BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A (CMT1A) is the demyelinating form of CMT that is significantly associated with PMP22 duplication. Some studies have found that the disease-related disabilities of these patients are correlated with their compound muscle action potentials (CMAPs), while others have suggested that they are related to the nerve conduction velocities. In the present study, we investigated the correlations between the disease-related disabilities and the electrophysiological values in a large cohort of Korean CMT1A patients. METHODS: We analyzed 167 CMT1A patients of Korean origin with PMP22 duplication using clinical and electrophysiological assessments, including the CMT neuropathy score and the functional disability scale. RESULTS: Clinical motor disabilities were significantly correlated with the CMAPs but not the motor nerve conduction velocities (MNCVs). Moreover, the observed sensory impairments matched the corresponding reductions in the sensory nerve action potentials (SNAPs) but not with slowing of the sensory nerve conduction velocities (SNCVs). In addition, CMAPs were strongly correlated with the disease duration but not with the age at onset. The terminal latency index did not differ between CMT1A patients and healthy controls. CONCLUSIONS: In CMT1A patients, disease-related disabilities such as muscle wasting and sensory impairment were strongly correlated with CMAPs and SNAPs but not with the MNCVs or SNCVs. Therefore, we suggest that the clinical disabilities of CMT patients are determined by the extent of axonal dysfunction.
Action Potentials ; Axons ; Charcot-Marie-Tooth Disease ; Cohort Studies ; Humans ; Muscles ; Neural Conduction

The publisher wishes to apologize for incorrectly displaying the author (Seok Beom Gwon) name. We correct his name from Seok Beom Gwon to Seok Beom Kwon.

PURPOSE: To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). METHODS: To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level (3.4 micrometer) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than 1,400 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (P=0.011). CONCLUSION: The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.
Cisplatin ; Disease-Free Survival ; Doxorubicin ; Extremities ; Humans ; Methotrexate ; Osteosarcoma

PURPOSE: To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). METHODS: To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX (12 g/m2), cisplatin (100 mg/m2), and doxorubicin (60 mg/m2). RESULTS: Totally, 204 courses of HD MTX were administered. The serial MTX levels (mean+/-SE) at 4 h (peak), 24 h, 48 h, and 72 h were 1292.14+/-12.83 micrometer, 9.29+/-3.89 micrometer, 1.73+/-1.37 micrometer, and 0.58+/-0.44 micrometer, respectively. The peak MTX serum level was 1292.14+/-12.83 micrometer. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level (3.4 micrometer) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than 1,400 micrometer (P=0.002) and mean 24-h MTX level of less than 3.4 micrometer (P=0.011). CONCLUSION: The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.
Cisplatin ; Disease-Free Survival ; Doxorubicin ; Extremities ; Humans ; Methotrexate ; Osteosarcoma

PURPOSE: Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Although survival rate of osteosarcoma patients has markedly improved, about 20-30% of patients still have a relapse. This study was aimed to find factors that influence postrelapse survival of osteosarcoma in childhood and adolescents. METHODS: Between 1985 and 2004, of 461 patients who were diagnosed and treated as osteosarcoma in Korean Cancer Center Hospital, 180 patients with recurrent osteosarcoma were retrospectively reviewed. We examined survival rates and analyzed prognostic factors, such as relapse site, post-relapse treatment methods, pathologic response to neoadjuvnat chemotherapy, metastasis at first diagnosis, and relapse free interval. RESULTS: The overall recurrence rate of patients with osteosarcoma was 39%. The 5-year and 10-year postrelapse survival rates in the recurrent osteosarcoma were 13% and 4%, respectively. The 5-year post-relapse survival rate was influenced by site of relapse (lung, 39%; local, 0%; lung & bone, 25%; others, 12%; P<0.05), relapse-free interval (<12 months, 13%; > or =12 months, 44%, P<0.05), and post-relapse treatment methods (with surgery, 38%; without surgery, 11%; P<0.05). CONCLUSION: The survival rate of recurrent case is very low after 10 years, so new second-line chemotherapy and active treatment is needed to increase survival. Aggressive surgery with the removal of recurrence sites combined with multi-agent chemotherapy could either cure patients with recurrent osteosarcoma or significantly prolong their survival.
Adolescent ; Child ; Humans ; Korea ; Lung ; Neoplasm Metastasis ; Osteosarcoma ; Recurrence ; Retrospective Studies ; Survival Rate

PURPOSE: This study aimed to assess whether a young age at the time of diagnosis with osteosarcoma has value to predict the prognosis. MATERIALS AND METHODS: Sixty-seven children with stage II osteosarcoma were stratified according to the age of 10. There were 32 preadolescents (< or =10 years) and 35 adolescents (10 < age < or = 15 years). The patients were analyzed for their clinical characteristics, the histologic response to preoperative chemotherapy, event-free survival (EFS) and the patterns of relapse. RESULTS: After a median follow-up of 54 months (range: 6~153 months), the 5-year EFS of the preadolescent and adolescent groups was 64.5+/-9.3% and 58.2+/-9.1%, respectively, and age did not have any statistical significance for survival (p=0.55). Cox regression analysis revealed that both the serum level of alkaline phosphatase and the histologic response to preoperative chemotherapy were significantly related to survival of the 67 patients. Those patients aged less than 7 years responded poorly to preoperative chemotherapy and their rate of amputation was 43%. However, their 5-year EFS was not statistically different from the older patients (57.1+/-18.7 vs 67.7+/-6.3%, respectively, p=0.58). CONCLUSIONS: We could not find any statistical difference in the clinical characteristics and survival from osteosarcoma for the preadolescents and adolescents, so the current approach of having the same protocol for both groups of patients seems to be reasonable.
Adolescent ; Alkaline Phosphatase ; Amputation ; Child* ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Osteosarcoma* ; Prognosis ; Recurrence ; Retrospective Studies*

BACKGROUND: Mitofusin 2 (MFN2) is a membrane protein and is an essential component of mitochondrial fusion machinery. Mitochondrial fusion is essential for various biological functions in mammalian cells. Thus mutations in MFN2 are the underlying cause of Charcot-Marie-Tooth neuropathy type 2A (CMT2A). However, there has been no reports investigating the MFN2 genes in Korean CMT patients. Therefore, we investigated to find the clinical and genetic characteristics in Korean patients with the MFN2 gene mutation. METHODS: We examined the mutations of the MFN2 gene in 137 Korean CMT families. According to criteria from the European CMT consortium, CMT2 was 45 families. Mutations were confirmed by both strands sequencing. Nerve conduction studies were carried out in CMT patients having each mutation. RESULTS: Eight pathogenic mutations were found in 10 families. Six mutations (Leu92Pro, Gly127Asp, His165Arg, Ser263Pro, Arg364Trp, Met376Thr) were determined to be novel, and those were not detected in the 100 healthy controls. A de novo missense mutation was found in three CMT families (30%). The frequency of the MFN2 mutation was 22.2%, which was higher than those found in the Cx32 mutation. In CMT2A, the frequencies with early age at onset (<10 years) and flat feet were 46.2%. CONCLUSIONS: We found MFN2 mutations in patients with sporadic or dominantly inherited CMT. In the majority of cases with CMT type 2, the axonal neuropathy, may be due to MFN2 mutations.
Axons ; Charcot-Marie-Tooth Disease ; Flatfoot ; Humans ; Membrane Proteins ; Mitochondrial Dynamics ; Mutation, Missense ; Neural Conduction

BACKGROUND: The N-terminal fragment of pro Brain Natriuretic Peptide (NT-pro BNP) is a neuro-hormone synthesized in the cardiac ventricles in response to increased wall tension. The purpose of this study was to assess the correlation between the NT-pro BNP levels and the New York Heart Association function class (NYHA Fc) of dyspnea and echocardiographic findings for the patients who visited our cardiology departments. METHODS: From October, 2002 to April, 2003, serum NT-pro BNP levels were measured in 348 patients who visited the Samsung Medical Center and the Jong Koo Lee Heart Clinic. RESULTS: The NT-pro BNP levels were increased with the progression of NYHA Fc of dyspnea (p< 0.001 by ANOVA), the increase in the systolic left ventricular internal dimension (p< 0.05), and the decrease in the ejection fraction (p< 0.01). For the NYHA Fc I patients, the NT-pro BNP levels were positively correlated with age (p< 0.001) and left atrial size (p< 0.001). For the patients with ischemic heart disease, the NT-pro BNP levels were also positively correlated with the NYHA Fc (p< 0.001 by ANOVA). The NT-pro BNP levels were increased with the increase in the systolic (p< 0.001) and diastolic pressure (p=0.017), the left ventricular internal dimension as well as the decrease in the ejection fraction (p< 0.001). The area under the receiver operating characteristic (ROC) curve for the NT-pro BNP levels was 0.994 (95% confidence interval, 0.979-0.999), and the most reliable cut-off level for the NT-pro BNP was 293.6 pg/mL. CONCLUSION: The NT-pro BNP levels were positively correlated with the NYHA Fc of dyspnea and the systolic dysfunction for the patients who visited our cardiology departments. A 300 pg/mL value for the NT-pro BNP cut-off point appears to be a sensitive level to differentiate dyspnea originating from an ailing heart or not for the patients who visited our cardiology departments.
Dyspnea/physiopathology ; Female ; Heart Failure, Congestive/*blood/*physiopathology ; Humans ; Male ; Middle Aged ; Nerve Tissue Proteins/*blood ; Peptide Fragments/*blood ; Prospective Studies ; *Severity of Illness Index ; Stroke Volume/physiology ; Systole/physiology ; Ventricular Dysfunction, Left/physiopathology

A 44-year-old man showed recurrent paroxysmal amnesic attacks following viral encephalitis which, despite antiepileptic treatment, developed into status epilepticus. Interestingly, the amnesic attacks mainly consisted of amnesia for retrograde events. After recovery from status, he showed a persistent amnesia which was characterized as disproportionate retrograde amnesia for the past 20 years. We attribute the amnesic attacks in the acute stage to a transient epileptic amnesia and the profound retrograde amnesia in the chronic stage to status- or infection-related focal brain damage.
Adult ; Amnesia ; Amnesia, Retrograde* ; Brain ; Encephalitis, Viral* ; Humans ; Status Epilepticus

BACKGROUND: Recent studies have suggested that the outcomes of the patients with acute renal failure (ARF) may related to delivered dose of dialysis. In such context, a number of investigators have reported about delivered dose of dialysis and its contribution to outcomes of ARF, using Kt/V. The purpose of the study was to evaluate actual delivered dose of dialysis in intermittent hemodialysis (HD) in critically ill ARF patients, clinical factors contributing delivery of dialysis dose, and relationship of delivered dialysis dose and survival. METHODS: Delivered and prescribed dose of dialysis, presented as Kt/V, were measured in ARF patients intermittent HD in intensive care unit of Inha University Hospital from January 1999, until December 1999, using single pool urea kinetic model. RESULTS: All subjects received intermittent HD of 6.4+/-4.8 times with mean of 225.6+/-40.4 min per session. Overall survival was 55.5%. Prescribed Kt/V in all subjects was 1.24+/-0.39, but actual delivered Kt/ V was 1.08+/-0.17. A mean delivered/prescribed Kt/V ratio was 87.1+/-43%. Duration of HD session (R= -0.547, p=0.019), Cleveland Clinic Foundation Severity Score (R=-0.486, p=0.041), and frequency of hypotensive episodes (R=-0.419, p=0.043) were significantly correlated with delivered/prescribed Kt/V ratio. Delivered dose was under 1.2 in 66.7% of the subjects. Survival rate of these patients was 50.0%, which was lower as compared to 66.6% of the patients with delivered dose over 1.2. Patients with low delivered dose (Kt/V<1.2) showed significantly low prescribed dose and short HD time (p<0.05). Delivered Kt/V was correlated with BUN at initiation of dialysis, HD duration, and prescribed Kt/V (p<0.05). Non-survivors showed significantly low initial serum creatinine, low CCF severity score, high frequency of hypotensive episodes, and less use of heparin (p< 0.05). Prescribed Kt/V was not different between survivors and non-survivor (1.22+/-0.30 vs 1.31+/-0.45), but delivered Kt/V (1.17+/-0.17 vs. 1.04+/-0.17; p<0.05) and delivered/prscribed Kt/V (95.9+/-22.6% vs. 73.9+/-15.6%; p<0.05) were significantly higher in survivors than in non-survivors. CONCLUSION: In ARF patients, the delivery of dialysis was significantly lower than as was expected. Delivered/prescribed Kt/V was about 87% and more than half of the patients received intermittent HD of Kt/V less than 1.2. Better survival was associated with higher delivered dose of dialysis. We need further prospective studies about the causal relationship between delivered dose of dialysis and outcomes in ARF patients.
Acute Kidney Injury* ; Creatinine ; Critical Illness ; Dialysis* ; Heparin ; Humans ; Intensive Care Units ; Prospective Studies ; Renal Dialysis* ; Research Personnel ; Survival Rate ; Survivors ; Urea