The Primary Biliary Cirrhosis Presenting with Raynaud's Disease and Digital Necrosis

Necrosis of the upper extremity occurs rarely in type 2 diabetic patients compared to lower extremity necrosis. We report a 69-year-old woman with type 2 diabetes mellitus who presented with necrosis of the left 5th finger tip. The patient had primary biliary cirrhosis accompanied by necrosis of the fingertip due to severe Raynaud's phenomenon. Primary biliary cirrhosis (PBC) is a typical autoimmune disease, which can in rare cases be accompanied by autoimmune symptoms including sicca symptom and Raynaud's phenomenon. Furthermore, autoimmune diseases, such as systemic sclerosis, rheumatoid arthritis and undifferentiated connective tissue disease (UCTD) can be associated. Although every type of vascular etiology should be considered as a cause of digital necrosis, Raynaud's phenomenon is usually not considered in diabetes. We report this case of finger tip necrosis due to severe Raynaud's phenomenon accompanied by PBC and UCTD in a diabetic patient.

Comparison of Surgical Outcomes and Long-term Survival between Limited and Major Hepatic Resection for Hepatocellular Carcinoma Less than 5 cm

PURPOSE: Though major hepatic resections including hemihepatectomy, trisectionectomy, and central bisectionectomy are most commonly employed for small (<5 cm) hepatocellular carcinoma (HCC), limited hepatic resection is indicated in some HCC patients with impaired liver function, poor physical condition, or tumors peripherally located. We compared the clinicopathological features and long-term survival between the patients who underwent major resection and limited resection. METHODS: From January 1998 to May 2007, 223 patients who underwent hepatic resection for small HCC were enrolled. 123 patients underwent limited resection and 100 patients underwent major resection. Clinocopathologic features, overall, and disease-free survival were compared between both groups. RESULTS: The limited resection group had lower mean serum albumin levels (3.86+/-0.41 vs. 4.11+/-3.61, P<0.0001) and higher mean ICG R15 (12.66+/-0.87 vs. 7.51+/-4.33, P<0.0001). Patients with esophageal varix and liver cirrhosis were more common in the limited resection group (34.1% and 73.1% versus 9% and 45% respectively). Morbidity and mortality were not different in both groups. Overall 1-, 3-, 5-year survivals in both limited resection and major resection groups were 89.4%, 77.3%, 43.8% and 87.8%, 76.5%, 62.1% respectively (P=0.161) and 1-, 3-, 5-year disease free survivals were 80.2%, 50.2%, 38.6% and 79.9%, 63.2%, 50.4% respectively (P=0.10). CONCLUSION: Despite indifference of overall and disease-free 5-year survival rates between limited and major resection groups, careful follow up is essential to detect late recurrence in the limited resection group, since limited resection tends to have more frequent recurrence, especially 2 years after surgery.

Effects of Neurotrophic Factors on the Generation of Functional Dopamine Secretory Neurons Derived from in vitro Differentiated Human Embryonic Stem Cells / 대한불임학회지

OBJECTIVE: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-alpha], particulary in dopaminergic neuron formation. METHODS: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA (10-6 M) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-alpha (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. RESULTS: The bFGF or RA treated hES cells were resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with BDNF or TGF-alpha during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5+/-62.8 pmol/mg) in bFGF and TGF-alpha sequentially treated hES cells than those in RA or BDNF treated hES cells. CONCLUSION: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-alpha addition in the bFGF induction protocol.

In vitro Neural Cell Differentiation of Genetically Modified Human Embryonic Stem Cells Expressing Tyrosine Hydroxylase / 대한불임학회지

OBJECTIVE: This study was to examine in vitro neural cell differentiation pattern of the genetically modified human embryonic stem cells expressing tyrosine hydroxylase (TH). MATERIALS AND METHODS: Human embryonic stem (hES, MB03) cell was transfected with cDNAs cording for TH. Successful transfection was confirmed by western immunoblotting. Newly transfected cell line (TH#2/MB03) was induced to differentiate by two neurogenic factors retinoic acid (RA) and b-FGF. Exp. I) Upon differentiation using RA, embryoid bodies (EB, for 4 days) derived from TH#2/MB03 cells were exposed to RA (10-6 M)/AA (5x10-2 mM) for 4 days, and were allowed to differentiate in N2 medium for 7, 14 or 21 days. Exp. II) When b-FGF was used, neuronal precursor cells were expanded at the presence of b-FGF (10 ng/ml) for 6 days followed by a final differentiation in N2 medium for 7, 14 or 21 days. Neuron differentiation was examined by indirect immunocytochemistry using neuron markers (NF160 & NF200). RESULTS: After 7 days in N2 medium, approximately 80% and 20% of the RA or b-FGF induced Th#2/MB03 cells were immunoreactive to anti-NF160 and anti-NF200 antibodies, respectively. As differentiation continued, NF200 in RA treated cells significantly increased to 73.0% on 14 days compared to that in b-FGF treated cells (53.0%, p<0.05), while the proportion of cells expressing NF160 was similarly decreased between two groups. However, throughout the differentiation, expression of TH was maintained (~90%). HPLC analyses indicated the increased levels of L-DOPA in RA treated genetically modified hES cells with longer differentiation time. CONCLUSION: These results suggested that a genetically modified hES cells (TH#2/MB03) could be efficiently differentiated in vitro into mature neurons by RA induction method.

Bilateral Breast Cancer: Mammographic and Clinical Findings

PURPOSE: To evaluate the mammographic and clinical features of bilateral breast cancer. MATERIALS AND METHODS: We retrospectively reviewed clinical records (n=23) and mammograms (n=15) of 23 patients with bilateral breast cancer. Patients' age, location of the tumor and pathologic staging were determined from clinical records. Mammographic features were classified as spiculated mass, nonspiculated mass, mass with microcalcification, microcalcification only, asymmetric density, and normal. RESULTS: Of the 23 cases of bilateral breast cancer, 8 (34.8%) were synchronous and 15 (65.2%) were metachronous. Age at diagnosis of cancer in the first breast was between 27 and 59 (mean 43) years; there was no statistically significant difference in mean age between patients with synchronous and metachronous cancer. The mean interval between the diagnosis of each lesion of themetachronous pairs was 9.1 years. In 11 of 23 cases (48%), tumors were located in the same quadrant, and in the other 12 cases (52%), they were in different quadrant. At mammography, five of 15 metachronous cancers (33%) were similar in appearance and 10 pairs (67%) were different. In 4 of 23 cases (17%), cancer in the first breast was at stage 0 and stage 1, and in 13 of 23 (57%), cancer in the second breast was at this same stage. CONCLUSION: In bilateral breast cancer, the two breasts frequently show different mammographic features. Cancer of the second breast was at an early stage; this suggest that regular examination and mammography are important and can allow early detection of contralateral breast cancer.