tbuckley/cabot-search huggingface dataset:
Hallucinations: theoretical and clinical overview
Authors: Ghazi Asaad, Bruce Shapiro
Journal: American Journal of Psychiatry (1986)

The authors review the literature on hallucinations; provide theoretical background on these phenomena from physiological, biochemical, and psychological points of view; and discuss the presentations of hallucinations in different diagnostic categories. The longstanding notion that hallucinations are to be equated with schizophrenia, they conclude, is clearly unfounded, and hallucinations are never pathognomonic of any given disorder but can be relatively specific for some conditions. Current knowledge and methods of research have produced no single mechanism to account for the etiology or pathogenesis of hallucinations. The authors present an integrated approach toward viewing the etiology and clinical presentation of hallucinations that involves concepts of biological vulnerability and psychological influences.
Combined Alcoholics Anonymous and professional care for addicted physicians
Authors: M Galanter, D Talbott, K Gallegos, E Rubenstone
Journal: American Journal of Psychiatry (1990)

The authors studied 100 impaired physicians who were successfully treated in a program that combined professionally directed psychotherapeutic treatment and peer-led self-help. An average of 33.4 months after admission they all reported being abstinent and rated Alcoholics Anonymous (AA) as more important to their recovery than professionally directed modalities. Feelings of affiliativeness to AA, which were very high, were strong predictors of the respondents' perceived support for their recovery. These feelings, and an identification with the role of care giver in addiction treatment, appeared to be central to their recovery process.
Determination of Recommended Phase 2 Dose of ABT-199 (GDC-0199) Combined with Rituximab (R) in Patients with Relapsed / Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
Authors: Andrew W. Roberts, Shuo Ma, Danielle M. Brander, Thomas J. Kipps, Jacqueline C. Barrientos, Matthew S. Davids, Mary Ann Anderson, Constantine Tam, Tanita Mason-Bright, Nikita K. Rudersdorf, Lori Gressick, Jianning Yang, Wijith Munasinghe, Ming Zhu, Elisa Cerri, Sari H. Enschede, Rod A. Humerickhouse, John F Seymour
Journal: Blood (2014)
Abstract 15561: Physician Decision-Making and Trends in Use of Cardiac Stress Testing to Diagnose Coronary Heart Disease in The United States
Authors: Joseph A Ladapo, Saul Blecker, Pamela S Douglas
Journal: Circulation (2013)

Introduction:  Utilization of cardiac stress testing for CHD has come under intense scrutiny because of concerns about explosive growth, high costs, and patient safety related to radiation exposure.   Hypothesis:  Changing population demographics and risk factors do not explain recent growth in stress testing.   Method:  We analyzed a nationally representative US sample of 839,354 adult ambulatory visits from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey from 1993 to 2010. Patients with CHD were excluded. The main outcome was survey-weighted incidence of referrals for or performance of stress testing. Multivariable logistic regression was used to test time trends, with year modeled as a linear predictor, and we included clinical risk factors (smoking, diabetes, dyslipidemia, and hypertension), whether the patient’s reason for visiting the physician was chest pain, physician specialty, sociodemographic characteristics, geographic location, and insurance status.   Result:  The annual number of adult ambulatory visits that resulted in a cardiac stress test being ordered or performed increased from 1.86 million in 1993-1997 (31 in 10,000 visits) to 3.89 million in 2006-2010 (46 in 10,000 visits). After adjusting for clinical and sociodemographic characteristics, there was no evidence of a time trend in stress testing use (P=0.48 for trend). However, the portion of cardiac stress tests performed with imaging increased from 64% (95% CI 48%-79%) in 1993-1997 to 87% (95% CI 79%-96%) in 2006-2010 (P   Conclusion:  Growth in physician use of stress testing may be attributable to changes in population demographics, but rising substitution of imaging for nonimaging tests makes tracking of stress imaging alone a misleading metric for utilization. Nonetheless, our findings support and further refine concerns voiced by professional societies and insurers about stress test utilization.
Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.
Authors: D P Wood, M Banerjee
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy. MATERIALS AND METHODS We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4). RESULTS Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival. CONCLUSION RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.
Noninvasive Detection of Fibrosis Applying Contrast-Enhanced Cardiac Magnetic Resonance in Different Forms of Left Ventricular Hypertrophy
Authors: Andre Rudolph, Hassan Abdel-Aty, Steffen Bohl, Philipp Boyé, Anja Zagrosek, Rainer Dietz, Jeanette Schulz-Menger
Journal: Journal of the American College of Cardiology (2009)
Alternatives to lithium for preventive treatment of bipolar disorder
Authors: R F Prien, A J Gelenberg
Journal: American Journal of Psychiatry (1989)

The authors review the research literature on drug treatment for the prevention of recurrences in bipolar disorder, emphasizing the available alternatives to lithium therapy. They discuss the need for alternative treatments and the current status of promising agents. Carbamazepine receives special attention because of its status as the most promising backup treatment for lithium. The authors conclude that despite the extensive literature on carbamazepine, there is strong need for carefully designed, prospective, double-blind studies to establish the efficacy of carbamazepine alone and in combination with lithium as a prophylactic treatment for bipolar disorder. Difficulties in developing and evaluating preventive maintenance are discussed.
Abstract 2948: Evidence of Coronary Microvascular Dysfunction in patients with Systemic Inflammatory Diseases
Authors: Alejandro Recio-Mayoral, M B Rubens, J C Kaski, O Harari, P G Camici
Journal: Circulation (2007)

Purpose: Accelerated coronary disease is a leading cause of morbidity and mortality in patients (pts) suffering from immune-mediated inflammatory diseases (IMID), such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We tested the hypothesis that inflammation, in the absence of conventional cardiovascular risk factors, could result in coronary microvascular dysfunction (CMD) which is known to precede atherosclerosis in large vessels in pts with cardiovascular risk factors. Methods: Myocardial blood flow (MBF, ml/min/g) was measured using positron emission tomography at rest and during i.v. adenosine (140 μg/Kg/min) in 8 SLE and 10 RA pts aged 47 ± 8 years without conventional cardiovascular risk factors and in 18 age and gender matched controls. In pts multislice (64 slices) CT coronary angiography was performed to exclude coronary stenoses. Results: Mean disease duration was 18 ± 11 and 14 ± 6 years in RA and SLE respectively. There was no difference in resting MBF between pts and controls (1.27 ± 0.25 vs 1.11 ± 0.23; p=0.06). However, adenosine MBF was diffusely reduced in pts compared with controls (2.72 ± 0.84 vs 4.20 ± 0.75; p&lt;0.0001) (Figure ). Coronary flow reserve (CFR; adenosine/resting MBF) was significantly reduced in pts (2.24 ± 0.74) compared with controls (4.00 ± 0.83; p&lt;0.0001). Six pts showed ECG changes during adenosine stress and had a more severe reduction in CFR (1.73 ± 0.88) compared with those without ECG changes (2.49 ± 0.54; p&lt;0.006). Conclusions: Patients with IMID and without conventional cardiovascular risk factors have evidence of CMD which can result in reductions of CFR severe enough to cause myocardial ischemia.
Half a century of ECT use in young people
Authors: J M Rey, G Walter
Journal: American Journal of Psychiatry (1997)

Objective: Pharmacological treatments for certain psychiatric disorders in young people are often ineffective and may cause major side effects; thus, it is important to investigate other treatments.This article reviews the literature on the efficacy and safety of ECT in this age group and examines the evidence for the suggestion that it may be used inappropriately.Method: All studies published in English and other languages on the use of ECT in persons 18 years of age or younger were obtained.The reports were systematically reviewed and rated according to the quality of the information in several domains, yielding an overall quality score for each study.Individual cases from each report were then examined and grouped according to diagnosis and response to ECT.Results: Sixty reports describing ECT in 396 patients were identified; most (63%) were single case reports.The overall quality was poor but improved in the more recent studies.There were no controlled trials.Rates of improvement across studies were 63% for depression, 80% for mania, 42% for schizophrenia, and 80% for catatonia.Serious complications were very rare, whereas minor, transient side effects appeared common.Conclusions: ECT in the young seems similar in effectiveness and side effects to ECT in adults.However, this conclusion is qualified by the lack of systematic evidence.More research and education of professionals and the public are needed.It is suggested that ECT registers be set up, that surveys and controlled trials be conducted, and that seizure thresholds, the optimal anesthetic, effects of concurrent medications, and cognitive consequences of ECT in the young be investigated.
Measles transmission associated with international air travel - Massachusetts and New York, July-August 2010.
Authors: N. Cocoros, R. Hernandez, N. Harrington, E. Rausch-Phung, C. R. Schulte, D. Blog, K. Gallagher, A. Klevos, C. Kim, N. Marano, F. Alvarado-Ramy
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
Female pattern hair loss: beyond an androgenic aetiology?
Authors: E.A. Langan, R. Paus
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, We read with great interest the intriguing case report by Cousen and Messenger describing female pattern hair loss (FPHL) occurring in a patient with complete androgen sensitivity syndrome, suggesting that mechanisms other than the effects of androgens contribute to this form of hair loss in women.1 The authors hypothesized that one potential mechanism may be via oestrogens, given that oestrogens inhibit hair growth in animal models, where they can arrest follicles in telogen and can prematurely induce catagen in growing (anagen) hair follicles.2, 3 The authors' argument is supported by the observation that 17β‐estradiol indeed exerts hair growth inhibitory properties in female organ‐cultured occipital scalp hair follicles.4 Furthermore, hair loss constitutes a common undesired effect of therapy in female patients undergoing treatment with aromatase inhibitors,5 and although not evidence‐based medicine, topical oestrogen treatment has been a mainstay of FPHL management in central Europe for decades.6 Thus, we are delighted to learn that the authors appear to agree with our concept that the relative importance of oestrogen in normal female scalp hair follicle function and in FPHL pathogenesis remains widely underestimated and may even exceed that of androgens.2, 4
Hypoxia Inducible Factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis
Authors: S. Huerta-Yepez, G. J. Baay-Guzman, I. G. Bebenek, R. Hernandez-Pando, M. I. Vega, L. Chi, M. Riedl, D. Diaz-Sanchez, E. Kleerup, D. P. Tashkin, F. J. Gonzalez, B. Bonavida, M. Zeidler, O. Hankinson
Journal: Allergy (2011)

To cite this article: Huerta-Yepez S, Baay-Guzman GJ, Bebenek IG, Hernandez-Pando R, Vega MI, Chi L, Riedl M, Diaz-Sanchez D, Kleerup E, Tashkin DP, Gonzalez FJ, Bonavida B, Zeidler M, Hankinson O. Hypoxia Inducible Factor promotes murine allergic airway inflammation and is increased in asthma and rhinitis. Allergy 2011; 66: 909–918. Background: New therapies are necessary to address inadequate asthma control in many patients. This study sets out to investigate whether hypoxia-inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment. Methods: Mice conditionally knocked out for HIF-1β were examined for their ability to mount an allergic inflammatory response in the lung after intratracheal exposure to ovalbumin. The effects of treating wild-type mice with either ethyl-3,4-dihydroxybenzoate (EDHB) or 2-methoxyestradiol (2ME), which upregulate and downregulate HIF, respectively, were determined. HIF-1α levels were also measured in endobronchial biopsies and bronchial fluid of patients with asthma and nasal fluid of patients with rhinitis after challenge. Results: Deletion of HIF-1β resulted in diminished AAI and diminished production of ovalbumin-specific IgE and IgG1. EDHB enhanced the inflammatory response, which was muted upon simultaneous inhibition of vascular endothelial growth factor (VEGF). EDHB and 2ME antagonized each other with regard to their effects on airway inflammation and mucus production. The levels of HIF-1α and VEGF increased in lung tissue and bronchial fluid of patients with asthma and in the nasal fluid of patients with rhinitis after challenge. Conclusions: Our results support the notion that HIF is directly involved in the development of AAI. Most importantly, we demonstrate for the first time that HIF-1α is increased after challenge in patients with asthma and rhinitis. Therefore, we propose that HIF may be a potential therapeutic target for asthma and possibly for other inflammatory diseases.
Anti-inflammatory effect of a novel inhaled dual PDE3/4 inhibitor RPL554 in man, a unique "first-in-class" drug for the treatment of COPD & asthma
Authors: Dave Singh, Fred Reid, Lui Franciosi, Michael Walker, Clive Page
Journal: European Respiratory Journal (2013)

Background: Current bronchodilators have limited efficacy in severe COPD & asthma & the neutrophilic inflammation is not well treated. RPL554 is a novel, well tolerated dual PDE 3/4 inhibitor with significant bronchodilator properties in COPD & asthma, bronchoprotective effects in asthmatics & is anti-inflammatory pre-clinically.

Aim: To evaluate the effect of RPL554 on inhaled lipopolysaccharide (LPS)-induced neutrophilia in sputum.

Methods: In a randomised, double-blind, placebo (PBO)-controlled crossover study in 21 healthy subjects, RPL554 (0.018mg/kg)was inhaled using a jet nebuliser via an oro-nasal mask o.d for 6 days. On day 6 an inhaled LPS challenge was performed 1h post RPL554 or PBO using a Mefar dosimeter. Sputum was induced 6 & 24h post-LPS & cells/g sputum calculated.

Results: RPL554 statistically significantly reduced total & individual cells, 6h post LPS vs PBO (Table 1). RPL554 was well-tolerated with AE’s being generally mild, transient & not different from PBO. RPL554’s PK properties were reproducible over 6 days.

View this table:

Table 1. Cells/g sputum





Conclusions: RPL554 produced significant airway anti-inflammatory effects, including reducing neutrophil infiltration & is the first drug demonstrating bronchodilator & anti-inflammatory properties in one molecule. RPL554 is thus a promising “bifunctional” first in class treatment for patients with COPD or asthma and not well controlled on existing treatment.
Incest: children at risk
Authors: Diane H. Browning, Bonny Boatman
Journal: American Journal of Psychiatry (1977)

The typical family constellation in this study of 14 cases of incest was that of a chronically depressed mother, an alcoholic and violent father or stepfather, and an eldest daughter who was forced to assume many of her mother's responsibilities, with ensuing role confusion. The authors stress the need for physicians to be alert to the possibility of incest in such high-risk families.
Abstract 3698: Transcoronary Delivery of Allogenic Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Model of Recent Myocardial Infarction
Authors: Hung Ly, Josephine Pressacco, Francois Marcotte, Bernard Thibault, Jean-Francois Tanguay
Journal: Circulation (2009)

Background: For cardiac cell therapy, intracoronary delivery remains a delivery method fraught with potential safety concerns, especially for bone-marrow mesenchymal stem cells (BM-MSCs).

Study Aim: To investigate the novel transcoronary delivery route (TCD) for BM-MSCs.

Methods: Anterior myocardial infarction (MI) was created in Yorkshire-Landrace swine. TCD was performed with the Cricket catheter, which allows delivery to the adventitial space thus circumventing concerns of cell washout or microembolization. Cardiac MRI studies were performed prior to and 1-month after cell injection.

Results: Seven swine survived MI creation (BM-MSC group, n=3; control group, n=4). Infarct sizes were comparable (BM-MSC, 35.2±7% vs. Controls, 29.6±5%; p=NS). While all infarcts were transmural, 2/3 BM-MSC swine had evidence of concomitant subendocardial hemorrhage. On day 7 post-MI, in the cell group, 50×10^6 allogenic BM-MSCs were injected (Figure[⇓][1]) whereas medium was injected in control swine. At 1-month, relative to baseline, MRI studies documented adverse LV remodeling in controls (LVEDV: 117.9±8.9ml vs. 153.7±15.5ml, respectively; p=0.02) compared to BM-MSC swine (LVEDV: 114.4±13.2ml vs. 113.4±34.7ml, respectively; p=NS). No complications occurred during TCD. Serial troponins, hs-CRP and pro-NT-BNP did not detect myocardial injury, inflammation or cardiac dysfunction following allogenic BM-MSC TCD. Moreover, post-injection electrophysiological assessment did not detect evidence of proarrhythmia.

Conclusion: For cardiac cell therapy, allogenic BM-MSC TCD is both safe and feasible in recently infarcted hearts with potential to impact adverse LV remodeling



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Cost‐effectiveness of hepatitis C treatment for patients in early stages of liver disease
Authors: Andrew J. Leidner, Harrell W. Chesson, Fujie Xu, John W. Ward, Philip R. Spradling, Scott D. Holmberg
Journal: Hepatology (2015)

New treatments for hepatitis C virus (HCV) may be highly effective but are associated with substantial costs that may compel clinicians and patients to consider delaying treatment. This study investigated the cost‐effectiveness of these treatments with a focus on patients in early stages of liver disease. We developed a state‐transition (or Markov) model to calculate costs incurred and quality‐adjusted life‐years (QALYs) gained following HCV treatment, and we computed incremental cost‐effectiveness ratios (cost per QALY gained, in 2012 US dollars) for treatment at different stages of liver disease versus delaying treatment until the subsequent liver disease stage. Our analysis did not include the potential treatment benefits associated with reduced non–liver‐related mortality or preventing HCV transmission. All parameter values, particularly treatment cost, were varied in sensitivity analyses. The base case scenario represented a 55‐year‐old patient with genotype 1 HCV infection with a treatment cost of $100,000 and treatment effectiveness of 90%. In this scenario, for a 55‐year‐old patient with moderate liver fibrosis (Metavir stage F2), the cost‐effectiveness of immediately initiating treatment at F2 (versus delaying treatment until F3) was $37,300/QALY. For patients immediately treated at F0 (versus delaying treatment until F1), the threshold of treatment costs that yielded $50,000/QALY and $100,000/QALY cost‐effectiveness ratios were $22,200 and $42,400, respectively. Conclusion : Immediate treatment of HCV‐infected patients with moderate and advanced fibrosis appears to be cost‐effective, and immediate treatment of patients with minimal or no fibrosis can be cost‐effective as well, particularly when lower treatment costs are assumed. (H epatology 2015;61:1860–1869)
Abstract 8690: The Junctophilin 2 Missense Mutation, E169K, Promotes Atrial Fibrillation in Mice
Authors: Sameer Ather, Sayali Dixit, Wei Wang, Mark McCauley, David Beavers, Alejandro Garbino, Andrew Landstrom, Lacopo Olivotto, Michael Ackerman, Xander Wehrens
Journal: Circulation (2011)

Background: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people. Recently, a patient with HCM with paroxysmal atrial fibrillation (AF) and sinoatrial block was found to have a missense mutation, E169K, in the junctophilin 2 (JPH2) protein. Loss of JPH2 has been shown to affect intracellular Ca2+ release in the heart. To date, no study has evaluated the effect of E169K mutation on Ca2+ handling and arrhythmogenesis. Hypothesis: The JPH2 E169K mutation promotes sarcoplasmic reticulum Ca2+ leak causing abnormal atrial conduction and AF. Methods and Results: We evaluated our hypothesis by generating 3 mice that overexpressed 1) JPH2 with E169K mutation (EK-Tg), 2) WT JPH2 (WT-Tg) and 3) JPH2 with inactive P584S mutation (PS-Tg). On Western Blot, JPH2 expression was increased by 2-3 fold in all the mouse groups compared to non-transgenic controls. Echocardiography at 6 months of age revealed normal fractional shortening in all mice. At baseline, EK-Tg mice had a shorter RR interval (104±1 ms, n=10) vs. WT-Tg (123±5 ms, n=8, p=0.001) and PS-Tg mice (121±5 ms, n=5, p&lt;0.001). EK-Tg mice also had a shorter PR interval (36±1 ms, n=10) vs. WT-Tg (41±1 ms, n=8, p=0.01) and PS-Tg mice (39±1 ms, n=5, p=0.15). On intracardiac electrophysiology studies, EK-Tg mice had shorter AVERP (39±2 ms, n=10) vs. WT-Tg (51±2 ms, n=8, p=0.005) and PS-Tg mice (48±3 ms, n=5, p=0.05). On overdrive pacing of the atria in the presence of epinephrine and caffeine, EK-Tg mice had a 57% incidence of AF (n=10) vs. 21% in WT-Tg (n=8, p&lt;0.05) and 33% in PS-Tg mice (n=5, p=0.2). Isolated cardiomyocytes from EK-Tg mice had a higher Ca2+ spark frequency (6.7±0.8 events/100 um/s, n=20) vs. cardiomyocytes from WT-Tg (1.8±0.5 events/100 um/s, n=10, p&lt;0.001) and PS-Tg mice (3.3±1.0 events/100 um/s, n=16, p&lt;0.05). Lastly, JPH2 levels were lower in RyR2 channels immunoprecipitated from EK-Tg mice vs. RyR2 from WT-Tg mice (65% vs. 100%, p&lt;0.05). Conclusion: The JPH2 mutation, E169K, leads to reduced binding of JPH2 with RyR2, increased SR Ca2+ leak, abnormal atrial conduction and AF. The data suggest that JPH2 may serve as a critical stabilizing molecule for RyR2; further approaches to stabilize this interaction may lead to improved control of AF in susceptible populations.