tbuckley/cabot-search huggingface dataset:
<i>TGFBR1</i>*6A and Cancer Risk: A Meta-Analysis of Seven Case-Control Studies
Authors: Virginia G. Kaklamani, Nanjiang Hou, Yiansong Bian, Jennifer Reich, Kenneth Offit, Loren S. Michel, W.S. Rubinstein, Alfred Rademaker, Boris Pasche
Journal: Journal of Clinical Oncology (2003)

TGFBR1*6A is a hypomorphic polymorphic allele of the type I transforming growth factor beta receptor (TGFBR1). TGFBR1*6A is a candidate tumor susceptibility allele that has been associated with an increased incidence of various types of cancer. This study was undertaken to analyze all published case-control studies on TGFBR1*6A and cancer and determine whether TGFBR1*6A is associated with cancer.All published case-control studies assessing the germline frequency of TGFBR1*6A were included. Studies assessing TGFBR1*6A in tumors were excluded. The results of seven studies comprising 2,438 cases and 1,846 controls were pooled and analyzed.Overall, TGFBR1*6A carriers have a 26% increased risk of cancer (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.07 to 1.49). Cancer risk for TGFBR1*6A homozygotes (OR, 2.53; 95% CI, 1.39 to 4.61) is twice that of TGFBR1*6A heterozygotes (OR, 1.26; 95% CI, 1.04 to 1.51). Analysis of various types of tumors shows that TGFBR1*6A carriers are at increased risk of developing breast cancer (OR, 1.48; 95% CI, 1.11 to 1.96), hematological malignancies (OR, 1.70; 95% CI, 1.13 to 2.54), and ovarian cancer (OR, 1.53; 95% CI, 1.07 to 2.17). Carriers of TGFBR1*6A who are from the United States are at increased risk of colorectal cancer (OR, 1.38; 95% CI, 1.02 to 1.86). However, Southern European TGFBR1*6A carriers have no increased colorectal cancer risk. There is no association between TGFBR1*6A and bladder cancer.TGFBR1*6A is emerging as a highfrequency, low-penetrance tumor susceptibility allele that predisposes to the development of breast, ovarian, and colorectal cancer, as well as hematologic malignancies.
On the Dye Spraying Method in Colonofiberscopy
Authors: M. Tada, S. Katoh, Y. Kohli, K. Kawai
Journal: Endoscopy (1976)

Dye spraying method was applied in colonofiberscopy; 111 cases of normal colonic mucosa and 26 cases of ulcerative colitis were examined by this method. Using indigocarmine in this method, we could recognize the fine mucosal changes more easily and clearly and get better information for differential diagnosis. Furthermore, the degree of staining of the mucosa by methylene blue, one of the ultra vital staining dye, is different according to the stage of the inflammatory process of colonic mucosa itself in ulcerative colitis. Namely the stainability of the colonic mucosa is corresponding to the healing process of the disease.
Color relations and the power of complexity
Authors: C. L. Hardin
Journal: Behavioral and Brain Sciences (1999)

Color-order systems highlight certain features of color phenomenology while neglecting others. It is misleading to speak as if there were a single “psychological color space” that might be described by a rather simple formal structure. Criticisms of functionalism based on multiple realizations of a too-simple formal description of chromatic pheno-menal relations thus miss the mark. It is quite implausible that a functional system representing the full complexity of human color phenomenology should be realizable by radically different qualitative states.
Abstract B17: Exploiting evolution to develop better personalized therapeutic strategies
Authors: Jill A. Gallaher, Alexander R. A. Anderson
Journal: Cancer Research (2015)

Abstract Targeted drugs have been emerging as the future direction for personalized medicine. These drugs focus on blocking specific pathways identified by genetic alterations, but often a single biopsy reveals only a portion of the genetic heterogeneity. Even upon complete characterization of a particular tumor, successful treatment relies on targeting all of the major driver mutations, which furthermore have a possibility to fail due to resistance. With a very heterogeneous disease, this is a point-and-shoot approach with many moving targets. While the genotypes become more heterogeneous over time, the phenotypes tend to converge as the environment selects for the most fit subtypes of cells. And while genetic mutation happens by chance, phenotypic adaptation in response to environmental changes are more predictable. By focusing on phenotypic traits, we are targeting the highest level of functional cell behavior. But even at this scale there is complexity. For example, how should a phenotype propagate - do all clones share the same phenotype, or is there some plasticity? The answer affects how the right timing and sequencing of drugs could shape the population into a more targetable one instead of into a mutationally resistant one. To explore this tangled web of genotypic and phenotypic progression and selection, we build an agent based model. This approach allows us to investigate interactions of single cells and evolution of the collective population in an environment with spatial competition. Utilizing this agent based approach we investigate how both sequence and timing of different therapeutic methods alter the intratumor heterogeneity both at the genotypic and phenotypic scales. Citation Format: Jill A. Gallaher, Alexander R. A. Anderson. Exploiting evolution to develop better personalized therapeutic strategies. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B17. doi:10.1158/1538-7445.CHTME14-B17
Antioxidants, Pro-oxidants, and Their Effects
Authors: Victor Herbert
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The May 11 issue of<i>JAMA</i><sup>1</sup>contains a two-page advertisement representing that the "antioxidant" vitamins are pure antioxidants and, therefore, helpful against coronary artery disease. In fact, they are redox agents, antioxidant in some circumstances, pro-oxidant in others. When present in physiological (recommended daily allowance [RDA]) amounts and when part of the balanced biochemistry of the more than 150 redox and nonredox chemicals in each fruit or vegetable, they tend to be antioxidant. When present in the pharmacologic (above-RDA) amounts found in supplements, they are unbalanced biochemistry, tend to be pro-oxidant, and also have many chemical actions unrelated to vitamin or redox activity. We reviewed these facts in 1994 in detail<sup>2</sup>and succinctly,<sup>3</sup>and we cited studies reporting harms from above-RDA amounts of "antioxidant" vitamins, including promotion of heart disease, cancer, and liver and kidney disease. The nonvitamin prohemorrhagic effect of pharmacologic (above-RDA) supplements
What is the real role of antimicrobial polypeptides that can mediate several other inflammatory responses?
Authors: Peter Elsbach
Journal: Journal of Clinical Investigation (2003)

Antimicrobial peptides are effector molecules of innate immunity with microbicidal and pro- or anti-inflammatory activities. Their role is now widening following evidence that one such multifunctional peptide, LL-37, induces angiogenesis, a process essential for host defense, wound healing, and tissue repair.
Pain and Profit: The Politics of Malpractice
Authors: Walter G. Gunn
Journal: JAMA (1978)

The literature of the medical malpractice crisis of the mid-1970s usually has an accumulation of historical information telling just how we got where we are today, but with a dearth of practical advice and methods on how to find a way ahead. The authors of this work provide insightful information on causes of the malpractice problem and some suggested solutions that, if adopted, would eliminate private practice and fee-for-service as we know them. The authors may have intended to attract interest (and therefore sales) by a catchy title, but I found that the title yields no hint of the considerable amount of medicolegal scholarship within. The title is, in fact, rather inaccurate in that the political process at federal, state, and local levels plays only a minor part in these pages. Even so-called medical politics is given short shrift. The authors are attorneys who write well and knowledgeably. Though superficial
Frequency and Importance of Postprandial Blood Pressure Reduction in Elderly Nursing-Home Patients
Authors: Peter V. Vaitkevicius, Donna M. Esserwein, Andrea K. Maynard, Frances C. O'Connor, Jerome L. Fleg
Journal: Annals of Internal Medicine (1991)

Objective: To determine the frequency and importance of postprandial reductions in systolic blood pressure in debilitated, elderly patients receiving nursing home care. Design: Cohort study. Setting: Community-based, university-affiliated, teaching nursing home. Patients: A total of 113 volunteer nursing-home residents with a mean (± SD) age of 78 ± 9 years; seven residents who refused the test meal served as controls. Intervention: Participants had sequential blood pressure measurements for 90 minutes after the administration of a standardized meal. Measurements and Main Results: Of 113 patients, 109 (96%) showed a postprandial reduction in systolic blood pressure (mean reduction, 17.9 ± 15.5 mm Hg) within 75 minutes; 41 patients (36%) had a reduction in systolic blood pressure of more than 20 mm Hg. Twelve patients (11%) had a reduction in systolic blood pressure to less than 100 mm Hg (mean systolic blood pressure, 88 ± 6.4 mm Hg); two of these patients became acutely symptomatic. Multiple regression analysis showed that higher premeal systolic blood pressure, a history of syncope, treatment with vasodilators, and dependent posture of the lower extremities during the postprandial period were all associated with a more severe postprandial decline in systolic blood pressure. Systolic blood pressure in noneating control subjects did not change during the same observation period. No significant differences in the mean systolic blood pressure nadir were found between the 14 patients who died during the follow-up period (mean follow-up, 6.1 ± 3.8 months) and those who survived. Conclusion: Postprandial reductions in systolic blood pressure among elderly nursing-home patients are common, often large, and potentially symptomatic, but they do not generally presage subsequent intermediate-term mortality.
Method of Sterilizing Rubber Gloves
Authors: Ray Ernest Smith
Journal: JAMA (1913)

<h3>To the Editor:</h3> —For three years I have been using the method of glove sterilization criticized by Dr. McDonald (The Journal, Nov. 8, 1913, p. 1735). Undoubtedly gloves covered with "blood, pus, serum or soap" would be impervious to the action of cyanid or alcohol; but in soap and hot water we have a very active agent for the removal of these "organic substances" from the smooth surface of the rubber glove, and most certainly the gloves are to be washed and rinsed, as stated in my article. Alcohol is conceded by most, if not all, authorities to be a most effective germicidal agent. Many of our most famous surgeons use no other method of hand sterilization than scrubbing with soap and water followed by alcohol. The gloves made clean by soap and water and sterilized by alcohol are protected from subsequent infection by the talccyanid powder. It was not
Event-Related Slow Brain Potentials, Cognitive Processes, and Alexithymia
Authors: F. Lolas
Journal: Psychotherapy and Psychosomatics (1978)

A psychophysiological approach to alexithymia involves the search for reliable neural correlates of cognitive and symbolic processes rendering meaningful indicators that can be entered as elements into the diagnostic process, framed within a theory, and tested against the clinical experience. Relevant work on event-related slow brain potentials is reviewed, and some recent data bearing on a psychophysiological differentiation between psychosomatic and psychoneurotic patients are presented and discussed within the framework of a modified concept of activation. In outlining certain research strategies and goals it is contended that they may provide an experimental data base complementing and expanding psychodynamically derived formulations.
Clotrimazole in rheumatoid arthritis.
Authors: J A Wojtulewski, P J Gow, J Walter, R Grahame, T Gibson, G S Panayi, J Mason
Journal: Annals of the Rheumatic Diseases (1980)

Forty-seven patients with active rheumatoid arthritis took part in an 8-week controlled study in which clotrimazole was compared with a standard nonsteroidal anti-inflammatory agent, ketoprofen. Although clotrimazole was shown to be effective in the treatment of the disease and superior to ketoprofen in certain measurements, if was also responsible for a high incidence of adverse effects. Improvement with clotrimazole took place more slowly but was more sustained than with ketoprofen. A significant rise in plasma cortisol and a fall in white cell count was observed in the clotrimazole treated patients.
The Biology of Tissue Transplantation
Authors: Paul S. Russell, Anthony P. Monaco
Journal: New England Journal of Medicine (1964)

EnhancementImmunologic enhancement may be defined as the successful establishment, or delayed rejection, of an allograft as a consequence of the presence of specific antiserum in the host.229 The existence of antigraft antibody as the effective agent in enhancement distinguishes this phenomenon from other types of immune unresponsiveness. The basic conditions for inducing enhancement have been worked out extensively in inbred mice and have been reviewed in detail.230 Although this phenomenon was discovered in experiments involving tumor transplantation and has since been studied extensively with similar systems, it should be emphasized that enhancement extends likewise to normal tissues although it . . .
Croup and Diphtheria
Authors: W. Cumming
Journal: BMJ (1875)

Scotch ones, or that my experiments were conducted under circum- stances materially different from those under which the experiments of the Edinburgh Committee were carried on, I could not decide; but it was indubitable that our results differed to a very serious degree.A new set of experimeints which was at once undertaken gave perfect distinctness to the divergence of our results.TABLE IX.-Showing the 31inimim Fatal Dose of C'hloral-Ilydrate in RaJbbits.No. Weight of Dose of Chloral-Result Rabbit.Hydrate in grs.66 3 lbs. 2 oz.30 Recovery 67 3 lbs.11 oz.30 68 4 lbs. 2 oz.35 9, 69 3 lbs.11l oz.35 Death in four hours 70 3 lbs.3 oz.36 Recovery 71 3 lbs. 10oz..44 Reovery 72 2 lbs.11 oz.40 Death in two hours 73 2 lbs.121 oz. 40 Dath in two hours and twenty minutes 74 3 lbs. 1 oz.42 Death in three hours and ten minutes 75 3 lbs. 2 oz.46 Death in one hour and twenty-five min.76 2 lbs.14 oz.46 Death in one hour and fifty-four minutes
Use of Visible Light Spectroscopy to Diagnose Chronic Gastrointestinal Ischemia and Predict Response to Treatment
Authors: Aria Sana, Leon M.G. Moons, Bettina E. Hansen, Pieter Dewint, Désirée van Noord, Peter B.F. Mensink, Ernst J. Kuipers
Journal: Clinical Gastroenterology and Hepatology (2014)
A Phase 1 Study of Pralatrexate in Combination with Paclitaxel or Docetaxel in Patients with Advanced Solid Tumors
Authors: Christopher G. Azzoli, Lee M. Krug, Jorge Gomez, Vincent A. Miller, Mark G. Kris, Michelle S. Ginsberg, Roxanne Henry, Jessica Jones, Leslie Tyson, Megan Dunne, Barbara Pizzo, Amy Farmer, Ennapadam Venkatraman, Robert Steffen, F.M. Sirotnak
Journal: Clinical Cancer Research (2007)

Pralatrexate is a rationally designed antifolate with greater preclinical antitumor activity than methotrexate. Pralatrexate was synergistic with paclitaxel and with docetaxel in mouse xenograft experiments. This phase 1 study was designed to determine the maximum tolerated dose and toxicity of pralatrexate plus paclitaxel or docetaxel in patients with advanced cancer.Pralatrexate was administered i.v. every 2 weeks (days 1 and 15) in a 4-week cycle. Depending on the taxane used and dose being tested, the taxane was administered on days 1 and 15; days 2 and 16; or days 1, 8, and 15. In the latter part of the study, patients in the docetaxel arm were treated with vitamin B(12) and folic acid supplementation to mitigate toxicity and allow pralatrexate dose escalation.For the combination of pralatrexate plus paclitaxel without vitamin supplementation, dose-limiting stomatitis and peripheral neuropathy were encountered at the lowest dose levels tested. For pralatrexate plus docetaxel plus vitamin supplementation, pralatrexate 120 mg/m(2) plus docetaxel 35 mg/m(2) administered on the same day every other week was defined as the maximum tolerated dose and schedule, with dose-limiting toxicities at higher dose combinations including stomatitis and asthenia. Significant antitumor activity was observed for this combination in patients with non-small-cell lung cancer.Pralatrexate (120 mg/m(2)) plus docetaxel (35 mg/m(2)) plus vitamin supplementation is well tolerated with signs of efficacy against non-small-cell lung cancer that merit phase 2 testing.
High Serum Transaminase Activity in Heart Disease
Authors: THOMAS KILLIP, MARY ANN PAYNE
Journal: Circulation (1960)

A survey of all patients with very high serum glutamic oxalacetic transaminase activity encountered during a 30-month period at The New York Hospital revealed 17 patients with cardiac disease who had 1 or more serum glutamic oxalacetic transaminase (SGOT) determinations exceeding 500 units. None had clinical evidence of primary liver or gallbladder disease. Eleven were admitted with acute myocardial infarction, 6 with severe heart failure. All 17 developed hypotension or shock and all but 1 right heart failure prior to high SGOT activity. Several patients had abnormalities of liver function when SGOT activity was very high. In 4 there was an excessive increase in prothrombin time following administration of anticoagulants. In the 8 patients who came to autopsy there was histologic evidence of acute hepatic central necrosis. In 4 there was necrosis of both heart and liver, in 4 necrosis of liver alone. Clinical and autopsy data from a control series of patients with heart disease selected without regard for the level of SGOT activity corroborate the association between hypotension, central necrosis of the liver, and increased SGOT activity. Increase in venous pressure in the absence of hypotension was not associated with acute central necrosis or elevated SGOT activity. It is concluded that very high SGOT activity (&gt;500 units) in patients with heart disease is at least in part caused by acute hepatic central necrosis secondary to a drop in cardiac output and reduced hepatic blood flow. Caution is urged in the interpretation of increased blood activity of intracellular enzyme systems as evidence for myocardial necrosis. Acute circulatory changes may result in hepatic necrosis and increased blood enzyme activity without myocardial infarction.
BMA offers guidance on secondary care by fundholders
Authors: L Beecham
Journal: BMJ (1994)

Since April 1993 general practice fundholders have been able to provide some secondary care services in their practices. The BMA's Central Consultants and Specialists Committee has consulted the medical royal colleges and the General Medical Services Committee and prepared guidelines on the levels of training and experience that might be appropriate.

Fundholders have to obtain regional consent in writing before providing any services or seeking reimbursement, but the CCSC has found that in many cases regional health authorities have not established appropriate approval mechanisms. The committee believes that consultants in the relevant specialties and general practitioners should be involved in all stages of the approval mechanism. Applicants should be able to show their training and competence in each procedure and give numbers of procedures undertaken of a similar nature and current specialist commitments.

The Association of Anaesthetists is preparing guidelines on the provision of general anaesthesia outside hospital. In the meantime, the CCSC believes that fundholders should adhere to the guidelines in the Royal College of Surgeons' booklet Guidelines for Sedation by Non- Anaesthetists.

The guidelines cover procedures in gynaecology; ear, nose, and throat; urology; pathology; ophthalmology; general surgery; and orthopaedics. In many instances the guidelines emphasise that resuscitation facilities and staff trained in life support must be available, particularly if the procedure is carried out under sedation.

Copies of the guidelines are available from the CCSC secretariat, BMA, BMA House, Tavistock Square, London WC1H 9JP.

There should be a campaign to warn the public of the dangers in the Department of Health's code for safeguarding confidentiality in the NHS, the BMA's medical ethics committee believes. The government issued its draft code (20-27 August, p 499) a week …
Effects of adrenalectomy and chronic adrenal corticosteroid replacement on potassium transport in rat kidney.
Authors: B Stanton, G Giebisch, G Klein-Robbenhaar, J Wade, R A DeFronzo
Journal: Journal of Clinical Investigation (1985)

Clearance experiments were carried out in pair-fed rats to examine the long-term effects of adrenalectomy and selective adrenal corticosteroid replacement in physiological amounts on renal potassium transport. To this end, clearance studies were conducted in rats that were sham operated, or adrenalectomized (ADX). ADX animals were given either vehicle, aldosterone (0.5 microgram/100 g body wt per day), dexamethasone (1.2 micrograms/100 g body wt per day), or aldosterone and dexamethasone, by osmotic minipump for 7-9 d whereupon clearance experiments were conducted. After chronic hormone treatment, during basal conditions when only Ringers solution was infused, all groups excreted similar amounts of potassium. However, in all ADX animals without mineralocorticoid replacement, the maintenance of urinary potassium excretion at control levels was associated with hyperkalemia, increased urine flow, and natriuresis; all are factors known to stimulate urinary potassium excretion. During acute potassium infusion, the increase in urinary potassium excretion was less in ADX rats than in controls. This functional deficiency in potassium excretion was partially corrected by dexamethasone and was uniformly associated with a significant increase in urine flow. Aldosterone replacement or aldosterone and dexamethasone given together chronically, sharply increased potassium excretion but did not restore excretion to control levels. Only acute aldosterone infusion (0.2 microgram/100 g body wt bolus plus 0.2 microgram/100 g body wt per hour), superimposed upon chronic aldosterone and dexamethasone treatment, fully restored potassium excretion to control levels. This aldosterone induced enhancement of potassium excretion, both chronic and acute, was not associated with hyperkalemia, and increased urine flow or natriuresis. Thus, physiological levels of both classes of adrenal corticosteroids stimulate renal potassium excretion albeit by different mechanisms. Mineralocorticoids stimulate tubular potassium excretion directly, whereas glucocorticoids augment excretion indirectly by increasing fluid and sodium delivery along the distal nephron.