tbuckley/cabot-search huggingface dataset:
Abstract OT1-1-05: A Phase I pharmacokinetics trial comparing PF-05280014 and trastuzumab in healthy volunteers (REFLECTIONS B327-01)
Authors: AD Ricart, C Zacharchuk, SD Reich, X Meng, KB Barker, CT Taylor, AG Hansson
Journal: Cancer Research (2012)

Abstract Background: Trastuzumab is a humanized recombinant monoclonal antibody that selectively binds the extracellular domain of human epidermal growth factor receptor 2 (HER2) and is approved for treatment of breast and gastric cancers. PF05280014 is being developed as a potential biosimilar to trastuzumab. In nonclinical evaluations, PF-05280014 has an identical amino acid sequence to trastuzumab and similar physicochemical and in vitro functional properties. The goal of this phase I trial is to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab sourced from both the United States (trastuzumab-US) and European Union (trastuzumab-EU). Trial design: In this double-blind, parallel group, single dose trial, subjects will be randomized 1:1:1 into 3 arms: PF-05280014; trastuzumab-US, and trastuzumab-EU (NCT01603264). Eligibility: Healthy male volunteers, 18–55 years of age with normal left ventricular ejection fraction are eligible. Multiple exclusion criteria common to Phase 1 trials are in effect. All subjects must provide informed consent. Aims: The primary objectives are to demonstrate the pharmacokinetic similarity of PF-05280014 to trastuzumab-US and trastuzumab-EU. Secondary objectives include evaluating the safety, tolerability, and immunogenicity of PF-05280014 compared with US-licensed and EU-approved trastuzumab products. Statistical methods: Pharmacokinetic similarity will be demonstrated if the 90% confidence interval of the ratio of the area under the concentration-versus-time curve from time 0 to the last time point with quantifiable concentration (AUCT) and maximum concentration (Cmax) of PF-05280014 to both trastuzumab-US and trastuzumab-EU are within 80%–125%. At least 93 subjects, 31/arm, will be needed to provide &amp;gt;81% power to demonstrate pharmacokinetic similarity for all comparisons. The planned enrolment is 105 subjects to account for subjects who may not complete the full follow-up period. The intent-to-treat (ITT) population is defined as all subjects who are randomized to receive treatment. The modified ITT population is defined as all subjects who are randomized and receive at least one dose of treatment and will be used to assess safety, tolerability, and immunogenicity. The per-protocol population is defined as all subjects who are randomized to and receive treatment and do not have any major protocol violations and will be used for the primary evaluation of pharmacokinetic parameters. Accrual: The target accrual is 105 subjects; present accrual is 17subjects. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT1-1-05.
A MEDICAL ASPECT OF CRIME.
Authors: A. C. CORR
Journal: JAMA (1896)

Aside from the uncivilized barbarism that would induce a barbarous or half civilized person to commit outrages on the individuals of a neighboring tribe or state while practicing obedience to his own tribal laws, there are exceptions in which the individual is not true to his own tribal or state laws. These he continually violates, through some unknown impelling force that makes him act in utter disregard of the good, safety and comfort or all. This latter violation is usually called crime. Now in all the mutations of the silent revolution that has wrought so wonderfully since the debut of an organized Christian civilization, we have room for so many different phases of a variation of progress that we have amid a high Christian civilization, great irregularities in which individuals are untrue to their assumed, acquired and inherited responsibilities and obligations, and tend frequently or constantly to violate those laws,
Accelerated Preclinical Testing Using Transplanted Tumors from Genetically Engineered Mouse Breast Cancer Models
Authors: Lyuba Varticovski, Melinda G. Hollingshead, Ana I. Robles, Xiaolin Wu, James Cherry, David J. Munroe, Luanne Lukes, Miriam R. Anver, John P. Carter, Suzanne D. Borgel, Howard Stotler, Carrie A. Bonomi, Nomelí P. Nunez, Stephen D. Hursting, Wenhui Qiao, Chuxia X. Deng, Jeff E. Green, Kent W. Hunter, Glenn Merlino, Patricia S. Steeg, Lalage M. Wakefield, J. Carl Barrett
Journal: Clinical Cancer Research (2007)

The use of genetically engineered mouse (GEM) models for preclinical testing of anticancer therapies is hampered by variable tumor latency, incomplete penetrance, and complicated breeding schemes. Here, we describe and validate a transplantation strategy that circumvents some of these difficulties.Tumor fragments from tumor-bearing MMTV-PyMT or cell suspensions from MMTV-PyMT, -Her2/neu, -wnt1, -wnt1/p53(+/-), BRCA1/p53(+/-), and C3(1)T-Ag mice were transplanted into the mammary fat pad or s.c. into naïve syngeneic or immunosuppressed mice. Tumor development was monitored and tissues were processed for histopathology and gene expression profiling. Metastasis was scored 60 days after the removal of transplanted tumors.PyMT tumor fragments and cell suspensions from anterior glands grew faster than posterior tumors in serial passages regardless of the site of implantation. Microarray analysis revealed genetic differences between these tumors. The transplantation was reproducible using anterior tumors from multiple GEM, and tumor growth rate correlated with the number of transplanted cells. Similar morphologic appearances were observed in original and transplanted tumors. Metastasis developed in >90% of mice transplanted with PyMT, 40% with BRCA1/p53(+/-) and wnt1/p53(+/-), and 15% with Her2/neu tumors. Expansion of PyMT and wnt1 tumors by serial transplantation for two passages did not lead to significant changes in gene expression. PyMT-transplanted tumors and anterior tumors of transgenic mice showed similar sensitivities to cyclophosphamide and paclitaxel.Transplantation of GEM tumors can provide a large cohort of mice bearing mammary tumors at the same stage of tumor development and with defined frequency of metastasis in a well-characterized molecular and genetic background.
1054 SAFETY, PHARMACOKINETICS AND ANTIVIRAL EFFECT OF BI 207127, A NOVEL HCV RNA POLYMERASE INHIBITOR, AFTER 5 DAYS ORAL TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C
Authors: D. Larrey, Y. Benhamou, A.W. Lohse, C. Trepo, C. Moelleken, J.-P. Bronowicki, K. Arastéh, M. Bourlière, M. Heim, J. Enríquez, A. Erhardt, J.-P. Zarski, R. Wiest, T. Gerlach, H. Wedemeyer, T. Berg, J. Stern, K. Wu, N. Abdallah, G. Nehmiz, W. Boecher, J. Steffgen
Journal: Journal of Hepatology (2009)
Locally Produced Tumor Necrosis Factor-α Mediates Interleukin-2Induced Lung Injury
Authors: R. Rabinovici, G. Feuerstein, F. Abdullah, M. Whiteford, P. Borboroglu, E. Sheikh, D.-R. Phillip, P. Ovadia, L. Bobroski, O. Bagasra, L.F. Neville
Journal: Circulation Research (1996)

Abstract Interleukin (IL)-2–induced microvascular lung injury is an experimental paradigm commonly used to investigate the pathogenesis of the adult respiratory distress syndrome. Since tumor necrosis factor-α (TNF-α) is known to induce such an injury in vivo and since TNF-α is involved in other models of lung injury, we postulated that it might also mediate pulmonary toxicity after IL-2 administration. The present study tested this hypothesis by evaluating the effect of TNF-α inhibition on IL-2–induced lung injury in the rat. Recombinant human IL-2 (10 6 U IV per rat, n=6) elevated lung water, myeloperoxidase activity, and protein accumulation in bronchoalveolar lavage fluid and induced tissue hypoxia. Also, IL-2 enhanced lung tissue TNF-α mRNA and peptide (1543±496 pg/g lung wet weight) localized to alveolar macrophages by in situ hybridization. In marked contrast, IL-2 failed to affect serum TNF-α, which remained at undetectable levels. Pretreatment with anti–TNF-α monoclonal antibody (25 mg/kg IV, n=7) or the TNF-α synthesis inhibitor rolipram (200 μg/kg IV, n=7) attenuated lung injury and reverted tissue hypoxia. Furthermore, TNF-α inhibition prevented the upregulation of lung tissue IL-1β, IL-6, cytokine-induced neutrophil chemoattractant, and E-selectin (ELAM-1) but not intercellular adhesion molecule-1 mRNAs in response to IL-2. These data imply that locally produced TNF-α mediates IL-2–induced lung inflammation and tissue injury and point to the potential utilization of TNF-α inhibitors in treating the pulmonary toxicity of IL-2 immunotherapy.
Splenectomy for Splenic Metastasis from Carcinoma of Colon
Authors: JAMES D. SLAVIN, JOHN MATHEWS, RICHARD P. SPENCER
Journal: Clinical Nuclear Medicine (1986)

An 81-year-old woman with carcinoma of the colon had a normal liver-spleen radiocolloid image at the time of surgery. Two years later, a defect was noted in the spleen on a follow-up radiocolloid study. A repeat examination showed that the mass was increasing in size. An abdominal CT examination also revealed an intrasplenic mass with spring of the liver. After splenectomy for a metastatic carcinoma of the colon, the patient has survived for over a year without symptoms referable to tumor spread. Mention is made of the apparent splenic "immunity" from metastases.
Lesley Alison Margaret Evans
Authors: I. Kelham
Journal: BMJ (2014)

Lesley Alison Margaret Evans (nee Wills) intended a career in tropical medical research (her MSc was in medical parasitology), but family illness made it impractical to go abroad. She spent a year doing pathology in Oxford, then returned to clinical medicine, developing an interest in hospice and palliative care. She helped to set up and run a small Macmillan continuing care unit in West Sussex in the 1970s. …
TWO CASES OF MULTIPLE INTESTINAL OBSTRUCTION
Authors: R. Ramsey
Journal: BMJ (1907)

1J96 , I'm M]ULTIPLE INTESTINAL OBSTRUCTION.[JUNE I, I9t7.and intestinal haemorrhage were regarded as the result of tuberculous ulceration of the intestines, and probably of tuberculosis ,more or less generalized throughout the body.Tuberculous ulceration of the intestines is, in our experience at least, hardly ever accompanied by profuse intestinal haemorrhage; but Professor Oeler speaks of having had several fatal cases from this 'cause.The occurrence of profuse haemorrbage of the stomach with- out haematemesis was presumably explained by the pressure exerted by the growth against the cardiac orifice, and -to some extent by the presence of the oesophageal growth, conditions which would-make vomit- ing impossible.Much stress cannot be laid on the obstructive influence of the latter, inasmuch as there was at no time any recognizable dysphagia.The same argu- ment might, indeed,' be raised with regard to the gastric growth; but it seems reasonable to believe that the gastric growth, which, did not quite reach the cardiac orifice, did not obstruct that orifice when the stomach was passive, but that in vigorous contraction of the stomach, such as would induce vomiting in a healthy person, the cardiac orifice became obstructed by the pressure of the growth.In otler words, that the obstruction was valvular.
Staffing Pattern of a Health Maintenance Organization
Authors: Archie S. Golden
Journal: JAMA (1978)

A systems analysis approach was applied to a study of health provider jobs in a health maintenance organization to develop a proposal for an improved staffing pattern and an appropriate training curriculum for the provider. Physicians reported performing 512 ambulatory care tasks; health associates, 372; and health assistants, 284. Overlap was found among each group, especially in data-gathering tasks. This led to reallocation of tasks, with the most complex but smallest number assigned to the physician, and the least complex but highest number assigned to the assistant. In turn, a staffing pattern was suggested whereby a team of two physicians, four associates, and eight assistants would be able to manage the visits of 10,000 patients.
Michael Heinz Salz
Authors: Maher Halawa
Journal: BMJ (2005)

Founder of the modern hospice movementCicely Saunders founded the first modern hospice and, more than anybody else, was responsible for establishing the discipline and the culture of palliative care.She introduced effective pain management and insisted that dying people needed dignity, compassion, and respect, as well as rigorous scientific methodology in the testing of treatments.St Christopher's Hospice opened in south west London in 1967.It is now one of many but is still the leader in the field.It was her personal achievement and has been imitated all over the world.She raised the funds for the hospice and contributed some of her own money.Saunders introduced the idea of "total pain," which included the physical, emotional, social, and spiritual dimensions of distress.A good listener, she paid systematic attention to patient narratives.One St Christopher's patient, transferred from another hospital, said, "They used to see how long I could go without an injection.I used to be pouring with sweat because of the pain.I couldn't speak to anyone and I was having crying fits.I think I've only cried once since I've been here . . .The biggest difference is feeling so calm.I don't get worked up or upset."Cicely Mary Strode Saunders was born in Barnet, Hertfordshire, in 1918.She was sent to Roedean School when she was 10.Taller than the other girls, she felt she never fitted in, which, she said, gave her a feeling for people who were outsiders.She also suffered from a painful and slightly crooked spine, and was made to lie flat on the floor for 40 minutes a day.Her father disapproved of her desire to be a nurse, and so instead she went to study at Oxford.After the outbreak of the second world war she abandoned her course and defied her parents' advice, enrolling as a student nurse at St Thomas' Hospital in 1944.However, her back was still painful, and she was advised to quit nursing.After returning to Oxford for a year she gained a "war degree" and qualified as a social worker, or what was then called a lady almoner, in 1947.Saunders was originally an agnostic, but, while on holiday in Cornwall with some
Cell-Free Nucleic Acids Circulating in the Plasma of Colorectal Cancer Patients Induce the Oncogenic Transformation of Susceptible Cultured Cells
Authors: Dolores C. García-Olmo, Carolina Domínguez, Mariano García-Arranz, Phillipe Anker, Maurice Stroun, José M. García-Verdugo, Damián García-Olmo
Journal: Cancer Research (2010)

It has been proposed that cell-free nucleic acids in the plasma participate in tumorigenesis and the development of metastases via transfection-like uptake of such nucleic acids by susceptible cells. This putative phenomenon is tentatively referred to as "genometastasis." In the present study, we examined the effects on cultured cells of plasma from healthy individuals and from patients with colon cancer. Cultures of NIH-3T3 cells and human adipose-derived stem cells (hASC) were supplemented with samples of plasma from patients with K-ras-mutated colorectal tumors or from healthy subjects using two different protocols: direct addition of plasma to cultures in standard plates and addition in the absence of contact between plasma and cells, which were separated by a membrane with 0.4-mum pores. In plasma-treated hASCs, no K-ras-mutated sequences were detected by real-time PCR. In contrast, in most cultures of plasma-treated NIH-3T3 cells (murine cells), the transfer of human DNA occurred, as verified by the detection of human K-ras sequences, p53 sequences, and beta-globin-encoding sequences. Moreover, NIH-3T3 cells that had been cultured with plasma from patients with colon cancer were oncogenically transformed, as shown by the development of carcinomas in nonobese diabetic-severe combined immunodeficient mice after the injection of such cells. Microscopic analysis of membranes that had separated plasma from cultured cells confirmed the complete absence of cells in the plasma. We only observed noncell particles, having diameters of <0.4 mum. Our results indicate that plasma from cancer patients is able to transform cultured cells oncogenically, supporting the previously proposed hypothesis of genometastasis.
Lipid peroxidation in adrenal and testicular microsomes.
Authors: W C Brogan, P R Miles, H D Colby
Journal: Environmental Health Perspectives (1981)

Studies were carried out to determine the actions of and interactions between ascorbate, NADPH, Fe2+, and Fe3+ on lipid peroxidation in adrenal and testicular microsomes. Ascorbate-induced malonaldehyde production was maximal in adrenal and testicular microsomes at an ascorbate concentration of 1 X 10(-4)M. Fe2+, at levels between 10(-6) and 10(-3)M, produced concentration-dependent increases in lipid peroxidation in adrenal and testicular microsomes; Fe2+ had a far greater effect than Fe3+ in both tissues. In liver microsomes, by contrast, Fe2+ and Fe3+ had quantitatively similar effects on lipid peroxidation. NADPH alone had no effect on malonaldehyde production in adrenal or testicular microsomes. However, in the presence of low Fe2+ concentrations (10(-6)M), NADPH stimulated adrenal malonaldehyde production. The stimulation of lipid peroxidation by NADPH plus low Fe2+ was not demonstrable in testicular microsomes nor in adrenal microsomes which had been heat-treated to inactivate microsomal enzymes. Testicular malonaldehyde production was stimulated by NADPH if Fe3+ (5 X 10(-5) to 1 X 10(-3)M) was added to the incubation medium; the stimulation was not demonstrable in heat-treated microsomes. Fe3+ plus NADPH had little effect on adrenal lipid peroxidation. In the presence of high Fe2+ levels (10(-3)M), NADPH produced a concentration-dependent inhibition of adrenal lipid peroxidation; the inhibition was fully demonstrable in heat-treated microsomes. NADPH similarly inhibited ascorbate-induced lipid peroxidation in adrenal microsomes. In testicular microsomes, NADPH did not inhibit ascorbate or Fe2+-induced lipid peroxidation. The results indicate that various endogenous substances may be important in the control of adrenal and testicular lipid peroxidation and that the nature of the regulation differs from tissue to tissue.
Impact of a T cell-based blood test for tuberculosis infection on clinical decision-making in routine practice
Authors: Sarah Gooding, Oni Chowdhury, Tim Hinks, Luca Richeldi, Monica Losi, Katie Ewer, Kerry Millington, Ruba Gunatheesan, Stefania Cerri, Jeremy McNally, Ajit Lalvani
Journal: Journal of Infection (2006)

New T cell-based blood tests for tuberculosis infection could improve diagnosis of tuberculosis but their clinical utility remains unknown. We describe the role of the ELISpot test in the diagnostic work-up of 13 patients presenting with suspected tuberculosis in routine practice. Of the seven patients with a final diagnosis of active tuberculosis, all were positive by ELISpot including three with false-negative tuberculin skin test results. Rapid determination of tuberculosis infection by ELISpot accelerated the diagnosis of tuberculosis, enabling early treatment initiation.
Abstract B49: The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer
Authors: Jimmy Belotte, Nicole Fletcher, Awoniyi Awonuga, Mitchell Alexis, Husam Abu-soud, Michael Diamond, Mohammed Saed, Ghassan Saed
Journal: Clinical Cancer Research (2013)

Abstract Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts were used. Total RNA was extracted and subjected to real-time RT-PCR to evaluate the expression of inducible nitric oxide synthase (iNOS) and glutathione reductase (GSR) in all cells. Nitrate/nitrite levels and GSR activity were also measured using colorimetric and ELISA assays respectively. Cell proliferation was assessed using Ki-67 immunostaining in all cells. Unpaired t-tests were used for statistical analysis at p-value &amp;lt;0.05 for significance. Results: Both EOC cisplatin sensitive cells manifested significant increase in the expression and activity of GSR as compared to their resistant counterparts (p&amp;lt;0.05). On the other hand, EOC sensitive cells manifested a decrease in iNOS expression as compared to their resistant counterparts (p&amp;lt;0.05). Nitrate/nitrite levels were significantly decreased in EOC sensitive cells as compared to their resistant counterparts (p&amp;lt;0.05). Ki-67 immunofluorescence staining revealed increased proliferation in cisplatin resistant cells compared to controls for the MDAH-277a and SKOV-3 cell lines. Conclusion: Our data suggests that the development of cisplatin resistance heighten the prooxidant state in EOC leading to a further increase in cell proliferation. Citation Format: Jimmy Belotte, Nicole Fletcher, Awoniyi Awonuga, Mitchell Alexis, Husam Abu-soud, Michael Diamond, Mohammed Saed, Ghassan Saed. The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B49.
Objective and subjective analysis of left ventricular angiograms.
Authors: B R Chaitman, H DeMots, J D Bristow, J Rösch, S H Rahimtoola
Journal: Circulation (1975)

In order to determine the reproducibility of analyses of left ventriculograms, 35 cineangiograms were evaluated by four observers, two using standard quantitative techniques to determine ventricular volumes and a newly devised quantitative system to evaluate wall motion and two others using only visual inspection of the angiograms. Objective analysis repeated by the same observer correlated well for end-diastolic and end-systolic volumes and ejection fraction (r = .98, .99, respectively) and only one of 105 (1%) wall segments were identified differently. Variability in assessments increased when comparisons were made with a second objective observer. Correlation coefficients for the three volumetric parameters were .93, .98, and .95 and there was disagreement in the assessment of 8% of wall segments. Wide variability was present between an objective and two subjective observers in analyses of end-diastolic volumes (r = .63, .64). Regional wall motion was assessed differently in 19% and 27% of segments, respectively. Though the correlation of objectively and subjectively determined ejection fractions was much better than the correlation for volume (r = .92, .84), it was not as good as the correlation between two objective observers. Occasional errors of clinical significance occurred. We conclude that subjective analysis has a significant error rate and that reproducibility and accuracy of analysis of left ventriculograms require objective analysis.