tbuckley/cabot-search huggingface dataset:
Abstract P6-13-04: Thymidylate Synthase (TS) and Thymidine Phosphorylase (TP) Expression as Predictive Markers of Capecitabine Mono-Chemotherapy for Patients with Anthracyclin-Taxane Pretreated Metastatic Breast Cancer (MBC)
Authors: SJ Lee, YL Choi, EY Cho, ST Kim, YH Park, JS Ahn, Y-H. Im
Journal: Cancer Research (2010)

Abstract Background: Capecitabine, one of the widely used cytotoxic agents for breast cancer, achieved high tumor control rate with low toxicity even in heavily-pretreated patients with metastatic breast cancer (MBC). Capecitabine (Xeloda®) is an oral fluoropyrimidine pro-drug that is transformed to fluorouracil (FU) in several steps, the last of which is conversion of 5'-deoxy-5-fluorouridine to FU by TP. And TS is a target enzyme of 5-FU. The primary purpose of this study was to evaluate the role of TS and TP as biomarkers to predict clinical outcomes of capecitabine monotherapy for MBC. Method: Of Three hundreds fifty-three patients with MBC treated with capecitabine at Samsung Medical Center from 2000 to 2008, ninety patients who were previously treated with anthracycline and taxanes containing regimens and had available tissues for immunohistochemical stainings with estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor-2 (HER2), TS, and TP were included in this analysis. All patients had received capecitabine 2000-2500mg/m2/day for 14days q 3 weeks. Results: The median age of these 90 patients was 49 (26-76) years. The response rate (RR) was 25.6% and the disease control rate (DCR) was 65.6%. The median progression-free survival (PFS) and overall survival (OS) from the 1st day of capecitabine monotherapy were 4.8 (95% C.I.; 3.1-6.5) and 26.7 (95% C.I.; 17.1-36.3) months, respectively. High TS expression (TS score ≥100) was more common in patients with triple negative (TN) subtype than in those with other subtypes (16% for HR+, 22% for HER2+, 44% for TN, p=0.023). Median PFS was significantly lower in high TS expression (6.6 vs. 3.0 months; p=0.017) and low TP expression (TP&amp;lt;50) patients (6.0 vs. 3.3 months; p=0.013). High TS score and low TP score were identified as unfavorable independent risk factors for PFS to capecitabine monotherapy in Cox regression multivariate analysis (Hazard Ratio (HR) 1.7, p=0.037 for high TS score; HR 1.8, p=0.014 for low TP score). And, high TS and low TP score were associated with poorer overall survival.(29.9 vs. 14.1 months; p=0.008 for TS /29.9 vs. 20.4 months; p=0.043 for TP) Conclusion: Our data suggests that high TS score and low TP score correlated with shorter PFS for capecitabine monotherapy of patients with anthracycline and taxane pretreated MBC. Potential role of TS, TP expression as predictive markers of capecitabine monotherapy in patient with MBC should be confirmed by prospective studies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-13-04.
Erythrokeratoderma variabilis without GJB3 or GJB4 mutation: a review of Japanese patients
Authors: M. Nakamura, O. Ishikawa
Journal: British Journal of Dermatology (2007)

Journal Article Erythrokeratoderma variabilis without GJB3 or GJB4 mutation: a review of Japanese patients Get access M. Nakamura, M. Nakamura Department of Dermatology, Gunma University Graduate School of Medicine, 3‐39‐22 Showamachi, Maebashi 371‐8511, Japan Correspondence: Motonobu Nakamura, Department of Dermatology, Kyoto University Graduate School of Medicine, 54 Kawahara‐cho, Shogoin, Sakyo‐ku, Kyoto 606‐8507, Japan. E‐mail: motonaka@med.gunma‐u.ac.jp; motonaka@kuhp.kyoto‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar O. Ishikawa O. Ishikawa Department of Dermatology, Gunma University Graduate School of Medicine, 3‐39‐22 Showamachi, Maebashi 371‐8511, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 2, 1 August 2007, Pages 410–411, https://doi.org/10.1111/j.1365-2133.2007.08023.x Published: 01 August 2007
Out of hours primary care—a shambles?
Authors: Iona Heath
Journal: BMJ (2007)

Until 2004, general practitioners were responsible for the care of their registered patients 24 hours a day and seven days a week.They did not have to provide that care themselves but remained responsible for arranging and coordinating it.As a result of the new GP contract, most general practitioners have now opted out of this responsibility and are contracted to work for the NHS from 8 am to 6 30 pm and for only five days a week.
Helping patients to help themselves: the future for management of ulcerative colitis?
Authors: P Moayyedi
Journal: Gut (2002)

Guided self management of ulcerative colitis with follow up on request, compared with traditional management, accelerates treatment provision, reduces visits to specialists and general practitioners, and does not increase morbidity Ivan Illich believes that "the medical establishment has become a major threat to health".1 He reasons that the rise of modern medicine has encouraged a culture of dependency on the medical establishment rather than promoting self caring approaches to illness. This extreme viewpoint has a surprising number of supporters,2 perhaps because it contains a grain of truth. Clinicians can be paternalistic and often set up services with little regard to patient preferences or whether this is the most cost effective method of delivering health care.3 It is therefore refreshing to read the paper by Robinson et al comparing guided self management with usual care for ulcerative colitis (UC) patients in a randomised controlled trial.4 Patients were more satisfied with guided self management, and patients with relapses took steroids earlier. There was also a statistically non-significant trend for relapses to be of shorter duration. The results seem compelling, so should there be widespread implementation of this management strategy for UC? Robinson A, Thompson DG, Wilkin D, … [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DRobinson%26rft.auinit1%253DA.%26rft.volume%253D358%26rft.issue%253D9286%26rft.spage%253D976%26rft.epage%253D981%26rft.atitle%253DGuided%2Bself-management%2Band%2Bpatient-directed%2Bfollow-up%2Bof%2Bulcerative%2Bcolitis%253A%2Ba%2Brandomised%2Btrial.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252801%252906105-0%26rft_id%253Dinfo%253Apmid%252F11583752%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(01)06105-0&link_type=DOI [3]: /lookup/external-ref?access_num=11583752&link_type=MED&atom=%2Fgutjnl%2F51%2F3%2F309.atom [4]: /lookup/external-ref?access_num=000171135300019&link_type=ISI
Cyclical Combination Chemotherapy for Advanced Breast Carcinoma
Authors: G. P. Canellos, V. T. Devita, G. L. Gold, B. A. Chabner, P. S. Schein, R. C. Young
Journal: BMJ (1974)

Twenty-five patients with advanced metastatic breast cancer were treated with the combination of methotrexate 60 mg/M(2) and 5-fluorouracil 700 mg/M(2) intravenously on the first and eighth days, and cyclophosphamide 100 mg/M(2) and prednisone 40 mg/M(2) by mouth daily for the first 14 days of a 28-day cycle. The patients had had no previous chemotherapy or extensive radiotherapy and all but two had not responded to hormonal therapy or endocrine ablation. The major metastatic lesions were: lung (12 patients), liver (four patients), bone (four patients), soft tissue (three patients), nodes (two patients). Seventeen of the 25 patients (68%) responded to treatment with seven complete remissions; these included patients suffering metastatic lesions in the lung, nodes, and soft tissue. The overall median duration of response was nine months (range 6-26 months). Toxicity was primarily haematological, but the group received an average of at least 75% of their calculated dose for each monthly cycle. Haematological toxicity was most pronounced in patients with liver dysfunction and bone marrow involvement. Out of eight nonresponders seven died, with a median survival of six months. Only six of 17 responders died, and the median survival in this group will exceed thirteen months. There was no correlation between the length of the metastasis-free interval after previous treatment and subsequent response to chemotherapy.
Biomechanical coupling in renin-releasing cells.
Authors: R M Carey, H E McGrath, E S Pentz, R A Gomez, P Q Barrett
Journal: Journal of Clinical Investigation (1997)

The renin-angiotensin system is a major regulatory system controlling extracellular fluid volume and blood pressure. The rate-limiting enzyme in this hormonal cascade is renin, which is synthesized and secreted into the circulation by renal juxtaglomerular (JG) cells. The renal baroreceptor is a key physiologic regulator of renin secretion, whereby a change in renal perfusion pressure is sensed by these cells and results in a change in renin release. However, the mechanism, direct or indirect, underlying pressure transduction is unknown. We studied the direct application of mechanical stretch to rat JG cells and human renin-expressing (CaLu-6) cells on the release of renin. JG cells released a low level of baseline renin, comprising < 5% of their total renin content. By contrast, renin secretion from CaLu-6 cells comprised approximately 30% of cellular stores, yet was also stimulated twofold by 10 microM forskolin (P </= 0.001). In JG cells, mechanical stretch inhibited basal renin release by 42% (P < 0.01) and forskolin-stimulated renin release by 25% (P < 0.05). In CaLu-6 cells, stretch inhibited basal- and forskolin-stimulated renin release by 30 and 26%, respectively (both P < 0.01). Northern blot analysis demonstrated a stretch-induced reduction in baseline renin mRNA accumulation of 26% (P < 0.05) in JG and 46% (P < 0.05) in CaLu-6 cells. The data demonstrate that mechanical stretch in renin-releasing cells inhibits basal and stimulated renin release accompanied by a decrease in renin mRNA accumulation. Further studies will be necessary to characterize the intracellular events mediating biomechanical coupling in renin-expressing cells and the relationship of this signaling pathway to the in vivo baroreceptor control of renin secretion.
Effect of ischaemia on the adrenergic neurons of the rat heart: a fluorescence histochemical and biochemical study
Authors: S HOLMGREN, T ABRAHAMSSON, O ALMGREN, B-M ERIKSSON
Journal: Cardiovascular Research (1981)

Left coronary artery ligation was performed in pentobarbitone anaesthetised rats. Following ½ and 2½ h of coronary artery occlusion or sham-operation the right and left ventricular myocardium and the interventricular septum were analysed for tissue content of catecholamines. In control rats and in rats with coronary artery ligation for various time periods (½, 2½ and 5 h), the Hillarp-Falck fluorescence histochemical technique was used to visualise the catecholamines of the ventricular myocardium. The tissue noradrenaline content of the left ventricle was markedly reduced after 2½ h of ischaemia while noradrenaline levels in the other parts of the ventricles were unaffected. The adrenergic innervation of the normal rat ventricles is described for the purpose of comparing the normal innervation picture with the appearance after ischaemia. A reduced catecholamine fluorescence was found mainly in the centre of the left ventricular free wall 30 min after coronary artery occlusion. After 2½ and 5 h large areas of the ischaemic myocardium were found to be completely devoid of fluorescent terminals. The border zone between the areas of fluorescence disappearance and normally innervated myocardial tissue was generally quite sharp and occasionally terminals with a diffuse appearance were found in this zone. It is concluded that coronary artery ligation caused a time-dependent loss of noradrenaline from the adrenergic nerve terminals in the ischaemic myocardium. Catecholamine thus released may activate myocardial adrenoceptors and hence be related to increased ischaemic damage and ventricular arrhythmias.
Fetal Surgery for Congenital Diaphragmatic Hernia
Authors: Katharine D. Wenstrom
Journal: New England Journal of Medicine (2003)

Diaphragmatic hernia occurs when any of the four separate structures making up the diaphragm (the septum transversum, pleuroperitoneal membranes, dorsal mesentery of the esophagus, and body wall) fail to grow toward each other or to fuse by the eighth week after conception. The resulting diaphragmatic defect becomes a portal through which abdominal structures can herniate into the thorax (see Figure). In many cases, abdominal organs slide in and out of the thorax intermittently throughout gestation, with apparently little permanent effect on the developing lungs and heart. If there are no other anomalies and the defect is not part of a . . .
Chemoprophylaxis in tuberculosis and HIV infection
Authors: J. Walley, J. Porter
Journal: BMJ (1995)

Should chemoprophylaxis with a course of antituberculous drugs be given to people infected with Mycobacterium tuberculosis and HIV to prevent the reactivation of latent tuberculosis? The decision depends on three factors: the efficacy of the treatment, its cost effectiveness, and whether it is financially and organisationally feasible.

The World Health Organisation estimates that 1700 million people are infected with M tuberculosis—one third of the world's population. Symptomatic tuberculosis is becoming an increasing problem owing to population growth, poverty, multidrug resistance, and HIV infection. The risk of active tuberculosis in dually infected people is 3-8% a year, with a lifetime risk of about 50% or more.1 The WHO has calculated that the global incidence in 1990 of about 7.5 million cases of tuberculosis will increase to about 12 million by 2005 (M C Raviglione, personal communication). Already, worldwide, tuberculosis is the most common cause of death due to a single infectious agent.

Chemoprophylaxis with isoniazid has an efficacy of 25-92% in various risk groups not infected with HIV.2 Some data are available in people infected with HIV. In a controlled trial in Zambia patients with HIV infection and with Walter Reed stages III and IV disease who were given a B vitamin placebo had an incidence of tuberculosis of 11.2 per 100 person years, which was four times the rate in those receiving daily isoniazid (D Wahhawan et al, eighth international conference on AIDS and third world congress on sexually transmitted diseases, Amsterdam, 1992).

In Haiti a 12 month course of prophylaxis with isoniazid reduced …
INFECTIVE ENDOCARDITIS IN DIALYSIS PATIENTS: IS IT WORTH OPERATING?
Authors: Sajjad Raza, Asif Ansari, Matteo Trezzi, Thomas Fraser, Jeevanantham Rajeswaran, Joseph F. Sabik, Eugene H. Blackstone, Gosta B. Pettersson
Journal: Journal of the American College of Cardiology (2013)
Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome
Authors: Ted J Kaptchuk, John M Kelley, Lisa A Conboy, Roger B Davis, Catherine E Kerr, Eric E Jacobson, Irving Kirsch, Rosa N Schyner, Bong Hyun Nam, Long T Nguyen, Min Park, Andrea L Rivers, Claire McManus, Efi Kokkotou, Douglas A Drossman, Peter Goldman, Anthony J Lembo
Journal: BMJ (2008)

<b>Objective</b> To investigate whether placebo effects can experimentally be separated into the response to three components—assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship—and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components. <b>Design</b> A six week single blind three arm randomised controlled trial. <b>Setting</b> Academic medical centre. <b>Participants</b> 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale. <b>Interventions</b> For three weeks either waiting list (observation), placebo acupuncture alone (“limited”), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence (“augmented”). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks. <b>Main outcome measures</b> Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life. <b>Results</b> At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) <i>v</i> 4.3 (SD 1.4) <i>v</i> 5.0 (SD 1.3) for waiting list versus “limited” versus “augmented,” respectively (P&lt;0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P&lt;0.001 for trend). The same trend in response existed in symptom severity score (30 (63) <i>v</i> 42 (67) <i>v</i> 82 (89), P&lt;0.001) and quality of life (3.6 (8.1) <i>v</i> 4.1 (9.4) <i>v</i> 9.3 (14.0), P&lt;0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P&lt;0.001), adequate relief of symptoms (P&lt;0.001), symptom severity score (P=0.007), quality of life (P=0.01).Results were similar at six week follow-up. <b>Conclusion</b> Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component. <b>Trial registration</b> Clinical Trials NCT00065403.
Fatal Syncytial Virus Pneumonia in a Laminar Airflow Room
Authors: Lawrence R. Crane, Julie A. Kish, Voravit Ratanatharathorn, Joseph R. Merline, M. F. T. Raval
Journal: JAMA (1981)

A rapidly progressive, fatal pneumonia occurred during the third week of hospitalization in an immunosuppressed man confined in a laminar airflow room. Respiratory syncytial virus was isolated from open lung biopsy tissue. Epidemiologic data suggested that the virus was community acquired. Respiratory syncytial virus should be considered in the differential diagnosis of pneumonia in severely immunocompromised adults. (<i>JAMA</i>1981;246:366-368)
Evacuee's Sore Throat and Shelter Tonsillitis
Authors: T. B. Layton
Journal: BMJ (1940)

There are two forms of tonsillitis in evidence at the present time which resemble one another in so far that, instead of their indicating tonsillectomy, this operation is definitely harmful.These forms may be called " evacuee's sore throat " and " shelter tonsillitis."Ev-acutee's Sore Tlhroat.-Thisdepends upon the fact that if a young person entirely changes his mode and site of living the hygiene of the upper respiratory tract is altered, and will take some time to adjust itself to the new surroundings.During this time he or she suffers from a series of sore throats that closely resemble the recurring attacks of tonsillitis for which tonsillectomy is so beneficial.The difference is that for these patients it will not cure the attacks, which are likely to continue longer than they would if the tonsils were left alone.I have had a considerable experience of this in the
Relationships between Academic Institutions and Industry in the Life Sciences — An Industry Survey
Authors: David Blumenthal, Nancyanne Causino, Eric Campbell, Karen Seashore Louis
Journal: New England Journal of Medicine (1996)

Despite growing acceptance of relationships between academia and industry in the life sciences, systematic, up-to-date information about their extent and the consequences for the parties involved remains scarce. We attempted to collect information about the prevalence, magnitude, commercial benefits, and potential risks of such relationships by surveying a representative sample of life-science companies in the United States to determine their relationships with academic institutions.
The Role of Inflammatory Mediators in the Synergistic Toxicity of Ozone and 1-Nitronaphthalene in Rat Airways
Authors: Kara R. Schmelzer, Åsa M. Wheelock, Katja Dettmer, Dexter Morin, Bruce D. Hammock
Journal: Environmental Health Perspectives (2006)

Ambient air is polluted with a mixture of pulmonary toxicants. Previous studies indicate that prior exposure to atmospheric oxidant pollutants such as ozone may significantly alter the response to other pollutants, such as 1-nitronaphthalene (1-NN) . 1-NN, a component of the particulate exhaust from diesel engines, has been found at low concentrations in ambient air. Using a metabolomic approach, we investigated inflammatory responses in arachidonic and linoleic acid biochemical cascades (35 metabolites) and the expression of 19 cytokines/chemokines at three time points (2, 6, and 24 hr) following exposure to 1-NN with and without prior long-term O3 exposure. Long-term O3 exposure is associated with biochemical changes that have been shown to render the lung resistant to further O3 exposure. This study indicates that airways of O3-tolerant rats exhibited a low level of chronic inflammation, rendering the lungs more susceptible to other environmental pollutants such as 1-NN. Specifically, a 12.5-mg/kg dose of 1-NN to O3-tolerant rats produced significantly higher levels of cysteinyl-leukotrienes in bronchiolar lavage fluid even when compared to a 50-mg/kg dose of 1-NN in rats exposed to filtered air. Collectively, these results indicate that the combination of exposures as encountered in polluted ambient air are considerably more injurious to the lung than would be anticipated from previous studies employing single exposures. The observed synergism between O3 and 1-NN may be causally related to a shift in a T-helper 1 to T-helper 2 immune response in the airways.
A patient's charter.
Authors: B B Zeitlyn
Journal: BMJ (1979)

In generations past, it was common practice for doctors to learn lifesaving technical skills on patients who had recently died. But this practice has lately been criticised on religious, legal, and ethical grounds, and has fallen into disuse in many hospitals and emergency departments. This paper uses four questions to resolve whether doctors in emergency departments should practise and teach non-invasive and minimally invasive procedures on the newly dead: Is it ethically and legally permissible to practise and teach non-invasive and minimally invasive procedures on the newly dead emergency-department patient? What are the alternatives or possible consequences of not practising non-invasive and minimally invasive procedures on newly dead patients? Is consent from relatives required? Should doctors in emergency departments allow or even encourage this use of newly dead patients?
NCI 8609: Multicenter Phase I Trial of PARP Inhibitor Veliparib with Carboplatin in Advanced Breast Cancer
Authors: B. Ramaswamy, S. Geyer, M. Lustberg, R. Wesolowski, E. Andreopoulou, M. Knopp, M. Villalona, A. Chen, M. Grever, C. Shapiro
Journal: Annals of Oncology (2013)