tbuckley/cabot-search huggingface dataset:
Advantages of intraoperative medical hyperspectral imaging (MHSI) for the evaluation of the breast cancer resection bed for residual tumor
Authors: J. E. Freeman, S. Panasyuk, A. E. Rogers, S. Yang, R. Lew
Journal: Journal of Clinical Oncology (2005)

709 Background: Medical Hyperspectral Imaging (MHSI) is a novel, camera-based method of imaging spectroscopy that integrates spatial & spectroscopic data from tissue in a simple image. Despite advances in surgery, adequate breast tumor resection is an issue with over 30% recurring locally. MHSI may provide noninvasive, rapid, & inexpensive evaluation of residual cancer in the tumor bed at the time of resection. Here, we demonstrate proof-of-principle in a preclinical rat model. Methods: Female Sprague-Dawley rats received 50mg/kg DMBA by gastric gavage at age 8wks to induce breast tumors. 21 rats developed multiple tumors. We studied 98 tumors and performed partial resection of 41 tumors, yielding 41 full tumor/partial resection/tumor bed sets for analysis. Tumor was exposed & resected, intentionally leaving a small (0.5mm) piece of residual tumor in the bed. Gross examination, MHSI & histopathology were recorded. MHSI using visible light system (HyperMed, Inc., Watertown, MA) provided 40μm resolution (field of view 4X6cm). Algorithms based on spectral characteristics of tissue type were developed to distinguish tumor & normal tissues. Primary endpoint was designation of tumor/normal tissue found to remain in the tumor bed by gross exam, MHSI algorithm, & histology. Results: Interim analysis on 16 full sets of tumor bed data (gross/MHSI/hist.) showed that MHSI correctly identified tumor in all cases & detected tumor in the resection bed of 0.5mm whereas standard histopathology failed to do so in 2 cases (agreement kappa = 0.75). Conclusions: MHSI may provide reliable data in near-real time with a convenient device for the surgeon in the operating room. MHSI shows promise for increasing sensitivity of detection of residual tumor over current surgical tissue sampling techniques. Follow-on studies in patients are planned. Supported by: CDMRP Concept Award, DAMD17-03-1-0767 BC024521, NIH-NIEHS I-P01 ES11624–03 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration HyperMed HyperMed HyperMed HyperMed
Towards a molecular profile of melanoma: Dysregulation of the Ras/Raf/ERK pathway
Authors: U. R. Hengge, A. Baer, W. Bardenheuer, S. Nambiar, A. Tannapfel, M. Schartl
Journal: Journal of Clinical Oncology (2004)

7555 Background: Signal transduction pathways are increasingly being studied in melanoma. However, only the advent of chip technology and mass spectrometry has enabled the simultaneous analysis of multiple genes and gene products from melanoma samples. Methods: We attempted to analyze the Ras/Raf/ERK pathway in malignant melanoma specimens and metastases in comparison with normal human melanocytes and several melanoma cell lines. Results: By multidimensional scaling plot analysis melanoma metastases clustered in three different groups: two groups had similar expression profiles with the melanoma cell line BLM being representative of one cluster. Further confirmation on the protein level was obtained for the mitogen-activated protein kinase kinase (MEK)-1 and 3, that was highly upregulated as well as the downstream regulated mitogen-activated protein kinases (MAPK) p38 and extracellular-regulated kinase (ERK)1/2 (p44/42) in the majority of the analyzed samples. Importantly, phosphorylated ERK1/2 (p44/42 MAPK) as the functionally active signaling kinase, was abundant in most analyzed melanomas (4 of 6) as evidenced by Western blot analysis and immunohistochemistry (17 of 24 specimens), respectively. Conclusions: In summary, the Ras/Raf/ERK pathway that is relevant for proliferation, survival and angiogenesis seems to be critically involved in the development of melanoma without the pre-requirement of activating B-raf mutations. Ultimately, such molecular profiling may lead to a molecular classification of melanoma and may help to identify particular subgroups with regard to response to therapy, metastasis, and perhaps even prognosis. No significant financial relationships to disclose.
Control of Expression of Differentiated Functions in Neuroblastoma Cell Hybrids12
Authors: Fred Gilbert
Journal: JNCI Journal of the National Cancer Institute (1976)

Cell hybrids have been extensively utilized for gene mapping; more than 50 enzymes and nonenzyme proteins have been assigned to individual human chromosomes. Hybrids have also been used in the study of differentiation; fusions involving mouse or human neuroblastoma cells and various nonneuronal lines resulted in hybrid cells that continued to express neuron-specific functions. The expression of the differentiated state is, however, not an all-or-none phenomenon: One neuronal trait may be evident in such hybrids, in the absence of others. The potential usefulness of the human neuroblastoma hybrids for the assignment of genes involved in the expression of differentiated functions to specific chromosomes is discussed.
Proton Pump Inhibitor (Ppis) Therapy May Impair Capecitabine (Cape) Efficacy in Metastatic Gastroesophageal Cancer (Gec), Results from the Trio-013/Logic Trial
Authors: M.P. Chu, J.R. Hecht, D. Slamon, A. Fontaine, K. King, S. Koski, K. Mulder, J. Price Hiller, A. Scarfe, J. Spratlin, Y. Bang, P.M. Hoff, A. Sobrero, S. Qin, K. Afenjar, V. Houe, Y.J. Huang, S. Khan-Wasti, N. Chua, M. Sawyer
Journal: Annals of Oncology (2014)
Bureaucracy is forcing GPs to quit under "euphemism of early retirement"
Authors: A. Rimmer
Journal: BMJ (2015)

Bureaucracy is forcing GPs to leave the profession under the “euphemism of early retirement,” a leading academic has said.

Speaking at the Royal College of General Practitioners’ City Health conference in London on Friday 1 May, Trish Greenhalgh, a professor at the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said that too many experienced doctors were leaving the profession.

“We need to stem …
Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy.
Authors: L H Wexler, L Weaver-McClure, S M Steinberg, J Jacobson, P Jarosinski, N Avila, P A Pizzo, M E Horowitz
Journal: Journal of Clinical Oncology (1996)

PURPOSE To evaluate whether recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. PATIENTS AND METHODS Thirty-seven newly diagnosed patients age 1 to 25 years were randomized to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 micrograms/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was &gt; or = 500/microliter on 2 consecutive days. RESULTS GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P &lt; .0001), but did not significantly affect the grade of granulocyte nadir. No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival. GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/microliter [range, 3,000 to 288,000] v 59,000/microliter [range, 3,000 to 309,000], P &lt; .0001; median time to recovery &gt; 75,000/microliter, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P &lt; .0001). CONCLUSION GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity.
Role of Dr-70 immunoassay in suspected malignant pleural effusion
Authors: Debraj Jash, Kaushik Saha, Amitabha Sengupta, Sourindra Nath Bannerjee
Journal: European Respiratory Journal (2013)

Introduction or background: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow up. Aims and objectives: To evaluate the role of DR-70 immunoassay in suspected malignant PE. Methods: We conducted a cross sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control. Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase (ADA) less than 30 U/L were taken as cases. We had selected normal subjects among relatives of patients having normal blood chemistry and radiological investigations. Results: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut off value of 2 mg/L.  Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (p = 0.08). Conclusion: DR-70 assay has high sensitivity in detecting underlying lung cancer but has no role in differentiating malignant PE from non-malignant PE.
Noninvasive Genotyping Using Digital Pcr Before and After Combination Therapy with Gefitinib and Pemetrexed (Pem) or S-1 for Non-Small Cell Lung Cancer (Nsclc) Resistant to Epidermal Growth Factor Receptor (Egfr) Tyrosine Kinase Inhibitors (Tki)
Authors: Y. Takagi, Y. Nakahara, Y. Hosomi, A. Kagei, T. Yamamoto, M. Yomota, Y. Okuma, S. Mikura, T. Okamura
Journal: Annals of Oncology (2014)
Comparison of interferon gamma assay and tuberculin skin test in household TB contacts
Authors: Svetlana Kasikovic Lecic, Slobodan Pavlovic, Vesna Kuruc, Miroslav Ilic, Darinka Kukavica
Journal: European Respiratory Journal (2012)

Background: Identification and treatment of active and latent TB infection among household contacts is an effective strategy for TB control.  Aim: To compare the QuantiFERON-TB Gold in tube assay (QFT) to tuberculin skin testing (TST) for detecting TB infection among household contacts.  Methods: The participants were 50 immunocompetent household TB contacts. All the participants were interviewed using a questionnaire and tested by the QFT and TST. TST results were analyzed at 5 mm and 15 mm cut-off. The QFT test was interpreted following the manufacturer′s criteria. In all the subjects with a positive TST (≥15mm)/QFT, X-ray was performed.  Results: All contacts had previously been vaccinated and revaccinated with BCG and they had been screened with the TST at least once in the past. 52% (26/50) household contacts had positive TST (≥5mm) results, and 12% (6/50) had TST≥15mm. 18% (9/50) had a positive QFT finding. The comparison of TST (threshold 5 mm) and QFT results revealed a low agreement: 62% (31/50); (k=0.259). The comparison of TST (threshold 15 mm) and QFT results revealed a moderate agreement: 90% (45/50); (k=0.611). Active TB was detected in 4% (2/50) subjects.  Conclusion: Despite the intense exposition of immunocompetent household TB contacts to a highly symptomatic index case, transmission of M. tuberculosis rarely occurred. The data indicate that a previous BCG vaccination and/or TST testing could be a reason for the false positive TST results. Two tests can be used in the diagnostic algorithm of TB infection in testing household contacts. In order to apply the TST a higher cut off values (≥15 mm) should be used for positivity. The QFT assay could replace the TST in BCG vaccinated population.
Endotracheal Intubation Skills of Medical Students
Authors: D O'Flaherty, A P Adams
Journal: Journal of the Royal Society of Medicine (1992)

The ability and confidence of clinical medical students to insert endotracheal tubes correctly and quickly and to recognize oesophageal misplacement was evaluated. Ten (33%) of the medical students intubated the trachea correctly at their first attempt but 14 (47%) incorrectly identified the position of the endotracheal tube. However, recognition improved by their second and third attempts (70% and 80% respectively). Ninety-three percent of students intubated correctly on their third attempt. Although medical students can obtain better results at correct tube placement with repeated attempts under optimum conditions--a practice effect--and do better at recognizing correct tube placement there is still a persistent failure to recognize endotracheal tube misplacement, ie oesophageal intubation. It is the ability to recognize oesophageal intubation promptly that is a life-saving skill. This essential skill should be taught during the introductory anaesthesia programme through the use of clinical patients.
A soluble guanylate cyclase stimulator, BAY 41-8543, preserves pulmonary artery endothelial function in experimental pulmonary embolism
Authors: John Watts, Michael Gellar, Mary-Beth Fulkerson, Hugh Quach, Jeffrey A. Kline
Journal: European Respiratory Journal (2013)

Background : BAY 41-8543 reduces pulmonary vascular resistance and right ventricle injury in experimental PE. Objective : Test if BAY 41-8543 protects pulmonary artery (PA) endothelial function in PE. Methods : PE was induced (anesthetized, Sprague-Dawley rats, 25 µm polystyrene microspheres, 1.95 million/100g, IV) with BAY 41-8543 (50 ug/kg, IV) or solvent treatment. Controls had vehicle for microspheres. Rings isolated from primary PA branches (5hr. PE) were contracted (phenylephrine, 10-6M) and dilation was endothelium-dependent (acetylcholine, 10-7M – 10-5M) or with BAY 41-8543 (10-8M – 10-6M). Oxidant stress was assessed: PA tissue 4-hydroxynoneal (4-HNE) immunohistochemistry; plasma malondialdehyde (MDA). Other Control rings received red blood cell (RBC) lysate. Results : PE inhibited dilation to acetylcholine vs. Control (dose x group interaction p=0.001), while dilation to BAY 41-8543 was minimally changed. PE raised plasma hemoglobin (30-fold, p=0.003), 4-HNE stain and plasma MDA (2.2-fold, p=0.009). Treating PE rats with BAY 41-8543 reduced plasma hemoglobin, 4-HNE and MDA to levels not different from Control. Dilation to acetylcholine significantly improved in PE + BAY 41-8543 rats vs. PE (dose x group interaction p=0.04). Addition of RBC lysate to Control rings reduced dilation to acetylcholine, while BAY 41-8543 responses remained strong. Conclusion : PE caused PA endothelial dysfunction, elevated plasma hemoglobin and oxidant stress. Treating rats with BAY 41-8543 lowered plasma hemoglobin, oxidant stress and endothelial dysfunction in PE. Treating isolated rings with BAY 41-8543 bypassed endothelial dysfunction with PE or RBC lysate.
Development of Spontaneous Pulmonary Tumors at High Altitude in Strain A Mice&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Pablo Mori-Chavez
Journal: JNCI Journal of the National Cancer Institute (1962)

The incidence and histologic characteristics of pulmonary tumors were studied in 171 strain A mice in the Peruvian Andes at 14,900 feet above sea level at Morococha, and in 200 mice at sea level in Lima. The incidence of spontaneous pulmonary tumors was greater at high altitude (61.4%) than at sea level (53.0%), but the percentage difference was not statistically significant. The average diameter of the tumors at high altitude was greater than at sea level. Associated with this increase in size, and evident both in male and female mice, was the greater frequency of large tumors of 4 mm and above. The mice at sea level weighed more than those at high altitude, regardless of whether they bore tumors. Four mice at high altitude and one at sea level developed pulmonary tumors with anaplastic or sarcomatous characteristics. It is believed that the tumors were alveologenic in origin.
Everolimus and pancreatic neuroendocrine tumors (PNETs): Activity, resistance and how to overcome it
Authors: Monica Capozzi, Ieranò Caterina, Chiara De Divitiis, Claudia von Arx, Piera Maiolino, Fabiana Tatangelo, Ernesta Cavalcanti, Elena Di Girolamo, Rosario Vincenzo Iaffaioli, Stefania Scala, Salvatore Tafuto
Journal: International Journal of Surgery (2015)
Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information
Authors: Valentina Nardi, Olja Pulluqi, Jeremy S. Abramson, Paola Dal Cin, Robert P. Hasserjian
Journal: American Journal of Hematology (2015)

Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma.
Loss of Resistance to Methotrexate in L5178Y Mouse Leukemia Grown &lt;italic&gt;In Vitro&lt;/italic&gt;
Authors: V. Doreen Courtenay, A. B. Robins
Journal: JNCI Journal of the National Cancer Institute (1972)

A highly resistant strain of the L5178Y mouse leukemle, able to survive continuous treatment with 500 µg/ml methotrexate (MTX), was obtained in vitro by continued treatment of cultures with increasing amounts of MTX. Measurements of dihydrofolate reductase in resistant cultures treated with MTX showed that enzyme levels were about 100 times higher than those in untreated cultures of the sensitive strain. During growth without MTX, both enzyme levels and resistance declined. At about 100 days after termination of treatment, enzyme levels were similar to those of sensitive cells. The growth rates of sensitive and resistant cultures did not differ and the enzyme level declined even in cultures cloned at the start, showing that this loss of resistance was not the result of cell selection processes. Scoring of the survival of clones in soft agar with different concentrations of MTX indicated that, after a period of growth without MTX, the cultures contained a mixture of cells of differing degrees of resistance. When treated with MTX, less resistant clones had partly or completely lost their ability to synthesize increased amounts of dihydrofolate reductase. This result appears to exclude the possibility that the enzyme level declined because of some physiological adaptive process in the cells. It suggests that the loss of resistance is due to the instability of the mutation controlling dihydrofolate reductase production. The rate of reversion from full resistance was 5 × 10-2.
Four-dimensional (4D) quantification of ventilation using dynamic MDCT imaging in a porcine model of ARDS
Authors: Johanna Laura Mayer, Claus Peter Heußel, Hans-Ulrich Kauczor, Klaus Markstaller, Michael Puderbach, Oliver Weinheimer, Stefan Boehme, Erik Hartmann, Ulrich Klein, Bastian Schmack, Gregor Pahn, Wolfram Stiller
Journal: European Respiratory Journal (2014)

In acute lung injury (ARDS) oxygenation is essential. It is determined by the volume of lungs ventilated during the entire respiratory cycle. Therefore, the central objective of this study is an image-based quantification of ventilated lung volume in order to determine the part of recruitable atelectasis with the goal of optimizing ventilation strategies.  Dynamic acquisitions of 11 mechanically ventilated pigs (PEEP 0 or 5 mbar) have been conducted using 128-slice MDCT before and after induction of ARDS by surfactant wash-out. Total acquisition time was 26s over a detector range of 8cm. At all-time points of the respiratory cycle, image volumes have been analyzed semi-automatically with a software (YACTA) developed in-house.  YACTA-based analysis shows a strong correlation of cyclic variations induced by respiration and lung parenchyma density values of morphologically well-ventilated (WV) lung volume [-900; -501HU], hypoventilated (HV) volume [-500; -101HU] and atelectasis (A) [-100; 100HU]. While the volume of HV lungs shows no shift, the WV lung volume increases (57% to 67%) and A decreases (18% to 12%) by increasing PEEP after ARDS induction. ARDS-induced A varies during the breathing cycle which corresponds to cyclic recruitment of lung parenchyma.  Through the use of dynamic CT and software-based evaluation it is possible to quantify effects of ARDS and the clinical effects of different automated mechanical ventilation regimes throughout the whole respiratory cycle for the first time. Translation of this setting into clinical treatment is technically feasible. It could make an important contribution to individualized optimization of ventilation parameters.
Papillomas on Fish Exposed to Chlorinated Wastewater Effluent&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J M Grizzle, P Melius, D R Strength
Journal: JNCI Journal of the National Cancer Institute (1984)

The presence of carcinogenic and mutagenic chemical(s) in the effluent of a wastewater treatment plant was indicated by papillomas developing on caged black bullheads (Ictalurus melas), hepatic enzyme induction in exposed fish, and Ames test mutagenicity of organic extracts of the wastewater. Although virus-like particles have been reported in papillomas of several other fish species, no evidence was obtained for the presence of viruses in the black bullhead papillomas. Mutagenic and carcinogenic chemicals were not identified in the wastewater, but chlorination was implicated as a factor contributing to the induction of the papillomas. The prevalence of papillomas on wild black bullheads exposed to the effluent decreased from 73 to 23% after the amount of residual chlorine (CAS: 7782-50-5) in the effluent leaving the chlorine contact chamber was reduced from 1.3-3.1 mg/liter to 0.25-1.2 mg/liter.