tbuckley/cabot-search huggingface dataset:
Evaluation of Progression-Free Survival as a Surrogate Endpoint for Survival in Chemotherapy and Targeted Agent Metastatic Colorectal Cancer Trials
Authors: Roger Sidhu, Alan Rong, Steve Dahlberg
Journal: Clinical Cancer Research (2013)

Pooled analyses of chemotherapy trials in metastatic colorectal cancer (mCRC) have suggested that progression-free survival (PFS) is a surrogate endpoint for overall survival (OS). However, this has not been evaluated under current standard-of-care regimens of chemotherapy in combination with targeted therapies. We conducted an analysis of published mCRC trials of chemotherapy and targeted therapies from 2000 to evaluate the surrogacy of PFS and response rate (RR) for OS. Study-level data was pooled from 24 randomized mCRC trials that evaluated fluoropyrimidine-based regimens and included trials conducted with targeted agents (panitumumab, cetuximab, bevacizumab, and aflibercept). A total of 69 treatment arms with a sample size of 20,438 patients was included. Linear regression analysis was carried out to estimate the correlation of PFS and RR with OS. The correlation coefficient between PFS HRs and OS HRs was 0.86 for all trials, 0.89 for 12 phase III trials of targeted agents in combination with chemotherapy, 0.95 for 8 first-line phase III trials of targeted agents, and 0.83 for 9 trials of anti-EGFR-targeted agents. In all cases, correlation coefficients between RR and OS HRs were lower than those between PFS HRs and OS HRs (range, 0.42-0.81). In this study-level analysis of randomized mCRC trials of chemotherapy and targeted agents, improvements in PFS are strongly correlated with improvements in OS. This suggests that PFS remains a valid surrogate endpoint for OS with current treatment regimens in the mCRC setting.
The Problem of Tobacco Habituation
Authors: Richard D. Chessick
Journal: JAMA (1964)

ACCORDING to a carefully presented argument in chapter 13 of the recent US Public Health Service report entitled<i>Smoking and Health</i>, it is not justifiable to use the term "tobacco addiction" in the strict sense of the term "addiction."<sup>1</sup>This does not imply, however, that it is easy to stop the tobacco habit, or that tobacco does not play an important and specific psychological and physiological role in the lives of people who habitually ingest it. The role tobacco plays is important in view of the serious danger to health engendered by the smoking habit, and many attempts are being made nationally to suppress it. A sympathetic-like constriction of the peripheral vascular bed, increase in blood pressure, and acceleration of heart rate are produced by each cigarette or injection of nicotine.<sup>1</sup>These effects occur in smokers, normal subjects, and those with coronary or peripheral vascular disease. No tolerance
Restructuring American health care financing: First of all, do no harm!
Authors: Paul D. Berk
Journal: Hepatology (1993)

Health care costs are climbing throughout the western world. Aging populations and the costs of advanced technology are the principal forces behind much of this global increase. No country has yet succeeded in containing these growing costs other than by some form of rationing. A variety of experimental strategies, including managed competition, are being considered or tested, but none is clearly effective. American health care expenditures differ, not in that they are rising, but in their enormously high starting point. Among other things, our higher costs reflect administrative costs of more than 20%, double those of Canada and nearly triple the European average; a malpractice system that, whatever its possible advantages, costs more than 10 times as much as it pays out to the injured; the enormous medical costs of poverty; maldistribution of physician specialties and incomes; and reimbursement systems that eliminate consumer input and oversight. Restructuring the system of health care financing to bring administrative costs in line with those of other nations could save at least $70 billion annually; another $25 billion or more could be saved by replacing the malpractice system with more cost-effective alternatives. These savings could defray the costs of insuring all those not now covered, without increasing either costs to the middle class, through taxation of benefits, or total health care expenditures. With all Americans covered, the necessary restructuring of the system of health care delivery could be conducted without the current pressure for immediate drastic reform, which carries with it the risk of serious error. In dealing with the sick, physicians are taught to apply two maxims: “primum non nocere” or “first of all, do no harm!”; and the rule of therapeutic restraint. The latter states that a severe chronic illness may respond better, and with fewer complications, to gradual corrective measures than to highly aggressive therapy. Both rules could well be applied to curing the American health care system.
Diagnostic Importance of an Increased Serum Anion Gap
Authors: Patricia A. Gabow, William D. Kaehny, Paul V. Fennessey, Stephen I. Goodman, Peter A. Gross, Robert W. Schrier
Journal: New England Journal of Medicine (1980)

Abstract Fifty-seven hospitalized patients with increased serum anion gaps, defined as [Na] − ([Cl] + [HCO3]), were studied to explore the biochemical basis and the diagnostic importance of the anion gap. We found that an anion gap greater than 30 meq per liter was usually due to an identifiable organic acidosis (lactic acidosis or ketoacidosis). However, 10 of 35 patients (29 per cent) with anion gaps of 20 to 29 meq per liter did not have lactic acidosis or ketoacidosis. In 22 patients, the composition of the anion gap was studied in detail. Lactate and ketoanions accounted for 62 per cent of the increments in anion gaps, and changes in the equivalents of total proteins, phosphorus, potassium, and calcium accounted for 15 per cent. However, nine patients had an increment in anion gap of 5.5 meq per liter or more (average, 8.7 meq per liter) that was not explained by any of the factors measured here. The possibility of unidentified anions or unrecognized changes in the ionic equivalents of normal plasma ...
247 INTRACELLULAR SIGNALING MEDIATED BY AKT IS EXACERBATED IN THE LIVER OF TRANSGENIC MICE OVEREXPRESSING GROWTH HORMONE
Authors: J.G. Miquet, C.S. Martinez, L. González, M.E. Díaz, E. Zotta, A. Bartke, D. Turyn, A.I. Sotelo
Journal: Journal of Hepatology (2009)
Infection of human synovial cells by human T cell lymphotropic virus type I. Proliferation and granulocyte/macrophage colony-stimulating factor production by synovial cells.
Authors: M Sakai, K Eguchi, K Terada, M Nakashima, I Yamashita, H Ida, Y Kawabe, T Aoyagi, H Takino, T Nakamura
Journal: Journal of Clinical Investigation (1993)

The present study was performed to clarify the relationship between human T cell lymphotropic virus type I (HTLV-I) infection and chronic inflammatory arthropathy. To determine the ability of HTLV-I to infect synovial cells and the effect on synovial cell proliferation, synovial cells were cocultured with the HTLV-I-producing T cell lines (MT-2 or HCT-1). After coculture with HTLV-I-infected T cells, the synovial cells expressed HTLV-I-specific core antigens, and HTLV-I proviral DNA was detected from the synovial cells by polymerase chain reaction. These cocultured synovial cells with HTLV-I-infected T cells proliferated more actively than the synovial cells cocultured with uninfected T cells. This stimulatory effect of HTLV-I-infected T cells on synovial cell proliferation seems necessary to contact each other. After being cocultured with MT-2 cells, synovial cells proliferated more actively than control cells even after several passages. Furthermore, HTLV-I-infected synovial cells produced significant amounts of granulocyte/macrophage colony-stimulating factor. These results suggest that HTLV-I can infect synovial cells, resulting their active proliferation and may be involved in the pathogenesis of proliferative synovitis similar to that found in rheumatoid arthritis.
REMOTE MAGNETIC NAVIGATION FOR ABLATION OF ATRIAL FIBRILLATION WITH THE OPEN IRRIGATION ABLATION CATHETER: ACUTE ENDPOINT WITH CIRCUMFERENTIAL ABLATION VERSUS CIRCULAR MAPPING GUIDED ABLATION
Authors: Luigi Di Biase, J. David Burkhardt, Dhanunjay Lakkireddy, Javier Sanchez, Jayasree Pillarisetti, Rodney Horton, G. Joseph Gallinghouse, Shane Bailey, Prasant Mohanty, Mitra Mohanty, Richard Hongo, Steven Hao, Salwa Beheiry, Pasquale Santangeli, Vladimir Astudillo, Dimpi Patel, Claude S. Elayi, Conor Barrett, Andrea Natale
Journal: Journal of the American College of Cardiology (2010)
Failure of Epinephrine to Provoke Flushing in Patients with Systemic Mastocytosis
Authors: ASHOK B. VAIDYA
Journal: Annals of Internal Medicine (1971)

The epinephrine provocative test was performed in five patients in whom the diagnosis of systemic mastocytosis had been established both by biopsy and by findings of high histamine levels in urine. In each patient the result of the epinephrine provocative test was negative. This finding supports the reliability of the epinephrine provocative test as an aid to the diagnosis of carcinoid syndrome by adding to the documentation of its specificity.
Differences and Differentials
Authors: J. M. Armitt
Journal: BMJ (1964)

after pyloroplasty.This is one of several reasons why gastro-enterostomy should be avoided.In cases of severe dumping the gastro-enterostomy is probably best taken down and replaced by pyloroplasty.May I, too, comment on gastrostomy after vagotomy and pyloroplasty-referred to by Professor A. W. Kay (28 March, p. 822) ?Hendry taught me to use neither naso-gastric intubation nor gastrostomy after this opera- tion, nor to use a naso-gastric tube before operation.In over 200 cases I can confirm his teaching.There is no need whatever for any form of gastric suction after vagotomy and pyloroplasty.Fluids by mouth in the immediate post-operative period need not be severely restricted.With "tubeless " vag- otomy fluids and electrolytes are not with- drawn and do not, therefore, need to be replaced.Post-operative intravenous fluids, or even rectal fluids, are not routinely neces- sary, though in hot weather we give saline in the theatre to combat fluid loss there and to allay post-operative thirst.-Iam, etc.,
POTASSIUM IODID IN CEREBRO-SPINAL MENINGITIS.
Authors: H. A. MOODY
Journal: JAMA (1898)

The object of this brief paper is to emphasize the value of potassium iodid in meningitis, especially in that severe and fatal form known as cerebro-spinal meningitis. Since deciding to present this subject I have looked through quite a number of the authorities most frequently consulted by the general practitioner, to form an approximate estimate of the appreciation in which this drug is held in the treatment of meningitis. I find that its use is recommended by many of them, but seldom during the stage in which I have found it most efficient. Biddle does not mention it in this connection; neither does Hare in his shorter work, the one most frequently consulted. Potter recommends a longer course of it during convalescence. Wood does not recommend it; neither does Stillé. Bartholow recommends it to remove adventitious products after the acute attack has subsided. Skinner reports Dr. Valten as asserting that
Israel bans import of sildenafil citrate after six deaths in the US
Authors: J. Siegel-Itzkovich
Journal: BMJ (1998)

Israel's health ministry has barred the personal import of the impotence drug sildenafil citrate (Viagra) until further notice, pending the results of a US Food and Drug Administration (FDA) investigation into the deaths of six American men who took the pills.

Pfizer, the manufacturer of sildenafil citrate, reported the six deaths to the FDA last week, although it is still unclear whether the deaths are related to the drug. The drug for erectile dysfunction has created unprecedented demand in the United States—the only place where it is licensed so far—and elsewhere in the world.

The Palestinian Authority health ministry has also …
Pulmonary eosinophilia associated with montelukast
Authors: J. Franco, M. J. Artes
Journal: Thorax (1999)

Antileukotriene drugs are new therapeutic agents that have recently been approved for the treatment of asthma. Several cases of eosinophilic conditions including Churg-Strauss syndrome have been reported to be associated with zafirlukast, a cysteinyl leukotriene type 1 receptor antagonist. So far no other leukotriene modifier has been associated with the syndrome. The case history is presented of a man with allergic rhinitis and asthma who had received intermittent pulse therapy with oral corticosteroids. Pulmonary eosinophilia developed while he was receiving treatment with montelukast, a chemically distinct cysteinyl leukotriene type 1 receptor antagonist. After discontinuation of montelukast therapy and administration of systemic corticosteroids the patient's symptoms reversed rapidly and there was prompt resolution of the pulmonary infiltrates. We believe that cysteinyl leukotriene type 1 receptor antagonists are safe and effective drugs for most patients with asthma but caution is needed for those with more severe disease who require systemic corticosteroids, especially if they show characteristics of the atypical allergic diathesis seen in the prodromal phase of Churg-Strauss syndrome.
Effect of Pancreatic Replacement Therapy on Metabolic Balance in Adolescent Fibrocystic Disease.
Authors: A. B. French
Journal: Annals of Internal Medicine (1968)

s1 May 1968Effect of Pancreatic Replacement Therapy on Metabolic Balance in Adolescent Fibrocystic Disease.A. B. French, M.D., F.A.C.P., H. B. Cook, M.R.A.C.P.A. B. French, M.D., F.A.C.P.Search for more papers by this author, H. B. Cook, M.R.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1147_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExcessive fecal fat and nitrogen losses occur in some patients with gross pancreatic insufficiency. The metabolic problems created by these losses may require an aggressive therapeutic program. Detailed knowledge of the effects of pancreatic replacement on losses of nutrients, electrolytes, and minerals is limited. Two adolescent boys with fibrocystic disease and fecal fat losses of 60 to 100 g/day were studied. Dietary intakes and fecal and urinary losses were measured for fat, nitrogen, sodium, potassium, chloride, calcium, phosphorus, and magnesium. Dose-response relationships were established with up to 150 tablets (55.7 g) of Viokase® (pancrepilase) daily for 17 periods of balance... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Ann Arbor, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1147-1147KeywordsAdolescentsCalciumFatsMagnesiumMetabolic disordersNutrientsPhosphorusPotassium chlorideSaltsSodium Issue Published: 1 May 1968 PDF downloadLoading ...
Practical effects of blood group incompatibility between mother and fetus.
Authors: C A Clarke
Journal: BMJ (1972)

It was Ford1 who first suggested that advantages and disad vantages, such as susceptibility to certain diseases, would be found to be associated with the human blood groups. Neverthe less, it was many years before practical work was started on the subject and only when Aird et al2 had shown that a signifi cantly high proportion of patients with cancer of the stomach belong to group A and of those with peptic ulcer to group O did the idea become widely accepted. Though of great theoretical interest, such associations between blood groups and disease are not of help to individual patients, and the purpose of this paper is to draw attention to other situations which do have medical (or veterinary) implications in particular cases and yet which also play a part in maintaining the polymorphisms. Such, for instance, are disorders due to interactions between the blood groups of mother and fetus which may result in the various types of haemolytic disease of the newborn, and, though this is more speculative, where blood group compatibility may influence the course of certain types of cancer. The keynote of haemolytic disease of the newborn, whether it be due to ABO or Rh incompatibility, is how ??frequently the fetus is affected compared with the chances of how often it might be. This is because there are several naturally occurring protective mechanisms, and it was one of these which led to a successful method of preventing rhesus haemolytic disease.
TGF-β and αvβ6 Integrin Act in a Common Pathway to Suppress Pancreatic Cancer Progression
Authors: Aram F. Hezel, Vikram Deshpande, Stephanie M. Zimmerman, Gianmarco Contino, Brinda Alagesan, Michael R. O'Dell, Lee B. Rivera, Jay Harper, Scott Lonning, Rolf A. Brekken, Nabeel Bardeesy
Journal: Cancer Research (2012)

Abstract The TGF-β pathway is under active consideration as a cancer drug target based on its capacity to promote cancer cell invasion and to create a protumorigenic microenvironment. However, the clinical application of TGF-β inhibitors remains uncertain as genetic studies show a tumor suppressor function of TGF-β in pancreatic cancer and other epithelial malignancies. Here, we used genetically engineered mouse models to investigate the therapeutic impact of global TGF-β inhibition in pancreatic cancer in relation to tumor stage, genetic profile, and concurrent chemotherapy. We found that αvβ6 integrin acted as a key upstream activator of TGF-β in evolving pancreatic cancers. In addition, TGF-β or αvβ6 blockade increased tumor cell proliferation and accelerated both early and later disease stages. These effects were dependent on the presence of Smad4, a central mediator of TGF-β signaling. Therefore, our findings indicate that αvβ6 and TGF-β act in a common tumor suppressor pathway whose pharmacologic inactivation promotes pancreatic cancer progression. Cancer Res; 72(18); 4840–5. ©2012 AACR.
Prevalence of TB in healthcare workers in south west London
Authors: T B L Ho
Journal: Thorax (2004)

In the UK, and London specifically, the rise in the incidence of tuberculosis (TB) has been ascribed to reactivation of latent disease and importation of infection from recent immigrants.1 The recent increase in the recruitment of healthcare workers from countries with a high prevalence of TB raises the possibility of healthcare workers being a significant source of disease. Previous estimates of TB infection among National Health Service (NHS) employees were calculated before the current levels of HIV infection and the mass migration of healthcare workers.2,3 The current number of healthcare workers with TB is unknown but an estimate of this would provide data on the risk that they pose for spreading TB infection.

We conducted a retrospective interrogation of the local TB database (Integrated Tuberculosis Surveillance System, ITSS) for all healthcare workers notified in 2002. Their medical notes were then reviewed and a basic dataset was collated. A healthcare …
Cytotoxicity of radiocontrast agents on polarized renal epithelial cell monolayers
Authors: C HALLER, C SCHICK, M ZORN, W KUBLER
Journal: Cardiovascular Research (1997)

Objective: Radiocontrast-induced nephropathy is a clinically important complication of coronary angiography. The cellular mechanisms of radiocontrast-induced renal dysfunction are not clear. Since tubular transport functions depend on the polarity of renal epithelial cells, we investigated the effects of radiocontrast agents on polarized tubular cells in vitro. Methods: We studied the effects of iso-iodine concentrations (37 and 74 mg iodine/ml) of an ionic (diatrizoate) and a non-ionic (iopamidol) monomeric radiocontrast agent and of hyperosmolal mannitol control solutions on filter-grown renal epithelial cell (MDCK, LLCPK) monolayers in vitro. The cytotoxicity was assayed by measurement of cell viability, transepithelial resistance, inulin permeability and (polarized) cellular enzyme release. The polarized MDCK cell phenotype was assessed by transmission electron microscopy and indirect immunofluorescence microscopy using monoclonal antibodies against specific apical (gp135) and basal (gp60, uvomorulin) MDCK surface markers. Results: The radiocontrast agents reduced cell viability to a greater extent than hyperosmolal mannitol solutions in both cell lines; diatrizoate was more toxic than iopamidol. LLCPK cells were more susceptible to radiocontrast cytotoxicity than MDCK cells. This cytotoxicity was associated with an alteration of MDCK cell polarity as assessed by the redistribution of surface marker proteins. Conclusions: Diatrizoate is more toxic than iopamidol, which is partly related to its higher osmolality. The cytotoxicity of radiocontrast agents induces a redistribution of polarized membrane proteins which could contribute to the pathophysiology of radiocontrast-induced nephropathy.
Children and sun protection
Authors: M. Berneburg, C. Surber
Journal: British Journal of Dermatology (2009)

Sun protection is a central measure to avoid the development of skin cancer and premature aging of the skin. In this context skin protection of children is of particular relevance since children spend a lot of time outdoors and they cannot provide themselves with sun protection measures as adults can. In addition to this sunburn reactions in childhood are particularly important in the development of melanoma skin cancer. This special situation of children with regards to sun protection has not only become aware to dermatologists but also to politicians, which is why a recent recommendation of the European Union explicitly points out the necessity of stringent sun protection of children. This review summarizes the current knowledge about sun protection of children. Underlying mechanisms of skin carcinogenesis in children, available sun protection measures as well as practical advice on daily sun protection of children are discussed.
CYSTS OF THE VERMIFORM APPENDIX.
Authors: E. E. MONTGOMERY
Journal: JAMA (1897)

Cysts of the vermiform appendix have until recently received but little attention. These cysts are without doubt inflammatory in origin. The inflammation results in destruction of a portion of the mucous lining and obliteration of the corresponding canal. The secretion of undestroyed portion of membrane forms a cyst. These cysts are usually of small size, although Virchow has reported one which attained to the size of the fist. Van Hook reports thirty-two cases. The writer removed one from a pregnant woman, in which there was marked hyperesthesia over the right inguinal and lumbar regions, more marked, indeed, than seemed justified by the local lesion. The patient miscarried the day following. Microscopic examination disclosed staphylococci in the contents of the cyst. It has always been with me a question as to how much the symptoms were due to the appendiceal lesion, and how much to the occurrence of an attack of
NICE's role in further developing the Quality and Outcomes Framework is in question
Authors: T. Stokes, N. Steel
Journal: BMJ (2014)

Guthrie and Morales highlight that radical change is coming to the clinical and public health indicator set of the UK’s Quality and Outcomes Framework (QOF) in 2014-15.1 2 3 They, however, only partially explore the roles of the National Institute for Health and Care Excellence (NICE) and NHS England in retiring indicators from QOF, …