tbuckley/cabot-search huggingface dataset:
Long-Term Cardiac Safety Analysis of NCCTG N9831 (Alliance) Adjuvant Trastuzumab Trial
Authors: Pooja P. Advani, Karla V. Ballman, Travis J. Dockter, Gerardo Colon-Otero, Edith A. Perez
Journal: Journal of Clinical Oncology (2015)

Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) -positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and long-term evaluation of its incidence and risk factors are warranted.NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models.The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C.The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracycline- and taxane-based therapy) continues to have a favorable benefit-risk ratio.
Urinary calcium oxalate crystal growth inhibitors.
Authors: E M Worcester
Journal: Journal of the American Society of Nephrology (1994)

Calcium stones occur because renal tubular fluid and urine are supersaturated with respect to calcium oxalate and phosphate. The process of stone formation includes crystal nucleation, growth, aggregation, and attachment to renal epithelia. Urine contains macromolecules that modify these processes and may protect against stone formation. Attention has focused especially on inhibitors of crystal growth, and several have been isolated from urine, including nephrocalcin, an acidic phosphorylated glycoprotein that contains several residues of gamma-carboxyglutamic acid per molecule; osteopontin (uropontin), a phosphorylated glycoprotein also found in bone matrix; uronic acid-rich protein, which contains a covalently bound glycosaminoglycan residue; and several others. Abnormalities in structure and/or function have been detected in some of these proteins in stone formers' urine. However, the overall ability of urinary macromolecules to inhibit calcium oxalate crystal growth is often normal in stone formers. Recently, attention has been focused on the ability of these molecules to inhibit other stages in stone formation. Nephrocalcin can inhibit crystal nucleation, for example, and both nephrocalcin and Tamm-Horsfall protein inhibit crystal aggregation. Nephrocalcin and Tamm-Horsfall protein from stone formers are less active in preventing aggregation, and under some conditions, Tamm-Horsfall protein may promote the formation of crystal aggregates, especially in the presence of high concentrations of calcium. The structural abnormalities responsible for impaired inhibitory activity are not completely understood.
Thirty-four Lines of Six Human Tumor Categories Established in Nude Mice&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: Jørgen Fogh, John Tiso, Thomas Orfeo, Francis E. Sharkey, Walter P. Daniels, Jens M. Fogh
Journal: JNCI Journal of the National Cancer Institute (1980)

Inoculation into Swiss nude mice of 246 human tumors sc resulted in tumor growth in 60 cases (24.4%). The percentages of tumors that grew in primary transplants varied significantly among the 6 tumor categories from 47.1% for lung tumors to 8.6% for breast tumors and were higher for metastases (34.4%) and recurrent tumors (42.9%) than for tumors from primary sites (19.0%). Thirty-four human tumor lines were established. Fifteen lines originated from lung tumors, 7 from breast tumors, 5 from bone tumors, 3 from head and neck tumors, 3 from soft-tissue sarcomas, and 1 from a female genital tumor. Metastases established lines in 23.4% of all attempts and from 72.7% of the tumors growing in primary transplant. Lines were established less frequently from primary tumors (8.3 and 43.8%). These lines have been carried up to passage 19. The primary transplant time (wk to geometric mean diameter of 10 mm) averaged 11.0 for tumors from which lines were established. Tumors derived from primary sites showed the longest time in primary transplant, 11.7 weeks, versus 11.0 weeks for metastases and 7.4 weeks for recurrent tumors. Average periods between passages varied from 1.6 to 22.6 weeks for individual lines. Average passage times were similar for lines derived from primary sites, metastases, and recurrent tumors (5.0, 6.9, and 5.1 wk, respectively). These times were significantly shorter than were primary transplant times, and a linear relationship established that passage times could be predicted when primary transplant time was known. The success in establishing lines was not dependent on the degree of differentiation of nude mouse-grown tumors. Less differentiated tumors grew more rapidly in primary transplant and passage. The growth analysis indicated that many of the tumors grew at rates sufficient to obtain enough tissue for experimental studies and to provide material for clinical screening of individual cases within reasonable times.
N-methylformamide: cytotoxic, radiosensitizer, or chemosensitizer.
Authors: K Clagett-Carr, G Sarosy, J Plowman, D F Hoth, B Leyland-Jones
Journal: Journal of Clinical Oncology (1988)

N-methylformamide (NMF), a polar solvent, is currently being evaluated by the National Cancer Institute (NCI) as an antineoplastic agent because of its activity against colon, mammary, and lung tumor xenografts. Results from preclinical studies suggest that it has radiosensitizing, chemosensitizing, and differentiating activity. Its mechanism of action remains unknown, but may involve cellular depletion of glutathione, cell membrane changes, or modulation of proto-oncogene expression. Preclinical toxicology studies conducted in mice, rats, and beagle dogs showed reversible hepatotoxicity to be dose-limiting. Clinically, NMF is administered both orally and by intravenous (IV) injection. The bioavailability with oral administration is 90% to 95%. The highest reported plasma concentration of NMF is approximately 4 mmol/L in a patient who received a dose of 2,000 mg/m2 of IV NMF. Biphasic elimination with IV NMF is seen on both the daily for five days and weekly for 3 weeks schedule. Approximately 5% to 7% of the total administered IV dose is excreted in the urine. In phase I studies, dose-limiting toxicities included reversible hepatotoxicity, a generalized malaise syndrome, and nausea and vomiting. One partial response has been reported in the 111 patients treated on phase II trials in colorectal, head and neck, and renal carcinomas. Suggestions for the future development of this drug are presented.
Modification by Ozone of Lung Tumor Development in Mice2
Authors: Jerold A. Last, Darren L. Warren, Elizabeth Pecquet-Goad, Hanspeter Witschi
Journal: JNCI Journal of the National Cancer Institute (1987)

Journal Article Modification by Ozone of Lung Tumor Development in Mice Get access Jerold A. Last, Jerold A. Last Search for other works by this author on: Oxford Academic PubMed Google Scholar Darren L. Warren, Darren L. Warren Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth Pecquet-Goad, Elizabeth Pecquet-Goad Search for other works by this author on: Oxford Academic PubMed Google Scholar Hanspeter Witschi Hanspeter Witschi Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 78, Issue 1, January 1987, Pages 149–154, https://doi.org/10.1093/jnci/78.1.149 Published: 01 January 1987 Article history Received: 13 March 1986 Accepted: 14 July 1986 Published: 01 January 1987
Primary, secondary, and quality-of-life endpoint results from the phase III AFFIRM study of MDV3100, an androgen receptor signaling inhibitor.
Authors: Johann Sebastian De Bono, Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N. Sternberg, Kurt Miller, Peter Mulders, Kim N. Chi, Andrew J. Armstrong, Mohammad Hirmand, Brian Selby, Howard I. Scher
Journal: Journal of Clinical Oncology (2012)

4519^ Background: MDV3100, a novel androgen receptor signaling inhibitor (ARSI), inhibits: 1) binding of androgens to AR, 2) AR nuclear translocation, and 3) association of AR with DNA. MDV3100 was active in a phase I-II trial enrolling pre- and post-docetaxel castration-resistant prostate cancer (CRPC) patients. The AFFIRM trial evaluated whether MDV3100 could provide benefit to men with post-docetaxel CRPC. Methods: In this double-blind, multinational phase III study, patients who had received docetaxel-based chemotherapy were randomized 2:1 to MDV3100 160 mg/day or placebo. Treatment with corticosteroids was allowed but not required. Patients were stratified by baseline ECOG and mean brief pain inventory score. The primary endpoint was overall survival (OS). Other efficacy endpoints included radiographic progression-free survival (rPFS), time to PSA progression (TTPP), soft tissue objective response (PR+CR), PSA response, and quality of life (QoL) response (FACT-P). Results: 800 patients were randomized to MDV3100 and 399 to placebo with respective median treatment durations of 8.3 and 3.0 months.Based on a planned interim analysis at 520 deaths, the Independent Data Monitoring Committee recommended the study be unblinded and placebo patients offered MDV3100. Efficacy results are presented (Table). The most common MDV3100 events with an incidence higher than placebo were fatigue (34% vs 29%), diarrhea (21% vs 18%), and hot flush (20% vs 10%). Grade &gt;3 events of interest were cardiac disorders (0.9% MDV3100 vs 2% placebo), fatigue (6% MDV3100 vs 7% placebo), seizure (0.6% MDV3100 vs. 0% placebo), and LFT abnormalities (0.4% MDV3100 vs 0.8% placebo). Conclusions: MDV3100, a novel ARSI, is well-tolerated and significantly prolongs OS, slows disease progression, and improves QoL in men with post-docetaxel CRPC. [Table: see text]
Sputum colour reported by patients is not a reliable marker of the presence of bacteria in acute exacerbations of chronic obstructive pulmonary disease
Authors: J.M.A. Daniels, C.S. de Graaff, F. Vlaspolder, D. Snijders, H.M. Jansen, W.G. Boersma
Journal: Clinical Microbiology and Infection (2009)
Medical issues in women's football
Authors: Jiri Dvorak, Astrid Junge, Colin Fuller, Paul McCrory
Journal: British Journal of Sports Medicine (2007)

We get terribly excited about the issue of drugs in sport. The fear of anabolic agents or stimulants producing superhuman performance has dominated Olympic and professional team sports for many years. It seems however that doping has been present virtually since competitive sports began, with apocryphal stories of various potions being used in ancient times just as pharmacological agents are used today.

The World Anti-Doping Agency (WADA) list of banned agents gets ever longer and more complex and yet we still seem to have high-level athletes testing positive on a regular basis. Does this mean the process actually works or does it reflect a fundamental failure of the doping control mechanisms in sport? Why, for example, are non-performance-enhancing agents (eg marijuana) banned, and why are chess and bridge players (yes, they are apparently athletes too according to WADA) banned for using β blockers in competition?

If the system …
Continuous Delivery of Endogenous Inhibitors from Poly(Lactic-Co-Glycolic Acid) Polymeric Microspheres Inhibits Glioma Tumor Growth
Authors: Ofra Benny, Maayan Duvshani-Eshet, Theresa Cargioli, Lorenzo Bello, Andreas Bikfalvi, Rona S. Carroll, Marcelle Machluf
Journal: Clinical Cancer Research (2005)

Abstract Purpose: There is an urgent need for modalities that can localize and prolong the administration of the antitumor agents, particularly antiangiogenic, to achieve long-term tumor inhibition. However, one of the major obstacles is designing a device in which the biological activity of sensitive endogenous inhibitors is retained. We have designed a biodegradable polymeric device, which provides a unique and practical means of localizing and continuously delivering hemopexin (PEX) or platelet factor 4 fragment (PF-4/CTF) at the tumor site while maintaining their biological activity. The potential and efficacy of this system is shown in vitro and in vivo in a human glioma mouse model. Experimental Design: Polymeric microspheres made of poly(lactic-co-glycolic acid) (PLGA) were loaded with very low amounts of PEX and PF-4/CTF. The release profiles of these factors from PLGA and their biological activity were confirmed in vitro using proliferation assays done on endothelial and tumor cells. Tumor inhibition using this system was studied in nude mice bearing a human s.c. glioma. Results: PEX and PF-4/CTF released in vitro from PLGA microspheres were biologically active and significantly inhibited the proliferation of human umbilical vein endothelial cells, bovine capillary endothelial cells, and U87-MG cells. A single local s.c. injection of PLGA microspheres loaded with low amounts of PEX or PF-4/CTF resulted in an 88% and 95% reduction in glioma tumor volume 30 days post-treatment. Immunohistochemical analysis of the treated tumors showed a marked decrease in tumor vessel density compared with untreated tumors. Conclusion: Our findings show that polymeric microspheres are a very promising approach to locally and efficiently deliver endogenous inhibitors to the tumor site leading to a significant inhibition of the tumor.
What is the significance of aspergillus fumigatus in BAL in children with cystic fibrosis
Authors: Rebecca Thursfield, Andrew Bush, Alex Adams, Andrew G. Nicholson, Katy Holden
Journal: European Respiratory Journal (2011)

Background: Aspergilllus fumigatus ( AF ) is frequently found in the airways of children with cystic fibrosis (CF) and recent evidence suggests this may be clinically important. (Chest 2006;130:222, Ped Pulm 2007;42:785)

Aims: In this retrospective study, we hypothesised that children with CF who have AF seen on direct staining of bronchoalveolar lavage (BAL) will have a worse clinical state than both those who only culture AF (positive controls) and those with no isolation (negative controls). Primary outcome was FEV1; secondary outcomes included BMI, IgE, IV antibiotics, steroids and antifungals.

Results: In the year prior to bronchoscopy (FOB), the groups were similar in terms of weight centile, IV antibiotics received and FEV1. One year post FOB, the groups with AF in their BAL, on cytology or microscopy, had a lower FEV1 despite receiving more IV antibiotics and more antifungal therapy.

View this table:

Patient groups





View this table:

Lung function





The group without AF had a greater increase in FEV1.

![Figure][1] 



Conclusion: The results add to the growing evidence that AF in the airways of children with CF is associated with a worse clinical state, whether identified on direct smear or culture.

 [1]: pending:yes
Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer.
Authors: A G Zeimet, M Widschwendter, C Knabbe, D Fuchs, M Herold, E Müller-Holzner, G Daxenbichler, F A Offner, O Dapunt, C Marth
Journal: Journal of Clinical Oncology (1998)

PURPOSE The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity. PATIENTS AND METHODS Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors. RESULTS Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P &lt; .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P &lt; .005) and overall (P &lt; .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P &lt; .03 for disease-free and P &lt; .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age. CONCLUSION In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression.
Abstract 203: Insulin Alleviates Cardiac Dysfunction After Mechanical Trauma by Inhibiting TNF-{alpha}--Mediated ROS Generation via the PI3K/Akt Pathway
Authors: Jia Li, Yi Liu, Ya F Feng, De X Wang, Wen C Liu, Xiao Q Cai, Feng Gao
Journal: Circulation (2011)

Background: Intensive insulin treatment protects injured myocardium and reduces mortality in surgical critically ill patients but the mechanisms involved remain unclear. This study was designed to ...
Problem Feet in Children
Authors: J A Fixsen
Journal: Journal of the Royal Society of Medicine (1998)

So-called variations of normal, as well as true foot deformities, are very obvious in childhood. They cause considerable parental anxiety, particularly if the child shows any delay in motor development or there is a family history of conditions such as flat feet or hallux valgus. The obvious foot abnormality is often blamed for delay in motor development, whereas in fact even those children with untreated severe abnormalities such as severe talipes equinovarus (club foot) or congenital vertical talus will walk remarkably well despite their foot deformity if their motor development is normal. If, however, they have an underlying neuromuscular problem or other abnormality causing motor delay, then correcting their foot deformity will not of itself correct the motor delay. Misunderstandings about the relation between apparent foot deformity and walking ability are common and require careful, sympathetic handling by the physician or surgeon advising parents and carers. A paediatric physiotherapist skilled in addressing the patient's overall motor abilities can be very helpful.
Immune Complexes in Serum and in Cerebrospinal Fluid in African Trypanosomiasis
Authors: P. H. Lambert, M. Berney, G. Kazyumba
Journal: Journal of Clinical Investigation (1981)

The possible occurrence of immune complexes (IC) in serum and in cerebrospinal fluid (CSF) has been studied in 36 patients with African trypanosomiasis (Trypanosoma brucei gambiense). In serum, very high levels of IC were detectable by the 125I-C1q-binding and by the conglutinin-binding assays with positive results in 94 and 87%, respectively, of untreated patients. Circulating IC were found in both early and late stages of the disease, without significant quantitative differences; their size was 15-25S. There was a significant negative correlation between C3 values and C1qBA. Our studies suggest that circulating IC occurring during trypanosomiasis may be the expression of a polyclonal B cell activation. Indeed, there was a significant correlation (P < 0.001) between the levels of circulating IC and either the levels of IgM (mean value 12.5±7.2 mg/ml) or with the levels of rheumatoid factor-like antiimmunoglobulin antibodies that were detected by solid phase radioimmunoassay in 74% of the patients.
Separation of Cells From a Murine Fibrosarcoma on the Basis of Size. II. Differential Effects of Cell Size and Age on Lung Retention and Colony Formation in Normal and Preconditioned Mice23
Authors: D. J. Grdina, L. J. Peters, S. Jones, E. Chan
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Separation of Cells From a Murine Fibrosarcoma on the Basis of Size. II. Differential Effects of Cell Size and Age on Lung Retention and Colony Formation in Normal and Preconditioned Mice Get access D. J. Grdina, D. J. Grdina 4Section of Experimental Radiotherapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, Tex. 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Peters, L. J. Peters 4Section of Experimental Radiotherapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, Tex. 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Jones, S. Jones 4Section of Experimental Radiotherapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, Tex. 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Chan E. Chan 4Section of Experimental Radiotherapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, Tex. 77030. 5Present address: Section of Experimental Pathology, The University of Texas System Cancer Center. 6We thank Dr. Kuo-Pao Yang, Section of Endocrinology, Department of Experimental Medicine, M. D. Anderson Hospital and Tumor Institute, for his help and the use of his laboratory for the performance of some of this research. We thank Mr. W. L. Wilborn and his staff, Section of Experimental Radiotherapy, The University of Texas System Cancer Center, for the supply and care of the mice used in these experiments. Finally, we thank Ms. Nehama Dubravsky, Section of Experimental Radiotherapy, The University of Texas System Cancer Center, for her help in acquiring the autoradiographic data used in this study. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 1, July 1978, Pages 215–220, https://doi.org/10.1093/jnci/61.1.215 Published: 01 July 1978 Article history Received: 07 October 1977 Accepted: 21 February 1978 Published: 01 July 1978