PURPOSE: Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) to antiepileptic drug (AED), are rare, but result in significant morbidity and mortality. We investigated the major culprit drugs, clinical characteristics, and clinical course and outcomes of AED-induced SCARs using a nationwide registry in Korea. METHODS: A total of 161 patients with AED-induced SCARs from 28 referral hospitals were analyzed. The causative AEDs, clinical characteristics, organ involvements, details of treatment, and outcomes were evaluated. We compared the clinical and laboratory parameters between SJS/TEN and DRESS according to the leading causative drugs. We further determined risk factors for prolonged hospitalization in AED-induced SCARs. RESULTS: Carbamazepine and lamotrigine were the most common culprit drugs causing SCARs. Valproic acid and levetiracetam also emerged as the major causative agents. The disease duration and hospital stay in carbamazepine-induced SJS/TEN were shorter than those in other AEDs (P< 0.05, respectively). In younger patients, lamotrigine caused higher incidences of DRESS than other drugs (P= 0.045). Carbamazepine, the most common culprit drug for SCARs, was associated with a favorable outcome related with prolonged hospitalization in SJS (odds ratio, 0.12; 95% confidence interval, 0.02-0.63, P= 0.12), and thrombocytopenia was found to be a risk factor for prolonged hospitalization in DRESS. CONCLUSION: This was the first large-scale epidemiological study of AED-induced SCARs in Korea. Valproic acid and levetiracetam were the significant emerging AEDs causing SCARs in addition to the well-known offending AEDs such as carbamazepine and lamotrigine. Carbamazepine was associated with reduced hospitalization, but thrombocytopenia was a risk factor for prolonged hospitalization. Our results suggest that the clinical characteristics and clinical courses of AED-induced SCARs might vary according to the individual AEDs.
Anticonvulsants ; Carbamazepine ; Cicatrix ; Drug Hypersensitivity Syndrome ; Epidemiologic Studies ; Hospitalization ; Humans ; Incidence ; Korea ; Length of Stay ; Mortality ; Referral and Consultation ; Risk Factors ; Stevens-Johnson Syndrome ; Thrombocytopenia ; Valproic Acid

Previous studies suggested that myelinated axons innervating rat molar pulps undergo morphological changes in their peripheral course. However, little information is available on the morphological feature of the parent axons at the site of origin. We therefore investigated the size of the myelinated parent axons and their morphological features at the proximal sensory root of the trigeminal ganglion by horseradish peroxidase (HRP) injection into rat upper molar pulps and subsequent light and electron microscopy. A total of 248 HRP-labeled myelinated axons investigated were highly variable in the size. Fiber area, fiber diameter, axon area (axoplasm area), axon diameter (axoplasm diameter), and myelin thickness were 11.32 +/- 8.36 microm2 (0.80~53.17 microm2), 3.99 +/- 1.53 microm (1.08~9.26 microm), 8.70 +/- 6.30 microm2 (0.70~41.83 microm2), 3.13 +/- 1.13 microm (0.94~7.20 microm) and 0.43 +/- 0.23 microm (0.07~1.06 microm), respectively. The g-ratio (axon diameter / fiber diameter) of the labeled axons was 0.79 +/- 0.05 (0.61~0.91). Axon diameter was highly correlated with myelin thickness (correlation coefficients,r=0.83) but little correlated with g-ratio (r=-0.33) of individual myelinated parent axons. These results indicate that myelin thickness of the myelinated parent axons innervating rat molar pulps increase with increasing axon diameter, thus maintaining a constant g-ratio.
Animals ; Axons* ; Dental Pulp ; Horseradish Peroxidase ; Humans ; Microscopy, Electron ; Molar* ; Myelin Sheath* ; Parents* ; Rats* ; Trigeminal Ganglion*

Ultrastructural parameters related to synaptic release and their correlation with synaptic connectivity were analyzed in the low-threshold mechanoreceptive vibrissa afferent boutons in laminae III and IV of the trigeminal caudal nucleus (Vc). Rapidly adapting vibrissa afferents were intra-axonally labeled, and quantitative ultrastructural analyses with serial sections were performed on the labeled boutons and their presynaptic endings (p-endings). The volume of the labeled boutons was widely distributed from small to large ones (0.8~12.3 microm3), whereas the p-endings were small and uniform in size. The volume of the labeled boutons was positively correlated with the ultrastructural parameters such as mitochondrial volume (correlation coefficient, r=0.96), active zone area (r=0.82) and apposed surface area (r=0.79). Vesicle density (r=-0.18) showed little correlation to the volume of labeled boutons, suggesting that the total vesicle number of a bouton is proportional to its volume. In addition, the bouton volume was positively correlated with the number of p-endings (r=0.52) and with the number of dendrites postsynaptic to the labeled bouton (r=0.83). These findings suggest that low-threshold mechanoreception conveyed through vibrissa afferents is processed in a bouton size-dependent manner in the Vc, which may contribute to the sensory-motor function of laminae III/IV in Vc.
Animals ; Cats ; Dendrites ; Mitochondrial Size ; Synapses ; Trigeminal Caudal Nucleus

BACKGROUND/AIMS: There are three types of PML-RAR alpha mRNA fusion transcripts associated with acute promyelocytic leukemia (APL): the short (S)-form, the long (L)-form and the variable (V)-form. No study on the Korean population has addressed the clinical significance of the specific types of PML-RAR alpha mRNA fusion transcripts for APL patients who receive the combination therapy of all-trans-retinoic-acid and idarubicin (AIDA regimen). METHODS: We performed a retrospective analysis on 94 patients with APL to evaluate differences in the therapeutic outcomes, such as the response rate, an event-free survival (EFS), and overall survival (OS), after remission following the induction of chemotherapy. We also analyzed whether differences in the pretreatment clinical characteristics depend on the PML-RAR alpha isoform. RESULTS: The median age of the patients was 41 years (range 15-85). Among the 94 patients, there were 58 L-form cases (62.1%), 32 S-form cases (34.0%), and 4 V-form cases (4.3%). The CR rate following remission induction treatment was 84.9%. The CR rate was higher in patients with an initial WBC <10.0x109/L, as compared to patients with an initial WBC higher than 10.0X109/L (93.5% vs. 65.4%, p=0.001). The AIDA induction regimen was associated with a better EFS than non-AIDA induction regimens (81.9% vs. 49.6%, p=0.006). The induction group was also a significant prognostic factor for EFS in the multivariate analysis (p=0.020). There were no differences in OS and EFS in patients with either isoform L or isoform S in the AIDA induction group. CONCLUSIONS: This retrospective study demonstrated that pretreatment clinical characteristics and treatment outcomes were not significantly different among patients with varying PML-RAR alpha isoform types in the AIDA induction group.
Disease-Free Survival ; Humans ; Idarubicin ; Leukemia, Promyelocytic, Acute ; Multivariate Analysis ; Protein Isoforms ; Remission Induction ; Retrospective Studies ; RNA, Messenger

To analyze the developmental changes in soma diameters of digastric motoneurons, wheat-germ agglutinin conjugated horseradish peroxidase (WGA-HRP) was injected into the digastric muscle and visualized the retrogradely HRP-labeled motoneurons through tungstate/tetramethylbenzidine (TMB) and following diaminobenzidine (DAB) reactions. The results obtained from Sprague-Dawley rats at postnatal days 1 (P1), 10 (P10) and 30 (P30) indicated as follows: firstly, soma diameters of digastric motoneurons showed unimodal distribution in all postnatal days examined; secondly, the period of P1 to P10 (period 1) showed about 2 times faster growth rate than that of P10 to P30 (period 2); thirdly, the smallest soma examined in each postnatal day exhibited slower growth rate with that of the largest one (increase ratio in soma diameters from P1 to P30, smallest vs. largest =1.62 : 1.93); Finally, relative growth rates a day showed again that period 1 had faster growth rate than that of period 2. Consequently, developmental changes in soma diameters of digastric motoneurons resulted in very different growth rates between both periods. This implies that the growth of the soma is almost completing within P10 and thereafter growing slowly. The period 1 and 2 are corresponding to sucking and sucking/masticatory period, respectively. Therefore present study providing morphological changes in soma diameters of digastric motoneurons suggests that both periods and their different growth rates of the motoneurons in each period may closely be related with each other.
Animals ; Carisoprodol* ; Horseradish Peroxidase ; Rats* ; Rats, Sprague-Dawley

The reversibility of arterial stenosis in arteritis of tuberculous meningitis (TBM) has been rarely reported. However, we report a 25-year-old man with TBM who developed arteritis. Initial TCD and MRA showed stenosis in the left middle cerebral and intracranial internal carotid arteries, which improved on follow-up TCD and MRA after antituberculous and steroid treatment. This case showed that the arterial stenosis in TBM could be reversed with proper management and that TCD with MRA can be useful diagnostic tools.
Adult ; Arteritis ; Carotid Artery, Internal ; Constriction, Pathologic ; Follow-Up Studies ; Humans ; Magnetic Resonance Angiography* ; Tuberculosis, Meningeal*

BACKGROUND: TGF - beta is known as a cell growth inhibitory factor to suppress almost all cells, including the epithelial cell. Unlike normal cells, cancer cells are not affected by TGF- beta growth inhibitory action and the lack of TGF- beta receptor expression or mutation is being reported as its mechanism, which is rarely studied in Korea. Therefore, we investigated this study to clarify the role of TGF - beta I and TGF - beta II receptors in gastric cancer. METHODS: 23 cases that underwent operations for gastric cancer provided RNA collected from their carcinoma tissues and adjacent normal tissues. We investigated the level of TGF - beta 1 and T beta R-II mRNA expression with semi- quantitatively reverse transcription PCR and analyzed the correlation with prognostic factors, such as tumor size, depth of invasion, tumor differentiation and lymph-node metastasis. RESULTS: (1) TGF- beta I and T beta R-II mRNA were expressed in all carcinoma tissues and adjacent normal tissues of the 23 cases without statistical difference in the level of the expression. (2) The level of TGF - beta 1 mRNA expression was higher in patients with gastric cancer invaded only at the mucosa and submucosa than in patients with gastric cancer invaded over muscular propria, and also higher in the patients without lymph-node metastasis or perineural invasion than in the patients with lymph-node metastasis or perineural invasion. There was no significant correlation between the level of T beta R-II mRNA expression and several parameters, such as age, gender, tumor size, location, differentiation, Lauren's classification and vascular invasion. (3) There was a significant correlation between the level of TGF - beta 1 and T beta R-II mRNA expression in carcinoma tissues. CONCLUSION: It indicated that TGF - beta 1 mRNA expression in gastric cancer might concern the early stage of gastric carcinogenesis and, unlike the earlier reports, it was higher in patients with early gastric cancer, negative lymph-nodes or negative perineural invasion. Further studies are required to clarify the role of TGF - beta 1 in gastric carcinogenesis with more patients.
Female ; Human ; Male ; Middle Age ; Prognosis ; RNA, Messenger/genetics/metabolism ; Receptors, Transforming Growth Factor beta/*genetics ; Stomach Neoplasms/*genetics/metabolism ; Transforming Growth Factor beta/metabolism

The solitary form of primary hepatic tuberculosis is a rare disease. We report an unusual case of primary solitary hepatic tuberculosis treated with surgical resection and second-line antituberculosis chemotherapy due to the recurrence after first-line antituberculosis chemotherapy alone. A 36-year-old man was presented with right upper abdominal discomfort, chills and weight loss for 2 months. Computerized tomography demonstrated the solitary space occupying lesion on the left lobe of liver suggesting a malignant disease. The open biopsy revealed chronic granulomatous inflammation with multinucleated giant cells and caseous necrosis. The patient was treated with antituberculosis chemotherapy for nine months and eighteen months respectively with the interval of eighteen months. But the hepatic lesion had become larger and symptoms were aggravated after the discontinuation of therapy. He underwent surgical excision of the lesioin. With second-line antituberculosis chemotherapy, the symptoms improved in postoperative days. Twenty four months later, no evidence of recurrence was noted in symptoms, laboratory findings and imaging studies.
Adult ; Biopsy ; Chills ; Drug Therapy* ; Giant Cells ; Humans ; Inflammation ; Liver* ; Necrosis ; Rare Diseases ; Recurrence ; Tuberculoma* ; Tuberculosis, Hepatic ; Weight Loss

BACKGROUND: Cystic tumors of the pancreas are uncommon, and frequently mistaken for pancreatic pseudocysts. Recently if the patient is a good surgical candidate and is symptomatic, resection is the treatment of the choice without the cytological and chemical analysis by the fine needle aspiration. But, we have no data in Korean population. The aim of this study was to evaluate the subclassification of the cystic tumors of the pancreas and the differential points between pancreatic pseudocysts and cystic tumors of the pancreas which had to be operated. METHODS: fifty-nine patients with cystic lesions of the pancreas have been operated at the Samsung Seoul Hospital from 1994 to 1999 and evaluated about the subclassification, frequency and the difference between pseudocysts and cystic tumors retrogradely. RESULTS: There were 14 mucinous cystic neoplasms (mucinous cystadenomas : 11 cases, mucinous cyst-adenocarcinomas : 3 cases), 10 serous cystadenomas, 9 solid and papillary epithelial neoplasms, 8 intra-ductal papillary mucinous neoplasms, 5 pseudocysts, 4 retention cysts, 3 endocrine tumors, 1 pancreatic ductal adenocarcinoma with cystic change, 1 solid pseudopapillary tumor, 1 pancreatic ductal adenocarci-noma with pseudocyst, 1 cavernous lymphangioma, 1 lymphoepithelial cyst and 1 simple cyst. 57.6% of the patients were females and the mean age was 50.0 years (16 years-77 years). The characteristics between pseudocysts and cystic tumors of the pancreas (sex differentiation, mean age, previous history of alcohol drinking and pancreatitis, communication with the main duct on the pancreatogram and the sign of the pancreatitis on the radiologic study) had no differences. CONCLUSION: We conclude there were no other methods to differentiate accurately the pseudocyst from the cystic tumor of the pancreas other than the operation.
Adenocarcinoma ; Alcohol Drinking ; Biopsy, Fine-Needle ; Cystadenoma ; Cystadenoma, Serous ; Female ; Humans ; Lymphangioma ; Mucins ; Neoplasms, Glandular and Epithelial ; Pancreas* ; Pancreatic Ducts ; Pancreatic Pseudocyst ; Pancreatitis ; Seoul

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a potent inhibitor of epithelial cell growth. However, carcinoma cells, unlike normal cells, can escape from negative regulation by TGF-beta through lack of expression or mutation of TGF-beta receptor gene. In this study, we investigated the role of TGF-beta1 and TGF-beta type II receptors (TbetaR-II) in the progression of gastric cancer. METHODS: We analyzed TGF-beta1 and TbetaR-II mRNA expression semi-quantitatively, measured by comparative RT-PCR using GAPDH, in 23 patients who underwent gastric resection for gastric cancer. We analyzed the relationship between the clinicopathologic findings and the level of the TGF-beta1 and TbetaR-II mRNA expression in carcinoma tissues and in adjacent normal tissues of gastric cancer. RESULTS: (1) TGF-beta1 and TbetaR-II mRNA were expressed in all of the carcinoma tissues and adjacent normal tissues without statistical difference in the level of the expression. (2) The level of TGF-beta1 mRNA expression was higher in patients with early gastric cancer, negative lymph nodes or negative perineural invasion. There was no significant correlation between the level of TGF-beta1 mRNA expression and several parameters such as age, gender, tumor size, differentiation, Lauren's classification, and vascular invasion. (3) There was no significant correlation between the level of TbetaR-II mRNA expression and several prognostic variables described above. (4) There was significant correlation between the level of TGF-beta1 and TbetaR-II mRNA in carcinoma tissues. CONCLUSION: The above data indicates that TGF-beta1 may contribute in the early stages of gastric carcinogenesis. Further studies are required to clarify the role of TGF-beta 1 in gastric carcinogenesis.
Carcinogenesis ; Classification ; Epithelial Cells ; Humans ; Lymph Nodes ; Receptors, Transforming Growth Factor beta ; RNA, Messenger ; Stomach Neoplasms* ; Transforming Growth Factor beta* ; Transforming Growth Factor beta1 ; United Nations