bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine transporter genotype modulation of neural responses to smoking cues: confirmation in a new cohort
Authors: Franklin Teresa R. , Wang Ze , Li Yin , Suh Jesse J. , Goldman Marina , Lohoff Falk W. , Cruz Jeffrey , Hazan Rebecca , Jens Will , Detre John A. , Berrettini Wade , O'Brien Charles P. , Childress Anna Rose
Published: February 2011

Previously we demonstrated profound effects of dopamine transporter (DAT) SLC6A3 genotype on limbic responses to smoking cues (SCs). Probands carrying at least one copy of the 9‐repeat allele (9‐repeat carriers) had greater neural responses to SCs in the anatomically interconnected rostral ventral striatum/medial orbitofrontal cortex (VS/mOFC), compared with homozygotes for the 10‐repeat allele (10/10‐repeats). To test the reliability of the initial findings, we examined perfusion functional magnetic resonance images acquired during SC exposure in a new cohort of smokers (N = 26) who were genotyped for the SLC6A3 polymorphism. In smokers overall, activity was enhanced in the VS/mOFC (t = 3.77). Contrasts between allelic groups revealed that 9‐repeat carriers had a greater response to SCs in the VS (t = 3.12) and mOFC (t = 3.19). In separate groups, 9‐repeat carriers showed increased activity in the VS (t = 5.47) and mOFC (T = 4.96), while no increases were observed in 10‐repeats. Subjective reports of craving correlated with increased activity in reward‐related structures including the extended amygdala, insula and post‐central gyrus, and decreased activity in the dorsolateral prefrontal cortex, and were DAT‐genotype dependent (r = 0.63–0.96). In secondary analyses, we found that The Fagerström Test for Nicotine Dependence scores correlated with enhanced SC‐induced perfusion in 10/10‐repeats in the insula, mOFC, medial temporal and superior frontal gyri (r = 0.50–0.82), while correlations were absent in 9‐repeat carriers. Despite heterogeneity introduced by a host of factors, including variance in other genes involved in smoking behavior, we confirm that DAT genotype predicts the direction and location of neural responses to SCs.
Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration
Authors: Afrin Lawrence B. , Afrin Jessica B.
Published: February 2011

Afrin LB, Afrin JB. Value of preemptive CYP2C19 genotyping in allogeneic stem cell transplant patients considered for pentamidine administration. Clin Transplant 2011: 25: E271–E275. © 2011 John Wiley & Sons A/S.

Abstract:  Pneumocystis jirovecii prophylaxis is standard in allogeneic stem cell transplantation (alloSCT), sometimes with pentamidine at a low dose inhaled monthly. Human metabolism of pentamidine depends on cytochrome P450 2C19 (CYP2C19). The frequency of mutant CYP2C19 forms with decreased function (from 2% of Caucasians to 30% of Asians and 79% of certain Polynesians), together with common use of CYP2C19 inhibitors in the alloSCT process, creates risk for impaired pentamidine clearance resulting in toxicity ordinarily expected only with high doses given for active infection. We examined the charts of 32 consecutive pentamidine‐prophylaxed alloSCT patients at our center. We assessed hospital charges for the management of toxicities unexplained at the time but likely attributable, in retrospect, to pentamidine. Twenty‐eight percent experienced significant toxicities (incurring added charges of at least US$5000). Thirteen percent suffered major toxicity (incurring added charges of at least US$25 000; median added charge $351 701) and shorter survival (326 vs. 622 d for all pentamidine recipients), including 6% who died of pentamidine toxicities [one proven postmortem to have a (non‐functional) homozygous CYP2C19*2 mutation]. Charges for care attributable to pentamidine toxicity exceeded what preemptive genotyping would have cost by 73‐fold. These findings encourage routine use of preemptive CYP2C19 genotyping in alloSCT patients considered for pentamidine.
Linkage disequilibrium between HLA‐G*0104 and HLA‐E*0103 alleles in Tswa Pygmies
Authors: Julie D. C. , Buhler S. , Frassati C. , Basire A. , Galicher V. , Baier C. , Essautier A. , Regnier A. , Granier T. , Lepfoundzou A. D. , Chiaroni J. , Picard C.
Published: February 2011

Nonclassical human leukocyte antigen (HLA)‐G and ‐E loci are separated by approximately 660 kb on the short arm of chromosome 6. Interestingly, some functional and expression characteristics are relatively identical or associated for both molecules. For example, expression of HLA‐E on the cell surface has been linked to preferential binding of nonameric leader peptides derived from the signal sequence of HLA‐G. It has been suggested that these two molecules act synergistically in modulating susceptibility to infectious or chronic inflammatory diseases. A possible explanation for these observations is that HLA‐E and HLA‐G are evolving under analogous selective pressures and have functions that place them under selective regimes differing from classical HLA genes. The purpose of this study was to investigate the consistency of this hypothesis based on the characterization of the molecular polymorphism of these two genes and their linkage disequilibrium (LD) in three populations, i.e. Southeastern French (n = 57), Teke Congolese (n = 84) and Tswa Pygmies (n = 74). Allelic frequencies observed for HLA‐G and HLA‐E and for 14‐bp ins/del polymorphism in the three populations were similar to those observed in the literature for populations from corresponding geographic areas. Only one of the recently described HLA‐G polymorphisms (HLA‐G*01:07‐01:16) was found, i.e. HLA‐G*01:15 in one individual from Congo. We showed that two haplotypes in Tswa Pygmies, i.e. HLA‐G*01:04‐E*01:03:01 and G*01:04‐E*01:01, exhibited highly significant positive and negative D′ values respectively. Although these LD could have functional implications, it is more likely because of the genetic drift as the two other populations did not display any significant LD.
Sequence‐based typing of major histocompatibility complex class I chain‐related gene A alleles by use of exons 2–5 information
Authors: Fürst D. , Solgi G. , Recker K. , Mytilineos D. , Schrezenmeier H. , Mytilineos J.
Published: February 2011

The polymorphic MICA (major histocompatibility complex class I chain‐related gene A) (Gene ID: 100507436) gene products are a ligand of the activating natural killer cell receptor, NKG2D. Their clinical importance spans from solid organ transplantation to bone marrow transplantation and disease susceptibility. Typing of MICA genes by sequencing is hampered by an exon 5 short tandem repeat, the definition of which is critical for the final allelic and functional assignment. We present a novel sequencing approach, which uses group‐specific (7T/8T) exon 5 polymerase chain reactions (PCRs) and facilitates hemizygous exon 5 MICA‐PCR in approximately 70% of the tested individuals. With this method we typed the International Histocompatibility Workshop Group MICA reference panel (40 cell lines) as well as 110 healthy South German blood donors. All ambiguities, with the exception of MICA*008:01/008:04 (synonymous substitution in exon 1) and MICA*009:01/049 (nonsynonymous substitution in exon 6), could be resolved with our method. Analysis of Hardy–Weinberg equilibrium for our cohort showed no significant difference between expected and observed frequencies of MICA alleles (P = 0.6142). The three most frequent alleles in our blood donor cohort were MICA*008:01/008:04 (40.5%), MICA*002:01 (13.2%), and MICA*009:01/049 (8.6%). The 7T polymorphism was observed in 67.7% and the 8T polymorphism in 32.3% of our blood donor cohort. Individuals (24.5%) tested were homozygous. The approach described in this paper is suitable for accurate sequencing of large sample numbers, including direct readout of exon 5 sequences. It is compatible with laboratory automation and commercial human leukocyte antigen analysis software tools. It may therefore be applied in large clinical trials.
‘Immunogenetics of Aging’: report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop
Authors: Naumova E. , Ivanova M. , Pawelec G. , Constantinescu I. , Bogunia‐Kubik K. , Lange A. , Qguz F. , Carin M. , Franceschi C. , Caruso C. , Middleton D.
Published: February 2011

‘Immunogenetics of Aging’ is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer‐cell immunoglobulin‐like receptors (KIRs) and mannose‐binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti‐inflammatory cytokine gene profiles, decreased frequency of interleukin‐10 (IL‐10) and transforming growth factor‐B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor‐A and IL‐12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2‐deficient haplotypes were found in the group with higher cytomegalovirus‐specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging.
A processed HLA‐A*24:02 pseudogene found in the peripheral blood of a father and his son
Authors: Ko S.‐Y. , Oh H.‐B. , Sohn Y.‐H. , Jun J. , Kwon O.‐J.
Published: February 2011

We encountered a case that exhibited a discrepancy in human leukocyte antigen‐A (HLA‐A) type determined by sequence‐based typing (SBT) and sequence‐specific primer (SSP) molecular typing. The child of this case was identified as A*02:01 homozygote and A*02, A*24, respectively. The HLA‐A type of his father was A*02:01, 26:01, but low‐resolution SSP also showed unexpected amplification with A*24 primers as with the child. Serologic typing of the child and the father was A2/blank and A2/A26, respectively. Sequencing analysis of the A*24 variant in the child and the father showed a complete deletion of all introns of the A*24:02 allele. Though rare, this type of processed pseudogene variant can be one of the causes of discrepancies between high‐ and low‐resolution HLA typing.
A multi‐site study using high‐resolution HLA genotyping by next generation sequencing
Authors: Holcomb C. L. , Höglund B. , Anderson M. W. , Blake L. A. , Böhme I. , Egholm M. , Ferriola D. , Gabriel C. , Gelber S. E. , Goodridge D. , Hawbecker S. , Klein R. , Ladner M. , Lind C. , Monos D. , Pando M. J. , Pröll J. , Sayer D. C. , Schmitz‐Agheguian G. , Simen B. B. , Thiele B. , Trachtenberg E. A. , Tyan D. B. , Wassmuth R. , White S. , Erlich H. A.
Published: February 2011

The high degree of polymorphism at human leukocyte antigen (HLA) class I and class II loci makes high‐resolution HLA typing challenging. Current typing methods, including Sanger sequencing, yield ambiguous typing results because of incomplete genomic coverage and inability to set phase for HLA allele determination. The 454 Life Sciences Genome Sequencer (GS FLX) next generation sequencing system coupled with conexio atf software can provide very high‐resolution HLA genotyping. High‐throughput genotyping can be achieved by use of primers with multiplex identifier (MID) tags to allow pooling of the amplicons generated from different individuals prior to sequencing. We have conducted a double‐blind study in which eight laboratory sites performed amplicon sequencing using GS FLX standard chemistry and genotyped the same 20 samples for HLA‐A, ‐B, ‐C, DPB1, DQA1, DQB1, DRB1, DRB3, DRB4, and DRB5 (DRB3/4/5) in a single sequencing run. The average sequence read length was 250 base pairs and the average number of sequence reads per amplicon was 672, providing confidence in the allele assignments. Of the 1280 genotypes considered, assignment was possible in 95% of the cases. Failure to assign genotypes was the result of researcher procedural error or the presence of a novel allele rather than a failure of sequencing technology. Concordance with known genotypes, in cases where assignment was possible, ranged from 95.3% to 99.4% for the eight sites, with overall concordance of 97.2%. We conclude that clonal pyrosequencing using the GS FLX platform and conexio atf software allows reliable identification of HLA genotypes at high resolution.
Identification of nine novel HLA‐DRB1 alleles, HLA‐DRB1*04:91, DRB1*07:18, DRB1*11:01:12, DRB1*12:02:05, DRB1*12:22, DRB1*12:23, DRB1*13:100, DRB1*15:45, and DRB1*15:46 by polymerase chain reaction–sequence‐based typing
Authors: Qu J.‐H. , Li J. , Chen H. , Zheng Z.‐Z. , Liao K.‐Z. , Shen M.‐Z.
Published: February 2011

Nine novel human leukocyte antigen‐DRB1 (HLA‐DRB1) alleles were identified in Chinese individuals.
Identification of new HLA‐DRB1 alleles in Kazakh individuals
Authors: Kuranov A. B. , Mukhamedyarov D. A. , Momynaliev K. T.
Published: February 2011

Seven novel human leukocyte antigen (HLA)‐DRB1 alleles were identified during routine sequence‐based typing (SBT) of healthy Kazakh individuals.
Renal allograft recipient with melioidosis of the urinary tract
Authors: Varughese S. , Mohapatra A. , Sahni R. , Balaji V. , Tamilarasi V.
Published: February 2011

S. Varughese, A. Mohapatra, R. Sahni, V. Balaji, V. Tamilarasi. Renal allograft recipient with melioidosis of the urinary tract. Transpl Infect Dis 2011: 13: 95–96. All rights reserved
Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’
Authors: Florescu D.F. , Mindru C. , Chambers H.E. , Kalil A.C.
Published: February 2011

D.F. Florescu, C. Mindru, H.E. Chambers, A.C. Kalil. Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’. Transpl Infect Dis 2011: 13: 411–415. All rights reserved

Abstract: Few cases of co‐infection with cytomegalovirus (CMV) and Clostridium difficile colitis have been reported previously. We describe 2 cases of CMV and C. difficile colitis, and review 7 previously published reports. We aim to raise awareness of possible CMV–C. difficile co‐infection, especially in refractory cases of C. difficile colitis.
Comparing endoscopic submucosal dissection with transanal resection for non‐invasive rectal tumor: A retrospective study
Authors: Kiriyama Shinsuke , Saito Yutaka , Matsuda Takahisa , Nakajima Takeshi , Mashimo Yumi , Joeng Henry KM , Moriya Yoshihiro , Kuwano Hiroyuki
Published: February 2011

Background and Aim:  Endoscopic submucosal dissection (ESD) is an alternative to transanal resection (TAR) in treating rectal adenomas, intramucosal cancers, and superficial submucosal cancers. The purpose of this study is to compare the clinical efficacy between ESD and TAR for non‐invasive rectal tumors.

Methods:  Between January 1998 and December 2006, 85 patients with preoperative diagnosis of non‐invasive rectal tumors were treated by ESD or TAR. En‐bloc resection, local recurrence, complication, procedure time, and hospital stay were evaluated retrospectively using a prospectively‐completed database.

Results:  Mean resection sizes were 40 mm and 39 mm in diameter for the ESD and TAR groups, respectively. En‐bloc resections with a negative resection margin were achieved in 67% (35/52) of the ESD group, which was significantly higher than the 42% (14/33) in the TAR group. Sixty‐three lesions were diagnosed as curative resection, histopathologically. There was no local recurrence in the ESD group, but five local recurrences developed in the TAR group. Two rectal perforations, one minor delayed bleeding, and one subcutaneous emphysema in the ESD group were successfully managed conservatively. There were one minor delayed bleeding and two anesthesia‐related complications in the TAR group. The ESD group had a shorter hospital stay than the TAR group (4.9 days vs 7 days), but a longer procedure time (131 min vs 63 min).

Conclusion:  ESD was more effective than TAR in treating non‐invasive rectal tumors, with a lower recurrence rate and shorter hospital stay.
Old age and male sex are associated with increased risk of asymptomatic erosive esophagitis: Analysis of data from local health examinations by the Korean National Health Insurance Corporation
Authors: Cho Jae Hee , Kim Hee Man , Ko Geun Jun , Woo Myoung Lyeol , Moon Chang Mo , Kim Yu Jin , Han Ki Jun , Song Si Young , Cho Hyeon Geun
Published: February 2011

Background and Aims:  Silent gastroesophageal reflux disease (GERD) is often detected during routine screening esophagogastroduodenoscopy (EGD). However, the risk factors and clinical implications of silent GERD remain unclear. In the present study, we investigated the risk factors for asymptomatic erosive esophagitis by analyzing the local area health examination data.

Methods:  The Korean National Health Insurance Corporation provides a bi‐annual health examination performed by qualified local hospitals for the early detection of cancer in medical insurance holders over 40 years of age. Participants who completed self‐reported questionnaires on health, followed by EGD at the Myongji Hospital (Goyang, Korea), were enrolled in this study.

Results:  The data of a total of 5301 participants who underwent EGD between January 2005 and December 2008 were analyzed. The prevalence of erosive esophagitis was 6%. In the multivariate analysis, erosive esophagitis was strongly associated with an age greater than 60 years (odds ratio [OR]: 0.7, 95% confidence interval [CI]: 0.6–1.0), male sex (OR: 2.3, 95% CI: 1.7–3.0), hiatus hernia (OR: 2.9, 95% CI: 2.1–4.0), duodenal ulcer (OR: 1.6, 95% CI: 1.1–2.5), hypertension (OR: 1.5, 95% CI: 1.2–2.0), and smoking (OR: 1.4, 95% CI: 1.0–1.8). Of the 320 participants with erosive esophagitis, 145 (45.3%) were asymptomatic participants, and those who were more frequently greater than 60 years (OR: 1.8, 95% CI: 1.1–3.1) and male (OR: 1.8, 95% CI: 1.1–3.2).

Conclusions:  Asymptomatic erosive esophagitis in adults older than 40 years is strongly associated with old age (≥ 60 years) and male sex compared with symptomatic erosive esophagitis.
Feeding the child with liver disease: A review and practical clinical guide
Authors: Smart Kathryn Mary , Alex George , Hardikar Winita
Published: February 2011

Nourishing children with liver disease is a challenging task; however, appropriate assessment and well‐timed nutritional interventions are paramount for a good long‐term outcome in these patients. An appropriate balance of macronutrients, micronutrients, and vitamins is important, as is the route of administration. This review aims to highlight the practical points in nutrition assessment and also provides a guide to the various nutritional interventions available for children with chronic liver disease.
Clinical outcomes and factors for response prediction after the first course of corticosteroid therapy in patients with active ulcerative colitis
Authors: Yoon Jin Young , Cheon Jae Hee , Park Jae Jun , Hong Sung Pil , Kim Tae Il , Kim Won Ho
Published: February 2011

Background and Aims:  Both clinical outcomes and factors predictive for poor response after an initial course of corticosteroids have not yet been well established in the treatment of moderate to severe ulcerative colitis (UC). We therefore evaluated the short‐ and long‐term effects of corticosteroids and prognostic factors in UC patients after such therapy.

Methods:  We recruited consecutive patients who had moderate to severe UC and were treated with the first course of systemic corticosteroids between November 1996 and December 2007 using the database of Severance Hospital in Seoul, Korea. We then evaluated clinical outcomes at 1 month, 3 months, and 1 year after the initiation of corticosteroid treatment.

Results:  Our study included a total of 177 patients. At 1 month, complete remission was achieved in 70 patients (39.5%) and partial remission in 88 (49.7%). Fifteen patients (8.5%) were refractory to the treatment, and four (2.3%) underwent proctocolectomy. We observed prolonged response in 111 (64.9%) at 3 months and 95 (59.4%) patients at 1 year, corticosteroid dependency in 49 (28.7%) and 51 (31.9%) patients, and no response in 11 (6.4%) and 14 (8.7%) patients. A higher initial Mayo score was found to be the only poor prognostic factor at 1 month (P = 0.032) and 1 year (P < 0.001).

Conclusions:  Our data showed that most Korean patients with active UC responded well to the first course of corticosteroid treatment. However, a considerable number of patients eventually turned out to be refractory to or dependent on this therapy. The initial higher Mayo score was strongly associated with poor outcomes.
Diagnostic accuracy of T‐cell interferon‐γ release assays in tuberculous pleurisy: A meta‐analysis
Authors: ZHOU QIONG , CHEN YI‐QIANG , QIN SHOU‐MING , TAO XIAO‐NAN , XIN JIAN‐BAO , SHI HUAN‐ZHONG
Published: February 2011

Background and objective:  The diagnosis of tuberculous pleurisy by analysis of pleural fluid using standard diagnostic tools is difficult. Recently, T‐cell interferon‐γ release assays (IGRA) have been introduced for the diagnosis of tuberculous pleurisy. The aim of the present meta‐analysis was to establish the overall diagnostic accuracy of IGRA on both pleural fluid and peripheral blood, for diagnosing tuberculous pleurisy.

Methods:  A systematic review was performed of English language publications. Sensitivity, specificity and other measures of the accuracy of IGRA for the diagnosis tuberculous pleurisy using both pleural fluid and blood were pooled using a random‐effects model or a fixed‐effects model. Receiver operating characteristic curves were used to summarize overall test performance.

Results:  Seven out of eight studies met the inclusion criteria. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value and diagnostic odds ratio were, for pleural fluid: 0.75, 0.82, 3.49, 0.24, 0.85, 0.70 and 19.04, respectively; and for blood: 0.80, 0.72, 2.86, 0.28, 0.78, 0.74 and 11.06, respectively.

Conclusions:  As almost 20% of non‐tuberculosis patients would be erroneously treated for tuberculosis and 25% of patients with tuberculous pleurisy would be missed, pleural fluid IGRA are not useful for the clinical diagnosis of tuberculous pleurisy.
Applying gene expression microarrays to pulmonary disease
Authors: CAMPBELL JOSHUA D. , SPIRA AVRUM , LENBURG MARC E.
Published: February 2011

Gene expression microarrays are high throughput technologies that can simultaneously measure the expression levels of most known genes in the human genome within a biological sample. The study of gene expression has revealed new understanding into the biological complexities of the cell and can impact the field of medicine by providing new insights into disease. Examining gene expression in samples from patients with pulmonary disease can elucidate molecular mechanisms responsible for disease pathogenesis or uncover novel molecular subtypes within a disease. Gene expression signatures of disease pathogenesis can further be used to suggest novel therapeutic compounds. Biomarkers can be developed from gene expression data that can aid clinicians in diagnosing disease or can guide clinicians in tailoring therapeutic strategies to individual patients. To demonstrate the applications of gene expression microarray technology, we will review several studies in pulmonary disease that utilize gene expression profiling techniques to gain biological insights into disease or to develop clinically relevant biomarkers for disease management.
A multicentre surveillance study on the characteristics, bacterial aetiologies and in vitro antibiotic susceptibilities in patients with acute exacerbations of chronic bronchitis
Authors: HUI DAVID S. , IP MARGARET , LING THOMAS , CHANG SHAN‐CHWEN , LIAO CHUN‐HSING , YOO CHUL‐GYU , KIM DEOG‐KYEOM , YOON HO‐IL , UDOMPANICH VISIT , MOGMEUD SOMKID , MUTTALIF RAZAK , SALLEH AZMI M. , ROA CAMILO , MENDOZA MYRNA , FAJARDO‐ANG CONCEPCION , SOEPANDI PRIYANTI , ISBANIAH FATHIYAH , BURHAN ERLINA , SUDARMONO PRATIWI , MANGUNNEGORO HADIARTO , LIU HANS H.
Published: February 2011

Background and objective:  Antimicrobial resistance is a global problem and the prevalence is high in many Asian countries.

Methods:  A prospective observational study of the prevalence of bacterial pathogens and their antimicrobial susceptibilities in patients with acute exacerbations of chronic bronchitis (AECB) was conducted in Indonesia, Philippines, Korea, Thailand, Malaysia, Taiwan and Hong Kong from August 2006 to April 2008. The diagnosis of AECB was based on increased cough and worsening of two of following: dyspnoea, increased sputum volume or purulence. Patients who had taken antibiotics within 72 h of presentation were excluded. All bacterial strains were submitted to a central laboratory for re‐identification and antimicrobial susceptibility testing to 16 antimicrobial agents according to Clinical and Laboratory Standards Institute.

Results:  Four hundred and seven isolates were identified among 447 patients of AECB. The most frequent organisms isolated were Klebsiella pneumoniae and associated species (n = 91 + 17), Haemophilus influenzae (n = 71), Pseudomonas aeruginosa (n = 63), Streptococcus pneumoniae (n = 32), Acinetobacter baumannii (n = 22) and Moraxella catarrhalis (n = 21). According to Clinical and Laboratory Standards Institute susceptibility breakpoints, 85.7% and >90% of these pathogens were susceptible to levofloxacin and cefepime respectively. Other options with overall lower susceptibilities include imipenem, ceftazidime, ceftriaxone and amoxicillin/clavulanate.

Conclusions:  Gram‐negative bacteria including Klebsiella spp., P. aeruginosa and Acinetobacter spp. constitute a large proportion of pathogens identified in patients with AECB in some Asian countries. Surveillance on the local prevalence and antibiotic resistance of these organisms is important in guiding appropriate choice of antimicrobials in the management of AECB.
Urological involvement in renal transplantation
Authors: Sackett Daniel D , Singh Pooja , Lallas Costas D
Published: February 2011

Historically, urologists were the primary surgeons in renal transplantation. Specialization and increased complexity of the field of transplantation, coupled with a de‐emphasis of vascular surgical training in urology, has created a situation where many renal transplants are carried out by surgeons with a general surgery background. Because of its genitourinary nature, however, urological input in renal transplantation is still vital. For living donors, a urologist should be involved to help evaluate and prepare certain patients for eventual donation. This could involve both medical and surgical intervention. Additionally, urologists who carry out living donor nephrectomy maintain a sense of ownership in the renal transplant process and provide a unique opportunity to the trainees of that particular program. For renal transplant recipients, preoperative evaluation of voiding dysfunction and other genitourinary anomalies might be necessary before the transplant. Also, occasional surgical intervention to prepare a patient for renal transplant might be necessary, such as in a patient with a small renal mass that is detected by a screening pretransplant ultrasound. Intraoperatively, for patients with complex urological reconstructions that might be related to the etiology of the renal failure (urinary diversion, bladder augmentation), a urologist who is familiar with the anatomy should be available. Postoperatively, urological evaluation and intervention might be necessary for patients who had a pre‐existing urological condition or who might have developed something de novo after the transplant. Although renal transplant programs could consult an on‐call urologist for particular issues on an as‐needed basis, having a urologist, who has repeated exposure to the particular issues and procedures that are involved with renal transplantation, and who is part of a dedicated multidisciplinary renal transplant team, provides optimal quality of care to these complex patients.
Radiographic osteoarthritis and pain are independent predictors of knee cartilage loss: a prospective study
Authors: Saunders J. , Ding C. , Cicuttini F. , Jones G.
Published: February 2011

Background:  There is controversy about whether pain and radiographic osteoarthritis (ROA) predict subsequent cartilage loss. The aim of this study was to describe the relationship between ROA, pain and cartilage loss in the knee.

Methods:  We studied randomly selected subjects at baseline and approximately 2.9 years later (n= 399). The presence of ROA was assessed at baseline with a standing anteroposterior semiflexed radiograph scored using the Osteoarthritis Research Society International atlas for osteophytes (OP) and joint space narrowing (JSN). Pain was assessed by the Western Ontario McMaster Osteoarthritis Index. Subjects' medial and lateral tibial cartilage volumes were determined by magnetic resonance imaging at both time points.

Results:  In cross‐sectional analysis, both medial and lateral tibial cartilage volumes were lower in those with ROA. Any medial ROA predicted medial tibial cartilage loss (3.2% (standard deviation (SD) 5.6) vs 1.9% (SD 5.3) per annum) while any lateral ROA predicted both medial (4.0% (SD 6.0) vs 2.2% (SD 5.3) per annum) and lateral (3.5% (SD 5.8) vs 1.6% (SD 4.2) per annum) tibial cartilage loss (all P < 0.05). In multivariate analysis, JSN and OP at both medial and lateral sites had independent dose–response associations with tibial cartilage loss at both sites. Pain was an independent predictor of lateral, but not medial, tibial cartilage loss after taking ROA into account.

Conclusions:  Subjects with ROA (either JSN or OP) and, to a lesser extent, pain lose cartilage faster than subjects without ROA and the more severe the ROA the greater the rate of loss. These findings have implications for the design of clinical trials.
Incretin‐based therapies – review of the physiology, pharmacology and emerging clinical experience
Authors: Martin J. H. , Deacon C. F. , Gorrell M. D. , Prins J. B.
Published: February 2011

Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose‐dependent insulinotropic peptide and glucagon‐like peptide‐1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase‐4, the enzyme responsible for the short half‐life of endogenous incretins, and administration of long‐acting dipeptidyl peptidase‐4‐resistant peptides that bind to and activate the glucagon‐like peptide‐1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.
Reporting clinical trial information: colorectal cancer trials at Sydney Cancer Centre
Authors: Chua W. , Horvath L. , Beale P. , Clarke S. J.
Published: February 2011

Background:  Clinical trial units are integral to the functioning of a medical oncology department with patient access to clinical trials an important component in patient care. There has been a paucity of potential key performance indicators in medical oncology and clinical trial information may be utilised for this purpose. The aim of this study was to record retrospectively and collate prospectively collected information regarding basic demographics, response rate, progression and survival plus grade 3 or 4 toxicity in patients enrolled in clinical trials for metastatic colorectal cancer at the Sydney Cancer Centre between 1999 and 2007.

Methods:  Baseline patient demographics, clinical response, progression dates, grade 3 or 4 toxicities plus treatment‐related fatalities were collected from individual clinical trials. Outcome measures were clinical response, progression‐free survival and overall survival.

Results:  There was a total of 14 trials undertaken during the defined period for patients with metastatic colorectal cancer. There was available information for 243 patient trials with sufficient information regarding response rates, toxicity, progression and survival. Tumour response rates ranged from 27% to 66% for first line chemotherapy trials and 0% to 20% for non‐first line chemotherapy trials. The overall progression‐free survival was 6.4 months and overall survival 14.0 months for all trials. There was one treatment‐related fatality on clinical trial during this period.

Conclusions:  Results of our clinical database have been used here to illustrate the concept and value of reporting clinical trial information in medical oncology. Public reporting of such information may allow for comparisons between units and for quality improvement.
Smoking cessation post‐discharge following nicotine replacement therapy use during an inpatient admission
Authors: Williams J. H. , Jones T. E.
Published: February 2011

Background: Cigarette smoking remains a health issue despite declining prevalence in Australia. The burden of tobacco‐related morbidity affects hospitals, particularly those in lower socioeconomic areas where prevalence is highest.

Aim: We have shown that nicotine replacement therapy (NRT) use during hospitalization increases motivation to quit post‐discharge. We postulated that subjects using the nicotine patch post‐discharge, in comparison to the inhaler, would have higher rates of abstinence at 12 months after discharge. The aim was to compare the efficacy of the nicotine patch or inhaler formulation for cessation post‐discharge, following use during admission.

Methods: Post‐discharge, subjects chose their preferred formulation (patch or inhaler) based on their experience with NRT during admission. Tailored, medium‐intensity support was provided with subsidized NRT during outpatient visits. Subjects were followed for 12 months. Exhaled breath CO confirmed non‐smoking.

Results: Of 123 subjects enrolled, 37 elected to use the inhaler, 50 the patch and 36 no NRT. At 12 months continuous abstinence rates were 38%, 38% and 25% respectively.

Discussion: This study built upon the ‘teachable moment’ provided by hospitalization and the inpatient use of NRT, encouraging cessation post‐discharge. Both NRT formulations provided similar 12 month cessation rates, and were superior to those achieved by subjects electing not to use NRT. Although the patch was the most popular formulation, the inhaler provided an equally efficacious alternative which addressed other facets of cigarette addiction. Subjects electing not to use NRT were less successful.

Continuous abstinence rates were equivalent to community‐based studies using NRT. We recommend a similar programme to other hospitals.
Myelodysplasia in the Wellington region 2002–2007: disease incidence and treatment patterns
Authors: Irwin J. , D'Souza A. , Johnson L. , Carter J.
Published: February 2011

Aims:  To obtain accurate incidence data for myelodysplasia in the Wellington Region of New Zealand (NZ), to analyse the treatment these patients received and to review their outcome.

Methods:  Patients diagnosed with myelodysplasia between 1 January 2002 and 1 September 2007 were identified. Their bone marrow biopsy, clinical record, cytogenetic analysis and transfusion record were analyzed.

Results:  Seventy myelodysplastic patients were identified yielding an incidence of 2.75 per 100 000 per year. Median survival was 23 months, and transformation to acute leukaemia occurred in five patients (7.1%). Three patients (4.3%) received an allogeneic bone marrow transplant, and five patients (7.1%) received disease modifying treatment. Fifty‐six of 70 patients (80%) received a blood transfusion, a mean of 32.9 red blood cell (RBC) units were transfused to each transfusion recipient during the study period of 68 months. One of 70 patients developed a clinical syndrome of iron overload.

Conclusion:  The incidence of myelodysplasia in Wellington, NZ is similar to incidence figures from previously published studies. The treatment these patients received was predominantly supportive through RBC transfusion. Effective iron chelation therapy measures were not used although there appeared to be a low incidence of clinical iron overload in the study population. The data in this study will be available for comparison with future studies to assess trends in incidence, treatment and outcome in myelodysplastic patients in NZ.
Socioeconomic deprivation, readmissions, mortality and acute exacerbations of bronchiectasis
Authors: Roberts M. E. , Lowndes L. , Milne D. G. , Wong C. A.
Published: February 2011

Background:  Bronchiectasis is known to cause significant morbidity in children in New Zealand. Little is known of the disease in adults.

Aim:  Our objective was to characterise a cohort of adults who presented to hospital with acute exacerbations of the disease.

Methods:  We retrospectively collected information on all exacerbations treated as inpatients from a single hospital in South Auckland, New Zealand during 2002.

Results:  We collected information on 307 exacerbations in 152 patients. Twenty‐seven per cent were of Maaori ethnic origin, and 44% Pacific. Seventy per cent lived in areas categorised as the 20% most deprived in New Zealand. Comorbid conditions were present in 80% of patients – most commonly chronic obstructive pulmonary disease, asthma, diabetes and cardiac disease. Seventy (46%) patients had at least one readmission and 32 patients (21%) died within 12 months of admission to hospital. Greater deprivation was associated with increased mortality at 12 months after admission after adjusting for other factors (OR 11, 95% CI 2.0–61, P= 0.006). In the subgroup who underwent high‐resolution computed tomographic scanning (93), increasing severity of bronchiectasis (modified Bhalla score) was associated with readmission within 12 months (P= 0.004), but not mortality (P= 0.419).

Conclusions:  We have shown that exacerbations of bronchiectasis in South Auckland are more common in patients who are predominantly of Maaori or Pacific descent and are socioeconomically deprived. Admission to hospital for an exacerbation is associated with high readmission and mortality rates.
Diagnostic utility of endobronchial ultrasound‐guided transbronchial needle aspiration compared with transbronchial and endobronchial biopsy for suspected sarcoidosis
Authors: Plit M. , Pearson R. , Havryk A. , Da Costa J. , Chang C. , Glanville A. R.
Published: February 2011

Background:  Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is an accurate and minimally invasive technique that has been shown to have excellent diagnostic yield in the investigation of mediastinal and hilar lymphadenopathy. There is, however, little evidence comparing this procedure to the traditional diagnostic approach of transbronchial lung (TBLB) and endobronchial (EB) biopsies combined with characteristic clinical and radiological features in sarcoidosis.

Aim:  To compare the diagnostic yield of EBUS‐TBNA, TBLB and EB in patients with suspected sarcoidosis.

Methods:  Data from 40 consecutive patients with suspected sarcoidosis who underwent combined EBUS‐TBNA with TBLB and EB biopsies were recorded.

Results:  A total of 37 patients was confirmed as sarcoidosis, and three had other diagnoses. There was no difference in diagnostic accuracy rates between EBUS‐TBNA and TBLB for all stages of sarcoidosis (84% vs 78%, P= 0.77). Combined EBUS‐TBNA and TBLB procedures yielded a diagnostic accuracy of 100%. There was a highly significant difference in diagnostic accuracy between EBUS‐TBNA and EB in stage I (80% vs 27%) (P < 0.01) and stage II disease (86% vs 27%) (P < 0.01). Similarly, a highly significant difference in diagnostic accuracy was seen between TBLB and EB (P < 0.01). No adverse events occurred.

Conclusion:  Endobronchial ultrasound‐guided transbronchial needle aspiration alone has a high diagnostic yield with a very low complication rate for patients with suspected sarcoidosis.
Prevalence and determinants of QT interval prolongation in medical inpatients
Authors: Pasquier M. , Pantet O. , Hugli O. , Pruvot E. , Buclin T. , Waeber G. , Aujesky D.
Published: February 2011

Background:  QT interval prolongation carries an increased risk of torsade de pointes and death.

Aim:  We sought to determine the prevalence of QT prolongation in medical inpatients and to identify determinants of this condition.

Methods:  We enrolled consecutive patients who were admitted to the internal medicine ward and who had an electrocardiogram performed within 24 h of admission. We collected information on baseline patient characteristics and the use of QT‐prolonging drugs. Two blinded readers manually measured the QT intervals. QT intervals were corrected for heart rate using the traditional Bazett formula and the linear regression‐based Framingham formula. We used logistic regression to identify patient characteristics and drugs that were independently associated with QTc prolongation.

Results:  Of 537 inpatients, 22.3% had a prolonged QTc based on the Bazett formula. The adjusted odds for QTc prolongation based on the Bazett correction were significantly higher in patients who had liver disease (OR 2.9, 95% CI: 1.5–5.6), hypokalaemia (OR 3.3, 95% CI: 1.9–5.6) and who were taking ≥1 QT‐prolonging drug at admission (OR 1.7, 95% CI: 1.1–2.6). Overall, 50.8% of patients with QTc prolongation received additional QT‐prolonging drugs during hospitalisation.

Conclusions:  The prevalence of QTc prolongation was high among medical inpatients but depended on the method used to correct for heart rate. The use of QT‐prolonging drugs, hypokalaemia and liver disease increased the risk of QTc prolongation. Many patients with QTc prolongation received additional QT‐prolonging drugs during hospitalisation, further increasing the risk of torsade de pointes and death.
An audit of laryngoscopes and application of a new ISO standard
Authors: Baker Paul A. , McQuoid Shane , Thompson John M.D. , Jacobs Robert J.
Published: February 2011

Objective:  The International Organization for Standardization (ISO) recently published an International Standard (ISO 7376:2009) which specifies illuminance levels and tests for illumination from hook‐on type laryngoscopes used for intubation. A clinical study examining luminance for laryngoscopy found that 100 cd·m−2 was the minimum level acceptable for laryngoscopy. The purpose of this study was to measure the quality of light from laryngoscopes available for use by anesthetists in an anesthetic department and compare them to the ISO illuminance standard and published minimum acceptable luminance limits.

Methods:  A measuring device was constructed to support each laryngoscope in a standardized manner. For 190 reusable laryngoscopes, illuminance was measured with a lux meter at the base of this device. Eighteen clinically available laryngoscopes were then examined in detail, as a snapshot study, with multiple light recordings according to the ISO Standard. We also measured the luminance provided by each laryngoscope.

Results:  Only two of the 18 laryngoscopes met the minimum illuminance level of 500 lux after 10 min. Nine laryngoscopes provided a luminance <100 cd·m−2, which is the reported minimum required luminance for laryngoscopy. None of the 18 laryngoscopes tested complied with the ISO standard for laryngoscope light distribution.

Conclusions:  Laryngoscope light should be regularly audited. Results from these audits can be used to retire or repair substandard laryngoscopes to maintain acceptable standards of laryngoscope light. Audit results produce tangible evidence that is useful when applying for capital expenditure. Light measurements are not easy to make. There needs to be a convenient device to reliably measure laryngoscope illumination.
Anesthesia can be safely provided for children in a high‐field intraoperative magnetic resonance imaging environment
Authors: Cox Robin G. , Levy Ron , Hamilton Mark G. , Ewen Alastair , Farran Peter , Neil Stuart G.
Published: February 2011

Objectives:  To describe the challenges associated with providing safe anesthesia and perioperative care for children in a remote intraoperative magnetic resonance (iMR) operating room (OR) and to identify perioperative anesthesia outcomes, including adverse events related to the iMR environment.

Background:  Increasingly, children undergo neurosurgical procedures in a high‐field iMR OR. We describe a 10‐year experience of providing anesthesia for children in this environment with a mobile 1.5‐Tesla magnet.

Methods:  A 10‐year retrospective analysis was conducted of children who underwent neurosurgical procedures in a high‐field mobile iMR OR. Primary outcomes related to perioperative adverse events and recovery profiles. Results were expressed as mean ± sd or median (range), as appropriate.

Results:  One hundred and five procedures were performed on 98 children, aged 4 months–18 years, weighing 6–112 kg. The commonest two diagnostic categories were tumor (n = 52) and seizures (n = 27). Median anesthetic time was 439 (185–710) mins. There were no significant adverse events related to the iMR environment. The mean postanesthetic care unit admission temperature was 37 ± 0.9°C and the mean modified Aldrete Score at 30 mins was 7.2 ± 0.9. Two patients experienced seizures in the immediate postoperative period, readily controlled with propofol. There was one breach of MR safety protocol, and no adverse events related to patient transport.

Conclusions:  Anesthesia and perioperative care of children in an iMR setting were associated with a very low incidence of complications, despite the duration of the procedures involved. Such success depends upon a cohesive team‐based approach.