tbuckley/cabot-search huggingface dataset:
Exploring Indirect Sources of Human Exposure to Perfluoroalkyl Carboxylates (PFCAs): Evaluating Uptake, Elimination, and Biotransformation of Polyfluoroalkyl Phosphate Esters (PAPs) in the Rat
Authors: Jessica C. D’eon, Scott A. Mabury
Journal: Environmental Health Perspectives (2010)

Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera.We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model.The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces.The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners.Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination.
Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services
Authors: A J Coull, J K Lovett, P M Rothwell
Journal: BMJ (2004)

To estimate the very early stroke risk after a transient ischaemic attack (TIA) or minor stroke and thereby inform the planning of effective stroke prevention services.Population based prospective cohort study of patients with TIA or stroke.Nine general practices in Oxfordshire, England, from April 2002 to April 2003.All patients who had a TIA (n = 87) or minor stroke (n = 87) during the study period and who presented to medical attention.Risk of recurrent stroke at seven days, one month, and three months after TIAs and minor strokes.The estimated risk of recurrent stroke was 8.0% (95% confidence interval 2.3% to 13.7%) at seven days, 11.5% (4.8% to 18.2%) at one month, and 17.3% (9.3% to 25.3%) at three months after a TIA. The risks at these three time periods after a minor stroke were 11.5% (4.8% to 11.2%), 15.0% (7.5% to 22.5%), and 18.5% (10.3% to 26.7%).The early risks of stroke after a TIA or minor stroke are much higher than commonly quoted. More research is needed to determine whether these risks can be reduced by more rapid instigation of preventive treatment.
Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1
Authors: Brendan Nichols, Prachi Jog, Jessica H. Lee, Daniel Blackler, Michael Wilmot, Vivette D'Agati, Glen Markowitz, Jeffrey B. Kopp, Seth L. Alper, Martin R. Pollak, David J. Friedman
Journal: Kidney International (2014)
Surgery of the Upper Respiratory System
Authors: Alan Marty
Journal: JAMA (1973)

The fine tradition of Boston-based books is upheld by this outstanding atlas, which details more than surgical technique. Indeed, the pathophysiologic rationale for almost every important operative step is given, complete with nearly 300 up-to-date references. Throughout, methods for making therapy-dependent, exact diagnoses are elucidated. As good as the text is, it is surpassed by the photography and layout, which could serve as a model for students of medical illustration. While the book is primarily aimed at otolaryngologists in training or practice, thoracic surgeons as well as those dealing with head and neck will welcome the exceptional and sorely needed 130-page section on tracheal surgery. The original sections on laryngeal or tracheal injury, complete with instructive case reports, stem from the author's extensive experience at the Massachusetts Eye and Ear Infirmary. Highlights of other chapters include a sensible approach to the treatment of cervical masses, block neck dissections, pedicled skin
Patients get four choices for NHS treatments: Choose and book will hinder development of good outpatient services
Authors: Jeremy Wood
Journal: BMJ (2006)

Editor—Is it not time that as a profession we state unequivocally that we are opposed to having choose and book imposed on us?1 There are also cogent reasons for resistance by the hospital sector, principally that choose and book will hinder the development of good outpatient services.

Specialist …
Abstract P6-03-03: Could We Reduce the Number of Exams in the Follow-Up of Breast Cancer Survivors?
Authors: AV Tallet, BP Farnault, LV Moureau-Zabotto, BA Esterni, N Salem, A Gonçalves, GF Houvenaeghel, JD Jacquemier, M. Resbeut
Journal: Cancer Research (2010)

Abstract Background. The aim of this retrospective study was to determine by which way was diagnosed any breast cancer recurrence after the end of the adjuvant treatment and to draw guidelines for exams for the follow-up. Materials and methods. Between January 1995 to December 2005, 5419 patients were treated for non metastatic breast cancer in our institute, out of which 662 experienced a relapse either local or metastatic. The charts of 608 of these patients were analysable, and retrospectively reviewed. For each case, we looked at the exams or clinical symptom which revealed the recurrence. Results. Among the 608 patients who recurred, 173 patients (28%) experienced an isolated local relapse, while 12 experienced a contralateral breast cancer (2%), 423 experienced either a metastatic or metastatic plus local relapse (65% and 5%, respectively). Local relapses were detected in most of cases either clinically (42%) or on mammography and mammary ultrasound (US) (55%). An isolated increase of blood tumor marker (CA 15.3) revealed the relapse in 24% of cases (in 33% of cases for distant relapses and 3% for isolated local relapses). The remaining 67% of cases with metastases were diagnosed by clinical symptoms in 47% of cases, imaging in 22% of cases (bone scan in 6%, liver US 5%, mammography 1%, TDM 5%, chest X-ray 2%). In these cases of radiographically detected metastases clinical exam and/or tumor markers levels were abnormal in 42% of cases. Conclusion. A follow-up with a systematically clinical exam, mammography and mammary US, and blood tumor markers assessment permits the diagnosis of 100 percent of local relapse, 100% of contralateral breast cancer, and 89% of metastatic disease. Thus imaging exams could be avoided routinely, with less stress for the patient and improvement of the health cost. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-03-03.
Role of Hypersensitivity in the Pathogenesis of Rheumatoid Arthritis. Heberden Oration, 1958
Authors: C. Ragan
Journal: Annals of the Rheumatic Diseases (1959)

William Heberden published his description of angina pectoris 192 years ago (Major, 1932).There are certain similarities between his thinking on this subject and our present approach to rheumatoid arthritis.Both are descriptive with glimmerings of possible pathogenic mechanisms.To-day, I propose to consider one such mechanism and I hope that my humility will be as obvious as was Heberden's.This discussion will pose a question, present the available evidence, and offer a tentative conclusion.It will be obvious that further data must be obtained before a final satisfactory conclusion can be reached.The question to be raised is "What is the pathogenesis of peripheral joint rheumatoid arthritis?"We shall, of course, be limited to pathogenic mechan- isms that might explain a self-perpetuating disease characterized by inflammation associated with the formation of granulomata.Hill (1958), in discussing the aetiology of this disease, has pointed out that no hypothesis rests on more than a few loosely connected pieces of evidence.He has summarized in excellent fashion the four chief theories.These are infection and focal sepsis, metabolic abnormality, endocrine abnormality, and hypersensitivity.The last is currently the most attractive hypothesis and will be the subject of this discussion.We are concerned solely with peripheral joint rheumatoid arthritis, excluding all variants such as spondylitis, the arthritis associated with psoriasis, ulcerative colitis, and Reiter's syndrome.Clinically, the disease covers a wide spectrum of severity and variability.It is a disease which, as far as we know, appears only in human beings.Although a female preponderance has been noted in most hospital studies (Ragan, 1949; Short, Bauer, and Reynolds, 1957), recent epidemiological work (Kellgren and
Serum Atypical Pseudocholinesterase and Genetic Factors in Leprosy
Authors: M. Thomas, C. K. Job
Journal: BMJ (1972)

The levels of pseudocholinesterase and its nature were studied in 390 leprosy patients and 343 control subjects. The levels of the enzyme in both leprosy patients and normal controls were comparable. The study of the nature of the enzyme by determining its dibucaine number showed that a statistically significant number of lepromatous patients had the atypical variety of the enzyme compared with normal controls or tuberculoid patients. Since the presence of the atypical variety of the enzyme is genetically determined it is suggested that genetic factors play an important part in deciding susceptibility to lepromatous leprosy.
Bcl-2 Overexpression Enhances Tumor-Specific T-Cell Survival
Authors: Jehad Charo, Steven E. Finkelstein, Navrose Grewal, Nicholas P. Restifo, Paul F. Robbins, Steven A. Rosenberg
Journal: Cancer Research (2005)

Although immunotherapy based on the adoptive transfer of tumor-specific T lymphocytes has been shown to result in dramatic clinical responses in some patients, the relatively low levels of engraftment and persistence of the adoptively transferred cells may limit these responses in many patients. In an attempt to develop strategies for prolonging the survival of adoptively transferred T cells, we have carried out studies in which T cells obtained from healthy donors as well as tumor-specific T cells were transduced with a retrovirus expressing the human Bcl-2 gene. Our results indicate that these transduced T cells overexpress Bcl-2, are resistant to death, and have a survival advantage following interleukin-2 withdrawal compared with control T cells transduced with a retrovirus expressing green fluorescent protein. Tumor-specific T cells overexpressing Bcl-2 maintained their ability to specifically recognize and respond to target cells. Furthermore, we show that adoptive immunotherapy of an established B16 tumor can be significantly enhanced by overexpressing Bcl-2 in melanoma-specific T-cell receptor transgenic T cells. Our data suggest that adoptive immunotherapy approaches to the treatment of cancer patients may be enhanced using Bcl-2-modified tumor-reactive T cells.
Abstract SY25-01: Functional genomics, transformation, and resistance
Authors: William C. Hahn
Journal: Cancer Research (2011)

Abstract Recent advances in genomics now make it possible to consider enumerating all of the genetic lesions in specific cancers. While these approaches will yield critical information regarding the identify, number, and types of alterations found in human tumors, a complementary approach to decipher the molecular basis of malignant transformation depends upon the application of genome scale tools to annotate the function of genes involved in cancer initiation and progression. Over the past several years, we have developed genome scale RNAi libraries and open reading frame expression libraries that permit a systematic evaluation of genes involved in cancer initiation and maintenance. Using these libraries, we have now performed screens in a panel of human cancer cell lines to systematically identify cancer vulnerabilities. By combining these functional approaches with information derived from mapping the structural abnormalities present in cancer genomes, we have identified several new oncogenes that contribute to cancer development. In addition, many commonly occurring and well-validated oncogenes and tumor suppressor genes remain refractory to molecularly targeted therapies. An alternative strategy for targeting such cancer drivers is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Through the use of systematic RNAi screens, we have identified several genes that act as synthetic lethal partners to known oncogenes. Taken together, these studies suggest that combining forward and reverse genetic approaches with information derived from the cancer genome characterization projects will yield a comprehensive list of cancer vulnerabilities and establish a general approach for the rational identification of oncogenic and co-dependent pathways in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr SY25-01. doi:10.1158/1538-7445.AM2011-SY25-01
The mechanism of dioxin toxicity: relationship to risk assessment.
Authors: L S Birnbaum
Journal: Environmental Health Perspectives (1994)

Risk characterization involves hazard identification, determination of dose-response relationships, and exposure assessment. Improvement of the risk assessment process requires inclusion of the best available science. Recent findings in the area of dioxin toxicity have led to a major effort to reassess its risk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to as "dioxin," is the most toxic member of a class of related chemicals including the polyhalogenated dibenzo-p-dioxins, dibenzofurans, biphenyls, naphthalenes, azo- and azoxy-benzenes, whose toxicities can be expressed as fractional equivalencies of TCDD. These chemicals exert their effects through interaction with a specific intracellular protein, the Ah receptor. While binding to the receptor is necessary, it is not sufficient to bring about a chain of events leading to various responses including enzyme induction, immunotoxicity, reproductive and endocrine effects, developmental toxicity, chloracne, tumor promotion, etc. Some of these responses appear to be linear at low doses. Immunotoxicity and effects on the reproductive system appear to be among the most sensitive responses. The Ah receptor functions as a transcriptional enhancer, interacting with a number of other regulatory proteins (heat shock proteins, kinases, translocases, DNA binding species). Interaction with specific base sequences in the DNA appear to be modulated by the presence of other growth factors, hormones and their receptors as well as other regulatory proteins. Thus, dioxin appears to function as a hormone, initiating a cascade of events that is dependent upon the environment of each cell and tissue. While Ah receptor variants exist, all vertebrates examined have demonstrated such a protein with similar numbers of receptors and binding affinity for TCDD. Most species respond similarly to dioxin and related compounds. While a given species may be an outlier for a given response, it will behave like other animals for other responses. For both in vivo and in vitro end points where animal and human data exist, such as enzyme induction, chloracne, immunotoxicity, developmental toxicity, and cancer, the sensitivity of humans appears similar to that of experimental animals. Current levels of environmental exposure to this class of chemicals may be resulting in subtle responses in populations at special risk such as subsistence fisherman and the developing infant, as well as in the general population. Increased understanding of the mechanism of dioxin's effects as well as elucidation of exposure-dose relationships is leading to the development of a biologically based dose-response model in the ongoing process of incorporating the best science into the risk assessment of TCDD and related compounds.
Alcohol With a Meal Has No Adverse Effects on Postprandial Glucose Homeostasis in Diabetic Patients
Authors: Veikko A Koivisto, Sirkku Tulokas, Markku Toivonen, Eliina Haapa, Risto Pelkonen
Journal: Diabetes Care (1993)

OBJECTIVE To examine the effect of moderate alcohol intake with a meal on gluco e homeostasis in diabetic patients. RESEARCH DESIGN AND METHODS Alcohol (1 g/kg, an aperitif before, wine during, and a drink after a meal) or an equal amount of mineral water was given during a dinner. Blood glucose and insulin concentrations were measured before, uring, and after the meal until the next morning. This study was conducted at the Helsinki University Hospital Metabolic Ward and the Finnish Diabetes Association Education Center. The participants in the study included 10 type I diabetic patients treated with insulin and 16 type II diabetic patients treated with diet alone or with diet and oral drugs. In each subject, we examined hypoglycemic episodes or differences in blood glucose or serum insulin concentrations between alcohol and the control study. RESULTS In type I diabetic patients, blood glucose and insulin concentrations were virtually identical in both studies. In type II diabetic patients, alcohol slightly enhanced the meal-induced insulin secretion resulting in lower blood glucose concentrations next morning. No hypoglycemic glucose concentrations were observed in either group after alcohol ingestion. CONCLUSIONS Moderate alcohol intake with a meal does not lead to hypo- or hyperglycemia in diabetic patients.
Impact of Ribavirin Dose Reductions in Hepatitis C Virus Genotype 1 Patients Completing Peginterferon Alfa-2a/Ribavirin Treatment
Authors: K. Rajender Reddy, Mitchell L. Shiffman, Timothy R. Morgan, Stefan Zeuzem, Stephanos Hadziyannis, Fayez M. Hamzeh, Teresa L. Wright, Michael Fried
Journal: Clinical Gastroenterology and Hepatology (2006)
Principles of Ophthalmology
Authors: David Shoch
Journal: JAMA (1966)

A cursory examination of three standard American textbooks of ophthalmology reveals that two of them are twice the size of this English import, and the third is 50% larger. However the tables of contents of all four are strikingly similar, and there seem to be no glaring omissions in the smaller volume. Each of the usual anatomic entities —lids, conjunctiva, lens, retina, etc —has been assigned a chapter, and a brief but adequate description is given of the frailties of each of these tissues. One notices the absence of a special section on "the eye in general disease"—a standard feature of American textbooks. However, this material has not been overlooked. It is incorporated where indicated, in the sections on the specific ocular tissues involved in systemic diseases. Further pages have been saved by eliminating extensive discussion of the treatment of ocular disease. This is a wise omission. Except for simple,
Hypothermia Precipitated by Ice-cold Beverages in a Wasted Dialysis Patient
Authors: M. W. El-Nachef
Journal: JAMA (1990)

To the Editor.—  A malnourished 67-year-old patient presented to the emergency department with hypothermia and obtundation after drinking ice-cold Diet Coke.  Report of a Case.—  A 67-year-old white woman with over 20 years' history of diabetes mellitus type I started maintenance hemodialysis 2 years ago when her diabetic nephropathy progressed to end-stage renal disease. She also developed severe autonomic neuropathy with recurrent vomiting and resultant malnutrition, muscle wasting, and weight loss of over 20 kg in less than 2 years.  In the night before her admission, the patient became very upset on hearing some news about her family. She felt as though her throat was set on fire, and she drank ice-cold Diet Coke all night long, consuming about 20 cans or 7 L containing 0.7 g of sodium. In the early hours of the morning, the family noticed that the patient's speech had become unclear. When she arrived at
[48] RETENTION OF TOXIC BILE ACIDS ACTIVATE THE MTOR, P70S6K/RPS6 SIGNALING PATHWAY IN MOUSE MODELS OF CHOLESTATIC LIVER INJURY
Authors: T. Moustafa, P. Fickert, P. Vesely, D. Silbert, J. Gumhold, A. Fuchsbichler, H. Denk, C. Guelly, M. Trauner
Journal: Journal of Hepatology (2007)
Patterns of General Practice
Authors: Samuel E. Paul
Journal: JAMA (1971)

To the Editor.—   Study of General  in Massachusetts, by Brown et al ( 216 :301, 1971) tabulated 12,835 patient visits to 15 Massachusetts' practitioners. It was not related to any population segment stated. There is limited knowledge concerning the kinds of problems patients presently bring to their physicians. I humbly suggest this is not true. I introduced The Pattern of General Practice in 1956. Dr. Braun of Austria introduced Cases Distribution Law of Nature in 1955. Subsequent reports have continued to verify this basic pattern of illness distribution at the level of the primary physician.  A study of this sort must be related to the total population. 1 This means tabulation of births and deaths, at least, to get some idea of the size and type of population covered. Additionally, hospital visits should be recorded as hospital admissions, medical or surgical, as these also are significant figures for a
Surgical Management of Cervical Adenitis Due to Atypical Mycobacteria in Children
Authors: Kenneth E. Salyer
Journal: JAMA (1968)

Thirty-eight cases of cervical adenitis in children, with infection due to atypical mycobacteria, have been seen at Children's Medical Center, Dallas. The clinical picture of this infection can be established as a specific entity. This consists of unilateral submandibular lymphadenopathy in the submaxillary gland area usually associated with erythema of the overlying skin and abscess formation. The age group affected is characteristic. The children have minimal systemic symptoms and normal roentgenograms of the chest. Skin tests for atypical organisms are strongly positive; skin tests for<i>Mycobacterium tuberculosis</i>are usually weakly positive. Surgical management is advocated and consists of total excision of involved lymph nodes and skin, closure without drainage, and postoperative drug therapy with (para)aminosalicylic acid (PAS) and isoniazid (INH).