bluuebunny/crossref_metadata_2025 huggingface dataset:
A gastrin precursor, gastrin‐gly, upregulates VEGF expression in colonic epithelial cells through an HIF‐1‐independent mechanism
Authors: Bertrand Claudine , Kowalski‐Chauvel Aline , Do Catherine , Résa Cécile , Najib Souad , Daulhac Laurence , Wang Timothy C. , Ferrand Audrey , Seva Catherine
Published: October 2009

One of the major angiogenic factor released by tumor cells is VEGF. Its high expression is correlated with poor prognosis in colorectal tumors. In colon cancer, gastrin gene expression is also upregulated. In these tumors, gastrin precursors are mainly produced and act as growth factors. Recently, a study has also shown that the gastrin precursor, G‐gly induced in vitro tubules formation by vascular endothelial cells suggesting a potential proangiogenic role. Here, we demonstrate that stimulation of human colorectal cancer cell lines with G‐gly increases the expression of the proangiogenic factor VEGF at the mRNA and protein levels. In addition, blocking the progastrin autocrine loop leads to a downregulation of VEGF. Although HIF‐1 is a major transcriptional activator for VEGF our results suggest an alternative mechanism for VEGF regulation in normoxic conditions, independent of HIF‐1 that involves the PI3K/AKT pathway. Indeed we show that G‐gly does not lead to HIF‐1 accumulation in colon cancer cells. Moreover, we found that G‐gly activates the PI3K/AKT pathway and inhibition of this pathway reverses the effects of G‐gly observed on VEGF mRNA and protein levels. In correlation with these results, we observed in vivo, on colon tissue sections from transgenic mice overexpressing G‐gly, an increase in VEGF expression in absence of HIF‐1 accumulation. In conclusion, our study demonstrates that gastrin precursors, known to promote colon epithelial cells proliferation and survival can also contribute to the angiogenesis process by stimulating the expression of the proangiogenic factor VEGF via the PI3K pathway and independently of hypoxia conditions.
CHEK2 mutations and HNPCC‐related colorectal cancer
Authors: Suchy Janina , Cybulski Cezary , Wokołorczyk Dominika , Oszurek Oleg , Górski Bohdan , Dębniak Tadeusz , Jakubowska Anna , Gronwald Jacek , Huzarski Tomasz , Byrski Tomasz , Dziuba Ireneusz , Gogacz Marek , Wiśniowski Rafał , Wandzel Piotr , Banaszkiewicz Zbigniew , Kurzawski Grzegorz , Kładny Józef , Narod Steven A. , Lubiński Jan
Published: October 2009

Recently, the 1100delC variant of cell cycle checkpoint kinase 2 (CHEK2) has been reported to confer a colorectal cancer risk in hereditary non‐polyposis‐colorectal cancer (HNPCC) and HNPCC‐related families in the Netherlands. To investigate whether CHEK2 mutations confer increased cancer risk in HNPCC and HNPCC‐related families in Poland, we genotyped 463 probands from HNPCC and HNPCC‐related families, and 5,496 controls for 4 CHEK2 alleles (1100delC, IVS2+1G>A, del5395, I157T). All 463 probands were screened for mutations in the HNPCC‐related genes MSH2, MLH1 and MSH6. A positive association was observed for HNPCC‐related cancer and the I157T missense CHEK2 mutation (OR = 1.7; p = 0.007), but not for the truncating alleles (OR = 1.0; p = 1.0). The association with the I157T was seen both for the 117 cases who fulfill Amsterdam criteria (OR = 1.9; p = 0.1) and for the 346 cases who do not fulfill the criteria (OR = 1.6; p = 0.03). One hundred forty‐five of the 463 families had a mutation in MSH2, MLH1 or MSH6 (MMR‐positive families). A positive association between the CHEK2 I157T mutation and HNPCC‐related cancer was observed only for MMR‐negative cases (OR = 2.1; p = 0.0004), but not for MMR‐positive cases (OR = 0.8; p = 0.9). The association with I157T was particularly strong for MMR‐negative cases with familial colorectal cancer (2 or more first‐degree relatives affected) (OR = 2.5; p < 0.0001). We conclude that the I157T variant of CHEK2 increases the risk of colorectal cancer among MMR‐negative, HNPCC/HNPCC‐related families in Poland.
Achievements and future of nutritional cancer epidemiology
Authors: Miller Anthony B. , Linseisen Jakob
Published: October 2009

We consider some of the earlier work and some recent results on diet and cancer (since the 2007 WCRF/AICR report on Diet and Cancer), discuss challenges facing nutritional cancer epidemiology, and consider the field from the perspective of the need to apply what we know in cancer control. We highlight 2 current difficulties; first, we are uncertain on the stage of carcinogenesis on which many nutritional factors act, second, we often do not know what dose of a nutritional factor is needed to achieve its expected protective effect in humans. Part of the difficulty is the measurement error associated with food frequency questionnaires. Calibration studies (as in the European Prospective Investigation on diet and Cancer) have helped to reduce this, and pooled studies have helped to clarify associations. However, there is too little work on new biomarkers of nutrition; with the new techniques available (especially proteomics, and metabolomics) it should be possible to identify more and better biomarkers that could be used in repeated blood or urine samples and give very good information on diet. In cancer control we need to determine how to reduce the prevalence of obesity and increase physical activity in populations, not whether they are causal factors. This could be achieved by community‐based interventions linked to some of the new cohort studies being initiated. We conclude we have reached the stage in nutritional cancer epidemiology where we need to concentrate more on applying the lessons we have learnt, than in seeking new aetiological associations.
Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer
Authors: Huang Zhaohui , Huang Dan , Ni Shujuan , Peng Zhilei , Sheng Weiqi , Du Xiang
Published: October 2009

MicroRNA (miRNA) opens up a new field for molecular diagnosis of cancer. However, the role of circulating miRNAs in plasma/serum in cancer diagnosis is not clear. The aim of this study was to investigate whether plasma miRNAs can be used as biomarkers for the early detection of colorectal carcinoma (CRC). We measured the levels of 12 miRNAs (miR‐134, −146a, −17‐3p, −181d, −191, −221, −222, −223, −25, −29a, −320a and −92a) in plasma samples from patients with advanced colorectal neoplasia (carcinomas and advanced adenomas) and healthy controls using real‐time RT‐PCR. We found that plasma miR‐29a and miR‐92a have significant diagnostic value for advanced neoplasia. MiR‐29a yielded an AUC (the areas under the ROC curve) of 0.844 and miR‐92a yielded an AUC of 0.838 in discriminating CRC from controls. More importantly, these 2 miRNAs also could discriminate advanced adenomas from controls and yielded an AUC of 0.769 for miR‐29a and 0.749 for miR‐92a. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.883 with 83.0% sensitivity and 84.7% specificity in discriminating CRC, and AUC of 0.773 with 73.0% sensitivity and 79.7% specificity in discriminating advanced adenomas. Collectively, these data suggest that plasma miR‐29a and miR‐92a have strong potential as novel noninvasive biomarkers for early detection of CRC.
Beta‐carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials
Authors: Druesne‐Pecollo Nathalie , Latino‐Martel Paule , Norat Teresa , Barrandon Emilie , Bertrais Sandrine , Galan Pilar , Hercberg Serge
Published: October 2009

The effect of beta‐carotene supplementation on cancer incidence has been investigated in several randomized controlled trials. The objective was to review the effect of beta‐carotene supplementation on cancer incidence in randomized trials by cancer site, beta‐carotene supplementation characteristics and study population. Relevant trials were retrieved by searching PubMed (up to April 2009). Authors involved in selected studies were contacted for additional information. Thirteen publications reporting results from 9 randomized controlled trials were included. Overall, no effect of beta‐carotene supplementation was observed on the incidence of all cancers combined (RR, 1.01; 95% CI, 0.98–1.04), pancreatic cancer (RR, 0.99; 95% CI, 0.73–1.36), colorectal cancer (RR, 0.96; 95% CI, 0.85–1.09), prostate cancer (RR, 0.99; 95% CI, 0.91–1.07), breast cancer (RR, 0.96; 95% CI, 0.85–1.10), melanoma (RR, 0.98; 95% CI, 0.65–1.46) and non melanoma skin cancer (RR, 0.99; 95% CI, 0.93–1.05). The incidence of lung and stomach cancers were significantly increased in individuals supplemented with beta‐carotene at 20–30 mg day−1 (RR, 1.16; 95% CI, 1.06–1.27 and RR, 1.34; 95% CI, 1.06–1.70), in smokers and asbestos workers (RR, 1.20; 95% CI, 1.07–1.34 and RR, 1.54; 95% CI, 1.08–2.19) compared to the placebo group. Beta‐carotene supplementation has not been shown to have any beneficial effect on cancer prevention. Conversely, it was associated with increased risk not only of lung cancer but also of gastric cancer at doses of 20–30 mg day−1, in smokers and asbestos workers. This study adds to the evidence that nutritional prevention of cancer through beta‐carotene supplementation should not be recommended.
pH‐dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity
Authors: De Milito Angelo , Canese Rossella , Marino Maria Lucia , Borghi Martina , Iero Manuela , Villa Antonello , Venturi Giulietta , Lozupone Francesco , Iessi Elisabetta , Logozzi Mariantonia , Mina Pamela Della , Santinami Mario , Rodolfo Monica , Podo Franca , Rivoltini Licia , Fais Stefano
Published: October 2009

Metastatic melanoma is associated with poor prognosis and still limited therapeutic options. An innovative treatment approach for this disease is represented by targeting acidosis, a feature characterizing tumor microenvironment and playing an important role in cancer malignancy. Proton pump inhibitors (PPI), such as esomeprazole (ESOM) are prodrugs functionally activated by acidic environment, fostering pH neutralization by inhibiting proton extrusion. We used human melanoma cell lines and xeno‐transplated SCID mice to provide preclinical evidence of ESOM antineoplastic activity. Human melanoma cell lines, characterized by different mutation and signaling profiles, were treated with ESOM in different pH conditions and evaluated for proliferation, viability and cell death. SCID mice engrafted with human melanoma were used to study ESOM administration effects on tumor growth and tumor pH by magnetic resonance spectroscopy (MRS). ESOM inhibited proliferation of melanoma cellsin vitroand induced a cytotoxicity strongly boosted by low pH culture conditions. ESOM‐induced tumor cell death occurredviarapid intracellular acidification and activation of several caspases. Inhibition of caspases activity by pan‐caspase inhibitor z‐vad‐fmk completely abrogated the ESOM‐induced cell death. ESOM administration (2.5 mg kg−1) to SCID mice engrafted with human melanoma reduced tumor growth, consistent with decrease of proliferating cells and clear reduction of pH gradients in tumor tissue. Moreover, systemic ESOM administration dramatically increased survival of human melanoma‐bearing animals, in absence of any relevant toxicity. These data show preclinical evidence supporting the use of PPI as novel therapeutic strategy for melanoma, providing the proof of concept that PPI target human melanoma modifying tumor pH gradients.
Therapy‐induced antitumor vaccination in neuroblastomas by the combined targeting of IL‐2 and TNFα
Authors: Balza Enrica , Carnemolla Barbara , Mortara Lorenzo , Castellani Patrizia , Soncini Debora , Accolla Roberto S. , Borsi Laura
Published: October 2009

L19‐IL2 and L19TNFα are fusion proteins composed of L19(scFv), specific for the angiogenesis‐associated ED‐B containing fibronectin isoform and IL‐2 or TNFα. Because of the tumor targeting properties of L19, IL‐2 and TNFα concentrate at therapeutic doses at the tumor vascular level. To evaluate the therapeutic effects of L19‐IL2 and L19mTNFα in neuroblastoma (NB)‐bearing mice, A/J mice bearing Neuro2A or NIE115 NB were systemically treated with L19‐IL2 and L19mTNFα, alone or in combination protocols. Seventy percent of Neuro2A‐ and 30% of NIE115‐bearing mice were cured by the combined treatment with L19‐IL2 and L19mTNFα, and further rejected a homologous tumor challenge, indicating specific antitumor immune memory. The immunological bases of tumor cure and rejection were studied. A highly efficient priming of CD4+T helper cells and CD8+CTL effectors was generated, paralleled by massive infiltration in the tumor tissue of CD4+and CD8+T cells at day 16 after tumor cell implantation, when, after therapy, tumor volume was drastically reduced and tumor necrosis reached about 80%. The curative treatment resulted in a long‐lasting antitumor immune memory, accompanied by a mixed Th1/Th2 type of response. Concluding, L19‐IL2 and L19mTNFα efficiently cooperate in determining a high percentage of NB cure that, in our experimental models, is strongly associated to the generation of adaptive immunity involving CD4+and CD8+T cells.
PSMD9 gene in the NIDDM2 locus is linked to type 2 diabetes in Italians
Authors: Gragnoli Claudia
Published: October 2009

Type 2 diabetes (T2D) has a replicated linkage on chromosome12q24.2, the non‐insulin‐dependent‐diabetes 2 (NIDDM2) locus. PSMD9 (which rarely causes T2D in Italians) lies in the NIDDM2 region and is implicated in beta cell insulin transcription and diabetes onset in mice. Thus, PSMD9 is a candidate T2D gene for the NIDDM2 locus. We aimed at identifying any linkage of the PSMD9 A/T/G haplotype, or of any of its single variants, to Italian T2D siblings/families. We screened 201 T2D siblings/families for PSMD9 variants and performed a parametric and non‐parametric linkage study, including linkage disequilibrium (LD) modeling and simulation analyses. Our results show a consistent significant LOD score in linkage with T2D for each single PSMD9 SNP variant (IVS3 + nt460A, P = 3.546E − 007, IVS3 + nt437T, P = 7.723E − 008, and 197G, P = 4.921E − 007) and for the haplotype (A/T/G for the above‐cited variants, P = 3.078E − 015) using the non‐parametric analysis, as well as the LD modeling test (P = 4.178E − 009) and the parametric linkage analysis. The strongest signal is present under the recessive model (P = 4.905E − 011). Our statistical power in the present study relies on the presence of T2D affected siblings, which represent an ideal dataset to identify linkage with a recessive disease model. Our 1,000 simulation analyses, performed for each single test, confirm that the results are not due to random chance. In summary, the A/T/G haplotype in PSMD9 is linked via the recessive allelic model to T2D in Italians. By our observation and testing, the linkage strategy can identify a gene contributing to T2D in a homogeneous subject dataset. J. Cell. Physiol. 222: 265–267, 2010. © 2009 Wiley‐Liss, Inc.
Dexamethasone counteracts the anti‐osteoclastic, but not the anti‐leukemic, activity of TNF‐related apoptosis inducing ligand (TRAIL)
Authors: Zauli Giorgio , Rimondi Erika , Celeghini Claudio , Milani Daniela , Secchiero Paola
Published: October 2009

We have analyzed the effect of the synthetic glucocorticoid dexamethasone, used alone or in combination with recombinant TRAIL, on in vitro osteoclastic differentiation of peripheral blood‐derived macrophages cultured in the presence of macrophage‐colony stimulating factor (M‐CSF) + RANKL for 12–14 days. Dexamethasone exhibited different effects based on the concentration used. Indeed, while at 10−7 M dexamethasone reduced the number of mature osteoclasts, at 10−8 M showed no significant effects and at 10−9 M significantly increased the number of mature osteoclasts, with respect to cells cultured with only M‐CSF + RANKL. On the other hand, the addition in culture of recombinant TRAIL inhibited the output of mature osteoclasts induced by M‐CSF + RANKL. However, the presence of dexamethasone (10−8 or 10−9 M) into the culture medium significantly counteracted the anti‐osteoclastic activity of TRAIL. In order to ascertain whether dexamethasone, might also interfere with the anti‐leukemic activity of TRAIL, the degree of apoptosis induced by TRAIL was evaluated in several myeloid (OCI, MOLM, HL‐60) and lymphoid (SKW6.4, MAVER, BJAB) leukemic cell lines. The levels of TRAIL‐triggered apoptosis were not significantly different between leukemic cells cultured in the absence or presence of dexamethasone. Concerning the molecular mechanism mediating the dexamethasone‐suppression of the TRAIL activity in pre‐osteoclasts, but not in leukemic cells, we found that dexamethasone induced a significant down‐regulation of the surface levels of TRAIL‐R2 in cells of the osteoclastic lineage but not in leukemic cells. The ability of dexamethasone to counteract the TRAIL pathway envisions a novel mechanism mediating the pro‐osteoclastic activity of dexamethasone in vivo. J. Cell. Physiol. 222: 357–364, 2010. © 2009 Wiley‐Liss, Inc.
The role of PET CT to evaluate the response to neoadjuvant chemotherapy in advanced breast cancer: Comparison with ultrasonography and magnetic resonance imaging
Authors: Choi Jae Hyuck , Lim Hye In , Lee Se Kyung , Kim Wan Wook , Kim Sang Min , Cho EunYoon , Ko Eun Young , Han Boo‐Kyung , Park Yeon Hee , Ahn Jin‐Seok , Im Young‐Hyuck , Lee Jeong Eon , Yang Jung‐Hyun , Nam Seok Jin
Published: October 2009

Background

Recently PET is emerged as a method to estimate the response of neoadjuvant chemotherapy (NAC) in advanced breast cancer. This study is aimed to estimate the predictive role of PET CT and other imaging modalities (ultrasound, MRI) through NAC.

Methods

PET CT was acquired before and after NAC from 41 patients. Pathologic results were classified as pathological complete response (pCR) and non‐pCR. The results of clinical responses were assessed with imaging indexes (postTx, postchemotherapy size or peak standardized uptake values (pSUV); delta, the size difference between treatment; RR, reduction rate of tumor size or pSUV), and they were compared with pathologic results.

Results

Seven patients (17.1%) showed pCR. As a result of comparison of the image index, all image indexes of MRI were predictive for pCR (P < 0.05). In contrast, only delta and RR of US, RR of PET CT were significant. The area under curve of delta and RR in MRI were higher (0.91, 0.90) than US (0.83, 0.80) and PET CT (0.62, 0.72). The MRI is superior to the US or PET CT.

Conclusions

We have concluded that the MRI is better than PET CT for monitoring the effect of NAC in advanced breast cancer. J. Surg. Oncol. 2010;102:392–397. © 2009 Wiley‐Liss, Inc.
Extra‐abdominal desmoid tumors: A report of 234 cases
Authors: Mankin Henry J. , Hornicek Francis J. , Springfield Dempsey S.
Published: October 2009

Background/Objectives

To report on the clinical presentation and outcome for 234 patients with extra‐abdominal desmoids tumors.

Methods

Since 1977, the authors have treated 234 patients with extra‐abdominal desmoid tumors. The patients had an average age of 36.7 and 61% were female. The tumors arose adjacent to muscles or bones and the largest number were in the foot, shoulder thigh and calf. All of the patients were treated by primary surgery. Thirty‐seven had additional radiation and eight had chemotherapy.

Results

Local recurrence occurred in 39 patients and 23% of the patients required additional surgery. Of great concern were 24 patients who developed multiple sites metachronously, which required further surgery and in many cases caused disability. None of the patients died of disease but 5 required amputations.

Conclusions

The authors concluded that despite the benign nature of the disease, these patients are difficult to treat and the results are sometimes considerably less than optimal. J. Surg. Oncol. 2010;102:380–384. © 2009 Wiley‐Liss, Inc.
PEG enhances viral clearance on ceramic hydroxyapatite
Authors: Snyder Mark A. , Ng Paul , Mekosh Heather , Gagnon Pete
Published: October 2009

Viral clearance across ceramic hydroxyapatite (CHT™) was examined in two elution systems: sodium chloride and sodium chloride plus poly(ethylene glycol) (PEG). In both cases clearance of xenotropic murine leukemia virus was significant (3–4 log) while that of minute virus of mice varied between 1.7 and 2.7 log; in addition, the addition of PEG to the elution buffer enhanced viral clearance. The data are in agreement with the previous results and demonstrate that additional clearance can be obtained by adding PEG to a ceramic hydroxyapatite buffer system.
Food analysis: A continuous challenge for miniaturized separation techniques
Authors: Asensio‐Ramos María , Hernández‐Borges Javier , Rocco Anna , Fanali Salvatore
Published: October 2009

One of the current trends of modern analytical chemistry is the miniaturization of the various tools daily used by a large number of researchers. Ultrafast separations, consumption of small amounts of both samples and reagents as well as a high sensitivity and automation are some of the most important goals desired to be achieved. For many years a large number of research laboratories and analytical instrument manufacturing companies have been investing their efforts in this field, which includes miniaturized extraction materials, sample pre‐treatment procedures and separation techniques. Among the separation techniques, capillary electromigration methods (which also include CEC), microchip and nano‐LC/capillary LC have received especial attention. Besides their well‐known advantages over other separation tools, the role of these miniaturized techniques in food analysis is still probably in an early stage. In fact, applications in this field carried out by CEC, microchip, nano‐LC and capillary LC are only a few when compared with other more established procedures such as conventional GC or HPLC. The scope of this review is to gather and discuss the different applications of such miniaturized techniques in this field. Concerning CE, microchip‐CE and CEC works, emphasis has been placed on articles published after January 2007.
A multiresidual method for the simultaneous determination of the main glycoalkaloids and flavonoids in fresh and processed tomato (Solanum lycopersicum L.) by LC‐DAD‐MS/MS
Authors: Dall'Asta Chiara , Falavigna Claudia , Galaverna Gianni , Sforza Stefano , Dossena Arnaldo , Marchelli Rosangela
Published: October 2009

A new multiresidual LC‐DAD‐MS/MS method for the simultaneous detection of the major flavonoids and glycoalkaloids occurring in tomatoes has been developed and applied to the characterization of seven varieties of raw tomatoes grown in Italy and to their processed products. The new method allowed to determine rapidly the concentration of these secondary metabolites in a single analysis, showing that their content can be quite variable among the different varieties considered. On the contrary, a great depletion in glycoalkaloids and flavonoids is observed after processing, probably due to the harsh thermal treatment, which prevents the recognition of the varieties in the processed products.
Comprehensive two‐dimensional GC after HPLC preseparation for the characterization of aromatic hydrocarbons of mineral oil origin in contaminated sunflower oil
Authors: Biedermann Maurus , Grob Koni
Published: October 2009

Many foods are contaminated with mineral oil at concentrations in the order of or above 10 mg/kg. Often, these mineral oils are of technical grade and contain around 20–30% aromatic hydrocarbons, as previously shown by an on‐line HPLC‐GC‐flame ionization detection method for determining in foods the sum of the mineral oil aromatic hydrocarbons (ranging from 1 to at least 5 aromatic rings). Now, a comprehensive two‐dimensional GC (GC×GC) method was added for characterizing these aromatics by ring number and degree of alkylation. In contrast to the polycyclic aromatic hydrocarbons originating from pyrolysis, mineral oil aromatic hydrocarbons are highly alkylated and form extremely complex mixtures. Through MS and addition of standards, sectors in the GC×GC plots were allocated to 1 to 5 ring aromatics in order to estimate the relative abundance of each group. The quantitative composition is approximated by integration of 2nd dimension chromatograms laid as a grid over the three‐dimensional hump of unresolved hydrocarbons of the GC×GC‐flame ionization detection plot. The procedure is applied to Ukrainian sunflower oils contaminated with mineral oil.
Blind analysis of fortified pesticide residues in carrot extracts using GC‐MS to evaluate qualitative and quantitative performance
Authors: Lehotay Steven J. , Gates Robert A.
Published: October 2009

Unlike quantitative analysis, which must commonly undergo an extensive method validation process in labs to assure quality of results, the quality of the qualitative results in the analysis of pesticide residues in food is generally ignored in practice. Instead, chemists tend to rely on advanced MS techniques and general subjective guidelines or fixed acceptability criteria when making analyte identifications. All analytes and matrices have unique characteristics that make this current approach less effective than desirable in many real‐world situations. Just as performed in quantitative method validation studies, collection of distinguishing factors of selectivity versus concentration, such as analyte retention time variabilities, ion ratios, matrix background evaluations, choice of ions, and the number of ions to use, provides specific information about the particular application to assess its quality. Empirical analysis of many blind samples to check the rates of false positives and negatives should be performed, at least to better evaluate LOD and reduce the chances of a serious qualitative problem. Familiarization training and review of results by the analyst(s) increase performance, and in any case, the traditional use of two independent analyses should still be relied upon to make chemical confirmations. In this study, an experimental approach to evaluate GC‐MS using SIM with a quadrupole instrument and an MS/MS (ion trap) was conducted to assess the qualitative factors of both methods for 16 pesticides fortified (or not) in carrot extracts. Rates of false positives and negatives were compared using different identification criteria, and no single set of conditions was found to be superior for all analytes.
Orthogonality of silver‐ion and non‐aqueous reversed‐phase HPLC/MS in the analysis of complex natural mixtures of triacylglycerols
Authors: Holčapek Michal , Velínská Hana , Lísa Miroslav , Česla Petr
Published: October 2009

The goal of this work is the study of possibilities of two basic separation modes used in the analysis of complex triacylglycerol (TG) samples of plant oils and animal fats, i.e. non‐aqueous reversed‐phase (NARP) and silver‐ion HPLC coupled with atmospheric pressure chemical ionization mass spectrometry (APCI‐MS). The orthogonality of both separation modes is tested for complex TG mixtures containing fatty acids (FAs) with different acyl chain lengths, different number, positions and geometry of double bonds (DBs) and different regioisomeric positions of FAs on the glycerol skeleton. The retention in NARP mode is governed by the equivalent carbon number, while the retention in silver‐ion chromatography increases with the increasing number of DBs with a clear differentiation between cis‐ and trans‐FAs. Moreover, silver‐ion mode enables at least the partial resolution of regioisomeric TG mixtures including cis‐/trans‐regioisomers, as illustrated on two examples of randomization mixtures. Off‐line 2D coupling of both complementary modes (NARP in the first dimension and silver‐ion in the second dimension) yields the superior chromatographic selectivity resulting in the highest number of identified TGs ever reported for studied samples. Off‐line 2D chromatograms are processed with the home‐made software providing various ways of data visualization.
Simultaneous determination of avermectins in bovine tissues by LC‐MS/MS
Authors: Inoue Koichi , Yoshimi Yukiko , Hino Tomoaki , Oka Hisao
Published: October 2009

Analytical method for the simultaneous quantification of avermectins (AVMs), abamectin B1a, abamectin 8,9‐Z isomer B1a, emamectine benzoate B1a, emamectine benzoate 8,9‐Z isomer B1a, ivermectin, eprinomectin B1a, doramectin and moxidectin in bovine tissues (muscle, liver and fat) was developed by LC‐MS/MS in electrospray positive ion mode. The separation was achieved on a short TSK‐GEL ODS 100V column with the mobile phase consisting of acetonitrile and aquatic 0.1 mM ammonium formate containing 0.1% formic acid v/v at a flow rate of 0.2 mL/min with gradient elution. Liquid–liquid extraction with isooctane was used for the sample extraction/preparation of analytes in bovine samples. The linearity of the calibration curves was excellent in matrix‐matched standards, and yielded the coefficients (r2=0.997–0.999, range from LOQ to 500, 1000 or 5000 ng/g) of determination of the target analytes. Recoveries were in the range of 87.9–99.8% with associated precision values (within‐day: 1.5–7.4%, n=6, and between‐day: 1.5–8.4% for 3 days) for repeatability and reproducibility. LC‐MS/MS method has been proven to be highly efficient and suitable for the simultaneous determinations of eight AVMs in bovine tissue samples.
Determination of hexabromocyclododecane isomers in sewage sludge by LC‐MS/MS
Authors: García‐Valcárcel Ana Isabel , Tadeo José Luis
Published: October 2009

A method has been developed to determine α, β and γ diastereoisomers of hexabromocyclododecane (HBCD), a brominated flame retardant, in sewage sludge, based on the ultrasonic‐assisted extraction (UAE) of samples with dichloromethane–ACN (1:1) and the subsequent clean‐up of extracts by dispersive solid phase extraction with primary–secondary amine. Levels of HBCD diastereoisomers were determined by LC coupled with ESI MS/MS. Evaluation of the matrix effect showed a high ion suppression for all the diastereoisomers studied, which was counteracted by using a mixture of labelled HBCD diastereoisomers as internal standards. This method yielded recoveries in the range of 79.6–112.5% with SDs equal or lower than 9.1 The limits of detection were 0.3 ng/g for α‐ and β‐HBCD and 0.2 ng/g for γ‐HBCD. The developed method was successfully applied to 19 sludge samples collected from the province of Madrid (Spain). In most of the samples, β‐HBCD was below the method detection limit, whereas α‐ and γ‐HBCD were quantified in all of the sludge samples, and γ‐HBCD was the predominant diastereoisomer in 63% of the analyzed samples and α‐HBCD predominated in the rest.
Temperature‐controlled ionic liquid‐dispersive liquid‐phase microextraction for preconcentration of chlorotoluron, diethofencarb and chlorbenzuron in water samples
Authors: Zhou Qingxiang , Zhang Xiaoguo , Xie Guohong , Xiao Junping
Published: October 2009

This article describes a new, rapid and sensitive method for the determination of chlorotoluron, diethofencarb and chlorbenzuron from water samples with temperature‐controlled ionic liquid‐dispersive liquid‐phase microextraction. In the preconcentration procedure, ionic liquid 1‐hexyl‐3‐methylimidazolium hexafluorophosphate [C6MIM] [PF6] was employed as the extraction solvent. The parameters, such as volume of [C6MIM] [PF6], sample pH, extraction time, centrifuging time, temperature and salting‐out effect, were investigated in detail. Under the optimal extraction conditions, it has been found that three analytes had excellent LODs (S/N=3) in the range of 0.04–0.43 μg/L. The RSDs (n=6) were in the range of 1.3–4.7%. The proposed method was evaluated with lake water, tap water and melted snow water samples. The experimental results indicated that the proposed method had excellent prospect and would be widely used in the future.
Tourism, health and income in Singapore
Authors: Lee Chew Ging , Hung Woan Ting
Published: October 2009

This paper employs Granger causality test to investigate the long‐run and the short‐run dynamic interactions among tourism, economic development and health care development in Singapore. The test reveals that there is long‐run unidirectional Granger causality from health care development to economic development and from tourism to economic development. Both health care and tourism have positive effects on economic development in the long run. In the short run, there is a unidirectional Granger causality from economic development to health care development and a bidirectional causality between health care development and tourism. Copyright © 2009 John Wiley & Sons, Ltd.
The holiday happiness curve: a preliminary investigation into mood during a holiday abroad
Authors: Nawijn Jeroen
Published: October 2009

We take holidays for pleasure, but how well do we actually feel during our holiday? This question was addressed in a study of 481 international tourists in the Netherlands, who answered questions about their mood of the day and about their satisfaction with life in general. Average mood appears to be high. Mood was somewhat lower among people who were in the first ‘travel phase’ of about 10% of the holiday duration. Mood was highest during the ‘core phase’, which covers about 70% of the holiday time. Mood then declines slightly, but increases during the last part of the holiday. Copyright © 2009 John Wiley & Sons, Ltd.
Knowledge use, capitalisation and sharing in the audit and consultancy professions
Authors: Mignon Sophie , Janicot Corinne
Published: October 2009

The introduction of knowledge management (KM) systems has become a key factor that potentially leads to competitive advantage. To take fully advantage of KM systems it is often necessary to make adjustments along a variety of dimensions to the organisations concerned. This paper proposes a KM model built around four factors: strategic; organisational; technical and informational; cultural and human. With special focus on the audit and consultancy profession, this paper identifies the respective influence of individual factors on the use and capitalisation of the knowledge contained in the KM system that is introduced into an organisation. The results show that use of the system is facilitated by technical and information systems (knowledge bases) developed as a significant part of the group's strategy and culture. However, despite organisational actions that focus o knowledge, knowledge capitalisation remains problematic, in large part, due to human and cultural reticence over sharing. Copyright © 2009 John Wiley & Sons, Ltd.
Pediatric cholesteatoma and variants in the gene encoding connexin 26
Authors: James Adrian L. , Chadha Neil K. , Papsin Blake C. , Stockley Tracy L.
Published: October 2009

Objectives/Hypothesis:

Connexin 26 is a gap junction protein encoded by the GJB2 gene. It is expressed in cholesteatoma, and mutations cause proliferative skin disorders and sensorineural hearing loss (SNHL). Deletions of GJB6, which encodes connexin 30, cause SNHL in a digenic manner with a heterozygous GJB2 mutation. We hypothesize that GJB2 and GJB6 mutations might influence the development of cholesteatoma.

Study Design:

Prospective observational study to identify GJB mutations in pediatric cholesteatoma.

Methods:

Peripheral blood samples from 98 children with cholesteatoma were screened for mutations in the GJB2 gene by direct sequencing of the coding region (exon 2 and the intron/exon boundary). Deletions of the GJB6 gene were tested using multiple ligation probe amplification methods. GJB status was compared with other populations and patient age and extent of cholesteatoma at presentation.

Results:

Fourteen children had at least one GJB2 variant (14%). Of these, three had two variants. Two of the variants were neutral polymorphisms. One child with the GJB2 genotype 35delG/35delG also had SNHL. No correlation was found between GJB2 status and patient age or cholesteatoma severity at presentation. No GJB6 deletions were found.

Conclusions:

GJB2 gene variants are present in a minority of children with cholesteatoma, but may be more common than in normal populations. It is conceivable that alterations of connexin 26 expression could contribute to the multifactorial disease process in cholesteatoma by modifying the cell‐to‐cell communication that is important in proliferation and migration of keratinocytes. Laryngoscope, 2010
Tissue‐engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation
Authors: Kim Dong Young , Pyun JungHee , Choi Jae Won , Kim Jang‐Hee , Lee Jin Seok , Shin Hyang Ae , Kim Hyun‐Jun , Lee Ha‐Neul , Min Byoung‐Hyun , Cha Heung Eok , Kim Chul‐Ho
Published: October 2009

Objectives/Hypothesis:

Treatment and management of tracheal defects remain challenging in head and neck surgery. Various reconstruction techniques have been used, with no consensus on the best approach. The purpose of this study was to explore a novel strategy to fabricate tissue‐engineered trachea by using fibrin/hyaluronic acid (HA) composite gel and evaluate the feasibility of creating tracheal cartilage.

Study Design:

A preliminary animal experiment.

Methods:

Chondrocytes from rabbit cartilage were expanded and seeded into a culture dish at high density to form mechanically stable allograft tracheal cartilage using fibrin/HA composite gel. After a longitudinal cervical skin incision, the trachea was exposed and a rectangular defect (1 × 0.5 cm) was created on the cervical trachea by scalpel on six rabbits. Tissue‐engineered cartilage using fibrin/HA composite was trimmed and fixed to defect boundaries with Tissucol (Baxter International, Deerfield, IL). Postoperatively, the site was evaluated endoscopically, histologically, radiologically, and functionally.

Results:

Postoperatively, rigid telescopic examination showed that the implanted scaffolds in all cases were completely covered with regenerated mucosa without granulation or stenosis. Histologic data showed ciliated epithelium regenerated at the operated site from 2 months postoperatively. Ciliary beat frequency of ciliated epithelium on implants was very similar to normal respiratory mucosa. Computed tomography images revealed fine luminal contour of the regenerated site. However, allograft cartilage implanted was found to be partially preserved on the postoperative specimen.

Conclusions:

The tracheal luminal contour and functional epithelial regeneration without graft rejection and inflammation were observed after repair of a tracheal resection using allogeneic implants with chondrocytes cultured with fibrin/HA. Laryngoscope, 2010
A new mouse laryngeal transplantation rejection grading system
Authors: Lott David G. , Shipchandler Taha Z. , Dan Olivia , Lorenz Robert R. , Strome Marshall
Published: October 2009

Objectives/Hypothesis:

Development of a rat laryngeal transplantation model allowed for the first total human laryngeal transplantation by the senior author in 1998. In an effort to further our knowledge of the immune system's role in laryngeal rejection, a change to the mouse model was required. Prior to initiating immunosuppressive research protocols, a reliable mouse larynx rejection classification had to be established.

Study Design:

Animal study.

Methods:

Thirty‐one mouse laryngeal transplants (C57 BL/6 donors to C3H recipients) were performed and allowed to reject. Six time points were evaluated histologically: 1, 3, 5, 7, 9, and 15 days post‐transplant. Eight anatomic sites were evaluated and assigned a point value. A linear regression model was constructed using the group number as the response and the scores from the eight histological criteria as predictors. Severity classifications were determined by observing patterns in the sum of scores of variables found to be significant contributors. Group 1 was normal; group 2, minimal rejection; groups 3, 4, and 5, moderate rejection; and group 6, severe rejection.

Results:

All mice survived the transplants. Of the observed histological changes, cartilage, fat, muscle, and magnitude of lymphocytic infiltration significantly correlated with rejection severity. The rejection model created demonstrated 100% accuracy in predicting the severity classification for the 31 specimens in the study.

Conclusions:

The model established provides an accurate and reliable way to classify rejection severity in mice receiving laryngeal allografts. This sets the stage for future advanced study of manipulating the immune system as a mechanism for establishing allograft tolerance. Laryngoscope, 2010
Spiral ganglion loss outpaces inner hair cell loss in endolymphatic hydrops
Authors: Momin Suhael R. , Melki Sami J. , Alagramam Kumar N. , Megerian Cliff A.
Published: October 2009

Objectives/Hypothesis:

Neuronal toxicity is thought to be important in Meniere's disease and experimental endolymphatic hydrops (ELH). This study quantifies the relationship between neuronal degeneration and hair cell degeneration in ELH to evaluate the hypothesis that a primary neural insult would yield greater loss in the spiral ganglion than at the inner hair cell level.

Study Design:

Following induction and histopathologic confirmation of endolymphatic hydrops in guinea pigs, the degree of hydrops, spiral ganglion loss, and hair cell degeneration were quantified and compared.

Methods:

Guinea pigs with surgically induced unilateral hydrops were sacrificed and their cochleas preserved. Hydrops severity and spiral ganglion density were quantified using automated methods. Hair cells were counted manually. Values were normalized against the contralateral ear to create loss indexes.

Results:

Inner hair cell (IHC) loss at the apex is significantly lower than corresponding neuronal loss. IHC loss at the base is also lower than neuron loss, although not significantly. Regression analysis shows a significant, positive correlation between neuron loss severity and IHC loss severity at the apex, but not at the base. There is no correlation between hydrops severity and inner hair cell loss.

Conclusions:

By confirming that spiral ganglion loss is more severe than hair cell loss, and that hair cell loss appears to worsen with neuronal degeneration, this study supports the theory that neuronal toxicity is the primary insult in ELH‐related disorders, such as Meniere's disease, and may provide the basis for designing treatment strategies. Laryngoscope, 2010
Management of the N0 neck in recurrent laryngeal squamous cell carcinoma
Authors: Bohannon Isaac A. , Desmond Renee A. , Clemons Lisa , Magnuson J. Scott , Carroll William R. , Rosenthal Eben L.
Published: October 2009

Objectives/Hypothesis:

To evaluate the utility of neck dissections in patients undergoing salvage laryngectomy with a clinically negative neck.

Study Design:

Retrospective cohort study.

Methods:

This retrospective review identified 71 patients with N0 necks who underwent salvage laryngectomy from 2001 to 2007. The standard practice of surgeons within our institution was different, thus neck dissections were performed on approximately one half of the patients, creating two groups for comparison. The number of neck dissections with positive metastasis were examined. Postoperative complications, overall survival, and site of recurrence were compared between patients with neck dissection and no neck dissection.

Results:

Thirty‐eight patients underwent 71 neck dissections concurrently with salvage laryngectomy. A total of 33 patients had salvage laryngectomy without neck dissection. Only three of 71 neck dissections (4%) had positive nodal metastasis. The rate of fistula, wound infection, hematoma/bleeding, chyle leak, wound dehiscence, and flap failure did not reveal any statistical differences. However, the overall complication rate in neck dissections patients was higher (42.2 %) than no neck dissections (21.3%; P = .04). Neck dissection patients had a higher proportion of fistulas (32%) than no dissections (18%; P = .2). Regional failure occurred in 7.9% of the patients with neck dissections and 15% of patients without neck dissection (P = .5). There was no survival advantage for patients who underwent neck dissection compared to no neck dissection (P = .47).

Conclusions:

There was no survival advantage gained by performing neck dissection in the clinically negative neck. However, a trend toward reduced regional failure with neck dissection must be balanced by the increased potential for complications and fistulae. Laryngoscope, 2010
Outcomes of minimally invasive endoscopic resection of anterior skull base neoplasms
Authors: Batra Pete S. , Luong Amber , Kanowitz Seth J. , Sade Burak , Lee Joung , Lanza Donald C. , Citardi Martin J.
Published: October 2009

Objectives/Hypothesis:

The objective of this study was to review clinical outcomes of minimally invasive endoscopic resection (MIER) for anterior skull base (ASB) neoplasms.

Study Design:

Retrospective data review.

Methods:

Data analysis was performed on all patients undergoing MIER from October 2000 to December 2008.

Results:

Thirty‐one patients with mean age of 58 years underwent MIER. Malignant and benign tumors were managed in 25 (80.6%) and six (19.4%) cases, respectively. Most common histopathologies were squamous cell carcinoma (six), esthesioneuroblastoma (five), mucosal melanoma (five), and sinonasal undifferentiated carcinoma (four). American Joint Committee on Cancer tumor staging was T3N0M0 and T4N0M0 in 14 (56%) and 11 (44%) of the malignant cases, respectively. Surgical resection with curative intent was performed in 28 cases (90.3%). Multilayered skull base reconstruction was performed in most patients; lumbar drains were used in eight cases (25.8%). Twenty‐one patients (67.7%) were disease free, five patients (16.1%) were dead from disease, three patients (9.7%) were alive with disease, and two patients (6.5%) died from unrelated causes at mean follow‐up of 31.7 months.

Conclusions:

This study validated technical feasibility of MIER for diversity of benign and malignant ASB histopathology. Majority of patients were able to avoid adjunct craniotomy, whereas lumbar drainage was utilized in selective cases. This surgical strategy resulted in low complication rate and acceptable disease‐free survival in patients with advanced T3 and T4 malignant lesions. Future studies should focus on multicenter trials to facilitate more robust survival analysis and comparison to open surgical approaches. Laryngoscope, 2010
Multifactorial dysphagia: Diffuse idiopathic skeletal hyperostosis and eosinophilic esophagitis
Authors: Nimmons Grace , Van Daele Douglas J. , Hoffman Henry T. , Rao Satish S. , Clark Charles R.
Published: October 2009

Swallowing is a complex, multistage event with oral, pharyngeal, and esophageal phases. A thorough clinical examination for swallowing complaints begins to differentiate whether the problem is due to anatomic, mechanical, or neurologic etiologies. Based on the clinical suspicion, additional tests may be beneficial, including fluoroscopic and direct imaging methods, and electrophysiologic measurements. A multidisciplinary approach may also be advantageous, as in this case of dysphagia from diffuse idiopathic skeletal hyperostosis and eosinophilic esophagitis, which incorporated care from otolaryngology, speech pathology, orthopedic surgery, and gastroenterology. Laryngoscope, 2010
Primary middle ear Epstein‐Barr virus‐related lymphoepithelial carcinoma: Case reports and systematic review
Authors: Clark Matthew P. A. , Westerberg Brian D. , Berean Kenneth W.
Published: October 2009

Objectives/Hypothesis:

To report two cases of primary lymphoepithelial carcinoma in the middle ear and to determine the optimal treatment for such lesions.

Study Design/Methods:

Case reports and a systematic review of the literature.

Results:

Primary lymphoepithelial carcinoma in the middle ear is an exceptionally rare condition with only two other cases reported in the literature. There appears to be an association with Epstein‐Barr virus infection and in those patients originating from the Guangdong province of China, much as is the case for similar lesions found in the nasopharynx. Piecemeal rather than en bloc excision, in combination with adjuvant radiotherapy, appears to adequately control the disease.

Conclusions:

Primary lymphoepithelial carcinoma of the middle ear is a rare lesion, which when treated has a good prognosis. Laryngoscope, 2010