bluuebunny/crossref_metadata_2025 huggingface dataset:
Symbolic flux analysis for genome-scale metabolic networks
Authors: Schryer David W , Vendelin Marko , Peterson Pearu
Published: May 2011

Background

With the advent of genomic technology, the size of metabolic networks that are subject to analysis is growing. A common task when analyzing metabolic networks is to find all possible steady state regimes. There are several technical issues that have to be addressed when analyzing large metabolic networks including accumulation of numerical errors and presentation of the solution to the researcher. One way to resolve those technical issues is to analyze the network using symbolic methods. The aim of this paper is to develop a routine that symbolically finds the steady state solutions of large metabolic networks.

Results

A symbolic Gauss-Jordan elimination routine was developed for analyzing large metabolic networks. This routine was tested by finding the steady state solutions for a number of curated stoichiometric matrices with the largest having about 4000 reactions. The routine was able to find the solution with a computational time similar to the time used by a numerical singular value decomposition routine. As an advantage of symbolic solution, a set of independent fluxes can be suggested by the researcher leading to the formation of a desired flux basis describing the steady state solution of the network. These independent fluxes can be constrained using experimental data. We demonstrate the application of constraints by calculating a flux distribution for the central metabolic and amino acid biosynthesis pathways of yeast.

Conclusions

We were able to find symbolic solutions for the steady state flux distribution of large metabolic networks. The ability to choose a flux basis was found to be useful in the constraint process and provides a strong argument for using symbolic Gauss-Jordan elimination in place of singular value decomposition.
Metformin therapy in a hyperandrogenic anovulatory mutant murine model with polycystic ovarian syndrome characteristics improves oocyte maturity during superovulation
Authors: Sabatini Mary E , Guo Lankai , Lynch Maureen P , Doyle Joseph O , Lee HoJoon , Rueda Bo R , Styer Aaron K
Published: May 2011

Background

Metformin, an oral biguanide traditionally used for the treatment of type 2 diabetes, is widely used for the management of polycystic ovary syndrome (PCOS)-related anovulation. Because of the significant prevalence of insulin resistance and glucose intolerance in PCOS patients, and their putative role in ovulatory dysfunction, the use of metformin was touted as a means to improve ovulatory function and reproductive outcomes in PCOS patients. To date, there has been inconsistent evidence to demonstrate a favorable effect of metformin on oocyte quality and competence in women with PCOS. Given the heterogeneous nature of this disorder, we hypothesized that metformin may be beneficial in mice with aberrant metabolic characteristics similar to a significant number of PCOS patients. The aim of this study was to gain insight into the in vitro and in vivo effects of metformin on oocyte development and ovulatory function.

Methods

We utilized metformin treatment in the transgenic ob/ob and db/db mutant murine models which demonstrate metabolic and reproductive characteristics similar to women with PCOS. Results: Metformin did not improve in vitro oocyte maturation nor did it have an appreciable effect on in vitro granulosa cell luteinization ( progesterone production) in any genotype studied. Although both mutant strains have evidence of hyperandrogenemia, anovulation, and hyperinsulinemia, only db/db mice treated with metformin had a greater number of mature oocytes and total overall oocytes compared to control. There was no observed impact on body mass, or serum glucose and androgens in any genotype.

Conclusions

Our data provide evidence to suggest that metformin may optimize ovulatory performance in mice with a specific reproductive and metabolic phenotype shared by women with PCOS. The only obvious difference between the mutant murine models is that the db/db mice have elevated leptin levels raising the questions of whether their response to metformin is related to elevated leptin levels and/or if a subset of PCOS women with hyperleptinemia may be responsive to metformin therapy. Further study is needed to better define a subset of women with PCOS that may be responsive to metformin.
Assessment of genome integrity with array CGH in cattle transgenic cell lines produced by homologous recombination and somatic cell cloning
Authors: Liu George E , Hou Yali , Robl James M , Kuroiwa Yoshimi , Wang Zhongde
Published: May 2011

Background

Transgenic cattle carrying multiple genomic modifications have been produced by serial rounds of somatic cell chromatin transfer (cloning) of sequentially genetically targeted somatic cells. However, cloning efficiency tends to decline with the increase of rounds of cloning. It is possible that multiple rounds of cloning compromise the genome integrity or/and introduce epigenetic errors in the resulting cell lines, rendering a decline in cloning. To test these possibilities, we performed 9 high density array Comparative Genomic Hybridization (CGH) experiments to test the genome integrity in 3 independent bovine transgenic cell lineages generated from genetic modification and cloning. Our plan included the control hybridizations (self to self) of the 3 founder cell lines and 6 comparative hybridizations between these founders and their derived cell lines with either high or low cloning efficiencies.

Results

We detected similar amounts of differences between the control hybridizations (8, 13 and 39 differences) and the comparative analyses of both "high" and "low" cell lines (ranging from 7 to 57 with a mean of ~20). Almost 75% of the large differences (>10 kb) and about 45% of all differences shared the same type (loss or gain) and were located in nearby genomic regions across hybridizations. Therefore, it is likely that they were not true differences but caused by systematic factors associated with local genomic features (e.g. GC contents).

Conclusions

Our findings reveal that large copy number variations are less likely to arise during genetic targeting and serial rounds of cloning, fortifying the notion that epigenetic errors introduced from serial cloning may be responsible for the cloning efficiency decline.
Effect of Very Small Tumor Size on Cancer-Specific Mortality in Node-Positive Breast Cancer
Authors: Wo Jennifer Y. , Chen Kun , Neville Bridget A. , Lin Nancy U. , Punglia Rinaa S.
Published: May 2011

Purpose

Traditionally, larger tumor size and increasing lymph node (LN) involvement have been considered independent predictors of increased breast cancer–specific mortality (BCSM). We sought to characterize the interaction between tumor size and LN involvement in determination of BCSM. In particular, we evaluated whether very small tumor size may predict for increased BCSM relative to larger tumors in patients with extensive LN involvement.

Patients and Methods

Using Surveillance, Epidemiology and End Results registry data, we identified 50,949 female patients diagnosed between 1990 and 2002 with nonmetastatic T1/T2 invasive breast cancer treated with surgery and axillary LN dissection. Primary study variables were tumor size, degree of LN involvement, and their corresponding interaction term. Kaplan-Meier methods, adjusted Cox proportional hazards models with interaction terms, and a linear trend test across nodal categories were performed.

Results

Median follow-up was 99 months. In multivariable analysis, there was significant interaction between tumor size and LN involvement (P < .001). Using T1aN0 as reference, T1aN2+ conferred significantly higher BCSM compared with T1bN2+ (hazard ratio [HR], 20.66 v 12.53; P = .02). A similar pattern was seen among estrogen receptor (ER) –negative patients with T1aN2+ compared with T1bN2+ (HR, 24.16 v 12.67; P = .03), but not ER-positive patients (P = .52). The effect of very small tumor size on BCSM was intermediate among N1 cancers, between that of N0 and N2+ cancers.

Conclusion

Very small tumors with four positive LNs may predict for higher BCSM compared with larger tumors. In extensive node-positive disease, very small tumor size may be a surrogate for biologically aggressive disease. These results should be validated in future database studies.
Randomized Phase II Study Comparing Gemcitabine Plus Dacarbazine Versus Dacarbazine Alone in Patients With Previously Treated Soft Tissue Sarcoma: A Spanish Group for Research on Sarcomas Study
Authors: García-del-Muro Xavier , López-Pousa Antonio , Maurel Joan , Martín Javier , Martínez-Trufero Javier , Casado Antonio , Gómez-España Auxiliadora , Fra Joaquín , Cruz Josefina , Poveda Andrés , Meana Andrés , Pericay Carlos , Cubedo Ricardo , Rubió Jordi , De Juan Ana , Laínez Nuria , Carrasco Juan Antonio , de Andrés Raquel , Buesa José M.
Published: May 2011

Purpose

To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm.

Patients and Methods

Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1,800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1,200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months.

Results

From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects.

Conclusion

The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.
Cytarabine Dose of 36 g/m2 Compared With 12 g/m2 Within First Consolidation in Acute Myeloid Leukemia: Results of Patients Enrolled Onto the Prospective Randomized AML96 Study
Authors: Schaich Markus , Röllig Christoph , Soucek Silke , Kramer Michael , Thiede Christian , Mohr Brigitte , Oelschlaegel Uta , Schmitz Norbert , Stuhlmann Reingard , Wandt Hannes , Schäfer-Eckart Kerstin , Aulitzky Walter , Kaufmann Martin , Bodenstein Heinrich , Tischler Joachim , Ho Anthony , Krämer Alwin , Bornhäuser Martin , Schetelig Johannes , Ehninger Gerhard
Published: May 2011

Purpose

To assess the optimal cumulative dose of cytarabine for treatment of young adults with acute myeloid leukemia (AML) within a prospective multicenter treatment trial.

Patients and Methods

Between 1996 and 2003, 933 patients (median age, 47 years; range 15 to 60 years) with untreated AML were randomly assigned at diagnosis to receive cytarabine within the first consolidation therapy at either a intermediate-dose of 12 g/m2 (I-MAC) or a high-dose of 36 g/m2 (H-MAC) combined with mitoxantrone. Autologous hematopoietic stem-cell transplantation or intermediate-dose cytarabine (10 g/m2) were offered as second consolidation. Patients with a matched donor could receive an allogeneic transplantation in a risk-adapted manner.

Results

After double induction therapy including intermediate-dose cytarabine (10 g/m2), mitoxantrone, etoposide, and amsacrine, complete remission was achieved in 66% of patients. In the primary efficacy analysis population, a consolidation with either I-MAC or H-MAC did not result in significant differences in the 5-year overall (30% v 33%; P = .77) or disease-free survival (37% v 38%; P = .86) according to the intention-to-treat analysis. Besides a prolongation of neutropenia and higher transfusion demands in the H-MAC arm, rates of serious adverse events were comparable in the two groups.

Conclusion

In young adults with AML receiving intermediate-dose cytarabine induction, intensification of the cytarabine dose beyond 12 g/m2 within first consolidation did not improve treatment outcome.
Oncogenic Targets, Magnitude of Benefit, and Market Pricing of Antineoplastic Drugs
Authors: Amir Eitan , Seruga Bostjan , Martinez-Lopez Joaquin , Kwong Ryan , Pandiella Atanasio , Tannock Ian F. , Ocaña Alberto
Published: May 2011

Purpose

The relationship between market pricing of new anticancer drugs and the magnitude of clinical benefit caused by them has not been reported.

Patients and Methods

Randomized clinical trials (RCTs) that evaluated approved new agents for solid tumors by the US Food and Drug administration since the year 2000 were assessed. Hazard ratios (HRs) and 95% CIs were extracted for time-to-event end points described for each RCT. HRs were pooled for three groups: agents directed against a specific molecular target, for which the target population is selected by a biomarker (group A); less specific biologic targeted agents (group B); and chemotherapeutic agents (group C). Monthly market prices of these different drugs were compared.

Results

For overall survival (OS), the pooled HR was 0.69 (95% CI, 0.59 to 0.81) for group A (six drugs, six trials); it was 0.78 (95% CI, 0.74 to 0.83) for group B (seven drugs, 14 trials); and it was 0.84 (95% CI, 0.79 to 0.90) for group C (eight drugs, 12 trials). For progression-free survival (PFS), the pooled HR was 0.42 (95% CI, 0.36 to 0.49) for group A (six drugs, seven trials); it was 0.57 (95% CI, 0.51 to 0.64) for group B (seven drugs, 14 trials); and it was 0.75 (95% CI, 0.66 to 0.85) for group C (six drugs, 10 trials). Tests for heterogeneity between subgroups were highly significant for PFS (P < .001) and OS (P = .02). The median monthly prices for standard doses of drugs were $5,375 for group A, $5,644 for group B, and $6,584 for group C (P = .87).

Conclusion

New agents with specific molecular targets are clinically the most beneficial, but their monthly market prices are not significantly different from those of other anticancer agents.
Writing Friendship, Mourning the Friend in Late Anglo-Saxon Rules of Confraternity
Authors: Saltzman Benjamin A.
Published: May 2011

Mourning the death of a friend posed a problem for late Anglo-Saxon monasticism. Newly reformed under the authority of the Benedictine Rule and the Regularis Concordia, religious were precluded from developing personal friendships so as to protect a world in which all things—including friends—must be held in common. Within this context, two Old English documents, so-called Rules of Confraternity, were inscribed in the early eleventh century into two manuscripts at New Minster, Winchester and Sherborne, establishing provisions for a reciprocal exchange of prayers following a death at a neighboring monastery. However, through scribal amendments and emendations, the Sherborne Rules subtly break apart and reformulate the sense of community upheld in contemporary monastic codes: by liturgically imagining the confraternity as a bond of friendship between two monastic institutions, the Sherborne Rules clear ground for the possibility that one friend might singularly mourn the death of another.
Notch destabilises maternal β-catenin and restricts dorsal-anterior development inXenopus
Authors: Acosta Helena , López Silvia L. , Revinski Diego R. , Carrasco Andrés E.
Published: May 2011

The blastula chordin- and noggin-expressing centre (BCNE) is the predecessor of the Spemann-Mangold's organiser and also contains the precursors of the brain. This signalling centre comprises animal-dorsal and marginal-dorsal cells and appears as a consequence of the nuclear accumulation of β-catenin on the dorsal side. Here, we propose a role for Notch that was not previously explored during early development in vertebrates. Notch initially destabilises β-catenin in a process that does not depend on its phosphorylation by GSK3. This is important to restrict the BCNE to its normal extent and to control the size of the brain.
A patient with acute lymphoblastic leukaemia presenting with an extremely high level (21.0%) of HbA1c
Authors: Suzuki Yuhko , Shichishima Tsutomu , Yamashiro Yasuhiro , Kimura Hirokazu , Ishii Ryuuji , Miyazaki Koji , Horie Ryouichi , Moriya Tatsumi , Hattori Yukio
Published: May 2011

A 52-year-old Japanese woman was referred to our hospital because of fever and coxalgia. She had a white blood cell count of 241 × 102/ μL with 59.6% blasts, which had a high nuclear/cytoplasmic ratio and variably condensed nuclear chromatin. Flow cytometry and chromosomal analysis of bone marrow cells indicated positive findings of CD10, CD19, CD34, HLA-DR antigens and t(9; 22)(q34; q11.2), respectively. No rearrangements of bcr/abl in peripheral blood neutrophils were found by fluorescence in situ hybridization, suggesting that she had B-acute lymphoblastic leukaemia with Ph chromosome. Blood glucose and HbA1c (glycated haemoglobin) levels on admission were 23.4 mmol/L and 21.0%, respectively. The results of 1.5 anhydro-d-glucitol and glycoalbumin tests revealed that she certainly had diabetes mellitus (DM). Insulin therapy was initiated. Her high level of HbA1c also suggested the possibility that the patient suffered from haemoglobinopathies in addition to DM. Sequencing analyses of α1-, α2- and β-globin genes were all normal. The patient achieved complete remission (CR) by one month after her first course of chemotherapy, and the HbA1c level decreased to 10.4% following insulin therapy and chemotherapy, which were initiated when she attained CR. Her extremely high HbA1c level was due mainly to DM. Also, suppression of erythropoiesis by proliferation of leukaemic cells and latent iron deficiency might have partially contributed to the increased HbA1c. This could result in a transient but extremely high HbA1c level. To our knowledge, this is the first report of an acute leukaemia patient who expressed an extremely high level of HbA1c.
Implementing electronic patient handover in a district general hospital
Authors: Brebner Judith , Sandhu Kanwaljit , Addison Clara , Kapadia Suneil
Published: May 2011

This paper discusses how we have improved patient handover by implementing an electronic system for weekend handover. We discuss the process of changing handover methods and the results of an audit comparing our old paper based book versus our new ‘e-handover’ system.
Patient Experience Tracker (PET) survey as measure of quality in the Neonatal Unit
Authors: Aladangady Narendra , Negus Jennie
Published: May 2011

In the current era of consumerism, patient assessments of care are increasingly being considered an important dimension of quality of care. Good communication with patient or relatives is an important element in General Medical Council's (GMC) guidance on ‘Good medical practice’. Providing proper parent communication may help in improving parental satisfaction with overall care provided in the neonatal unit.

The Patient Experience Tracker (PET) device is a small wireless electronic handset used to gather real time report on patient experience. The neonatal unit PET survey was started after discussion and agreement with all departmental staff. Initial resistances by some staff overcome by open and honest discussion. A good uptake and accurate response depends on the information provided to parents and family about the PET device and survey. The questions should be appropriate to the department conducting the PET survey. Staff should be prepared to respond to the PET survey findings to improve patient satisfaction and thereby patient care. Ongoing support from Hospital Management is essential to ensure the information is disseminated in a constructive manner to all concerned and appropriate actions are taken to improve overall patient experience. The PET system has the flexibility to decide on questions, and more importantly to track performance and improvement progress.
Learning lessons from claims
Authors: Bartholomew Alison
Published: May 2011

The NHS Litigation Authority (NHSLA) has a remit to contribute to improvements in the safety of NHS patients and staff, and this article describes the ways in which information on the clinical negligence and non clinical liability claims managed by the Authority are used for risk management purposes. In March 2011, the NHSLA delivered a pioneering conference on Learning from mistakes in conjunction with claimant solicitors, Irwin Mitchell which considered the ways in which lessons have been learned from errors and explored opportunities for further improvements. The article concludes that the NHSLA has done much to promote learning from claims.
Dilute acid pretreatment of starch-containing rice hulls for ethanol production
Authors: López Yoney , Gullón Beatriz , Puls Jürgen , Parajó Juan C. , Martín Carlos
Published: May 2011

Rice hulls are potential low-cost feedstocks for fuel ethanol production in many countries. Most of the relevant publications are devoted to homogenous (high quality) hulls generated in industrial mills. On the other hand, small-scale mills give rise to hulls containing grain fragments and bran. In the present work, the dilute-acid pretreatment of such heterogeneous rice hulls was investigated based on a central composite rotatable experimental design. The variables were: temperature (140–210°C), biomass load (5–20%), and sulfuric acid concentration (0.5–1.5% based on reaction mixture). A total of 16 experimental runs were carried out, including a 23-plan, two replicates at the central point and six star points. Low temperatures were found to be favorable for the hydrolysis of xylan and of the easily hydrolyzable glucan fraction. High glucose formation (up to 15.3% of the raw material dry weight), attributable to starch hydrolysis, was detected in the hydrolysates obtained under the least severe pretreatment conditions. Several models were developed for predicting the effect of the operational conditions on the yield of pretreated solids, xylan and glucan conversion upon pretreatment, and on enzymatic convertibility of cellulose. The pretreatment temperature exerted the most significant effect on the conversion of the polysaccharides. Optimum results were predicted for the conversion of easily-hydrolyzable glucan in the material pretreated at 140.7°C, and for the enzymatic saccharification of cellulose in the material pretreated at 169°C. These results are interpreted that a two-step acid hydrolysis may be the best pretreatment strategy for heterogeneous rice hulls produced in small mills.
Visions and Reality: Reconsidering the Creation and Development of Lowell's National Park, 1966–1992
Authors: Weible Robert
Published: May 2011

For more than four decades, historians, historic preservationists, journalists, and public officials have debated the purpose and appropriateness of a national park in Lowell, Massachusetts. This article, written by the first NPS historian in Lowell, builds on existing literature and interprets the founding and early development of Lowell National Historical Park in the context of changing national politics. It locates the concept for the park in the Great Society, documents the contested debate over the park's founding in the 1970s, and argues that the park developed very differently than planned during the radically changed political environment of the 1980s.
Targeting protein kinase C by Enzastaurin restrains proliferation and secretion in human pancreatic endocrine tumors
Authors: Molè Daniela , Gagliano Teresa , Gentilin Erica , Tagliati Federico , Pasquali Claudio , Ambrosio Maria Rosaria , Pansini Giancarlo , degli Uberti Ettore C , Zatelli Maria Chiara
Published: May 2011

Dysregulation of the protein kinase C (PKC) signaling pathway has been implicated in tumor progression. In this study, we investigate the effects of a PKC inhibitor, Enzastaurin, in human pancreatic neuroendocrine neoplasms (PNN) primary cultures and in the human pancreatic endocrine cancer cell line, BON1. To this aim six human PNN dispersed in primary cultures and BON1 cells were treated without or with 1–10 μM Enzastaurin and/or 100 nM IGF1 in the presence or absence of serum. Cell viability and apoptosis were evaluated after 48–72 h; Chromogranin A (CgA) and/or insulin secretion was assessed after 6 h of incubation. PKC expression was investigated by immunofluorescence and western blot. We found that Enzastaurin significantly reduced human PNN primary culture cell viability, as well as CgA and insulin secretion. Moreover, in the BON1 cell line Enzastaurin inhibited cell proliferation at 5 and 10 μM by inducing caspase-mediated apoptosis, and reduced phosphorylation of glycogen synthetase kinase 3β (GSK3β) and of Akt, both downstream targets of PKC pathway and pharmacodynamic markers for Enzastaurin. In addition, Enzastaurin blocked the stimulatory effect of IGF1 on cell proliferation, and reduced CgA expression and secretion in BON1 cells. Two different PKC isoforms are expressed at different levels and have partially different subcellular localization in BON1 cells. In conclusion, Enzastaurin reduces cell proliferation by inducing apoptosis, with a mechanism likely involving GSK3β signaling, and inhibits secretory activity in PNNin vitromodels, suggesting that Enzastaurin might represent a possible medical treatment of human PNN.
Sperm proteasome and fertilization
Authors: Sutovsky Peter
Published: May 2011

The omnipresent ubiquitin–proteasome system (UPS) is an ATP-dependent enzymatic machinery that targets substrate proteins for degradation by the 26S proteasome by tagging them with an isopeptide chain composed of covalently linked molecules of ubiquitin, a small chaperone protein. The current knowledge of UPS involvement in the process of sperm penetration through vitelline coat (VC) during human and animal fertilization is reviewed in this study, with attention also being given to sperm capacitation and acrosome reaction/exocytosis. In ascidians, spermatozoa release ubiquitin-activating and conjugating enzymes, proteasomes, and unconjugated ubiquitin to first ubiquitinate and then degrade the sperm receptor on the VC; in echinoderms and mammals, the VC (zona pellucida/ZP in mammals) is ubiquitinated during oogenesis and the sperm receptor degraded during fertilization. Various proteasomal subunits and associated enzymes have been detected in spermatozoa and localized to sperm acrosome and other sperm structures. By using specific fluorometric substrates, proteasome-specific proteolytic and deubiquitinating activities can be measured in live, intact spermatozoa and in sperm protein extracts. The requirement of proteasomal proteolysis during fertilization has been documented by the application of various proteasome-specific inhibitors and antibodies. A similar effect was achieved by depletion of sperm-surface ATP. Degradation of VC/ZP-associated sperm receptor proteins by sperm-borne proteasomes has been demonstrated in ascidians and sea urchins. On the applied side, polyspermy has been ameliorated by modulating sperm-associated deubiquitinating enzymes. Diagnostic and therapeutic applications could emerge in human reproductive medicine. Altogether, the studies on sperm proteasome indicate that animal fertilization is controlled in part by a unique, gamete associated, extracellular UPS.
Equimolar Nitrous Oxide/Oxygen Versus Placebo for Procedural Pain in Children: A Randomized Trial
Authors: Reinoso-Barbero Francisco , Pascual-Pascual Samuel I. , de Lucas Raul , García Santos , Billoët Catherine , Dequenne Violaine , Onody Peter
Published: May 2011

OBJECTIVE:

This randomized, single-dose, double-blind, Phase III study was designed to compare the level of procedural pain after use of premixed equimolar mixture of 50% oxygen and nitrous oxide (EMONO) or placebo (premixed 50% nitrogen and oxygen).

METHODS:

Patients aged 1 to 18 years were randomly assigned to receive EMONO (n = 52) or placebo (n = 48) delivered by inhalation through a facial mask 3 minutes before cutaneous, muscle, or bone/joint procedures. Pain was evaluated (on a scale from 0–10) using a self-reported Faces Pain Scale–Revised (FPS-R) or a Spanish observational pain scale (LLANTO). Rescue analgesia (with propofol or sevoflurane) was administered if pain scores were greater than or equal to 8. Collaboration, acceptance, ease of use and safety were evaluated by the attending nurse.

RESULTS:

There were significant differences between the 2 groups (EMONO versus placebo) for both scales (mean values): LLANTO: 3.5 vs 6.7, respectively (P = .01) and FPS-R: 3.2 vs 6.6, respectively (P = .0003). Patients not receiving EMONO (P = .0208)—in particular those aged younger than 3 years (P < .0001)—required more rescue analgesia. There were also significant differences between the 2 groups (EMONO versus placebo) for adequate collaboration (80% vs 35%; P < .0001) and acceptance (73% vs 25%; P < .0001). Ease of use was not significantly different between groups (98.1% vs 95.8%; P > .05). Only 2 patients (in the EMONO group) presented with mild adverse events.

CONCLUSIONS:

EMONO inhalation was well tolerated and had an estimated analgesic potency of 50%, and it is therefore suitable for minor pediatric procedures.
Prenatal or Early-Life Exposure to Antibiotics and Risk of Childhood Asthma: A Systematic Review
Authors: Murk William , Risnes Kari R. , Bracken Michael B.
Published: May 2011

CONTEXT:

The increasing prevalence of childhood asthma has been associated with low microbial exposure as described by the hygiene hypothesis.

OBJECTIVE:

We sought to evaluate the evidence of association between antibiotic exposure during pregnancy or in the first year of life and risk of childhood asthma.

METHODS:

PubMed was systematically searched for studies published between 1950 and July 1, 2010. Those that assessed associations between antibiotic exposure during pregnancy or in the first year of life and asthma at ages 0 to 18 years (for pregnancy exposures) or ages 3 to 18 years (for first-year-of-life exposures) were included. Validity was assessed according to study design, age at asthma diagnosis, adjustment for respiratory infections, and consultation rates.

RESULTS:

For exposure in the first year of life, the pooled odds ratio (OR) for all studies (N = 20) was 1.52 (95% confidence interval [CI]: 1.30–1.77). Retrospective studies had the highest pooled risk estimate for asthma (OR: 2.04 [95% CI: 1.83–2.27]; n = 8) compared with database and prospective studies (OR: 1.25 [95% CI: 1.08–1.45]; n = 12). Risk estimates for studies that adjusted for respiratory infections (pooled OR: 1.16 [95% CI: 1.08–1.25]; n = 5) or later asthma onset (pooled OR for asthma at or after 2 years: OR: 1.16 [95% CI: 1.06–1.25]; n = 3) were weaker but remained significant. For exposure during pregnancy (n = 3 studies), the pooled OR was 1.24 (95% CI: 1.02–1.50).

CONCLUSIONS:

Antibiotics seem to slightly increase the risk of childhood asthma. Reverse causality and protopathic bias seem to be possible confounders for this relationship.
Trends in the Prevalence of Developmental Disabilities in US Children, 1997–2008
Authors: Boyle Coleen A. , Boulet Sheree , Schieve Laura A. , Cohen Robin A. , Blumberg Stephen J. , Yeargin-Allsopp Marshalyn , Visser Susanna , Kogan Michael D.
Published: May 2011

OBJECTIVE:

To fill gaps in crucial data needed for health and educational planning, we determined the prevalence of developmental disabilities in US children and in selected populations for a recent 12-year period.

PARTICIPANTS AND METHODS:

We used data on children aged 3 to 17 years from the 1997–2008 National Health Interview Surveys, which are ongoing nationally representative samples of US households. Parent-reported diagnoses of the following were included: attention deficit hyperactivity disorder; intellectual disability; cerebral palsy; autism; seizures; stuttering or stammering; moderate to profound hearing loss; blindness; learning disorders; and/or other developmental delays.

RESULTS:

Boys had a higher prevalence overall and for a number of select disabilities compared with girls. Hispanic children had the lowest prevalence for a number of disabilities compared with non-Hispanic white and black children. Low income and public health insurance were associated with a higher prevalence of many disabilities. Prevalence of any developmental disability increased from 12.84% to 15.04% over 12 years. Autism, attention deficit hyperactivity disorder, and other developmental delays increased, whereas hearing loss showed a significant decline. These trends were found in all of the sociodemographic subgroups, except for autism in non-Hispanic black children.

CONCLUSIONS:

Developmental disabilities are common and were reported in ∼1 in 6 children in the United States in 2006–2008. The number of children with select developmental disabilities (autism, attention deficit hyperactivity disorder, and other developmental delays) has increased, requiring more health and education services. Additional study of the influence of risk-factor shifts, changes in acceptance, and benefits of early services is needed.
Single‐Flap Approach for Surgical Debridement of Deep Intraosseous Defects: A Randomized Controlled Trial
Authors: Trombelli Leonardo , Simonelli Anna , Schincaglia Gian Pietro , Cucchi Alessandro , Farina Roberto
Published: May 2011

Background: The single‐flap approach (SFA) consists of the elevation of a limited mucoperiosteal flap to allow surgical access to periodontal defects from either the buccal or oral aspect only, leaving the interproximal supracrestal gingival tissues intact. The aim of the present randomized controlled trial is to assess the effectiveness of a buccal SFA used for the surgical debridement of deep intraosseous defects compared to the double‐flap approach (DFA).

Methods: Fourteen patients were treated according to SFA principles and 14 patients received the DFA. In all patients, root surfaces and defects were thoroughly debrided, and conditions for the primary intention healing and blood clot stability were ensured by a proper flap design and suture technique. The clinical attachment level (CAL), probing depth (PD), and gingival recession (REC) were assessed immediately before surgery and at 6 months post‐surgery.

Results: The results of the study indicate that: 1) the SFA and DFA resulted in significant CAL gains and PD reductions at 6 months post‐surgery; and 2) the SFA was similarly effective compared to the DFA in terms of CAL gain and PD reduction.

Conclusion: The surgical debridement of intraosseous periodontal defects resulted in comparable, substantial CAL gains and PD reductions as well as limited postoperative REC increases when defects were accessed with the SFA or DFA.
Levels of Serum Immunoglobulin G Specific to Bacterial Surface Protein A of Tannerella forsythia are Related to Periodontal Status
Authors: Hall Lindsay M. , Dunford Robert G. , Genco Robert J. , Sharma Ashu
Published: May 2011

Background: Tannerella forsythia (Tf) is a Gram‐negative anaerobe implicated in the development of periodontal disease. Bacterial surface protein A (BspA) is a surface‐expressed and ‐secreted protein that is recognized as an important virulence factor of Tf. This study was undertaken to determine whether Tf BspA induces an antibody response in periodontal disease. We hypothesized that serum immunoglobulin (Ig)G antibody levels against BspA correlate with the disease of patients.

Methods: Sera were obtained from 100 patients with cardiac disorders and periodontal disease and 73 patients who experienced myocardial infarction but were periodontally healthy. Sera samples were assayed for anti‐BspA antibody (total IgG and IgG subtypes) by enzyme‐linked immunosorbent assay (ELISA). Antibody levels were measured in ELISA units by using an arbitrary patient as a standard.

Results: A negative correlation was found with BspA‐specific total IgG antibody titers and the severity of disease measured as the clinical attachment level (CAL) when healthy and diseased groups were analyzed separately (healthy group: [−0.23, correlation value] Student's t value [73 degrees of freedom] = 1.99; P = 0.05; diseased group: [−0.21] t [100 degrees of freedom] = 2.12; P = 0.03]). However, there was a positive correlation ([0.18 correlation value] Student's t value [173 degrees of freedom] = 2.39; P = 0.017) when healthy and diseased groups were combined. A strong positive correlation ([0.338 correlation value] Student's t value [173 degrees of freedom] = 4.69; P <0.0001) between the BspA‐specific IgG titers and periodontal probing depth was observed when healthy and disease groups were combined.

Conclusions: Data demonstrated that antibodies to Tf BspA were elicited in patients with periodontal disease, and antibody levels were associated with the disease severity. Furthermore, data suggested that anti‐BspA IgG might have a protective function in periodontal disease by minimizing the loss of tooth attachment tissue.
The Influence of Experience upon Imagery Perspectives in Adolescent Sport Performers
Authors: Parker John K , Lovell Geoff
Published: May 2011

Current imagery literature suggests that imagery perspectives may be subject to a default position (Morris & Spittle, 2001), with experience influencing how successfully individuals can utilize internal and external visual imagery. According to this proposition, the default imagery perspective is an internal 1st person perspective. However, few imagery inventories have been designed to differentiate and accurately measure these imagery perspectives (see Morris, Spittle, & Watt, 2005). Fewer still have considered athletic populations, in particular adolescent cohorts. Consequently, the current research examined the use of internal visual imagery (IVI), external visual imagery (EVI), and kinesthetic imagery (KI) amongst adolescent sport performers and whether the amount of hours engaged in practice outside of competition influenced their adoption. Eighty-seven (36 male, 51 female) county level participants from sports academies in the United Kingdom (M age = 14.0, SD = 1.92), from 6 interactive sports, completed the Vividness of Movement Imagery Questionnaire-2 (VMIQ-2; Roberts et al., 2008). Participants were grouped relative to the amount of practice they had engaged in since playing their current sport competitively. A repeated measures ANOVA recorded significant differences amongst participants vividness of imagery, Wilkes ? F (2, 85) = 3.166, p < 0.05, ?² = .07, post hoc pairwise comparisons using a Bonferroni adjustment revealed no significant differences between sub-scales. Results to MANOVA recorded no significant differences between VMIQ-2 sub-scales and three accumulated practice groupings, Wilkes ? F (3, 82) = 436.14, p > 0.32, ?² = .04. The results demonstrate adolescent sport performers possess between clear and reasonably vivid to moderately clear and vivid imagery ability when using IVI, EVI, and KI. Future research should consider the impact of environmental factors that influence the development of these modalities and perspectives.
Pancreaticoduodenal Artery Pseudoaneurysm Embolization
Authors: Popov Petar , Sagic Dragan , Radovanovic Dragan , Antonic Zelimir , Nenezic Dragoslav , Radak Djordje
Published: May 2011

We report a case of successful transcatheter arterial embolization of a pancreaticoduodenal artery pseudoaneurysm (PSA) caused by erosion of the pancreatic pseudocyst content near pancreaticoduodenal arteries. A 55-year-old man was admitted to a local hospital for investigation of severe, stabbing epigastric pain confined to the upper abdomen. He had a history of previous alcohol abuse, chronic pancreatitis, and a duodenal ulcer. Upper gastrointestinal endoscopy revealed narrowing in the pyloric channel along with an ulcer located at the first and second portions of the duodenum with oozing beneath an adherent cloth and duodenal distortion. Computed tomography additionally revealed an enlarged head of the pancreas with numerous spot calcifications and round cystic formation inside, with a diameter of 30 × 25 mm. Following two surgical procedures for duodenal ulcers, selective angiography revealed a PSA located inside the pancreas head and high-grade stenosis > 90% of the celiac trunk and hepatic artery that rose separately from the aorta. Fiber coil embolization was used to occlude the PSA sac successfully. There was no complication after completion of the last embolic procedure. The patient was doing well after 26 months.
Optimal Prosthetic Graft Design for Small Diameter Vascular Grafts
Authors: Nishibe Toshiya , Kondo Yuka , Muto Akihito , Dardik Alan
Published: May 2011

Autogenous vein and arterial grafts, such as great saphenous veins and internal mammary and radial arteries, remain the gold standard conduits for vascular reconstruction. Expanded polytetrafluoroethylene (PTFE) grafts, which exhibit little inflammatory and thrombogenic reactivity, are the most commonly used material of choice for small diameter vascular grafts when autogenous grafts are not available. Several modifications of the basic graft have been attempted to enhance graft healing of expanded PTFE grafts, and little but definite experimental and clinical improvement has been achieved so far. The technique of vascular tissue engineering, in combination with stem cell research, may hold the key for the creation of a practical and successful small diameter prosthetic graft.
Mitochondriopathy of Peripheral Arterial Disease
Authors: Makris Konstantinos I. , Nella Aikaterini A. , Zhu Zhen , Swanson Stanley A. , Casale George P. , Gutti Tanuja L. , Judge Andrew R. , Pipinos Iraklis I.
Published: May 2011

The signs and symptoms of peripheral arterial occlusive disease (PAD), including claudication, rest pain, and tissue loss, are consequences of compromised bioenergetics and oxidative tissue injury within the affected lower extremities. Compromised bioenergetics is the result of a combination of low blood flow through diseased arteries and diminished adenosine triphosphate production by dysfunctional mitochondria. The tissue injury appears to be secondary to increased production of reactive oxygen species by dysfunctional mitochondria and by inflammation, in association with ischemia and ischemia/reperfusion. In this review, we present the current histomorphologic, physiologic, and biochemical evidence defining the nature of this mitochondriopathy and discuss its contribution to the pathogenesis and clinical manifestations of PAD.
Chemokines and Diabetic Wound Healing
Authors: Ochoa Oscar , Torres Francis M. , Shireman Paula K.
Published: May 2011

Chemokines are critical for white blood cell recruitment to injured tissues and play an important role in normal wound healing processes. In contrast, impaired wound healing in diabetic patients is accompanied by decreased early inflammatory cell infiltration but persistence of neutrophils and macrophages in the chronic, nonhealing wounds. These changes in inflammatory cell recruitment occur in conjunction with alterations in chemokine and growth factor expression. In addition to leukocyte trafficking, many different cell types, including endothelial cells, fibroblasts, and keratinocytes, produce and respond to chemokines, and these interactions are altered in diabetic wounds. Thus, the chemokine system may have both direct and inflammatory-mediated effects on many different aspects of diabetic wound healing. The potential roles of chemokines and inflammatory or immune cells in nonhealing diabetic wounds, including impairments in growth factor expression, angiogenesis, extracellular matrix formation, and reepithelialization, are examined.
Screening for Significant Carotid Artery Disease among a Cohort of 1,000 Egyptian Patients
Authors: Bishara Rashad A. , Taha Wassila , AlFarouk Mohamed Omar , Milik Ihab A. , Wilson Nagwa
Published: May 2011

The objective of this study was to determine the prevalence of significant carotid artery disease (SCAD) in a cohort of Egyptian patients to compare it with matched groups of patients in published data of Western populations. One thousand consecutive patients referred for color flow duplex scanning of the carotid arteries were included. SCAD was defined as carotid stenosis ≥ 50% or occlusion. There were 567 males (56.7%), and the mean age was 60.4 years. There were 382 (38.2%) patients presenting with and 617 (61.7%) patients without specific carotid territory symptoms. SCAD was significantly more prevalent in patients aged ≥ 60 (13.2%, vs 6.25%; p < .001), in symptomatic patients (16.45% vs 6.32%; p < .001), in diabetics (15.96% vs 7.39%; p < .001), in patients with ischemic heart disease (17.65% vs 7.22%; p < .001), in hypertensive patients (12% vs 7.54%; p = .025), and in patients with dyslipidemia (12.53% vs 6.56%; p < .025). The prevalence of SCAD in this cohort of Egyptian patients was similar to that of matched patients of Western populations. Screening for SCAD in patients with specific carotid territory symptoms is recommended. Screening of asymptomatic subjects could be considered if they are ≥ 60 years of age and have three or more associated risk factors.
Form And Function Of Vena Cava Filters: How Do Optional Filters Measure Up?
Authors: Proctor Mary C. , Greenfield Lazar J.
Published: May 2011

The function of vena cava filters, preventing pulmonary embolism while maintaining caval patency, is associated with the design. Several characteristics have been reported. This report evaluates retrievable filter designs in comparison with previously marketed designs with respect to efficacy and safety. Three inferior vena cava (IVC) filters (Gunther Tulip, Bard Recovery, and the Cordis OptEase) were compared on the basis of design characteristics associated with function, shape, number of trapping levels, and fixation. Adverse events reported in the literature and to the US Food and Drug Administration Manufacturers and User Facility Device Experience Database (MAUDE) were summarized. The major differences among device types include the fixation, the volume and number of trapping levels, and the amount of metal in the IVC. The MAUDE registry reported adverse events that had been hypothesized from the analysis of in vitro and in vivo testing. The Recovery and OptEase filters had the highest number of clinically important reports. From 12 to 57% were retrieved between 3 days and 11 months. Adaptations made to facilitate retrieval led to unacceptable sequelae. The small number removed, the length of time they are left in place, and the risks associated with retrieval suggest that optional filters may not be equivalent to approved permanent devices.