tbuckley/cabot-search huggingface dataset:
Abstract 1306: A Phase 1b/2a study of CRLX101, a novel nanopharmaceutical of camptothecin, in solid tumor cancer patients who have failed standard therapy
Authors: Glen Weiss, Yun Yen, Jeffrey Neidhart, Cissy S. Young, Sara Weiss, John Ryan
Journal: Cancer Research (2011)

Abstract Results from a 24-patient dose-escalation safety and tolerability Phase 1 study of CRLX101 were presented at the 22nd EORTC-NCI-AACR symposium in November 2010. A Phase 2a expansion study of CRLX101 has been initiated to investigate the biological activity and tolerability in cancer patients with specific tumor types at the maximum-tolerated dose (MTD) of 15 mg/m2. Specifically, a focus of the Phase 2a expansion study is to evaluate CRLX101 biological activity in non-small cell lung carcinoma (NSCLC), amongst other target indications. In this Phase 2a expansion study, thirty-six (36) patients will be enrolled from three (3) clinical sites in the United States. Fifteen (15) patients treated with CRLX101 thus far were patients with advanced NSCLC. Stable disease of greater than 6 months in multiple NSCLC patients treated with CRLX101 has been observed. Dose-limiting bone marrow toxicities of thrombocytopenia and neutropenia were addressed with the longer dosing interval of an every-other-week dosing schedule, which accommodates for the prolonged half-life of CRLX101. Hemorrhagic cystitis, the classic camptothecin toxicity, has not been observed. No other significant adverse events have been observed in the current study. The Phase 2a study will be fully enrolled by the end of 2010 with extensive follow-up on most patients by April of 2011. All of the safety, tolerability, and biological activity data will be presented. At this time, twenty-one (21) of the thirty-six (36) patients have been enrolled. To date, three (3) NSCLC patients have received 4 cycles of therapy and are continuing on study. One (1) NSCLC patients is receiving the seventh cycle of therapy. A controlled, randomized Phase 2 study of CRLX101 in NSCLC is planned and will be initiated in early 2011. CRLX101's favorable tolerability profile may enable combination therapy with other cytotoxic drugs including carboplatin and gemcitabine without added toxicities. Preclinical data on the efficacy and tolerability of such combinations will also be presented. In addition, the dual activity of CRLX101 against both topoisomerase-1 and HIF1α suggest that combination with VEGF antagonists could be synergistic. Similarly, pre-clinical data on the dual mechanism inhibition by CRLX101 based on its pharmacokinetics will be presented. 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 1306. doi:10.1158/1538-7445.AM2011-1306
Case Records of the Massachusetts General Hospital — Continuing to Learn from the Patient
Authors: Nancy Lee Harris
Journal: New England Journal of Medicine (2003)

Virtually every physician in the world has, at one time or another, read the Case Records of the Massachusetts General Hospital (the reports of the Clinicopathological Conferences [CPCs]) in the Journal. Based on the case method of teaching medicine espoused by Dr. Walter Cannon,1 these conferences were established at the Massachusetts General Hospital by Dr. Richard Cabot, an internist and faculty member at Harvard Medical School, during the first decade of the 20th century.2 Under his direction, the teaching of medicine through the study of "actual cases of disease" became a popular feature at Harvard Medical School, at the . . .
Abstract 560: The use of molecular biomarkers to quantify drug distribution in solid tumors
Authors: Jasdeep K. Saggar, Ian F. Tannock
Journal: Cancer Research (2011)

Abstract The tumor microenvironment plays a critical role in the efficacy of chemotherapy. The disorganized vasculature within solid tumors leads to decreased drug delivery to the tumor and poor penetration of drugs from blood vessels to the tumor cells. Our laboratory has shown limited distribution of the auto-fluorescent drugs doxorubicin and mitoxantrone using quantitative immunohistochemistry. However, most anti-cancer drugs are not fluorescent and do not have antibodies that recognize them. The aim of the present study is to characterize the spatial distribution within solid tumors of biomarkers of drug effect: cleaved caspase 3 (a marker of apoptosis), γH2aX (a marker of DNA damage) and Ki67 (a marker of cell proliferation) in relation to blood vessels (recognized by an antibody to CD31). We have quantified the time-dependent distribution of these biomarkers in two models: human breast cancer MDA-MB-231 xenografts and murine mammary EMT6 syngeneic tumors following treatment with doxorubicin and melphalan respectively. Biomarker distributions have been compared to distributions of doxorubicin fluorescence. Melphalan's distribution within a solid tumor has been assessed for the first time with the use of a melphalan-DNA adduct recognizing monoclonal antibody. These studies are designed to provide a basis for selecting biomarkers to reflect the distribution of other non-fluorescent agents. The distribution of doxorubicin decreases exponentially with increasing distance from blood vessels, and is similar to the distribution of γH2aX at 10 minutes after drug injection. The activation of cleaved caspase 3 (indicating apoptosis) at 24 and 48 hours following treatment also mirrors the distribution of doxorubicin. The analysis of biomarker distributions in EMT6 tumors following treatment with melphalan in relation to tumor blood vessels is in progress. The results of these studies will be applied to quantify the intratumoral distribution of other non-fluorescent anticancer drugs (hypoxia-activated pro-drugs). 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 560. doi:10.1158/1538-7445.AM2011-560
Plasma neurohormonal changes in response to cardiac resynchronization therapy in patients with congestive heart failure
Authors: Guido Boerrigter, Susan C. Madden, Lisa C. Costello-Boerrigter, Alessandro Cataliotti, Denise M. Heublein, William T. Abraham, Michael R. Hill, John C. Burnett
Journal: Journal of the American College of Cardiology (2003)
Transmission and Severity of Measles Acquired in Medical Settings-Reply
Authors: Ronald M. Davis
Journal: JAMA (1986)

In Reply.—  Dr Foulon and colleagues have made the important observation that persons who acquire measles in the hospital are more likely to develop serious complications of the disease than those who acquire measles in other settings. We have previously advised that transmission of measles in medical settings is of particular concern because of possible spread to those with a higher risk of complications. 1 The age groups that, according to our data, are more likely to acquire measles in medical settings—infants and young adults—are also the age groups at higher risk of complications. 2 In addition, those acquiring measles in medical facilities may be at greater risk of complications because of other, underlying illnesses.  Data on complications among all 241 medical setting cases included in our report are not available. However, such data are available for an outbreak in 1983 in Kern County, California, in which transmission in medical
Psychological Diagnosis in Clinical Practice with Applications in Medicine, Law, Education, Nursing, and Social Work
Authors: Murray Wexler
Journal: JAMA (1968)

In 1882 Francis Galton established a laboratory in the South Kensington Museum for the purpose of making an inventory of mental abilities of Englishmen. Since that time the use of psychological tests has grown into a gigantic enterprise. Its impact on our national life was dramatically underscored recently by a congressional investigation which sought to determine if tests infringe on the rights of privacy. Whatever the political and legal conclusions of these debates are, tests have proved to be highly useful tools in medicine, psychology, education, and research. The present volume provides an effective introduction to the use of tests as psychodiagnostic tools, particularly for those working in medical, psychiatric, or private practice setting. The book is divided into two sections. In part 1 the authors provide a brief but informative description of the development, education, methods, and professional problems of clinical psychology. This is followed by a chapter which
Cost-effectiveness studies
Authors: T Davies, P Smith
Journal: BMJ (1978)

compared with atenolol and propranolol (6%,, 10%, and 27% respectively).We have carried out several studies on the hypotensive effect of pindolol administered in a single daily dose.In agreement with Dr Wilcox we think it is very important to evaluate a 24-h effect and therefore we also measured blood pressure in the morning before the administration of the daily dose of pindolol.In a multicentre study4 we found that 44 patients who were satisfactorily controlled on multiple doses of a beta-blocker could be maintained adequately with a mean dose of 13 mg of pindolol given once daily.In another study 16 patients received increasing single daily doses of pindolol from 5 to 20 mg, and the mean supine blood pressure was lowered from 181/ 111 nmm Hg after three weeks, placebo treat- ment to 150/91 mm Hg after 16 weeks' drug treatment.2Our results are in good agreement with those of Gordon,5 who also found a satisfactory lowering of blood pressure throughout a 24-h period with single daily doses of pindolol.Recently a multicentre study has been published by Rosenthal6 in which more than 7000 patients were treated with pindolol once daily, with good success in 750°/.
CS gas injury to the eye
Authors: J.-P. Yih
Journal: BMJ (1995)

the same time as both the committee and the health departments were recommending the opposite.Unless firm action is taken swiftly, the entire system of delivering genetic services, which the present report sees as the foundation for the future, may be damaged beyond repair.This thorough, well informed, and critical report has implications for all fields of medicine, including primary care.Genetics can no longer be left to a small group of specialists; it increasingly permeates all areas of medicine and biomedical research and is already having a profound impact on the values and concerns of the whole of society.Reassuringly, the British parliamentary system has been able to examine this field constructively; let us hope that the government moves
Management of cutaneous viral warts
Authors: Magnus D Lynch, Jane Cliffe, Rachael Morris-Jones
Journal: BMJ (2014)

#### Summary points

The prevalence of cutaneous viral warts in the general population is estimated to be 7-12%. Many patients present to primary care with pain and discomfort along with other concerns, such as cosmetic appearance. Although cutaneous viral warts are ubiquitous, no definitive treatment exists. Nevertheless, most warts resolve spontaneously and a large proportion of the remainder respond to simple recommended treatment. For these reasons, potential treatments must have minimal side effects and a favourable risk profile.

#### Sources and selection criteria

We searched Medline, Embase, and the Cochrane databases for evidence relating to the treatment of cutaneous viral warts. Although a large number of trials have been published, the quality of evidence varied and only a few were randomised and of adequate sample size. Proof of efficacy is challenging, with relatively high rates of spontaneous resolution; furthermore, studies of second and third line treatments are limited as these treatments are typically reserved for recalcitrant warts.

High quality evidence based studies are lacking in this discipline owing to confounding factors such as high rates of spontaneous resolution and a subpopulation of warts that seem recalcitrant to most treatments. Occasionally in medicine the longer the list of potential treatments the less effective they seem to be, and this situation is exemplified by viral warts.1 2 This article focuses on the preferred treatment of viral warts in primary care and alternative management in secondary care.

Viral warts are benign papillomas that arise from infection of epidermal or mucosal cells with …
A PATHOLOGICAL CONDITION OF THE LUNGS, HITHERTO UNDESCRIBED IN THIS COUNTRY, BUT WHICH IS NOT INFREQUENT.Read by Title in the Section of the Practice of Medicine and Physiology at the Forty-second Annual Meeting of the American Medical Association, at Washington, D. C., May, 1891.
Authors: F. PEYRE PORCHER
Journal: JAMA (1891)

During the course of a very prolonged service in hospitals, I have repeatedly observed a condition of the lungs which is markedly distinct and characteristic, which I have not seen described. A full account of this appeared in the<i>New York Medical Record</i>, October 19, 1889. I will give here a succinct review of the main features and symptoms, in order that we may decide whether it is only a pathological state, or whether it should rank as a distinct disease. Patients presented the following symptoms: Dulness or sub-dulness, generally at the middle, lateral orposterior portions of the chest; there was always imperfect respiration; scarcely any râle present, or if so sparsely disseminated, and generally the subcrepitant; or perhaps there was only rough breathing. The condition was consequent on antecedent morbid states, and was discoverable weeks before death, if a fatal result ensued. There was not necessarily fever or
Prognostic implications of an early peak in plasma MB creatine kinase in patients with acute myocardial infarction
Authors: David A. Cox, Peter H. Stone, James E. Muller, Corette Parker, Tyler D. Hartwell, John D. Rutherford, Robert Roberts, Allan S. Jaffe, Donald B. Hackel, Eugene R. Passamani, Thomas Robertson, Burton E. Sobel, James T. Willerson, Eugene Braunwald
Journal: Journal of the American College of Cardiology (1987)
Abstract LB-180: Prevention of NNK-induced lung cancer in mice by anti-estrogen therapy
Authors: Jill M. Siegfried, Mary E. Rothstein, Diana Lenzner, Christopher T. Gubish, Stephanie R. Land, Laura P. Stabile
Journal: Cancer Research (2010)

Abstract Discussion 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-180.
Quebec faces severe pressure on casualty departments
Authors: D. Spurgeon
Journal: BMJ (1999)

Quebec's provincial government is injecting $C20m (£ 48m; $77m) into its hospitals as a short term measure to help solve the worst emergency room overcrowding crisis in recent memory.

That's $C5m more than the health and social services minister, Pauline Marois, promised two weeks earlier. She got the additional funds by appealing to Prime Minister, Lucien Bouchard, after widespread media coverage of an overflow of patients in several centres, notably Montreal and Quebec City.

On one Wednesday in February, 11emergency rooms were …
1039-199 Reduction of QRS duration after pulmonary valve replacement in adult fallot patients is related to degree of reduction of right ventricular volume
Authors: Bart Hooft van Huysduynen, Cees A Swenne, Arie C Maan, Alexander van Straten, Henk J Ritsema van Eck, Martin J Schalij, Ernst E van der Wall, Albert de Roos, Mark G Hazekamp, Hubert W Vliegen
Journal: Journal of the American College of Cardiology (2004)
Weight-Loss Maintenance — Mind over Matter?
Authors: David S. Ludwig, Cara B. Ebbeling
Journal: New England Journal of Medicine (2010)

Many people can lose weight in the short term by reducing their intake of calories with the use of a variety of diets, ranging from low-fat to very-low-carbohydrate. However, few people successfully maintain their weight loss.1 One explanation for the poor efficacy of conventional diets relates to psychological factors, since the motivation to adhere to restrictive regimens diminishes with time, especially in an environment with virtually instantaneous availability of food. A second, perhaps more fundamental, explanation is that weight loss elicits physiological adaptations — principally an increase in hunger and a decrease in resting energy expenditure2 — that oppose ongoing . . .
Independent risk factors for hepatocellular carcinoma in french drinkers
Authors: Thierry Poynard, Alain Aubert, Yasmina Lazizi, Pierre Bedossa, Bernard Hamelin, Benoit Terris, Sylvie Naveau, Pascal Dubreuil, Jacques Pillot, Jean-Claude Chaput
Journal: Hepatology (1991)

The aim of this study was to assess whether markers of hepatitis B virus or hepatitis C virus infection are independent risk factors for hepatocellular carcinoma in drinkers after adjustment for three known risk factors: cirrhosis, age and male sex. Among 2,015 consecutive drinkers admitted, hepatitis C virus antibodies were found by sensitive radioimmunoassay in 1,259. The following five factors have been identified and ranked as risk factors for hepatocellular carcinoma in unidimensional and regression analysis: cirrhosis (p less than 0.001), age (p less than 0.001), male sex (p less than 0.001), presence of HBsAg (p less than 0.001) and presence of hepatitis C virus antibodies (p less than 0.03). Among drinkers with cirrhosis, the patients with hepatocellular carcinoma were older (64 +/- 11 yr vs. 56 +/- 9 yr; p less than 0.001), were more often male (93% vs. 65%; p less than 0.0001) and had higher prevalence of HBsAg (9% vs. 2%; p = 0.02) and hepatitis C virus antibodies (41% vs. 26%; p = 0.02). A simple algorithm permitted us to identify a high-risk population of drinkers: the male cirrhotic patient older than 50 yr. The relative risk of hepatocellular carcinoma in this selected population was 17.7 (95% confidence interval = 9.0 to 37.5; p less than 0.0001). From a pragmatic point of view, the detection of HBsAg or hepatitis C virus antibodies, although independently associated with hepatocellular carcinoma, is not useful in increasing the diagnostic value of this algorithm because of the poor sensitivity of these tests. The weak relationships observed between hepatitis C virus antibodies and hepatocellular carcinoma needs confirmation by more accurate tests.
Quantitative thallium-201 redistribution with a fixed coronary stenosis in dogs.
Authors: J Leppo, J Rosenkrantz, R Rosenthal, R Bontemps, T Yipintsoi
Journal: Circulation (1981)

The redistribution of thallium-201 (201Tl) after coronary vasodilation was studied in 14 dogs with a proximal stenosis of the left circumflex coronary artery that did not reduce basal flow but attenuated reactive hypermia. During an 8-10-minute i.v. infusion of adenosine, radioactive microspheres and 201Tl were injected into the left atrium. Sequential cardiac scintiscans and microsphere injections permitted subsequent determination of coronary blood flow during the redistribution of 201Tl. After 15-220 minutes of observation, the dogs were killed and the hearts removed for the measurement of the activity of 201Tl and the radioactive microspheres in the normal (left anterior descending coronary artery [LAD]) and flow-restricted (left circumflex coronary artery [LCX]) regions. The ratios of the activity in LAD/LCX for microspheres (TRmic) and for 201Tl (RT1) were compared with the activity ratio determined from the scintiscan (Rscan). Rmic for the microsphere simultaneously injected with 201Tl can be compared with the initial Rscan, which showed a significant hourly decrease from an initial value of 1.26 +/- 0.12 to a mean final value of 1.02 +/- 0.09 by 3-4 hours. The final Rscan (mean 1.07 +/- 0.10) in each experiment also correlated significantly (r = 0.854) with the final true myocardial RT1 (mean 1.26 +/- 0.25). Rscan underestimated Rmic (average 2.25 +/- 0.48) when both 201Tl and microspheres were simultaneously injected; Rscan also underestimated RT1, but the directional changes were similar. A further analysis of the Rmic, Rscan and RT1 in two groups of dogs with either relatively high or low coronary flow during adenosine infusion suggests that the net loss of cellular 201Tl from the normal scintigraphic area is the mechanism underlying the resolution of these initial defects.
Echinococcal Cyst of the Pericardium
Authors: F M Hall
Journal: New England Journal of Medicine (1995)

Figure 1. A 56-year-old man from Saudi Arabia presented with dyspnea. A chest film (Panel A) revealed a large mass in the left hemithorax, with contralateral mediastinal shift and depression of the gas-filled stomach (arrow). Computed tomography after the injection of intravenous contrast medium (Panel B and Panel C) showed a large multilocular cyst in the left hemithorax with contralateral displacement of mediastinal structures, including the trachea (T), the ascending aorta (AA) and the descending aorta (DA), the superior vena cava (SVC), and the right pulmonary artery (RPA). The left main bronchus (arrow) and left pulmonary artery (LPA) were compressed. . . .
Merian Frederick's Story
Authors: Carol Poenisch
Journal: New England Journal of Medicine (1998)

My mother, Merian Frederick, suffered from amyotrophic lateral sclerosis (ALS) for four years. She ended her suffering with the assistance of Jack Kevorkian in 1993, at the age of 72. She was in control and made the decision herself.My husband and I were living with our first child in Europe when my mother's symptoms first appeared. That was in 1989. On the telephone, I heard her slurred speech, even before she was aware of it. I worried about alcoholism. Shortly afterward, we moved back to Ann Arbor, Michigan, where my mother lived and I had been raised. Connie, one . . .
EXTRA-UTERINE PREGNANCY.
Authors: F. F. LAWRENCE
Journal: JAMA (1902)

To those who have looked upon a ruptured tubal pregnancy, I need not attempt to paint in words the picture of this terrible complication. That the surgeon is still so frequently called upon after a tubal pregnancy has ruptured and the patient is exsanguinated, all too forcibly emphasizes the fact that the importance of this subject has not yet been fully grasped by our obstetric teachers. That it is practical to diagnosticate the condition before rupture has been demonstrated so thoroughly that if the medical profession were fully awake to the needs of the hour very few of these cases would ever reach the stage of rupture. In 1892 I made the diagnosis before rupture—which operation verified —of extra-uterine pregnancy, and, since that time, have diagnosed this condition no less than nineteen times before rupture. I have always considered that the diagnosis could be made, and was unaware that it