Occurrence Of Agranulocytosis Research Articles

Evaluation of Clozapine-induced Toxicities in Psychic Patients in Mental Health Care Hospitals in the Southern Region of the Saudi Arabia Kingdom

Background: Clozapine is a psychiatric medication that may cause various side effects, some of them may be serious and fatal adverse effects, such as severe neutropenia, agranulocytosis, lymphocytopenia, myocarditis, and orthostatic hypotension, that have been associated to an increased risk of death. Objective: This study aimed to evaluate the serious and potentially fatal adverse effects of clozapine toxicity in psychic patients at mental health care hospitals in the Southern region of the Kingdom of Saudi Arabia. Methods: By using a survey, data were retrospectively collected from 193 adult psychic patient reports who have been administrated clozapine with regular follow-ups, in mental health hospitals in the Southern region of Saudi Arabia between 2019 and 2021. Then, these data are recorded and analyzed Statistically using SPSS software, with suitable tests, and predetermined statistical significance (p-value) of less than 0.001. Results: The occurrence of agranulocytosis, neutropenia, hypotension, and seizures showed a highly significant correlation with higher doses of clozapine administration (i.e. p < 0.001). Similarly, agranulocytosis and neutropenia were significantly associated with the occurrence of both hypotension and seizures (i.e. p < 0.001). Conclusion: The collected data in this study showed an increased incidence of agranulocytosis and neutropenia associated with clozapine-treated psychic patients in the Southern region of the Kingdom of Saudi Arabia which warrants further clinical studies to find this correlation.

5613464 INTEGRATION OF PHARMACOKINETIC AND PHARMACODYNAMIC MODELS TO MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR PROSPECTIVE ASSESSMENT OF THE RISK-BENEFIT RATIO OF ORAL IRON CHELATORS IN PAEDIATRIC PATIENTS WITH TRANSFUSION-DEPENDENT HAEMOGLOBINOPATHIES

Background: Current therapies for the treatment of thalassaemia and other hereditary rare haemoglobinopathies are symptomatic and aim at controlling or reducing iron overload by chelation of iron from a very early age. Iron chelation ultimately prevents complications or comorbidities that can significantly reduce patient survival. Given the processes underlying iron homeostasis and current understanding of the chelation mechanism of available chelating agents, it may be possible to implement alternative, more efficient approaches for evidence generation in support of the dose rationale and their use across different populations affected by transfusion-dependent haemoglobinopathies. Aim: This study aimed to characterise the benefit-risk balance (BRB) of deferiprone in different populations, including children < 2 years old and paediatric sickle cell patients, using a nonlinear mixed effects modelling approach in conjunction extrapolation concepts and multicriteria decision analysis (MCDA). Methods: Based on the underlying pharmacokinetic-pharmacodynamic relationships as well as on the incidence of adverse events, extrapolation concepts were applied to predict the BRB of treatment in young adults, paediatric patients younger than 2 years, and paediatric sickle cell disease patients receiving deferiprone. Using individual patient-level data from a randomised controlled clinical trial (DEEP-2, EudraCT 2012-000353-31), preference elicitation methods were applied to select and prioritise endpoints or outcomes to be used in the evaluation of the BRB across the populations of interest. Subsequently, model parameter estimates obtained from each model/endpoint were used in a set of clinical simulation scenarios in which the effect of chelation therapy was evaluated during 12 months in a virtual cohort of patients. Results: Five endpoints were selected and ranked by the experts involved in the preference elicitation process (Fig.1). ‘Absence or prevention of complications (diabetes/hypothiroidism)’ and ‘occurrence of agranulocytosis’ were the most important criteria, while ‘incidence of arthralgia’ and ‘occurrence of neutropenia’ were considered less important. Clinical trial simulations revealed that the overall benefit score of deferiprone was higher for the treatment of paediatric SCD patient compared with the reference population (i.e. DEEP-2 study). Small but statistically significant differences were observed for the use of DFP in children younger than 2 years old and adolescents or young adults. Table 1 summarises the clinical and demographic baseline characteristics of the DEEP-2 study and virtual cohort of patients included in the different simulation scenarios. Conclusion: This study has shown that MCDA can be utilised in combination with modelling and simulation principles to prospectively assess the effect of interventions in subgroups of patients for which clinical data generation is challenging or not feasible. It also offers an opportunity to evaluate the implications of dose adjustment as well as changes in the clinical management of these patients, providing a less empirical basis for dose selection and treatment choices in rare paediatric conditions such as transfusion-dependent haemoglobinopathies. Table 1 - Demographics of the populations in the MCDA analysis. Reference population reflects the actual patients in the DEEP-2 study, whilst scenarios reflect the baseline characteristics from the virtual patient population. Population Age (years) Weight (kg) Blood consumption (mL/kg/year) Baseline ferritin (ng/mL) Reference population (DEEP-2 study) 8.9 (2.7-17.2) 26.5 (12.1-53.5) 155.4 (17.6-404.3) 1991 (586.2-6488.7) Scenario 1: Adolescents and young adults 17.6 (11.3-33.8) 58 (29-83.6) 139.7 (28.5-347.6) 1933 (432-10106) Scenario 2: Children < 2 years old 1.3 (0.6-1.9) 6.3 (1.1-9.3) 162.2 (21-382.9) 726.3 (253.3-1757) Scenario 3: Paediatric sickle cell patients 14.5 (12.4-17.8) 39 (30-62.4) 139.5 (23.8-338.2) 1598.4 (476.3-8993.9)

Chemotherapy-related agranulocytosis as a predictive factor for germline BRCA1 pathogenic variants in breast cancer patients: a retrospective cohort study.

Carriers of germline pathogenic variants of theBRCA1gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predictgBRCA1pathogenic variants. The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouringgBRCA1pathogenic variants among patients presenting agranulocytosis during C1. Three hundred seven BC patients were included: 32 (10.4%)gBRCA1, 27 (8.8%)gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes,gBRCA1heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive forgBRCA1pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predictinggBRCA1were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used forgBRCA1evaluation. Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1detection in non-metastatic BC patients.

Sex-dependent effects of long-term clozapine or haloperidol medication on red blood cells and liver iron metabolism in Sprague Dawley rats as a model of metabolic syndrome

BackgroundPatients with liver diseases often have some form of anemia. Hematological dyscrasias are known side effects of antipsychotic drug medication and the occurrence of agranulocytosis under clozapine is well described. However, the sex-dependent impact of clozapine and haloperidol on erythrocytes and symptoms like anemia, and its association with hepatic iron metabolism has not yet been completely clarified. Therefore, in the present study, we investigated the effect of both antipsychotic drugs on blood parameters and iron metabolism in the liver of male and female Sprague Dawley rats.MethodsAfter puberty, rats were treated orally with haloperidol or clozapine for 12 weeks. Blood count parameters, serum ferritin, and liver transferrin bound iron were determined by automated counter. Hemosiderin (Fe3+) was detected in liver sections by Perl’s Prussian blue staining. Liver hemoxygenase (HO-1), 5’aminolevulinate synthase (ALAS1), hepcidin, heme-regulated inhibitor (HRI), cytochrome P4501A1 (CYP1A1) and 1A2 (CYP1A2) were determined by Western blotting.ResultsWe found anemia with decreased erythrocyte counts, associated with lower hemoglobin and hematocrit, in females with haloperidol treatment. Males with clozapine medication showed reduced hemoglobin and increased red cell distribution width (RDW) without changes in erythrocyte numbers. High levels of hepatic hemosiderin were found in the female clozapine and haloperidol medicated groups. Liver HRI was significantly elevated in male clozapine medicated rats. CYP1A2 was significantly reduced in clozapine medicated females.ConclusionsThe characteristics of anemia under haloperidol and clozapine medication depend on the administered antipsychotic drug and on sex. We suggest that anemia in rats under antipsychotic drug medication is a sign of an underlying liver injury induced by the drugs. Changing hepatic iron metabolism under clozapine and haloperidol may help to reduce these effects of liver diseases.

Eosinophilia associated with clozapine therapy

Clozapine is used in the management of treatment‐resistant schizophrenia. However, its utility is limited by the occurrence of agranulocytosis, neutropenia, and leukopenia in up to 3% of patients, necessitating regular monitoring of hematological laboratory indices. In addition, several cases of self‐limiting eosinophilia have been reported in the literature, with most cases occurring 4 weeks after treatment initiation and rarely exceeding a 35% relative eosinophil count (percentage of white blood cells that are eosinophils).

Development of Agranulocytosis after Discontinuation of Methimazole: An Unusual Case.

Agranulocytosis is a rare and critical adverse effect of antithyroid drugs (ATD). The occurrence of agranulocytosis in continuous ATD treatment patients is well known; however, a case of ATD agranulocytosis occurring following the discontinuation of methimazole (MMI) treatment is not a usual situation. We herein describe a case of a 41-year-old woman who was previously administered methimazole (MMI) for ten days and developed ATD-induced agranulocytosis and symptoms of an upper respiratory tract infection after three weeks following discontinuation of MMI treatment. A thorough hematologic and serological evaluation did not disclose an alternative cause for the agranulocytosis. After receiving empirical antibiotic treatment, she responded successfully with clinical improvement of her symptoms and resolved neutropenia on the seventh day. This case is atypical because agranulocytosis developed after discontinuation of MMI, which strengthens the importance of remaining alert for signs of agranulocytosis even after discontinuation of ATD treatment.

P01-22 - 12 Years of refractory mania in extensive metabolizers

ObjectivesAlert for the efficiency of the clozapina, in high doses, in refractory mania to pharmacological treatment.MethodsReview of literature relevant after the description of a clinical case example.ResultsDescription of a clinical case: Woman 30 years, ethnicity african, with bipolar disease type 1, with 12 years of evolution, and 11 treatments with around 1 year duration. Specifics took place with medication, such as intolerance to mood stabilizers, including lithium and valproate. Last inpatient care, with 5 months, it was for outbreak manic characterized by huge dysphoria and easy irritability with aggressiveness. There were administered antipsychotics, in high doses, and attempted electroconvulsive therapy, without success. Clinical remission has been achieved by the gradual increase of clozapina, in accordance with the patient tolerance, until 1400 mg daily without occurrence of agranulocytosis. The only intercurrence was a epileptic seizure, controlled with phenytoin.ConclusionsRefractory mania is treated with clozapina in high doses, which must be administered according to the patient tolerance and clinical improvement. The risk of agranulocytosis (1-3%) is low, and is the only formal indication to suspend the treatment. The extensive metabolizers do not respond to conventional doses of psychotropic substances, they need larger doses and are more frequent in african people.

Toxicité médullaire des phénothiazines : à propos d’un cas d’agranulocytose sous chlorpromazine

We report the case of a 50-year-old man, treated with chlorpromazine for schizophrenia, who developed an agranulocytosis. Three mechanisms of drugs-induced agranulocytosis have been reported: toxic, genetic and immune. Phenothiazines are responsible for drug-induced agranulocytosis. This patient had been treated with first and second generation antipsychotic drugs during his life and had already been exposed to chlorpromazine or other phenotiazines without any signs of toxicity. However, two months after the introduction of chlorpromazine he presented an agranulocytosis (leukocytes 1.4G/L and neutrophils 0.2G/L). After discontinuation of chlorpromazine, blood count returned to normal. The role of chlorpromazine in inducing toxic agranulocytosis was based on: (i) normal blood count before the introduction of chlorpromazine; (ii) occurrence of agranulocytosis within the first weeks of chlorpromazine treatment; (iii) normal bone marrow and blood count after discontinuation of chlorpromazine; (iv) chlorpromazine was the only new drug prescribed to this patient at the time the agranulocytosis occurred. Risk factors for toxic agranulocytosis in this patient were: old age, association of phenothiazine with other drugs known to be able to induce agranulocytosis, and past history of use of high doses of chlorpromazine. This case report highlights the risk of chlorpromazine in inducing agranulocytosis, a risk underestimated in regard of the clozapine risk to induce agranulocytosis or neutropenia. For this reason, it seems reasonable to recommend performing a blood count before introduction of phenothiazine in patients with risk factors for toxic drug-induced agranulocytosis (old age, female, receiving other drugs with a high potential to induce agranulocytosis and having received high doses of phenothiazine for a long time).

Neutropenia in Patients Treated With Thienopyridines and High‐Dose Oral Prednisone after Percutaneous Coronary Interventions

Oral treatment with prednisone has demonstrated efficacy in reducing restenosis after percutaneous coronary interventions (PCI). However, administration of steroids at high dose may raise concerns in terms of applicability and tolerability. Monitoring the occurrence of possible side-effects is therefore mandatory. Secondary effects of oral prednisone in this setting is analyzed. The "expected" secondary effects of the steroid treatment are described, together with the "unexpected" occurrence of likely drug-induced neutropenia observed in patients prescribed prednisone and thienopyridines simultaneously after PCI. Two-hundred and twenty patients were monitored for the occurrence of side-effects of the prednisone therapy. Twenty-eight patients (14%) had side-effects likely related to the prednisone treatment: gastric pain (4%), increment of arterial pressure needing upgrading of antihypertensive treatment (4%), edema (1.8%), and concomitant infections (1.4%). In three patients (1.4%), agranulocytosis was detected at the time of the routine blood cell count scheduled 4 weeks after PCI in otherwise asymptomatic patients. Neutropenia subsided completely after withdrawal of prednisone and thienopyridine in all cases and the blood cell formula normalized within 3 weeks. Side-effects of oral prednisone given after PCI to reduce restenosis occur in less than 15% of patients. Complaints are mild and reversible and can be easily managed with adjunctive diuretic and antacid drugs. The occurrence of agranulocytosis after prednisone had never been reported before, but was observed in 1.4% of our patients receiving simultaneously a thienopyridine. To explain such an unusual event we propose the hypothesis of a possible metabolic interaction between prednisone and thienopyridines.

Combined clozapine-lithium treatment for schizophrenia and schizoaffective disorder

Three adolescent and two adult patients suffering from chronic excited psychoses (either schizophrenia or schizoaffective disorder) resistant to traditional neuroleptics and clozapine were treated with combined clozapine-lithium. Improvement was assessed with the Positive and Negative Symptoms Scale, the Brief Psychiatric Rating Scale and the Clinical Global Impressions, administered before and during combined clozapine-lithium treatment. All patients demonstrated a significant improvement with this combination. There was no occurrence of agranulocytosis, neuroleptic malignant syndrome or other clinically significant adverse effects.

ICI 204, 636: A New Atypical Antipsychotic Drug

The therapeutic effects of ‘classic’ (typical) antipsychotic agents lie in their ability to block central dopaminergic receptors – a property that is also responsible for the frequent occurrence of undesirable extrapyramidal side-effects (EPS). In contrast to these typical agents, clozapine alone has distinguished itself in humans – by virtue of its enhanced antipsychotic action and lack of concurrent EPS – as an atypical antipsychotic. However, the use of clozapine has been limited by the occurrence of agranulocytosis and, to a lesser extent, seizures (Alvir et al, 1993; Haring et al, 1994). The mechanism underpinning the atypical profile of clozapine remains elusive. One hypothesis suggests that it lies in clozapine's higher serotonin 5-HT2: D2 binding ratio, when compared with typical agents – a factor being considered as a predictor of atypicality (Meltzer, this issue; Meltzer et al, 1989). However, an emerging view is that it is not a single pharmacological action, but rather multiple properties that may define an atypical, clozapine-like compound (Lieberman, 1993).

Clozapine-Induced Agranulocytosis -- Incidence and Risk Factors in the United States

Clozapine is an atypical antipsychotic agent that is more effective than standard neuroleptic drugs in the treatment of patients with refractory schizophrenia. Unlike classic neuroleptic agents, clozapine is not associated with the development of acute extrapyramidal symptoms or tardive dyskinesia. The main factor limiting its use is the risk of potentially fatal agranulocytosis, estimated to occur in 1 to 2 percent of treated patients. After clozapine was approved by the Food and Drug Administration, it became available for marketing in the United States in February 1990 only as part of a special surveillance system (the Clozaril Patient Management System, or CPMS), in which a weekly white-cell count was required for the patient to receive a supply of the drug. We evaluated the CPMS data for February 1990 through April 1991 by survival analysis to determine the incidence of agranulocytosis and the effects of potential risk factors such as age and sex. Data were available for 11,555 patients who received clozapine during the period after marketing began. Agranulocytosis developed in 73 patients, resulting in death from infectious complications in 2 patients. Episodes of agranulocytosis occurred in 61 patients within three months after they began treatment. The cumulative incidence of this side effect was 0.80 percent (95 percent confidence interval, 0.61 to 0.99) at 1 year and 0.91 percent (95 percent confidence interval, 0.62 to 1.20) at 1 1/2 years. The risk of agranulocytosis increased with age and was higher among women. The occurrence of agranulocytosis is a substantial hazard of the administration of clozapine, but this hazard can be reduced by monitoring the white-cell count. The increasing risk of agranulocytosis with age and the reduced incidence after the first six months of treatment provide additional guidelines for the prescription and monitoring of clozapine treatment in the future.

Pharmacokinetics and Pharmacodynamics of Clozapine

The introduction of clozapine has given clinicians a unique agent for treating patients with schizophrenia that is refractory to other neuroleptics. Despite its efficacy, the drug continues to be prescribed with trepidation due to the incidence of agranulocytosis. This article reviews the pharmacokinetic and pharmacological properties of clozapine and the clinical implications for monitoring plasma concentrations. Various assays have been developed for clozapine that include gas-liquid chromatography, radioimmunoassay and high performance liquid chromatography. Only a few studies have examined the pharmacokinetics of clozapine in patients with schizophrenia. These studies have revealed a wide interpatient variability in pharmacokinetic parameters that include: time to reach peak plasma concentrations 1.1 to 3.6h; elimination half-life 9.1 to 17.4h; clearance 8.7 to 53.3 L/h; and a volume of distribution of 1.6 to 7.3 L/kg. Clozapine is metabolised via the hepatic microsomal enzyme system into 2 principle metabolites: demethyl-clozapine and clozapine N-oxide. Urine samples have reported the ratio of clozapine:demethyl:N-oxide to be 1:1:2. The clozapine N-oxide binding affinity with 3H-haloperidol was 4 times lower than clozapine and its conversion back to clozapine is hypothesised. Although the exact pharmacological mechanism of action of clozapine is not fully understood, the drug does possess significant binding affinity for different dopamine receptors, with recent evidence supporting binding to the D4 receptor subtype. Clozapine transiently increases serum prolactin levels with minimal changes in homovanillic acid plasma levels. Limited studies investigating the relationship between clinical response and plasma clozapine concentrations have investigated the range between 100 and 800 micrograms/L. In the treatment of patients with refractory schizophrenia, a minimum concentration of 350 micrograms/L was suggested as needed. The occurrence of agranulocytosis could have a genetic basis and patients should be rigorously monitored during treatment. The incidence of tardive dyskinesia and extrapyramidal side effects is minimal. Clozapine can lower the seizure threshold in a dose- and time-dependent manner. Careful patient selection and monitoring are required when clozapine therapy is used in patients with schizophrenia.

Treatment of psychosis subsequent to phenothiazine-induced agranulocytosis

Most psychiatric patients receive phenothiazine preparations for the amelioration of psychopathological symptoms. During the course of phenothiazine treatment, agranulocytosis or granulocytopenia and severe leukopenia are not infrequent. In the face of unrelenting psychopathology and occurrence of agranulocytosis, this complication has to be treated first. Subsequently, the unabated psychopathology can be treated by various therapeutic techniques; withdrawal of medication, rechallenging with the same medication with caution, substitutions with the same medication with caution, substitutions with another phenothiazine preparation or butyrophenone or thioxanthine, and administration of ECT. The particular therapeutic technique depends on the circumstances and drug history of the individual patient. The treatment of patients with unrelenting psychopathology after drug-induced agranulocytosis is described in this paper.

Agranulocytosis resulting from methimazole (tapazole); report of three cases.

Since the introduction of methimazole (1-methyl2-mercaptoimidazole; Tapazole), in 1949, it has been utilized as a potent antithyroid drug. Stanley and Astwood 1 found methimazole to be approximately 100 times as active as thiouracil. In recent years it has almost completely replaced thiouracil and propylthiouracil in the medical treatment of hyperthyroidism. However, a number of toxic reactions have been observed with the use of this agent. The occurrence of agranulocytosis following the administration of this drug constitutes a real hazard to life. It is our purpose to direct further attention to this possible dangerous toxic effect of methimazole by reporting three instances of agranulocytosis induced by this drug, one terminating fatally. Schultz 2 first described agranulocytic angina, an apparently new disease, in 1922. Since then many persons have died after the ingestion of medicaments prescribed for such diseases as hyperthyroidism, arthritis, cardiovascular diseases, allergic diatheses, epilepsy, and the psychoses. Kracke 3

Gastric ulcer with massive hemorrhage following use of phenylbutazone; report of a case.

Phenylbutazone (Butazolidin) has currently gained general acceptance as an effective agent in the treatment of arthritis and allied rheumatic conditions. That its use is attended with the risk of clinical toxicity is now being noted with increasing frequency. Kuzell and co-workers 1 describe such toxic manifestations of phenylbutazone as rash, edema, nausea, activation of peptic ulcer, vertigo, and pain at the site of injection. The occurrence of agranulocytosis has been documented by others. 2 Stephens and co-workers 3 recorded hematemesis of serious degree in two patients, both of whom had a previous history of duodenal ulcer. The following case is one of gastric ulcer with massive hemorrhage occurring in a patient who had no previous history or symptoms of peptic ulcer. A search of the available literature reveals no similar instance of initiation of gastric ulcer with massive hemorrhage during phenylbutazone therapy. REPORT OF A CASE A 72-year-old white woman

The present status of therapy in acute leukemia.

Editorial1 August 1952THE PRESENT STATUS OF THERAPY IN ACUTE LEUKEMIAMILTON S. SACKS, M.D.MILTON S. SACKS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-37-2-400 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAfter many years of fruitless investigation, from a therapeutic standpoint, of the etiology and control of acute leukemia, a small break in the completely dark horizon occurred in 1948 with the introduction of the folic acid antagonists.1This was followed, in 1950, by observations that the hormones ACTH and cortisone also exerted a temporary beneficial effect upon certain types of acute leukemia.2From the mass of literature which has accumulated in the past four years a few facts have emerged and become crystallized. It is quite apparent that these are but the veriest beginnings of an understanding of this inexorably...1 FarberDiamondMercerSylvesterWolff SLKRDRFJA: Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroylglutamic acid (aminopterin), New England J. Med. 238: 787, 1948. CrossrefMedlineGoogle Scholar2 PearsonElielTalbotBurchenalPetroPoppellCraver OHLPTRJRATJWLF: The use of ACTH and cortisone in acute leukemia, Blood 5: 786, 1950. Google Scholar3 Furth J: Recent studies on the etiology and nature of leukemia, Blood 6: 964, 1951. CrossrefMedlineGoogle Scholar4 Dreyfus B: Les remissions de la leucemie aigue, Sang 1: 35, 1948. Google Scholar5 BirgeJenksDavis RFALSK: Spontaneous remission in acute leukemia, J. A. M. A. 140: 589, 1949. CrossrefMedlineGoogle Scholar6 DiamondLuhby LKLA: The pattern of "spontaneous" remissions in leukemia in childhood. A review of 26 remissions in 300 cases, Am. J. Med. 10: 236, 1951. CrossrefGoogle Scholar7 BassenKohn FAJL: Multiple spontaneous remissions in a child with acute leukemia: the occurrence of agranulocytosis and aplastic anemia in acute leukemia and their relationship to remissions, Blood 7: 37, 1952. CrossrefMedlineGoogle Scholar8 Farber S: Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia, Blood 7 (Supplement): 107, 1952. Google Scholar9 Heinle RW: Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia, Blood 7 (Supplement): 113, 1952. Google Scholar10 Burchenal J: Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia, Blood 7 (Supplement): 115, 1952. Google Scholar11 Sacks MS: Unpublished observations. Google Scholar12 BiermanCohenMcClellandShimkin HRPJWMB: The effect of transfusions and antibiotics upon the duration of life in children with lymphogenous leukemia, J. Pediat. 37: 455, 1950. CrossrefMedlineGoogle Scholar13 Williams JH: Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia, Blood 7 (Supplement): 100, 1952. Google Scholar14 JukesBroquistStokstad THAPER: Vitamin B12 and "citrovorum factor" in the nutrition of Lactobacillus leichmanii and Leuconostoc citrovorum , Arch. Biochem. 26: 157, 1950. Google Scholar15 SavberlichBaumann HECA: A factor required for the growth of Leuconostoc citrovorum 8081, J. Biol. Chem. 176: 165, 1948. CrossrefMedlineGoogle Scholar16 NicholWelch CAAD: On the mechanism of action of aminopterin, Proc. Soc. Exper. Biol. and Med. 74: 403, 1950. CrossrefMedlineGoogle Scholar17 Heinle RW: Proceedings of the Second Conference on Folic Acid Antagonists in the Treatment of Leukemia, Blood 7 (Supplement): 170, 1952. Google Scholar18 SwendseidSwansonMeyersBethell MALMCFH: The nutritional status of folic acid in persons with leukemia and its possible relationship to effects of aminopterin therapy, Blood 7: 307, 1952. CrossrefMedlineGoogle Scholar19 Law LW: Response of a resistant variant of leukemic cells to an antagonist of pteroylglutamic acid, Proc. Soc. Exper. Biol. and Med. 77: 340, 1951. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1952Volume 37, Issue 2Page: 400-403KeywordsAdrenocorticotropic hormoneEtiologyFolic acidHormones Issue Published: 1 August 1952 PDF downloadLoading ...

Multiple Spontaneous Remissions in a Child with Acute Leukemia: The Occurrence of Agranulocytosis and Aplastic Anemia in Acute Leukemia and Their Relationship to Remissions

Abstract1. A case of acute leukemia with four observed spontaneous remissions is presented.2. Spontaneous remissions in acute leukemia are infrequent and multiple remissions rare.3. Spontaneous remissions in acute leukemia follow a pattern in that they occur after the development of a leukopenic agranulocytic phase and hypoplasia or aplasia of the marrow.4. Remissions in acute leukemia when therapeutically induced probably follow a similar pattern.5. The significance of agranulocytosis in acute leukemia has been discussed. When it occurs, before the diagnosis of leukemia is definitely made, and recovery ensues, one should be alerted for the possible later development of a characteristic picture of leukemia.6. The possibility that idiopathic aplastic anemia is no more than a phase of acute leukemia has been discussed.

A SUGGESTED THERAPY FOR THE PREVENTION OF GRANULOCYTOPENIA INDUCED BY THIOUREA

The administration of thiourea and its derivatives and the sulfonamides to animals results in the development of a state of hypothyroidism.1These substances produce this effect by interfering with the synthesis of normal thyroid hormone.2Clinical studies have shown that thiourea and thiouracil are effective in the treatment of hyperthyroidism.3The possibility of the occurrence of agranulocytosis in patients treated with these drugs has been indicated in the work of Astwood.4The present work will demonstrate that a neutrophilic granulocytopenia also results from feeding thiourea to adult rats. Since the granulocytopenia produced in weanling rats fed sulfonamides has been corrected by liver,5it was decided also to test the effects of solubilized liver6on the thiourea-induced neutropenia. Eighteen adult male rats weighing 200 to 240 Gm. were fed a standard laboratory ration containing 0.5 per cent thiourea for fifty-eight days. Six animals of another

PROLONGED ADMINISTRATION OF SULFAPYRIDINE IN SUBACUTE BACTERIAL ENDOCARDITIS; REPORT OF CASE FOLLOWING ADMINISTRATION OF 621 GRAMS

Case Reports1 August 1942PROLONGED ADMINISTRATION OF SULFAPYRIDINE IN SUBACUTE BACTERIAL ENDOCARDITIS; REPORT OF CASE FOLLOWING ADMINISTRATION OF 621 GRAMSMORRIS WILBURNE, M.D., THOMAS A. MCGOLDRICK, M.D.MORRIS WILBURNE, M.D.Search for more papers by this author, THOMAS A. MCGOLDRICK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-2-333 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe literature is replete with reports of the various toxic effects of sulfapyridine. Of principal importance are the effects on the blood, urinary tract, and liver. The occurrence of agranulocytosis was originally reported by Johnston,1later followed by Coxon and Forbes,2Barnett et al.,3Shullenberger,4and others. Acute hemolytic anemia was noted by Long and associates5in 0.6 per cent of 297 cases treated with sulfapyridine. The deposition of acetylsulfapyridine calculi in the urinary tract of experimental animals was first reported by Antopol and Robinson,6and by Gross, Cooper and Lewis,7and shortly afterward Southworth and Cooke8described the occurrence...Bibliography1. JOHNSTON FD: Agranulocytosis following treatment with M & B 693, Lancet, 1938, ii, 1200. CrossrefGoogle Scholar2. COXONFORBES RVJR: Agranulocytic angina following administration of M & B 693, Lancet, 1938, ii, 1412-1413. CrossrefGoogle Scholar3. BARNETTHARTMANPERLEYRUHOFF HLAFAMMB: The treatment of pneumococcic infections in infants and children with sulfapyridine, Jr. Am. Med. Assoc., 1939, cxii, 518-527. CrossrefGoogle Scholar4. SHULLENBERGER WA: Agranulocytosis following treatment of bacterial infections with sulfapyridine, Jr. Indiana State Med. Assoc., 1939, xxxii, 415-417. Google Scholar5. LONGHAVILANDEDWARDSBLISS PHJWLBEA: The toxic manifestations of sulfanilamide and its derivatives, Jr. Am. Med. Assoc., 1940, cxv, 364-368. CrossrefGoogle Scholar6. ANTOPOLROBINSON WH: Urolithiasis and renal pathology after oral administration of 2 (sulfanilylamino) pyridine (sulfapyridine), Proc. Soc. Exper. Biol. and Med., 1939, xl, 428-430. CrossrefGoogle Scholar7. GROSSCOOPERLEWIS PFBM: Urinary concretions caused by sulfapyridine, Proc. Soc. Exper. Biol. and Med., 1939, xl, 448-449. CrossrefGoogle Scholar8. SOUTHWORTHCOOKE HC: Hematuria, abdominal pain and nitrogen retention associated with sulfapyridine, Jr. Am. Med. Assoc., 1939, cxii, 1820-1821. Google Scholar9. LONGWOOD PHWB: Observations upon the experimental and clinical use of sulfapyridine. II. The treatment of pneumococcal pneumonia with sulfapyridine, ANN. INT. MED., 1939, xiii, 487-512. Google Scholar10. Cited by LONG et al.5 Google Scholar11. RAKEVAN DYKECORWIN GHBWC: Pathologic changes following prolonged administration of sulfathiazole and sulfapyridine, Am. Jr. Med. Sci., 1940, cc, 353-362. Google Scholar12. PLUMMERMCLELLAN NF: The production of sulfapyridine renal calculi in man, Jr. Am. Med. Assoc., 1940, cxiv, 943-946. Google Scholar13. LONG PH: Personal communication to the authors. Google Scholar14. PLUMMER N: Personal communication to the authors. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication November 28, 1940.From the 2nd Medical Division, Welfare Hospital, Department of Hospitals, Welfare Island, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1942Volume 17, Issue 2Page: 333-339KeywordsBloodEndocarditisHemolytic anemiaLiver ePublished: 1 December 2008 Issue Published: 1 August 1942 PDF downloadLoading ...