tbuckley/cabot-search huggingface dataset:
The incremintal value of chest computed tomography on chest radiographs in the diagnosis of pneumonia in bedridden patients
Authors: Hamdy Ali Mahmoud, Sayed Waar Ahmad
Journal: European Respiratory Journal (2013)

Objectives: to assess the diagnostic value of chest radiographs for the diagnosis of pneumonia in old senile bedridden patients and comparing it with the non-enhanced high resolution chest tomography(CT). Materials and methods: We prospectively evaluted bedridden patients hospitalized with moderate to high clinical propability of pneumonia. Chest radiographs were interpreted in ablind fashion by 3observers and classified as definite, normal or uncertain for pneumonia. Chest CT was done within 12 hours of the chest radiograph. We applied Bayesian analysis to assess the accuracy of chest radiographs in the diagnosis of pneumonia. Results: In 24 month period, 60 patients (36 females and 24 males) were evaluated. Their chest radiographs were interpreted as positive, uncertain or negative for pneumonia in 15(25%), 14(23%) and 31(52%) patients, respectively, while CT confirmed pneumonia in 12(80%), 10(71%) and 11(35%). The sensitivity of the chest radiography to diagnose pneumonia was 65%, the specificity was 83%, the positive and negative predictive values were 83%, and 65% respectively, while the overall accuracy was 70%(95% confidence interval, 50% to 79%). Conclusion:In bedridden patients with suspected pneumonia, regular chest radiography could not rule out the diagnosis and so chest CT scanning should be done to provide valuable diagnostic information.
Evolution of retroposons by acquisition or deletion of retrovirus-like genes.
Authors: M A McClure
Journal: Molecular Biology and Evolution (1991)

The retroid family consists of all genetic elements that encode a potential reverse transcriptase (RT). Members of this family include a diversity of eukaryotic genetic elements (viruses, transposable elements, organelle introns, and plasmids) and the retrons of prokaryotes. Some retroid elements have, in addition to the RT gene, other genes in common with the retroviruses. On the basis of RT sequence similarity, the retroposon group is defined as the eukaryotic long interspersed nuclear elements, the transposable elements of (1) Drosophila melanogaster (I and F factors), (2) Trypanosoma brucei (ingi element), (3) Zea mays (Cin4), (4) Bombyx mori (R2Bm), and members of the group II introns and plasmids of yeast mitochondria. The data presented here elucidate the extent of the relationships between the retroposons and other retroid-family members. Protein-sequence alignment data demonstrate that subsets of the retroposons contain different assortments of retroviral-like genes. Sequence similarities can be detected between the capsid, protease, ribonuclease H, and integrase proteins of retroviruses and several retroposon sequences. The relationships among the retroposon capsid-like sequences are congruent with the RT sequence phylogeny. In contrast, the similarity between ribonuclease H sequences varies in different subbranches of the retroposon lineage. These data suggest that xenologous recombination (i.e., the replacement of a homologous resident gene by a homologous foreign gene) and/or independent gene assortment have played a role in the evolution of the retroposons.
Clinical features, outcome and factors associated with mortality in patients with Nocardia pneumonia
Authors: Irfan Muhammad, Ahmed S. Haque, Kauser Jabeen, Wasay Hafiz Abdul, Safia Awan, Fasih Ur Rehman
Journal: European Respiratory Journal (2012)

Background:  Nocardia pneumonia has emerged as an important cause of mortality and morbidity in both immunocompetent and immunocompromised hosts. In this study, risk factors, clinical features, outcomes and factors associated with mortality in nocardia pneumonia were reported.  Materials and Methods:  Clinical records of all cases diagnosed with nocardia pneumonia during 2001-2010 were reviewed. Identification of Nocardia species was based on positive Gram stain and positive modified acid-fast stain results, colonial morphology, and conventional biochemical reactions. Data was analyzed using SPSS version 17. Factors associated with mortality was assessed by univariate and multivariate analysis.  Results:  Fifty Five cases were identified. Fever, cough and dyspnea were the most common presentations. Most important risk factors were chronic steroid administration (69%) and an underlying malignancy (24%). Most common complications observed were respiratory failure (27%) and septicemia (27%). 19(34.5%) patients died. Factors associated with mortality were Smoking (p 0.01), decreased appetite (p 0.007), leukocytosis (p 0.006), mechanical ventilation (p   Conclusion:  We report underlying malignancy and chronic corticosteroid therapy as a risk factor for development of nocardiosis in our patients. High mortality rate in this cohort were observed. Septicemia was found to be independent risk factor for mortality. Clinicians should keep a high index of suspicion for early diagnosis and management to decrease mortality.
HER family ligand traps (Hermodulins) inhibit tumor cell proliferation in vitro and growth of subcutaneous tumors in nude mice
Authors: H. Shepard, Pei Jin, Malgorzata Beryt, Juan Zhang, Lisa Turin, Cathleen Brdlik, Ying Feng, John Huang, Xiaomei Bai, Jeffrey Higaki, Daniel Maneval
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

A2 

Resistance to single-targeted anti-HER agents has been attributed to multiple HER co-activation that occurs through receptor dimerization. We constructed and purified novel molecules comprising HER1/EGFR and HER3 ligand binding domains tethered to a human Ig Fc region. By design, these Hermodulins bind the majority of HER ligands and provide a therapeutic anti-cancer strategy similar to clinically-proven molecules developed for both TNF-alpha and VEGF-related diseases. RB200, a prototypic Hermodulin, was evaluated for activity against a spectrum of cell lines derived from human malignancies. Effects on monolayer cell growth in the presence of serum were measured. Dose-dependent inhibition of cell growth by RB200 was demonstrated in many cell lines. Synergistic growth inhibition in vitro was also demonstrated when RB200 was combined with small molecule tyrosine kinase inhibitors (TKIs) and conventional cytotoxic chemotherapies. Nude mice bearing established subcutaneous human NSCLC tumors, derived from the H1437 tumor cell line, were used to evaluate in vivo activity of RB200. Mice (N=10/group) were treated with RB200, PBS or cetuximab. Tumor sizes were measured via external calipers. These studies showed ~70% inhibition of tumor growth at 10 mg/kg vs. PBS control. Greater anti-tumor effects were observed when RB200 was combined with the TKIs. Optimized versions of Hermodulins with enhanced activity are being developed.
Association of ERG-PTEN expression profile of prostate biopsy with PSA velocity.
Authors: Amit Algotar, Anne Cress, Ray Nagle, Mitchell Sokoloff, Parminder Singh, Roxanna Behnejad, Steven Stratton
Journal: Journal of Clinical Oncology (2015)

92 Background: Although ERG and PTEN expression has demonstrated to have a role in prostate carcinogenesis, its association with important clinical markers such as PSA velocity (rate of prostate specific antigen [PSA] change over time) is currently unknown. This novel pilot study presents the results of the above association with the aim of understanding its clinical utility. Methods: Data for this study was obtained from men enrolled in a phase 2 clinical trial conducted to determine the effect of selenium supplementation on prostate cancer progression. All men in this trial were diagnosed with prostate cancer and opted for watchful waiting as their treatment modality. Biopsy tissue collected at randomization was stained for ERG and PTEN using immunohistochemistry techniques. PSA was measured at baseline and at each follow-up visit (every three months). PSA velocity was calculated using mixed effects regression models and the study group was divided into three tertiles. Results: Data from 77 subjects indicates ERG and PTEN expression is independently associated with lower PSA velocity (p = 0.02 and 0.037 respectively). Joint effect of ERG and PTEN expression on PSA velocity was also analyzed using logistic regression. As compared to the wild type (ERG+/PTEN-), ERG-/PTEN- and ERG-/PTEN+ subjects demonstrated increased risk for high PSA velocity. Odds ratios (95% confidence intervals) are: 4.05 (0.68, 24.1) and 1.71 (0.12, 23.1), respectively. These models were adjusted for age, race and Gleason score. Conclusions: This is the first study to report on an association between ERG-PTEN expression and PSA velocity, an important clinical marker of aggressive prostate cancer. Results of this study are counterintuitive to the current understanding of ERG-PTEN mechanism in prostate carcinogenesis indicating presence of yet undiscovered molecular pathways. Hence further research is needed to delineate these pathways and determine clinical utility of ERG and PTEN expression in prostate cancer.
Is Bad Luck the Main Cause of Cancer?
Authors: C. R. Weinberg, D. Zaykin
Journal: JNCI Journal of the National Cancer Institute (2015)

A recent study reports that the log lifetime incidence rate across a selection of 31 cancer types is highly correlated with the log of the estimated tissue-specific lifetime number of stem cell divisions. This observation, which underscores the importance of errors in DNA replication, has been viewed as implying that most cancers arise through unavoidable bad luck, leading to the suggestion that research efforts should focus on early detection, rather than etiology or prevention. We argue that three statistical issues can, if ignored, lead analysts to incorrect conclusions. Statistics for traffic fatalities across the United States provide an example to demonstrate those inferential pitfalls. While the contribution of random cellular events to disease is often underappreciated, the role of chance is necessarily difficult to quantify. The conclusion that most cases of cancer are fundamentally unpreventable because they are the result of chance is unwarranted.
Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer.
Authors: L Gianni, L Viganò, A Locatelli, G Capri, A Giani, E Tarenzi, G Bonadonna
Journal: Journal of Clinical Oncology (1997)

PURPOSE We performed a pharmacologic investigation of paclitaxel (PTX) infused over 3 hours and bolus doxorubicin (DOX) to assess the role of sequence, interval between drugs, and duration of doxorubicin infusion on paclitaxel and anthracycline plasma disposition. We also explored possible mechanisms of pharmacokinetic interference involving the physiologic role of the multidrug resistance phenotype in anthracycline and taxane biliary excretion. PATIENTS AND METHODS Pharmacokinetics was performed in 80 cycles and 36 women with previously untreated metastatic breast cancer. PTX, DOX, and their metabolites 6 alpha-hydroxyl-PTX (6 alpha OH-PTX) and doxorubicinol (DOL) were measured by high-pressure liquid chromatography (HPLC). Human breast cancer MCF-7 wild-type (WT) and resistant (TH) cell lines were cultured in whole human plasma to study anthracycline retention after treatment with different combinations of PTX, Cremophor EL (CEL) (PEG35 castor oil; BASF, Parsippany, NJ), and DOX. RESULTS Pharmacokinetic interference between PTX and DOX was responsible for nonlinearity of DOX plasma disposition and increased concentrations of DOX and DOL. These effects were PTX dose-dependent, DOX concentration-dependent, and likely a result of interference at the level of liver elimination. In view of the physiologic role of P-glycoproteins (P-gp) in xenobiotic biliary excretion, retention of DOX was assessed in MCF-7 WT and MCF-7 TH cells. Intracellular was significantly higher in MCF-7 WT than MCF-7 TH (P &lt; .05). However, concomitant exposure to DOX, PTX, and CEL caused similar DOX retention in both MCF-7 WT and TH cells. CONCLUSION PTX, as clinically formulated in CEL, is responsible for a nonlinear disposition of DOX and DOL. Nonlinearity is PTX- and DOX-dependent, and possibly caused by competition for biliary excretion of taxanes and anthracyclines mediated by P-gp. Nonlinearity indicates that even minor modifications of dose and infusion duration of DOX and PTX may lead to unpredictable pharmacodynamic consequences. The postulated role of P-gp suggests that CEL is clinically active, and advises caution in designing combinations of PTX with other drugs that are substrate for P-gp.
The value of obtaining brushing samples in addition to biopsy and washings in the diagnosis of lung cancer
Authors: Sharjeela Tariq, Timothy Howes
Journal: European Respiratory Journal (2013)

Background:  The British Thoracic Society recommends ‘obtaining a combination of biopsy, brushings and washings in cases of endoscopically visible tumour’ 1.   Aim:  We performed this study to evaluate the value of obtaining endobronchial brushings in addition to biopsy and washings during fiberoptic bronchoscopy in the diagnosis of broncho-centric lung cancer, in cases of visible and invisible endobronchial abnormality.  Methods:  We retrospectively collected data on 100 consecutive cases of proven lung cancer, where all 3 sampling techniques including biopsy, brushings and washings were used during bronchoscopy.  Results:  The tumour was visible endobronchially in 85% of cases, 5% of cases had external compression and 5% had abnormal mucosa. In the remaining 5%, there was no endobronchial lesion and no mucosal abnormality.  In 3 cases, biopsy and washings were both normal, a diagnosis was made solely on brushings; of these, there was no endobronchial lesion or visible mucosal abnormality in 1 case and only mucosal abnormality seen in the remaining 2.  In 5 cases, the biopsy was negative, ‘suspicious cells’ were found on washings and the diagnosis was only confirmed on brushings.  In a further 5 cases, ‘suspicious cells’ were seen on biopsy, the wash was negative and the diagnosis confirmed on brushing.  Conclusion:  Our data suggest that there is a diagnostic value in performing brushings in all cases of suspected ‘broncho-centric’ lung cancer whether or not there is a visible endobronchial abnormality.  References:  British Thoracic Society Guidelines on Diagnostic Flexible Bronchoscopy  Thorax  2001.  56 : (Suppl I); i1-i 21.
Dying in the dark: sunshine, gender and outcomes in myocardial infarction
Authors: Kathleen M Beauchemin, Peter Hays
Journal: Journal of the Royal Society of Medicine (1998)

We report a natural experiment that took place in a cardiac intensive care unit (CICU). We had been alerted to the possibility that sunny rooms would be conducive to better outcomes by our findings in the psychiatric unit, and by reports that depressed cardiac patients did less well than those in normal mood. The 628 subjects were patients admitted directly to the CICU with a first attack of myocardial infarction (MI). Outcomes of those treated in sunny rooms and those treated in dull rooms were retrospectively compared for fatal outcomes and for length of stay in the CICU. Patients stayed a shorter time in the sunny rooms, but the significant difference was confined to women (2.3 days in sunny rooms, 3.3 days in dull rooms). Mortality in both sexes was consistently higher in dull rooms (39/335 dull, 21/293 sunny). We conclude that illumination may be relevant to outcome in MI, and that this natural experiment merits replication.
Causes of delay in the diagnosis of pulmonary tuberculosis
Authors: Joana Alves, Denisa Mendonça, Ana Correia, Raquel Duarte
Journal: European Respiratory Journal (2011)

Background:  Early diagnosis of tuberculosis and its treatment are essential in a control program, as it reduces the severity, mortality and transmission of the disease in the community.   Aim:  To determine the time between symptom onset and demand of health services (patient delay) and between first consultation and start of treatment (health care delay). For each interval, determinants of possible delays were analyzed.   Methods:  A cross-sectional study was performed in Porto (North of Portugal), based on data from the national tuberculosis surveillance system, including confirmed cases of pulmonary tuberculosis diagnosed during 2008/2009. We defined 3 weeks for patients9 and 1 week for health cares9 delays as cut off points to dichotomize the sample into either delay or non delay. Chi-square test were used to analyze associations (α=0.05).   Results:  We analyzed 165 individuals and of those, 122 (76.5%) were male and the mean age 48 years old. Median patient delay was 4 weeks. Patient delay was more frequently associated (although not statistically significant -  p >0.1) with unemployment (68.4%  vs  61.4%), alcoholism (76.5%  vs  62.7%) and other co-morbidities (72.2%  vs  64.9%). The median time of health care delay was 1 week. Negative sputum smear was significantly associated (69.7%  vs  34.2% -  p =0.001) with this delay.   Conclusion:  We could not identify target groups significantly associated with patient delay. Strategies should be directed to general population in order to increase awareness about the disease. Negative sputum smear was associated with health care delay which can be justified by the time needed to study these patients.
Exercise-Induced Post-Ischemic Left Ventricular Delayed Relaxation or Diastolic Stunning
Authors: Katsuhisa Ishii, Makoto Imai, Tamaki Suyama, Motoyoshi Maenaka, Takahiro Nagai, Masaki Kawanami, Yutaka Seino
Journal: Journal of the American College of Cardiology (2009)
Effect of energy food intake on exhaled breath temperature in healthy subjects
Authors: Tanya Kralimarkova, Roxana Mincheva, Ryan Kadavil, Jasmine John, Dimitar Tihomirov, Vasil Dimitrov, Todor Popov
Journal: European Respiratory Journal (2012)

Background:  Evaluation of the exhaled breath temperature (EBT) is a non-invasive approach to assess airway inflammation. Measuring it by a portable handheld device (PHD) has made it applicable for field studies and as an individual device for monitoring. Different activities and ambient influences may act as potential confounders. The aim of this study was to assess the effect of eating easily utilized energy food on the level and time course of EBT.   Methods:  Eleven non-smoking healthy subjects (3 men) at a mean age of 23 years volunteered for the study. They were trained to measure EBT with a portable handheld device (X-halo, Delmedica, Singapore). They measured their EBT and axillary temperature (AxT) in the morning before and 5, 30, 60 and 120 minutes after eating one bar of Snickers characterized by high energy content (382 kilocalories). On the next day they repeated the measurement after eating 2 bars of Snickers.   Results:  As opposed to AxT, EBT was affected by eating one bar of Snickers:   *  = Significant change from baseline.  The same pattern was repeated on the day when the subjects had two bars of Snickers. We did not find significant dose-response relationship between EBT and the single or double dose of the energy food intake.   Conclusions:  Food ingestion affects the level of EBT in healthy subjects over 60 minutes. The failure to establish a dose response relationship between EBT and the different caloric regimens may indicate that they both happen to be on a plateau of the dose-response slope.
Psychosocial effects of continuous oxygen therapy in hypoxaemic chronic obstructive pulmonary disease patients
Authors: A Lahdensuo, M Ojanen, A Ahonen, J Laitinen, H Poppius, Y Salorinne, R Tammivaara, P Tukiainen, K Venho, V Vilkka
Journal: European Respiratory Journal (1989)

Twenty six hypoxaemic patients with severe and stable chronic obstructive pulmonary disease (COPD) were treated with continuous domiciliary oxygen for a six month period. The patients were evaluated 1, 3 and 6 months after the start of oxygen therapy. In addition to blood gas analysis, 15 coping skills were evaluated by the patient and by the nurse, who also rated the general activity of the patients. Depression was measured by Beck Depression Inventory (BDI) at the start of the trial and after six months' oxygen therapy. The general psychosocial response was meagre; no significant changes were observed in any psychosocial measures. The response was slightly better in younger and less hypoxaemic patients. We conclude that the psychosocial response to oxygen therapy in severely hypoxaemic COPD patients is limited.
Heidelberg retina tomography and optical coherence tomography in normal, ocular-hypertensive, and glaucomatous eyes11The authors have no financial interest in any device or technique described in this article.
Authors: Andrea Mistlberger, Jeffrey M Liebmann, David S Greenfield, Mauricio E Pons, Sek-Tien Hoh, Hiroshi Ishikawa, Robert Ritch
Journal: Ophthalmology (1999)
Effects of Estrogenic Hormones on the Mammary Tissue of Agent-Free and Agent-Bearing Male Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: William T. Hall, Dan H. Moore
Journal: JNCI Journal of the National Cancer Institute (1966)

Three-week-old male (C3H × A)F1 × C3H agent-bearing backcrossed hybrid mice were castrated and given injections of diethyl-stilbestrol thrice weekly. Agent-free (C3Hf × Ax)F1 × C3Hf backcrossed hybrids from the same strains were similarly prepared and given injections of diethylstilbestrol or delestrogen. Mammary adenocarcinomas developed during the 7th to 11th months in 90 percent of the agent-bearing mice given injections. All the mammary glands were enlarged and filled with milk. The epithelial cells of the tumors and the nontumorous glands of the agent-bearing animals had budding B particles, and the intracellular spaces contained an abundance of mature B particles like those seen in female mice. None of the agent-free mice produced either a mammary tumor or B particles. These findings indicate that mice free of virus particles do not develop mammary tumors from steroid hormone treatment alone.
Clinical reproducibility of the pedriatric sleep questionnaire (PSQ)
Authors: José Luis Fernández Sánchez, Amparo Rosa Sánchez Serrano, Paola Gudiel Arriaza, Sergio Cadenas Menéndez, Susana Carmen García Vicente, Juan Márquez Márquez, Mateo Torracchi Carrasco, Irene Alaejos Pascual, María José Bernabé Barrios
Journal: European Respiratory Journal (2011)

The Pediatric Sleep Questionnaire (PSQ) has two versions: a shorter one, which has been validated for sleep-related breathing disorders, and an extended version, which deals with a wider range of sleep disturbances. The Spanish version of the PSQ could be a suitable tool both for screening patients who require medical tests and for epidemiological research. Our objective was to evaluate its reproducibility in the clinical setting.

Material and methods: 62 patients in pediatric age were gathered consecutively, 53% were male with a mean age of 5.15 years old (± 3.05) to whom a conventional polysomnography (PSG) was performed because of a probable diagnosis of SAHS. The 24 items of the PSQ (validated Spanish version for sleep- related breathing disorders) were completed at the Pediatric Outpatient Clinic and the night before the sleep study performed at the Respiratory Care Sleep Unit, both data were compared to let show discrepancies between PSQ scores.

Results: The mean PSQ score at the Pediatric Outpatients Clinic was 9,42 (± 4,77) and the previous score prior the PSG at the Sleep Unit was 8,7±4,99, with a correlation between both of 0,66 (p <0,0001). The statistical concordance between the two determinations of PSQ was moderate considering the cut line when 33% of the items were positive (kappa index 0.4, p= 0.003).

Conclusion: The PSQ score is highly variable when administered sequentially to a clinical pediatric population being evaluated for a potential sleep-related breathing disorder.