tbuckley/cabot-search huggingface dataset:
Phase II Trial of Anastrozole Plus Goserelin in the Treatment of Hormone Receptor–Positive, Metastatic Carcinoma of the Breast in Premenopausal Women
Authors: Robert. W. Carlson, Richard Theriault, Christine M. Schurman, Edgardo Rivera, Cathie T. Chung, See-Chun Phan, Banu Arun, Kristine Dice, Vivian Y. Chiv, Marjorie Green, Vicente Valero
Journal: Journal of Clinical Oncology (2010)

To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin.Premenopausal women with estrogen and/or progesterone receptor-positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity.Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities.The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor-positive metastatic breast cancer.
Electrocardiographic Abnormalities in Individuals With Long-Duration Type 1 Diabetes
Authors: Barbara E.K. Klein, Ronald Klein, Patrick E. McBride, Scot E. Moss, Ronald J. Prineas, Jennifer O. Reinke
Journal: Diabetes Care (2005)

Individuals with diabetes are more likely to experience cardiovascular morbidity and mortality than those without diabetes (1–4). We sought to investigate prevalence relationships of electrocardiogram (ECG) abnormalities and risk indicators that might be intervened upon in people with long-duration type 1 diabetes.

The study was population based. It consisted of survivors of a cohort (identified in 1979–1980) who were diagnosed with diabetes before 30 years of age, taking insulin, and receiving care in 11 counties in Wisconsin (5). The institutional review board approved the study, which conformed to the principles of the Declaration of Helsinki. Informed consent was obtained. Participants have been seen every 4–6 years for examinations (6) and are contacted annually. At the 2000–2001 examination, the following measures were added: waist and hip circumference; sitting (7), standing, and supine blood pressures; peak expiratory flow rate (PEFR) (8); and ECG. Standard fundus photographs were omitted from the 2000–2001 examination. Blood was obtained for measurement of LDL (9) and HDL (10) cholesterol and serum triglycerides (11), fasting blood glucose (12), and GHb (13). A standard medical history …
Activation of E-prostanoid4 and E-prostanoid2 receptors inhibits TNF- release from human alveolar macrophages
Authors: M. J. Ratcliffe, A. Walding, P. A. Shelton, A. Flaherty, I. G. Dougall
Journal: European Respiratory Journal (2007)

Prostaglandin (PG)E 2 has been shown to inhibit mediator release from human alveolar macrophages (AMs), but the prostanoid receptor(s) mediating this response have not yet been documented. To investigate this, the present authors conducted a range of pharmacological and expression-based studies in monocyte-derived macrophages (MDMs) and AMs. MDMs were obtained by in vitro differentiation of monocytes from the peripheral blood of healthy human volunteers. Human AMs were obtained by perfusion of lung tissue from carcinoma resection patients. In MDMs, PGE 2 potently inhibited lipopolysaccharide-induced tumour necrosis factor (TNF)-α release (p[A] 50 8.51±0.11, maximum inhibition 95.9±4.8%). In human AMs, PGE 2 also inhibited TNF-α release but the observed concentration–effect curve was very flat and inhibition was incomplete. The shape of the PGE 2 curve in AMs suggested that its effects were mediated by activation of a heterogeneous receptor population. Expression studies combined with the use of various E-prostanoid (EP) receptor agonists and a selective EP 4 -receptor antagonist (Ono-AE2-227) confirmed that the inhibitory effects of PGE 2 in both AMs and MDMs were mediated by activation of EP 4 and EP 2 receptors. These data indicate that both E-prostanoid 4 and E-prostanoid 2 selective agonists may have anti-inflammatory properties in lung diseases where macrophages play a role.
Enzymatic and morphometric evidence for Crohn's disease as a diffuse lesion of the gastrointestinal tract.
Authors: W T Dunne, W T Cooke, R N Allan
Journal: Gut (1977)

Intestinal disaccharidase and dipeptidase activities were measured in mucosal biopsies from the proximal jejunum in 20 patients with Crohn9s disease apparently confined to the distal ileum or large bowel, 14 patients with ulcerative colitis, and 14 healthy volunteers who acted as controls. The dissecting microscopy and histological appearance of the biopsies were normal (Gd 0-1) except for two which showed grade 2 changes. tbiopsy morphometry showed a reduction of jejunal mucosal surface area and an increase in mucosal volume in patients with Chron9s disease when compared with the other two groups. The mucosal enzymes studies demonstrated that patients with Crohn9s disease had a significant reduction in brush-border enzymes (disaccharidase) but no change in cytoplasmic enzyme activity (dipeptidases). The enzyme levels in patients with ulcerative colitis did not differ from the healthy controls. The reduction of brush-border enzymes with normal cytoplasmic enzymes in the presence of abnormal morphometry is further evidence of the concept of Crohn9s disease as a diffuse lesion of the gastrointestinal tract. It also suggests that there is either specific damage to the microvilli or some other abnormality such as impairment of enzyme synthesis.
Targeting the Cytoprotective Chaperone, Clusterin, for Treatment of Advanced Cancer
Authors: Amina Zoubeidi, Kim Chi, Martin Gleave
Journal: Clinical Cancer Research (2010)

Many strategies used to kill cancer cells induce stress-responses that activate survival pathways to promote emergence of a treatment resistant phenotype. Secretory clusterin (sCLU) is a stress-activated cytoprotective chaperone up-regulated by many varied anticancer therapies to confer treatment resistance when overexpressed. sCLU levels are increased in several treatment recurrent cancers including castrate resistant prostate cancer, and therefore sCLU has become an attractive target in cancer therapy. sCLU is not druggable with small molecule inhibitors, therefore nucleotide-based strategies to inhibit sCLU at the RNA level are appealing. Preclinical studies have shown that antisense oligonucleotide (ASO) or siRNA knockdown of sCLU have preclinical activity in combination with hormone- and chemotherapy. Phase I and II clinical trial data indicate that the second generation ASO, custirsen (OGX-011), has biologic and clinical activity, suppressing sCLU expression in prostate cancer tissues by more than 90%. A randomized study comparing docetaxel-custirsen to docetaxel alone in men with castrate resistant prostate cancer reported improved survival by 7 months from 16.9 to 23.8 months. Strong preclinical and clinical proof-of-principle data provide rationale for further study of sCLU inhibitors in randomized phase III trials, which are planned to begin in 2010.
Suramin Therapy in AIDS and Related Disorders
Authors: Bruce D. Cheson
Journal: JAMA (1987)

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5,1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 μmol/L or higher (≥2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemopneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS. (<i>JAMA</i>1987;258:1347-1351)
Functional resemblance and the internalization of rules
Authors: Gerard O'Brien, Jon Opie
Journal: Behavioral and Brain Sciences (2001)

Kubovy and Epstein distinguish between systems that follow rules, and those that merely instantiate them. They regard compliance with the principles of kinematic geometry in apparent motion as a case of instantiation. There is, however, some reason to believe that the human visual system internalizes the principles of kinematic geometry, even if it does not explicitly represent them. We offer functional resemblance as a criterion for internal representation. [Kubovy &amp; Epstein]
Topical immunomodulators for the treatment of external genital warts, cutaneous warts and molluscum contagiosum
Authors: U.R. Hengge, M. Cusini
Journal: British Journal of Dermatology (2003)

Topical immunomodulators (TIMs) include both immunostimulatory and immunosuppressive agents. Newer immunostimulatory compounds such as imidazoquinolines (e.g. imiquimod) act by cytokine secretion from monocytes/macrophages (interferon-α, interleukin-12, tumour-necrosis factor-α), leading to a Th1-dominance and cell-mediated immunity. This immune milieu has been clinically used to treat viral infections such as human papillomavirus (condyloma and common warts), herpes simplex virus and mollusca in immunocompetent and immunosuppressed patients.
Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines.
Authors: A L Glasebrook, F W Fitch
Journal: The Journal of Experimental Medicine (1980)

Several T cell clones have been derived by limiting dilution of secondary mixed leukocyte culture cells stimulated by H-2- and M locus (Mls)-disparate spleen cells. When examined for the expression of cytolytic activity and the ability to proliferate, these cell clones can be classified into two major categories. One type of cell is noncytolytic; when cultured with irradiated spleen cells, such clones proliferate in response to Mls determinants. Some, but not all, of these clones express Lyt-1 alloantigens. The other type of cell is cytolytic; these clones do not proliferate when cultured with irradiated allogeneic spleen cells unless supernatant fluid (SF) is added. These cytolytic clones express Lyt-2 alloantigens. Some cytolytic clones are specific for H-2Kd and others for H-2Dd alloantigens. Still other cytolytic cell clones exhibit cross-reactive lysis of different H-2-bearing tumor and Con A blast target cells. Noncytolytic T cell clones, when stimulated by Mls antigens, were examined for their ability to promote proliferation of cytolytic T cell clones. All of the noncytolytic cell clones tested were able to promote proliferation of cytolytic cell clones with the concomitant expression of cytolytic activity directed toward the original stimulating alloantigen (H-2d). Amplification of cytolytic activity was dependent upon stimulation of the noncytolytic amplifier T cell clones by Mls antigens. Specific alloantigen (signal 1), however, was not required for proliferation of the cytolytic cell clones; the amplifying signal (signal 2), delivered by the amplifier cell clones, was sufficient alone to promote proliferation of the cytolytic cell clones. Whereas proliferation of the amplifier cells was radiosensitive, the generation of the soluble amplifying signal was radioresistant. Amplification of cytolytic activity was observed when either amplifier cells were physically separated from responding cytolytic cells in Marbrook cultures or when cytolytic cells were cultured with SF collected from amplifier cell cultures. The amplifying factors were neither antigen specific nor strain specific and could be produced by Lyt-1- cells. The availability of cloned T cell lines that retain specific biologic function offers unique opportunities to characterize cell surface proteins and cell-cell interactions.
The Manitoba Inflammatory Bowel Disease Cohort Study: Prolonged Symptoms Before Diagnosis—How Much Is Irritable Bowel Syndrome?
Authors: Twila Burgmann, Ian Clara, Lesley Graff, John Walker, Lisa Lix, Patricia Rawsthorne, Cory McPhail, Linda Rogala, Norine Miller, Charles Noah Bernstein
Journal: Clinical Gastroenterology and Hepatology (2006)
Plasmacytoid dendritic cells of melanoma patients present exogenous proteins to CD4+ T cells after FcγRII-mediated uptake
Authors: Daniel Benitez-Ribas, Gosse J. Adema, Gregor Winkels, Ina S. Klasen, Cornelis J.A. Punt, Carl G. Figdor, I. Jolanda M. de Vries
Journal: The Journal of Experimental Medicine (2006)

Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune responses by producing type I interferons. Although human pDCs can induce T cell responses upon viral infection, it remains unclear if pDCs can present exogenous antigens. Here, we show that human pDCs exploit FcγRII (CD32) to internalize antigen–antibody complexes, resulting in the presentation of exogenous antigen to T cells. pDCs isolated from melanoma patients vaccinated with autologous monocyte-derived peptide- and keyhold limpet hemocyanin (KLH)–loaded dendritic cells, but not from nonvaccinated patients or patients that lack a humoral response against KLH, were able to stimulate KLH-specific T cell proliferation. Interestingly, we observed that internalization of KLH by pDCs depended on the presence of serum from vaccinated patients that developed an anti-KLH antibody response. Anti-CD32 antibodies inhibited antigen uptake and presentation, demonstrating that circulating anti-KLH antibodies binding to CD32 mediate KLH internalization. We conclude that CD32 is an antigen uptake receptor on pDCs and that antigen presentation by pDCs is of particular relevance when circulating antibodies are present. Antigen presentation by pDCs may thus modulate the strength and quality of the secondary phase of an immune response.
The Effect of Third-Party Payment on the Practice of Psychotherapy
Authors: PAUL CHODOFF
Journal: American Journal of Psychiatry (1972)

Many issues are raised by the use of third-party mechanisms such as health insurance to pay for psychotherapeutic services. These include such questions as confidentiality, diagnostic and reporting practices, the medical versus the nonmedical model, and transference-countertransference relationships. The role of peer review and other quality control mechanisms will undoubtedly increase as psychiatry is asked to document more fully than in the past the criteria for various forms of psychotherapy and to demonstrate their effectiveness.
Illegitimacy—A Professional Concern
Authors: Kenneth W. Sell
Journal: JAMA (1977)

Despite the availability of liberalized abortions and surgical sterilization procedures as well as a wide assortment of contraceptive drugs and devices, the number of illegitimate children is escalating. More than 1,700,000 illegitimate children were born in the five-year period between 1966 and 1970. In contrast to the overall birth rate, which is declining, the rate of illegitimate births has been increasing and now exceeds 10% of all births. In many urban areas illegitimacy stands at 40%, and in some it exceeds 50%. "New life styles" and the reduced social stigma of illegitimacy have combined to produce the highest proportion of births out of wedlock on the American record. It is not surprising that the law and legal practice in the United States are adapting to changing and unchanging social facts—changing in terms of the increased acceptability of illegitimacy, and unchanging in terms of each child's right to, and need of,
Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels
Authors: Atfa Sassi, Sandra Lazaroski, Gang Wu, Stuart M. Haslam, Manfred Fliegauf, Fethi Mellouli, Turkan Patiroglu, Ekrem Unal, Mehmet Akif Ozdemir, Zineb Jouhadi, Khadija Khadir, Leila Ben-Khemis, Meriem Ben-Ali, Imen Ben-Mustapha, Lamia Borchani, Dietmar Pfeifer, Thilo Jakob, Monia Khemiri, A. Charlotta Asplund, Manuela O. Gustafsson, Karin E. Lundin, Elin Falk-Sörqvist, Lotte N. Moens, Hatice Eke Gungor, Karin R. Engelhardt, Magdalena Dziadzio, Hans Stauss, Bernhard Fleckenstein, Rebecca Meier, Khairunnadiya Prayitno, Andrea Maul-Pavicic, Sandra Schaffer, Mirzokhid Rakhmanov, Philipp Henneke, Helene Kraus, Hermann Eibel, Uwe Kölsch, Sellama Nadifi, Mats Nilsson, Mohamed Bejaoui, Alejandro A. Schäffer, C.I. Edvard Smith, Anne Dell, Mohamed-Ridha Barbouche, Bodo Grimbacher
Journal: Journal of Allergy and Clinical Immunology (2014)
How Can Physicians Keep Up-to-Date?
Authors: Christine Laine, MD, MPH, David S. Weinberg, MD, MSc
Journal: Annual Review of Medicine (1999)

Keeping one's personal fund of knowledge current is one of the most formidable challenges that physicians face. This article considers a few strategies that may help physicians as they struggle to keep their knowledge up-to-date. Physicians need to develop their own goals for staying current, systematically and periodically search the literature for high-quality material relevant to the topics on their agendas, become facile with critical appraisal of the literature, and schedule time for reading. One of the responsibilities of any professional is to maintain expertise, and this responsibility is probably nowhere more critical, or more difficult, than in the profession of medicine.
Impact of risk factors on outcomes in early-stage Hodgkin's lymphoma: an analysis of international staging definitions
Authors: B. Klimm, H. Goergen, M. Fuchs, B. von Tresckow, B. Böll, J. Meissner, A. Glunz, V. Diehl, H. T Eich, A. Engert, P. Borchmann
Journal: Annals of Oncology (2013)
Experimental haemarthrosis produces mild inflammation associated with intracellular Maltese crosses.
Authors: S J Choi, H R Schumacher, G Clayburne
Journal: Annals of the Rheumatic Diseases (1986)

Injection of autologous blood into rabbit joints induces an inflammatory reaction with Maltese cross-like birefringent spherulites. Similar microspherules seen in human joint fluids may be formed by lipids derived from breakdown of erythrocytes and other cells.
Impact of peripheral neuropathy on bone density in patients with type 1 diabetes.
Authors: M Rix, H Andreassen, P Eskildsen
Journal: Diabetes Care (1999)

To investigate whether peripheral neuropathy (PN), as part of the microangiopathic complex, affects bone mineral density (BMD) of the peripheral or the axial skeleton in patients with type 1 diabetes.Three study groups were examined. Group 1 comprised 21 males with type 1 diabetes and severe PN with a mean (range) duration of diabetes of 28 (9-59) years and an HbA1c of 8.2% (6.3-10.4). Group 2 comprised 21 male type 1 diabetic patients with absent or mild PN matched to patients of group 1 regarding age, weight, and duration of diabetes. Group 3 comprised 21 control subjects. BMD was measured by dual-energy x-ray absorptiometry (DEXA) and by quantitative ultrasound of the calcaneus. PN was determined by biothesiometry. Levels of physical activity were assessed through guided questionnaires.In group 1, BMD was significantly reduced at all measured sites, compared with an expected Z score of 0 (spine, -1.01 +/- 0.34; femur, -0.94 +/- 0.25; forearm, -1.10 +/- 0.36). To a lesser extent, but still significantly, group 2 also showed reduced BMD values (spine, -0.60 +/- 0.26; femur, -0.55 +/- 0.25; forearm, -1.05 +/- 0.36), whereas group 3 had normal BMD values (-0.23 +/- 0.25, -0.10 +/- 0.21, -0.07 +/- 0.25, respectively). Group 1 had lower mean BMD levels than group 2 and group 3 at all measured sites, but a significant difference was found only between groups 1 and 3 at the site of the femur (analysis of variance, P < 0.05). Broadband ultrasound attenuation (BUA) of the calcaneus was significantly reduced in group 1 compared with groups 2 and 3 (108 +/- 3 vs. 115 +/- 2 and 115 +/- 2). Significant correlations between all DEXA measurements and BUA were demonstrated in both groups 1 and 2 (r values between 0.54 and 0.75). No significant differences in physical activity levels or body composition were demonstrated between the two patient groups.The present results suggest that in patients with type 1 diabetes, PN may be an independent risk factor for reduced BMD in the affected limbs as well as in the skeleton in general.
Refractory asthma in the UK: cross-sectional findings from a UK multicentre registry
Authors: L. G. Heaney, C. E. Brightling, A. Menzies-Gow, M. Stevenson, R. M. Niven
Journal: Thorax (2010)

<h3>Introduction</h3> Refractory asthma represents a significant unmet clinical need where the evidence base for the assessment and therapeutic management is limited. The British Thoracic Society (BTS) Difficult Asthma Network has established an online National Registry to standardise specialist UK difficult asthma services and to facilitate research into the assessment and clinical management of difficult asthma. <h3>Methods</h3> Data from 382 well characterised patients, who fulfilled the American Thoracic Society definition for refractory asthma attending four specialist UK centres—Royal Brompton Hospital, London, Glenfield Hospital, Leicester, University Hospital of South Manchester and Belfast City Hospital—were used to compare patient demographics, disease characteristics and healthcare utilisation. <h3>Results</h3> Many demographic variables including gender, ethnicity and smoking prevalence were similar in UK centres and consistent with other published cohorts of refractory asthma. However, multiple demographic factors such as employment, family history, atopy prevalence, lung function, rates of hospital admission/unscheduled healthcare visits and medication usage were different from published data and significantly different between UK centres. General linear modelling with unscheduled healthcare visits, rescue oral steroids and hospital admissions as dependent variables all identified a significant association with clinical centre; different associations were identified when centre was not included as a factor. <h3>Conclusion</h3> Whilst there are similarities in UK patients with refractory asthma consistent with other comparable published cohorts, there are also differences, which may reflect different patient populations. These differences in important population characteristics were also identified within different UK specialist centres. Pooling multicentre data on subjects with refractory asthma may miss important differences and potentially confound attempts to phenotype this population.