tbuckley/cabot-search huggingface dataset:
Abstract LB-286: Use of circulating tumor cells to monitor pharmacodynamic responses of patients in early-stage clinical trials
Authors: Robert J. Kinders, Lihua Wang, Shivaani Kummar, Thomas Pfister, Ralph Parchment, Joseph Tomaszewski, James Doroshow
Journal: Cancer Research (2010)

Abstract Circulating tumor cells (CTCs) in peripheral blood of cancer patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. We have developed and validated an assay that directly examines increases in the number of cells positive for the nuclear DNA-damage marker H2AX in individual CTCs of patients treated with DNA-damaging chemotherapeutic agents. The method uses AexaFluor 488-conjugated monoclonal anti- H2AX (JBW301), to stain putative CTCs collected from blood by the CellSearch AutoPrep instrument, followed by enumeration and fluorescence analysis on the CellTracks Analyzer. Patient baselining studies demonstrated that in the absence of treatment the number of CTCs per blood aliquot is relatively constant over short time periods (2 weeks off therapy). CTC measurements are currently in use supporting four NCI new agent trials, two with cytotoxic agents and two with targeted agents (aTOP1 inhibitor and a tyrosine kinase inhibitor, TKI). CTC changes in 40 patients have been monitored on therapy to date. H2AX positive cells increased in 7/14 patients on cytotoxic therapies, 3/14 were unchanged and 4/14 were unevaluable; the fraction of H2AX positive CTCs did not decrease in any patient on cytotoxic therapy, and did not change in patients treated with TKI. The increased H2AX signal in patients on cytotoxic agents appears definitive for the cycle of therapy in which it is measured. Interestingly, 10/40 patients had increased CTC numbers immediately post-therapy, and several of these patients had few or no CTC immediately prior to therapy, suggesting that the cells were mobilized or shed from the tumor as a consequence of drug exposure. Six patients had decreases in CTC number, 12 were unchanged and 12 were unevaluable due to low CTC numbers. These data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs, in addition to a CTC count alone, to rapidly assess drug pharmacodynamic activity, in clinical trials of cytotoxic agents and targeted anti-cancer therapeutics, as well as for translational research. This method may have the potential to inform the development of new anti-cancer agents and enable longitudinal monitoring of target response. Funded by NCI Contract No. HHSN261200800001E. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-286.
The Weight of Evidence
Authors: Leonard Tushnet
Journal: JAMA (1970)

My lords, the happenings of this case are, to wit: Robert the Surgeon, of Friday Street, rented a house and tavern to one Symon, in St. Martin's parish, there to conduct his trade. Said Symon had a servant, Roger from Westminster, who, in the night following St. Nicholas's Day, December sixth, in the fifth year of King Edward, 1277, did most foully murder his master. And the manner of the murder was thus: Roger cut the throat of the said Symon, asleep in his bed, and did cut off the head entirely from the body, after which he dragged the body to a dark and secret place, a bin between two walls in the house, wherein coals were wont to be kept, such place being long, and not quite two feet wide. The next day, dissembling, the said Roger did put out the bench in front of the tavern and
Hepatitis B Carriers in the Classroom
Authors: Saul Krugman
Journal: JAMA (1985)

Ten years have elapsed since enactment of the Congressional Education for All Handicapped Children Act (PL94-142). This legislation mandated public education for children with retarded mental development as well as for those with other handicaps. During the past decade many thousands of children, formerly residents of large state institutions, have been admitted to special education classes in public and private schools throughout the nation. Extensive seroepidemiological surveys by many investigators have revealed that the risk of a child contracting hepatitis B in a large state institution may range between 50% and 90%. Moreover, about 5% to 20% of those infected may become hepatitis B carriers.<sup>1,2</sup>In contrast, mentally retarded children who have lived at home since birth have the same negligible risk of infection as do normal children. Thus, more than 95% of these children are susceptible. Extrapolating from extensive serologic studies in blood donors, it is likely that
Trend analysis of socioeconomic differentials in deaths from injury in childhood in Scotland, 1981-95
Authors: A. Morrison, D. H Stone, A. Redpath, H. Campbell, J. Norrie
Journal: BMJ (1999)

Socioeconomic category influenced the use of the Glasgow Emergency Medical Service, with increased contact rates by children and adults from deprived areas.For elderly people, the highest contact rate was among the most affluent.While the effect of affluence on raising expectations and service use has been reported, this association has not previously been linked to age. 5 After contacting the emergency service, adults and elderly people from deprived areas were most likely to receive a home visit.The reasons for this are unclear and require further investigation.The lack of association between socioeconomic category and centre visit rates may be attributable to the provision of patient transport for anyone asked to attend a centre: those from deprived areas were far more likely to use the service.The cost of this service for 1998-9 will be around £240 000, yet may still be cheaper than taxi fares or home visits.While this requires economic evaluation, the evidence suggests that a free and accessible patient transport service may contribute to equity of access to out of hours primary care across the socioeconomic spectrum.
Number of UK patients offered participation in clinical trials will be boosted
Authors: Zosia Kmietowicz
Journal: BMJ (2008)

More patients in the United Kingdom will be offered the chance to take part in research trials and contribute to the improvement of medicine, under new plans announced this week by the government.

Researchers will be able to use electronic patient records to make patients aware of research trials that may be relevant to them, said the health secretary, Alan Johnson, at a research summit to commemorate 60 years of NHS research. Patients will be able to take part if they meet the entry criteria.

“I want every patient in the NHS to have the …
A NEW FORM OF MERCURY SPHYGMOMETER
Authors: L. Hill
Journal: BMJ (1910)

WHILE engaged recently in an investigation of the equality or difference of pressure in the arm and leg arteries-an investigation which showed a marked difference in all cases of aortic regurgitationl I contrived a new and con- venient form of mercury sphygmometer.This mercury manometer consists of a single tube, the lower end of which is sealed into a small reservoir, and opens near the bottom of this, as is shown in the enlarged figure of this part of the instrument.The armlet tube is attached to the end of the glass tube, which is also sealed into the reservoir, and opens into the upper part by a capillary
Psoriasis During Hemodialysis
Authors: GUIDO O. PEREZ
Journal: Annals of Internal Medicine (1979)

To the editor: Recent uncontrolled trials of dialytic therapy of psoriasis suggest a remarkable clinical improvement (1-3). However, this disease may manifest spontaneous improvements and exacerbations (4); thus, assessment of the effects of dialysis is difficult to interpret. In this regard, Friedman and Delano have described in the January 1979 issue (5) a case of psoriasis developing de novo during hemodialysis. We report the clinical course of two patients who began dialysis several years after the onset of psoriasis. A 43-year-old man with diabetic nephropathy developed typical cutaneous lesions of psoriasis in 1976. The diagnosis was confirmed by skin biopsy.
Whole genome sequencing in support of wellness and health maintenance
Authors: Chirag J Patel, Ambily Sivadas, Rubina Tabassum, Thanawadee Preeprem, Jing Zhao, Dalia Arafat, Rong Chen, Alexander A Morgan, Gregory S Martin, Kenneth L Brigham, Atul J Butte, Greg Gibson
Journal: Genome Medicine (2013)

Whole genome sequencing is poised to revolutionize personalized medicine, providing the capacity to classify individuals into risk categories for a wide range of diseases. Here we begin to explore how whole genome sequencing (WGS) might be incorporated alongside traditional clinical evaluation as a part of preventive medicine. The present study illustrates novel approaches for integrating genotypic and clinical information for assessment of generalized health risks and to assist individuals in the promotion of wellness and maintenance of good health.Whole genome sequences and longitudinal clinical profiles are described for eight middle-aged Caucasian participants (four men and four women) from the Center for Health Discovery and Well Being (CHDWB) at Emory University in Atlanta. We report multivariate genotypic risk assessments derived from common variants reported by genome-wide association studies (GWAS), as well as clinical measures in the domains of immune, metabolic, cardiovascular, musculoskeletal, respiratory, and mental health.Polygenic risk is assessed for each participant for over 100 diseases and reported relative to baseline population prevalence. Two approaches for combining clinical and genetic profiles for the purposes of health assessment are then presented. First we propose conditioning individual disease risk assessments on observed clinical status for type 2 diabetes, coronary artery disease, hypertriglyceridemia and hypertension, and obesity. An approximate 2:1 ratio of concordance between genetic prediction and observed sub-clinical disease is observed. Subsequently, we show how more holistic combination of genetic, clinical and family history data can be achieved by visualizing risk in eight sub-classes of disease. Having identified where their profiles are broadly concordant or discordant, an individual can focus on individual clinical results or genotypes as they develop personalized health action plans in consultation with a health partner or coach.The CHDWB will facilitate longitudinal evaluation of wellness-focused medical care based on comprehensive self-knowledge of medical risks.
Metronidazole-lnduced Gynecomastia
Authors: Timothy C. Fagan
Journal: JAMA (1985)

METRONIDAZOLE is usually prescribed for therapeutic courses of one to ten days, but in rare instances it may be administered for longer periods. Two such circumstances involve treatment of recurrent antibioticinduced colitis and treatment of inflammation in a Kock pouch (an internal reservoir and nipple valve created from distal ileum in patients undergoing total colectomy).<sup>1</sup>This inflammation of the pouch is characterized clinically by profuse, watery diarrhea and occasionally by bleeding and incontinence. The symptoms respond to antibiotics, making a bacterial cause seem most likely. Metronidazole is the most effective drug for this condition, but sometimes other antibiotics are effective.<sup>1</sup> <h3>Report of a Case</h3> A 36-year-old man with ulcerative colitis underwent total colectomy and creation of a Kock pouch in May 1983. Recurrent episodes of pouch inflammation, characterized by profuse watery diarrhea and mild right lower-quadrant aching, responded transiently to short courses (five to ten days) of either
Randomised controlled trials in cardiovascular medicine: past achievements, future challenges
Authors: S. Yusuf
Journal: BMJ (1999)

Clinical trials have played a crucial role in the development of treatment strategies for cardiovascular disease: the earliest trials were conducted in the 1950s, but it was not until the 1970-80s that the results of clinical trials had a major impact on the choice of treatments. Relieving symptoms and improving quality of life have always been treatment goals. Over the centuries, the choice of treatment has evolved through several periods (box ). The approaches are not necessarily distinct from each other, and current treatment strategies for cardiovascular disease are based on a mixture of goals aimed at the improvement of symptoms (for example, breathlessness), correcting markers of disease (improved ventricular function, etc), and improving clinical outcomes (fewer admissions to hospital, prolonged survival, etc). What characterises the current era is the expectation that theory, observations in animals, and human physiological studies alone are not enough to determine the value of a treatment. Rather, these observations should be verified by providing unequivocal evidence of net clinical benefit on the basis of reliable studies using the methods of randomised controlled trials.

#### Summary points

Reliable knowledge (derived from well designed randomised controlled trials) of which treatments do or do not work has become the basis for evidence based practice

Unbiased randomisation is the key methodological basis of randomised controlled trials

Other major methodological advances that make randomised controlled trials efficient are extreme simplicity (which makes large trials feasible) and factorial designs (which enable the testing of more than one hypothesis simultaneously)

Large trials and meta-analyses have both contributed to the reliable evaluation of treatments

Future challenges are the conduct of studies in developing countries and among neglected high risk groups, minimisation of unnecessary bureaucracy, waste, and high costs in conducting trials, and the conduct of more trials of generic issues—for example, population based prevention strategies and other …
Microchimerism
Authors: Kristina M. Adams, J. Lee Nelson
Journal: JAMA (2004)

Recent studies indicate cells transfer between fetus and mother during pregnancy and can persist in both decades later. The presence within one individual of a small population of cells from another genetically distinct individual is referred to as microchimerism. Naturally acquired microchimerism has recently been investigated in autoimmune diseases, including scleroderma, thyroiditis, primary biliary cirrhosis, Sjögren syndrome, systemic lupus, dermatomyositis, and neonatal lupus. Iatrogenic chimerism has been investigated in transplantation and following blood transfusion. Considering findings of naturally acquired microchimerism along with iatrogenic microchimerism suggests microchimerism can have detrimental and/or beneficial effects in both settings. Recent identification of tissue-specific microchimerism either from naturally acquired or iatrogenic microchimerism (eg, cardiac myocytes) raises the possibility that microchimerism can be a target of autoimmunity or alternatively contribute to tissue repair. Advances in this new frontier of research with varied and numerous implications for human health are summarized.
A SECOND CASE OF GASTRO-INTESTINAL ALLERGY DUE TO INSULIN
Authors: John R. Williams
Journal: JAMA (1933)

In 1930 I<sup>1</sup>reported a case of allergy due to insulin affecting the gastro-intestinal tract and producing severe symptoms. Briefly, a boy of 12 years, having had diabetes since the age of 7, began to have severe attacks of abdominal pain, nausea and vomiting. These were so severe in each instance as to precipitate coma. After a short stay in the hospital, with treatment consisting of free intravenous infusions of salt solution and dextrose, the child would return home, to repeat the experience when his usual diet and insulin therapy were resumed. Several such attacks occurred. In the last one, while the patient was moribund, the possibility of an insulin allergic reaction was considered. A change from an insulin of pork to one of beef origin was made. The patient obtained immediate and permanent relief and has been well since, after an interval of three years. The case was
A Left to Right Hemisphere Callosal Transfer Deficit of Nonlinguistic Information in Alexithymia
Authors: Ratnin Dewaraja, Yuji Sasaki
Journal: Psychotherapy and Psychosomatics (1990)

Schalling-Sifneos and MMPI Alexithymia Scales were used to screen 730 Japanese subjects. The 27 subjects scoring highest and the 26 scoring lowest on both scales were designated high and low alexithymic respectively. The two groups were tested by tachistoscopically presenting them with a lateralized visual matching task, which incorporated both linguistic and nonlinguistic stimuli. Differences in ipsilateral and contralateral hand reaction times were used as an indicator of callosal transfer speed. The results indicated that the two groups did not differ in the callosal transfer of linguistic information. They differed significantly, however, in the right to left hemisphere transfer of nonlinguistic information. This result is suggestive of a physiological basis in alexithymia.
Total and effective coronary blood flow in coronary and noncoronary heart disease.
Authors: D Mymin, G P Sharma
Journal: Journal of Clinical Investigation (1974)

There are no data available concerning total coronary blood flow to the whole heart (CBF) in man. "Effective" or "nutrient" coronary blood flow to the whole heart (MBF), supposedly a measure of flow through exchanging channels of the coronary circulation, has been measured but its validity has not been established. Accordingly, CBF and MBF were measured in 9 normal subjects, 26 patients with coronary heart disease (CHD), and 19 with noncoronary, mostly valvular heart disease (NCHD), by coincidence counting 84Rb technique. Two methods were used: single bolus (24 cases) and continuous infusion (30 cases). Various other parameters including myocardial oxygen utilization (MVO2) and lactate extraction ratio were determined. In the normal subjects CBF (386 +/- 77 ml/min) was significantly higher (P < 0.05) than in CHD (288 +/- 124 ml/min) and NCHD (292 +/- 111 ml/min). Likewise the normal MBF (380 +/- 81 ml/min) was significantly higher (P < 0.01) than in CHD (251 +/- 105 ml/min) as well as NCHD (258 +/- 104 ml/min). The myocardial Rb extraction ratio epsilon Rb) was significantly lower in normal subjects (39 +/- 9%) than in CHD (50 +/- 7%) and NCHD (52 +/- 11%) and this supports the view that epsilon Rb is flow-dependent. In both CHD and NCHD there was significant diminution of MVO2 as well as CBF. In CHD this was accompanied by a significant anaerobic trend but in NCHD it was not. It might therefore appear that in CHD, MVO2 is determined by perfusion whereas in NCHD, perfusion is determined by MVO2. In comparing CBF with MBF by paired observation testing, there was no significant difference in the normals (P > 0.3), whereas the differences were significant in CHD (P < 0.01) and NCHD (P < 0.02). This was merely a reflection of a reduced ratio of myocardial to total body epsilon Rb in CHD and NCHD, and available evidence indicates that this may be an expression of depressed transport of Rb+ rather than true shunting.
Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced Rubidium-82
Authors: K. Lance Gould, Richard A. Goldstein, Nizar A. Mullani, Richard L. Kirkeeide, Wai-Hoi Wong, Timothy J. Tewson, Marc S. Berridge, Leonard A. Bolomey, Ross K. Hartz, Richard W. Smalling, Francisco Fuentes, Akira Nishikawa
Journal: Journal of the American College of Cardiology (1986)
AMA Drug Evaluations: The Reference Book for Drug Use
Authors: Hugh H. Hussey
Journal: JAMA (1980)

The recently published<i>AMA Drug Evaluations</i>, ed 4, is to the practicing physician what a dictionary or a thesaurus is to a professional writer—an indispensable desk-top reference source. In this respect, for physicians,<i>AMA Drug Evaluations</i>has no equal. As a reference book, it is not meant to be read cover-to-cover in the manner one would read a monograph devoted to a single subject. I know of no one who has read a reference text completely, unless it may have been William Sydney Porter (O. Henry), who once wrote a humorous review of his dictionary. Certainly, anyone who acquires<i>AMA Drug Evaluations</i>should read the preface and the first five chapters on "General Information." After that, the book should rest until need arises for information about a specific drug or a group of drugs. Then the user will quickly find the source of information by consulting the index, the table
Self Assessment Colour Review of Gastroenterology
Authors: S P L TRAVIS
Journal: Gut (2001)

Self Assessment Colour Review of Gastroenterology . Edited by A Forbes, NH Gilinsky (Pp 188; illustrated). UK: Manson Publishing, 1999. ISBN 1 874545 47 2.

Recertification or subspecialty exit examinations may trigger a proliferation of self assessment texts, although candidates for part 2 MRCP are currently this book's main market in the UK. On the whole it serves its purpose …
Outcomes of curative treatment for hepatocellular cancer in nonalcoholic steatohepatitis versus hepatitis C and alcoholic liver disease
Authors: Srinevas K. Reddy, Jennifer L. Steel, Hui-Wei Chen, David J. DeMateo, Jon Cardinal, Jaideep Behari, Abhinav Humar, Wallis J. Marsh, David A. Geller, Allan Tsung
Journal: Hepatology (2011)

Concomitant increasing incidences of hepatocellular carcinoma (HCC) and nonalcoholic steatohepatitis (NASH) suggest that a substantial proportion of HCC arises as a result of hepatocellular injury from NASH. The aim of this study was to determine differences in severity of liver dysfunction at HCC diagnosis and long-term survival outcomes between patients undergoing curative therapy for HCC in the background of NASH compared to hepatitis C virus (HCV) and/or alcoholic liver disease (ALD). Patient demographics and comorbidities, clinicopathologic data, and long-term outcomes among patients who underwent liver transplantation, hepatic resection, or radiofrequency ablation for HCC were reviewed. From 2000 to 2010, 303 patients underwent curative treatment of HCC; 52 (17.2%) and 162 (53.5%) patients had NASH and HCV and/or alcoholic liver disease. At HCC diagnosis, NASH patients were older (median age 65 versus 58 years), were more often female (48.1% versus 16.7%), more often had the metabolic syndrome (45.1% versus 14.8%), and had lower model for end-stage liver disease scores (median 9 versus 10) (all P < 0.05). NASH patients were less likely to have hepatic bridging fibrosis or cirrhosis (73.1% versus 93.8%; P < 0.001). After a median follow-up of 50 months after curative treatment, the most frequent cause of death was liver failure. Though there were no differences in recurrence-free survival after curative therapy (median, 60 versus 56 months; P = 0.303), NASH patients had longer overall survival (OS) (median not reached versus 52 months; P = 0.009) independent of other clinicopathologic factors and type of curative treatment.Patients with HCC in the setting of NASH have less severe liver dysfunction at HCC diagnosis and better OS after curative treatment compared to counterparts with HCV and/or alcoholic liver disease.