tbuckley/cabot-search huggingface dataset:
A phase II study of IMGN242 (huC242-DM4) in patients with CanAg-positive gastric or gastroesophageal (GE) junction cancer
Authors: L. W. Goff, K. Papadopoulos, J. A. Posey, A. T. Phan, A. Patnaik, J. G. Miller, S. Zildjian, J. J. O'Leary, A. Qin, A. Tolcher
Journal: Journal of Clinical Oncology (2009)

e15625 Background: IMGN242 is a conjugate of the cytotoxic maytansinoid DM4 and the monoclonal antibody huC242, which binds to CanAg. In a Phase I study, the maximum tolerated dose for IMGN242 was determined to be 168 mg/m 2 , with ocular changes the primary dose-limiting toxicity. This Phase II study was initiated to assess IMGN242 for the treatment of gastric cancer. Methods: In this open-label, multi-center study, IMGN242 is given as a single IV infusion every three weeks to patients with CanAg-expressing metastatic or locally-advanced gastric or GE junction cancer. Patients must have been treated with at least one prior therapy to qualify for enrollment. The study has a 2-step design: If ≥1 objective response is achieved among the first 23 patients (Step 1), a total of 39 response-evaluable patients will be enrolled (Step 2). Results: Overall, 9 patients have received IMGN242. The first 6 were treated with 168 mg/m 2 , and 1 of these patients showed a marked biologic response by the FDG-PET scan in Cycle 1 followed by an unconfirmed partial response based on CT scan in Cycle 2. However, 3 of these 6 patients developed ocular toxicities assessed to be study drug related. Only patients with low plasma CanAg levels (&lt;1000 U/ml) developed ocular toxicities, and clinical pharmacokinetic and pharmacodynamic (PK/PD) analyses revealed that plasma CanAg affects study drug exposures. The study was amended to differentiate the IMGN242 doses (126 mg/m 2 or 168 mg/m 2 ) administered based on the patient's plasma CanAg levels (&lt; or &gt;1000 U/mL). To date, 3 patients have received IMGN242 with this dosing strategy and no ocular toxicities have been reported. Conclusions: IMGN242 showed preliminary evidence of activity in this patient population. A novel Phase II dosing strategy is being used that should enhance tolerability. Patient enrollment is ongoing and updated results will be reported. [Table: see text]
Zika Virus in the Americas — Yet Another Arbovirus Threat
Authors: Anthony S. Fauci, David M. Morens
Journal: New England Journal of Medicine (2016)

The explosive pandemic of Zika virus infection in South and Central America is the most recent of four unexpected arrivals of important arthropod-borne viral diseases in the Western Hemisphere over the past 20 years. Is this an important new disease-emergence pattern?
Cytotoxicity and Sister Chromatid Exchanges Induced In Vitro by Six Anticancer Drugs Developed in the People's Republic of China&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C C Huang, C S Han, X F Yue, C M Shen, S W Wang, F G Wu, B Xu
Journal: JNCI Journal of the National Cancer Institute (1983)

Growth inhibition in the Chinese hamster cell line V79 and in the human lymphoid cell line Raji and induction of sister chromatid exchange(s) (SCE) in V79 cells after treatment with six anticancer drugs [harringtonine (HRT), homoharringtonine (HHRT), camptothecin (CPT), hydroxycamptothecin (HCPT), lycobetaine (LBT), and oxalysine (OXL)] developed in the People's Republic of China were studied. OXL is a new antibiotic; all other drugs are plant extracts. All drugs caused a dose-dependent growth inhibition in both cell types, as evidenced by decreases in plating efficiencies of V79 cells and in viable cell counts of Raji. However, the degree of inhibition differed widely among the drugs. HRT, HHRT, CPT, and HCPT were the most potent growth inhibitors, LBT was next, and OXL was the least effective inhibitor. SCE analyses were made in V79 cells treated with a drug in the presence or absence of the metabolic activation system S9 mixture (S9 mix), except for the HRT assay in which the S9 mix was not used. CPT, HCPT, and LBT induced a dose-dependent increase in SCE frequencies, while HRT, HHRT, and OXL caused no SCE induction at any dose level used. CPT was the most powerful SCE inducer. HCPT induced SCE but at a much reduced rate when compared to that of CPT. LBT was a weak SCE inducer; SCE induction was seen only in cultures treated with 40 micrograms or more LBT/ml. Addition of the S9 mix did not alter SCE frequencies, indicating that the drugs were direct-acting agents. HRT and HHRT were highly toxic, but they induced no increases in SCE frequency, indicating that cytotoxicity of a compound does not necessarily correlate with SCE induction.
Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States
Authors: Veronica H. Flood, Pamela A. Christopherson, Joan Cox Gill, Kenneth D. Friedman, Sandra L. Haberichter, Daniel B. Bellissimo, Rupa A. Udani, Mahua Dasgupta, Raymond G. Hoffmann, Margaret V. Ragni, Amy D. Shapiro, Jeanne M. Lusher, Steven R. Lentz, Thomas C. Abshire, Cindy Leissinger, W. Keith Hoots, Marilyn J. Manco-Johnson, Ralph A. Gruppo, Lisa N. Boggio, Kate T. Montgomery, Anne C. Goodeve, Paula D. James, David Lillicrap, Ian R. Peake, Robert R. Montgomery
Journal: Blood (2016)
Mortality in sarcoidosis, results from one centre, long term observational study
Authors: Elzbieta Puscinska, Adam Nowinski, Anna Goljan-Geremek, Michal Bednarek, Dariusz Kaminski, Anna Kowalska, Dorota Gorecka
Journal: European Respiratory Journal (2014)

Aim : The aim of the study was to examine mortality and underlying causes of death among decedents with sarcoidosis in our Department between 2007-2011. Materials and methods : The study was designed in 2007. The cohort of the patients(pts) with histologically confirmed sarcoidosis was observed. Between 2007 and 2011, 557 pts were admitted to our Department. In Jan 2014 a surveillance follow-up was performed using the Electronic Beneficiary Entitlement Verification platform provided by the National Health Insurance System. Pts who were not in the system were contacted personally to confirm their status.  Results:  Among 557 pts(291men, 266 women) with mean age 48,4 ±12,0 yrs, 16 died (6 women and 10 men) with mean age 57,6±7,8y. At the time of diagnosis 12pts were classified as radiological stage II, 4 pts as stage III. Extrapulmonary sarcoidosis was found in 9 pts (56%) and only 2 pts(12.5%) were not treated with steroids and/or methotrexat. Most frequent comorbidities were hypertension 12(75%), hyperlipidemia 4(25%), thyroid disease 3(18,7%), diabetes 1, chronic renal disease 1, uterine cancer 1 and aortic stenosis 1.  7 pts died of causes unrelated to sarcoidosis (cancers), whereas death was related to sarcoidosis in 7 pts. The most prevalent cause of death was advanced pulmonary involvement (5pts) with various late complications: cardiorespiratory failure, fungal infections or extrapulmonary sarcoidosis: cardiac(1pt) and central nervous system(1pt). Others causes included stroke and complications from a stenosis surgery.    Conclusion: The leading cause of death in sarcoid patients in our Department were cancers, but just as often, sarcoidosis was the underlying cause of death.
Abstract 188: Neuroprognostication After Pediatric Cardiac Arrest
Authors: Matthew P Kirschen, Judy Illes, Alexis A Topjian, Robert A Berg, Vinay M Nadkarni, Nicholas S Abend
Journal: Circulation (2012)

Objective: Management decisions and parental counseling following pediatric cardiac arrest depend on the ability of physicians to make accurate and timely predictions regarding neurological recovery. This study examined the level of agreement in neuroprognostication among neurologists and among intensivists, and prediction accuracy in terms of time post cardiac arrest. Methods: Pediatric neurologists (N=10) and intensivists (N=9) each reviewed 18 cases of children successfully resuscitated from a cardiac arrest and managed in the pediatric ICU. Cases were sequentially presented in three sections: Day 1, Days 2-4, and Days 5-7 post arrest, with updated examinations, neurophysiologic data, and neuroimaging data as available. At each time point, physicians predicted outcome by Pediatric Cerebral Performance Category (PCPC). Predicted PCPC (p) vs. actual hospital discharge PCPC (a) outcomes were compared. Prediction accuracy was defined as Exact Accuracy (p-a = 0) and Close Accuracy (p-a = ±1). Descriptive statistics, Kappa coefficients (Κ) and generalized estimating equation were performed. Results: Agreement among neurologists improved over time (Day 1 Κ 0.27, Days 2-4 Κ 0.43, Days 5-7 Κ 0.62), as did agreement among intensivists (Day 1 Κ 0.30, Days 2-4 Κ 0.44, Days 5-7 Κ 0.57). For all physicians, prediction accuracy did not improve from Day 1 to Days 2-4, but did improve from Days 2-4 to Days 5-7 (p=0.001) [Exact Accuracy Days 2-4 and Days 5-7: 35% vs. 43%; Close Accuracy Days 2-4 and Days 5-7: 77% vs. 89%]. Prediction accuracy did not differ significantly between physician groups at any time point (p=NS). At Days 5-7, 16 of 19 physicians predicted PCPC = 5-6 at least once when actual PCPC ≤ 4. All physicians predicted PCPC ≤ 4 at least once when actual PCPC = 5-6. Conclusions: Inter-rater agreement among neurologists and among intensivists improved over time and converged to moderate-good levels at later time points. For all physicians, prediction accuracy improved over time; however, even at later time points, incorrect outcome predictions occurred. The ethical implications of these findings for clinical decision-making and allocation of health care resources after pediatric cardiac arrest are considerable.
CSF 5-HIAA and HVA concentrations in elderly depressed patients who attempted suicide
Authors: J S Jones, B Stanley, J J Mann, A J Frances, J R Guido, L Traskman-Bendz, R Winchel, R P Brown, M Stanley
Journal: American Journal of Psychiatry (1990)

CSF findings distinguished 12 elderly depressed patients who attempted suicide from nine depressed patients who did not and from seven normal control subjects. Psychosocial factors and measures of psychopathology did not differentiate suicidal from nonsuicidal patients. Biochemical factors may be important in evaluating suicide risk in the elderly.
Fibrotic Transformation of the Rat Pancreas as Response to the Nitric Oxide Deficiency
Authors: B.F. Shevchenko, A.M. Babiy, N.Y. Oshmyanska, V.A. Makarchuk
Journal: GASTROENTEROLOGY (2013)

Non-specific inhibitor of nitric oxide NG-nitro-L-arginine was administrated for the duration of the experiment, and the most significant changes (discirculation and dissecretion) were observed on the 12th day, whereupon the reaction slows due to a compensatory response. On the 30th day of experiment tiny bands of fibrous tissue were formed, which also evidenced by the increase of collagen synthesis markers in blood — protein-bound hydroxyproline (p &lt; 0.05). Incompetence of pancreatic cells was manifested by the reduced activity of pancreatic enzymes (p &lt; 0.05), and the visible hyposecretion of acinar cells on the morphological study. The maximum decrease of nitrite/nitrate concentration was observed after the first day (p &lt; 0.05), with a gradual increase to a maximum on 12th day (p &lt; 0.05).
A polymorphism in the 3′UTR region of E-cadherin associates with recurrence of breast cancer
Authors: K. M. Hirshfield, D. Kulkarni, J. Kostialik
Journal: Journal of Clinical Oncology (2008)

22101 Background: Maintenance of epithelial integrity plays a major role in tumor suppression but may also be important in metastasis and recurrence of cancer. Loss of E-cadherin (CDH1) is implicated in invasive lobular carcinomas of the breast. Furthermore, a polymorphic variant in the CDH1 promoter has been reported in association studies. We investigated the association of polymorphic variants in CDH1 with recurrence of breast cancer. Methods: TaqMan allelic discrimination assays were performed on genomic DNA prepared from whole blood of breast cancer patients. Genotyping was determined for several loci in CDH1 and were linked to clinical information. Results: CDH1 genotypes for the 3’UTR Ex16+246C>T polymorphism are in Hardy-Weinberg equilibrium with frequencies of: CC 69%, CT 27%, and TT 4%. Population-specific genotype frequencies were observed. There were no frequency differences between invasive ductal and invasive lobular carcinomas, but a trend toward a 4-year earlier age of onset of the latter associated with the low frequency allele. Seventeen percent of women in this cohort recurred, nearly half representing progesterone receptor-negative (PgR−) and half progesterone receptor-positive (PgR+) breast cancers. The recurrence rate for each genotype was 14.3%, 26%, and 7.1% for CC, CT, and TT genotypes, respectively. In women without recurrence, the genotype distribution was the same for PgR+ and PgR− disease. However, in those that recur, women with the CC genotype were more likely to be PgR− OR 2.32 CI [1.13–4.77] with a p value=0.023. The converse could not be evaluated due to small numbers. Conclusions: A polymorphic variant in the 3’UTR region of CDH1 is associated with recurrence of breast cancer. This association is strongest in recurrence of progesterone receptor-negative breast cancers. Recurrence in this SNP association study may reflect the effect of progesterone on proteins in adherence junctions or desmosomes or the role of CDH1 in the beta-catenin pathway. Support was from the New Jersey Commission on Cancer Research. No significant financial relationships to disclose.
Malingering and Feigned Sickness.
Journal: JAMA (1913)

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
Different measurement criteria give different tumor response classifications in patients with metastatic renal cancer (MRCC)
Authors: S. Negrier, P. Thiesse, C. Vincent, L. Ollivier, N. Tubiana-Mathieu, E. Blanc, C. Segura, F. Chauvin, B. Escudier
Journal: Journal of Clinical Oncology (2004)

6013 Background: Since the publication of RECIST criteria (J Natl Cancer Inst. 2000), most investigators have used them, rather than WHO criteria, for evaluating response in clinical trials. Though comparisons on retrospective data evidenced differences between the two classifications, these were not prospectively investigated. The Groupe Français d'Immunothérapie conducts one randomized trial in MRCC patients, then compares the effect of intravenous Interleukin-2 (IL2) and Interferon (IFN) with subcutaneous IL2+IFN in good prognosis patients. The response review committee has agreed to evaluate the response status of patients using both classifications. Methods: 68 patients were randomly designated for review. All documents, specially CT-scan images before treatment start and at first tumor response evaluation, were reviewed. The radiological images of 7 patients were not evaluable; 61 were finally assessed using both WHO and RECIST criteria. Results: Median age was 58 years (25–71); sex ratio was 13 females / 48 males, number of metastatic organ sites was 1 in 42 patients and ≥2 in 19. Organ sites involved were lungs (42), mediastinal (12) or abdominal (9) lymph nodes, pleura (9), liver (5), nephrectomy bed (5), others (6). Response rates were 9/61 (14.7%) vs. 7/61 (11.4%) (P=0.5), and progression rates were 27/61 (44.3%) vs. 35/61 (57.3%) (P=0.008) with RECIST and WHO, respectively. Conclusions: Using RECIST criteria slightly improves response rates, while significantly underscoring progression, as compared with the tumor response classification obtained using WHO criteria. This is important when time to progression represents the major end-point, as in studies investigating some new biological agents in MRCC. Moreover, a number of patients could be proposed longer exposures to potentially non-active but toxic agents. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Abstract P137: Aerobic, Resistance or Combination Exercise Training does not Reduce C-Reactive Protein Levels in Individuals with Type 2 Diabetes
Authors: Damon L Swift, Neil M Johannsen, Conrad P Earnest, Steven N Blair, Timothy S Church
Journal: Circulation (2012)

Introduction: Type 2 diabetes is associated with elevated C-reactive protein levels (CRP), which is an independent risk factor for cardiovascular disease. Aerobic exercise training especially with weight/adiposity reduction has been shown to improve CRP, however few studies have evaluated the effect of other exercise training modalities (aerobic, resistance or combination training) on CRP in individuals with type 2 diabetes. Hypothesis: We hypothesize that combination training will improve CRP to a greater extent than other modalities of exercise training, and change in CRP levels will be associated with changes in weight and adiposity. Methods: The present study is a secondary analysis of the Health Benefits of Aerobic and Resistance Training in Individuals with Type 2 Diabetes (HART-D) study. Participants (n=204) were randomized to aerobic exercise (aerobic), resistance exercise (resistance) or a combination of both (combination) for nine months. Results: Baseline CRP was correlated with fat mass, waist circumference, BMI, and inversely correlated with VO2 peak (p&lt;0.05). CRP was not reduced in the aerobic (0.16 mg•L-1, 95% CI: -1.0, 1.3), resistance (-0.03 mg•L-1, 95% CI: -1.1, 1.0) or combination (-0.49 mg•L-1, 95% CI: -1.5 to 0.6) groups compared to control (0.35 mg•L-1, 95% CI: -1.0, 1.7). Change in CRP was associated with change in fasting glucose (r=0.20, p= 0.009), glycated hemoglobin (HbA1C) (r=0.21 p=0.005), and fat mass (r=0.19, p=0.016), but not change in fitness or weight (p &gt; 0.05). Conclusions: In conclusion, aerobic, resistance or a combination of both did not reduce CRP levels in individuals with type 2 diabetes. However, exercise related improvements in HbA1C, fasting glucose, and fat mass were associated with reductions in CRP.
The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells
Authors: C. Kurkjian, N. B. Janakiram, S. Guruswamy, C. V. Rao, H. Ozer
Journal: Journal of Clinical Oncology (2007)

1537 Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p&lt;0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p &lt;0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21 WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer. No significant financial relationships to disclose.
Baseline Depression Severity as Moderator of Depression Outcomes Between Cognitive Behavioral Therapy vs Pharmacotherapy
Authors: Erica S. Weitz, Steven D. Hollon, Jos Twisk, Annemieke van Straten, Marcus J. H. Huibers, Daniel David, Robert J. DeRubeis, Sona Dimidjian, Boadie W. Dunlop, Ioana A. Cristea, Mahbobeh Faramarzi, Ulrich Hegerl, Robin B. Jarrett, Farzan Kheirkhah, Sidney H. Kennedy, Roland Mergl, Jeanne Miranda, David C. Mohr, A. John Rush, Zindel V. Segal, Juned Siddique, Anne D. Simons, Jeffrey R. Vittengl, Pim Cuijpers
Journal: JAMA Psychiatry (2015)

IMPORTANCECurrent guidelines recommend treating severe depression with pharmacotherapy.Randomized clinical trials as well as traditional meta-analyses have considerable limitations in testing for moderators of treatment outcomes.OBJECTIVES To conduct a systematic literature search, collect primary data from trials, and analyze baseline depression severity as a moderator of treatment outcomes between cognitive behavioral therapy (CBT) and antidepressant medication (ADM).