bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and severity of self-reported asthma in young adults, 1976–2004
Authors: Browatzki A. , Ulrik C. S. , Lange P.
Published: July 2009

The aim of the present study was to describe the prevalence and severity of asthma in young Danish adults over three decades.

Males and females aged 20–35 yrs were sampled from the population of Copenhagen for the three surveys (1976–1978, 1991–1993 and 2001–2004). A total of 3,285 (46% male) subjects answered a questionnaire, and had their height, weight, forced expiratory volume in 1 s (FEV1) and forced vital capacity measured.

The prevalence of self-reported asthma was 1.5, 4.7 and 6.9%, respectively, in the three surveys (p<0.001). An increasing prevalence of asthma was observed in both males and females, although it was highest among females. The difference in FEV1between asthmatic and nonasthmatic subjects gradually increased, being 2.3 (p = 0.56) and 14.2% of the predicted value (p<0.001), respectively, in 1976–1978 and 2001–2004. From the 1991–1994 survey, increasing body mass index, especially >30 kg·m−2, was associated with a lower percentage predicted FEV1(p≤0.005), and further analyses suggested an additive effect of asthma and obesity on FEV1. The proportion of smokers declined from 60 to 38% (p<0.001).

The prevalence and severity of asthma have continued to increase over the last three decades among young Danish adults, and the observed increase in severity seems, at least partly, to be related to the increase in prevalence of obesity.
Control of breathing in children with mild sleep apnoea: a 6-year follow-up study
Authors: Rice A. , Costy-Bennett S. , Goodwin J. L. , Quan S. F. , Fregosi R. F.
Published: July 2009

We have previously shown that children (average age 9 yrs) with mildly elevated obstructive apnoea/hypopnoea indices (OAHI) retained CO2at rest. Here, we report the results of a 6-yr follow-up study on 14 children from that study.

Minute ventilation (V′E) and end-tidal CO2partial pressure (PET,CO2) were measured during hypercapnic challenge.

OAHI decreased from 7.5±4.7 events·h−1at age 9 yrs to 2.5±1.8 events·h−1at age 15 yrs (p<0.001), despite an increase in body mass index from 20±4.6 kg·m−2to 26±5.7 kg·m−2(p<0.0001). EupneicV′Eincreased from 4.1±0.31 L·min−1·m−2to 5.9±0.4 L·min−1·m−2(p<0.01), whilePET,CO2fell from 44.1±0.8 to 33±1.0 mmHg (p<0.001). TheV′E–PET,CO2obtained during hypercapnia was left shifted, such thatV′Eat aPET,CO2of 50 mmHg increased from 24 L·min−1at age 9 yrs to 36 L·min−1at age 15 yrs. Central respiratory drive did not change.

We hypothesise that somatic growth of the pharynx coupled with a regression of tonsillar tissue mass with age leads to enlargement of the upper airway lumen, a reduction in airway resistance and increased respiratory airflow at a given level of ventilatory drive.
CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD
Authors: Machado M-C. L. , Vollmer W. M. , Togeiro S. M. , Bilderback A. L. , Oliveira M-V. C. , Leitão F. S. , Queiroga F. , Lorenzi-Filho G. , Krishnan J. A.
Published: July 2009

Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic obstructive pulmonary disease (COPD). The present prospective cohort study tested the effect of OSAS treatment with continuous positive airway pressure (CPAP) on the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment would be associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving long-term oxygen therapy (LTOT).

Prospective study participants attended two outpatient advanced lung disease LTOT clinics in São Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and 34 did not accept or were not adherent and were considered not treated.

The 5-yr survival estimate was 71% (95% confidence interval 53–83%) and 26% (12–43%) in the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting for several confounders, patients treated with CPAP showed a significantly lower risk of death (hazard ratio of deathversusnontreated 0.19 (0.08–0.48)).

The present study found that CPAP treatment was associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.
Does unrestrained single-chamber plethysmography provide a valid assessment of airway responsiveness in allergic BALB/c mice?
Authors: Zhang Qingling , Lai Kefang , Xie Jiaxing , Chen Guoqin , Zhong Nanshan
Published: July 2009

Background

Unrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial.

Objective

To investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice.

Methods

Ovalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness) and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge.

Results

Compared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed higher responsiveness than their controls (P < 0.05). The nasal mucosa was infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or nasal rubbing in allergic groups appeared more frequent than that in the control groups.

Conclusion

Penh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure), must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.
Role of ERK/MAPK in endothelin receptor signaling in human aortic smooth muscle cells
Authors: Chen Qing-wen , Edvinsson Lars , Xu Cang-Bao
Published: July 2009

Background

Endothelin-1 (ET-1) is a potent vasoactive peptide, which induces vasoconstriction and proliferation in vascular smooth muscle cells (VSMCs) through activation of endothelin type A (ETA) and type B (ETB) receptors. The extracellular signal-regulated kinase 1 and 2 (ERK1/2) mitogen-activated protein kinases (MAPK) are involved in ET-1-induced VSMC contraction and proliferation. This study was designed to investigate the ETAand ETBreceptor intracellular signaling in human VSMCs and used phosphorylation (activation) of ERK1/2 as a functional signal molecule for endothelin receptor activity.

Results

Subconfluent human VSMCs were stimulated by ET-1 at different concentrations (1 nM-1 μM). The activation of ERK1/2 was examined by immunofluorescence, Western blot and phosphoELISA using specific antibody against phosphorylated ERK1/2 protein. ET-1 induced a concentration- and time- dependent activation of ERK1/2 with a maximal effect at 10 min. It declined to baseline level at 30 min. The ET-1-induced activation of ERK1/2 was completely abolished by MEK1/2 inhibitors U0126 and SL327, and partially inhibited by the MEK1 inhibitor PD98059. A dual endothelin receptor antagonist bosentan or the ETAantagonist BQ123 blocked the ET-1 effect, while the ETBantagonist BQ788 had no significant effect. However, a selective ETBreceptor agonist, Sarafotoxin 6c (S6c) caused a time-dependent ERK1/2 activation with a maximal effect by less than 20% of the ET-1-induced activation of ERK1/2. Increase in bosentan concentration up to 10 μM further inhibited ET-1-induced activation of ERK1/2 and had a stronger inhibitory effect than BQ123 or the combined use of BQ123 and BQ788. To further explore ET-1 intracellular signaling, PKC inhibitors (staurosporin and GF109203X), PKC-delta inhibitor (rottlerin), PKA inhibitor (H-89), and phosphatidylinositol 3-kinase (PI3K) inhibitor (wortmannin) were applied. The inhibitors showed significant inhibitory effects on ET-1-induced activation of ERK1/2. However, blockage of L-type Ca2+channels or calcium/calmodulin-dependent protein kinase II, chelating extracellular Ca2+or emptying internal Ca2+stores, did not affect ET-1-induced activation of ERK1/2.

Conclusion

The ETAreceptors predominate in the ET-1-induced activation of ERK1/2 in human VSMCs, which associates with increments in intracellular PKC, PKA and PI3K activities, but not Ca2+signalling.
Association of virulence plasmid and antibiotic resistance determinants with chromosomal multilocus genotypes in Mexican Salmonella enterica serovar Typhimurium strains
Authors: Wiesner Magdalena , Zaidi Mussaret B , Calva Edmundo , Fernández-Mora Marcos , Calva Juan J , Silva Claudia
Published: July 2009

Background

Bacterial genomes are mosaic structures composed of genes present in every strain of the same species (core genome), and genes present in some but not all strains of a species (accessory genome). The aim of this study was to compare the genetic diversity of core and accessory genes of a Salmonella enterica subspecies enterica serovar Typhimurium (Typhimurium) population isolated from food-animal and human sources in four regions of Mexico. Multilocus sequence typing (MLST) and macrorestriction fingerprints by pulsed-field gel electrophoresis (PFGE) were used to address the core genetic variation, and genes involved in pathogenesis and antibiotic resistance were selected to evaluate the accessory genome.

Results

We found a low genetic diversity for both housekeeping and accessory genes. Sequence type 19 (ST19) was supported as the founder genotype of STs 213, 302 and 429. We found a temporal pattern in which the derived ST213 is replacing the founder ST19 in the four geographic regions analyzed and a geographic trend in the number of resistance determinants. The distribution of the accessory genes was not random among chromosomal genotypes. We detected strong associations among the different accessory genes and the multilocus chromosomal genotypes (STs). First, the Salmonella virulence plasmid (pSTV) was found mostly in ST19 isolates. Second, the plasmid-borne betalactamase cmy-2 was found only in ST213 isolates. Third, the most abundant integron, IP-1 (dfrA12, orfF and aadA2), was found only in ST213 isolates. Fourth, the Salmonella genomic island (SGI1) was found mainly in a subgroup of ST19 isolates carrying pSTV. The mapping of accessory genes and multilocus genotypes on the dendrogram derived from macrorestiction fingerprints allowed the establishment of genetic subgroups within the population.

Conclusion

Despite the low levels of genetic diversity of core and accessory genes, the non-random distribution of the accessory genes across chromosomal backgrounds allowed us to discover genetic subgroups within the population. This study provides information about the importance of the accessory genome in generating genetic variability within a bacterial population.
How can accelerated development of bioenergy contribute to the future UK energy mix? Insights from a MARKAL modelling exercise
Authors: Clarke Donna , Jablonski Sophie , Moran Brighid , Anandarajah Gabrial , Taylor Gail
Published: July 2009

Background

This work explores the potential contribution of bioenergy technologies to 60% and 80% carbon reductions in the UK energy system by 2050, by outlining the potential for accelerated technological development of bioenergy chains. The investigation was based on insights from MARKAL modelling, detailed literature reviews and expert consultations. Due to the number and complexity of bioenergy pathways and technologies in the model, three chains and two underpinning technologies were selected for detailed investigation: (1) lignocellulosic hydrolysis for the production of bioethanol, (2) gasification technologies for heat and power, (3) fast pyrolysis of biomass for bio-oil production, (4) biotechnological advances for second generation bioenergy crops, and (5) the development of agro-machinery for growing and harvesting bioenergy crops. Detailed literature searches and expert consultations (looking inter alia at research and development needs and economic projections) led to the development of an 'accelerated' dataset of modelling parameters for each of the selected bioenergy pathways, which were included in five different scenario runs with UK-MARKAL (MED). The results of the 'accelerated runs' were compared with a low-carbon (LC-Core) scenario, which assesses the cheapest way to decarbonise the energy sector.

Results

Bioenergy was deployed in larger quantities in the bioenergy accelerated technological development scenario compared with the LC-Core scenario. In the electricity sector, solid biomass was highly utilised for energy crop gasification, displacing some deployment of wind power, and nuclear and marine to a lesser extent. Solid biomass was also deployed for heat in the residential sector from 2040 in much higher quantities in the bioenergy accelerated technological development scenario compared with LC-Core. Although lignocellulosic ethanol increased, overall ethanol decreased in the transport sector in the bioenergy accelerated technological development scenario due to a reduction in ethanol produced from wheat.

Conclusion

There is much potential for future deployment of bioenergy technologies to decarbonise the energy sector. However, future deployment is dependent on many different factors including investment and efforts towards research and development needs, carbon reduction targets and the ability to compete with other low carbon technologies as they become deployed. All bioenergy technologies should become increasingly more economically competitive with fossil-based technologies as feedstock costs and flexibility are reduced in line with technological advances.
Nuclear accumulation of polyglutamine disease proteins and neuropathology
Authors: Havel Lauren S , Li Shihua , Li Xiao-Jiang
Published: July 2009

There are nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansion in various disease proteins. Although these polyglutamine proteins have different functions and are localized in different subcellular regions, all the polyQ diseases share a common pathological feature: the nuclear accumulation of polyQ disease proteins and the formation of inclusions. The nuclear accumulation of polyQ proteins in turn leads to gene transcriptional dysregulation and neuropathology. Here we will discuss potential mechanisms behind the nuclear accumulation of mutant polyQ proteins, since an understanding of how polyQ proteins accumulate in the nucleus could help elucidate the pathogenesis of these diseases and develop their treatment.
Dynamics of different-sized solid-state nanocrystals as tracers for a drug-delivery system in the interstitium of a human tumor xenograft
Authors: Kawai Masaaki , Higuchi Hideo , Takeda Motohiro , Kobayashi Yoshio , Ohuchi Noriaki
Published: July 2009

Introduction

Recent anticancer drugs have been made larger to pass selectively through tumor vessels and stay in the interstitium. Understanding drug movement in association with its size at the single-molecule level and estimating the time needed to reach the targeted organ is indispensable for optimizing drug delivery because single cell-targeted therapy is the ongoing paradigm. This report describes the tracking of single solid nanoparticles in tumor xenografts and the estimation of arrival time.

Methods

Different-sized nanoparticles measuring 20, 40, and 100 nm were injected into the tail vein of the female Balb/c nu/nu mice bearing human breast cancer on their backs. The movements of the nanoparticles were visualized through the dorsal skin-fold chamber with the high-speed confocal microscopy that we manufactured.

Results

An analysis of the particle trajectories revealed diffusion to be inversely related to the particle size and position in the tumor, whereas the velocity of the directed movement was related to the position. The difference in the velocity was the greatest for 40-nm particles in the perivascular to the intercellular region: difference = 5.8 nm/s. The arrival time of individual nanoparticles at tumor cells was simulated. The estimated times for the 20-, 40-, and 100-nm particles to reach the tumor cells were 158.0, 218.5, and 389.4 minutes, respectively, after extravasation.

Conclusions

This result suggests that the particle size can be individually designed for each goal. These data and methods are also important for understanding drug pharmacokinetics. Although this method may be subject to interference by surface molecules attached on the particles, it has the potential to elucidate the pharmacokinetics involved in constructing novel drug-delivery systems involving cell-targeted therapy.
Maternal Diabetes Causes Mitochondrial Dysfunction and Meiotic Defects in Murine Oocytes
Authors: Wang Qiang , Ratchford Ann M. , Chi Maggie M.-Y. , Schoeller Erica , Frolova Antonina , Schedl Tim , Moley Kelle H.
Published: July 2009

The adverse effects of maternal diabetes on embryo development and pregnancy outcomes have recently been shown to occur as early as the one-cell zygote stage. The hypothesis of this study was that maternally inherited mitochondria in oocytes from diabetic mice are abnormal and thus responsible in part for this latency of developmental compromise. In ovulated oocytes from diabetic mice, transmission electron microscopy revealed an alteration in mitochondrial ultrastructure, and the quantitative analysis of mitochondrial DNA copy number demonstrated an increase. The levels of ATP and tricarboxylic acid cycle metabolites in diabetic oocytes were markedly reduced compared with controls, suggesting a mitochondrial metabolic dysfunction. Abnormal distribution of mitochondria within maturing oocytes also was seen in diabetic mice. Furthermore, oocytes from diabetic mice displayed a higher frequency of spindle defects and chromosome misalignment in meiosis, resulting in increased aneuploidy rates in ovulated oocytes. Collectively, our results suggest that maternal diabetes results in oocyte defects that are transmitted to the fetus by two routes: first, meiotic spindle and chromatin defects result in nondisjunction leading to embryonic aneuploidy; second, structural and functional abnormalities of oocyte mitochondria, through maternal transmission, provide the embryo with a dysfunctional complement of mitochondria that may be propagated during embryogenesis.
Perspective—Finding the Organization in Organizational Theory: A Meta-Theory of the Organization as a Social Actor
Authors: King Brayden G. , Felin Teppo , Whetten David A.
Published: July 2009

Organization theory is a theory without a protagonist. Organizations are typically portrayed in organizational scholarship as aggregations of individuals, as instantiations of the environment, as nodes in a social network, as members of a population, or as a bundle of organizing processes. This paper hopes to highlight the need for understanding, explicating, and researching the enduring, noun-like qualities of the organization. We situate the organization in a broader social landscape by examining what is unique about the organization as a social actor. We propose two assumptions that underlie our conceptualization of organizations as social actors: external attribution and intentionality. We then highlight important questions and implications forming the core of a distinctively organizational analytical perspective.
General Paediatric Surgical Provision of Percutaneous Endoscopic Gastrostomy in a District General Hospital – A 12-Year Experience
Authors: Sathesh-Kumar T , Rollins Hazel , Cheslyn-Curtis Sarah
Published: July 2009

INTRODUCTION

A small, but significant, number of children require long-term nutritional support. The aim of this study was to demonstrate the safety and efficacy of providing a percutaneous endoscopic gastrostomy (PEG) service for children in a district general hospital and to raise awareness of the suitability of the procedure to be performed on paediatric surgery lists in similar hospitals across the UK.

PATIENTS AND METHODS

A multidisciplinary paediatric nutrition team was established and all children accepted for PEG insertion between 1995 and 2007 were entered onto a database prospectively and are included in this study. PEG tubes were inserted by the standard pull-through technique under general anaesthetic.

RESULTS

A total of 172 procedures were performed in 76 children. The median age at first tube insertion was 3 years (range, 0.5–18 years). Length of follow-up ranged from 1 month to 12.6 years. Fifty-eight children (76%) had a neurological abnormality, the commonest being cerebral palsy. All but one procedure were performed successfully, of which 63 (37%) were new insertions, 99 change of tube, 4 changed from surgical gastrostomy and 6 from PEG to button gastrostomy. The median hospital stay was 2 days (range, 2–7 days) for new insertions and 1 day for tube changes. There were 10 (6%) early complications within 30 days, the commonest being peritubal infection (6). The 39 late complications included 16 peritubal infection/granulomata, 9 ‘buried bumpers’, 4 worsening of gastro-oesophageal reflux disease, 2 gastrocolic fistulae, 3 gastrocutaneous fistulae and 4 tubal migration. There was no mortality.

CONCLUSIONS

We have demonstrated that paediatric PEG procedures and continuing management by a supporting team can be successfully and efficiently provided in the district general hospital. It should be possible for the majority of similar hospitals to provide local access and increase the availability of PEG feeding for children.
Distal Revascularisation with Interval Ligation (DRIL): An Experience
Authors: Field M , Blackwell J , Jaipersad A , Wall M , Silva MA , Morgan RH , Pherwani AD
Published: July 2009

INTRODUCTION

The global increase of chronic renal failure has resulted in a growing number of patients on haemodialysis using arteriovenous fistulas (AVFs). By virtue of their very function, AVFs at times shunt blood away from regions distally, resulting in an ischaemic steal syndrome. Distal revascularisation with interval ligation (DRIL) has been described as a procedure to treat symptomatic ischaemic steal. We present our experience in the management of this complication.

PATIENTS AND METHODS

Six patients with severe ischaemic steal were treated using a DRIL procedure between May 2004 and June 2007. There were three males and three females, all with elbow brachiocephalic AVFs. Symptoms ranged from severe rest pain to digital gangrene. Published results from international studies of 135 DRIL procedures were also reviewed.

RESULTS

Vascular access was maintained along with the elimination of ischaemic symptoms in the six patients using an ipsilateral reversed basilic vein graft. Interval ligation of the distal brachial artery was performed at the same time. All patients showed immediate and sustained clinical improvement of symptoms with a demonstrable increase in digital pulse oximetry.

CONCLUSIONS

DRIL is a beneficial treatment option that has proven successful at alleviating ischemic steal symptoms and preserving vascular access. This avoids placement of central lines, its associated risks, and the need to create an alternative sited fistula.
The EndoAssist™ Robotic Camera Holder as an Aid to the Introduction of Laparoscopic Colorectal Surgery
Authors: Gilbert JM
Published: July 2009

INTRODUCTION

Introducing laparoscopic colorectal surgery is a challenge to the whole surgical team. It is usual for an assistant to hold the laparoscope and be responsible for the surgeon's view of the operative field and a lack of expertise in the assistant can add significant difficulties. The EndoAssist™ is a robotic device that replaces the human assistant and ensures steady visualisation of the operative field and a view which can be controlled by the surgeon. This study describes its use in the introduction of laparoscopic colorectal surgery to a unit.

PATIENTS AND METHODS

The EndoAssist was employed for the introduction of laparoscopic colorectal surgery in a unit with previous experience of this device for laparoscopic cholecystectomy. It was used in a consecutive series of 77 laparoscopic colectomy operations.

RESULTS

The robotic device proved successful in the whole range of colorectal operations and a reliable assistant. No problems specific to the device were encountered.

CONCLUSIONS

The EndoAssist robot is a useful laparoscopic assistant and aided in the introduction of laparoscopic colorectal surgery.
A Prospective Audit of Endoscopic Vein Harvesting for Coronary Artery Bypass Surgery
Authors: Waqar-Uddin Zakariya , Purohit Manoj , Blakeman Nadene , Zacharias Joseph
Published: July 2009

INTRODUCTION

The objectives of this study were to: (i) assess the feasibility of minimally invasive endoscopic harvesting of the long saphenous vein or radial artery for use as conduit during coronary artery bypass surgery in the NHS setting; and (ii) investigate the results of endoscopic vein harvesting with regards to postoperative complications, ability to mobilise, and patient satisfaction.

PATIENTS AND METHODS

In this prospective audit, 25 consecutive patients, aged 52–90 years, undergoing either coronary artery bypass grafting alone or together with valve surgery or atrial fibrillation ablation were studied. All data were entered in purpose-designed proforma. Pre-operative risk factors including increasing age, diabetes, peripheral vascular disease, obesity, renal impairment, tobacco consumption and steroid use were documented. Time taken for harvest and conversion to traditional open vein harvest, quality of harvested vein in terms of number of repairs and vein damage were recorded. Postoperatively, we recorded harvest site wound complications, number of days to mobilise and total hospital stay. Pain score and patient satisfaction were also assessed.

RESULTS

There was one death due to myocardial infarction; another patient had postoperative cerebrovascular accident. A total of 43 lengths of grafts were harvested, 41 were long saphenous vein and two radial artery. Vein harvest time reduced significantly from a maximum of 94 min to 34 min for two lengths of long saphenous vein. Three patients required conversion from endoscopic vein harvesting to open vein harvest. The only postoperative complication directly related to endoscopic harvesting was bruising along the tunnel created by the passage of the instruments. None of the patients had any wound complication; none required antibiotics or wound debridement. Mean time to mobilise was 3.4 days. All patients who underwent successful endoscopic vein harvesting expressed satisfaction with regards to postoperative pain and cosmetic result.

CONCLUSIONS

Competence and ability to harvest conduit in an acceptable time frame are obtainable after a relatively low number of cases. The procedure is associated with a low number of postoperative complications and very high patient satisfaction.
Correlation between Rotator Cuff Tears and Repeated Subacromial Steroid Injections: A Case-Controlled Study
Authors: Bhatia M , Singh B , Nicolaou N , Ravikumar KJ
Published: July 2009

INTRODUCTION

Concern exists regarding potential damage to the rotator cuff from repeated corticosteroid injections into the subacromial space.

PATIENTS AND METHODS

In this retrospective, case-controlled study, 230 consecutive patients presenting to three orthopaedic units with subacromial impingement and investigated as an end-point with magnetic resonance imaging (MRI) of the shoulder were divided into groups having received less than three or three or more subacromial injections of corticosteroids.

RESULTS

With no significant difference in age and sex distribution, analysis by MRI showed no significant difference between the two groups in the incidence of rotator cuff tear (P < 1.0).

CONCLUSIONS

This suggests that corticosteroid use in patients with subacromial impingement should not be considered a causative factor in rotator cuff tears.
Feeding Patients Following Pancreaticoduodenectomy: A UK National Survey
Authors: Phillips Mary , Lordan Jeffrey T , Menezes Neville , Karanjia Nariman D
Published: July 2009

INTRODUCTION

Providing nutrition for patients following pancreaticoduodenectomy (PD) is vital but can be challenging. Due to the lack of UK national guidelines for the provision of nutrition and nutritional pre-operative assessment regarding PD, a national survey was conducted.

PATIENTS AND METHODS

A questionnaire was sent to the Department of Nutrition and Dietetics at each of the 31 specialist pancreatic centres listed with the Pancreatic Society of Great Britain and Ireland. Questions were asked regarding the nutritional assessment and treatment of patients undergoing classical PD and pylorus-preserving PD (PPPD) resections.

RESULTS

Twenty-two centres responded to the questionnaire. With regard to PD and PPPD, 82% routinely feed patients following resection, 32% have a regimen for staring feeds, 18% carry out pre-operative nutritional assessment, five centres have funding for an hepatobiliary dietition, and only four centres have a specialist hepatobiliary dietition employed. There was no consensus regarding the type or route of feeding, and at least one centre reported using parenteral nutrition exclusively.

CONCLUSIONS

Very few centres in the UK have funding for a hepatobiliary dietition. Hence pre-operative nutritional assessment in patients undergoing PD and PPPD does not receive much input. Although the importance of postoperative feeding in these patients is appreciated in all major units, there is no consensus with regards to feeding regimens. The authors hope this observational study will address these issues with this important message and stimulate further study in this area.
Ultrasensitive Prostate Specific Antigen Assay Following Laparoscopic Radical Prostatectomy – An Outcome Measure for Defining the Learning Curve
Authors: Viney R , Gommersall L , Zeif J , Hayne D , Shah ZH , Doherty A
Published: July 2009

INTRODUCTION

Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon.

OBJECTIVES

To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon's learning curve.

PATIENTS AND METHODS

Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery.

RESULTS

Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of ≤ 0.01 ng/ml at 3 months is 73% for the first 100 patients. This is statistically lower when compared with 83% (P < 0.05) for the second 100 patients and 80% for the third 100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66% patients with pT3 disease had a uPSA of ≤ 0.01 ng/ml at 3 months. Pre-operative PSA, PSA density and Gleason score were not correlated with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months. Positive margins correlate with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months but operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had no adverse effect on achieving a uPSA of ≤ 0.01 ng/ml at 3 months.

CONCLUSIONS

uPSA can be used as an early end-point in the analysis of oncological outcomes after radical prostatectomy. It is one of many measures that can be used in calculating a surgeon's learning curve for laparoscopic radical prostatectomy and in bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of ≤ 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.
Surgical Management of Boerhaave's Syndrome in a Tertiary Oesophagogastric Centre
Authors: Sutcliffe Robert P , Forshaw Matthew J , Datta Gourab , Rohatgi Ashish , Strauss Dirk C , Mason Robert C , Botha Abraham J
Published: July 2009

INTRODUCTION

The aim of this study was to review the management and outcome of patients with Boerhaave's syndrome in a specialist centre between 2000–2007.

PATIENTS AND METHODS

Patients were grouped according to time from symptoms to referral (early, < 24 h; late, > 24 h). The effects of referral time and management on outcomes (oesophageal leak, reoperation and mortality) were evaluated.

RESULTS

Of 21 patients (early 10; late 11), three were unfit for surgery. Of the remaining 18, immediate surgery was performed in 8/8 referred early and 6/10 referred late. Four patients referred late were treated conservatively. Oesophageal leak (78% versus 12.5%; P < 0.05) and mortality (40% versus 0%; P < 0.05) rates were higher in patients referred late. For patients referred late, mortality was higher in patients managed conservatively (75% versus 17%; not significant).

CONCLUSIONS

The best outcomes in Boerhaave's syndrome are associated with early referral and surgical management in a specialist centre. Surgery appears to be superior to conservative treatment for patients referred late.
Patient perception of doctors' attire within the orthopaedic outpatient department
Authors: Swindells MG , Rajan RA
Published: July 2009

The Department of Health recently announced new guidance on the clothing of staff including doctors within the NHS. The policy states: 'There is no conclusive evidence that uniforms (or other work clothes) pose a significant hazard in terms of spreading infection'. It goes on to say:'It seems that the public believe there is a risk'. This guidance received significant publicity through the media as a government push to reduce hospital infections. The health secretary described the guidance as 'a clear signal to patients that doctors, nurses and other clinical staff are taking their safety seriously'.
Bare below the… What do patients want their doctor to wear?
Authors: Henderson J , Budd H , Wimhurst J
Published: July 2009

In January 2008 NHS trusts adopted a new dress-code policy for doctors as part of a series of initiatives set out by the secretary of state for health to reduce hospital-acquired infections. Generally referred to as 'bare below the elbows,' the dress code forbids long sleeves, long neckties, white coats, wristwatches and jewellery except for a single plain (wedding) band from all clinical areas, including outpatient clinics.
Introducing NHS Evidence – surgery, anaesthesia, perioperative and critical care
Authors: Larvin Mike , Setterfield Polly
Published: July 2009

Over the past year the library team at The Royal College of Surgeons of England has been developing NHS Evidence – surgery, anaesthesia, perioperative and critical care. This is the collection formerly known as the Specialist Library for Surgery, Theatres and Anaesthesia. The collection now includes the field of critical care and was officially launched on 1 June 2009. We would like to thank all those in the critical care community, our topic advisors and external reference panel for their unfailing advice, enthusiasm and constructive feedback over the past year as we have developed the collection.
Development for DCPs: a growing success story
Authors: Hunter Sally
Published: July 2009

On 1 August 2008, mandatory continuing professional development (CPD) was introduced for dental care professionals (DCPs). To maintain registration with the General Dental Council (GDC), DCPs are required to undertake 50 hours of verifiable CPD over a five-year period. The CPD requirement is an important part of regulation and professional responsibilities, and the increasing availability of CPD programmes and courses provide an additional opportunity for DCPs to develop their careers and raise standards of patient care.
Leadership training for SAS doctors
Authors: Lamont Suzy
Published: July 2009

Staff grade and associate specialist (SAS) doctors comprise differing proportions of a trust's workforce depending on specialty and are involved in the delivery of service and teaching. SAS surgeons will at times be the lead surgeon in the theatre and as such will need to display leadership qualities as part of the theatre team. For this reason in late 2008 the London Deanery commissioned the Royal College of Surgeons to provide a programme to develop the leadership skills for SAS surgeons within the deanery.
A very personal journey
Authors: Giddings Tony
Published: July 2009

The College has recently approved a two-part film entitled, The Journey about the safety of patients in the operating theatre. It is designed to provoke discussion and has certainly ensured a widespread and at times heated response from surgeons. The film's subject is not the technical but the non-technical skills required to work with others in a safe team. Such factors are now known to be the original cause of about three quarters of surgical 'accidents'.
Flaming June
Authors: Black John
Published: July 2009

The campaign the College is leading on behalf of surgeons for an opt-out from the 48-hour-week European Working Time Directive (EWTD) had some good publicity recently. I was asked to write an article for The Mail on Sunday of sufficient length to put all the arguments. This resulted in a series of media appearances including GMTV and the BBC Breakfast show, and a thunderous editorial in The Daily Telegraph. I cannot believe there is any politician in the land who is now not aware that surgeons know that the EWTD is dangerous for patients, bad for training and a risk to proper provision of hospital care. Sooner or later they will have to act.
e-Den: a new way of learning for a new world
Authors: Brunton Paul
Published: July 2009

The way in which colleagues, new and old, learn has changed so much in recent years. Formal teaching has become a little passé and we are now in an exciting era of self-directed learning, the pace and direction of which is determined according to an individual's learning needs at that particular stage in his or her development. Many connect this with the death of formal lectures, the demise of more traditional libraries and the fact that newer graduates have almost stopped purchasing textbooks.
Pharmacogenomics of Tamoxifen Therapy
Authors: Brauch Hiltrud , Mürdter Thomas E , Eichelbaum Michel , Schwab Matthias
Published: July 2009

Background: Tamoxifen is a standard endocrine therapy for the prevention and treatment of steroid hormone receptor–positive breast cancer.

Content: Tamoxifen requires enzymatic activation by cytochrome P450 (CYP) enzymes for the formation of active metabolites 4-hydroxytamoxifen and endoxifen. As compared with the parent drug, both metabolites have an approximately 100-fold greater affinity for the estrogen receptor and the ability to inhibit cell proliferation. The polymorphic CYP2D6 is the key enzyme in this biotransformation, and recent mechanistic, pharmacologic, and clinical evidence suggests that genetic variants and drug interaction by CYP2D6 inhibitors influence the plasma concentrations of active tamoxifen metabolites and the outcomes of tamoxifen-treated patients. In particular, nonfunctional (poor metabolizer) and severely impaired (intermediate metabolizer) CYP2D6 alleles are associated with higher recurrence rates.

Summary: Accordingly, CYP2D6 (cytochrome P450, family 2, subfamily D, polypeptide 6) genotyping before treatment to predict metabolizer status may open new avenues for individualizing endocrine treatment, with the maximum benefit being expected for extensive metabolizers. Moreover, strong CYP2D6 inhibitors such as the selective serotonin reuptake inhibitors paroxetine and fluoxetine, which are used to treat hot flashes, should be avoided because they severely impair formation of the active metabolites.
Method for the Selective Measurement of Amino-Terminal Variants of Procalcitonin
Authors: Struck Joachim , Strebelow Martina , Tietz Sonja , Alonso Christine , Morgenthaler Nils G , van der Hoeven Johannes G , Pickkers Peter , Bergmann Andreas
Published: July 2009

Background: Procalcitonin (PCT) is an established marker for diagnosing and monitoring bacterial infections. Full-length PCT [116 amino acids that make up procalcitonin (PCT1–116)] can be truncated, leading to des-Ala-Pro-PCT (des-Alanin-Prolin-Procalcitonin; PCT3–116). Current immunoassays for PCT (“total PCT”) use antibodies directed against internal epitopes and are unable to distinguish amino-terminal PCT variants. Here we describe the development of monoclonal antibodies recognizing the amino-termini of PCT1–116 and PCT3–116 and their use in the selective measurement of these PCT species.

Methods: With newly developed monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116, and an antibody against the katacalcin moiety of PCT, we developed and characterized immunoluminometric assays for the 2 PCT peptides. We comparatively assessed the kinetics of PCT variants in a human endotoxemia model.

Results: Monoclonal antibodies against the amino-termini of PCT1–116 and PCT3–116 showed <1% cross-reactivity with other PCT-related peptides. The sandwich assays for PCT1–116 and PCT3–116 had functional assay sensitivities of 5 and 1.2 pmol/L, respectively, and exhibited recoveries within 20% of expected values. Plasma PCT1–116 was stable for 6 h at 22 °C and 24 h at 4 °C, and PCT3–116 was stable for at least 24 h at both temperatures. During experimental endotoxemia in healthy people, both PCT1–116 and PCT3–116 increased early in parallel with total PCT, but further increases in PCT1–116 were significantly slower than for PCT3–116 (P = 0.0049) and total PCT (P = 0.0024).

Conclusions: The new assays selectively measure PCT1–116 and PCT3–116. Both PCT species increase early during endotoxemia but differ in their kinetics thereafter. The selective measurement of PCT species with different in vivo kinetics may be useful in improving PCT-guided therapies.
A Commutable Cytomegalovirus Calibrator Is Required to Improve the Agreement of Viral Load Values between Laboratories
Authors: Caliendo Angela M , Shahbazian Mona D , Schaper Carl , Ingersoll Jessica , Abdul-Ali Deborah , Boonyaratanakornkit Jerry , Pang Xiao-Li , Fox Julie , Preiksaitis Jutta , Schönbrunner E Ralf
Published: July 2009

Background: Viral load testing for cytomegalovirus (CMV) is an important diagnostic tool for the management of transplant recipients and immunocompromised individuals; however, inconsistency among laboratories in quantitative measurements of viral load limits interinstitutional comparisons. These inconsistencies stem from the lack of assays cleared by the US Food and Drug Administration, the absence of international standards, the wide variety of CMV-extraction and -detection methods, and differences in materials used for calibration. A critical component of standardization is the use of calibrators that are traceable and commutable.

Methods: Bland–Altman plots and prediction ellipses were used to test the commutability of 2 CMV calibrators for 2 different quantification methods.

Results: Tests with 2 methods showed 1 calibrator to be commutable and the other to be noncommutable. The results for the commutable calibrator were within the 95% prediction interval of the clinical samples in the Bland–Altman plot and within the 95% prediction ellipse for a simulated commutable calibrator, whereas the results for the noncommutable calibrator were not within these prediction intervals. When used to calibrate patient results, only the commutable calibrator, the OptiQuant® CMVtc Calibration Panel, significantly improved the comparability of viral loads for the 2 different measurement methods.

Conclusions: This study demonstrates that an important goal in the effort to improve healthcare for patients with CMV-related disease is the establishment of traceable and commutable reference materials, including both calibrators and controls. .
Circulating Concentrations of Follistatin-Like 1 in Healthy Individuals and Patients with Acute Coronary Syndrome as Assessed by an Immunoluminometric Sandwich Assay
Authors: Widera Christian , Horn-Wichmann Rüdiger , Kempf Tibor , Bethmann Kerstin , Fiedler Beate , Sharma Sarita , Lichtinghagen Ralf , Leitolf Holger , Ivandic Boris , Katus Hugo A , Giannitsis Evangelos , Wollert Kai C
Published: July 2009

Background: Follistatin-like 1 (FSTL1) is a 308–amino acid secreted glycoprotein. Tissue levels of FSTL1 are induced in animal models and patients with chronic inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be measured in the human circulation and used as a biomarker in acute coronary syndrome (ACS).

Methods: We developed an immunoluminometric assay (ILMA), assessed the preanalytic characteristics of FSTL1, and determined circulating FSTL1 concentrations in 120 apparently healthy individuals and 216 patients with ACS.

Results: The assay had a limit of detection of 0.17 μg/L, limit of quantification of 1.02 μg/L, intraassay imprecision of ≤12.7%, and interassay imprecision of ≤15.4%. Selectivity was demonstrated with size-exclusion chromatography and lack of cross-reactivity with related proteins. The assay was not appreciably influenced by unrelated biological substances. FSTL1 in serum or whole blood was stable at room temperature for 48 h and was resistant to 4 freeze-thaw cycles. Measured FSTL1 concentrations in citrated plasma and heparin-treated plasma were 18% and 17% lower, respectively, than concentrations measured in serum. Apparently healthy individuals presented with a median FSTL1 serum concentration of 7.18 (range 1.06–18.49) μg/L. Serum FSTL1 concentrations were increased in ACS and related to the risk of all-cause mortality during follow-up.

Conclusions: The ILMA permits detection of FSTL1 in human serum and plasma. We expect that the favorable preanalytic characteristics of FSTL1 and the reference limits defined here for apparently healthy individuals will facilitate future studies of FSTL1 as a biomarker in various disease settings, including ACS.