Developmental trajectories of tobacco use and risk factors from adolescence to emerging young adulthood: a population-based panel study.

BACKGROUND: Adolescence to young adulthood is a critical developmental period that determines lifelong patterns of tobacco use. We examined the longitudinal trajectories of tobacco use, and risk factors for its use, and explored the association between the trajectories of mobile phone dependency and smoking throughout the life-course among adolescents and young adults. METHODS: Data of 1,723 subjects (853 boys and 870 girls) were obtained from six waves of the Korean Children and Youth Panel Survey (mean age = 13.9-19.9 years). To identify trajectories of smoking and mobile phone dependency, group-based trajectory modelling (GBTM) was conducted. A multinomial logistic regression analysis was performed to identify the characteristics of the trajectory groups. RESULTS: GBTM identified four distinct smoking trajectories: never smokers (69.1%), persistent light smokers (8.7%), early established smokers (12.0%), and late escalators (10.3%). Successful school adjustment decreased the risk of being an early established smoker (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.27-0.78). The number of days not supervised by a guardian after school was positively associated with the risk of being an early established smoker (OR 1.96, 95% CI 1.23-3.13). Dependency on mobile phones throughout the life-course was positively associated with the risk of being a persistent light smoker (OR 4.04, 95% CI 1.32-12.34) or early established smoker (OR 8.18, 95% CI 4.04-16.56). CONCLUSIONS: Based on the group-based modeling approach, we identified four distinctive smoking trajectories and highlight the long-term effects of mobile phone dependency, from early adolescence to young adulthood, on smoking patterns.

Superficial inferior epigastric artery-supercharged deep inferior epigastric artery perforator flap-based breast reconstruction for a thin patient: A case report.

Although a bipedicled deep inferior epigastric artery perforator (DIEP) flap is widely accepted for slim patients with large breasts, we suggest DIEP flap-based breast reconstruction in which the superficial inferior epigastric artery (SIEA) is supercharged to the branch of thoracodorsal vessel as an alternative, which has not previously been well described. We report the case of a 48-year-old breast cancer patient who had a normal body mass index of 23.01 and relatively thin abdominal tissue, with large and ptotic (grade II ptosis) breasts. The mastectomy specimen weighed ~890 g, and the harvested abdominal tissue weighed ~700 g with a size of 32 × 12 cm2 . The elliptical-shaped flap was inset with a 90° counterclockwise rotation, and the lower one-third of the flap was folded to create a projection. Perfusion of flap was augmented by microvascular anastomosis between the contralateral SIEA and the serratus branch of a thoracodorsal vessel. With a supercharged DIEP flap, nearly the whole lower abdominal tissue (696 g, 99.4% of the elevated flap) could be transferred to obtain a symmetric contour, and there were no complications such as vascular obstruction, flap necrosis, and delayed wound healing during the postoperative course. Using the SIEA pedicle for contralateral abdominal perfusion with elongated branch of the thoracodorsal vessel, aesthetic inset and contouring of the reconstructed breast could be technically enhanced. The DIEP flap with the contralateral SIEA supercharged to the serratus branch of thoracodorsal vessel may be a feasible option for large ptotic breast reconstruction in thin patients.

The natural history and hip geometric changes of primary hyperparathyroidism without parathyroid surgery.

There have been few reports on changes in bone geometry in asymptomatic patients with primary hyperparathyroidism (PHPT) not treated surgically. We reviewed the records concerning biochemical parameters, bone mineral density (BMD), and hip geometry in 119 PHPT patients who did not undergo parathyroidectomy, followed up at one of three hospitals affiliated to Seoul National University from 1997 to 2013. We examined biochemical parameters over 7 years and BMD and hip geometry over 5 years of follow-up. We further compared hip geometry and BMD derived from dual-energy X-ray absorptiometry (DXA) between patients and age- and sex-matched controls. The median follow-up duration of 56 patients for whom surgery was not indicated was 33.9 months (range 11.2-131.2 months), and 19.6 % of these patients had disease progression during follow-up. Serum calcium levels remained stable for 7 years in all 119 patients. From a comparison of the PHPT patients for whom surgery was not indicated with controls, both male and postmenopausal female patients had significantly lower hip axis length (P < 0.001), cross-sectional moment of inertia (P < 0.001), cross-sectional area (P < 0.001), and section modulus (P < 0.001). In addition, cortical thickness was significantly decreased at 5 years compared with individual baseline values (P = 0.003). However, there was no significant change in BMD for the duration of the 5-year follow-up. DXA-derived geometry can detect skeletal change in asymptomatic PHPT patients for whom surgery is not indicated, supporting the concept that even mild PHPT can eventually compromise the cortical bones. Hip geometry is a potential tool for monitoring skeletal complication in asymptomatic PHPT patients.

Best candidates for dopamine agonist withdrawal in patients with prolactinomas.

PURPOSE: Dopamine agonist (DA) therapy is recommended as the first-line treatment for prolactinomas. However, it requires long treatment duration, and a high recurrence rate after DA withdrawal has been reported. We aimed to elucidate the predictors for long-term remission following DA withdrawal and propose the best candidates who can achieve complete remission after DA withdrawal. METHODS: In a retrospective cohort study, we included 89 patients with prolactinoma who have withdrawn DAs with normal prolactin (PRL) levels at Seoul National University Hospital, from 2000 to 2016. Patient's data were retrieved from the electronic medical records. RESULTS: The median age and median treatment duration of the study patients were 33 (15-73) years and 69.5 (8.3-277.4) months, respectively. The recurrence rate after drug withdrawal was 57.3% during the 23.9 (3.0-176.8) month follow-up period. Age, gender, baseline PRL level, and baseline maximum tumor diameter were similar between the remission and recurrence group. In the Cox-proportional hazard model analysis, the significant predictors for remission were nadir PRL level of <1 ng/dL (hazard ratio [95% confidence interval] = 0.37 [0.18-0.74]), invisible tumors on magnetic resonance imaging (MRI) (0.42 [0.24-0.74]), and treatment duration of >72 months (0.54 [0.30-0.96]). Of the subjects who met all the three criteria, 66.7% achieved long-term remission. CONCLUSIONS: Patients who have no tumor visible on MRI, have a nadir PRL level <1 ng/dL during drug treatment, and received drug treatment for >6 years may be the best candidates for DA withdrawal.

Outcomes analysis of surgical and medical treatments for patients with primary aldosteronism.

Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using mineralocorticoid receptor antagonists (MRAs). However, the outcomes of surgical and medical treatment for primary aldosteronism (PA) remain unclear. Therefore, we compared the outcomes of surgical and medical treatment for PA and aimed to identify a specific subgroup that might benefit from medical treatment. We identified 269 patients who were treated for PA (unilateral excess: 221 cases; bilateral excess: 48 cases) during 2000-2015 at the Seoul National University Hospital and two other tertiary centers. The main outcomes were the amelioration of hypertension and hypokalemia. Treatment improved hypertension in the surgical treatment group (78.2%) and the medical treatment group (55.6%) (p = 0.001). At the last follow-up, hypokalemia was normalized in the surgical treatment group (97.1%) and the medical treatment group (93.7%, p = 0.046). Among patients with unilateral aldosterone excess, surgery provided advantages in resolving hypertension without worsening renal function. Among patients who were >60 years old or had impaired renal function, surgical and medical treatment provided similar amelioration of hypokalemia and hypertension. Three patients developed hyperkalemia after surgery, and no patients developed hyperkalemia after initiating medical treatment. The surgical treatment group exhibited a lower postoperative estimated glomerular filtration rate (eGFR) and higher serum potassium levels, compared to the medical treatment group. Surgical treatment provided better hypertension and hypokalemia outcomes among patients with PA, compared to medical treatment. However, MRAs may be appropriate for elderly patients with impaired renal function.

Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.

Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 µg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.

Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group.

PURPOSE: Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group. METHODS: A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII). RESULTS: The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m2) contributed to a higher risk of metabolic syndrome. CONCLUSIONS: The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.

Femoral geometry, bone mineral density, and the risk of hip fracture in premenopausal women: a case control study.

BACKGROUND: The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women. METHODS: The participants in this case-control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI-adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements. RESULTS: The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 ± 0.123 vs. 0.899 ± 0.115, p <0.001 for the femoral neck BMD and 0.724 ± 0.120 vs. 0.923 ± 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group. CONCLUSIONS: BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered.

Viscoelastic interactions between polydeoxyribonucleotide and ophthalmic excipients.

This study investigated the interaction between polydeoxyribonucleotide (PDRN) and several ionic and nonionic isotonic agents, thickeners and a preservative that were employed as excipients in ophthalmic preparations. Interaction of each individual excipient and PDRN aqueous solution was evaluated by analyzing their rheological properties. Rheological properties of PDRN solutions were evaluated by dynamic oscillatory shear tests and values of elastic modulus (G'), viscous modulus (G″) and loss tangent (tan δ) were used to assess the relative changes in viscoelastic properties. At given concentrations, sodium chloride was found to show alteration in viscoelastic properties of PDRN solution while nonionic isotonic agents like d-glucose and d-sorbitol did not alter them. Similarly, nonionic water soluble polymers like polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) also did not interact with PDRN to alter the viscoelastic properties. However, there were changes observed when carbopol 940 was used as a thickener. Therefore, PDRN was found to interact with ionic excipients and the interactions were negligible when nonionic materials were examined, which suggests that nonionic excipients are suitable to be formulated with PDRN.

Frequency of existence, numbers, and location of the accessory infraorbital foramen.

The aim of this study is to analyze the frequency of existence, numbers, and location of the accessory infraorbital foramen (AIOF).In a PubMed search, 166 articles resulted using the term infraorbital foramen (IOF). The abstracts were read, and 15 full-text articles were reviewed. Among them, 13 articles were analyzed.The frequency of the skull containing the AIOF varied (0.8%-27.3%). The overall frequency of the skull having AIOF was 16.9% ± 8.6% (17.0% ± 9.4% in dry skulls and 15.8% ± 3.6% in cadavers). Most (92.2%) of the AIOF were located on the superomedial side of the IOF, whereas 5 (7.8%) were located inferomedially. The AIOFs were found in similar frequency according to the laterality (right, 42.7%; left, 45%; bilateral, 12%; P = 0.794 [binominal test]). The frequency of the AIOF varied according to latitude. Skulls collected greater than 60 degrees had a higher frequency of an AIOF (28.7%) than between 30 and 60 degrees (19.0%) or less than 30 degrees (18.2%) (P = 0.000 [Pearson Chi-squared test], P = 0.000 [trend test]). There was a positive correlation between latitude and frequency of AIOF (y = 0.062x + 18.02, Pearson correlation coefficient = 0.140, P = 0.000).During anesthetization of the infraorbital area or in surgical maneuvering in the maxillofacial region, surgeons should remember the frequency of the AIOF (16.9% ± 8.6%) and its location (92.2% at the superomedial side of the IOF).

In vivo deletion of CAR resulted in high bone mass phenotypes in male mice.

Constitutive androstane receptor (CAR) was originally identified as xenobiotic sensor that regulates the expression of cytochrome P450 genes. However, recent studies suggest that this nuclear receptor is also involved in the regulation of energy metabolism including glucose and lipid homeostasis. This study investigated the role of CAR in the regulation of bone mass in vivo using CAR(-/-) mice. Endogenous mRNA expression of CAR was observed in both primary osteoblasts and osteoclast precursors. CAR(-/-) mice have exhibited significant increase in whole body bone mineral density (BMD) by 9.5% (P < 0.01) and 5.5% (P < 0.05) at 10 and 15 weeks of age, respectively, compared with WT mice in males. Microcomputed tomography analysis of proximal tibia demonstrated a significant increase in trabecular bone volume (62.7%), trabecular number (54.1%) in male CAR(-/-) mice compared with WT mice. However, primary culture of calvarial cells exhibited no significant changes in osteogenic differentiation potential between CAR(-/-) and WT. In addition, the number of tartrate-resistant acid-phosphatase positive osteoclasts in the femur and serum level of CTx was not different between CAR(-/-) and WT mice. The higher BMD and microstructural parameters were not observed in female mice. Interestingly, serum level of testosterone in male CAR(-/-) mice was 2.5-fold higher compared with WT mice and the mRNA expressions of Cyp2b9 and 2b10 in the liver, which regulate testosterone metabolism, were significantly down-regulated in male CAR(-/-) mice. Furthermore, the difference in BMD between CAR(-/-) and WT mice disappeared at 8 weeks after performing orchiectomy. CAR(-/-) mice also exhibited significant increase in serum 1,25(OH)2 D3 levels but Cyp 27B1 which converts 25(OH)D3 to 1,25(OH)2 D3 was significantly down-regulated compared to WT mice. These results suggest that in vivo deletion of CAR resulted in higher bone mass, which appears to be a result from reduced metabolism of testosterone due to down-regulation of Cyp2b.

Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score.

AIMS/HYPOTHESIS: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM. METHODS: This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors. RESULTS: Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36 ± 0.92 vs 8.78 ± 1.07; p < 1.56 × 10(-7)). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p = 0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p = 7.0 × 10(-5)). CONCLUSIONS/INTERPRETATION: In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.

Nationwide survey of acromegaly in South Korea.

CONTEXT: It was previously reported in Korea that there were 1.4 case per million per year of acromegaly. This was low in comparison with the extrapolated values of Western European countries. We expected that the incidence of acromegaly would be much higher now because of recently improved medical facilities, diagnostic tools and coverage of medical insurance to all the population of South Korea. OBJECTIVE: The purpose of this nationwide survey was to examine the incidence and prevalence of patients with acromegaly, mode of treatment and outcome of surgical treatment of recent 5 years. DESIGN AND PATIENTS: We requested and collected the medical records of all possible patients with acromegaly from 74 secondary or tertiary medical institutes in Korea from 2003 to 2007 retrospectively. MEASUREMENTS: Date of diagnosis and treatment, tumour size, pre- and postoperative hormonal level, treatment modality and usage of medication were collected. RESULTS: During 5 years, 1350 patients with acromegaly had been registered. The average annual incidence was 3.9 cases per million during this period, and prevalence had increased up to 27.9 cases per million in 2007. Male/female ratio was 1:1.2, and mean age at diagnosis was 44.1 years. Macroadenoma was dominant (82.9%). Transsphenoidal adenoidectomy was used the most as primary treatment (90.4%). CONCLUSIONS: This Korean acromegaly survey offers a realistic overview of the predominant epidemiological characteristics of acromegaly in Korea. Annual incidence was at a similar level with western countries. Efforts to diagnose and control the disease earlier are recommended.

Clinical characteristics of the responders to dipeptidyl peptidase-4 inhibitors in Korean subjects with type 2 diabetes.

We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (ΔHbA1c). The Student's t-test between good responders (GR: ΔHbA1c > 1.0%) and poor responders (PR: ΔHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with ΔHbA1c. In the multivariate analysis, age (r(2) = 0.006), duration of diabetes (r(2) = 0.019), HbA1c (r(2) = 0.296), and creatinine levels (r(2) = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.

Impact of Micellar Vehicles on in situ Intestinal Absorption Properties of Beta-Lapachone in Rats.

The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.

The prevalence and risk factors of vertebral fractures in Korea.

We investigated the prevalence and risk factors of vertebral fractures in Korea. In a community-based prospective epidemiology study, 1,155 men and 1,529 women (mean age 59 years, range 43-74) were recruited from Ansung, a rural Korean community. Prevalent vertebral fractures were identified on the lateral spinal radiographs at T11 to L4 using vertebral morphometry. Bone mineral density (BMD) was measured at the lumbar spine, femur neck and total hip. Of the 2,684 subjects, 137 (11.9%) men and 227 (14.8%) women had vertebral fractures and the standardized prevalence for vertebral fractures using the age distribution of Korean population was 8.8% in men and 12.6% in women. In univariate analysis, older age, low hip circumference, low BMD, low income and education levels in both sexes, previous history of fracture in men, high waist-to-hip circumference ratio, postmenopausal status, longer duration since menopause, and higher number of pregnancies and deliveries in women were associated with an increased risk of vertebral fractures. However, after adjusting for age, only low BMD in both sexes and a previous history of fracture in men were significantly associated with an increased risk of vertebral fractures. Vertebral fractures are prevalent in Korea as in other countries. Older age, low BMD and a previous history of fracture are significant risk factors for vertebral fractures.

Value of adrenal venous sampling for lesion localization in primary aldosteronism.

BACKGROUND: Distinguishing between unilateral and bilateral adrenal lesions is mandatory for surgical treatment of primary aldosteronism (PA). Adrenal venous sampling (AVS) is considered the gold standard for identification and localization of the lesion or lesions causing PA. The objective of the present study was to determine the usefulness of AVS in PA patients. PATIENTS AND METHODS: From January 2001 to October 2011, 86 patients with the biochemical diagnosis of PA were retrospectively analyzed. The study group included 45 males and 41 females with a mean age of 50.7 ± 12.6 years, and all patients underwent adrenal computed tomography (CT) and AVS. RESULTS: The catheterization success rate of AVS was 82.69 % (86/104). In addition, AVS revealed bilateral lesions in 15/75 patients with unilateral abnormalities diagnosed by CT. These patients underwent medical treatment instead of surgery. One patient had an adrenal mass on the right side, but AVS localized the lesion on the left side. This patient underwent left adrenalectomy. Furthermore, AVS revealed a unilateral lesion in 2/5 patients with bilateral abnormalities demonstrated by CT. These patients underwent unilateral adrenalectomy. Finally, AVS demonstrated localization in 1/6 of patients with no CT abnormalities who were subjected to surgery. Fifty-three patients with unilateral lesion and one patient with bilateral hypersecretion underwent surgical removal of the affected gland(s). All patients had resolution of hypokalemia and clinical improvement of hypertension. CONCLUSIONS: Many patients (19/86, or 22.09 %) would have been inappropriately managed if decision making had been based solely on CT findings. Therefore, AVS is recommended before determining definitive PA management.

Recurrence of Cushing's disease after primary transsphenoidal surgery in a university hospital in Korea.

Successful long-term management of patients with Cushing's disease (CD) remains a challenge. To date, studies on the long-term outcome of patients with CD have been conducted mainly in Caucasians. Our objective was to assess the recurrence rate in patients who underwent transsphenoidal surgery (TSS) in the management of CD and to identify predictive markers for the long-term outcomes of CD in Korea. The long-term outcome in 54 patients who underwent TSS for the treatment of CD from 1984 to 2010 was retrospectively reviewed. Recurrence was defined as an elevated serum cortisol or an elevated 24 hour urine free cortisol or a suppressed serum cortisol by dexamethasone higher than 138 nmol/L. Mean age at diagnosis was 35.8 ± 12.8 years and median follow-up duration was 50.7 months. Initial successful TSS was obtained in 38 patients (70.4%). Among these 38 patients, 18 (47.4%) patients had a recurrence of CD. Preoperative serum cortisol level was significantly associated with recurrence. Pathologic confirmation of an adenoma was marginally associated with lower risk of recurrence. Positive results of imaging study and presence of microadenoma were not associated with risk of recurrence. Recurrence rate of CD after initial successful TSS was 32.4% at 5 years and 54.6% at 10 years, respectively. Following initial successful TSS, close long-term endocrine surveillance is mandatory as the recurrence rate increases with time. Preoperative serum cortisol level and pathologic confirmation of an adenoma may have a predictive value for recurrence of CD after TSS.

Preoperative predictive factors for parathyroid carcinoma in patients with primary hyperparathyroidism.

This study was conducted to review the clinical characteristics of parathyroid carcinoma (PC) and to evaluate potential preoperative predictive factors for PC in patients with primary hyperparathyroidism (PHPT). We performed a retrospective review of electronic medical records of 194 patients with pathologically confirmed PHPT in affiliated teaching hospitals of Seoul National University from January 2000 to March 2011. Adenoma was diagnosed in 171 patients, hyperplasia in 12, and carcinoma in 11. Several biochemical measurements were higher in patients with PC than in patients with benign disease, including serum total calcium (P < 0.001), intact parathyroid hormone (P = 0.003), and alkaline phosphatase (ALP) (P < 0.001). Tumors were larger in PC than in benign disease (P < 0.001). Multivariate analysis revealed that serum ALP level (P < 0.001) and tumor size were associated with PC (P = 0.03). Tumor size and serum ALP level were evaluated as preoperative predictive factors for PC using ROC analyses: a tumor size of 3.0 cm (sensitivity 90.9%, specificity 92.1%) and serum ALP level of 285 IU/L (83.3%, 97.0%) had predictive value for the diagnosis of PC in patients with PHPT. In conclusion, elevated serum ALP and a large parathyroid mass at the time of diagnosis can be helpful to predict PC in patients with PHPT.

Development of self-microemulsifying bilayer tablets for pH-independent fast release of candesartan cilexetil.

The aim of this study was to design self-microemulsifying tablets for pH-independent fast release of poorly soluble candesartan cilexetil (CDC). To improve the solubility of CDC, a self-microemulsifying drug delivery system (SMEDDS) was prepared composed of Capryol 90, Tween 80 and tetraglycol at a ratio of 5:35:60. Drug containing SMEDDS was adsorbed onto Fujicalin and Neusilin UFL2, respectively, used as solidification carriers and subsequently compressed into tablets (self-microemulsifying tablet, SMET). SMET using Fujicalin exhibited immediate CDC release in pH 1.2 medium while Neusilin UFL2-based SMET showed fast release, especially at pH 6.5. Thus, optimized SMET could be produced with one layer of Fujicalin and the other layer with Neusilin UFL2, demonstrating CDC release of 75% of the initial dose within 15 min in all pH conditions (1.2, 4.5, and 6.5). The average diameter of emulsion droplets formed from SMET was less than 200 nm. It was thus expected that Fujicalin and Neusilin UFL2-based bi-layer SMET would overcome low oral bioavailability of CDC due to its limited solubility at physiological pH conditions in the gastrointestinal tract.