tbuckley/cabot-search huggingface dataset:
High prevalence of resistant bacterial infections in patients with tracheostomy due to neuromuscular disease (NMD)
Authors: Fabrizio Rao, Paola Francesca Castellotti, Chiara Vismara, Elisa Falcier, Giovanni Gesu, Valeria Sansone
Journal: European Respiratory Journal (2014)

NMD involve respiratory muscles causing severe restriction.Management of respiratory failure including tracheostomy is an option in these diseases.There is limited information on epidemiology of infections in patients with tracheostomy due to NMD. To investigate the prevalence of bacterial infections and antibiotic resistance in patients with tracheostomy due to NMD, to identify ways to better control the spread of infection and to verify the appropriate use of antibiotics. We conducted a retrospective observational analysis in 61 adult patients admitted in 2013 (motor neuron disease, n = 52; muscular dystrophies, n =4, myasthenia gravis, n = 1, neuropathies, n = 4). Positive microbiology samples, clinical symptoms, inflammatory parameters, chest X-ray results were recorded.We identified that 98% of patients had a positive sample.  In 51 cases antibiotic therapy was started, but only 33 (65%) of these events were supported by clinical data and were identified as an active infection.Sepsis occurred only in 3 patients.The high prevalence of highly-resistant micro-organisms suggests that it is necessary to discriminate between infection and colonization to allow a more responsible use of antibiotics. Future studies should be focused on interventions to increase infection control.
Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.
Authors: F Roila, M Tonato, C Basurto, M Bella, R Passalacqua, D Morsia, F DiCostanzo, D Donati, E Ballatori, G Tognoni
Journal: Journal of Clinical Oncology (1987)

We designed a multicenter, double-blind randomized study to determine the safety and antiemetic effectiveness of intravenous (IV) methylprednisolone (P) combined with high-dose IV metoclopramide (MTC) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy. One hundred eighty-five patients were evaluable for treatment efficacy. MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes (P = .001 and P = .0008, respectively) and the maximal intensity of nausea (P = .0124 with a score system; P = .0155 with a linear analogue scale) and length of nausea (P = .0056). The subgroup with a major incidence of nausea and vomiting was women, especially young women, outpatients, and those treated with higher doses of cisplatin. Side effects were low and equally distributed between the two treatment groups. We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy.
High-Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation in Multiple Myeloma: Up-front or Rescue Treatment? Results of a Multicenter Sequential Randomized Clinical Trial
Authors: Jean-Paul Fermand, Philippe Ravaud, Sylvie Chevret, Marine Divine, Véronique Leblond, Coralie Belanger, Margaret Macro, Edouard Pertuiset, François Dreyfus, Xavier Mariette, Catherine Boccacio, Jean-Claude Brouet
Journal: Blood (1998)
T cell and B cell immunological responses by tuberculous antigens in Japanese populations with different bacterial antigen expressions
Authors: Yumi Sakakibara, Mamiko Niki, Takuro Sakagami, Haruyuki Ariga, Sohkichi Matsumoto, Naohiko Inase, Hideaki Nagai, Pedro A. Reche, Yoshihiko Hoshino
Journal: European Respiratory Journal (2013)

[Background] Although IFN-γ releasing assay is replacing conventional tuberculin skin test, the immunological responses to various tuberculous antigens were not precisely investigated. [Objective] To examine T cell and B cell responses elicited by active and dormant antigens. To find promising markers of re-activation and/or keeping dormancy through the following of the clinical evaluation of individuals with active, past and latent TB infection (LTBI) [Method] Study populations were 10 active, 20 past, 30 LTBI and 20 healthy controls. We used recombinant proteins of active antigens like CFP-10, ESAT-6, TB7.7 and dormant antigens like Acr, HrpA, MDP-1, and HBHA. Overlapping peptides of active antigens were prepared for epitope mapping. B cell responses were assayed by ELISA and T cell responses by IFN-γ ELISPOT. [Result] Approximately 55% possess HLA A*2402 and 25% HLA DRB1*0901. Duration from the last treatment was 69.7±5.6 months (past TB patients) and from the assay 35.4±0.5 months. T cell response to CFP-10 and/or ESAT-6 was positive in most cases while only one patient was positive for TB7.7. Antigenic regions of active antigens were detected. Some patients revealed positive ELISPOT to dormant antigens,especially Acr and MDP-1. There is a discrepancy between the B cell and T cell response elicited by dormant antigen. Auto-antibody to IFN-γ was negative in all patients. [Conclusion] While there was similar tendency in active TB patients, the immune response to tuberculous antigen was variable among past TB and LTBI patients. The response frequency, antigen variability, molecular features of antigen, and association with HLA will be discussed.
Multivariate analysis of risk factors in stage 4 neuroblastoma patients over the age of one year treated with megatherapy and stem-cell transplantation: a report from the European Bone Marrow Transplantation Solid Tumor Registry.
Authors: R Ladenstein, T Philip, C Lasset, O Hartmann, A Garaventa, R Pinkerton, J Michon, J Pritchard, T Klingebiel, B Kremens, A Pearson, C Coze, P Paolucci, D Frappaz, H Gadner, F Chauvin
Journal: Journal of Clinical Oncology (1998)

PURPOSE The European Bone Marrow Transplantation (EBMT) Solid Tumor Registry (STR) contains detailed information on children with advanced neuroblastoma who, after standard-dose induction chemotherapy and surgery, received myeloablative megatherapy (MGT) followed by stem-cell transplantation (SCT). This data base was analyzed to identify factors that predict event-free survival (EFS). PATIENTS AND METHODS Eligibility criteria were stage IV neuroblastoma, age over 1 year at diagnosis, and no relapse before MGT/SCT. Between February 1978 and July 1992, 549 patients were registered by 36 European transplant centers. The median age at diagnosis was 36 months (range, 13 to 216 months) and the male-female ratio was 1:45. Before MGT, 157 patients were in complete remission (CR), 156 in very good partial remission (VGPR), and 208 in partial remission (PR), whereas 24 had had only a minor response (MR). One hundred ten of 546 patients had undergone two successive MGT procedures. The median observation time was 60 months (range, 12 to 187 months). RESULTS Actuarial EFS is 26% at 5 years. Multivariate analysis by the Cox proportional hazards regression model included 529 patients with complete data sets. After adjustment for treatment duration before MGT and double MGT procedures, two adverse, independent risk factors that influenced EFS were identified: (1) persisting skeletal lesions before MGT as defined by technetium (99TC) scans and/or meta-iodobenzylguanidine (mIBG) scans (P = .004) and (2) persisting bone marrow involvement before MGT (P = .03). CONCLUSION After induction treatment, persisting skeletal disease as defined above and persisting bone marrow involvement may be predictive of a particularly poor outcome. Physicians may consider this an additional important tool to decide the patient's management.
Abstract 12506: Therapeutic Strategy for Efficient Reduction of Serum Uric Acid With Allopurinol versus Benzbromarone in Hyperuricemic Patients With Cardiovascular Disease ~ A Randomized Crossover Study (TERAO study) ~
Authors: Sunao Kojima, Shinobu Kojima, Hirofumi Soejima, Hisao Ogawa
Journal: Circulation (2014)

Introduction: Hyperuricemia is considered to be a marker of future cardiovascular events. Uricosuric agents and urate synthesis inhibitors has been widely used in hyperuricemic patients. Hypothesis: We assessed the hypothesis that the different mechanism of these drugs has an impact on urine albumin-creatinine ratio (ACR) associated with cardiovascular risks. Methods: A total of 14 hyperuricemic patients (serum uric acid levels &gt;7 mg/dL) with cardiovascular disease were randomly assigned and treated with either benzbromarone, 25mg once daily, or allopurinol, 200 mg twice daily for 2 weeks, followed by a 2-week washout period, then a 2-week crossover phase. Results: Serum uric acid levels were comparable and similarly reduced with benzbromarone (8.4±1.1→4.8±1.3 mg/dL, P&lt;0.0001) and allopurinol (8.4±1.0→5.1±0.9 mg/dL, P&lt;0.0001). However, allopurinol significantly reduced urine ACR compared with benzbromarone (Figure 1). A logistic regression analysis revealed that influential clinical factors on reduced urine ACR were not observed except for allopurinol administration. The change of urine ACR was positively correlated with the change of urinary urate-creatinine ratio (UCR), indicating a substitution for xanthine oxidase activity (Figure 2). Conclusions: In this short-term, crossover study in hyperuricemic patients with cardiovascular disease, a treatment with xanthine oxidase inhibitor resulted in a reduction of urine ACR. These results represent a novel potential therapeutic approach with antioxidant strategy, which may lead to a reduction of future cardiovascular events. These preliminary findings require confirmation in larger clinical trials.
A prothrombotic state is associated with increased mortality in idiopathic pulmonary fibrosis
Authors: Vidya Navaratnam, Andrew Fogarty, Tricia McKeever, Norma Thompson, Gisli Jenkins, Simon Johnson, Gerard Dolan, Maruti Kumaran, Kate Pointon, Richard Hubbard
Journal: European Respiratory Journal (2013)

Background: Studies have suggested that the clotting cascade is activated in fibrotic lungs. It is unclear if a prothrombotic state alters survival in people with idiopathic pulmonary fibrosis (IPF).  Objectives: To investigate if a prothrombotic alters the prognosis in terms of survival amongst people with IPF.  Methods: We recruited incident cases of IPF from 5 teaching hospitals and 8 district general hospitals in England and Wales. Participants had a venous blood sample taken to test for inherited and acquired clotting defects. We also collected high resolution computed tomography (HRCT) scans which were reviewed by two thoracic radiologists to confirm the diagnosis of IPF. We used Kaplan-Meir methods and Cox regression modelling for our survival analysis.  Results: We had 211 individuals with definite or probable IPF in who were followed up for a median time of 1.1 years. There were 56 deaths, and 52 (92.9%) of those individuals had at least one inherited or acquired clotting defect. People with IPF and at least one clotting defect were associated with an almost 3.5 fold increase in mortality (Hazard Ratio 3.50, 95% Confidence Interval: 1.09-9.75; p  Conclusion: A prothrombotic stated is strongly associated with increased mortality amongst people with IPF.
Profiling signal transduction pathways in ascites tumor cells of gastric cancer.
Authors: J. Lee, P. S. Kim, J. M. Sun, L. Liu, S. H. Park, A. Fithian, J. O. Park, K. Magonova, H. Y. Lim, X. Liu, S. Singh, W. K. Kang
Journal: Journal of Clinical Oncology (2011)

e14583 Background: Malignant ascites is a manifestation of end stage events in a variety of cancers and associated with a poor prognosis with limited options for therapies. We evaluated the potential use of tumor cells isolated in ascites collected from gastric cancer (GCA) patients. Here we demonstrate successful profiling of signal transduction pathway proteins in isolated ascites-tumor cells (ATCs) and their modulations in response to drug treatments. Methods: The collaborative enzyme enhanced reactive-immunoassay (CEER) is a multiplexed protein microarray platform requiring co-localization of two detector enzyme-conjugated-antibodies. Once target proteins are captured on the microarray-surface, channeling events between two detector enzymes in proximity enable the profiling of the target proteins with high sensitivity. In this study, ATCs were isolated from ascites fluid obtained from advanced GCA patients and analyzed for HER1, HER2, HER3, cMET, cKIT, IGF-1R, PI3K, and other pathway proteins for their expression/activation and the degree of pathway modulation in response to targeted drug treatments. Results: Here, we report successful profiling of activation and expression of proteins in RTK pathway in ATCs of GCA patients. Varying levels of HER2 expression was detected in some patients and with significant levels of activation in subset of these patients. A complete in vitro ablation of phosphorylation of HER2 was observed when EpCAM positive ATCs were treated with HER2 targeted inhibitor in one GCA patient. Differential patterns of other RTKs profile and downstream pathway proteins were also observed. Conclusions: The ATCs from GCA are suitable resource for real-time profiling for the status of proteins in RTK and downstream proteins in signal transduction pathways. Monitoring the profile shift of pathway proteins over time, either treatment-related or due to the natural history of disease in GCA patients, may allow more effective selection and adjustment of targeted therapy for an individual patient. As CEER requires limited amounts of sample, real-time biopsy can be performed on tumor cells obtained from ascites, FNA or CTCs for therapy optimization (combination/sequencing) during the course of treatments.
Why the drug development pipeline is not delivering better medicines
Authors: Huseyin Naci, Alexander W Carter, Elias Mossialos
Journal: BMJ (2015)

Despite the large number of new medicines entering the market every year, few offer important clinical advantages for patients. <b>Huseyin Naci</b>, <b>Alexander Carter</b>, and <b>Elias Mossialos</b> explain the reasons for this innovation deficit and offer some solutions
Sequence evolution in mitochondrial ribosomal and ND-1 genes in lepidoptera: implications for phylogenetic analyses.
Authors: D P Pashley, L D Ke
Journal: Molecular Biology and Evolution (1992)

A 2,256-bp sequence of the mitochondrial genome of a lepidopteran (Spodoptera frugiperda) contains tRNAs for valine and leucine, the 16S rRNA, and three-quarters of the ND-1 presumptive protein-coding gene. A 64-bp stretch of unknown function was located between the rRNA and leucine tRNA. Sequence divergence in the 16S rRNA obtained from alignment with published insect sequences is consistent with phylogenetic hypotheses, in that Diptera and Lepidoptera are more closely related to each other (24% sequence divergence) than either is to Hymenoptera (31%). Within the ND-1 gene, sequences for four additional Lepidoptera were generated for a 314-bp region and contrasted with published sequences for the locust and Drosophila. Sequence divergence in this region was consistent with accepted phylogenetic relationships, but results of parsimony analyses were not. Cladograms consistently recovered accepted higher level relationships (monophyly of Lepidoptera), despite high homoplasy, but were unable to resolve superfamily and family relationships within Lepidoptera, regardless of the outgroup or character subset analyzed. Character analysis indicated that homoplasy was decreased at higher levels when first- and second-codon sites were used exclusively. At the lowest level (families), resolution was enhanced by inclusion of third-codon sites. Inability of molecular data to recover a well-established phylogeny may be rectified by additional characters or taxa, but it is clear that homoplasy is sufficiently high to caution against the acceptance of relationships generated with this molecular region that are not extremely robust.
Should prophylactic anticonvulsants be administered to patients with newly-diagnosed cerebral metastases? A retrospective analysis.
Authors: N Cohen, G Strauss, R Lew, D Silver, L Recht
Journal: Journal of Clinical Oncology (1988)

We analyzed a retrospective series of 195 patients with documented intracerebral metastases (ICM) to assess the frequency of late seizure development and the impact of prophylactic anticonvulsants. Eighteen percent of the patients presented with seizures. Of the remaining patients, 40% received prophylactic anticonvulsants (diphenylhydantoin [DPH] in greater than 90%). Ten percent developed late seizures at an interval from the diagnosis of ICM ranging from 1 to 59 weeks. No patient with a posterior fossa lesion developed seizure; conversely, patients with evidence on initial examination of cerebral hemispheric dysfunction had a higher incidence of late seizure development. The incidence of seizure was virtually identical in patients who received DPH compared with those in whom it was withheld, although two thirds of patients who developed seizure while on DPH had a serum anticonvulsant level that was subtherapeutic. Based on the above findings and until prospective data become available, we recommend that anticonvulsants be withheld in newly-diagnosed patients with ICM until the first seizure.
Elimination of the Effect of the <italic>A<sup>y</sup></italic> Gene on Pulmonary Tumors in Mice by Alteration of Its Effect on Normal Growth
Authors: W. E. Heston, George Vlahakis
Journal: JNCI Journal of the National Cancer Institute (1961)

Yellow (A × Y)F1 mice had more methylcholanthrene-induced pulmonary tumors and greater body weight and body size than did their brown litter mates. This confirmed earlier observations of the effect of the lethal yellow gene Ay on increasing pulmonary tumors and normal growth. When the difference in normal growth due to this gene was reduced by injection of goldthioglucose, which raised the weight of the browns almost to that of the yellows (whose weight was only slightly increased), the difference in tumor response due to the gene was eliminated. The average number of tumors in the treated browns was raised to a level comparable to that in the treated yellows. Inhibiting the effect of Ay on normal growth by restricting the food intake of the yellows—holding their weight to the level of the browns—reduced the average number of tumors in the yellows to that in the browns. These results suggest that the action of Ay in increasing the occurrence of pulmonary tumors is related to its action in increasing normal growth.
Multimodality treatment of stage IIIA non-small-cell lung carcinoma: a critical review of the literature and strategies for future research.
Authors: G M Strauss, M P Langer, A D Elias, A T Skarin, D J Sugarbaker
Journal: Journal of Clinical Oncology (1992)

PURPOSE AND DESIGN Stage IIIA non-small-cell lung carcinoma (NSCLC) is composed of regionally advanced yet potentially resectable disease. Many trials have evaluated a variety of therapeutic strategies. Most have been single-arm phase II trials, although a number of comparative phase III trials have also been performed. This review critically evaluates the existing literature on the treatment of stage IIIA NSCLC, particularly the various multimodality approaches that have been used. RESULTS A review of the existing literature does not establish the optimal treatment of stage IIIA NSCLC. Although radiation therapy alone remains the most commonly administered therapy for apparently unresectable disease, the status of radiation as a "standard" therapy can be seriously challenged based on existing data. Similarly, although a number of studies have established that surgical resection is clearly feasible in selected patients with stage IIIA disease, the efficacy of surgery also remains to be definitively established. Many studies have explored neoadjuvant chemotherapy, either in conjunction with radiation or surgery, with results that are best described as conflicting and controversial. CONCLUSIONS Without question, randomized phase III trials are required at this time to define what is to be considered optimal treatment. An attempt is made to define the most important questions that should be addressed in future phase III trials. Additionally, a number of study designs are suggested to best answer the therapeutic questions posed.
Reply: Antipsychotic Agents and Delirium
Authors: S. Jean Hsieh, Graciela J. Soto, Aluko A. Hope, Ana Ponea, Michelle N. Gong
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

We thank Dr. Song for his questions regarding our article.In our cohort, a larger proportion of delirious patients received antipsychotics (i.e., haloperidol and risperidone) compared with nondelirious patients (33% vs. 5%; P , 0.001) (1).Because the timing of antipsychotic administration relative to the development of delirium was not measured, we cannot comment on the relationship between antipsychotic use and the severity and duration of delirium.Although longer-term use of typical and atypical antipsychotics in older patients with dementia-related psychosis has been associated with an increased risk for sudden cardiac death (2-4), short-term antipsychotic use in the intensive care unit (ICU) and in perioperative settings has been shown to be safe (5-7).Furthermore, as Dr. Song indicated, limited evidence suggests that administration of antipsychotics to critically ill patients may improve clinical outcomes (7, 8).We did not find an association between antipsychotics and in-hospital mortality in bivariate analyses, and the addition of antipsychotic use to our multivariate model did not significantly alter the associations among acute respiratory distress syndrome, ICU delirium and coma, and in-hospital mortality.Modifying the Impact of ICU-Associated Neurological Dysfunction-USA (MIND-USA; www.clinicaltrials.gov,NCT 01211522), an ongoing large, multicenter, randomized placebo-controlled trial, will hopefully provide more definitive answers regarding the efficacy and safety of typical and atypical antipsychotics for the treatment of ICU delirium.
SV40 Enhances the Risk of Malignant Mesothelioma among People Exposed to Asbestos: A Molecular Epidemiologic Case-Control Study
Authors: Alfonso Cristaudo, Rudy Foddis, Agnese Vivaldi, Rodolfo Buselli, Vittorio Gattini, Giovanni Guglielmi, Francesca Cosentino, Franco Ottenga, Eugenio Ciancia, Roberta Libener, Rosangela Filiberti, Monica Neri, PierGiacomo Betta, Mauro Tognon, Luciano Mutti, Riccardo Puntoni
Journal: Cancer Research (2005)

Abstract We conducted a case-control study on asbestos exposure and presence of SV40 in tumor samples of malignant mesotheliomas (MMs) and bladder urotheliomas (BUs). PCR analysis revealed the presence of SV40 DNA (SV40+) in eight (42.1%) MMs and 6 (33.3%) BUs. The odds ratio for MM Asb− and SV40+ was 0.4 [95% confidence interval (95% CI), 0.03-4.0], for Asb+ and SV40− was 3.6 (95% CI, 0.6-21.0), and for Asb+ and SV40+ was 12.6 (95% CI, 1.2-133.9). Our results suggest that SV40 increases the risk of MM among individuals exposed to asbestos.