bluuebunny/crossref_metadata_2025 huggingface dataset:
Percentage Area of Intimal Surface of the Infra-Renal Segment of Abdominal Aorta Affected by Atherosclerosis - A Postmortem Study
Authors: Nahar Saifun , Naushaba Humaira , Begum Jesmin Ara , Akhter Naznin
Published: August 2009

Context: Atherosclerosis and its complications are still the major source of morbidity and mortality in the industrial world, and estimates have been offered that at its present rate of growth, will be the major cause of death from this disease by the year 2020 in the entire world, (Joseph 2004).The seemingly increased incidence of atherosclerotic disorders in the country, their fatal consequences and the paucity of relevant data, the present study was carried out to assess the percentage of area involved in atherosclerotic lesion of abdominal aorta of Bangladeshi males. Study design: Descriptive cross-sectional. Place & time of study: In the department of Anatomy, Sir Salimullah Medical College, Dhaka, during the study period of July 2005 to June 2006. Method: Abdominal aorta were collected from fifty Bangladeshi male dead bodies who underwent routine postmortem examination due to accidental death. Sudy was done to find out the macroscopic extent of atherosclerotic lesion of abdominal aorta (below the origin of renal arteries) from Bangladeshi male of different ages. The subjects were divided into lower (8-29), middle (30-40), higher (42-92) age groups. The atherosclerotic lesions were stained red by treating the aorta with sudden IV. The percentage of area on the intimal surface showing atherosclerotic lesion were measured by AutoCAD. Result: The percentage of area involved in atherosclerotic lesion was increase with advancing age. Unpaired student ‘t' test for statistical analysis revealed significant difference. (P<0.01) in between lower & higher age groups. Key words: Abdominal aorta, Atherosclerosis   doi: 10.3329/bja.v7i1.3013 Bangladesh Journal of Anatomy January 2009, Vol. 7 No. 1 pp. 22-25
Effect of Fenugreek (Methi) on Cortical Thickness of the Thymus in Streptozotocin-Induced Diabetic Rats
Authors: Mondal DK , Moinuddin MMA , Saha MM , Khanom AM , Yousuf BMA , Talukder MSA , Ara S
Published: August 2009

Objective: To find out microscopically whether Trigonella foenumgraecum (fenugreek seeds/methi seeds) has got any preventive role against the lowering of cortical thickness of the thymic lobules in diabetes mellitus. Design: An experimental study on Long Evans rats which were divided into three equal groups depending on their different shorts of dietary feeding and drug treatment. Setting: Anatomy department of IPGMR (Institute of Post Graduate Medicine and Research) at present BSMMU (Bangabandhu Sheikh Mujib Medical University) and BIRDEM (Bangladesh Institute of Research and Rehabilitation in diabetes, Endocrine & Metabolic Disorders). Subjects: Fifty eight healthy young Long Evans rats of either sex weighing 72 to 174gm aged between 50 to 60 days were used in this study. Main outcome measures: Variation of cortical thickness of the thymic lobules in different groups of rat. Result: Cortical thickness in the nondiabetic control group, which ranges from 30.17 to 36.99. and the mean was 34.83 ± 0.60. In diabetic control group the cortical thickness ranges from 17.78 to 26.46 and the mean was 21.85 ± 1 On the other hand, in the fenugreek- treated diabetic rats the cortical thickness ranges from 25.71 to 32.95 and mean cortical thickness was 30.49 ± 0.75. Conclusion: Fenugreek showed a tendency of acting against lowering of the cortical thickness of the thymic lobule of Streptozotocin-induced diabetes mellitus. However, further investigations are recommended for establishing fenugreek as a safe, useful effective agent to preserve the cortical thickness improving the diabetic condition by acting as antidiabetogenic agent. Key words: Diabetes mellitus, Differential lymphocyte count, Fenugreek, Thymus   doi: 10.3329/bja.v7i1.3017 Bangladesh Journal of Anatomy January 2009, Vol. 7 No. 1 pp. 37-41
Views of Teachers Regarding Course Contents of Anatomy in Post Graduate MD Internal Medicine Curriculum
Authors: Banu Laila Anjuman , Ali M Shomsher
Published: August 2009

Context: Anatomy is a compulsory subject for postgraduate medical courses of Bangladesh. MD internal medicine is a clinical course run by different universities of Bangladesh. To maintain a standard of medical education a curriculum is essential for a course. Again course content is an essential part of a curriculum. Doctor of Medicine (MD) courses consist of three parts. In Part-I, students study the basic medical subjects for six months. To produce clinicians with appropriate anatomical knowledge in a short time within six months period proper customized (relevant) course content regarding Anatomy part is necessary. But the problem is that in our postgraduate course much subjectivity is present in every aspects of curriculum. This subjectivity is due to inclusion of more general aspects of Anatomy and exclusion of specific deeper relevant Anatomy. Realizing this problem the present study was designed to formulate some principles for selecting course contents for the Anatomy portion of MD Internal Medicine course. Study Design: This was a descriptive study. Place & Period of study: Center for Medical Education, Dhaka from July 2007-June 2008. Method: It was based on analyses of opinion of students and teachers through focus group discussion involving teachers of Internal Medicine and Anatomy. These people were chosen through two stage random sampling within clusters. Two Focus group discussions were used to get feedback on the importance of various anatomical topics that should be included as course content. Of a total of 18 teachers response in focus group discussion. In FGD 83% response was received from the teachers in Anatomy and 66 % on teachers in Medicine. Result: Opinion derived from the FGD indicate that for the selection of the course content following concluding remarks should be made: Cardiovascular anatomy, respiratory anatomy and anatomy of the nervous system should be considered important for the Internal Medicine. For knowing the anatomical landmarks all of the surface anatomy should receive attention for Medicine. Functional implication and effect of obliteration of arterial supply, lymphatic drainage and nerve supply receives importance. Sectional and radiological anatomy is considered important for the course for interpretation of X-ray, CT scan and MRI. Anatomical variation should be considered important as well as congenital anomalies of cardiovascular and genitourinary system. Knowledge of the structure of the mucous membrane is important for clinical correlation of the biopsy reports. Basic genetics, cell biology should be important but kept in mind that repetition should be avoided in others subjects as in Biochemistry and Physiology. Key words: Anatomy, Course content, MD Internal medicine.   doi: 10.3329/bja.v7i1.3027 Bangladesh Journal of Anatomy January 2009, Vol. 7 No. 1 pp. 55-61
Properties of the Statistical Complexity Functional and Partially Deterministic HMMs
Authors: Löhr Wolfgang
Published: August 2009

Statistical complexity is a measure of complexity of discrete-time stationary stochastic processes, which has many applications. We investigate its more abstract properties as a non-linear function of the space of processes and show its close relation to the Knight’s prediction process. We prove lower semi-continuity, concavity, and a formula for the ergodic decomposition of statistical complexity. On the way, we show that the discrete version of the prediction process has a continuous Markov transition. We also prove that, given the past output of a partially deterministic hidden Markov model (HMM), the uncertainty of the internal state is constant over time and knowledge of the internal state gives no additional information on the future output. Using this fact, we show that the causal state distribution is the unique stationary representation on prediction space that may have finite entropy.
Hepatitis C Virus Infection: Molecular Pathways to Steatosis, Insulin Resistance and Oxidative Stress
Authors: Clément Sophie , Pascarella Stéphanie , Negro Francesco
Published: August 2009

The persistent infection with hepatitis C virus is a major cause of chronic liver disease worldwide. However, the morbidity associated with hepatitis C virus widely varies and depends on several host-related cofactors, such as age, gender, alcohol consumption, body weight, and co-infections. The objective of this review is to discuss three of these cofactors: steatosis, insulin resistance and oxidative stress. Although all may occur independently of HCV, a direct role of HCV infection in their pathogenesis has been reported. This review summarizes the current understanding and potential molecular pathways by which HCV contributes to their development.
Testing an OMERACT MRI Scoring System for Peripheral Psoriatic Arthritis in Cross-sectional and Longitudinal Settings
Authors: McQUEEN FIONA , LASSERE MARISSA , DUER-JENSEN ANNE , WIELL CHARLOTTE , CONAGHAN PHILIP G. , GANDJBAKHCH FRÉDÉRIQUE , HERMANN KAY-GEERT A. , BIRD PAUL , BØYESEN PERNILLE , PETERFY CHARLES , EJBJERG BO , HAAVARDSHOLM ESPEN A. , COATES LAURA , ØSTERGAARD MIKKEL
Published: August 2009

Objective.

Magnetic resonance imaging (MRI) is increasingly used to measure articular inflammation and damage in patients with psoriatic arthritis (PsA). We evaluated the reliability of a new OMERACT PsA MRI scoring system, PsAMRIS, in PsA fingers.

Methods.

In 2 separate studies, MRI scans were obtained from patients with clinical evidence of synovitis or dactylitis of the fingers. For the first cross-sectional study, images were obtained at one timepoint. For the second longitudinal study, images were obtained at 2 timepoints, 6 weeks apart. Scans were scored using PsAMRIS in an international multireader setting, for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosions, and bone proliferation.

Results.

Global status scores from both datasets revealed moderate to high reliability for scoring most features, although reliability was poor for periarticular inflammation in the cross-sectional study. Change scores that reflected inflammatory activity also exhibited moderate to good reliability in the longitudinal exercise, despite there being very little absolute change in MRI synovitis or tenosynovitis observed in this dataset. At the distal interphalangeal joints, reliability for change scores was acceptable only for synovitis and tenosynovitis.

Conclusion.

Further development and testing of the PsAMRIS is planned to improve its performance as a clinical and research tool to identify and measure pathology in peripheral joint PsA.
Proposal for Levels of Evidence Schema for Validation of a Soluble Biomarker Reflecting Damage Endpoints in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis, and Recommendations for Study Design
Authors: MAKSYMOWYCH WALTER P. , FITZGERALD OLIVER , WELLS GEORGE A. , GLADMAN DAFNA D. , LANDEWÉ ROBERT , ØSTERGAARD MIKKEL , TAYLOR WILLIAM J. , CHRISTENSEN ROBIN , TAK PAUL-PETER , BOERS MAARTEN , SYVERSEN SILJE W. , BATHON JOAN M. , RITCHLIN CHRISTOPHER J. , MEASE PHILIP J. , BYKERK VIVIEN P. , GARNERO PATRICK , GEUSENS PIET , EL-GABALAWY HANI , ALETAHA DANIEL , INMAN ROBERT D. , KRAUS VIRGINIA BYERS , KVIEN TORE K. , van der HEIJDE DÉSIRÉE
Published: August 2009

Objective.

At OMERACT 8 a framework for levels of evidence was proposed for the validation of biomarkers as surrogate outcome measures. We aimed to adapt this scheme in order to apply it in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). We also aimed to generate consensus on minimum standards for the design of longitudinal studies aimed at validating biomarkers.

Methods.

Before the meeting, the Soluble Biomarker Working Group prepared a preliminary framework and discussed various models for association and prediction related to the statistical strength domain. In addition, 3 Delphi exercises addressing longitudinal study design for RA, PsA, and AS were conducted within the working group and members of the Assessments in SpondyloArthritis International Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). This formed the basis for discussions among OMERACT 9 participants.

Results.

The proposed framework was accepted by consensus. In the study design domain a requirement for both prospective observational studies and randomized controlled trials (RCT) in different drug classes was noted. A template for determining the level of statistical strength was proposed. The addition of a new domain on biomarker assay performance was considered essential, and participants suggested that for any biomarker this domain should be addressed first, i.e., before starting clinical validation studies. Participants agreed on most elements of a longitudinal study design template. Where consensus was lacking the working group has drafted solutions that constitute a basis for prospective validation studies.

Conclusion.

The OMERACT 9 Soluble Biomarker Group has successfully formulated a levels of evidence scheme and a study design template that will provide guidance to conduct validation studies in the setting of soluble biomarkers proposed to replace the measurement of damage endpoints in RA, PsA, and AS.
Vibration Analysis of Cracked Stepped Laminated Composite Beams
Authors: Borneman Stephen R. , Hashemi Seyed M. , Alighanbari Hekmat
Published: August 2009

The free vibration of piecewise uniform defective laminated composite beams is investigated. The governing differential equations of motion are coupled both in torsional and bending deformations. A Dynamic Finite Cracked Element (DFCE) is developed and is applied to slender beams, characterized by an offset between inertial and bending axes. The hybrid DFCE is a combination of the conventional Finite Element Method (FEM) formulation and frequencydependent interpolation functions stemmed from the exact Dynamic Stiffness Matrix (DSM) method. The defect, a through-thickness edge crack, is then represented by a set of stiffness terms evaluated from the beam compliance matrix at the crack location. A number of stepped beam configurations are investigated by reducing the base, thickness, or both. The natural frequencies and modes of free vibration of the beams are examined for single through-thickness edge crack configurations.
Proton Transport from Dendritic Helical‐Pore‐Incorporated Polymersomes
Authors: Kim Anthony J. , Kaucher Mark S. , Davis Kevin P. , Peterca Mihai , Imam Mohammad R. , Christian Natalie A. , Levine Dalia H. , Bates Frank S. , Percec Virgil , Hammer Daniel A.
Published: August 2009

The ability to add synthetic channels to polymersome (polymer vesicle) membranes could lead to novel membrane composites with unique selectivity and permeability. Proton transport through two different synthetic pores, self‐assembled from either a dendritic dipeptide, (6Nf‐3,4‐3,5)12G2‐CH2‐Boc‐L‐Tyr‐L‐Ala‐OMe, or a dendritic ester, (R)‐4Bp‐3,4‐dm8G1‐COOMe, incorporated into polymersome membranes are studied. Polymersomes provide an excellent platform for studying such transport processes due to their robustness and mechanical and chemical stability compared to liposomes. It is found that the incorporated dendritic dipeptide and dendritic ester assemble into stable helical pores in the poly(ethylene oxide)‐polybutadiene (PEO‐PBD) polymersomes but not in the poly(2‐methyloxazoline)‐poly(dimethylsiloxane)‐poly(2‐methyl oxazoline) (PMOX‐PDMS‐PMOX) polymersomes. The incorporation is confirmed by circular dichroism (CD), changes in purely synthetic mechanical strength (e.g., areal expansion modulus) as assessed by micropipette aspiration, and cryo‐TEM. In addition to the structural analyses, a transport measurement shows the incorporated dendritic helical pores allow facile transport of protons across the polymersome membranes after up to one month of storage. This integration of synthetic porous channels with polymersome substrates could provide a valuable tool for studying active transport processes in a composite membrane. These composites will ultimately expand the family of biologically inspired porous‐membrane mimics.
In vivo Engineering of Tissues: Biological Considerations, Challenges, Strategies, and Future Directions
Authors: Shastri V. Prasad
Published: August 2009

Moving forward materials‐based regenerative medicine faces many challenges to ensure clinical success. Many of these challenges lie at the interface of molecular/structural biology and materials science. This review discusses this issue from a biological and material view‐point, highlighting key biological processes and variables that can impact the repair processes. From a materials design stand point, developing materials that can promote healing over scarring is the key. All indicators suggest that polymeric materials are most well‐suited for de novo engineering of tissues. In addition to biomolecular signals that are involved in controlling the fate of cells and neo‐tissue morphogenesis at the site of implantation, this review also discusses recent advances in design of highly functional injectable biomaterials, that show promise in controlling local biological processes.
Experimental and thermal analysis of washing the packed ice bed in wash columns
Authors: Qin Frank G. F. , Yang Min Lin , Yang Xiao Xi , Chen Xiao Dong , Abeynaike Arjan
Published: August 2009

In the process of freeze concentration (FC), the main problems in operating the counter‐current wash column used for separating ice from ice slurries are channeling and viscous fingering. These phenomena lead to the mixing of pure water and mother liquid, as well as entrainment of mother liquid within the removed ice. Experimental and thermal analysis of the wash front interface in this research relates ice melting and wash front breakthrough with the operating conditions (such as the wash water temperature, ice bed temperature and porosity). Criteria for wash front stability are proposed. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Brief communication: Puncture and crushing resistance scores of Tana river mangabey (Cercocebus galeritus) diet items
Authors: Wieczkowski Julie
Published: August 2009

Cercocebus mangabeys are characterized by dental traits that have been interpreted as adaptations to eat hard diet items. Although there are data that mangabeys include a large proportion of fruit and especially seeds in their diets, no hardness measurements have been done on mangabeys' food items. This study measured puncture and crushing resistance of food items in the diet of the Tana River mangabey (C. galeritus). Feeding data were collected by the use of scan samples from one mangabey group from August 2000 to July 2001 and from July 2005 to June 2006. Food items were collected during the latter period only, and from the same tree in or under which mangabeys had been observed eating. A portable agricultural fruit tester was used to measure the puncture resistance of fruit and a valve spring tester was used to measure the crushing resistance of seeds. The average puncture resistance of fruit was 1.7 kg/mm2, and the average crushing resistance of seeds was 12.8 kg. There were no correlations between puncture resistance, crushing resistance, or all resistance scores and frequency contribution to the diet. Resistance scores measured in this study were within the range of hardness scores of fruit and exceeded hardness scores of seeds eaten by other hard object feeders. Although this study supports the interpretation that Cercocebus dental traits are adaptations to hard object feeding, future research should investigate other material properties of food, as well as the role hard diet items play in niche separation and as fallback foods. Am J Phys Anthropol 2009. © 2009 Wiley‐Liss, Inc.
Local institutional review board (IRB) review of a multicenter trial: Local costs without local context
Authors: Ravina Bernard , Deuel Lisa , Siderowf Andrew , Dorsey E. Ray
Published: August 2009

Multicenter clinical research involves parallel Institutional Review Board (IRB) reviews based on the premise that local review reflects aspects of the research environment. We examined the costs and effects of local IRB review of the consent and protocol in a multicenter clinical trial in Parkinson disease. Seventy‐six percent of changes to the consent reflected standard institutional language, with no substantive changes to the protocol. The costs of this process exceeded $100,000. These findings support initiatives by the Office of Human Research Protections (OHRP) and the National Cancer Institute (NCI) to facilitate centralized reviews. This may be an opportune time for the National Institute of Neurological Disorders and Stroke (NINDS) to adopt a central review model. ANN NEUROL 2010;67:258–260
An operant approach to teaching joint attention skills to children with autism
Authors: Isaksen Jørn , Holth Per
Published: August 2009

A lack of joint attention skills may constitute a core impairment in autism. In the present study, a training protocol was developed, based on the literature on joint attention and on behavioral interventions. The training was organized into a sequence of three main parts respectively aimed at establishing each of the following skills: (1) responding to joint attention bids, (2) engaging in turn‐taking activities based on joint attention skills, and (3) initiating joint attention. Two novel components were incorporated in the training: (a) a discrimination training procedure aimed at establishing the adult's nods as conditioned reinforcers and (b) tasks based on turn‐taking, where joint attention skills were targeted and reinforced. The study was conducted according to a single‐subject experimental design, in which joint attention skills were measured before and after intervention, using the “behavioral assessment of joint attention.” Four 3.5–5.5 year‐old children diagnosed with autism participated in the study. All four children completed the training successfully and made significant progress in engaging in joint attention and in initiating joint attention skills. Following the completion of training and at 1 month follow‐up, parents reported that their children used their skills in different settings. Moreover, at follow‐up, all four children were reported to engage in joint attention behaviors and to enjoy doing so. Copyright © 2009 John Wiley & Sons, Ltd.
Feasibility of randomized controlled trials in liver surgery using surgery-related mortality or morbidity as endpoint
Authors: van den Broek M A J , van Dam R M , Malagó M , Dejong C H C , van Breukelen G J P , Olde Damink S W M
Published: August 2009

Background

There is a shortage of randomized controlled trials (RCTs) on which to base guidelines in liver surgery. The feasibility of conducting an adequately powered RCT in liver surgery using the dichotomous endpoints surgery-related mortality or morbidity was examined.

Methods

Articles published between January 2002 and November 2007 with mortality or morbidity after liver surgery as primary endpoint were retrieved. Sample size calculations for a RCT aiming to show a relative reduction of these endpoints by 33, 50 or 66 per cent were performed.

Results

The mean operative mortality rate was 1·0 per cent and the total morbidity rate 28·9 per cent; mean rates of bile leakage and postresectional liver failure were 4·4 and 2·6 per cent respectively. The smallest numbers of patients needed in each arm of a RCT aiming to show a 33 per cent relative reduction were 15 614 for operative mortality, 412 for total morbidity, 3446 for bile leakage and 5924 for postresectional liver failure.

Conclusion

The feasibility of conducting an adequately powered RCT in liver surgery using outcomes such as mortality or specific complications seems low. Conclusions of underpowered RCTs should be interpreted with caution. A liver surgery-specific composite endpoint may be a useful and clinically relevant solution to pursue.
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

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 < 0·001). Quality of life measured on a scale from 0 to 100 improved from 52 to 69 (P = 0·009) and 64 (P < 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

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

Background

The 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.

Methods

Data 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.

Results

Some 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).

Conclusion

Diverting 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

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

Candida 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

Background

Mental 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.

Hypothesis

We 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.

Methods

Participants 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.

Results

Vascular 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%.

Conclusion

We 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

Bivalent 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

Novel 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

Background

In 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.

Methods

Seven 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.

Results

Compared 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.

Conclusion

High‐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

Modulation 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

Background

The 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.

Methods

HUVECs 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.

Results

Light 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.

Conclusion

The 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.
High‐risk, high‐grade (T1G3) bladder cancer
Authors: Herr Harry W.
Published: August 2009

Can the morbidity of cystectomy be justified in elderly, sick patients? Certainly, cystectomy is associated with significant complications, which appear to be more pronounced in the elderly. However, in experienced hands, cystectomy appears to be safe; and in high‐volume centers, only 1% of patients are deemed too ill to tolerate cystectomy.
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

BACKGROUND:

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

BACKGROUND:

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.