tbuckley/cabot-search huggingface dataset:
Key opinion leaders, your time is up
Authors: Fiona Godlee
Journal: BMJ (2008)

We’re lucky in medicine to have an unending supply of mysteries to ponder. Some of these—like why vitamin A supplementation benefits some children while harming others—are amenable to scientific research (doi: 10.1136/bmj.39575.486609.80;doi: 10.1136/bmj.39542.509444.AE). But there are mysteries of a different sort, ones that are in our power as a profession to resolve. Why, for example, is it considered normal for medical leaders to accept personal payment for promoting a company’s drug or device?

This week Ray Moynihan asks whether paid “key opinion leaders” can be independent or are just drug representatives in disguise (doi: 10.1136/bmj.39575.675787.651). His interview with former …
Limitations of computed tomography in leaking abdominal aortic aneurysms.
Authors: R. A. Greatorex, A. K. Dixon, C. D. Flower, R. W. Pulvertaft
Journal: BMJ (1988)

6 observations d'anevrysmes de l'aorte abdominale; dans les 6 cas la tomographie informatisee n'indique pas de fuite, et lors de l'operation on trouve des fuites dans 5 cas et une rupture dans un cas. Dans 3 cas la reparation est faite et le malade survit, les 3 autres malades sont morts (dont un non opere, atteint d'un cancer recidivant)
St Louis Encephalitis
Authors: Kenneth E. Powell
Journal: JAMA (1977)

In 1975, 229 laboratory-documented cases of St Louis encephalitis, 36 of which resulted in death, occurred in Mississippi. A total of 58% of these persons had encephalitis, 15% had aseptic meningitis, 21% had a febrile illness with no known CNS involvement, and 6% had other syndromes. Attack rates and case-fatality ratios increased with age. Although 60% of the cases occurred in a four-county area of northwest Mississippi, cases occurred in 42 of the 82 counties throughout the state. The epidemic erupted almost simultaneously, with variable intensity, in widely separated areas. Mosquito-control measures were applied, but the results were not quantified. (<i>JAMA</i>237:2294-2298, 1977)
Abstract 1513: Functional analysis of <i>TGFBR1</i> mutations in breast cancer associated fibroblasts
Authors: Lakisha D. Moore-Smith, Kanika Manne, Charisma Caldwell, Andra Frost, Boris Pasche
Journal: Cancer Research (2012)

Abstract The TGFBR1*6A variant consists of a GCG repeat deletion resulting in a three-alanine deletion in the TGFBR1 coding region which has been linked to breast cancer risk. We have screened 30 breast cancer cell lines including: 20 epithelial (2 from normal breast) and 10 CAFs (2 from normal breast) for the presence of this mutation. Initial screening indicates that 45% of the epithelial cell lines screened harbor the *6A mutation. Of the 8 fibroblast screened 67% harbored TGFBR1*6A. The following CAF cell lines were used for the remainder of our functional studies: Hs748 (9A/9A), Hs841.T (9A/6A) and Hs742.T (6A/6A) genotypes. CAFs were treated with 100pM TGF-β resulting in decreased growth inhibitory response of 20% for Hs742.T (*6A/*6A) cells when compared to Hs841.T (9A/*6A) cells with 42% inhibition. Invasion assays, using a matrigel-coated Boyden Chamber, indicated a higher invasive capacity for Hs841.T (9A/6A) fibroblast cell line than in the Hs742.T (6A/6A) or Hs748.T (9A/9A). Western blot analysis was used to determine cell differentiation status. Cells which harbor TGFBR1*6A showed an increased expression of α-sma when compared to the WT fibroblasts indicating progression to a more aggressive myofibroblast phenotype. Studies are underway to reproduce these data in additional CAF cell lines, however, this preliminary data suggest that TGFBR1*6A enhances breast cancer development by enhancing tumor-associated fibroblast oncogenic properties in addition to its direct effect on breast tumor cells. TGF-β signaling was altered in TGFBR1*6A cells which may alter normal tumor-stromal signaling pathways. Future studies, using primary cell lines derived from a transgenic mouse model harboring the TGFBR1*6A allele will provide an optimal system to dissect the functional effects of this mutation in tumor and stromal cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1513. doi:1538-7445.AM2012-1513
Acute respiratory failure after aspiration of activated charcoal with recurrent deposition and release from an intrapulmonary cavern
Authors: Roland C. E. Francis, Joerg C. Schefold, Sven Bercker, Bettina Temmesfeld-Wollbrück, Wilko Weichert, Claudia D. Spies, Steffen Weber-Carstens
Journal: Intensive Care Medicine (2008)
Pathogenetic Mechanisms of Prolapsing Aortic Valve and Aortic Regurgitation Associated With Ventricular Septal Defect
Authors: KATSUHIKO TATSUNO, SOUJI KONNO, MASAHIKO ANDO, SHIGERU SAKAKIBARA
Journal: Circulation (1973)

The developmental mechanisms of prolapse and regurgitation of the aortic valve which complicate ventricular septal defect (VSD) were investigated from the anatomical, angiographic, and surgical viewpoints on the basis of autopsied heart specimens, preoperative thoracic aortography, and surgical records. Two major, conceptually distinct but functionally interdependent factors contribute to the aortic valve's prolapse into the VSD. The major feature of the first category is the lack of anatomical support for the valve. In subpulmonary VSD, a regional defect of the conal septal musculature which supports a section of the right coronary sinus and the annulus was observed. In infracristal VSD, a deficiency of the sinus of Valsalva was noted. The hemodynamic effects, which actually produce prolapse of the anatomically unsupported valve into the VSD, is the second contributing factor. The left-to-right shunt of blood through the VSD during the early systolic phase pulls the sagging aortic valve into the defect. The distinctive feature of the second category is that prolapse of the anatomically unsupported valve is produced by hemodynamic effects. Diastolic aortic pressure does not appear to contribute greatly to bulging of the aortic valve into the right ventricular cavity. However, in the diastolic phase, the closed valve is subject to intra-aortic pressure, causing the free margin of the prolapsed cusp to hang down, to gradually become elongated, and finally to separate from the free margin of the other two cusps, and thus be rendered incompetent.
Evaluation of Hollow Fiber and Spiral Coil Membrane Oxygenators Designed for Cardiopulmonary Bypass in Infants
Authors: ROBERT E. RAWITSCHER, ROBERT C. DUTTON, L. HENRY EDMUNDS
Journal: Circulation (1973)

Fourteen 1.4 m 2 hollow fiber and 23 1.5 m 2 spiral coil membrane oxygenators that were designed for total cardiopulmonary bypass in infants were evaluated. Operating procedures and toxicity were studied during total cardiopulmonary bypass and one hour of circulatory arrest at 15° C (rectal) in four monkeys. Oxygen and carbon dioxide transfer, water loss, production of emboli, transmission of pulse waves, and pressure-flow relationships were studied at three different blood flow rates, at hematocrits of 25% and 40%, and at 25° C and 37° C during partial venoarterial bypass in 33 dogs. Linear regression equations were calculated for oxygen and carbon dioxide transfer and for pressure-flow relationships at the different flows, temperatures, and hematocrits. Rated flow (Rf), defined as the blood flow rate at which inlet O 2 saturation of 65% increases to an outlet O 2 saturation of 95%, was calculated for each oxygenator at hematocrit 40 (Rf 40) or hematocrit 25 (Rf 25). The hollow fiber oxygenator had a priming volume of 140 ml, an Rf 40 of 800 ml/min, and an Rf 25 of 1200 ml/min. The spiral coil oxygenator had a priming volume of 208 ml, an Rf 40 of 1400 ml/min, and an Rf 25 of 1800 ml/min. At Rf 40 and inlet pCO 2 50 torr, the hollow fiber oxygenator transferred 8.9 ml CO 2 /100 ml and the spiral coil 5.7 ml CO 2 /100 ml. The performance of the two oxygenators differed, but both functioned very satisfactorily.
Serum PBDEs in a North Carolina Toddler Cohort: Associations with Handwipes, House Dust, and Socioeconomic Variables
Authors: Heather M. Stapleton, Sarah Eagle, Andreas Sjödin, Thomas F. Webster
Journal: Environmental Health Perspectives (2012)

Polybrominated diphenyl ethers (PBDEs) are persistent, bioaccumulative, and endocrine-disrupting chemicals.
<i>KRAS</i> Mutation: Should We Test for It, and Does It Matter?
Authors: Patrick J. Roberts, Thomas E. Stinchcombe
Journal: Journal of Clinical Oncology (2013)

Lung cancer is the leading cause of cancer mortality in the United States and worldwide. Previously, lung cancer was simplistically divided into non–small-cell lung cancer (NSCLC) and small-cell lung cancer. However, in the last decade, we have gone from a simplistic binary system of classifying lung cancer to defining NSCLC on the basis of molecular subsets. KRAS mutations represent the most common molecular change in NSCLC. The presence of KRAS mutation has been shown to be associated with a poor prognosis in NSCLC, but this is of little clinical utility. More important is determining the clinical utility of KRAS mutational analysis for predicting benefit of chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), anti-EGFR monoclonal antibodies, or other novel therapeutics. Current data does not support the routine use of KRAS mutational analysis for predicting chemotherapy benefit. Additionally, there was significant interest in using KRAS status to select patients for EGFR TKI and anti-EGFR monoclonal antibodies. However, the EGFR mutational status has demonstrated significant predictive value in the selection of patients for EGFR TKI therapy and is now the preferred test. An association between KRAS mutational status and benefit of anti-EGFR monoclonal antibodies has not been demonstrated in NSCLC. Here we review, in the context of NSCLC, the underlying biology of KRAS mutations, the predictive value of KRAS mutations for therapeutic intervention, and the integration of KRAS mutational testing into our current clinical paradigms.
The Coming Era of Nanomedicine
Authors: Fritz Allhoff
Journal: The American Journal of Bioethics (2009)

This essay presents some general background on nanomedicine, particularly focusing on some of the investment that is being made in this emerging field. The bulk of the essay, however, consists of explorations of two areas in which the impacts of nanomedicine are likely to be most significant: diagnostics and medical records and treatment, including surgery and drug delivery. Each discussion includes a survey some of the ethical and social issues that are likely to arise in these applications.
The uneven distribution of fears and phobias: A nonassociative account
Authors: Ross G. Menzies
Journal: Behavioral and Brain Sciences (1995)

Abstract A review of data concerning the uneven distribution of phobias suggests that nonassociative, ethological models can account for most of tile important findings that cannot be attributed to expectancy biases. The origin of a variety of fears that appear in fixed developmental patterns across divergent cultures and species can best be explained by biological models.
Battle Hospital: Medics at War
Authors: Bill Kirkup
Journal: BMJ (2004)

Channel 4, 27 February at 7 30 pm Rating: ![Graphic][1]</img>![Graphic][2]</img> As the conventional phase of the recent Iraq war ended, the padre conducting a service for the personnel of 202 Field Hospital said, “We have stood up against tyranny and won.” The rest of this documentary on the work of the hospital would have given most viewers a different impression. Nearly all admissions were Iraqi civilian victims of trauma, many of them children. Cue close-up after grisly close-up of surgical debridement, skin grafting, unstable fractures, punctured bowel. Modern war inevitably generates such scenes, and television lets us all share the resulting sense of horror and futility. Battle Hospital followed the 650 men … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Should the Patient Know?
Authors: Simon N. Whitney
Journal: JAMA (1979)

<h3>To the Editor.—</h3> I was glad to see the recent contributions by Emil J Freireich, MD, Samuel Vaisrub, MD (241:928, 1979), and Novack et al concerning what physicians should, and do, tell their cancer patients. Dr Vaisrub is right to point out that sometimes we can tell patients more than is good for them, but he is wrong in implying that most thanatologists believe that patients should be told the whole unvarnished truth. It is a question of attitude. Elisabeth Kübler-Ross, MD,<sup>1</sup>never tells patients "the truth about their hopeless outlook." As she puts it: I do not tell the patient that he is dying or that he is terminally ill. I simply tell him that he is seriously ill and that we are doing everything humanly possibly to help him function as well as he can.... No patient should be told that he is dying.... If a patient
Gangrenous caecal volvulus after colonoscopy
Authors: J. Baillie
Journal: BMJ (1983)

Poor prognosis of acute lymphoblastic leukaemia in non-European children SIR,-The results of treatment of acute lymphoblastic leukaemia in Asian children living in the United Kingdom (12 March, p 839-41) are similar to those found in Algerian children with acute lymphoblastic leukaemia treated with chemotherapy.As far as modern medicine is concerned communica- tion difficulties exist between doctors and patients' families in developing countries.From 1978 to 1982 54 children (under 15) were treated in our clinic (32 boys and 22 girls), and their clinical state was assessed on 1 March 1981.Initial treatment included
Oral Silibinin Inhibits <i>In vivo</i> Human Bladder Tumor Xenograft Growth Involving Down-Regulation of Survivin
Authors: Rana P. Singh, Alpna Tyagi, Girish Sharma, Sarumathi Mohan, Rajesh Agarwal
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Chemoprevention is an upcoming approach to control bladder cancer, which is one of the commonly diagnosed malignancies showing recurrence rate of 70% or even higher. Recently, we observed the in vitro efficacy of silibinin, a flavanolignan, in human bladder transitional cell papilloma RT4 cells. Here, we investigated the antitumor efficacy and associated mechanisms of silibinin in RT4 tumor xenograft. Experimental Design: RT4 tumor xenograft was implanted s.c. in athymic nude mice, and then animals were oral gavaged with silibinin at 100 and 200 mg/kg doses, 5 days/week for 12 weeks. Tumor growth, body weight, and diet consumption were recorded, and tumors were analyzed for proliferation, apoptosis, and angiogenesis biomarkers and molecular alterations by immunohistochemistry, immunoblot analysis, and ELISA. p53 small interfering RNA was used in cell culture to examine the role of p53 in survivin expression. Results: Silibinin feeding inhibited tumor xenograft growth without any gross signs of toxicity. Silibinin decreased tumor volume by 51% to 58% (P ≤ 0.01) and tumor weight by 44% to 49% (P &amp;lt; 0.05). Silibinin moderately (P &amp;lt; 0.001) decreased cell proliferation and microvessel density and strongly (P &amp;lt; 0.001) increased apoptosis in tumors. Silibinin robustly decreased survivin protein expression and its nuclear localization, as well as tumor-secreted level in mouse plasma, but increased p53 and cleaved caspase-3 levels in tumors. Silibinin-caused decrease in survivin was independent of p53. Conclusion: These findings identified in vivo antitumor efficacy of silibinin against human bladder tumor cells involving down-regulation of survivin and an increase in p53 expression together with enhanced apoptosis.
THE MILK-SUPPLY OF CITIES: CAN IT BE IMPROVED?.
Authors: HENRY O. MARCY
Journal: JAMA (1898)

Sanitation has made rapid strides in the protection of the public from a great variety of dangers, and more and more each year are emphasized the interdependence and correlation of the entire body politic. This is especially true in urban life, and many of the relations which were thought to be purely personal and individualistic are now accepted as common, and are to be most satisfactorily dealt with under general supervision and control. The development of the water-supply and sewerage of cities is an illustration of common needs, more and more demanding a union of public interests, supervised by men of the highest talent, specially trained for this service. Modern science has pointed out many dangers to which the individual is exposed, and it is with special satisfaction that we refer to the labors of this generation in having defined the causation and limitation of a large class of the
Vitamin D Supplementation in Patients With Osteoarthritis
Authors: Changhai Ding, Flavia Cicuttini, Graeme Jones
Journal: JAMA (2013)

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Trajectories of Life-Space Mobility After Hospitalization
Authors: Cynthia J. Brown
Journal: Annals of Internal Medicine (2009)

Background: Life space is a measure of where a person goes, the frequency of going there, and the dependency in getting there. It may be a more accurate measure of mobility in older adults because it reflects participation in society as well as physical ability. Objective: To assess effects of hospitalization on life space in older adults, and to compare life-space trajectories associated with surgical and nonsurgical hospitalizations. Design: Prospective observational study. Setting: Central Alabama. Participants: 687 community-dwelling Medicare beneficiaries at least 65 years of age with surgical (n = 44), nonsurgical (n = 167), or no (n = 476) hospitalizations. Measurements: Life-Space Assessment (LSA) scores before and after hospitalization (range, 0 to 120; higher scores reflect greater mobility). Results: Mean age of participants was 74.6 years (SD, 6.3). Fifty percent were black, and 46% were male. Before hospitalization, adjusted LSA scores were similar in participants with surgical and nonsurgical admissions. Life-space assessment scores decreased in both groups immediately after hospitalization; however, participants with surgical hospitalizations had a greater decrease in scores (12.1 more points [95% CI, 3.6 to 20.7 points]; P = 0.005) than those with nonsurgical hospitalizations. However, participants with surgical hospitalizations recovered more rapidly over time (gain of 4.7 more points [CI, 2.0 to 7.4 points] per ln [week after discharge]; P < 0.001). Score recovery for participants with nonsurgical hospitalizations did not significantly differ from the null (average recovery, 0.7 points [CI, −0.6 to 1.9 points] per ln [week after discharge]). Limitation: Life space immediately before and after hospitalization was self-reported, often after hospital discharge. Conclusion: Hospitalization decreases life space in older adults. Surgical hospitalizations are associated with immediate marked life-space declines followed by rapid recovery, in contrast to nonsurgical hospitalizations, which are associated with more modest immediate declines and little evidence of recovery after several years of follow-up. Primary Funding Source: National Institute on Aging.
Successful umbilical cord blood transplantation for Fanconi anemia using preimplantation genetic diagnosis for HLA‐matched donor
Authors: Bella Bielorai, Mark R. Hughes, Arleen D. Auerbach, Arnon Nagler, Ron Loewenthal, Gideon Rechavi, Amos Toren
Journal: American Journal of Hematology (2004)

Fanconi anemia is a rare autosomal recessive disease characterized by bone marrow failure, developmental anomalies, and a high incidence of myelodysplasia and acute myeloid leukemia. Stem cell transplantation is the only curative treatment. In the absence of matched- sibling donor, an alternative mismatched family or matched unrelated donor can be used, but the results are inferior to the matched-sibling transplant and carry a high risk of morbidity and mortality. Preimplantation genetic diagnosis (PGD) has been increasingly used in recent years for mutation analysis for many genetic disorders and results in the birth of healthy children, saving the need for the termination of pregnancy of an affected embryo. The use of PGD for combined analysis of mutation and HLA-matching was reported for the first time in 2001. This enables the birth of an unaffected child who can serve as a donor for an affected sibling in need for stem cell transplantation. We report successful cord blood transplantation for a Fanconi anemia patient from his HLA-matched sibling, born after PGD that included mutation analysis for Fanconi anemia and HLA typing. PGD can provide an unaffected donor for a sibling affected by genetic disease in the absence of a compatible related donor.
Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNγ-dependent iNOS expression in the vasculature of healthy mice
Authors: Jonathan Morton, Barbara Coles, Kate Wright, Awen Gallimore, Jason D. Morrow, Erin S. Terry, Peter B. Anning, B. Paul Morgan, Vincent Dioszeghy, Hartmut Kühn, Pavlos Chaitidis, Adrian J. Hobbs, Simon A. Jones, Valerie B. O'Donnell
Journal: Blood (2008)

Whether leukocytes exert an influence on vascular function in vivo is not known. Here, genetic and pharmacologic approaches show that the absence of neutrophils leads to acute blood pressure dysregulation. Following neutrophil depletion, systolic blood pressure falls significantly over 3 days (88.0 +/- 3.5 vs 104.0 +/- 2.8 mm Hg, day 3 vs day 0, mean +/- SEM, P < .001), and aortic rings from neutropenic mice do not constrict properly. The constriction defect is corrected using l-nitroarginine-methyl ester (L-NAME) or the specific inducible nitric oxide synthase (iNOS) inhibitor 1400W, while acetylcholine relaxation is normal. iNOS- or IFNgamma-deficient mice are protected from neutropenia-induced hypotension, indicating that iNOS-derived nitric oxide (NO) is responsible and that its induction involves IFNgamma. Oral enrofloxacin partially inhibited hypotension, implicating bacterial products. Roles for cyclooxygenase, complement C5, or endotoxin were excluded, although urinary prostacyclin metabolites were elevated. Neutrophil depletion required complement opsinization, with no evidence for intravascular degranulation. In summary, circulating neutrophils contribute to maintaining physiological tone in the vasculature, at least in part through suppressing early proinflammatory effects of infection. The speed with which hypotension developed provides insight into early changes that occur in the absence of neutrophils and illustrates the importance of constant surveillance of mucosal sites by granulocytes in healthy mice.