tbuckley/cabot-search huggingface dataset:
Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.
Authors: M S Visner, C E Arentzen, D G Parrish, E V Larson, M J O'Connor, A J Crumbley, R J Bache, R W Anderson
Journal: Circulation (1985)

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparative metabolism of chloroacetamide herbicides and selected metabolites in human and rat liver microsomes.
Authors: S Coleman, R Linderman, E Hodgson, R L Rose
Journal: Environmental Health Perspectives (2000)

Acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methyl-phenyl)-acetamide], alachlor [N-(methoxymethyl)-2-chloro-N-(2, 6-diethyl-phenyl)acetamide], butachlor [N-(butoxymethyl)-2-chloro-N-(2,6-diethyl-phenyl)acetamide], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide] are pre-emergent herbicides used in the production of agricultural crops. These herbicides are carcinogenic in rats: acetochlor and alachlor cause tumors in the nasal turbinates, butachlor causes stomach tumors, and metolachlor causes liver tumors. It has been suggested that the carcinogenicity of these compounds involves a complex metabolic activation pathway leading to a DNA-reactive dialkylbenzoquinone imine. Important intermediates in this pathway are 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) produced from alachlor and butachlor and 2-chloro-N-(2-methyl-6-ethylphenyl)acetamide (CMEPA) produced from acetochlor and metolachlor. Subsequent metabolism of CDEPA and CMEPA produces 2,6-diethylaniline (DEA) and 2-methyl-6-ethylaniline (MEA), which are bioactivated through para-hydroxylation and subsequent oxidation to the proposed carcinogenic product dialkylbenzoquinone imine. The current study extends our earlier studies with alachlor and demonstrates that rat liver microsomes metabolize acetochlor and metolachlor to CMEPA (0.065 nmol/min/mg and 0.0133 nmol/min/mg, respectively), whereas human liver microsomes can metabolize only acetochlor to CMEPA (0.023 nmol/min/mg). Butachlor is metabolized to CDEPA to a much greater extent by rat liver microsomes (0.045 nmol/min/mg) than by human liver microsomes (< 0.001 nmol/min/mg). We have determined that both rat and human livers metabolize both CMEPA to MEA (0.308 nmol/min/mg and 0.541 nmol/min/mg, respectively) and CDEPA to DEA (0.350 nmol/min/mg and 0.841 nmol/min/mg, respectively). We have shown that both rat and human liver microsomes metabolize MEA (0.035 nmol/min/mg and 0.069 nmol/min/mg, respectively) and DEA (0.041 nmol/min/mg and 0.040 nmol/min/mg, respectively). We have also shown that the cytochrome P450 isoforms responsible for human metabolism of acetochlor, butachlor, and metolachlor are CYP3A4 and CYP2B6.
Use of antibiotics in suspected haemolytic-uraemic syndrome
Authors: Bob Phillips, Kay Tyerman, Simon M Whiteley
Journal: BMJ (2005)

An 11 year old girl was admitted to our specialist paediatric intensive care unit under the joint care of paediatric intensivists and nephrologists. She had presented to her local hospital with a four day history of vomiting, diarrhoea, and becoming progressively more unwell. Initial blood tests showed acute renal failure and thrombocytopenia. We tentatively diagnosed haemolytic uraemic syndrome, although sepsis with renal dysfunction was part of the differential. These uncertainties arose because her blood film was not typical of haemolytic uraemic syndrome, she had a clotting abnormality, and we had no microbiological confirmation. Treatment with broad spectrum antibiotics was proposed. Some doubt remained about this treatment, however, because of a well publicised study suggesting that giving antibiotics to patients with Escherichia coli 0157:H7 enteritis could worsen haemolytic uraemic syndrome. We used a five step evidence based approach to address this problem.

The first step in our approach was to formulate an answerable clinical question: In children with suspected haemolytic uraemic syndrome, particularly associated with E coli 0157:H7 infection, does treatment with antibiotics lead to increased morbidity, particularly progressive haemolytic uraemic syndrome …
THE CONDITION OF THE DENTINE IN PULPLESS TEETH.Read in the Section of Oral and Dental Surgery, at the Forty-third Annual Meeting of the American Medical Association, held at Detroit, Mich., June, 1892.
Authors: W. C. BARRETT
Journal: JAMA (1893)

I had promised the Secretary of this Section that I would prepare and read a paper at this meeting upon the "Condition of the Dentine in Pulpless Teeth." It was a subject upon which I had bestowed some thought, but with the literature of which I had not made myself thoroughly acquainted. I had read Prof. Miller's work on "The Microörganisms of the Human Mouth," and his communications to the various journals, notably<i>The Dental Cosmos</i>, but not with this special subject in mind. I had not collocated his writings on this theme, and hence had not collated them. When this had been done, I was astonished at the thorough manner in which the ground had been covered. Had I examined my subject earlier, I should not have attempted an excursion in the field, but having engaged to present this paper, I will endeavor to redeem my promise, premising that
Phase I Study of Lapatinib in Combination With Chemoradiation in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Kevin J. Harrington, Iman A. El-Hariry, Clare S. Holford, Antoine Lusinchi, Christopher M. Nutting, Dominique Rosine, Mary Tanay, Eric Deutsch, Jennifer Matthews, Consuelo D'Ambrosio, Simon J. Turner, Jagannatha S. Pandeshwara, Jean Bourhis
Journal: Journal of Clinical Oncology (2009)

This study (EGF100262) sought to establish the recommended phase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).Patients were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500 mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100 mg/m(2) on days 1, 22, and 43 of radiotherapy. End points included safety/tolerability and clinical activity.Thirty-one patients were enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one patient in the 500-mg cohort and transient elevation of liver enzymes in one patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort. Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drug-related symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. The overall response rate was 81% (65% at the recommended phase II dose).The recommended phase II dose is lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy have been initiated.
Pathophysiology of Spironolactone-Induced Gynecomastia
Authors: LESLIE I. ROSE
Journal: Annals of Internal Medicine (1977)

Peripheral blood levels of testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone and the metabolic clearance rates of testosterone and estradiol, as well as the peripheral conversion of testosterone into estradiol, were measured in 16 patients with hypertension. Six of these patients were treated with spironolactone and developed gynecomastia. The other 10 patients served as control subjects. The blood testosterone level in the spironolactone-treated group (2.7 ± 0.5 ng/ml) was significantly less (P < 0.02) than in the control group (4.4 ± 0.4 ng/ml). On the other hand, blood estradiol levels in the spironolactone group (30 ± 4 pg/ml) were significantly greater (P < 0.01) than in the control group (13 ± 2 pg/ml). These changes were primarily due to significant increases in the metabolic clearance rate of testosterone (P < 0.02) and in the rate of peripheral conversion of testosterone into estradiol (P < 0.001) in the spironolactone-treated group. Thus, spironolactone does alter the peripheral metabolism of testosterone resulting in changes in the ratio of testosterone to estradiol, which could contribute to the production of gynecomastia.
Science and Technology in Medicine: An Illustrated Account Based on Ninety-Nine Landmark Publications from Five Centuries
Authors: Arpan K Banerjee
Journal: BMJ (2006)

S electing a list of 99 of the most significant discoveries of the past 500 years from the vast medical literature is no easy task. Gesner, the author of the pioneering Bibliotheca Universalis (1554-5), classified and listed the 12 000 works known at that time. Today, there are many millions of citations in Index Medicus, and on PubMed and the internet. A collection like this is often more memorable for its exclusions rather than inclusions and, to an extent, Andras Gedeon's choice is a …
<i>HLA-B*13:01</i>and the Dapsone Hypersensitivity Syndrome
Authors: F.-R. Zhang, H. Liu, A. Irwanto, X.-A. Fu, Y. Li, G.-Q. Yu, Y.-X. Yu, M.-F. Chen, H.-Q. Low, J.-H. Li, F.-F. Bao, J.-N. Foo, J.-X. Bei, X.-M. Jia, J. Liu, H. Liany, N. Wang, G.-Y. Niu, Z.-Z. Wang, B.-Q. Shi, H.-Q. Tian, H.-X. Liu, S.-S. Ma, Y. Zhou, J.-B. You, Q. Yang, C. Wang, T.-S. Chu, D.-C. Liu, X.-L. Yu, Y.-H. Sun, Y. Ning, Z.-H. Wei, S.-L. Chen, X.-C. Chen, Z.-X. Zhang, Y.-X. Liu, S.L. Pulit, W.-B. Wu, Z.-Y. Zheng, R.-D. Yang, H. Long, Z.-S. Liu, J.-Q. Wang, M. Li, L.-H. Zhang, H. Wang, L.-M. Wang, P. Xiao, J.-L. Li, Z.-M. Huang, J.-X. Huang, Z. Li, J. Liu, L. Xiong, J. Yang, X.-D. Wang, D.-B. Yu, X.-M. Lu, G.-Z. Zhou, L.-B. Yan, J.-P. Shen, G.-C. Zhang, Y.-X. Zeng, P.I.W. de Bakker, S.-M. Chen, J.-J. Liu
Journal: New England Journal of Medicine (2013)

Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli.
Authors: O Levy, C E Ooi, J Weiss, R I Lehrer, P Elsbach
Journal: Journal of Clinical Investigation (1994)

Affinity purification of crude acid extracts of rabbit polymorphonuclear leukocytes using Escherichia coli (J5) as adsorbent yields the bactericidal/permeability-increasing protein (BPI), two 15-kD species (p15s), and the two most potent (cationic) defensin species (neutrophil peptides [NP] -1 and -2). Tested in buffered isotonic medium, the relative antibacterial potency of these proteins against E. coli J5 is BPI (IC50 0.2 nM) > p15A (10 nM) > NP -1 (400 nM). Sublethal doses of p15A or NP-1 can synergize with BPI to decrease the dose required to inhibit the growth of E. coli by up to 50-fold. BPI and p15A display similar features of antibacterial action distinct from defensin NP-1, but NP-1 acts synergistically only with BPI and not with p15A. All aspects of the combined action of BPI and NP-1 resemble those observed with higher concentrations of BPI alone, implying that NP-1 enhances BPI potency. Neither NP-1 nor p15A alter the amount of BPI binding to E. coli but BPI enhances binding of p15A to E. coli, raising the possibility that synergy between these two proteins may occur at least partially at the level of binding. The potent synergistic actions of these proteins can also be demonstrated against serum-resistant clinical isolates of encapsulated E. coli tested in whole blood and plasma ex vivo, suggesting that such combined action may contribute to host defense in vivo.
Effects of fish oil supplementation in rheumatoid arthritis.
Authors: H van der Tempel, J E Tulleken, P C Limburg, F A Muskiet, M H van Rijswijk
Journal: Annals of the Rheumatic Diseases (1990)

Sixteen patients with rheumatoid arthritis entered a trial to determine the clinical and biochemical effects of dietary supplementation with fractionated fish oil fatty acids. A randomised, double blind, placebo controlled crossover design with 12 week treatment periods was used. Treatment with non-steroidal anti-inflammatory drugs and with disease modifying drugs was continued throughout the study. Placebo consisted of fractionated coconut oil. The following results favoured fish oil rather than placebo: joint swelling index and duration of early morning stiffness. Other clinical indices improved but did not reach statistical significance. During fish oil supplementation relative amounts of eicosapentaenoic acid and docosahexaenoic acid in the plasma cholesterol ester and neutrophil membrane phospholipid fractions increased, mainly at the expense of the omega-6 fatty acids. The mean neutrophil leucotriene B4 production in vitro showed a reduction after 12 weeks of fish oil supplementation. Leucotriene B5 production, which could not be detected either in the control or in the placebo period, rose to substantial quantities during fish oil treatment. This study shows that dietary fish oil supplementation is effective in suppressing clinical symptoms of rheumatoid arthritis.
Gene Transfer into Baboon Repopulating Cells: A Comparison of Flt-3 Ligand and Megakaryocyte Growth and Development Factor versus IL-3 during ex Vivo Transduction
Authors: Peter Kurre, Julia Morris, Peter A. Horn, Michael A. Harkey, Robert G. Andrews, Hans-Peter Kiem
Journal: Molecular Therapy (2001)

Oncoretroviral vectors require division of target cells for successful transduction. In the case of hematopoietic repopulating cells this can be achieved by cytokine stimulation using growth factor combinations which facilitate gene transfer and maintain engraftment. Interleukin-3 (IL-3) has been widely used in growth factor combinations, although more recent data in the mouse showed reduced engraftment in the presence of IL-3. Here, we used a competitive repopulation assay to study the influence of IL-3 and the early acting cytokines megakaryocyte growth and development factor (MGDF) and Flt3-ligand (Flt3-L) on gene transfer efficiency during ex vivo transduction of hematopoietic repopulating cells. In a direct comparison, baboon CD34-enriched cells were transduced on CH-296 fibronectin fragment in the presence of either IL-6, stem cell factor (SCF), Flt3-L, and MGDF or IL-3, IL-6, and SCF. Animals were followed for up to 55 weeks, and analysis of peripheral blood leukocytes by semiquantitative polymerase chain reaction showed that both cytokine combinations achieved marking of repopulating cells. A trend toward increased gene marking, especially early after transplant (P = 0.06), was seen with the combination of IL-6, SCF, Flt3-L, and MGDF. However, the highest gene marking was achieved when IL-3 was combined with early acting cytokines, suggesting that the difference observed in this study was probably due to the addition of MGDF and Flt3-L and not due to a negative effect of IL-3 on engraftment.
GM-CSF along with IL-4 but not alone is indispensable for the differentiation of human dendritic cells from monocytes
Authors: Sahana Holla, Meenu Sharma, Janakiraman Vani, Srini V. Kaveri, Kithiganahalli N. Balaji, Jagadeesh Bayry
Journal: Journal of Allergy and Clinical Immunology (2014)
Cancer's Molecular Sweet Tooth and the Warburg Effect
Authors: Jung-whan Kim, Chi V. Dang
Journal: Cancer Research (2006)

Abstract More than 80 years ago, the renowned biochemist Otto Warburg described how cancer cells avidly consume glucose and produce lactic acid under aerobic conditions. Recent studies arguing that cancer cells benefit from this phenomenon, termed the Warburg effect, have renewed discussions about its exact role as cause, correlate, or facilitator of cancer. Molecular advances in this area may reveal tactics to exploit the cancer cell's “sweet tooth” for cancer therapy. (Cancer Res 2006; 66(18): 8927-30)
Unnecessary Prescribing of NSAIDs and the Management of NSAID-Related Gastropathy in Medical Practice
Authors: Robyn Tamblyn
Journal: Annals of Internal Medicine (1997)

Background: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for hospitalization and death from gastrointestinal bleeding and perforation. Objectives: To 1) estimate the extent to which NSAIDs are prescribed unnecessarily and NSAID-related side effects are inaccurately diagnosed and inappropriately managed and 2) identify the physician and visit characteristics associated with suboptimal use of NSAIDs. Design: Prospective cohort study. Setting: Montreal, Canada. Participants: 112 physicians representing academically affiliated general practitioners, community-based general practitioners, and residents in family medicine and internal medicine. Interventions: Blinded, office-based assessment of the management of two clinical cases (chronic hip pain due to early osteoarthritis and NSAID-related gastropathy) using elderly standardized patients. Measurements: Quality of drug management and potential predictors of suboptimal drug management. Results: Unnecessary prescriptions for NSAIDs or other drugs were written during 41.7% of visits. Gastropathy related to NSAID use was correctly diagnosed in 93.4% of visits and was acceptably managed in 77.4% of visits. The risk for an unnecessary NSAID prescription was greater when the contraindications to NSAID therapy were incompletely assessed (odds ratio, 2.3 [95% CI, 1.0 to 5.2]) and when the case was managed by residents in internal medicine (odds ratio, 4.1 [CI, 1.2 to 14.7]). The risk for suboptimal management of NSAID-related side effects was increased by incorrect diagnosis (odds ratio, 16.6 [CI, 3.6 to 76.5]) and shorter visits. Conclusions: Unnecessary NSAID prescribing and suboptimal management of NSAID-related side effects were sufficiently common to raise questions about the appropriateness of NSAID use in the general population. If these results reflect current practice, prescribing patterns may contribute to avoidable gastrointestinal morbidity in elderly persons.
Controlled trial of propranolol to prevent recurrent variceal bleeding in patients with non-cirrhotic portal fibrosis.
Authors: C. F. Kiire
Journal: BMJ (1989)

Fifty patients with non-cirrhotic portal fibrosis who were admitted to hospital because of upper gastrointestinal bleeding were randomly assigned to treatment with either oral propranolol given in doses that reduced the resting pulse rate by 25% (25 patients) or with a placebo (25 patients). One year after the start of the study 20 patients in the propranolol group and five patients in the placebo group were free from recurrent gastrointestinal bleeding (p less than 0.0001). Giving continuous oral propranolol treatment is therefore effective in preventing recurrent upper gastrointestinal bleeding in patients with non-cirrhotic portal fibrosis.