bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oesophageal acid hypersensitivity is not a contraindication to Nissen fundoplication
Authors: Broeders J A , Draaisma W A , Bredenoord A J , de Vries D R , Rijnhart-de Jong H G , Smout A J , Gooszen H G 
Published: August 2009

Abstract

Background
The Rome III criteria classify patients with a positive relationship between symptoms and reflux episodes but a physiological oesophageal acid exposure time as having gastro-oesophageal reflux disease (GORD) with an acid hypersensitive oesophagus. The long-term outcome of antireflux surgery in these patients was investigated.

Methods
Outcomes of Nissen fundoplication in 28 patients with GORD refractory to proton-pump inhibitors (PPIs) and oesophageal acid hypersensitivity (group 1) were compared with those of 126 patients with pathological acid exposure (group 2).

Results
Fundoplication had a similar effect in both groups. Three months after surgery, total acid exposure time and the prevalence of oesophagitis had decreased, whereas mean lower oesophageal pressure had increased. The percentage of patients using PPIs was reduced from 83 to 4 per cent in group 1 and from 86·1 to 7·4 per cent in group 2 (both P &lt; 0·001). Quality of life measured on a scale from 0 to 100 improved from 52 to 69 (P = 0·009) and 64 (P &lt; 0·001) respectively. The percentage of patients with resolved or improved symptoms at 5 years was similar.

Conclusion
Patients with oesophageal acid hypersensitivity benefit from Nissen fundoplication as much as those with pathological acid exposure.
Prospective randomized trial using cost–utility analysis of early versus delayed laparoscopic cholecystectomy for acute gallbladder disease
Authors: Macafee D A L , Humes D J , Bouliotis G , Beckingham I J , Whynes D K , Lobo D N 
Published: August 2009

Abstract

Background
This randomized controlled trial compared the cost–utility of early laparoscopic cholecystectomy with that for conventional management of newly diagnosed acute gallbladder disease.

Methods
Adults admitted to hospital with a first episode of biliary colic or acute cholecystitis were randomized to an early intervention group (36 patients, operation within 72 h of admission) or a conventional group (36, elective cholecystectomy 3 months later). Costs were measured from a National Health Service and societal perspective. Quality-adjusted life year (QALY) gains were calculated 1 month after surgery.

Results
The mean(s.d.) total costs of care were £5911(2445) for the early group and £6132(3244) for the conventional group (P = 0·928), Mean(s.d.) societal costs were £1322(1402) and £1461(1532) for the early and conventional groups respectively (P = 0·732). Visual analogue scale scores of health were 72·94 versus 84·63 (P = 0·012) and the mean(s.d.) QALY gain was 0·85(0·26) versus 0·93(0·13) respectively (P = 0·262). The incremental cost per additional QALY gained favoured conventional management at a cost of £3810 per QALY gained.

Conclusion
In this pragmatic trial, the cost–utilities of both the early and conventional approaches were similar, but the incremental cost per additional QALY gained favoured conventional management. Registration number: ISRCTN81663421 (http://www.controlled-trials.com).
Multicentre analysis of oncological and survival outcomes following anastomotic leakage after rectal cancer surgery
Authors: den Dulk M , Marijnen C A M , Collette L , Putter H , Påhlman L , Folkesson J , Bosset J-F , Rödel C , Bujko K , van de Velde C J H 
Published: August 2009

AbstractBackgroundThe association between diverting stomas and symptomatic anastomotic leakage after rectal cancer surgery was studied, as well as the impact of leakage on local recurrence, distant metastasis, and disease-free, overall and cancer-specific survival.MethodsData from the Swedish Rectal Cancer Trial, Dutch TME trial, CAO/ARO/AIO-94 trial, EORTC 22921 trial and Polish Rectal Cancer Trial were pooled (n = 5187). All eligible patients without distant metastases at the time of low anterior resection were selected (n = 2726); overall survival was studied in patients aged 75 years or less (n = 2480). Multivariable models were used to study the association between diverting stomas and anastomotic leakage, and between leakage and recurrence or survival.ResultsSome 9·7 per cent of patients were diagnosed with a symptomatic anastomotic leak; diverting stomas were negatively associated with leakage (11·6 per cent without and 7·8 per cent with a stoma; P = 0·002). Anastomotic leakage was negatively associated with overall survival in the multivariable analysis (hazard ratio (HR) 1·29 (95 per cent confidence interval 1·02 to 1·63); P = 0·034), but not with cancer-specific survival (HR 1·12 (0·83 to 1·52); P = 0·466).ConclusionDiverting stomas were associated with less symptomatic anastomotic leakage. Oncological outcome was not significantly influenced by leakage, but overall survival was reduced.
Meta-analysis of defunctioning stomas in low anterior resection for rectal cancer Br J Surg (Br J Surg 2009; 96: 462–472)
Authors: Nash G 
Published: August 2009

Abstract
The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses should be sent electronically via the BJS website (www.bjs.co.uk). All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length.
Molecular Basis for the Stereoselective Ammoniolysis of N‐Alkyl Aziridine‐2‐Carboxylates Catalyzed by Candida antarctica Lipase B
Authors: Park Jae‐Hoon , Ha Hyun‐Joon , Lee Won Koo , Généreux‐Vincent Tobie , Kazlauskas Romas J. 
Published: August 2009

AbstractCandida antarctica lipase B catalyzed the stereoselective ammoniolysis of N‐alkyl aziridine‐2‐carboxylates in tBuOH saturated with ammonia and yielded the (2S)‐aziridine‐2‐carboxamide and unreacted (2R)‐aziridine‐2‐carboxylate. Varying the N‐1 substituent on the aziridine ring changed the rate and stereoselectivity of the reaction. Substrates with a benzyl substituent or a (1′R)‐1‐phenylethyl substituent reacted approximately ten times faster than substrates with a (1′S)‐1‐phenylethyl substituent. Substrates with a benzyl substituent showed little stereoselectivity (E=5–7) while substrates with either a (1′R)‐ or (1′S)‐1‐phenylethyl substituent showed high stereoselectivity (D>50). Molecular modeling by using the current paradigm for enantioselectivity—binding of the slow enantiomer by an exchange‐of‐substituents orientation—could not account for the experimental results. However, modeling an umbrella‐like‐inversion orientation for the slow enantiomer could account for the experimental results. Steric hindrance between the methyl in the (1′S)‐1‐phenylethyl substituent and Thr138 and Ile189 in the acyl‐binding site likely accounts for the slow reaction. Enantioselectivity likely stems from an unfavorable interaction of the methine hydrogen with Thr40 for the slow enantiomer and from subtle differences in the orientations of the other three substituents. This success in rationalizing the enantioselectivity supports the notion that an umbrella‐like‐inversion orientation can contribute to enantioselectivity in lipases.
Usefulness of Peripheral Arterial Tonometry in the Detection of Mental Stress‐Induced Myocardial Ischemia
Authors: Hassan Mustafa , York Kaki M. , Li Haihong , Li Qin , Lucey Dorian G. , Fillingim Roger B. , Sheps David S. 
Published: August 2009

AbstractBackgroundMental stress‐induced myocardial ischemia (MSIMI) identifies a subset of coronary arterial disease (CAD) patients at increased risk for adverse cardiovascular events. Peripheral arterial vasoconstriction has been consistently reported as an underlying mechanism for ischemia development in this setting and as such affords a unique opportunity for the noninvasive detection of this phenomenon.HypothesisWe studied the usefulness of a peripheral arterial tonometry (PAT) technique in the detection of MSIMI. We sought to identify response patterns that would predict the development of MSIMI.MethodsParticipants were 211 patients with documented CAD. Mental stress testing was performed using a public speaking task. Rest‐stress myocardial perfusion imaging was the gold standard for ischemia detection. PAT responses were assessed during the 2 phases of the stressful task (stress anticipation and the task performance) and were calculated as a ratio of stress to the resting pulse wave amplitude.ResultsVascular response during the stress anticipation period (speech preparation) was more pronounced than during the actual speaking task (the mean preparation index was 0.64 ± 0.53; the mean speech index was 0.72 ± 0.60; P < 0.001). PAT response during speech preparation had modest accuracy for predicting MSIMI (area under the curve [AUC] was 0.63; 95% confidence interval [CI]: 0.53–0.74, P = 0.015). A PAT index ≤ 0.52 was identified as the best cut off value for detecting MSIMI with a sensitivity of 76% and a specificity of 56%.ConclusionWe identified a pattern of peripheral arterial response to mental stress that has a relatively modest accuracy in predicting MSIMI. Further research is needed to validate the findings of this study. Copyright © 2009 Wiley Periodicals, Inc.
Bivalent Argininamide‐Type Neuropeptide Y Y1 Antagonists Do Not Support the Hypothesis of Receptor Dimerisation
Authors: Keller Max , Teng Shangjun , Bernhardt Günther , Buschauer Armin 
Published: August 2009

AbstractBivalent ligands are potential tools to investigate the dimerisation of G‐protein‐coupled receptors. Based on the (R)‐argininamide BIBP 3226, a potent and selective neuropeptide Y Y1 receptor (Y1R) antagonist, we prepared a series of bivalent Y1R ligands with a wide range of linker lengths (8–36 atoms). Exploiting the high eudismic ratio (>1000) of the parent compound, we synthesised sets of R,R‐, R,S‐ and S,S‐configured bivalent ligands to gain insight into the “bridging” of two Y1Rs by simultaneous interaction with both binding sites of a putative receptor dimer. Except for the S,S isomers, the bivalent ligands are high‐affinity Y1R antagonists, as determined by Ca2+ assays on HEL cells and radioligand competition assays on human Y1R‐expressing SK‐N‐MC and MCF‐7 cells. Whereas the R,R enantiomers are most potent, no marked differences were observed relative to the corresponding meso forms. The difference between R,R and R,S diastereomers was most pronounced (about sixfold) in the case of the Y1R antagonist containing a spacer of 20 atoms in length. Among the R,R enantiomers, linker length and structural diversity had little effect on Y1R affinity. Although the bivalent ligands preferentially bind to the Y1R, the selectivity toward human Y2, Y4, and Y5 receptors was markedly lower than that of the monovalent argininamides. The results of this study neither support the presence of Y1R dimers nor the simultaneous occupation of both binding pockets by the twin compounds. However, as the interaction with Y1R dimers cannot be unequivocally ruled out, the preparation of a bivalent radioligand is suggested to determine the ligand–receptor stoichiometry. Aiming at such radiolabelled pharmacological tools, prototype twin compounds were synthesised, containing an N‐propionylated amino‐functionalised branched linker (Ki≥18 nM), a tritiated form of which can be easily prepared.
Novel Antitumor L‐Arabinose Derivative of Indolocarbazole with High Affinity to DNA
Authors: Kaluzhny Dmitry N. , Tatarskiy Victor V. , Dezhenkova Lyubov G. , Plikhtyak Irina L. , Miniker Tatyana D. , Shchyolkina Anna K. , Strel'tsov Sergey A. , Chilov Ghermes G. , Novikov Fedor N. , Kubasova Irina Yu. , Smirnova Zoya S. , Mel'nik Stalina Ya. , Livshits Mikhail A. , Borisova Olga F. , Shtil Alexander A. 
Published: August 2009

AbstractNovel indolocarbazole derivative 12‐(α‐L‐arabinopyranosyl)indolo[2,3‐α]pyrrolo[3,4‐c]carbazole‐5,7‐dione (AIC) demonstrated high potency (at submicromolar concentrations) against the NCI panel of human tumor cell lines and transplanted tumors in vivo. In search of tentative targets for AIC, we found that the drug formed high affinity intercalative complexes with d(AT)20, d(GC)20 and calf thymus DNA (binding constants (1.6×106) M−1≤Ka≤(3.3×106) M−1). The drug intercalated preferentially into GC pairs of the duplex. Importantly, the concentrations at which AIC formed the intercalative complexes with DNA (C≤1 μM) were identical to the concentrations that triggered p53‐dependent gene reporter transactivation, the replication block, the inhibition of topoisomerase I‐mediated DNA relaxation and death of HCT116 human colon carcinoma cells. We conclude that the formation of high affinity intercalative complexes with DNA is an important factor for anticancer efficacy of AIC.
Regional quantitative analysis of small animal myocardial sympathetic innervation and initial application in streptozotocin induced diabetes
Authors: Goethals Lode R. , Weytjens Caroline D. , De Geeter Frank , Droogmans Steven , Caveliers Vicky , Keyaerts Marleen , Vanhove Chris , Van Camp Guy , Bossuyt Axel , Lahoutte Tony 
Published: August 2009

AbstractBackgroundIn several disease models it is known that heterogeneous dysinnervation occurs in the sympathetic nervous system. We therefore adapted the 123I‐MIBG imaging procedure in small animals to allow quantification of both global and regional uptake and wash‐out rate using high specific activity 123I‐MIBG in the myocardium of rats. After evaluation of the image procedure in normal animals, we then applied our imaging protocol to visualize the regional dysinnervation in cardiac autonomic neuropathy occurring in streptozotocin‐induced diabetes.MethodsSeven normal Lewis rats underwent 123I‐MIBG pinhole SPECT with low specific activity 123I‐MIBG (lsa MIBG) and high specific activity 123I‐MIBG (hsa MIBG) with a 2 week interval. Twelve normal rats and 12 rats 8 weeks after streptozotocin injection underwent the same hsa MIBG imaging protocol. The imaging protocol consisted of two SPECT acquisitions for every animal. The imaging sequence started at 20 min after tracer injection. The percentage of injected activity (%IA) and the wash‐out rate in the global myocardium were measured. Left ventricular regional MIBG kinetics were analyzed in the six midventricular segments of the 17 segment model.ResultsCompared with lsa MIBG, the wash‐out rate of hsa MIBG was significantly slower, in association with a higher cardiac uptake. Regional analysis showed a maximal uptake in the anterolateral segment, without significant differences between segments. We noted a significantly higher global wash‐out rate in the streptozotocin group compared to controls (p < 0.05). Regional analysis confirmed the increased wash‐out rate, reaching statistical significance in the inferior and the inferoseptal walls.ConclusionHigh‐quality 123I‐MIBG images and accurate measurements can be obtained using hsa 123I‐MIBG with image acquisitions performed at relatively early time points. Small animal MIBG SPECT imaging allows for regional analysis of the myocardium. In the streptozotocin group, wash‐out of MIBG is globally increased, compatible with a higher sympathetic tonus or decreased reuptake of MIBG. The highest increase is located in the inferior, inferoseptal and anteroseptal walls. These findings further suggest the occurrence of diabetic cardiomyopthy after streptozotocin injection. Copyright © 2009 John Wiley & Sons, Ltd.
Modulation of water exchange in Eu(III) DOTA–tetraamide complexes: considerations for in vivo imaging of PARACEST agents
Authors: Mani Tomoyasu , Tircsó Gyula , Togao Osamu , Zhao Piyu , Soesbe Todd C. , Takahashi Masaya , Sherry A. Dean 
Published: August 2009

AbstractModulation of water exchange in lanthanide(III)–DOTA type complexes has drawn considerable attention over the past two decades, particularly because of their application as contrast agents for magnetic resonance imaging. LnDOTA–tetraamide complexes display unusually slow water exchange kinetics and this chemical property offers an opportunity to use these complexes as a new type of contrast agent based upon the chemical exchange saturation transfer (CEST) mechanism. Six new DOTA–tetraamide ligands having side‐chain amide arms with varying hydrophobicity and polarity were prepared and the water exchange characteristic of complexes formed with europium(III) complexes were investigated. The results show that introduction of steric bulk into the amide side‐chain arms of the europium(III) complexes not only favors formation of the mono‐capped twisted square antiprism coordination isomers, the isomer that is generally less favourable for CEST, but also accelerates water exchange in the mono‐capped square antiprism isomers. However, converting single methyl groups on these bulky arms to carboxyl or carboxyl ethyl esters results in a rather dramatic decrease in water exchange rates, about 50‐fold. Thus, steric bulk, polarity and hydrophobicity of the amide side‐chains each contribute to organization of water molecules in the second hydration sphere of the europium(III) ion and this in turn controls water exchange in these complexes. Copyright © 2009 John Wiley & Sons, Ltd.
Proliferating and quiescent human umbilical vein endothelial cells (HUVECs): a potential in vitro model to evaluate contrast agents for molecular imaging of angiogenesis
Authors: Vag Tibor , Schramm Tiemo , Kaiser Werner A. , Hilger Ingrid 
Published: August 2009

AbstractBackgroundThe design of highly specific contrast agents for molecular imaging of angiogenesis requires the availability of adequate in vitro models. In this context, we investigated the applicability of a potential in vitro model based on human umbilical vein endothelial cells (HUVECs) mimicking physiological and angiogenic vasculature.MethodsHUVECs in supplemented medium were used to mimic proliferating neovasculature (stimulated HUVECs), whereas quiescent non‐proliferating endothelium was modeled by alteration of medium supplements (unstimulated HUVECs). The features of both culture subsets were compared with features of angiogenic and physiological vessels in vivo described in the literature using different techniques. Testing of the cell model was performed by specific labeling of CD105 and VEGFR2 with fluorophores and consecutive imaging using a planar near‐infrared fluorescence (NIRF) imager.ResultsLight microscopy revealed tubular alignment of unstimulated HUVECs, which was absent in stimulated HUVECs. Proliferation assay confirmed a high level of proliferation in stimulated HUVECs but almost no cell proliferation in unstimulated HUVECs. Flow cytometry revealed an up‐regulation of CD105, but not of VEGFR2 on stimulated HUVECs. CD105 and VEGFR2 gene expression was detectable both in proliferating and in non‐proliferating cells. NIRF‐imaging revealed highest fluorescence signal for CD105 in proliferating endothelial cells. No relevant fluorescence signal could be observed for VEGFR2.ConclusionThe established cell model exhibits features of physiological and angiogenic vasculature. NIRF‐imaging using the proposed model was feasible. We conclude that the presented cell model might be useful in future angiogenesis applications, like evaluating new fluorophores and other contrast media. Copyright © 2009 John Wiley & Sons, Ltd.
Radiation dose escalation for localized prostate cancer
Authors: Wong William W. , Vora Sujay A. , Schild Steven E. , Ezzell Gary A. , Andrews Paul E. , Ferrigni Robert G. , Swanson Scott K. 
Published: August 2009

AbstractBACKGROUND:In the current study, the effects of dose escalation for localized prostate cancer treatment with intensity‐modulated radiotherapy (IMRT) or permanent transperineal brachytherapy (BRT) in comparison with conventional dose 3‐dimensional conformal radiotherapy (3D‐CRT) were evaluated.METHODS:This study included 853 patients; 270 received conventional dose 3D‐CRT, 314 received high‐dose IMRT, 225 received BRT, and 44 received external beam radiotherapy (EBRT) + BRT boost. The median radiation doses were 68.4 grays (Gy) for 3D‐CRT and 75.6 Gy for IMRT. BRT patients received a prescribed dose of 144 Gy with iodine‐125 (I‐125) or 120 Gy with palladium‐103 (Pd‐103), respectively. Patients treated with EBRT + BRT received 45 Gy of EBRT plus a boost of 110 Gy with I‐125 or 90 Gy with Pd‐103. Risk group categories were low risk (T1‐T2 disease, prostate‐specific antigen level ≤10 ng/mL, and a Gleason score ≤6), intermediate risk (increase in value of 1 of the factors), and high risk (increase in value of ≥2 factors).RESULTS:With a median follow‐up of 58 months, the 5‐year biochemical control (bNED) rates were 74% for 3D‐CRT, 87% for IMRT, 94% for BRT, and 94% for EBRT + BRT (P <.0001). For the intermediate‐risk group, high‐dose IMRT, BRT, or EBRT + BRT achieved significantly better bNED rates than 3D‐CRT (P <.0001), whereas no improvement was noted for the low‐risk group (P = .22). There was no increase in gastrointestinal (GI) toxicity from high‐dose IMRT compared with conventional dose 3D‐CRT, although there was more grade 2 genitourinary (GU) toxicity (toxicities were graded at the time of each follow‐up visit using a modified Radiation Therapy Oncology Group [RTOG] scale). BRT caused more GU but less GI toxicity, whereas EBRT + BRT caused more late GU and GI toxicity than IMRT or 3D‐CRT.CONCLUSIONS:The data from the current study indicate that radiation dose escalation improved the bNED rate for the intermediate‐risk group. IMRT caused less acute and late GU toxicity than BRT or EBRT + BRT. Cancer 2009. © 2009 American Cancer Society.
Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy
Authors: Shayne Michelle , Culakova Eva , Wolff Debra , Poniewierski Marek S. , Dale David C. , Crawford Jeffrey , Lyman Gary H. 
Published: August 2009

AbstractBACKGROUND:This prospective study evaluated patient and treatment characteristics that contributed to hematologic toxicity in older breast cancer patients treated with curative intent in the community setting.METHODS:Data were collected on 1224 patients with stage I through III breast cancer, of whom 207 were aged ≥65 years (grading determined according to the American Joint Committee on Cancer staging system). Primary outcome measures included anemia, thrombocytopenia, severe neutropenia, febrile neutropenia, and both planned and actual relative dose intensity (RDI). Comparisons between older and younger patients regarding hematologic toxicity and reductions in RDI were based on univariate and multivariate logistic regression analyses.RESULTS:The neutropenic complication rate in older patients (45.1%) was not significantly different from that in the younger patients (43.7%). There were also no significant differences in rates of anemia or thrombocytopenia. Approximately 34.0% of the older patients received RDI <85% compared with 20.0% among younger patients (P < .01). Fewer older patients received anthracycline‐based chemotherapy (64.3% compared with 83.8% in younger patients, P < .01). Fewer older patients received prophylactic white blood cell colony‐stimulating factor (18.4%) compared with younger patients (28.0%) (P < .01).Conclusions:There were no significant differences noted with regard to chemotherapy‐related hematologic toxicities between older and younger breast cancer patients in this large prospective observational study. This may be explained, in part, by more frequent reductions in RDI and less frequent utilization of anthracyclines among older patients. Cancer 2009. © 2009 American Cancer Society.