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The association between ankle brachial index (ABI) and outcomes in diabetic subjects is controversial. The purpose of this study was to evaluate whether the ABI is more strongly associated with cardiovascular outcomes comparing with non-high-density lipoprotein cholesterol (non-HDL-c).A total of 452 type 2 diabetic subjects followed up for a mean of 5.8 years were grouped by ABI (0.9 versus ≥0.9) and non-HDL-c (100mg/dL versus ≥100mg/dL). Primary outcomes were composite events including all-cause mortality, hospitalization for coronary artery disease, stroke, revascularization, amputation and diabetic foot, and the secondary end point was all-cause mortality.Intergroup differences in percentage of men, duration of diabetes, hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, triglycerides and estimated glomerular filtration rate were significant. A total of 64 composite events and 17 deaths were recorded. A higher number of composite events occurred in the group with abnormal ABI but optimal non-HDL-c than in those with suboptimal non-HDL-c but normal ABI (29% versus 11%, P0.05). A similar trend was observed in all-cause mortality (11% versus 1%, P0.05). The ABI was the dominant risk factor for both end points after adjusting other factors (for composite events, hazard ratio = 0.02, 95% CI: 0.00-0.10, P0.001 and for all-cause mortality, hazard ratio = 0.01, 95% CI: 0.00-0.28, P = 0.006).The ABI was more strongly associated with outcomes in diabetes than non-HDL-c. The ABI should be routinely screened in diabetes even without symptom.

Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.

Objective Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. Methods A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (

Although thyroid diseases exist in patients with renal failure, thyroid function tests are not routine tests in patients on chronic hemodialysis (HD). Therefore, the impact of thyroid diseases on erythropoietin (EPO) dosage in HD patients is not well defined. This study evaluated the relationship between the dose of EPO and the presence or absence of thyroid dysfunction in HD patients.This study included 1013 adult patients on HD who did not have a malignancy, liver cirrhosis, thalassemia, iron deficiency, gastrointestinal bleeding, or a major operation within 6 months. Patients were characterized as being euthyroid, or having the sick euthyroid syndrome, primary hypothyroidism, subclinical hypothyroidism, hyperthyroidism, or subclinical hyperthyroidism based on thyroid function tests. Routine biochemistry profiles including an index of the efficiency of HD, along with clinical data over the previous 6-month period, were collected and analyzed. Multiple regression models were employed to assess the relationship between the dose of EPO and the presence or absence of thyroid status.The mean monthly EPO dosages were 77.7±37.0, 70.2±40.6, 90.8±68.4, 78.5±46.7, and 82.3±41.2 μg, respectively, in the sick euthyroid syndrome, euthyroid patients, hypothyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism groups (p0.05). After adjustment of all other variables in multiple regression, the mean monthly EPO dosage was 19.00±8.59 μg more in hypothyroid patients compared with euthyroid patients (p=0.027). Further, considering an interaction with the presence of diabetes, the mean monthly EPO dosage in patients with either hypothyroidism or subclinical hypothyroidism and diabetes was 54.66±17.12 μg (p=0.001) and 31.51±10.38 μg more than that of euthyroid patients, respectively (p=0.002).In HD patients, the EPO dosage required to maintain the target hemoglobin level is significantly higher in patients having both hypothyroidism or subclinical hypothyroidism and diabetes than in euthyroid patients.

Systemic microvascular complications are related to the presence of diabetic neuropathy. This study investigated the associations of blood flow oscillations with peripheral neuropathy in 25 controls and 3 diabetic groups including clinical (24), subclinical (27) and without neuropathy (26). Laser Doppler skin perfusion was transformed into three low-frequency subintervals corresponding to endothelial, neurogenic and myogenic vasomotor controls. The average vasomotion was significantly reduced in clinical neuropathy group and characterized by endothelial and neural but not smooth muscle–related changes. The normalized spectrums revealed a relative increase of myogenic and decrease of neurogenic activity in subclinical neuropathy group. The myogenic component showed a statistically inverse correlation with postural fall in systolic blood pressure (r = −0.32, p < 0.01). The diabetic patients with decreased low-frequency vasomotor responses were associated with increased odds ratio of peripheral neuropathy [odds ratio = 3.51 (95% confidence interval = 1.19–10.31), p = 0.02]. This study elucidated possible interaction between impaired microvascular flow motion and diabetic peripheral neuropathy. The vasomotor changes of skin microcirculation could be detected even in the absence of overt cardiovascular dysfunction.

In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion.

Impaired cutaneous blood flow and sweating dysfunction might be among the earliest manifestations of diabetic autonomic neuropathy. This study assessed the pathophysiological basis underlying skin vasomotion changes and their relation with progressive sudomotor dysfunction and other autonomic and somatic measures in subclinical diabetic feet. Laser Doppler skin perfusion was assessed on 68 diabetic and 25 control subjects. The low-frequency vasomotion was transformed into three frequency intervals 0.0095-0.021, 0.021-0.052 and 0.052-0.145 Hz, respectively, for the investigation of endothelial, neurogenic and myogenic effects on microcirculatory alterations. The diabetic patients were categorized into three groups by increasing severity of sudomotor dysfunction: SSR+ (sympathetic skin response present; 27 patients), SSR- (SSR absent; 23 patients) and at-risk (SSR absent and of preulcerative cracked skin; 18 patients). All diabetic patients underwent nerve conduction and cardiovascular autonomic studies. The total spectral and endothelial activity was significantly decreased only in the at-risk group. The SSR- group had lower neurogenic vasomotion than the SSR+ group (p

Summary Objectives Most patients with Cushing’s disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response. Designs A prospective study of 29 patients with CD. Methods Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry. Results Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients. Conclusions We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.

Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.

Hypothyroidism is a common disorder in older people, and may be asymptomatic and hard to be diagnosed. The main purpose of this study was to evaluate the distribution of serum thyrotropin (thyroxin-stimulating hormone, TSH) among asymptomatic older people in Taiwan, and to evaluate the relationship between age and serum TSH. In 2007, all subjects participating in the annual elderly health examinations at Taipei Veterans General Hospital were invited for study and were enrolled when they were fully consented. In total, 1716 asymptomatic elderly people (mean age: 73.2 ± 4.4 years, 56.3% males) participated in this study after careful exclusion of 38 subjects with past history of thyroid disorders. All participants were divided into two groups: (1) younger old (age 65–79) and (2) older old (age over 80) for further analysis. The mean serum levels of TSH were similar between younger old and older old groups (2.43 ± 5.36 μIU/ml for younger old and 2.36 ± 3.51 μIU/ml for older old, p = 0.444). The overall prevalence of suspected hypothyroidism was 9.2% among asymptomatic older people in Taiwan, which was significantly lower than in Caucasians. The prevalence of suspected hypothyroidism may reach 25.9% if the TSH cutoff was lowered to 2.5 μIU/ml. Further study is needed to determine the normal reference range of serum TSH in older people.

This work presents a simple approach for the synthesis of multilayered titanium-diamond-like carbon (multilayered Ti-DLC) films on a Si substrate by a filtered cathodic vacuum arc (FCVA) system using Ti-coated graphite target to supply carbon as well as the dopant titanium. This study focuses on the characterization of microstructure, surface roughness, mechanical strength and electrical resistivity. The results indicated that the multilayered Ti-DLC films exhibit better mechanical properties than the Ti-free and Ti-implanted DLC films, and both multilayered Ti- and Ti-implanted DLC films have similar Ti atomic concentrations. The surface roughness of the multilayered Ti-DLC films shows a value much lower than the other films. The film microstructure consists in TiC nanocrystals precipitated in the amorphous carbon matrix with a multilayered structure. Because of the high hardness and low roughness, the multilayered Ti-DLC films can be used as biomedical, wear-resistant and solid lubricant coatings.

Background Hemoglobin A1c (HbA1c) and fructosamine can be used to monitor glycemic control in diabetic patients with normal kidney function, but their validity in patients with chronic kidney disease (CKD) has not been evaluated. In this study, we evaluated the correlation and accuracy of these 2 measures of glycemic control in type 2 diabetic patients with CKD stages 3-4. Study Design Diagnostic test study. Setting & Participants Type 2 diabetic patients with normal (n = 30) and abnormal kidney function (n = 30) were recruited in Taipei Veterans General Hospital, Taiwan. Index Tests HbA1c and fructosamine. Reference Test Self-monitoring of blood glucose levels. Measurements Blood glucose measurements consisted of 6 preprandial, 6 postprandial, and 2 bedtime assessments in a week with a cycle of 4-week intervals for 12 weeks. Results Correlation coefficients between HbA1c level or fructosamine-albumin ratio and mean blood glucose levels were 0.836 and 0.645 in participants with normal kidney function and 0.813 and 0.649 in participants with CKD stages 3-4, respectively. In patients with CKD stages 3-4, mean blood glucose levels in weeks 1-12 were 21.9 mg/dL (95% CI, 11.6-32.5) higher than estimated average glucose (eAG) levels calculated from HbA1c levels in participants with normal kidney function. In patients with CKD stages 3-4, mean blood glucose levels in weeks 10-12 were 15.5 mg/dL (95% CI, 5.2-30.5) higher than eAG levels calculated from fructosamine levels in participants with normal kidney function, but without statistical significance when eAG calculated from fructosamine level was corrected for serum albumin level (difference of 5.6 mg/dL; 95% CI, −8.6 to 19.8). Limitations Relatively small number of participants with limited amount of blood glucose measurement data. Conclusion Our data show that eAG calculated from HbA1c and fructosamine levels might underestimate mean blood glucose levels in patients with CKD stages 3-4. References ranges may need to be modified when interpreting results of measurements of glycemic control in type 2 diabetic patients with CKD.

Metformin-associated lactic acidosis is a very rare but critical condition. It is seen in patients with type 2 diabetes mellitus who take metformin and attempt suicide with a metformin overdose. Here, we report a 43-year-old woman with type 2 diabetes mellitus and chronic renal insufficiency who developed hypoglycemia, hypothermia, tachycardia and lactic acidosis after a suicide attempt with a metformin overdose. She was successfully treated by continuous venovenous hemofiltration, and adequate hemodynamic and ventilatory support. Although metformin does not usually cause hypoglycemia when administered as monotherapy, hypoglycemia can occur in a condition coexistent with lactic acidosis secondary to metformin overdose. Metformin intoxication should be suspected when patients present with high anion gap metabolic acidosis after attempting suicide by ingesting drugs, particularly when comorbidities such as renal failure are present. Early diagnosis and rapid correction of the metabolic acidosis using hemodialysis or hemofiltration, together with concomitant cardiovascular support, and maintenance of blood glucose and core body temperature, provide the possibility of a positive outcome.

Fluorine-doped amorphous carbon (a-C:F) films were deposited using a 90°-bend magnetic filtered cathodic arc plasma system with CF 4 as a precursor and the addition of argon gas. The microstructure, composition and chemical bonding nature of the a-C:F films were investigated by Raman scattering spectroscopy and X-ray photoelectron spectroscopy. The surface morphology and roughness of a-C:F films were observed through an atomic force microscope. Hardness was measured by nano-indentation. Water contact angles were measured by the sessile drop method. The fluorine content of the films increases with the argon flux. Because of the increase of the fluorine content in the films, the film surface becomes rougher; the hardness decreases, and the contact angle increases from 76.2° to 87.8°. This work demonstrates that an appropriate amount of the admitted argon to the plasma would promote the doping of the films with fluorine, and influences the properties of the a-C:F films.

To determine the relationships between cardiovascular autonomic neuropathy (CAN) and autonomic symptoms, clinical parameters and diabetic complications in type 2 diabetes (T2DM).The results of autonomic symptoms, clinical parameters, diabetes complications and cardiovascular reflex (CVR) tests of 674 T2DM were analyzed.Significant correlations were found between CAN risk and age (p=0.019), duration of diabetes (p=0.008), HbA1c (p0.001), systolic blood pressure (p=0.006), nephropathy (p0.001), retinopathy (p0.001), and QTc interval (p0.001), but not BMI and hyperlipidemia. Patients with retinopathy or proteinuria had increase risk of CAN, and proliferative diabetic retinopathy (PDR) was the most significant risk factor (odds ratio: 6.85; 95% CI: 2.32-20.20) for CAN. Eighty-three percent of patients complained of autonomic symptoms; and the more symptoms complained, the higher the prevalence of CAN. Impotence was the only single symptom associated with CAN risk. Additional CAN risks were also observed when patients with multiple symptoms and/or complications in combinations.Our results implied that patients with multiple symptoms and/or complications in combinations have increased CAN risk, and this may provide additional information for clinicians to identify T2DM at risk of having CAN.

Aims To establish the longitudinal relationship of foot complications to neuropathy based on a 4-year follow-up of diabetic patients stratified by sudomotor dysfunctions. Methods One hundred and nineteen Type 2 diabetic patients and 36 non-diabetic subjects were initially registered in the prospective cohort study. Plantar skin temperature and sympathetic skin response (SSR) were used to monitor sympathetic mediated thermoregulation and sudomotor function. Peripheral somatic and central autonomic functions were studied using clinical, nerve conduction and cardiovascular reflex tests. At enrolment, the diabetic patients were classified into one of three groups by the progressive stages of sudomotor dysfunction: SSR+ (SSR present; 49 patients), SSR− (SSR absent; 41 patients) and at-risk group (SSR absent but with cracked skin involving partial thickness of the dermis; 29 patients). Results The at-risk group had 13.4 times (95% confidence interval 1.4–125.7) higher plantar ulceration rates than the other two patient groups during the 4 years. Skin temperature elevation occurred in parallel with development of foot sweating problems. There were no significant differences between the three patient groups in the ratios of abnormal heart rate variation, orthostatic test and clinical neuropathy score at follow-up. After 4 years of follow-up, nerve conduction abnormalities were more frequent in the at-risk and SSR− groups than in the SSR+ group. Conclusions Early deterioration of small sympathetic fibres could not be quantified accurately by the clinical, somatic and autonomic tests. Assessing skin integrity and sudomotor function in at-risk individuals identifies early peripheral sympathetic neuropathy, even if the patients have no overt clinical symptoms.

OBJECTIVE—To evaluate whether treatment with insulin is advantageous compared with oral antidiabetes agents in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. RESEARCH DESIGN AND METHODS—Newly diagnosed type 2 diabetic patients with severe hyperglycemia were hospitalized and treated with intensive insulin injections for 10–14 days. The oral glucose tolerance test (OGTT) was performed after intensive insulin treatment. After discharge, the patients were randomized to receive either insulin injections or oral antidiabetes drugs (OADs) for further management. The OGTT was repeated 6 months later, and β-cell function and insulin sensitivity were evaluated again. These subjects were continually followed up for another 6 months to evaluate their long-term glycemic control. RESULTS—At the 6th month of the study, the A1C level was significantly lower in the insulin group than in the OAD group (6.33 ± 0.70% vs. 7.50 ± 1.50%; P = 0.002). During the follow-up visit, the A1C level was still better in the insulin group (6.78 ± 1.21% vs. 7.84 ± 1.74%; P = 0.009). All parameters regarding β-cell function measured in the OGTT were improved significantly in both groups after 6 months of treatment. Compared with the OAD group, the homeostasis model assessment of β-cell function index, insulin area under the curve, and insulinogenic index were better in the insulin group. CONCLUSIONS—A 6-month course of insulin therapy, compared with OAD treatment, could more effectively achieve adequate glycemic control and significant improvement of β-cell function in new-onset type 2 diabetic patients with severe hyperglycemia.

Background/PurposeIodine deficiency causes a broad spectrum of disorders across all ages. Mandatory salt iodization in Taiwan successfully reduced the goiter rate from 21.6% to 4.3% in schoolchildren surveyed in 1971. The program continued until 2003 when salt iodization was changed from mandatory to voluntary. The purpose of this study was to investigate the iodine status of Taiwanese individuals after the change in the iodine policy.MethodsUrinary iodine (UI) was measured in samples from adults in the Nutrition and Health Survey in Taiwan 2005–2008.ResultsThe median UI level was 100 μg/L, and the percentage of populations with UI levels below 100 μg/L and 50 μg/L was 50.1% and 15.1%, respectively, indicating that the iodine status was borderline adequate. Men had a higher UI level than women (102 μg/L vs. 98 μg/L, p = 0.003), and older individuals (age > 60 years) had a lower UI level than younger people, particularly in women. The iodine status of the population < 50 years was sufficient, but it was insufficient in older groups. Mild iodine insufficiency was noted in all areas of Taiwan except the Southern area and Penghu islands, with the lowest UI level of 79 μg/L in the Mountain area. Although the UI level of women of childbearing age (19–44 years) was 103 μg/L, there may be a risk of iodine deficiency during pregnancy.ConclusionThe iodine nutrition of the Taiwanese population in 2005–2008 was borderline adequate, with insufficiency in some subgroups. Further monitoring of the iodine status is necessary.

OBJECTIVE Noninsulinoma pancreatogenous hypoglycaemia syndrome (NIPHS), characterized by postprandial neuroglycopaenia, negative prolonged fasts and negative perioperative localization studies for insulinoma, but positive selective arterial calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas, is a rare hypoglycaemic disorder of undetermined aetiology. We analysed the clinical, morphological and immunohistological features to further clarify the aetiology and pathogenesis of this rare disease. PATIENTS Ten consecutive patients with NIPHS (nine men and one woman, aged 29-78 years) were included in the study. Six of the 10 received a gradient-guided subtotal (70%) or distal (50%) pancreatectomy. In the remaining four patients, diazoxide treatment was initiated and the precise mechanism of its action was assessed by meal tests. RESULTS All of the patients showed a combination of postprandial neuroglycopaenia, negative prolonged fasts (except one patient) and negative localization studies for insulinoma, but positive calcium stimulation tests and nesidioblastosis in the gradient-guided resected pancreas. Immunohistological studies of the resected pancreatic tissues revealed neither an increased rate of proliferation of beta-cells nor an abnormal synthesis and/or processing of either proinsulin or amylin. Evidence of overexpression of the two pancreatic differentiation factors, PDX-1 and Nkx-6.1, as well as the calcium sensing receptor (CaSR) was absent. Nevertheless, abnormal expression of islet neogenesis-associated protein (INGAP), a human cytokine expressed only in the presence of islet neogenesis, in ducts and/or islets, was identified in three of the five patients studied. All of the six patients who received a surgical operation were relieved of further neuroglycopaenic attacks, but one patient who received a subtotal pancreatectomy developed diabetes. In the remaining four patients who received diazoxide treatment, hypoglycaemic episodes were satisfactorily controlled with an attenuated response of beta-cell peptides to meal stimulation. CONCLUSIONS Our results strengthen the existence of this unique clinical hypoglycaemic syndrome from beta-cell hyperfunction as well as the value of the selective arterial calcium stimulation test in its correct diagnosis and localization. The mechanisms underlying beta-cell hyperfunction and release of insulin to calcium, however, remain poorly characterized. Nevertheless, in a subset of patients with NIPHS, there exists some, as yet undefined, pancreatic humoral/paracrine factor(s) other than proinsulin, amylin, PDX-1, Nkx-6.1 and possibly glucagon-like peptide-1 (GLP-1) that are capable of inducing the INGAP gene and, if activated, will initiate ductal proliferation and islet neogenesis. As for the treatment, we recommend that diazoxide be tried first in each patient and, should it fail, a gradient-guided subtotal or distal pancreatectomy be attempted.

The relationship of plantar skin temperature to diabetic neuropathy was studied using clinical, nerve conduction and autonomic evaluations. The sympathetic skin response (SSR) was found present in both feet of 25 control subjects and 29 (out of 69) diabetic patients (SSR+ group). For those diabetic patients absent with the SSR in both feet, 18 patients (at-risk group) had preulcerative skin lesions (dry and fissured skin) and 22 did not (SSR- group). The at-risk group showed significantly higher mean foot temperature (30.2+/-1.3 degrees Celsius) than the SSR- (27.9+/-1.7 degrees Celsius), the SSR+ (27.1+/-2.0 degrees Celsius) and the control group (26.8+/-1.8 degrees Celsius). The SSR- group had smaller temperature differences (7.2+/-1.7 degrees Celsius versus 8.6+/-1.6 degrees Celsius, p

Thyroid cancer is among the 10 most common malignancies in populations in the Asia Pacific region, where access to various relevant health care resources varies widely.An expert consensus conference was held to define regional patterns of practice and guidelines for optimal management of well-differentiated epithelial thyroid carcinomas.Practice patterns vary from country to country, as would be anticipated form their variety of ethnic and racial populations, health care systems, economies, and cultures. Thyroid cancer care is provided by a number of medical and surgical specialists, usually including endocrinologists. The thyroid surgical skills, experience, and outcomes vary widely in the region. Radioiodine is available, to a greater or lesser extent, is almost all countries. Laboratory services for thyroid function monitoring are universally accessible; thyroglobulin assays are available in most countries. Recombinant thyrotropin is approved for use in only two countries, but can be accessed in some others on a "named patient" compassionate need basis. Access to advanced imaging, for exampke, positron emission tomography (PET) scanning, is limited to a few countries.In light of these realities, appropriate strategies for initial treatment and postoperative monitoring of patients with thyroid cancer have been defined, and these are presented and discussed.

A 27-year-old male developed Philadelphia chromosome-positive chronic myeloid leukemia (CML) 13 years after a first dose of radioiodine (131I) therapy for papillary thyroid carcinoma. He had received a cumulative 131I dose of 670 mCi, in 8 divided doses over 8 years, up to April 1998, for ablation of 131I avid tissues over the anterior neck region. The leukemogenic potential of radioactive iodine has been pointed out by many authors, but most reported cases have been acute leukemias. A literature review disclosed only 9 cases similar to ours. At present, there is no evidence to prove whether the development of CML after thyroid carcinoma represents a treatment-induced complication, a coincidence, or an increased susceptibility to secondary malignancies due to the malignant process itself.

Insulin autoimmune syndrome, characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia, is a rare cause of hypoglycemia. We report a patient with pulmonary tuberculosis who developed recurrent spontaneously post-absorptive hyperinsulinemic hypoglycemia after treatment with anti-tuberculous drugs. Imaging studies of the pancreas were unremarkable, and selective intra-arterial calcium stimulation with hepatic venous sampling for insulin failed to show a gradient, thus almost completely excluding the possibility of occult insulinoma or nesidioblastosis. Examinations of sera, however, disclosed a high titer of polyclonal insulin-binding autoantibodies containing at least 2 classes of binding sites, 1 with high affinity but low capacity, and the other with low affinity but high capacity. An oral glucose tolerance test revealed high serum levels of total insulin associated with relatively low levels of free insulin, but not of C-peptide, suggesting binding of the released insulin to autoantibodies. Regretfully, shortly after the withdrawal of isoniazid, the patient died of respiratory failure unrelated to hypoglycemia, and whether these antibodies were induced by isoniazid remains unknown. We recommend that insulin autoimmune syndrome be one of the differential diagnoses in patients with hyperinsulinemic hypoglycemia.

Objective Anorexia nervosa (AN) is an eating disorder that occurs mainly among young females and its prevalence has increased in recent decades. Methods We reported a patient with AN with spontaneous diffuse soft tissue emphysema and bicytopenia, both of which are very rare complications of AN. Our patient, a 20-year-old woman, had lost 41.6% of her previous body weight within 9 months. Her body mass index was 10.8 and amenorrhea had persisted for 5 months. Results After admission, she was diagnosed with AN-restrictive subtype. She was noted to have crunching sounds in the neck and upper chest wall during hospitalization. A chest X-ray and chest computed tomography scan both revealed diffuse soft tissue emphysema including subcutaneous emphysema, pneumomediastinum, and pneumoretroperitoneum. Discussion Diffuse soft tissue emphysema improved gradually and completely resolved on the 21st day of hospitalization. This condition seems to be benign and only a short period of hospitalization is required. © 2005 by Wiley Periodicals, Inc.

We report an unusual case of primary hypothalamic lymphoma with hypopituitarism presenting as Stiff-man syndrome (SMS). A 64-year-old man was hospitalized due to a 3-week history of general weakness, anorexia, vomiting, weight loss, and muscle pain and spasms precipitated by motion and tactile stimuli resulting in muscle stiffness and difficulty in mobility. Physical examination revealed normal sensorimotor function and reflexes, except for bitemporal visual field defect. Routine laboratory and gastrointestinal examinations provided no remarkable clues. Endocrine assessment revealed low levels of morning cortisol, thyroxine, and anterior pituitary hormones but an increase in prolactin level. The patient's muscle pain and stiffness improved dramatically within 2 days after hydrocortisone therapy and thyroxine replacement. Magnetic resonance imaging (MRI) of the brain confirmed an 18-mm enhancing hypothalamic tumor with optic chiasm involvement, which proved to be a B-cell lymphoma. The results of the extensive studies for systemic lymphoma were negative, suggesting a primary hypothalamic lymphoma. The tumor regressed completely and was invisible on MRI scan after adjuvant radiotherapy. The patient's condition was satisfactory and there was no recurrence of SMS during the 2-year follow-up period. This case demonstrated that primary hypothalamic lymphoma complicated with adrenal insufficiency may manifest as SMS. Early diagnosis and prompt intervention can lead to a favorable outcome and reduce morbidity.

The structural evolution in Ge+ implantation amorphous Si has been investigated by high-resolution transmission electron microscopy in conjunction with auto-correlation function (ACF) analysis. Si(0 0 1) wafers were implanted with 5 keV Ge+ to a dose of 5×1015 ions/cm2. A high density of embedded nanocrystallites was found to be present in as-implanted amorphous Si. After 350 °C annealing, the density of nanocrystallites was found to decrease, but increase after annealing at 400 °C or higher temperatures. The observation indicated that the implanted silicon became more randomized upon annealing up to 350 °C. The results are discussed in terms of energy variation in the system.

The existence of medium-range ordering structures or nanocrystallites in as-deposited amorphous SiGe thin films has been demonstrated by high-resolution transmission electron microscopy in conjunction with auto-correlation function analysis. The density of nanocrystallites decreases in amorphous SiGe samples annealed at 300–350 °C then increases in samples annealed at 400–450 °C with annealing temperature. The observations can be interpreted in terms of free energy change with annealing temperature.

Deflazacort (DFZ, a prodrug) is well absorbed and rapidly metabolized into the active metabolite 21-hydroxydeflazacort (21-OH DFZ) after oral administration. The aim of this study is to evaluate the pharmacokinetic properties of 21-OH DFZ in healthy Chinese volunteers after a single and multiple oral administration of DFZ tablets under fed condition. Twelve volunteers (six males and six females) were administered a single dose of 6 mg or 12 mg or 24 mg of DFZ in three different periods separately, according to the 3 x 3 Latin square design. Between each administration period there was a washout period of one week. The multiple-dose study of 12 mg dose DFZ per day for 7 consecutive days was started after a 1 w washout period when the single-dose study completed. The pharmacokinetic parameters of 21-OH DFZ after the single oral administration of 6 mg, 12 mg and 24 mg DFZ tablets were as follows: (37.7 +/- 11.6), (61.5 +/- 17.7) and (123 +/- 23) ng x mL(-1) for C(max); (1.90 +/- 0.32), (1.96 +/- 0.27) and (2.13 +/- 0.34) h for t1/2; (96.6 +/- 25.9), (190 +/- 44) and (422 +/- 107) ng x h x mL(-1) for AUC(0-14 h), respectively. After the multiple dose administration, the mean plasma concentration at steady-state C(av) was (7.00 +/- 1.66) ng x mL(-1) and the degree of plasma concentration fluctuation DF was 7.7 +/- 1.2. The results showed that the pharmacokinetic characteristics of 21-OH DFZ in healthy Chinese volunteers were linear over the dose range of 6 to 24 mg. No significant gender differences were found in the pharmacokinetics of 21-OH DFZ in healthy Chinese volunteers. After the multiple dose administration of 12 mg DFZ for 7 d, no accumulation of 21-OH DFZ in healthy Chinese volunteers was observed.

Taiwan was an iodine deficiency area and endemic goiter was common in 1940's. Mandatory salt iodization started in 1967, and a 1971 survey indicated that goiter rates in children decreased from 21.6% to 4.3%. To understand iodine status before the change of national salt iodization program in 2003, from mandatory to voluntary salt iodization, we retrospectively measured urinary iodine concentrations of samples collected from children in the Nutrition and Health Survey in Taiwan 2001-2002. The median UI level for children aged 6-12 years was 123 μg/L (no differences between males and females). Females aged 10-12 years had the lowest urinary iodine levels. The percentages of this population with urinary iodine levels below 100, 50, and 20 μg/L were 35.2% ± 1.0%, 4.4% ± 0.4%, and 0.2% ± 0.1%, respectively. Older children were more likely to have low urinary iodine levels. People living in different areas of Taiwan had a median urinary iodine levels ranged from 113 μg/L to 164 μg/L (males: 113-153 μg/L; females: 105-174 μg/L), with the highest level in Penghu islands, and the lowest level in the eastern and southern (Southern area 2) areas. According to international criteria, iodine status in 2001-2002 was adequate, comparable to the surveyed goiter rates (4.3%, classified as iodine sufficiency) in 1971, inferring that iodine nutrition remained adequate and stable during this period. The present study is of great importance in documenting the iodine status of Taiwan before the change from mandatory to voluntary salt iodization to serve as a baseline data for future trend analysis in iodine nutrition.過去台灣是屬於缺碘地區，地方性甲狀腺腫在1940 年代時十分流行。台灣自 1967 年開始實施強制性食鹽加碘以來，學童的甲狀腺腫大率由當時的21.6%降 至1971 年的4.3%。為瞭解國家食鹽加碘政策，在2003 年從強制改為自願加 碘前的碘營養狀況，我們回顧性檢測2001-2002 台灣學童營養健康調查所收集 尿液標本的碘濃度。發現6-12 歲學童的尿碘中位數是123 微克/升(男女沒有差 異)，當中以10-12 歲女生的尿碘濃度最低。學童尿碘濃度低於100、50 和20 微克/升的人口百分比分別是35.2% ± 1.0%、4.4% ± 0.4%和0.2% ± 0.1%，年紀 較大的學童尿碘濃度較容易偏低。台灣各地區層的學童尿碘中位數介於113 微 克/升至164 微克/升之間 (男生113 - 153 微克/升；女生105 - 174 微克/升)，當 中最高是澎湖，最低是東部層和南二層。根據國際標準，台灣在2001-2002 年 時的碘營養狀況是足夠的，相較於1971 年時的甲狀腺腫大率4.3% (定義為碘 足夠)，並無多大差別，推測這段期間台灣的碘營養維持正常和穩定。本研究 記錄台灣食鹽加碘政策從強制改為自願加碘前的碘營養狀況，提供日後碘營養 變化、趨勢分析和比較極為重要的基礎數據。

Peripheral arterial disease (PAD) could be an additional risk factor for the clinical outcomes in different populations. The purpose of this study was to evaluate the influence of PAD on patients with diabetic kidney disease.362 persons with type 2 diabetes were followed-up for a mean 4.8 years grouped by ankle brachial index (ABI) (0.9 vs. ≧0.9) and albuminuria (with or without). Primary and secondary outcomes were composite events (all-cause mortality, hospitalization for coronary artery disease, stroke, re-vascularization, amputation, and diabetic foot) and all-cause mortality.Inter-group differences in duration of diabetes, glycated hemoglobin, creatinine, and estimated glomerular filtration rate were significant. During the follow-up period, 53 composite events were recorded (14.7%) and 13 (3.5%) individuals died. Subjects with albuminuria plus ABI0.9 had higher risk of composite events than those with albuminuria but normal ABI (p0.05). The only trend difference between the two groups was in all-cause mortality. Albuminuria plus ABI0.9 was associated with risk of composite events (hazard ratio [HR] 4.20, 95% confidence interval [CI] 1.77-9.92, p=0.001) and all-cause mortality (HR 17.77, 95% CI 1.93-162.20, p=0.011).PAD might be an additional risk factor for adverse outcomes in patients with diabetic kidney disease. Further prospective data are required to validate this conclusion.

In general, most thyroid cancers are indolent and have a slowly progressive course. The exception is anaplastic thyroid cancer. It is one of the most fatal neoplasms in humans, with median survival of 4-12 months. Here, we present a patient with anaplastic thyroid cancer who survived for more than 10 years after diagnosis. A 68-year-old man was incidentally found to have anaplastic thyroid cancer during operation for follicular neoplasm. Total thyroidectomy was performed and hyperfractionated radiotherapy was carried out. After operation, annual follow-up examinations were negative for residual tumor or metastatic lesions. The patient also had chronic obstructive pulmonary disease and unfortunately died of pneumonia in a local hospital 10 years after thyroid operation.

Introduction Emphysematous pyelonephritis (EPN) is a rare but severe infection of renal parenchyma. Risk factors of renal failure in patients survived from EPN are not clear. Methods The authors retrospectively reviewed the patients with a diagnosis of EPN at Taipei Veterans General Hospital from January 1, 1995, to December 31, 2009. The authors analyzed the demographic, characteristics and the treatment modalities of those patients. The renal function of survivors after EPN episode had been followed for 1year. Results A total of 23 patients with a mean age of 62.8±17.1years were enrolled. Mean hospital duration was 31.8±21.6days. Fifteen (65.2%) patients had a history of diabetes mellitus. Mean serum HbA1c level among the diabetic patients was 11.7±3.3. More than half of patients had Escherichia coli in culture. Eleven (47.8%) patients received antibiotic treatment alone. Twelve (52.2%) patients received the concurrent percutaneous drainage and antibiotics. The overall mortality rate was 8.6%. Shock, long hospital duration and the extensive classes of computed tomography image were correlated with poor outcome. A higher initial serum creatinine level (2.8±1.4 versus 1.6±0.8, P =0.015) and receiving invasive therapy (67.7% versus 12.5%, P =0.017) significantly contributed to chronic kidney disease in the follow-up. Shock is also an independent predictor of the poor outcome in those patients ( P =0.026). Conclusions In the current era, antibiotics alone provide a high success rate for the treatment of EPN. Invasive therapy is a predictor of development of chronic kidney disease. Initial resuscitation and antibiotic therapy are still the cornerstone and have the benefit of the preservation of renal function.

Most patients with Cushing's disease (CD) respond to corticotrophin-releasing hormone (CRH) or desmopressin with increased corticotrophin (ACTH) and cortisol levels. Although the vasopressin receptor subtype located on normal corticotrophs is the V3 receptor (V3R), desmopressin is a selective V2 receptor (V2R) agonist and it is unclear whether corticotrophinomas exhibit aberrant V2R expression. Furthermore, no studies have determined the relationship between the in vivo response of CD patients to desmopressin and vasopressin receptor expression, or between the response to CRH and CRH receptor (CRHR) expression. Therefore, the aim of this study was to investigate the expression of vasopressin receptors (V1R, V2R, and V3R) and CRHR on corticotroph tumours and its possible relation to the in vivo response.A prospective study of 29 patients with CD.Patients underwent desmopressin and CRH stimulation tests before surgery. The expression of vasopressin receptors and CRHR on corticotrophinomas was determined by immunocytochemistry.Most of the corticotrophinomas exhibited abundant expression of V1R, V3R, and CRHR, whereas the expression of V2R varied greatly and was lower in macroadenomas than in microadenomas. Both the percentage increment of ACTH and net area under the curve (AUC) of ACTH in the desmopressin stimulation test were found to be correlated with tumour volume. After adjustment for tumour volume, a positive correlation was found between the percentage increment of ACTH and the degree of V2R expression, but not between that of V1R or V3R. No relationship between the level of expression of CRHR on tumour tissues and the percentage increment or netAUC of ACTH to CRH was observed in CD patients.We concluded that V2R was expressed on corticotrophinomas and that the level of its expression correlated well with the ACTH response to desmopressin in CD patients, although abundant expression of V1R and V3R was also found in almost all corticotroph tumours. Further studies are needed to elucidate the role of these receptors in the pathogenesis of CD.

Aims We investigated dialysis duration, dose of erythropoietin (EPO), and clinical manifestations in peritoneal dialysis (PD) patients with subclinical hypothyroidism. Methods This cross-sectional study, performed in 3 centers, assessed 122 adult patients on PD for more than 6 months with regard to demographic data, dialysis duration, thyroid function, biochemical data, EPO dose, and clinical manifestations. Thyroid dysfunction was determined by serum thyroid-stimulating hormone, free thyroxine, total thyroxine, total triiodothyronine, antithyroid peroxidase antibodies, and auto-antibodies against thyroglobulin. Results Of the 122 study patients, 98 (80.3%) were assessed as having euthyroidism; 19 (15.6%), subclinical hypothyroidism; and 5 (4.1%), subclinical hyperthyroidism. The proportion of women (74.2% vs. 57.1%, p = 0.038), the mean duration of PD (58.1 months vs. 37.9 months, p = 0.032), and the weighted mean monthly EPO dose (1.22 μg/kg vs. 1.64 μg/kg, p = 0.009) were significantly higher in the subclinical hypothyroidism group than in the euthyroidism group, but the prevalences of coronary artery disease and cerebrovascular disease were not. From the multivariate model, PD duration was more significant than sex as a risk factor for subclinical hypothyroidism ( p = 0.0132). Conclusions Subclinical hypothyroidism is frequent in PD patients, especially female patients and patients with a longer PD duration. Compared with euthyroid patients, patients with subclinical hyperthyroidism need a higher dose of EPO to maintain a stable hemoglobin level.

BackgroundMetformin is a worldwide accepted biguanide antidiabetic agent, and its effectiveness and benefit have already been well established. Among the side effects of metformin, lactate acidosis is the most problematic because of a high mortality rate, which impedes its use in clinical practice, especially in elderly patients with type 2 diabetes. Aging is associated with a decreased renal function and increasing comorbidities, but few data are available regarding plasma lactate levels in this unique population. In this study, we assessed fasting plasma lactate levels in ambulatory, elderly Taiwanese patients with type 2 diabetes, who were taking the drug, metformin, to identify independent risk factors for hyperlactemia in this group.MethodsSixty-six ambulatory type 2 diabetic patients, > 80 years of age (mean, 83.6 years; range, 80-90 years), receiving metformin therapy, were enrolled, from January 2005 to September 2009, in the Diabetes Case Management Program. A further 79 younger patients (also type 2 diabetics on metformin) served as controls (mean age, 59.9 years; range, 37-79 years). Fasting serum electrolytes, creatinine, bicarbonate, glycated hemoglobin, plasma glucose and lactate levels were determined.ResultsLactate levels did not differ between the elderly and control groups (13.2 +/− 5.2 mg/dL and 13.5 +/− 4.8 mg/dL, respectively). None of the patients fulfilled the lactic acidosis criteria. Patients in the elderly group had a significantly lower daily metformin dose, higher creatinine levels, and lower estimated creatinine clearance, compared with the control group (all p < 0.05). Estimated creatinine clearance was negatively associated with lactate levels in the elderly group (p < 0.05, r = −0.27), but not in the control group. Patients with fasting plasma glucose levels > 130 mg/dL had a 2.8-fold increased risk of developing hyperlactemia.ConclusionPlasma lactate levels in ambulatory elderly patients with type 2 diabetes receiving metformin therapy did not differ from those in a younger age group. Patients with fasting plasma glucose levels > 130 mg/dL had a 2.8-fold risk of developing hyperlactemia, but none of them developed lactate acidosis.

Context Acromegaly is associated with a significant increase in mortality. With the development of new modalities of treatment, it has become important to identify prognostic factors relating to mortality. Objective This study aimed to determine the all-cause mortality of patients with acromegaly after trans-sphenoidal surgery, and assess the impact of biochemical markers on survival. Design Two hundred thirty-four patients were admitted to the Taipei Veterans General Hospital for acromegaly between 1979 and 2007. Of the 163 patients who underwent trans-sphenoidal surgery, 142 had data available for insulin-like growth factor-1 (IGF-1), and their survival status was analyzed. Serial data for fasting growth hormone (GH) and IGF-1 were collected. This study also used the last follow-up data for mortality analysis. The patients with acromegaly were grouped according to the last follow-up GH level (≤ 2 or > 2 μg/L) and IGF-1 SD score (≤ 2 or > 2). All-cause mortality was followed to the end of 2007 and compared to the general Taiwanese population by standardized mortality ratios. Results Serial GH and IGF-1 data revealed that the GH levels in the first 3 years after surgery were important predictors of mortality in acromegaly. However, there are insufficient IGF-1 data for deceased patients to determine the significance of a raised IGF-1 immediately following treatment. Comparison of crude death rates suggests that a fasting GH level of 2 μg/L and normalization of the IGF-1 level are appropriate targets. After subgroup analysis to assess the impact of discordant GH and IGF-1 levels on survival, the data showed that the elevated GH group had a trend toward a higher mortality than the elevated IGF-1 group. Conclusions An elevated GH value in the first 3 years after surgery may be the best predictor of mortality. Thus, the follow-up of patients with acromegaly at relatively frequent intervals after trans-sphenoidal surgery should be routine.

Background: Diabetic foot care has yet to be enhanced in a universal health-care system in which specialized podiatric medical services are unavailable. This baseline assessment surveyed diabetic patients attending group education to improve current foot-care practices. Methods: Of 302 diabetic patients receiving usual outpatient care, 155 received group patient education on general diabetes-related information, which included foot care and an annual checkup by a diabetes association during the previous 2 years, and 147 did not. Patient foot-care behaviors, physician practice patterns, and patient self-perceived foot risk as cross-checked with the neurologic and vascular assessments were investigated by conducting retrospective medical record reviews and structured interviews. Results: More than half of the patients in both groups reported inappropriate self-care behaviors (eg, walking barefoot and heating or soaking their feet). The percentages of patients receiving documented examinations and referrals for foot problems were low in both groups and were not significantly different. Among at-risk patients, 56% of the diabetes association group but only 30% of the non–diabetes association group perceived themselves to be at risk for future foot problems (P < .01). Conclusions: Many diabetic patients were not offered adequate foot-specific information during group lectures, even those with high-risk foot problems. To improve this, combining caregiver and patient education in foot-care practices is important, and systems of networked multidisciplinary professionals are believed to be needed, particularly in delivering customized interventions to at-risk patients based on the initial evaluation. (J Am Podiatr Med Assoc 99(4): 295–300, 2009)