bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting adverse drug reaction (ADR) reports as hospital patient safety incidents
Authors: Davies Emma C. , Green Christopher F. , Mottram David R. , Pirmohamed Munir
Published: March 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Adverse drug reactions (ADRs) are a reporting category in the National Patient Safety Agency (NPSA) incident reporting system, though the Medicines and Healthcare Products Regulatory Agency (MHRA) pharmacovigilance system is the more established method for collecting ADR data.

WHAT THIS STUDY ADDS

• The majority of ADRs were shown to be of moderate risk to the patient, though some have a severe or catastrophic impact. Classification and reporting of ADRs according to NPSA guidance is possible but offers limited additional value to efforts to improve patient safety over and above the Yellow Card Scheme.

AIM

In the UK, the National Patient Safety Agency (NPSA) includes adverse drug reactions as a reporting category, while the MHRA Yellow Card Scheme also collects data regarding adverse drug reactions (ADRs). In this study, we aimed to assess ADRs using NPSA criteria and discuss the resulting implications.

METHODS

ADRs identified in a 6‐month prospective study of 3695 inpatient episodes were assessed according to their impact on the patient and on the organization, using tools developed by the NPSA.

RESULTS

Seven hundred and thirty‐three (100%) ADRs were assessed. In terms of impact on the patient, 537 (73.3%) were categorized as ‘low’ (minor treatment), 181 (24.7%) as ‘moderate’ (moderate increase in treatment, no permanent harm), 14 (1.91%) as ‘severe’ (permanent harm) and 1 (0.14%) was categorized as ‘catastrophic’ (direct cause of death). In terms of impact on the organization, none was categorized as ‘no harm/ no risk’, 508 (69.3%) as ‘insignificant’, 188 (25.6%) as ‘minor’, 25 (3.4%) as ‘moderate’, 12 (1.6%) as ‘major’ and none was classed as ‘catastrophic’. Less than 2% of ADRs would be eligible for detailed analysis according to the NPSA guidance. The ADRs that cause incidents of greater significance relate to bleeding, renal impairment and Clostridium difficile infection.

CONCLUSIONS

Classification of ADRs according to NPSA guidance offers limited additional value over and above that offered by the Yellow Card System. A consistent message needs to be sent to prospective reporters of ADRs; the availability of more than one system is likely to confuse reporters and does not aid patient safety.
Effect of high‐dose cranberry juice on the pharmacodynamics of warfarin in patients
Authors: Mellen Chadwick K. , Ford Marjorie , Rindone Joseph P.
Published: March 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Case reports suggest an association between cranberry juice and potentiation of warfarin. Studies using 240 ml of cranberry juice daily demonstrated no interaction. It is unknown if higher amounts of cranberry juice will interact with warfarin.

WHAT THIS STUDY ADDS

Cranberry juice at 240 ml twice daily does not alter the pharmacodynamics of warfarin.

AIM

To determine if high‐dose cranberry juice (240 ml twice daily) alters the pharmacodynamic action of warfarin.

METHODS

Ten male patients taking stable doses of warfarin were given cranberry juice at 240 ml twice daily for 7 days. Prothrombin times were drawn at baseline and days 2, 6 and 8 after administration of the juice. Prothrombin times were averaged for each day and mean times were compared from each study day to baseline using repeated measures anova.

RESULTS

There was no statistical difference between mean prothrombin time at baseline and any day tested during juice administration.

CONCLUSIONS

Cranberry juice (240 ml twice daily for 1 week) did not alter the pharmacodynamics of warfarin in patients.
Rapid recovery of lymphocyte subsets is not associated with protection from relapse of myelodysplastic syndromes and acute myeloid leukaemia after haematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab
Authors: Matthews Katie , Lim ZiYi , Pearce Laurence , Pagliuca Antonio , Alejandro Madrigal J. , Mufti Ghulam J. , Barber Linda D.
Published: March 2010

Graft‐versus‐leukaemia (GvL) and graft‐versus‐host disease (GvHD) are both caused by alloreactive lymphocytes. We previously reported that GvHD correlated with higher numbers of effector CD4 T cells and Natural Killer cells early after allogeneic transplantation using a regimen comprising fludarabine, busulphan and alemtuzumab. Here, we assessed immune cell subset recovery in these patients in the context of early myeloid malignant disease relapse. Despite the close relationship between the GvL and GvHD immune responses, rapid recovery of lymphocyte subsets was not associated with protection from disease relapse. These results indicated that GvL may be weak in this treatment setting for patients with myelodysplastic syndromes and acute myeloid leukaemia. Consistent with low GvL activity, we previously reported that mixed T cell chimaerism had no detrimental effect on relapse in this treatment setting and instead correlated with better outcome because of reduced GvHD incidence. We now report that patients with significantly higher lymphocyte numbers prior to transplantation subsequently maintained the mixed T cell chimaeric state. This pre‐transplant profile, together with absence of the early post‐transplant signature indicative of GvHD predisposition, could potentially be used to identify patients suitable for early withdrawal of immunosuppression and prophylactic donor leucocyte infusion to boost GvL activity.
Pandemic influenza A (2009 H1N1) in children with acute lymphoblastic leukaemia
Authors: Launes Cristian , Rives Susana , Català Albert , Berrueco Rubén , Toll Teresa , Camós Mireia , Muñoz‐Almagro Carmen , García‐García Juan J. , Estella Jesús
Published: March 2010

Pandemic influenza A (2009‐H1N1) usually results in mild clinical illness, but in some individuals it can be life‐threatening. There are no reports of this disease among paediatric patients with acute lymphoblastic leukaemia (ALL). We report ten consecutive patients with ALL and pandemic influenza treated in a single institution. Median age was 7 years (range: 3–12). All were treated with oseltamivir. There were no deaths. Two patients under intensive chemotherapy developed pneumonia and one required ventilatory support. ALL patients under maintenance treatment had mild disease. In conclusion, in our series only patients under intensive treatment developed a moderate to severe disease.
Bottled drinking waters: are the fluoride concentrations shown on the labels accurate?
Authors: WEINBERGER S. J.
Published: March 2010

Summary: The fluoride concentration of 17 bottled waters was measured and compared to the concentration of fluoride reported on the label of each product. There was a great variation in fluoride concentration between the products, ranging from very low in distilled waters to over 4 ppm in a mineral water. The fluoride concentration in seven of the products was more than 0.1 ppm higher than shown on the labels, and the concentration in two of the products was more than 0.1 ppm lower. Due to the high content of fluoride, some of these waters are unacceptable for a child's diet. Conversely, some products contain insignificant amounts of fluoride which may deprive the child of the optimal daily fluoride requirement.

Résumé. Nous avons mesuré la concentration en fluor de 17 eaux minerales en bouteilles et comparé concentration décrite sur l'étiquette de chaque produit. Nous avons observé une grande variation de concentration dans les eaux distillées à plus de 4 ppm dan l'eau minerale. Dans sept de ces produits la concentration en fluor etait de plus de 0.1 ppm plus élevée que celle indiquée sur l'étiquette, et dans 2 de produits de plus de 0.1 ppm moins elevee. Certaines de ces eaux ne sont pas indiquées pour les enfants en raison de leur concentration elevée en fluor. D'autre part, certains de ces produits, par leur carenee en fluor, ne fournissent pas a l'enfant le dose journalière minimale requise.

Zusammefassung. Die Fluoridkonzentration in 17 verschiedenen Flaschen abgefüllte Wasser wurden untersucht und mit den Angaben auf dem Etikett verglichen. Eine grosse Variation in der Fluoridkonzentration wurde festgestellt. Von einer sehr niedrigen im distellierten Wasser bis zu 4 ppm in einem Mineralwasser. In 7 Produkten war die gemessene Konzentration 0,01 höher als angegeben, und in 2 weiteren war sie mehr als 0,1 ppm niedriger. Wegen dem hohen Gehalt an Fluoriden sind einige ungeeignet für Kinder, im Gegensatz zu anderen welche eine ungenügende Konzentration aufweisen.

Resumen. La concentración de flúor de 17 aguas potables embotelladas feuron comparadas con la concentración de flúor reportada en la etiqueta de la botellas de cada producto. Hubo una gran variación en la concentración de flúor entre los productos, desde muy baja concentración en aguas destiladas hasta mas de 4 ppm en agua mineral. La concentración de flúor en siete de los productos fue de mas de 0.1 ppm y en dos, de menos de 0.1 ppm. Debido al alto contenido de flúor, algunas de estas aguas no son aceptables para la dieta de los niños. Sin embargo, algunos de los productos contienen cantidades insignificantes de flúor no ofreciendo a los noños la cantidad óptima de flúor diaria requerida.
Dilaceration of a primary tooth
Authors: KILPATRICK N. M. , HARDMAN P. J. , WELBURY R. R.
Published: March 2010

Summary: A case is presented in which a non‐vital maxillary primary incisor failed to resorb, its root apex appeared in the labial sulcus and further investigation showed it to be dilacerated.

Résumé. Nous presentes un cas de non resorption d'une incisive primaire maxillaire non essentielle, ou la racine apparat dans le sillon labial et qui se trouva lacére apres test complementaires.

Zusammefassung. Fallbeschreibung eines devitalen zentralen Milchfrontzahnes dessen Wurzel nicht resorbierte. Diese Wurzel war denudiert und zeigte sich in der labialen Umschlagsfalter. Aetiologie und Therapie werden diskutiert.

Resumen. Se presenta un caso en el cual en incisivo maxilar no‐vital no se reabsorbió. El ápice radicular apareció en el labial y la subsequente investigación mostró su dislaceración.
Traumatic herniation of the buccal fat pad into the oral cavity
Authors: HARIA S. , KIDNER G. , SHEPHERD J. P.
Published: March 2010

Summary: A case is described of traumatic herniation of the buccal pad of fat intra‐orally in a 4‐year‐old boy, which presented as a soft pedunculated swelling projecting from the buccal mucosa at occlusal level. The herniated fat was removed under general anaesthesia. The aetiology and treatment of the condition are discussed.

Résumé. Description d'un cas de hernie traumatique du coussin gras de la bouche chez en garcon de 4 ans, se presentant sous la forme d'une grosseur pedunculee de la muqueuse buccale au niveau d'occlusion.

Zusammefassung. Fallbeschreibung eines 4 jährigen Knabens mit einer gestielten Fettgeschulst ausgehend von der bukkalen Mulora auf der Okklusionsebene. Das Geschwulst wurde in Vollnarkose entfernt. Die Aetiologie und die Behandlung werden beschrieben.

Resumen. Se describe un caso de hernia traumática en el tejido liposo bucal en un niño de 4 años de edad. La lesion presentó un aspecto inflamado, pedunculado, proyectandose desde la mucosa bucal hasta el nivel oclusal. La hernia de tejido graso fue removida bajo anestesia general. Se presenta la etiología y tratamiento de la condición.
Enhancing inpatient rehabilitation through the engagement of patients and nurses
Authors: Pryor Julie , Buzio Amanda
Published: March 2010

pryor j. & buzio a. (2010) Enhancing inpatient rehabilitation through the engagement of patients and nurses. Journal of Advanced Nursing 66(5), 978–987.

Title.  Enhancing inpatient rehabilitation through the engagement of patients and nurses

Aim.  This paper is a report of a study conducted to describe nurses’ knowledge, experiences and perceptions of a rehabilitation nursing practice development project conducted in their workplace.

Background.  Several studies over the past two decades have led to increasing clarity about the nursing role in rehabilitation. Practice development is a useful vehicle for using the findings of such studies to enhance person‐centred practice in rehabilitation settings.

Method.  This qualitative study, in which grounded theory informed data collection and analysis, involved interviews with 21 nurses working in an inpatient rehabilitation unit in Australia about their knowledge, experiences and perceptions of a rehabilitation nursing practice development project conducted in their workplace. The three rounds of interviews were conducted as follows: 1) December 2005–January 2006; 2) June–July 2006; and 3) October 2006.

Findings.  Practice development was an effective vehicle for developing rehabilitation nursing practice. While collaboration and leadership were critical to the effectiveness of the project, the use of a clinically credible practice development facilitator and a focus on the development of collective nursing practice also seem to have been important. Through the introduction of new activities, both patient and nurse engagement in rehabilitation was enhanced and, as a consequence, the nurses developed a deeper appreciation of their role in rehabilitation.

Conclusion.  Carefully and collaboratively designed and sensitively implemented work‐based practice development initiatives can change the context and culture of inpatient care. The use of a facilitator with relevant clinical nursing expertise to engage staff individually and collectively with research findings and to reflect on their practice and skill development is worth exploring in similar initiatives.
A granular variant of CD63 is a regulator of repeated human mast cell degranulation
Authors: Schäfer T. , Starkl P. , Allard C. , Wolf R. M. , Schweighoffer T.
Published: March 2010

To cite this article: Schäfer T, Starkl P, Allard C, Wolf RM, Schweighoffer T. A granular variant of CD63 is a regulator of repeated human mast cell degranulation. Allergy 2010; 65: 1242–1255.

Background:  Mast cells are secretory immune cells whose degranulation can provoke acute allergic reactions. It is presently unclear, however, whether an individual mast cell can repeatedly degranulate or turns dysfunctional after a single antigen stimulus. This work thus aims to better define the mast cell life cycle, with particular focus on new target structures for therapeutic or diagnostic approaches in allergy.

Methods:  Monoclonal antibodies were raised against degranulated cord blood‐derived human mast cells. A subset of these antibodies that exclusively recognized degranulated mast cells, but did not cross‐react with quiescent mast cells or other hematopoietic cell types, became key reagents in subsequent experiments.

Results:  We identified a granular variant of tetraspanin CD63 as an exclusive molecular marker of degranulated human mast cells. Mutant analyses indicate that a cysteine cluster around residue C170 and protein glycosylation at residue N172 account for the antibody specificity. Here, we show that mast cells, which underwent an initial FcεRI‐mediated degranulation, can be degranulated for at least another cycle in vitro. Repeated degranulation, however, requires an IgE/antigen stimulus that differs from the preceding one. Furthermore, the new variant‐specific anti‐CD63 antibodies effectively impair repeated cycles of mast cell degranulation.

Conclusion:  Our findings indicate that mast cells are stable, multiple‐use cells, which are capable of surviving and delivering several consecutive hits. Surface expression of the novel CD63 variant is a distinguishing feature of such primed cells. Reagents directed against this molecular hallmark may thus become valuable diagnostic and therapeutic agents.
Conversion of Th17‐type into Th2‐type inflammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung
Authors: Moon H.‐G. , Tae Y.‐M. , Kim Y.‐S. , Gyu Jeon S. , Oh S.‐Y. , Song Gho Y. , Zhu Z. , Kim Y.‐K.
Published: March 2010

To cite this article:Moon H‐G, Tae Y‐M, Kim Y‐S, Gyu Jeon S, Oh S‐Y, Song Gho Y, Zhu Z, Kim Y‐K. Conversion of Th17‐type into Th2‐type inflammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung.Allergy2010;65: 1093–1103.

Background: Allergen‐specific T‐cell responses orchestrate airway inflammation, which is a characteristic of asthma. Recent evidence suggests that noneosinophilic asthma can be developed by mixed Th1 and Th17 cell responses when exposed to lipopolysaccharide (LPS)‐containing allergens.

Objective: To evaluate the therapeutic or adverse effects of acetyl salicylic acid (ASA) on the expression of Th1‐type and Th17‐type inflammation induced by airway exposure to LPS‐containing allergens.

Methods: Th1 + Th17 asthma and Th2 asthma mouse models were generated by intranasal sensitization with ovalbumin (OVA) and LPS and intraperitoneal sensitization with OVA and alum, respectively. Therapeutic or adverse effects were evaluated after allergen challenge using pharmacologic and transgenic approaches.

Results: Lung infiltration of eosinophils was enhanced in OVA/LPS‐sensitized mice by ASA treatment, which was accompanied by the enhanced production of eotaxin. These changes were associated with the down‐regulation of Th17 cell response, which was partly dependent on adenosine receptor A1 and A3 subtypes, but up‐regulation of allergen‐specific IL‐13 production from T cells. Lung inflammation induced by LPS‐containing allergen was markedly reduced in IL‐13‐deficient mice in the context of ASA treatment, but not without ASA. Meanwhile, adenosine levels in the lung were enhanced by ASA treatment. Moreover, lung infiltration of eosinophils induced by ASA treatment was reversed by co‐treatment of a xanthine oxidase inhibitor (allopurinol).

Conclusion: These findings suggest that ASA changes Th17‐type into Th2‐type inflammation mainly via the adenosine and uric acid metabolic pathway in the lung.
Processed pseudogenes are located preferentially in regions of low recombination rates in the human genome
Authors: LIU G. , LI H. , CAI L.
Published: March 2010

The aim of this article is to demonstrate possible recombination‐associated evolutionary forces affecting the genomic distribution of processed pseudogenes. The relationship between recombination rate and the distribution of processed pseudogenes is analysed in the human genome. The results show that processed pseudogenes preferentially accumulate in regions of low recombination rates and this correlation cannot be explained by indirect relationships with GC content and gene density. Several explanatory models for the observation are discussed. A model of selection against ectopic recombination is tested based on the difference in distribution pattern between two classes of processed pseudogenes, which differ in the possibility of stimulating ectopic recombination. Our results indicate that the correlation between processed pseudogene density and recombination rate is probably results, in part, from the selection against ectopic recombination between closely located homologous processed pseudogenes. We also found a length effect in processed pseudogene distribution, namely long processed pseudogenes are located more preferentially in regions of low recombination rates than short ones.
Retracted:De novo protein synthesis in mature platelets: a consideration for transfusion medicine
Authors: Schubert P. , Devine D. V.
Published: March 2010

Platelet function in thrombosis and haemostasis is reasonably well understood at the molecular level with respect to the proteins involved in cellular structure, signalling networks and platelet interaction with clotting factors and other cells. However, the natural history of these proteins has only recently garnered the attention of platelet researchers. De novo protein synthesis in platelets was discovered 40 years ago; however, it was generally dismissed as merely an interesting minor phenomenon until studies over the past few years renewed interest in this aspect of platelet proteins. It is now accepted that anucleate platelets not only have the potential to synthesize proteins, but this capacity seems to be required to fulfil their function. With translational control as the primary mode of regulation, platelets are able to express biologically relevant gene products in a timely and signal‐dependent manner. Platelet protein synthesis during storage of platelet concentrates is a nascent area of research. Protein synthesis does occur, although not for all proteins found in the platelet protein profile. Furthermore, mRNA appears to be well preserved under standard storage conditions. Although its significance is not yet understood, the ability to replace proteins may form a type of cellular repair mechanism during storage. Disruption by inappropriate storage conditions or processes that block protein synthesis such as pathogen reduction technologies may have direct effects on the ability of platelets to synthesize proteins during storage.
The latitudinal and bathymetric ranges of marine fishes: a global analysis to test the application of Rapoport′s Rule
Authors: Fortes Rafael R. , Absalão Ricardo S.
Published: March 2010

We evaluated the applicability of Rapoport’s Rule (RR) to the marine bony fishes of the world. The biogeographical pattern predicted by RR has been the subject of a large number of studies, some supporting it and some not. In this exercise, we attempted to generate results free of biases from taxonomy or geographic scale. The study area encompassed all world oceans. Our analysis was based on secondary data. We tested the relationship of the geographic range and the bathymetric range to the latitude gradient, using the method of Stevens (American Naturalist 1989, 133, 240–256). We compared all known species of marine bony fishes together, and performed a second analysis limited to the non‐pelagic species. Our results were generated from a databank including 13,957 species. The results indicated that RR (latitudinal range) is valid for 11 regions. However, there were exceptions for the northern part of the Eastern Atlantic and Pacific, the northern part of the Western Indian, and the Arctic Oceans. The analyses of RR (bathymetric range) were supported for 13 regions. We found only one exception, for the northern part of the Western Indian Ocean. The applicability of RR and its relationship to energy supply, represented here by the temperature variability of the marine water masses, was clear. The exceptions appeared when some feature associated with the distribution of water masses was superposed on the latitudinal gradient, or when some life trait characteristic of a taxon, for instance body size, was confounded with the effect of climate variability.
Randomised controlled trial comparing two school furniture configurations in the printing performance of young children with cerebral palsy
Authors: Ryan Stephen E. , Rigby Patricia J. , Campbell Kent A.
Published: March 2010

Aim:  This randomised controlled trial compared the same‐session effects of two different school furniture configurations on printing legibility.

Methods:  A total of 30 school‐age children with ambulatory cerebral palsy participated in this study. Each child provided one near‐point printing sample of up to 34 letters while positioned on Mandal‐type specialty school furniture and on standard school furniture. An assessor who was unaware of the intervention assignment scored printing errors.

Results:  No significant difference in legibility score mean values between the interventions was detected and the effect size was small.

Conclusions:  Compared with standard school furniture, the use of specialty school furniture did not lead to immediate gains in printing legibility and other printing performance areas for children with cerebral palsy. Further study of the influence of functional abilities, other contextual factors and the longer‐term use of school furniture on handwriting performance is recommended.
Long‐term follow‐up of patients with hepatitis B e antigen negative chronic hepatitis B
Authors: Bekku Dan , Arai Makoto , Imazeki Fumio , Yonemitsu Yutaka , Kanda Tatsuo , Fujiwara Keiichi , Fukai Kenichi , Sato Kenichi , Itoga Sakae , Nomura Fumio , Yokosuka Osamu
Published: March 2010

Background and Aim:  After hepatitis B virus (HBV) e antigen (HBeAg) seroconversion, HBV‐DNA continues to replicate, and HBeAg‐negative patients still face the risk of liver disease progression. We investigated the predictive factors for alanine aminotransferase (ALT) elevation, antiviral drug use, and hepatocellular carcinoma (HCC) occurrence in HBeAg‐negative patients.

Methods:  Age, sex, ALT, platelet counts, HBV‐DNA levels, genotype, antidiabetic drug use, body mass index, smoking, and alcohol consumption were analyzed for a total of 244 HBV carriers who were HBeAg‐negative.

Results:  Of 244 HBeAg‐negative patients, 158 (64.8%) showed normal ALT levels at baseline. Multivariate Cox hazard regression analysis identified high HBV‐DNA levels and high ALT at baseline as independent risk factors for ALT elevation in the patients with normal ALT at baseline. The threshold ALT and HBV‐DNA levels were determined to be 31 IU/L and 5.3 logcopies/mL, respectively. Seventeen (7.0%) patients used antiviral drugs. Multivariate Cox hazard regression analysis identified high HBV‐DNA levels (threshold, 5.7 log copies/mL), the use of antidiabetic drugs, and daily alcohol consumption at baseline as an independent risk factor for the use of antiviral drugs in HBeAg‐negative patients. In 10 patients (4.1%), HCC was detected, and a low platelet count (threshold, 10.0 × 104/mm3) was associated with the occurrence of HCC.

Conclusion:  This study identified predictors of future active liver disease in HBeAg‐negative patients, i.e. ALT elevation, unavoidable use of antiviral drugs, and occurrence of HCC.
Acute allograft rejection in human liver transplant recipients is associated with signaling through toll‐like receptor 4
Authors: Testro Adam G , Visvanathan Kumar , Skinner Narelle , Markovska Vesna , Crowley Peter , Angus Peter W , Gow Paul J
Published: March 2010

Background and Aims:  Toll‐like receptor (TLR) signaling is a crucial step in initiating adaptive immune responses. In addition to recognizing endotoxin, TLR4 also recognizes endogenous ligands (‘damage‐associated structures’), which are released into the circulation in the peri‐transplantation period. TLR2 to a lesser extent also recognizes these endogenous ligands. Multiple studies involving solid organ transplants demonstrate a clear association between TLR4 and allograft rejection. In the present study we assessed whether an association exists between TLR4 and TLR2‐dependent responses and acute liver allograft rejection.

Methods:  The sample included 26 liver transplant recipients. Blood was taken pre‐transplant and at multiple points over the first 14 days post‐transplant. Monocytes were stimulated with TLR4 and TLR2 ligands, lipopolysaccharide and Pam‐3‐Cys, respectively. Monocyte TLR expression was determined using flow cytometry; enzyme‐linked immunosorbent assays measured tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) production.

Results:  Nine (34.6%) patients experienced rejection. No differences existed in age, sex, disease or immunosuppression between rejectors and non‐rejectors. Baseline TLR4 expression was significantly higher in rejectors (1.36 vs 1.02, P = 0.01). There was no difference in TLR2 expression. In rejectors, baseline TLR4‐ and TLR2‐dependent production of TNF‐α and IL‐6 was also significantly increased. Post‐transplant, the two groups differed with regard to TLR4‐dependent TNF‐α production, with rejectors demonstrating progressive downregulation over the first week.

Conclusions:  Prior to liver transplantation, patients who subsequently experience rejection demonstrate robust TLR4‐dependent immune responses, which are not seen in those who do not reject. This supports the theory that damage‐associated structures signaling through TLR4 may be responsible for the early activation of alloimmune T‐cells, favoring allograft rejection.
Spleen stiffness measurement using fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients
Authors: Stefanescu Horia , Grigorescu Mircea , Lupsor Monica , Procopet Bogdan , Maniu Anca , Badea Radu
Published: March 2010

Background and Aim:  Splenomegaly in a common finding in liver cirrhosis that should determine changes in the spleen's density because of portal and splenic congestion and/or because of tissue hyperplasia and fibrosis. These changes might be quantified by elastography, so the aim of the study was to investigate whether spleen stiffness measured by transient elastography varies as liver disease progresses and whether this would be a suitable method for the noninvasive evaluation of the presence of esophageal varices.

Patients and Methods:  One hundred and ninety‐one patients (135 liver cirrhosis, 39 chronic hepatitis and 17 healthy controls) were evaluated by transient elastography for measurements of spleen and liver stiffness. Cirrhotic patients also underwent upper endoscopy for the diagnosis of esophageal varices.

Results:  Spleen stiffness showed higher values in liver cirrhosis patients as compared with chronic hepatitis and with controls: 60.96 vs 34.49 vs 22.01 KPa (P < 0.0001). In the case of liver cirrhosis, spleen stiffness was significantly higher in patients with varices as compared with those without (63.69 vs 47.78 KPa, P < 0.0001), 52.5 KPa being the best cut‐off value, with an area under the receiver operating characteristic of 0.74. Using both liver and spleen stiffness measurement we correctly predicted the presence of esophageal varices with 89.95% diagnostic accuracy.

Conclusion:  Spleen stiffness can be assessed using transient elastography, its value increasing as the liver disease progresses. In liver cirrhosis patients spleen stiffness can predict the presence, but not the grade of esophageal varices. Esophageal varices' presence can be better predicted if both spleen and liver stiffness measurements are used.
Reversal of hepatic steatosis by omega‐3 fatty acids measured non‐invasively by 1H‐magnetic resonance spectroscopy in a rat model
Authors: Marsman Hendrik A , Heger Michal , Kloek Jaap J , Nienhuis Syert L , van Werven Jochem R , Nederveen Aart J , ten Kate Fiebo JW , Stoker Jaap , van Gulik Thomas M
Published: March 2010

Background and Aim:  Living donors with marked (> 33%) macrovesicular steatosis (MaS) are excluded from living donor liver transplantation procedures. Experimental studies have shown that the development of steatosis can be prevented by supplementation with omega‐3 fatty acids (FA), but no studies have investigated the reduction of steatosis using omega‐3 FA. The aim of the present study was to investigate whether administration of omega‐3 FA is effective in reducing steatosis.

Methods:  After fatty liver (FL) induction by a 3‐week methionine/choline‐deficient (MCD) diet, male Wistar rats were daily administered per gavage omega‐3 FA (FL+Omega‐3), omega‐3‐poor lipid solution (FL+Lipid), or NaCl (FL+NaCl) during 2 weeks. Control animals received standard chow without treatment. Determination of steatosis degree was performed before, during, and after treatment by clinical 3.0T 1H‐magnetic resonance spectroscopy (1H‐MRS) and by histology and gas chromatography at the end of the 2‐week treatment period.

Results:  Hepatic fat content (1H‐MRS) was significantly reduced after 1 and 2 weeks of omega‐3 FA treatment. Histological analysis revealed a mild (5–33%) MaS degree in omega‐3‐treated animals vs severe (> 66%) MaS in the FL+Lipid and FL+NaCl groups. Hepatic omega‐6 : 3 FA ratio and total FA content were reduced in the FL+Omega‐3 group. Furthermore, de novo lipogenesis (C16, C16 : 1ω7, C18 : 1ω9) was also lowered. The reduction in hepatic fat content was associated with decreased lobular inflammation and hepatic tumor necrosis factor‐ α and interleukin levels as well as an increased antioxidative capacity.

Conclusion:  Omega‐3 FA are capable of reversing severe hepatic MaS and ameliorating pathophysiological features of non‐alcoholic steatohepatitis such as hepatocellular damage, lobular inflammation, and a reduced antioxidative capacity.
Epimorphin protects hepatocytes from oxidative stress by inhibiting mitochondrial injury
Authors: Kinoshita Nobukatsu , Horie Yasuo , Ohshima Shigetoshi , Hirai Yohei , Dohmen Takahiro , Jin Mario , Matsuhashi Tamotsu , Sasaki Junko , Sasaki Takehiko , Iizuka Masahiro , Ohnishi Hirohide
Published: March 2010

Background and Aims:  Many investigations have demonstrated that cell injuries caused by generation of reactive oxygen species (ROS) is a common mechanism of various hepatic disorders. Recently, we have demonstrated that epimorphin, originally cloned as a mesenchymal protein, protects cultured intestinal epithelial cells from ROS. We therefore examine whether epimorphin protects primary cultured hepatocytes from ROS‐induced cell injury.

Methods:  We explored the cell viability and the intracellular ROS levels of purified murine hepatocytes after exposure to 0.5 mM H2O2 with or without pretreatment of epimorphin. Then, we observed mitochondrial permeability transition (MPT) and depolarization using confocal microscopy to make clear the mechanism that epimorphin inhibited cell injuries after exposure to H2O2. In addition, to clarify the signaling pathways related to cell survival, we carried out Western blotting analysis with phosphorylated stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) polyclonal antibody to evaluate the inhibition of JNK by epimorphin. Finally, we evaluated the cell viability in hepatocytes administered JNK inhibitor.

Results:  Epimorphin protected primary cultured hepatocytes from H2O2‐induced cell injuries independent of intracellular ROS levels. Epimorphin also inhibited onset of MPT, depolarization of the mitochondrial membrane potential, and eventually cell killing. The cell protective function of epimorphin after exposure to H2O2 was not dependent on Akt signaling but on JNK signaling.

Conclusion:  Epimorphin can protect hepatocytes from MPT‐dependent cell injury induced by ROS. Since hepatic disorders could be caused by MPT‐dependent cell injuries with excessive ROS, epimorphin might open a new therapeutic avenue for hepatic disorders.
Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population
Authors: Chan Stephen L , Mo Frankie K F , Johnson Philip J , Liem Giok S , Chan Tung C , Poon Ming C , Ma Brigette B Y , Leung Thomas W T , Lai Paul B S , Chan Anthony T C , Mok Tony S K , Yeo Winnie
Published: March 2010

Background and Aim:  Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems.

Methods:  We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor‐node‐metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared.

Results:  A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow‐up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child‐Pugh‐stage, alpha‐fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3‐month survival while CLIP performed better in predicting the outcome of 6‐ and 12‐month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance.

Conclusion:  We have validated CUPI in a population composed of predominant HBV‐related HCC. CUPI is an appropriate staging system for HBV‐related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.
Agreement of invasive versus non‐invasive blood pressure in preterm neonates is not dependent on birth weight or gestational age
Authors: Meyer Sascha , Sander Julia , Gräber Stefan , Gottschling Sven , Gortner Ludwig
Published: March 2010

Purpose:  Blood pressure constitutes an important parameter in the assessment of the cardiovascular status in preterm infants. Invasive arterial blood pressure (IBP) is considered the ‘gold‐standard’, but non‐invasive blood pressure (NIBP) is used frequently in preterm infants. The aim of this prospective study was to compare mean IBP and mean NIBP arterial blood pressure measurements in three subsets of preterm infants (>1500 g; 1000–1500 g, and <1000 g, and >31 weeks, 28–31 weeks, and <28 weeks of gestation).

Methods:  Prospective, simultaneous assessment of both IBP and NIBP measurements in 50 preterm neonates at 6, 12, 18, 24 h after birth in a tertiary University centre.

Results:  Mean gestational age was 26.7 ± 2.2 (24–32) in group I (n= 18), 29.6 ± 2.0 (27–34) in group II (n= 19) and 32.2 ± 1.9(30–36) weeks in group III (n= 13), respectively; mean birth weight was 777 ± 161 (495–995), 1251 ± 154 (1010–1490) and 2010 ± 332 (1590–2550) g. Mean IBP and mean NIBP increased significantly during the first 24 h of life in all three sub‐groups (P < 0.01); IBP and NIBP measurements were significantly correlated, and showed good agreement, irrespective of birth weight and gestational age.

Conclusions:  Although IBP monitoring is considered the ‘gold standard’, NIBP values showed good agreement with those obtained invasively irrespective of gestational age and birth weight. We conclude that NIBP monitoring constitutes an important parameter in the assessment of the cardiovascular status even in extremely low birth weight infants.
Improving compliance with pulse oximetry alarm limits for very preterm infants?
Authors: Mills Bernice A , Davis Peter G , Donath Susan M , Clucas Luisa M , Doyle Lex W
Published: March 2010

Objective:  To determine if participation in a randomised controlled trial of different oxygen saturation targets improved compliance with oximeter alarm limit guidelines.

Design:  Eligible infants were born after the commencement of the BOOST II trial. Data on alarm limits were collected on all infants <32 weeks' gestational age or birth weight <1500 g, who were born at The Royal Women's Hospital, Melbourne between February and June 2007, and receiving supplemental oxygen at the time of the audit. The proportions of infants in oxygen with correct alarm limits (upper 94%; lower 85% or 86%) were compared, between those in the BOOST II trial and those who were not, and with an earlier audit.

Results:  Of 100 infants surveyed, 56 had received oxygen (mean gestational age at birth 26.7 weeks, mean birth weight 913 g). Compliance with lower limits was good in both periods, irrespective of post‐menstrual age or participation in the trial. Compliance with upper limits improved after trial commencement, but only for infants enrolled in the trial and only whilst they were <36 weeks' post‐menstrual age.

Conclusions:  Starting a clinical trial of oxygen targeting was associated with improved compliance with upper alarm limits for participants receiving supplemental oxygen, but only whilst they were <36 weeks; with little effect outside the trial.
Delayed diagnosis of anorectal malformations: are current guidelines sufficient?
Authors: Wilson Brooke E , Etheridge Claire E , Soundappan Soundappan VS , Holland Andrew JA
Published: March 2010

Aim:  To determine the frequency and presenting features of infants with delayed diagnosis of anorectal malformations (ARM) referred to an Australian tertiary paediatric institution.

Methods:  Infants referred to our institution with a final diagnosis of ARM were retrospectively reviewed between 2001 and 2009. The first cohort consisted of patients that were referred between November 2001 and November 2006 with the diagnosis of an ARM that had been delayed for more than 48 h. The second cohort was those referred between December 2006 and May 2009 with whom the diagnosis of ARM had not been made within 24 h of birth.

Results:  Nineteen infants were referred with delayed diagnosis of an ARM over the 7.5 years of the study. Of 44 patients referred to our institution between December 2006 and May 2009, diagnosis of an ARM was delayed more than 24 h in 14 (32%). There was no difference in gender, birth weight, prematurity, type of malformation or presence of associated anomalies between those with timely and delayed diagnosis of their ARM. A significantly greater proportion of those with a delayed diagnosis presented with obstructive symptoms (86% vs. 27%, P < 0.001), including abdominal distension (57%) and delayed passage of meconium or stool (29%). Despite undergoing neonatal examination, the diagnosis of ARM was missed in 12 patients overall.

Conclusion:  Delayed diagnosis of an ARM appears to be common, occurring in approximately 32% of patients referred to our institution over the last 2.5 years. Current guidelines appear insufficient to ensure prompt diagnosis of ARM.
Update on tuberculous pleural effusion
Authors: LIGHT Richard W.
Published: March 2010

The possibility of tuberculous pleuritis should be considered in every patient with an undiagnosed pleural effusion, for if this diagnosis is not made the patient will recover only to have a high likelihood of subsequently developing pulmonary or extrapulmonary tuberculosis Between 3% and 25% of patients with tuberculosis will have tuberculous pleuritis. The incidence of pleural tuberculosis is higher in patients who are HIV positive. Tuberculous pleuritis usually presents as an acute illness with fever, cough and pleuritic chest pain. The pleural fluid is an exudate that usually has predominantly lymphocytes. Pleural fluid cultures are positive for Mycobacterium tuberculosis in less than 40% and smears are virtually always negative. The easiest way to establish the diagnosis of tuberculous pleuritis in a patient with a lymphocytic pleural effusion is to generally demonstrate a pleural fluid adenosine deaminase level above 40 U/L. Lymphocytic exudates not due to tuberculosis almost always have adenosine deaminase levels below 40 U/L. Elevated pleural fluid levels of γ‐interferon also are virtually diagnostic of tuberculous pleuritis in patients with lymphocytic exudates. In questionable cases the diagnosis can be established by demonstrating granulomas or organisms on tissue specimens obtained via needle biopsy of the pleura or thoracoscopy. The chemotherapy for tuberculous pleuritis is the same as that for pulmonary tuberculosis.
Interventional radiology of the thorax
Authors: DUNCAN Mark , WIJESEKERA Nevin , PADLEY Simon
Published: March 2010

Interventional radiology of the thorax encompasses an expanding variety of procedures, ranging from simple diagnostic pleural fluid aspiration to complex therapeutic procedures such as bronchial artery embolization and radiofrequency ablation of lung tumours. Physicians of many specialties will encounter patients undergoing such procedures and knowledge of possible complications is therefore desirable. We aim to briefly outline the role of the most commonly undertaken radiological thoracic interventions and review the associated complications, their subsequent management and the steps that can be taken to minimize the risk of these complications occurring.
SCHISTOSOMIASIS JAPONICA IDENTIFIED BY LAPAROSCOPIC AND COLONOSCOPIC EXAMINATION
Authors: Hosho Keiko , Ikebuchi Yuichiro , Ueki Masaru , Nakamura Keiko , Yashima Kazuo , Maeda Naoto , Koda Masahiko , Murawaki Yoshikazu , Suou Takeaki , Inoue Masayuki
Published: March 2010

A 45‐year‐old Philippine woman who came from Mindanao Island was admitted to our hospital with a complaint of epigastric discomfort. Abdominal ultrasonography and computed tomography demonstrated a network pattern and linear calcification in the liver. Laparoscopic examination showed numerous yellowish, small speckles over the liver surface. The liver surface was separated into many small blocks by groove‐like depressions, demonstrating a so‐called tortoise shell pattern. Conventional colonoscopy and narrow‐band imaging showed irregular areas of yellowish mucosa, and diminished vascular network and increased irregular microvessels extending from the descending colon to the rectum. Liver biopsy showed many Schistosoma japonicum eggs in Glisson's capsule and colon biopsy showed many S. japonicum eggs in the submucosal layer. These findings established a diagnosis of schistosomiasis japonica. The present case is imported schistosomiasis japonica. Even though new cases have not occurred recently in Japan, we should remain aware of schistosomiasis japonica for patients who came from foreign epidemic areas.
LONG‐TERM OUTCOME OF ENDOSCOPIC PAPILLOTOMY FOR CHOLEDOCHOLITHIASIS WITH CHOLECYSTOLITHIASIS
Authors: Fujimoto Tatsuya , Tsuyuguchi Toshio , Sakai Yuji , Sugiyama Harutoshi , Miyakawa Kaoru , Eto Reiko , Yasui Shin , Ishihara Takeshi , Yokosuka Osamu
Published: March 2010

Aim:  To assess long‐term outcome of endoscopic papillotomy alone without subsequent cholecystectomy in patients with choledocholithiasis and cholecystolithiasis.

Methods:  Retrospective review of clinical records of patients treated for choledocholithiasis and cholecystolithiasis from 1976 to 2006. Of 564 patients subjected to endoscopic papillotomy and endoscopic stone extraction, 522 patients (279 men, 243 women; mean age 66.2 years) were followed up and predisposing risk factors for late complications were analyzed.

Results:  The mean duration of follow up was 5.6 years. Cholecystitis and recurrent choledocholithiasis occurred in 39 (7.5%) and 60 (11.5%) patients, respectively. Cholecystitis, including one severe case, resolved with conservative treatment. Recurrent choledocholithiasis was successfully treated endoscopically except in one case. Pneumobilia was found to be a significant risk factor for cholecystitis (P = 0.019) and recurrent choledocholithiasis (P = 0.013). Biliary tract cancer occurred in 16 patients; gallbladder cancer in 13 and bile duct cancer in three. Gallbladder cancer developed within 2 years after endoscopic papillotomy in seven of the 13 patients (53.8%).

Conclusion:  Pneumobilia was the only significant risk factor for cholecystitis and recurrent choledocholithiasis in our study population. As for the long‐term outcome, it was unclear whether endoscopic papillotomy contributed to the occurrence of biliary tract cancer.
UNUSUAL GASTROINTESTINAL METASTASES FROM AN ALVEOLAR SOFT PART SARCOMA
Authors: Lee Gyeong‐Won , Kim Tae Hyo , Min Hyun Ju , Kim Hyun Jin , Jung Woon Tae , Lee Ok‐Jae , Ko Gyung Hyuck
Published: March 2010

Alveolar soft part sarcoma (ASPS) is a rare subtype of soft tissue sarcoma that occurs predominantly in young patients. Despite its relatively indolent course, it generally has a poor prognosis with widespread metastases. The common metastatic sites from an ASPS include the lung, brain and bone. However, metastasis of an ASPS to the gastrointestinal tract is extremely rare. Here, we report a rare case of upper gastrointestinal bleeding and jejunal intussusception due to gastrointestinal metastases from an ASPS.