tbuckley/cabot-search huggingface dataset:
Increased Susceptibility to Skin Carcinogenesis in TREX2 Knockout Mice
Authors: David Parra, Joan Manils, Bàrbara Castellana, Arnau Viña-Vilaseca, Eva Morán-Salvador, Nuria Vázquez-Villoldo, Gemma Tarancón, Miquel Borràs, Sara Sancho, Carmen Benito, Sagrario Ortega, Concepció Soler
Journal: Cancer Research (2009)

TREX2 is a proofreading 3'-5' exonuclease that can be involved in genome maintenance; however, its biological role remains undefined. To better understand the function and physiologic relevance of TREX2, we generated mice deficient in TREX2 by targeted disruption of its unique coding exon. The knockout mice are viable and do not show relevant differences in growth, survival, lymphocyte development, or spontaneous tumor incidence compared with their wild-type counterparts over a period of up to 2 years. Also, we did not observe chromosomal instability or defects in cell proliferation and cell cycle upon loss of TREX2. We have observed that TREX2 expression is not ubiquitous, being expressed preferentially in tissues with stratified squamous epithelia, such as the skin or esophagus, and specifically in keratinocytes. Interestingly, TREX2-null mice are more susceptible to skin carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) compared with wild-type mice. This phenotype correlates with a reduction of DMBA-induced apoptosis in both the epidermis and keratinocytes of TREX2-null mice. Altogether, our results suggest a tumor suppressor role for TREX2 in skin carcinogenesis through which it contributes to keratinocyte apoptosis under conditions of genotoxic stress.
Host Failure in Treatment of Malaria with Sulfalene and Pyrimethamine
Authors: GORDON M. TRENHOLME
Journal: Annals of Internal Medicine (1975)

An individual infected with a multidrug-resistant strain of Plasmodium falciparum failed to respond to treatment with sulfalene and pyrimethamine. Subinoculation studies showed that parasite resistance to the drug combination was not present. Plasma levels of sulfalene and pyrimethamine in this individual were similar to those of three individuals, subinoculated from him, who were cured by the drug combination. Erythrocyte levels of sulfalene in this individual were similar to those in an individual, subinoculated from him, who was cured by the drug combination. After treatment with the drug combination, in-vitro tests showed similar antimalarial activity in the serum of this individual in comparison with the serum of an individual subinoculated from him. The failure of this individual to respond to treatment with sulfalene and pyrimethamine is attributed to an undefined host factor (or factors) that appear(s) to be present in his erythrocytes.
Association of Hospital Spending Intensity With Mortality and Readmission Rates in Ontario Hospitals
Authors: Therese A. Stukel, Elliott S. Fisher, David A. Alter, Astrid Guttmann, Dennis T. Ko, Kinwah Fung, Walter P. Wodchis, Nancy N. Baxter, Craig C. Earle, Douglas S. Lee
Journal: JAMA (2012)

The extent to which better spending produces higher-quality care and better patient outcomes in a universal health care system with selective access to medical technology is unknown.To assess whether acute care patients admitted to higher-spending hospitals have lower mortality and readmissions.The study population comprised adults (>18 years) in Ontario, Canada, with a first admission for acute myocardial infarction (AMI) (n = 179,139), congestive heart failure (CHF) (n = 92,377), hip fracture (n = 90,046), or colon cancer (n = 26,195) during 1998-2008, with follow-up to 1 year. The exposure measure was the index hospital's end-of-life expenditure index for hospital, physician, and emergency department services.The primary outcomes were 30-day and 1-year mortality and readmissions and major cardiac events (readmissions for AMI, angina, CHF, or death) for AMI and CHF.Patients' baseline health status was similar across hospital expenditure groups. Patients admitted to hospitals in the highest- vs lowest-spending intensity terciles had lower rates of all adverse outcomes. In the highest- vs lowest-spending hospitals, respectively, the age- and sex-adjusted 30-day mortality rate was 12.7% vs 12.8% for AMI, 10.2% vs 12.4% for CHF, 7.7% vs 9.7% for hip fracture, and 3.3% vs 3.9% for CHF; fully adjusted relative 30-day mortality rates were 0.93 (95% CI, 0.89-0.98) for AMI, 0.81 (95% CI, 0.76-0.86) for CHF, 0.74 (95% CI, 0.68-0.80) for hip fracture, and 0.78 (95% CI, 0.66-0.91) for colon cancer. Results for 1-year mortality, readmissions, and major cardiac events were similar. Higher-spending hospitals had higher nursing staff ratios, and their patients received more inpatient medical specialist visits, interventional (AMI cohort) and medical (AMI and CHF cohorts) cardiac therapies, preoperative specialty care (colon cancer cohort), and postdischarge collaborative care with a cardiologist and primary care physician (AMI and CHF cohorts).Among Ontario hospitals, higher spending intensity was associated with lower mortality, readmissions, and cardiac event rates.
Ambient sulfate aerosol deposition in man: modeling the influence of hygroscopicity.
Authors: T B Martonen, A E Barnett, F J Miller
Journal: Environmental Health Perspectives (1985)

Atmospheric sulfate aerosols [H2SO4, (NH4)2SO4, and NH4HSO4] are of international concern because of their global prevalence and potential irritant or toxic effects on humans. To assess hazards following inhalation exposure, the total dose delivered to the human respiratory tract and its regional distribution must be determined. The mass median aerodynamic diameter of the inhaled aerosol will influence the sites of deposition in the respiratory tract. Atmospheric sulfate aerosols are hygroscopic and will have changing particle sizes and densities as they absorb water vapor in the humid environment of the human respiratory tract. Experimental and theoretical data that describe particle size as a function of temperature and relative humidity were used in computer subroutines of an aerosol deposition model in order to calculate the dose dispersion of H2SO4, (NH4)2SO4, and NH4HSO4 aerosols in man. Different temperature and relative humidity environments that approximately correspond to nasal and oral breathing were studied. The predicted deposition patterns are very different from those of nonhygroscopic aerosols with identical inhaled mass median aerodynamic diameter values.
Immunohistology of rheumatoid nodules and rheumatoid synovium.
Authors: N A Athanasou, J Quinn, C G Woods, J O Mcgee
Journal: Annals of the Rheumatic Diseases (1988)

The immunohistological features of rheumatoid nodules and rheumatoid synovium were examined using monoclonal and polyclonal antibodies raised against macrophages, HLA-DR, leucocyte common antigen, and immunoglobulin components. The palisading cells surrounding the necrotic centre of the rheumatoid nodule were shown to be HLA-DR positive leucocytes, mostly histiocytes. The inflammatory infiltrate associated with rheumatoid nodules showed many immunohistochemical similarities to that of rheumatoid synovium, including a preponderance of IgG positive plasma cells, and a similar number and microanatomical pattern of distribution of HLA-DR positive cells. The significance of these findings for the cellular immunopathology and aetiology of the rheumatoid lesion is discussed.
Isolated left main coronary ostial stenosis in oriental people: Operative, histopathologic and clinical findings in six patients
Authors: Kwang Kon Koh, Hweung Kon Hwang, Pan Gum Kim, Sang Hoon Lee, Sang Kyoon Cho, Sam Soo Kim, Jae Jin Han, Young Tak Lee, Pyo Won Park, Dong Heon Yoon
Journal: Journal of the American College of Cardiology (1993)
Alcohol and drug problems in older people
Authors: C. Holmwood
Journal: BMJ (2011)

Are increasing and underdiagnosed, resulting in high levels of unmet need

The recent report from the Royal College of Psychiatrists, Our Invisible Addicts , highlights a range of problems around the use of alcohol and other drugs by older people in the United Kingdom.1 The UK is one of a small group of European Union members whose per capita consumption of alcohol is rising.2 In addition, the number of people in the UK over 65 years of age will continue to increase over the next 40 years. The report notes that the proportion of older people drinking alcohol in excess of recommended levels is increasing. Inappropriate prescribing of benzodiazepines and other psychotropic drugs is estimated to occur in a quarter of people aged over 65.3 Accordingly, it is likely that alcohol and drug related problems will become more prevalent in older people over this period as well as in other age groups.

The age of people accessing addiction related services has been increasing since 2005-6. There is also an ageing cohort effect in heroin and cocaine users, with a decrease in the number of younger people presenting for treatment, but an increase in the number of people over 40 years of age presenting. Although rates of alcohol and illicit drug use in older people are less than in other age groups, the report highlights that, for older people, recognition rates by treating clinicians are low, and unmet need is high.

These changes in the demographics of substance use …
Adolescent Grief
Authors: Grace H. Christ, Karolynn Siegel, Adolph E. Christ
Journal: JAMA (2002)

In the United States, more than 2 million children and adolescents (3.4%) younger than 18 years have experienced the death of a parent. When death can be anticipated, as with a terminal illness, and even when the death is sudden, as in the September 11, 2001, attacks on the World Trade Center and Pentagon, physicians and other health care professionals have an opportunity to ameliorate the impact of the loss. Developmental factors shape adolescents' reactions and responses to the death of a parent. Recent research in childhood and adolescent bereavement shows how health professionals can support the adolescent's coping strategies and prepare the family to facilitate an adolescent's mastery of adaptive tasks posed by the terminal phase of the parent's illness, the death, and its aftermath. Robert, a bereaved 14-year-old, illustrates some of these adaptive challenges.
Characterization of a membrane pore-forming protein from Entamoeba histolytica.
Authors: J D Young, T M Young, L P Lu, J C Unkeless, Z A Cohn
Journal: The Journal of Experimental Medicine (1982)

We describe the partial purification and characterization of a pore-forming material (PEM) from Entamoeba histolytica. The formation of ion channels by PFM was examined in three systems. (a) PFM depolarizes J774 macrophages and mouse spleen lymphocytes as measured by [3H]TPP+ uptake. (b) PFM induces rapid monovalent cation flux across the membrane of phosphatidylcholine-cholesterol vesicles. (c) PFM confers a voltage-dependent conductance to artificial planar bilayers, which is resolved as a summation of opening of individually conducting steps of 67 pS in 0.1 M KCl. Monomers of PFM are functional; however, a preferential aggregation occurs in the planar bilayer. Activity is pronase, trypsin, and heat sensitive and is stable between pH 5-8. PFM is not secreted by unstimulated amoebae but after exposure to the calcium ionophore A23187, concanavalin A, and E. coli lipopolysaccharide, 5-10% of the total cell content of PFM is released into the medium within 5-10 min. High-performance gel filtration results in an approximately 1,000-fold purification of PFM and gives an Mr of 30,000. This protein may play a role in the cytotoxicity mediated by E. histolytica.
Long-term outcome of patients undergoing surgical repair of isolated pulmonary valve stenosis. Follow-up at 20-30 years.
Authors: S L Kopecky, B J Gersh, M D McGoon, D D Mair, C J Porter, D M Ilstrup, D C McGoon, J W Kirklin, G K Danielson
Journal: Circulation (1988)

In a group of 191 consecutive patients who underwent operation at the Mayo Clinic for isolated pulmonary valve stenosis between 1956 and 1967, late results were excellent. In patients surviving operation before the age of 21 years, long-term survival was similar to that in an age- and sex-matched control population. In the other patients, late survival and functional status were good, but survival was poorer than in the control population. This late attrition, most likely due to the sequelae of long-standing right ventricular hypertrophy, suggests the need for continued surveillance. Late sudden death occurred in only three patients, between 10 and 21 years postoperatively. The finding of normal life expectancy for such patients who survive operation before age 21 is important for actuarial purposes and for the patients' career and employment plans.
Intracellular pH regulation in cultured human pleural mesothelial cells.
Authors: Y S Liaw, P C Yang, C J Yu, S H Kuo, K T Luh, Y J Lin, M L Wu
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

The human pleural space is lined by a single layer of mesothelial cells, the intracellular pH (pH(i)) of which has never been investigated. In the present study, the intrinsic buffering power of H+ ions (beta(i)) and the pH(i) regulatory systems were investigated in primary cultures of human pleural mesothelial cells (PMCs) with microspectrofluorimetry. We found: (1) that at the resting pH(i), the beta(i) was low and increased as the pH(i) decreased; (2) that the pH(i) recovery was largely inhibited either with Na+-free medium or nominally HCO3 free medium containing ethyl-isopropyl amiloride (EIPA); (3) a 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS)-sensitive, Na+/HCO3-dependent, but Cl(-)-independent acid extrusion mechanism in CO2/HCO3 buffer; and (4) that in the same buffer, a DIDS- sensitive but Na+-independent alkalosis was induced by intracellular Cl- depletion. We therefore conclude that at least three membrane pH(i) regulators are involved in regulating the pH(i) in PMCs, these being the EIPA-sensitive Na+-H+ exchanger; a novel electroneutral, DIDS-sensitive Na+-HCO3 cotransporter; and the DIDS-sensitive Cl(-)-HCO3 exchanger. Furthermore, under physiologic conditions, the Na+-HCO3 cotransporter plays a more important role in extrusion of excess intracellular H+ ions than does the Na+-H+ exchanger.
Erratum: Corrigendum: LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity
Authors: Loukia Parisiadou, Jia Yu, Carmelo Sgobio, Chengsong Xie, Guoxiang Liu, Lixin Sun, Xing-Long Gu, Xian Lin, Nicole A Crowley, David M Lovinger, Huaibin Cai
Journal: Nature Neuroscience (2014)
A Critique of External Forces in Medical Education
Authors: C. Arden Miller
Journal: JAMA (1965)

Criticism of influences in medical education supposes at the very least an awareness of what these influences are. Some are readily identified; others are so subtle or disguised that they defy easy recognition; and all of them change almost as soon as they are recognized. The editor of the<i>Journal of the American Academy of Arts and Sciences</i>recently wrote<sup>1</sup>: In a time of rapid changes, when almost all institutions assume new forms or show evidence of strain in seeking to accommodate themselves to unprecedented situations, there will always be a certain amount of disagreement about what in fact is taking place. There will seldom be disagreement that what is taking place will be resented by persons or agencies whose presumed interests are served by continuing circumstances without change. A story is told about a man who lived in a village outside Paris. During the revolution he met a
The Posthospital Phase of Myocardial Infarction
Authors: ARTHUR J. MOSS, JOHN DECAMILLA, FREDERICK ENGSTROM, WILLIAM HOFFMAN, CHARLES ODOROFF, HENRY DAVIS
Journal: Circulation (1974)

A prospective follow-up study was carried out on 100 patients recovering from acute myocardial infarction in order to develop a method for identifying those patients who are at high risk of late cardiac death. Variables, which were recorded just prior to the patient's hospital discharge after the acute attack, included six rhythm parameters from a six-hour tape ECG recording, three indices of severity of the acute coronary event, and seven nonspecific variables. Seventy-nine of the 100 patients survived a two-year follow-up, and 17 of 21 patients who died succumbed from cardiac-related problems. A stepwise discriminant analysis program was used to derive a formula which would predict the likelihood of surviving two years after a myocardial infarction. The population was divided into two groups on the basis of the presence (Group A, N = 67) or absence (Group B, N = 29) of ventricular premature beats on the initial ECG tape recording. In Group A, 91% of both the survivors and nonsurvivors were correctly identified by a discriminant combination of three arrhythmia parameters and age. In Group B, 75% of the survivors and 100% of the nonsurvivors were properly classified simply from age and one index of severity.
Two pictures of South Africa
Authors: H. Gray
Journal: BMJ (1987)

AIMS: To evaluate the sensitivity of the Roche Cobas, Roche Amplicor plate kit, ligase chain reaction (LCR), and an in house polymerase chain reaction (PCR) by titration of purified elementary bodies (EB) and also to test 245 urethral and endocervical specimens for Chlamydia trachomatis by the four assays as well as conventional culture. STUDY DESIGN: EB titrations were run in duplicate in each commercial assay and six times in the in house PCR. Clinical samples were aliquoted and tested by each assay and were considered positive if C trachomatis was detected by two or more separate tests or if the sample was either culture or immunofluorescence positive. Major outer membrane protein (MOMP) specific primers were used as a confirmatory assay for the in house PCR. RESULTS: The in house PCR, Roche Cobas Amplicor, LCR, and Amplicor plate kit gave detection limits of approximately 1, 1-2, 2, and 2-4 EBs respectively. By the criteria described above for definition of a C trachomatis positive result in clinical samples we identified 23 true positives among the 245 clinical specimens. The in house PCR detected all 23 giving a sensitivity of 100% and a specificity of 98%. The Roche Cobas Amplicor, Roche Amplicor plate kit, and LCR detected 21, 19, and 19 of these respectively giving sensitivities of 87.5%, 82%, and 82% respectively and specificities of 99.5%, 99%, and 100% respectively. The culture gave a sensitivity of 78% and specificity of 100%. CONCLUSION: All four amplification assays had a greater sensitivity than the culture used routinely in this laboratory. The in house plasmid PCR had the greatest sensitivity and when combined with confirmation by immunofluorescence detected the greatest number of positives. This increased sensitivity is likely to have been achieved by the use of a DNA purification step and of nested primers in the amplification stage and their combined use in routine diagnostic assays for chlamydia might increase the frequency of C trachomatis detections. However, this assay is much less user friendly than the two semiautomated commercial assays investigated in this study.
Experimental Validation of a New Ultrasound Method for the Simultaneous Assessment of Radial and Longitudinal Myocardial Deformation Independent of Insonation Angle
Authors: Stian Langeland, Jan D’hooge, Patrick F. Wouters, H. Alex Leather, Piet Claus, Bart Bijnens, George R. Sutherland
Journal: Circulation (2005)

Strain and strain rate have been proposed as tools to quantify regional myocardial function. One of the major pitfalls of the current methodology is its angle dependency. To overcome this problem, we have developed a new method for the estimation of strain, independent of angle. The aim of this study was to validate this new methodology in an experimental setting using sonomicrometry.In 5 open-chest sheep, ultrasound data were acquired. The new methodology was used to perform simultaneous measurements of radial and longitudinal strain in the inferolateral wall. Segment-length sonomicrometry crystals were used as the reference. After baseline acquisitions, deformation was modulated by pharmacologically changing the inotropic state of the myocardium and by inducing ischemia. Ultrasonically estimated radial and longitudinal strain were validated against sonomicrometry by means of Bland-Altman analysis and the intraclass correlation coefficient. For both strain components, good agreements were found between the ultrasound and the sonomicrometry measurements as shown by Bland-Altman statistics. The intraclass correlation coefficients were found to be 0.72 and 0.80 for the radial and longitudinal components, respectively.A new technique for the estimation of myocardial deformation was validated. It was shown that the current problem of angle dependency was solved and that 2 deformation components could be estimated simultaneously and accurately. Furthermore, the technique was less time-consuming, because anatomic tracking was performed automatically. This approach could potentially accelerate the clinical acceptance of ultrasound deformation imaging in cardiology.
THE VALUE OF LARGE PROBES IN THE TREATMENT OF LACHRYMAL STRICTURE.
Authors: H. O. REIK
Journal: JAMA (1898)

Knowing that the treatment of lachrymal stricture would be one of the subjects of discussion at this meeting, and knowing also that there exists among ophthalmic surgeons a very wide difference of opinion concerning the use of large probes for this condition, I thought it might be of interest to review and report upon the cases treated under the observation of Dr. Samuel Theobald, whom all of you know as the author and chief exponent of the really large probes. At the outset it would seem advisable to consider what is meant by "large probes," for notwithstanding the fact that Dr. Theobald has so frequently explained this point, and insisted on the difference between his probes and those of Bowman, we still see in literature frequent references to Bowman's No. 6 as a large probe. Then again, the probes obtained from the instrument-maker under the name of Theobald are not
Multidisciplinary Systems Approach to Chemotherapy Safety: Rebuilding Processes and Holding the Gains
Authors: Richard B. Womer, Ellen Tracy, Winson Soo-Hoo, Betsy Bickert, Susan DiTaranto, Jane H. Barnsteiner
Journal: Journal of Clinical Oncology (2002)

The problem of medication safety came to public attention largely through a chemotherapy error, and the high toxicity and low therapeutic index of anticancer medications make safety in their prescription and administration critical. We have undertaken a thorough revision of our systems for inpatient chemotherapy.We participated in a multi-institutional collaborative effort of the Institute for Healthcare Improvement, and used their rapid cycle change method. Particularly powerful systems change concepts were driving out fear, "trapping" errors and learning from them, focusing on outcome rather than on input, simplifying and standardizing, using constraints and "forcing functions," reducing handoffs, and paying attention to human factors.Applying these concepts to our chemotherapy delivery system, we have achieved an 84% decrease in the number of chemotherapy errors that actually reach patients per 1,000 chemotherapy doses, and have sustained that improvement for 5 years.Factors contributing to our success include the rapid cycle change method, strong support from hospital administration, grassroots participation, and a tradition of interdisciplinary cooperation. Computerized direct physician order entry and cooperative group participation have had mixed effects. Continued efforts at improvement have been key to holding our gains. Although specific problems and changes may not be relevant to other organizations, the concepts and methods we used are generally applicable.