bluuebunny/crossref_metadata_2025 huggingface dataset:
Photoluminescence enhancement of Er-doped silica containing Ge nanoclusters
Authors: Guzman J. , Shin S. J. , Liao C. Y. , Yuan C. W. , Stone P. R. , Dubón O. D. , Yu K. M. , Beeman J. W. , Watanabe M. , Ager J. W. , Chrzan D. C. , Haller E. E.
Published: November 2009

The photoluminescence (PL) of Er-doped silica films containing Ge nanoclusters synthesized by ion implantation was investigated. The area of the 1540 nm Er3+ PL peak was enhanced by up to a factor of 200 by the addition of Ge nanoclusters. The PL enhancement was found to be proportional to the concentration of Ge atoms. Control experiments with argon ion implantation were used to show that the enhancement is due to the presence of Ge and not radiation damage. Furthermore, the Er3+ PL was found to be strongly influenced by the postgrowth annealing and the crystallinity of the Ge nanoclusters.
Fully bendable polymer light emitting devices with carbon nanotubes as cathode and anode
Authors: Yu Zhibin , Hu Liangbing , Liu Zhitian , Sun Mingliang , Wang Meiliang , Grüner George , Pei Qibing
Published: November 2009

Polymer light emitting devices were fabricated by roll lamination using single-walled carbon nanotubes as both anode and cathode. The devices exhibited a low turn-on voltage of 3.8 V, high brightness of 1400 cd/m2 at 10 V and maximum efficiency of 2.2 cd/A at 480 cd/m2. The devices are also highly transparent and exhibited very high flexibility. No failure was observed after bending the devices down to 2.5 mm radius.
Theoretical Investigation of Square-Planar MXe42+ (M = Cu, Ag, Au) Cations
Authors: Zhang PingXia , Zhao YongFang , Song XiuDan , Zhang GuoHua , Wang Yang
Published: November 2009

The structures, stabilities, and bonding mechanism of the square-planar doubly charged MXe42+ (M = Cu, Ag, Au) cations have been investigated at the UB3LYP and UMP2 theoretical levels. At the best theoretical estimate, the M–Xe bond lengths are calculated to be 266.2, 273.6, and 273.8 pm, and the corresponding binding energies with respect to M2+ and four xenon atoms are 771.49, 820.57, and 908.47 kJ mol–1, respectively, along the series Cu – Ag – Au. Owing to an unusually high relativistic effect, gold evidently tends to be strongly bonded to the noble gas atoms in comparison with copper and silver. The electrostatic interactions play an important role in divalent noble-gas–noble-metal bonding. Apart from CuXe42+, the square-planar MXe42+ cations are stable enough to be prepared in experiments.
The synaptic proteins neurexins and neuroligins are widely expressed in the vascular system and contribute to its functions
Authors: Bottos Alessia , Destro Erika , Rissone Alberto , Graziano Stefania , Cordara Gabriele , Assenzio Barbara , Cera Maria Rosaria , Mascia Luciana , Bussolino Federico , Arese Marco
Published: November 2009

Unlike other neuronal counterparts, primary synaptic proteins are not known to be involved in vascular physiology. Here, we demonstrate that neurexins and neuroligins, which constitute large and complex families of fundamental players in synaptic activity, are produced and processed by endothelial and vascular smooth muscle cells throughout the vasculature. Moreover, they are dynamically regulated during vessel remodeling and form endogenous complexes in large vessels as well as in the brain. We used the chicken chorioallantoic membrane as a system to pursue functional studies and demonstrate that a monoclonal recombinant antibody against β-neurexin inhibits angiogenesis, whereas exogenous neuroligin has a role in promoting angiogenesis. Finally, as an insight into the mechanism of action of β-neurexin, we show that the anti-β-neurexin antibody influences vessel tone in isolated chicken arteries. Our finding strongly supports the idea that even the most complex and plastic events taking place in the nervous system (i.e., synaptic activity) share molecular cues with the vascular system.
Regulation of hematopoiesis by the K63-specific ubiquitin-conjugating enzyme Ubc13
Authors: Wu Xuefeng , Yamamoto Masahiro , Akira Shizuo , Sun Shao-Cong
Published: November 2009

The ubiquitin-conjugating enzyme Ubc13 mediates lysine-63-specific protein ubiquitination involved in signal transduction by immune receptors; however, the in vivo physiological functions of Ubc13 remain incompletely understood. Using Ubc13 conditional knockout mice, we show that somatic deletion of the Ubc13 gene causes severe loss of multi lineages of immune cells, which is associated with profound atrophy of the thymus and bone marrow, as well as lethality of the mice. Ubc13 has a cell-intrinsic function in mediating hematopoiesis and is essential for the survival and accumulation of hematopoietic stem cells in the bone marrow. Interestingly, loss of Ubc13 results in accumulation of β-catenin and hyperexpression of Wnt target genes, a condition known to cause impaired hematopoiesis. These results establish Ubc13 as a crucial regulator of hematopoiesis and suggest a role for Ubc13 in the control of Wnt signaling in hematopoietic stem cells.
Clonal expansions in ulcerative colitis identify patients with neoplasia
Authors: Salk Jesse J. , Salipante Stephen J. , Risques Rosa Ana , Crispin David A. , Li Lin , Bronner Mary P. , Brentnall Teresa A. , Rabinovitch Peter S. , Horwitz Marshall S. , Loeb Lawrence A.
Published: November 2009

Chronic inflammation predisposes to a variety of human cancers. Affected tissues slowly accumulate mutations, some of which affect growth regulation and drive successive waves of clonal evolution, whereas a far greater number are functionally neutral and serve only to passively mark expanding clones. Ulcerative colitis (UC) is an inflammatory bowel disease, in which up to 10% of patients eventually develop colon cancer. Here we have mapped mutations in hypermutable intergenic and intronic polyguanine tracts in patients with UC to delineate the extent of clonal expansions associated with carcinogenesis. We genotyped colon biopsies for length altering mutations at 28 different polyguanine markers. In eight patients without neoplasia, we detected only two mutations in a single individual from among 37 total biopsies. In contrast, for 11 UC patients with neoplasia elsewhere in the colon, we identified 63 mutations in 51 nondysplastic biopsies, and every patient possessed at least one mutant clone. A subset of clones were large and extended over many square centimeters of colon. Of these, some occurred as isolated populations in nondysplastic tissue, considerably distant from neoplastic lesions. Other large clones included regions of cancer, suggesting that the tumor arose within a preexisting clonal field. Our results demonstrate that neutral mutations in polyguanine tracts serve as a unique tool for identifying fields of clonal expansions, which may prove clinically useful for distinguishing a subset of UC patients who are at risk for developing cancer.
A progeria mutation reveals functions for lamin A in nuclear assembly, architecture, and chromosome organization
Authors: Taimen Pekka , Pfleghaar Katrin , Shimi Takeshi , Möller Dorothee , Ben-Harush Kfir , Erdos Michael R. , Adam Stephen A. , Herrmann Harald , Medalia Ohad , Collins Francis S. , Goldman Anne E. , Goldman Robert D.
Published: November 2009

Numerous mutations in the human A-type lamin gene (LMNA) cause the premature aging disease, progeria. Some of these are located in the α-helical central rod domain required for the polymerization of the nuclear lamins into higher order structures. Patient cells with a mutation in this domain, 433G>A (E145K) show severely lobulated nuclei, a separation of the A- and B-type lamins, alterations in pericentric heterochromatin, abnormally clustered centromeres, and mislocalized telomeres. The induction of lobulations and the clustering of centromeres originate during postmitotic nuclear assembly in daughter cells and this early G1 configuration of chromosomes is retained throughout interphase. In vitro analyses of E145K-lamin A show severe defects in the assembly of protofilaments into higher order lamin structures. The results show that this central rod domain mutation affects nuclear architecture in a fashion distinctly different from the changes found in the most common form of progeria caused by the expression of LAΔ50/progerin. The study also emphasizes the importance of lamins in nuclear assembly and chromatin organization.
Clinical trials update from the European Society of Cardiology Meeting 2009: AAA, RELY, PROTECT, ACTIVE‐I, European CRT survey, German pre‐SCD II registry, and MADIT‐CRT
Authors: Cleland John G.F. , Coletta Alison P. , Yassin Ashraf , Buga Laszlo , Torabi Azam , Clark Andrew L.
Published: November 2009

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the European Society of Cardiology held in Barcelona in 2009. The AAA study does not support the routine use of aspirin for the prevention of vascular events in patients with asymptomatic atherosclerosis. RELY suggests that dabigatran may be more effective than warfarin for the prevention of stroke in patients with atrial fibrillation. Rolofylline was not superior to placebo in improving outcomes in patients with acute heart failure enrolled in the PROTECT study, but dyspnoea was improved. Data from ACTIVE‐I suggest that irbesartan does not provide additional therapeutic benefit in patients with atrial fibrillation who are well controlled on current therapy. The European cardiac resynchronization therapy (CRT) survey provides interesting epidemiological data on current CRT device usage. The German pre‐SCD II registry identified a low prevalence of patients with a reduced ejection fraction following myocardial infarction. Implantation of CRT‐D rather than an implantable cardioverter defibrillator in patients with mild heart failure and QRS ≥130 ms reduced the risk of hospitalization for heart failure in MADIT‐CRT; mortality was similarly low with each device.
Mitigating Absenteeism in Hospital Workers During a Pandemic
Authors: Garrett Andrew L. , Park Yoon Soo , Redlener Irwin
Published: November 2009

Objectives: An influenza pandemic, as with any disaster involving contagion or contamination, has the potential to influence the number of health care employees who will report for duty. Our project assessed the uptake of proposed interventions to mitigate absenteeism in hospital workers during a pandemic.

Methods: Focus groups were followed by an Internet-based survey of a convenience sample frame of 17,000 hospital workers across 5 large urban facilities. Employees were asked to select their top barrier to reporting for duty and to score their willingness to work before and after a series of interventions were offered to mitigate it.

Results: Overall, 2864 responses were analyzed. Safety concerns were the most frequently cited top barrier to reporting for work, followed by issues of dependent care and transportation. Significant increases in employee willingness to work scores were observed from mitigation strategies that included preferential access to antiviral medication or personal protective equipment for the employee as well as their immediate family.

Conclusions: The knowledge base on workforce absenteeism during disasters is growing, although in general this issue is underrepresented in emergency planning efforts. Our data suggest that a mitigation strategy that includes options for preferential access to either antiviral therapy, protective equipment, or both for the employee as well as his or her immediate family will have the greatest impact. These findings likely have import for other disasters involving contamination or contagion, and in critical infrastructure sectors beyond health care. (Disaster Med Public Health Preparedness. 2009;3(Suppl 2):S141–S147)
Vaginal colonization and activity of the probiotic bacterium Lactobacillus fermentum L23 in a murine model of vaginal tract infection
Authors: Pascual Liliana , Ruiz Francisco , Giordano Walter , Barberis Isabel Lucila
Published: November 2009

A strain of Lactobacillus, identified as Lactobacillus fermentum L23, was selected from among 100 strains isolated from vaginal swabs of healthy, non-pregnant, pre-menopausal women. L. fermentum L23 was chosen on the basis of its bacteriocinogenic ability and its properties relevant to colonization, i.e. self-aggregation, adherence to vaginal epithelial cells and co-aggregation with bacterial pathogens. The antimicrobial preventative and curative effects produced by the probiotic L. fermentum L23 administered locally against Escherichia coli in a murine vaginal tract infection model were studied. One dose of the human strain L23 containing 108 c.f.u. ml−1 colonized and persisted in the vaginal tract of the female BALB/c mice for 5 days. Infection with the pathogen at 106 c.f.u. ml−1 in the vaginal tract was maintained for more than 7 days. A single dose of L23 administered 24 h pre-infection inhibited E. coli growth on day 3 post-infection, showing the preventative effect displayed by this Lactobacillus strain. Treatment with L. fermentum L23 during the post-infection period showed complete inhibition of pathogen growth from day 5. Thus, this in vivo study indicated that the probiotic bacterium L. fermentum L23 produced both preventative and curative effects on E. coli growth. The beneficial properties and the production of antimicrobial metabolites may act in situ to inhibit a pathogenic micro-organism within the vaginal environment. Strain L23 could be a good natural alternative to other therapies used for genital infections.
Maternal and neonatal sepsis caused by Haemophilus influenzae type d
Authors: Warren S. , Tristram S. , Bradbury R. S.
Published: November 2009

A 29-year-old pregnant woman was admitted to hospital with signs of sepsis and threatened pre-term labour. The premature neonate also showed signs of sepsis.Haemophilus influenzaebiotype III was cultured from a midstream urine sample taken from the mother, maternal placental swabs and neonatal blood cultures. The placental and neonatal isolates were both found to be serotype d by PCR, and were indistinguishable by PFGE.
Restricted cytosolic growth of Francisella tularensis subsp. tularensis by IFN-γ activation of macrophages
Authors: Edwards Jessica A. , Rockx-Brouwer Dedeke , Nair Vinod , Celli Jean
Published: November 2009

The intracellular bacteriumFrancisella tularensisensures its survival and proliferation within phagocytes of the infected host through phagosomal escape and cytosolic replication, to cause the disease tularemia. The cytokine interferon-γ(IFN-γ) is important in controlling primary infectionsin vivo, andin vitrointracellular proliferation ofFrancisellain macrophages, but its actual effects on the intracellular cycle of the bacterium are ambiguous. Here, we have performed an extensive analysis of the intracellular fate of the virulentF. tularensissubsp.tularensisstrain Schu S4 in primary IFN-γ-activated murine and human macrophages to understand how this cytokine controlsFrancisellaproliferation. In both murine bone marrow-derived macrophages (muBMMs) and human blood monocyte-derived macrophages (MDMs), IFN-γcontrolled bacterial proliferation. Schu S4 growth inhibition was not due to a defect in phagosomal escape, since bacteria disrupted their phagosomes with indistinguishable kinetics in both muBMMs and MDMs, regardless of their activation state. Rather, IFN-γactivation restricted cytosolic replication of Schu S4 in a manner independent of reactive oxygen or nitrogen species. Hence, IFN-γinduces phagocyte NADPH oxidase Phox- and inducible nitric oxide synthase (iNOS)-independent cytosolic effector mechanisms that restrict growth of virulentFrancisellain macrophages.
Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination
Authors: Fei Teng , Xia Kai , Li Zhongwei , Zhou Bing , Zhu Shanshan , Chen Hua , Zhang Jianping , Chen Zhang , Xiao Huasheng , Han Jing-Dong J. , Chen Ye-Guang
Published: November 2009

Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.
Genetic Resources for Maize Cell Wall Biology
Authors: Penning Bryan W. , Hunter Charles T. , Tayengwa Reuben , Eveland Andrea L. , Dugard Christopher K. , Olek Anna T. , Vermerris Wilfred , Koch Karen E. , McCarty Donald R. , Davis Mark F. , Thomas Steven R. , McCann Maureen C. , Carpita Nicholas C.
Published: November 2009

Grass species represent a major source of food, feed, and fiber crops and potential feedstocks for biofuel production. Most of the biomass is contributed by cell walls that are distinct in composition from all other flowering plants. Identifying cell wall-related genes and their functions underpins a fundamental understanding of growth and development in these species. Toward this goal, we are building a knowledge base of the maize (Zea mays) genes involved in cell wall biology, their expression profiles, and the phenotypic consequences of mutation. Over 750 maize genes were annotated and assembled into gene families predicted to function in cell wall biogenesis. Comparative genomics of maize, rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana) sequences reveal differences in gene family structure between grass species and a reference eudicot species. Analysis of transcript profile data for cell wall genes in developing maize ovaries revealed that expression within families differed by up to 100-fold. When transcriptional analyses of developing ovaries before pollination from Arabidopsis, rice, and maize were contrasted, distinct sets of cell wall genes were expressed in grasses. These differences in gene family structure and expression between Arabidopsis and the grasses underscore the requirement for a grass-specific genetic model for functional analyses. A UniformMu population proved to be an important resource in both forward- and reverse-genetics approaches to identify hundreds of mutants in cell wall genes. A forward screen of field-grown lines by near-infrared spectroscopic screen of mature leaves yielded several dozen lines with heritable spectroscopic phenotypes. Pyrolysis-molecular beam mass spectrometry confirmed that several nir mutants had altered carbohydrate-lignin compositions.
Patients with sporadic duodenal adenoma are a high‐risk group for advanced colorectal neoplasia: results of a case–control study
Authors: PEQUIN P. , MANFREDI S. , QUENTIN V. , HERESBACH D. , BOYER J. , SIPROUDHIS L. , BRETAGNE J.‐F.
Published: November 2009

Aim To evaluate colorectal cancer risk among patients with sporadic duodenal neoplasia using a case–control protocol.

Methods Cases were 35 patients referred for the management of sporadic duodenal adenoma and who underwent colonoscopy. Colonoscopy findings among cases were compared with those from a control group matched for age and sex (two controls per case) without duodenal adenoma. Colonoscopy findings were categorized as adenoma, advanced adenoma, cancer or advanced neoplasia. The two groups were compared using the chi‐squared test. Odds ratio and 95% confidence intervals were calculated.

Results Colorectal adenoma was present in 31% of cases vs. 24% of controls, advanced neoplasia in 29% vs. 4%, advanced adenoma in 23% vs. 3% and adenocarcinoma in 6% vs. 1%. The relative risks of advanced colorectal adenoma and advanced colorectal neoplasia in cases were 10.1 (95% CI: 1.8–100.1, P = 0.003) and 8.9 (95% CI: 2.1–53.3, P = 0.001), respectively.

Conclusions The relative risk of advanced colorectal adenoma and advanced neoplasia in cases was nine‐ to 10‐fold that among controls. Patients with sporadic duodenal adenoma represent a high‐risk group for advanced colorectal neoplasia and should therefore undergo complete colonoscopy.
MMX Multi Matrix System® mesalazine for the induction of remission in patients with mild‐to‐moderate ulcerative colitis: a combined analysis of two randomized, double‐blind, placebo‐controlled trials
Authors: SANDBORN W. J. , KAMM M. A. , LICHTENSTEIN G. R. , LYNE A. , BUTLER T. , JOSEPH R. E.
Published: November 2009

Background  MMX™ mesalazine [LIALDA™ (US), MEZAVANT™ XL (UK and Ireland) MEZAVANT™ (elsewhere)] utilizes MMX Multi Matrix System® (MMX) technology which delivers mesalazine throughout the colon. Two phase III studies have already evaluated MMX mesalazine in patients with active, mild‐to‐moderate ulcerative colitis.

Aim  To provide more precise estimates of the efficacy of MMX mesalazine over placebo by combining the patient populations from the two phase III studies.

Methods  Combined data from two 8‐week, double‐blind, placebo‐controlled trials were analyzed. Patients randomized to MMX mesalazine 2.4 g/day (once daily or 1.2 g twice daily), 4.8 g/day (once daily) or placebo were reviewed. The primary end point was clinical and endoscopic remission (modified Ulcerative Colitis‐Disease Activity Index of ≤1 calculated as: rectal bleeding and stool frequency scores of 0, a combined Physician’s Global Assessment and sigmoidoscopy score of ≤1, no mucosal friability and a ≥1‐point reduction in sigmoidoscopy score from week 0).

Results  Data from 517 patients were analysed. 8‐week remission rates were 37.2% and 35.1% in the MMX mesalazine 2.4 g/day and 4.8 g/day groups, vs. 17.5% on placebo (P < 0.001, both comparisons). 8‐week complete mucosal healing rates were 32% in both MMX mesalazine groups compared with 16% on placebo. Adverse event frequency was similar in all groups.

Conclusion  MMX mesalazine is effective and generally well tolerated for inducing clinical and endoscopic remission of active, mild‐to‐moderate ulcerative colitis.
Review article: nutrition, obesity and colorectal cancer
Authors: JOHNSON I. T. , LUND E. K.
Published: November 2009

Background  The age‐adjusted incidence of colorectal cancer is higher in prosperous industrialized countries than elsewhere. Dietary factors may account for 75% of sporadic colorectal cancer in the west, but the mechanisms remain obscure.

Aim  To review evidence for the effects of overweight and obesity, physical activity and specific dietary components on colorectal neoplasia.

Methods  English language papers cited on MEDLINE, obtained using search terms related to colorectal cancer, physical activity and body mass and specific food components were reviewed.

Results  There is evidence for adverse effects of overweight and obesity and protective effects of high physical activity against colon, but not for rectal cancer. These effects may reflect metabolic stress and chronic low‐grade inflammation. There are also modest adverse effects of red and processed meat. There is evidence for protective effects of dietary fibre, but for fruits and vegetables the evidence remains weak and inconclusive. There is some evidence for protective effects of n‐3 polyunsaturated fatty acids from fish, some micronutrients and possibly phytochemicals. The effects of many dietary constituents may depend upon genetic polymorphisms affecting a variety of genes.

Conclusion  Further research should focus particularly on the effects of insulin‐resistance, impaired glucose tolerance and chronic low‐grade inflammation on the colonic mucosa.
The burden of constipation on quality of life: results of a multinational survey
Authors: WALD A. , SCARPIGNATO C. , KAMM M. A , MUELLER‐LISSNER S. , HELFRICH I. , SCHUIJT C. , BUBECK J. , LIMONI C. , PETRINI O.
Published: November 2009

Background The impact of constipation on quality of life (QoL) may vary in different cultural or national settings.

Aim We studied QoL in a multinational survey to compare different social and demographic groups with and without constipation (defined according to Rome III criteria) and to detect country‐specific differences among the groups studied.

Methods Health‐related QoL (HRQoL) was assessed with the Short Form 36 (SF‐36) questionnaire in 2870 subjects in France, Germany, Italy, UK, South Korea, Brazil and USA.

Results Respondents were mainly middle‐aged, married or living together and part‐ or full‐time employed. General health status, measured by the SF‐36 questionnaire, was significantly worse in the constipated vs. non‐constipated populations. Results were comparable in all countries. QoL scores correlated negatively with age. Constipated women reported more impaired HRQoL than constipated men. Brazilians were most affected by constipation as to their social functioning (35.8 constipated vs. 51.3 non‐constipated) and general health perception (29.4 constipated vs. 54.4 non‐constipated).

Conclusions There are significant differences in HRQoL between constipated and non‐constipated individuals and a significant, negative correlation between the number of symptoms and complaints and SF‐36 scores. The study detected a correlation of constipation with QoL and the influence of social and demographic factors on HRQoL in constipated people.
Estimation of lean body weight in older community‐dwelling men
Authors: Mitchell Sarah J. , Kirkpatrick Carl M. J. , Le Couteur David G. , Naganathan Vasi , Sambrook Philip N. , Seibel Markus J. , Blyth Fiona M. , Waite Louise M. , Handelsman David J. , Cumming Robert G. , Hilmer Sarah N.
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?

• Lean mass decreases with age while total body fat increases, leading to changes in the pharmacokinetics and pharmacodynamics of drugs.

• Dual‐energy X‐ray absorptiometry (DXA) is a useful reference method to measure lean body weight but may not be readily utilized clinically.

• Limited methods for measurement of lean body weight using easily obtainable participant characteristics, such as height and weight, have been validated for use in people aged ≥65 years.

WHAT THIS STUDY ADDS

• This study has shown that lean body weight can be estimated using three different equations from easily obtainable participant characteristics with results comparable to DXA‐derived estimates.

• These equations may be useful tools to estimate lean body weight in situations where DXA is not practical.

AIMS

Lean body weight (LBW) decreases with age while total body fat increases, altering drug pharmacokinetics. The aim of this study was to evaluate the ability of the LBW equation to predict dual‐energy X‐ray absorptiometry (DXA)‐derived fat free mass (FFMDXA) in older community‐dwelling males compared with that of two existing FFM equations: the Heitmann and Deurenberg equations.

METHODS

Data were obtained from 1655 older men enrolled in the Concord Health and Ageing in Men Project. The predictive performance of the LBW and FFM equations to predict FFMDXA accurately was assessed graphically using Bland–Altman plots and quantitatively for precision and bias using the method of Sheiner and Beal in all participants and in frailty and body mass index (BMI) subgroups.

RESULTS

The LBW and Heitmann equations consistently overestimated FFMDXA for all frailty and BMI subgroups with a mean difference [95% confidence interval (CI)] of 5.5 kg (−0.65, 11.63 kg) and 3.34 kg (−2.84, 9.64 kg), respectively. The Deurenberg equation overestimated FFMDXA for overweight participants but underestimated FFMDXA for not‐frail participants, with a mean difference (95% CI) of 1 kg (−7.23, 5.25 kg) for all participants.

CONCLUSION

LBW and FFM estimated using these equations give results comparable to DXA‐derived FFM. The LBW and Heitmann equations provide a more consistent estimate of FFMDXA in all frailty and BMI groups despite the Deurenberg equation having the smallest mean difference. Further studies to determine whether the LBW equation is a clinically useful substitute for weight when determining drug dose in older people appear warranted.
Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure
Authors: Orlando Rocco , De Martin Sara , Andrighetto Laura , Floreani Maura , Palatini Pietro
Published: November 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The selective serotonin reuptake inhibitor fluvoxamine is a first‐choice antidepressant agent for treatment of depression and anxiety disorders in elderly subjects and patients with cardiovascular diseases.

• Limited and conflicting data are available regarding age‐related modifications of fluvoxamine pharmacokinetics.

• No study has yet investigated the possible alterations of fluvoxamine pharmacokinetics in elderly patients with chronic heart failure (CHF).

WHAT THIS STUDY ADDS

• The oral disposition kinetics of fluvoxamine is significantly impaired in elderly subjects, mean oral clearance being halved with respect to young adults.

• In elderly patients with CHF, fluvoxamine pharmacokinetics is not altered with respect to age‐matched healthy subjects.

AIMS To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine.

METHODS A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h.

RESULTS With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 ± 19 vs. 15 ± 9 ng ml−1; difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration–time curve was almost three times higher [885 ± 560 vs. 304 ± 84 ng h ml−1; difference (95% CI) 581 (205, 957), P < 0.05]; half‐life was prolonged by 63% [21.1 ± 6.2 vs. 12.9 ± 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 ± 0.77 vs. 2.25 ± 0.66 l h−1 kg−1; difference (95% CI) −1.13 (−1.80, −0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=−0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects.

CONCLUSIONS Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF.
Does gastric acid suppression increase the risk of drug allergies?
Authors: Pickard C. , Sampson A. P.
Published: November 2009

Cite this as: C. Pickard and A. P. Sampson, Clinical & Experimental Allergy, 2010 (40) 362–364.
Langerhans cell histiocytosis in lymph nodes – cytomorphological diagnosis and pitfalls
Authors: Kakkar S. , Kapila K. , Verma K.
Published: November 2009

Background Langerhans cell histiocytosis (LCH) is a rare disorder of unknown aetiology that may present as a multisystem or unisystem disease. The Lymph nodes can be involved as part of disseminated disease, as a metastatic site draining a focus of LCH or may be a unisystem involvement. Paucity of literature on the cytomorphology of LCH in lymph nodes led us to undertake this study.

Materials and methods Nine cases with a confirmed histological diagnosis of LCH and a prior lymph node aspirate were retrieved over a 12 year period (1988–1999). Five more cases were reviewed where the cytological diagnosis of LCH was rendered on a background of clinical and radiological findings. Papanicolaou and May Grunwald–Giemsa‐stained smears were examined. S‐100 protein staining was available in four cases.

Results and conclusions Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. There were eleven males and three females; age ranged from five months to 27 years. The cytological diagnosis of LCH had been rendered in six, suspected in four and missed in four. Of the latter, two were reclassified as LCH on review, one as reactive lymphadenitis and in one a necrotising lesion was suspected. The pathognomonic ‘LCH cell’ was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in only six cases. In conclusion lymph node involvement by LCH can be identified on aspirates. However, LCH must be differentiated from dermatopathic lymphadenitis, sinus histiocytosis with massive lymphadenopathy and Hodgkin's disease.
Matrix metalloproteinases, IL‐8 and glutathione in the prognosis of workers exposed to chlorine
Authors: Maghni K. , Malo J.‐L. , L’Archevêque J. , Castellanos L. , Gautrin D.
Published: November 2009

To cite this article: Maghni K, Malo J‐L, L’Archevêque J, Castellanos L, Gautrin D. Matrix metalloproteinases, IL‐8 and glutathione in the prognosis of workers exposed to chlorine. Allergy 2010; 65: 722–730.

Background:  Workers exposed to chlorine may be at risk of deterioration in FEV1.

Methods:  A prospective study of 72 workers examined over a 5.8 ± 1.9 year period. A sample of induced sputum for cells and mediators was obtained in 69 subjects at baseline (Vb) and in 36 both at Vb and at follow‐up (Vf).

Results:  Sixty‐four workers (89%) experienced at least one accidental inhalation of chlorine in the interval. The mean decrease in FEV1 was 30 ml/year and thus was within normal limits. Among the analysed remodelling markers, the level of the MMP‐9‐TIMP‐1 complex, but not of free MMP‐9 and TIMP‐1, significantly diminished from Vb to Vf. We found significant correlations between neutrophils, IL‐8, MMP‐9 and MMP9‐TIMP‐1 complex at Vb and Vf. While levels of total glutathione, IL‐8, MMP9, TIMP‐1 and MMP9‐TIMP‐1 complex were highly correlated with each other at Vb, this was inconstant at Vf. Levels of MMP9‐TIMP1 complex and of TIMP1 at Vf were significantly lower in workers reporting chlorine puffs with mild acute respiratory symptoms between visits compared to those who had no, or asymptomatic inhalations (P = 0.03 and 0.02, respectively). The fall in FEV1 from Vb to Vf was significantly correlated with levels of glutathione at Vb. Cough between visits was associated with a decrease in FEV1 (P = 0.06).

Conclusion:  Although no accelerated loss in FEV1 was documented in these workers exposed to chlorine, subjects with a greater fall in FEV1 were more likely to report cough and have higher levels of total glutathione at Vb.
Evidence for the insufficient evaluation and undertreatment of chronic hepatitis B infection in a predominantly low‐income and immigrant population
Authors: Jung Chin W , Tan Jennifer , Tan Nelly , Kuo Melissa N , Ashok Ashwin , Eells Samantha J , Miller Loren G
Published: November 2009

Background and Aim:  Many physicians remain unaware of contemporary treatments for chronic hepatitis B (HBV) infection and do not treat their HBV‐infected patients or refer them for treatment. The aim of the present study was to determine the rates of laboratory evaluation and treatment of HBV infection in a predominantly low‐income and immigrant population.

Methods:  We identified adult patients who tested positive for hepatitis B surface antigen between 1 January 1994 and 30 April 2006. We reviewed patients' medical records to determine two outcomes: (i) receipt of pretreatment evaluation of HBV infection; and (ii) receipt of HBV treatment. We then examined clinical and demographic factors associated with these outcomes.

Results:  Twenty‐eight percent of 1231 HBV surface antigen‐positive patients received additional laboratory evaluation of their infection. In a multivariate analysis, receipt of a HBV evaluation was independently associated with (P < 0.05) female sex, longer duration of HBV infection, more visits to a gastroenterology clinic and less recent health‐care contact. Data on treatment were available for 56% of patients; among these, 16% received HBV treatment. In the multivariate analysis, receipt of HBV treatment was independently associated with (P < 0.05) HIV co‐infection, receipt of liver biopsy, testing for hepatitis B e antigen or HBV DNA, longer duration of HBV infection, more visits to a gastroenterology clinic and more recent health‐care contact. When excluding HIV‐infected patients, only 10% of patients received HBV treatment.

Conclusions:  After the diagnosis of HBV infection, few patients in our population received laboratory evaluation to determine eligibility for HBV treatment. Furthermore, only a small percentage received HBV treatment. Further research needs to be done to validate these findings in other populations and understand barriers to receiving HBV treatment.
Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients
Authors: Hiraoka Atsushi , Michitaka Kojiro , Horiike Norio , Hidaka Satoshi , Uehara Takahide , Ichikawa Soichi , Hasebe Aki , Miyamoto Yasunao , Ninomiya Tomoyuki , Sogabe Ichiro , Ishimaru Yoshihiro , Kawasaki Hideki , Koizumi Yohei , Hirooka Masashi , Yamashita Yoshimasa , Abe Masanori , Hiasa Yoichi , Matsuura Bunzo , Onji Morikazu
Published: November 2009

Background and Aim:  With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively.

Methods:  Two hundred six patients with HCC, who were within the Milan criteria, with low‐grade performance status (0 or 1) and a Child‐Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e‐HCC group; ≥ 75, n = 63) and non e‐HCC group (< 75, n = 143), and their clinical data and survival rates were compared.

Results:  Age and the level of protein induced by vitamin K absence or antagonist (PIVKA‐II) were higher in the e‐HCC group as compared with the non e‐HCC group (78.3 ± 3.2 vs 64.2 ± 7.5 years, 676.3 ± 2643.7 vs 142.4 ± 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child‐Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e‐HCC group: 82.5% and 49.7%, respectively; non e‐HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e‐HCC group.

Conclusions:  Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.
Prevalence, human leukocyte antigen typing and strategy for screening among Asian first‐degree relatives of children with celiac disease
Authors: Srivastava Anshu , Yachha Surender Kumar , Mathias Amrita , Parveen Farah , Poddar Ujjal , Agrawal Suraksha
Published: November 2009

Background and Aim:  Data on prevalence, human leukocyte antigen (HLA) typing and small bowel histology among first‐degree relatives of subjects with celiac disease (CD) is scarce. This prospective study evaluated the prevalence and role of HLA DQ2/8 testing in screening of first‐degree relatives of children with CD.

Methods:  Thirty confirmed children with CD and 91/94 first‐degree relatives (parents and siblings) were enrolled. HLA DQ2/8 testing was carried out in all index CD cases. Clinical evaluation with a questionnaire, total serum immunoglobulin A (IgA), human IgA‐tissue transglutaminase (IgA‐tTGA) and HLA DQ2/8 testing was carried out in all first‐degree relatives. Subjects who were positive for IgA‐tTGA were recommended endoscopic duodenal biopsy to document histological changes of CD.

Results:  Nine first‐degree relatives were positive for IgA‐tTGA, seven underwent duodenal biopsy and four subjects had Marsh IIIa changes suggestive of CD. The prevalence of histologically confirmed CD in first‐degree relatives was 4.4%. The prevalence of potential CD was 9.8%. IgA‐tTGA‐positive subjects (4/9) were significantly more often symptomatic than IgA‐tTGA‐negative first‐degree relatives (2/82). Twenty‐nine (96.6%) index cases of CD and all IgA‐tTGA‐positive first‐degree relatives were positive for HLA DQ2. None of the index CD cases or first‐degree relatives were HLA DQ8‐positive. A total of 85% of the first‐degree relatives were positive for HLA DQ2 and thus at risk of developing CD.

Conclusions:  In this first Asian study on a limited number of families of children with CD, 4.4% of the first‐degree relatives had CD. Only 15% of the first‐degree relatives were negative for HLA DQ2/DQ8. Initial evaluation with HLA and serology followed by only serial serology in HLA‐positive relatives is recommended.
Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation
Authors: Choi Ji‐Kyung , Küstermann Ekkehard , Dedeoglu Alpaslan , Jenkins Bruce G.
Published: November 2009

We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased N‐acetyl aspartate and glutamate and increased glutamine, taurine and myo‐inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild‐type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%), reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on N‐acetyl aspartate loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention, leading to a 13% increase in weight between 120 and 130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models.
Robotic partial nephrectomy without renal hilar occlusion
Authors: White Wesley M. , Goel Raj K. , Haber Georges‐Pascal , Kaouk Jihad H.
Published: November 2009

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To evaluate operative outcomes among patients undergoing robotic partial nephrectomy (RPN) without renal hilar clamping.

PATIENTS AND METHODS

This was a prospective observational study of patients undergoing RPN under perfused conditions (pRPN). Patients with solitary, radiographically enhancing renal cortical lesions gave consent for pRPN. Salient demographic data, including age, body mass index (BMI) and preoperative tumour size were obtained. Operative data, including mean operative time, estimated blood loss (EBL), and the presence of any complications, were collected. Renal function was evaluated before and after RPN. Remote adverse events were noted. The pRPN group was then retrospectively compared to a contemporary group of patients who had RPN with renal hilar occlusion. Endpoints for comparison included operative time, warm ischaemia time, EBL, length of hospitalization, and the rate of adverse events.

RESULTS

Between February 2008 and December 2008, eight had underwent pRPN; the mean age was 59.3 years, mean BMI 28.7 kg/m2, mean operative time 167 min, mean EBL 569 mL and mean hospitalization 3.75 days. Pathology showed renal cell carcinoma in five patients and oncocytoma in three; the mean tumour size was 2.4 cm. Final pathological margins were negative in all patients. Adverse events included one transfusion and one deep venous thrombosis. When compared to the contemporary group who had RPN with hilar clamping, the operative time was shorter (P = 0.035) and EBL greater (P = 0.018) in the pRPN group. There was no significant difference between the groups in transfusion rate, and no significant difference in renal function before and after surgery either group.

CONCLUSIONS

For selected small renal cortical masses, RPN is safe without renal hilar occlusion. The EBL was higher during pRPN but with no significant difference in the rate of transfusion.
Vocabulary Competence in Early Childhood: Measurement, Latent Construct, and Predictive Validity
Authors: Bornstein Marc H. , Haynes O. Maurice
Published: November 2009

We systematically examined relations among 6 measures of child language derived from 3 sources, including observations of the child's speech with mother, experimenter assessments, and maternal reports. A total of 184 20‐month‐olds and their mothers contributed complete information about child language comprehension and expression. Correlations of child language measures with socioeconomic status and maternal education were accounted for, as were correlations of child language measures with mothers' verbal intelligence, maternal report measures with mothers' tendency to respond in a socially desirable fashion, and experimenter assessments with child social competence. Structural equation modeling supported (1) strong relations among child language measures derived from observations of the child's speech with mother, experimenter assessments, and maternal reports; (2) the loading of multiple measures of child language from different sources on a single latent construct of vocabulary competence; and (3) the predictive validity of the vocabulary competence latent variable at 20 months, as well as receptive vocabulary specifically, for both verbal and performance IQ (verbal better than performance) at 48 months. Neither an index of child monologing (a nonvocabulary language measure) nor symbolic play (a nonlinguistic representational measure) covaried with vocabulary competence. Girls consistently outperformed boys on individual language measures, but no differences emerged in any model in the fit for boys and girls.
Children's Use of Looking Behavior as a Cue to Detect Another's Goal
Authors: Montgomery Derek E. , Back Leslie M. , Moran Christy
Published: November 2009

Three studies examined children's understanding of the role that looking behavior plays in revealing another's desired goal. In each study, participants were asked which of 2 objects a protagonist wanted to obtain. Four‐year‐olds did not infer that an object examined via prolonged looking was more likely to be the protagonist's goal than an object that was either glanced at or inadvertently touched. Instead, they were accurate only when the protagonist looked at one of two potential goals. In contrast, the majority of 6‐year‐olds (and adults in Experiment 1) consistently regarded prolonged looking as the more important cue of the protagonist's goal. These age differences suggest that development is characterized by an increasing appreciation that goal is revealed by comparative differences in the quality of perceptual connectedness to objects in the world. One explanation for these age differences is that preschoolers are limited in their understanding of the difference between perceiving with full attention and without it.