STUDY OBJECT: Clozapine has been known to induce variety of side effects. Amongst of all, the hematological abnormalities, especially agranulocytosis, has prohibited the wide-spread use of this drug. There have been a lot of efforts to predict the hematological abnormalities based upon the demographical and clinical characteristics. In addition, although only a few, prediction by the initial hemodynamic change was also attempted. This study was carried out as an attempt to find a reliable predictor of clozapine-induced hematological abnormalities based upon the baseline hematological status and the initial hemodynamic change by clozapine. METHOD: Regardless of the diagnosis, the complete blood count data of every patient who had received clozapine in Seoul National University Hospital from 1996 to the present were analyzed. The risk group was defined as the patient whose absolute neutrophil count(ANC) had dropped below 1500mm3 equal or more than 3 times during the one year after clozapine trial. The occurrences of future clozapine-induced hematological abnormalities were predicted by the baseline ANC and the initial ANC change. RESULT: The baseline ANC immediately before clozapine trial, the degree of ANC declining during the first week, and that of ANC rising during the 2nd and 3rd week all showed significant difference between the risk group and the safe group. The likelihood ratio of risk was 7.75(95% confidence interval: 2.77-21.3) implying significant risk of hematological abnormalities when the baseline ANC was below 2000mm3, and the likelihood ratio of risk was 0.372(0.159-0.798) when the baseline ANC was above 4000mm3. In likewise manner, the interval likelihood ratios of risk associated with the ANC rising during the first 3 weeks were calculated. These two predictor variables contributed mutually independent information in predicting future hematological abnormalities. CONCLUSION: The baseline ANC and the initial hemodynamic change after clozapine trial could help predicting future clozapine-induced hematological abnormalities. If the more reliable predictors can be found, prescreening high risk patients using these predictors and the close hematological monitoring of these patients may not only decrease the risk associated with clozapine usage, but also widen the indication of clozapine by relieving much of the burden currently imposed upon the doctors.
Agranulocytosis ; Blood Cell Count ; Clozapine ; Diagnosis ; Hemodynamics* ; Humans ; Neutrophils ; Schizophrenia ; Seoul

BACKGROUND: Most patients with gastric cancer have metastatic disease at first diagnosis and need palliative chemotherapy. Unfortunately, the response duration of the first line chemotherapy is usually short and most patients need the second line therapy during their disease process. The action mechanism of continuous infusion of 5-FU is different from bolus 5-FU and we can expect that among patients who failed on bolus 5-FU, some patients will achieve response to infusional 5-FU. So, we planned to evaluate the efficacy and safety of leucovorin and infusional 5-FU as a second line regimen for the metastatic gastric cancer refractory to regimen containing bolus 5-FU. METHODS: Patients with recurred or metastatic gastric cancer unresponsive to regimen containing bolus 5-FU were entered into this study. The mixture of 5-FU 1,000 mg/m2/day and leucovorin 50 mg/m2/day was infused continuously for four days and this treatment was repeated by every three weeks. RESULTS: From March, 1996 to July 2001, 25 patients were enrolled in this study. One patient showed a partial remission, 9 stable disease and 15 progressive disease. The overall response rate was 4%. The median time to progression was 73 days and the median duration of overall survival was 140 days. Among total of 92 cycle chemotherapy, leukopenia, granulocytopenia and thrombocytopena of WHO grade 3 or 4 were observed in 7.6%, 12.0% and 14.1%, respectively. Stomatitis, nausea or vomiting of WHO grade 3 or 4 were 13.1%, 5.4%, respectively. Neutropenic infection occurred in two patients. CONCLUSION: The LF regimen was well tolerated with minimal toxicities and showed low effect as the second line chemotherapy for the patients with gastric cancer.
Agranulocytosis ; Diagnosis ; Drug Therapy ; Fluorouracil* ; Humans ; Leucovorin* ; Leukopenia ; Nausea ; Stomach ; Stomach Neoplasms* ; Stomatitis ; Vomiting

Three cases of hisiocytic medullary reticulosis occurring in children aged 6 years, 9 years and 14 years, are described. In all children the diagnosis was based on anemia, granulocytopenia, thrombocytopenia and marked erythrophagocytosis by bone marrow and lymph node atypical histiocytes. They all showed immediate remission with combined chemotherapy of vinblastine and prednisolone, but Case 1 eventually died at 6 months after onset of this rapidly progressive, fatal illness and Case 2, 3 are alive 14 months after onset of their illness.
Agranulocytosis ; Anemia ; Bone Marrow ; Child ; Diagnosis ; Drug Therapy ; Histiocytes ; Humans ; Lymph Nodes ; Prednisolone ; Thrombocytopenia ; Vinblastine

OBJECTIVES: To study the application value of metagenomic next-generation sequencing (mNGS) for pathogen detection in childhood agranulocytosis with fever. METHODS: A retrospective analysis was performed on the mNGS results of pathogen detection of 116 children with agranulocytosis with fever who were treated from January 2020 to December 2021. Among these children, 38 children with negative mNGS results were enrolled as the negative group, and 78 children with positive results were divided into a bacteria group (n=22), a fungal group (n=23), and a viral group (n=31). Clinical data were compared between groups. RESULTS: For the 116 children with agranulocytosis and fever, the median age was 8 years at diagnosis, the median turnaround time of mNGS results was 2 days, and the positive rate of mNGS testing was 67.2% (78/116). Compared with the negative group, the bacterial group had a higher procalcitonin level (P<0.05), the fungal group had higher level of C-reactive protein and positive rate of (1,3)-β-D glucan test/galactomannan test (P<0.05), and the fungal group had a longer duration of fever (P<0.05). Among the 22 positive microbial culture specimens, 9 (41%) were consistent with the mNGS results. Among the 17 positive blood culture specimens, 8 (47%) were consistent with the mNGS results. Treatment was adjusted for 28 children (36%) with the mNGS results, among whom 26 were cured and discharged. CONCLUSIONS The mNGS technique has a shorter turnaround time and a higher sensitivity for pathogen detection and can provide evidence for the pathogenic diagnosis of children with agranulocytosis and fever.
Agranulocytosis/diagnosis* ; Bacteria ; Child ; Fever/diagnosis* ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Metagenomics/methods* ; Retrospective Studies ; Sensitivity and Specificity

Is it necessary to intake anthelmintics every year in Korea? To answer to this question, the recent nation-wide egg positive rate of the intestinal nematodes in Korea was presented. The anthelminthics which are purchasable without physician's prescription were also introduced with their pharmacological reaction and indication. The egg positive rate of Ascaris lumbricoides in 2012 was 0.025%. Those of Trichuris trichiura and Enterobius vermicularis were 0.27% and 0.004%, respectively. In 2018, purchasable anthelmintics without physician's prescription in Korea were albendazole and flubendazole only. Those two anthelmintics were derivatives of benzimidazole that may cause some side effects such as hepatitis, increase of hepatic enzymes, granulocytopenia, or pancytopenia. These anthelmintics showed excellent effect to ascariasis; while, they are not sufficient to treat trichuriaiss. For treatment of enterobiasis, repeated taking 3 times with 3 weeks interval and mass treatment of the family of egg positive person are required. In conclusion, it is not necessary to take anthelmintics every year without specific diagnosis because of negligible egg positive rate of intestinal nematodes and complicated therapeutic module for enterobiasis. There was no specific symptom of ascariasis or trchuriasis if worm burden is not high. The common symptoms of enterobiasis were pain or itching at the perianal area, sleep difficulty, or diarrhea. If intestinal nematode infection is suspected, stool examination or perianal swab should be done before prescribing anthelmintics.
Agranulocytosis ; Albendazole ; Anthelmintics ; Ascariasis ; Ascaris lumbricoides ; Diagnosis ; Diarrhea ; Enterobiasis ; Enterobius ; Hepatitis ; Humans ; Korea ; Nematode Infections ; Ovum ; Pancytopenia ; Prescriptions ; Pruritus ; Trichuris

Granulocytopenia, which can be seen in patients with Graves' disease during treatment with antithyroid agents, could be a self resolving transient episode or can imply the beginning of life threatening agranulocytosis requiring a change in treatment modality. Transient granulocytopenia could be a manifestation of hyperthyroidism itself, or a mild side effect of antithyroid drugs. Aganulocytosis is a rare, but major complications of the termination drug, propylthiouracil (PTU), requiring prompt termination of the medication, and intensive care. Therefore, differentiation of agranulocytosis and transient granulocytopenia, is important, but is not practically easy. We introduce a case of transient granulocytopenia, which was detected in a patient with Graves'Disease, accompanied by underlying type 1 diabetes mellitus, during treatment with PTU. Diagnosis of transient granulocytopenia was made by a normal granulocyte count following a single injection of G-SCF, and the patient was treated with conservative therapy. This case confirms a diagnostic tool for differentiating transient granulocytopenia and PTU-induced agranulocytosis.
Agranulocytosis* ; Antithyroid Agents ; Beginning of Human Life ; Diabetes Mellitus, Type 1* ; Diagnosis ; Diagnosis, Differential* ; Granulocyte Colony-Stimulating Factor* ; Granulocytes ; Graves Disease* ; Humans ; Hyperthyroidism ; Critical Care ; Propylthiouracil

We report a case of agranulocytosis caused by ethambutol in a 79-year-old man with pulmonary tuberculosis. He was referred for fever and skin rash developed on 21th day after antituberculosis drugs (isoniazid, rifampicin, ethambutol, and pyrazinamide) intake. Complete blood count at the time of diagnosis of pulmonary tuberculosis was normal. On the seventh admission day, agranulocytosis was developed with absolute neutrophil count of 70/microL. We discontinued all antituberculosis drugs, and then treated with granulocyte colony-stimulating factor. Three days later, the number of white blood cell returned to normal. We administered isoniazid, pyrazinamide, and ethambutol in order with an interval. However, fever and skin rash developed again when adding ethambutol, so we discontinued ethambutol. After these symptoms disappeared, we added rifampicin and ethambutol in order with an interval. However after administering ethambutol, neutropenia developed, so we discontinued ethambutol again. He was cured with isoniazid, rifampicin, and pyrazinamide for 9 months.
Aged ; Agranulocytosis* ; Blood Cell Count ; Diagnosis ; Ethambutol* ; Exanthema ; Fever ; Granulocyte Colony-Stimulating Factor ; Humans ; Isoniazid ; Leukocytes ; Neutropenia ; Neutrophils ; Pyrazinamide ; Rifampin ; Tuberculosis, Pulmonary*

Invasive infections with Aspergillus species may occur in patients with severe immune deficits and have been described rarely in systemic lupus erythematosus. We present two cases of pulmonary aspergillosis in steroid-treated systemic lupus erythematosus(SLE). Both patients had active SLE treated with high dose corticosteroids and prescribed with broad spectrum antibiotics. One patient had combined infection with pulmonary tuberculosis and the other present granulocytopenia. The diagnosis was delayed because symptoms and radiologic findings were confused with lupus pneumonitis and bacterial infections. This was similar to those reported previously. Diagnosis was confirmed by identification of the typical septated hyphae within tissue. We prescribed high dose amphotericin B to both patients. But one died with sepsis. Aspergillosis should be suspected in patients with active SLE who are immunocompromised and sustain concomitant bacterial infections. More aggressive diagnostic investigation and treatment may be needed to improve poor prognosis.
Adrenal Cortex Hormones ; Agranulocytosis ; Amphotericin B ; Anti-Bacterial Agents ; Aspergillosis* ; Aspergillus ; Bacterial Infections ; Diagnosis ; Humans ; Hyphae ; Lupus Erythematosus, Systemic* ; Pneumonia ; Prognosis ; Pulmonary Aspergillosis ; Sepsis ; Tuberculosis, Pulmonary

Both Graves disease and Guillain-Barre syndrome (GBS) are autoimmune disorders caused by impaired self-tolerance mechanisms and triggered by interactions between genetic and environmental factors. GBS in patients who suffer from other autoimmune diseases is rarely reported, and the development of postinfectious GBS in a patient with Graves disease has not been previously reported in the literature. Herein, we report a patient with Graves disease who developed postinfectious GBS during a course of methimazole-induced agranulocytosis.
Agranulocytosis/*chemically induced/diagnosis/therapy ; Antithyroid Agents/*adverse effects ; Female ; Graves Disease/diagnosis/*drug therapy ; Guillain-Barre Syndrome/diagnosis/*etiology/therapy ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Methimazole/*adverse effects ; Middle Aged ; Opportunistic Infections/diagnosis/*etiology/therapy ; Thyroidectomy ; Treatment Outcome

Eosinopenia, a biomarker for infection, has recently been shown to be a predictor of adult mortality in the intensive care unit (ICU). Our study assessed the usefulness of eosinopenia as a mortality and an infection biomarker in the pediatric ICU (PICU). We compared the PICU mortality scores, eosinophil count and percentage at ICU admission between children who survived and those who did not survive and between children with infection and those without infection. A total of 150 patients were evaluated. The initial eosinophil count and percentage were significantly lower in the group that did not survive when compared to those that did survive (P < 0.001; P < 0.001). However, there was no significant difference in the eosinophil count and percentage seen in patients with and without infection. Eosinopenia, defined as an eosinophil count < 15 cells/microL and an eosinophil percentage < 0.25%, (hazard ratio [HR]: 2.96; P = 0.008) along with a Pediatric Index of Mortality (PIM) 2 (HR: 1.03; P = 0.004) were both determined to be independent predictors of mortality in the PICU. The presence of eosinopenia at the ICU admission can be a useful biomarker for mortality in children, but is not useful as a biomarker for infection.
Agranulocytosis/*diagnosis ; Area Under Curve ; Biological Markers/blood ; Child ; Child, Preschool ; Eosinophils/*cytology ; Female ; *Hospital Mortality ; Humans ; Infant ; Infection/mortality/pathology ; *Intensive Care Units, Pediatric ; Leukocyte Count ; Male ; Predictive Value of Tests ; Prognosis ; ROC Curve ; Survival Rate