A case of multiple endocrine neoplasia type 1 combined with papillary thyroid carcinoma.

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.

The effects of pioglitazone on cerebrovascular resistance in patients with type 2 diabetes mellitus.

Atherosclerosis is one of the major causes of morbidity and mortality in patients with type 2 diabetes mellitus. Pioglitazone has been reported to have antiatherogenic effects. The aim of this study was to investigate whether pioglitazone affects pulsatility index (PI) of the cerebral arteries and the carotid intima-media thickness in type 2 diabetic patients. A total of 40 type 2 diabetic patients were included in this study. They were divided into 2 groups: the pioglitazone-treated group (pioglitazone 15 mg/d with gliclazide 80-320 mg/d for 12 weeks) and the gliclazide-treated group (gliclazide 80-320 mg/d for 12 weeks). Transcranial Doppler ultrasonography was performed for each cerebral artery, and PI was calculated as (systolic velocity-diastolic velocity)/mean velocity. The pioglitazone treatment significantly increased high-density lipoprotein cholesterol and decreased triglyceride levels and insulin resistance. This study revealed that the change in mean intima-media thickness was not significant in both groups, but the change in PI was significantly decreased with pioglitazone compared to gliclazide. In conclusion, pioglitazone decreased PI and improved cerebrovascular resistance in type 2 diabetic patients.

Relationship of low-density lipoprotein particle size to insulin resistance and intima-media thickness in nondiabetic Koreans.

The aim of this study was to investigate whether low-density lipoprotein (LDL) particle size is associated with insulin resistance and to explore the association between LDL particle size and preclinical atherosclerosis in nondiabetic Korean population. We measured the carotid intima-media thickness (IMT), LDL particle size, and insulin resistance in 136 nondiabetic subjects. Low-density lipoprotein particle size was significantly correlated with insulin resistance, but the independent risk factors of LDL particle size determined by the multiple regression analysis were age, triglyceride, and high-density lipoprotein cholesterol (HDL-C). Carotid IMT was associated with traditional risk factors of atherosclerosis, which are age, HDL-C, LDL cholesterol, systolic and diastolic blood pressure, but LDL particle size was not correlated with carotid IMT. We conclude that LDL particle size was associated with insulin resistance, but age, triglyceride, and HDL-C contributed independently to the variability in LDL particle size, and LDL particle size was not a predictor of preclinical atherosclerosis in nondiabetic Koreans.

Bilateral peripheral facial palsy in a patient with Human Immunodeficiency Virus (HIV) infection.

Neurological complications are important causes of morbidity and mortality in patients with human immunodeficiency virus (HIV) infection. They can occur at any stage of the disease and can affect any level of the central or peripheral nervous systems. In the literature, several cases of HIV-associated facial paralysis have been reported; however, bilateral facial palsy is rarely reported. In this paper, we present the first case in Korea, of a bilateral facial palsy occurring as the first clinical manifestation of HIV infection.

Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study.

BACKGROUND/AIMS: A close relationship has been established between nonalcoholic fatty liver disease (NAFLD) and an elevated risk of coronary heart disease (CHD), but little is known about the association between alcoholic fatty liver disease (AFLD) and CHD risk. The aim of this study was to determine whether AFLD is associated with elevated CHD risk. METHODS: We retrospectively enrolled 10,710 subjects out of 11,469 individuals who visited the Konkuk University Health Care Center for a routine health checkup in 2010. AFLD was diagnosed made when the usual amount of alcohol consumption exceeded 210 g/week in males and 140 g/week in females for the previous 2 years and when hepatic steatosis was detected by liver ultrasonography. The 10-year risk for CHD was estimated using the Framingham Risk Score. RESULTS: Hepatic steatosis was diagnosed in 4,142 of the 10,710 individuals (38.7%); the remainder (i.e., n=6,568) became the control group. The 4,142 individuals with hepatic steatosis were divided into two groups: NAFLD (n=2,953) and AFLD (n=1,189). The risk of CHD was higher in AFLD (6.72±0.12) than in the control group (5.50±0.04, P<0.001), and comparable to that in NAFLD (7.32±0.07, P=0.02). CONCLUSIONS: Individuals with AFLD have an elevated 10-year risk of CHD that is comparable to those with NAFLD. Therefore, AFLD should be considered a significant risk for future CHD, and preventive measures should be considered earlier.

Usefulness of brachial-ankle pulse wave velocity as a predictive marker of multiple coronary artery occlusive disease in Korean type 2 diabetes patients.

Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and frequently observed coronary artery disease in type 2 diabetes patients, but no simple, non-invasive screening tool is available yet. The aim of this study is to evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle pulse wave velocity (baPWV), to demonstrate the correlation between arterial stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and eighty-one diabetes and 262 non-diabetes patients were enrolled in the study. Routine anthropometric and serologic data were collected. baPWV was measured the day before coronary angiography, and the severity of CAOD was assessed with Gensini score after angiography. baPWV and Gensini score were significantly increased in diabetes patients and Gensini score had a positive correlation with baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for predicting multiple CAOD, especially in type 2 diabetes patients.

Cerebral arterial pulsatility and insulin resistance in type 2 diabetic patients.

Diabetic patients have a threefold risk for cerebrovascular disease compared with nondiabetic controls. The aim of the present study was to investigate the association of insulin resistance with the pulsatility index (PI) of cerebral arteries in type 2 diabetic patients. We compared a group of 90 patients with stroke-free, type 2 diabetes and an age- and sex-matched control group of 45 healthy subjects without diabetes. We then evaluated the PI of the middle cerebral artery (MCA) by transcranial Doppler ultrasonography (TCD), and insulin resistance was determined by a short insulin tolerance test. The PI was significantly higher in diabetic patients than in healthy controls (p<0.05) and also higher in patients with insulin resistance than that seen in insulin sensitive diabetic patients (p<0.05). The PI of the MCA was significantly correlated with age (R=0.465, p<0.01), duration of diabetes (R=0.264, p=0.025) and hypertension (R=0.285, p=0.015) and inversely correlated with the insulin resistance index (Kitt: R=-0.359, p=0.030). A multiple regression analysis was performed with PI as the dependent variable and insulin resistance as an independent variable along with known clinical risk factors. Age (beta=0.393, p<0.01) and duration of diabetes (beta=0.274, p=0.043) exhibited a significant independent contribution to PI. PI could be a useful marker in the detection of diabetic cerebrovascular changes, and insulin resistance showed correlations with PI, but age and the duration of diabetes contributed independently to the variability in the PI.

Association of abdominal obesity with atherosclerosis in type 2 diabetes mellitus (T2DM) in Korea.

The aim of this study was to investigate the relationship between obesity, insulin resistance and atherosclerosis in type 2 diabetes mellitus (T2DM) patients. Total 530 patients with T2DM were included. To evaluate the severity of atherosclerosis, we measured the coronary artery calcification (CAC) score, intima-media thickness (IMT) of the common carotid artery, and the ankle-brachial pressure index (ABPI). Subjects were classified according to body mass index (BMI), a marker of general obesity, and waist-to-hip ratio (WHR), a marker of regional obesity. The insulin sensitivity index (ISI) was measured by the short insulin tolerance test. All subjects were classified into four groups, according to BMI: the under-weight group, the normal-weight (NW) group, the over-weight (OW) group, and the obese (OB) group. WHR and systolic blood pressure, triglycerides (TG), HDL-cholesterol (HDLC), free fatty acids (FFA), fibrinogen, and fasting c-peptide levels were significantly different between BMI groups. TG, HDL-C, FFA, fibrinogen and ISI were significantly different between patients with and without abdominal obesity. In the OW group as well as in the NW group, carotid IMT, ABPI and CAC score were significantly different between patients with and without abdominal obesity. This study indicates that abdominal obesity was associated with atherosclerosis in T2DM patients.

Visceral fat thickness predicts fatty liver in Koreans with type 2 diabetes mellitus.

Our aim was to study whether visceral adiposity is a predictor of diabetic fatty liver in Korean type 2 diabetes mellitus. In this study, abdominal ultrasonography was used to assess the presence of fatty liver in 1,898 patients with type 2 diabetes. We measured visceral fat thickness by high-resolutional ultrasonography and insulin resistance by Kitt. Half of the cohort had a fatty liver (50.2%). High visceral fat thickness had the highest odds ratio for developing fatty liver in both sexes (odds ratio [S.D]: 3.14 [2.24-4.69], p<0.00 in male, 2.84 [2.04-3.93], p<0.00 in female). In addition, visceral fat thickness of 42.45 and 37.7 mm in men and women, respectively, were chosen as the discriminating value to predict the presence of fatty liver with a sensitivity of 71% and 73% and a specificity of 70% and 70% in men and women, respectively. The area under the receiver-operating characteristics curve was 0.759 in men and 0.764 in women. Therefore we could conclude that the degree of visceral adiposity predicts the presence of fatty liver type 2 diabetes mellitus, whether centrally obese or not, suggesting that hepatic fat accumulation in a diabetic fatty liver may be influenced by visceral fat accumulation regardless of waist circumference.

Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control.

OBJECTIVE: We aimed to evaluate the combined effects of GH treatment and diet restriction on lipolysis and anabolism, insulin resistance and atherosclerotic risk factors in obese patients with type 2 diabetes mellitus (T2DM). SUBJECTS: This randomized, double-blind, placebo-controlled study included 24 obese T2DM patients (male : female = 12 : 12, mean age 53.7 +/- 7.2 years) with poor glycaemic control (fasting plasma glucose 10.673 +/- 1.121 mmol/l, HbA(1C) 9.9 +/- 2.3%). Sixteen of these patients were treated with recombinant human GH (1-1.5 units/day, 5 days/week) while undergoing diet restriction and exercise for 12 weeks. METHODS: Anthropometric and bioelectrical impedance measurements were undertaken to determine the lean body mass and total body fat. Computed tomography (CT) was performed to estimate visceral and subcutaneous fat distribution at the umbilicus level and the muscle area of the midthigh. Insulin resistance was measured by the insulin tolerance test (ITT) and by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: The ratios VSR (visceral fat area/subcutaneous fat area) and VMR (visceral fat area/thigh muscle area) were significantly decreased in the GH-treated group compared to the control group. An increase in lean body mass was observed in the GH-treated group. Levels of total cholesterol, triglyceride, free fatty acid (FFA), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were significantly decreased after GH treatment. Fasting glucose levels decreased similarly (P < 0.05 anova) in both groups during the treatment period. Fasting C-peptide levels significantly increased, whereas insulin levels significantly decreased, in the GH-treated group, but no changes were observed in the control group. The insulin sensitivity index (ISI) was significantly increased in the GH-treated group (1.3 +/- 1.4 vs. 1.9 +/- 1.0%/min, P < 0.05). CONCLUSIONS: GH treatment in obese T2DM patients with poor glycaemic control is beneficial in decreasing the amount of visceral fats, and may therefore result in improvements in insulin resistance, atherosclerotic risk factors and dyslipidaemia.

Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer.

PURPOSE: With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens. Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS: Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS: Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION: The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.