tbuckley/cabot-search huggingface dataset:
Quantitative nuclear DNA content in fine needle aspirates of pancreatic cancer.
Authors: A R Weger, K S Glaser, G Schwab, D Oefner, E Bodner, G U Auer, G Mikuz
Journal: Gut (1991)

The quantitative nuclear DNA content of nuclei from fine needle aspirations from 70 patients with pancreatic cancer was measured using an image analyser system. Retrospective analysis of patients indicated that cases with tumour stemlines in the diploid region had the best chance for radical surgery (p less than 0.006) and the best probability of survival (p less than 0.0004). The prognosis for patients with tetraploid stemlines was intermediate and was poorest for patients with no stemlines in the diploid-tetraploid region. From those parameters assessed postoperatively, only the tumour stage added appreciable information on prognosis to the preoperative quantitative DNA content obtainable. Therefore, in patients with pancreatic cancer the quantitative DNA content should be taken into account in planning treatment and assessing prognosis. Furthermore, the quantitative DNA content may have a major role in stratification for further treatment trials.
Disease phenotype of a ferret CFTR-knockout model of cystic fibrosis
Authors: Xingshen Sun, Hongshu Sui, John T. Fisher, Ziying Yan, Xiaoming Liu, Hyung-Ju Cho, Nam Soo Joo, Yulong Zhang, Weihong Zhou, Yaling Yi, Joann M. Kinyon, Diana C. Lei-Butters, Michelle A. Griffin, Paul Naumann, Meihui Luo, Jill Ascher, Kai Wang, Timothy Frana, Jeffrey J. Wine, David K. Meyerholz, John F. Engelhardt
Journal: Journal of Clinical Investigation (2010)

Cystic fibrosis (CF) is a recessive disease that affects multiple organs. It is caused by mutations in CFTR. Animal modeling of this disease has been challenging, with species- and strain-specific differences in organ biology and CFTR function influencing the emergence of disease pathology. Here, we report the phenotype of a CFTR-knockout ferret model of CF. Neonatal CFTR-knockout ferrets demonstrated many of the characteristics of human CF disease, including defective airway chloride transport and submucosal gland fluid secretion; variably penetrant meconium ileus (MI); pancreatic, liver, and vas deferens disease; and a predisposition to lung infection in the early postnatal period. Severe malabsorption by the gastrointestinal (GI) tract was the primary cause of death in CFTR-knockout kits that escaped MI. Elevated liver function tests in CFTR-knockout kits were corrected by oral administration of ursodeoxycholic acid, and the addition of an oral proton-pump inhibitor improved weight gain and survival. To overcome the limitations imposed by the severe intestinal phenotype, we cloned 4 gut-corrected transgenic CFTR-knockout kits that expressed ferret CFTR specifically in the intestine. One clone passed feces normally and demonstrated no detectable ferret CFTR expression in the lung or liver. The animals described in this study are likely to be useful tools for dissecting CF disease pathogenesis and developing treatments.
Managing impotence in diabetes. Two drugs are better than one.
Authors: C G Eden, J F Bellringer, P G Carter, J P Pryor, C Coker
Journal: BMJ (1993)

Two drugs are better than one EDITOR,-We disagree with some of D E Price's views on managing erectile dysfunction in diabetes.'The erectile dysfunction is not always organic in origin since psychogenic factors based on anxiety are as common in diabetic patients as in the general population.A total lack of erections under all circumstances, including during sleep and on waking, may indeed be due to neurogenic impotence, but patients with this are a minority.Patients more commonly complain of a partial erection during sexual activity, which suggests a vasculogenic rather than a neurogenic cause.Intracavernous injection of a vasoactive agent is a simple means of distinguishing vasculogenic from psychogenic and neurogenic impotence.More sophisticated investigations are rarely neces- sary except to investigate the possibility of occult neurological problems or of arterial disease worth treating surgically-that is, in young non-smoking men under 40 who do not have diabetes or hypertension.The use of intracavernous agents for erectile dysfunction has indeed revolutionised the management of this problem, but, at least in theory, papaverine should not now be used alone because of the occurrence of penile fibrosis and priapism.The incidence of these complications is diminished by the addition of phentolamine, but prostaglandin E1 is safer, although a suitable formulation for general use is not yet available.
Ultrasound assessment of diaphragmatic movement.
Authors: G Drummond
Journal: Thorax (1994)

Letters to the Editor other three dimensions.We believe that a gap of one day between both measurements is justifiable to obtain test-retest reliability of the CRQ in this particular group of patients.Perhaps the most fundamental mis- understanding is that our research was fo- cused on the prediction of a specific criterion (criterion validity) based on the scores of the CRQ.In our research we investigated the validity of the four dimensions of the CRQ by relating these dimensions to comparable dimensions of the SCL-90.Thus, the prin- cipal focus was not on the prediction of a criterion (according to Mrs Jones, the scores of the SCL-90), but on the ability of the CRQ to measure the four dimensions.From a methodological point of view it should be noted that the scores on the CRQ are based on psychological properties of individuals.As a consequence it is often impossible to find a single satisfactory real world criterion avail- able for the evaluation of its validity.The SCL-90 can never serve as such a naturally occurring criterion.Content validity and con- struct validity are powerful tools to establish our understanding ofwhat dimensions ofspe- cific measurement instruments intend to measure, and that was, indeed, the core issue of our research.
Accessing the Internet is far from easy
Authors: T J David
Journal: BMJ (1996)

EDITOR,—According to Andrew Millman and colleagues, “accessing the Internet is very easy,”1 but tales of woe in articles and correspondence in British magazines devoted to the Internet tell another story. Who is telling the truth?

My attempts to get dial up connection to the first Internet service provider I tried took several weeks because of an almost complete lack of advice, difficult …
A possible survival advantage in adults with acute leukemia receiving ABO‐identical platelet transfusions
Authors: Joanna Mary Heal, Naomi Kenmotsu, Jacob M. Rowe, Neil Blumberg
Journal: American Journal of Hematology (1994)

Abstract In a small cohort of leukemic patients participating in a randomized trial of ABO‐identical vs. ABO‐unmatched platelet transfusions, a statistically significant decrease in remission duration and increase in mortality were observed in patients receiving ABO‐unmatched platelet transfusions. This difference was unexplained by previously described prognostic factors for remission duration and survival. Further study of this association is warranted. © 1994 Wiley‐Liss, Inc.
'Home Is the Sailor'
Authors: Alvan G. Foraker
Journal: JAMA (1982)

World War II is said to have been the last "popular" war, whose veterans returned to warm welcome, lavish government aid, and open job opportunities. This may be so, but let me tell you about my reception by the resident staff of a certain university hospital. I was 23 years old when I received my MD degree from a Midwest medical school in June 1939, and the world was my oyster. I vowed to spend the next seven years in graduate medical training, research, and education. I would not try to make a dime, just be self-supporting and studious. I wanted to do biochemical research in internal medicine, but this was flexible. With such a program I planned to astound the world with my brilliance and success—beginning at age 30. In early 1940, during the latter part of a rotating internship at a nonuniversity hospital, I began to feel the
TUBERCULINS AND THEIR USE.
Authors: E. A. DE SCHWEINITZ
Journal: JAMA (1900)

During the past years two different preparations have been used under the name "tuberculin" for the treatment of tuberculosis. They have been distinguished by the names "old tuberculin" and "T. R." As they are not the same in their composition, a word or two in regard to the methods of their preparation may be in place. The old tuberculin is prepared by using a culture-medium containing beef broth, salt, peptone and 5 to 7 per cent. glycerin. The sterilized medium is inoculated with the tubercle bacilli and the cultures then allowed to grow in the thermostat for several weeks, until the germs are well developed. When the development of the germ has advanced sufficiently the flasks containing the well-grown cultures are placed in the sterilizing oven and heated for about one-half hour at a temperature of 120 C. They are then removed from the oven, the contents of each flask
Pathological basis of orthopaedic and rheumatic disease: N A Athanasou. (Pp385, pound95.) London: Edward Arnold, 2001. ISBN 0-3407-6382-5
Authors: C A Seemayer
Journal: Annals of the Rheumatic Diseases (2002)

The author provides an overview of the pathology of orthopaedic and rheumatic diseases which could help pathologists in finding the correct diagnosis and also support clinicians and rheumatic disease oriented researchers in obtaining information about a broad range of distinct pathological disorders.

There are eight chapters starting with skeletal structure development and progressing to injuries, infections, disorders of the skeletal …
Doctors should discuss advance care planning with dying patients and those with chronic illness, RCP says
Authors: C. Dyer
Journal: BMJ (2009)

Advance care planning should be offered as part of routine clinical practice to patients with long term conditions and those receiving care at the end of life, says guidance from the Royal College of Physicians and eight other professional and patients’ groups.

Efforts to promote greater choice and autonomy for patients are at the core of current healthcare policy but can be difficult to achieve if individuals lose the capacity to make decisions about treatment, the guidance points out.

A review of the literature shows that 60% to 90% of people support advance care planning, although only 8% of people in England and Wales have completed any form …
Postoperative Management of Diabetes Mellitus: Steady-State Glucose Control With Bedside Algorithm for Insulin Adjustment
Authors: Nelson B Watts, Suzanne S P Gebhart, Richard V Clark, Lawrence S Phillips
Journal: Diabetes Care (1987)

An algorithm was developed to determine whether an individualized insulin infusion could maintain plasma glucose in a desirable steady state after surgery. In 24 patients, insulin was provided according to a “glucose-feedback” formula to maintain plasma glucose between 120 and 180 mg/dl (6.7–10.0 mM). Initial plasma glucose was elevated, 218 ± 16 mg/dl (mean ± SE 12.1 ± 0.9 mM), but reached the target range after 8 h and remained steady for the rest of the study period. Insulin requirements varied considerably, 0.5–5.0 U/h. Infusion rates were correlated with initial plasma glucose but not with previous insulin dose, HbAlc, or percent ideal body weight. Although insulin needs cannot be predicted, plasma glucose can be maintained in a desirable range after surgery via a simple formula suitable for implementation by general ward nurses.
A Common B-Cell Precursor in Composite Lymphomas
Authors: Katrin Kerl, Christophe Girardet, Bettina Borisch
Journal: New England Journal of Medicine (1999)

To the Editor: Brauninger et al. (April 22 issue)1 identified a common germinal-center B-cell precursor for both Reed–Sternberg cells and non-Hodgkin's lymphoma cells in two patients with composite...
Work Speed as a Measure of an Equivalent Exercise Stress in Subjects of Different Weights
Authors: B. VAN LINGEN, P. D. SEAWARD, W. A. ODENDAAL, I. M. Kennedy
Journal: Circulation (1965)

The use of work speed, as opposed to work load, as a predictive variable for heart rate during steady state submaximal exercise, increased the correlation and decreased the standard error of the prediction around the regression line. In addition, the relationship of pulse rate and work speed was shown to be independent of body weight, while the relationship of pulse rate and work load was influenced by the body weight. The establishment of a submaximal exercise test, which would be an equivalent physiologic stress in subjects of different weights, would require that they perform exercise at a similar work speed rather than at a constant work load. Such recommendations, in addition, are at variance with those previously made in regard to subjecting individuals of different weights to an equivalent exercise stress.
A novel combination therapy with histone deacetylase inhibitor and Aurora kinase inhibitor for “triple negative” breast cancers.
Authors: T Samuel, W Fiskus, C Buser, K Bhalla
Journal: Cancer Research (2009)

Abstract Abstract #401 Background: Aurora A and B are essential for normal mitosis. Aurora A (AA) is amplified and/or co-overexpressed with Aurora B (AB) in over 50% of breast cancers, including the basaloid variety, “Triple Negative” breast cancers. MK-0457 (M) is a pan-Aurora kinase inhibitor that inhibits in vitro and in vivo tumor growth, as well as induces apoptosis of cancer cells. Aurora kinases are chaperoned by hsp90, and their down regulation is known to sensitize transformed cells to paclitaxel. Vorinostat (V) is a pan-histone deacetylase inhibitor (HA-HDI) that induces in vitro growth arrest, differentiation and apoptosis of human breast cancer cells. By inhibiting HDAC6 and inducing hyper-acetylation and inhibition of hsp90, V depletes the levels of hsp90 chaperoned proteins, including AA and AB kinase. Methods: AA amplification in MB-231 (“Triple Negative”) and BT-474 (HER-2 amplified) cells were determined by FISH and array-CGH. The cells were treated with M (50 to 250 nM) and/or V (0.5 to 2.0 μM) for 24 to 48 hours. Cell cycle status, DNA endoreduplication (PI staining) and apoptosis (Annexin V/PI staining) were determined by flow cytometry. Intracellular protein levels of p-AA or p-AB, AA and AB, p-survivin, survivin, were determined by immunoblot analyses. Results: Treatment with M or V induces cell cycle G2/M phase accumulation and apoptosis of the breast cancer cells. Dose-dependently, treatment with M depleted phosphorylated (p)-AA, -survivin, and -Ser10 H3 levels. V induced hsp90 acetylation and depleted the levels of AA, AB and survivin. Both M and V induced formation of multi-polar aberrant mitotic spindles. Co-treatment with M and V mediated more depletion of p-survivin, AA and AB levels, as well as synergistically induced apoptosis of MB-231 and BT-474 cells. In the orthotopic MB-231 xenograft breast cancer model, co-treatment with M and V caused significantly more tumor growth delay, lung metastases and survival than treatment with either agent alone. Treatment with V induced in vivo hsp90 hyper-acetylation in the mouse xenografts, as well as in the accessible tumors from patients with breast cancer. This was determined by immunoblot analysis of post-treatment versus pre-treatment tumors with the anti-acetylated-K69-hsp90 antibody, which was developed for these studies. Hsp90 hyper-acetylation was associated with in vivo depletion of AA and AB levels in the mouse xenografts. Co-treatment with M and V, versus treatment with either M or V, also led to greater in vivo attenuation of AA, AB and p-survivin. Conclusion: These studies support the rationale to evaluate the safety and efficacy of the combination of M and V, without or with paclitaxel, against breast cancers with AA amplification and/or overexpression. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 401.
Identification of a Novel HIP1-ALK Fusion Variant in Non–Small-Cell Lung Cancer (NSCLC) and Discovery of ALK I1171 (I1171N/S) Mutations in Two ALK-Rearranged NSCLC Patients with Resistance to Alectinib
Authors: Sai-Hong Ignatius Ou, Samuel J. Klempner, Joel R. Greenbowe, Michele Azada, Alexa B. Schrock, Siraj M. Ali, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller
Journal: Journal of Thoracic Oncology (2014)
A Randomised Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy (IMRT) for Early Breast Cancer: Interim Results at 2 Years Follow-Up.
Authors: C. Coles, G. Barnett, J. Wilkinson, A. Moody, C. Wilson, N. Twyman, A. Hoole, N. Burnet, G. Wishart
Journal: Cancer Research (2009)

Abstract Background: This large single centre trial was designed to investigate whether correction of dose inhomogeneities using IMRT reduces late toxicity and improves quality of life in patients with early breast cancer. We report interim results at 2 years follow-up.Materials and Methods: Standard tangential breast radiotherapy plans of 1145 trial patients were assessed for dose inhomogeneity as defined by ICRU recommendations. Patients with inhomogeneous plans were randomised to either IMRT or standard radiotherapy. Patients with homogenous plans were treated with standard radiotherapy, but were followed up within the trial as per randomised patients. The primary endpoint of the trial was photographic assessment of breast shrinkage. Secondary endpoints included photographic assessment of final cosmesis, clinical assessment of toxicity, and patient-reported symptoms and quality of life. All endpoints were scored using validated assessment methods. Data were collected on potential confounding factors which included: age at randomisation, smoking history, body mass index, co-morbidity such as diabetes mellitus, cardiovascular and peripheral vascular disease, use of hormones and/or chemotherapy, treated breast volume, and presence or absence of breast boost.Results: 330/1145 (29%) of patients had adequate dosimetry with standard 2D radiotherapy and were not randomised. In the 815 randomised patients, dosimetry was significantly improved in the interventional (IMRT) arm compared to the control. Currently, data from 632 randoimsed patients who have reached 2 years of follow up have been analysed. This interim analysis demonstrates that the incidence of telangiectasia in the control arm was significantly greater than in the interventional group (P = 0.024). Pre-radiotherapy surgical cosmesis significantly affected photographic assessment of final cosmesis, and clinical assessment of breast shrinkage and induration (P &amp;lt; 0.0001). In randomised patients who had good surgical cosmesis, there was a significant difference improvement in final cosmesis with the use of IMRT (P = 0.038). The quality of life data has not been analysed at this stage.Discussion: This trial shows that the use of forward-planned IMRT can significantly improve dose homogeneity, and suggests that this translates into improvements in late toxicity at only 2 years from completion of radiotherapy. Surgical cosmesis appears to be a very important determinant of overall final cosmesis after 2 years of follow-up, and may mask any beneficial effects of IMRT at this early stage. It is highly likely that these trial patients will have not expressed their final level of toxicity at 2 years post-radiotherapy, and re-analysis is planned at 5 years from completion of radiotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 71.
Shock: The Reversible Stage of Dying
Authors: Richard W. Carlson
Journal: JAMA (1989)

Dr Hardaway is a suitable choice to organize a treatise on circulatory shock. The editor is a distinguished senior investigator and clinician who has made many contributions to this field. He was previously the commanding officer at the William Beaumont General Hospital and presently serves as professor of surgery at Texas Tech University School of Medicine. For the present project Dr Hardaway has assembled a multidisciplinary group of contributors who might constitute a "Who's Who" of researchers and clinicians involved in shock. This is appropriate, as Hardaway points out that the understanding and treatment of shock involve practically every type of physician and that the clinical condition is nearly universal as a prelude to death. It is fitting, therefore, that the goal of the book is to assemble a summary of the combined knowledge of shock that includes clinical and experimental research and to present this information with the hope
Adenine nucleotide release from isolated perfused guinea pig hearts and extracellular formation of adenosine.
Authors: M M Borst, J Schrader
Journal: Circulation Research (1991)

The quantification of adenine nucleotides released from the heart is hampered by their rapid dephosphorylation to adenosine in the extracellular space catalyzed by highly active ectonucleotidases. To determine the total release of adenine nucleotides from isolated Langendorff-perfused guinea pig hearts, ecto 5'-nucleotidase was effectively blocked by infusion of alpha, beta-methylene-ADP (AOPCP, 50 microM). Adenine nucleotides were measured in the coronary venous effluent by the luciferin-luciferase method after enzymatic rephosphorylation to ATP. In hearts perfused at a constant flow rate (10 ml/min) with normoxic buffer (95% O2, 5% CO2) the release +/- SEM of adenine nucleotides and adenosine was 0.06 +/- 0.01 (n = 11) and 0.04 +/- 0.01 (n = 13) nmol/min. In the presence of AOPCP, the release of adenine nucleotides increased to 0.43 +/- 0.04 nmol/min (n = 9; p less than 0.05), whereas adenosine remained unchanged. Hypoxic perfusion (10% O2, 85% N2, 5% CO2) caused a threefold increase in adenine nucleotide release but a 40-fold increase in adenosine. In contrast, global ischemia (30 seconds) caused adenine nucleotide and adenosine release to rise to similar values of 1.06 +/- 0.10 and 0.80 +/- 0.14 nmol/min (n = 9). Stimulation of hearts with isoproterenol (4 nM) likewise increased the release of adenine nucleotides (0.50 +/- 0.04 nmol/min) and adenosine (0.87 +/- 0.21 nmol/min) (n = 6). To determine the cellular source of adenine nucleotides released from the heart, the coronary endothelial adenine nucleotide pool was selectively prelabeled by [3H]adenosine. Global ischemia increased the specific radioactivity of released adenine nucleotides by 57%. The findings indicate that 1) adenine nucleotides and adenosine are released at the same order of magnitude from the well-oxygenated heart; 2) beta-adrenergic stimulation and ischemia stimulate the release of adenine nucleotides and adenosine, both purines reaching vasoactive concentrations in the effluent perfusate; 3) during hypoxic perfusion only the release of adenosine is greatly enhanced; and 4) the coronary endothelium preferentially contributes to the ischemia-induced adenine nucleotide release.