tbuckley/cabot-search huggingface dataset:
S-1 Plus Cisplatin Combination Chemotherapy in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Yukito Ichinose, Kozo Yoshimori, Hiroshi Sakai, Yushi Nakai, Takahiko Sugiura, Masaaki Kawahara, Hisanobu Niitani
Journal: Clinical Cancer Research (2004)

Abstract Purpose: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non–small-cell lung cancer (NSCLC) patients. Experimental Design: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m2 twice a day for 21 consecutive days while cisplatin (60 mg/m2) was administered intravenously on day 8. This schedule was repeated every 5 weeks. Results: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1–12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34–61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%). Conclusions: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.
A cytokine-mediated link between innate immunity, inflammation, and cancer
Authors: Wan-Wan Lin, Michael Karin
Journal: Journal of Clinical Investigation (2007)

It has been established that cancer can be promoted and/or exacerbated by inflammation and infections. Indeed, chronic inflammation orchestrates a tumor-supporting microenvironment that is an indispensable participant in the neoplastic process. The mechanisms that link infection, innate immunity, inflammation, and cancer are being unraveled at a fast pace. Important components in this linkage are the cytokines produced by activated innate immune cells that stimulate tumor growth and progression. In addition, soluble mediators produced by cancer cells recruit and activate inflammatory cells, which further stimulate tumor progression. However, inflammatory cells also produce cytokines that can limit tumor growth. Here we provide an overview of the current understanding of the role of inflammation-induced cytokines in tumor initiation, promotion, and progression.
Abstract 15002: Towards Unmasking Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy in the Early Concealed Stage
Authors: Thomas P Mast, Arco J Teske, Jeroen F vd Heijden, Judith A Groeneweg, Pieter A Doevendans, Peter Loh, Richard N Hauer, Maarten J Cramer
Journal: Circulation (2014)

Background: The concealed stage of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is associated with increased risk of sudden cardiac death. However, particular at this stage disease detection is hampered by absence of criteria. Activation delay (AD) is a hallmark of arrhythmogenesis in ARVD/C. Echocardiographic tissue Doppler imaging (TDI) may unmask AD in the absence of electrocardiographic (ECG) abnormalities. Methods: Three groups were compared 1) symptomatic definite ARVD/C patients with a mutation in the Plakophilin-2 ( PKP2) gene (n=37), 2) asymptomatic PKP2 mutation carriers (n=20) and 3) healthy controls (n=30). All groups underwent full echocardiographic examination with additional TDI of the right ventricular (RV) free wall and a routine 12-lead ECG recording. As surrogate for AD the electro-mechanical interval (EMI) was measured, defined as time between local first electrical deflection and local onset of mechanical shortening. EMI was measured in the subtricuspid, mid and apical region of the RV free wall. Detailed ECG analysis of depolarization (AD analysis) and repolarization abnormalities was performed in all subjects. Results: EMI was prolonged in all RV segments in ARVD/C patients compared to controls. Abnormal depolarization and repolarization was recorded in respectively 23 and 27 ARVD/C patients. In asymptomatic mutation carriers EMI was significantly prolonged in the subtricuspid area (Table 1). However, the ECG showed in 5/20 subjects only prolonged terminal activation duration and no repolarization abnormalities. Conclusion: TDI unmasks AD in both ARVD/C patients and asymptomatic mutation carriers. In asymptomatic mutation carriers EMI is prolonged in the subtricuspid area, whereas ECG appeared normal in the large majority. AD in the subtricuspid area is an early sign of disease in the concealed ARVD/C stage and may contribute to advanced risk stratification. Table 1: Results
Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles.
Authors: W S Pear, J C Aster, M L Scott, R P Hasserjian, B Soffer, J Sklar, D Baltimore
Journal: The Journal of Experimental Medicine (1996)

Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells.
BTS guidelines for the management of community acquired pneumonia in adults: update 2009
Authors: W S Lim, S V Baudouin, R C George, A T Hill, C Jamieson, I Le Jeune, J T Macfarlane, R C Read, H J Roberts, M L Levy, M Wani, M A Woodhead
Journal: Thorax (2009)

A summary of the initial management of patients admitted to hospital with suspected community acquired pneumonia (CAP) is presented in fig 8. Tables 4 and5, respectively, summarise (1) the relevant microbiological investigations and (2) empirical antibiotic choices recommended in patients with CAP. Investigations (Section 5)When should a chest radiograph be performed in the community?BTS guidelines
Active Surveillance Is the Preferred Approach to Clinical Stage I Testicular Cancer
Authors: Craig R. Nichols, Bruce Roth, Peter Albers, Lawrence H. Einhorn, Richard Foster, Siamak Daneshmand, Michael Jewett, Padraig Warde, Christopher J. Sweeney, Clair Beard, Tom Powles, Scott Tyldesley, Alan So, Christopher Porter, Semra Olgac, Karim Fizazi, Brandon Hayes-Lattin, Peter Grimison, Guy Toner, Richard Cathomas, Carsten Bokemeyer, Christian Kollmannsberger
Journal: Journal of Clinical Oncology (2013)

Craig R. Nichols, Virginia Mason Medical Center, Seattle, WA Bruce Roth, Washington University School of Medicine, St Louis, MO Peter Albers, University Hospital Heinrich-Heine, University of Dusseldorf, Dusseldorf, Germany Lawrence H. Einhorn and Richard Foster, Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN Siamak Daneshmand, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA Michael Jewett and Padraig Warde, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Christopher J. Sweeney and Clair Beard, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA Tom Powles, Bart’s Cancer Institute, St Bartholomew’s Hospital, Queen Mary University of London, London, United Kingdom Scott Tyldesley and Alan So, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada Christopher Porter and Semra Olgac, Virginia Mason Medical Center, Seattle, WA Karim Fizazi, Institute Gustave Roussy, University of Paris Sud, Paris, France Brandon Hayes-Lattin, Knight Cancer Institute, Oregon Health and Science University, Portland, OR Peter Grimison, Royal Prince Alfred Hospital, Sydney Cancer Centre, University of Sydney, Sydney, New South Wales, Australia Guy Toner, Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Victoria, Australia Richard Cathomas, Kantonsspital Graubuenden, Chur, Switzerland Carsten Bokemeyer, University Medical Centre Eppendorf, Hamburg University, Hamburg, Germany Christian Kollmannsberger, British Columbia Cancer Agency–Vancouver Cancer Centre, University of British Columbia, Vancouver, British Columbia, Canada
Surveillance of Duodenal Adenomas in Familial Adenomatous Polyposis Reveals High Cumulative Risk of Advanced Disease
Authors: Jean-Christophe Saurin, Christelle Gutknecht, Bertrand Napoleon, Annick Chavaillon, René Ecochard, Jean-Yves Scoazec, Thierry Ponchon, Jean-Alain Chayvialle
Journal: Journal of Clinical Oncology (2004)

Purpose The development of high-grade dysplasia (HGD) on duodenal or jejunal adenomas and of late-stage (stage IV) duodenal polyposis are major clinical events for familial adenomatous polyposis (FAP) patients. Our aim was to determine their respective frequency, risk factors, and cumulative risk. Patients and Methods A prospective, optimized, endoscopic surveillance protocol was applied to 58 FAP patients in a university hospital. The number, size, and histology of duodenojejunal polyps were assessed, and the Spigelman’s score was calculated at each endoscopy. Cox regression and linear regression analysis were used to determine risk factors for HGD development and the cumulative risk of stage IV duodenal polyposis, respectively. Results During a median (± standard deviation) follow-up of 47.9 ± 15.6 months, 35 patients with at least two consecutive examinations had 107 duodenojejunal examinations. The Spigelman’s score increased in 21 patients (60.0%), and HGD developed in 12 patients (34.2%). High initial Spigelman’s score (&gt; 7 points), but not age or APC mutation site, was a risk factor for HGD development. Estimated cumulative risk of developing stage IV duodenal polyposis was of 42.9% at age 60 (95% CI, 35.7% to 50.0%) and 50.0% at age 70 (95% CI, 42.9% to 57.1%). Conclusion This prospective series shows a higher duodenal polyposis progression rate and cumulative risk of late-stage (stage IV) duodenal polyposis in FAP patients compared with previous series. These results suggest that current modalities for surveillance and management of these patients need revision.
Factors associated with infection by Pseudomonas aeruginosa in adult cystic fibrosis
Authors: D. Chambers
Journal: European Respiratory Journal (2005)

Cross-infection with Pseudomonas aeruginosa is an emerging issue in the care of patients with cystic fibrosis (CF). This study sought to determine the extent of, and patient factors associated with, cross-infection in a tertiary referral adult CF centre. P. aeruginosa isolates were genotyped into two groups between November 2001 and February 2003, using pulsed-field gel electrophoresis after DNA digestion by the SpeI endonuclease, and identified as clustered if there was >80% homology in the macrorestriction profiles. Patient factors and measures of disease severity were identified a priori. In total, 157 out of 227 patients had a P. aeruginosa isolate genotyped. Of these, 94 patients (60%) were infected with clustered genotypes and 47 (30%) were infected with the newly described "Midlands 1" (Md1) genotype. A further 18 patients were infected with the previously identified "Liverpool" genotype and two with the "Manchester" genotype. Logistic regression analysis revealed that the predominant predictor of infection with Md1 was age at the time of referral to the centre, suggesting that infection may have occurred prior to referral in some patients. Md1 demonstrated a relatively benign anti-biogram and did not appear to be associated with more severe disease. In conclusion, the present study provides further evidence of the emerging importance of Pseudomonas aeruginosa cross-infection in cystic fibrosis.
Genotype-Phenotype Correlations as a Guide in the Management of Familial Adenomatous Polyposis
Authors: Mary H. Nieuwenhuis, Lisbeth M. Mathus–Vliegen, Frederik J. Slors, Gerrit Griffioen, Fokko M. Nagengast, Wim R. Schouten, Jan H. Kleibeuker, Hans F.A. Vasen
Journal: Clinical Gastroenterology and Hepatology (2007)
Intermediate-Term Outcome After Intracardiac Repair of Associated Cardiac Defects in Patients With Atrioventricular and Ventriculoarterial Discordance
Authors: Tetsuya Sano, Thomas Riesenfeld, Tom R. Karl, James L. Wilkinson
Journal: Circulation (1995)

Background Limited information is available concerning long-term results, especially systemic right ventricular (RV) or tricuspid valvular function, after intracardiac repair of anomalies associated with discordant atrioventricular (AV) and ventriculoarterial (VA) connections (“congenitally corrected transposition of the great arteries”). Methods and Results We retrospectively reviewed the intermediate-term follow-up of 28 patients, totaling 158 patient-years (median, 60 months), after intracardiac repair involving closure of a ventricular septal defect (VSD) with or without additional surgery. Seven patients had VSD closure alone, 5 had VSD repair with pulmonary stenosis relief, and 16 had VSD closure with conduit insertion between left ventricle and main pulmonary artery. Hospital mortality was 4% (1 of 28 patients; 70% confidence limits, 0.07% to 12%) and the 1-, 5-, and 10-year actuarial survival probabilities were 89%, 83%, and 83%, respectively. Twenty-one of 24 long-term survivors were in New York Heart Association functional class I and 3 were in class II. Sixteen of 24 patients showed increasing tricuspid regurgitation (TR) of more than moderate degree, which occurred within 3 years after surgery in 7 patients. Twelve of 22 patients showed deterioration of RV pump function, mainly (9 of 12 patients) within 3 years postoperatively. The pulmonary to systemic flow ratio at the preoperative cardiac catheter study was significantly ( P &lt;.05) higher in patients who developed RV dysfunction (2.3±1.0, mean±SD) than in those with well-maintained RV function (1.4±0.6). Conclusions Intermediate-term results of intracardiac repair for AV and VA discordance were satisfactory in terms of survival and clinical functional status; however, there is concern about systemic RV dysfunction with development of TR relatively early after the operation. Alternative surgical approaches such as anatomic correction or Fontan repair for cases unsuitable for biventricular repair may improve the long-term results, including ventricular and valvular function.
Effect of somatostatin-induced suppression of postprandial insulin response upon the hypertriglyceridemia associated with a high carbohydrate diet.
Authors: H N Ginsberg, A Jacobs, N A Le, J Sandler
Journal: Journal of Clinical Investigation (1982)

In an attempt to define the relationship between plasma insulin and triglyceride concentrations, we have studied the effect of suppression of the postprandial insulin response upon the secretion and plasma concentration of very low density lipoprotein (VLDL)-triglycerides. Eight nondiabetic subjects with a wide range of fasting plasma triglyceride levels (100-358 mg/dl) were studied during three dietary periods: base line, high carbohydrate (80% calories), and high carbohydrate (80% calories) with a daily intravenous infusion of somatostatin (SRIF) (1.3 micrograms/min) between 800 and 2,100 h. The significant increase in postprandial insulin response observed during high carbohydrate vs. base line was completely abolished during high carbohydrate-SRIF. However, plasma triglyceride levels rose in all subjects during each high carbohydrate period (with/without SRIF) vs. base line and the mean values reached during each period were the same (476 +/- 165 vs. 482 +/- 152 mg/dl, respectively). The secretion of VLDL-triglyceride into plasma was higher in four subjects, the same in two subjects, and lower in one subject during high carbohydrate-SRIF vs. high carbohydrate alone. The mean production rate of VLDL-triglyceride (mg/kg per h) was 25.6 +/- 4.9 during the high carbohydrate and 40.9 +/- 28.1 during the high carbohydrate-SRIF periods. These values were not significantly different. Postprandial glucose levels were slightly increased during high carbohydrate-SRIF, but overnight glucose concentrations were not affected. Plasma FFA levels were not different during the two high carbohydrate periods. Plasma glucagon levels did not appear to affect the results either. This study indicates that postprandial hyperinsulinemia during a high carbohydrate diet is not necessary for induction of hypertriglyceridemia.
Local Regulation of Vascular Cross Section during Changes in Femoral Arterial Blood Flow in Dogs
Authors: MONS LIE, OLE M. SEJERSTED, FREDRIK KIIL
Journal: Circulation Research (1970)

Diameters of the exposed femoral artery of anesthetized dogs were continuously measured with ultrasonic elements of lead zirconate titanate. In 13 of 16 dogs vascular diameters increased following a sudden increment in arterial blood flow induced by the injection of vasodilating agents (acetylcholine, histamine) peripheral to the recording level, by opening an arteriovenous shunt, or after tetanic stimulation of the sciatic nerve. The dilatation response occurred despite slight reductions in femoral blood pressure, and was present after ganglionic blockade, blockade of alpha and beta receptors with phenoxybenzamine and propranolol, atropinization and injection of an antihistamine. The dilatation response was also observed after transsection of the femoral artery distal to the recording level and is therefore not dependent on the retrograde propagation of nervous or myogenous impulses along the vascular wall.
Quantitative Statistical Methods for Image Quality Assessment
Authors: Joyita Dutta, Sangtae Ahn, Quanzheng Li
Journal: Theranostics (2013)

Quantitative measures of image quality and reliability are critical for both qualitative interpretation and quantitative analysis of medical images.While, in theory, it is possible to analyze reconstructed images by means of Monte Carlo simulations using a large number of noise realizations, the associated computational burden makes this approach impractical.Additionally, this approach is less meaningful in clinical scenarios, where multiple noise realizations are generally unavailable.The practical alternative is to compute closed-form analytical expressions for image quality measures.The objective of this paper is to review statistical analysis techniques that enable us to compute two key metrics: resolution (determined from the local impulse response) and covariance.The underlying methods include fixed-point approaches, which compute these metrics at a fixed point (the unique and stable solution) independent of the iterative algorithm employed, and iteration-based approaches, which yield results that are dependent on the algorithm, initialization, and number of iterations.We also explore extensions of some of these methods to a range of special contexts, including dynamic and motion-compensated image reconstruction.While most of the discussed techniques were developed for emission tomography, the general methods are extensible to other imaging modalities as well.In addition to enabling image characterization, these analysis techniques allow us to control and enhance imaging system performance.We review practical applications where performance improvement is achieved by applying these ideas to the contexts of both hardware (optimizing scanner design) and image reconstruction (designing regularization functions that produce uniform resolution or maximize task-specific figures of merit).
Waiting in the NHS
Authors: Terry Hamblin
Journal: Journal of the Royal Society of Medicine (2002)

Dr Devlin and her colleagues (May 2002 JRSM1) ask what mechanisms have been used in Dorset to achieve a sustained reduction in waiting times. The answer is many.

First, Dorset is a pleasant part of the country. As a consequence many of the people who chose to live here can afford private health insurance, which takes a load from the NHS. Because it is a nice place to live, there is competition for medical posts leading to the appointment of general practitioners and consultants of very high quality. This has engendered happy relationships between doctors, without feuds that characterize metropolitan health providers and that so impair efficiency. The best managers are also attracted.

Second, numerous large houses, once family hotels, have been converted to private nursing homes, and the availability of these means that relatively few ‘bed-blockers’ occupy acute medical beds.

Third, the cooperation between the two largest hospitals in Bournemouth and Poole has meant that services can be shared rationally across the county without vain competition. For example, beds for elective orthopaedics are separated from acute trauma. It has thus been possible to avoid wasting money on trying to staff small inadequate units, merely to maintain a presence of that specialty in a district general hospital.

Fourth, the main purchaser has been single-minded in wanting to abolish waiting lists and has spent money wisely to remove bottlenecks, without regard to political dogma. Nevertheless, he has listened to the doctors and always responded to genuine concerns for other parts of the service while not being fooled by ‘kite-flying’ operations.

Fifth, the whole medical community has been visionary in spotting new developments. For example, cancer services were developed and new oncologists appointed while the new drugs had only numbers and had not yet been named, and before the shortage of trainees in oncology began to bite.

Finally, the relative affluence of the community has made it possible to fund from non-exchequer sources a good deal of capital improvement.

Most of these factors are site-specific; they will not work in Croydon or Workington. But several health authorities with similar populations have been much less successful, and the reason cannot simply be that their beaches are covered with pebbles while ours have seven miles of golden sand.