tbuckley/cabot-search huggingface dataset:
The advantages and limitations of an in vivo test system for investigating the cytotoxicity and fibrogenicity of fibrous dusts.
Authors: S E Sykes, A Morgan, S R Moores, W Davison, J Beck, A Holmes
Journal: Environmental Health Perspectives (1983)

The acute response of the rat lung to a range of fibrous materials has been investigated by bronchopulmonary lavage, at dose levels of 0.5 and 1.0 mg, 1 and 7 days after their administration by intratracheal instillation. The materials chosen for study included UICC chrysotile A, amosite, crocidolite and anthophyllite, and samples of S. African "long" amosite and glass fiber. In addition, the subacute response to 1, 2 and 3 mg of chrysotile and amosite has been studied at 50 and 100 days after instillation. In the acute phase at 1 day after instillation, the response to chrysotile was greater than that to any of the other materials, but by 7 days there was no gradation in the response to different dusts. In the subacute phase, cell recoveries were low, and it was not possible to assess the long-term cytotoxic or fibrogenic effects of amosite and chrysotile by analyses of lung washes, even though biochemical and histological methods indicated gross changes in lung pathology.
Anthony William Inglis Hall
Authors: Philippa Hall
Journal: BMJ (2004)

General practitioner who helped put harm reduction on the map of British drugs policy Tom Waller was a campaigning general practitioner who worked ceaselessly for a better deal for people with alcohol and drug problems.In his calm, determined, and persistent way he helped put harm reduction on the map of British drugs policy from the mid-1980s onwards.When harm reduction fell from the policy agenda in the late 1990s he vigorously worked to alert civil servants and ministers to the dangers of ignoring drug related harms, especially HIV and hepatitis C infection.He worked as a London general practitioner from 1973 to 1988, with a stint as GP trainer and tutor at London medical schools and then lecturer in general practice at University College Hospital/Middlesex Medical Schools.His initiation into problems of drug use came when he was the first medical adviser to the City Road crisis hostel for drug users in London (1978-83).The experience led to the first publication for GPs on treating drug users, Drug Addiction and Poly-drug Abuse: The Role of the GP.He joined the Ministerial Advisory Council on the Misuse of Drugs (ACMD) in 1983.He served on the ACMD working group whose 1988 report AIDS and Drug Misuse was the blueprint for the UK response to injecting related HIV infection.The insights in that document, including the view that "HIV is a greater threat to public health than drug misuse," helped support pragmatic public health oriented harm reduction interventions, including syringe exchange and methadone prescribing.These interventions subsequently kept the HIV rate among drug injectors in the United Kingdom at an extremely low level.
Tension and Coronary Attacks
Authors: Henry I. Russek
Journal: JAMA (1963)

<h3>To the Editor:</h3> —Reference is made to the digest of an article which appeared under the heading "Tensions of Modern Living Not Responsible for Physician Coronaries, Cardiologists Claim" (<i>JAMA</i><b>182:</b>Adv p 30 [Dec 15] 1962.) This title does not accurately reflect the content of the various statements made by the eight prominent cardiologists interviewed. Morever, the comments of some of these authorities either had little or nothing to do with the question of the etiological significance of emotional stress in coronary disease or left the reader in doubt as to the personal views held on the subject. If the stress of modern living is considered unimportant in the pathogenesis of coronary atherosclerosis and its complications, one may reasonably question the respective recommendations of these cardiologists: (1) "to regulate our lives in defiance of the demands placed upon us"; (2) "to take a nap after lunch"; (3) to apply "the
US students face national examination on simulated patients
Authors: S. Gottlieb
Journal: BMJ (2002)

A test of clinical skills that only graduates of foreign medical schools seeking US medical licences have been required to pass may be expanded to include graduates of US medical schools as well.

But US medical schools are objecting that the test, required for non-US students since 1998, costs too much and would impose an unfair burden on medical students.

The test involves actors pretending to be ill and is given to foreign students who have passed the first two steps of the three part national medical licensing examination, which all medical …
Abstract 4918: Predicting the effect of drug combination schedules on xenograft growth using the Virtual Tumor
Authors: David Orrell, Eric Fernandez, Damien Cronier, Lawrence M. Gelbert, David A. Fell, Dinesh De Alwis, Christophe Chassagnole
Journal: Cancer Research (2011)

Abstract Since the early 1960s, drug combination therapy has been used to treat cancer, because of the limited number of malignancies that could respond to single-agent chemotherapy. Combination chemotherapy regimens have been designed on the basis of mechanism of action of the drugs, tumor cell specificity, balance between effectiveness and toxicity, and synergy between drugs. But when multiple drugs, combination schedules, sequences and doses are considered, the number of possibilities increases combinatorically, and can not be realistically tested either clinically or in animal models. We have developed a “Virtual Tumor” model to aid with the design of optimal drug schedules. The model combines disparate data, at the cell and tumor level, into a consistent picture, and leverages them to make testable predictions about tumor response. Thousands of simulations can be performed if necessary to find the best treatment regime. We present here a validation study of our Virtual Tumor. We predicted xenograft growth of two anti-cancer drug combinations using experimental data collected from single drug exposure uniquely. We accurately predicted the xenograft course for two different regimens – one simultaneous and one sequential – of the two drugs, which were compared with experimental results in a single-blind test. We show how a computational approach helps explain how multiple drug exposure and correct sequence leads to synergy, and how it can be used to subsequently design optimal schedule and combination treatments. 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 4918. doi:10.1158/1538-7445.AM2011-4918
Cardiorespiratory Fitness and the Progression of Carotid Atherosclerosis in Middle-Aged Men
Authors: Timo A. Lakka, Jari A. Laukkanen, Rainer Rauramaa, Riitta Salonen, Hanna-Maaria Lakka, George A. Kaplan, Jukka T. Salonen
Journal: Annals of Internal Medicine (2001)

Background: Good cardiorespiratory fitness has been associated with reduced risk for clinical events of atherosclerotic vascular diseases, but whether it is related to slower progression of early atherosclerosis is unclear. Objective: To study the association between cardiorespiratory fitness and the progression of early carotid atherosclerosis. Design: 4-year follow-up study. Setting: Eastern Finland. Participants: Population-based sample of 854 men 42 to 60 years of age. Measurements: Maximal oxygen uptake (Vo 2 max [mL/kg per minute]) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Carotid atherosclerosis was assessed by using B-mode ultrasonography. Results: After adjustments for age, technical covariates, and cigarette smoking, Vo 2 max had strong, inverse, and graded associations with 4-year increases in maximal intima–media thickness (IMT) (standardized regression coefficient β = −0.120; P = 0.002), plaque height (β = −0.140; P < 0.001), surface roughness (β = −0.147; P < 0.001), and mean IMT (β = −0.080; P = 0.035). These associations weakened but remained statistically significant after additional adjustment for systolic blood pressure, serum levels of apolipoprotein B, diabetes, and plasma fibrinogen levels. The increases in maximal IMT, surface roughness, and mean IMT (23%, 31%, and 100%, respectively) were larger among men in the lowest quartile of Vo 2 max (<26.1 mL/kg per minute) than among those in the highest quartile (>36.2 mL/kg per minute). Conclusions: Good cardiorespiratory fitness is associated with slower progression of early atherosclerosis in middle-aged men. These findings are important because they emphasize that middle-aged men can be evaluated for cardiorespiratory fitness to estimate their future risk for atherosclerotic vascular diseases. Additional research is warranted to investigate a possible causal relationship between cardiorespiratory fitness and atherosclerosis.
Fatal Opportunistic Fungus Disease
Authors: Gerald F. Parkhurst
Journal: JAMA (1967)

Fatal disseminated mycotic disease has been seen with increasing frequency since the introduction of steroid and cytotoxic drugs, medications that apparently interfere with the immunologic defenses of the host. These mycoses are most often associated with malignant tumors, especially leukemia and lymphoma. Of 14 significant fungus infections found at autopsy, Phycomycetes was found in six. Thrombosis and infarction caused by the fungus were seen in multiple organs, most commonly in the lungs, heart, and kidney, and were a major contributory cause of death.
Predictors of Extensively Drug-Resistant Pulmonary Tuberculosis
Authors: Kai Kliiman
Journal: Annals of Internal Medicine (2009)

Background: About 40 000 cases of extensively drug-resistant tuberculosis emerge worldwide annually, but the predictors of extensive drug resistance are unclear. Objective: To identify risk factors for extensively drug-resistant tuberculosis and multidrug-resistant but non–extensively drug-resistant tuberculosis in patients with culture-confirmed pulmonary tuberculosis. Design: Cross-sectional, countrywide study. Setting: Estonia, a country with 1 of the world's highest rates of extensively drug-resistant and multidrug-resistant tuberculosis. Patients: All patients with culture-confirmed pulmonary tuberculosis with clinical or radiologic evidence of active disease detected from January 2003 to December 2005. Measurements: Risk determinants from patients' demographic characteristics, socioeconomic variables, and tuberculosis-related data or HIV status. Results: Of 1163 patients, 60 (5.2%) had extensively drug-resistant tuberculosis and 196 (16.9%) had multidrug-resistant but non–extensively drug-resistant tuberculosis. Previous antituberculosis treatment (adjusted odds ratio [OR], 10.54 [95% CI, 5.97 to 18.62]), HIV infection (OR, 3.12 [CI, 1.31 to 7.41]), homelessness (OR, 2.73 [CI, 1.15 to 6.48]), and alcohol abuse (OR, 1.98 [CI, 1.08 to 3.64]) increased risk for extensive drug resistance. Previous treatment (OR, 4.11 [CI, 2.77 to 6.08]) and age 24 years or younger (OR, 2.57 [CI, 1.09 to 6.06]), 25 to 44 years (OR, 2.64 [CI, 1.35 to 5.16]), and 45 to 64 years (OR, 2.06 [CI, 1.06 to 3.99]) were determinants of multidrug resistance. In patients age 24 years or younger, female sex (OR, 6.23 [CI, 1.02 to 37.99]) and birth outside of Estonia (OR, 82.04 [CI, 3.46 to 1945.47]) increased risk for multidrug resistance. Limitation: Patients' comorbid conditions and drug abuse history were not incorporated into analyses because of inconsistent source data. Conclusion: Previous treatment is a common risk factor for extensively drug-resistant and multidrug-resistant tuberculosis. Reducing relapses; screening persons younger than 65 years and immigrants; and combating against HIV infection, alcoholism, and homelessness are key issues for decreasing the spread of highly drug-resistant tuberculosis. Primary Funding Source: Estonian Health Insurance Fund.
Cardiolipin Remodeling by ALCAT1 Links Oxidative Stress and Mitochondrial Dysfunction to Obesity
Authors: Jia Li, Caroline Romestaing, Xianlin Han, Yuan Li, Xinbao Hao, Yinyuan Wu, Chao Sun, Xiaolei Liu, Leonard S. Jefferson, Jingwei Xiong, Kathryn F. LaNoue, Zhijie Chang, Christopher J. Lynch, Huayan Wang, Yuguang Shi
Journal: Cell Metabolism (2010)
OPERATIVE TREATMENT OF THE FAUCIAL TONSILSWITH A VIEW TO THE PREVENTION OF CERVICAL ADENITIS.
Authors: ROBERT C. MYLES
Journal: JAMA (1904)

The recognition of the interdependence of the tonsils and pathologic conditions in other, sometimes remotely situated parts of the body, represents one of the important advances in medicine during recent decades. A variety of diseases have been traced to a primary involvement of the tonsils, and among them are rheumatism, septic infection, tuberculosis, and in a recent report<sup>1</sup>appendicitis and infectious jaundice. The anatomic structure of the tonsil predisposes to the entrance of the bacilli, for the covering epithelium is always porous, owing to the constant migration of leucocytes, and may be absent over small areas. Microbes usually invade the tonsils through the crypts, which constitute good hiding places and breeding spots. The enlargement and the surface irregularities associated with chronic hypertrophy greatly favor infection, and the resistance of the tissues under these conditions is diminished by the accompanying catarrh and the loosening and casting off of the epithelium. The
110. Investigation of Biochemical Factors That May Influence Immunogencity of AAV2 Vectors
Authors: Bernd Hauck, Federico Mingozzi, Valder Arruda, Katherine A. High, J. Fraser Wright
Journal: Molecular Therapy (2006)

Top of pageAbstract
Recombinant AAV2 expressing human coagulation factor IX has been demonstrated to efficiently transduce human hepatocytes leading to expression of therapeutic levels of human factor IX in a human subject. However a T cell response directed to the AAV2 capsid was reported that resulted in elimination of transduced cells (Manno et al, Nat. Med. 2006). In order to better understand determinants of immunogenicity, we report here preliminary assessment of biochemical features that may influence vector immunogenicity. We tested whether purposely induced vector aggregation or oxidation could lead to increased immune responses in a mouse model. To induce aggregation, a common concentrated stock (E14 particles / mL) of highly purified, non aggregated AAV2 empty capsids in PBS was subjected to conditions of reduced ionic strength (60min) followed by readjustment to physiological ionic strength. A control sample was adjusted to the same final volume and concentration by addition of PBS only. To induce oxidation, capsid was treated with 1|[mu]|M Cu2+ (60min). Modified and control capsid preparations were administered via portal vein injecftion to C57/BL6 mice previouly immunized with AAV2 empty capsids. Assessment of anti-AAV2 IgG antibody titers post administration showed no significant difference between mice receiving control, aggregated or oxidized vector. Similarly T lymphocytes isolated from spleens of animals in each group did not secrete IFNgamma in response to AAV2 capsid-derived peptides as assessed by ELISPOT and intracellular cytokine staining.

A third biochemical feature that we begun to investigate is structure and provenance of the nucleic acids packaged by AAV vectors. The bacterial plasmid DNA used as a template for the transgene cassette in AAV vectors produced using transient transfection may be incorporated into vector particles. If so, a subpopulation of vector particles would be predicted to contain pathogen associated molecular patterns such as non-methylated CpG motifs. We looked for evidence of packaging of bacterial DNA by AAV2 by producing AAV2 vectors (GFP) by transient transfection using a vector plasmid prepared using the thymidine analogue BrdU. The resulting vector was purified and fractionated by CsCl gradient ultracentrifugation, and fractions were tested for transduction on HEK293 cells. We observed the major (expected) vector band at approx 1.39 g/mL, and a minor higher density band at approx. 1.44 g/mL. These data support that a subpopulation of AAV2 vectors produced using transient transfection contains bacterial plasmid DNA, which may contribute to activation of innate immune responses following in vivo administration. In vivo testing is required to further assess this parameter.
Direct In Vivo Visualization of Intravascular Destruction of Microbubbles by Ultrasound and its Local Effects on Tissue
Authors: Danny M. Skyba, Richard J. Price, Andre Z. Linka, Thomas C. Skalak, Sanjiv Kaul
Journal: Circulation (1998)

Background —Our aim was to observe ultrasound-induced intravascular microbubble destruction in vivo and to characterize any resultant bioeffects. Methods and Results —Intravital microscopy was used to visualize the spinotrapezius muscle in 15 rats during ultrasound delivery. Microbubble destruction during ultrasound exposure caused rupture of ≤7-μm microvessels (mostly capillaries) and the production of nonviable cells in adjacent tissue. The number of microvessels ruptured and cells damaged correlated linearly ( P &lt;0.001) with the amount of ultrasound energy delivered. Conclusions —Microbubbles can be destroyed by ultrasound, resulting in a bioeffect that could be used for local drug delivery, angiogenesis, and vascular remodeling, or for tumor destruction.
Christian Science and the Care of Children
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1983)

Physicians have long been concerned about the Christian Science view of human illness and its implications for the treatment of the sick. In focusing on the belief that disease "is in the last analysis produced by a radically limited and distorted view of the true spiritual nature and capacities of men and women" (see below), it seems to ignore remediable physical factors and rely almost entirely on the putative healing powers of prayer.Although no experienced clinician would doubt that religious faith can help in the therapeutic process, few would want their devout patients denied the assistance of medical and . . .
Prevalence of Celiac Disease among Children in Finland
Authors: Markku Mäki, Kirsi Mustalahti, Jorma Kokkonen, Petri Kulmala, Mila Haapalahti, Tuomo Karttunen, Jorma Ilonen, Kaija Laurila, Ingrid Dahlbom, Tony Hansson, Peter Höpfl, Mikael Knip
Journal: New England Journal of Medicine (2003)

Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that positive findings correlate with specific HLA haplotypes.
Trial shows azithromycin is no better than vitamin C for bronchitis
Authors: R. Dobson
Journal: BMJ (2002)

An antibiotic commonly prescribed for acute bronchitis is no better than low doses of vitamin C, according to new research.

A double blind, randomised controlled trial has concluded that azithromycin is ineffective and should not be prescribed for acute bronchitis.

A report of the research ( Lancet 2002;359:1648-54) says that every year in the United States some 10 million adults seek treatment for acute bronchitis …
CD69 expression on eosinophils is a marker of activation in the lung following allergen provocation*1
Authors: H. Wang, S.I. Ochkur, M.P. McGarry, K.R. O'Neill, D.C. Colbert, S.A. Cormier, N.A. Lee, H.H. Shen, J.J. Lee
Journal: Journal of Allergy and Clinical Immunology (2004)
Evidence of a Critical Period of Airway Instability during Central Apneas in Preterm Infants
Authors: ROBERT P. LEMKE, NNANAKE IDIONG, SAAD AL-SAEDI, KIM KWIATKOWSKI, DON B. CATES, HENRIQUE RIGATTO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The timing and magnitude of airway narrowing in central apneas is unknown. We have developed a method of apnea classification that relies on the transmission of cardiac airflow oscillation to indicate airway patency. Using a theoretical model, we showed that the amplitude of the cardiac airflow oscillation is proportional to airway diameter for small lumens. While in the majority of central apneas the amplitude of the cardiac airflow oscillation remains nearly constant, in a subset of events the waveform decreases with time, suggesting airway narrowing. We hypothesized that this is not a random occurrence but reflects a critical period of airway instability during central apnea. To test this hypothesis we studied 41 preterm infants. Of 4,456 central apneas, 585 had a decrease in the amplitude of the cardiac oscillation. The amplitude of the cardiac airflow oscillation during an apnea was recorded to provide a dynamic measure of changes in airway diameter with time. To allow for comparisons between patients the amplitude of each cardiac airflow oscillation was expressed as a proportion of the maximum amplitude observed in each infant. We then compared the amplitude at multiple successive 0.5 s intervals with the amplitude of the cardiac airflow oscillation observed at the apnea outset using ANOVA. We found a significant decrease in cardiac airflow oscillation after only 1 s irrespective of the apnea duration (3 to 16 s). We conclude that airway narrowing during central apnea is not a random occurrence but appears shortly after the onset of the apnea. We speculate that the phenomenon is secondary to passive airway relaxation.
The juvenile variant of papular-purpuric gloves and socks syndrome and its association with viral infections
Authors: M.Y. Hsieh, P.H. Huang
Journal: British Journal of Dermatology (2004)

Papular-purpuric gloves and socks syndrome (PPGSS) occurs mostly in adults and has been shown to be related to several possible viral infections. However, childhood-onset PPGSS seems to be not so rare as previously thought in our clinical experience.To survey the general characteristics of childhood-onset PPGSS and to determine the possible association between this juvenile variant of PPGSS and various viral infections.Thirty-three children with erythematopurpuric papular eruptions on the hands and/or feet were enrolled. Detailed history-taking and physical examination were performed on all of them. Blood samples were obtained from 25 patients about 1-5 weeks after the appearance of cutaneous eruptions to check complete blood counts, differential white blood cell counts, and IgM and IgG antibodies to parvovirus B19, cytomegalovirus (CMV), viral capsid antigen of Epstein-Barr virus (EBV) and measles.The median age of these 33 patients was 23 months. The mean duration of the skin eruption was 4.8 weeks (SD 2.7, 95% CI 3.9-5.0). Lymphocytosis was present in 13 patients (52%) while mild eosinophilia occurred in only three patients (12%). Five patients (20%) were positive for IgM antibodies against CMV and seven (28%) were positive for IgM antibodies against EBV. Only one patient (4%) was detected to have IgM antibodies against parvovirus B19.Childhood-onset PPGSS shows somewhat different clinical features from the adult type. It may represent a nonspecific manifestation of several viral infections, including CMV, EBV and parvovirus B19 infections.
Bridge to Life — Cardiac Mechanical Support
Authors: Kenneth L Baughman, John A Jarcho
Journal: New England Journal of Medicine (2007)

Even with well-managed care, many patients with severe heart failure reach a stage at which medical therapy is insufficient to sustain an acceptable level of cardiac function. It is estimated that 0.2% of persons over 45 years of age in the United States, or nearly 200,000 people, may fit this description.1 Since only approximately 2000 donor hearts are available in the United States each year for transplantation, the need for another approach to cardiac replacement is well established.Investigators and the medical-device industry have been pursuing the development of mechanical cardiac support for more than four decades. The earliest forms . . .