, María V; Garay, Osvaldo U; Papale, Rosa M; Bignone, Inés; Bologna, Viviana G; Brandolini, Andrés; Prokopez, Cintia R; Balasini, Juan I; Baldessarini, Ross J; Daray, Federico M


    The risks of severe leukopenia and agranulocytosis have varied over time and among geographical regions and cultures, with little information available on South American populations. Accordingly, we reviewed and analyzed data from a 6-year experience monitored by an Argentine national registry to which reporting of adverse events reports is required. We analyzed data for 2007-2012 from the pharmacovigilance program of the Argentine drug-regulatory agency (ANMAT) using standard bivariate and multivariate statistical methods and survival analysis. We identified 378 cases of adverse hematological events over 6 years among an average of 12 305 individuals/year treated with clozapine (308±133 mg/day) to estimate the mean annualized rates of leukopenia [0.19 (95% confidence interval [CI] 0.11-0.27)], neutropenia [0.38 (95% CI 0.34-0.43)], and agranulocytosis [0.05 (95% CI 0.02-0.08)] % per year [median latency 2 (95% CI 1.3-2.1) months]; fatalities related to agranulocytosis averaged 4.2 (95% CI 0.0-9.2) per 100 000 treated individuals/year. Factors associated significantly and independently with agranulocytosis were female sex, older age, and use of other drugs in addition to clozapine. With monitoring by international standards, recent risks of clozapine-associated agranulocytosis in Argentina were lower, but fatality rates were higher than that in other regions of the world. Risk factors include the use of multiple psychotropic drugs, female sex, and older age.

  9. Hydroxychloroquine-induced agranulocytosis in a patient with long-term rheumatoid arthritis. (United States)

    Sames, Edward; Paterson, Heather; Li, Charles


    Agranulocytosis is a rare and little-known side effect of hydroxychloroquine use. This report describes the case of a 71-year-old woman with poorly controlled rheumatoid arthritis who developed agranulocytosis after several months of hydroxychloroquine therapy. She had been on several different disease-modifying antirheumatic drugs, including methotrexate and leflunomide, for her rheumatoid arthritis. Treatment became complicated following a diagnosis of leflunomide-induced pulmonary fibrosis that was discovered after an intensive care unit (ICU) admission for severe Pseudomonas pneumonia. All treatment was stopped apart from steroids and hydroxychloroquine. Because of persistent disabling symptoms, rituximab infusions were given, which improved the disease control. A second admission occurred after a routine blood test revealed agranulocytosis. Hydroxychloroquine was stopped, and after 24 h, she was discharged home. Blood counts returned to normal within 2 weeks of hydroxychloroquine cessation; hence, after the review of investigations, a diagnosis of hydroxychloroquine-induced agranulocytosis was made. This report considers current literature on hydroxychloroquine-induced agranulocytosis and explores the potential causes for this occurrence.

  10. Incidence of aplastic anemia and agranulocytosis in Latin America: the LATIN study

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    Nelson Hamerschlak

    Full Text Available CONTEXT AND OBJECTIVE: Aplastic anemia and agranulocytosis are rare but life-threatening disorders, often caused by drugs and other environmental exposures. Reported incidence of these diseases seems to vary between different geographic regions, and few data on their incidence are available for Latin American countries. The aim of this work is to determine the incidence of agranulocytosis and aplastic anemia in Brazil. DESIGN AND SETTING: Incidence study. Seven centers took part in the pilot phase, so as to represent all Brazilian regions. METHODS: Each center conducted an active search for new cases in a defined region by means of regular contacts with all hematologists, main clinical laboratories and clinicians in hospitals of the region. RESULTS: 74 patients with aplastic anemia and 16 with agranulocytosis were identified. Patients with agranulocytosis had a median age of 31 years (interquartile range, IQR: 12.5-48.2; 32.2% were male and 81.2% were white. The median age of aplastic anemia patients was 21 years (IQR 15.0-35.2; 62.2% were male, 50.0% were white and 39.2% mulatto. The incidence of agranulocytosis was estimated to be 0.5 cases per million individuals per year, ranging from 0.0 to 1.1 cases per million per year between regions. The incidence of aplastic anemia was 2.7 cases per million per year, ranging from 1.1 to 7.1 cases per million per year between regions. CONCLUSIONS: Aplastic anemia and agranulocytosis are rare diseases in Brazil. However, there is considerable variability in their incidences between different regions.

  11. [Risk minimization evolution of agranulocytosis caused by the administration of pharmaceutical products containing Clozapine in Argentina]. (United States)

    Bergman, Maximiliano; Bignone, Inés; Bisio, Agustina; Bologna, Viviana; Sabatini, Analía


    Clozapine is an antipsychotic medication used in the treatment of schizophrenia. Compared to other drugs, Clozapine has shown remarkable advantages. However, its use entails a serious risk of causing hematologic alterations (including granulocytopenia/agranulocytosis). Such alterations may result in death if they are not detected early. Clozapine was recalled from the worldwide market and it was reintroduced some years later, but a mandatory hematologic monitoring program was implemented. The program was established in Argentina by ANMAT's regulation 935/00. It helped to monitor of the use of the drug. Currently, the incidence of agranulocytosis in our country is lower than the international incidence rates.

  12. Agranulocytosis and acute coronary syndrom in apathetic hyperthyreoidism

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    Ivović Miomira


    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

  13. Dapsone-induced agranulocytosis leading to perianal abscess and death: a case report

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    Kitamura Nobuya


    Full Text Available Abstract Introduction Dapsone (diaminodiphenylsulfone is used for the treatment of intractable skin diseases such as pemphigus and leprosy. The side effects of Dapsone are anemia, leukopenia, and liver dysfunction. Here, we present a case of agranulocytosis-induced septic shock, which was a side effect of Dapsone. Case presentation An 82-year-old Japanese woman was transferred to our hospital with fever, leucopenia, and respiratory arrest. At the previous hospital, she had been administered Dapsone for linear IgA bullous dermatosis. At the time of admission, she presented with methemoglobinemia and septic shock, which was due to immunosuppression caused by the normal dose of Dapsone. Although her overall health initially improved, her condition deteriorated because of septic shock caused by an anal fistula. She died of sepsis on hospital day 80. Conclusion One of the side effects of Dapsone is agranulocytosis. Patients with agranulocytosis may be in danger of developing anal fistula. Therefore, care must be taken if a patient with agranulocytosis develops a decubitus ulcer in the sacral region, since it could develop into a fistula-in-ano.


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    We report the use of granulocyte-macrophage colony stimulating factor (GM-CSF) in a case of rheumatoid arthritis with sulfasalazine induced agranulocytosis, leading to a rapid bone marrow recovery within 7 days. This case and 2 others reported in the literature emphasize the need for further researc

  15. Severe Agranulocytosis following Simultaneous Administration of Chlorpromazine and Trimethoprim-Sulfamethoxazole in a Patient with Sepsis: A Possible Toxic Combination

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    Anil Jha


    Full Text Available Background. Chlorpromazine and trimethoprim-sulfamethoxazole (TMP/SMX are two commonly prescribed medications by physicians. Either of those medications could cause fatal drug-induced agranulocytosis, with an unclear underlying mechanism. The likelihood of simultaneous prescription of both medications is high and could hypothetically result in severe agranulocytosis that is resistant to treatment. Case Presentation. We are presenting a case of a patient with psychosis on chlorpromazine who was prescribed TMP/SMX for a urinary tract infection. Consequently, the patient developed severe agranulocytosis and septicemia. Patient was managed by granulocyte colony-stimulating factor; however, the time to neutrophil recovery was delayed when compared to the average reported time published by previous studies. Conclusions. Simultaneous use of chlorpromazine and TMP/SMX is a possible toxic combination that could induce severe agranulocytosis. Further reports are needed to confirm this observation.

  16. A Report of Three Girls with Antithyroid Drug-Induced Agranulocytosis; Retrospective Analysis of 18 Cases Aged 15 Years or Younger Reported between 1995 and 2009. (United States)

    Minamitani, Kanshi; Oikawa, Junko; Wataki, Kunio; Kashima, Kyoko; Hoshi, Mari; Inomata, Hiroaki; Ota, Setsuo


    Agranulocytosis is an extremely serious, although rare, adverse effect of antithyroid drugs (ATDs), including methimazole (MMI) and propylthiouracil (PTU), in children and adolescents. There are few reports about the characteristics of ATD-induced agranulocytosis in Japanese children and adolescents. This report presents the cases of three girls with ATD-induced agranulocytosis and a retrospective analysis of 18 patients with ATD-induced agranulocytosis, whose cases had been referred to the drug manufacturer, Chugai Pharmaceutical Co., Ltd. Our 3 patients, ranging in age from 12 to 14 yr, developed ATD-induced agranulocytosis between the 15th and 57th day of ATD treatment for hyperthyroidism. Fever and sore throat were the earliest symptoms of agranulocytosis. The patients were rescued by ceasing ATD therapy and administering antibiotics, potassium iodide, glucocorticoid, immunoglobulin and granulocyte colony-stimulating factor (G-CSF). We retrospectively analyzed 18 cases of ATD-induced agranulocytosis treated with MMI in 16 cases and PTU in 2 cases. Twelve patients were treated with 20-45 mg/d MMI. Agranulocytosis developed between the 15th and 1,344th day of therapy. In conclusion, considering the risk of ATD-induced agranulocytosis, we recommend low-dose MMI therapy for treatment of Graves' disease.

  17. Agranulocytosis in a patient with acute Parvovirus B19 infection: a case study

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    Carlo Di Donato


    Full Text Available The definition of neutropenia is the reduction in the absolute number of neutrophils below 1.5×109. The chapter about acquired neutropenias affecting the adult population is of particular interest to the internist. PC, 75 years old man, was hospitalized because of fever, asthenia. In anamnesis: recent diagnosis of ulcerative pancolitis treated with mesalazine and corticosteroid therapy. During the hospitalization, to the fever resolution, we witnessed to a gradual reduction in the value of neutrophils leucocytes until the complete agranulocytosis. We set a therapy with granulocytes colony stimulating factors, and antifungal. The osteo-medullar biopsy confirmed a pure aplasia of the granulocyte marrow series without any evidence of cancer. The subsequent clinical development was favorable, with stable apyrexia and recovery of leucocytes count. Few days after, we received the positive response on the research of anti-Parvovirus B19 immunoglobulin M and in qualitative polymerase chain reaction. The patient was discharged with diagnosis agranulocytosis in patient with acute infection of Parvovirus B19. Neutropenia associated with Parvovirus infection is not frequent and is related to the presence of hematological diseases or condition of immunosuppression. The peculiarity of the case described is the complete agranulocytosis found: in fact in literature, only rare cases are described. Patient gave his informed consent.

  18. 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;


    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...... in immunogenetic phenotypes and adverse drug responses for other medications, and provide insight into the pathophysiology of CIAG....

  19. Clozapine-induced agranulocytosis in schizophrenic Caucasians: confirming clues for associations with human leukocyte class I and II antigens. (United States)

    Dettling, M; Cascorbi, I; Opgen-Rhein, C; Schaub, R


    Clozapine-induced agranulocytosis (CA) is still among the least understood adverse drug reactions in psychopharmacology. In particular, its genetic background is far from being clarified. Within the framework of a case-control study, we performed human leukocyte antigen (HLA) genotyping and haplotype analyses in 42 non-Jewish Caucasian schizophrenic patients (N=42) suffering from CA and 75 non-Jewish Caucasian schizophrenic patients treated with clozapine without developing CA. While controlling for age (Pgenes might play a role, but currently, only HLA associations with CA are identified as clinically relevant.

  20. Exploring off-targets and off-systems for adverse drug reactions via chemical-protein interactome--clozapine-induced agranulocytosis as a case study.

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    Lun Yang


    Full Text Available In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI, which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs.

  1. Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis

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    Christina Voulgari


    Full Text Available Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophrenia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis. Clozapine-induced thromboembolism of the common femoral and right proximal iliac vein, as well as allergic vasculitis, was diagnosed. She achieved full remission on granulocyte-colony stimulating factor and specific antibiotic treatment. Early detection of severe clozapine-induced absolute neutropenia and agranulocytosis enabled the effective treatment of two among its most severe complications. Additional evidence to the previously reported possible causal relation between clozapine and venous thromboembolism is offered. Finally, clozapine-induced allergic vasculitis is confirmed as a late adverse effect of clozapine therapy.

  2. Involvement of myeloperoxidase and NADPH oxidase in the covalent binding of amodiaquine and clozapine to neutrophils: implications for drug-induced agranulocytosis. (United States)

    Lobach, Alexandra R; Uetrecht, Jack


    Amodiaquine (AQ) and clozapine (CLZ) are associated with a relatively high incidence of idiosyncratic agranulocytosis, a reaction that is suspected to involve covalent binding of reactive metabolites to neutrophils. Previous studies have shown that both AQ and CLZ are oxidized to reactive intermediates in vitro by activated neutrophils or by the combination of hydrogen peroxide and myeloperoxidase (MPO). Neutrophil activation leads to an oxidative burst with activation of NADPH oxidase and the production of hydrogen peroxide. However, the importance of this pathway in covalent binding in vivo has not been examined. In this study, we found that the binding of both AQ and CLZ to neutrophils from MPO knockout mice ex vivo decreased approximately 2-fold compared to neutrophils from wild-type mice, whereas binding to activated neutrophils from gp91 knockout (NADPH oxidase null) mice decreased 6-7-fold. When the AQ studies were performed in vivo, again the binding was decreased in MPO knockout mice to about 50% of the binding in wild-type mice; however, covalent binding was significant in the absence of MPO. Surprisingly, there was no significant decrease in covalent binding of AQ to neutrophils in vivo in gp91 knockout mice. In addition, there was extensive binding of AQ to many types of bone marrow cells and to peripheral lymphocytes. These results indicate that MPO is not the only neutrophil enzyme involved in the oxidation of AQ and that NADPH oxidase is not the major source of peroxide. There was also no decrease in AQ binding to neutrophils in COX-1 or COX-2 knockout mice. We were not able to readily reproduce the AQ in vivo studies with CLZ because of its acute toxicity in mice. These are the first studies to examine the enzymes involved in the bioactivation of AQ by neutrophils in vivo.

  3. 药物性白细胞减少和粒细胞缺乏症临床分析%Clinical analysis of pharmacologic leukopenia and agranulocytosis

    Institute of Scientific and Technical Information of China (English)



    目的 分析一组临床常用药物致白细胞减少和粒细胞缺乏的临床表现,提高对药物所致血液系统损害的认识,促进合理用药,提高临床用药安全性.方法 收集1990年1月至2010年12月经我院血液科诊治的66例药物性白细胞减少和粒细胞缺乏患者的临床资料进行回顾性分析.结果 66例药物性白细胞减少和粒细胞缺乏患者中,抗甲状腺功能亢进药所致者16例,占24.2%,抗菌药物9例,占13.6%;抗精神病药物9例,占13.6%;抗癫痫病药物9例,占13.6%;抗类风湿性关节炎药物6例,占9.1%;抗痛风药物4例,占6.1%;降糖药物3例,占4.5%;治疗系统性红斑狼疮皮肤损害的药物3例,占4.5%;治疗胃、十二指肠球部溃疡的药物2例,占3.0%;解热镇痛药物2例,占3.0%;预防乳腺癌根治术后复发的抗雌激素药物2例,占3.0%;口腔科治疗牙痛的中成药制剂1例,占1.5%.临床表现有:白细胞下降(54例,81.8%),粒细胞缺乏(12例,18.2%),骨髓造血功能停滞(3例,4.5%),高热(23例,34.8%),皮肤损害(10例,15.1%),继发各种感染(58例,89%),重症感染(10例,15.1%),感染性休克(3例,4.5%),真菌性败血症(2例,3%),肝功能衰竭(1例,1.5%),肾功能衰竭(1例,1.5%),死亡(3例,4.5%).结论 临床部分常用药物可致白细胞减少、粒细胞缺乏而继发各种感染,可导致病情急剧变化,甚至危及生命,所以要高度重视药物使用的安全性.%Objective By describing the clinical manifestation of a group of commonly used medicines causing pharmacologic leukopenia and agranulocytosis,obtain a better understanding of damage to the blood system by medicines,call attention to rational medication and increase the pharmic safety.Methods Retrospectively analyze the clinical data of the 66 patients of the Department of Hematology in my working hospital from January 1990 to December 2010.Results Among the 66 patients,ADR of 16(24.2

  4. 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


    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。

  5. Clinical Features of Patients with Antithyroid Drugs Induced Agranulocytosis Complicated by Infection%抗甲状腺药物致粒细胞缺乏患者合并感染的临床特点研究

    Institute of Scientific and Technical Information of China (English)

    杨靖; 谢翠松; 陈亚军; 钟警; 洪涛; 文格波


    Objective To investigate the clinical features of patients with agranulocytosis induced by antithyroid drugs ( ATD ) and infection complication. Methods Retrospective analysis was conducted on clinical data of 36 ATD induced agranulocytosis inpatients complicated by infection in three affiliated hospitals of South China University. Results Among the 36 patients there were 27 induced by methimazole ( MMI ) and 9 induced by propylthiouracil ( PTU ), and the foci of the complicated infection were mainly in respiratory tract, followed by urinary tract, digestive tract, skin and soft tissue. Blood or secretions were cultured for 31 patients after admission, of which 24 specimens got pathogens, including 10 stains of G+ cocci, 13 strains of G-bacillus and 3 strains of fungal ( 2 with mixed infection ) . Conclusion The ATD induced agranulocytosis patients are susceptible to secondary mlections, witn respiratory mlection being the most common, Tne mlections by G+ cocci and G- bacillus are similar, but the fungal infections are not rare. It is of important significance to confirm the pathogenic bacteria by culture the secretions or blood timely so as to guide rational application of antibiotics.%目的 了解抗甲状腺药物(ATD)治疗导致粒细胞缺乏症患者合并感染的临床特点.方法 对36例服用ATD导致粒细胞缺乏且合并感染的住院患者临床资料进行回顾性分析.结果 36例粒细胞缺乏患者中27例由甲巯咪唑所致,9例由丙基硫氧嘧啶所致,主要感染部位为呼吸道,其次为泌尿系、消化道及皮肤软组织.31例患者住院后进行了血或分泌物培养,24份标本培养出致病菌,其中革兰阳性(G+)球菌10株,革兰阴性(G-)杆菌13株,真菌3株(有2例患者为混合感染).结论 ATD导致粒细胞缺乏患者容易继发各种感染,其中呼吸道感染最为常见,感染致病菌中G-杆菌与G+球菌相当,真菌感染并不少见,及时行分泌物及血培养对明确致病菌及指导

  6. Micofenolato mofetil na síndrome de Sjögren primária: uma opção para o tratamento da agranulocitose Mycophenolate mofetil in primary Sjögren's syndrome: a treatment option for agranulocytosis

    Directory of Open Access Journals (Sweden)

    Sonia Cristina de Magalhães Souza Fialho


    Full Text Available A síndrome de Sjögren (SS é uma doença autoimune caracterizada pela presença de infiltrado linfocítico nas glândulas salivares e lacrimais. Manifestações hematológicas da síndrome de Sjögren primária (SSp geralmente consistem em anemia leve, trombocitopenia, neutropenia moderada e linfopenia. Agranulocitose é raramente descrita e, em geral, responde bem ao tratamento de imunossupressão. Neste trabalho, descrevemos o caso de uma paciente portadora de SSp que apresentou quadro de agranulocitose refratária ao tratamento. A biópsia de medula revelou medula óssea hipocelular com maturação normal da série granulocítica. A paciente foi sucessivamente tratada com prednisona em altas doses, fator estimulador de colônia de macrófagos e ciclosporina, todos sem resposta hematológica. Micofenolato mofetil (MMF foi iniciado, e após dois meses houve aumento na contagem das células brancas. Após um ano de seguimento a paciente não apresentou novos episódios de neutropenia, nem complicações infecciosas. Concluímos que, na agranulocitose refratária associada à SSp, o tratamento com MMF pode ser uma opção eficaz e bem tolerada.The Sjögren's syndrome (SS is an autoimmune disease characterized by a lymphocytic infiltration of salivary and lacrimal glands. Hematological manifestations of primary SS (pSS usually consist of mild anemia, thrombocytopenia, moderate neutropenia, and lymphopenia. Agranulocytosis is rarely reported and usually responds to immunosuppression. We report the case of a pSS patient who presented with refractory agranulocytosis. Bone marrow biopsy disclosed a hypocellular bone marrow with normal maturation of the granulocytic series. The patient was successively treated with high-dose prednisone, granulocyte-macrophage colony stimulation factor, and cyclosporine, with no hematological response. Mycophenolate mofetil (MMF was initiated and after two months there was a rise on the white blood cell count. After

  7. 白血病化疗后粒细胞缺乏伴真菌感染患者抗菌药物的应用研究%Study on use of antimicrobial drugs by leukemia patients complicated with agranulocytosis and fungal infections after chemotherapy

    Institute of Scientific and Technical Information of China (English)

    古力巴旦木·艾则孜; 袁海龙; 曹海洲; 陈刚; 曲建华


    目的 探讨白血病化疗后粒细胞缺乏伴真菌感染患者抗菌药物的应用,为临床白血病治疗提供药物治疗依据.方法 回顾性分析2013年8月-2014年10月医院收治的120例白血病化疗后粒细胞缺乏伴真菌感染患者临床资料;所有中性粒细胞<0.5×109/L患者均应用粒细胞集落刺激因子,白血病粒细胞缺乏伴发热患者首先经验性抗细菌治疗,直至获得准确的病原学培养结果 选用抗菌药物;对疑似真菌感染的患者,先给予氟康唑治疗5~12 d;拟诊或临床诊断以及确诊真菌感染后分层使用抗真菌药物;调查患者治疗后临床症状改善情况,采用SPSS 20.0软件对数据进行统计分析.结果 120例感染患者检出真菌以白色假丝酵母菌为主,占60.8%;经抗真菌药物治疗后治疗有效112例,有效率为93.3%;治疗24~48 h后体温下降,临床症状有所改善;患者应用粒细胞集落刺激因子3~5 d后,血白细胞升至1.0×109/L以上,中性粒细胞升至0.5×109/L以上;8例患者因感染性休克死亡,病死率6.7%;16例发生不良反应,发生率13.3%.结论 白血病患者化疗后粒细胞缺乏伴真菌感染患者,应根据病原菌鉴定和药敏试验的结果 合理选择抗菌药物,并对真菌感染患者采用预防性抗真菌治疗.%OBJECTIVE To explore the use of antibiotics by leukemia patients complicated with agranulocytosis and fungal infections after chemotherapy so as to provide guidance for drug therapy .METHODS The clinical data of 120 leukemia patients complicated with agranulocytosis and fungal infections after chemotherapy who were treated in the hospital from Aug 2013 to Oct 2014 were retrospectively analyzed .The patients with neutrophils counts less than 0 .5 × 109/L were treated with granulocyte colony stimulating factors ,the leukemia agranulocytosis patients complicated with fever were firstly given the empirical antibacterial treatment and then treated with antibiotics till the

  8. Urinary Tract Infection (UTI) Caused by Fusarium proliferatum in an Agranulocytosis Patient and a Review of Published Reports. (United States)

    Su, Huilin; Zhang, Qiangqiang; Li, Li; Zhao, Ying; Zhu, Junhao; Zhu, Min


    Infections caused by Fusarium species are increasing in frequency among immunocompromised hosts, but urinary tract infection (UTI) due to Fusarium proliferatum has not been reported in the literature so far. We describe a case of UTI caused by F. proliferatum in a 47-year-old man who was diagnosed with rectal cancer and metastasis. He underwent radical resection of rectal carcinoma and local resection of hepatic metastases. After the first adjuvant chemotherapy, the patient presented the obvious high fever, severely diarrhea and progressive decline of the white blood cell count. The direct microscopic examination of fungi in urine was positive, and the fungal cultures showed white, cotton-like colony. After the DNA sequencing, it was identified as F. proliferatum. We gave the patient itraconazole and other antibiotics to fight the infection. A month later, the temperature dropped to normal and the results of the direct microscopic examination and culture of fungi in urine turn negative. The itraconazole is effective against F. proliferatum.

  9. Death due to diarrhea and agranulocytosis caused by irinotecan%伊立替康相关腹泻及粒细胞缺乏致死亡

    Institute of Scientific and Technical Information of China (English)

    曹凯; 司继刚; 孙敏


    A 62-year-old man with colon cancer was given irinotecan at a dose of 80 mg by intravenous administration on day 1 and day 8. After the treatment, diarrhea was followed lasting for 11 days, and it aggravated with fever on day 13. The patient was sent to the emergency for the further therapy. The laboratory examination revealed that WBC was 0.34×109·L-1, NEUT was 5.94%, L was 85.34%, RBC was 3.84×1012·L-1, Hb was 114.0 g·L-1, PLT was 33×109·L-1, blood urea nitrogen was 13.71 mmol·L-1 and serum creatinine was 291μmol·L-1. The patient received a serial of therapy, including anti-infection with cefpirome, enhancing leukocytes with recombinant human granulocyte colony stimulating factor injection, immune regulation, controlling diarrhea, protecting the renal functions and lfuid resuscitation, etc. On the second day of admission, the patient appeared septic shock while the anti-shock treatment was adopted. On the third day, the patient was in deep coma and blood pressure was dififcult to maintain. The patient eventually died of circulatory and respiratory failure.%1例62岁结肠癌男性患者,接受伊立替康80 mg静脉滴注d1、d8化疗。化疗后反复腹泻11 d,化疗第13天腹泻加重伴发热,急诊入院。查血常规示:WBC 0.34×109·L-1,NEUT 5.94%,L 85.34%,RBC 3.84×1012·L-1,Hb 114.0 g·L-1, PLT 33×109·L-1。BUN 13.71 mmol·L-1,Scr 291μmol·L-1。给予头孢匹罗抗感染,重组人粒细胞集落刺激因子升白细胞,免疫调节,止泻、护肾、补液等对症治疗,入院第2天出现感染性休克,给予抗休克等治疗。第3天出现深度昏迷,血压难以维持。最终因循环、呼吸衰竭死亡。

  10. Multiple Animal Studies for Medical Chemical Defense Program in Soldier/ Patient Decontamination and Drug Development (United States)


    for micronuclei determination. Particular emphasis is placed on evaluating any transient leucopenia , leucocytosis, and/or agranulocytosis as a function...for micronuclei determination. Particular emphasis is placed on evaluating any transient leucopenia , leucocytosis, and/orU agranulocytosis as a

  11. A Health and Environmental Effects Data Base Assessment of U.S. Army Waste Material, Phase 2 (United States)


    lymphadenopathies may occur; fata aplastic anemia has occured in a small proportion of patients; agranulocytosis, thrombo cytopenia, and leucopenia ...occurred in a small proportion of patients; agranulo- cytosis, thrombocyto- penia, and leucopenia have been reported; antithyroid activity Human contact NS

  12. 卡泊芬净在中性粒细胞缺乏伴持续发热患者经验性抗真菌治疗中的疗效观察%Clinical evaluation of caspofungin as empirical antifungal therapy in patients with persistent fever and agranulocytosis

    Institute of Scientific and Technical Information of China (English)

    黎纬明; 邹萍; 游泳; 陈智超


    卡泊芬净(caspofungin acetate,亦称MK20991,L2743872)是第一个批准用于临床的棘白菌素。此类药物毒性低,对大多数临床分离的念珠菌属和曲霉属均有快速杀菌作用。在血液科恶性肿瘤接受化疗或进行造血干细胞移植、再生障碍性贫血等发生中性粒细胞缺乏的患者中,侵袭性真菌感染是其重要的死亡原因。本研究报道5例中性粒细胞缺乏患者经验性应用卡泊芬净的疗效与不良反应。

  13. Respiratory failure caused by intrathoracic amoebiasis

    Directory of Open Access Journals (Sweden)

    Toshinobu Yokoyama


    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

  14. Chronic myelomonocytic leukemia blast crisis in a patient with advanced non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors. (United States)

    Ogata, Hiroaki; Okamoto, Isamu; Yoshimoto, Goichi; Obara, Teppei; Ijichi, Kayo; Iwama, Eiji; Harada, Taishi; Akashi, Koichi; Nakanishi, Yoichi


    A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis. Physicians should be aware of such risks and monitor EGFR-TKI-treated patients with myeloid neoplasms accordingly.

  15. Treatment of Malaria (United States)


    Diarrhoea, constipation, pruritus, and nervousness have also been described, Rarely encountered serious reactions include urticaria , bronchospasm... angioedema of the face, mucous membranes and the lungs, deafness, blindness or amblyopia, haemolytic anaemia, and agranulocytosis. The deafness and...ToxicitY. Silphionarniides are generally well tolerated, but they can cause 190 S. L. HOFFMAN hepatitis, urticaria , erythema multiforme, Stevens

  16. Malaria Chemoprophylaxis in Military Aircrew (United States)


    for WHO Group 1I endemic deficiency, including macrocytic anemia , areas. aphthous ulcers, and stomatitis. - Chemoprophylaxis for WHO Group III endemic...deficiency is an absolute contraindication because of the risk of -- docetaxel (Taxotere®) hemolytic anemia . This defect is known to affect...headache shown such a property. - accommodation disorders - agranulocytosis, anemia and CONCLUSION methemoglobinemia The choice of malaria

  17. Haematological toxicity of clozapine and some other drugs used in psychiatry

    NARCIS (Netherlands)

    Nooijen, Patty M. M.; Carvalho, Felix; Flanagan, Robert J.


    Objective To review recent work on the haematological toxicity of clozapine and some other drugs used in psychiatry concerning especially (i) the mechanism of antipsychotic-induced neutropenia/agranulocytosis, (ii) criteria for clozapine prescribing in benign ethnic neutropenia, (iii) options in the

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

    DEFF Research Database (Denmark)

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


    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...... of agranulocytosis (1 in pregnancy) and 10 cases of liver failure (1 in pregnancy). This corresponded to 41/11 cases of agranulocytosis/liver failure per 5 million inhabitants during a 10-year period (agranulocytosis: 0.16% of ATD exposed (MMI: 0.11% vs. PTU: 0.27%, p=0.02); liver failure: 0.03% of ATD exposed (MMI......: 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...

  19. Beyond White Blood Cell Monitoring : Screening in the Initial Phase of Clozapine Therapy

    NARCIS (Netherlands)

    Cohen, Dan; Bogers, Jan P. A. M.; van Dijk, Daniel; Bakker, Bert; Schulte, Peter F. J.


    Objective: Clozapine is the preferred option for treatment-resistant schizophrenia. However, since 1975, clozapine has been known to cause agranulocytosis. In the clozapine screening guidelines, white blood cell count is mandatory. In the past 20 years, after its reintroduction, 3 other serious side

  20. Meldingen van vermoedelijke bijwerkingen bij het Bureau Bijwerkingen Geneesmiddelen; onderzoeksactiviteiten in 1993

    NARCIS (Netherlands)

    Stricker, B H; Ottervanger, J P; van der Klauw, M M


    In 1993, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs received 1585 reports of suspected adverse reactions. The most important reports concerned myocardial infarction due to sumatriptan, cholestatic hepatitis due to itraconazole, agranulocytosis due to trazodone and bleeding d

  1. Successful clozapine re-challenge in a patient with three previous episodes of clozapine-associated blood dyscrasia. (United States)

    Foster, Jessica; Lally, John; Bell, Victoria; Shergill, Sukhi


    A case is presented of a 30-year-old female with treatment-resistant schizoaffective disorder who was referred to a tertiary-level specialist psychosis service. We describe the history of clozapine trials and associated episodes of agranulocytosis and neutropenia, followed by the successfully tolerated third clozapine re-challenge within our service.

  2. Clozapine underutilization and discontinuation in African Americans due to leucopenia. (United States)

    Kelly, Deanna L; Kreyenbuhl, Julie; Dixon, Lisa; Love, Raymond C; Medoff, Deborah; Conley, Robert R


    Clozapine use has been notably lower in African American patients than in Caucasians. It has been suggested that lower normal ranges for white blood cell (WBC) counts in African Americans, known as benign ethnic neutropenia, may account partially for the disparity. We examined the rates of leucopenia and agranulocytosis as reasons for discontinuation of clozapine in a sample of 1875 patients with schizophrenia treated in the State of Maryland. Between 1989 and 1999, 5.3% (31/588) of African Americans and 2.4% (31/1287) of Caucasians discontinued clozapine treatment due to leucopenia (chi square = 10.35, df = 1, P = 0.001). No African American patients developed agranulocytosis while 8 Caucasian patients (0.62%) developed this blood dyscrasia. Discontinuations due to leucopenia occurred throughout treatment. Discontinuations due to agranulocytosis occurred primarily in the first 18 weeks (7/8; 87.5% patients with agranulocytosis). It is likely that African Americans had clozapine discontinued unnecessarily due to benign ethnic neutropenia. We concur with recent recommendations to acknowledge differences in WBC values in African Americans and to modify prescribing guidelines or formally acknowledge benign ethnic leucopenia like in other countries in order to facilitate greater use of clozapine in these patients.

  3. Delayed onset of clozapine-induced leucopenia. (United States)

    Nongpiur, Arvind; Praharaj, Samir Kumar; Sarkar, Sukanto; Das, Basudeb


    Clozapine has been reported to cause agranulocytosis, neutropenia, and leucopenia that usually occur within 18 weeks of initiation of treatment. We report a case of delayed onset leucopenia after 11 years of treatment with clozapine, which reversed within a few days after discontinuation of medication.

  4. Levamisole induced necrosis of the skin and neutropenia following intranasal cocaine use: a newly recognized syndrome. (United States)

    Mouzakis, John; Somboonwit, Charurut; Lakshmi, Seetha; Rumbak, Mark; Sinnott, John; Cherpelis, Basil; Keshishian, Jonathan


    Levamisole is a veterinary anti-helminthic used to treat several autoimmune conditions but also commonly utilized as an additive in cocaine distribution. Toxicity resulting in agranulocytosis and cutaneous necrosis in association with cocaine use is an infrequently described phenomenon of an emerging problem. Although levamisole is found extensively in the cocaine supply of the United States, relatively few cases of necrotic skin lesions associated with intranasal use have been reported. The skin necrosis secondary to levamisole toxicity is characterized by variable findings on biopsy, ranging from leukocytoclastic vasculitis to occlusive vasculopathy. The following case describes a 54-year-old male who developed fever, agranulocytosis, p-ANCA autoantibodies and extensive skin necrosis following heavy intranasal cocaine use. Necrosis of greater than 50% of the patient's total body surface area resulted and was followed by thorough wound debridement.

  5. Traditional Chinese and Western Medicine Treatment of Hyperthyroidism Crisis%甲亢危象的中西医治疗

    Institute of Scientific and Technical Information of China (English)



    This paper summarizes the etiology,pathogenesis,diagnosis,treatment of traditional Chinese and Western medicine methods of hyperthyroidism crisis and hyperthyroidism crisis with neutropenia or agranulocytosis.A case of the portent with agranulocytosis was reported and analysed,so as to provide reference for the clinical treatment.%文章总结了甲亢危象及甲亢危象合并粒细胞减少或缺乏的病因、发病机制、诊断、中西医治疗方法.并报道分析了甲亢危象先兆合并粒细胞缺乏临床病案一例,为临床治疗提供借鉴.

  6. Diagnosis and Treatment of Thyroid Disorders


    磯崎, 収; ISOZAKI, Osamu


    The incidence of thyroid disorders including subclinical diseases is compatible with that of diabetes mellitus, one of the most epidemic metabolic disorders causing social problems. Graves' disease accounts for more than 90% thyrotoxicosis in Japan. However painless thyroiditis, which is self-limiting, should be ruled out before treatment. One of the important issues for the treatment of Graves' disease with antithyroid drugs is how to manage the agranulocytosis, one of the most serious side ...

  7. [Rare side effects in management of hyperthyroidism. Case report]. (United States)

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


    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.

  8. Final Programmatic Environmental Impact Statement for Defense Threat Reduction Agency (DTRA) Activities on White Sands Missile Range, New Mexico. Volume 1 (United States)


    the quality or condition of causing death. lethargic- not very alert or active. leucopenia - an abnormal lowering of the white blood cell count...perchlorate has produced fatal aplastic anemia along with other blood disorders which include agranulocytosis, thrombocytopenia, and leucopenia . It reduces...condition of causing death. lethargic - not very alert or active. leucopenia - an abnormal lowering of the white blood cell count. M maximum

  9. Adverse effects of levamisole in cocaine users: a review and risk assessment. (United States)

    Brunt, Tibor Markus; van den Berg, Jorrit; Pennings, Ed; Venhuis, Bastiaan


    The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

  10. Dapsone and sulfapyridine. (United States)

    Paniker, U; Levine, N


    Dapsone and sulfapyridine are structurally related compounds with anti-microbial and anti-inflammatory effects. Dapsone remains the most important drug for leprosy and is useful in the prophylaxis of Pneumocystis pneumonia in patients with HIV disease. The medical treatment of choice for dermatitis herpetiformis is dapsone; and sulfapyridine also can be used for those patients who are intolerant of dapsone. Other neutrophilic disorders also may respond to these drugs. Toxic side effects of both dapsone and sulfapyridine are mediated through the hydroxylamine metabolite. These include hemolysis, methemoglobinemia, and agranulocytosis. Careful monitoring for possible adverse reactions includes frequently performing complete blood counts and regular blood chemistry profile determinations.

  11. Clozapine-Induced Myocarditis: Is Mandatory Monitoring Warranted for Its Early Recognition?

    Directory of Open Access Journals (Sweden)

    T. A. Munshi


    Full Text Available Clozapine is an atypical antipsychotic used for treatment resistant schizophrenia. Its potential to induce agranulocytosis is well known but it can also cause myocarditis. Clozapine is the only antipsychotic known to induce this side effect, typically early in the treatment, and literature is scarce on this condition. We are presenting a case report of a 21-year-old schizophrenic male who developed myocarditis within 3 weeks of starting on clozapine for his treatment resistant psychosis. We then aim to review some of the available literature and raise awareness among physicians as this condition can potentially be fatal if not detected early.

  12. [Haematological adverse effects caused by psychiatric drugs]. (United States)

    Mazaira, Silvina


    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.

  13. Levamisole-Induced Vasculitis with Renal Involvement. (United States)

    Chawdhary, Karan; Parke, Ann


    A significant amount of cocaine used in the United States today is adulterated with levamisole. In some instances, prolonged use of contaminated cocaine is associated with the development of levamisole-induced vasculitis (LIV) with features of cutaneous vasculitis and agranulocytosis along with other constitutional symptoms and arthritis. We describe a case of a crack cocaine user with LIV, who developed significant renal disease secondary to crescentic glomerulonephritis, confirmed on renal biopsy. Renal vasculitis is an uncommon feature of LIV and significantly affects clinical course and management.

  14. COKE LIVe: recurrent vasculitis secondary to cocaine contaminated with levamisole. (United States)

    Sandys, Vicki; Mahabir, Shanti; Byrne, Declan; Wynne, Bairbre


    Levamisole-induced vasculitis (LIV) is becoming an increasingly common entity secondary to both rising cocaine use in the UK and high levels of adulteration of cocaine with various contaminants. We report the first documented case of LIV secondary to adulterated cocaine in Ireland, which presented as a 6-year history of recurrent vasculitis of unknown aetiology. Classically, LIV is diagnosed by a combination of positive ANCA serology and agranulocytosis however, given the frequency of cocaine use, we urge acute physicians to consider the diagnosis in cases of typical retiform (angulated) purpura in association with a history of cocaine use.

  15. Complications Associated With Use of Levamisole-Contaminated Cocaine: An Emerging Public Health Challenge (United States)

    Lee, Kachiu C.; Ladizinski, Barry; Federman, Daniel G.


    Levamisole is an immunomodulatory agent that was used to treat various cancers before being withdrawn from the United States market in 2000 because of adverse effects. Levamisole is currently approved as an antihelminthic agent in veterinary medicine, but is also being used illicitly as a cocaine adulterant. Potential complications associated with use of levamisole-laced cocaine include neutropenia, agranulocytosis, arthralgias, retiform purpura, and skin necrosis. Treatment is primarily supportive, and skin lesions typically resolve with cessation of cocaine use. The incidence of hospitalizations related to use of levamisole-contaminated cocaine continues to increase and clinicians should be aware of the more common clinical manifestations. PMID:22677078

  16. Old drug new trick: levamisole-adulterated cocaine causing acute kidney injury. (United States)

    Ammar, Abeer T; Livak, Mark; Witsil, Joanne C


    Levamisole is an agent previously used in humans and later withdrawn from the US drug market due to concerns of agranulocytosis.It is currently used as an adulterating agent in cocaine, bringing to light toxicities typically manifested by vasculitis and skin necrosis.We report a case of a 36-year-old crack cocaine user who presented with a purpuric rash on her face and limbs. Levamisole-induced vasculitis was suspected, and she therefore underwent an extensive work-up. In addition to these findings, she also presented with acute kidney injury of unknown etiology, which was later attributed to levamisoleadulterated cocaine.

  17. HLA types in patients with rheumatoid arthritis developing leucopenia after both gold and sulphasalazine treatment.


    Bliddal, H; Eiberg, B; Helin, P; Svejgaard, A.


    HLA types, especially HLA-DR3, are associated with the development of toxic reactions in patients with rheumatoid arthritis after treatment with gold or D-penicillamine. In this study, after treatment with sulphasalazine, leucopenia was observed in three patients, who all had a history of leucopenia after previous gold treatment. The HLA types of these patients did not include HLA-DR3; the two patients developing mild leucopenia had HLA-DR2 and the one developing agranulocytosis had HLA-DR4.

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

    Directory of Open Access Journals (Sweden)

    Arvind Kumar


    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

  19. Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Corinna Barkam


    Full Text Available Valganciclovir (VGC, an oral prodrug of ganciclovir (GCV, has been shown to clear cytomegalovirus (CMV viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT, apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79% than non-VGC therapies (69%. The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients, we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%, we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66 compared to non-VGC (25 days (0–115, without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.

  20. Toxicities associated with 1-month treatment with propylthiouracil (PTU) and methimazole (MMI) in male rats. (United States)

    Nambiar, Prashant R; Palanisamy, Gopinath S; Okerberg, Carlin; Wolford, Angela; Walters, Karen; Buckbinder, Leonard; Reagan, William J


    Thionamides such as propylthiouracil (PTU) and methimazole (MMI) have been used for more than 50 years to treat the more common causes of thyrotoxicosis/hyperthyroidism such as Graves' disease. Serious adverse effects associated with thionamides in humans include idiosyncratic liver damage, agranulocytosis, aplastic anemia, and vasculitis. Both prospective and retrospective clinical studies with these drugs have failed to identify predictive biomarker for these adverse effects. To assess whether rat is a good model for predicting drug-related adverse events in the liver and in the bone marrow, we conducted a comprehensive study in male rats with multiple doses of PTU and MMI. As expected, euthyroid animals became hypothyroid along with several secondary changes associated with hypothyroidism. There were slight reductions in red blood cell parameters along with some marginal effects on the bone marrow elements. However, there was no evidence of significant neutropenia and liver injury in both PTU-treated and MMI-treated cohorts. MMI-related effects were noted in the seminiferous tubules of the testes. Overall, 1-month daily treatment of euthyroid rats with PTU or MMI resulted in hypothyroidism, minor bone marrow effects, and several secondary effects associated with hypothyroidism, but without any evidence of adverse effects reported in humans including liver injury and agranulocytosis.

  1. Levamisole-induced necrosis of skin, soft tissue, and bone: case report and review of literature. (United States)

    Ching, Jessica A; Smith, David J


    This represents the largest case of skin necrosis related to levamisole, a common cocaine contaminant, requiring closure with skin grafts, and is the only case resulting in nasal amputation, central upper lip excision, extremity bone necrosis, and above knee amputation. The case report is followed by a review of the literature. Unique considerations for the full-thickness necrosis induced by levamisole vasculitis are highlighted, including antibody level monitoring, need for multiple excisions, timing of skin grafting, and potential for soft tissue and bone necrosis as well. A 54-year-old man presented to an outside facility with fever, generalized weakness, and agranulocytosis, with a history of cocaine use 3 weeks before. After admission, he developed generalized violaceous lesions and an elevated p-antineutrophilic cytoplasmic antibody and was diagnosed with disseminated vasculitis and agranulocytosis secondary to levamisole-contaminated cocaine exposure. On transfer to the authors' facility, 52% TBSA was involved with violaceous, nonblanching lesions, which progressed to full-thickness necrosis. Local wound care continued until necrotic areas fully demarcated and progressive necrosis stabilized, and skin grafting for closure was not performed until antibody levels normalized. Current treatment of levamisole-induced skin rash or necrosis focuses on discontinuation of levamisole. As demonstrated by this case, extensive necrosis secondary to levamisole-induced vasculitis can be successfully treated with multiple excisions until necrosis stabilizes, and then, split-thickness autografts may be applied. In areas with poor vascular supply or areas with poor functional prognosis, amputation may ultimately be required.

  2. Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia (United States)

    Legge, Sophie E; Hamshere, Marian L; Ripke, Stephan; Pardinas, Antonio F; Goldstein, Jacqueline I; Rees, Elliott; Richards, Alexander L; Leonenko, Ganna; Jorskog, L Fredrik; Chambert, Kimberly D; Collier, David A; Genovese, Giulio; Giegling, Ina; Holmans, Peter; Jonasdottir, Adalbjorg; Kirov, George; McCarroll, Steven A; MacCabe, James H; Mantripragada, Kiran; Moran, Jennifer L; Neale, Benjamin M; Stefansson, Hreinn; Rujescu, Dan; Daly, Mark J; Sullivan, Patrick F; Owen, Michael J; O’Donovan, Michael C; Walters, James T R


    The antipsychotic clozapine is uniquely effective in the management of schizophrenia, but its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown although genetic factors play an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed HLA alleles, exome array, and copy number variation analyses. We then combined associated variants in a meta-analysis with data from the Clozapine-Induced Agranulocytosis Consortium (up to 163 cases and 7970 controls). In the largest combined sample to date, we identified a novel association with rs149104283 (OR=4.32, P=1.79×10-8), intronic to transcripts of SLCO1B3 and SLCO1B7, members of a family of hepatic transporter genes previously implicated in adverse drug reactions including simvastatin-induced myopathy and docetaxel-induced neutropenia. Exome array analysis identified gene-wide associations of uncommon non-synonymous variants within UBAP2 and STARD9. We additionally provide independent replication of a previously identified variant in HLA-DQB1 (OR=15.6, P = 0.015, positive predictive value = 35.1%). These results implicate biological pathways through which clozapine may act to cause this serious adverse effect. PMID:27400856

  3. [Successful second cord blood transplantation (CBT) for late graft failure associated with several immune disorders after the initial CBT in a patient with acute myeloid leukemia]. (United States)

    Mori, Minako; Yonezawa, Akihito; Kitagawa, Tomoya; Sasaki, Yuya; Onaka, Takashi; Imada, Kazunori


    A 64-year-old woman underwent reduced-intensity conditioning cord blood transplantation (RIC-CBT) for refractory acute myeloid leukemia (AML). A 6/6 antigen-level HLA-identical cord blood from a male infant was transfused. After successful engraftment with complete donor chimerism, the patient developed mixed chimera (XX 8.8%) on day 82. Tapering of tacrolimus was started on day 96. Bone marrow chimerism analysis showed a decreasing recipient cell population (XX 2.2%) on day 117 and tacrolimus was discontinued with no clinical signs of GVHD on day 123. However, pancytopenia with agranulocytosis was detected on day 138. She was diagnosed as having secondary graft failure associated with Coombs-positive immune hemolytic anemia and immune thrombocytopenia (ITP). At the same time, the percentage of recipient T cell chimerism in peripheral blood was about 50% and the B cell population showed lambda light chain restriction. On day 180, she received a second RIC-CBT due to lack of improvement of agranulocytosis. A single dose of rituximab was administered on day - 11 before the second CBT to eliminate the activated B cells. Prompt neutrophil engraftment was achieved and both hemolytic anemia and ITP also showed resolution. She is currently well (30 months after the second CBT), showing normal blood cell counts and complete second donor chimerism of marrow cells.

  4. 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


    morbidity in infants. Volunteers were stratified according to parasitaemia status and randomly assigned 20 participants each arm to three days treatment with either AQ or chloroquine (CQ). The level of difference of selected haematological and hepatological values pre-and post-trial were marginal and within......-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....

  5. Clozapine: A new revolt in treatment of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Maleki H


    Full Text Available Clozapine is the first antipsycotic drug with a great efficacy. Thirty to fifty percent of treatment-resistant schizophrenics markedly improved with clozapine. Approximately, 25% of long-term patients, treated with clozapine, could be discharged. This improvement included negative as well as positive symptom areas. Clozapine produced no extrapyramidal side effects. Tardive dyskinesia, a major side effect of antipsychotics is not probably induced by the drug. Agranulocytosis that occurs in 1-2% of patients treated with clozapine is the most dangerous side effect with a high mortality rate. So, weekly monitoring of white blood cell count is necessary for safe and effective use of clozapine because fatal outcomes can be reduced and even completely prevented by the early detection of the reduction in white blood cell count. Clozapine offers considerable promise for better antipsychotic effect than currently available drugs, but its high cost causes substantial problems for patients with limited financial income

  6. Invasive aspergillosis: results of multicenter study

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    N. N. Klimko


    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.

  7. Evidence for the use of pimavanserin in the treatment of Parkinson’s disease psychosis (United States)

    Sarva, Harini; Henchcliffe, Claire


    Parkinson’s disease (PD) is a progressive neurodegenerative disorder with both motor and nonmotor symptoms (NMS), leading to significant morbidity and caregiver burden. Psychosis is common but is under recognized by physicians. When present, it increases the patient’s risk of hospitalization and nursing home placement and caregiver burden. Although the atypical antipsychotic agent, clozapine, has been considered the gold standard treatment, severe agranulocytosis in 0.38% of patients and more commonly milder leukopenia, resulting in frequent blood testing, limit its use. Pimavanserin, a 5HT2A receptor inverse agonist, has been shown to reduce psychosis in PD without worsening motor symptoms. It is therefore a welcome therapeutic option for this devastating NMS. PMID:27800022

  8. [Clozapine for the treatment of psychosis in 3 elderly patients with Parkinson's disease]. (United States)

    Diraoui, S; van Melick, E J M; Jansen, P A F


    Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

  9. Levamisole-Induced Vasculitis: A Characteristic Cutaneous Vasculitis Associated With Levamisole-Adulterated Cocaine. (United States)

    Roberts, Jordan A; Chévez-Barrios, Patricia


    Levamisole-induced vasculitis is a characteristic cutaneous vasculitis syndrome associated with the use of levamisole-adulterated cocaine. Patients will typically present with a painful, purpuric rash in a retiform or stellate pattern with or without central necrosis involving the extremities, trunk, nasal tip, digits, cheeks, and/or ears. A history of cocaine abuse can be elicited. Histologic features include microvascular thrombi and/or leukocytoclastic vasculitis involving small vessels of the superficial and deep dermis. Epidermal involvement is variably seen. Laboratory findings include leukopenia, neutropenia (including agranulocytosis), elevated erythrocyte sedimentation rate, normal coagulation studies, and positive autoantibodies including perinuclear and cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibody, and lupus anticoagulant. Differential diagnosis includes other microscopic vasculitides, and clinical and laboratory correlation with histologic findings is essential. Lesions typically resolve with the cessation of cocaine use. Because of the treatment implications and rising incidence of this entity, rapid and accurate diagnosis is essential.

  10. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

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    Giovanni D'Arena


    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.

  11. Hematological Side Effects of Atypical Antipsychotic Drugs

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    Serap Erdogan


    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

  12. Periodontal disease associated to systemic genetic disorders. (United States)

    Nualart Grollmus, Zacy Carola; Morales Chávez, Mariana Carolina; Silvestre Donat, Francisco Javier


    A number of systemic disorders increase patient susceptibility to periodontal disease, which moreover evolves more rapidly and more aggressively. The underlying factors are mainly related to alterations in immune, endocrine and connective tissue status. These alterations are associated with different pathologies and syndromes that generate periodontal disease either as a primary manifestation or by aggravating a pre-existing condition attributable to local factors. This is where the role of bacterial plaque is subject to debate. In the presence of qualitative or quantitative cellular immune alterations, periodontal disease may manifest early on a severe localized or generalized basis--in some cases related to the presence of plaque and/or specific bacteria (severe congenital neutropenia or infantile genetic agranulocytosis, Chediak-Higiashi syndrome, Down syndrome and Papillon-Lefévre syndrome). In the presence of humoral immune alterations, periodontal damage may result indirectly as a consequence of alterations in other systems. In connective tissue disorders, bacterial plaque and alterations of the periodontal tissues increase patient susceptibility to gingival inflammation and alveolar resorption (Marfan syndrome and Ehler-Danlos syndrome). The management of periodontal disease focuses on the control of infection and bacterial plaque by means of mechanical and chemical methods. Periodontal surgery and even extraction of the most seriously affected teeth have also been suggested. There are variable degrees of consensus regarding the background systemic disorder, as in the case of Chediak-Higiashi syndrome, where antibiotic treatment proves ineffective; in severe congenital neutropenia or infantile genetic agranulocytosis, where antibiotic prophylaxis is suggested; and in Papillon-Lefévre syndrome, where an established treatment protocol is available.

  13. Can we prevent blood dyscrasia (leucopenia, thrombocytopenia) and epileptic seizures induced by clozapine. (United States)

    Herceg, Miroslav; Muzinić, Lana; Jukić, Vlado


    Clozapine is associated with various haematological adverse effects, including leukopenia, neutropenia, agarnulocytosis, leukocytosis, anaemia, eosinophilia, thrombocytopenia and thrombocythaemia. Recognition and treatment of clozapine-related seizures also will become increasingly important as clozapine use grows in the 1990s. The decision to stop clozapine as a result of haematological adverse effects or seizures is a frustrating one for the clinician, and frequently disastrous for the patient. Cessation of treatment results in relapse. In case that patient is unresponsive to other antipsychotic, restarting clozapine should be consider, despite the risk involved. As the risk of a second agranulocytosis is much higher in those patients, various methods of militating against repeat blood dyscrasias have been treated, including granulocyte colony-stimulating factor and lithium. The decision to restart clozapine should be taken on case-by-case basis and should take into account the likely risks and benefits of restarting. Prior response to clozapine and magnitude of patient deterioration on stopping treatment are important factors to take into this consideration. Clozapine-related seizures did not preclude successful treatment with clozapine. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. With careful haematologyc control, the risk of agranulocytosis can be minimized and in case of clozapine related seizures recommendations include dose reduction, electroencephalogram (EEG), plasma-level monitoring and prophylactic antiepileptic treatment. Re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring.

  14. Efficacy of voriconazole in treatment of invasive fungal infections in elderly patients with hematological malignancies%伏立康唑治疗老年恶性血液病侵袭性真菌感染疗效分析

    Institute of Scientific and Technical Information of China (English)

    陆敏秋; 白砚霞; 李真; 左杏果; 吴梦青; 石磊; 褚彬


    OBJECTIVE To clarify the efficacy of voriconazole for the invasive fungal infections (IFI) in the elderly patients with hematological malignancies and observe the adverse reactions. METHODS The clinical data of 50 elderly IFI patients with hematological malignancies who were treated with voriconazole from May 2007 to Dec 2011 were analyzed retrospectively. RESULTS There were 4 cases confirmed, 20 cases clinically diagnosed, and 26 cases suspected; there were 14 cases treated with initial therapy, 36 cases with rescue therapy; the total effective rate was 74. 0%, 4 confirmed cases were proven effective to voriconazok, the effective rate of the clinically . diagnosed cases was 70. 0 %, the suspected diagnosis group 73. 1 %; the effective rate of the initial therapy was 85. 7 % , the rescue therapy 89. 4 % ; the effective rate of the patients receiving intravenous injection was 76. 3 %, the patients treated with simple oral administration 66. 7% , the differences were not statistically significant; there were totally 10 patients infected with Aspergillus, 5 cases were effective and Aspergillus were eradicated. Agranulocytosis affected the efficacy of voriconazole, the response rate of agranulocytosis group was 58. 4% , lower than 88. 5% of the non-agranulocytosis group (P<0. 05) ; the abnormal liver function, visual impairment,and hallucination were the main adverse reactions, which disappeared as drugs were withdrawn, the renal toxicity and cardiac toxicity were not observed. CONCLUSION Voriconazole is effective and safe, as is applied for the treatment of invasive fungal infections in elderly patients with hematologic malignancies.%目的 探讨伏立康唑在老年恶性血液病侵袭性真菌感染患者中的临床疗效及不良反应.方法 对2007年5月-2011年12月的50例老年恶性血液病侵袭性真菌感染患者的临床资料进行回顾性分析.结果 确诊4例,临床诊断20例,拟诊26例;14例患者为初始治疗,36例患者为挽

  15. Clinical analysis of 64 cases with propylthiouracil-induced granulocytopenia%丙基硫氧嘧啶致粒细胞减少症64例临床分析

    Institute of Scientific and Technical Information of China (English)

    高峰; 胡秀芬


    [Objective] To clarify the onset, development, clinical manifestations and management of propylthiouracil (PTU)-induced granulocytopenia. [ Methods ] 64 outpatients with PTU-induced granulocytopenia, who had complete medical records and were encountered during the past two years, were statistically analyzed in terms of their clinical features and treatment. [Results] In most cases the granulocytopenia occurred between 2 to 8 weeks after the drug administration and was related to the dose of PTU. Clinically the majority of the patients developed dizziness and weakness. All the subjects continued to use PTU and simultaneously received leukogenic agents or subcutaneous injection with granulocyte colony-stimulating factor (G-CSF). As a result granulocytes were restored to the normal in all the cases and none progressed into agranulocytosis. [Conclusions] The initial dose for PTU is proposed not to exceed 300 mg per day. And the peripheral leucocytes should be closely monitored especially within 1 to 2 months after PTU treatment. Either oral leukogenic agents or injectile G-CSF is effective for the leucocytes normalization, thus preventing the occurrence of agranulocytosis.%目的了解丙基硫氧嘧啶(PTU)致粒细胞减少症的发病情况、临床表现及治疗对策.方法对近2年门诊有完整记录的64例PTU致粒细胞减少症的临床特征及治疗情况进行统计分析.结果粒细胞减少症多数发生在服药后2~8周,且与PTU的剂量有关.多数病例有头昏、乏力的临床症状.全部病例继续使用PTU,加用口服升白药或皮下注射粒细胞集落刺激因子(G-CSF),粒细胞均恢复正常,无1例发生粒细胞缺乏症.结论PTU起始剂量不宜超过300mg/d,使用头1、2个月内应密切观察外周血白细胞计数,口服升白药或注射G-CSF对白细胞恢复是有效的,并可避免粒细胞缺乏症的发生.

  16. Histamine H3-receptor inverse agonists as novel antipsychotics. (United States)

    Ito, Chihiro


    Schizophrenia (SZ) that is resistant to treatment with dopamine (DA) D2 antagonists may involve changes other than those in the dopaminergic system. Recently, histamine (HA), which regulates arousal and cognitive functions, has been suggested to act as a neurotransmitter in the central nervous system. Four HA receptors-H1, H2, H3, and H4-have been identified. Our recent basic and clinical studies revealed that brain HA improved the symptoms of SZ. The H3 receptor is primarily localized in the central nervous system, and it acts not only as a presynaptic autoreceptor that modulates the HA release but also as a presynaptic heteroreceptor that regulates the release of other neurotransmitters such as monoamines and amino acids. H3-receptor inverse agonists have been considered to improve cognitive functions. Many atypical antipsychotics are H3-receptor antagonists. Imidazole-containing H3-receptor inverse agonists inhibit not only cytochrome P450 but also hERG potassium channels (encoded by the human ether-a-go-go-related gene). Several imidazole H3-receptor inverse agonists also have high affinity for H4 receptors, which are expressed at high levels in mast cells and leukocytes. Clozapine is an H4-receptor agonist; this agonist activity may be related to the serious side effect of agranulocytosis caused by clozapine. Therefore, selective non-imidazole H3-receptor inverse agonists can be considered as novel antipsychotics that may improve refractory SZ.

  17. 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.

  18. Acute thiopurine overdose: analysis of reports to a National Poison Centre 1995-2013. (United States)

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


    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.

  19. Molecularly targeted therapy for Kaposi's sarcoma in a kidney transplant patient: case report, "what worked and what did not"

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    Correa-Rotter Ricardo


    Full Text Available Abstract Background Imatinib is a tyrosine-kinase inhibitor; for which there is limited information regarding its effects on AIDS Kaposi's sarcoma and none in patients with transplant-associated Kaposi's sarcoma. Sirolimus, an immunosuppressive drug used for kidney transplant, exhibits antiangiogenic activity related to impaired production of VEGF (vascular endothelial growth factor, clinical benefit has been reported in Kaposi's sarcoma associated with renal graft. Case Presentation Here we report a case of an 80 year old male, who developed Kaposi's Sarcoma nine months after receiving a living non-related donor kidney transplant at age 74. Three years after treatment with different chemotherapeutic agents for progressive cutaneous Kaposi's Sarcoma with no visceral involvement, he was prescribed Imatinib (200 mg/day for two weeks followed by 400 mg/day after four weeks of treatment he developed anasarca, further progression of KS and agranulocytosis. Imatinib was discontinued and there was significant clinical recovery. One year later his immunosuppressive therapy was changed to Sirolimus and regression of the Kaposi's sarcoma occurred. Conclusion The lack of benefit and severe toxicity associated with the use of Imatinib in this patient should alert clinicians of potentially adverse consequence of its use in patients with transplant associated Kaposi's sarcoma. On the other hand the positive response seen in this patient to Sirolimus even after a long evolution of Kaposi's sarcoma, multiple chemotherapy regimens and extensive cutaneous disease further suggest it therapeutical utility for transplant associated Kaposi's sarcoma.

  20. Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer (United States)

    Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; Chang, Jianhua; Wei, Qingyi


    The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings. PMID:26993769

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


    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.

  2. Severe Bone Marrow Suppression Accompanying Pulmonary Infection and Hemorrhage of the Digestive Tract Associated with Leflunomide and Low-dose Methotrexate Combination Therapy (United States)

    Qu, Caihong; Lu, Ying; Liu, Weimin


    A 60-year-old male patient developed hyperpyrexia, cough, expectoration with blood-stained sputum, mouth ulcers, and suppurative tonsillitis after receiving 35 days of combination treatment with leflunomide (LEF) and low-dose methotrexate (MTX) for active rheumatoid arthritis. On admission, routine blood tests showed severe thrombocytopenia, agranulocytosis, and decreased hemoglobin concentration compared with the relatively normal results of 1 month previously during the first hospitalization. Chest radiography revealed inflammation in both lungs, and a fecal occult blood test was positive. Given this presentation, severe bone marrow suppression accompanying pulmonary infection and hemorrhage of the digestive tract associated with LEF and MTX combination therapy was diagnosed. After 28 days of symptomatic treatment, the patient's complications subsided gradually. This case highlighted that bone marrow suppression associated with MTX and LEF combination therapy could be very serious, even at a normal dose or especially at the beginning of treatment. MTX and LEF combination therapy should be used with caution or be limited in those with a history of pulmonary disease, hemorrhage of the digestive tract, or other relevant diseases.

  3. Clozapine induces oxidative stress and proapoptotic gene expression in neutrophils of schizophrenic patients. (United States)

    Fehsel, Karin; Loeffler, Stefan; Krieger, Klaus; Henning, Uwe; Agelink, Markus; Kolb-Bachofen, Victoria; Klimke, Ansgar


    The present study examined cellular effects of the atypical antipsychotic drug clozapine on blood cells of treated patients with and without clozapine-induced agranulocytosis (CA). Blood from one patient who commenced clozapine treatment was examined at weekly intervals for 128 days. Olanzapine-treated (n = 5) and polymedicated (n = 14) schizophrenic patients, as well as healthy subjects (n = 19) and septic shock patients (n = 8), were studied for comparison. We observed dramatically increased numbers of native neutrophils stained for superoxide anion production (P genes p53 (P genes did not correlate to the percentage of apoptotic neutrophils (2.0% +/- 1.3%), but in CA patients about 37% of the neutrophils show morphologic signs of apoptosis (P genes decreased significantly. In conclusion, high production of reactive oxygen species in neutrophils of clozapine-treated patients, together with increased expression of proapoptotic genes, suggests that neutrophils are predisposed to apoptosis in schizophrenic patients under clozapine therapy. The correlation between drug and proapoptotic markers was highest for clozapine and bax alpha as well as superoxide anion radicals. This indicates oxidative mitochondrial stress in neutrophils of clozapine-treated patients which probably contributes to the induction of apoptosis and sudden loss of neutrophils and their precursors in CA patients.

  4. Evidences of possible side effects of neuroleptic drugs:A systematic review

    Institute of Scientific and Technical Information of China (English)

    Prashant Tiwari; Rajnikant Panik; Arin Bhattacharya; Dheeraj Ahirwar; Anish Chandy


    The premise that chronic neuroleptic treatment may induce decline in some schizophrenic patients has received considerable attention. This effect, typically called super sensitivity psychosis, has been accredited to neuroleptic induced changes in mesolimbic or mesocortical dopaminergic receptors. Both typical and atypical antipsychotics generations of medication tend to block receptors in the brain's dopamine pathways which offers a number of harmful and undesired (adverse) effects including lowered life expectancy, extrapyramidal effects on motor control including akathisia (an inability to sit still), trembling, and muscle weakness weight gain, decrease in brain volume, enlarged breasts e.g. gynecomastia in men and milk discharge in men and women (galactorrhea due to hyperprolactinaemia), lowered white blood cell count (agranulocytosis), involuntary repetitive body movements (tardive dyskinesia), diabetes, and sexual dysfunction. In evaluating the risk of neuroleptic medication, the occurrence of its common side effects and uneasiness connected with these side effects should be determined. However, research has not established that neuroleptics cause the projected effect, and considerations of mechanism have not been alienated from those of causation. The focus of research in this area should be the concern or repudiation of a causal relationship between chronic neuroleptic use and psychotic relapse, even though at hand article would eradicate to researchers to find out a compiled revision on probable side effects of neuroleptic drugs.

  5. Vasculitis por Propiltiouracilo: reporte de un caso

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    Donato A. Salas-Segura


    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.

  6. Risks and benefits of rapid clozapine titration

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    Jeannie D. Lochhead


    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.

  7. A comparative study of deferasirox and deferiprone in the treatment of iron overload in patients with myelodysplastic syndromes. (United States)

    Cermak, Jaroslav; Jonasova, Anna; Vondrakova, Jana; Cervinek, Libor; Belohlavkova, Petra; Neuwirtova, Radana


    One hundred thirteen patients with myelodysplastic syndromes (MDS) with deferasirox in a daily dose of 10-40 mg/kg (65 patients). Median duration of treatment was 10,9 months for deferiprone and 13,7 months for deferasirox. A substantial reduction of iron stores evaluated as a decrease in serum ferritin of more than 50% of pretreatment level was achieved in 18 patients in deferasirox group (27.7%) but not in any patient treated with deferiprone, The incidence of adverse effects (mostly gastrointestinal symptoms) was similar after administration of both the drugs. The symptoms of deferasirox toxicity were mild and mostly transient and no drug related myelosuppresive effect was observed in contrast to deferiprone where agranulocytosis occurred in 4% of patients and the treatment had to be discontinued due to side effects in 20% of patients. The results confirmed the usefulness of deferasirox as an effective and safe iron chelator in MDS patients and indication of deferiprone as an alternative treatment only in patients with mild or moderate iron overload clearly not indicated for deferasirox.

  8. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis

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    Lohit Garg


    Full Text Available Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  9. Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases. (United States)

    Carlson, Adam Q; Tuot, Delphine S; Jen, Kuang-Yu; Butcher, Brad; Graf, Jonathan; Sam, Ramin; Imboden, John B


    Exposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine.

  10. Pauci-Immune Glomerulonephritis in Individuals With Disease Associated With Levamisole-Adulterated Cocaine (United States)

    Carlson, Adam Q.; Tuot, Delphine S.; Jen, Kuang-Yu; Butcher, Brad; Graf, Jonathan; Sam, Ramin; Imboden, John B.


    Abstract Exposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine. PMID:25398064

  11. Levamisole/Cocaine Induced Systemic Vasculitis and Immune Complex Glomerulonephritis. (United States)

    Garg, Lohit; Gupta, Sagar; Swami, Abhishek; Zhang, Ping


    Levamisole is an antihelminthic and immunomodulator medication that was banned by the USFDA in 1998. It has been increasingly used to adulterate cocaine due to its psychotropic effects and morphological properties. Adverse reactions including cutaneous vasculitis, thrombocytopenia, and agranulocytosis have been well described. Despite systemic vasculitis in this setting, renal involvement is uncommon. We report here a case of ANCA positive systemic vasculitis with biopsy proven immune complex mediated glomerulonephritis likely secondary to levamisole/cocaine. A 40-year-old Caucasian male with no past medical history presented with 3-week history of fatigue, skin rash, joint pains, painful oral lesions, oliguria, hematuria, worsening dyspnea on exertion, and progressive lower extremity edema. He had a history of regular tobacco and cocaine use. Lab testing revealed severe anemia, marked azotemia, deranged electrolytes, and 4.7 gm proteinuria. Rheumatologic testing revealed hypocomplementemia, borderline ANA, myeloperoxidase antibody, and positive atypical p-ANCA. Infectious and other autoimmune workup was negative. Kidney biopsy was consistent with immune mediated glomerulonephritis and showed mesangial proliferation and immune complex deposition consisting of IgG, IgM, and complement. High dose corticosteroids and discontinuing cocaine use resulted in marked improvement in rash, mucocutaneous lesions, and arthritis. There was no renal recovery and he remained hemodialysis dependent.

  12. Proteomic profile of aminoglutethimide-induced apoptosis in HL-60 cells: Role of myeloperoxidase and arylamine free radicals. (United States)

    Khan, Saifur R; Baghdasarian, Argishti; Nagar, Prarthna H; Fahlman, Richard; Jurasz, Paul; Michail, Karim; Aljuhani, Naif; Siraki, Arno G


    In this study, the cellular effects resulting from the metabolism of aminoglutethimide by myeloperoxidase were investigated. Human promyelocytic leukemia (HL-60) cells were treated with aminoglutethimide (AG), an arylamine drug that has a risk of adverse drug reactions, including drug-induced agranulocytosis. HL-60 cells contain abundant amounts of myeloperoxidase (MPO), a hemoprotein, which catalyzes one-electron oxidation of arylamines using H2O2 as a cofactor. Previous studies have shown that arylamine metabolism by MPO results in protein radical formation. The purpose of this study was to determine if pathways associated with a toxic response could be determined from conditions that produced protein radicals. Conditions for AG-induced protein radical formation (with minimal cytotoxicity) were optimized, and these conditions were used to carry out proteomic studies. We identified 43 proteins that were changed significantly upon AG treatment among which 18 were up-regulated and 25 were down-regulated. The quantitative proteomic data showed that AG peroxidative metabolism led to the down-regulation of critical anti-apoptotic proteins responsible for inhibiting the release of pro-apoptotic factors from the mitochondria as well as cytoskeletal proteins such as nuclear lamina. This overall pro-apoptotic response was confirmed with flow cytometry which demonstrated apoptosis to be the main mode of cell death, and this was attenuated by MPO inhibition. This response correlated with the intensity of AG-induced protein radical formation in HL-60 cells, which may play a role in cell death signaling mechanisms.

  13. Protein malnutrition impairs the immune response and influences the severity of infection in a hamster model of chronic visceral leishmaniasis.

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    Eugenia Carrillo

    Full Text Available Leishmaniasis remains one of the world's most devastating neglected tropical diseases. It mainly affects developing countries, where it often co-exists with chronic malnutrition, one of the main risk factors for developing the disease. Few studies have been published, however, on the relationship between leishmaniasis progression and malnutrition. The present paper reports the influence of protein malnutrition on the immune response and visceral disease development in adult hamsters infected with Leishmania infantum fed either standard or low protein diets. The low protein diet induced severe malnutrition in these animals, and upon infection with L. infantum 33% had severe visceral leishmaniasis compared to only 8% of animals fed the standard diet. The infected, malnourished animals showed notable leukocyte depletion, mild specific antibody responses, impairment of lymphoproliferation, presence of parasites in blood (16.67% of the hamsters and significant increase of the splenic parasite burden. Animals fed standard diet suffered agranulocytosis and monocytopenia, but showed stronger specific immune responses and had lower parasite loads than their malnourished counterparts. The present results show that protein malnutrition promotes visceral leishmaniasis and provide clues regarding the mechanisms underlying the impairment of the immune system.

  14. [The history of adverse drug reactions, relief for these health damage and safety measures in Japan]. (United States)

    Takahashi, Haruo


    The first remarkable adverse drug reaction (ADR) reported in Japan was anaphylactic shock caused by penicillin. Although intradermal testing for antibiotics had been exercised as prediction method of anaphylactic shock for a long time, it was discontinued in 2004 because of no evidence for prediction. The malformation of limbs, etc. caused by thalidomide was a global problem, and thalidomide was withdrawn from the market. Teratogenicity testing during new drug development has been implemented since 1963. Chinoform (clioquinol)-iron chelate was detected from green tongue and green urine in patients with subacute myelo-optic neuropathy (SMON) and identified as a causal material of SMON in 1970. Chinoform was withdrawn from the market, and a fund for relief the health damage caused by ADR was established in 1979. The co-administration of sorivudine and fluorouracil anticancer agents induced fatal agranulocytosis, and sorivudine was withdrawn from the market after being on sale for one month in 1993. The guidelines for package inserts were corrected with this opportunity, and early phase pharmacovigilance of new drugs was introduced later. Since acquired immune deficiency syndrome, and hepatitis B and C were driven by virus-infected blood products, the Ministry of Health, Labor and Welfare tightened regulations regarding biological products in 2003, and a fund for relief of health damage caused by infections driven from biological products was established in 2004. The other remarkable ADRs were quadriceps contracture induced by the repeated administration of muscular injection products and Creutzfeldt-Jakob disease caused by the transplantation of human dry cranial dura matter, etc. The significance of safety measures for drugs based on experiences related to ADRs is worthy of notice. New drugs are approved based on a benefit-risk assessment, if the expected therapeutic benefits outweigh the possible risks associated with treatment. Since unexpected, rare and serious

  15. Pharmacological characteristics of metamizole. (United States)

    Jasiecka, A; Maślanka, T; Jaroszewski, J J


    Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.




    A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented. Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases. Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages. Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive

  17. Development of a novel mouse model of amodiaquine-induced liver injury with a delayed onset. (United States)

    Metushi, Imir G; Cai, Ping; Dervovic, Dzana; Liu, Feng; Lobach, Alexandra; Nakagawa, Tetsuya; Uetrecht, Jack


    Amodiaquine (AQ) treatment is associated with a high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. Evidence suggests that AQ-induced IDILI is immune mediated. A significant impediment to mechanistic studies of IDILI is the lack of valid animal models. This study reports the first animal model of IDILI with characteristics similar to mild IDILI in humans. Treatment of female C57BL/6 mice with AQ led to liver injury with delayed onset, which resolved despite continued treatment. Covalent binding of AQ was detected in the liver, which was greater in female than in male mice, and higher in the liver than in other organs. Covalent binding in the liver was maximal by Day 3, which did not explain the delayed onset of alanine aminotransferase (ALT) elevation. However, coincident with the elevated serum ALT, infiltration of liver and splenic mononuclear cells and activation of CD8 T-cells within the liver were identified. By Week 7, when ALT levels had returned close to normal, down-regulation of several inflammatory cytokines and up-regulation of PD-1 on T-cells suggested induction of immune tolerance. Treatment of Rag1(-/-) mice with AQ resulted in higher ALT activities than C57BL/6 mice, which suggested that the adaptive immune response was responsible for immune tolerance. In contrast, depletion of NK cells significantly attenuated the increase in ALT, which implied a role for NK cells in mild AQ-induced IDILI. This is the first example of a delayed-onset animal model of IDILI that appears to be immune-mediated.

  18. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats. (United States)

    Lobach, Alexandra R; Uetrecht, Jack


    Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF). Employing a rat model of clozapine treatment, we set out to determine if the neutrophilia observed at the start of treatment is characteristic of G-CSF-associated bone marrow stimulation. Female Sprague-Dawley rats were treated with 30 mg/kg/day of clozapine for 10 days, and sustained neutrophilia was evident after 1 week of treatment paired with spikes in G-CSF. Within the bone marrow, clozapine was found to induce proliferation of the granulocyte progenitor colonies as measured by a methylcellulose assay. This led to elevated granulopoiesis observed by H&E and myeloperoxidase staining of bone marrow slices. Increased release of neutrophils from the marrow to the circulation was measured through 5-bromo-2'-deoxyuridine labeling in vivo, and these neutrophils appeared to be less mature based on (a) a decrease in the nuclear lobe count and (b) increased expression of surface CD62L. Furthermore, faster transit of the neutrophils through the marrow was suggested by a shift toward elevated numbers of neutrophils in the bone marrow maturation pool and increased CD11b and CD18 staining on the less mature neutrophils residing in the marrow. Taken together, these data indicate that clozapine stimulates the bone marrow to produce more neutrophils in a manner that is characteristic of endogenous G-CSF stimulation, and it is consistent with the inflammatory response observed in patients treated with clozapine.

  19. 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


    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.

  20. Characteristic purpura of the ears, vasculitis, and neutropeniae–a potential public health epidemic associated with levamisole-adulterated cocaine (United States)

    Chung, Catherine; Tumeh, Paul C.; Birnbaum, Ron; Tan, Belinda H.; Sharp, Linda; McCoy, Erin; Mercurio, Mary Gail; Craft, Noah


    Background Dermatologists at the University of California, San Francisco recently reported two patients in the online Journal of the American Academy of Dermatology with purpura presumably induced by levamisole in contaminated cocaine. Levamisole-induced vasculitis and neutropenia has been reported elsewhere in the United States and Canada. Up to 70% of cocaine in the United States could be contaminated. Objective We sought to describe similar cases of vasculitis associated with cocaine use. Methods This is a retrospective case series. Results We report 6 remarkably similar patients seen over just the past few months with retiform purpura on the body and tender purpuric eruptions, necrosis, and eschars of the ears after cocaine use in New York and California. All of these patients had positive perinuclear antineutrophil cytoplasmic antibody values and 3 of the 6 also had an associated neutropenia. Direct immunofluorescence studies suggested an immune complex–mediated vasculitis. Limitations This case series is descriptive in nature and, because testing is not easily performed, we did not test for levamisole in the serum or blood to prove this is the causative agent. Conclusion It appears the use of cocaine is associated with the peculiar clinical findings of ear purpura, retiform purpura of the trunk, and neutropenia. We believe this case series may represent the tip of the iceberg as a looming public health problem caused by levamisole. Although the direct causal relationship may be difficult to establish, the astute dermatologist or primary care physician should be able to recognize the characteristic skin lesions and should be wary of the potential development of agranulocytosis. (J Am Acad Dermatol 2011;65:722-5.) PMID:21658797

  1. Rare and very rare adverse effects of clozapine

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    De Fazio P


    Full Text Available Pasquale De Fazio,1 Raffaele Gaetano,1 Mariarita Caroleo,1 Gregorio Cerminara,1 Francesca Maida,2 Antonio Bruno,3 Maria Rosaria Muscatello,3 Maria Jose Jaén Moreno,4 Emilio Russo,2 Cristina Segura-García1 1Department of Health Sciences, School of Specialization in Psychiatry, 2Department of Health Sciences, School of Specialization in Pharmacology, University “Magna Graecia”, Catanzaro, 3Department of Neurosciences, School of Specialization in Psychiatry, University of Messina, Messina, Italy; 4Department of Social Health Sciences, Radiology and Physical Medicine, University of Cordoba, Cordoba, Spain Abstract: Clozapine (CLZ is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate

  2. Electroanalysis of trimethoprim on metalloporphyrin incorporated glassy carbon electrode. (United States)

    Rajith, Leena; Kumar, Krishnapillai Girish


    Trimethoprim (TMP) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors. Its use is associated with idiosyncratic reactions, including liver toxicity and agranulocytosis. In order to determine TMP electrochemically, a metalloporphyrin modified glassy carbon electrode was prepared by coating [5,10,15,20- tetrakis(4-methoxyphenyl) porphyrinato]Mn (III)chloride (TMOPPMn(III)Cl) solution on the surface of the electrode. The electrochemical behaviour of TMP in Phosphate buffer solution (PBS) on TMOPPMn(III)Cl modified glassy carbon electrode (TMOPPMn(III)Cl/GCE) was explored using differential pulse voltammetry (DPV). The voltammograms showed enhanced oxidation response at the TMOPPMn (III)Cl/GCE with respect to the bare GCE for TMP, attributable to the electrocatalytic activity of TMOPPMn(III)Cl. Electrochemical parameters of the oxidation of TMP on the modified electrode were analyzed. The electro-oxidation of TMP was found to be irreversible, pH dependent and adsorption controlled on the modified electrode. It is found that the oxidation peak current is proportional to the concentration of TMP over the range 6 × 10⁻⁸ - 1 × 10⁻⁶ M with a very low detection limit of 3 × 10⁻⁹ M at 2 min open circuit accumulation. The repeatability expressed as relative standard deviation (RSD) for n = 9 was 3.2% and the operational stability was found to be 20 days. Another striking feature is that equimolar concentration of sulfamethoxazole did not interfere in the determination of TMP. Applicability to assay the drug in urine and tablet samples has also been studied.

  3. Binding of levomepromazine and cyamemazine to human recombinant dopamine receptor subtypes

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    Lalit K. Srivastava

    Full Text Available Background and Objectives: Clozapine (CLOZ and levomepromazine (LMP improve treatment-resistant schizophrenia. The superior efficacy of CLOZ compared with other antipsychotic agents has been attributed to an effect on D1-like and D4 receptors. We examined the binding of LMP, CLOZ and cyamemazine (CMZ, a neuroleptic analog of LMP, to human recombinant dopamine (rDA receptor subtypes. Methods: Binding studies were performed on frozen membrane suspensions of human rDA receptor subtypes expressed in Sf9 cells. Results: (i LMP has a high affinity (Ki, nM for rD2 receptor subtypes (rD2L 8.6; rD2S 4.3; rD3 8.3; rD4.2 7.9; (ii LMP and CLOZ have comparable affinities for the rD1 receptor (54.3 vs 34.6; (iii CMZ has high affinities for rD2-like and rD1-like receptors (rD2L 4.6; rD2S 3.3; rD3 6.2; rD4.2 8.5; rD1 3.9; rD5 10.7; (iv CMZ is 9 times more potent than CLOZ at the rD1 receptor and 5 times more potent than CLOZ at the rD4.2 receptor; (v CMZ has high affinities for rD1 and rD5 receptor subtypes compared with LMP and CLOZ. Conclusions: If D1 and D4 receptors are important sites for the unique action of CLOZ, the present study points to a need for clinical trials comparing CMZ with CLOZ in schizophrenia and in particular, treatment-resistant schizophrenia, especially given the risk for agranulocytosis with CLOZ.

  4. Binding of levomepromazine and cyamemazine to human recombinant dopamine receptor subtypes

    Directory of Open Access Journals (Sweden)

    Lalit K. Srivastava


    Full Text Available Background and Objectives: Clozapine (CLOZ and levomepromazine (LMP improve treatment-resistant schizophrenia. The superior efficacy of CLOZ compared with other antipsychotic agents has been attributed to an effect on D1-like and D4 receptors. We examined the binding of LMP, CLOZ and cyamemazine (CMZ, a neuroleptic analog of LMP, to human recombinant dopamine (rDA receptor subtypes. Methods: Binding studies were performed on frozen membrane suspensions of human rDA receptor subtypes expressed in Sf9 cells. Results: (i LMP has a high affinity (Ki, nM for rD2 receptor subtypes (rD2L 8.6; rD2S 4.3; rD3 8.3; rD4.2 7.9; (ii LMP and CLOZ have comparable affinities for the rD1 receptor (54.3 vs 34.6; (iii CMZ has high affinities for rD2-like and rD1-like receptors (rD2L 4.6; rD2S 3.3; rD3 6.2; rD4.2 8.5; rD1 3.9; rD5 10.7; (iv CMZ is 9 times more potent than CLOZ at the rD1 receptor and 5 times more potent than CLOZ at the rD4.2 receptor; (v CMZ has high affinities for rD1 and rD5 receptor subtypes compared with LMP and CLOZ. Conclusions: If D1 and D4 receptors are important sites for the unique action of CLOZ, the present study points to a need for clinical trials comparing CMZ with CLOZ in schizophrenia and in particular, treatment-resistant schizophrenia, especially given the risk for agranulocytosis with CLOZ.

  5. 耐甲氧西林表皮葡萄球菌医院感染危险因素分析%Risk factors of nosoeomial infection caused by methicillin resistant staphylococcus aureus

    Institute of Scientific and Technical Information of China (English)

    王爱; 康京花; 周炯; 赵丽珍; 冷晓梅; 马小军; 刘海燕


    Objective To investigate the risk factors of nosocomial infection caused by methicillin resistant Staphylococcus aureus (MRSE). Methods The clinical data of 184 patients admitted 2009 - 2011, 104 males and 84 females, aged (48.3 ± 22.2), from whose specimens MRSE were detected, were analyzed retrospectively. Results 96 of the 184 patients were diagnosed as with nosocomial infection of MRSE and 88 of the 96 cases were diagnosed as infection with colonizers. The infection rates of MRSE were not significantly different in sex, tracheal intubation, arteriovenous catheterization, use of antibiotics within the 3 months before the infection, agranulocytosis, chronic renal insufficiency, malignant tumor, cardiovascular diseases, chronic bronchitis, blood diseases, major operation, cirrhosis, and immune diseases between the MRSE infection group and non-infection group (all R>0.05). However, the MRSE infection rates of those older, with indwelling urinary catheter, treated with immunosuppressant drug or steroid within one year, with diabetes or neurologic disease were all significantly higher than those without these factors (all P0.05),而在有否留置导尿、一年内有否应用免疫抑制剂、激素治疗、糖尿病、老龄、颅脑疾病差异有统计学意义(P<0.05).结论 留置导尿、免疫抑制剂应用、激素治疗、糖尿病、老龄、颅脑疾病为MRSE感染的危险因素.

  6. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells. (United States)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro


    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100μM) and doxorubicin (0.2µM) decreased the cell survival rate, but olanzapine (1-100µM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation.

  7. Conventional and atypical antipsychotics in the elderly : a review. (United States)

    Gareri, Pietro; De Fazio, Pasquale; Stilo, Mariagrazia; Ferreri, Guido; De Sarro, Giovambattista


    Psychoses are major mental disorders marked by derangement of personality and loss of contact with reality, and are common in the elderly. Various hypotheses suggest the pivotal role of abnormal neurotransmitter and neuropeptide systems in psychotic patients, the most studied of which are the dopaminergic, serotonergic and glutamatergic systems. In particular, long-term treatment with antagonists at dopamine (D) and serotonin (5-hydroxytryptamine; 5-HT) receptors and agonists at glutamate receptors may improve symptoms. Treatment with antipsychotics is very common in the elderly and often indispensable. However, for successful treatment it is essential to have an adequate multidimensional assessment of the geriatric patient and of his or her polypathology and polypharmacy, together with knowledge of age-dependent pharmacokinetics and pharmacodynamic changes and drug-drug interactions.Conventional antipsychotics such as haloperidol, chlorpromazine, promazine, tiapride and zuclopenthixol are D(2)-receptor antagonists and inhibit dopaminergic neurotransmission in a dose-related manner. They decrease the intensity of all psychotic symptoms, although not necessarily to the same extent and with the same time course. Negative symptoms may persist to a much more striking extent than delusions, hallucinations and thought disorders, and there is a dose-related incidence of extrapyramidal side effects (EPS). Newer antipsychotics, such as clozapine, olanzapine, risperidone, quetiapine and ziprasidone, have a different receptor-binding profile, interacting with both D and 5-HT receptors; they less frequently cause EPS and are better tolerated in the elderly. Their use is advantageous because they are effective both on positive and negative symptoms of schizophrenia and may also be used in the treatment of behavioural disturbances in elderly and/or demented individuals. The use of clozapine is limited by the onset of agranulocytosis, whereas olanzapine, risperidone, quetiapine

  8. Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.

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    David J Bell

    Full Text Available BACKGROUND: In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ since sulfadoxine-pyrimethamine (SP replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART+SP or AQ+SP for the treatment of uncomplicated falciparum malaria. METHODOLOGY AND FINDINGS: 455 children aged 1-5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR rate for SP was 25%, inferior to each of the three combination therapies (p<0.001. AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81% and ART+SP (70%, p<0.001. Nineteen children developed a neutropenia of

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

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    Munshi T


    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

  10. Safety issues of thiourea antithyroid drugs%硫脲类抗甲状腺药物的安全性问题

    Institute of Scientific and Technical Information of China (English)



    Thiourea antithyroid drugs have an inhibitory effect on the production of thyroid hormone and are used in the treatment of hyperthyroidism in clinical practice. The commonly used thiourea antithyroid drugs are methimazole and propylthiouracil. Their adverse reactions include drug eruption, agranulocytosis, serious hepatic injures, ANCA-associated vasculitis and teratogenicity. Severe hepatic injures and ANCA-associated vasculitis are mainly related to propylthiouracil, while teratogenicity is caused by methimazole. Methimazole is a first-choice drug for treating children and non-pregnant women with hyperthyroidism, while propylthiouracil is a first-choice drug for treating pregnant and breast-feeding women. The measures of the prevention and treatment of adverse reactions to thiourea antithyroid drugs are as follows; rational drug use, regular monitoring, drug withdrawl immediately after developing related adverse reactions and treatment.%硫脲类抗甲状腺药物具有抑制甲状腺激素生成的作用,临床上用于治疗甲状腺功能亢进症.常见的硫脲类抗甲状腺药物有丙硫氧嘧啶和甲巯咪唑.其不良反应包括药疹、粒细胞缺乏症、严重肝损伤、抗中性粒细胞胞质抗体(ANCA)相关性血管炎等,并有一定的致畸作用.严重肝损伤和ANCA相关性血管炎的发生多与丙硫氧嘧啶有关,致畸作用主要见于甲巯咪唑.儿童和非妊娠期甲状腺功能亢进症患者的治疗首选甲巯咪唑,妊娠和哺乳期患者首选丙硫氧嘧啶.防治硫脲类抗甲状腺药物不良反应的措施包括:合理用药、定期监测、出现不良反应及时停药,以及对症治疗.

  11. 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

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    André Leandro Knappmann


    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.

  12. 血液系统疾病并发院内感染的治疗%Antimicrobial Therapy of Nosocomial Infectious Complications in Patients with Hematological Diseases

    Institute of Scientific and Technical Information of China (English)

    黄洪晖; 陈芳源; 方智雯; 韩洁英; 朱学宏; 邵念贤


    Objective To evaluate the clinical efficacy of imipenem/cilastatin in the treatment of nosocomial infectious complications in patients with hematological diseases. Methods 52 patients were treated with imipenem/cilastatin alone or in combination with other antibiotics. It was administered intravenously at a dosage of 1.5~2g per day. Results 1. The overall response rate of imipenem/cilastatin was 59.6%. 2. For Grme - positive and Grme - negative aerobes infections the clinical response rates were 44.4% and 60.0%, respectively. 3. The response rate of imipenem/cilastatin in patients who failed to respond to the third generation cephalosporins was 56.4%. 4. The response rate in febrile agranulocytosis patients was 51.9%. Conclusion Imipenem/cilastatin is a highly effective and broad-spectrum antibacterial agent for the treatment of nosocomial infectious complications in patients with hematologic diseases.%目的观察亚胺培南/西司他丁对血液系统疾病并发院内感染的治疗效果。方法 52例患者,单一使用亚胺培南/西司他丁或亚胺培南/西司他丁与其他抗菌素合用。亚胺培南/西司他丁每日剂量15~2g,静脉滴注。结果 1.亚胺培南/西司他丁治疗的总有效率为59.6%;2.对G+需氧菌及G需氧菌感染的临床有效率分别为44.4%,60.0%;3.应用第三代头孢菌素无效的患者用亚胺培南/西司他丁治疗,总有效率达56.4%;4.粒细胞缺乏合并感染患者中的有效率为51.9%。结论亚胺培南/西司他丁具有高效、广谱的抗菌作用,是治疗血液系统疾病院内感染的有效药物。

  13. Retrospective analysis and clinical nursing experience of Tripterygium wilfordii agents to blood system toxicity adverse reactions%雷公藤制剂致血液毒性反应的回顾性分析及临床护理启示

    Institute of Scientific and Technical Information of China (English)

    刘苗; 孟凡慧; 张玉萌


    目的:通过对雷公藤制剂所致血液系统毒性反应病例进行回顾性分析,从临床护理角度提高认识及应对。方法:检索中国生物医学文献数据库、中国期刊全文数据库及中文科技期刊数据库,收集雷公藤制剂引起血液系统毒性反应的病例,对毒性反应的发生特点进行归纳总结。结果:共检索到文献19篇,病例25例,其毒性反应主要表现为:全身不适,腹痛,腹泻,伴发热,重度贫血、鼻出血、皮肤瘀斑等,严重者可致急性再生障碍性贫血、粒细胞缺乏症、骨髓抑制、类白血病反应等。结论:雷公藤制剂具有血液毒性,在用药过程中应严格掌握其适应证和禁忌证,临床护理工作非常重要,关注配伍减毒、控制给药时间以及观察药物毒性反应等。%Objective: To retrospectively analyze the blood system toxicity caused by tripterygium wilfordii agents reported in literatures of adverse reaction cases in order to put forward advice and countermeasures from the perspective of nursing. Methods: To retrieve the Chinese biomedical literature database, China journal full-text database and Chinese science and technology periodical database, collect cases of toxicity of tripterygium wilfordii agents leading to blood system and summarize the characteristic of its adverse reactions. Results: 19 references, 25 cases were collected with main manifestations of the whole body discomfort, abdominal pain, diarrhea, associated with fever, severe anemia, nose bleeding, skin ecchymosis, severe cases with acute aplastic anemia and pure red aplastic anemia and agranulocytosis, bone marrow suppression, type of leukemia, etc. Conclusion:Due to Tripterygium wilfordii agents with blood system toxicity, nursing is very important in the process of drug, the nursing should strictly follow the indications and contraindications, reasonable control of delivery time and focus on compatibility attenuated

  14. 恶性血液病患者化疗后并发败血症的临床分析%Clinical analysis of septicemia in hematologic malignancies patients after chemotherapy in

    Institute of Scientific and Technical Information of China (English)

    常晓丽; 董征; 孙琪云; 乔建辉; 余长林; 胡锴勋; 艾辉胜; 郭梅


    OBJECTIVE To investigate the susceptible factors,bacterial distribution,infection site,prognosis and treatment of septicemia in the hematologic malignancies patients after chemotherapy so as to guide the rational use of antibiotics.METHODS A total of 80 cases of hematologic malignancies patients complicated with septicemia,who underwent the chemotherapy from Jan 2008 to Dec 2011,were enrolled in the study,then the clinical data and the result of drug susceptibility testing were retrospectively analyzed.RESULTS Of totally 80 cases of hematologic malignancies patients complicated with septicemia,85.0% (68 cases) happened during the period of granulocytopenia.The Escherichia coli,Pseudomonas aeruginosa,and Klebsiella pneumoniae were the top three species of pathogens,accounting for 32.5%,20.0%,and 8.8%,respectively.Meropenem and linezolid were the most sensitive antibiotics against the gram-negative bacteria and the gram-positive bacteria.81.6% of the pathogenic bacteria causing the septicemia could be covered by empirical use of carbapenems antibiotics.CONCLUSION The gram-negative bacteria are the predominant pathogens in the hematologic malignancies patients complicated with septicemia after chemotherapy.The de-escalation therapy dominated by the carbapenems antibiotics can improve the cure rate of sepsis.The agranulocytosis,complication of pulmonary infection,septic shock,hematologic disease,empirical medication,and accordance to the drug susceptibility were the factors that could influence the prognosis.%目的 研究恶性血液病患者化疗后并发败血症的易感因素、病原菌分布、感染部位、预后及治疗,为临床合理使用抗菌药物提供参考依据.方法 回顾性分析2008年1月-2011年12月80例恶性血液病患者化疗后并发败血症的临床资料及药敏试验结果.结果 80例恶性血液病并发败血症患者中有68例处于化疗后粒细胞缺乏期占85.0%,;大肠埃希菌、铜绿假单胞

  15. 恶性血液病合并败血症的临床分析%Clinical analysis of malignant hematological disease combined with septicemia

    Institute of Scientific and Technical Information of China (English)

    叶海燕; 陈焯文; 吴奎海; 邓善威


    目的 研究恶性血液病合并败血症的临床特点、病原菌、药敏情况及防治措施.方法 回顾性分析2009年1月至2013年6月收治的95例恶性血液病合并败血症患者的临床资料.结果 95例患者一共发生110例次败血症,69.1%(76/110)为急性白血病患者,82.7%(91/110)患者中性粒细胞计数< 0.5×109/L,66.4%(73/110)患者粒细胞缺乏时间>7d,致病菌以革兰阴性菌为主,主要为大肠埃希菌(30.9%,34/110)、肺炎克雷伯杆菌(14.5%,16/110)、铜绿假单胞菌(12.7%,14/110).药敏以碳青霉烯类及阿米卡星最为敏感,经治疗110例次败血症中有98例次治愈或好转,95例患者中12例死亡,病死率12.6%(12/95),其中15例发生感染性休克的患者,7例死亡.结论 恶性血液病合并败血症病情重,进展迅速,容易发生感染性休克,病死率高,需对患者进行早期防治,并进行强有力的抗感染及积极支持治疗.%Objective To study the clinical characteristics,pathogens,drug sensitivity and prevention measures in malignant hematological disease combined with septicemia.Methods The clinical data of 95 malignant hematological disease combined with septicemia patients from January 2009 to June 2013 were retrospectively analyzed.Results One hundred and ten episodes of septicemia occurred in all the 95 patients,among which acute leukemia patients accounted for 69.1% (76/110),patients with neutrophil counts <0.5 × 109/L accounted for 82.7% (91/110),and patients with agranulocytosis time >7 days accounted for 66.4%(73/110).Major pathogenic bacteria was gram negative bacteria,including Escherichia coli 30.9%(34/110),Klebsiella pneumoniae (14.5%,16/110),Pseudomonas aeruginosa (12.7%,14/110).Carbapenems and amikacin was the most sensitive in susceptibility testing.Ninety-eight episodes of septicemia cured or improved,and 12 patients died,with a mortality of 12.6% (12/95).Fifteen patients had septic shock,of whom 7 patients

  16. 急性白血病患者侵袭性真菌病的临床研究与分析%The clinical study and analysis of acute leukemia patients with invasive fungal disease

    Institute of Scientific and Technical Information of China (English)

    李志敏; 夏瑞祥


    Objective To learn the risk factors and clinical features of acute leukemia patients with invasive fungal disease to pro-vide guidance for the diagnosis and treatment of invasive fungal disease. Methods The clinical data of 1 272 cases of acute leukemia pa-tients were studied retrospectively, and the risk factors associated with invasive fungal disease and its clinical features were statistically ana-lysed. Results The number of invasive fungal disease which occurred in 1 272 cases of acute leukemia patients was 124, the infection rate was 9. 75% and the site of infection was mainly in the lung and blood. The number of days in hospital, agranulocytosis duration and joint use time of broad-spectrum antibiotics were independent risk factors of invasive fungal infection. The main pathogen was Candida albicans, most of which was sensitive to amphotericin B and voriconazole. Conclusion Patients associated with acute leukemia are susceptible to invasive fungal disease. Candida albicans is the main pathogen, and during the treatment of primary disease, shortening the length of hospital stay, time to neutrophil recovery and strengthening support for treatment and rational use of broad-spectrum antibiotics can effectively reduce the in-cidence of invasive fungal disease.%目的:分析急性白血病( AL)患者侵袭性真菌病( IFD)的相关危险因素和临床特点,为IFD的诊断和治疗提供指导。方法对1272例AL患者进行回顾性研究,统计分析IFD的相关危险因素及临床特点。结果 1272例AL患者中发生IFD 124例,感染率为9.75%,感染部位以肺部和血液为主;住院天数、粒细胞缺乏持续时间和广谱抗菌药物联合使用时间是侵袭性真菌感染的独立危险因素;病原菌以白色念珠菌为主,多对两性霉素B和伏立康唑敏感。结论 AL患者是IFD的易感人群,以白色念珠菌感染为主,在治疗原发病的同时,缩短住院天数、粒细胞恢复时间,加强支

  17. Misdiagnosis Analysis of 31 Cases of Atypical Hyperthyroidism%非典型甲状腺功能亢进症31例误诊分析

    Institute of Scientific and Technical Information of China (English)

    李中珂; 徐波


    Objective To analyze the cause of misdiagnosis of hyperthyroidism, and to propose preventive measures.Methods The clinical data of 31 misdiagnosed cases of hyperthyroidism admitted in our hospital during January 2000 and October 2008 were retrospectively analyzed.Results The initial symptoms included chronic diarrhea complaints, fatigue and weight loss (9 cases), periodic limb flaccid paralysis(7 cases), palpitations and chest tightness (5 cases), tension and irritability (3 cases), mental disorder(2 cases), anorexia and abdominal distension(2 cases), fever and fatigue (1 case), jaundice and tired of greasy food (1 case) and insomnia( 1 case).In the group, 9 cases were earlier misdiagnosed as chronic colitis, 7 cases as hypokalemic periodic paralysis, 3 cases as neurosis, myocarditis and menopause syndrome respectively, 2 cases as coronary heart disease and mental illness respectively, and 1 case as jaundice hepatitis and agranulocytosis respectively.The misdiagnosis average time was (6.7 ± 1.2) months.All patients were diagnosed by thyroid function, thyroid ultrasound and other tests.After anti-thyroid drugs and symptomatic treatment, all the patients were cured.Conclusion Hyperthyroidism has complex and diverse clinical manifestations, and it is easily misdiagnosed when the primary symptoms and main performance appears as a systematic symptom, so more attention should be paid to thyroid function tests to avoid misdiagnosis.%目的 分析甲状腺功能亢进症(甲亢)的误诊原因并提出防范措施.方法 对我院2000年1月~2008年10月收治并误诊的31例甲亢的临床资料进行回顾性分析.结果 本组初诊时诉首发症状为慢性腹泻、乏力、消瘦9例,周期性四肢软瘫7例,心悸、胸闷5例,紧张、烦躁3例,精神异常2例,食欲缺乏、腹胀2例,发热、乏力1例,黄疸、厌油1例,失眠1例.本组早期误诊为慢性结肠炎9例,低血钾性周期性麻痹7例,神经症、心肌炎、更年期综合征各3

  18. Clozapine and Fever: A Case of Continued Therapy With Clozapine. (United States)

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


    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

  19. 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


    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,

  20. 恶性血液病合并侵袭性真菌感染76例临床观察%The clinical study of invasive fungal infection in 76 cases of hematologic diseases

    Institute of Scientific and Technical Information of China (English)

    仵菲斐; 孙慧; 甘思林; 马杰; 刘延方; 谢新生; 孙玲; 刘林湘; 万鼎铭


    目的 探讨恶性血液病合并侵袭性真菌感染(IFI)的易感因素、临床特点、疗效和不良反应.方法 回顾性分析76例恶性血液病合并IFI患者的易感因素、临床特点,比较伊曲康唑与两性霉素B的疗效及安全性.结果 76例恶性血液病合并IFI患者应用广谱抗生素者68例(89.5%),化疗2个疗程以上者64例(84.2%),中性粒细胞缺乏者43例(56.6%),长期应用糖皮质激素者34例(44.7%),中心或外周静脉置管者27例(35.5%).伊曲康唑和两性霉素B治疗恶性血液病合并IFI的总有效率为60.5%和61.5% (P =0.929);两组间不良反应对比只在低钾血症方面有差异(14.0%比42.4%,P=0.005).结论 化疗、应用广谱抗生素、中性粒细胞缺乏等是恶性血液病合并IFI的易感因素.伊曲康唑治疗恶性血液病IFI疗效与两性霉素B相当,但不良反应较少且轻微.%Objective To investigate the risk factors,clinical features,efficacy and adverse reactions in patients of hematologic diseases with invasive fungal infections(IFI).Methods The risk factors and clinical features were retrospectively analyzed to compare the efficacy and safety of itraconazole with amphotericin B in treatment of IFI in 76 patients with hematologic diseases.Results Of the 76 patients,68 (89.5%) used broad-spectrum antibiotics,64 (84.2%) were treated with more than 2 courses chemotherapy,43 (56.6%) were under agranulocytosis,34 (44.7%) were using glucocorticoid for long terms,27 (35.5%) were with peripheral or central venous catheter.The overall effective rates of itraconazole and amphotericin B were 60.5% and 61.5% respectively (P =0.929).There was a significant difference between itraconazole and amphotericin B in hypokalemia (14.0% vs 42.4%,P =0.005) while no other differences in adverse reactions were found.Conclusions The risk factors of patients in hematologic diseases with IFI include chemotherapy,using broad septum antibiotics and

  1. 重型再生障碍性贫血免疫抑制治疗后恶性克隆造血临床分析%Clinical analysis on malignant clonal hematopoiesis in severe aplastic anemia patients with immunosuppressive therapy

    Institute of Scientific and Technical Information of China (English)

    崔宁博; 付蓉; 瞿文; 阮二宝; 王晓明; 王国锦; 吴玉红; 刘鸿; 关晶


    that they had no response to IST after 6 months,high monocyte percentage in one month after IST combined with recombinant human granulocyte colony stimulating factor (rHu-GCSF) and agranulocytosis in 3 months after IST.Conclusion Poor myeloid response to IST suggests malignant clonal hematopoiesis and poor prognosis in SAA patients.

  2. 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


    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.

  3. Epidemiology and antimicrobial resistance of clinical isolates about hospital infection from patients with hematological diseases%2005-2011年血液系统疾病院内感染流行病学及耐药性变迁

    Institute of Scientific and Technical Information of China (English)

    邓琦; 李青; 林雪梅; 李玉明


    Objective To investigate the epidemiology and antibiotic resistance of isolates from hospitalized patients with hematological disease from 2005 to 2011. Methods A total of 1453 bacterial strains were isolated from patients with hematological disease from January 2005 to December 2011. Antimicrobial susceptibility testing was performed by micro-dilution method. Results ①The majority of the bacterial strains were respiratory passage examples (57.5%). The pertage of blood examples in our division(13.60%) was higher than of whole hospital (6.26%), with lower positive rate of bacterial culture (52.37%) than of whole hospital (60.24%). Chemotherapy-induced agranulocytosis was the main reason for hospital infection. 578(39.8%)bacterial strains were gram positive, and 875(60.2%)gram negative bacillus. Staphylococcus epidermidis strains and glucose nonfermenters had a tendency of ascensus. ②Methicillin resistant staphylococcus aureus (MRSA) accounted for 72.8% antibiotic resistance. Detection rates of ESBLs in Escherichia coli and Kleb-siella pneumoniae were 18.9% and 10.4%, respectively. ③No obvious changes of antimicrobial resistances of Staphylococcus and Enterococcus were observed during these years. The Enterobacteriaceae strains showed lowest resistance rates to Carbopenems, next to Cefoperazone/sulbactam and Piperacillin/tazobactam. But the resistance rates of Escherichia coli to Cefepime and Ceftazidime were gradually increasing during the past years. Pseudomonas aeruginosa and Acinetobacter baumannii of glucose nonfermenters showed lowest resistance rates to Cefoperazone/sulbactam, but the resistance rate of Pseudomonas aeruginosa to Carbopenems increased. Conclusions Escherichia coli was the highest in quantity of gram negative bacillus and glucose nonfermenters had a tendencv of ascensus. The resistance rates of Escherichia coli to Cefepime and Ceftazidime, Pseudomones aeruginosa to Carbopenems were gradually increasing in the past years.%目的 分析2005

  4. 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


    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.

  5. 22O例医院感染病例分析%Analysis of 220 cases of nosocomial infections

    Institute of Scientific and Technical Information of China (English)

    翟红岩; 李小宝; 白玉红; 蒋静; 艾建红; 左大鹏


    infection were nosocomial infection pneumonia 43.82%, infectious fever 11.98%, sepsis 10.49%, urinary tract infection 7.87%, upper respiratory tract infection and oral infection 7.87%, respectively. The top 5 pathogens causing nosocomial infections in turn were Pseudomonas aeruginosa , Acinetobacter baumannii , Streptococcus viridans , Staphylococcus aureus, Candida albicans and E. coli; with the constituent ratios 14.54%, 10.57%, 8.81%, 7.49% and 6.61%, respectively. CONCLUSION The patients of blood and cancer receiving and treatment objects are mainly in our hospital, presenting the characteristic of bone marrow transplantation, Therefore, Laminar flow unit, blood ward and intensive care unit are the departments with higher incidences of nosocomial infection. Hospital acquired pneumonia, infectious fever and sepsis listed in the top three diseases. To strengthen the management of the patients with infections and actively take effective measures to prevent nosocomial infection is very important,especially when the patients occurred agranulocytosis.

  6. 成年血液病患者医院感染危险因素分析%Risk factors of nosocomial infections in adult patients with hematologic diseases

    Institute of Scientific and Technical Information of China (English)

    李鹏; 陈立兵; 杜明梅; 邢玉斌; 索继江; 曹圣山; 刘伯伟; 刘运喜


    OBJECTIVE To investigate the risk factors of nosocomial infections in adult patients with hematologic diseases so as to reduce the incidence of nosocomial infections.METHODS A case-control study was conducted for 5555 patients with hematologic diseases who were hospitalized from Jan 2010 to Oct 2012,including 712 cases in the infection group and 4843 cases in the non-infection group.The factors were classified into the patients selffactors and the iatrogenic factors,then the indicators were quantified in hierarchy,the variables with the statistical significance were screened out through the univariate analysis,finally the multivariate logistic regression analysis was carried out to analyze the risk factors of nosocomial infections in the adult patients with hematologic diseases.RESULTS The incidence of nosocomial infections in the adult patients with hematologic diseases was 12.82 %,and the case-time infection rate was 16.47%.The respiratory tract ranked the first place of the infection sites (57.81%),followed by the blood system (15.41%),and the patients with unknown infection sites also took a certain proportion.The gram-negative bacteria were the main pathogens causing nosocomial infections,accounting for 45.64%,followed by the fungi (25.28%).The multivariate logistic regression analysis showed that the hematopoietic stem cell transplantation,agranulocytosis,chemotherapy,use of immunosuppressive agents,central venous catheterization,leukemia,and community-acquired infections were the main risk factors,and the area under ROC was 0.885.CONCLUSION The incidence of nosocomial infections is high in the patients with hematologic diseases; it is necessary to strengthen the monitoring of nosocomial infections and take effective prevention measures according to the main risk factors so as to reduce the incidence of nosoeomial infections.%目的 探讨成年血液病患者发生医院感染的危险因素,以降低医院感染发生率.方法 对2010年1

  7. Outcomes and survival analysis of patients with AML and high risk MDS treated by CAG regimen%CAG方案治疗AML和高危MDS患者的疗效及生存分析

    Institute of Scientific and Technical Information of China (English)

    倪蓓文; 陈芳源; 韩洁英; 钟华; 钟璐; 黄洪晖; 沈莉菁; 肖菲


    CAG were observed. Short-term efficacy was evaluated based on clinical manifestation, peripheral blood and bone marrow cytologic examinations. Patients were followed up, overall survival ( OS) and disease free survival ( DFS) were analysed, and long-term efficacy of CAG regimen was evaluated. The factors influencing long-term survival were analysed by Log-rank test of survival curve. Results After a course of treatment by CAG regimen, the total effective rate was 71% , and 34 patients (49%) experienced complete remission. The median time of follow up was 45 months, the median OS was 28 months, and the median DFS was 23 months. Age, level of lactate dehydrogenase (LDH), remission condition after a course of treatment by CAG regimen and adoption of HD-Ara-C regimen as consolidation treatment were influencing factors for OS and DFS. The dominant clinical adverse effects were bone marrow depression, with 13 d as the median duration of agranulocytosis ( neutrophil <0.5 ×10~9/L) and 9 d as the median duration of thrombocytopenia (platelet <20 ×10~9/L). Conclusion CAG regimen may lead to favourable therapeutic effects in treatment of primary, refractory and relapsed AML and high risk MDS, and may yield less adverse effects and better long-term therapeutic effects. Age, level of LDH, remission condition after a course of treatment and adoption of HD-Ara-C regimen as consolidation treatment are dominant influencing factors for survival.