Journals
2012 EN
Irina Enache · G. Noël · M-Young Jeung
+7 more
Background A large increase in nitric oxide fraction (FeNO) after radiotherapy (RT) for lung cancer may predict RT-induced lung toxicity. Methods In this study, we assessed the relationships between FeNO variations and respiratory symptoms, CT scan changes or dose volume histogram (DVH) parameters after RT. We measured FeNO before RT, 4, 5, 6, 10 weeks, 4 and 7.5 months after RT in 65 lung cancer patients. Results Eleven lung cancer patients (17%) complained of significant respiratory symptoms and 21 (31%) had radiation pneumonitis images in >1/3 of the irradiated lung after RT. Thirteen patients (20%) showed increases in FeNO >10 ppb. The sensitivity and specificity of a >10 ppb FeNO increase for the diagnosis of RT-associated respiratory symptoms were 18% and 83%, respectively. There was no correlation between DVH parameters or CT scan changes after RT and FeNO variations. Three patients (5%) showed intriguingly strong (2 or 3-fold, up to 55 ppb) and sustained increases in FeNO at 4 and 5 weeks, followed by significant respiratory symptoms and/or radiation-pneumonitis images. Conclusion Serial FeNO measurements during RT had a low ability to identify lung cancer patients who developed symptoms or images of radiation pneumonitis. However, three patients presented with a particular pattern which deserves to be investigated.
Journals
2012 EN
Péter Vasas · Tom Wiggins · Asif Chaudry
+2 more
Aims To compare emergency and elective presentation of gastric cancer by mode of clinical presentation, initial stage, intervention and prognosis. Methods Data were collected prospectively for all cases of gastric cancer presenting to a tertiary referral centre between 2003 and 2010. This was stratified by emergency and elective presentation and was analysed for mode of presentation, initial stage and outcome. Statistical analysis was performed using unpaired t-test and Chi 2 test. Results A total of 291 patients presented: Forty-two (14.43%) were emergencies and 249 (85.57%) elective presentations. Analysis of the emergency cohort showed 25 patients presented with obstruction (59.52%), 15 presented with haematemesis (35.71%) and 2 with perforation (4.76%). Eighteen of the emergency patients (45%) presented with stage 4 disease compared to 60 (25.42%) in the elective group (p < 0.005). Fourteen of the emergency patients were treated with curative intent (33.3%) compared with 130 (55.56%) in the elective group (p < 0.01). Over 6 years only 2 patients needed operation within 24 hours of presentation. Overall survival at one year for emergency patients was 48.3% compared to 63.4% in elective patients (p < 0.05). There were no survivors from the emergency group after 3 years but 32.46% of the elective patients survived (p < 0.02). Elective presentation with disease stage 1A-3B had a two year survival rate of 54.95% compared to only 20% in the emergency group (p < 0.05). Of patients who underwent operative intervention 67.44% of patients who presented electively survived to 2 years. This compared to just 25% presenting as emergencies (p < 0.001). Conclusions Emergency presentation of gastric cancer is rare; is associated with higher stage of disease at presentation and lower rates of operability. The necessity to perform emergency operation within 24 hours is exceedingly rare. Emergency presentation is a marker of poor long term outcome for equivalent cancer stage in non-advanced (stages 1A-3B) disease.
Journals
2012 EN
Catherine A. Dye · Charles W. Abbott · Kelly J. Huffman
Background Anatomically and functionally distinct sensory and motor neocortical areas form during mammalian development through a process called arealization. This process is believed to be reliant on both activity-dependent and activity-independent mechanisms. Although both mechanisms are thought to function concurrently during arealization, the nature of their interaction is not understood. To examine the potential interplay of extrinsic activity-dependent mechanisms, such as sensory input, and intrinsic activity-independent mechanisms, including gene expression in mouse neocortical development, we performed bilateral enucleations in newborn mice and conducted anatomical and molecular analyses 10 days later. In this study, by surgically removing the eyes of the newborn mouse, we examined whether early enucleation would impact normal gene expression and the development of basic anatomical features such as intraneocortical connections and cortical area boundaries in the first 10 days of life, before natural eye opening. We examined the acute effects of bilateral enucleation on the lateral geniculate nucleus of the thalamus and the neocortical somatosensory-visual area boundary through detailed analyses of intraneocortical connections and gene expression of six developmentally regulated genes at postnatal day 10. Results Our results demonstrate short-term plasticity on postnatal day 10 resulting from the removal of the eyes at birth, with changes in nuclear size and gene expression within the lateral geniculate nucleus as well as a shift in intraneocortical connections and ephrin A5 expression at the somatosensory-visual boundary. In this report, we highlight the correlation between positional shifts in ephrin A5 expression and improper refinement of intraneocortical connections observed at the somatosensory-visual boundary in enucleates on postnatal day 10. Conclusions Bilateral enucleation induces a positional shift of both ephrin A5 expression and intraneocortical projections at the somatosensory-visual border in only 10 days. These changes occur prior to natural eye opening, suggesting a possible role of spontaneous retinal activity in area border formation within the neocortex. Through these analyses, we gain a deeper understanding of how extrinsic activity-dependent mechanisms, particularly input from sensory organs, are integrated with intrinsic activity-independent mechanisms to regulate neocortical arealization and plasticity.
Journals
2012 EN
Jérôme Stirnemann · Marie Vigan · Dalil Hamroun
+23 more
Background Clinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described. Methods All patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables. Results Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%). Conclusion This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.
Journals
2012 EN
Erin Amerson · Nathan Buziba · Henry Wabinga
+15 more
Author(s): Amerson, Erin; Buziba, Nathan; Wabinga, Henry; Wenger, Megan; Bwana, Mwebesa; Muyindike, Winnie; Kyakwera, Catherine; Laker, Miriam; Mbidde, Edward; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Musick, Beverly; LeBoit, Philip; McCalmont, Tim; Ruben, Beth; Volberding, Paul; Maurer, Toby; Martin, Jeffrey
Journals
2012 EN
Dave Lee · Kieran Smallbone · Warwick B. Dunn
+5 more
Background Constraint-based analysis of genome-scale metabolic models typically relies upon maximisation of a cellular objective function such as the rate or efficiency of biomass production. Whilst this assumption may be valid in the case of microorganisms growing under certain conditions, it is likely invalid in general, and especially for multicellular organisms, where cellular objectives differ greatly both between and within cell types. Moreover, for the purposes of biotechnological applications, it is normally the flux to a specific metabolite or product that is of interest rather than the rate of production of biomass per se . Results An alternative objective function is presented, that is based upon maximising the correlation between experimentally measured absolute gene expression data and predicted internal reaction fluxes. Using quantitative transcriptomics data acquired from Saccharomyces cerevisiae cultures under two growth conditions, the method outperforms traditional approaches for predicting experimentally measured exometabolic flux that are reliant upon maximisation of the rate of biomass production. Conclusion Due to its improved prediction of experimentally measured metabolic fluxes, and of its lack of a requirement for knowledge of the biomass composition of the organism under the conditions of interest, the approach is likely to be of rather general utility. The method has been shown to predict fluxes reliably in single cellular systems. Subsequent work will investigate the method’s ability to generate condition- and tissue-specific flux predictions in multicellular organisms.
Springer Science+Business Media
Journals
2012 EN
Catherine Jayapandian · Meng Zhao · Rob M. Ewing
+2 more
Background One of the primary challenges in translational research data management is breaking down the barriers between the multiple data silos and the integration of 'omics data with clinical information to complete the cycle from the bench to the bedside. The role of contextual metadata, also called provenance information, is a key factor ineffective data integration, reproducibility of results, correct attribution of original source, and answering research queries involving " W hat", " W here", " W hen", " W hich", " W ho", "Ho w ", and " W hy" (also known as the W7 model). But, at present there is limited or no effective approach to managing and leveraging provenance information for integrating data across studies or projects. Hence, there is an urgent need for a paradigm shift in creating a "provenance-aware" informatics platform to address this challenge. We introduce an ontology-driven, intuitive Sem antic P r o teomics D ashboard ( SemPoD ) that uses provenance together with domain information (semantic provenance) to enable researchers to query, compare, and correlate different types of data across multiple projects, and allow integration with legacy data to support their ongoing research. Results The SemPoD platform, currently in use at the Case Center for Proteomics and Bioinformatics (CPB), consists of three components: (a) Ontology-driven Visual Query Composer, (b) Result Explorer, and (c) Query Manager. Currently, SemPoD allows provenance-aware querying of 1153 mass-spectrometry experiments from 20 different projects. SemPod uses the systems molecular biology provenance ontology (SysPro) to support a dynamic query composition interface, which automatically updates the components of the query interface based on previous user selections and efficientlyprunes the result set usinga "smart filtering" approach. The SysPro ontology re-uses terms from the PROV-ontology (PROV-O) being developed by the World Wide Web Consortium (W3C) provenance working group, the minimum information required for reporting a molecular interaction experiment (MIMIx), and the minimum information about a proteomics experiment (MIAPE) guidelines. The SemPoD was evaluated both in terms of user feedback and as scalability of the system. Conclusions SemPoD is an intuitive and powerful provenance ontology-driven data access and query platform that uses the MIAPE and MIMIx metadata guideline to create an integrated view over large-scale systems molecular biology datasets. SemPoD leverages the SysPro ontology to create an intuitive dashboard for biologists to compose queries, explore the results, and use a query manager for storing queries for later use. SemPoD can be deployed over many existing database applications storing 'omics data, including, as illustrated here, the LabKey data-management system. The initial user feedback evaluating the usability and functionality of SemPoD has been very positive and it is being considered for wider deployment beyond the proteomics domain, and in other 'omics' centers.
Springer Science+Business Media
Journals
2012 EN
B. Maetz · R. Abbou · Jean Baptiste Andreoletti
+1 more
Since the 1980s, leeches have been ingeniously used in the management of venous flap congestion. The presence of anticoagulative substances in their saliva improves the blood drainage. Their digestive tract contains several bacterial species, the main ones being Aeromonas hydrophila and Aeromonas veronii biovar sobria, which contribute to the digestion of ingested blood. These bacteria can be the cause of infections. Case presentation We report two cases of septicemia related to Aeromonas veronii biovar sobria that presented after leeches had been applied to congested transverse rectus abdominis myocutaneous flaps for delayed mammary reconstructions. Patient number 1 was a 55-year-old Caucasian woman who underwent a delayed breast reconstruction procedure. On the sixth postoperative day she showed a clinical presentation of septicemia. Aeromonas veronii biovar sobria was identified in the patient’s skin and blood bacteriological samples. Her fever ceased after 4 days of antibiotic treatment. Patient number 2 was a 56-year-old Caucasian woman who underwent a delayed breast reconstruction procedure. On the seventh postoperative day we noticed that she showed a clinical presentation of septicemia. Aeromonas veronii biovar sobria was identified in the patient’s blood cultures and local bacteriological samples. An antibiogram showed resistance to amoxicillin/clavulanic acid. Her fever ceased on the eleventh postoperative day after 4 days of antibiotic treatment. Conclusion The rate of infection after application of leeches is not negligible. The concentration of Aeromonas inside the digestive tracts of leeches largely decreases when the patient is under antibiotic therapy. These germs are sensitive to third-generation cephalosporins and fluoroquinolones and resistant to amoxicillin/clavulanic acid. We recommend preventive treatment based on classical measures of asepsis and on oral antibioprophylaxy with a fluoroquinolone during the whole period of treatment by leeches.
Journals
2012 EN
Catherine Abbo · Elialilia S. Okello · Seggane Musisi
+2 more
Objective To determine the naturalistic outcome of treatment of psychosis by traditional healers in Jinja and Iganga districts of Eastern Uganda. Method A cohort of patients with psychosis receiving treatment from traditional healers’ shrines were recruited between January and March 2008 and followed up at three and six months. The Mini International Neuropsychiatry Interview (MINI Plus) was used for making specific diagnosis at the point of contact. For specific symptoms, Positive and Negative Symptom Scale (PANSS), Young Mania Rating Scale (YMRS) and Montgomery Asberg Depression Rating Scale (MADRS) were used to measure severity of schizophrenia, mania and psychotic depression, respectively. The Clinical Global Impression (CGI) and Global Assessment of Functioning (GAF) were used for objective assessments. The Compass Mental Health Index measured well being. Mean scores of the scales were computed using one way ANOVA for independent samples. Associations between outcome and categorical variables were examined at bivariate and multivariate levels. Results All the symptom scales had a percentage reduction of more than 20% at three and six months follow up. The differences between the mean scores of the scales at baseline and 3 months, baseline and 6 months, and 3 and 6 months were all significant (P < 0.0001). The post test for pair wise comparisons, the Tukey HSD (Honestly Significant Difference) test was also all significant at P < 0.01 except for MADRS where there was no significant difference between 3 and 6 months for depression severity. Over 80% of the participants used biomedical services for the same symptoms in the study period. At 3 months follow up, patients who combined treatment were less likely to be cases (P = 0.002; OR 0.26 [0.15-0.58]), but more likely to be cases at 6 months follow up (P = 0.020; OR 2.05 [1.10-3.189]). Being in debt was associated with caseness both at 3 and 6 months. Conclusion This study suggests that there may be some positive effects for patients with psychosis who combine both biomedical services and traditional healing . Further research in the area of naturalistic outcome of traditional healing is necessary .
Journals
2012 EN
Catherine Crowe · Eoin Noctor · LA Carmody
+5 more
The ATLANTIC-DIP (diabetes in pregnancy) programme showed 18% of women with gestational diabetes mellitus (GDM) screened with a 75g oral glucose tolerance test (OGTT) 12 weeks post-partum demonstrated glucose intolerance. However, long-term data on progression to type 2 diabetes (T2DM) post gestational diabetes (GDM) in an Irish population is lacking.