bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal stimulation for CD70 induction on human monocyte‐derived dendritic cells and the importance of CD70 in naive CD4+ T‐cell differentiation
Authors: Arimoto‐Miyamoto Kazue , Kadowaki Norimitsu , Kitawaki Toshio , Iwata Satoshi , Morimoto Chikao , Uchiyama Takashi
Published: February 2010

Studies in mice have shown that CD70 on dendritic cells (DCs) is sufficient to convert T‐cell tolerance into immunity and hence induce anti‐tumour immune responses. Therefore, it is important to investigate (i) optimal stimuli to induce CD70 on human monocyte‐derived DCs (MoDCs), which are widely used for tumour immunotherapy, and (ii) the role of CD70 in functional differentiation of naive CD4+ and CD8+ T cells stimulated with MoDCs. We show that interferon‐α (IFN‐α) is a key cytokine to differentiate monocytes into DCs with the capacity to express CD70 upon maturation. CD70 expression on IFN‐α‐induced MoDCs was elicited by different categories of maturation‐inducing factors (Toll‐like receptor ligands, CD40 ligand and pro‐inflammatory mediators), among which prostaglandin E2 was most effective. Naive T cells stimulated with MoDCs also expressed CD70. Stimulation with MoDCs promoted naive CD4+ T cells to acquire the ability to produce T helper type 1 and 2 cytokines in a CD70‐dependent manner. In contrast, the CD70–CD27 interaction diminished the production of an immunoregulatory cytokine IL‐10. The CD27 signal did not play a dominant role in the induction of effector molecules in naive CD8+ T cells during the stimulation with MoDCs. This study adds a novel function to the versatile cytokines, type I IFNs, that is, the induction of CD70 on MoDCs. CD70 promotes naive CD4+ T cells to acquire immunostimulatory activity through the DC–T‐cell and T‐cell–T‐cell interactions during the stimulation with MoDCs. Hence, the CD70–CD27 interaction may play an important role in inducing effective immune responses in DC‐based immunotherapy.
An expansion of the genome size dataset for the insect order Hymenoptera, with a first test of parasitism and eusociality as possible constraints
Authors: Ardila‐Garcia A. M. , Umphrey G. J. , Gregory T. R.
Published: February 2010

Although the Hymenoptera represent a remarkably diverse and socioeconomically important group that is of considerable interest in genome biology, they remain understudied in terms of genome size. This study reports new genome size estimates for 89 species of ants, bees and wasps, representing 17 families and four superfamilies. These are used in a test of the hypothesis that genome sizes are constrained by traits associated with parasitism or eusociality. Not all parasitoid wasps exhibit small genomes, though a relationship based on specific types of parasitism may still occur; by contrast, there was no convincing evidence of a constraint relating to eusociality. The data provided here can be used to guide future research aimed at understanding the evolution of large‐scale genomic properties in this order.
Two novel Salp15‐like immunosuppressant genes from salivary glands of Ixodes persulcatus Schulze tick
Authors: Mori A. , Konnai S. , Yamada S. , Hidano A. , Murase Y. , Ito T. , Takano A. , Kawabata H. , Onuma M. , Ohashi K.
Published: February 2010

Salp15, a 15‐kDa tick salivary gland protein, is known for several suppressive activities against host immunity and critical functions for the transmission of Lyme borrelia in Ixodes scapularis and Ixodes ricinus, the major vectors found in North America and Western Europe. Salp15 inhibits the activation of cluster of differentiation (CD)4+T‐cells through the repression of T‐cell receptor (TCR)‐triggered calcium fluxes and interleukin (IL)‐2 production. Furthermore, Salp15 adheres to the spirochaeta and specifically interacts with its outer surface protein C. The binding of Salp15 to Borrelia burgdorferi protects it from antibody‐mediated killing in vitro. The aim of this study is to identify the Salp15 genes in Ixodes persulcatus Schulze, the specific vector for human Lyme borreliosis in Japan. Two cDNA clones encoding the Salp15‐like sequence were obtained from salivary glands of fed female ticks. These genes encode 135‐ and 132‐amino acid proteins, designated Salp15 Iper‐1 and Salp15 Iper‐2, respectively, both having signal peptide sequences and predicted to be secretory proteins. Salp15 Iper‐1 and ‐2 showed 51.8 and 68.2% similarity to I. scapularis Salp15, respectively. Reverse transcriptase PCR analysis showed that Salp15 Iper genes were expressed specifically in the salivary glands throughout life cycle stages of the ticks and were up‐regulated by blood feeding. In the I. persulcatus‐derived sequences, the C‐terminal part, which is the binding domain to the CD4 molecule of T‐cells in I. scapularis Salp15, was well conserved. In the future, it will be necessary to analyse immunosuppressive functions of I. persulcatus Salp15 and their interaction with Borrelia spp. in Japan.
Competition modulates the adaptation capacity of forests to climatic stress: insights from recent growth decline and death in relict stands of the Mediterranean firAbies pinsapo
Authors: Linares Juan Carlos , Camarero Jesús Julio , Carreira José Antonio
Published: February 2010

1.Long‐term basal area increment (BAI) inAbies pinsapowas studied to investigate the way density‐dependent factors modulate the responses of radial growth to climatic stresses in relict stands of a drought‐sensitive Mediterranean fir.

2.First, we verified that spatially explicit competition predicts meanA. pinsapoBAI at our study site; i.e. it modulates the degree to which the average climate‐driven potential for growth is expressed. Second, we verified that the long‐term pattern of temperature predicts the long‐term pattern of BAI, estimated as the main trend over a time period ofc.40 years. Finally, we assessed whether the intensity of tree‐to‐tree competition restrains the potential improvements achieved by our model of BAI when a short‐term, high‐frequency stressor such as drought (inter‐annual precipitation variability) is introduced.

3.We applied Dynamic Factor Analysis (DFA) to characterize regional climatic trends and to test the hypothesis that trees subjected to contrasting competition intensity may differ in their growth pattern. Significant long‐term climate trends obtained by DFA were used as predictors of long‐term BAI.

4.The mean BAI was mainly determined by competition, whereas growth trends obtained by DFA did not differ among dominant, suppressed and dying trees. Common trends of growth decline were strongly related to long‐term, late‐winter to summer temperatures, while the residuals were related to total annual precipitation, although with decreasing significance as competition increased. Our results support the contention that the reported patterns ofA. pinsapogrowth decline and death occur as a result of the interacting effects of both competition and climate stressors acting at long‐ and short‐term time scales.

5.Synthesis. Long‐term climatic drought stress was the main driving factor of growth decline inA. pinsapo. Moreover, trees already suffering from competition (a long‐term stress) were predisposed to decline given an additional short‐term stress, such as a severe drought.
Evaluation of the ability of people with intellectual disabilities to ‘weigh up’ information in two tests of financial reasoning
Authors: Willner P. , Bailey R. , Parry R. , Dymond S.
Published: February 2010

Background  An assessment of mental capacity includes an evaluation of the ability to ‘weigh up’ information, but how to do this is uncertain. We have previously used a laboratory decision‐making task, temporal discounting, which involves a trade‐off between the value and the delay of expected rewards. Participants with intellectual disabilities (ID) showed very little evidence of ‘weighing up’ of information: only a third of participants showed consistent temporal discounting performance, and when present, consistent performance was usually impulsive; and the ability to perform consistently was more strongly related to executive functioning than to IQ. The aim of the present study was to replicate these observations and extend them to a more realistic financial decision‐making task.

Methods  We administered a temporal discounting task and a financial decision‐making task, as well as tests of executive functioning and IQ, to 20 participants who attended day services for people with learning disabilities (mean Full‐Scale IQ = 59), and to 10 staff members.

Results  Performance in both decision‐making tasks was related more strongly to executive functioning than to IQ. In both tasks, decisions by service users were made largely on the basis of a single item of information: there was very little evidence in either task that information from two sources was being ‘weighed’.

Conclusions  The results suggest that difficulty in ‘weighing up’ information may be a general problem for people with ID, pointing to a need for psycho‐educational remediation strategies to address this issue. The importance of executive functioning in decision‐making by people with ID is not recognized in the legal test for mental capacity, which in practice includes a possibly irrelevant IQ criterion.
Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis
Authors: Liu F. , Zhang J. , Liu Y. , Zhang N. , Holtappels G. , Lin P. , Liu S. , Bachert C.
Published: February 2010

To cite this article: Liu F, Zhang J, Liu Y, Zhang N, Holtappels G, Lin P, Liu S, Bachert C. Inflammatory profiles in nasal mucosa of patients with persistent vs intermittent allergic rhinitis. Allergy 2010; 65: 1149–1157.

Background:  To date there is little information on the inflammatory profiles of patients suffering from persistent (PER) and intermittent allergic rhinitis (IAR). Also, it is not clear whether differences exist in eosinophilic inflammation and/or T‐helper cell sub‐populations and their markers. The aim of this study was to primarily evaluate the inflammatory profiles of patients with moderate/severe PER and IAR.

Methods:  Inferior nasal turbinate tissue was obtained from 12 PER, 12 IAR and 12 nonallergic nonrhinitic (control) patients, and symptoms (visual analogue scales, VAS) and impairment of life was monitored. All tissues were assessed for eosinophil and mast cell numbers by immunohistochemistry; IL‐5, ECP and IgE concentrations by immunoassay; mRNA for transcription factors GATA‐3, T‐bet, FOXP3 and RORc by quantitative real‐time polymerase chain reaction; and IgE‐induced release of LTC4/D4/E4 and PGD2in vitro.

Results:  Eosinophils and mast cells were significantly increased in patients with PER and patients with IAR compared to control subjects; by patients with PER demonstrating even significantly greater increase of both cell types than patients with IAR. Similarly, ECP IL‐5, GATA‐3 mRNA expression and IgE‐induced release of LTC4/D4/E4 and PGD2 from mast cells were significantly increased in patients with PER compared to patients with IAR. In contrast, the expression of T‐bet, FOXP3 or RORc mRNA was not significantly different in the PER, IAR or control patients.

Conclusion:  The findings from the present study suggest that PER is characterized by a significantly greater eosinophilic and predominantly Th2 cell‐mediated nasal inflammatory profile compared to IAR.
Mycophenolic acid trough level monitoring: relevance in acute and chronic graft versus host disease and its relation with albumin
Authors: Hiwarkar P. , Shaw B.E. , Tredger J.M. , Brown N.W. , Kulkarni S. , Saso R. , Evans S. , Treleaven J. , Davies F.E. , Ethell M.E. , Morgan G.J. , Potter M.N.
Published: February 2010

Hiwarkar P, Shaw BE, Tredger JM, Brown NW, Kulkarni S, Saso R, Evans S, Treleaven J, Davies FE, Ethell ME, Morgan GJ, Potter MN. Mycophenolic acid trough level monitoring: relevance in acute and chronic graft versus host disease and its relation with albumin.  Clin Transplant 2011: 25: 222–227. © 2010 John Wiley & Sons A/S.

Abstract:  Mycophenolate mofetil (MMF) is used to treat acute and chronic graft versus host disease (GvHD). There is scant evidence in the literature about mycophenolic acid (MPA) trough level monitoring in GvHD. We therefore reviewed 32 patients treated with MMF for acute (n = 19) or chronic GvHD (n = 13). Twelve (63%) of 19 patients with acute GvHD and nine (69%) of 13 with chronic GvHD showed a good response. In all 21 patients who responded to MMF, their mean total MPA levels were therapeutic (1–3.5 mg/L), whereas five of 11 patients who did not respond had sub‐therapeutic mean MPA levels (p = 0.002). Sixteen (66%) of 24 steroid refractory or dependent patients responded to MMF. Associations between the mean total MPA level for each patient and the corresponding mean serum albumin concentration showed therapeutic mean total MPA levels for all 23 patients with mean albumin ≥31 g/L but sub‐therapeutic mean total MPA levels in five of nine patients with mean albumin <31 g/L (p = 0.0006). In conclusion, MMF is efficacious in steroid refractory and dependent acute or chronic GvHD with statistically significant correlation between therapeutic plasma total MPA trough levels and clinical response. Serum albumin levels should be taken into account when considering MMF dose adjustments.
Cuscuta reflexa invasion induces Ca2+ release in its host
Authors: Albert M. , Van Der Krol S. , Kaldenhoff R.
Published: February 2010

Cuscuta reflexa induces a variety of reaction in its hosts. Some of these are visual reactions, and it is clear that these morphological changes are preceded by events at the molecular level, where signal transduction is one of the early processes. Calcium (Ca2+) release is the major second messenger during signal transduction, and we therefore studied Ca2+ spiking in tomato during infection with C. reflexa. Bioluminescence in aequorin‐expressing tomato was monitored for 48 h after the onset of Cuscuta infestation. Signals at the attachment sites were observed from 30 to 48 h. Treatment of aequorin‐expressing tomato leaf disks with Cuscuta plant extracts suggested that the substance that induced Ca2+ release from the host was closely linked to parasite haustoria.
To Feed or Not to Feed? Testing Different Hypotheses on Rut‐Induced Hypophagia in a Mountain Ungulate
Authors: Brivio Francesca , Grignolio Stefano , Apollonio Marco
Published: February 2010

In many ruminant species, males dramatically reduce forage intake during the rut. To date, different hypotheses have been suggested to explain this rut‐induced hypophagia. To assess the predictions of the main hypotheses, we analysed Alpine ibex (Capra ibex) activity budget and compared the behaviour of males and females before, during, and after the rut. Only males spent significantly less time foraging during the rut than outside of it, whereas females allocated a similar proportion of time to foraging before, during, and after the rut. Our results showed that during the rut males also reduced lying time, while the ratio of time spent feeding to time spent lying did not change for males among periods. In conclusion, during the breeding season males maximized energy intake when not actively engaged in mating activities and rut‐induced hypophagia appeared to result from time budget constraints generated by mating‐related activities. Accordingly, the foraging constraint hypothesis seems appropriate to explain this phenomenon in Alpine ibex males.
Population structure and genetic diversity of worldwide Nova Scotia Duck Tolling Retriever and Lancashire Heeler dog populations
Authors: Mäki K.
Published: February 2010

The aim of this study was to research the population structure and genetic diversity of the Nova Scotia Duck Tolling Retriever (NS) and the Lancashire Heeler (LH) dog breeds. Data consisted of nearly all the worldwide registration history for both breeds, including 28 668 NS and 4 782 LH individuals. A reference population, including the females born between 1999 and 2008, was defined for genetic analyses for each breed. Average depth of the pedigrees known for the reference population dogs was 12.9 complete generation equivalents in the NS and 6.0 in the LH. Only a small fraction of the born dogs were used later for breeding. Effective number of founders was 9.8 in the NS and 15.2 in the LH. More than 50% of the genetic diversity in the reference population was explained by two ancestors in the NS and five in the LH. Average inbreeding coefficients in the reference populations were 0.26 in the NS and 0.10 in the LH. Average kinships were 0.26 and 0.08 and realised effective population sizes 18 and 28, respectively. Failure to use available genetic resources for sustainable breeding has resulted in depletion of genetic variation in both breeds. To increase genetic variation, a larger proportion of the dogs should be used in reproduction and the contributions of reproducing animals should be equalized. In the LH, it is necessary to use the unregistered farm dogs in breeding. In the NS, crosses with another breed are needed.
A robust method for simultaneous estimation of single gene and polygenic effects in dairy cows using externally estimated breeding values as prior information
Authors: Buske B. , Szydlowski M. , Gengler N.
Published: February 2010

The aim of this study was to develop a robust method to estimate single gene and random polygenic animal effects simultaneously in a small field dataset with limited pedigree information. The new method was based on a Bayesian approach using additional prior information on the distribution of externally estimated breeding values. The field dataset consisted of 40 269 test‐day records for milk performance traits for 1455 genotyped dairy cows for the 11 bp‐deletion in the coding sequence of the myostatin gene. For all traits, estimated additive effects of the favoured wild‐type allele (‘+’ allele) were smaller when applying the new method in comparison with the application of a conventional mixed inheritance test‐day model. Dominance effects of the myostatin gene showed the same behaviour but were generally lower than additive effects. Robustness of methods was tested using a data‐splitting technique, based on the correlation of estimated breeding values from two samples, with one‐half of the data eliminated randomly from the first sample and the remaining data eliminated from the second sample. Results for 100 replicates showed that the correlation between split datasets when prior information included was higher than the conventional method. The new method led to more robust estimations for genetic effects and therefore has potential for use when only a small number of genotyped animals with field data and limited pedigree information are available.
Speziesdiagnostik: Von der Agarplatte zur Molekularbiologie
Authors: Willinger B.
Published: February 2010

Lange Zeit war neben mikroskopischen Nachweisverfahren die Kultur die einzige Möglichkeit, den Erreger von Pilzinfektionen nachzuweisen. Die Kultur nimmt nach wie vor einen wichtigen Stellenwert ein, obwohl sie vielfach erst nach einigen Tagen positiv wird, die Sensitivität teilweise gering ist und es nicht immer möglich ist, zwischen Kontamination, Besiedelung und Infektion zu unterscheiden. Allerdings ermöglicht die Kultur, den Erreger bis auf Speziesebene zu identifizieren und eine Resistenzprüfung durchzuführen. Molekularbiologische Techniken ermöglichen eine besonders schnelle Testung und erzielen einen deutlich höheren Informationsgewinn als phänotypische Methoden. Hier stehen neben der Polymerasekettenreaktion die Fluoreszenz in situ Hybridisierung (FISH) und DNA‐Microarrays zur Verfügung. Erst wenn diese Assays ausreichend evaluiert und in weiterer Folge standardisiert sein werden, wird es möglich sein, mit Hilfe dieser Techniken invasive Pilzinfektionen in allen mikrobiologischen Laboratorien frühzeitig und relativ rasch nachzuweisen. Bis dahin ist eine Kombination der verschiedenen Testmethoden notwendig, um zu einem zuverlässigen Nachweis des Erregers zu kommen.
Fusarium als Verursacher dermatologischer Krankheitsbilder
Authors: Seyfarth F. , Hipler U.‐C.
Published: February 2010

Die Bedeutung von Schimmelpilzinfektionen beim Menschen nimmt zu. Für die Dermatologie relevante Gattungen sind unter anderem Alternaria, Cladosporium, Scopulariopsis und Fusarium. Fusarium ist dabei durch charakteristische Makrokonidien und eine typische Kulturmorphologie gekennzeichnet. Die eigentlich als Pflanzenschädlinge bekannten Vertreter dieser Gattung können beim Menschen sowohl Intoxikationen als auch Infektionen hervorrufen. Letztere stellen bei immunkompetenten Menschen eine Rarität dar. Gefürchtet ist Fusarium als Erreger von Augeninfektionen, die vor allem bei Kontaktlinsenträgern beschrieben wurden und schwer therapierbar sind. An der Haut ruft Fusarium Nekrosen, Ulcera, papulo‐pustulöse Hautveränderungen, Abszesse und Paronychien hervor, die bei immunsupprimierten Patienten in generalisierte Pilzinfektionen übergehen können und eine Differentialdiagnose beim neutropenischen Fieber darstellen. Dabei finden sich bei systemischen Fusariosen überdurchschnittlich häufig generalisierte Hautveränderungen in Form von Papeln und Knoten, die sekundär zentral ulzerieren bzw. von einem targetoid konfigurierten Erythem umgeben sein können. Insgesamt muss die Prognose einer systemischen Fusariose als schlecht bezeichnet werden. Deshalb kommt der frühzeitigen Erkennung dieser Erkrankung durch den Dermatologen, vor allem im Rahmen der Tätigkeit als Konsiliar auf hämatologisch‐onkologischen Stationen, eine entscheidende Bedeutung zu.
Leitliniengerechte Therapie: Candidämie/invasive Candidiasis
Authors: Glöckner A.
Published: February 2010

Invasive Mykosen werden auf der Intensivstation hauptsächlich durch Arten der Gattung Candida verursacht und treten zumeist als Candidämie auf. Trotz verbesserter therapeutischer Möglichkeiten in den letzten zwei Jahrzehnten ist die Letalität der invasiven Candidiasis mit 20 bis 50% weiterhin hoch. Seit Anfang des Jahrtausends steht mit den Echinocandinen eine weitere Klasse von Antimykotika zur Verfügung, dessen Wirkspektrum die klinisch relevanten Spezies von Candida und Aspergillus umfasst. Die Echinocandine haben in mehreren multizentrischen, überwiegend doppelblinden Studien bei Candidämie und invasiver Candidiasis eine überzeugende Wirksamkeit nachgewiesen. In den Studien wurden jeweils bisher etablierte Standardtherapien mit den Echinocandinen Anidulafungin, Caspofungin und Micafungin verglichen. Diese konnten eine Nichtunterlegenheit der neuen Präparate bzw. im Falle von Anidulafungin vs. Fluconazol die Überlegenheit des Echinocandins nachweisen. Diese Studienergebnisse haben zu einer Modifikation der aktuellen Empfehlungen zur Therapie der Candidämie und invasiven Candidiasis geführt. Echinocandine sind bei der Candidämie insbesondere bei Intensivpatienten, die in der Regel ein akutes Ein‐ oder Mehrorganversagen haben und zumeist multiple Medikationen mit entsprechend unübersichtlichen Interaktionen erhalten, Mittel der ersten Wahl.
Chronisch nekrotisierende pulmonale Aspergillose (CNPA)
Authors: Rüchel R.
Published: February 2010

Obwohl nur mäßig immunkompromittiert, erkrankte eine ältere Patientin an Pleuritis, die auf einer Aspergillus fumigatus‐Mykose beruhte. Trotz annähernd 6 Monaten Therapie mit oralem Itraconazol erlag die Patientin schließlich der CNPA. Chronische Pleuritis ist offenbar häufig mit dieser seltenen Verlaufsform der Aspergillose assoziiert, die häufig eine schlechte Prognose aufweist.
Die pathologische Diagnostik – Kosten und Nutzen
Authors: Schwesinger G. , Knoke M. , Bernhardt H.
Published: February 2010

Die Zahl der Sektionen hat in Deutschland drastisch abgenommen und liegt jetzt unter 10%. Die möglichen Ursachen werden diskutiert. Dazu gehört auch der zunehmende Sparzwang, obwohl die Kosten für eine Autopsie nicht allzu hoch sind. Hingewiesen wird auf die erhebliche Diskrepanz zwischen der klinisch vermuteten Todesursache und der durch die Autopsie erbrachten Diagnose von 40–60%. Das gilt besonders auch für die Mykosen. In Deutschland werden im Jahr mindestens 1 200 Tötungsdelikte und 11 000 nich natürliche Todesfälle durch eine fehlende Sektion übersehen. Ein weiterer wichtiger Aspekt einer genügenden Anzahl von Autopsien ist in der Qualitätssicherung von Diagnostik, Therapie sowie in der Aus‐ und Weiterbildung von Ärzten und Studenten zu sehen.
A randomized, assessor‐blind, parallel‐group, multicentre, phase IV comparative trial of a suffocant compared with malathion in the treatment of head lice in children
Authors: Greive Kerryn A , Lui Ada H , Barnes Tanya M , Oppenheim VM Jane
Published: February 2010

Background/Objectives:  There are concerns about the effectiveness of head lice treatments because of increasing resistance and safety. This trial compared the safety and efficacy of a suffocant‐based head lice treatment to malathion in children.

Methods:  The trial used strict entry criteria, standardized treatment and assessment regimens, sibling treatment where appropriate and a primary efficacy end‐point defined as the absence of live head lice.

Results:  A total of 216 children were enrolled. One hundred and sixty‐nine were per‐protocol. The suffocant was significantly more effective than malathion for the intention‐to‐treat population (53.9% vs 40.4% louse‐free, unadjusted P = 0.052; adjusted P = 0.024), as well as for the per‐protocol population (57.8% vs 43.0% louse‐free, unadjusted P = 0.054; adjusted P = 0.045). Adverse events were limited to itching or stinging and there were no serious or systemic adverse events. Repeat insult patch testing with the suffocant resulted in no adverse reactions. In vitro tests confirmed that the suffocant is a potent ovicide and pediculicide with 100% mortality of eggs and lice following a 20‐min contact time.

Conclusions:  The suffocant is shown to be significantly more effective in eliminating head lice than malathion in children, while being associated with a low incidence of mild, transient adverse events.
Hidradenitis suppurativa responding to treatment with infliximab
Authors: Lasocki Anita , Sinclair Rodney , Foley Peter , Saunders Helen
Published: February 2010

A series of four cases of severe recalcitrant hidradenitis suppurativa treated with infliximab is presented. All patients had failed to respond to prior medical and surgical management. Baseline Quantiferon‐TB Gold and chest radiograph were carried out before commencement of treatment. No patients had associated Crohn's disease. All patients received induction infusions of infliximab 5 mg/kg at weeks 0, 2 and 6, followed by eight weekly maintenance infusions. The total number of infusions varied between 4 and 6. Skin photography with Sartorius scoring was used to evaluate response to treatment. All patients experienced marked improvement in their disease activity, with a mean 48% improvement in Sartorius score after one infusion (week 2, P < 0.01), and 70% improvement after three infusions (week 14, P < 0.01). Time to relapse following cessation of therapy ranged from 6 weeks to 4 months. Further studies examining the efficacy of infliximab and its effect on the course of the disease, particularly relating to long‐term management, are required.
Metastatic Merkel cell carcinoma with an unknown primary tumour presenting as lichenoid dermatitis
Authors: Wong Kenneth Kien Siang , Oliver Guy Fergus
Published: February 2010

Metastatic Merkel cell carcinoma uncommonly presents with an unidentified primary tumour. We report a patient who first presented with lichenoid dermatitis and was found to have Merkel cell carcinoma involving lymph nodes with an unknown primary site. With the rising incidence of Merkel cell carcinoma, it is important to recognize unusual manifestations of this disease as they may become more common in the future.
CCl4‐induced hepatic injury in mice fed a Western diet is associated with blunted healing
Authors: Allman Monique , Gaskin Latausha , Rivera Chantal A
Published: February 2010

Background and Aims:  Feeding a Western diet (WD) enriched in saturated fat protects against chronic alcoholic hepatitis. However, saturated fat induces lipotoxicity in cultured hepatocytes. The purpose of the present study was to elucidate the influence of WD on acute hepatic injury and healing.

Methods:  Male C57BL/6 mice were fed a purified control diet (CD) or WD enriched in palmitate and cholesterol. After 3 weeks, carbon tetrachloride (CCl4) was administered (0.1 µL/g, intraperitoneally). Hepatic inflammation and proliferation were assessed by immunostaining for neutrophils and intracellular adhesion molecule‐1, and Ki67, respectively. Cytokine expression was analyzed by real‐time polymerase chain reaction. Protein levels of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) were assessed by western blotting.

Results:  Feeding a WD resulted in markedly greater histological evidence of necrosis and enhanced alanine aminotransferase activity (188 ± 6.2 U/L) compared to CD‐fed mice (99.1 ± 6.3 U/L) by day 2 post‐CCl4. In contrast, WD blunted leukocyte accumulation in necrotic areas and the expression of cytokines (tumor necrosis factor‐α and interleukin‐6) involved in tissue regeneration. Diminished repair was further indexed by lower collagen‐αI and Ki67 expression in the mice fed a WD. Finally, feeding a WD, as well as the treatment of cultured hepatocytes with palmitic acid, upregulated the expression of PPAR‐γ, which has been previously shown to prevent hepatic repair following CCl4 exposure.

Conclusions:  These findings suggest that impaired healing in WD‐fed mice blunted recovery from acute injury and underscored the complex relationship between diet and hepatic injury.
Autologous bone‐marrow‐derived mesenchymal stem cell transplantation into injured rat urethral sphincter
Authors: Kinebuchi Yoshiaki , Aizawa Naoki , Imamura Tetsuya , Ishizuka Osamu , Igawa Yasuhiko , Nishizawa Osamu
Published: February 2010

Objectives:  To evaluate the functional and histological recovery by autologous bone‐marrow‐derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters.

Methods:  BMSC were harvested from female Sprague–Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham‐operated rats and injured rats injected with cell‐free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green‐fluorescence‐protein‐labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining.

Results:  LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group.

Conclusions:  Despite a clear trend towards recovery of LPP in BMSC‐transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.
Efficacy of low dose tamsulosin in medical expulsive therapy for ureteral stones in Japanese male patients: A randomized controlled study
Authors: Kaneko Tomoyuki , Matsushima Hisashi , Morimoto Hirohiko , Tsuzaka Yasuo , Homma Yukio
Published: February 2010

Objective:  To evaluate the efficacy of low dose tamsulosin for facilitating spontaneous passage of ureteral stones in Japanese male patients.

Methods:  A total of 71 patients with symptomatic ureteral stones, 10 mm or smaller in size, were randomly allocated into groups 1 and 2. Group 1 received tamsulosin (0.2 mg/day) for a maximum of 4 weeks and group 2 received no medication. The primary endpoint was the stone expulsion rate and the secondary endpoints were stone expulsion time and analgesic use.

Results:  There were no significant differences between the groups in terms of age, stone size and location. The stone expulsion rate was significantly higher in group 1 than in group 2 (77% vs 50%, P = 0.002). No significant differences were noted in the stone expulsion time and analgesic use between the groups.

Conclusion:  Low dose tamsulosin can significantly facilitate spontaneous passage of ureteral stones without significant side‐effects in Japanese male patients.
External analysis of the Randleman Ectasia Risk Factor Score System: a review of 36 cases of post LASIK ectasia
Authors: Chan Colin CK , Hodge Christopher , Sutton Gerard
Published: February 2010

Abstract

Background: To validate Randleman's model of ectasia risk factor scores using a large unbiased sample of unpublished cases.

Methods: Data were collected retrospectively on 36 eyes with ectasia post laserin situkeratomileusis treated by two surgeons at Vision Eye Institute. The data were then entered into Randleman's risk factor score system. Data were also collected about posterior maximum elevation (PME) and posterior maximum elevation position (PMEP); and these were compared with a control group of 50 eyes.

Results: Of the 36 eyes, 9 (25%) were classified as low risk, 7 (19%) as moderate risk and 20 (56%) as high risk. On average, the most points were scored in the topography and topography was abnormal in 69% of cases. Topography points also correlated the most strongly with the increasing risk scores (P < 0.0001). PME or PMEP was not significantly different between our ectasia group and the control group.

Conclusion: Randleman's ectasia risk factor scale can miss a significant proportion of patients at risk of ectasia. Other factors must play a role in ectasia risk. Abnormal corneal topography appears to be the most important preoperative risk factor.
Inhibition of corneal neovascularization after alkali burn: comparison of different doses of bevacizumab in monotherapy or associated with dexamethasone
Authors: Hoffart Louis , Matonti Frederic , Conrath John , Daniel Laurent , Ridings Bernard , Masson Guillaume S , Chavane Frederic
Published: February 2010

Abstract

Background:  To compare the effects of different doses of bevacizumab with both saline and dexamethasone on inflammatory angiogenesis in the rat cornea induced by small chemical lesions.

Methods:  Corneal chemical cauterization was performed on 24 rats. Animals were divided randomly into six groups and received a daily subconjunctival injection for 7 days of: balanced salt solution 0.1 mL or dexamethasone phosphate 4 mg/day or bevacizumab 2.5 mg/day, 3.75 mg/day, 5.0 mg/day or bevacizumab 5.0 mg/day + dexamethasone phosphate 4 mg/day. Clinical examination under slit lamp was performed daily for 7 days to evaluate corneal opacity and vessel size evolution. Computer‐assisted quantitative image analysis was used to measure the total corneal area covered by neovascularization.

Results:  At final examination, the dexamethasone, bevacizumab 5.0 mg/day and dexamethasone + bevacizumab groups showed a significant lowering in corneal opacity score as compared with control (P = 0.024, P = 0.006 and P = 0.013, respectively). Also, a significant reduction on new vessels size score was observed. Surface of corneal neovascularization was significantly reduced in dexamethasone, bevacizumab 5.0 mg/day and dexamethasone + bevacizumab groups compared with control (P = 0.045, P = 0.047 and P = 0.044, respectively).

Conclusion:  Our study demonstrates the ability of a 5.0 mg/day bevacizumab subconjunctival injection, in monotherapy or associated with dexamethasone, to cause a short‐term involution of corneal neovascularization after corneal alkali burn. Combination of both of these treatments may have advantages to monotherapy approaches.
Clinical study of Acrysof IQ aspheric intraocular lenses
Authors: Luo Min , Ji Jing , Zhao Chun , Fan Xianqun
Published: February 2010

Abstract

Purpose:  To determine whether implantation of an aspheric intraocular lens (SN 60 WF Alcon) results in reduced spherical aberration and improved contrast sensitivity after cataract surgery.

Methods:  Randomized, prospective study. 260 patients/eyes were randomized to receive two intraocular lens types: Alcon Acrysof Natural (136 eyes) and Acrysof IQ (124 eyes). Quality of vision was measured by visual acuity and contrast sensitivity under mesopic and photopic conditions. Ocular aberrations for 4.0‐ and 6.0‐mm pupil were measured with Allegretto Wavelight Analyzer. All ophthalmologic were performed 7, 30 and 90 days postoperatively. Visual function index (VF‐14) questionnaires for cataract symptoms were performed 90 days after surgery by all the patients.

Results:  After 90 days, all eyes had mean postoperative best spectacle‐corrected visual acuity 0.75. Eyes with the Acrysof IQ had significantly higher contrast sensitivity than eyes with the Acrysof Natural at high and middle spatial frequencies. A significant reduction in spherical aberration after Acrysof IQ implantation was achieved. The Acrysof IQ also had lower values of high‐order aberration with 4.0‐ and 6.0‐mm pupil when compared with the AcrySof Natural.

Conclusion:  Results show the aspheric Acrysof IQ induced significantly less high‐order aberration and spherical aberration compared with the Acrysof Natural. Contrast sensitivity revealed better values with the Acrysof IQ intraocular lens.
Primary external dacryocystorhinostomy versus primary endonasal dacryocystorhinostomy: a review
Authors: Lee Dior WX , Chai Charmaine HC , Loon Seng Chee
Published: February 2010

Abstract

This paper aims to compare the efficacy, mean operative time and adverse effects of primary external dacryocystorhinostomy (DCR) versus primary endonasal DCR in treating acquired nasolacrimal duct obstruction. Searches were performed for studies comparing the two procedures. Two reviewers independently extracted data from 14 eligible studies. A random effects model was used to analyse the studies. Outcome measures were defined as patency of the nasolacrimal canal and mean operative time, and adverse effects as cutaneous scarring and bleeding. Both procedures were comparable in efficacy in terms of full success, partial success and anatomic patency. Subgroup analysis showed no significant difference between prospective and retrospective studies as well as between non‐laser endonasal DCR versus external DCR and laser endonasal DCR versus external DCR. Endonasal DCR had a significantly shorter mean operative duration, be it laser endonasal DCR (mean difference: 37.65 min, 95% confidence intervals: 3.54–71.75 min, P: 0.03) or non‐laser endonasal DCR (mean difference: 19.22 min, 95% confidence intervals: 2.15–36.28 min, P: 0.03). The odds of postoperative bleeding was not significantly different between the two procedures, whereas postoperative cutaneous scarring was unique to external DCR and occurred in 50 out of 402 (12.44%) external DCRs recorded. Endonasal DCR has comparable success rates with external DCR and has a shorter operative time and no cutaneous scar. However, drawbacks include the steep learning curve and higher costs.
Non‐lethal foraging by bell miners on a herbivorous insect: Potential implications for forest health
Authors: HAYTHORPE KATHRYN M. , McDONALD PAUL G.
Published: February 2010

Tree health is often negatively linked with the localized abundance of parasitic invertebrates. One group, the sap‐sucking psyllid insects (Homoptera: Psyllidae) are well known for their negative impact upon vegetation, an impact that often culminates in the defoliation and even death of hosts. In Australia, psyllid‐infested forest in poor health is also frequently occupied by a native honeyeater, the bell miner (Manorina melanophrys; Meliphagidae), so much so that the phenomenon has been dubbed ‘bell miner‐associated dieback’ (BMAD). Bell miners are thought to be the causative agent behind BMAD, in part because the species may selectively forage only upon the outer covering (lerp) exuded by psyllid nymphs, leaving the insect underneath to continue parasitizing hosts. As bell miners also aggressively exclude all other avian psyllid predators from occupied areas, these behavioural traits may favour increases in psyllid populations. We examined bell miner foraging behaviour to determine if non‐lethal foraging upon psyllid nymphs occurred more often than in a congener, the noisy miner (M. melanocephala; Meliphagidae). This was indeed the case, with bell miners significantly more likely to remove only the lerp covering during feeding, leaving the insect intact underneath. This arose from bell miners using their tongue to pry off the lerp cases, whereas noisy miners used their mandibles to snap at both the lerp and insect underneath. Furthermore, psyllids left behind following a bell miner foraging event were significantly more likely to be viable and regrow a lerp covering than those exposed by noisy miners. Together, this behaviour supports the theory that non‐lethal foraging behaviour of bell miners may contribute to high psyllid abundance, consistent with the mechanisms by which BMAD is thought to develop.
Intravenous zoledronic acid and oral alendronate in patients with a low trauma fracture: experience from an osteoporosis clinic
Authors: Craig S. J. , Youssef P. P. , Vaile J. H. , Sullivan L. , Bleasel J. F.
Published: February 2010

Background/Aims: Oral bisphosphonates have been shown to be effective in treating osteoporosis. However, there has been a significant problem with compliance. Newer intravenous bisphosphonates are available for osteoporosis management, but have not been compared with oral bisphosphonates in a clinical setting. The aim of this study was to compare the safety and effectiveness of intravenous zoledronic acid (ZOL) and oral alendronate (ALN) in osteoporotic patients following a low trauma fracture.

Methods: A non‐randomized, retrospective cohort study was conducted of 169 patients with a low trauma fracture and reduced bone mineral density (BMD). Patients were treated with either an infusion of 4 mg ZOL or ALN 70 mg weekly. The outcomes measured were change in BMD after 12 months of treatment with either bisphosphonate, and new osteoporotic fractures. All adverse events were documented.

Results: Lumbar spine BMD (L2–L4) improved 5.6% in the ZOL group (P < 0.001) and 5.5% in the ALN group (P < 0.001). Total hip BMD improved 2% in the ZOL group (P < 0.01) and 2.5% in the ALN group (P < 0.001). There was no significant difference in BMD change between the groups. There were significantly more new fractures (P < 0.001) in the ZOL group (7.2%) than the ALN group (1%). The ZOL group were significantly older (P < 0.01) and had a significantly higher proportion of males (P < 0.05) at baseline. There were no serious adverse reactions in either group.

Conclusion: ZOL and ALN both produce a significant increase in BMD and are well tolerated in patients with osteoporotic, low trauma fractures. Yearly ZOL provides a safe, convenient alternative to weekly oral bisphosphonates.
JAK2 mutations in Asian patients with essential thrombocythaemia
Authors: Wong G‐C. , Kam G. L. S. , Koay E. S. C.
Published: February 2010

Background/Aim: JAK2V617F is an acquired mutation present in a considerable proportion of patients with chronic myeloproliferative disorders. Its reported prevalence in European and US studies of patients with essential thrombocythaemia (ET) is 23–57%. This study was conducted to determine the prevalence of the JAK2 mutation in Asian ET patients, and to examine their disease profile.

Methods: Asian patients with ET were either recruited to the study or registry data were analysed retrospectively. Blood samples were collected for analysis of JAK2 mutation status during routine patient follow up. Clinical data on these patients (including demographics and disease profiles) and complications at diagnosis were recorded.

Results: The JAK2 mutation was detected in 35/102 (34%) patients. Females were more likely than males to have JAK2 mutation (P= 0.031). At diagnosis, JAK2‐mutated patients were found to be older (P= 0.012), have higher leucocyte counts (P= 0.036) and high‐risk disease (P= 0.039). There were no other statistically significant differences between mutated and wild‐type JAK2 ET patients.

Conclusion: The prevalence of JAK2 mutations in this population of Asian ET patients was 34%. Patients with the JAK2 mutation were significantly more likely to have high‐risk disease. Further studies are required to assess the role of JAK2 mutations in risk stratification in ET and compare the phenotype of Asian patients with other populations.
Randomized cross‐over trial comparing inpatient and outpatient administration of high‐dose cisplatin
Authors: Cox K. M. , Goel S. , O'Connell R. L. , Boyer M. , Beale P. J. , Simes R. J. , Stockler M. R.
Published: February 2010

Background/Aims: Treatment with high‐dose cisplatin (HDC) previously required inpatient (IP) admission with overnight hospitalization, but recently practice has shifted to outpatient (OP) therapy. We aimed to determine whether it is preferable to give HDC as an IP or OP using a two‐period cross‐over trial.

Methods: Eligible patients were starting chemotherapy with ≥2 cycles of HDC (≥100 mg/dose) and were suitable for OP treatment. All patients received an IP cycle and OP cycle: the order was randomly allocated. Pre‐hydration, anti‐emetics and chemotherapy were identical for IP and OP. Post‐hydration varied by group (3 L normal saline (NS) for IP, 2 L NS for OP). The primary outcome was patient preference for IP versus OP treatment. Secondary outcomes included aspects of health‐related quality of life, adverse events (dose delays and reductions, elevated creatinine and unplanned readmissions) and resource use.

Results: Fifty‐nine patients were randomized, 53 completed two cycles of HDC. Most patients preferred OP treatment (36 vs 13, P= 0.002). There were no significant differences in patients' ratings of nausea, vomiting, fatigue, anxiety, depression or overall quality of life. Adverse events were few and unrelated to IP versus OP treatment. Nursing time was longer for IP than OP (163 vs 104 min, P < 0.001).

Conclusion: OP treatment was preferred by most patients, appeared safe and used less resources.
NT‐pro‐BNP predicts worsening renal function in patients with chronic systolic heart failure
Authors: Pfister R. , Müller‐Ehmsen J. , Hagemeister J. , Hellmich M. , Erdmann E. , Schneider C. A.
Published: February 2010

Background: Worsening renal function (WRF) is frequently observed in patients with heart failure and is associated with worse outcome. The aim of this study was to examine the association of the cardiac serum marker N‐terminal pro‐B‐type natriuretic peptide (NT‐pro‐BNP) and WRF.

Methods: A total of 125 consecutive patients of a tertiary care outpatient clinic for heart failure prospectively underwent evaluation of renal function every 6 months. The association of baseline NT‐pro‐BNP with WRF was analysed during a follow up of 18 months.

Results: Twenty‐eight (22.4%) patients developed WRF (increase in serum creatinine ≥0.3 mg/dL). Patients with WRF (2870 pg/mL, interquartile range (IQR) 1063–4765) had significantly higher baseline NT‐pro‐BNP values than patients without WRF (547 pg/mL, IQR 173–1454). The risk for WRF increased by 4.0 (95% CI 2.1–7.5) for each standard deviation of log NT‐pro‐BNP. In multivariable analysis including age, baseline renal function, ejection fraction, New York Heart Association class and diuretic dose, only NT‐pro‐BNP and diabetes were independent predictors of WRF. At a cut‐off level of 696 pg/mL, NT‐pro‐BNP showed a sensitivity of 92.9% and a negative predictive value of 96.4% for WRF.

Conclusion: NT‐pro‐BNP is a strong independent predictor of WRF within 18 months in patients with systolic heart failure with a high negative predictive value. Further studies are needed to evaluate reno‐protective strategies in patients with elevated NT‐pro‐BNP.