tbuckley/cabot-search huggingface dataset:
Carcinoembryonic Antigen as a Target for Therapeutic Anticancer Vaccines: A Review
Authors: Neil L. Berinstein
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To describe the features of carcinoembryonic antigen (CEA) that are important for its use in vaccination approaches and review the clinical experience with therapeutic vaccines targeting CEA. METHODS: A PubMed search was performed on CEA, along with various qualifiers such as cancer vaccines, epitopes, and function. Relevant articles were reviewed. RESULTS: CEA is a member of the immunoglobulin supergene family and may play a role in tumorigenesis. CEA protein is processed and presented on major histocompatibility complex (MHC) proteins for multiple alleles, including HLA A2, A3, and A24. T lymphocytes from healthy volunteers and cancer patients can recognize the processed epitopes of CEA and can become activated to lyse CEA-expressing tumors. Therapeutic vaccination approaches that have targeted CEA include vaccination with recombinant CEA protein, CEA anti-idiotype antibodies, and dendritic cells pulsed with agonist epitopes of CEA. Humoral responses have predominantly been induced with the first two approaches, whereas CD4 and CD8 responses, disease stabilization, and even objective clinical responses have been seen with the dendritic cell approach. Recently, CEA-poxvirus vectors encoding CEA and costimulatory molecules such as B7.1 have been shown to be safe and to induce increases in the frequency of T-cell precursors that recognize processed epitopes of CEA presented on MHC class 1 molecules. Disease stabilization has been seen in up to 37% of patients treated with these vaccines. CONCLUSION: Tolerance to CEA in patients with cancer can be overcome with several different vaccination approaches, and such vaccinations are safe and immunologically active. Poxvirus-based vaccines can reproducibly generate T-cell responses to CEA and to tumors expressing CEA. Clinical activity has been seen with poxvirus or dendritic cell approaches. Other approaches are also being explored.
Comparison of Phosphatase Isoenzymes PAP and PSA with Bone Scan in Patients with Prostate Carcinoma
Authors: SALVATORE AMICO, JEAN CLAUDE LIEHN, BERNARD DESOIZE, HÉLÈNE LARBRE, GÉRARD DELTOUR, JACQUES VALEYRE
Journal: Clinical Nuclear Medicine (1991)

The aim of this study was to assess the diagnostic value of five biological markers--prostate acid phosphatase (PAP), prostate specific antigen (PSA), tartrate resistant (Tr-ACP), and tartrate labile (TI-ACP) acid phosphatases, and alkaline phosphatase bone isoenzyme (B-ALP)--for the detection of bone metastases in patients with prostate carcinoma. Using the Tc-99m HMDP bone scans of 80 patients scored from 0 (normal) to 2 (diffuse bone involvement) as the "gold standard," a receiver operating characteristic (ROC) analysis was performed. This method allows the determination of different threshold values (corresponding to different couples of sensitivity and specificity) for the assays. An ROC curve comparison was also performed. Results show that B-ALP is the best test for such detection (area under the ROC curve = 0.93; Spearman Rank correlation with bone scan r' = 0.81). Among the other markers, PSA was found to be the best (area under the ROC curve = 0.81; Spearman Rank correlation with bone scan r' = 0.58). In addition to the prostatic tumor markers (PSA and PAP), we suggest the use of the low-cost B-ALP assay in the follow-up of prostate carcinoma patients to determine the optimum moment to perform a bone scan. A normal result of this assay indicates a very low probability of bone metastasis; conversely, raising of B-ALP concentration must lead to a bone scan.
TCT-760 All-Cause Mortality after Surgical or Trans-Catheter Aortic Valve Replacement in Patients with Low-Flow Low-Gradient Aortic Stenosis
Authors: Mahboob Alam, Salman Bandeali, Sukhdeep Basra, Salim S. Virani, Hani Jneid, David Paniagua, Biswajit Kar, Faisal G. Bakaeen, Joseph S. Coselli, Todd K. Rosengart, Neal Kleiman, Christie M. Ballantyne, Nasser M. Lakkis
Journal: Journal of the American College of Cardiology (2013)
Primary gastric small-cell neuroendocrine carcinoma
Authors: A. Shpaner, T. Yusuf
Journal: Endoscopy (2007)

Primary nonbronchogenic small-cell carcinoma has been decribed in a number of extrapulmonary sites, including the salivary glands, prostate, breast, esophagus, bladder, and cervix [1]. Primary small-cell gastric neuroendocrine carcinomas are extremely rare, representing less than 0.1 % of all primary gastric cancers [2] [3] [4] [5].
Less medicine is more
Authors: F. Godlee
Journal: BMJ (2009)

It would be fair to say that the BMJ tends towards less rather than more medicine. We’ve published a lot over the years on the risks of overtreatment and the problems of medicalisation. It’s not a bad default to have in times of economic hardship, although I hope we also do our bit to highlight evidence of undertreatment where it exists. In a recent letter David Oliver warned that, although ageing should not be routinely medicalised, there is a risk of “socialising” treatable problems in older people such as incontinence and falls ( BMJ 2009;338:b1200).

With that proviso, I’m drawn to several articles this week that …
The Closing of Shasta General Hospital-Reply
Authors: Andrew B. Bindman
Journal: JAMA (1991)

In Reply.—  The letter by Pugno et al highlights the value of multiple perspectives in evaluating policy changes. While they did not perceive a change in the availability of health care services in Shasta County after the public hospital closed, the patients who used that hospital provided a very different opinion. Physicians' and administrators' opinions do not substitute for the patients' point of view.  Pugno et al assert that we did not communicate with them in performing our evaluation. In fact, we consulted with many of Shasta County's health care providers and community leaders and the chief executive officers of Mercy Medical Center and Redding Medical Center, and the county health officer and the state assemblyman from Shasta wrote letters to support our proposal to funding agencies.  We were aware of the transition of the Family Practice Residency from Shasta General Hospital to Mercy Medical Center and hoped that this
Risk factors for recurrent emergency department visits for asthma.
Authors: R E Dales, I Schweitzer, P Kerr, L Gougeon, R Rivington, J Draper
Journal: Thorax (1995)

BACKGROUND--Patients presenting with asthma to emergency departments have lost control of their disease, have significant airways obstruction, and frequently require admission to hospital. Although even one visit is not desirable, there is a more disturbing subgroup who repeatedly visit the emergency department. METHODS--To investigate the reasons for multiple emergency visits, a questionnaire was given to 448 consecutive patients presenting to the two largest adult emergency departments in Ottawa, Canada between November 1989 and April 1991. Within this cohort, those who had made at least three visits in the past year were compared with controls (only one visit in the past year). RESULTS--Although inhaled corticosteroid use increased with multiple visits (indicating increased asthma severity), only 60% of those visiting at least three times in the past year were taking inhaled corticosteroids. Chronic undermedication relative to disease severity was apparent among the cases. The number of visits was associated with nocturnal asthma on a regular basis, work and school absenteeism, frequent visits to their regular physician, and frequent admissions to hospital. Visits were not related to psychological health, environmental allergens/irritants, or lack of perceived asthma severity. CONCLUSIONS--The recommendations of current asthma guidelines are not reaching these patients. The issue of translating guidelines from paper to practice must be addressed before highly effective medications can have an important impact on the frequency of emergency department visits.
Abstract 3338: IGFBP2 promotes EGFR/STAT3 nuclear crosstalk in glioma
Authors: YingXuan Chua, Yuexin Liu, Limei Hu, Kirsi Granberg, Maartje Verploegen, Wei Zhang
Journal: Cancer Research (2014)

Abstract Insulin-like growth factor binding protein 2 (IGFBP2) is a pleiotropic secreted protein that is overexpressed in various cancers including glioma. Extracellular IGFBP2 binds and modulates the activity of insulin growth factors I and II (IGFI and IGFII) while cytoplasmic IGFBP2 interacts with signaling pathways essential for cell proliferation and survival. The versatility of IGFBP2 as a secreted or cytoplasmic signaling effector is widely characterized; however, the functions of nuclear IGFBP2 remain largely unknown. Through genomic and functional analyses of glioma, we mechanistically elucidated the role of nuclear IGFBP2 and discovered a functional interaction of IGFBP2 with epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3) proteins. Our findings established a signaling hierarchy of IGFBP2-EGFR-STAT3; IGFBP2 not only upregulates EGFR/STAT3 signaling activity, but also facilitates EGFR nuclear translocation and subsequent nuclear EGFR/STAT3 activity. Furthermore, mutation of the nuclear localization signal of IGFBP2 demonstrated that nuclear translocation of IGFBP2 is critical to promote the nuclear activity of EGFR. By identifying the role of IGFBP2 in perpetuating nuclear crosstalk between EGFR/STAT3, our study further reveals the importance of exploiting IGFBP2 as a target for glioma therapy. Citation Format: YingXuan Chua, Yuexin Liu, Limei Hu, Kirsi Granberg, Maartje Verploegen, Wei Zhang. IGFBP2 promotes EGFR/STAT3 nuclear crosstalk in glioma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3338. doi:10.1158/1538-7445.AM2014-3338
Informed Choice in Cancer Screening
Authors: H. Gilbert Welch
Journal: JAMA Internal Medicine (2013)

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Observations on the Assessment of Cardiac Hypertrophy Utilizing a Chamber Partition Technique
Authors: KEVIN E. BOVE, DAVID T. ROWLANDS, RALPH C. SCOTT
Journal: Circulation (1966)

Three hundred fifty-four adult human hearts were dissected utilizing a technique similar to those previously described by Müller 1 and Lewis. 2 A classification was synthesized on the basis of anatomic characteristics of 100 normal hearts. Presumptive evidence of either left or right ventricular overload, provided by clinical and autopsy observation, served as essential corollary data in establishing normal limits. The existence of hypertrophy was readily recognized in hearts in which one or both ventricles increased in mass sufficiently to surpass the defined upper limit. Isolated ventricular hypertrophy of mild degree was recognized as a consequence of an abnormal LV+S/RV ratio in 58 hearts in which ventricular weights were within the normal range. Factors which would be expected to result in left or right ventricular overload were demonstrable in 42 of these cases. Atrial hypertrophy correlated well with hypertrophy of the corresponding ventricle and served as an invaluable aid in recognition of mild degrees of combined ventricular hypertrophy. This classification constitutes the basis for a subsequent correlative electrocardiographic study.
Paediatricians “have grave concerns” about GMC procedures for child protection work
Authors: Owen Dyer
Journal: BMJ (2008)

The annual meeting of the Royal College of Paediatrics and Child Health has chosen not to back a strongly worded motion that condemned the UK General Medical Council’s handling of cases of misconduct in child protection work.

But the meeting did pass a motion that voiced milder criticism of the GMC, which many paediatricians accuse of giving too much weight to vexatious and serial complaints against child protection specialists.

The proposed motion would have declared that the college had “no confidence” in GMC procedures, but the motion that was passed refers only to the college’s “grave concerns.”

Apart from that change the motion was passed as originally …
LOCAL USE OF GUAIACOL IN THE TREATMENT OF FREQUENT, PAINFUL URINATION.
Authors: JESSE HAWES
Journal: JAMA (1900)

I wish to present guaiacol as a remedy for the treatment of painful urination, which, so far as I am aware, has not been mentioned in the therapeutics of this annoying disorder. Frequent urination is a symptom of various affections, but guaiacol is applicable only to those cases in which the cause of the symptom is located in the extreme inner portion of the urethra, usually in a space ¾ to 1¼ inches external to the urethrovesical orifice. Many diseases of the genitourinary system cause urgent micturition, yet it is probable that all other causes combined furnish fewer cases of frequent painful urination than the one condition under consideration. Disease of the deep urethra is, I believe, usually mistaken by the majority of general practitioners for cystitis or "irritable bladder." I am quite sure that nearly all the cases which years ago I called cystitis and irritable bladder were not
Donor Blood Labeling by Race
Authors: Robert T. K. Leardi
Journal: JAMA (1973)

<h3>To the Editor.—</h3> A topic in the Jan 8, 1973, issue of<i>JAMA</i>in the Q&amp;A section deserves comment. The question concerns labeling of blood by race of donor. Some medical benefit can be obtained by knowing not only the race but the sex of the blood donor. It is unfortunate that such a topic gets involved with accusations of racism, as well as nonscientific hysteria. I agree that there is no scientific evidence of incompatibility on a racial basis. Individuals with diseases such as sickle cell anemia are not accepted as donors, and therefore blood from these people does not appear on the blood bank shelf. Any blood banker who has attempted to crossmatch blood for an actively bleeding patient with an atypical antibody knows that this can be a long and difficult task, usually involving the screening of many possible donor units. I am including a table showing
Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients
Authors: Paul Feuerstadt, Ari L. Bunim, Heriberto Garcia, Jordan J. Karlitz, Hatef Massoumi, Amar J. Thosani, Andrew Pellecchia, Allan W. Wolkoff, Paul J. Gaglio, John F. Reinus
Journal: Hepatology (2009)

Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody–negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients. (HEPATOLOGY 2010.)
Specific Roles of the p110α Isoform of Phosphatidylinsositol 3-Kinase in Hepatic Insulin Signaling and Metabolic Regulation
Authors: Victoria Rotter Sopasakis, Pixu Liu, Ryo Suzuki, Tatsuya Kondo, Jonathon Winnay, Thien T. Tran, Tomoichiro Asano, Graham Smyth, Mini P. Sajan, Robert V. Farese, C. Ronald Kahn, Jean J. Zhao
Journal: Cell Metabolism (2010)
Transient Hemiplegia following Injection of Sodium Morrhuate
Authors: W. S. Gardner
Journal: BMJ (1947)

SUPPRESSION OF SYPHILIS AND PRECOCIOUS TERTIARISMMEDBcALTIJ 613 apparently unaltered.Penicillin treatment was purposely de- layed so that non-specific effects could be excluded.Ten days after* beginning treatment, penicillin in oil-wax suspen- sion having been superimposed on the arsenic-bismuth therapy, only scattered pigmentation remained on the face and the gum- matous lesion was obviously healing rapidly. ConclusionsIt seems probable that in November, 1945, this man had secondary syphilis, possibly masked by scabies, and that the small amount of penicillin (about 600,000 units) given at that time was sufficient temporarily to suppress the diFease.The relapse lesions, appearing 18 months later, were of a secondo-tertiary type.This case suggests that penicillin in inadequate dosage over a short period can, like the arsphenamines, produce the phenomenon of precocious tertiarism.It illustrates the importance of making an accurate diagnosis in any dermato- logical condition before using penicillin by injection.
Exercise-induced regional dysfunction with subcritical coronary stenosis.
Authors: J D Lee, T Tajimi, B Guth, R Seitelberger, M Miller, J Ross
Journal: Circulation (1986)

The hypothesis was tested that regional myocardial contractile dysfunction can detect subtle regional coronary blood flow maldistribution induced by exercise. In seven dogs, left ventricular pressure (micromanometer), regional systolic wall thickening (WTh, sonomicrometry), and myocardial blood flow (MBF, microspheres) were measured when mild degrees of coronary artery stenosis were produced during treadmill exercise. During exercise without coronary stenosis, WTh increased by 21 +/- 12% (SD), and transmural MBF increased uniformly. In each dog, two levels of coronary stenosis were produced during exercise by adjusting the coronary hydraulic cuff: (1) St-Ex I, where WTh during exercise failed to increase significantly (average change 0 +/- 7%), and (2) St-Ex II, where WTh during exercise decreased moderately from the resting control value (average -20 +/- 8%). In the potentially ischemic zone coronary hyperemia occurred with each run: resting subendocardial MBF was 1.09 +/- 0.30 mg/g/min, and it was 3.04 +/- 0.83 during control exercise, 2.48 +/- 0.75 during St-Ex I, and 1.55 +/- 0.59 ml/g/min during St-Ex II (p less than .01 compared with control exercise and control area). The subendocardial-subepicardial blood flow ratio fell from 1.32 +/- 0.27 during control exercise to 1.07 +/- 0.20 (p less than .05) during St-Ex I, and to 0.64 +/- 0.15 (p less than .01) with St-Ex II. Changes in the subendocardial electrogram and reactive hyperemia occurred more consistently during St-Ex II than St-Ex I. Thus, failure of regional function to increase during exercise detected slight maldistribution of regional MBF, whereas reduction of regional function during exercise of 10% or more below the resting value was a reliable marker of a regional flow defect and was always associated with other evidence of ischemia. Therefore, regional dysfunction during exercise can detect subcritical but functionally significant coronary stenosis, which may allow regional wall motion to be used for detecting coronary artery disease at a relatively early stage.
Abstract S1-5: Interaction between Goserelin and Tamoxifen in a Controlled Clinical Trial of Adjuvant Endocrine Therapy in Premenopausal Breast Cancer.
Authors: A Sverrisdottir, H Johansson, U Johansson, J Bergh, S Rotstein, LE Rutqvist, T. Fornander
Journal: Cancer Research (2010)

Abstract Background: Ovarian ablation improves survival in premenopausal women with early breast cancer, but the potential added value by luteinizing hormone-releasing hormone agonists (LHRH-a) to tamoxifen, is still not clear. There has been lack of data reported separately for patients who underwent randomization to both LHRH-a and tamoxifen. Patients and Methods: In Stockholm, 927 patients assigned to the Zoladex in Premenopausal Patients (ZIPP) trial, were included in a 2 x 2 factorial randomization to goserelin (3.6 mg subcutaneously, q 28d), tamoxifen (40 mg daily), the combination of goserelin and tamoxifen or no endocrine therapy for two years, with or without chemo-and/or radiotherapy. The trial was designed to examine the effect of goserelin and the role of interaction between goserelin and tamoxifen in adjuvant therapy of premenopausal breast cancer. We examined as well, the impact of different estrogen receptor (ER) content on treatment effect. The definition of first event was breast cancer recurrence, contra lateral breast cancer or death. The ER content was determined by isoelectric focusing on polyacrylamide gel and receptor values normalized to DNA content. Results: After a median follow up of 12.3 years, goserelin reduced the risk of first event by 32% (p=0.005) in the absence of tamoxifen and tamoxifen reduced the risk by 27% (p=0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (p=0.021) and there was a significant interaction between goserelin and tamoxifen (p=0.025). In highly ER positive tumours, there were 29% fewer events among goserelin treated (p=0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, p=0.007). For tamoxifen, there was not a significant risk reduction at different ER levels, but there was a trend towards interaction between goserelin and tamoxifen effect among the highly ER positive (p=0.076). Discussion: In this strictly randomized cohort of endocrine responsive premenopausal breast cancer, goserelin as well as tamoxifen, reduces the risk of recurrence. However, the combination of goserelin and tamoxifen is not superior to either modality alone. The effect of goserelin seems to be modified by ER levels, whereas tamoxifen effect is not. Women with strongly estrogen receptor positive tumours may benefit more from goserelin treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-5.