tbuckley/cabot-search huggingface dataset:
Differentiation between squamous cell carcinoma (SCC) and adenocarcinoma (AC): Expression of immunohistochemical (IHC) markers in a tissue microarray (TMA) of >1000 NSCLC
Authors: Philipp A. Schnabel, Esther Herpel, Thomas Muley, Hans Hoffmann, Peter Schirmacher, Arne Warth
Journal: European Respiratory Journal (2011)

Introduction:  Distinguishing SCC from AC has become crucial for tailored therapies of NSCLC. Many patients are inoperable at the time of diagnosis of NSCLC, >65% of the diagnoses are performed in small biopsies (Bx). The “IASLC/ATS/ERS international multidisciplinary classification of lung adenocarcinoma” (Travis W.D., Brambilla E.  et al.  JTO 2011; 6:244-85) firstly includes diagnostics in Bx in addition to resection specimen. We investigated the expression of IHC markers in a TMA simulating Bx.   Materials and methods:  The IHC markers CK5/6, p63, desmocollin-3, CK7, TTF1, and napsin were investigated in a TMA from a primary cohort of 1005 patients with resected NSCLC.   Results:  For SCC, desmocollin-3 showed the highest, CK5/6 a medium, and p63 the lowest specifity. The sensitivity of desmocollin-3 was similar to the combined sensitivity of CK5/6 and p63. Desmocollin-3 was expressed in about 85%, CK5/6 and p63 in >90% of all SCC.  For AC, TTF1 and napsin revealed a considerably higher specifity than CK7. The sensitivity of napsin did not exceed the combined sensitivity of CK7 and TTF1. CK7 was expressed in >95% of all AC, TTF1 in    Conclusions:  To spare tumor tissue for further (e.g. molecular) analyses, diagnostic algorithms for NSCLC Bx must be established. If histology alone cannot distinguish between SCC and AC, a combination of TTF1, napsin, CK5/6 and desmocollin-3 can serve as initial diagnostic marker panel. CK7 and p63 could be used subsequently, if necessary, because of lower specifity. Currently a TMA of 300 further NSCLC is investigated, data from all 1300 NSCLC will be presented.
Therapeutic Drug Monitoring of Mood Stabilizers in Medicaid Patients With Bipolar Disorder
Authors: Steven C. Marcus, Mark Olfson, Harold A. Pincus, Deborah A. Zarin, David J. Kupfer
Journal: American Journal of Psychiatry (1999)

The authors' goal was to determine the extent and pattern of blood serum monitoring of mood stabilizers in Medicaid patients with bipolar disorder.Data were drawn from a Medicaid medical claims data set from Pittsburgh and the surrounding region. The authors identified bipolar patients using lithium, valproate, and carbamazepine (N = 718) and then examined the patient demographic, diagnostic, and service use variables associated with therapeutic drug monitoring.A substantial proportion of lithium users (36.5%), valproate users (42.4%), and carbamazepine users (42.2%) with bipolar disorder diagnoses did not receive therapeutic drug level testing during the 12-month study period. Carbamazepine users who were male or in the 30-49-year age range were significantly less likely to be tested for serum drug level. Lithium users who did not receive partial-hospitalization psychiatric services and valproate users who received mental health case management were also less likely to be tested for serum drug level. Over one-half of the lithium users (54.1%) did not receive thyroid function tests, and few (4.2%) received renal function tests. Patients who did receive tests for serum drug level were likely to receive the other recommended tests.Many Medicaid patients with bipolar disorder received no therapeutic drug monitoring. Patient sociodemographic characteristics contributed little to explaining this omission, although some types of service utilization were related to rates of serum drug level testing.
Validity of COPD assessment test (CAT) in patients with cardiovascular co-morbidities
Authors: Ivan Vishnivetsky, Yuriy Mostovoy, Iryna Boychenko
Journal: European Respiratory Journal (2013)

Introduction. Some significant cardiovascular co-morbidities (CVCM) frequently coexist with COPD and possibly influence COPD-specific patient-reported outcomes such as CAT.  Objectives. To evaluate the validity of CAT in COPD patients (pts) with CVCM.  Methods. We performed a cross-sectional study in 3 groups of male pts tightly matched by age, co-morbidities and\or lung function (17 pts with COPD and CVCM (group 1), 17 pts with COPD without CVCM (group 2) and 17 pts with cardiac diseases without lung pathology (group 3)). All groups were assessed with CAT and Patient Health Questionnaire (PHQ-9) for depression as a possible confounder. In group 1 we also evaluated patient- and physician-reported perceptions regarding the “pivotal disease” (heart or lung), playing the key role in the health status impairment in every patient. For this purpose we used “CAT-like” scale (0 to 5).  Results. In all groups CAT scores were high. In group 1 mean CAT score (23.1±4.9 did not significantly differ to group 2 (19.2±4.3, p>0.05), and was higher than in group 3 (17.2±6.1, p=0.023). Most of group 3 pts (15/17, 88,2%) scored 10 or more by CAT. CAT scores significantly correlated with PHQ-9 depression scores in group 1 (r=0.58, p=0.03), but not in the other groups (p>0,05). In group 1 neither pts9 nor physicians9 perceptions about the “pivotal disease” significantly correlated with pts9 CAT scores. This indicates the difficulties in differentiating pulmonary and cardiac genesis of symptom burden and its role in the health status impairment.  Conclusions. CAT scores may be significantly distorted by CVCM and, possibly, depression. Further validation of CAT in COPD pts with CVCM and other co-morbidities is warranted.
Giant Perianal Mass
Authors: Goran Šantak, Damir Matokovic, Irena Gašparic
Journal: JAMA Surgery (2015)

A 65-year-old man had a painful anal mass and fecal incontinence. The anal lesion appeared 1 year earlier and grew slowly to the current size. The patient reported bleeding from the rectum after defecation and denied weight loss or fever. What is your diagnosis?
Living with COPD: Views of patients, carers and respiratory nurses
Authors: Sheelagh Martindale, Audrey Stephen, Graham Devereux, Mary Addo
Journal: European Respiratory Journal (2013)

COPD is the fifth biggest killer globally and is predicted to be the third leading cause of death by 2020. Self-management plans may empower patients to take control of their condition and act early, reducing exacerbations. The real life situation of patients and their carers in living with COPD requires to be understood. This qualitative study was designed to draw on the perspectives of COPD patients, carers, and respiratory nurses, to develop a self care model to test out in a subsequent pilot intervention study.  Methods:  A phenomenology study design was adopted where 13 patient participants with moderate or severe COPD, 5 of their carers and 4 respiratory nurses were recruited into the study. Each participant was interviewed using a semi-structured format, the data was analysed using thematic analysis.  Findings:  The age of the patient participant group ranged from 45 to 80 years of age and consisted of 7 male participants. The carer participants ranged from 35 to 74 years of age. Factors relating to daily activities and dependence and independence were repeatedly identified by the patients’ and carers’ groups, as were attitudes and stresses and other quality of life and lifestyle themes.  Conclusions:  The patient and their carer in general had concerns about how the other coped with COPD. Older participants felt quite isolated but stress, anxiety and the stigma of the disease was portrayed by both patients and carers of all ages. There’s a difference of opinion in relation to the use of self management plans between patients, and the nurses. This study provides important evidence to develop a model of self management which will build towards a change in practice for the management of the COPD patient.
Chlamydia increases risk of cervical cancer
Authors: D. Josefson
Journal: BMJ (2001)

Infection with certain subtypes of chlamydia, a bacterium which is commonly transmitted sexually, greatly increases the risk of cervical cancer, according to a new report ( JAMA 2001;285:47-51).

Although infections with oncogenic strains of human papillomavirus remain the prime cause of cervical cancer, infection with some strains of Chlamydia trachomatis seem to contribute to that risk.

The finding is important because chlamydia, though frequently asymptomatic, is one of the most common sexually transmitted diseases and can be treated with appropriate antibiotics. In the United States, between four million and eight million new cases of chlamydia are reported yearly.

The bacterium—which, when symptomatic, causes purulent discharge, dysuria, and urethritis—can also cause ascending infections leading …
A phase I safety and pharmacokinetic study of XL765 (SAR245409), a novel PI3K/TORC1/TORC2 inhibitor, in combination with temozolomide (TMZ) in patients (pts) with newly diagnosed malignant glioma.
Authors: P. L. Nghiemphu, A. M. Omuro, T. Cloughesy, I. K. Mellinghoff, A. D. Norden, L. T. Nguyen, K. Rajangam, P. Y. Wen
Journal: Journal of Clinical Oncology (2010)

3085 Background: PI3K pathway dysregulation has been implicated in resistance to TMZ in preclinical glioma models. XL765, a potent and selective inhibitor of class I PI3K isoforms and TORC1 and TORC2, has demonstrated dose-dependent target modulation in both tumor xenograft models and in normal brain tissue in preclinical studies. Methods: Pts with WHO grade III and IV astrocytic tumors who have received standard chemoradiation with TMZ followed by at least one cycle of maintenance TMZ (200 mg/m2/day × 5 q 28 days) are eligible. XL765 is dose escalated following a standard 3 + 3 design and administered in combination with a fixed dose of TMZ. Results: 18 pts have been treated with XL765 in combination with TMZ across 4 dose levels of XL765 (30, 40, 50, and 60 mg qd). The maximum administered dose (MAD) of XL765 is 60 mg for the qd schedule; 2 of 6 pts experienced DLTs. The most common (≥ 10%) treatment-related AEs were nausea, hyperglycemia, constipation, fatigue, thrombocytopenia, and skin disorders. Grade ≥ 3 treatment related AEs were observed in four pts: grade 3 brain edema and grade 4 thrombocytopenia (one pt, also reported as a DLT), grade 3 rash (one pt, also reported as a DLT), grade 3 thrombocytopenia (one pt), and grade 4 increased transaminases (one pt). Based on comparison with single agent data, no major PK interaction between XL765 and TMZ is evident. At the 30 and 40 mg qd XL765 dose levels, inhibition of PI3K pathway (pAKT-T308, pAKT-S473, and p4EBP1) signaling has been demonstrated in skin. Based on assessment of archival tumor material, the most common molecular alterations detected include MGMT promoter methylation, PTEN point mutations, and EGFR gene amplification. Of the first 18 pts enrolled, seven pts have remained on study for > 16 weeks, one of whom continued on study for 62 weeks. Conclusions: XL765 in combination with TMZ is generally well tolerated at doses up to 40 mg qd. There is no apparent PK interaction between XL765 and TMZ. MTD determinations for qd and bid schedules are ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Exelixis Exelixis Exelixis Exelixis, Genentech, Schering-Plough
SPTBN1-FLT3 in Atypical Chronic Myeloid Leukemia Transforms Ba/F3 Cells to IL-3 Independence and Is Sensitive to Both Tyrosine Kinase Inhibitors and Immunotherapy.
Authors: Francis H. Grand, Sameena Iqbal, Lingyan Zhang, Nigel H. Russell, Andrew Chase, Nicholas C.P. Cross
Journal: Blood (2005)
Trypanosoma cruzi infection in a non-endemic country: epidemiological and clinical profile
Authors: F. Salvador, B. Trevióo, E. Sulleiro, D. Pou, A. Sánchez-Montalvá, J. Cabezos, A. Soriano, N. Serre, J. Gómez i Prat, A. Pahissa, I. Molina
Journal: Clinical Microbiology and Infection (2013)
Familial Occurrence of Letterer-Siwe Disease
Authors: V W SCHOECK, R D PETERSON, R A GOOD
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A novel three-dimensional “all human” in vitro brain tumor invasion model
Authors: S. Murray, H. Rooprai, R. Selway, Geoff Pilkington
Journal: Neuro-Oncology (2005)

In order to study brain tumor invasion in vitro, previous three-dimensional model systems have utilized pre-cultured chick heart fragment and rat brain as targets in co-culture with human brain tumor. We have now succeeded in establishing a novel three-dimensional model whereby human neoplastic glial cell spheroids are juxtaposed with spheroids derived from non-neoplastic human brain tissue. Spheroids are developed from either established glioma-derived cell lines or from primary cultures of glioma biopsy as well as brain resected from patients who have undergone surgery for epilepsy, short-term astrocyte-rich cell cultures derived therefrom. Using the “hanging drop” method, 45,000 cells were inversely suspended from a petri dish in 20 ml of DMEM. After either 24 h (fast-growing cells) or 48 h (slower growing cells) in their gravity pools, spheroids are transferred to agar-coated petri dishes for a further 24 h prior to confrontation. Cells were tracked with the use of fluorescent cell trackers; progress was recorded every 3 days for up to 15 days. Fluorescent cell trackers were also employed for time-lapse video microscopy in the most invasive combination over 5 days. We are further developing the model in utilizing human serum instead of fetal calf serum, which has been shown to alter antigenic expression and growth rate of human glioma cells in two-dimensional cultures within our laboratories. The effects of various agents that may impede local brain tumor invasion are currently under investigation. To these ends we are utilizing scanning and transmission electron microscopy, confocal microscopy, total internal reflected fluorescence (TIRF) microscopy, and live cell imaging utilizing Improvision Velocity and Openlab software on a Zeiss inverted axiovert 200M microscope. This work was supported by the Dr Hadwen Trust
Epigenetic deregulated translation control of C/EBP-alpha leads to increased mesothelioma cell proliferation
Authors: Jun Zhong, Nicola Miglino, Michael Tamm, Didier Lardinois, Lukas Bubendorf, John Szilard, Michael Roth
Journal: European Respiratory Journal (2011)

Malignant pleural mesothelioma (MM) resists all available anticancer therapies. A major pathology of MM is the uncontrolled cell proliferation and the fast local spreading with rare metastasis. Therefore the inhibition of proliferation is a major therapeutic target. Proliferation of MM cells was linked to mitogen activated protein kinase (MAPK) activity. In this study we characterised the regulation of MAPK regulated CCAAT/Enhancer binding proteins (C/EBP) and their role in MM cell proliferation. In five human MM cell lines, cytosolic and nuclear protein expression was determined by immuno-blotting and immuno-chemistry in tissue sections. Transcription of C/EBPs was determined by real time PCR and translation by a translation reporter assay. We observed a cell compartment specific expression pattern of p38-α, -β and -γ MAPK in MM cells. Erk1/2 and p38 MAPK together up-regulated the expression of C/EBP-β and -δ, while C/EBP-α was not expressed. Compared to mesothelial cells C/EBP-α translation was reduced in MM, while the mRNA was constitutively expressed. MM cells expressed a relative high level of the C/EBP-α translation suppressor calreticulin, while eIF4E was not significantly modified. Cell proliferation was inhibited by either the blockade of Erk1/2, or p38-β and -γ MAPK, or C/EBP-β. Transfection with a C/EBP-α expression vector reduced proliferation and increased the MM cell's sensitivity to steroids. Our data implies that in human MM cells an epigenetic mechanism deregulates the translation control of the cell differentiation factor C/EBP-α which leads to increased proliferation and drug resistance.
Significant contribution of TCR gamma gene rearrangement testing to accurate diagnosis and staging of T cell lymphomas
Authors: Milena Cankovic, Adrian Ormsby, Robert Hawley, Koichi Maeda, Richard Zarbo
Journal: Cancer Research (2007)

2721    Introduction:  In  majority  of hematologic malignancies, morphology supplemented with immunohistochemistry (IHC) and/or flow cytometric (FCM) immunophenotyping can discriminate between a malignant and reactive lymphoproliferation. In about 10% of cases, additional ancillary studies such as T cell receptor (TCR) gamma gene rearrangement and immunoglobulin heavy chain (IgH) gene rearrangement are ordered to provide additional evidence that “suspicious” histological changes may represent a malignant process. T cell lymphomas in particular are often difficult to distinguish from atypical T cell proliferations. Our study focuses on the contribution of TCR gamma clonality assessment assay towards accurate diagnosis and staging of hematologic malignancies.   Methods:  From January to October 2006, 111 specimens were evaluated for TCR gamma clonality in the AP Molecular Pathology laboratory at Henry Ford Hospital. Histologic evaluation, IHC, and sometimes FCM evaluations were also performed on all cases. Specimen types were as follows: skin biopsy (74), lymph node biopsy (15), peripheral blood (7), bone marrow (5), and miscellaneous extranodal lymphoid proliferations (10). DNA was isolated and subjected to PCR amplification for TCR gene rearrangement (TCR Gamma Gene Rearrangement Assay, In Vivo Scribe, San Diego, CA). The amplified PCR products were analyzed by capillary electrophoresis. Gene rearrangement test results were correlated with other histologic and clinical features.   Results:  Of the111 specimens, 50 demonstrated clonal TCR gamma gene rearrangement (31 skin, 8 lymph node, 5 blood, 4 bone marrow, and 2 breast biopsy specimens). For 15 of these, all other histological, IHC and FCM (when available) findings were inconclusive. Positive gene rearrangement results prompted closer monitoring of these patients, and T cell malignancies were subsequently confirmed in most of these cases. TCR gamma gene rearrangement testing was negative in 52 cases of atypical lymphoid proliferation, confirming other histologic findings. Nine of the specimens (7 skin and 2 lymph node) gave what appeared to be false negative results. Four of these subsequently demonstrated T cell clonality when repeat biopsies were tested. Conclusion:  As with many diseases with a spectrum of clinical and pathologic findings, demonstration of clonal T cell proliferation can confirm diagnosis, or help to raise suspicion of a T cell lymphoma. In cases of atypical lymphoid proliferation, negative results are highly suggestive of a reactive process. The results of this study demonstrate that, in addition to histologic diagnosis, ancillary gene rearrangement studies can further define difficult cases, especially difficult to diagnose dermatologic malignancies.
Clinical pharmacists help prescribers and patients make informed decisions
Authors: A. V. Gilbert
Journal: BMJ (2015)

McCartney reminds us that sweet temptations gifted with education by drug companies are never “free.”1

I am a pharmacist in a tertiary teaching hospital, in psychiatry. Aripiprazole long acting injection (ALAI) was recently added to the Australian Pharmaceutical Benefits Scheme (PBS). A pharmaceutical representative educated our prescribers on ALAI at the medical weekly meeting. The rep provided lunch.

Her opening line “I’m not here to sell anything, I am …
Cardiac Effects of Methylphenidate
Authors: Steven Roose, Bret Rutherford
Journal: American Journal of Psychiatry (2015)

correction was applied.When adjusting for individual therapy attendance during the first 3 months, the magnitudes of effect by strata were comparable to our initial results: ,12 sessions: hazard ratio50.27,95% CI50.00-2.75,p50.48; $12 sessions: hazard ratio50.35,95% CI50.14-0.88,p50.03.Participants were next stratified into quartiles according to the number of individual therapy sessions attended during the entire follow-up (i.e., 0-12, 13-24, 25-48, and 491 sessions).The estimated attempt-free probabilities at 6 months and at 24 months are displayed in Table 1 by treatment group.When adjusting for the total number of individual sessions attended during follow-up, brief CBT continued to be associated with significantly reduced risk for suicide attempt (hazard ratio50.39,95% CI50.16-0.87,p50.03).Adjusted results by strata favored brief CBT in all cases, though there was insufficient power to detect statistically significant differences: 1st quartile: hazard ratio50.10,95% CI50.00-1.10,p50.188; 2nd quartile: hazard ratio50.27,95% CI50.p50.111; 3rd quartile: hazard ratio50.91,p50.912; 4th quartile: hazard ratio50.39,p50.228.Overall, results of these post hoc analyses suggest the effects of brief CBT on the likelihood of follow-up suicide attempts remain reasonably stable even when accounting for the nonspecific effect of individual therapy dose.It is difficult to elucidate treatment effects given the overall study N, but the enduring impact of a brief treatment for suicidal behavior raises interesting questions regarding the unique, effective elements of care.
Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma
Authors: Christian Schmithals, Verena Köberle, Hüdayi Korkusuz, Thomas Pleli, Bianca Kakoschky, Eduardo Alonso Augusto, Ahmed Atef Ibrahim, Jose M. Arencibia, Vida Vafaizadeh, Bernd Groner, Horst-Werner Korf, Bernd Kronenberger, Stefan Zeuzem, Thomas J. Vogl, Oliver Waidmann, Albrecht Piiper
Journal: Cancer Research (2015)

Abstract iRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting. We found that iRGD improved the delivery of marker substances to the tumors of HCC-bearing mice about three-fold without a parallel increase in normal tissues. Control peptides lacking the critical CendR motif had no effect. Similarly, iRGD also selectively increased the signal intensity from tumors in Gd-DTPA–enhanced MRI. In terms of antitumor efficacy, iRGD coadministration significantly augmented the individual inhibitory effects of sorafenib and doxorubicin without increasing systemic toxicity. Overall, our results offered a preclinical proof of concept for the use of iRGD coadministration as a strategy to widen the therapeutic window for HCC chemotherapy, as monitored by Gd-DTPA–enhanced MRI as a noninvasive, clinically applicable method to identify iRGD-reactive tumors. Cancer Res; 75(15); 3147–54. ©2015 AACR.