A case of PTU(propylthiouracil)-induced agranulocytosis in Graves' disease: additional cases of antithyroid drug-induced agranulocytosis in Yonsei University Hospital last 10 years / 대한내과학회지

Since introduce of antithyroid drugs (ATDs) in 1941, they have been widely used for treatment of Graves' disease and other hyperthyroid disorders. However, agranulocytosis, the most serious adverse effect of ATD treatment, has been occasionally reported. Agranulocytosis should be diagnosed and be treated promptly due to possible fatality.We have experienced a 17 year-old girl with PTU (propylthiouracil)-induced agranulocytosis. Initial graulocyte count was 400/mm2, and presenting symtoms were fever and sore throat. She has recovered from agranulocytosis without complications after use of G-CSF (granulocyte-colony stimulating factor). We reviewed and analyzed additional 7 cases of ATD-induced agranulocytosis in Yonsei University Hospital (From 1988 to 1998). We found that ATD-induced agranulocytosis, of which incidence is known to be ranged from 0.1 to 1 per cent, does not seem to have a distinct correlation with sex, age, dosage, and the kind of ATD. Event of agranulocytosis has a tendency to occur within 3 months, and in a few case it has been occasionally detected in asymptomatic patients, routine monitoring of the white blood cell count within 3 months after the start of ATD medication can be helpful in predicting and in detecting agranulocytosis. The treatment of ATD-induced agranulocytosis has been mainly composed of conservative care, but according to introduction and popular application of G-CSF, the use of G-CSF seems to be a promise of a reduction in morbidity and mortality.

The validity of random urine specimen albumin measurement as a screening test for diabetic nephropathy

To assess the validity of urine albumin concentration (UAC) and the urine albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105 RUSs after completing a timed 24 hour urine collection. Albumin was measured by immunonephelometry. According to the timed urinary albumin excretion rate (UAER) measured in the 24 hour collection (criterion standard), samples were classified normoalbuminuric (UAER 200 micrograms/min; n = 25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80) and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted. Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81 and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100% diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The sensitivity and specificity of the cut-off points for microalbuminuria were 77% and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for UACR. In present study, no difference was observed when comparing the performance of UAC and UACR based on a statistical comparison by McNemar test. The repeated measurements of UAC and UACR in the same individual were statistically similar and were correlated with each other. Based on these results, albumin measurements (UAC and UACR) in a RUS were considered as a valid test for screening diabetic nephropathy.

A Case of Ticlopidine-induced Neutropeina Treated with rhG-CSF

There are many conditions which are associated with neutropenia, such as infections, chemical and physical agents, and hematopoietic diseases. But ticlopidine-induced neutropenis is rarely reported in Korea. We experienced a case of neutropenia which developed after approximately 1 month of ticlopidine administrarion to a stable angina pectories patient. A 59 year-old woman with stable angina pectoris was placed on ticlopidine. Forty days later, she was admitted for high fevers and shaking chills. On admission, leukocyte count was 900/mm (3) (neutrophil 0/mm (3)), hemoglobin was 11.8g/dl, and platelet count was 440.000/mm (3). After confirming ticlopidine-induced neutropenia by bone marrow aspiration and biopsy, we administated rhG-CSF (neutrogen (r), Choongwae. Co. Korea) at a dose of 3-5ug/kg daily. On the 25th day of treatment, leukocyte count reached 2,890/mm (3). She experienced no adverse effects of rhG-CSF treatment and recorved completely. We assume that the rapid recovery of granulocytes was attributable to rhG-CSF, and we suggest that rhG-CSF should be tried in a patients with ticlopidine-induced neutropenia with depletion of myeloid precursors in the hypocelluar bone marrow.

A Case of Gastropleural Fistula Treated by Endoscopic lnjection of Histoacryl(R) / 대한소화기내시경학회지

Gastropleural fistula is an uncommon condition which can be induced by a trauma, gastroesophagectomy, subphrenic abscess, malignancy, and or hiatal hernia. In the patient with a predisposing factor, gastropleural fistula must be considered when pneumothorax, pyothorax, hemothorax, or food materials in the chest tube is detected. Diagnosis can be confirmed by an esophagogastrogram or endoscopy. The prognosis is often very poor with conservative care needed, along with a fistulectomy reguiring repair of orifice. We experienced a case of gastropleural fistula treated by endoscopic injection of Histoacryl and report it here with a review of related literature.

A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia / 대한암학회지

PURPOSE: We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial. MATERIALS AND METHODS: Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days. RESULTS: Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship. CONCLUSION: When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.