bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance
Authors: Swiecki Melissa , Colonna Marco
Published: February 2010

Summary:  Plasmacytoid dendritic cells (pDCs) are bone marrow‐derived cells that secrete large amounts of type I interferon (IFN) in response to viruses. Type I IFNs are pleiotropic cytokines with antiviral activity that also enhance innate and adaptive immune responses. Viruses trigger activation of pDCs and type I IFN responses mainly through the Toll‐like receptor pathway. However, a variety of activating and inhibitory pDC receptors fine tune the amplitude of type I IFN responses. Chronic activation and secretion of type I IFN in the absence of infection can promote autoimmune diseases. Furthermore, while activated pDCs promote immunity and autoimmunity, resting or alternatively activated pDCs may be tolerogenic. The various roles of pDCs have been extensively studied in vitro and in vivo with depleting antibodies. However, depleting antibodies cross‐react with other cell types that are critical for eliciting protective immunity, potentially yielding ambiguous phenotypes. Here we discuss new approaches to assess pDC functions in vivo and provide preliminary data on their potential roles during viral infections. Such approaches would also prove useful in the more specific evaluation of how pDCs mediate tolerance and autoimmunity. Finally, we discuss the emergent role of pDCs and one of their receptors, tetherin, in human immunodeficiency virus pathogenesis.
Syk‐coupled C‐type lectin receptors that mediate cellular activation via single tyrosine based activation motifs
Authors: Kerrigan Ann M. , Brown Gordon D.
Published: February 2010

Summary:  Different dendritic cell (DC) subsets have distinct specialized functions contributed in part by their differential expression of pattern recognition receptors (PRRs). C‐type lectin receptors (CLRs) are a group of PRRs expressed by DCs and other myeloid cells that can recognize endogenous ligands as well as a wide range of exogenous structures present on pathogens. Dual roles in homeostasis and immunity have been demonstrated for some members of this receptor family. Largely due to their endocytic ability and subset specific expression, DC‐expressed CLRs have been the focus of significant antigen‐targeting studies. A number of CLRs function on the basis of signaling via association with immunoreceptor tyrosine‐based activation motif (ITAM)‐containing adapter proteins. Others contain ITAM‐related motifs or immunoreceptor tyrosine‐based inhibitory motifs (ITIMs) in their cytoplasmic tails. Here we review CLRs that induce intracellular signaling via a single tyrosine‐based ITAM‐like motif and highlight their relevance in terms of DC function.
Origin and functional heterogeneity of non‐lymphoid tissue dendritic cells in mice
Authors: Helft Julie , Ginhoux Florent , Bogunovic Milena , Merad Miriam
Published: February 2010

Summary:  Dendritic cells (DCs) have been extensively studied in mice lymphoid organs, but less is known about the origin and the mechanisms that regulate DC development and function in non‐lymphoid tissues. Here, we discuss recent evidence establishing the contribution of the DC‐restricted lineage to the non‐lymphoid tissue DC pool and discuss the mechanisms that control the homeostasis of non‐lymphoid tissue DCs. We also review recent results underlining the functional specialization of tissue DCs and discuss the potential implications of these findings in tissue immunity and in the development of novel vaccine strategies.
LMA SupremeTM insertion by novices in manikins and patients
Authors: Howes B. W. , Wharton N. M. , Gibbison B. , Cook T. M.
Published: February 2010

The LMA Supreme™ has been suggested for use in emergency situations by medical personnel with no experience in endotracheal intubation. We evaluated the LMA Supreme when inserted by non‐anaesthetists, firstly in a manikin and then in patients. Fifty airway novices inserted a LMA Supreme in a manikin without any complications so we proceeded to the patient phase. Fifty airway novices inserted the LMA Supreme in anaesthetised patients undergoing elective surgery. First time insertion success rate was 86% and overall insertion success rate was 100%. Mechanical ventilation was successful in all cases. Median (IQR [range]) time to establish an airway was 34 s (26‐40 [18–145] s). Median (IQR [range]) pharyngeal seal pressure was 23 cmH2O (19‐28 [13–40] cmH2O). There were no important complications. Results are consistent with previous studies of use of the LMA Supreme by airway experts. We conclude that the LMA supreme is suitable for use by airway novices. Further research is needed before it may be recommended for cardiopulmonary resuscitation and emergency airway use.
Effect of a new synbiotic mixture on atopic dermatitis in infants: a randomized‐controlled trial
Authors: Van Der Aa L. B. , Heymans H. S. , Van Aalderen W. M. , Sillevis Smitt J. H. , Knol J. , Ben Amor K. , Goossens D. A. , Sprikkelman A. B. ,   the Synbad Study Group
Published: February 2010

Background
Clinical trials investigating the therapeutic effect of probiotics on atopic dermatitis (AD) show inconsistent results. Better results can possibly be achieved by combining probiotics with prebiotics, i.e. synbiotics.

Objective
To investigate the therapeutic effect of a synbiotic mixture on the severity of AD in infants.

Methods
In a double‐blind, placebo‐controlled multi‐centre trial, 90 infants with AD [SCORing Atopic Dermatitis (SCORAD) score 15], aged <7 months and exclusively formula fed, were randomly assigned to receive either an extensively hydrolysed formula with Bifidobacterium breve M‐16V and a galacto‐/fructooligosaccharide mixture (Immunofortis®), or the same formula without synbiotics for 12 weeks. The primary outcome was severity of AD, assessed using the SCORAD index. A secondary outcome measure was intestinal microbiota composition.

Results
There was no difference in SCORAD score improvement between the synbiotic and the placebo group. The synbiotic group did have a significantly higher percentage of bifidobacteria (54.7% vs. 30.1%, P<0.001) and significantly lower percentages of Clostridium lituseburense/Clostridium histolyticum (0.5 vs. 1.8, P=0.02) and Eubacterium rectale/Clostridium coccoides (7.5 vs. 38.1, P<0.001) after intervention than the placebo group. In the subgroup of infants with IgE‐associated AD (n=48), SCORAD score improvement was significantly greater in the synbiotic than in the placebo group at week 12 (−18.1 vs. −13.5 points, P=0.04).

Conclusions
This synbiotic mixture does not have a beneficial effect on AD severity in infants, although it does successfully modulate their intestinal microbiota. Further randomized‐controlled trials should explore a possible beneficial effect in IgE‐associated AD.

Cite this as: L. B. van der Aa, H. S. Heymans, W. M. van Aalderen, J. H. Sillevis Smitt, J. Knol, K. Ben Amor, D. A. Goossens, A. B. Sprikkelman and the Synbad Study Group, Clinical & Experimental Allergy, 2010 (40) 795–804.
Could T cell component‐resolved diagnosis differentiate between food sensitization and food allergy?
Authors: Turcanu V.
Published: February 2010

Cite this as: V. Turcanu, Clinical & Experimental Allergy, 2010 (40) 531–533 .
The simultaneous inference of zooplanktivorous fish and macrophyte density from sub‐fossil cladoceran assemblages: a multivariate regression tree approach
Authors: DAVIDSON THOMAS A. , SAYER CARL D. , PERROW MARTIN , BRAMM METTE , JEPPESEN ERIK
Published: February 2010

1. Quantitative palaeolimnology has traditionally sought to quantify species‐environment relationships to use alterations in biological assemblages to reflect past environmental change. Transfer functions have used regression techniques, such as weighted averaging, to define taxon optima and tolerance for a single chemical or biological variable.

2. Cladoceran assemblages and their sub‐fossil remains in shallow lakes are shaped by a combination of interacting factors. Partial constrained ordination of sub‐fossil cladoceran assemblages from 39 shallow lakes (29 in Norfolk, U.K. and 10 in Denmark) indicated that both zooplanktivorous fish (ZF) density and submerged macrophyte abundance significantly influenced community composition. These dual structuring forces precluded the use of a transfer function as one of the key assumptions of this approach was not met, namely that environmental variables apart from the variable being modelled have negligible influence on species distribution or that there is a linear relationship between the two. Separate transfer functions for ZF and macrophyte abundance were developed but had poor performance diagnostics with low bootstrapped r2, high root mean square error of prediction (RMSEP) and large bias.

3. To obviate the problem of multiple structuring forces a multivariate regression tree (MRT) was employed, which allows for more than one explanatory variable within a model. The MRT analysis defined six groups with discrete ranges of ZF and macrophyte densities. The technique identified critical values or ‘break points’ in ZF and macrophyte abundances which result in significant alterations in the sub‐fossil cladoceran assemblage. In addition, the MRT groups had different summer mean values for chlorophyll‐a, Secchi depth, total phosphorus and nitrate‐nitrogen.

4. The predictive abilities of the model were assessed by comparing the observed versus predicted MRT group membership. In general group membership was reliably predicted, suggesting sub‐fossil cladoceran assemblages reliably reflect ZF and macrophyte density in shallow lakes. For a relatively small number of sites there were differences between the observed and predicted MRT group membership. These failures of prediction may result, at least in part, from the disparity of the time period represented by the environmental data and the surface sediment cladoceran assemblage.
Back to the future: using palaeolimnology to infer long‐term changes in shallow lake food webs
Authors: RAWCLIFFE RUTH , SAYER CARL D. , WOODWARD GUY , GREY JONATHAN , DAVIDSON THOMAS A. , IWAN JONES J.
Published: February 2010

1. Shallow lakes are often cited as classic examples of systems that exhibit trophic cascades but, whilst they provide good model systems with which to test general ecological theory and to assess long‐term community change, their food web linkages have rarely been resolved, so changes associated with the structure and dynamics of the ecological network as a whole are still poorly understood.

2. We sought to redress this, and to demonstrate the potential benefits of integrating palaeolimnological and contemporary data, by constructing highly resolved food webs and stable isotope derived measures of trophic interactions and niche space, for the extant communities of two shallow U.K. lakes from different positions along a gradient of eutrophication. The contemporary surface sediment cladoceran and submerged macrophyte assemblages in the less enriched site, Selbrigg Pond, matched the palaeolimnological assemblages of the more enriched site, Felbrigg Hall Lake, in its more pristine state during the 1920s. Thus, Selbrigg was a temporal analogue for Felbrigg, from which the consequences of long‐term eutrophication on food web structure could be inferred. These data represent the first steps towards reconstructing not only past assemblages (i.e. nodes within a food web), but also past interactions (i.e. links within a food web): a significant departure from much of the previous research in palaeolimnology.

3. The more eutrophic food web had far fewer nodes and links, and thus a less reticulate network, than was the case for the more pristine system. In isotopic terms, there was vertical compression in δ15N range (NR) and subsequent increased overlap in isotopic niche space, indicating increased trophic redundancy within Felbrigg. This structural change, which was associated with a greater channelling of energy through a smaller number of nodes as alternative feeding pathways disappear, could lead to reduced dynamic stability, pushing the network towards further simplification. These changes reflected a general shift from a benthic‐dominated towards a more pelagic system, as the plant‐associated subweb eroded.

4. Although these data are among the first of their kind, the palaeo‐analogue approach used here demonstrates the huge potential for applying food web theory to understand how and why these ecological networks change during eutrophication. Furthermore, because of the rich biological record preserved in their sediments, shallow lakes represent potentially important models for examining long‐term intergenerational dynamics, thereby providing a means by which models and data can be integrated on meaningful timescales – a goal that has long proved elusive in food web ecology.
Ecological influences on larval chironomid communities in shallow lakes: implications for palaeolimnological interpretations
Authors: LANGDON PETER G. , RUIZ ZOE , WYNNE SHIRLEY , SAYER CARL D. , DAVIDSON THOMAS A.
Published: February 2010

1. To correctly interpret chironomid faunas for palaeoenvironmental reconstruction, it is essential that we improve our understanding of the relative influence of ecosystem variables, biotic as well as physicochemical, on chironomid larvae. To address this, we analysed the surface sediments from 39 shallow lakes (29 Norfolk, U.K., 10 Denmark) for chironomid head capsules, and 70 chironomid taxa (including Chaoborus) were identified.

2. The shallow lakes were selected over large environmental gradients of aquatic macrophytes, total phosphorus (TP) and fish communities. Redundancy analysis (RDA) identified two significant variables that explained chironomid distribution: macrophyte species richness (P < 0.001) and TP (P < 0.005). Generalised linear models (GLM) identified specific taxa that had significant relationships with both these variables. Macrophyte percentage volume infested (PVI) and species richness were significant in classifying the lake types based on chironomid communities under twinspan analysis, although other factors, notably nutrient concentrations and fish communities, were also important, illustrating the complexities of classifying shallow lake ecosystems. Lakes with plant species richness >10 all had relatively diverse (Hill’s N2) chironomid assemblages, and lakes with Hill’s N2 >10 all had TP <250 μg L−1 and total fish densities <2 fish per m2.

3. Plant density (PVI), and perhaps more importantly species richness, were primary controls on the distribution of chironomid communities within these lakes. This clearly has implications for palaeoenvironmental reconstructions using zoobenthos remains (i.e. chironomids) and suggests that they could be used to track changes in benthic/pelagic production and could be used as indicators of changing macrophyte habitat.

4. Measuring key biological gradients, in addition to physicochemical gradients, allowed the major controls on chironomid distribution to be assessed more directly, in terms of plant substrate, food availability, competition and predation pressure, rather than implying indirect mechanisms through relationships with nutrients. Many of these variables, notably macrophyte abundance and species richness, are not routinely measured in such studies, despite their importance in determining zoobenthos in temperate shallow lakes.

5. When physical, chemical and ecological gradients are considered, as is often the case with palaeo‐reconstructions rather than training sets chosen to maximise one gradient, complex relationships exist, and attempting to reconstruct a single trophic variable quantitatively may not be appropriate or reliable.
Seasonal dynamics of macrophytes and phytoplankton in shallow lakes: a eutrophication‐driven pathway from plants to plankton?
Authors: SAYER CARL D. , DAVIDSON THOMAS A. , JONES JOHN IWAN
Published: February 2010

1. Seasonal relationships between macrophyte and phytoplankton populations may alter considerably as lakes undergo eutrophication. Understanding of these changes may be key to the interpretation of ecological processes operating over longer (decadal‐centennial) timescales.

2. We explore the seasonal dynamics of macrophytes (measured twice in June and August) and phytoplankton (measured monthly May–September) populations in 39 shallow lakes (29 in the U.K. and 10 in Denmark) covering broad gradients for nutrients and plant abundance.

3. Three site groups were identified based on macrophyte seasonality; 16 lakes where macrophyte abundance was perennially low and the water generally turbid (‘turbid lakes’); 7 where macrophyte abundance was high in June but low in August (‘crashing’ lakes); and 12 where macrophyte abundance was high in both June and August (‘stable’ lakes). The seasonal behaviour of the crashing and turbid lakes was extremely similar with a consistent increase in nutrient concentrations and chlorophyll‐a over May–September. By contrast in the stable lakes, seasonal changes were dampened with chlorophyll‐a consistently low (<10–15 μg L−1) over the entire summer. The crashing lakes were dominated by one or a combination of Potamogeton pusillus, Potamogeton pectinatus and Zannichellia palustris, whereas Ceratophyllum demersum and Chara spp. were more abundant in the stable lakes.

4. A long‐term loss of macrophyte species diversity has occurred in many shallow lakes affected by eutrophication. One common pathway is from a species‐rich plant community with charophytes to a species‐poor community dominated by P. pusillus, P. pectinatus and Z. palustris. Such compositional changes may often be accompanied by a substantial reduction in the seasonal duration of plant dominance and a greater tendency for incursions by phytoplankton. We hypothesise a slow‐enacting (10–100 s years) feedback loop in nutrient‐enriched shallow lakes whereby increases in algal abundance are associated with losses of macrophyte species and hence different plant seasonal strategies. In turn such changes may favour increased phytoplankton production thus placing further pressure on remaining macrophytes. This study blurs the distinction between so‐called turbid phytoplankton‐dominated and clear plant‐dominated shallow lakes and suggests that plant loss from them may be a gradual process.
Combining contemporary ecology and palaeolimnology to understand shallow lake ecosystem change
Authors: SAYER CARL D. , DAVIDSON THOMAS A. , JONES JOHN IWAN , LANGDON PETER G.
Published: February 2010

1. Palaeolimnology and contemporary ecology are complementary disciplines but are rarely combined. By reviewing the literature and using a case study, we show how linking the timescales of these approaches affords a powerful means of understanding ecological change in shallow lakes.

2. Recently, palaeolimnology has largely been pre‐occupied with developing transfer functions which use surface sediment‐lake environment datasets to reconstruct a single environmental variable. Such models ignore complex controls over biological structure and can be prone to considerable error in prediction. Furthermore, by reducing species assemblage data to a series of numbers, transfer functions neglect valuable ecological information on species’ seasonality, habitat structure and food web interactions. These elements can be readily extracted from palaeolimnological data with the interpretive assistance of contemporary experiments and surveys. For example, for one shallow lake, we show how it is possible to infer long‐term seasonality change from plant macrofossil and fossil diatom data with the assistance of seasonal datasets on macrophyte and algal dynamics.

3. On the other hand, theories on shallow lake functioning have generally been developed from short‐term (<1–15 years) studies as opposed to palaeo‐data that cover the actual timescales (decades–centuries) of shallow lake response to stressors such as eutrophication and climate change. Palaeolimnological techniques can track long‐term dynamics in lakes whilst smoothing out short‐term variability and thus provide a unique and important means of not only developing ecological theories, but of testing them.

4. By combining contemporary ecology and palaeolimnology, it should be possible to gain a fuller understanding of changing ecological patterns and processes in shallow lakes on multiple timescales.
Synchronous tumours of the female genital tract
Authors: Singh Naveena
Published: February 2010

Singh N (2010) Histopathology56, 277–285

Synchronous tumours of the female genital tract

About 1–2% of women with gynaecological cancers are found to have two or more simultaneous independent primary malignancies. Low stage multiple primaries must be distinguished from metastasis from one to other site for correct management. Synchronous tumours in the ovary and endometrium are the commonest combination. Most of these can be accurately categorised by standard histological criteria. Molecular testing has been advocated for valuable adjunctive information in ambiguous cases but must be interpreted with clinicopathological correlation: loss of heterozygosity, pTEN or beta‐catenin gene mutational analysis, microsatellite instability and most recently gene expression profiling have all been used. The pattern of beta‐catenin immunohistochemical expression has been reported to be of value. A very low percentage of women with synchronous primaries in the uterus and ovary are HNPCC patients and testing for mismatch repair gene mutations is unnecessary in all cases, even if young; the diagnosis of HNPCC should be based on standard criteria. Women with endometrial cancer under 50 are more likely than older patients to have a synchronous ovarian cancer. Rarer combinations of synchronous tumours are less well studied but may also represent a mixture of unusual patterns of metastasis and multifocal origin; these are discussed briefly.
Clinicopathological correlates and prognostic significance of maspin expression in 450 patients after potentially curative resection of node‐positive colonic cancer
Authors: Fung Caroline L‐S , Chan Charles , Jankova Lucy , Dent Owen F , Robertson Graham , Molloy Mark , Bokey Les , Chapuis Pierre H , Lin Betty P C , Clarke Stephen J
Published: February 2010

Fung C L‐S, Chan C, Jankova L, Dent O F, Robertson G, Molloy M, Bokey L, Chapuis P H, Lin B P C & Clarke S J (2010) Histopathology56, 319–330

Clinicopathological correlates and prognostic significance of maspin expression in 450 patients after potentially curative resection of node‐positive colonic cancer

Aims:  The tumour suppressor maspin has been investigated for its association with conventional histopathological features in colorectal cancer and for its potential as an independent predictor of survival and response to adjuvant chemotherapy. The aim of this study was to examine associations between maspin expression, other histopathology and survival in a large consecutive series of patients after potentially curative resection of node‐positive colonic adenocarcinoma.

Methods and results:  Nuclear and cytoplasmic maspin expression in both superficial and deep parts of the tumour were assessed retrospectively by tissue microarray and immunohistochemistry in specimens from 450 patients whose other histopathology had been recorded in a prospective hospital registry of large bowel cancer resections from 1971 to 2001 with a minimum follow‐up of 5 years. Among 13 clinicopathological features examined, the only associations that persisted across all four maspin assessments were stronger expression in right‐ than in left‐sided tumours (P = 0.001–0.011) and stronger expression in high‐grade tumours (P < 0.001–0.007). There was no significant association between intensity of maspin expression and overall survival.

Conclusions:  In this large and thoroughly documented series of patients with clinicopathological stage C colonic tumour, maspin expression was correlated with few other conventional histopathology variables and was not a significant prognostic factor.
Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis
Authors: Enoki Yasuyuki , Katoh Genichi , Okabe Hidetoshi , Yanagisawa Akio
Published: February 2010

Enoki Y, Katoh G, Okabe H & Yanagisawa A (2010) Histopathology56, 384–394

Clinicopathological features and CD57 expression in renal cell carcinoma in acquired cystic disease of the kidneys: with special emphasis on a relation to the duration of haemodialysis, the degree of calcium oxalate deposition, histological type, and possible tumorigenesis

Aims:  Acquired cystic disease of the kidney (ACDK) in patients undergoing haemodialysis is known to develop into renal cell carcinoma (RCC), but its pathogenesis remains unclear. The aims were to analyse the histological findings of ACDK‐RCC and to determine its histogenesis.

Methods and results:  Twenty‐nine RCCs in 23 patients with ACDK were classified into three groups according to the duration of haemodialysis and were analysed for histological type, calcium oxalate (Oxa) deposition, and cyst and atypical cyst (AC) formation. Histologically, 21 tumours were ACDK‐RCC and eight were clear cell carcinoma (CCC). The ratio of ACDK‐RCC and the numbers of cysts and ACs increased as the duration of haemodialysis was prolonged. The degrees of intratumoral Oxa deposition and cyst and AC formation of ACDK‐RCCs were higher than those of CCCs (Oxa, P = 0.028; cyst, P < 0.0001; AC, P = 0.0002). Many ACDK‐RCCs (85.7%) and some CCCs (50%) had characteristics of the thin ascending loop of Henle as assessed by CD57 (HNK‐1) expression, which was rarely expressed in the 29 control cases.

Conclusions:  ACDK‐RCCs reveal characteristics of Henle’s loop, which may be related to their peculiar pathological features, including intratumoral oxalate deposition and cyst and AC formation.
Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas
Authors: Mankey Cohra C , McHugh Jonathan B , Thomas Dafydd G , Lucas David R
Published: February 2010

Mankey C C, McHugh J B, Thomas D G & Lucas D R (2010) Histopathology 56, 364–371

Can lymphangiosarcoma be resurrected? A clinicopathological and immunohistochemical study of lymphatic differentiation in 49 angiosarcomas

Aims:  The term lymphangiosarcoma has largely been abandoned in the current classification of endothelial neoplasms. Recently, a number of lymphatic‐associated antibodies have been developed for immunohistochemistry, which frequently stain angiosarcomas, implying lymphatic or mixed lymphatic and blood vascular differentiation is common. The aim was to investigate further lymphatic antigen expression, and to explore the relation of immunohistochemistry to morphological and clinical findings.

Methods and results:  Forty‐nine angiosarcomas in tissue microarrays were analysed with D2‐40 and antibodies to Prox‐1 and vascular endothelial growth factor receptor (VEGFR)‐3. D2‐40 was positive in 53%, Prox‐1 in 76%, and VEGFR‐3 in 57%. Tumours with features attributable to lymphatic differentiation such as hobnail and kaposiform morphologies were more often positive with these markers, including a statistical association between D2‐40 and hobnailing. Ten tumours had features suggestive of lymphatic differentiation, namely well‐differentiated histology, interanastomosing channels devoid of red cells, prominent hobnailing, lymphoid aggregates, and multi‐antigen expression of D2‐40 (100%), Prox‐1 (100%) and VEGFR‐3 (60%), which might be deserving of the appellation lymphangiosarcoma. Nine were cutaneous scalp/facial tumours in elderly patients and one arose within chronic lymphoedema.

Conclusions:  Lymphatic differentiation is common in angiosarcoma, certain subsets show greater lymphatic differentiation than others, and lymphangiosarcoma may be defined pathologically, rather than clinically.
Semiquantitative assessment of immunohistochemistry for mismatch repair proteins in Lynch syndrome
Authors: Barrow Emma , Jagger Emma , Brierley Judith , Wallace Andrew , Evans Gareth , Hill James , McMahon Ray
Published: February 2010

Barrow E, Jagger E, Brierley J, Wallace A, Evans G, Hill J & McMahon R (2010) Histopathology56, 331–344

Semiquantitative assessment of immunohistochemistry for mismatch repair proteins in Lynch syndrome

Aims:  To assess semiquantitative immunohistochemistry as used in the diagnosis of Lynch syndrome.

Methods and Results:  Tumour sections from 51 mutation carriers and 17 controls were stained with antibodies against MLH1, MSH2, MSH6 and PMS2. Intensity of immunoreactivity and percentage positivity were recorded on scales of 0–3 and 0–4, respectively. These scores were multiplied for a score of 0–12 per slide. Receiver–operator characteristic (ROC) curves of staining performance for the identification of mutation carriers were evaluated, and optimum cut‐offs calculated. The area under the MLH1 ROC curve was 0.981 [95% confidence interval (CI) 0.952, 1.000]. The area under the MSH2 ROC curve was 0.899 (95% CI 0.796, 1.000). For MLH1 staining, a score ≤4 gives a sensitivity of 100.0% (95% CI 84.0, 100.0) and a specificity of 91.5% (95% CI 79.6, 97.6) for identifying MLH1 mutation carriers. For MSH2 staining, a score ≤4 gives a sensitivity of 87.5% (95% CI 61.7, 98.4) and specificity of 88.5% (95% CI 76.5, 95.6) for identifying MSH2 mutation carriers.

Conclusions:  This study supports a semiquantitative slide assessment method. Protein expression may occur in the context of known pathogenic mutations, a potential pitfall in the screening process.
Spindle proteins in resected pancreatic head adenocarcinomas: BubR1 is an independent prognostic factor in pancreatobiliary‐type tumours
Authors: Gladhaug Ivar P , Westgaard Arne , Schjølberg Aasa R , Burum‐Auensen Espen , Pomianowska Ewa , Clausen Ole Petter F
Published: February 2010

Gladhaug I P, Westgaard A, Schjølberg A R, Burum‐Auensen E, Pomianowska E & Clausen O P F (2010) Histopathology56, 345–355

Spindle proteins in resected pancreatic head adenocarcinomas: BubR1 is an independent prognostic factor in pancreatobiliary‐type tumours

Aims:  Spindle proteins such as Aurora A, Mad2 and BubR1 are important for chromosome segregation during mitosis. Dysfunction of these proteins is implicated in the development of many cancers. The aim was to examine their possible prognostic impact in resected adenocarcinomas in the pancreatic head.

Methods and results:  Two hundred and eighteen consecutively resected pancreatobiliary‐type (n = 145) and intestinal‐type (n = 73) adenocarcinomas involving the pancreatic head were examined for expression of Aurora A, Mad2 and BubR1 by immunohistochemistry on tissue microarrays. Aurora A (P < 0.001) and Mad2 (P = 0.003) were expressed more often and at higher levels in intestinal‐type compared with pancreatobiliary‐type tumours, whereas BubR1 was equally expressed in both histological types. Expression of BubR1, Aurora A and Mad2 was not associated with ploidy status. None of the spindle proteins was significantly associated with prognosis in intestinal‐type tumours. In pancreatobiliary‐type tumours, any BubR1 expression was sufficient to predict poor prognosis (P = 0.006), whereas Aurora A and Mad2 expression was not significantly associated with prognosis (P = 0.86 and P = 0.87, respectively). On adjusted Cox regression analysis, BubR1 expression independently predicted poor prognosis [P =0.002; hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.26, 2.79)], particularly in small tumours (P = 0.001; HR 2.93, 95% CI 1.53, 5.62).

Conclusion:  BubR1 expression is a novel, independent adverse prognostic factor after pancreatoduodenectomy of pancreatobiliary‐type adenocarcinomas.
Structure and measurement properties of the Patient Assessment of Chronic Illness Care instrument
Authors: Gugiu Cristian , Coryn Chris L. S. , Applegate Brooks
Published: February 2010

Objective  In this study, the authors investigated the psychometric properties of a modified version of the Patient Assessment of Chronic Illness Care (PACIC) – a self‐report instrument designed to measure the extent to which patients with chronic illness receive care congruent with the chronic care model.

Research design and method  Five hundred and twenty‐nine (529) type 2 diabetics were surveyed with a modified‐PACIC.

Results  An exploratory and confirmatory factor analysis was conducted that accounted for the ordinal nature of the PACIC items. Ordinal alpha (0.972) and omega (0.973) reliability coefficients were calculated on the latent factor underlying the modified‐PACIC. Correlation analyses were used to investigate the relationship between the modified‐PACIC and numerous clinical labs related to diabetes. Validity for the original five‐factor structure proposed by developers of the PACIC could not be confirmed.

Conclusions  More research focusing on the instrument's psychometric properties is necessary before researchers use it to investigate the chronic care model and patient health. Researchers will need to ensure that the composite scores underlying the instrument are normally distributed and correlated with behavioural and health indexes.
Effectiveness of a cognitive behavioural workbook for changing beliefs about antipsychotic polypharmacy: analysis from a cluster randomized controlled trial
Authors: Thompson Andrew , Sullivan Sarah , Barley Maddi , Moore Laurence , Rogers Paul , Sipos Attila , Harrison Glynn
Published: February 2010

Rationale, aims and objectives  Educational workbooks have been used in psychiatry to influence patient but not clinician behaviour. Targeted education interventions to change prescribing practice in other areas of medicine have only looked at changes in prescribing and not attitudes or beliefs related to the prescribing. We aimed to examine whether clinicians' beliefs about a common prescribing issue in psychiatry (antipsychotic polypharmacy prescription) changed alongside behaviour as a result of a complex intervention.

Method  Medical and nursing staff were recruited from 19 general adult psychiatry units in the south‐west of the UK as part of a cluster randomized controlled trial. A questionnaire was used to assess beliefs on the prescribing of antipsychotic polypharmacy as a secondary outcome before and after completion of a cognitive behavioural ‘self‐help’ style workbook (one part of a complex intervention). A factor analysis suggested three dimensions of the questionnaire that corresponded to predetermined themes. The data were analysed using a random‐effects regression model (adjusting for clustering) controlling for possible confounders.

Results  There was a significant change in beliefs on both of the factors: antipsychotic polypharmacy (coefficient = −0.89, P < 0.01) and rapid tranquilization (coefficient = −0.68, P = 0.01) specifically targeted by the workbook. There was a modest but statistically significant change in antipsychotic polypharmacy prescribing (odds ratio 0.43, 95% confidence intervals 0.21–0.90).

Conclusions  The workbook appeared to change staff beliefs about antipsychotic polypharmacy, but achieving substantial changes in clinician behaviour may require further exploration of other factors important in complex prescribing issues.
Keeping vulnerable elderly patients free from pressure ulcer is associated with high caregiver burden in informal caregivers
Authors: Yamamoto Yosuke , Hayashino Yasuaki , Higashi Takahiro , Matsui Miho , Yamazaki Shin , Takegami Misa , Miyachi Yoshiki , Fukuhara Shunichi
Published: February 2010

Rationale and objectives  The effect of the presence of pressure ulcers on burden of caregivers is unknown. We investigated the relationship between the state of pressure ulcers in vulnerable elderly patients and the burden on their informal caregivers.

Methods  This cross‐sectional study enrolled 137 patients aged ≥40 years with limited activity and mobility at 10 home care service facilities in Japan. We assessed pressure ulcer status from medical records and caregiver burden using scores from both the Burden Index of Caregivers (BIC) and the Japanese short version of the Zarit Burden Interview (ZBI).

Results  Among patients, mean age was 80.9 years, 31.4% were men, and 83.9% were free from pressure ulcers. Multivariable analysis showed that caregivers whose patients were free from pressure ulcers had significantly higher caregiver burden as assessed by both the BIC [β‐coefficient = 3.18, 95% confidence interval (CI): 1.42–4.95, P = 0.003] and ZBI scores (β‐coefficient = 1.94; 95%CI = 0.30–3.58; P = 0.03).

Conclusions  Our results suggest that the continuous effort involved in keeping patients free from pressure ulcers may be associated with high caregiver burden in informal caregivers.
The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review
Authors: Cummings A. J. , Knibb R. C. , King R. M. , Lucas J. S.
Published: February 2010

To cite this article: Cummings AJ, Knibb RC, King RM, Lucas JS. The psychosocial impact of food allergy and food hypersensitivity in children, adolescents and their families: a review. Allergy 2010; 65: 933–945.

Food allergy affects 6% of children but there is no cure, and strict avoidance of index allergens along with immediate access to rescue medication is the current best management. With specialist care, morbidity from food allergy in children is generally low, and mortality is very rare. However, there is strong evidence that food allergy and food hypersensitivity has an impact on psychological distress and on the quality of life (QoL) of children and adolescents, as well as their families. Until recently, the measurement of QoL in allergic children has proved difficult because of the lack of investigative tools available. New instruments for assessing QoL in food allergic children have recently been developed and validated, which should provide further insights into the problems these children encounter and will enable us to measure the effects of interventions in patients. This review examines the published impact of food allergy on affected children, adolescents and their families. It considers influences such as gender, age, disease severity, co‐existing allergies and external influences, and examines how these may impact on allergy‐related QoL and psychological distress including anxiety and depression. Implications of the impact are considered alongside avenues for future research.
Ratio of M2 macrophage expression is closely associated with poor prognosis for Angioimmunoblastic T‐cell lymphoma (AITL)
Authors: Niino Daisuke , Komohara Yoshihiro , Murayama Toshihiko , Aoki Ryosuke , Kimura Yoshizo , Hashikawa Keiko , Kiyasu Junichi , Takeuchi Masanori , Suefuji Nobuko , Sugita Yasuo , Takeya Motohiro , Ohshima Koichi
Published: February 2010

Angioimmunoblastic T‐cell lymphoma (AITL) is a peripheral T‐cell lymphoma characterized by systemic disease with polymorphous infiltrate including macrophages. Although many studies of tumor‐associated macrophage (TAM) populations in various malignant tumors have been published, only a few have dealt with activation of macrophage phenotypes such as M1 and M2 in tumor tissue. Because M2 macrophages highly express CD163, we suspected that CD163 may be a useful marker for identification of activation of macrophage phenotypes in AITL. We performed a retrospective study of immunohistochemical expression using two markers for macrophages [CD68 (PG‐M1), CD163] and of the correlation of these expressions with overall survival of 42 AITL patients. The number of CD68‐positive cells in AITL tissues did not correlate with overall survival (P= 0.59), whereas the number of CD163‐positive cells and overall survival correlated to some extent (P= 0.08). Meanwhile, a higher ratio of CD163‐positive to CD68‐positive cells in AITL significantly correlated with worse overall survival (P= 0.036). Considering that this ratio reflects the proportion of macrophages polarized to the M2 phenotype, our findings indicate that activation of macrophages towards the M2 phenotype correlates with worse prognosis. Our findings indicate that the ratio of M2 macrophages expressed may be a useful marker for prognosis of AITL.
Assessment of hepatic fibrosis by transient elastography in patients with chronic hepatitis B
Authors: Zhang Yu‐Guo , Wang Bao‐En , Wang Tai‐Ling , Ou Xiao‐Juan
Published: February 2010

Hepatic ultrasonic transient elastography (FibroScan) is a new diagnostic method for the assessment of hepatic fibrosis. There are limited data available on its use as a follow‐up tool for patients with chronic hepatitis B. In this study, 134 patients were enrolled. Hepatic fibrosis was evaluated by liver stiffness measurement and biopsy. The biopsy criteria of the Chinese Program of Prevention and Cure for Viral Hepatitis, Metavir classification, and the modified Chevalier's semiquantitative system were used for histological assessment. The liver stiffness value was correlated with fibrosis stage (r = 0.565, P < 0.001) and fibrosis semiquantitative score (r = 0.727, P < 0.001). The liver stiffness value of G2 was significantly higher than that of G1 within the same fibrosis stage for S1, S3, and S4, respectively. Three patients were graded as G1S1, and had moderate steatosis without distinct fibrosis in the portal area and lobule, while their liver stiffness values were higher than 6.2 kPa. Although belonging to the same fibrosis stage, for thinner thicknesses of the fibrous septa, the liver stiffness value and semiquantitative score were correspondingly lower. Liver stiffness values had a good correlation with hepatic collagen content. However, inflammatory activity and steatosis can influence liver stiffness values to some extent. Transient elastography may be useful as an ideal non‐invasive post‐treatment follow‐up tool.
Male infertility in cancer patients: Review of the literature
Authors: Dohle Gert R
Published: February 2010

The number of men surviving cancer at a young age has increased dramatically in the past 20 years as a result of early detection and improved cancer treatment protocols; more than 75% of young cancer patients nowadays are long‐term survivors. Quality of life has become an important issue in childhood and adult cancer patients. The commonest cancers in patients of reproductive age are leukaemia, Hodgkin's lymphomas and testicular germ cell tumors. Fertility is often impaired after chemotherapy and radiation therapy. Cryopreservation of semen before cancer treatment starts is currently the only method to preserve future male fertility. In some malignancies, especially in germ cell tumors, sperm quality is already abnormal at the time of diagnosis. In approximately 12% of men, no viable spermatozoa are present for cryopreservation before the start of chemotherapy. Cytotoxic therapy influences spermatogenesis at least temporarily and in some cases permanently. The amount of damage inflicted by chemotherapy on spermatogenesis depends on the combination of drugs used and on the cumulative dose given for cancer treatment. Alkylating agents, such as cyclophosphamide and procarbazine, are most detrimental to germ cells. Radiation therapy, especially whole‐body irradiation, is also associated with the risk of permanent sterility. Besides the cancer treatment, tumor type and pretreatment fertility are of prognostic value for future fertility in male cancer survivors. After cancer treatment, many men need artificial reproductive techniques to achieve fatherhood; usually in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is indicated for successful treatment. About 15% of men will use their cryopreserved semen because of persistent azoospermia after cancer treatment. Treatment results with cryopreserved semen are generally good and comparable to general IVF and ICSI results. So far, no studies have reported an increased rate of congenital abnormalities or malignancies in children born from fathers who had cancer treatment is the past, but close follow up is warranted, especially in children born after IVF/ICSI.
Aciclovir‐resistant herpes keratitis
Authors: Choong Keat , Walker Nathan J , Apel Andrew JG , Whitby Michael
Published: February 2010

Abstract

Herpes simplex virus (HSV) keratitis is a common cause of ocular morbidity. Resistance to aciclovir is probably under recognized. We describe three cases of aciclovir‐resistant herpes simplex virus keratitis treated with systemic foscarnet and present a review of the pharmacological options available to manage this condition.
Value of dual biometry in the detection and investigation of error in the preoperative prediction of refractive status following cataract surgery
Authors: Charalampidou Sofia , Dooley Ian , Molloy Laura , Beatty Stephen
Published: February 2010

Abstract

Purpose:  To report the value of dual biometry in the detection of biometry errors.

Methods:  Study 1: retrospective study of 224 consecutive cataract operations. The intraocular lens power calculation was based on immersion biometry. Study 2: immersion biometry was compared with optical coherence biometry (OCB) in terms of axial length, anterior chamber depth, keratometry readings and the recommended lens power to achieve emmetropia. Study 3: prospective study of 61 consecutive cataract operations. Both immersion and OCB were performed, but lens power calculation was based on the latter.

Results:  Study 1: 115 (86%), 101 (75.4%), 90 (67.2%) and 50 (37.3%) of postoperative spherical equivalents were within ±1.5 dioptres (D), ±1.25 D, ±1 D and ±0.5 D of the target, respectively. Study 2: excellent agreement between axial length readings, anterior chamber depth readings and keratometry readings by immersion biometry and OCB was observed (reflected in a mean bias of −0.065 mm, −0.048 mm and +0.1803 D, respectively, in association with OCB). Agreement between the lens power recommended by each technique to achieve emmetropia was poor (mean bias of +1.16 D in association with OCB), but improved following appropriate modification of lens constants in the Accutome A‐scan software (mean bias with OCB = −0.4 D). Study 3: 37 (92.5%) and 23 (57.5%) of operated eyes achieved a postoperative refraction within ±1 D and ±0.5 D of target, respectively.

Conclusion:  Systematic errors in biometry can exist, in the presence of acceptable postoperative refractive results. Dual biometry allows each biometric parameter to be scrutinized in isolation, and identify sources of error that may otherwise go undetected.
Micropulse transscleral diode laser cyclophotocoagulation in the treatment of refractory glaucoma
Authors: Tan Anna M , Chockalingam Muthuraman , Aquino Maria C , Lim Zena I‐L , See Jovina L‐S , Chew Paul TK
Published: February 2010

Background:  Transscleral diode laser cyclophotocoagulation (TSCPC) is an established method of treatment for refractory glaucoma, but is associated with significant complications. This study evaluates the efficacy and safety of a new form of TSCPC using micropulse diode laser and trans‐pars plana treatment with a novel contact probe.

Methods:  Prospective interventional case series of 40 eyes of 38 consecutive patients with refractory glaucoma treated with micropulse TSCPC with a novel probe. Outcomes measured were success, hypotony and response rates.

Results:  The mean age of patients was 63.2 ± 16.0 years. The mean follow‐up period was 16.3 ± 4.5 months. The mean intraocular pressure (IOP) before micropulse TSCPC was 39.3 ± 12.6 mmHg. Mean IOP decreased to 31.1 ± 13.4 mmHg at 1 day, 28.0 ± 12.0 mmHg at 1 week, 27.4 ± 12.7 mmHg at 1 month, 27.1 ± 13.6 mmHg at 3 months, 25.8 ± 14.5 mmHg at 6 months, 26.6 ± 14.7 mmHg at 12 months and 26.2 ± 14.3 mmHg at 18 months (P < 0.001 at all time points). No patient had hypotony or loss of best‐corrected visual acuity. The overall success rate after a mean of 1.3 treatment sessions was 72.7%.

Conclusion:  Micropulse TSCPC is a safe and effective method of lowering IOP in cases of refractory glaucoma and is comparable with conventional TSCPC.