tbuckley/cabot-search huggingface dataset:
Hypertension: Value of Treatment
Authors: Hugh H. Hussey
Journal: JAMA (1974)

This year, 1974, will be remembered for many events, among them the resignation of a President under threat of impeachment, continuing inflation, and military activities that imperiled world peace. Worries in the House of Medicine included such things as HMOs, PSROs, and National Health Insurance. On the scientific side, perhaps 1974 will be remembered as the year of high blood pressure, because the medical profession fully recognized that many hypertensive persons are unaware of their affliction and must be sought out by every means possible and brought to treatment. The reasons for that attitude derived principally from the facts that in recent decades effective chemotherapy for hypertension had been developed and that such treatment forestalled the appearance of serious complications. For example, the Veterans Administration Cooperative Study Group on Antihypertensive Agents, under the chairmanship of Edward D. Freis, MD, had demonstrated the value of treatment in male hypertensive patients whose
Systemic gas embolism complicating pulmonary contusion. Diagnosis and management using transesophageal echocardiography.
Authors: M Saada, J P Goarin, B Riou, J J Rouby, Y Jacquens, R Guesde, P Viars
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Systemic air embolism has been frequently reported after penetrating thoracic trauma. In blunt thoracic trauma, systemic air embolism has been rarely diagnosed, and then only after an invasive procedure such as thoracotomy. Transesophageal echocardiography has been recently introduced for the early assessment of trauma patients and is considered a sensitive noninvasive procedure to diagnose air embolism. We report three cases of systemic air embolism in patients with pulmonary contusion secondary to a blunt thoracic trauma requiring controlled ventilation. Transesophageal echocardiography was performed for evaluation of hemodynamic instability, and it showed air bubbles in the left atrium and left ventricle during the insufflation phase, which disappeared during apnea. A decrease in airway pressure (release of PEEP, low tidal volume, high frequency jet ventilation) significantly reduced the systemic air embolism. We concluded that systemic air embolism can occur after blunt thoracic trauma, and transesophageal echocardiography enables a rapid and accurate diagnosis that may be useful for therapeutic management.
Relief of Cancer Pain by Surgical and Nerve Blocking Procedures
Authors: Donlin M. Long
Journal: JAMA (1980)

WHILE virtually any cancer is capable of causing pain, those that most frequently require pain therapy are the invasive head and neck cancers, carcinoma of the lung, carcinoma of the breast, carcinoma of the pancreas, colorectal cancer, and carcinoma of the cervix. When making a decision about cancer pain therapy, it is important to recognize the phase of the disease, estimate the patient's longevity, and make an accurate diagnosis concerning the cause of the pain. The aphorism that pain in a cancer patient is due to the tumor until proved otherwise is undoubtedly true, but other causes of pain do exist and must be carefully separated from the pain of the cancer itself, for the therapies may be extremely different. As a general rule, destructive procedures should not be used in the early phases of cancer pain, for the primary therapy offers the best chance of pain relief. During an
Modeling the Residential Infiltration of Outdoor PM<sub>2.5</sub>in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)
Authors: Ryan W. Allen, Sara D. Adar, Ed Avol, Martin Cohen, Cynthia L. Curl, Timothy Larson, L.-J. Sally Liu, Lianne Sheppard, Joel D. Kaufman
Journal: Environmental Health Perspectives (2012)

Background: Epidemiologic studies of fine particulate matter [aerodynamic diameter ≤ 2.5 μm (PM2.5)] typically use outdoor concentrations as exposure surrogates. Failure to account for variation in residential infiltration efficiencies (Finf) will affect epidemiologic study results.Objective: We aimed to develop models to predict Finf for > 6,000 homes in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a prospective cohort study of PM2.5 exposure, subclinical cardiovascular disease, and clinical outcomes.Methods: We collected 526 two-week, paired indoor–outdoor PM2.5 filter samples from a subset of study homes. PM2.5 elemental composition was measured by X-ray fluorescence, and Finf was estimated as the indoor/outdoor sulfur ratio. We regressed Finf on meteorologic variables and questionnaire-based predictors in season-specific models. Models were evaluated using the R2 and root mean square error (RMSE) from a 10-fold cross-validation.Results: The mean ± SD Finf across all communities and seasons was 0.62 ± 0.21, and community-specific means ranged from 0.47 ± 0.15 in Winston-Salem, North Carolina, to 0.82 ± 0.14 in New York, New York. Finf was generally greater during the warm (> 18°C) season. Central air conditioning (AC) use, frequency of AC use, and window opening frequency were the most important predictors during the warm season; outdoor temperature and forced-air heat were the best cold-season predictors. The models predicted 60% of the variance in 2-week Finf, with an RMSE of 0.13.Conclusions: We developed intuitive models that can predict Finf using easily obtained variables. Using these models, MESA Air will be the first large epidemiologic study to incorporate variation in residential Finf into an exposure assessment.
A TRANSFUSION REACTION FOLLOWING THE USE OF UNIVERSAL BLOOD
Authors: Niels C. Klendshoj
Journal: JAMA (1942)

It is difficult to evaluate the frequency and severity of reactions ascribable to the presence of isoantibodies in universal blood (O blood). Minor reactions may occur frequently while severe and fatal reactions with demonstrable hemolysis or agglutination are relatively rare. The statistical approach to the problem is obviously difficult. However, the literature contains a number of reports some of which state observations only during and following reactions while others include detailed laboratory data necessary for a study of the factors involved. Without attempting to review the literature completely, we shall cite some papers pertaining to the question of the high titered donor. Levine and Mabee<sup>1</sup>and Freeman and Whitehouse<sup>2</sup>on the basis of their "in vitro" studies cautioned against the use of "dangerous" universal blood. Wildegans<sup>3</sup>discussed the universal donor and referred to several specific accidents. An extensive analysis of reactions to transfusions of group O blood
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation
Authors: Chang-Jun Li, Peng Cheng, Meng-Ke Liang, Yu-Si Chen, Qiong Lu, Jin-Yu Wang, Zhu-Ying Xia, Hou-De Zhou, Xu Cao, Hui Xie, Er-Yuan Liao, Xiang-Hang Luo
Journal: Journal of Clinical Investigation (2015)

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.
Reiter's Syndrome
Authors: Charles W. Denko
Journal: JAMA (1963)

Serious complications occur so rarely in Reiter's disease that they are frequently overlooked. A detailed clinicopathological study of a fatal case revealed generalized multi-systemic changes with concomitant abnormal laboratory findings. Cytotoxic degenerative changes were noted in affected organs such as lymph nodes. Death was due to necrosis of gastric mucosa and massive gastric hemorrhage. Colonies of pleomorphic organisms were found in the gastric tissue removed ante mortem. Such changes are thought compatible with hypersensitivity.
Postextrasystolic Ventricular Pressure Responses
Authors: W. BECK, E. CHESLER, V. SCHRIRE
Journal: Circulation (1971)

The peak postextrasystolic ventricular pressure was examined in tracings obtained during routine catheterization of the right and left ventricles in 252 cases. The invariable response in the apparently "normal" left ventricle was a fall or no change in peak systolic pressure, whereas in the obstructed left ventricle, the failed left ventricle, the severely volume-overloaded left ventricle, and in mitral stenosis the more usual pattern was a rise in postextrasystolic ventricular pressure. On the right side the usual response both in the normal and abnormal was a rise in postextrasystolic pressures. Significant exceptions were found when the right ventricle ejected against the aortic impedance and in constrictive pericarditis. In the intact circulation the outflow impedance and its rate of decline during the compensatory pause would appear to be the major determinant of the postextrasystolic pressure response. There is some evidence that alterations in the extent and time course of ventricular filling may be a factor, but the effects of variations in the degree of postextrasystolic potentiation based on variations in the prematurity of the extrasystole, which can so easily be demonstrated under controlled conditions, appear to be largely obscured except when fixed outflow obstruction is present. The only practical value of this observation may be the ability to recognize an "abnormal" left ventricle when the postextrasystolic beat shows a higher peak ventricular pressure and to recognize a right ventricle in free communication with the aorta when the peak right ventricular postextrasystolic pressure fails to rise. Conversely, a lower peak left ventricular systolic pressure following a premature beat should not be misinterpreted as being due to a failure of postextrasystolic potentiation and augmentation, as it is in fact a normal phenomenon.
Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study
Authors: Mitchell M. Levy, Andrew Rhodes, Gary S. Phillips, Sean R. Townsend, Christa A. Schorr, Richard Beale, Tiffany Osborn, Stanley Lemeshow, Jean-Daniel Chiche, Antonio Artigas, R. Phillip Dellinger
Journal: Intensive Care Medicine (2014)
Serum Cholinesterase Inhibition in Relation to Paraoxonase-1 (PON1) Status among Organophosphate-Exposed Agricultural Pesticide Handlers
Authors: Jonathan N. Hofmann, Matthew C. Keifer, Clement E. Furlong, Anneclaire J. De Roos, Federico M. Farin, Richard A. Fenske, Gerald van Belle, Harvey Checkoway
Journal: Environmental Health Perspectives (2009)

Animal studies have demonstrated that low paraoxonase-1 (PON1) status (i.e., low catalytic efficiency and/or low plasma PON1 activity) is associated with neurotoxic effects after exposure to several organophosphate (OP) insecticides. However, few human studies have investigated associations between PON1 status and intermediate end points, such as serum cholinesterase [butyrylcholinesterase (BuChE)] inhibition, among OP-exposed individuals.
US judge rules that patents on breast cancer genes are unlawful
Authors: C. Dyer
Journal: BMJ (2010)

A United States federal judge in New York has overturned US patents covering genes linked to breast and ovarian cancer, in a decision that has rocked the biotech industry.

US district judge Robert Sweet held that claims in seven patents on BRCA1 and BRCA2 held by the biotech firm Myriad Genetics and the University of Utah were invalid because the genes are products of nature, which cannot be patented.

The lawsuit challenging the patents was filed by the American Civil Liberties Union with the Public Patent Foundation at Benjamin …
Nursing Homes and Fax Machines-Reply
Authors: Eric G. Tangalos, Phyllis I. Freeman
Journal: JAMA (1990)

<h3>In Reply.—</h3> We are happy to respond to Dr Patrick's question on confidentiality. This concern was also a major factor in our initial inquiries. Our fax machine is located in the geriatric nurse practitioner's office, which is the hub of nursing home activities. Each nursing home telephone number is programmed into the machine and given its own autodial button and label. Each nursing home name is also keyboard entered at the time of programming. When a nursing home is called using the autodial feature, a visual display confirms where the call is being sent. The only numbers entered into our machine are those of the local nursing homes. We have on occasion pressed the wrong button and sent an order to the wrong nursing home, but given the configuration of our system, we have never called for a pizza or an attorney. Because of the manner in which medication
Abstract 4749: New benzazepine BET-inhibitors with improved oral bioavailability
Authors: Norbert Schmees, Bernard Haendler, Pascale Lejeune, Antje Stresemann, Roland Neuhaus, Stephan Siegel, Amaury Ernesto Fernandez-Montalvan, Hilmar Weinmann, Volker Gekeler
Journal: Cancer Research (2014)

Abstract Bromodomain protein 4 (BRD4), a member of the bromodomain and extra-terminal domain (BET) protein family, binds to acetylated histone tails via its two bromodomains BD1 and BD2. It forms a complex with the positive transcription elongation factor b which controls phosphorylation of RNA polymerase II, ultimately leading to stimulation of transcription elongation. An essential role of BRD4 in cell proliferation and cancer growth has been reported in several recent studies. The benzodiazepine JQ-1 is a strong antagonist of the binding of BRD4 to acetylated histone tails and has been used to elucidate the functions of the BET protein family members. JQ-1 is active in vivo in several therapeutic models but reveals a poor pharmacokinetic profile with high clearance and low oral bioavailability in animal studies. We investigated the benzodiazepine core of JQ-1 with the aim of optimization of oral bioavailability. Several possible core variations were identified that kept overall cellular activity but increased metabolic stability. The benzazepine BAY6356 was selected as a potent BET inhibitor with an improved overall pharmacokinetic profile and oral bioavailability between 60 and 100% in mouse, rat and dog. The strong antiproliferative activity observed in vitro in acute myeloid leukemia (AML) and multiple myeloma (MM) cell lines was confirmed in vivo in the MOLM-13 (AML) and MOLP-8 (MM) tumor models implanted in SCID mice. Daily oral treatment at the Maximal Tolerated Dose of 30 mg/kg led to strong tumor reduction in MOLM-13 (17% T/C on day 13 post tumor implantation) and in MOLP-8 (4% T/C on day 19 post tumor implantation) xenografts (T/C≤ 40% = active, T/C≤10% = highly active, according to NCI criteria). In the MOLM-13 model, c-Myc down-regulation was shown in vivo. Furthermore, for a same total dose, intermittent dosing every other day or twice a week in the MOLP-8 model proved to be as active as daily dosing, demonstrating exposure-driven efficacy. These favorable preclinical data support the evaluation of BAY6356 for further development. Citation Format: Norbert Schmees, Bernard Haendler, Pascale Lejeune, Antje Stresemann, Roland Neuhaus, Stephan Siegel, Amaury Ernesto Fernandez-Montalvan, Hilmar Weinmann, Volker Gekeler. New benzazepine BET-inhibitors with improved oral bioavailability. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4749. doi:10.1158/1538-7445.AM2014-4749
Wheat allergy: A double-blind, placebo-controlled study in adults
Authors: Joseph Scibilia, Elide A. Pastorello, Giuliana Zisa, Anna Ottolenghi, Carsten Bindslev-Jensen, Valerio Pravettoni, Elena Scovena, Anna Robino, Claudio Ortolani
Journal: Journal of Allergy and Clinical Immunology (2006)
Mechanisms of Resistance to Beta-lactam Antibiotics in Strains of Staphylococcus aureus
Authors: L. D. SABATH
Journal: Annals of Internal Medicine (1982)

There are three major mechanisms of resistance of Staphylococcus aureus to beta-lactam antibiotics: enzyme mediated (penicillinase or beta-lactamase) by which the antibiotic is inactivated; intrinsic, which is not due to drug inactivation, and accounts for methicillin-resistance; and tolerance, in which there is a dissociation of the inhibitory and killing actions of beta-lactam antibiotics. In enzyme-mediated resistance, there are at least three different staphylococcal beta-lactamases, which probably account for differences in the inoculum effect with different cephalosporins. The intrinsic resistance is associated with differences in the affinity of beta-lactams for penicillin-binding proteins, but intrinsic resistance is probably more complex, because the pH of the medium, chelating agents, visible light, and temperature also effect its expression. Tolerance is clearly due to decreased autolytic enzyme activity (reflecting persistance of an enzyme inhibitor) of those tolerant organisms that need 32 (or more) times as much antibiotic for a bactericidal effect as for simple inhibition.
Pathology of Partnerships. All partnership are brittle.
Authors: D Metcalfe
Journal: BMJ (1982)

Background: Inactivation of the tumour suppressor gene SMAD4 is a genetically late event in gastrointestinal carcinogenesis. SMAD4 is a transmitter of growth-inhibitory effects of transforming growth factor-β (TGF-β), an important tumour promoter capable of inducing an epithelial to mesenchymal transition (EMT). The role of SMAD proteins in late, tumour-promoting effects of TGF-β is not well understood. Materials and Methods: The change of molecular differentiation markers typical for EMT upon SMAD4 re-expression in SW480 cells was determined using Western blotting, immunohistochemistry and confocal laser microscopy. The influence of SMAD4 on the migration of SW480 cells was assessed in wound healing and pore migration assays. Results: SMAD4 suppresses invasiveness and mediates reversion of SW480 cells from a mesenchymal-like to a polarized epithelial phenotype, with features of enterocyte-like differentiation. Moreover, SMAD4 reconstitution was associated with down-regulation of endogenous TGF-β cytokines, suggesting that autocrine TGF-β signaling may be involved in the EMT. Conclusion: These results provide further evidence for a role of SMAD4 as a regulator of invasion, a process of prime importance in carcinogenesis but hitherto poorly understood in molecular terms.
Treating severe malaria
Authors: Christopher J M Whitty, Evelyn Ansah, Hugh Reyburn
Journal: BMJ (2005)

Treating severe malariaRectal artemether may be as good as intravenous quinine E very year over a million children die of malaria in Africa.In many settings, especially rural ones, most fatalities due to malaria occur outside hospital, although a substantial proportion of these children will have made contact with some level of healthcare in their final illness. 1 Of those who arrive at hospital, many are moribund and up to half of malaria deaths in hospitals occur within 24 hours of admission. 2Buying time by being able to start effective treatment for those with severe malaria in the community therefore has the potential to save many lives.Conventional treatment for severe malaria in Africa is intravenous or intramuscular quinine.Providing parenteral treatment with quinine in the community is usually impractical and potentially hazardous.Even in hospitals, staff are often overstretched and have some difficulty managing intravenous quinine safely.In this issue Aceng et al report a randomised trial of intravenous quinine compared with rectal artemether in cerebral malaria. 3They found that the effects of intravenous quinine and rectal artemether were comparable, both in terms of efficacy and time to recover.The rectal artemether group had a non-significant survival advantage.These are encouraging results.As Aceng et al acknowledge, a single trial of this size cannot alone be the basis for policy change.The current study would only be able to detect a relatively large mortality difference.The mortality in the quinine group was also on the high side compared with some other studies.5][6] Rectal quinine could potentially be used in a similar way.A Cochrane review found no clear evidence of difference in outcome between rectal and parenteral quinine, although it noted that most trials are small and confidence intervals around outcomes in the meta-analysis are wide. 7se of an artemisinin suppository rather than nothing for cases of suspected severe malaria as they are referred to hospital seems to be justified, and further convincing evidence of effectiveness will probably not become available as few would consider it ethical on current evidence to compare this to placebo.Community health workers and traditional healers can be trained to recognise symptoms of cerebral malaria and to administer suppositories.It would be possible to incorporate rectal antimalarial treatment while sick
Lessons learned in developing community mental health care in North America
Authors: ROBERT E. DRAKE, ERIC LATIMER
Journal: World Psychiatry (2012)

This paper summarizes the findings for North America of the WPA Task Force on Steps, Obstacles and Mistakes to Avoid in the Implementation of Community Mental Health Care. Community mental health has evolved over five decades in the United States and Canada. The United States has led the world in innovation and spending, but provide variable quality of care; Canada has steadily developed a more uniform public health system for less cost. Lessons learned from North America include: team-based approaches and other evidence-based practices, when implemented with high fidelity, can improve outcomes in routine mental health care settings; recovery ideology and peer support enhance care, though they have not been studied rigorously; effective community-based care for people with serious mental disorders is expensive.