tbuckley/cabot-search huggingface dataset:
Writing as therapy
Authors: T. Greenhalgh
Journal: BMJ (1999)

Recently JAMA published a trial of a “get it off your chest” writing exercise.1 Seventy one patients with asthma or rheumatoid arthritis were randomised to write about the most stressful experience they had ever had or about their plans for the day for three separate 20 minute periods over a few days and then to drop their completed essay into a sealed box. The study apparently showed a significant improvement in standard measures of disease severity in both conditions four months later. An accompanying editorial exhorted readers to abandon the Cartesian split between mind and body, and acknowledge the growing evidence in support of behavioural interventions that reduce emotional stress as therapies for diseases that are mediated in part by the immune system.2 Do these results stand up, and is it therefore time to heed this call?

Therapeutic writing is a hot topic on both sides of the Atlantic. In the United Kingdom the focus tends to be on descriptive accounts and somewhat speculative psychodynamic explanations for subjective improvements in health status. A recent book provides moving case studies of patients who came to terms with physical or psychological illness through creative writing and …
Self-blame–Selective Hyperconnectivity Between Anterior Temporal and Subgenual Cortices and Prediction of Recurrent Depressive Episodes
Authors: Karen E. Lythe, Jorge Moll, Jennifer A. Gethin, Clifford I. Workman, Sophie Green, Matthew A. Lambon Ralph, John F. W. Deakin, Roland Zahn
Journal: JAMA Psychiatry (2015)

Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional magnetic resonance imaging connectivity (fMRI) between the right superior anterior temporal lobe (RSATL) and the subgenual cingulate cortex and adjacent septal region (SCSR) when experiencing self-blaming emotions relative to emotions related to blaming others (eg, "indignation or anger toward others").This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, "feeling guilty for everything"), known to have a key role in cognitive vulnerability to MDD.It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments.OBJECTIVE To use fMRI in remitted MDD at baseline to test the hypothesis that RSATL-SCSR connectivity for self-blaming relative to other-blaming emotions predicts subsequent recurrence of depressive episodes. DESIGN, SETTING, AND PARTICIPANTSA prospective cohort study from June 16, 2011, to October 10, 2014, in a clinical research facility completed by 75 psychotropic medication-free patients with remitted MDD and no relevant comorbidity.In total, 31 remained in stable remission, and 25 developed a recurring episode over the 14 months of clinical follow-up and were included in the primary analysis.Thirty-nine control participants with no personal or family history of MDD were recruited for further comparison. MAIN OUTCOMES AND MEASURESBetween-group difference (recurring vs stable MDD) in RSATL connectivity, with an a priori SCSR region of interest for self-blaming vs other-blaming emotions. RESULTSWe corroborated our hypothesis that during the experience of self-blaming vs other-blaming emotions, RSATL-SCSR connectivity predicted risk of subsequent recurrence.The recurring MDD group showed higher connectivity than the stable MDD group (familywise error-corrected P < .05over the a priori SCSR region of interest) and the control group.In addition, the recurring MDD group also exhibited RSATL hyperconnectivity with the right ventral putamen and claustrum and the temporoparietal junction.Together, these regions predicted recurrence with 75% accuracy. CONCLUSIONS AND RELEVANCETo our knowledge, this study is the first to provide a robust demonstration of an fMRI signature of recurrence risk in remitted MDD.Additional studies are needed for its further optimization and validation as a prognostic biomarker.
Pediatric Tumors
Authors: Martin Benesch, Reinhold Kleinert, Elke Spork, Hans Georg Eder, Christian Urban
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.1.274 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11134224 Pediatric Tumors Case 2. Anaplastic Meningioma in a 3 1/2-Year-Old Girl Martin BeneschxMartin BeneschSearch for articles by this author , Reinhold KleinertxReinhold KleinertSearch for articles by this author , Elke SporkxElke SporkSearch for articles by this author , Hans Georg EderxHans Georg EderSearch for articles by this author , Christian UrbanxChristian UrbanSearch for articles by this author Show More University of Graz, Graz, Austria https://doi.org/10.1200/JCO.2001.19.1.274 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Clinical and bacterial characteristics in Danish adults with pleural empyema
Authors: Karin Armbruster, Christian Niels Meyer, Michael Kemp, Trine Rolighed Thomsen, Alice Friis-Moeller, Ram Benny Dessau
Journal: European Respiratory Journal (2014)

Recent studies have focused on change in bacterial aetiology and concequences for treatment of pleural infection.  Aims and objectives  Our aim was to supplement the microbiological data with further identification of species using molecular methods and with further information on clinical and therapeutic factors in patients with pleural infection.  Methods  Cases were identified by combining ICD-diagnosis DJ860-869 and results of microbiology from the laboratory information systems. Clinical, biochemical, and microbiology data are presented of the first 157 patients (out of 480 cases) with pleural infection, collected retrospectively from 8 Danish hospitals (2008-2011). In a subgroup of cases, frozen samples were collected prospectively for direct identification by molecular methods (sequencing combined with RipSeq analysis and the 16S rRNA gene cycle).  Results  Among males (66%) and females (34%), age range was similar with a median of 64 years (range 22-97, IQR 54-73). Mortality was 10%. Risk factors (alcoholism, diabetes, rheumatic diseases, immune deficiencies, HIV, cancer, COPD, neurological diseases) were present in 64% of cases. Community acquired infections accounted for 82% of cases. Treatment included intra-pleural fibrinolysis in 35% of cases, and 13% were referred for thoracic surgery. Bacterial DNA was identified in 15 (of 72) samples of which 7 were also culture positive, and particularly anaerobic bacteria were frequent among the non-cultured bacterial species.  Conclusion  Treatment and outcome data, combined with microbiological and clinical characteristic among patients with pleural infection are described, and new data on microbiological identification using molecular methods are presented.
Discussing the Implications of Genetic Testing With Patients
Authors: Steven M. Sorscher
Journal: Journal of Clinical Oncology (2015)

TO THE EDITOR: On March 20, 2015, the American Society of Clinical Oncology submitted a letter to the US Food and Drug Administration, Division of Dockets Management, to note that next-generation sequencing (NGS) is increasingly used to identify patients at high risk for developing cancer. Recently, in Journal of Clinical Oncology, Jagsi et al repeatedly stressed the critical need for physicians to discuss with patients the potential results of genetic testing before it is ordered so that patients can make informed decisions regarding genetic testing. Although NGS testing is typically explained to patients as a tool that might identify actionable molecular abnormalities, which suggests the potential benefit of a targeted therapy, NGS also might suggest that the patient harbors a germline mutation characteristic of an inherited syndrome. Furthermore, a mutation first suggested in this context might have a far different or unknown penetrance than one identified when the patient is tested because clinical criteria for the inherited syndrome is met. I agree with both the American Society of Clinical Oncology statement that strongly supports additional exploration of NGS and that of Jagsi et al to remind clinicians that, before we order genetic testing with such profound implications, a thorough discussion is essential. Before NGS is ordered, the clinician should also discuss the possibility that the test might imply a germline mutation of uncertain significance, even if the test is ordered primarily to identify somatic mutations that might direct therapy.
‘I Thought it Would Go Away’: Patient Denial in Breast Cancer
Authors: M Phelan, J Dobbs, A S David
Journal: Journal of the Royal Society of Medicine (1992)

A significant proportion of patients with cancer present late to the doctor. The characteristics of these patients and the reasons behind their delaying behaviour is poorly understood. In this study a group of 30 women with breast cancer who delayed their presentation were compared with a randomly selected group with the same disease. The women who presented late did not appear to fit into any particular socio-demographic category, but examination of their histories revealed widespread denial of illness and a diversity of beliefs and behaviour.
PKCα deficiency in mice is associated with pulmonary vascular hyperresponsiveness to thromboxane A2 via increased TXA2 receptor expression
Authors: Christoph Tabeling, Elena Noe, Jan Naujoks, Jan-Moritz Doehn, Stefan Hippenstiel, Bastian Opitz, Norbert Suttorp, Robert Klopfleisch, Martin Witzenrath
Journal: European Respiratory Journal (2014)

Introduction:  Pulmonary vascular hyperresponsiveness is a main characteristic of pulmonary arterial hypertension (PAH) and elevated levels of thromboxane A 2  (TXA 2 ) and endothelin-1 (ET-1) in PAH patients have been described. Downstream signaling of TXA 2  and ET-1 involves activation of the protein kinase C (PKC) family, and PKC inhibition has been proposed as therapeutic strategy in PAH. However, the effects of PKC isoenzyme alpha deficiency (PKCα -/- ) on pulmonary vascular responsiveness have not been investigated.   Methods:  Pulmonary vascular responsiveness to TXA 2  receptor analog U46619 and ET-1 was investigated in isolated perfused and ventilated lungs of PKCα -/-  and corresponding wildtype mice (wt), with or without prior administration of pan-PKC inhibitor bisindolylmaleimide. TXA 2  receptor and PKC isoenzyme mRNA expression of microdissected pulmonary arteries and whole lung tissue was quantified.   Results:  Surprisingly, isolated lungs of PKCα -/-  mice showed pulmonary vascular hyperresponsiveness to U46619 compared to wt mice, whereas pulmonary vascular responsiveness to ET-1 was reduced in PKCα -/-  mice and after pan-PKC inhibition. mRNA analysis showed increased TXA 2  receptor expression in PKCα -/-  pulmonary arteries compared to wt, while PKC isoenzyme expression was comparable between PKCα -/-  and wt.   Conclusion:  PKCα deficiency was associated with increased pulmonary vascular responsiveness to TXA 2  due to increased pulmonary arterial TXA 2  receptor expression.
Hospital Acquisition of Physician Groups
Authors: James D. Reschovsky, Eugene Rich
Journal: JAMA Internal Medicine (2015)

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Cigarette Smoking, Obesity, Diuretic Use, and Coffee Consumption as Risk Factors for Renal Cell Carcinoma&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: M C Yu, T M Mack, R Hanisch, C Cicioni, B E Henderson
Journal: JNCI Journal of the National Cancer Institute (1986)

Cigarette Smoking, Obesity, Diuretic Use, and Coffee Consumption as Risk Factors for Renal Cell Carcinoma Get access Mimi C. Yu, Mimi C. Yu Search for other works by this author on: Oxford Academic PubMed Google Scholar Thomas M. Mack, Thomas M. Mack Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosemarie Hanisch, Rosemarie Hanisch Search for other works by this author on: Oxford Academic PubMed Google Scholar Carla Cicioni, Carla Cicioni Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian E. Henderson Brian E. Henderson Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 77, Issue 2, August 1986, Pages 351–356, https://doi.org/10.1093/jnci/77.2.351 Published: 01 August 1986 Article history Received: 30 July 1985 Revision received: 10 February 1986 Accepted: 26 February 1986 Published: 01 August 1986
Efficient drug delivery to the lungs from a continuously operated open-vent nebulizer and low pressure compressor system
Authors: SP Newman, GR Pitcairn, G Hooper, M Knoch
Journal: European Respiratory Journal (1994)

A comparison of aerosol delivery has been made between two open-vent Pari jet nebulizers. Intermittent and continuous delivery were compared for one of the nebulizers. Ten healthy volunteers inhaled 99mTc-labelled diethylenetriamine penta-acetic acid (DTPA) aerosols on three occasions. The Pari LC device was operated both intermittently (by a manual interrupter that generated aerosol only in synchrony with inhalation) and continuously. The Pari LL nebulizer was operated only in the intermittent mode. A system of inspiratory and expiratory valves was fitted to each nebulizer in order to direct airflow. Both nebulizers were powered by Pari Boy compressors. The mean (SD) whole lung deposition for the LL nebulizer was 11.1 (4.0)% of the nominal dose, compared to 15.3 (12.8)% and 12.8 (7.9)% for the LC used with intermittent and continuous operation, respectively. These differences were not statistically significant. Regional deposition patterns within the lungs were similar for the three nebulizer systems. These data show that efficient nebulizer systems using relatively low power compressors are possible, and suggest that continuously operated open-vent nebulizers may be designed to give lung deposition comparable to that achieved by nebulizers fitted with manual interrupters.
Confocal microscopic features of scarring alopecia: preliminary report
Authors: M. Agozzino, A. Tosti, L. Barbieri, E. Moscarella, C. Cota, E. Berardesca, M. Ardigò
Journal: British Journal of Dermatology (2011)

Lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) are the most common causes of lymphocytic primary cicatricial alopecia. The management of scarring alopecia can be difficult. The combination of clinical, dermoscopy and reflectance confocal microscopy (RCM), a noninvasive, high-resolution imaging technique, examinations have already been demonstrated to be useful for choosing the correct biopsy site in patients with inflammatory skin disease and obtaining microscopic diagnostic criteria.We evaluated the usefulness in practice of RCM for the identification of criteria for LPP and DLE involving the scalp and their management during therapeutic follow-up.Seven white patients with a previously established histological diagnosis of DLE (three) and LPP (four), were included in the study. RCM criteria for primary scarring alopecia were selected: epidermal disarray, spongiosis, exocytosis of inflammatory cells in the epidermis, interface dermatitis, peri- and intra-adnexal infiltration of inflammatory cells, dilated vessels in the dermis, dermal infiltration of inflammatory cells and melanophages and dermal sclerosis. All patients were followed up using RCM during the treatment. During follow-up the RCM evolution of the epidermal, junctional and dermal inflammation were evaluated.A series of RCM features of scalp LPP and DLE were identified that show correlation with the histopathological evaluation. During the treatment follow-up of the cases RCM was shown to be sensitive for the identification of therapeutic response.In our preliminary study the effective usefulness of RCM for the diagnosis of scarring alopecia and follow-up seemed to be evident. Moreover, RCM seems to be also promising for differential diagnosis between the different entities.
CHER LOB Trial: Preoperative chemotherapy plus trastuzumab, lapatinib or both in HER2-positive operable breast cancer—Safety report as per Independent Data Monitoring Committee (IDMC) and preliminary activity data
Authors: V. Guarneri, A. Frassoldati, K. Cagossi, A. Bottini, A. Michelotti, L. Cavanna, G. Jovic, F. Piacentini, C. Oliva, P. F. Conte
Journal: Journal of Clinical Oncology (2008)

580 Background: We conducted a phase IIb randomized trial of preoperative chemotherapy (CT) plus trastuzumab (T), lapatinib (L), or the combination of T+L in HER2+ operable breast cancer > 2cm. Primary endpoint is the % of pathologic complete response (pCR) in breast and axillary nodes. Secondary endpoints: breast objective response, % of breast conservative surgery, safety, molecular responses, gene expression related to pCR. Methods: Patients with HER2+ stage II-IIIA breast cancer are randomized to Arm A: CT+T; Arm B: CT+L; Arm C: CT+T+L. CT consists of paclitaxel (P) 80 mg/m2 weekly for 12 weeks followed by 4 cycles of FE75C q3weeks. T is administered at 2 mg/kg weekly in arms A and C; L is administered at 1,500 mg po daily in arm B, and at 1,000 mg po daily in arm C. Both T and L are administered throughout the duration of CT. Left ventricular ejection fraction (LVEF) is evaluated at baseline, before the start of FEC, and at the completion of treatment. The planned sample size, calculated with the two steps Simon's design, includes 120 patients. Safety analyses by the IDMC are planned at the following time-points: 1) after the first 15 patients treated for ≥3 months; 2) after the first 30 patients treated for ≥3 months. If no safety concerns, further analyses are planned for every 30 patients until study closure. Results: 28 patients have been randomized: 8 in Arm A, 9 in Arm B, 11 in Arm C. A total of 187 doses of weekly P+T, L or T+L, and 46 courses of FEC+T, L or T+L are evaluable. Hematologic toxicity: grade (G) 3–4 neutropenia in 9.6% of weekly P and in 52% of FEC cycles. Nonhematologic toxicity (excluding nausea and vomiting) reported for >5% of cycles were: diarrhea (G1–2: 26%; G3: 4%), G1–2 skin toxicity (23%), and G1 neurotoxicity (10%) during weekly P; G1–2 diarrhea (20%), G1–2 skin toxicity (28%) and G1 neurotoxicity (20%) during FEC therapy. The mean LVEF was 64% (range 54–74%) at baseline, 63% (60–71%) after 12 weeks, and 61% (60–63%) at the end of therapy. Conclusions: The preliminary safety data on the combination of T and L with an anthracycline-containing regimen seem encouraging. The first 2 evaluations as per IDMC and preliminary activity data will be presented at the Meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Ethical issues in phase I oncology research: a comparison of investigators and institutional review board chairpersons.
Authors: E Kodish, C Stocking, M J Ratain, A Kohrman, M Siegler
Journal: Journal of Clinical Oncology (1992)

PURPOSE Phase I research trials assess the safety of agents never before administered to humans. In the field of oncology, this practice raises several important ethical questions. We examined the ethics of these trials by surveying phase I oncology investigators and institutional review board (IRB) chairpersons at major cancer research centers around the country. METHODS Questionnaires were mailed to 78 investigators and 47 chairpersons to obtain their views on the ethical propriety of conducting phase I oncology research, and on institutional practice regarding these trials. The response rate was 68% in each group. RESULTS The majority of each group reported that phase I oncology trials face no more scrutiny or resistance in their institution's IRB process than other research protocols. Nevertheless, IRB chairpersons were more likely than investigators to favor special procedural safeguards to protect subjects in phase I oncology trials. Nearly all respondents agreed that although actual medical benefit was very uncommon, most patients entered for a chance at a therapeutic effect. Investigators were more likely than chairpersons to report that patients obtained psychologic benefit from participation in phase I trials. CONCLUSION Although individual IRB chairpersons and oncology investigators may have important differences of opinion concerning the ethics of phase I trials, these disagreements do not represent a widespread area of ethical conflict in clinical research.
Hypoxia induces inflammasome activation and influx of neutrophils and T-cells in the lungs
Authors: Fadila Telarevic Cero, Karl Otto Larsen, Geir Christensen, Ole Henning Skjønsberg
Journal: European Respiratory Journal (2013)

Background: Inflammasomes are molecular platforms which are part of the innate immunity and activate IL-18 and IL-1β through caspase-1. They can be activated by microorganisms and physical stress (K. Schroder & J.Tschopp, Cell, 2010). Increased levels of interleukin (IL)-18 have been found during experimental alveolar hypoxia (K.O. Larsen et al. Cardiovasc Res, 2008), but it is not known whether hypoxia activates inflammasomes leading to increased IL-18 and IL-1β levels.

Objectives: To study inflammasome activation and cell infiltration in mouse lungs during hypoxia exposure.

Methods: Lungs were harvested from C57Bl/6j mice at 1-7 days of hypoxia exposure (10%) for histological and Western blot analyses. Active caspase-1, IL-18 and IL-1β were measured.

Results: Histology revealed perivascular infiltration of inflammatory cells and inflammasome components at day 1-7, with neutrophil granulocytes dominating from day 1-3, and T-cells dominating from day 4-7. Active caspase-1 and IL-18 were significantly increased at day 3, 7 and 4 weeks of hypoxia compared to normoxic controls (both p<0.05). IL-1β showed upregulation, but it did not reach statistical significance.

Conclusions: Active Caspase-1 was induced during hypoxia indicating activation of the innate immune system through inflammasomes. Both IL-18 and IL-1β were upregulated, but IL-1β did not reach significance. Activation of the inflammasome may play a role for the inflammatory cell influx and the cytokine mediated progression of lung disease in hypoxic patients.

Acknowledgements: We are grateful to Almira Hasic and Ingeborg Lostegaard Goverud for technical assistance.