tbuckley/cabot-search huggingface dataset:
Diagnosis and Treatment of Breast Cancer: International Clinical Forum
Authors: William G. Abel
Journal: JAMA (1982)

In most countries of the world, breast cancer remains the most serious malignant neoplasm of women. During the first half of the 20th century, the radical mastectomy of Halsted was the "gold standard" by which any new treatment method was evaluated. In the latter half of this century it is clear that less radical methods of treatment may produce similar results, but the definition of "less radical" has engendered a variety of approaches, each with its staunch supporters equipped with convincing statistics. Improvements in radiation equipment and techniques now make local tumor control possible, but long-term follow-up in this country is necessary before full acceptance of this method as an alternative treatment. Other current issues are endocrine manipulation, timing and composition of chemotherapy, and the role of immunotherapy. The Society for Continuing Education and The Johns Hopkins Hospital, being aware of the prolific ongoing research in this field, with the
Sawdust: A Health Hazard
Authors: Benjamin Becker
Journal: JAMA (1977)

<h3>To the Editor.—</h3> Recently, we have isolated<i>Thermoactinomyces</i>organisms (a cause of hypersensitivity pneumonitis) from 28 of 123 samples of weathered sawdust received from 32 states, Nova Scotia, and the Philippines. The samples were obtained either personally or mailed in by cooperating forest products companies. The samples were incubated at 55 °C in a sealed plastic bag from one to five days. Previously,<i>Thermoactinomyces</i>organisms were found in overheated hay, grain, and bagasse as well as in home no-frost refrigerators, heating systems, air conditioners, and humidifiers (236:344, 1976). All of these sources fulfill the three criteria for growth of<i>Thermoactinomyces:</i>the presence of moisture, nutrients, and an elevated temperature. We recommend drying of the sawdust as a means of preventing growth of mesophilic microorganisms. Otherwise, metabolic heat accumulates during growth and provides the proper temperature conditions for the subsequent germination and growth of<i>Thermoactinomyces</i>spores.
Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Inhibitors for Primary Prevention of Colorectal Cancer: A Systematic Review Prepared for the U.S. Preventive Services Task Force
Authors: Alaa Rostom, Catherine Dubé, Gabriela Lewin, Alexander Tsertsvadze, Nicholas Barrowman, Catherine Code, Margaret Sampson, David Moher
Journal: Annals of Internal Medicine (2007)

Purpose: To examine the benefits and harms of nonaspirin (non-ASA) nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX-2) inhibitors for the prevention of colorectal cancer (CRC) and adenoma. Data Sources: MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Register of Controlled Trials, Cochrane Collaboration's registry of clinical trials, Cochrane Database of Systematic Reviews. Study Selection: Randomized, controlled trials and case–control and cohort studies of the effectiveness of NSAIDs for the prevention of CRC and colorectal adenoma were identified by multilevel screening by 2 independent reviewers. Systematic reviews of harms were sought. Data Extraction: Data abstraction, checking, and quality assessment were completed in duplicate. Data Synthesis: A single cohort study showed no effect of non-ASA NSAIDs on death due to CRC. Colorectal cancer incidence was reduced with non-ASA NSAIDs in cohort studies (relative risk, 0.61 [95% CI, 0.48 to 0.77]) and case–control studies (relative risk, 0.70 [CI, 0.63 to 0.78]). Colorectal adenoma incidence was also reduced with non-ASA NSAID use in cohort studies (relative risk, 0.64 [CI, 0.48 to 0.85]) and case–control studies (relative risk, 0.54 [CI, 0.4 to 0.74]) and by COX-2 inhibitors in randomized, controlled trials (relative risk, 0.72 [CI, 0.68 to 0.77]). The ulcer complication rate associated with non-ASA NSAIDs is 1.5% per year. Compared with non-ASA NSAIDs, COX-2 inhibitors reduce this risk but, in multiyear use, have a higher ulcer complication rate than placebo. Cyclooxygenase-2 inhibitors and nonnaproxen NSAIDs increase the risk for serious cardiovascular events (relative risk, 1.86 [CI, 1.33 to 2.59] for COX-2 inhibitors vs. placebo). Limitations: Heterogeneity in the dose, duration and frequency of use necessitated careful grouping for analysis. Conclusions: Cyclooxygenase-2 inhibitors and NSAIDs reduce the incidence of colonic adenomas. Nonsteroidal anti-inflammatory drugs also reduce the incidence of CRC. However, these agents are associated with important cardiovascular events and gastrointestinal harms. The balance of benefits to risk does not favor chemoprevention in average-risk individuals.
Sleep disordered breathing in a 4 year old child with Down's syndrome
Authors: D S Urquhart, L Perry, A Gupta, M Rosenthal
Journal: BMJ (2008)

A 4 year old boy with Down’s syndrome has a long history of sleep disturbance. He snores at night, his sleep is very restless, and he sleeps for long periods during the day while at nursery. He was admitted for an overnight sleep study, a six hour epoch of which is displayed below (fig 1)⇓. A treatment intervention improved sleep quality. Fig 1 Overnight sleep study showing transcutaneous carbon dioxide (CO2), oxygen saturation (SaO2), and heart recordings ### Short answers Fig 2 Overnight sleep study showing abnormalities in transcutaneous carbon dioxide (CO2), oxygen saturation (SaO2), and heart recordings
Signal transducer and activator of transcription 3 is a major kinase-independent target of sorafenib in hepatocellular carcinoma
Authors: Wei-Tien Tai, Ann-Lii Cheng, Chung-Wai Shiau, Hsiang-Po Huang, Jui-Wen Huang, Pei-Jer Chen, Kuen-Feng Chen
Journal: Journal of Hepatology (2011)
A Protease Inhibitor Specifically Inhibits Growth of HPV-Infected Keratinocytes
Authors: David A. Drubin, Margaret E. McLaughlin-Drubin, Gary A. Clawson, Craig Meyers
Journal: Molecular Therapy (2006)

Protease inhibitors have been known to exhibit anticarcinogenic activity in a variety of model systems, although the biological target(s) and mechanism remain enigmatic. Human papillomavirus (HPV) is the primary etiological agent of cervical cancer. Here we show that a nuclear chymotrypsin-like protease activity (NCLPA), which appears to be involved in transformation in several different experimental models, is significantly elevated in keratinocytes infected with high-risk HPV. Further, we demonstrate a marked growth inhibition of organotypic raft cultures, which is specific for cells infected with high-risk HPV types, using a chloromethyl ketone inhibitor previously shown to be relatively selective for the NCLPA. Surprisingly, this HPV-dependent inhibitory effect is independent of any alterations in the NCLPA. This finding has clear implications for the development of novel therapeutics specifically targeted to cervical dysplasias with HPV-infected cells.
James Robertson Angus White
Authors: P. J White
Journal: BMJ (2009)

James Robertson Angus White (“Jim”) was born in Anstruther, Fife, and educated at the Waid Academy and St Andrews University, graduating in 1936. In 1939 he gained the FRCS Edinburgh. At the start of the second world war he worked at Dudley Road Hospital, Birmingham, and during the Midlands Blitz. There he met his wife (Edna Doreen Bates) and married in April 1941.

He entered the army in 1942, serving as surgeon to the Combined Operations Training Unit at Inverary. Thereafter he was given command …
Obstetric accidents: a review of 64 cases.
Authors: M Ennis, C A Vincent
Journal: BMJ (1990)

To identify the causes of obstetric accidents.Analysis of case records at the Medical Protection Society's London office covering the five years 1982-6.Cases that had come to litigation which had resulted in stillbirth, perinatal or neonatal death, central nervous system damage to the baby, or maternal death and in which there was an opinion from a senior obstetrician consulted by the society. Of 147 cases reviewed, 64 met the criteria for the study.The principal findings of the expert reviewers.Three major topics of concern emerged common to most of the 64 cases. These were inadequate fetal heart monitoring, mismanagement of forceps, and inadequate supervision by senior staff. In 11 of the 64 cases cardiotocography was omitted, in 19 cases the trace was missing, in six cases the trace was unreadable, and in 14 of the remaining 28 cases signs of fetal distress went unnoticed or were ignored. In 31 cases forceps were used to aid delivery or were tried and abandoned in favour of caesarean section. In 16 cases two or more attempts to use forceps were made. Five infant deaths were directly attributed to mismanaged forceps. In 20 cases senior staff were criticised by the expert reviewer for failure to come to the labour ward. In many of these cases they may have given advice over the telephone, but the inadequacy of records made it impossible to tell. In these cases the labour and birth were managed by junior staff, usually a senior house officer. In six cases when senior staff did come they suggested that no action was needed.These few cases should not be dismissed as isolated incidents in obstetric practice in Britain. They reflect more general problems--namely, concerning the ability of junior doctors to interpret fetal heart traces accurately, their ability to use forceps, and the participation of senior staff in running a labour ward and delivery suite.
Reliability of Measurements of Tricyclic Levels-Reply
Authors: David A. Johnson
Journal: JAMA (1984)

In Reply.—  We agree with Dr Bank's contention that the reliability of a drug level needs to be questioned and that laboratory error is always a possibility. Use of a well-established laboratory with a standardized methodology for withdrawing and processing blood samples minimizes this potential for error.1In our case, a local medical school laboratory was used and the assay technique was well established with internal quality control assays done routinely. Furthermore, serial blood levels of our patient demonstrated one other toxic range level of 1,040 ng/mL and a subsequent graduated decline over the initial hospital course. We believe that the potential for laboratory error in this case was minimal. We believed that a comment on the possible lower cardiotoxicity of doxepin was beyond the scope of our report. Although one report has suggested that this is the case in animals,2we know of no controlled study definitively
A Sonographic Lesion Index for Crohn's Disease Helps Monitor Changes in Transmural Bowel Damage During Therapy
Authors: Francesca Zorzi, Elisa Stasi, Gerolamo Bevivino, Patrizio Scarozza, Livia Biancone, Sara Zuzzi, Carla Rossi, Francesco Pallone, Emma Calabrese
Journal: Clinical Gastroenterology and Hepatology (2014)
DIAGNOSIS AND TREATMENT OF ACQUIRED HEMOLYTIC ANEMIA
Authors: Milton S. Sacks
Journal: JAMA (1952)

In the early years of this century several French workers 1 described a form of hemolytic anemia in which autoagglutination of the patient's red blood cells was frequently observed and a circulating hemolysin often demonstrable. This entity was described as acquired hemolytic anemia to distinguish it from the congenital variety. The concept did not receive widespread acceptance for a number of years, and many such cases were undoubtedly misclassified as hereditary hemolytic anemias. In 1938, Dameshek and associates 2 demonstrated that hemolytic anemias of varying degrees of severity could be experimentally produced by the injection of anti-red-blood-cell serums. The erythrocytes of animals so treated became spherocytic, a characteristic previously considered pathognomonic for the congenital type of hemolytic anemia. Nevertheless, until some seven years ago the demonstration of anti-red-blood-cell antibodies in human beings with hemolytic anemia was possible in only a fraction of the cases. The introduction of new techniques, derived
Effect of sodium nitroprusside and diethylcarbamazine on hypoxic pulmonary vasoconstriction and regional distribution of pulmonary blood flow in experimental pneumonia.
Authors: R B Light
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The interaction between the effects of indomethacin and sodium nitroprusside or diethylcarbamazine infusion on the efficacy of hypoxic pulmonary vasoconstriction (HPV) and regional distribution of lung blood flow was studied in 15 pentobarbital-anesthetized dogs with acute pneumonia caused by Pseudomonas aeruginosa. After induction of pneumonia central hemodynamics, gas exchange, and regional distribution of lung blood flow (radionuclide-labeled microsphere method) were measured during ventilation of both lungs with oxygen and again with one lung ventilated with nitrogen. The dogs were then randomly assigned to one of three treatment groups: Group I (n = 5) received indomethacin alone (2 mg/kg); Group I-D received indomethacin and diethylcarbamazine (50 mg/kg over 20 min followed by 1 mg/kg/min for the rest of the experiment); Group I-N (n = 5) received indomethacin with sodium nitroprusside to achieve a 20- to 30-mm Hg reduction in mean blood pressure. All measurements were then repeated during both oxygen ventilation and one-lung nitrogen ventilation. In all three groups there was no effect of nitrogen inhalation on distribution of lung blood flow prior to drug treatment, indicating absence of HPV. After treatment, in Group I, perfusion of the pneumonic lung fell from 0.27 +/- 0.08 to 0.10 +/- 0.03 (p < 0.05) of total lung blood flow, and nitrogen ventilation of the left lung reduced perfusion to that region from 0.23 +/- 0.02 to 0.13 +/- 0.02 (p < 0.05), indicating restoration of HPV. In Groups I-D and I-N, HPV was persistently absent or markedly attenuated after treatment, but the percentage of the cardiac output perfusing the pneumonia region fell by an amount similar to that in Group I (0.26 +/- 0.07 to 0.11 +/- 0.04 in Group I-D and 0.35 +/- 0.03 to 0.21 +/- 0.06 in Group I-N, both p < 0.05). Because these two chemically unrelated pulmonary vasodilators effectively blocked HPV restoration but had no effect on vasoconstriction in the pneumonia region after indomethacin, it is concluded that regional lung blood flow redistribution in pneumonia is mediated by a mechanism other than HPV.
Effect of Volume Expansion on the Anginal Threshold
Authors: FAREEDUDDIN KHAJA, VIJAY SANGHVI, ALEXANDER MARK, JOHN O. PARKER
Journal: Circulation (1971)

The clinical and hemodynamic effects of rapid atrial pacing were studied in 13 patients with coronary artery disease and four normal subjects before and following acute expansion of blood volume with low molecular weight dextran. Five patients developed angina during the initial pacing period. In two of these five patients angina recurred with infusion alone, and all five of them experienced pain during the second pacing period. The anginal threshold averaged 5 min (range, 1 to 8 min) before infusion and 1.8 min (range, 0 to 5 min) following infusion. Four patients with coronary artery disease remained free of pain during the first pacing period, one of these developed pain with infusion alone, and all developed pain during pacing following infusion, the anginal threshold being 2 min (range, 0 to 3 min). The remaining four patients with coronary artery disease did not develop angina during either pacing period. Administration of dextran was accompanied by an increase in left ventricular end-diastolic pressure in all patients during sinus rhythm and during atrial pacing. Although left ventricular volume was not determined, changes in left ventricular end-diastolic pressure were interpreted as showing directional changes in left ventricular volume. Analysis of the factors affecting myocardial oxygen requirements during the two pacing periods indicated that heart rate, systemic arterial pressure, and maximal rate of rise of left ventricular pressure were similar. Although the tension-time index rose 10.6%, the major change was the increase in left ventricular end-diastolic pressure and presumably in left ventricular volume. This increase in left ventricular volume is considered responsible for the increase in myocardial oxygen requirements following infusion of dextran as determined by the decrease in the anginal threshold in each patient of the angina group.
Systemic Delivery of SapC-DOPS Has Antiangiogenic and Antitumor Effects Against Glioblastoma
Authors: Jeffrey Wojton, Zhengtao Chu, Haritha Mathsyaraja, Walter H Meisen, Nicholas Denton, Chang-Hyuk Kwon, Lionel ML Chow, Mary Palascak, Robert Franco, Tristan Bourdeau, Sherry Thornton, Michael C Ostrowski, Balveen Kaur, Xiaoyang Qi
Journal: Molecular Therapy (2013)

Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a nanotherapeutic which effectively target and destroy cancer cells. Here, we explore the systemic use of SapC-DOPS in several models of brain cancer, including glioblastoma multiforme (GBM), and the molecular mechanism behind its tumor-selective targeting specificity. Using two validated spontaneous brain tumor models, we demonstrate the ability of SapC-DOPS to selectively and effectively cross the blood–brain tumor barrier (BBTB) to target brain tumors in vivo and reveal the targeting to be contingent on the exposure of the anionic phospholipid phosphatidylserine (PtdSer). Increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS–induced killing efficacy, and tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. Apart from cancer cell killing, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo. Interestingly, unlike traditional chemotherapy, hypoxic cells were sensitized to SapC-DOPS–mediated killing. This study emphasizes the importance of PtdSer exposure for SapC-DOPS targeting and supports the further development of SapC-DOPS as a novel antitumor and antiangiogenic agent for brain tumors. Saposin C-dioleoylphosphatidylserine (SapC-DOPS) nanovesicles are a nanotherapeutic which effectively target and destroy cancer cells. Here, we explore the systemic use of SapC-DOPS in several models of brain cancer, including glioblastoma multiforme (GBM), and the molecular mechanism behind its tumor-selective targeting specificity. Using two validated spontaneous brain tumor models, we demonstrate the ability of SapC-DOPS to selectively and effectively cross the blood–brain tumor barrier (BBTB) to target brain tumors in vivo and reveal the targeting to be contingent on the exposure of the anionic phospholipid phosphatidylserine (PtdSer). Increased cell surface expression of PtdSer levels was found to correlate with SapC-DOPS–induced killing efficacy, and tumor targeting in vivo was inhibited by blocking PtdSer exposed on cells. Apart from cancer cell killing, SapC-DOPS also exerted a strong antiangiogenic activity in vitro and in vivo. Interestingly, unlike traditional chemotherapy, hypoxic cells were sensitized to SapC-DOPS–mediated killing. This study emphasizes the importance of PtdSer exposure for SapC-DOPS targeting and supports the further development of SapC-DOPS as a novel antitumor and antiangiogenic agent for brain tumors.
EFFECTS OF EPIVASCULAR CARDIAC NERVE STIMULATION ON HEART RATE, LEFT VENTRICULAR CONTRACTILITY AND HEMODYNAMICS
Authors: Mariko Kobayashi, Seiichiro Sakurai, Tohru Takaseya, Akira Shiose, Hyun-Il Kim, Masako Fujiki, Jamshid H. Karimov, Raymond Dessoffy, Alex Massiello, Allen Borowski, David R. Van Wagoner, Eugene Jung, Kiyotaka Fukamachi
Journal: Journal of the American College of Cardiology (2011)
Haplotype and Cell Proliferation Analyses of Candidate Lung Cancer Susceptibility Genes on Chromosome 15q24-25.1
Authors: Yan Liu, Pengyuan Liu, Weidong Wen, Michael A. James, Yian Wang, Joan E. Bailey-Wilson, Christopher I. Amos, Susan M. Pinney, Ping Yang, Mariza de Andrade, Gloria M. Petersen, Jonathan S. Wiest, Pamela R. Fain, Ann G. Schwartz, Adi Gazdar, Colette Gaba, Henry Rothschild, Diptasri Mandal, Elena Kupert, Juwon Lee, Daniela Seminara, John Minna, Marshall W. Anderson, Ming You
Journal: Cancer Research (2009)

Recent genome-wide association studies have linked the chromosome 15q24-25.1 locus to nicotine addiction and lung cancer susceptibility. To refine the 15q24-25.1 locus, we performed a haplotype-based association analysis of 194 familial lung cases and 219 cancer-free controls from the Genetic Epidemiology of Lung Cancer Consortium (GELCC) collection, and used proliferation and apoptosis analyses to determine which gene(s) in the 15q24-25.1 locus mediates effects on lung cancer cell growth in vitro. We identified two distinct subregions, hapL (P = 3.20 x 10(-6)) and hapN (P = 1.51 x 10(-6)), which were significantly associated with familial lung cancer. hapL encompasses IREB2, LOC123688, and PSMA4, and hapN encompasses the three nicotinic acetylcholine receptor subunit genes CHRNA5, CHRNA3, and CHRNB4. Examination of the genes around hapL revealed that PSMA4 plays a role in promoting cancer cell proliferation. PSMA4 mRNA levels were increased in lung tumors compared with normal lung tissues. Down-regulation of PSMA4 expression decreased proteasome activity and induced apoptosis. Proteasome dysfunction leads to many diseases including cancer, and drugs that inhibit proteasome activity show promise as a form of cancer treatment. Genes around hapN were also investigated, but did not show any direct effect on lung cancer cell proliferation. We concluded that PSMA4 is a strong candidate mediator of lung cancer cell growth, and may directly affect lung cancer susceptibility through its modulation of cell proliferation and apoptosis.
Medical Selection of Life Risks: A Comprehensive Guide to Life Expectancy for Underwriters and Clinicians
Authors: Jerzy Gajewski
Journal: JAMA (1985)

In recent years insurance medicine has become a separate specialty, recognized by the American Medical Association and governed by a separate Board of Insurance Medicine, with strict requirements for Board certification.<i>Medical Selection of Life Risks</i>, originally published in 1978, has long been recognized as one of the principal textbooks of insurance medicine, and it is only natural that a new, revised edition is made available. R. D. C. Brackenridge, an internationally recognized authority in insurance medicine, has produced a unique textbook based not only on a thorough literature research, but also—most importantly—on his own vast experience. Part 1 contains a comprehensive introduction to the concept and history of insurance as well as a fairly detailed outline of the organization and function of life insurance companies. Although mainly describing the British system, Brackenridge (who lives in London) makes frequent references to numerous differences characterizing the North American (US and Canadian)
REMARKS ON THE SURGICAL TREATMENT OF THE MALIGNANT DISEASES OF THE UTERUS.
Authors: WM. H. BYFORD
Journal: JAMA (1884)

Presented to Section of Obstetrics and Diseases of Women of American Medical Association, May, 1884. The malignant diseases that more frequently attack the uterus are: 1st. Epithelioma. 2nd. Medullary carcinoma; and 3rd. Sarcoma. They occur, according to my observation, in the order of frequency here mentioned. Probably not less frequently than the sarcoma is found the epithelial or corroding ulcer. Preparatory to the surgical treatment of these affections I desire to make some observations, particularly as to the tissues sues first invaded by them, their mode of development and manner of destruction. My idea of an epithelioma is that the deposit occurs on the free surface of the mucous membrane, in its epithelial stratum, and consists essentially of extreme multiplication of epithelial cells which, after great development of the tissue in which the process is going on, die, causing sloughs of greater or less size. This form of malignant disease