bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct cytokine and regulatory T cell profile at pleural sites of dual HIV/tuberculosis infection compared to that in the systemic circulation
Authors: Toossi Z , Hirsch C S , Wu M , Mayanja-Kizza H , Baseke J , Thiel B
Published: February 2011

Pleural tuberculosis (TB) remains a common presentation of Mycobacterium tuberculosis (MTB) infection in HIV/TB dually infected subjects, and both cellular and acellular components of the pleural milieu promote HIV-1 replication; however, they remain uncharacterized. Using cytokine array of pleural fluid and real-time reverse transcription–polymerase chain reaction (RT–PCR) and immunophenotype analysis, pleural fluid mononuclear cells (PFMC) were compared to systemic counterparts [i.e. plasma and peripheral blood mononuclear cells (PBMC)]. Significant increases in pleural fluid cytokines compared to plasma were limited to interleukin (IL)-6, IL-8, interferon (IFN)-γ and transforming growth factor (TGF)-β, and did not include other T helper type 1 (Th1) (IL-2, IL-15), Th2 or Th17 cytokines. Patterns and levels of cytokines were indistinguishable between pleural fluid from HIV/TB and TB patients. Forkhead box P3 (FoxP3) mRNA in PFMC was increased significantly and correlated highly with levels of IL-6 and IL-8, less with TGF-β, and not with IFN-γ. Among CD4 T cells, FoxP3-reactive CD25hi were increased in HIV/TB dually infected subjects compared to their PBMC, and up to 15% of FoxP3+ CD25hi CD4 T cells were positive for IL-8 by intracellular staining. These data implicate a dominant effect of MTB infection (compared to HIV-1) at pleural sites of dual HIV/TB infection on the local infectious milieu, that include IL-6, IL-8, IFN-γ and TGF-β and regulatory T cells (Treg). A correlation in expansion of Treg with proinflammatory cytokines (IL-6 and IL-8) in pleural fluid was shown. Treg themselves may promote the inflammatory cytokine milieu through IL-8.
Raised tryptase without anaphylaxis or mastocytosis: heterophilic antibody interference in the serum tryptase assay
Authors: Sargur R , Cowley D , Murng S , Wild G , Green K , Shrimpton A , Egner W
Published: February 2011

Mast cell tryptase (MCT) is a key diagnostic test for mastocytosis and anaphylaxis. High serum tryptase levels are also one of the risk factors for adverse reaction in venom immunotherapy, yet occasional patients are seen with raised levels in the absence of either diagnosis. False positive results can be due to assay interference by heterophilic antibodies such as rheumatoid factor (RF) and human anti-mouse antibodies (HAMA). We therefore investigated heterophilic antibody interference by rheumatoid factor activity and HAMA as a cause of raised MCT results in the Phadia tryptase assay. Serum samples from 83 patients were assayed for MCT and rheumatoid factor before and after the use of heterophilic antibody blocking tubes (HBT). Samples with more than 17% reduction in MCT with detectable RF were then assayed for HAMA. Fourteen (17%) of the 83 samples with positive RF showed a >17% decrease in mast cell tryptase after HBT blocking. Post-HBT, eight of 14 (57%) reverted from elevated to normal range values with falls of up to 98%. RF levels were also decreased significantly (up to 75%). Only one of the 83 tested was apparently affected by HAMA in the absence of detectable IgM RF. In conclusion, any suspicious MCT result should be checked for heterophilic antibodies to evaluate possible interference. False positive MCT levels can be caused by rheumatoid factor. We suggest a strategy for identifying assay interference, and show that it is essential to incorporate this caveat into guidance for interpretation of MCT results.
Allogeneic haematopoietic stem cell transplantation in patients with human immunodeficiency virus: the experiences of more than 25 years
Authors: Hütter G , Zaia J A
Published: February 2011

For treatment of several malignancies, transplantation of allogeneic haematopoietic stem cells (HSCT) derived from bone marrow or peripheral blood has been used as a therapeutic procedure for decades. In the past, HSCT has been suggested as a treatment option for infection with the human immunodeficiency virus type 1 (HIV-1), but these attempts were mostly unsuccessful. Today, after the introduction of an active anti-retroviral therapy, the lifetime expectancy of HIV-infected patients has improved substantially, but nevertheless the incidence rate of malignancies in these patients has increased considerably. Therefore, it can be assumed that there will be a rising necessity for HIV-1-infected patients with malignancies for allogeneic HSCT. At the same time, there is increasing interest in treatment methods which might target the HIV-1 reservoir more effectively, and the question has been raised as to whether allogeneic HSCT could be linked to such strategies. In this paper the data of more than 25 years experience with allogeneic HSCT in patients with HIV-1 are reviewed and analysed.
Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer
Authors: Vaisman F. , Shaha A. , Fish S. , Michael Tuttle R.
Published: February 2011

Objective  To describe the risk of structural disease recurrence in a cohort of patients with differentiated thyroid cancer selected for treatment with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation (RRA).

Design  Retrospective review.

Patients  A total of 289 patients were selected for either thyroid lobectomy (n = 72) or total thyroidectomy (n = 217) without RRA and followed with modern disease detection tools in a tertiary referral centre. Most patients had papillary thyroid cancer (89%) without clinically evident lymph node metastases (91%). However, 55% (156/289) of patients had primary tumours that were >1 cm and 10% (28/289) had minor extrathyroidal extension.

Measurements  The primary endpoint was detection of recurrent/persistent structural disease.

Results  After a 5‐year median follow‐up, structural disease recurrence was detected in 2·3% (5/217) of patients treated with total thyroidectomy without RRA, and in 4·2% (3/72) of patients treated with thyroid lobectomy. Size of the primary tumour, the presence of cervical lymph node metastases and American Thyroid Association risk category were all statistically significant predictors of recurrence. Changes in serum thyroglobulin were not helpful in identifying the presence of persistent/recurrent structural disease. Importantly, 88% (7/8) of the patients that had recurrent disease were rendered clinically disease free with additional therapies.

Conclusions  Initial risk stratification is able to identify a cohort of patients with differentiated thyroid cancer with a very low risk of structural disease recurrence following treatment with either thyroid lobectomy or total thyroidectomy without RRA. Our data strongly support a selective approach to the initial management of thyroid cancer.
GrazeIn: a model of herbage intake and milk production for grazing dairy cows. 2. Prediction of intake under rotational and continuously stocked grazing management
Authors: Delagarde R. , Faverdin P. , Baratte C. , Peyraud J.L.
Published: February 2011

Decision support tools to help dairy farmers gain confidence in grazing management need to be able to predict performance of grazing animals with easy‐to‐obtain variables on farm. This paper, the second of a series of three, describes the GrazeIn model predicting herbage intake for grazing dairy cows. The model of voluntary intake described in the first paper is adapted to grazing situations taking account of sward characteristics and grazing management, which can potentially affect intake compared to indoor feeding. Rotational and continuously stocked grazing systems are considered separately. Specific effects of grazing management on intake were quantified from an extensive literature review, including the effect of daily herbage allowance and pre‐grazing herbage mass in rotational grazing systems, sward surface height in continuously stocked grazing systems, and daily time at pasture in both grazing systems. The model, based on iterative procedures, estimates many interactions between cows, supplements, sward characteristics and grazing management. The sensitivity of the prediction of herbage intake to sward and management characteristics, as well as the robustness of the simulations and an external validation of the GrazeIn model with an independent data set, is presented in a third paper.
Efficacy of a 2‐dose regimen of a sustained release ceftiofur suspension in horses withStreptococcus equisubsp. zooepidemicusbronchopneumonia
Authors: McCLURE S. , SIBERT G. , HALLBERG J. , BADE D.
Published: February 2011

McClure, S., Sibert, G., Hallberg, J, Bade, D. Efficacy of a 2‐dose regimen of a sustained release ceftiofur suspension in horses withStreptococcus equisubsp. zooepidemicusbronchopneumonia.J. vet. Pharmacol. Therap.34, 442–447.

The efficacy and safety of sustained release ceftiofur administered twice, 4 days apart, for treatment of horses with naturally acquiredStreptococcus equisubsp.zooepidemicus(Strep. zoo.) pneumonia was evaluated in a multicenter, placebo‐controlled, double‐blinded, randomized clinical trial. The study included 373 horses (278 treated and 95 placebos) with naturally acquired pneumonia. Inclusion in the statistical analyses for treatment efficacy forStrep. zoo.required recovery of ≥104 CFU/mL ofStrep. zoo.on the primary isolation plate which resulted in 201 cases (145 treated and 56 placebos) with confirmedStrep. zoo.pneumonia evaluable for treatment success. Therapeutic success was defined by clinical improvement of lower respiratory tract infection at 4 and 9 days after initial dosing, resolution of clinical signs by 15 days, and no recurrence by 25 days. Of the 278 treated horses, 239 (85.9%) completed the 25 day study without additional therapy compared to 50 of the 95 (53.6%) placebo horses. In confirmedStrep. zoo.cases, a clinical cure was achieved in 66.9% of 145 treated horses compared to 32.1% of 56 placebo horses (P = 0.0286). Two doses of sustained release ceftiofur suspension were effective and safe in the treatment of naturally acquired lower respiratory tract infection associated withStrep. zoo.in horses under field use conditions.
Serum phosphate and outcome at one year after deceased donor renal transplantation
Authors: Stevens K.K. , Morgan I.R. , Patel R.K. , Geddes C.C. , Mark P.B. , Jardine A.G. , Delles C.
Published: February 2011

Stevens KK, Morgan IR, Patel RK, Geddes CC, Mark PB, Jardine AG, Delles C. Serum phosphate and outcome at one year after deceased donor renal transplantation.  Clin Transplant 2011: 25: E199–E204. © 2011 John Wiley & Sons A/S.

Abstract:  Traditional risk factors do not adequately explain the increased prevalence of cardiovascular disease in renal patients. This study considered a “non‐traditional” risk factor, serum phosphate and outcome in renal transplant recipients. Data from 377 patients who received a first deceased donor renal transplant between January 1, 1999, and December 31, 2008, were recorded; 10% (n=38) had diabetes, 16.7% (n=63) were smokers, and 18.8% (n=71) had a history of vascular disease. Three hundred and thirty‐three patients were alive at the time of the analysis. Survivors were significantly younger, less likely to be smokers or diabetic, and had a higher estimated glomerular filtration rate at one yr post‐transplantation. Serum phosphate was significantly lower in these patients (0.95±0.23 vs. 1.04±0.26, p=0.031). Analysis of recipient survival, stratified by serum phosphate at one yr post‐transplant, revealed that serum phosphate >1.11 mMol/L was a significant predictor of all‐cause mortality (p=0.006). Serum phosphate between 0.9 and 1.11 mMol/L afforded the best outcome. In multivariate analysis, serum phosphate remained a significant predictor of mortality (p=0.016). Serum phosphate at one yr after transplant seems to have a J‐shaped relationship with mortality, and this effect is independent of traditional cardiovascular risk factors.
Extended criteria donors in liver transplant candidates with hepatorenal syndrome
Authors: Briceño Javier , Ciria Ruben , de la Mata Manuel , Montero José Luis , Rufián Sebastián , López‐Cillero Pedro
Published: February 2011

Briceño J, Ciria R, de la Mata M, Montero JL, Rufián S, López‐Cillero P. Extended criteria donors in liver transplant candidates with hepatorenal syndrome. Clin Transplant 2011: 25: E257–E263. © 2011 John Wiley & Sons A/S.

Abstract:  Hepatorenal syndrome (HRS) is a complication of cirrhosis with a poor prognosis without transplantation. The aim of this study is to analyze the influence of extended criteria donors (ECD) on the postoperative outcome of recipients with HRS. The last 498 patients were divided according to pre‐transplant type 1 or 2 HRS. Sixty‐six (13.25%) recipients fulfilled HRS criteria. Three‐month graft survival was 84% with at‐listing recipient serum creatinine ranging from 0–0.8 mg/dL; 80% with s‐creatinine = 0.9–1.5 mg/dL; 79% with s‐creatinine = 1.6–2.5 mg/dL; and 58% with s‐creatinine >2.6 mg/dL (log‐rank = 18.039; p = 0.001). Recipients with HRS presented higher levels of pre‐transplant creatinine and lower levels of sodium, more episodes of hemodialysis and ascitis, and higher model of end‐stage liver disease‐scores. Three‐month graft survival in recipients with HRS relative to ECD‐variables showed differences in univariate analysis according to graft steatosis (85% in absent steatosis = 0–10%; 78% in mild steatosis = 10–30%; 76% in moderate steatosis = 30–60%; and 49% when severe steatosis >60%; log‐rank = 5.146; p = 0.023). Cox‐proportional‐hazard‐model revealed that graft macrosteatosis per‐30%‐increments (p = 0.000; HR = 1.303 [1.24–1.33] per‐30%‐increment) and donors >65 yr (p = 0.089; HR = 1.622 [1.17–1.94]) were independent predictors of graft loss in recipients with HRS. In conclusion, the use of ECD in recipients with cirrhosis and HRS is a good option. However, grafts from moderate‐to‐severe steatosis and those from aged donors must be carefully allocated in candidates with HRS.
Does facilitating pollinator learning impede deceptive orchid attractiveness? A multi‐approach test of avoidance learning
Authors: Juillet N. , Salzmann C. C. , Scopece G.
Published: February 2011

It has often been proposed that nectarless deceptive orchid species exploit naïve pollinators in search of food before they learn to avoid their flowers, and that intraspecific floral trait polymorphism, often noted in this plant group, could prolong the time needed for learning, thus increasing orchid reproductive success. We tested the importance of avoidance learning in a European deceptive orchid, Anacamptis morio, which has been reported to have a highly variable fragrance bouquet among individuals. We used an indirect approach, i.e. we facilitated pollinators’ ability to learn to avoid A. morio by adding anisaldehyde to selected inflorescences, a scent compound that is easily perceived by the natural pollinators and produced in large quantities by the closely related, nectar producing Anacamptis coriophora, a species that shares pollinator species with A. morio. In a series of three experiments (in artificial arrays, in natural populations and in bumblebee behavioural observations), we consistently found no difference either of reproductive success of or visitation rates to scent‐added versus control inflorescences. We also found that the decrease of reproductive success over time in artificial populations of this deceptive species was not as important as expected. Together, these data suggest that pollinators do not fully learn to avoid deceptive inflorescences, and that pollinator avoidance behaviour alone may explain the lower reproductive success usually found in deceptive orchids. We discuss the possible explanations for this pattern in deceptive orchids, particularly in relation to pollinator cognition and learning abilities. Lastly, in light of our results, the potential for higher average reproductive success in deceptive orchids with high phenotypic variability driven by avoidance learning thus appears to be challenged.
Over‐expression of gsh1 in the cytosol affects the photosynthetic apparatus and improves the performance of transgenic poplars on heavy metal‐contaminated soil
Authors: Ivanova L. A. , Ronzhina D. A. , Ivanov L. A. , Stroukova L. V. , Peuke A. D. , Rennenberg H.
Published: February 2011

Recent studies of transgenic poplars over‐expressing the genes gsh1 and gsh2 encoding γ‐glutamylcysteine synthetase (γ‐ECS) and glutathione synthetase, respectively, provided detailed information on regulation of GSH synthesis, enzymes activities and mRNA expression. In this experiment, we studied quantitative parameters of leaves, assimilating tissues, cells and chloroplasts, mesophyll resistance for CO2 diffusion, chlorophyll and carbohydrate content in wild‐type poplar and transgenic plants over‐expressing gsh1 in the cytosol after 3 years of growth in relatively clean (control) or heavy metal‐contaminated soil in the field. Over‐expression of gsh1 in the cytosol led to a twofold increase of intrafoliar GSH concentration and influenced the photosynthetic apparatus at different levels of organisation, i.e., leaves, photosynthetic cells and chloroplasts. At the control site, transgenic poplars had a twofold smaller total leaf area per plant and a 1.6‐fold leaf area per leaf compared to wild‐type controls. Annual aboveground biomass gain was reduced by 50% in the transgenic plants. The reduction of leaf area of the transformants was accompanied by a significant decline in total cell number per leaf, indicating suppression of cell division. Over‐expression of γ‐ECS in the cytosol also caused changes in mesophyll structure, i.e., a 20% decrease in cell and chloroplast number per leaf area, but also an enhanced volume share of chloroplasts and intercellular airspaces in the leaves. Transgenic and wild poplars did not exhibit differences in chlorophyll and carotenoid content of leaves, but transformants had 1.3‐fold fewer soluble carbohydrates. Cultivation on contaminated soil caused a reduction of palisade cell volume and chloroplast number, both per cell and leaf area, in wild‐type plants but not in transformants. Biomass accumulation of wild‐type poplars decreased in contaminated soil by more than 30‐fold, whereas transformants showed a twofold decrease compared to the control site. Thus, poplars over‐expressing γ‐ECS in the cytosol were more tolerant to heavy metal stress under field conditions than wild‐type plants according to the parameters analysed. Correlation analysis revealed strong dependence of cell number per leaf area unit, chloroplast parameters and mesophyll resistance with the GSH level in poplar leaves.
Evaluation of the RPi‐ber late blight resistance gene for tuber resistance in the field and laboratory
Authors: Mayton Hilary , Rauscher Gilda , Simko Ivan , Fry William E.
Published: February 2011

With 4 figures and 1 table

The purpose of this research was to evaluate the efficacy in tubers of a late blight resistance gene, RPi‐ber, originating from Solanum berthaultii. Experiments were conducted in the field and laboratory. Inoculation of tubers in field trials occurred via sporangia produced on infections in the foliage. Laboratory trials were conducted by inoculating whole tubers and tuber slices with sporangia of Phytophthora infestans. In all trials, those progeny with RPi‐ber were essentially immune to strains of P. infestans that were incompatible with RPi‐ber in the foliage. However, even when tested against strains of P. infestans that were compatible with RPi‐ber in the foliage, there was still a resistance effect at the RPi‐ber region.
Stability of tissue PO2in the face of altered perfusion: a phenomenon specific to the renal cortex and independent of resting renal oxygen consumption
Authors: Evans Roger G , Goddard Duncan , Eppel Gabriela A , O’Connor Paul M
Published: February 2011

1. Oxygen tension (PO2) in renal cortical tissue can remain relatively constant when renal blood flow changes in the physiological range, even when changes in renal oxygen delivery (DO2) and oxygen consumption (VO2) are mismatched. In the current study, we examined whether this also occurs in the renal medulla and skeletal muscle, or if it is an unusual property of the renal cortex. We also examined the potential for dysfunction of the mechanisms underlying this phenomenon to contribute to kidney hypoxia in disease states associated with increased renal VO2.

2. In both the kidney and hindlimb of pentobarbitone anaesthetized rabbits, whole organ blood flow was reduced by intra‐arterial infusion of angiotensin‐II and increased by acetylcholine infusion. In the kidney, this was carried out before and during renal arterial infusion of the mitochondrial uncoupler, 2,4‐dinitrophenol (DNP), or its vehicle.

3. Angiotensin‐II reduced renal (−34%) and hindlimb (−25%) DO2, whereas acetylcholine increased renal (+38%) and hindlimb (+66%) DO2. However, neither renal nor hindlimb VO2were altered. Tissue PO2varied with local perfusion in the renal medulla and biceps femoris, but not the renal cortex. DNP increased renal VO2(+38%) and reduced cortical tissue PO2(−44%), but both still remained stable during subsequent infusion of angiotensin‐II and acetylcholine.

4. We conclude that maintenance of tissue PO2in the face of mismatched changes in local perfusion and VO2is an unusual property of the renal cortex. The underlying mechanisms remain unknown, but our current findings suggest they are not compromised when resting renal VO2is increased.
Sphincter of Oddi manometry by choledochoscope in patients with duodenobiliary reflux
Authors: Sun Shaolong , Wu Shuodong , Cui Dongxu , Liu Baolin , Dai Xianwei , Xu Weina , Yu Shupeng
Published: February 2011

Background and Aim:  Previous research has confirmed that duodenobiliary reflux exists in patients with choledocholithiasis. The objective of this study was to investigate whether the motor activity of the sphincter of Oddi (SO) has an effect on duodenobiliary reflux.

Methods:  A total of 51 patients orally ingested 1 mL water containing technetium‐99m diethylenetriaminepentaacetatic acid, and a 2‐h bile collection was obtained from the T tube. Technetium counts in the collected bile were performed using an RM905 radioactivity meter. The patients were divided into two groups: reflux group (duodenobiliary reflux positive) and control group (duodenobiliary reflux negative). Next, 33 cases were randomly selected and double blinded to receive SO manometry by choledochoscope.

Results:  Of the 51 total cases, 16 bile samples exhibited radioactivity. The average SO basal pressure and contraction pressure values were 7.2 ± 3.9 mmHg and 53.5 ± 24.5 mmHg, respectively, in the reflux group, and 14.7 ± 11.0 mmHg and 117.2 ± 65.6 mmHg, respectively, in the control group. The choledochus pressure values were 5.1 ± 1.6 mmHg and 11.5 ± 7.4 mmHg in the reflux group and the control group, respectively. The differences between the groups were statistically significant; however, the SO contraction frequency, SO contraction duration, and duodenum pressure values were not significantly different between the groups.

Conclusion:  The decreases in the SO basal pressure and SO contraction pressure, and the decrease in choledochus pressure, might play a role in duodenobiliary reflux.
Prebiotic treatment in experimental colitis reduces the risk of colitic cancer
Authors: Komiyama Yutaka , Mitsuyama Keiichi , Masuda Jyunya , Yamasaki Hiroshi , Takedatsu Hidetoshi , Andoh Akira , Tsuruta Osamu , Fukuda Masanobu , Kanauchi Osamu
Published: February 2011

Background and Aim:  Germinated barley foodstuff (GBF) is a prebiotic product that reduces colonic mucosal inflammation and the clinical symptoms observed in ulcerative colitis (UC). The risk of contracting colorectal cancer is higher in patients with UC than in that of the general population. The aim of this study is to apply this prebiotic approach to control chronic colitis and to reduce the incidence of colitic cancer.

Methods:  Repeated and intermitted dextran sulfate sodium administration to male Sprague–Dawley rats was used for the chronic and subacute colitis models. GBF was added as the diet (10% w/v). The incidence of adenomatous high‐grade dysplasia, and pathophysiological observations, including the proliferative cell nuclear antigen (PCNA) labeling index, and clinical score, cecal organic acid profile, and the accompanying β‐glucosidase activity were determined.

Results:  In the chronic phase, the incidence of adenomatous dysplasia was only confirmed in the control group, and the GBF group had no dysplasia in the entire colon; the stratified squamous epithelium area of GBF was significantly lower than that of the controls. GBF treatment significantly lowered the cecal succinate content and significantly increased β‐glucosidase activity compared to the controls. In addition, colonic mucosal inflammatory damage was comparable between the two groups, while the PCNA labeling index of the colonic mucosa in the GBF group was significantly lower than that of the control group. However, in the subacute phase, the mucosal damage score of GBF was significantly attenuated, and the PCNA labeling index of the colonic mucosa in the GBF group was significantly higher than that of the control group.

Conclusion:  This preliminary study demonstrated that GBF effectively prevents colitis‐related dysplasia and inflammatory change in chronic and subacute colitis models by modulating the intestinal environment as a prebiotic. This prebiotic might contribute to the prevention of mucosal damage, to show different proliferative effects on the epithelium in the regeneration and steady states.
Genetic background is different between sentinel and recurrent acute pancreatitis
Authors: Masamune Atsushi , Ariga Hiroyuki , Kume Kiyoshi , Kakuta Yoichi , Satoh Kennichi , Satoh Akihiko , Shimosegawa Tooru
Published: February 2011

Background and Aim:  Previous studies have shown an association of variants in trypsin‐associated genes, such as cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type‐1 (SPINK1) with pancreatitis. However, whether these genetic variants are associated with acute pancreatitis (AP) remains largely unknown, especially when the first attack is separated from recurrent attacks.

Methods:  A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the −2518G > A variant in the monocyte chemoattractant protein‐1 gene by polymerase chain reaction–restriction enzyme digestion and direct sequencing.

Results:  Patients with recurrent attacks were younger. The proportions of biliary pancreatitis and severe cases were lower, and that of idiopathic pancreatitis was higher in patients with a sentinel attack than in those with recurrent attacks. The frequencies of the genetic variants examined did not differ between controls and patients with sentinel pancreatitis. The frequencies of the PRSS1 p.R122H mutation, SPINK1 p.N34S variant, and PRSS3 p.E32del variant, but not other genetic variants, were higher in patients with recurrent attacks than in controls or those with a sentinel attack.

Conclusions:  The PRSS1 p.R122H mutation, SPINK1 p.N34S, and PRSS3 p.E32del variants were associated with recurrent, but not sentinel AP. The genetic background could possibly be different between sentinel and recurrent AP.
Management of asymptomatic hyperuricaemia in patients with chronic kidney disease by Japanese nephrologists: A questionnaire survey
Authors: NAKAYA IZAYA , NAMIKOSHI TAMEHACHI , TSURUTA YUKI , NAKATA TAKESHI , SHIBAGAKI YUGO , ONISHI YOSHIHIRO , FUKUHARA SHUNICHI
Published: February 2011

Aim:  Hyperuricaemia is associated with chronic kidney disease (CKD) progression and cardiovascular events (CVE). In a US study, only 4% of rheumatologists initiated urate‐lowering therapy in patients with asymptomatic hyperuricaemia (AHU). The present study aimed to clarify how Japanese board‐certified nephrologists manage AHU in CKD patients.

Methods:  Questionnaires on management of AHU in CKD stage 3 or more were mailed to 1500 Japanese board‐certified nephrologists, excluding paediatricians and urologists, randomly selected from the directory of the Japanese Society of Nephrology (n = 2976).

Results:  Five hundred and ninety‐five nephrologists (40%) responded. Most nephrologists (84–89%) recommended that AHU in patients in CKD stages 3–5 should be treated, but fewer nephrologists (63%) recommended that AHU in patients of CKD stage 5D should be treated. The serum urate level to start urate‐lowering therapy and the target serum urate level to be achieved (mg/dL) were 8.2 ± 0.9 and 6.9 ± 0.9, 8.4 ± 0.9 and 7.0 ± 1.0, 8.6 ± 1.0 and 7.3 ± 1.1, and 9.1 ± 1.2 and 7.8 ± 1.3 at stages 3, 4, 5 and 5D, respectively. The most frequently used maximal dosage of allopurinol was 100 mg/day at each stage. Benzbromarone was used in 52% of patients at stage 3, but only in 29%, 13% and 5% of patients at stages 4, 5 and 5D, respectively. The most important reasons to treat AHU at CKD stages 3–5 were prevention of CKD progression (45%), CVE (33%), gout (18%) and urolithiasis (3%).

Conclusion:  Most Japanese nephrologists treat AHU in pre‐dialysis CKD with an aim to prevent CKD progression or CVE mainly by allopurinol.
Renoprotective efficacy of valsartan in chronic non‐diabetic proteinuric nephropathies with renin–angiotensin system gene polymorphisms
Authors: LEE YU‐JI , JANG HYE RYOUN , KIM SEONG GYUN , CHAE DONG‐WAN , DO JUN‐YOUNG , LEE JUNG EUN , HUH WOOSEONG , KIM DAE JOONG , OH HA YOUNG , KIM YOON‐GOO
Published: February 2011

Aim:  The renoprotective effects of angiotensin receptor blockers vary considerably among individuals. We investigated the renoprotective effects of valsartan according to polymorphisms of the renin–angiotensin system and transforming growth factor‐b1 (TGFB1) genes in patients with chronic non‐diabetic proteinuric nephropathies.

Methods:  Two hundred and thirty‐nine non‐diabetic patients with proteinuria of at least 1 g/day were enrolled. Patients received 80 mg of valsartan daily, followed by 160 mg/day after 6 weeks. The follow‐up period was 18 months. The status of the angiotensin‐converting enzyme (ACE) insertion/deletion, angiotensinogen (AGT) M235T, type 1 angiotensin II receptor (ATR1) A1166C, and TGFB1 C509 and T869C polymorphisms was determined in 162 patients.

Results:  Valsartan treatment caused a significant reduction in proteinuria from baseline throughout the study in patients with each genotype of the ACE, AGT and TGFB1 genes. However, patients with the ATR1 AC genotype had no significant reduction in proteinuria from baseline throughout the study course. The median reductions in proteinuria after 6 months were 45.7% and 10.8% in the patients with the ATR1 AA and AC genotypes, respectively (P = 0.034). The annual change in the estimated glomerular filtration rate did not differ significantly among the genotypes for each gene. On multiple regression analysis, the change in proteinuria after 6 months of treatment was independently associated with the ATR1 genotype and the change in blood pressure (P = 0.005 and 0.019, respectively).

Conclusion:  Valsartan treatment significantly reduced the blood pressure and urinary protein excretion of patients with chronic non‐diabetic proteinuric nephropathies. Interindividual differences in the anti‐proteinuric effect of valsartan may be related partly to the ATR1 A1166C polymorphism.
Gene expression of TWEAK/Fn14 and IP‐10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis
Authors: LU JIANXIN , KWAN BONNIE CHING‐HA , LAI FERNAND MAC‐MOUNE , CHOI PAUL CHEUNG‐LUNG , TAM LAI‐SHAN , LI EDMUND KWOK‐MING , CHOW KAI‐MING , WANG GANG , LI PHILIP KAM‐TAO , SZETO CHEUK‐CHUN
Published: February 2011

Aim:  The role of the tumour necrosis factor‐like weak inducer of apoptosis (TWEAK)/Fn14 and interferon‐inducible protein (IP‐10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied.

Methods:  The mRNA expression of TWEAK, Fn14, IP‐10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls.

Results:  As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = −0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = −0.447; P = 0.029).

Conclusion:  In patients with lupus nephritis, there is an increase in intra‐renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra‐renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP‐10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis.
Prognostic value of dynamic soluble triggering receptor expressed on myeloid cells in bronchoalveolar lavage fluid of patients with ventilator‐associated pneumonia
Authors: WU CHIEN‐LIANG , LU YEN‐TA , KUNG YU‐CHUNG , LEE CHAO‐HSIEN , PENG MING‐JEN
Published: February 2011

Background and objective:  The aim of this study was to investigate the time course, and correlation with prognosis, of BAL fluid concentrations of soluble triggering receptor expressed on myeloid cells (sTREM‐1) in patients with ventilator‐associated pneumonia (VAP).

Methods:  The study included 35 patients with clinically diagnosed VAP, eight of whom were BAL fluid culture‐negative and 27 BAL fluid culture‐positive (16 survivors, 11 non‐survivors). sTREM‐1 levels were measured in BAL fluid of these mechanically ventilated patients, at the time of diagnosis, on days 4–5 and on days 7–9. The time course of this biomarker and its prognostic value for outcome in patients with culture‐positive VAP were assessed.

Results:  sTREM‐1 concentrations were significantly greater in culture‐positive VAP patients than in culture‐negative VAP patients. sTREM‐1 levels decreased significantly with time in surviving patients with culture‐positive VAP, but increased significantly with time in non‐survivors. In contrast, PaO2/fraction of inspired oxygen (FiO2) increased significantly with time in survivors and decreased significantly with time in non‐survivors. At a cut‐off value of −10 pg/mL 7–9 days after initial diagnosis, sTREM levels had a sensitivity of 90% and a specificity of 87.5% for predicting mortality.

Conclusions:  sTREM‐1 concentrations in BAL fluid are of potential prognostic value in patients with VAP.
Split stoma in resectional surgery of high‐risk patients with ileocolonic Crohn’s disease
Authors: Myrelid P. , Söderholm J. D. , Olaison G. , Sjödahl R. , Andersson P.
Published: February 2011

Aim  The aim of this retrospective study of ileocolonic resection in patients with Crohn’s disease was to compare the outcome of primary anastomosis with that of split stoma and delayed anastomosis in a high‐risk setting.

Method  From 1995 to 2006, 132 patients had 146 operations for ileocolonic Crohn’s disease. Preoperative data, including risk factors for complications, were obtained from a prospectively registered database. Operations on patients who had two or more preoperative risk factors (n = 76) were considered to be high‐risk operations and formed the main study. Primary outcome variables were postoperative anastomotic complications and the alteration in the number of preoperative risk factors achieved by a delayed anastomosis. Secondary outcome was time in hospital and the number of operations performed.

Results  Early anastomotic complications were diagnosed in 19% (11/57) of patients receiving a primary anastomosis compared with 0% (0/19) of patients after a delayed anastomosis (P = 0.038). The mean number of risk factors in the split stoma group was 3.5 at the time of resection and 0.2 when the split stoma was reversed (P < 0.0001). The total number of operations was 1.9 ± 1.5 (mean ± SD) after a primary anastomosis and 2.0 ± 0.2 after a split stoma (P = 0.70). Total in‐hospital time for all operations was 20.9 ± 35.6 days after a primary anastomosis and 17.8 ± 10.4 days after a delayed anastomosis (P = 0.74).

Conclusion  Delayed anastomosis after ileocolonic resection in high‐risk Crohn’s disease patients was associated with a reduction in the number of preoperative risk factors and fewer anastomotic complications. Hospital stay and number of operations were similar after delayed and primary anastomosis in high‐risk patients.
People living with diabetes resident in nursing homes—assessing levels of disability and nursing needs
Authors: Gadsby R. , Barker P. , Sinclair A.
Published: February 2011

Diabet. Med. 28, 778–780 (2011)

Aims  To describe the degree of disability and nursing need of people living with diabetes resident in nursing homes in one Primary Care Trust in the UK.

Methods  A retrospective case notes review of 75 people with known diabetes who were resident in the 11 nursing homes in Coventry Teaching Primary Care Trust.

Results  Very significant levels of disability and nursing need were documented in areas of continence, feeding, mobility and communication. Each individual had a mean of four co‐morbidities (range 1–8), excluding diabetes. Using the definition of terminal illness based on a negative answer to the question ‘would I be surprised if my patient were to die in the next 12 months’ it is likely that the majority of individuals described in this study would be classified as being terminally ill.

Conclusion  Using four practical clinical measures, this study has shown very significant levels of disability and nursing care need in this population of mainly elderly people resident in nursing homes in Coventry. In addition, it has demonstrated that a large proportion of nursing home residents with diabetes can be considered to be in the terminal phase of life, a period where many other factors interplay in how care should be delivered and what outcomes are appropriate. In fact, residents in this category may well be candidates for a considered withdrawal of treatments, but not of care.
PRIMITIVE CAUSAL RELATIONS AND THE PAIRING PROBLEM
Authors: Audi Paul
Published: February 2011

There is no doubt that spatial relations aid us in pairing up causes and effects. But when we consider the possibility of qualitatively indiscernible things, it might seem that spatial relations are more than a mere aid – they might seem positively required. The belief that spatial relations are required for causal relations is behind an important objection to Cartesian Dualism, the pairing problem. I argue that the Cartesian can answer this objection by appeal to the possibility of primitive causal relations, a possibility I defend. This topic is of importance beyond the philosophy of mind; the possibility that causal relations might sometimes hold brutely is of general metaphysical importance. I close with a discussion of what Cartesians should say about embodiment, and how that bears on issues of mental causation.
APOLOGIZING WITHOUT REGRET
Authors: Barnum‐Roberts Brooke Natalie
Published: February 2011

A common belief about the nature of agent regret is that regretting some event E is closely linked to being sorry for the occurrence of E. Or more specifically, that if one is sorry for E then she must regret E. I will call this ‘the sorry‐regret hypothesis’. My contention is that one may be sorry for some action but not regret it. I take the rejection of this ‘truism’ to be a positive development. I offer two lines of argument for rejecting the sorry‐regret hypothesis. One line of argument is based on counterexamples. The second attacks the validity of a reconstructed argument for the sorry‐regret hypothesis. It is desirable to reject the sorry‐regret hypothesis since there is a component of regret that many will not wish to be saddled with as a condition of apologizing. To regret an act, one must wish that she had not performed that act. Since a person is the person she is (speaking loosely) because of the actions she has performed, for many actions, if one regrets an action, then she wishes that she were a different person. This is a worrisome consequence.
THE PROBLEM OF HEAVEN
Authors: Ribeiro Brian
Published: February 2011

An argument against the rationality of desiring to go to heaven might be put in the form of a trilemma: (1) any state of being that both lasts eternally and preserves me as the person I am would be hellish and therefore would not be a state of being that I could have any reason to desire; (2) any state of being that lasts eternally and yet fails to preserve my personhood by turning me into a non‐person would not be a state of being that I (qua person that I am) could have any reason to desire; and (3) any state of being that lasts eternally and yet fails to preserve my personhood by turning me into some other person would not be a state of being that I (qua person that I am) could have any reason to desire. This paper offers defenses of each of the three horns of this trilemma and concludes that there is no rationally compelling reason for any human being to desire to go to heaven.
VALUES, DESIRES, AND LOVE: REFLECTIONS ON WOLLHEIM'S MORAL PSYCHOLOGY
Authors: Wong Ching‐wa
Published: February 2011

In The Thread of Life, Richard Wollheim argues that a person's sense of value is grounded in the power of love to generate certain favourable perceptions of an object. Following from his view is a psychoanalytic conception of valuing as constituted by the imaginative force of phantasy, rather than rational deliberation. In this paper, I shall defend this conception with a view to explaining the relation between values and desires. I suggest that valuing qua phantasy‐making can ‘tune up’ a person's desires to fit his perception of the good. Such power of phantasy is to be contrasted with various types of motivational failure in moral imagination. Finally, I argue that ‘effective valuing’, which makes us capable of desiring what we perceive to be good, requires an affective kind of imagination which assures us that we have the ability to love and to be loved.
SELF‐OWNERSHIP AND THE STATE: A DEMOCRATIC CRITIQUE
Authors: Ypi Lea
Published: February 2011

Libertarians often invoke the principle of self‐ownership to discredit distributive interventions authorized by the more‐than‐minimal state. But if one takes a democratic approach to the justification of ownership claims, including claims of ownership over oneself, the validity of the self‐ownership principle is theoretically inseparable from the normative justification of the state. Since the idea of the state is essential to the very assertion (not just the positive enforcement) of the principle of self‐ownership, invoking the principle to discredit a distribution of ownership authorized by the state commits libertarians also to weakening that principle's validity. Put differently, appealing to the self‐ownership principle to circumscribe the state's power to distribute property is problematic when the state is necessary to assert the validity of that principle. This is because anytime the self‐ownership principle is used to undermine a state‐based distribution of property it is also implicitly eroding the ground for asserting its own validity.1
VISUALISATION OF SOCIO‐SPATIAL ISOLATION BASED ON HUMAN ACTIVITY PATTERNS AND SOCIAL NETWORKS IN SPACE‐TIME
Authors: LEE JAE YONG , KWAN MEI‐PO
Published: February 2011

Few previous studies of socio‐spatial isolation have explored both its spatial and temporal dimensions. This study proposes and implemented four visual methods for analysing socio‐spatial isolation using graphic representation of people's social networks and activity patterns in space and time: 3D space‐time paths, time windows, 3D activity density surfaces, and ring‐based visualisation of social networks. These visualisations utilise both activity‐travel data and social network information. The data used were collected through a specially designed activity‐travel diary survey with a sample of Koreans in the Columbus metropolitan area in Ohio (USA). The results show that these visualisations can considerably enhance our understanding of the relationships between people's activities in space‐time and their social interactions. Combining social network analysis with activity pattern analysis can lead to a better understanding of socio‐spatial isolation.
Mixture Modelling as an Exploratory Framework for Genotype–Trait Associations
Authors: Au Kinman , Lin Rongheng , Foulkes Andrea S.
Published: February 2011

We propose a mixture modelling framework for both identifying and exploring the nature of genotype–trait associations. This framework extends the classical mixed effects modelling approach for this setting by incorporating a Gaussian mixture distribution for random genotype effects. The primary advantages of this paradigm over existing approaches include that the mixture modelling framework addresses the degrees-of-freedom challenge that is inherent in application of the usual fixed effects analysis of covariance, relaxes the restrictive single normal distribution assumption of the classical mixed effects models and offers an exploratory framework for discovery of underlying structure across multiple genetic loci. An application to data arising from a study of antiretroviral-associated dyslipidaemia in human immunodeficiency virus infection is presented. Extensive simulations studies are also implemented to investigate the performance of this approach.
Interaction Trees: Exploring the Differential Effects of an Intervention Programme for Breast Cancer Survivors
Authors: Su Xiaogang , Meneses Karen , McNees Patrick , Johnson Wesley O.
Published: February 2011

The breast cancer education intervention (BCEI) is a tailored psychoeducational intervention programme aiming to improve the quality of life of breast cancer survivors. Borrowing the idea of recursive partitioning and following the convention of classification and regression trees, an exploratory procedure, termed interaction trees, is proposed to understand better the differential effects of the BCEI on longitudinal quality-of-life data. The resultant tree model identifies several objectively defined subgroups: in some groups the BCEI is quite effective whereas in others it may not be. Based on the final tree structure, a permutation test is used to assess the overall treatment-by-covariate interaction. In addition, a variable importance ranking feature is facilitated via random forests of interaction trees to help to determine important effect modifiers of the BCEI.