tbuckley/cabot-search huggingface dataset:
The Pathogenesis of Sepsis
Authors: Roger C. Bone
Journal: Annals of Internal Medicine (1991)

▪Sepsis and its sequelae (sepsis syndrome and septic shock) are increasingly common and are still potentially lethal diagnoses. Many mediators of the pathogenesis of sepsis have recently been described. These include tumor necrosis factor α (TNFα), interleukins, platelet activating factor, leukotrienes, thromboxane A2, and activators of the complement cascade. Neutrophil and platelet activation may also play a role. Other agents that may participate in the sepsis cascade include adhesion molecules, kinins, thrombin, myocardial depressant substance, β-endorphin, and heat shock proteins. Endothelium-derived relaxing factor and endothelin-1 are released from the endothelium and seem to exert a regulatory effect, counterbalancing each other. A central mediator of sepsis does not seem to exist, although TNFα has been commonly proposed for this role. Animal studies are difficult to extrapolate to the clinical setting because of cross-species differences and variations in experimental design. Rather than being caused by any single pathogenic mechanism, it is more likely that sepsis is related to the state of activation of the target cell, the nearby presence of other mediators, and the ability of the target cell to release other mediators. Also important is the downregulation or negative feedback of these mediators or the generation of natural inflammation inhibitors, such as interleukin-4 and interleukin-8. Endothelial damage in sepsis probably results from persistent and repetitive inflammatory insults. Eventually, these insults produce sufficient damage that downregulation can no longer occur; this leads to a state of metabolic anarchy in which the body can no longer control its own inflammatory response.
Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta.
Authors: M S Sawdey, D J Loskutoff
Journal: Journal of Clinical Investigation (1991)

The regulation of type 1 plasminogen activator inhibitor (PAI-1) gene expression was studied in vivo employing a murine model system. Nuclease protection analysis revealed relatively high concentrations of PAI-1 mRNA in the aorta, adipose tissue, heart, and lungs of untreated CB6 (BalbC X C57B16) mice. Treatment of CB6 mice with LPS, TNF-alpha, or transforming growth factor-beta (TGF-beta) increased the steady-state levels of PAI-1 mRNA within 3 h in all tissues examined. However, the greatest responses to TGF-beta were observed in adipose tissue and the kidney, while LPS and TNF-alpha strongly stimulated PAI-1 gene expression in the liver, kidney, lung, and adrenals. In C3H/HeJ mice, which exhibit defective TNF-alpha release in response to LPS, the response of the PAI-1 gene to LPS was severely attenuated. However, injection of these mice with TNF-alpha increased PAI-1 mRNA in a tissue-specific pattern strikingly similar to that observed in LPS-treated CB6 mice. These results demonstrate that the PAI-1 gene is regulated in a complex and tissue-specific manner in vivo, and suggest a role for TNF-alpha in the response of the PAI-1 gene to sepsis.
Setbp1 promotes the self-renewal of murine myeloid progenitors via activation of Hoxa9 and Hoxa10
Authors: Kevin Oakley, Yufen Han, Bandana A. Vishwakarma, Su Chu, Ravi Bhatia, Kristbjorn O. Gudmundsson, Jonathan Keller, Xiongfong Chen, Vasyl Vasko, Nancy A. Jenkins, Neal G. Copeland, Yang Du
Journal: Blood (2012)
THE SURGICAL TREATMENT OF CANCER
Authors: E. STARR JUDD
Journal: JAMA (1925)

The surgical treatment of cancer begins with the treatment of precancerous conditions. Whether we believe in specifying these lesions as precancerous, or whether we feel that they are cancerous from the beginning, nevertheless, there is a period in which they do not present the usual cellular picture of cancer, and in which it is impossible to determine definitely whether they ever will. The eradication of the disease in the early stages brings about a cure of the condition. The so-called premalignant lesions are not all of the same type, and usually differ in different areas. One of the most striking examples of a benign disease which later becomes malignant is that of leukoplakia, which occurs so frequently on the mucous membrane of the buccal cavity. In many instances, leukoplakia is syphilitic in origin, but in others, it occurs independent of any systemic infection. It often exists for a considerable period
Imaging in Myocardial Infarction
Authors: BRUCE G. PITTS
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 June 1978Imaging in Myocardial InfarctionBRUCE G. PITTS, M.D.BRUCE G. PITTS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-6-844_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Berger, Gottschalk, and Zaret (Ann Intern Med 88:145-154, 1978) provide interesting data on the usefulness of combining thallium-201 and technetium-99m stannous pyrophosphate imaging in the evaluation of acute myocardial infarction. Their data show that the method is 100% sensitive. If the patient has had a myocardial infarction, the combined scan will be positive; there are no falsely negative tests using their method. A word of caution is necessary, however, in attempting to apply this method in the clinical setting.Berger and associates do not offer data on the frequency of false-positive tests using dual radionuclide scanning, and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: BRUCE G. PITTS, M.D.Affiliations: Temple University Health Sciences Center Philadelphia, PA 19140 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1978Volume 88, Issue 6Page: 844-844KeywordsAcute myocardial infarctionMyocardial infarctionRadionuclide scanning ePublished: 1 December 2008 Issue Published: 1 June 1978 PDF downloadLoading ...
Cases Successfully Treated by Bromoiodine Water of Woodhall Spa, Horncastle
Authors: R. Cuffe
Journal: BMJ (1873)

sists of three principal parts-viz. (i) a double tram, (2) a travelling pulley on each tram, and (3) a strongly webbed hammock.The trams are placed about two feet ten inches apart, and are six feet six inches long.Each consists of a stout bar of wrought iron, with a squared section of two inches vertical and half an inch transverse diameter.The bars are bent at right angles, on the flat at each end, where they are firmly secured by nut-screws into the joints, leaving a space of three inches between the horizontal tram and the ceiling.Depending from the bar is a Y-shaped hanger, consisting of flat iron straps which clasp the bar, with small solid rollers fixed between the same to run on the bar.Upon this hanger is hooked one of "Weston's patent pulleys", which are fitted with endless chains in.stead of ropes, and which possess this advantage, that the chain locks itself at every pull, and thus saves any strain upon the person pulling.The hammock, which should be somewhat longer than the height of the patient, is made of double ticking or of stout sailcloth, and strength- ened by bands of broad webbing, placed six or eight inches apart, and sewn to the ticking throughout.The sides of the hammock are pierced with nine iron eyes, through which pass the hooks of the "crowsfoot" or leash of cords, which are gathered on each side into an iron ring.As the patient lies in bed the hammock remains spread under him, with a small blanket (and, if necessary, a waterproof sheet also) be- tween.When he is to be taken out of bed the "crowsfeet" are hooked on; and the rings of the opposite sides are connected by an iron bow, similar in construction to a large bucket-handle, with a loop or ring in the centre.These bows are attached to the hooks of the pulleys, and the apparatus is complete.It is astonishing with what ease and comparatively slight exertion a person weighing eighteen or twenty stone is raised in this manner, run along the tram, and lowered into a chair or couch, without the least jolting or discomposure.I have found it convenient to have two hammocks.so as to afford a chance occasionallv.~~~~~~~~~~~~~~~~~~~~n ..
Abstract PD08-06: Significant Clinical impact of recurrent <i>BRCA1</i> and <i>BRCA2</i> (<i>BRCA</i>) mutations in Mexico
Authors: C Villarreal-Garza, LA Herrera, J Herzog, D Port, A Mohar, C Perez-Plasencia, J Clague, RMa Alvarez, M Santibanez, KR Blazer, JN Weitzel
Journal: Cancer Research (2012)

Abstract Background: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cancer cause of death in Hispanic women. Although the incidence of breast cancer in Hispanics is less than that for non-Hispanic white women, our studies on the prevalence of deleterious mutations in the BRCA genes among high-risk Hispanics in the US suggest that BRCA mutations may account for a higher proportion of BC in this population. However, a lack of research on BRCA mutations in Hispanics has limited the implementation of prevention efforts and the scope of comparative studies of genetic factors that influence BC and ovarian cancer (OC) risk within Hispanic populations – this is especially true of Mexico where there has been little access to clinical BRCA gene analyses. Objective/Methods: We used an economic panel assay (HISPANEL) on a mass spectroscopy platform (Sequenom) to analyze DNA from 189 cancer cases (92 unselected OC; 97 BC) from the National Cancer Institute in Mexico City for recurrent BRCA mutations, including a large rearrangement (BRCA1 ex9-12del) that we hypothesize is a Mexican founder mutation. Results: Overall, 14% (27/189) harbored a germline BRCA mutation (25 BRCA1, 2 BRCA2) detected by the HISPANEL (17% in OC; 11% in BC). BRCA1 ex9-12del was detected in 9.8% (9/92) of unselected OC cases, representing 56% of the 16 BRCA mutations. It also represented 36% (4/11) of the BRCA mutations detected in the BC cases. Mean age at onset of BC for BRCA-associated cases (n = 11) was 46 years old (range 31–63); 8/11 were triple negative BC (TNBC) – a BRCA mutation was detected in 24% (8/34) of all TNBC cases. Conclusions: The remarkable frequency of the BRCA1 ex9-12del mutation, accounting for 56% of BRCA mutations in the OC cases and 36% of BC cases, supports our hypothesis of regional origin of this Mexican founder mutation approximately 1,474 years ago. Similar to our experience in the Mexican American population, the HISPANEL, which includes recurrent BRCA mutations found in women of Hispanic ancestry, appears to have high sensitivity and thus is likely to have clinical utility while reducing overall genotyping cost among underserved women in Mexico. Both in the US Hispanic populations and in Mexico, the prevalence of the Mexican founder mutation make it a significant public health issue, and presents an opportunity for cost effective in BC and OC prevention. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD08-06.
Effects of Catecholamine Stress on Diastolic Function and Myocardial Energetics in Obesity
Authors: Oliver J. Rider, Jane M. Francis, Mohammed K. Ali, Cameron Holloway, Tammy Pegg, Matthew D. Robson, Damian Tyler, James Byrne, Kieran Clarke, Stefan Neubauer
Journal: Circulation (2012)

Obesity is characterized by impaired cardiac energetics, which may play a role in the development of diastolic dysfunction and inappropriate shortness of breath. We assessed whether, in obesity, derangement of energetics and diastolic function is further altered during acute cardiac stress.Normal-weight (body mass index, 22±2 kg/m(2); n=9-17) and obese (body mass index, 39±7 kg/m(2); n=17-46) subjects underwent assessment of diastolic left ventricular function (cine magnetic resonance imaging volume-time curve analysis) and cardiac energetics (phosphocreatine/ATP ratio; (31)P-magnetic resonance spectroscopy) at rest and during dobutamine stress (heart rate increase, 65±22% and 69±14%, respectively; P=0.61). At rest, obesity was associated with a 22% lower peak filling rate (P<0.001) and a 15% lower phosphocreatine/ATP ratio (1.73±0.40 versus 2.03±0.28; P=0.048). Peak filling rate correlated with fat mass, left ventricular mass, leptin, waist-to-hip ratio, and phosphocreatine/ATP ratio. On multivariable analysis, phosphocreatine/ATP was the only independent predictor of peak filling rate (β=0.50; P=0.03). During stress, a further reduction in phosphocreatine/ATP occurred in obese (from 1.73±0.40 to 1.53±0.50; P=0.03) but not in normal-weight (from 1.98±0.24 to 2.04±0.34; P=0.50) subject. For similar levels of inotropic stress, there were smaller increases in peak filling rate in obesity (38% versus 70%; P=0.01).In obesity, cardiac energetics are further deranged during inotropic stress, in association with continued diastolic dysfunction. Myocardial energetics may play a key role in the impairment of diastolic function in obesity.
Effect of rituximab on human in vivo antibody immune responses
Authors: Mark D. Pescovitz, Troy R. Torgerson, Hans D. Ochs, Elizabeth Ocheltree, Paula McGee, Heidi Krause-Steinrauf, John M. Lachin, Jennifer Canniff, Carla Greenbaum, Kevan C. Herold, Jay S. Skyler, Adriana Weinberg
Journal: Journal of Allergy and Clinical Immunology (2011)
Association of Dietary Patterns With Cancer Recurrence and Survival in Patients With Stage III Colon Cancer
Authors: Jeffrey A. Meyerhardt, Donna Niedzwiecki, Donna Hollis, Leonard B. Saltz, Frank B. Hu, Robert J. Mayer, Heidi Nelson, Renaud Whittom, Alexander Hantel, James Thomas, Charles S. Fuchs
Journal: JAMA (2007)

Dietary factors have been associated with the risk of developing colon cancer but the influence of diet on patients with established disease is unknown.To determine the association of dietary patterns with cancer recurrences and mortality of colon cancer survivors.Prospective observational study of 1009 patients with stage III colon cancer who were enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients reported on dietary intake using a semiquantitative food frequency questionnaire during and 6 months after adjuvant chemotherapy. We identified 2 major dietary patterns, prudent and Western, by factor analysis. The prudent pattern was characterized by high intakes of fruits and vegetables, poultry, and fish; the Western pattern was characterized by high intakes of meat, fat, refined grains, and dessert. Patients were followed up for cancer recurrence or death.Disease-free survival, recurrence-free survival, and overall survival by dietary pattern.During a median follow-up of 5.3 years for the overall cohort, 324 patients had cancer recurrence, 223 patients died with cancer recurrence, and 28 died without documented cancer recurrence. A higher intake of a Western dietary pattern after cancer diagnosis was associated with a significantly worse disease-free survival (colon cancer recurrences or death). Compared with patients in the lowest quintile of Western dietary pattern, those in the highest quintile experienced an adjusted hazard ratio (AHR) for disease-free survival of 3.25 (95% confidence interval [CI], 2.04-5.19; P for trend <.001). The Western dietary pattern was associated with a similar detriment in recurrence-free survival (AHR, 2.85; 95% CI, 1.75-4.63) and overall survival (AHR, 2.32; 95% CI, 1.36-3.96]), comparing highest to lowest quintiles (both with P for trend <.001). The reduction in disease-free survival with a Western dietary pattern was not significantly modified by sex, age, nodal stage, body mass index, physical activity level, baseline performance status, or treatment group. In contrast, the prudent dietary pattern was not significantly associated with cancer recurrence or mortality.Higher intake of a Western dietary pattern may be associated with a higher risk of recurrence and mortality among patients with stage III colon cancer treated with surgery and adjuvant chemotherapy. Further studies are needed to delineate which components of such a diet show the strongest association.
New Developments in the Therapy of Allergic Disorders and Asthma
Authors: J P R Hartley
Journal: BMJ (1994)

Ed S Z Langer, M K Church, B B Vargaftig, S Nicosia Karger, pp 136 ISBN 3-8055-5748-8

It is more than 80 years since Dale and his colleagues described the actions of a substance called beta iminazolylethyl amine, and the role of histamine, as it was later called, is still debated in meetings on allergy and asthma. Histamine seems to be most important in rhinitis and urticaria - where H1 antihistamines are thus valuable in treatment - and much less important in asthma. Despite extensive, and continuing, research, H1 antihistamines have not been found to be helpful for most …
Tamoxifen in the Treatment of Breast Cancer
Authors: Sewa Singh Legha
Journal: Annals of Internal Medicine (1988)

Tamoxifen, an antiestrogen, is a competitive inhibitor of estradiol, blocking its effects on the target organs. During the 10 years it has been used in the United States it has become preferred over estrogens for treating postmenopausal women with metastatic breast cancer. Recently, tamoxifen has been used in treating premenopausal women with recurrent breast cancer, and its efficacy has been proved equal to that of ovarian ablation. In comparative trials, tamoxifen has been as effective as alternative endocrine treatments, and has greatly reduced toxicity and no irreversible side effects. Because of the high risk for systemic relapse in patients with breast cancer with regional lymph node metastases, (stage II), tamoxifen has been evaluated as adjuvant therapy after local treatment of the tumor. The results of these trials have shown a significant increase in the disease-free survival of postmenopausal women treated with tamoxifen, particularly in patients with hormone-receptor-positive tumors. Tamoxifen has not been as useful as adjuvant treatment in premenopausal women, for whom combination chemotherapy is the treatment of choice.
Determination of the Drug Sensitivity of Plasmodium falciparum
Authors: Karl H. Rieckmann
Journal: JAMA (1971)

Chloroquine-resistant infections of malaria are prevalent in many areas of Southeast Asia and South America and their importation into the United States will remain a problem during the foreseeable future. The sensitivity of<i>Plasmodium falciparum</i>to chloroquine and other antimalarial drugs can be determined by a simple in vitro technique. It provides an expedient method for identifying drug-resistant strains and is useful in assessing the blood schizontocidal activity of some antimalarial agents. During studies with the recently solated Vietnam (Marks) strain of<i>P falciparum</i>, parasites showed a marked degree of resistance to chloroquine in vivo and in vitro, but they were significantly more susceptible to amodiaquine. The findings suggest that some<i>P falciparum</i>infections resistant to chloroquine may respond more favorably to treatment with another 4-aminoquinoline.
Physicians Focus on Primary Care for Patients With HIV
Authors: Bridget M. Kuehn
Journal: JAMA (2013)

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Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care
Authors: K. Khunti, L. J. Gray, T. Skinner, M. E. Carey, K. Realf, H. Dallosso, H. Fisher, M. Campbell, S. Heller, M. J. Davies
Journal: BMJ (2012)

<b>Objective</b> To measure whether the benefits of a single education and self management structured programme for people with newly diagnosed type 2 diabetes mellitus are sustained at three years. <b>Design</b> Three year follow-up of a multicentre cluster randomised controlled trial in primary care, with randomisation at practice level. <b>Setting</b> 207 general practices in 13 primary care sites in the United Kingdom. <b>Participants</b> 731 of the 824 participants included in the original trial were eligible for follow-up. Biomedical data were collected on 604 (82.6%) and questionnaire data on 513 (70.1%) participants. <b>Intervention</b> A structured group education programme for six hours delivered in the community by two trained healthcare professional educators compared with usual care. <b>Main outcome measures</b> The primary outcome was glycated haemoglobin (HbA<sub>1c</sub>) levels. The secondary outcomes were blood pressure, weight, blood lipid levels, smoking status, physical activity, quality of life, beliefs about illness, depression, emotional impact of diabetes, and drug use at three years. <b>Results</b> HbA<sub>1c</sub> levels at three years had decreased in both groups. After adjusting for baseline and cluster the difference was not significant (difference −0.02, 95% confidence interval −0.22 to 0.17). The groups did not differ for the other biomedical and lifestyle outcomes and drug use. The significant benefits in the intervention group across four out of five health beliefs seen at 12 months were sustained at three years (P&lt;0.01). Depression scores and quality of life did not differ at three years. <b>Conclusion</b> A single programme for people with newly diagnosed type 2 diabetes mellitus showed no difference in biomedical or lifestyle outcomes at three years although there were sustained improvements in some illness beliefs. <b>Trial registration</b> Current Controlled Trials ISRCTN17844016.