tbuckley/cabot-search huggingface dataset:
Targeted Temperature Management for Comatose Survivors of Cardiac Arrest
Authors: Michael Holzer
Journal: New England Journal of Medicine (2010)

A 62-year-old man collapses on the street and is found to be in cardiac arrest. He is resuscitated at the scene by emergency medical personnel, but he is comatose. Targeted temperature management, which involves cooling the patient to a core body temperature of 32 to 34°C for 24 hours, is recommended.
616 RELATIONSHIP BETWEEN PRO-INFLAMMATORY CYTOKINES AND CEREBRAL EDEMA IN ACUTE-ON-CHRONIC LIVER FAILURE
Authors: V.A. Saraswat, M. Rangan, S.K. Yadav, R.K.S. Rathore, M.A. Thomas, K.N. Prasad, C.M. Pandey, R.K. Gupta
Journal: Journal of Hepatology (2011)
Molecular profiles of breast cancer in Ilorin, Nigeria.
Authors: K. A. Adeniji, D. Huo, A. Khramtsov, C. Zhang, O. I. Olopade
Journal: Journal of Clinical Oncology (2010)

1602 Background: Breast cancer is a complex disease with diversity between tumors and within tumor. Major differences exist in incidence and mortality rates across populations, making it imperative to investigate molecular pathogenesis in various populations. Methods: To identify molecular subtypes of breast cancer we collected Formalin-fixed and Paraffin-Embedded (FFPE) tissue blocks from Ilorin. Pathologic features and patients' data were extracted from histology reports. Tissue microarrays were constructed from FFPE tumor samples and adjacent normal breast tissue at the University of Chicago. Immunohistochemical assays were performed using a DAKO immunostainer (DAKO, Carpinteria, CA) with antibodies and antigen unmasking. Breast cancer subtypes were defined as luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+, and/or EGFR+), HER2+/ER- (HER2+, ER-, PR-), and unclassified (negative for all five markers). Results: From 2003 to 2007, 203 histologicaly confirmed breast cancer patients were enrolled, including 5 males and 5 bilateral breast cancers. Median age at diagnosis was 46 yrs. Majority of patients (59%) presented with large tumors (≥ 5 cm) as median time from symptoms onset to cancer diagnosis was 6 months (interquartile range 3-12 months). Proportion of ER+, PR+ and HER2+ tumors were 27%, 16%, and 30%, respectively. Commonest breast cancer subtype was basal-like (25%), followed by unclassified (24%), luminal A (20%), HER2+/ER- (19%), and luminal B (11%). Patients with ER+ tumors had longer duration of symptoms (median 8 months) than patients with ER- tumors (5 months) but ER+ patients had smaller tumors (median 5 cm) than ER- patients (6 cm, p = 0.02). Conclusions: This study replicates previous findings that triple negative breast cancer was over-represented in African population in a different geographic region of North Central Nigeria as found in the Southwest earlier on. Patients seek medical help after many months of cancer symptoms, suggesting lack of awareness of breast cancer in the population. Study also showed that ER- breast cancer grows faster than ER+ breast cancer, underscoring urgent need to develop effective breast cancer awareness and early detection programs in Africa. No significant financial relationships to disclose.
Surrogate Tumor Antigen Vaccination Induces Tumor-Specific Immunity and the Rejection of Spontaneous Metastases
Authors: Jennifer D. Lewis, Michael H. Shearer, Ronald C. Kennedy, Robert K. Bright
Journal: Cancer Research (2005)

Abstract The nonimmunogenic 4T1 murine mammary carcinoma model and a model surrogate tumor antigen (sTA) were employed to explore the possibility of inducing tumor-specific immunity through active immunization in the absence of defined tumor-associated antigens. Immunization of naive mice with protein-based sTA resulted in protection from s.c. challenge, with 4T1 modified to express the sTA (4T1.sTA), or from a sTA-expressing unrelated tumor cell line (mKSA). Immunization had no effect on parental 4T1 tumor growth or the formation of parental 4T1 spontaneous lung metastases. Mice that were sTA immunized and successfully rejected 4T1.sTA challenge also rejected a subsequent challenge in the contralateral flank with parental 4T1 and strikingly prevented the formation of spontaneous parental 4T1 lung metastases. The rejection of parental 4T1 seemed to be specific for and associated with unknown 4T1 tumor-associated antigens, because rejection of mKSA did not induce cross-protection against a challenge with parental 4T1. To evaluate the effect of this vaccine approach on established disease, mice were simultaneously challenged on day 0 with 4T1.sTA and parental 4T1 in contralateral flanks and then immunized on days 3, 10, 17, and 24 with sTA protein. Tumor growth and metastasis were delayed in four of five animals, and 20% (2 of 5) of the animals were tumor free at the completion of the experiment. Together, these data suggest that prior vaccination with a sTA followed by inoculation with poorly immunogenic tumor cells modified to express the sTA activates determinant spreading and the induction of systemic tumor immunity resulting in indigenous tumor rejection.
Dialectical Behavior Therapy for Borderline Personality Disorder
Authors: Thomas R. Lynch, William T. Trost, Nicholas Salsman, Marsha M. Linehan
Journal: Annual Review of Clinical Psychology (2006)

Since the introduction of Linehan's treatment manuals in 1993, dialectical behavior therapy (DBT) has been widely disseminated throughout multiple therapeutic settings and applied to a variety of diagnoses. The enthusiasm with which it was embraced by clinicians early on led some to question whether DBT's popularity was outstripping its empirical foundation. Most of the specific concerns raised regarding DBT's early empirical base have been meaningfully addressed in subsequent randomized controlled trials. This review provides a brief introduction to DBT, followed by a critical appraisal of empirical support for the treatment and a discussion of current research trends.
Activation block and trapping of penticainide, a disopyramide analogue, in the Na+ channel of rabbit cardiac Purkinje fibers.
Authors: E Carmeliet
Journal: Circulation Research (1988)

The blocking mechanism of the Na+ channel by penticainide, a disopyramide analogue, was studied in rabbit cardiac Purkinje fibers. Na+ channel activity was measured directly by recording the slowly inactivating Na+ current or indirectly by measuring Vmax. The two-microelectrode technique was used to measure currents under voltage-clamp conditions or to impose different degrees and durations of depolarizing pulses. The experimental results show 1) that penticainide exerted a pronounced use-dependent block not dependent on the duration of the depolarizing pulse, 2) that no block was observed in the absence of stimulation, even when the membrane was depolarized by conditioning prepulses, and 3) that recovery was slower the more negative the holding potential but could be accelerated by repeating the depolarizing pulse; there was not only use-dependent block but also use-dependent unblock. It is concluded that penticainide binds to the open Na+ channel and is trapped when the activated channel returns to the rested state.
Outcomes of Medicare Beneficiaries With Ventricular Assist Devices
Authors: Leslie W. Miller
Journal: JAMA (2009)

care. Low-cost generic drugs offer substantial advantages over their brand-name counterparts, as numerous studies have shown that patients’ spending on prescription drugs strongly influences their adherence to essential medication regimens. This effect is even more pronounced among low-income and other high-risk patient populations. To avoid all generic substitution in cardiovascular disease on the basis of such limited findings could create its own important problems for patients and the public health. Dr Reiffel takes issue with our failure to include case reports of harmful patient outcomes that he attributes to generic substitution of antiarrhythmic drugs. While case reports can be useful for generating hypotheses, we excluded them because, without a comparison group, it is impossible to draw valid causal inferences about associations. His comments about potential variability of potency also apply to differences among batches from one brand-name manufacturer, as well as to differences among brand-name products. Our analysis found no evidence that brand-name drugs were clinically superior to generic drugs even among narrow therapeutic index products, a category that includes antiarrhythmic agents. Physicians should be reassured by our findings indicating a lack of evidence of clinical superiority of brand-name cardiovascular medications when they choose to prescribe generic medications that are both effective and affordable. However, as our article acknowledged, the available data have limitations, so it is reasonable for physicians to be alert to possible idiosyncratic reactions and to be particularly vigilant with higher-risk patients when substituting different versions of certain life-saving drugs. Persistent concerns about the safety of generic verapamil or antiarrhythmic drugs in specific populations are best addressed by designing more definitive studies. This would help determine whether the anecdotal experiences and theoretical concerns described can be replicated in carefully conducted clinical trials.
Local Expression of Bovine Decorin by Cell-Mediated Gene Transfer Reduces Neointimal Formation After Balloon Injury in Rats
Authors: Jens W. Fischer, Michael G. Kinsella, Monika M. Clowes, Stephanie Lara, Alexander W. Clowes, Thomas N. Wight
Journal: Circulation Research (2000)

Abstract —Decorin is an extracellular matrix (ECM) proteoglycan that may modify vascular smooth muscle cell (SMC) function by altering the response to growth factors and the accumulation of ECM proteins during vascular injury. To investigate these possibilities in vivo, decorin was overexpressed at the site of arterial injury by cell-mediated gene transfer. Fischer rat SMCs were transduced in vitro with a retroviral construct that contained the bovine decorin gene and were subsequently seeded into injured rat carotid arteries. A species-specific antibody to bovine decorin and polymerase chain reaction primers were used to detect bovine decorin and distinguish it from endogenous rat decorin. Immunohistochemical and Northern analyses of rat carotid arteries revealed only low levels of rat decorin expression up to 8 weeks after balloon injury. However, after cell-mediated transfer of bovine decorin, strong expression of bovine decorin was verified by immunohistochemistry and reverse transcriptase–polymerase chain reaction. Four weeks after injury, the intimal area in vessels seeded with bovine decorin–overexpressing SMCs was significantly reduced by 35±4% (mean±SEM, n=9; P &lt;0.01). Decorin overexpression also induced a higher intimal nuclear density and decreased volume of ECM. Specifically, immunostaining for versican and fibronectin was markedly reduced. In contrast, immunostaining for collagen type I was increased, and electron microscopy confirmed that collagen accumulation was altered. Bromodeoxyuridine labeling indicated that intimal SMC proliferation was not affected by the expression of bovine decorin. In summary, we demonstrate that gene transfer of the ECM proteoglycan, decorin, into the injured arterial wall reduces intimal ECM volume and alters the composition of the ECM.
Staging Reclassification Affects Breast Cancer Survival
Authors: Ivo A. Olivotto, Pauline T. Truong, Caroline H. Speers
Journal: Journal of Clinical Oncology (2003)

The Art of Oncology: When the Tumor Is Not the Target is a section within the Journal of Clinical Oncology.It has attracted a series of interesting and enjoyable articles.However, the title of the section refers to the divisions between biologic and nonbiologic care, rather than their integration, and likens biologic therapy to target eradication.Should the title be reconsidered?The title Simultaneous Care: Treatment and Palliative Care Throughout Disease 1 is representative of the theme and ethos of the articles within the section.It describes the improvement of patient well-being-be it biologic, psychological, social, or spiritual-at all stages of the course of disease.The article from which this title is quoted discusses integrated therapy, the communication between patients and doctors of the uncertainties associated with treatment outcome, and the role of clinical research.Many patients and fellow health professionals see oncologists as having a key responsibility in delivering and integrating care.The oncologist is in an authoritative position because of his or her knowledge and experience.Oncologists also understand the value of collaboration by the team of caregivers, as well as the influence of the doctor-patient relationship on all the aforementioned aspects of patient well-being.The title of the section should thus emphasize integration of therapies, rather than their divisions.The metaphor of target eradication for biologic therapy is military in nature and is not appropriate for therapy and healing.It arouses associations of victory or failure, collateral damage, and a "fight to the end."It is not an accurate reflection of conventional anticancer therapies, which have always included the need to make weighted decisions on the likely benefits and harms of therapy.In particular, it does not reflect developments in anticancer therapy, which is increasingly directed toward the understanding and regulation of biologic behavior.Are there alternative metaphors?The metaphor of art itself might be considered and the section titled The Art of Oncology only.Art is created through intelligent and skilful responses to the complexities of life and the world around us.It is vital and transforming.It is in a continuous process of development and study.It is individual but also resonates in the broader world.At its best, The Art Of Oncology will reflect the principles that emerge after working through the complexities of integrated patient care.Would such a metaphor add the much needed weight to nonbiologic aspects of patient care?It should, and one knows that the published articles will do so.Are there any other offers?
Pancreatic islet beta cells drive T cell-immune responses in the nonobese diabetic mouse model.
Authors: E Larger, C Bécourt, J F Bach, C Boitard
Journal: The Journal of Experimental Medicine (1995)

The role of autoantigens and that of target organs in which tissue lesions develop remains elusive in most spontaneous models of autoimmune diseases. Whether the presence of target autoantigens is required for the recruitment of autoreactive lymphocytes is unknown in most cases. To evaluate the importance of islet cells in the development of autoimmunity in the nonobese diabetic (NOD) mouse, we generated beta cell-deprived mice by injecting a high dose of alloxan, a toxic agent specific for beta cells. In contrast with spleen cells from 6-mo-old naive NOD mice which transfer diabetes in irradiated 8-mo-old male recipients, spleen cells from age-matched NOD mice which received a single injection of alloxan at 3 wk of age did not transfer diabetes. With the exception of the ability to transfer diabetes, beta cell-deprived NOD mice showed maintained immune competence. Furthermore, sialitis developed with the expected intensity and prevalence in beta cell-deprived mice. Already committed "diabetogenic" spleen cells collected from spontaneously diabetic mice also showed a reduced capacity to transfer diabetes after their removal from the diabetic mice and transient "parking" in beta cell-deprived mice. Taken together, our data bring evidence that involvement of autoreactive T cells detected by the capacity to transfer diabetes requires the presence of target beta cells.
First Human Challenge Testing of a Pneumococcal Vaccine. Double-Blind Randomized Controlled Trial
Authors: Andrea M. Collins, Angela D. Wright, Elena Mitsi, Jenna F. Gritzfeld, Carole A. Hancock, Shaun H. Pennington, Duolao Wang, Ben Morton, Daniela M. Ferreira, Stephen B. Gordon
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vaccine candidates.Using our safe and reproducible experimental human pneumococcal colonization model, we aimed to determine the effect of 13-valent pneumococcal conjugate vaccine (PCV) on colonization.A total of 100 healthy participants aged 18-50 years were recruited into this double-blind randomized placebo-controlled trial. They were randomly assigned to PCV (n = 49) or hepatitis A (control, n = 50) vaccination and inoculated with 80,000 CFU/100 μl of Streptococcus pneumoniae (6B) per naris.Participants were followed up for 21 days to determine pneumococcal colonization by culture of nasal wash. The PCV group had a significantly reduced rate of 6B colonization (10% [5 of 48]) compared with control subjects (48% [23 of 48]) (risk ratio, 0.22; confidence interval, 0.09-0.52; P < 0.001). Density of colonization was reduced in the PCV group compared with the control group following inoculation. The area under the curve (density vs. day) was significantly reduced in the PCV compared with control group (geometric mean, 259 vs. 11,183; P = 0.017).PCV reduced pneumococcal colonization rate, density, and duration in healthy adults. The experimental human pneumococcal colonization model is a safe, cost-effective, and efficient method to determine the protective efficacy of new vaccines on pneumococcal colonization; PCV provides a gold standard against which to test these novel vaccines. Clinical trial registered with45340436.
Tumor Genetic Analyses of Patients with Metastatic Renal Cell Carcinoma and Extended Benefit from mTOR Inhibitor Therapy
Authors: Martin H. Voss, A. Ari Hakimi, Can G. Pham, A. Rose Brannon, Ying-Bei Chen, Luis F. Cunha, Oguz Akin, Han Liu, Shugaku Takeda, Sasinya N. Scott, Nicholas D. Socci, Agnes Viale, Nikolaus Schultz, Chris Sander, Victor E. Reuter, Paul Russo, Emily H. Cheng, Robert J. Motzer, Michael F. Berger, James J. Hsieh
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Rapalogs are allosteric mTOR inhibitors and approved agents for advanced kidney cancer. Reports of clonal heterogeneity in this disease challenge the concept of targeted monotherapy, yet a small subset of patients derives extended benefit. Our aim was to analyze such outliers and explore the genomic background of extreme rapalog sensitivity in the context of intratumor heterogeneity. Experimental Design: We analyzed archived tumor tissue of 5 patients with renal cell carcinoma, who previously achieved durable disease control with rapalogs (median duration, 28 months). DNA was extracted from spatially separate areas of primary tumors and metastases. Custom target capture and ultradeep sequencing was used to identify alterations across 230 target genes. Whole-exome sequence analysis was added to investigate genes beyond this original target list. Results: Five long-term responders contributed 14 specimens to explore clonal heterogeneity. Genomic alterations with activating effect on mTOR signaling were detected in 11 of 14 specimens, offering plausible explanation for exceptional treatment response through alterations in two genes (TSC1 and MTOR). In two subjects, distinct yet functionally convergent alterations activated the mTOR pathway in spatially separate sites. In 1 patient, concurrent genomic events occurred in two separate pathway components across different tumor regions. Conclusions: Analysis of outlier cases can facilitate identification of potential biomarkers for targeted agents, and we implicate two genes as candidates for further study in this class of drugs. The previously reported phenomenon of clonal convergence can occur within a targetable pathway which might have implications for biomarker development beyond this disease and this class of agents. Clin Cancer Res; 20(7); 1955–64. ©2014 AACR.
Drug resistance among tuberculosis cases in the European Union and European Economic Area, 2007 to 2012
Authors: Marieke J. Van der Werf, Csaba Ködmön, Vahur Hollo, Andreas Sandgren, Phillip Zucs
Journal: European Respiratory Journal (2014)

Resistance to tuberculosis (TB) drugs complicates the treatment and control of TB. The European Union and European Economic Area (EU/EEA) tuberculosis (TB) surveillance system collects detailed information on resistance to TB drugs. Using this information, we aim to provide an overview of the current TB drug resistance situation and trends in the EU/EEA by performing a descriptive analysis, including analysis of treatment outcomes, of the TB cases reported between January 2007 and December 2012.  About 90% of the new laboratory-confirmed cases were reported as pan-susceptible, 6% as mono-drug-resistant, 2% as poly-drug-resistant, 2% as multidrug drug resistant TB (MDR TB), excluding extensively drug resistant TB (XDR TB), and 0.2% as XDR TB. These percentages have remained stable in the study period. In previously treated laboratory-confirmed TB cases, the percentage with MDR excluding XDR TB declined until 2010 to 16%. The percentage of cases with mono-drug-resistant and poly-drug-resistant TB remained constant at about 8% and 2% whereas the percentage of XDR TB cases increased slightly to 2.6%. During the study period, treatment outcome results for all cases have been stable with overall 77.9% of the pan-susceptible cases, 69.6% of the monoresistant cases, 68.2% of the polyresistant cases, 32.2% of the MDR TB cases (excluding XDR TB), and 19.1% of the XDR TB cases treated successfully.  The treatment success rate target for new pulmonary culture-positive MDR TB cases of 70% has not been reached. In addition, drug resistance surveillance can be improved by more complete reporting of drug susceptibility results and treatment outcome.
PERFORATED DUODENAL ULCER SIMULATING ACUTE APPENDICITIS
Authors: K. C. L. Paddle
Journal: BMJ (1928)

THiJOYBxL 699 vi`tliin the related foramen may be so seriously lessenrd as to set up sciatic pain.In' these -cases thle maximum telnderness is over the affected articulation, anid protective sciatic scoliosis is usually p)reselit.Treatment must be' by prolonged recum- bencv and immobilization of the spine, if necessary in a plaster slhell, combinied with hyperaemia.In the con- valescent stage a supportive brace must be wvorn and postural r-e-education begun.In one resistant case Putti resected the diseased posterior articulatioins, with good effects.CONCLUSIONS.;Cases of low backache and sciatica form a distinet ortliopaedic group.They are capable of definite scientific analvsis and classification.To study them ilntelligently requires an appreciation of certain main problems wlhich are inidicated.The factors of trauma, anatomical type, good and bad posture, of anatomical variations, and of pathological le.sions of* the spiile are all concerned in wlhat is reall' a conibination problem.To jlmake ouir diagn-osis more accurate a routtine and systematic method of physical examiination is requiired.-Skilleld interpretation of good x-ra'y photographs, by those familiar with tlle clinical picture, is the most valuable a ccessorv aid in support of the diagniosis made.by the liitorv all(d examination.REFER1ENCES.