Polymorphism in Codons 10 and 25 of the Transforming Growth Factor-beta1 Gene in Korean Population and in Patients with Liver Cirrhosis and Hepatocellular Carcinoma / 대한소화기학회지

BACKGROUND/AIMS: The genetic polymorphism of transforming growth factor-beta1 (TGF-beta1) at codons 10 and 25 which influences the production of TGF-beta1 is related to fibrogenesis in the lung and liver. We evaluated the genetic polymorphism at codons 10 and 25 in controls and in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). METHODS: Blood samples were collected from controls (n=35), patients with LC (n=64), and HCC (n=49). Genomic DNA was isolated and polymerase chain reaction (PCR) was done for a segment including codons 10 and 25. The results of direct sequencing for PCR products were compared between the controls and the patients. RESULTS: There was no genetic polymorphism at codon 25 and three types of genetic polymorphism at codon 10. The leucine homozygous genotype (CTG/CTG) at codon 10 was more common in patients with LC than the controls (p=0.01) and especially in patients with LC caused by HBV (p=0.004). The polymorphism at codons 10 in patients with HCC was similar to the controls. However, leucine homozygous genotype was more common in patients with HCC of uninodular morphology than those of massive morphology (p=0.007). CONCLUSIONS: The genetic polymorphism of TGF-beta1 at codon 10 might be associated with LC and morphology of HCC. The potential usefulness of TGF-beta1 genotyping needs further studies in large scale.

Clinical and Virologic Characteristics of Lamivudine Resistance in HBV-associated Chronic Liver Disease / 대한간학회지

BACKGROUND/AIMS: Lamivudine therapy in chronic hepatitis B has been shown to be effective in inhibiting HBV replication. However, lamivudine resistance has been developed with prolonged use. We studied to determine the prevalence, predictive factors, and clinical outcomes of lamivudine resistance. Mutations in YMDD motif of HBV polymerase, which have been associated with lamivudine resistance, were also assessed. METHODS: 170 patients with HBV-associated chronic liver disease who have received lamivudine for at least one year, were studied. The clinical, biochemical, and virologic characteristics were analyzed and compared according to presence (resistance group) or absence (non-resistance group) of DNA breakthrough. Their clinical outcomes were regularly followed. Stored sera before treatment and after DNA breakthrough were examined for detection of HBV polymerase mutation by direct sequencing and/or RFLP. RESULTS: Cumulative rates of lamivudine resistance after one and two years of treatment were 11% and 34%, respectively. In the resistance group, as compared to the non-resistance group, age, the presence of HBeAg before treatment, and disappearance of HBeAg during treatment, were significantly different. The predictive factors associated with lamivudine resistance were not found. ALT and HBV-DNA level after lamivudine resistance was variable, but jaundice or hepatic failure was absent. Mutation in YMDD motif was detected in 73% and other variable mutations were detected before treatment and after DNA breakthrough. CONCLUSIONS: Lamivudine resistance increases the longer the duration of treatment and clinical outcomes are variable. The mutation in YMDD motif was found in about 2/3 of cases. Other causes for lamivudine resistance may be considered.

A Case of Adrenalectomy after Preterm Delivery in Cushing's Syndrome of Third Trimester Pregnant Woman / 대한내분비학회지

A renin- or angiotensin-II responsive aldosterone producing tumor is a rare cause of primary hyperaldosteronism. This tumor can be identified by tests that show that the aldosterone producing adrenal tumor is not fully autonomous. In other words partially it is responsible for the stimulation of aldosterone secretion that results aldosterone levels in an increase in serum in response to the upright posture and spironolactone treatment. Furthermore, the urinary 18-hydroxycortisol level is within the normal range. Because of different responses to surgical removal, the differential diagnosis of the causes of primary aldosteronism can't be overemphasized even for rare causes of primary aldosteronism such as unilateral nodular hyperplasia or a renin-responsible aldosterone producing tumor. We should consider renin or angiotensin-II responsive adrenal adenoma in the differential diagnosis of primary aldosteronism when biochemical data shows atypical results. Here we present the first case in Korea of a renin-responsive aldosterone producing adrenal adenoma which was fully accessible and was successfully treated by surgical removal. Also, sampling for aldosterone secretion just above the insertion site in the left renal vein before surgery showed a suspiciously abberant left adrenal vein drainage into the IVC, This was very helpful information during adrenal vein ligation in laparoscopic adrenalectomy.

Cytarabine and Idarubicin Induction Chemotherapy in Patients with Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: About 60~80% of previously untreated patients with acute myelogenous leukemia (AML) achieve complete remission (CR) when treated with cytarabine and anthracycline. Anthracycline is one of the most important chemotherapeutic agents in AML. It has been claimed that idarubicin showed superior complete remission rate than daunorubicin, which is not completely established. We evaluated idarubicin in combination with cytarabine (AI) as an induction chemotherapy in patient with AML. METHODS: Thirty one patients with newly diagnosed acute myelogenous leukemia were enrolled. Remission induction emotherapy was consisted of cytarabine (100mg/m2 IV over 24 hours on day 1~7) and idarubicin (12mg/m2 IV over 30 minutes on day 1~3). After achievement of CR, patients underwent consolidation therapy with high- dose cytarabine and/or bone marrow transplantation. RESULTS: Median age of the patients was 43 years (range; 17~62) and M2 was the most common subtype. The CR rate was 71% (22/ 31). The median overall and disease-free survival were 67 weeks (95% confidence interval, CI; 43~91) and 65 weeks (95% CI; 26~104), respectively with a median follow-up of 48 weeks. Major toxicities were fever and infection during the neutropenic period. There were three treatment-related mortalities. Causes of death were refractory AML in 1 patient and infection in 2 patients. CONCLUSION: AI induction chemotherapy seems to be effective and safe regimen as an induction chemotherapy in AML.

A Case of Waldenstrom's Macroglobulinemia Presented as a Compression Fracture of Spine / 대한혈액학회지

Waldenstrom's macroglobulinemia is a rare disease of plasmacytoid lymphocyte proliferation usually presented without bone lesion which is the common presenting symptom in multiple myeloma. We report a 50-year-old female with Waldenstrom's macroglobulinemia presented as a bony lesion without many other features common in this diesease. She was admitted with the chief complaint of low back pain and low extremity paresthesia for two months. Bone marrow biopsy and aspiration, protein and immune electrophoresis showed findings consistent with Waldenstr m's macroglobulinemia. Magnetic resonance imaging of thoracic spine showed pathologic compression fracture in T6 and T7 with posterior epidural mass at T6 to T7 level. We report this unusual case of Waldenstrom's macroglobulinemia presented as compression fracture of thoracic spine with a review of literatures.

An Unusual Case of Guide Wire Fracture during Coronary Artery Stenting for Bifurcation Lesion

The complications associated with the use of a guide wire, used during angioplasy, are rare and often go unrecognized. However, occasionally the guide wire itself may cause serious complications such as perforation or dissection of the distal coronary artery. A guide wire fracture during angioplasty is a rare complication, however entrapment and uncoiling of the guide wire can cause fracture. We report a case of guide wire fracture that developed by entrapment of the distal bending portion during stenting for bifurcation lesion. The broken free end of the guide wire remained within the stent strut, and urgent surgical intervention was necessary for its retrieval. We experienced a case of entrapment and fracture of the guide wire during stenting that was successfully surgically removed.

Prognostic value of AML1/ETO fusion transcripts in patients with acute myelogenous leukemia / 대한내과학회지

BACKGROUND: The t (8;21) (q22;q22), which produces the fusion gene AML1/ETO, is associated with relatively good prognosis and, in particular, with a good response to cytosine arabinoside. Analysis of t (8;21) positive leukemic blasts has shown characteristic morphological and immunological features. We performed this study to investigate the incidence of AML1/ETO rearrangement in adult AML, especially in M2 subtype, to make a comparison of morphologic, immunophenotypic and clinical characteristics between AML1/ETO rearrangement positive and negative group in patient with AML and to analyze the correlation with other biological parameters. METHODS: From May 1995 to Sep. 2000, fifty-nine patients with AML including twenty-nine AML-M2 were studied. RNAs were extracted from leukemic cells and reverse transcriptase mediated polymerase chain reaction (RT-PCR) for AML1/ETO fusion transcript was done. Chromosome study, immunophenotypic, and clinical characteristics were analysed and statistical analysis was done. RESULTS: The male to female ratio was 32:27 in AML and 17:12 in AML-M2. The median age was 43 years (range 14-86) in AML and 43 years (range 14-77) in AML-M2. The incidence of AML1/ETO fusion transcripts was 22.0% in AML and 44.8% in AML-M2. The morphologic finding of bone marrow in AML-M2 showed higher incidence of Auer rods, large blast with prominent golgi and abnormal granules in AML1/ETO positive patients. There was no significant difference of immunophenotype. AML patients with AML1/ETO rearrangement had a tendency of higher complete remission rate (81.8% vs 56.6%, p=0.13). The overall survival (median 82.2 weeks vs 34.4 weeks, p=0.02) and progression free survival (median 50.9 weeks vs 20.4 weeks, p=0.02) of AML1/ETO positive group were longer than those of negative group in AML. AML-M2 patients with AML1/ETO rearrangement had also a tendency of longer overall survival and progression free survival, although there was no significant difference between both group (median OS 82.4 weeks vs 15.6 weeks, p=0.07, median PFS 50.9 weeks vs 16.0 weeks, p=0.09). CONCLUSION: Our data suggest that AML1/ETO rearrangement is detected frequently in AML, especially M2, and is a favorable prognostic factor. Thus, molecular diagnostic approaches should be used routinely to identify patients with this genetic subtype of AML.