Microvascular reactivity using laser Doppler measurement in type 2 diabetes with subclinical atherosclerosis.

Microangiopathy should be noted in diabetes with subclinical vascular diseases. Little is known about whether various surrogate markers of systemic arterial trees exacerbate simultaneously in preclinical atherosclerosis. To clarify the association of skin microvascular reactivity with arterial stiffness is essential to elucidating early atherosclerotic changes. The post-occlusive reactive hyperemia of skin microcirculation was evaluated in 27 control and 65 type 2 diabetic subjects, including 31 microalbuminuria (MAU) and 34 normoalbuminuria (NAU) patients. The laser Doppler skin perfusion signals were transformed into three frequency intervals for the investigation of endothelial, neurogenic, and myogenic effects on basal and reactive flow motion changes. The analysis of spectral intensity and distribution provided insight into potential significance of microvascular regulation in subclinical atherosclerotic diseases. Systemic arterial stiffness was studied by the brachial ankle pulse wave velocity (baPWV). Following occlusive ischemia, the percent change of endothelial flow motion was lower in MAU than in NAU and control groups. The MAU group revealed a relative increase in myogenic activity and a decrease in endothelial activity in normalized spectra. The baPWV showed more significant associations with reactive endothelial change (r = - 0.48, P < 0.01) and normalized myogenic value (r = - 0.37, P < 0.05) than diabetes duration and HbA1c. By multivariate regression analysis, only endothelial vasomotor changes independently contributed to the decreased baPWV (OR 3.47, 95% CI 1.63-7.42, P < 0.05). Impaired microcirculatory control is associated with increased arterial stiffness in preclinical atherosclerosis. To identify the early manifestations is necessary for at-risk patients to prevent from further vascular damage.

Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer.

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.

Iodine status of adults in Taiwan 2005-2008, 5 years after the cessation of mandatory salt iodization.

BACKGROUND/PURPOSE: Iodine 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. METHODS: Urinary iodine (UI) was measured in samples from adults in the Nutrition and Health Survey in Taiwan 2005-2008. RESULTS: The 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. CONCLUSION: The 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.

[Pharmacokinetics of deflazacort tablets in healthy Chinese volunteers].

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.

Molecular dynamics simulation of cation-phospholipid clustering in phospholipid bilayers: possible role in stalk formation during membrane fusion.

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.

Plasma corticotrophin response to desmopressin in patients with Cushing's disease correlates with the expression of vasopressin receptor 2, but not with that of vasopressin receptor 1 or 3, in their pituitary tumours.

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.

Impaired microvascular flow motion in subclinical diabetic feet with sudomotor dysfunction.

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<0.05). Although no statistical difference was noted between any group in absolute myogenic spectrum, the SSR- group had higher normalized myogenic activity than the SSR+ group (p<0.01). The larger drop in orthostatic pressure was paralleled by a reduction in the myogenic amplitude (r=-0.33, p<0.01). These results suggested that early impairment of low-frequency flow motion correlated closely with the presence of sudomotor dysfunction of subclinical feet mainly in neurogenic and endothelial components. Impaired systemic vascular tone as manifested by orthostatic hypotension was proportional to the degree of myogenic dysregulation in diabetic patients.

Unusual manifestations of adrenal insufficiency: A case report of hypopituitarism and Well's syndrome after apoplexy of a silent pituitary gonadotropic adenoma.

RATIONALE: Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease. PATIENT CONCERNS: A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache. DIAGNOSES: Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy. INTERVENTIONS: Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly. OUTCOMES: His symptoms and laboratory data recovered after the operation and medical treatment. LESSONS: This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.

Hemoglobin A(1c) and fructosamine for assessing glycemic control in diabetic patients with CKD stages 3 and 4.

BACKGROUND: Hemoglobin A(1c) (HbA(1c)) 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: HbA(1c) 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 HbA(1c) 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 HbA(1c) 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 HbA(1c) 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.

Improving preventive foot care for diabetic patients participating in group education.

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.

Successful treatment of severe lactic acidosis caused by a suicide attempt with a metformin overdose.

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.

Pyogenic liver abscess associated with septic pulmonary embolism.

BACKGROUND: Septic pulmonary embolism (SPE) is one of the metastatic foci of pyogenic liver abscess. The purpose of this study was to investigate the clinical presentations of, and management options for patients with pyogenic liver abscess complicated with SPE. METHODS: A retrospective chart review was conducted from January 1, 1999 to December 31, 2005 inclusively, in a medical center in northern Taiwan. We collected and analyzed the clinical presentations, diagnostic modalities, treatment programs and prognoses for all pyogenic liver abscess patients with SPE. RESULTS: The association between liver abscess affected with the complication of SPE and diabetes mellitus was significant. There were 9 patients who had pyogenic liver abscess with SPE. Abnormal chest radiograph (CXR) findings with multiple ill-defined peripheral round densities were noted in all patients. Seven patients were diabetic, fever occurred in 5 patients, respiratory symptoms were noted in 6 patients, and abdominal pain occurred in 3 patients. Endophthalmitis coexisted in 3 patients, meningitis in 1 patient, and necrotizing fasciitis in 2 patients. Microbiological studies revealed Klebsiella pneumoniae in 9 patients. Computed tomography (CT) demonstrated metastatic nodules in both lung lobes, some of which featured cavitation, in all 9 patients. Three patients soon advanced to acute respiratory failure, and later died due to acute respiratory distress syndrome and/or septic shock. The remaining 6 patients survived without complication during their hospital course. CONCLUSION: There is diagnostic value in performing a chest CT scan in diabetic patients who have liver abscess plus abnormal CXR findings with multiple ill-defined peripheral round densities, in order to detect SPE, which has a relatively poor outcome in patients with liver abscess.

Hyperglycemia correlates with outcomes in patients receiving total parenteral nutrition.

BACKGROUND: Hyperglycemia is associated with higher mortality rates after myocardial infarction, stroke, and in critically ill patients. This study was made to determine the associations between hyperglycemia and adverse outcomes in patients receiving total parenteral nutrition (TPN). METHODS: A retrospective cohort study included total 457 patients (age, 66.4 +/- 16.3 years) receiving TPN in 2004. The patients were divided by mean glucose level into quartiles: quartile 1 (<114 mg/dL, Q1), quartile 2 (114 to 137 mg/dL, Q2), quartile 3 (137 to 180 mg/dL, Q3), and quartile 4 (>180 mg/dL, Q4). A logistic regression analysis was performed to determine whether the degree of hyperglycemia was associated with the adverse outcomes. RESULTS: The odds ratio of death was significantly increased in quartile 2 (OR, 2.1 [95% CI: 1.1 to 4.0]) (P = 0.02), quartile 3 (OR, 2.3 [95% CI: 1.2 to 4.5]) (P = 0.01), and quartile 4 (OR, 5.0 [95% CI: 2.4 to 10.6]) (P < 0.01) as compared with quartile 1. Each 10-mg/dL increase in mean blood glucose level was associated with an increased risk factor of infection (OR, 1.09 [95% CI: 1.05 to 1.13]) (P < 0.01), cardiac complications (OR, 1.10 [95% CI: 1.03 to 1.17]) (P < 0.01), acute renal failure (OR, 1.07 [95% CI: 1.03 to 1.11]) (P < 0.01), and respiratory failure (OR, 1.08 [95% CI: 1.02 to 1.14]) (P < 0.01). The risk of adverse outcomes increased with hyperglycemia, independent of age, sex, body weight, prior diagnosis of diabetes, ICU stay, insulin therapy, blood sugar readings before TPN treatment, and frequency of blood sugar measurements. CONCLUSIONS: Hyperglycemia in patients receiving TPN correlates with morbidities and mortality. A prospective, randomized, controlled study instituting aggressive hyperglycemic control is required to determine whether the control of blood glucose can improve outcomes in patients receiving TPN.

Pheochromocytoma and adrenocortical adenoma in the same gland.

A right adrenal tumor was found incidentally during abdominal computed tomography exam in a 51-year-old female patient, who had had diabetes and hypertension for more than 10 years. The computed tomography scan was arranged for possible pancreatic lesion by a neurologist. Norepinephrine level was high in the plasma and urine. Vanillylmandelic acid level was elevated in the urine. Diurnal cortisol rhythm, plasma adrenocorticotropic hormone and urine free cortisol were all normal,but the plasma cortisol concentration could not be suppressed after a standard low-dose dexamethasone suppression test. Therefore, adrenal cortical adenoma with subclinical Cushing's syndrome was highly suspected; however, further imaging studies, including magnetic resonance image and 131I-6beta-iodomethylnorcholesterol adrenal scintigraphy failed to discriminate an additional tumor. After right adrenalectomy, a small adrenal cortical adenoma and a large pheochromocytoma were noted. This is an extremely rare case of an adrenal incidentaloma consisting of both medullary and cortical tumors in the same gland.

Pituitary apoplexy after thyrotropin-releasing hormone stimulation test in a patient with pituitary macroadenoma.

Pituitary apoplexy is a rare complication of pituitary tumors. We report a case of a 41-year-old female with acromegaly due to a pituitary macroadenoma, who developed pituitary apoplexy after a thyrotropin-releasing hormone (TRH) 200 microgram intravenous injection stimulation test. Neither emergency computed tomography (CT) scans nor magnetic resonance imaging (MRI), performed 6 hours and 12 hours, respectively, after the active episode, disclosed the evidence of acute hemorrhage or infarction. Two days later, the pituitary mass, removed by transsphenoidal approach, showed ischemic necrosis and acute hemorrhage. The TRH test is generally safe for evaluating pituitary function, but pituitary apoplexy may occur after the procedure. CT and MRI may miss the diagnosis of pituitary apoplexy, especially if performed immediately after the acute episode.

Assessment of bilateral inferior petrosal sinus sampling (BIPSS) in the diagnosis of Cushing's disease.

BACKGROUND: The differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS) remains a challenging issue for clinical endocrinologists. In this respect, bilateral inferior petrosal sinus sampling (BIPSS) appears to be the most sensitive and specific test. Here, we report our 15-year experience of analyzing the performance of BIPSS, both in the correct diagnosis and in the precise lateralization of tumors in patients with Cushing's disease (CD). METHODS: Between 1992 and 2006, 18 patients with CD (16 females, 2 males; age range, 14-56 years) were admitted to Taipei Veterans General Hospital and subjected to BIPSS plus ovine corticotropin-releasing hormone (oCRH) stimulation. Four of them had previously undergone transsphenoidal hypophysectomy (TSH) and had a recurrence thereafter. BIPSS was performed by inserting a catheter in the right and left inferior petrosal sinus for ACTH assay via a femoral vein puncture. An inferior petrosal sinus/peripheral ACTH ratio (C/P ratio) > or = 2 at baseline > or = 3 after oCRH injection indicated a pituitary origin of ACTH secretion, and an interpetrosal ACTH gradient (IPS ratio) > or = 1.4 at baseline or after oCRH indicated evidence of lateralization. RESULTS: Positive BIPSS results were found in 16 patients at baseline and in 17 patients after oCRH injection. In 17 out of 18 patients, TSH was subsequently carried out and a pituitary source was confirmed on histopathologic examination. The only 1 false-negative test result was noted in a patient who had undergone previous TSH. Thus, the sensitivities of BIPSS for the diagnosis of CD before and after oCRH stimulation were 89% and 94%, respectively. Moreover, using an IPS ratio > or = 1.4 as a criterion, BIPSS correctly lateralized the tumor in 9 of 17 and 10 of 17 patients at baseline and after oCRH stimulation, respectively, including in 2 patients who had a centrally located tumor and who had an IPS ratio < 1.4. Thus, the sensitivities of lateralization of BIPSS were 53% and 59%, respectively. None of the 4 patients who had previous TSH were precisely localized by BIPSS. If these 4 patients were excluded, the sensitivities of BIPSS for localizing in the patients who had not undergone previous operation increased to 70% (9/13) at baseline and 77% (10/13) after oCRH stimulation, respectively. CONCLUSION: BIPSS combined with oCRH stimulation is a safe and reliable examination both in the differential diagnosis of CD and in the correct lateralization of pituitary microadenoma in patients without previous pituitary surgery. Nevertheless, this procedure may provide misleading results in patients who have received previous pituitary surgery.

Insulin deficiency downregulated heat shock protein 60 and IGF-1 receptor signaling in diabetic myocardium.

Heat shock protein (Hsp)60 and IGF-1 receptor signaling protect cardiac muscle against injury. The abundance of cardiac IGF-1 receptor can be upregulated by Hsp60, but how diabetes modulates cardiac muscle Hsp60 has not yet been defined. We investigated the changes of Hsp60 and IGF-1 receptor signaling in the diabetic myocardium and studied how diabetes modulates Hsp60 and IGF-1 receptor in diabetic myocardium. In the streptozotocin (STZ)-induced diabetic rat, downregulation of Hsp60 and IGF-1 receptor occurred 4 days after induction of diabetes. IGF-1 activation of IGF-1 receptor, Mek, and Akt were reduced accordingly in the diabetic myocardium. The independent effect of insulin and hyperglycemia on Hsp60 was investigated in primary cardiomyocytes. Incubating cardiomyocytes with insulin was associated with dose-dependent increase of Hsp60 protein. In contrast, the abundance of Hsp60 was not affected by high concentration of glucose in these cells. To further determine the independent effects of hyperglycemia and insulin deficiency on the changes of myocardial Hsp60 and IGF-1 receptor, we used phlorizin to normalize blood glucose in diabetic rats. In the phlorizin-treated diabetic rats, myocardial Hsp60 was lower than that of the normal controls. In contrast, insulin treatment normalized myocardial Hsp60 in the diabetic rats. Because phlorizin does not alter insulin secretion, Hsp60 expression was modulated by insulin and not by hyperglycemia. Similar changes of Hsp60 and IGF-1 receptor were observed in the skeletal muscle of STZ-induced diabetic rats. These findings suggest that insulin deficiency is a novel mechanism that leads to downregulation of Hsp60 in diabetic muscle tissues. The development of diabetic cardiomyopathy might have involved downregulation of Hsp60 and subsequent reduction of IGF-1 receptor signaling.

Downregulation of the constitutively expressed Hsc70 in diabetic myocardium is mediated by insulin deficiency.

The 70 kDa heat shock protein family plays important cardiac protective roles against myocardial injuries. Reduced myocardial protection is a common feature of diabetic myocardium. This study was carried out to define the changes in the 70 kDa heat shock protein family in the myocardium in the of streptozotocin-diabetes rats, and to explore the mechanisms through which diabetes alters the abundance of Hsp70/Hsc70 in cardiac muscle. In the diabetic myocardium, the abundance of Hsc70 was significantly reduced. The abundance of Hsp70 was low in cardiac muscle and was not induced in the diabetic myocardium. Unlike Hsp60, Hsp70 and Hsc70 did not augment insulin-like growth factor-I receptor signaling in cardiac muscle cells. In cultured cardiomyocytes, insulin directly increased the abundance of Hsc70, whereas insulin could not modulate Hsp70. Treating diabetic rats with insulin restored myocardial Hsc70 level, but phlorizin treatment failed to restore myocardial Hsc70. These in vivo and in vitro studies showed that downregulation of Hsc70 in diabetic myocardium was secondary to insulin deficiency. Thus, insulin played a major role in maintaining adequate expression of Hsc70 in cardiac muscle.

Well-differentiated epithelial thyroid cancer management in the Asia Pacific region: a report and clinical practice guideline.

CONTEXT: 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. OBJECTIVE: An expert consensus conference was held to define regional patterns of practice and guidelines for optimal management of well-differentiated epithelial thyroid carcinomas. RESULTS: 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. CONCLUSIONS: 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.

Relationship of skin temperature to sympathetic dysfunction in diabetic at-risk feet.

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<0.05) and smaller normalized temperature (referencing to the forehead temperature) (0.19 versus 0.24, p<0.01) than the SSR+ group. Although the three diabetic groups had no significant differences in clinical and cardiovascular abnormalities, the at-risk group showed more nerve conduction abnormalities than the SSR- and SSR+ groups (55% versus 23% and 14%, p<0.02). This study indicated that the thermoregulatory sweating abnormality signified early sympathetic damage in diabetic feet. Assessing skin conditions and sudomotor activities should help identify small fiber neuropathy in diabetic patients with at-risk feet conditions.