tbuckley/cabot-search huggingface dataset:
A memorable teacher: Serendipity
Authors: David Crosby
Journal: BMJ (2004)

In retrospect, my belief in serendipity began in the summer of 1951. I was between my first and second years as a clinical medical student at the Welsh National School of Medicine when I was attracted to a medical secretary working in the MRC unit at nearby Llandough Hospital.

She told me that the unit was looking for two medical students who, for a modest stipend, would assist in an MRC survey of coal miners' chest diseases in one of the South Wales mining valleys. Apart from the attractions of the secretary, no stipend was too modest for me at that time, and I applied. Having been interviewed by Archie Cochrane, who was running the survey, I was the third choice of the four who applied. One of the first two dropped out, so I was in.

During that long distant summer, I cannot recall having been given any important duties beyond arranging x ray envelopes in alphabetical order. But I do remember many hours in the company of Archie Cochrane. It was a small team, and we spent long hours classifying chest x rays and poring over the data, which were well beyond my comprehension. We also spent time in his Jaguar car, of which he was quite proud, visiting individual miners in their homes who for many diverse and interesting reasons did not wish to be x rayed. Considerable energy was expended in ensuring that the survey should be 100%.

Once or twice he had a migraine, which meant a longer session the next day. To me, he was kind and quizzical. I doubt that I ever gave him any of the answers he wanted, but he tried hard to make me think.

Subsequent distractions of examinations and surgical training meant that I knew little of him again until I became a consultant in Cardiff in 1966 and was able to meet him on more equal terms. By this time he had become an international figure on healthcare policy, which was later crystallised in his 1972 classic monograph Effectiveness and Efficiency: Random Reflections on Health Services. To my mind, this remains the definitive work on the functioning of the NHS and, at only 92 pages, should be compulsory reading for all clinicians and managers who work in it.

I cannot now remember much about the medical secretary, but I remain most grateful to her for telling me about that holiday job in 1951. Because of it, I came to know a really remarkable man and, to a certain extent, to understand what made him tick. He died in 1988. I feel sure that all the current talk of “integrated medicine” must be making him turn in his grave.
Mannitol challenge testing in clinical practice and its role in identifying aiways hyperreactivity
Authors: Alison Gill, Ian Clifton
Journal: European Respiratory Journal (2012)

Introduction   Mannitol challenge testing can be useful in asthma diagnosis, to demonstrate objective evidence of airways hyperreactivity (AH).   Aim   To review mannitol testing locally, identify characteristics of those with positive and negative tests, and look at outcomes in terms of diagnosis and clinical improvement.   Methods   We reviewed all tests in our Trust between 2009 and 2011, compared baseline spirometry between positive and negative tests, and looked at immunological evidence of atopy. We reviewed clinic letters for change in diagnosis or management, as well as symptomatic improvement and whether patients were discharged from follow-up (representing clinical stability).   Results   Tests were performed on 177 patients between April 2009 and October 2011. The positive and negative groups were compared in terms of spirometry and immunological evidence for atopy (total IgE and IgE to inhaled allergen mix and aspergillus). The test was positive in 40 patients (22.6%). Of these, immunological evidence of atopy was greater than in those with negative tests (mean total IgE 275 vs. 132; IgE to IAM 5.48 and 4.73; IgE to aspergillus 0.6 and 0.25 respectively). Baseline spirometry tended towards more airflow obstruction in the positive group though the means were both within normal range (89% and 97% predicted). Of the 126 patients for whom we had data the mannitol challenge resulted in changes in treatment and improved symptoms in 115 (91.2%).   Conclusion   Bronchial provocation testing is useful in identifying those with AH, and for guiding treatment leading to symptomatic improvement.
Long-acting octreotide for the treatment of symptoms of bowel obstruction and intermittent obstruction in advanced ovarian cancer
Authors: U. Matulonis, C. Krasner, T. Atkinson, R. Penson
Journal: Journal of Clinical Oncology (2004)

5148 Background: Bowel obstruction and symptoms of chronic bowel obstruction are common complications reported in up to 40% of patients (pts) with recurrent ovarian cancer. Reasons for bowel obstruction include carcinomatosis with multiple points of obstruction, drug-induced intestinal immobility, and less commonly intraluminal obstruction. Octreotide inhibits gastrointestinal hormonal secretion and decreases splanchnic blood flow. Sandostatin LAR (LAR) is a long-acting depot form of octreotide given IM monthly. Methods: The objectives of this trial are to assess efficacy and toxicities of LAR in ovarian cancer pts with chronic or intermittent bowel obstruction. Eligible pts must have recurrent ovarian or primary peritoneal cancer, symptoms related to a non-surgically amenable bowel obstruction, and have a life expectancy of >2 months. Following a test dose of short-acting octreotide to rule out skin toxicity, SQ octreotide was started at a dose of 100 mcg 3x/day x 2 weeks (in order to quickly achieve therapeutic serum levels) simultaneously with LAR 30 mg IM qmonth. IM LAR was given until symptom progression or toxicity. EORTC QOL surveys were followed qmonth. Results: Since the study's initiation in 9/02, 10 pts have been enrolled. The mean age of pts is 56 yrs of age. Because one enrolled pt never received any study drug, data is available for 9 pts. Of the 10 pts enrolled, 8 have died from their cancer. One pt received a successful test dose and one LAR injection, but was removed from study per her request. Of the patients who received >2 months of therapy (6 pts), the duration of therapy ranged from 2 to 9 months with a median of 3.5 months duration of LAR. There were no grade 3/4 toxicities related to LAR, and LAR was overall well tolerated. 2 pts had skin reactions, one which necessitated removal of the pt from trial. Conclusions: LAR octreotide is well tolerated following successful administration of a test dose of SQ octreotide. In this ovarian cancer population with inoperable bowel obstruction, LAR octreotide has activity in the management of symptoms of bowel obstruction. No significant financial relationships to disclose.
Late mortality in two-year survivors of hematopoietic cell transplantation (HCT) performed in children and adolescents: Report from the BMT-Survivor Study
Authors: S. Bhatia, L. Francisco, K. S. Baker, N. K. C. Ramsay, L. L. Robison, S. J. Forman, J. G. Gurney
Journal: Journal of Clinical Oncology (2004)

8507 Background: We assessed overall and cause-specific late mortality [death occurring 2 or more years (yrs) after HCT] in a retrospective cohort of 862 patients (pts), unedrgoing HCT between 1974 and 1998, before the age of 21 yrs, and surviving at least 2 yrs. Methods: Vital status information was obtained from medical records, National Death Index, and Social Security Death Index. Age- and sex-standardized mortality ratios (SMR) were calculated using US population mortality data. Results: Primary diagnoses included ALL (n=212), AML (n=205), SAA (n=113), HD/NHL (n=67), inborn errors of metabolism (IEM: n=81), and other diagnoses (n=184). Types of HCT included related donor (RD: n=496), unrelated donor (URD: n=186), and autologous (A-HCT: n=180). Median age at HCT was 9.3 yrs (0.1–20.9) and length of follow-up 10.1 yrs (2.0–28.4). A total of 182 (21%) late deaths were observed. The cohort was at a 20-fold increased risk of late death when compared with the general population. Leading causes of deaths included recurrence of original cancer (61%) and chronic graft vs. host disease (cGVHD) (12%). Excess mortality rates were also seen due to pulmonary complications (SMR=41.5, 95%CI,18.8–73.1) and SMs (SMR=24.0, 95%CI,13.1–38.2). The probability of living 10 or more yrs was 79.5±1.9%. Multivariate analysis for RD/URD-HCT revealed the risk of late death to be significantly higher in pts receiving TBI (RR=4.4,p<0.001), busulfan (RR=2.8,p=0.03), and those with cGVHD (RR=1.9,p<0.001). Use of cyclosporine (RR=0.5,p<0.001) and methotrexate (RR=0.6,p=0.03) were associated with decreased risk. Among pts receiving A-HCT, the risk of late death was significantly higher in females (RR=1.9,p=0.02). Conclusions: Late mortality rates remain elevated 15 yrs after HCT. Leading causes of death include relapse, pulmonary complications and SMs. No significant financial relationships to disclose.
Genotyping of extended spectrum-β-lactamases (ESBLs) detected cephalosporin-resistant escherichia coli and klebsiella species in Japan
Authors: Naohiro Shibata, Yasuhito Iwashima, Hiroyuki Nosaka
Journal: European Respiratory Journal (2013)

Introduction: Escherichia coli and Klebsiella species are an opportunistic human pathogen. Outbreaks of these ESBL producers have occurred also in Japan, so cephalosporin-resistant strains were collected and analyzed for genotyping of their ESBLs. Methods: Fifty-six cefpodoxime-resistant (MIC, >4 μg/ml) strains collected from 6 hospital in Aichi and Gifu prefectures in Japan between Jan., 2010 and Dec., 2011. 32 Escherichia coli , 16 Klebsiella pneumoniae and 8 K. oxytoca were subjected to specific primer sets for detection of genetic determinants for TEM-1, SHV-, CTX-M-1 group, CTX-M-2 group, CTX-M-8 group, and CTX-M-9 group, extended spectrum β-lactamases (ESBLs), respectively. Each PCR amplicon was analyzed by direct sequencing. Results: Twenty-six(81.2%) of E. coli strains were found to carry genes for CTX-M-type ESBLs. Twenty K. pneumoniae carried CTX-M-type and SHV-type β-lactamases, respectively. However, no strain carrying genes for TEM-type, SHV-type or CTX-M-type β-lactamases was found in K. oxytoca . Most frequent variant types were CTX-M-3 and CTX-M-14, although this has been reported to be predominant in each group outside of Japan. Conclusion: These findings suggested that newly identified variants of ESBLs might well emerged and selected independently from those found in Europe by preferential use of carbapenems in Japanese clinical environments.
Enzyme-functionalized vascular grafts catalyze in-situ release of nitric oxide from exogenous NO prodrug
Authors: Zhihong Wang, Yaxin Lu, Kang Qin, Yifan Wu, Yingping Tian, Jianing Wang, Jimin Zhang, Jingli Hou, Yun Cui, Kai Wang, Jie Shen, Qingbo Xu, Deling Kong, Qiang Zhao
Journal: Journal of Controlled Release (2015)
Sub-group analysis of response, overall survival, and quality of life (QoL) with gemcitabine-cisplatin (G-C) in anthracycline and taxane pretreated metastatic breast cancer
Authors: F. M. Peria, L. G. Brito, D. G. Tiezzi, F. E. Zola, T. C. Motta, H. H. Carrara, J. M. Andrade
Journal: Journal of Clinical Oncology (2008)

12000 Background: Chemotherapy is an important treatment of metastatic breast cancer (MBC) and G-C is an option to taxane and anthracycline pretreated patients. The main objective is to analyze the impact of tumor and patients characteristics in G-C response, overall survival (OS) and QoL and identify predictive and prognostic factors. Methods: From February 2005 to December 2007, 49 MBC patients treated with G-C were prospective analyzed. They received IV G 750mg/m2 and C 30mg/m2, both D1 and D8 every three weeks. All patients were submitted to FACT-B quality of life questionnaire. Results: Twenty six patients were menopaused with medium age of 50 years old. Breast cancer initial diagnoses were locally advanced in 77.54% cases. Hormonal receptor status were positive in 25/49 patients and Her-2 tests were negative in 77.47% cases. All patients received chemotherapy during neoadjuvant, adjuvant or metastatic treatments with: taxane and epirrubicin (87.75%), epirrubicin (FEC, EC) (57.14%) or CMF (36.73%). The G-C protocol was the first line palliative chemotherapy in 53.06% cases and the media number of cycles/patient were 4. The most frequent sites of metastasis were lung (75.51%), hepatic (55.10%). According to RECIST criteria there were 2 complete responses, 6 partial responses, 21 stable diseases and 20 cases of disease progression. Secondary to a patient feeling, 73.47% related clinical improvement with minimal/mild collateral effects in 85.71%. Anemia (40.82%) and leucopenia (51.02%) were the main important hematological toxicity and there was one case of febrile neutropenia with death. Fatigue (53.06%) and nausea (49%) were the principal other toxicities. Following 34 months, the OS was 13.12 months and the time to progression was 6.58 months. Objective response was associated with improvement of Qol (p<0,01) and the OS was associated with chemotherapy response (p<0,01). Her-2 over expression was a prognostic factor with reduced OS in G-C treated MBC (p<0,01). Conclusions: G-C was effective, tolerable and associated with QoL improvement in objective responded patients. This chemotherapy schedule did not change the adverse prognosis of Her-2 over expression metastatic breast cancer. No significant financial relationships to disclose.
Caregiver satisfaction research using the FAMCARE questionnaire at the Palliative Care Services, Tata Memorial Centre.
Authors: B. Duraisamy, M. A. Muckaden, M. Dighe, S. Chandorkar, S. Dhumal, K. Midigiri, J. Kanakraj, M. Marathe
Journal: Journal of Clinical Oncology (2010)

e19685 Background: We at the palliative care services (PCS), TMC wanted to study the feasibility of using the FAMCARE questionnaire which indicates the satisfaction levels of patients/caregivers with the services they receive. Methods: 88 Mumbai patients, registered with the PCS [mean period registration – 5.7 months; min 1; max 18 months] and currently on regular follow up [mean number of follow-up visits – 11.8; min 2, max 47] were accrued for the study. The FAMCARE scale was translated to Marathi and the translations were validated by back translations to English and necessary changes were made till the questionnaire was deemed satisfactory. The primary care givers, who consented orally, were interviewed, over the phone and the responses were recorded and analyzed. Results: 59 valid responses were analyzed (22 males; 37 females, mean age 53.4 years). The mean symptom score was 6.6 (min 0, max 17) at presentation. 10 (17%) received extra help/aid. Maximum dissatisfaction (D) was with Q14 – time to diagnosis 24% (14) followed by Q4- information on side effects 12% (7), Q16 – information on pain management 10% (6), Q1- pain control 8.5% (5 patients), and Q13- coordination of care 8.5% (5 patients). None of them were very dissatisfied (VD) with any of the services. Conclusions: FAMCARE questionnaire is a simple audit tool and can be used to study the satisfaction levels of Indian cancer patient. The results reveal aspects of care which are not satisfactory to patients/care givers, especially pain control. No significant financial relationships to disclose.
One-step nucleic acid amplification for detecting lymph node metastasis of head and neck cancer
Authors: H. Goda, K. Nakashiro, T. Yoshimura, T. Sumida, H. Wakisaka, N. Hato, M. Hyodo, H. Hamakawa
Journal: Journal of Clinical Oncology (2009)

6028 Background: Lymph node stage is an important prognostic factor in squamous cell carcinoma of the head and neck (SCCHN). We previously reported the clinical usefulness of sentinel lymph node (SLN) biopsy diagnosed by concurrently performing histological examination using semiserial sections and genetic analysis by quantitative RT-PCR. However, these methods took about 3 hours. In this study, we have attempted to develop a more efficient method for intraoperative genetic detection of lymph node metastasis in SCCHN. Methods: A total of 291 lymph nodes (59 patients) resected on SLN biopsy for cN0 SCCHN or neck dissection for cN1/2 SCCHN were diagnosed by one-step nucleic acid amplification (OSNA) method using GD-100. The primary site was tongue, gingiva, oral floor, buccal mucosa, and pharynx in 44% (26), 37% (22), 10% (6), 5% (3), and 3% (2), respectively. OSNA consists of a short homogenization step followed by amplification of cytokeratin 19 (CK19) mRNA directly from the lysate. It is characterized by the use of 4 different primers specifically designed to recognize 6 distinct regions, so the CK19 primers do not amplify the known CK19 pseudogenes. The reaction process proceeds at a constant temperature (65°C) during strand displacement reaction. Amplification and detection of CK19 mRNA can be completed in a single step. Each lymph node was divided into two halves to diagnose metastasis. An alternative half was used for the OSNA assay with cytokeratin 19 (CK19) mRNA, and the remaining block was subjected to semiserial sectioning, sliced at 200-μm intervals and then examined by H&amp;E and cytokeratin AE1/AE3 immunohistochemical staining. Results: Fifty-four of 291 lymph nodes were pathologically metastasis-positive. The optimal cut-off for the copy number of CK19 mRNA in assessing lymph node metastasis was 300 copies/μl, which had the highest diagnostic accuracy. The sensitivity and specificity of OSNA assay with CK19 mRNA was 92.6% (50/54) and 97% (230/237), respectively. An overall concordance rate between the OSNA assay and histopathology was 96.2%. The OSNA assay could be completed within 30 minutes. Conclusions: The OSNA assay showing high sensitivity and specificity can be used as a novel genetic detection tool of lymph node metastasis in SCCHN patients. No significant financial relationships to disclose.
Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors
Authors: Vivek D. Badwaik, Emilio Aicart, Yawo A. Mondjinou, Merrell A. Johnson, Valorie D. Bowman, David H. Thompson
Journal: Biomaterials (2016)
ATREUS Trial: A Phase II Study On The Activity Of Trabectedin In Pretreated Epithelioid Or Biphasic/Sarcomatoid Malignant Pleural Mesothelioma (MPM)
Authors: L. Hollander, D. Cortinovis, I. Floriani, F. Grosso, G.L. Ceresoli, P.A. Zucali, M. D'Incalci, M. Tiseo, M.I. Abbate, S. Canova, F. Ugo, S. Marchini, P. Allavena, M. Bianchi, O. Corli, S. Vukcaj, S. Zai, P. Bidoli
Journal: Annals of Oncology (2015)
Sulindac inhibits colon tumor cell proliferation in xenograft mice
Authors: Pamela Rice, Matthew Sericati, Matthew Quallick, Nathan Susnow, Linda Driggers, Dennis Ahnen
Journal: Cancer Research (2007)

3215  Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of colorectal cancer (CRC) development. The NSAID, sulindac, prevents development of human adenomatous polyps and inhibits colon tumor formation in animal models. The mechanisms by which sulindac prevents colon tumor growth in vivo are complex and poorly understood. Inhibition of COX-1 and -2, the classical targets of NSAIDs, does not adequately explain sulindac9s growth inhibitory effects in vitro or in vivo. Several COX-independent mechanisms have been described for sulindac, including the extracellular signal-regulated kinase (ERK1/2) pathway. Sulindac metabolites inhibit ERK1/2 activation, and this inhibition is both necessary and sufficient for apoptosis of human colon cancer cells in vitro. The goal of this study was to determine if sulindac treatment inhibits ERK1/2 activity and stimulates apoptotic cell death in vivo, using the xenograft mouse model. Athymic mice were injected s.c. with HT29 human CRC cells and tumors allowed to grow to a palpable size. Mice were then placed on diets containing 0 or 320 ppm sulindac for 15 days. Tumors were measured with calipers, harvested and prepared for immunohistochemistry using KI67 (a marker of proliferation), cleaved caspase-3 (a marker of apoptosis) and phospho-ERK1/2 antibodies. Sulindac treatment inhibited tumor growth, and this inhibition was associated with a significant decrease in Ki67 staining. Sulindac-induced growth inhibition was also associated with increased cleaved caspase-3 staining and decreased phospho-ERK1/2 staining, however these results were not statistically significant. Together these results suggest that inhibition of tumor cell proliferation - and not induction of apoptosis - is the biological mechanism by which sulindac prevents tumor formation in vivo.
Abstract P278: Prevalence, Patterns and Correlates of Physical Activity Among the Adult Population of Four Cities in the Southern Cone of Latin America: Results from the CESCAS I study
Authors: Rosana Poggio, María G Matta, Pamela Serón, Laura Gutierrez, Vilma Irazola, Adolfo Rubinstein
Journal: Circulation (2015)

Introduction: In the Southern Cone of Latin America physical inactivity has become the fifth most important determinant of death. There is no published data describing and comparing physical activity (PA) patterns among different cities in this region. METHODS: CESCAS I is an observational, prospective cohort study entailing a probabilistic sample of 7524 representing the general adult population in four middle-size cities of the Southern Cone of Latin America. PA was assessed through the transcultural adapted questionnaire from the International Physical Activity Questionnaire long form. The indicator of PA intensity was expressed continuously, in metabolic equivalent task (MET) per minutes per week. We expressed the total PA score per week as “Total MET-minutes/week” constituted by the sum of Walking, Moderate and Vigorous MET minutes/week scores. Insufficient PA was defined as &lt; Total 600 MET-minutes/week. Analyses were based on weighted data taking into account individual probabilities of inclusion and calibrated on national census data. Multiple linear regressions were conducted as secondary analyses to model for the predictors of low PA. RESULTS: Thirty-five percent of the population is insufficiently active, showing the highest prevalences in Temuco (42.0%), women (41.3%), and “retired or unemployed” status (44.4%). Considering the overall population, women spend one third of energy compared to men (median 989 vs. 2763 MET-minutes/week respectively) mainly because only 12.9% of women performed vigorous activities compared to 39.9% in men. Among those subjects who reported performing vigorous activities, the energy expended by women was much lower than that expended by men (median 2384 vs. 5567 MET-minutes/week, respectively). When the overall population by domain was analyzed, the highest energy expenditure was seen in occupational at the expense of the manual labor category (2856 and 4588 MET-minutes/week for women and men respectively). Analyzing those who reported expending some energy in occupational, we found that men expended more than double the energy compared to women at the expense of vigorous activities (7055 vs. 2803 MET-minutes/week, respectively). In the multivariable analysis insufficient PA was strongly related with the categories retired or unemployed (OR 2.22; 1.87- 2.64), office or clerical work (OR 1.96; 1.60- 2.40), being women (OR 1.56; 1.36- 1.78), obesity (OR 1.47; 1.24- 1.74) and college or university education (OR 1.29; 1.07- 1.56). CONCLUSIONS: At least one third of the population did not reach the recommended PA levels necessary for promoting health and preventing diseases. Intervention strategies to promote leisure-time physical activity should be considered a health priority, especially in women.
G05 : Exome sequencing of 243 liver tumors identifies new mutational signatures and potential therapeutic targets
Authors: K. Schulze, S. Imbeaud, E. Letouzé, L.B. Alexandrov, J. Calderaro, S. Rebouissou, G. Couchy, C. Meiller, F. Soysouvanh, A.-L. Calatayud, R. Pinyol, L. Pelletier, C. Balabaud, A. Laurent, J.-F. Blanc, V. Mazzaferro, F. Calvo, A. Villanueva, J.-C. Nault, P. Bioulac-Sage, M.R. Stratton, J.M. Llovet, J. Zucman-Rossi
Journal: Journal of Hepatology (2015)