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To evaluate the causes of acute cholangitis without biliary dilatation and to compare the clinical characteristics and the imaging findings between patients with acute cholangitis with and without biliary dilatation.93 patients diagnosed with acute cholangitis underwent contrast-enhanced CT. Among them, 17 patients were classified as not having biliary dilatation (Group 1) and 76 patients were classified as having biliary dilatation (Group 2). The causes of acute cholangitis were evaluated in both groups. Clinical characteristics and imaging findings were compared between the two groups.The causes of acute cholangitis without biliary dilatation included common bile duct (CBD) stones (n=11), CBD sludge (n=3), a passed stone (n=1) and unknown causes (n=2). The total bilirubin levels of Group 1 were significantly lower than those of Group 2 (p=0.001). By contrast, Group 1 had higher median alanine aminotransferase (ALT) levels than Group 2 (p=0.04). The length of hospital stay was significantly longer in Group 2 than in Group 1 patients (p0.001). In the imaging findings, the extent of transient hepatic attenuation differences (THADs) (p=0.003) were significantly smaller in Group 1 than in Group 2.CBD stones and sludge were the most common causes of acute cholangitis in patients without biliary dilatation. These patients showed lower levels of bilirubin and higher levels of ALT than those with acute cholangitis with biliary dilatation, and had a shorter duration of hospital stay. The extent of THADs was the only discriminative CT finding between the two groups.Acute cholangitis can present without biliary dilatation on imaging, and the most common causes are CBD stones and sludge. The patients with acute cholangitis without biliary dilatation have different clinical characteristics and imaging findings compared with those with acute cholangitis presenting with biliary dilatation.

Background/Objectives: The purpose of this study was to examine the long-term effect of Tai Chi exercise on exercise self-efficacy and self-perceived health status in the elderly. Methods/Statistical Analysis: Sixty older adults were participated in this study. Their ages ranged from 70 to 75, with a mean age of 72.4 years. The participants were randomly assigned to one of two experimental conditions: (1) Tai Chi exercises group (n=30), (2) control group (n=30). Data was analyzed using two-way Analysis Of Variances (ANOVAs) with repeated measures of groups (Tai Chi exercise group and control group) and time (pre-test and post-test). Dependent variables were exercise self-efficacy and self-perceived health status. Findings: The result of this study indicated Tai Chi exercise group had a significantly higher score than control group in exercise self-efficacy and perceived health status. Applications/Improvement: It was found that Tai Chi exercise helped to improve the exercise self-efficacy and the perceived health status in the elderly.

Perforation usually requires emergency surgery and may affect the prognosis of patients with gastrointestinal tumours. Accurate pre-operative diagnosis of these conditions is important because proper management such as curative surgical treatment may be needed. The aims of this article are to illustrate CT appearances of perforated tumours of the gastrointestinal tract and to discuss their impact on clinical management.

Deferoxamine (DFO), an FDA-approved iron chelator used for treatment of iron poisoning, affects bacteria as iron availability is intimately connected with growth and several virulence determinants. However, little is known about the effect on oral pathogens. In this study, the effect of DFO on Porphyromonas gingivalis, a major periodontopathogen which has an essential growth requirement for hemin (Fe(3+)-protoporphyrin IX), was evaluated. The viability of P. gingivalis W83 was not affected by 0.06-0.24 mM DFO, whereas the doubling time of the bacterium was considerably prolonged by DFO. The inhibitory effect was evident at earlier stages of growth and reduced by supplemental iron. UV-visible spectra using the pigments from P. gingivalis cells grown on blood agar showed that DFO inhibited μ-oxo bisheme formation by the bacterium. DFO decreased accumulation and energy-driven uptake of hemin by P. gingivalis. Antibacterial effect of H(2)O(2) and metronidazole against P. gingivalis increased in the presence of DFO. Collectively, DFO is effective for hemin deprivation in P. gingivalis suppressing the growth and increasing the susceptibility of the bacterium to other antimicrobial agents such as H(2)O(2) and metronidazole. Further experiments are necessary to show that DFO may be used as a therapeutic agent for periodontal disease.

Klebsiella pneumoniae is one of the organisms most commonly isolated from pyogenic liver abscesses in Asian populations. We compared CT findings in liver abscesses caused by K. pneumoniae with those caused by other bacterial pathogens.Of 214 patients with liver abscesses examined over a 5 year period, 129 patients with positive blood or aspirate cultures were enrolled. The patients were divided into two groups: the K. pneumoniae monomicrobial liver abscess (KLA) group (n = 59) and the non-K. pneumoniae monomicrobial or polymicrobial liver abscess (non-KLA) group (n = 70). Two radiologists blinded to the culture results evaluated the CT images, recording the number, size, location and configuration of abscesses, the thickness of the abscess wall, the pattern of rim enhancement, septal enhancement, the double target sign, internal necrotic debris, internal gas bubbles and underlying biliary disease. The presence of diabetes and metastatic infection was also compared between groups. Statistical analyses were performed using univariate (Student's t-test and χ(2) test) and multivariate analyses.Multivariate analysis showed that a thin wall, necrotic debris, metastatic infection and the absence of underlying biliary disease were the most significant predictors of KLA. When three of the four criteria were used in combination, a specificity of 98.6% was achieved for the diagnosis of KLA.A thin-walled abscess, internal necrotic debris, the presence of metastatic infection and the absence of underlying biliary disease may be useful CT findings in the early diagnosis of K. pneumoniae liver abscesses.

Background Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans. Methods To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy. Results In the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%. Conclusion We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

We analyzed the medical records of 884 type 2 DM patients who were taking different antiplatelet agents for more than 2 years. Based on the records, occurrences of cardiovascular events for 10 years were evaluated. The composite disease-free survival rate for cilostazol monotherapy group was similar to aspirin subgroup (p = 0.133).

Both IFG and IGT are prediabetic conditions that can progress to type 2 DM. However, previous studies have shown that these are not identical. This study was conducted on 307 drug naive prediabetic adults who did not meet the diagnostic criteria for diabetes based on the OGTT. According to the OGTT, the subjects were divided into isolated IFG (i-IFG), isolated IGT (i-IGT), and combined glucose intolerance (CGI) group. We also measured insulin resistance indices (HOMA-IR, WBISI), an insulin secretion indices (insulinogenic index [IGI], AUC I/G 0–120 , disposition index [DI]), and compared each of the three groups. The OGTT measurements showed that 87 subjects were diagnosed with i-IFG, 75 subjects had i-IGT, and 145 subjects had CGI. With respect to the insulin resistance indices, HOMA-IR and WBISI were not significantly different. However, insulin secretory capacity, the IGI and DI were significantly higher for the i-IFG group. Moreover, after confounders were adjusted, HOMA-IR, IGI, AUC I/G 0–120 , and the DI were significantly higher for the i-IFG group and WBISI was significantly higher for the i-IGT group. These results demonstrate that the pathogenesis of IFG is more closely associated with insulin resistance, and the pathogenesis of IGT is more closely associated with impaired insulin secretion.

BACKGROUND/AIMS Based on the results of well designed clinical studies, intensive insulin therapy has been established to improve glycemic control in newly diagnosed diabetes. However, discrepancies exist between the findings of clinical trials and experiences in general practice. Furthermore, the efficacy of an early insulin therapy (EIT) - commonly used in general practice - on long-term glycemic control has not been established. Therefore, we evaluated the effects of EIT on pancreatic β-cell function and glycemic control using insulin-based methods widely employed in general practice. METHODS We performed a retrospective cohort study that initially involved reviewing patients' medical records. Following a thorough review, 61 patients who received either biphasic or prandial EIT at the time of diagnosis were enrolled. We then evaluated changes in β-cell function and glycemic control during a 48-month follow-up period. RESULTS Mean HbA1c decreased significantly as a result of EIT from 10.7 ± 1.8% to 6.2 ± 1.1% (p < 0.001). On average, 2.6 months was required to achieve an HbA1c value < 7%. EIT significantly improved the insulinogenic index. Glycemic control was well maintained for 48 months. More than 70% of patients were able to maintain glycemic control following lifestyle modifications or treatment with oral antidiabetic drugs. No significant differences were identified between patients receiving biphasic EIT and prandial EIT in terms of glycemic control or pancreatic β-cell function. CONCLUSIONS Our results suggest that regardless of the method of delivery, EIT significantly improves β-cell function and facilitates long-term glycemic control in patients with newly diagnosed type 2 diabetes mellitus.

During the progression of Type 2 diabetes, glucose toxicity is likely to contribute importantly to progressive beta cell failure. Oxidative stress is an important aspect of glucose toxicity in pancreatic beta cells, and reducing sugars, such as 2-deoxy-D-ribose (dRib), produce reactive oxygen species. Furthermore, many of the biological properties of flavonoids are likely to be related to their antioxidant and free-radical scavenging abilities. Accordingly, in the present study, we investigated whether kaempferol (a flavonol) protects beta cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24h. Cell survivals, amounts of reactive oxygen species (ROS) generated, apoptosis, and lipid peroxidation were measured. dRib was found to dose-dependently reduce cell survival and to markedly increase intracellular ROS levels, apoptosis, and lipid peroxidation. However, kaempferol (10 microM) suppressed dRib (20 mM) induced intracellular ROS, apoptosis, and lipid peroxidation. So, we demonstrate that kaempferol reduces dRib-mediated beta cell damage interfering with ROS metabolism and protective effects against lipid peroxidation. Our findings indicate that kaempferol protects HIT-T15 cells from dRib-induced associated oxidative damage.

Epigallocatechin-3-gallate (EGCG) is the main polyphenolic constituent in green tea and is believed to function as an antioxidant. However, increasing evidence indicates that EGCG produces reactive oxygen species (ROS) and subsequent cell death. In this study, we investigated the prooxidative effects of EGCG on the HIT-T15 pancreatic beta cell line. Dose-dependent cell viability was monitored with the cell counting kit-8 assay, while the induction of apoptosis was analyzed by a cell death ELISA kit and comet assay. Extracellular H(2)O(2) was determined using the Amplex Red Hydrogen Peroxide Assay Kit. Intracellular oxidative stress was measured by fluorometric analysis of 2',7'-dichlorofluorescin (DCFH) oxidation using DCFH diacetate (DA) as the probe. Treatment with EGCG (5-100 microM) decreased the viability of pancreatic beta cells, caused concomitant increases in apoptotic cell death, and increased the production of H(2)O(2) and ROS. Catalase, the iron-chelating agent diethylenetriaminepentaacetic acid, and the Fe(II)-specific chelator o-phenanthroline all suppressed the effects of EGCG, indicating the involvement of both H(2)O(2) and Fe(II) in the mechanism of action of EGCG. The antioxidant N-acetyl-cysteine and alpha-lipoic acid also suppressed the effects of EGCG. Furthermore, EGCG did not scavenge exogenous H(2)O(2), but rather, it synergistically increased H(2)O(2)-induced oxidative cell damage in pancreatic beta cells. Together, these findings suggest that in the HIT-T15 pancreatic beta cell line, EGCG mediated the generation of H(2)O(2), triggering Fe(II)-dependent formation of a highly toxic radical that in turn induced oxidative cell damage.

Summary Objectives Osteoporosis is a disease that increases the fracture rates and it is the major cause of increased mortality and morbidity in the elderly people. To determine which component of body composition is most important to bone health, we analysed the relationship between elements of the body composition and bone mineral density (BMD) in Korean women. Design Cross-sectional clinical study. Patients Totally 1694 women (mean age 51 years) were selected from subjects who participated in a medical check-up program. Measurements Body composition analysis was performed by segmental bioelectric impedance method and lean mass, fat mass and per cent body fat measured. Waist : hip ratio (WHR) was assessed as a marker for visceral fat. Lumbar spine (l-spine) BMD was measured by dual X-ray absorptiometry (DEXA). As menopausal status could not be confirmed in all subjects, we divided the subjects into two groups according to the age > 50 years and

The purpose of this study was to examine the emotions experienced by spectators when their favorite team wins or loses a soccer match using fMRI. Those who watched winning scenes showed activation of the right and left occipital lobes, left temporal lobe, left limbic lobe, middle occipital gyrus, superior temporal gyrus, cuneus, and uncus. Those who watched losing scenes showed activation of the right frontal lobe and right limbic lobe. This result suggests that emotional suppression is much stronger in negative emotional responses than in positive responses.

The objective of the present study was to determine differences in neural networks between expert and novice archers during an archery pre-performance routine period (PPR). The experiment was conducted with eight world-class competitor or Olympic medalist archers and eight novices. In the experiment, the task was to shoot (by clicking a mouse with the right hand) if an archery target appeared on an LCD embedded in an functional magnetic resonance imaging (fMRI) scanner. The resultant fMRI data showed that when the experts were aiming, the occipital gyrus and temporal gyrus were activated, but when the novices were aiming, the frontal area was mainly activated. In addition, the anterior cingulate and posterior cingulate gyrus of the limbic lobe were also activated in the expert and novice groups, respectively. Our results demonstrated that expert and novice archers differed in levels of brain activation during the PPR period of a simulated archery task.

The aims of this study were to clarify changes in total ghrelin within the somatotropic axis in severe burn subjects with or without inhalation injury as well as the responsiveness of GH, IGF-1, and IGFBP-3 to the different severity of burn injuries.Twenty-three patients with severe burn injuries (30% of 2nd degree burns or10% of 3rd degree burns) were classified into 2 groups according to inhalation injury: group I with inhalation injury (n=9) and group II without inhalation injury (n=14). The evaluations of serum GH, IGF-1, IGFBP-3, and total ghrelin were done on post-burn injury days 3, 7, 14, 21, and 40. Cortisol levels were measured from 24-h urine collections on post-burn injury days 7 and 21.In all subjects, the levels of GH fluctuated throughout the observation period whereas IGF-1 showed an initial decline with nadir on day 7 and a subsequent increase through day 40. The levels of IGFBP-3 and total ghrelin showed a progressive increase with nadir on day 3. Compared with the group II, the GH levels were increased in the group I on post-burn days 3, 7, and 14, of which day 7 showed statistical significance (p0.05). The levels of IGF-1 (days 7 and 21; p0.05) and IGFBP-3 (days 7, 14, 21, and 40; p0.05, p0.01, p0.05, p0.05, respectively) were lower in the group I than in the group II throughout the study period. On post-burn injury days 3, 7, 14, and 21, total ghrelin levels were lower in the group I than in the group II with statistical significance on post-burn day 7 (p0.001).Our present data show a concurrence of elevated GH levels and decreased IGF-I, IGFBP-3, and total ghrelin levels during the early burn injury period, in addition to more GH burst amplitude as well as greater falling of IGF-I, IGFBP-3 and total ghrelin levels proportional to the severity of burn injury. Further studies are needed to ascertain whether acyl- and desacyl-ghrelin instead of total ghrelin are completely independent of increased GH or other stress mediators, and whether GH-releasing hormone (GHRH) mainly stimulates the production and release of GH in acute critical conditions.

In this paper, fundamental driving method and selective driving each cells of charged particle type display are described. To fabricate panel, mask patterns with cell area of are designed. Gain of driving voltage due to increase of cell gap is observed on the basis of fundamental driving method. To selectively drive each cells of charged particle type display that is driven by passive matrix method, selective driving of charged particle type display is achieved after establishing interrelation of voltage of select cell and unselect. And than crosstalk of the driven panel is observed. It can be found that the last image is maintained without additional voltage by memory effect.

This study was conducted to present the development direction of the contents of rehabilitation exercise program for person with disabilities using motion recognition technology. Through the literature review, we selected for those who needed rehabilitation service focusing on exercise. They have difficulties in an exercise for the upper extremity, learning and mobility within a community due to physical and mental disability, brain injury and autism. To set a goal for rehabilitation exercise program, we analyzed preceding literature related to the needs of the disabled persons and 17 evaluation tools for daily living skills in occupational therapy. Accordingly, the goal was set for improving activities of daily living and the goal activities specifically focused on dressing/taking off clothes, eating and personal hygiene. Then, the functional motion elements consisting of each activity and their levels were defined and analyzed. In the rehabilitation program, the motion elements of the goal activity that could be measured by motion recognition sensor were presented. The motion elements of the goal activity involved muscle strength and range of motion that could be measured, so that the development direction of rehabilitation exercise program contents was specifically presented for improving daily living skills. The study presented the possibility that virtual reality program contents developed for rehabilitation for the disabled could attribute to not only simple physical and/or cognitive improvement but also to the actual daily living skills.

OBJECTIVE: Acute hyperglycemia stimulates somatostatin (SRIH) release by the hypothalamus which, in turn, suppresses growth hormone (GH) secretion from the anterior pituitary gland. Although it has been suggested that the cholinergic pathway mediates glucose-induced SRIH release, other regulatory systems have not been examined. Therefore, we investigated whether blocking or activating the beta-adrenergic pathway alters glucose-mediated inhibition of GH release. DESIGN AND METHODS: One set of experiments was performed with a beta-adrenergic antagonist, propranolol, and the other set with a beta-adrenergic agonist, isoproterenol. Each set of experiments was performed in ten healthy subjects and consisted of four tests. Test 1, a 100 microg GHRH bolus i.v. at 0 min; test 2, 100 g glucose orally at -30 min, followed by a 100 microg GHRH bolus at 0 min; test 3, after a 100 microg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 microg/kg) was administered between 0 and 120 min; test 4, after a 100 g glucose oral load at -30 min, and a 100 microg GHRH bolus i.v. at 0 min, a continuous infusion of propranolol (0.2 mg/kg) or isoproterenol (0.012 microg/kg) was administered between 0 and 120 min. Blood was drawn every 10 min from -30 min to 120 min to measure GH and glucose concentrations. RESULTS: Pretreatment with glucose significantly suppressed GHRH-induced GH secretion. Propranolol infusion significantly increased the GHRH-induced GH secretion, but it did not block glucose-induced suppression of GH secretion. Isoproterenol infusion alone significantly suppressed GHRH-induced GH secretion and augmented the inhibitory action of glucose on GH release. CONCLUSION: This study demonstrates that glucose-induced suppression of GHRH-stimulated GH release is independent of beta-adrenergic tone. Since previous data supports a role for SRIH in both glucose and beta-adrenergic suppression of GH release, the current results suggest that subsets of SRIH neurons are differentially responsive to these external cues. Therefore, a combined glucose and isoproterenol test may provide a useful assessment of hypothalamic somatostatinergic activity.

Endothelial cell apoptosis has been postulated as the initial trigger of the progression of microvascular disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [3H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial cell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5 mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.

A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH), prolactin (PRL), and thyroid stimulating hormone (TSH). Staining for pituitary-specific transcription factor-1 (Pit-1) was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.

Objectives This study examined the effect of cilostazol, a potent phosphodiesterase inhibitor, on the progression of neuropathies associated with streptozotocininduced diabetes mellitus in Sprague-Dawley rats. Methods Eight weeks after streptozotocin treatment, a pelleted diet containing 0.03% cilostazol (15mg/kg body weight) was given for four weeks. Body weight, blood glucose level, motor nerve conduction velocity(MNCV), myelinated fiber density and size distribution of sciatic nerves were compared between age-matched normal rats (Group 1), control diabetic rats (Group 2) and cilostazol-treated diabetic rats (Group 3). Results Body weight was significantly reduced and blood glucose level was significantly increased in diabetic rats (Group 2 and 3) compared to normal rats. MNCV and cAMP content of sciatic nerves were significantly reduced in diabetic rats 12 weeks after streptozotocin treatment. Myelinated fiber size and density were also significantly reduced, and thickening of the capillary walls and duplication of the basement membranes of the endoneural vessels were observed in the diabetic rats. Whereas both body weight and blood glucose level of Group 3 did not differ significantly from those of Group 2, cilostazol treatment significantly increased MNCV and cAMP content of sciatic nerves in Group 3 but not to the levels observed in Group 1. MNCV positively correlated with cAMP content of sciatic nerves (r=0.86; p < 0.001). Cilostazol treatment not only restored myelinated fiber density and size distribution but reversed some of the vascular abnormalities. Conclusion These findings suggest that a reduced cAMP content in motor nerves may be involved in the development of diabetic neuropathy, and that cilostazol may prevent the progression of diabetic neuropathy by restoring functional impairment and morphological changes of peripheral nerves.

Oral glucose administration suppresses the TRH-induced TSH response by enhancing the hypothalamic somatostatinergic activity (HSA). We assessed the HSA in 13 acromegalic patients by measuring glucose-induced suppression of TRH-stimulated TSH secretion. The HSA showed wide variation with up to 64% suppression. The mean HSA of the patients (25 ± 6%) did not differ from that in normal young men (19 ± 4%) in our previous study. Six patients had normal or low HSA, and the other 7 patients had high HSA. The mean TRH-stimulated TSH levels of the patients with normal or low HSA was significantly lower than that of the patients with high HSA (5.13 ± 0.10 vs. 11.30 ± 2.80 mU/L). The HSA did not relate to sex, age, tumor size, basal GH levels, the paradoxical responses to TRH and GnRH, octreotide response, or the gsp oncogene. In the combined glucose-TRH test, glucose pretreatment completely suppressed the paradoxical increase in GH level at 30 min in 4 patients. However, it could suppress the paradoxical GH response by only 6–51% in the other 5 patients who also showed the paradoxical response in TRH test. The tumor diameter of patients with good response to the HSA was significantly larger than that of the patients with poor response (31 ± 5 vs. 14 ± 2 mm) as was the tumor grade (3.3 ± 0.3 vs. 1.7 ± 0.2). This study supports the idea that a reduction of HSA is not a primary cause of acromegaly, and the HSA seems to increase to suppress the autonomous secretion of GH from the pituitary adenomas. HSA as well as the response of tumors to HSA do not determine tumor growth.

We report a case of oncogenic osteomalacia associated with a phosphaturic mesenchymal tumor in a 31-year-old woman. She was presented with severe generalized bone and muscle pain and was restricted to bed. She lost 20cm in height over the 8 years since she had first noticed a pain in her thigh. A walnut-sized, hard, soft tissue tumor was found very easily beside her lower molar teeth. Radiologic examination revealed a remarkable decrease in bone density and multiple pathologic fractures of spine, femur and phalangeal bones. Severe hypophosphatemia, hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D3 level and high plasma PTH level were disclosed at presentation. Histomorphometric examination revealed an extensive area of unmineralized osteoid and little mineralizing activity. A pharmacologic dose of 1α-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 slightly increased the serum phosphate level and renal tubular reabsorption of phosphate, and slightly decreased plasma PTH level without any symptomatic improvement. Histologic examination of the tumor revealed a mixed connective tissue tumor that consisted of central woveh bones and surrounding primitive spindle cells with prominent vascularities. After removal of the tumor, all biochemical, hormonal and radiologic abnormalities disappeared with remarkable symptomatic improvement.

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (ΔGHIO), and between the OGTT and the OST at the same time point (ΔGHOS) were compared according to the size of the tumor and the response pattern to the OST. ΔGHIO of macroadenomas (n=22) was non-significantly higher than those of microadenomas while ΔGHOS of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. ΔGHOS showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.

It is important to be able to identify patients with an increased risk of venous thromboembolism (VTE) in order to minimise the risk of an event. We investigated the incidence and risk factors for post-operative VTE in 168 consecutive patients with a malignancy of the lower limb. The period of study included ten months before and 12 months after the introduction of chemical thromboprophylaxis. All data about the potential risk factors were identified and classified into three groups (patient-, surgery- and tumour-related). The outcome measure was a thromboembolic event within 90 days of surgery. Of the 168 patients, eight (4.8%) had a confirmed symptomatic deep-vein thrombosis and one (0.6%) a fatal pulmonary embolism. Of the 28 variables tested, age > 60 years, higher American Society of Anesthesiologists grade and metastatic tumour were independent risk factors for VTE. The overall rate of symptomatic VTE was not significantly different between patients who received chemical thromboprophylaxis and those who did not. Knowledge of these risk factors may be of value in improving the surgical outcome of patients with a malignancy of the lower limb. Cite this article: Bone Joint J 2013;95-B:558–62.

OBJECTIVES It was suggested that glucocorticoid exerts cell-specific effects on thyrotropin-releasing hormone (TRH) gene expression at the transcriptional level. Although there is no typical palindromic glucocorticoid response element (GRE) on the rat TRH gene promoter, a perfect GRE half-site is found between -205 bp and -211 bp. We investigated whether the segment between -242 bp and -200 bp of the rat TRH gene promoter is responsible for glucocorticoid response. METHODS For the 5' deletion study of the TRH gene, four different plasmid constructs, pTRH(- 554/84), pTRH(-242/84), pTRH(-200/6), pTRH(-113/84) were used for transient transfection study. The plasmid pMAMneo-LUC was used as a positive control and pRSV-GR expression vector, as a co-transfection study. Transfection was performed by the modified calcium precipitation method with 2 micrograms of each lasmid on the HeLa cells. RESULTS Dexamethasone (DEX) stimulated the transcriptional activity of pTRH(-554/84)-LUC and pTRH(-242/84)-LUC by approximately 3.2 fold at 10(-8) M and 5.4 fold at 10(-8) M. On the contrary, deletion of the region between -242 to -200 bp reduced the basal transcriptional activity by 90% and also completely abolished the DEX-induced transcriptional activation of the luciferase gene. The DEX-induced transcriptional activation of pTRH(-242/84)-LUC was in dose-dependent manner. While the co-transfection of glucocorticoid receptor expression vector (pRSV-GR) did not increase the basal transcriptional activity of pMAMneo-LUC, it increased the basal transcription of pTRH(-242/84)-LUC by 1.8 fold. The pRSV-GR co-transfection and DEX treatment further increased the transcription of pTRH(-242/84)-LUC by 2-4 fold at the concentration of 10(-8) M. CONCLUSION These findings suggest that a cis-acting element(s) which is important for the basal transcriptional activation and glucocorticoid response of the rat TRH gene is located between -242 bp and -200 bp. The gene has a weak GRE glucocorticoid response and seems to be mediated by an interaction between glucocorticoid receptor and other transcriptional factor (s).

Yang I, Woo J, Kim S, Kim J, Kim Y, Choi Y. Combined pyridostigmine–thyrotrophin-releasing hormone test for the evaluation of hypothalamic somatostatinergic activity in healthy normal men. Eur J Endocrinol 1995;133:457–62. ISSN 0804–4643 Pyridostigmine (PST), a cholinesterase inhibitor, induces a clear growth hormone (GH) release in man by suppression of hypothalamic somatostatin (SRIH). Somatostatin suppresses thyrotrophin (TSH) release in rats and men. Earlier studies showed that the thryotrophin-releasing hormone (TRH)-induced TSH response was not altered by 60–120 mg of PST. We studied whether a larger dose (180 mg) of PST can increase the TSH response to TRH. Six healthy young men were studied with the following six tests: (Test 1) 200 μg of TRH iv; (Test 2) 180 mg of PST po; (Test 3) three different doses of PST (60, 120, 180 mg) + TRH; (Test 4) 100 μg of octreotide (SMS) iv; (Test 5) SMS + TRH; (Test 6) PST + SMS + TRH. A large dose of PST (180 mg) significantly augmented GH, TSH and prolactin responses to TRH, while smaller doses of PST (60 and 120 mg) did not significantly increase the responses of GH and TSH. While the increased TRH-induced prolactin response by PST was not suppressed by SMS, the increased responses of GH and TSH were suppressed remarkably by SMS. Most of the subjects noticed a mild to moderate abdominal pain, nausea and muscular fasciculation after the administration of a large dose of PST administration. These data suggest that suppression of hypothalamic SRIH secretion by 180 mg of PST can augment the TSH response to TRH. However, the considerable side effects should be minimized before clinical application of the combined PST–TRH test. Inmyung Yang, Division of Endocrinology, Department of Internal Medicine, Kyunghee University School of Medicine, 1 Hoiki-dong, Dongdaemoon-ku, Seoul, 130–702, Korea

The prevesical space is the largest potential space within the pelvic extraperitoneal space. Located anterosuperior to the bladder, it has complex communications with the adjacent pelvic extraperitoneal spaces, rectus sheath, and retroperitoneum. The prevesical space is also the site of various pathological processes, and can act as a conduit for the spread of these conditions. Therefore, awareness of the detailed anatomy and potential routes of communication may help radiologists in making accurate diagnoses of pathological conditions involving the prevesical space.

The aim of this study was to retrospectively assess the diagnostic performance of multidetector CT (MDCT) for the diagnosis of acute cholangitis using a new scoring method.Of 80 patients with suspected biliary disease who underwent biphasic CT and endoscopic retrograde cholangiography, 39 were diagnosed as having acute cholangitis (Group 1) and 41 patients were classified as suspected biliary disease (Group 2). 100 age-matched patients without evidence of biliary disease were selected randomly as a control group (Group 3). Each patient's axial scan was scored by two independent radiologists for the extent of transient hepatic attenuation difference, the presence of biliary dilatation and identification of a biliary obstructive lesion. The difference in the scores among the three groups was evaluated and the optimal cut-off score for the diagnosis of acute cholangitis was determined. Interobserver agreement was also evaluated.The total scores (mean ± standard deviation) for Groups 1, 2 and 3 were 7.0 ± 2.0, 4.4 ± 2.4 and 0.9 ± 1.2, respectively, for Reviewer 1 and 7.2 ± 2.7 and 0.7 ± 1.1, respectively, for Reviewer 2. Significant differences were found for the subscores and the total scores among the three groups (p0.001). Using a cut-off score of ≥ 5, the sensitivity and specificity for diagnosing acute cholangitis were 84.6% and 83.7%, respectively, for Reviewer 1 and 89.7% and 83.7%, respectively, for Reviewer 2. Agreement for the subscores between readers was good to excellent (κ = 0.74-0.86).Based on dynamic MDCT and the described CT scoring method, the diagnosis of acute choangitis can be made with high sensitivity and specificity.

Glucose toxicity contributes to progressive β-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic β-cells. We investigated whether the flavonoid apigenin protects pancreatic β-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic β-cells were cultured with or without apigenin in the presence of dRib. Time- and dose-dependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨ(m)) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2',7'-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨ(m), while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic β-cells via oxidative stress-related signaling.

Background There have been no systematic observations regarding changes in early phase insulin secretion among Korean prediabetes and early stage type 2 diabetes mellitus (T2DM) patients. Methods We conducted 75-g oral glucose tolerance tests (OGTT) in 873 subjects with suspected abnormal glucose tolerance. All subjects were diagnosed as having normal glucose tolerance (NGT), prediabetes (preDM), or T2DM according to the OGTT results and the insulin secretory and insulin resistance indices of each subject were calculated. Additionally, we analyzed the changes in early phase insulin secretion according to changes in fasting (Glc(0)), post-prandial (Glc(120)) glucose and HbA1c (A1c) levels. Results As compared to subjects with NGT, the insulin secretory indices of the preDM and T2DM subjects progressively declined, and the insulin resistance indices were progressively aggravated. Early phase insulin secretion decreased rapidly according to the increments of Glc(0), Glc(120) and A1c, and these changes were most prominent in the NGT stage. Compared to the control group, the early phase insulin secretion levels of the preDM or T2DM subjects were less than 50% when Glc(0) was over 100 mg/dL, Glc(120) was over 145 mg/dL, and A1c was over 5.8%. Conclusion This study suggests that progressive beta cell dysfunction in Koreans may be initiated and rapidly aggravated during the period generally designated as 'normal.'

Insulin-like growth factor I (IGF-I) mediates many of the systemic growth-promoting effects of growth hormone and also functions as a locally acting growth stimulator. In mammals, IGF-I gene expression is complicated, as the gene is transcribed and processed into multiple mRNAs (ranging in length from less than 1 to nearly 7.5 kb) that encode at least two protein precursors. As a step toward understanding the regulation of IGF-I, we report the complete organization of the rat IGF-I gene, including identification of the structural determinants for all IGF-I mRNA species, and an initial functional analysis of its promoters. The gene is composed of 6 exons distributed over nearly 80 kb of chromosomal DNA and is structurally heterogeneous. Several transcription start sites were identified within IGF-I exons 1 and 2, adjacent to presumptive promoters 1 and 2, respectively, and at least three polyadenylation sites were mapped to exon 6. To test promoter function, fusion genes were constructed linking fragments of IGF-I DNA to a reporter plasmid. Chimeric genes containing at least 395 bp of DNA from the 5'-flanking region of exon 1 enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line, while fusion plasmids containing up to 1,300 bp of DNA from the 5'-flanking region of exon 2 were inactive. Relative levels of IGF-I mRNAs containing exons 1 or 2 varied among different rat tissues, although in response to acute or chronic growth hormone treatment both classes of transcripts were induced coordinately in rat liver. These observations represent the first thorough characterization of a mammalian IGF-I gene, and provide a starting point for defining the mechanisms by which growth hormone and other trophic factors regulate IGF-I gene expression.

During the progression of Type 2 diabetes, glucose toxicity is likely to contribute importantly to progressive beta cell failure. Oxidative stress is an important aspect of glucose toxicity in pancreatic beta cells, and reducing sugars, such as 2-deoxy-D-ribose (dRib), produce reactive oxygen species. Furthermore, many of the biological properties of flavonoids are likely to be related to their antioxidant and free-radical scavenging abilities. Accordingly, in the present study, we investigated whether kaempferol (a flavonol) protects beta cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24h. Cell survivals, amounts of reactive oxygen species (ROS) generated, apoptosis, and lipid peroxidation were measured. dRib was found to dose-dependently reduce cell survival and to markedly increase intracellular ROS levels, apoptosis, and lipid peroxidation. However, kaempferol (10 microM) suppressed dRib (20 mM) induced intracellular ROS, apoptosis, and lipid peroxidation. So, we demonstrate that kaempferol reduces dRib-mediated beta cell damage interfering with ROS metabolism and protective effects against lipid peroxidation. Our findings indicate that kaempferol protects HIT-T15 cells from dRib-induced associated oxidative damage.

Reducing sugar, 2-deoxy-D-ribose (dRib), produces reactive oxygen species through autoxidation and protein glycosylation and causes osteoblast dysfunction. Kaempferol, a natural flavonoid, was investigated to determine whether it could influence dRib-induced cellular dysfunction and oxidative cell damage in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with 30 mM dRib in the presence or absence of kaempferol (10(-9)-10(-5) M) and markers of osteoblast function and lipid peroxidation were subsequently examined. Kaempferol (10(-9)-10(-5) M) significantly inhibited the dRib-induced decrease in growth of MC3T3-E1 osteoblastic cells. In addition, treatment with kaempferol resulted in a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and mineralization in the cells. Treatment with kaempferol increased osteoprotegerin (OPG) secretion and decreased malondialdehyde (MDA) contents of MC3T3-E1 osteoblastic cells in the presence of 30 mM dRib. Taken together, these results suggest that kaempferol inhibits dRib-induced osteoblastic cell damage and may be useful for the treatment of diabetes-related bone disease.

We have identified and characterized a promoter regulatory region for the human insulin-like growth factor-I (IGF-I) gene. The 5'-ends of IGF-I mRNAs were first mapped to a series of sites within a 158-nucleotide portion of exon 1 that was found to be structurally similar to the recently delineated transcription start region of the chicken IGF-I gene. In both species multiple initiation sites are probably a reflection of the absence of typical transcriptional regulatory signals, such as a TATA or CCAAT box, in the proximal promoter, although neither gene sequence resembles a GC-rich housekeeping promoter, which also controls a dispersed initiation region. To test promoter function, hybrid genes were constructed linking human IGF-I DNA to a promoterless reporter plasmid. Fusion genes containing from 385-4300 nucleotides of the IGF-I 5'-flanking region enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line. A plasmid with 1630 nucleotides of 5'-DNA gave maximal activity and directed accurate initiation of the hybrid gene while the same promoter fragment inserted in the reverse orientation was inert. Although cognate recognition sequences were identified for several transcription factors in the 1630 nucleotides 5' to the transcription start region, no sites were found that resembled the putative GH response element recently mapped to the proximal promoter of the rat Spi2.1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

We undertook a retrospective review of 24 arthroscopic procedures in patients with symptomatic ossicles around the malleoli of the ankle. Most of the patients had a history of injury and localised tenderness in the area coinciding with the radiological findings. Contrast-enhanced three-dimensional fast-spoiled gradient-echo MRI was performed and the results compared with the arthroscopic findings. An enhanced signal surrounding soft tissue corresponding to synovial inflammation and impingement was found in 20 patients (83%). The arthroscopic findings correlated well with those of our MRI technique and the sensitivity was estimated to be 91%. At a mean follow-up of 30.5 months (20 to 86) the mean American Orthopaedic Foot and Ankle Society score improved from 74.5 to 93 points (p < 0.001). Overall, the rate of patient satisfaction was 88%. Our results indicate that symptomatic ossicles of the malleoli respond well to arthroscopic treatment.