BRAF V600E Mutation Lacks Association with Poorer Clinical Prognosis in Papillary Thyroid Carcinoma.

BACKGROUND: Previous literatures showed wide range of prevalence of BRAF V600E in papillary thyroid carcinoma (PTC). The correlation of BRAF V600E mutation with aggressive tumor characteristics and poor prognosis is controversial. The present study was designed to evaluate the association between BRAF V600E mutation with clinicopathological factors and tumor recurrence. PATIENTS AND METHODS: We performed a retrospective chart review of 672 patients who underwent thyroid surgery for PTC during 2013 and 2018. The prevalence of the BRAF V600E mutation was studied. Its correlation with clinicopathologic characteristics and aggressive features, including macroscopic extrathyroidal extension, lymph node metastasis, and distant metastasis, were analyzed with Fisher's exact test. RESULTS: A total of 672 patients who underwent surgical treatment for PTC were included in this study with a mean age of 49.7 (± 13.2) years; 76.8% of the patients were detected with BRAF V600E mutation. Mean tumor size was 1.30 (± 1.07) cm. A significant association was demonstrated between negative BRAF V600E and larger primary tumor size, distant metastasis, and advanced staging (p < 0.05), whereas there was no significant association with age, sex, lymph node metastasis, extrathyroidal extension, and multicentricity. Kaplan-Meier curve showed similar disease-free survival rate between the two groups. CONCLUSIONS: Negative BRAF V600E tumors show more aggressive behavior with a higher risk of developing distant metastasis in patients with PTC. The usefulness of BRAF in predicting the prognosis of PTC remains questionable. Further molecular analysis should be conducted for contribution to aggressive tumor phenotype.

Printing a Three-Dimensional Patient-Specific Safety Device for Reducing the Potential Risk of Mental Nerve Injury During Transoral Thyroidectomy.

BACKGROUND: Thyroidectomy transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe and cosmetically appealing alternative for well-selected patients undergoing thyroidectomy. However, during TOETVA, placement of the two lateral trocars and/or manipulation of the surgical instruments through the trocars may potentially injure and/or compress the mental nerve (MN) because the actual location of the nerve foramen may vary among individuals. The MN injury rate was reported to be as high as 75% in the initial period of robotic-assisted TOETVA. To reduce the potential risk of MN injury, we implemented a three-dimensional printing technology to develop a safety device for TOETVA. METHODS: The patient-specific safety device (PSSD) was a brace with an exact fit to the lower teeth and two safety markers on each side to indicate the location of the mental foramen. For patient in whom the brace would not be applicable, a 3D mandibular model was printed as a PSSD instead. We analyzed 66 patients undergoing TOETVA at our institution from March 2017 to March 2019. The preoperative details and complication profiles were also analyzed. RESULTS: With incorporation of the PSSD into our TOETVA procedure, there have been no cases of MN injury. CONCLUSIONS: Our own TOETVA series has demonstrated that the implementation of the PSSD has been successful in preoperatively identifying and preventing the potential risk of MN injury. Although the additional requirements of preoperative CT and time for fabricating the device impose limitations, the influence of the PSSD in TOETVA is positive.

CD133-expressing thyroid cancer cells are undifferentiated, radioresistant and survive radioiodide therapy.

PURPOSE: (131)I therapy is regularly used following surgery as a part of thyroid cancer management. Despite an overall relatively good prognosis, recurrent or metastatic thyroid cancer is not rare. CD133-expressing cells have been shown to mark thyroid cancer stem cells that possess the characteristics of stem cells and have the ability to initiate tumours. However, no studies have addressed the influence of CD133-expressing cells on radioiodide therapy of the thyroid cancer. The aim of this study was to investigate whether CD133(+) cells contribute to the radioresistance of thyroid cancer and thus potentiate future recurrence and metastasis. METHODS: Thyroid cancer cell lines were analysed for CD133 expression, radiosensitivity and gene expression. RESULTS: The anaplastic thyroid cancer cell line ARO showed a higher percentage of CD133(+) cells and higher radioresistance. After γ-irradiation of the cells, the CD133(+) population was enriched due to the higher apoptotic rate of CD133(-) cells. In vivo (131)I treatment of ARO tumour resulted in an elevated expression of CD133, Oct4, Nanog, Lin28 and Glut1 genes. After isolation, CD133(+) cells exhibited higher radioresistance and higher expression of Oct4, Nanog, Sox2, Lin28 and Glut1 in the cell line or primarily cultured papillary thyroid cancer cells, and lower expression of various thyroid-specific genes, namely NIS, Tg, TPO, TSHR, TTF1 and Pax8. CONCLUSION: This study demonstrates the existence of CD133-expressing thyroid cancer cells which show a higher radioresistance and are in an undifferentiated status. These cells possess a greater potential to survive radiotherapy and may contribute to the recurrence of thyroid cancer. A future therapeutic approach for radioresistant thyroid cancer may focus on the selective eradication of CD133(+) cells.

Targeting signal transducer and activator of transcription 3 pathway by cucurbitacin I diminishes self-renewing and radiochemoresistant abilities in thyroid cancer-derived CD133+ cells.

Anaplastic thyroid cancer (ATC) is a lethal solid tumor with poor prognosis because of its invasiveness and its resistance to current therapies. Recently, ATC-CD133+ cells were found to have cancer stem cell (CSC) properties and were suggested to be important contributors to tumorigenicity and cancer metastasis. However, the molecular pathways and therapeutic targets in thyroid cancer-related CSCs remain undetermined. In this study, ATC-CD133+ cells were isolated and found to have increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared with ATC-CD133 cells. Microarray bioinformatics analysis suggested that the signal transducer and activator of transcription 3 (STAT3) pathway could be important in regulating the stemness signature in ATC-CD133+ cells; therefore, the effect of the potent STAT3 inhibitor cucurbitacin I in ATC-CD133+ cells was evaluated in this study. Treatment of ATC-CD133+ cells with cucurbitacin I diminished their CSC-like abilities, inhibited their stemness gene signature, and facilitated their differentiation into ATC-CD133⁻ cells. Of note, treatment of ATC-CD133+ cells with cucurbitacin I up-regulated the expression of thyroid-specific genes and significantly enhanced radioiodine uptake. Furthermore, cucurbitacin I treatment increased the sensitivity of ATC-CD133+ cells to radiation and chemotherapeutic drugs through apoptosis. Finally, xenotransplantation experiments revealed that cucurbitacin I plus radiochemotherapy significantly suppressed tumorigenesis and improved survival in immunocompromised mice into which ATC-CD133+ cells were transplanted. In summary, these results show that the STAT3 pathway plays a key role in mediating CSC properties in ATC-CD133+ cells. Targeting STAT3 with cucurbitacin I in ATC may provide a new approach for therapeutic treatment in the future.

Magnolol attenuates the lung injury in hypertonic saline treatment from mesenteric ischemia reperfusion through diminishing iNOS.

BACKGROUND: Hypertonic saline (HTS) administration can decrease the inflammation following ischemia reperfusion. Magnolol is a potent antioxidant. The present study investigated whether combined treatment of magnolol and HTS could provide further protection in mesenteric ischemia reperfusion injury. METHODS: Male C3H/HeOuJ mice were randomly segregated into the following groups: sham-operated (sham), vehicle treatment and mesenteric ischemia reperfusion (MSIR) (vehicle-treated), magnolol treatment and MSIR (magnolol-treated), HTS treatment and MSIR (HTS-treated), as well as co-administration of magnolol plus HTS and MSIR (combined-treated). In MSIR, mice were subjected to mesenteric ischemia for 60 min followed by reperfusion for 30 min. Lung injury was evaluated by lung edema (water ratio) and myeloperoxide (MPO) activity; RNA expression of inducible nitric oxide synthetase (iNOS), TNF-α, and IL-6 were assayed by real time RT-PCR. The formation of peroxynitrite in plasma was assayed by the peroxynitrite-dependent oxidation of dihydrorhodamine 123 (DHR 123) to rhodamine. RESULTS: Compared with those in the sham-treated group, lung edema and MPO activity, expressions of iNOS, TNF-α and IL-6, and plasma peroxynitrite were significantly increased in the vehicle-treated group. Significant attenuations of these parameters were found in the magnolol-treated or HTS-treated animals. Combined treatment of magnolol and HTS further suppressed the lung edema, iNOS, and TNF-α expressions, and plasma peroxynitrite, compared with the results of a single treatment of magnolol or HTS. CONCLUSIONS: Compared with single-agent use, co-administration of magnolol and HTS further decreases iNOS expression and plasma peroxynitrite as well as the degree of lung injury from MISR. These results may provide another treatment measure for post-injury immunomodulation.

Relation of signal in mononuclear cell with endotoxin response and clinical outcome after trauma.

BACKGROUND: We investigated the correlation of proinflammatory transcript nuclear factor κB (NF-κB) and antioxidative gene transcript nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in peripheral blood mononuclear cells (PBMCs) with the tumor necrosis factor α (TNF-α) response after endotoxin stimulation and the clinical outcome of severely injured patients. METHODS: Thirty-two severe blunt trauma patients (injury severity score>16) with systemic inflammatory response syndrome were enrolled. Age- and sex-matched healthy persons were the controls. Patients' blood samples were obtained at 24 and 72 hours after injury. Peripheral blood mononuclear cells were isolated, and measurements for NF-κB p65 translocation, Nrf2 and phosphorylated inhibitory κB-α expressions, and TNF-α levels were assayed after endotoxin stimulation. RESULTS: In the trauma patients, TNF-α hyporesponse, depressed NF-κB p65 translocation, and phosphorylated inhibitory κB-α expression in PBMCs were found at 24 and 72 hours after injury; the Nrf2 expressions in PBMCs were not significantly different between patients and controls. The TNF-α levels had significant correlation with the NF-κB translocation and the trend of negative correlation with Nrf2 expression. Fifteen patients had critical injury (injury severity score≥25). Patients with critical injury had a lower NF-κB signal and a lower TNF-α response than did the counter group. Twelve patients developed organ failure; their Nrf2 expressions were significantly lower than those of patients without organ failure. CONCLUSIONS: The endotoxin hyporesponse associated with NF-κB and Nrf2 signal alternations in PBMCs of injured patients develops early after injury. The hyporesponse of PBMCs with a lower TNF-α level correlates with a lower NF-κB signal and is associated with critical injury, whereas a depressed Nrf2 expression in PBMCs is associated with later organ failure in trauma patients.

Parathyroidectomy for dialysis patients in the era of calcimimetics: The surgeons' point of view.

Calcimimetics is a new drug for lowering serum parathyroid hormone (PTH), calcium and phosphate in patients with hyperparathyroidism (HPT) on long-term dialysis. It became available on market in 2006. The impact of calcimimetics on the treatment by parathyroidectomy (PTx) was reviewed from the surgeons' point of view. Cure of renal HPT by calcimimetics is not feasible, but calcimimetics can improve preoperative cardiac ventricle ejection fractions by lowering serum PTH. Heart failure is not necessarily a contraindication for PTx. PTx should be done before irreversible organ damage occurs. Limb gangrenes is an ominous sign and should be prevented by frequent checkup for peripheral arterial circulation. The impact of renal osteodystrophy on the quality of life and as indirect cause of mortality deserves more attention in patients with renal HPT. Delayed referral to PTx leads to more complicated patients. A consensus between nephrologists and surgeons about propitious timing for PTx is necessary. Future prospect on the surgical treatment of renal HPT is proposed. Supplemental figure; http://links.lww.com/ASAIO/A782.

Usefulness of triggering receptor expressed on myeloid cells-1 in differentiating between typical and atypical community-acquired pneumonia.

OBJECTIVES: The purpose of this study is to investigate the clinical use of inflammatory marker triggering receptor expressed on myeloid cells (TREM)-1 at admission for differentiating between typical and atypical bacterial community-acquired pneumonia (CAP). METHODS: A prospective, noninterventional study of patients with CAP hospitalized through the emergency department was performed. Surface expression of TREM-1 was analyzed using flow cytometry on peripheral blood cells, and soluble TREM-1 (sTREM-1) concentration was determined in plasma. RESULTS: Eighty-eight patients with clinical suspicion of CAP were eligible. The causative pathogen was identified in 39 patients (44.3%). After excluding 4 mixed pneumonia cases, 21 typical and 14 atypical bacterial infections were enrolled. Patients with typical bacterial CAP demonstrated increased TREM-1 surface expression on monocytes and neutrophils. Median plasma sTREM-1 levels at admission were 65.2 pg/mL (range, 17.6-138.1 pg/mL) in patients with typical CAP and 25.9 pg/mL (range, 11.5-54.8 pg/mL) in patients with atypical CAP (P < .001). Soluble TREM-1 had good discriminative value to differentiate typical from atypical pathogens with an area under the receiver operating characteristic curve of 0.87 (95% confidence interval, 0.75-0.98). At a cutoff level of 44.2 pg/mL, sTREM-1 yielded a sensitivity of 81%, a specificity of 79%, a positive likelihood ratio of 3.79, and a negative likelihood ratio of 0.24. CONCLUSIONS: In newly admitted patients with CAP, determination of the TREM-1 levels may provide useful additional diagnostic information on the bacterial etiology.

Goiter disease in traditional Chinese medicine: Modern insight into ancient wisdom.

Goiter is a disease with history perhaps as long as human has been around. Almost all the available references are in Western language works of literature while information concerning the occurrence of goiter disease in ancient China and the comparison between the treatment in traditional Chinese medicine (TCM) with current Western medicine remains lacking. In this article, the description of goiter, the history of surgical intervention for goiter disease, and the general concept of goiter disease treatment in ancient China literature such as seaweed decoction and acupuncture analgesia for surgery were reviewed.

Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO.

The incidence of thyroid cancer increases with age, and it is twice in women as common as in men. The undifferentiated thyroid cancer (UTC) is the most aggressive of all thyroid cancers. Unfortunately, there are almost no efficacious therapeutic modalities. It is important to develop some new effective therapies. Evodiamine is a chemical extracted from a kind of Chinese herb named Wu-Chu-Yu and has been demonstrated to be effective in preventing the growth of a variety of cancer cells. In the present study, the mechanism by which evodiamine inhibited the undifferentiated thyroid cancer cell line ARO was examined. Based on 3-(4,5-dimethylthiazol -2-yle)2,5-diphenyltetrazolium bromide (MTT) assay, cell proliferation rate was reduced dose-dependently by evodiamine, but not by rutaecarpine. According to the flow cytometric analysis, evodiamine treatment resulted in G2/M arrest and DNA fragmentation in ARO cells. The G2/M arrest was accompanied with an increase of the expression of cdc25C, cyclin B1, and cdc2-p161 protein, and it was also with a decrease of the expression of cdc2-p15. Furthermore, by using the TUNEL assay, evodiamine-induced apoptosis was observed at 48 h and extended to 72 h. Western blotting demonstrated that evodiamine treatment induced the activation of caspase-8, caspase-9, caspase-3, and the cleavage of poly ADP-ribose polymerase (PARP). These results suggested that evodiamine inhibited the growth of the ARO cells, arrested them at M phase, and induced apoptosis through caspases signaling.

Spleen artery embolization aggravates endotoxin hyporesponse of peripheral blood mononuclear cells in patients with spleen injury.

BACKGROUND: : Spleen artery embolization (SAE) increases the success of nonoperative management of spleen injury; however, the immune alternation after SAE is unclear. This study searched the endotoxin responses of peripheral blood mononuclear cells (PBMCs) in injured patients who received SAE. METHODS: : Patients were subsequently enrolled when their spleen injuries were confirmed by computed tomographic scan. Peripheral blood samples were obtained within first, at third, fifth, and seventh postinjury days. PBMCs were isolated; nuclear factor (NF)-kB translocations, phosphorylated I-kB expressions, and in vitro tumor necrosis factor (TNF)-alpha levels were assayed after endotoxin stimulation (ES). RESULTS: : Sixteen patients who received nonoperative managements were enrolled. Five patients received SAE (embolized patients) and 11 patients did not (nonembolized patients). Compared with those in controls, NF-kB translocations, phosphorylated I-kB expressions, and TNF-alpha levels after ES decreased significantly early in injured patients. NF-kB translocation and TNF-alpha levels after ES were indifferent at seventh day between nonembolized patients and controls, whereas significantly lower NF-kB p65 translocation and TNF-alpha levels after ES were found at seventh postinjury day in embolized patients than in controls. Compared with nonembolized patients, embolized patients had significantly lower levels of NF-kBp50 translocations after ES from first to third postinjury days and lower levels of NF-kB p65 translocations, TNF-alpha, and phosphorylated I-kB expressions after ES from first to fifth postinjury days. CONCLUSIONS: : SAE dysregulates the NF-kB system and aggravates the cytokine hyporesponse upon ES of PBMCs in patients with spleen injury. These results implicate that SAE alters immune response and may increase susceptibility to infections in injured patients.

Diagnosis of unrecognized primary overt hypothyroidism in the ED.

OBJECTIVE: The aims of the study were to evaluate the incidence of newly diagnosed primary overt hypothyroidism among adults admitted through the emergency department (ED) and to assess how previously undiagnosed hypothyroidism presents. METHODS: From July 1, 2002 to June 30, 2006, 56 adult patients were enrolled for further analysis. RESULTS: The incidence of newly diagnosed primary overt hypothyroidism among adults admitted through the ED is 0.1%. The mean age of the patients was 75.8 ± 12.8 years (range, 27-98 years). Most of our patients presented in the winter. Individual symptoms and signs were not sensitive. Drugs (13 patients, 23%), nongoitrogenous autoimmune thyroiditis (12 patients, 21%), and previous surgery or irradiation related (11 patients, 20%) are frequent causes of unrecognized hypothyroidism in this iodine-replete region. Only 21% of patients were admitted with a correct initial impression. Half of myxedema coma patients were missed during the initial ED stay. Thirty-three patients (59%) had cardiomegaly on chest x-ray receiving further echocardiography examination. Pericardial effusion was found in 18 patients. Of these, 7 patients had moderate to large pericardial effusion, but none had cardiac tamponade. Only 6 patients have depressed left ventricular ejection fraction (<40%). CONCLUSIONS: The diagnosis of hypothyroidism is often missed during the ED evaluation of patients at risk for this uncommon disease. Hypothyroidism should always be considered in patients who present with nonspecific symptoms suggestive of the disease, including weakness, cold intolerance, and alterations in mental status, and receive drugs impairing thyroid function or treatment of advanced head and neck cancer. In addition, patients with stable chronic heart failure or unexplained pericardial effusion warrant serum thyroid testing.

Bajiaolian poisoning-a poisoning with high misdiagnostic rate.

BACKGROUND: One of the oldest Chinese herbal medicine, bajiaolian is widely used in traditional therapy. In Taiwan, bajiaolian is the fifth highest cause of poisoning among herbal medicines. The diagnosis is difficult because physicians are unfamiliar with this medicine's multiple presentations in different stages of intoxication. PROCEDURES: The records of 4 major poison centers in Taiwan were searched for all bajiaolian intoxication from July 1985 (the opening of first poison center) to March 2003. Two emergency physicians with toxicologic training reviewed the admission charts and visited case patients for follow-up. FINDINGS: Seventeen patients were identified, of which 15 (88.2%) had been misdiagnosed initially. In the beginning of their medical care, 14 cases were diagnosed as acute gastroenteritis. CONCLUSION: Bajiaolian intoxication is probably misdiagnosed because of early gastrointestinal symptoms followed by neurologic symptoms. A detailed patient history should be taken, and symptoms should be reviewed systemically to improve diagnostic accuracy.

Alternations of heart rate variability at lower altitude in the predication of trekkers with acute mountain sickness at high altitude.

OBJECTIVE: To determine the change and relationship of spectral components of heart rate variability (HRV) measurements in subjects with or without acute mountain sickness (AMS) at both low and high altitude. DESIGN: A prospective study. SETTING: A 12-day itinerary by trekking to the Namche Bazaar, 3440 m in Nepal. PARTICIPANTS: A total of 32 subjects were recruited. INTERVENTIONS: The alternations were measured by heart rate (HR), arterial oxygen saturation (SpO(2)), and spectral analysis of HRV at sea level, 1317 m, 3440 m, 1317 m, and sea level, respectively. MAIN OUTCOME MEASURES: Spectral analysis of HRV. RESULTS: There were statistically significant increases in HR and decreases in SpO(2) in all subjects at high altitude. In HRV, the values of R-R interval, total variance, high frequency (HF), low frequency (LF), and HF% were significantly lower at 3440 m than at sea level, respectively (P < 0.05). The subjects with AMS had significantly lower total variance, HF, and HF%, respectively, but higher LF:HF ratio (P < 0.05) at 3440 m. Subjects with both HF% < 20% (nu) and LF:HF ratio > 1.3 measured at 1317 m had odds ratios of 7.00 (95% confidence interval, 1.11 to 44.06; P = 0.047) to get AMS at 3440 m. CONCLUSIONS: The HRV measurements in total variances, HF, and HF% in trekkers with AMS were statistically significantly lower at high altitude. HF% < 20% (nu) or LF:HF ratio > 1.3 at lower altitudes could be an important predication parameter of trekkers with AMS at higher altitudes.

Emergency femoral hemodialysis catheter placement complicated by prevesical hematoma.

The femoral vein is the most popular location for temporary catheterization during emergency hemodialysis. Common complications are infection, thrombosis, arterial puncture, and groin hematoma. We report herein a patient with femoral vein perforation and prevesical hematoma.

Combination of peroxisome proliferator-activated receptor gamma and retinoid X receptor agonists induces sodium/iodide symporter expression and inhibits cell growth of human thyroid cancer cells.

BACKGROUND: Thyroid tumors are the most frequent neoplasm of the endocrine system. The major treatment is surgical intervention followed by radioiodine therapy. The sodium/iodide symporter (NIS) has positive expression in thyroid carcinomas with good prognoses and plays a critical role in radioiodine therapy response. Low expression of NIS always leads to tumor recurrence or treatment failure. Redifferentiation therapy is more tumor specific than chemotherapy. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists and retinoids are two types of redifferentiating agents. In this study, we examined whether the PPARγ agonist rosiglitazone and retinoid X receptor (RXR) agonist bexarotene could increase NIS expression and exhibit anticancer activity in human thyroid cancer cells. METHODS: Using a TCGA data set, we analyzed the expression of NIS (SLC5A5), PPARγ, and RXR in clinical thyroid tumors and assessed their correlations with the relapse-free survival (RFS) of thyroid tumor patients. Moreover, two human thyroid cancer cell lines, differentiated thyroid papillary BCPAP cells and follicular follicular thyroid cancer-131 cells, were treated with different concentrations of the PPARγ agonist rosiglitazone alone or in combination with the RXR agonist bexarotene. Cell growth was analyzed by the MTT assay. NIS protein expression was determined by Western blotting. RESULTS: From analysis of the TCGA data set, we found that thyroid tumors have lower expression of both NIS (SLC5A5) and PPARγ than nontumor controls. Higher expression levels of NIS, PPARγ, and RXR are associated with higher RFS in patients with thyroid tumors. Moreover, rosiglitazone treatment reduced cell growth and increased NIS protein expression in thyroid cancer cells under normoxic or hypoxic conditions. In addition, bexarotene potentiated the effects of rosiglitazone on cell growth and NIS protein expression. CONCLUSION: Our results suggest that the combination of PPARγ and RXR agonists has potential as a chemotherapeutic strategy for thyroid cancer.

Clodronate-induced cell apoptosis in human thyroid carcinoma is mediated via the P2 receptor signaling pathway.

Clodronate, a halogenated bisphosphonate, can inhibit the growth of human thyroid carcinoma (TC) cells. Previously, we found that a clodronate-induced Ca(2+) transient was correlated with clodronate-induced growth inhibition in TC cells. However, the details of the signaling process underlying the antiproliferative effect of clodronate on TC cells are not clear. In this study, we investigated the antiproliferative mechanism of clodronate on papillary TC (PTC) cells and xenotransplanted animals using a combination of pharmacological drugs. Reverse transcription-polymerase chain reaction analysis confirmed the endogenous expression of P2Y receptor isoforms in PTC cells. The P2 antagonist suramin not only inhibited the antiproliferative effect of clodronate and ATP on TC cells but also blocked all the Ca(2+) transients induced by clodronate and ATP. The release of Ca(2+) from the endoplasmic reticulum and membrane depolarization of mitochondria was observed during the clodronate-induced Ca(2+) transients. The results of terminal deoxynucleotidyltransferase dUTP nick-end labeling assays and flow cytometry with annexin V and caspase-3 staining suggest that both ATP and clodronate induce apoptosis. Significant inhibition of tumor invasion and colony formation was also observed in clodronate-treated PTC cells. We further demonstrated that only the cAMP inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), and not inhibitors of phospholipase C [1-[6-[[17beta-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122)] or store-operated Ca(2+) entry (2-aminoethyl diphenylborinate), can significantly reverse the effect of clodronate. Finally, in vivo animal and green fluorescent protein imaging studies further proved that the tumor inhibitory effect of clodronate on xenotransplanted CG3 cells can be reversed by treatment with suramin. In conclusion, we demonstrated that clodronate-induced PTC cell apoptosis and tumor inhibition are partially mediated by the P2Y receptor-cAMP cascade.

Specific activation of sodium iodide symporter gene in hepatoma using alpha-fetoprotein promoter combined with hepatitis B virus enhancer (EIIAPA).

BACKGROUND: This study aimed to develop a novel tumor-specific promoter gene linking sodium iodide symporter (NIS) gene to specifically target hepatocellular carcinoma in a mouse tumor model. MATERIALS AND METHODS: A tumor-specific chimeric promoter for alpha-fetoprotein gene (AFP) was combined with hepatitis B virus (HBV) enhancer II to investigate radioiodine uptake in vitro and in vivo in hepatoma (HepG2) and nonhepatoma (ARO) cell lines after transfer of hNIS gene. A lentiviral vector carrying the hNIS gene was employed in vitro and in vivo. Radionuclide imaging was acquired for 30 min at 60 min after administration of 1241 to monitor hNIS gene expression in vivo using microPET. RESULTS: The highest radioiodide uptake of ARO and HepG2 clones which stably expressed hNIS gene were 87- and 208-fold higher than that of parental cells, respectively. After infection of lentivirus, hNIS gene controlled by cytomegavirus (CMV) promoter was expressed in both ARO and HepG2 cells, and hNIS gene induction by EIIAPA promoter was higher than by CMV promoter in HepG2 cells but not in ARO cells. A similar result was observed in vivo, hNIS controlled by CMV promoter was highly expressed in both HepG2 and ARO tumors. The HepG2 tumor multi-infected with LV-EIIAPA-hNIS virus specifically, but the ARO tumor did not activate the EIIAPA promoter and further express the hNIS protein. CONCLUSION: Transduction of the hNIS gene controlled by the novel EIIAPA chimeric promoter successfully induces iodide transport in hepatoma.

Potentially inappropriate medication for emergency department visits by elderly patients in Taiwan.

PURPOSE: The potential for adverse drug events caused by potentially inappropriate medication (PIM) use in elderly patients at emergency department (ED) visits is a growing concern. The objects of this study were to determine the prevalence, characteristics and risk factors of PIM use among elderly ED visits in Taiwan. METHODS: The nationwide computerized claims database of elderly ED visits under the National Health Insurance (NHI) in Taiwan during 2001-2004 was accessed. PIM, independent of diseases diagnoses or conditions and should be generally be avoided in elderly people, was evaluated using the updated 2003 Beers criteria. RESULTS: Between 2001 and 2004, 14.7% of total 1 429 463 elderly ED visits with prescriptions had PIM, and 19.3% of elderly people who visited ED received at least one PIM annually. Odds ratio for PIM prescriptions to ED elderly was higher for visits at which more drugs were prescribed, visits at local community hospital, female and older physicians, patients aged 65-69 years and female patients. Common PIM categories were short acting nifedipine, muscle relaxants and anti-spasmodics, antihistamines and ketorolac. When health care resource utilization was compared in 2004, subjects receiving PIM at ED visit had significantly more mean ambulatory care visits, ED visits and hospital admissions than subjects who did not receive PIM. CONCLUSIONS: About one fifth of elderly people who visited ED received PIM annually in Taiwan. The public and physicians should be educated, and a computerized drug surveillance system might be needed to avoid PIM prescriptions to the ED elderly patients.

The management of high-risk patients with primary hyperparathyroidism - minimally invasive parathyroidectomy vs. medical treatment.

OBJECTIVE: Parathyroidectomy (PTx) for high-risk primary hyperparathyroidism (PHPT) patients poses a surgical challenge. We hypothesize that a minimally invasive parathyroidectomy (MIP) under local anaesthesia may minimize the perioperative risks and facilitate easier clinical care than medical treatment for these patients. DESIGN AND PATIENTS: We performed a prospective, nonrandomized, controlled study of 33 PHPT patients evaluated as poor general anaesthesia risks. The outline of the diseased parathyroids and the thyroid were mapped by Tc(99m) sestamibi scan and focused sonogram. MIPs were performed under local anaesthesia (group 1, 19 patients). Medical treatment with bisphosphonates was continued for patients refusing operation (group 2, 14 patients). MEASUREMENTS: Serum Ca, PO(4), and i-PTH were measured the following morning, every 6 months in the first postoperative year and then yearly for group 1 patients, or every 3 months for group 2 patients. American Society of Anaesthesiologists (ASA) and New York Heart Association (NYHA) class designations were re-evaluated every 3 months. RESULTS: In group 1, there were no operative complications, mortality or recurrent hypercalcaemia during a mean follow-up of 35.5 months. Group 2 patients had a significantly higher incidence of episodes of hypercalcaemic crisis, deteriorating renal function and weight-bearing bone fractures, while group 1 patients had a higher incidence of improved ASA and NYHA class, better 3-year overall survival rate (83.1%vs. 60.8%, P = 0.032), and less medical costs. CONCLUSION: MIP can be safely performed under local anaesthesia and it facilitates clinical care in high-risk PHPT patients. It is recommended for those selected by image localization.