A case of sclerosing cholangitis showing response to prednisolone]

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive fibrosis and destruction of intra- and extrahepatic bile ducts resulting in hepatic failure and death. Only the liver transplantation is the possible treatment for patients to survive. There has been a few reports that steroid is an effective treatment in autoimmune variant sclerosing cholangitis, which is thought to be a familial diseases with different etiology, and steroid responsive biliary strictures be named as immunoglobulin G4 (IgG4)-associated cholangitis (IAC). There is no reliable data regarding effective steroid treatment in autoimmune variant sclerosing cholangitis in Korea. We report a case of 32-year-old male with sclerosing cholangitis, who was diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) and liver biopsy, showing favorable response to prednisolone therapy.     

Association of polymorphisms in the insulin-degrading enzyme gene with type 2 diabetes in the Korean population

Insulin-degrading enzyme (IDE) is a metalloproteinase which degrades insulin and terminates its action. Homologous deletion of IDE gene resulted in hyperinsulinemia and glucose intolerance in a rat model of type 2 diabetes mellitus. Several genetic association studies examined IDE as a susceptibility gene for type 2 diabetes in European descents. Here we investigated the genetic association of IDE polymorphisms with the risk of type 2 diabetes and its related phenotypes in the Korean population. Among six single nucleotide polymorphisms analyzed, g.-179T>C (OR=1.73, P=0.04), and g.IVS18+99G>A (OR=1.23, P=0.02) revealed borderline association with increased risk of type 2 diabetes. Combining our results with previous data obtained from the European population, g.-179T>C (OR=1.11, P=0.03), and g.IVS24-64A>T (OR=1.18, P=0.005) showed significant association with type 2 diabetes. Haplotype consisting of common alleles of the six polymorphisms was associated with decreased risk of type 2 diabetes (OR=0.82, P=0.02). However, none of the polymorphisms was significantly associated with metabolic phenotypes. We can conclude that variations in IDE might contribute to diabetes susceptibility in the Korean population.     

The influence of serum aldosterone and the aldosterone-renin ratio on pulse wave velocity in hypertensive patients

OBJECTIVE: The aldosterone-renin ratio (ARR) is widely used to screen for primary aldosteronism, and may reflect a relative excess of aldosterone secretion compared with renin secretion. Excess aldosterone may have a detrimental effect on vascular stiffness. We therefore hypothesized that ARR and aldosterone are independently correlated with pulse wave velocity (PWV) in hypertensive patients. METHODS: The study consisted of 438 hypertensive patients. Serum aldosterone and plasma renin activity were measured in a sitting position using standard techniques. The PWV was determined by measuring the heart to femoral PWV (hfPWV) and brachial to ankle PWV with a VP-2000 pulse wave unit. RESULTS: Group 1 was defined as patients with ARR of at least 20 (n = 53) with serum aldosterone >or= 12 ng/dl, while the remainder comprised group 2. Comparisons between the two groups reveal group 1 tended to have higher age, significantly higher proportion of women and higher systolic/diastolic blood pressure. Patients in group 1 also had a significantly higher index of central arterial stiffness (hfPWV 1048 +/- 202 vs 978 +/- 182, P = 0.010) compared with group 2. Multiple linear regression revealed that aldosterone, but not the ARR, is significantly associated with hfPWV but not brachial to ankle PWV, after controlling for age, systolic blood pressure and heart rate at the time of PWV measurement, body mass index, gender, low-density lipoprotein-cholesterol, triglyceride, high-density lipoprotein-cholesterol, blood pressure medication and statins. CONCLUSIONS: Serum aldosterone is significantly associated with central aortic PWV in hypertensive patients. The results demonstrate a possible role for aldosterone in developing central aortic stiffness and increased PWV in hypertensive patients.     

A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model

OBJECTIVES: We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model. METHODS: Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia, gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology. RESULTS: Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77+/-0.13 in control groups, including the AGV-null group, and 0.91+/-0.14 in the AGV-SPK group (P<0.05). Angiographic vessel counts were significantly increased (8.0+/-2.1 at baseline and 11.8+/-3.2 on day 30, P<0.001) in the AGV-SPK group. Histologic analysis showed that microscopic total vessel counts on day 30 were 3.5+/-1.8/field in the control and AGV-null group and 5.4+/-1.0/field in the AGV-SPK group. Arterioles (AGV-SPK; 3.0+/-0.8 versus control and AGV-null; 2.1+/-1.1, P<0.05) were significantly increased in the AGV-SPK group. CONCLUSIONS: This study shows that SPK promotes arteriogenesis, as evidenced by the maximal improvement in the blood pressure restoration and collateral vessel counts. SPK may be an important angiogenic target to improve perfusion in ischemic tissues.     

Sirolimus- versus paclitaxel-eluting stent implantation for unprotected left main coronary artery stenosis

We performed this study in order to compare the immediate and mid-term outcomes of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in lesions of the unprotected left main coronary artery (LMCA). We assessed 54 patients from 5 centers who had undergone unprotected LMCA stenting (35 SES and 19 PES). The procedural success rates were 100 and 95%, respectively, in the SES and PES patients (p = 0.19). At the 6-month clinical follow-up, the event-free probability was 100% in the SES group, and 88% in the PES group (p = 0.07). At the 6-month angiographic follow-up (n = 24), the SES group exhibited a slightly lower late loss than did the PES group (0.24 +/- 0.44 vs. 0.65 +/- 0.60 mm, p = 0.09), and the restenosis rates were 8 and 9% (p = 0.94) in the SES and PES patients, respectively. In conclusion, both groups exhibited excellent in-hospital and 6-month outcomes with no significant differences between them.     

Current status of diabetes management in elderly Koreans with diabetes

Knowledge about the current status of diabetes management is indispensable for the improvement of diabetes management. We performed a survey to investigate the current trend of diabetes management in elderly Koreans, at eight hospitals located throughout the country. A total of 539 patients with type 2 diabetes older than 65 years (men=224, women=315) were recruited. Their mean age was 71.5+/-4.9 years and BMI 24.3+/-3.4 (men=23.6+/-2.8, women=24.9+/-3.7)kg/m(2), and 38.2% of the patients were obese (BMI> or =25 kg/m(2), men=29.5%, women=44.4%). The mean duration of the diabetes was 13.1+/-9.2 years. Although 37.3% of the patients had A1C below 7.0%, 33.8% of the patients had A1C more than 8.0%. Three hundred and sixty three patients (67.4%) were treated with oral hypoglycemic agents and 175 patients (32.5%) were treated with insulin or combination with oral agents. The glycemic control was better in patients treated with oral agents (oral agent group=7.7+/-4.6%, insulin group=8.5+/-1.9%). Although mean SBP and DBP were 131.4+/-16.7 and 75.9+/-10.4 mmHg, respectively, 67.4% of the patients had hypertension and 38.2% of the patients with hypertension did not reach the goal (<130/80 mmHg). Of 539 elderly patients, 253 patients (47.4%) had dyslipidemia (LDL-C> or =4.1 mmol/l and/or triglyceride> or =2.5 mmol/l and/or HDL-C<1.1 mmol/l) and 72.7% of the patients with dyslipidemia took the lipid lowering agents. However, 47.4% of them did not achieve the goal (LDL-C<2.6 mmol/l and/or triglyceride<1.7 mmol/l and/or HDL-C>1.1 mmol/l). Twenty-eight patients (5.5%) had been admitted to the hospital because of severe hypoglycemia. Half of the patients (57%) had microvascular complications (retinopathy, neuropathy or overt proteinuria), and 28% of the patients had macro-vascular complications (CVD, stroke or peripheral vascular disease). As elderly diabetic patients are usually polymorbid, diabetes mellitus in old age is needed a more comprehensive approach to not only the treatment of hyperglycemia but also of hypertension, dyslipidemia and other associated diseases.     

ADMA regulates angiogenesis: genetic and metabolic evidence

Endothelium-derived nitric oxide (NO) plays an important role in transducing the effects of angiogenic factors. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We used a murine model of hindlimb ischemia to investigate whether genetic or metabolic changes in ADMA levels could impair angiogenic response in vivo. Hindlimb ischemia was surgically induced in C57BL/6J mice, apo E-deficient mice, or transgenic mice overexpressing dimethylarginine dimethylaminohydrolase (DDAH). Some animals were also treated with the NOS antagonist L-nitro-arginine, or the NO precursor L-arginine. Angiogenesis was quantified in the hindlimb skeletal muscle by capillary/myocyte ratio. Plasma or tissue ADMA levels were measured by HPLC. In normal mice, hindlimb ischemia increased tissue ADMA twofold, and reduced DDAH and NOS expression. This was associated with a reduced NOS activity (by over 80%) three days following surgery. On day seven, a threefold increase in DDAH expression and a fall in tissue ADMA levels were associated with a sevenfold increase in NOS activity, whereas NOS expression did not increase above baseline. In DDAH transgenic mice, the elevation of ADMA and decrement in NOS activity was blunted during hindlimb ischemia. Plasma ADMA levels were increased in apo E-mice (1.79 +/- 0.45 versus 1.07 +/- 0.08 pmol/l; p = 0.008). Capillary index was significantly reduced in apo E-mice up to seven weeks after surgery (0.25 +/- 0.05 versus 0.62 +/- 0.08; p < 0.001). The effect of hypercholesterolemia on capillary index was reversed by L-arginine, and (in wild-type mice) mimicked by administration of the NOS antagonist L-nitro-arginine. In conclusion, metabolic or genetic changes in plasma and tissue ADMA levels affect tissue NO production and angiogenic response to ischemia.     

Clinical and epidemiological analysis of gallstone patients focused on 25-year experience of surgically treated patients]

BACKGROUND/AIMS: To investigate the epidemiologic changing patterns of gallstone diseases in Korea during past 25 years. METHODS: A total of 5,671 gallstone patients who underwent surgery in our center during 1981-2005 were analyzed. The patients were divided into 5 periods: period I (1981-1985, n=831), period II (1986-1990, n=888), period III (1991-1995, n=1,040), period IV (1996-2000, n=1,261) and period V (2001-2005, n=1,651). Korean literatures published from 1961 to 2005 were reviewed to elucidate the nationwide trends of gallstone diseases. RESULTS: Number of gallstone disease cases were gradually increasing. Female predominance was not noted (male/female ratio, 1.07-1.37). Patients with common bile duct (CBD) stone were older than those with gallbladder (GB) stone or intrahepatic duct (IHD) stone. During past 25 years, relative proportion of GB stone cases increased from 53.0% to 89.7%, while that of CBD stone cases decreased from 68.0% to 15.1%. Relative proportion of IHD stone patients remained stationary. In rural areas, tendency of increasing GB stone and decreasing CBD stone disappeared since period III. However, in urban areas, these tendencies remained till period V. Relative frequency of IHD stone group remained unchanged in two areas. The body mass indexes of the GB stone group, CBD stone group, and IHD stone group were higher than that of the average population. CONCLUSIONS: In gallstone disease, increasing tendency of GB stone and decreasing tendency of CBD stone in rural area have disappeared. However, relative frequency of IHD stone is still high in Korea.     

Is there any clinical or radiologic feature as a preoperative marker for differentiating mass-forming pancreatitis from early-stage pancreatic adenocarcinoma?

BACKGROUND/AIMS: The differential diagnosis of early-stage pancreatic cancer and mass-forming pancreatitis is still unsettled. The purpose of the present study was to define the differential feature of focal mass-forming pancreatitis and malignant mass using aspects of clinical, laboratory and imaging features on pancreatogram or computed tomography (CT). METHODOLOGY: Between April 1995 and May 2003, 15 patients confirmed as inflammatory mass after surgical resection for pancreatic mass and 21 patients with early-stage pancreatic adenocarcinoma among the patients diagnosed as pancreatic malignancy were included in our study. Hospital records, laboratory results, findings of imaging studies and pathological findings were reviewed retrospectively. RESULTS: Regarding the clinical characteristics, the history of previous pancreatitis was distinguished in group with mass-forming pancreatitis. Incidence of jaundice was higher in the group with adenocarcinoma than in the mass-forming pancreatitis group. For laboratory results, CA19-9 level and alkaline phosphatase level were significantly elevated in the malignant group. Findings such as hyperattenuation on portal venous phase of CT scans and gradual tapering stricture on pancreatogram were differential diagnostic markers between the two groups. A portion of patients with mass-forming pancreatitis demonstrated the pathologic characteristics of autoimmune pancreatitis. CONCLUSIONS: Our 9-year experience suggests that imaging findings such as attenuation pattern on the delayed phase of CT scan and tapering pattern of pancreatic ductal stricture on pancreatogram can help to differentiate mass-forming pancreatitis from early-stage pancreatic adenocarcinoma.     

Prevalence of the Brugada-type ECG recorded from higher intercostal spaces in healthy Korean males.

BACKGROUND: Electrocardiograms (ECGs) recorded from the higher intercostal spaces (ICSs) are reported to be helpful for the diagnosis of Brugada syndrome (BS). However, the prevalence of Brugada-type ECG changes recorded from the higher ICSs is unknown in the healthy Korean population. METHODS AND RESULTS: A total of 225 healthy Korean male subjects with a mean age of 44+/-13 (20-69) years with no syncope or family history of sudden death were enrolled in the present study. ECGs were taken from 4th, 3rd, and 2nd ICSs and examined for Brugada-type ECG changes. There were none on the routine 12-lead ECGs, but 3 (1.3%) of the 225 subjects had a Brugada-type ECG recorded from the higher ICSs and 1 of them had a Brugada-type ECG recorded at both the 2nd and 3rd ICSs. The prevalence of the Brugada-type ECG was 1.3% at the 3rd ICS, 0.4% at the 2nd ICS. All were type 2. CONCLUSION: Some healthy Korean males with normal routine ECGs show Brugada-type 2 changes on ECGs recorded from higher ICSs.