tbuckley/cabot-search huggingface dataset:
Use of ECT in the United States in 1975, 1980, and 1986
Authors: J W Thompson, R D Weiner, C P Myers
Journal: American Journal of Psychiatry (1994)

The objective was to analyze nationally representative data from the National Institute of Mental Health (NIMH) to update trends in the use of ECT in the United States.The data are estimates from the NIMH Sample Survey Program for 1975, 1980, and 1986, which include representative samples of inpatients in psychiatric facilities in the United States. The authors' analyses use trend data from public general hospitals, private general hospitals, private psychiatric hospitals, and state and county mental hospitals. They report on 126,739 patients who received ECT in 1975, 1980, and 1986, focusing on data from 1980 and 1986.In 1986, 36,558 patients received ECT. This represents a decrease from the 1975 figure (58,667 patients) but no change from 1980 (31,514 patients). ECT was used primarily in private general hospitals (64%) and private psychiatric hospitals and much less often in public general hospitals and state and county mental hospitals. In 1986 over 90% of ECT recipients were white, and 84% had an affective disorder diagnosis. Although 71% of the patients who received ECT were women, hospital type and age were more important than gender in predicting ECT use. Individuals 65 years of age and older received ECT out of proportion to their numbers in inpatient care.The declining use of ECT in the United States ended in the 1980s. Few African Americans receive ECT, and its use is becoming more targeted toward patients with affective disorders. The amount of services research done on this modality is very small. Basic questions have yet to be answered, including who refers patients for ECT and why, and how ECT fits into the overall course of treatment.
Exploration of failure on the subspecialty examination for child and adolescent psychiatry
Authors: T Shapiro, D Juul, S C Scheiber
Journal: American Journal of Psychiatry (1996)

The purposes of this study were to compare first-time performance on the oral examination for certification in child and adolescent psychiatry with first-time performance on the written and oral examinations for certification in general psychiatry and to identify factors that contribute to failure on the child and adolescent psychiatry oral examination.To address the first question, two successive cohorts of first-time child and adolescent psychiatry candidates were identified, and chi-square analyses were used to explore the relationship between first-time performance on the different examinations. For the second question, a special checklist was developed and completed for all candidates who failed any section of the oral examination for child and adolescent psychiatry three successive times.There was no relationship between passing or failing the written and oral examinations for general psychiatry on the first attempt and passing or failing the child and adolescent psychiatry oral examination on the first attempt. The checklist results suggested that the failing candidates had difficulty in organizing and integrating case material. Other weaknesses were related to the specific sections of the oral examination.The results suggest that the knowledge and skills that are required to pass the child and adolescent psychiatry oral examination are different from those of the general psychiatry examination. The information about weaknesses should be of interest to general and child and adolescent psychiatric educators, candidates, and service delivery agencies.
Abstract 2199: Effects of Beta-Blocker on Dynamic Repolarization Measured by 24-hr Electrocardiography in LQT1 and LQT2 Forms of Congenital Long-QT Syndrome
Authors: Yutaka Take, Yuko Yamada, Koji Miyamoto, Hideo Okamura, Takashi Noda, Kazuhiro Suyama, Takashi Kurita, Naohiko Aihara, Shiro Kamakura, Wataru Shimizu
Journal: Circulation (2007)

Backgrounds:Effects of β-blocker on dynamic ventricular repolarization in relation to heart rate (HR) change in patients with genotyped congenital long-QT syndrome (LQTS) are largely unknown. Metho...
Toscana virus meningitis in Portugal, 2002-2005
Authors: L Santos, J Simões, R Costa, S Martins, H Lecour
Journal: Eurosurveillance (2007)

Toscana virus infection is endemic in Italy, but has also been documented in other Mediterranean countries. Our aim was to investigate the occurrence of Toscana virus (TOSV) meningitis in children and young adults in a metropolitan area in the north of Portugal. Cerebrospinal fluid samples from 308 patients with the diagnosis of meningitis and with negative bacterial culture were tested for enteroviruses and herpesviruseses by reverse transcription PCR. Those samples that proved negative for enterovirus and herpesvirus were tested for Toscana virus with a commercial reverse transcription nested PCR assay. In total, we investigated 106 samples, collected between May and September during the four-year period between 2002 and 2005 from patients younger than 30 years old. Toscana virus was the cause of meningitis in six (5.6%) of the cases, three children and three young adults. All had a benign course and self-limited disease. Since a first case report of TOSV infection 1985 and another in 1996, both in foreign tourists, these six cases of Toscana virus meningitis are, to our knowledge, the first diagnosed in Portuguese inhabitants, and they underline the need for more studies on the prevalence of this virus in Portugal.
Abstract 556: Early, Simple, Noninvasive Predictors of Left Main or 3-Vessel Disease in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Masami Kosuge, Kazuo Kimura, Toshiyuki Ishikawa, Kazuaki Uchino, Toshiaki Ebina, Kiyoshi Hibi, Noriaki Iwahashi, Kengo Tsukahara, Jyun Okuda, Satoshi Umemura
Journal: Circulation (2008)

In patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), identification of left main or 3-vessel disease (LM/3VD) is crucial for deciding whether to initiate early treatment wi...
Sensitivity to erlotinib (Tarceva) depends on cyclin-dependent kinase 2 activity
Authors: Fumiyuki Yamasaki, Gabriel N. Hortobagyi, Kaoru Kurisu, Naoto T. Ueno
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

1670 

The epidermal growth factor receptor (EGFR, HER1) is highly expressed in a variety of solid tumors. Activation of EGFR signaling pathways in tumor cells has been linked with increased proliferation, angiogenesis and metastasis and decreased apoptosis, and hence EGFR has been proposed as a target for anticancer therapy. Erlotinib, an orally available, quinazoline-based agent, inhibits EGFR tyrosine kinase (TK) by competing with ATP, inhibiting phosphorylation of this kinase. Some reports indicate that EGFR expression level does not predict sensitivity to EGFR-TK inhibitors such as erlotinib (R. Bailey et al, Lung Cancer 2003; Sirotnak FM et al, Clin Cancer Res 2000; Baselga J, J Clin Oncol 2004), while other reports suggest that somatic mutations in the TK domain of EGFR reflect the sensitivity of lung cancer cells to EGFR-TK inhibitors (Lynch TJ, et al, N Engl J Med 2004; Paez JG, et al, Science 2004). Thus far, such mutations have been found only in non-small cell lung cancer, and other factors for predicting response to EGFR-TK inhibitors are yet to be defined. We assessed whether cyclin-dependent kinase 2 (CDK2), a final downstream target in EGFR signaling pathways, is involved in sensitivity to erlotinib in 1 epidermoid carcinoma cell line (A431) and 10 breast cancer cell lines (MDA-231, -361, -435, -453, -468; SKBr-3, BT-20, BT-474, T47D, and MCF-7). MTT assays showed that A431 and SKBr3 cells were quite sensitive to erlotinib (A431, IC50 = 1.531 uM, IC25 = 4.748 uM; SKBr-3, IC50 = 3.980 uM, IC25 = 10.628 uM) and BT-474 and T47D cells were moderately so (BT-474, IC50 = 5.005uM, IC25 > 20uM; T47D, IC50 = 9.803uM, IC25 > 20uM). Flow cytometry confirmed that erlotinib-sensitive cell lines showed G1 arrest and increases in sub-G1 cells. EGFR overexpression (detected in A431, MDA-468, and BT-20 cells by western blotting) was not associated with sensitivity to erlotinib, even though EGFR phosphorylation was inhibited in both sensitive (A431) and resistant cell lines (MDA-468, BT-20). However, loss of CDK2 activity after erlotinib treatment strongly correlated with sensitivity to erlotinib. Restoration of CDK2 activity by transfecting cells with an adenovirus containing wild-type CDK2 partially restored proliferation in A431 cells and SKBr3 cells treated with erlotinib (A431, IC50 = 4.630uM, IC25 > 20uM 4.748uM; SKBr3, IC50 > 20uM). These results indicate that sensitivity to erlotinib depends in part on CDK2 activity; that suppression of CDK2 is critical to the activity of erlotinib regardless of erlotinib’s upstream molecular effects; and that measurement of CDK2 activity after a brief exposure to erlotinib may prove to be a predictive marker of sensitivity to erlotinib.
Characterization of the interacting mechanisms between Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) and the small subunits of human Ribonucleotide Reductase
Authors: Jimin Shao, Bingsen Zhou, Lijun Zhu, Angel J. Di Bilio, Leila Su, Yate-Ching Yuan, Yun Yen
Journal: Cancer Research (2005)

4108   Ribonucleotide reductase (RR) is an important therapeutic target for anticancer drugs. The enzyme consists of two nonidentical subunits, M1 and M2 or p53R2. Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone) is a new potent RR inhibitor currently in phase II clinical trials. It is known that the compound is an iron chelator and targets the small subunits of RR. However, the interacting mechanisms of the compound with the small subunits remain unclear. We have studied the effects of Triapine and its iron complexes on pure recombinant RR subunit proteins. In vitro RR activity assays were carried out using two forms of the holoenzyme (M2/M1 and p53R2/M1) both in the presence and absence of iron in the reaction mixture. We showed that in the absence of iron in the reaction mixture, the Triapine/Fe complex was more potent than Triapine alone, in addition to demonstrating a stronger effect on the p53R2/M1 holoenzyme compared to the M2/M1 holoenzyme with respect to RR activity. In contrast to this, when iron was introduced to the reaction mixture, we found that the potency of the Triapine/Fe complex for p53R2/M1 was reduced to almost the same level as for M2/M1. These data suggest that inhibition and regeneration of RR activity occurs simultaneously. The enzymatic activities regenerate with the addition of iron and DTT in the reaction mixture. Electron Paramagnetic Resonance (EPR) measurements showed that inhibition of RR activity was accompanied by reduction of the tyrosyl radical of the small subunits. The potency of radical quenching for both small subunit proteins increased in the order Triapine  3 H] Triapine-protein binding assay using wild-type and mutant M2 and p53R2 proteins and computer-assistant docking are still ongoing. Our findings may contribute to the design of more potent and subunit-selective RR inhibitors as novel anticancer agents. (Supported by NCI R01 Grant CA72767)
Abstract B74: Minimally invasive ablative therapy for mucinous cystic neoplasms (MCN) in a genetically engineered mouse model
Authors: Carlos Cuevas, Ashley M. Dotson, Sunil R. Hingorani
Journal: Cancer Research (2015)

Abstract Pancreatic cystic neoplasms are an increasing health problem in the adult population due to their inherent potential to progress to invasive adenocarcinomas. The only available treatment is resection with the consequential significant morbidity and mortality associated with pancreatic surgery. Direct percutaneous injection of an ablative substance represents a potential new approach to this problem. Limited studies performed in human subjects speak to the potential feasibility of this approach, but no systematic or rigorous assessment of agents and outcomes has been possible. We have undertaken an effort to evaluate the effectiveness of intracystic injections of different chemical ablative substances (including ethanol and sodium tetradecyl sulfate) or chemotherapeutic drugs (including gemcitabine and paclitaxel) for the treatment of mucinous cystic neoplasms (MCN) in a murine model of the disease. We have developed a genetically engineered mouse model of MCN (KrasLSL-G12D;Dpc4fl/fl;Cre) that recapitulates the prototypical features of the human correlate, including development of an ovarian-type stroma with estrogen receptor (ER) and progesterone receptor (PR)-positive cells. An MCN is first identified in the mouse with high-resolution ultrasound imaging (HRUS) and the cyst fluid aspirated; the cyst is then injected with one of the treatment regimens. Study feasibility was first established with image-guided India ink injections followed by necropsy to evaluate successful aspiration and injection. Following treatment, disease response is evaluated by serial HRUS and detailed histopathologic and molecular analyses on recovered tissues at study termination. Through these studies we hope to define the optimal therapeutic regimen for non-surgical management of MCN in anticipation of a future clinical trial. We have successfully identified, aspirated and injected MCN with either saline (control) or ablative substances under real time ultrasound guidance in a longitudinal cohort. Challenges to this approach are also discussed including the posterior localization of the treated lesions within the diffusely abnormal pancreas typically found in this animal model. Citation Format: Carlos Cuevas, Ashley M. Dotson, Sunil R. Hingorani. Minimally invasive ablative therapy for mucinous cystic neoplasms (MCN) in a genetically engineered mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B74.
Elucidation of the antagonistic mechanisms of various anti-FLT3 antibodies via binding epitope dissection
Authors: Brent Williams, Gayani Fernando, Haifan Zhang, Xenia Jimenez, Dan Lu, Zhenping Zhu
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4110 

FMS-like tyrosine kinase 3 (FLT3), a receptor consisting of 5 immunoglobulin (Ig)-like extracellular domains, a trans-membrane domain and an intracellular kinase domain, is highly expressed in an array of hematological malignancies including ~90% of acute myelogenous leukemia. FLT3 ligand (FL) stimulation of the receptor promotes the survival and proliferation of leukemia cells. We previously identified several antibodies to FLT3, including EB10, NC7 and D4-3, and demonstrated that these antibodies could effectively block FLT3/FL interaction and inhibit the growth of leukemia cells, irrespective of whether the cells express the ligand-dependent wild-type receptor or the ligand-independent receptor mutants. Here we perform studies in an attempt to elucidate the mechanisms of the inhibitory activity of these antibodies, via dissecting the binding epitope(s) of the antibodies on the receptor. While EB10 and D4-3 only bind to recombinant FLT3 protein that was indirectly coated on a plastic surface via a capturing anti-tag antibody, NC7 binds to the receptor protein that was either indirectly coated or directly immobilized on the plastic surface. Both EB10 and D4-3 monovalent Fab fragments, but not NC7 Fab, block FLT3 from binding to its ligand. However, all three block FLT3/ligand interaction when in the form of bivalent IgG. Epitope-mapping studies using a series of domain-deletion mutants revealed that extracellular Ig domain 1 to 4 of FLT3 is required for FL binding. The binding epitope(s) for both EB10 and D4-3 was mapped to Ig domain 4, and that for NC7 was located in Ig domain 5. These results indicate that EB10 and D4-3 inhibit FLT3 receptor activation through direct competition with ligand and/or blocking of receptor dimerization whereas NC7 IgG antagonistic activity is by steric hindrance. Taken together, our study not only yields significant insight on the mechanism(s) of action of the three anti-FLT3 antibodies, but may also provide strong guidance in the search for more potent and specific FLT3 antagonists.
Patients should be seen by an experienced orthopaedic surgeon
Authors: R. Mackenzie, D. Edwards, A. K Dixon
Journal: BMJ (1996)

EDITOR,—R Watura and colleagues' recommendations regarding direct access to magnetic resonance imaging of the knee for general practitioners merit further discussion.1 The appropriate use of such imaging for knee problems is the subject of considerable research. In selected patients magnetic resonance imaging can help with management decisions and an expensive, invasive arthroscopy can be avoided.2 3 4 It is less certain whether recommending direct access magnetic resonance imaging to avoid an orthopaedic consultation is appropriate.

Watura and …
Comorbidity of axis I and axis II disorders
Authors: J M Oldham, A E Skodol, H D Kellman, S E Hyler, N Doidge, L Rosnick, P E Gallaher
Journal: American Journal of Psychiatry (1995)

In light of continuing controversies concerning the DSM-III-R system for diagnosing personality disorders, their construct validity, and the assignment of disorders to a particular axis, the authors studied patterns of axis I-axis II comorbidity.Semistructured interviews were used to assess axis I and axis II disorders in 200 inpatients and outpatients. Odds ratios were calculated to determine significant comorbidity between classes of current axis I disorders and axis II personality disorders diagnosed according to two methods and defined at two diagnostic thresholds. Distributions of personality disorder traits were also compared in patients with and without axis I disorders.Significantly elevated odds ratios were found for co-occurrence of current mood disorders with avoidant and dependent personality disorders; anxiety disorders with borderline, avoidant, and dependent personality disorders; psychotic disorders with schizotypal, borderline, and dependent personality disorders; psychoactive substance use disorders with borderline and histrionic personality disorders; and eating disorders with schizotypal, borderline, and avoidant personality disorders. These results held when conservative and liberal definitions of personality disorders were used. Non-specific axis I and axis II associations were confirmed for distributions of personality disorder traits.Significant associations occurred between most axis I classes of disorders and axis II disorders and traits in more than one cluster. All axis I classes of disorders except mood disorders co-occurred with borderline personality disorder; however, patients with mood disorders had elevated levels of borderline traits. When any personality disorder was present, there were significant odds that a mood, anxiety, psychotic, or eating disorder would also be present; psychoactive substance use disorders, in contrast, significantly co-occurred with borderline and histrionic personality disorders.
EBF1-PDGFRΒ Fusion in Paediatric Acute Lymphoblastic Leukaemia (ALL): Genetic Profile and Clinical Implications
Authors: Claire Schwab, Rebecca Andrews, Lucy Chilton, Alannah Elliott, Gerald Keil, Stacey Richardson, Sarra L. Ryan, Christopher Wragg, John Moppett, Michelle Cummins, Nicholas Goulden, Ajay J. Vora, Anthony V. Moorman, Christine J. Harrison
Journal: Blood (2014)
Abstract 18285: ARI-3037MO, a Novel Niacin Analog, Significantly Improves Plasma Lipid Levels in the Hyperlipidemic Golden Syrian Hamster
Authors: Beth A Connolly, Daniel P O'Connell, Daniel F LeBlanc, Yu-Lin Kuang, Ernst J Schaefer, Stefania Lamon-Fava, Claude R Benedict, Christopher P Kiritsy, William W Bachovchin
Journal: Circulation (2011)

Introduction: ARI-3037MO is a once-a-day structural analog of niacin currently in Phase I clinical trials for treatment of dyslipidemia. In preclinical studies in multiple species, ARI-3037MO did not induce cutaneous flushing, an adverse event that is commonplace with existing niacin preparations. Hypotheses: We hypothesized that ARI-3037MO would significantly improve the lipoprotein profile of hamsters with diet-induced hyperlipidemia. Methods: Golden Syrian hamsters (n=30, 111-120 g, 56-61 days old) were fed a diet consisting of 11.5% corn oil, 11.5% coconut oil, 0.5% cholesterol, and 0.25% deoxycholate and were provided water containing 10% fructose for 20 days. Animals remained on the atherogenic diet and were dosed P.O. with either vehicle (n=12), 1200 mg/kg/day (9.8 mmol/kg/day) niacin (n=9), or 1400 mg/kg/day (5.8 mmol/kg/day) ARI-3037MO (n=9) for 18 days. At the end of the dosing period, hamsters were sacrificed via CO2 asphyxiation, blood was collected via cardiac puncture, and tissues were harvested. Results: Compared to vehicle, ARI-3037MO significantly reduced plasma levels of TC (mean±SEM; 857±122 vs. 343±66 mg/dL, -60%, p&lt;0.01), LDL-C (253±24 vs. 114±30 mg/dL, -55%, p&lt;0.001), TG (1065±140 vs. 138±28 mg/dL, -87%, p&lt;0.001), and free fatty acids (FFA) (1.96±0.16 vs. 0.75±0.05 mmol/L, -62%, p&lt;0.001). Niacin, administered at a higher molar dose than ARI-3037MO, showed a less pronounced lipid modulating effect (TC, -39%, p=0.05; LDL-C, -33%, p&lt;0.05; no significant changes in TG or FFA). Compared to vehicle, the increase in plasma HDL-C with ARI-3037MO was borderline significant (139±9 vs. 186±25 mg/dL, +33%, p=0.06); however, fast pressure liquid chromatography analysis of pooled plasma indicated an increase in the HDL-C fraction of the ARI-3037MO treated animals. Also, relative to vehicle, ARI-3037MO significantly increased liver Apo-A1 and ATP-Binding Cassette Transporter (ABC) A1 mRNA levels (+66%, p&lt;0.001 and +55%, p&lt;0.01, respectively). Conclusions: Relative to vehicle, ARI-3037MO was more effective than niacin at significantly reducing pro-atherogenic lipoproteins in the hyperlipidemic hamster. In addition, ARI-3037MO increased the proportion of HDL-C, possibly through liver apoAI- and ABCA1-mediated mechanisms.
Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial
Authors: Sheena McCormack, David T Dunn, Monica Desai, David I Dolling, Mitzy Gafos, Richard Gilson, Ann K Sullivan, Amanda Clarke, Iain Reeves, Gabriel Schembri, Nicola Mackie, Christine Bowman, Charles J Lacey, Vanessa Apea, Michael Brady, Julie Fox, Stephen Taylor, Simone Antonucci, Saye H Khoo, James Rooney, Anthony Nardone, Martin Fisher, Alan McOwan, Andrew N Phillips, Anne M Johnson, Brian Gazzard, Owen N Gill
Journal: The Lancet (2015)

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect.