tbuckley/cabot-search huggingface dataset:
Hypertension (HTN) and proteinuria (PTN) as biomarkers of efficacy in antiangiogenic therapy for metastatic colorectal cancer (mCRC).
Authors: Y. K. Zee, N. Murukesh, G. Kumaran, R. Swindell, M. P. Saunders, A. R. Clamp, J. W. Valle, G. Wilson, G. C. Jayson, J. Hasan
Journal: Journal of Clinical Oncology (2010)

e13580 Background: There are no known predictive markers for the efficacy of vascular endothelial growth factor (VEGF) pathway-targeted therapies. HTN and PTN are known side effects of anti-VEGF therapy. The aim of our study was to assess if HTN and/or PTN with bevacizumab (Bev) or VEGF receptor tyrosine kinase inhibitors (TKI) are associated with clinical outcomes in patients (pts) with mCRC. Methods: We conducted a retrospective analysis of pts with histologically proven mCRC treated with either Bev or TKI in combination with chemotherapy at The Christie Hospital from 2006 to 2009. Results: Of 90 pts evaluated, 50 were eligible. 17 (34%), 4 (8%), and 3 (6%) pts developed Common Toxicity Criteria (CTC) (v 3.0) Grade (Gr) 1, Gr 2 and Gr 3 HTN, respectively. None developed ≥ Gr 4 HTN. Median time to onset of ≥ Gr 2 HTN was 9 (range 2-22) weeks. Response rates (RR) were 42% for pts with Gr 0-1 HTN compared to 86% for pts with ≥ Gr 2 HTN (p=0.043). Median progression free survival (PFS) was 9.4 months for pts with Gr 0-1 HTN and 10.9 months for pts with ≥ Gr 2 HTN (p=0.336). Median overall survival (OS) was 21.6 months for pts with Gr 0-1 HTN and 25.2 months for pts with ≥ Gr 2 HTN (p=0.270). 12 pts (24%) developed Gr 1 PTN and 4 pts (8%) developed ≥ Gr 2 PTN. Median time to onset of ≥ Gr 2 PTN was 12 (range 4-29) weeks. Median OS was 23.9 months for pts with Gr 0-1 PTN and 4.2 months for those with ≥ Gr 2 PTN (p=0.028). No pt with ≥ Gr 2 PTN had pre-existing renal disease. 2/4 pts with ≥ Gr 2 PTN had HTN which was controlled prior to starting antiangiogenic therapy. There was no significant correlation between the development of PTN with either PFS or RR. No significant association was found between the development of HTN and PTN on therapy. Conclusions: To our knowledge, this is the first study demonstrating the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for mCRC. Whilst HTN is predictive of a significantly higher RR, the development of PTN during treatment with Bev or TKI portends poorer survival and should be evaluated prospectively. Gr 0-1 HTN ≥ Gr 2 HTN P value Gr 0-1 PTN ≥ Gr 2 PTN P value RR (%) 42 86 0.043 45 75 0.271 PFS (m) 9.4 10.9 0.336 9.4 4.1 0.362 OS (m) 21.6 25.2 0.270 23.9 4.2 0.028 No significant financial relationships to disclose.
Growth of a Human Carcinoma of the Cervix in Mice Thymectomized at Birth&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: D Osoba, N Auersperg
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Growth of a Human Carcinoma of the Cervix in Mice Thymectomized at Birth Get access David Osoba, David Osoba Department of Medicine, Faculty of Medicine, University of British Columbia, and British Columbia Cancer Institute, Vancouver, B.C., Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Nelly Auersperg Nelly Auersperg Department of Medicine, Faculty of Medicine, University of British Columbia, and British Columbia Cancer Institute, Vancouver, B.C., Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 3, March 1966, Pages 523–527, https://doi.org/10.1093/jnci/36.3.523 Published: 01 March 1966 Article history Received: 28 June 1965 Published: 01 March 1966
The Role of Temozolomide and Radiation Therapy in Elderly Patients with Glioblastoma: a Monoinstitutional Retrospective Study
Authors: P. Farina, G. Lombardi, L. Bellu, P. Fiduccia, F. Berti, F. Navarria, A. Della Puppa, V. Zagonel
Journal: Annals of Oncology (2014)
Longitudinal microbiology of children with primary ciliary dyskinesia
Authors: Woolf Walker, Claire Jackson, Amanda Harris, Samantha Packham, Jane Lucas
Journal: European Respiratory Journal (2012)

Introduction 

Longitudinal changes in the respiratory microbiology of cystic fibrosis is well characterised; Staphylococcus aureus & Haemophilus influenzae are initially isolated before chronic Pseudomonas aeruginosa colonisation. However there is a paucity of similar microbiological data for primary ciliary dyskinesia (PCD).

Aims 

Longitudinal assessment of respiratory microbiology in paediatric PCD patients in a UK specialist centre.

Methods 

Results of sputum and cough swab microbiology from PCD patients (aged 2.1-19.3 years old, n=17) between January 2003–January 2012, were reviewed. Results were divided into 5-year cohorts corresponding to patient age at time of sample acquisition(table 1).

Results 

168/341 (49.1%) cultures were positive. H. influenzae was most prevalent (61/168, 36.3%) followed by S. aureus (32/168, 19%), Streptococcus pneumoniae (27/168, 16%) and P. aeruginosa (16/168, 9.5%). The predominance of H. influenzae continued throughout childhood apart from in 5-10 year olds where there were equivalent numbers of H. influenzae , P aeruginosa , S. aureus & S. pneumoniae (table 1).

View this table:

Table 1 – Percentage prevalence of bacteria in PCD children in a tertiary follow up clinic in the UK (overall and in age bands)





Conclusion 

H. influenzae is the predominant pathogen in our PCD patients throughout childhood, particularly >10 years old. The progression to chronic P. aeruginosa colonization seen in CF is not evident in our PCD population.
Late-breaking abstract: Inhaled pan-selectin antagonist bimosiamose in COPD: A double-blind, randomized, placebo-controlled phase II study
Authors: Henrik Watz, Daniel Bock, Michael Meyer, Kartin Schierhorn, Karin Vollhardt, Christiane Woischwill, Frauke Pedersen, Anne Kirsten, Kai-Michael Beeh, Wolfgang Meyer-Sabellek, Helgo Magnussen, Jutta Beier
Journal: European Respiratory Journal (2011)

Background: Bimosiamose a pan-selectin antagonist, previously attenuated ozone-induced airway-inflammation in healthy volunteers. Here we investigated the safety and efficacy of Bimosiamose in a cross-over, double-blind, randomized, placebo-controlled, multi-center trial in patients with COPD.

Methods: 77 moderate to severe COPD patients (GOLD II-III) were enrolled. Bimosiamose (10 mg) or placebo was inhaled by the breath actuated nebulizer Akita2 Apixneb™ for 28 days twice daily on top of standard bronchodilator therapy. Efficacy was assessed by cellular and non-cellular parameters in induced sputum at baseline and day 28 of both treatment periods. Lung function (FEV1, FVC, PEF, IC) was measured by standardized spirometry.

Results: The total AE ratio of Bimosiamose compared to placebo treatment was balanced. In induced sputum, as compared to placebo, treatment with Bimosiamose led to a reduction of absolute numbers of non-squamous cells (-23%), neutrophils (-24%), lymphocytes (-44%), eosinophils (-34%) and macrophages (-49%), IL-8 (-27%), MMP-9 (-16%) and MPO (-7%). Treatment difference was statistically significant for IL-8 (p=0.009) and macrophages (p=0.012). Compared to baseline, Bimosiamose improved FEV1 by 50 mL (-15 to 115; 95%CI) and IC by 117 ml (11 to 222; 95%CI) at day 28. Treatment difference was statistically significant for FVC (p=0.036).

Conclusions: Inhalation of Bimosiamose for 28 days was safe and well tolerated. It led to an attenuation of airway inflammation and trend towards lung function improvements. These findings support the potential of Bimosiamose as a new anti-inflammatory therapy for COPD.
The clinical significance of radiographically detected pulmonary neoplastic lesions in patients with head and neck cancer.
Authors: J P Malefatto, B S Kasimis, E M Moran, R B Wuerker, J J Stein
Journal: Journal of Clinical Oncology (1984)

The histopathologic features of pulmonary lesions found in 36 patients with head and neck cancer ( HNC ) whose chest radiograms had abnormalities suggestive of a neoplasm were reviewed. Ten patients (28%) had benign lesions but cancer was diagnosed in 26 patients (72%) by lung biopsy or at autopsy. Second primary lung cancer was found in 19 (53%) and metastatic HNC in seven (19%) of the 36 patients examined. The second lung primaries occurred in seven (100%) patients with HNC in stage I or II and in 12 (63%) of those in stage III or IV. The histologic examination revealed squamous cell carcinoma of the lung in eight (42%) of 19 patients, small cell carcinoma in six (31.5%), adenocarcinoma in three (16%), and large-cell carcinoma in two (10.5%). These findings indicate that a prompt histologic examination of radiographically detected neoplastic pulmonary lesions in patients who have, or have had HNC is mandatory because a second primary cancer of the lung may be found and cured with early treatment. Furthermore, a substantial number of the patients in this retrospective analysis had small-cell carcinoma of the lung and could benefit from current therapeutic advances for this type of tumor.
Association Between Risk of Recurrence Assessment and Adjuvant Treatment (Tx) Duration in Patients (Pts) with Resected Gastrointestinal Stromal Tumors (Gists)
Authors: A. Guerin, M. Sasane, C. Keir, G. Gauthier, A. Macalalad, E. Wu, A.P. Conley
Journal: Annals of Oncology (2014)
Geriatric medication management: Evaluation of pharmacist interventions and potentially inappropriate medication (PIM) use in older (≥65 years) cancer patients
Authors: S. M. Lichtman, M. K. Boparai
Journal: Journal of Clinical Oncology (2009)

9507 Background: Polypharmacy and inappropriate drug use are risk factors for adverse drug reactions (ADR) and poor compliance in older cancer patients. Drug evaluations in the past have not focused on this group. An evaluation of the prevalence of PIMs, pharmacist interventions, and the number and type of medications was performed. An educational component helped patients with drug management to increase adherence, avoid drug-drug and drug-disease interactions. Methods: A geriatric clinical pharmacist reviewed patient's medications, assessed understanding of their drugs, evaluated adherence, reviewed for PIMs (Beer's criteria), identified possible ADR and side effects, and provided detailed instructions. The pharmacist collaborated with the oncologist to determine appropriate therapy for the patient. Only patients over the age of 65 were eligible for this clinic. Consults were performed from March 2008 to June 2008, this includes new and follow up visits. An additional retrospective chart review was performed on 100 patients ≥ 65 years of age seen from July 2007 to November 2007. Results: There were 154 patients who underwent a prospective consultations; 74 yrs (65–91; 58% female). The interventions were: an alternative agent was recommended (31pts/20%), drug - drug interactions identified (15/10%), problems with adherence (58/37%), drugs discontinued (54/35%), additional medication (64/42%), dose change (17/11%), pain management (28/18%) and cost issues (19/12%). More then one issue was addressed during visits. In the retrospective study, median age 72 (65 - 90), 48% were females; medications: median 8 (range 0–23). Most common classes of medications were anti-hypertensives (52%), vitamins/herbals (46%), proton pump inhibitors (32%) and lipid lowering agents (29%). The prevalence of PIMs was 11%. The most common were propoxyphene, high doses of long-acting benzodiazepines and diphenhydramine. Conclusions: A geriatric medication management evaluation resulted in 50% of patients requiring specific interventions and identification of PIMs in 11% of patients. This type of intervention can optimize care by increasing adherence and avoiding adverse drug events and their serious sequelae. No significant financial relationships to disclose.
Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma
Authors: Luca Ceriani, Maurizio Martelli, Pier Luigi Zinzani, Andrés J. M. Ferreri, Barbara Botto, Caterina Stelitano, Manuel Gotti, Maria Giuseppina Cabras, Luigi Rigacci, Livio Gargantini, Francesco Merli, Graziella Pinotti, Donato Mannina, Stefano Luminari, Anastasios Stathis, Eleonora Russo, Franco Cavalli, Luca Giovanella, Peter W. M. Johnson, Emanuele Zucca
Journal: Blood (2015)
Elemental microanalysis of organelles in proximal tubules. I. Alterations in transport and metabolism.
Authors: A LeFurgey, A J Spencer, W R Jacobs, P Ingram, L J Mandel
Journal: Journal of the American Society of Nephrology (1991)

Oxygen deprivation to the kidney causes a multifactorial series of morphological, physiological, and biochemical alterations that occur as a function of time. One of the earliest events involves significant changes in the cellular contents of the physiologically important elements (ions) Na and K. Controversy exists as to the nature of changes in the content of the regulatory ion Ca, in either its free or bound form, and much less is known regarding in situ distribution and amounts of other elements such as Mg, P, S, and Cl during physiological or pathophysiological states. The objective of these studies was to evaluate element compartmentation in proximal renal tubules by using quantitative electron probe x-ray microanalysis, during specific conditions which are at least partially manifested during oxygen deprivation. Cells from control proximal tubule suspensions were compared with those exposed to (1) ouabain, to inhibit (Na+, K+)-ATPase; (2) mitochondrial uncouplers, to rapidly deplete ATP content; or (3) calcium ionophores, to cause a rapid elevation in cytoplasmic free calcium. In parallel with electron probe x-ray microanalysis imaging of subcellular elemental content, total cell potassium and ATP contents, enzyme release, oxygen consumption, cytoplasmic free calcium levels, and ultrastructural alterations were assessed. Results indicated that ATP depletion was, in the short term, more deleterious to renal proximal tubules than any of the tested ionic alterations. Intracellular organelles including mitochondria and nuclei appeared to be readily permeable to Na, K, and Cl, altering their concentrations of these ions in parallel with cytoplasmic concentrations. Lysosomes exhibited evidence of Cl accumulation, consistent with an inwardly directed proton ATPase with accompanying Cl transport. Whereas in the cytoplasm Na, K and Cl appeared to be mostly free, a large fraction of these ions within intracellular organelles seemed bound.
BNP is a predictor of mortality following COPD exacerbations
Authors: Martin Knolle, David Meek, Linda Pearce, Sarah Tarrant, Clare Laroche, Thomas Pulimood
Journal: European Respiratory Journal (2011)

Introduction:  There is a scarcity of biomarkers to predict mortality following exacerbations of chronic obstructive pulmonary disease (COPD). Pro-Brain Natriuretic Peptide (pBNP) is an indicator of cardiac function, elevated pBNP levels indicate cardiac failure. We measured pBNP levels in addition to standard assessments in patients referred to our COPD admission avoidance (AA) service.   Methods:  33 patients (current or ex-smokers) referred for AA over a one year period had their pBNP levels checked. 6 were excluded from analysis (3 troponin positive, 1 too well, 1 refused hospital admission, 1 admitted for cardiac failure). In addition to pBNP levels, most patients had several other assessments of their lung function performed. Of the 27 patients, 4 died over the following 12 months.  Statistical analysis was performed using Sigma Plot ™; data are mean + SEM.   Results:  Patient mortality was associated with higher levels of pBNP (8564 + 1703 pg/mL non-survivors vs 1162 + 553 pg/mL survivors, p = 0.004). There were no significant differences in spirometry, MRC scores or oxygen saturations.  Only 2 patients in the mortality group had a previous diagnosis of heart failure, while 7 in the non-mortality group did. Only 2 patients in the mortality group were treated for congestive cardiac failure with diuretics. None were on ACE-inhibitors or other heart failure treatment.   Discussion:  Despite the limitations of our study (small sample size, single center, relatively homogeneous population) pBNP may prove to be a powerful predictor for mortality following an exacerbation of COPD. In addition, our findings raise the question whether any element of underlying heart failure should be treated more aggressively in patients with COPD.
Role of fibreoptic bronchoscopy in early diagnosis of sputum smear negative pulmonary tuberculosis
Authors: Raj Kumar, Nitesh Gupta
Journal: European Respiratory Journal (2014)

Background: Fiberoptic bronchoscopy (FOB) is an alternative method to obtain respiratory specimens for diagnosis in clinical and radiological suspected sputum smear negative pulmonary tuberculosis (SSN-PTB).  Aim and Objective: The aim is to evaluate the diagnostic yield of various FOB procedures in SSN-PTB cases.  Method: 118 SSN-PTB, HIV negative patients (16-60 yrs; 71 males) underwent FOB for purpose of diagnosis. The FOB procedures performed were bronchial aspirate (BA), bronchoalveolarlavage (BAL), endobronchial (EBLB) and transbronchial biopsies (TBLB). Transbronchial needle aspiration (TBNA) was carried out in appropriate cases. The diagnosis of PTB was established in presence of either an acid fast bacilii on microscopy or positive culture or a caseating granuloma in biopsy specimen.  Results: Of 116 SSN-PTB suspected patients, 88 (75.86%) were diagnosed to be pulmonary tuberculosis. The predominant symptom was cough (86.2%); hemoptysis present in 14%. The commonly observed radiological patterns were cavitation (52.1%), consolidation (38.2%), multiple nodules (31.4%) and lymphadenopathy (19.6%). On inspection of tracheo-bronchial tree, endobronchial erythema (16.2%) and nodules (9.4%) were observed. The BAL from the suspected segment was diagnostic in 63 and bronchial aspirate in 29 patients, achieving a combined yield of 72.4%. The diagnostic yields of the biopsies demonstrating caseating granulomas were EBLB (8.7%), TBLB (13.5%) and TBNA (30.6%). The collective diagnostic yield of a FOB in SSN-PTB cases was 75.8%.  Conclusion:In tuberculosis endemic region, bronchoscopy may prove to be a beneficial technique in the assessment of suspected cases, which are sputum smear-negative.
The Course of Functional Impairment in Older Homeless Adults
Authors: Theora Cimino, Michael A. Steinman, Susan L. Mitchell, Yinghui Miao, Monica Bharel, Caroline E. Barnhart, Rebecca T. Brown
Journal: JAMA Internal Medicine (2015)

Discussion | Although the results of the 2014 congressional midterm elections in the United States may have constituted an important political shift toward the Republicans, the majority of physicians continued to be aligned with the Democrats.Of physicians who contributed to federal campaigns in the 2013-2014 election cycle, 55% contributed to Democratic candidates, 45% to Republican candidates.Political divisions among physicians will almost certainly persist.Given the increasing numbers of women physicians and salaried physicians, who typically ally with the Democrats, in contrast to surgeons, who typically ally with the Republicans, our findings suggest that the medical profession will be challenged to achieve consensus on health policy issues.The profession is unlikely to speak with one voice on questions such as the provision of health insurance or controlling the costs of medical care.The polarization among physicians, however, may spur both political parties to work harder to maintain and increase physicians' support.Thus, the political divisions among physicians may have the unintended effect of enhancing the political standing of the medical profession.
Non-Secretory Adenomas of the Pituitary Treated by Trans-Ethmoidal Sellotomy
Authors: G R Shone, S H Richards, M D Hourihan, R Hall, J P Thomas, M F Scanlon
Journal: Journal of the Royal Society of Medicine (1991)

A consecutive series of 35 clinically non-secretory pituitary adenomas treated surgically by the trans-ethmoidal approach is presented. Mean age at presentation was 60 years, with a male-to-female ratio of 2:1. These tumours present later than hormone secreting tumours: 90% were over 2 cm in diameter at operation. Seventy-one per cent of patients had impaired vision and 89% had hypopituitarism. Surgical treatment relieved or significantly improved visual fields in 79% of patients with impaired vision. Ninety-one per cent required permanent hormone replacement. Mean follow-up was for 4.4 years. Five tumours recurred, causing recurrent visual symptoms. No tumours recurred in those patients treated with postoperative radiotherapy, but follow-up in this group was only for a mean of 2.7 years.
Species Difference in Liver Microsomal Enzymes Involved in Mutagenic Activation &lt;italic&gt;N&lt;/italic&gt;-Hydroxy-&lt;italic&gt;N&lt;/italic&gt;-2-fluorenylacetamide&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: S Kaneda, T Seno, K Takeishi
Journal: JNCI Journal of the National Cancer Institute (1981)

The mutagenic activations of N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) by subcellular fractions of the livers of the Sprague-Dawley rat, C57BL mouse, Hartley guinea pig, Syrian golden hamster, and Macaca fuscata fuscata monkey were examined for sensitivity to paraoxon, which inhibits a deacetylase but not an arylhydroxamic acid acyltransferase. The mutagenic activation by liver microsomes was almost entirely mediated by a paraoxon-sensitive enzyme in all the animals tested. In contrast, the mutagenic activation by liver cytosol was mediated mostly by a paraoxon-sensitive enzyme in mice and guinea pigs, mostly by a paraoxon-resistant enzyme in rats and hamsters, and by both enzyme types in the monkey. In rats and guinea pigs, attempts were made to identify the enzymes causing mutagenic activation in the liver cytosol by a comparison of the elution positions of these enzymes in gel filtration and DEAE-cellulose column chromatography with those of known enzymes. In the rat liver cytosol, the mutagenic activation was mediated not only by acyltransferase but also by an unknown enzyme, which was resistant to paraoxon and differed from acyltransferase in chromatographic behavior. In the guinea pig liver cytosol, the activation was due to deacetylase activities, which could be separated into four fractions by gel filtration. These data indicate that species differ in the kinds of liver cytosolic enzymes involved in mutagenic activation of N-OH-2-FAA but not in the kind of liver microsomal enzyme involved.
Genotyping for HLA-A, B and C alleles in Japanese patients with pemphigus: prevalence of Asian alleles of the HLA-B15 family
Authors: S. Miyagawa, H. Niizeki, Y. Yamashina, T. Kaneshige
Journal: British Journal of Dermatology (2002)

Summary Background There have been only limited reports on major histocompatibility complex class I antigens in pemphigus. Objectives To characterize HLA‐A, B and C class I alleles by genotyping in Japanese patients with pemphigus, and to analyse the possible association of class I alleles with disease susceptibility within a relatively homogeneous ethnic population. Methods Alleles of HLA‐A, B and C, and DRB1 and DQB1 loci were fully determined in 51 Japanese patients with pemphigus. Results Asian alleles of the HLA‐B15 family, including the allele B*1507, which was significantly increased in comparison with normal controls, were prevalent in patients with pemphigus vulgaris (PV). The prevalence of B*15 alleles in patients with PV was not due to linkage disequilibrium with HLA‐DR4 or DR14 alleles, which have been shown to confer strong susceptibility to PV across racial barriers. In contrast to the unique distribution of the HLA‐B alleles, HLA‐A and C alleles were unremarkable in patients with PV when compared with normal control subjects. Conclusions These results suggest that there may be differences in the ethnic concentrations of different HLA‐B alleles in patients with PV.