tbuckley/cabot-search huggingface dataset:
Abstract P341: Nonalcoholic Fatty Liver Disease (NAFLD) and Risk of Incident Cognitive Impairment
Authors: Kristine S Alexander, Neil A Zakai, Sarah R Gillett, Steven D Lidofsky, Peter W Callas, Fred Unverzagt, Virginia Wadley, Suzanne E Judd, Mary Cushman
Journal: Circulation (2015)

Background:  Nonalcoholic fatty liver disease (NAFLD) is the most prevalent form of liver disease in the United States and is often considered the hepatic manifestation of the metabolic syndrome. Despite other types of liver disease being associated with cognitive dysfunction, little is known about the impact of NAFLD on cognition.   Hypothesis:  NAFLD is associated with incident cognitive impairment in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.   Methods:  REGARDS recruited 30,239 black and white U.S. men and women to study regional and racial differences in stroke mortality. Among participants with normal baseline cognitive function, we identified 495 cases of incident cognitive impairment over 3.4 years, using 3 cognitive domain tests: list learning, list recall, and verbal fluency. Thresholds for impaired function were defined adjusting for age, race, sex, and education level. The Fatty Liver Index (FLI), a validated surrogate marker for NAFLD, was determined in cases and 587 controls, with FLI >60 considered a positive score. Excluding 36 participants with heavy alcohol consumption, logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of cognitive impairment for NAFLD and its components. The contribution of diabetes to this risk was estimated with bootstrapping.   Results:  NAFLD was associated with increased odds of cognitive impairment in both models (table). Of the components of FLI, only waist circumference was associated in the fully adjusted model (see table). Diabetes explained 28% of the increased odds for cognitive impairment with NAFLD by (95% CI: 7%, 58%). There were no differences in associations of NAFLD with cognitive impairment by race, sex, age or diabetes status (interaction p values all >0.10).   Discussion:  NAFLD, as determined by FLI, was associated with increased risk of incident cognitive impairment, independent of other risk factors. Further research is needed to understand the mechanisms behind this association.
Abstract 36: Changes in HDL Particle Traits in Response to Regular Exercise: Results from the HERITAGE Family Study
Authors: Mark A Sarzynski, Tuomo Rankinen, Arthur S Leon, Dabeeru C Rao, James S Skinner, Jean-Pierre Després, Claude Bouchard
Journal: Circulation (2014)

Given the controversy around HDL-C as a therapeutic target, there is a need to investigate other features of HDL and how they respond to various preventive interventions. We tested the hypothesis that regular exercise would have beneficial effects on HDL particle (HDL-P) traits in sedentary adults. Methods: The following HDL-P traits were measured via NMR (Liposcience Inc.) before and after completion of a 20-week exercise program in the HERITAGE Family Study (N=715): concentration of total, large, medium, and small HDL-P and mean HDL-P size. ANCOVA was used to test for aggregation of HDL-P trait responses in families controlling for age, sex, and baseline BMI and trait value. Results: The concentration of large HDL-P significantly increased in response to regular exercise in both Black and White participants, while the increase was significantly larger in females compared to males (Table 1). In general, regular exercise decreased the concentration of medium and small HDL-P. Together, these responses contributed to a significant increase in the average cholesterol content of HDL particles. Exercise-induced changes in large HDL-P were inversely correlated with changes in fat mass and systolic blood pressure. Moreover, changes in BMI were significantly associated with changes in all of the HDL-P traits, but not with HDL-C. We found significant evidence of familial aggregation for the exercise-induced changes in HDL-P traits in both races, as there was 1.4 to 1.6 times more variance between than within families for the changes in total (p=0.02 in Whites) and large HDL-P (p=0.004 in Whites, p=0.02 in Blacks) and HDL-P size (p=0.0009 in Whites, p=0.009 in Blacks). Conclusion: The HDL-P subclass profile favorably responded to regular exercise in sedentary Black and White adults, highlighted by increases in the concentration of large HDL-P, and may be influenced by a significant genetic component. We provide evidence that regular exercise could potentially be used as an HDL-based therapy designed to target beneficial subfractions.
Drug points: Painful dysaesthesia with ciprofloxacin
Authors: D Zehnder, R Hoigne, K A Neftel, R Sieber
Journal: BMJ (1995)

Dr D ZEHNDER, Professor R HOIGNE, Professor K A NEFTEL, and Dr R SIEBER (Zieglerspital, 3001 Berne, Switzerland) write: Fluoroquinolones have been associated with various adverse effects.1 2 One case of peripheral neuropathy has been reported.3 We report two cases of generalised painful dysaesthesia due to ciprofloxacin, a reaction not previously associated with this particular fluoroquinolone.

A healthy 30 year old …
Abstract 426: The Diovan Reduction Of Proteinutria (Drop) Study: Albuminuria Response to High-Doses Of Valsartan in Type 2 Diabetes Mellitus
Authors: Norman K Hollenberg, Hans-Henrik Parving, Giancarlo Viberti, Giuseppe Remuzzi
Journal: Circulation (2006)

We evaluated whether high doses of valsartan (V), an angiotensin receptor blocker (ARB), are superior to conventional doses to reduce urinary albumin excretion rates (UAER) in type 2 diabetes mellitus (T2DM). In a multicenter, double-blind study, 391 hypertensive patients with T2DM and UAER 20 –700 g/min were randomized to V160 mg (V160), 320 mg (V320) or 640 mg (V640). All patients received V160 for the first 4 wks, then treatment was maintained in one group and increased in the other two groups to V320 or V640 for a total of 30 wks. Comparable UAER reductions from baseline were seen in all groups at wk 4 (P
ALL of Burkitt's type (L3) showing a Complex Karyotype including translocations t(14;18) (q32;q21) and t(3;8) (q27;q24) with BCL2 and BCL6 involvement.
Authors: G Schilling, Lucienne Michaux, J. Dierlamm, Joseph Meyer, T Mende, D Seeger, P Leberecht, DK Hossfeld
Journal: Annals of Oncology (2000)
Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients [published erratum appears in Am J Psychiatry 1991 Oct;148(10):1427]
Authors: P J Perry, D D Miller, S V Arndt, R J Cadoret
Journal: American Journal of Psychiatry (1991)

Clozapine, an atypical antipsychotic, has been estimated to be effective in 30% of treatment-refractory schizophrenic patients. The authors hypothesized that if a dose-response relationship was obvious for this drug, the response rate could be significantly amplified.Following an 8-24-day dose titration phase, 29 inpatients with treatment-resistant schizophrenia diagnosed according to DSM-III-R were given a clozapine dose of approximately 400 mg/day for 4 weeks; blood samples were obtained weekly during this period.A receiver operator curve demonstrated that the threshold clozapine plasma concentration for therapeutic response was 350 ng/ml. Sixty-four percent of the patients with clozapine plasma concentrations greater than 350 ng/ml responded, whereas only 22% of the patients with concentrations less than 350 ng/ml responded.Use of clozapine blood levels as a predictor for treatment response in treatment-refractory schizophrenic patients appears worthwhile, since the measurement's sensitivity for response was 64% and the specificity for nonresponse was 78%.
Leukotriene B4 as an early predictor of carotid atherosclerosis in patients with obstructive sleep apnea
Authors: Ibrahim Ibrahim, Ahmed Shawky, Yousef Mansour, Khaled Rashed, Wafik Bahnasy, Elsiagy Abd Elaziz
Journal: European Respiratory Journal (2014)

There is an increased risk of cardiovascular and cerebrovascular events in patients with obstructive sleep apnea (OSA). An increased intima-media thickness (IMT)in the carotid arteries is a marker of atherosclerosis, associated with a high risk of stroke. Leukotriene B4 (LTB4) is a powerful pro-inflammatory mediator in several inflammatory diseases,including atherosclerosis. The aim was to elucidate the relationship between LTB4 and carotid atherosclerosis in OSA patients without known cardiovascular,cerebrovascular disease.methods:10 healthy volunteer as a control group (groupI) and 40 patients known to have obstructive sleep apnea (groupII). Doppler ultrasonography used to measure carotid IMT. leukotriene B4 levels were measured.Obstructive sleep apnea was diagnosed by polysomnography.serum leukotriene B4 levels were significantly higher in the OSA group. This high level was positively correlated with desaturation index, AHI and with the IMT. Conclusion:patients with OSA have elevated levels of leukotriene B4,a marker of inflammation and an independent risk predictor for atherosclerosis reference:Levy P, Pepin JL,Mach F.Obstructive sleep apnea and atherosclerosis. Prog Cardiovasc Dis. 2009 Mar-Apr;51(5).
Abstract P6-12-08: The effects of the BKM120 in combination with herceptin on HER2+ BC cells and BCSCs
Authors: Jin Zhang, Feng Yu, Jingjing Liu, Xiaobei Zhang, Yunhui Hu
Journal: Cancer Research (2015)

Abstract Introduction: Breast cancer stem cells (BCSCs) are suspected to be responsible for tumour recurrence, metastasis as well as chemo-resistance. Dysregulated PI3K/Akt signaling is implicated in the pathogenesis of a number of breast cancers, including the HER2+ breast cancer. This study evaluated the efficacy of BKM120 monotherapy and BKM120 plus Herceptin in treatment of normal cells and the BCSCs of the HER2+ breast cancer . Methods:The BCSCs of SK-BR-3 cells were isolated by Serum free cells suspension culture. The impacts of BKM120 monotherapy and BKM120 combined with Herceptin on normal breast cancer cells and BCSCs were assayed by MTT assay, wound-healing assay and plate clone formation assay. The mammosphere-forming efficiency (MFE) of breast cancer cells treated with BKM120 and BKM120 plus Herceptin were also calculated. The nature of the drug interaction of BKM120 and Herceptin was evaluated by using the combination index (CI) according to the method of Chou and Talalay. The impacts of BKM120 monotherapy and BKM120 combined with Herceptin in PI3K/AKT pathway on the normal cancer cells and BCSCs of SK-BR-3 were assayed by Western bloting. Results: BKM120 showed significant antiproliferative activity in the BCSCs, as well as in normal SK-BR-3 cells. After treated with BKM120, invasion abilities of SK-BR-3 cells was significantly weakened(P&amp;lt;0.01).The colony forming efficiency and the MFE was also decreased compared with the control (P&amp;lt;0.01). Additionally, the pAKT and pS6 expression levels were inhibited. The effects of BKM120 in combination with Herceptin were investigated, which was called Combination Index, showed synergism between the two agents in BCSCs as well as in the normal cells. Furthermore, BKM120 plus Herceptin showed more significantly suppression on following aspects in BCSCs and normal cancer cells : proliferation, invasion ability, colony forming as well as MFE. In addition, the levels of pAKT,pS6 in the BKM120 plus Herceptin group were decreased more obviously than those in control and monotherapy group respectively(p&amp;lt;0.05). Conclusions:BKM120 can inhibit the growth of normal cancer cells and BCSCs of SK-BR-3, by inhibiting cell proliferation, impairing the invasion abilities and the MFE, and reducing the expression of pAKT(Thr308,S473)and pS6(Thr389).Moreover, these results suggest that the combination of PI3K Inhibitor BKM120 with Herception may provide a novel therapy strategy for HER2+ BC. Citation Format: Jin Zhang, Feng Yu, Jingjing Liu, Xiaobei Zhang, Yunhui Hu. The effects of the BKM120 in combination with herceptin on HER2+ BC cells and BCSCs [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-12-08.
EGFR mutation analysis and treatment outcomes with tyrosine kinase inhibitors in EGFR mutants: The Manchester Lung Cancer Group Experience.
Authors: Rahul Peck, Elizabeth Connolly, Paul Taylor, Corinne Faivre-Finn, Fiona Hellen Blackhall, Andrew Wallace, Lip Lee, Neil Bayman, Paul Burt, Yvonne J. Summers
Journal: Journal of Clinical Oncology (2012)

e18095 Background: The presence of Epidermal Growth Factor Receptor (EGFR) activating mutations in patients with NSCLC was first described in 2005. Tumours exhibiting these mutations show sensitivity to treatment with an oral Tyrosine Kinase Inhibitor. Testing for EGFR mutations in patients with non-squamous NSCLC began in the Greater Manchester and Cheshire network in the last quarter of 2009. Methods: We audited the notes of consecutive patients who were identified with an activating EGFR mutation by the Central Manchester Genetics Laboratory between November 2009 and October 2011. Results: A total of 110 mutations were identified in tumour tissue from 98 patients. 13.6% were in exon 18, 38.2% in exon 19, 15.4% in exon 20 and 32.8% in exon 21. 65% of patients were female. The median age was 69 years (36-89). Notes were available for 85 patients, 59 of whom received treatment with an EGFR TKi. 7 had previously received radical treatment and 19 never received treatment. 7% were current smokers, 40% were ex-smokers, 30.6% had never smoked and smoking history was not documented in 22.4%. An initial response to treatment was seen in 55%, with stable disease in 15%.The mean duration of treatment was 7.6 months (2 weeks – 23 months), with 24 patients still receiving a TKi at the time of data analysis. The most commonly seen toxicities were diarrhoea and rash. Only 1 patient had no documented toxicity from their TKi. 17 patients (29%) had treatment discontinued or interrupted because of toxicity. In 8 of these, treatment was re-introduced at a reduced dose, and 3 patients went back to full dose. Conclusions: Our results confirm that treatment with a TKi is effective for those patients whose tumours harbour EGFR mutations, with a side effect profile consistent with published data.
Bosutinib As Third-Line Therapy in Patients (Pts) with Chronic Phase Chronic Myeloid Leukemia (CP CML) Following Failure with Imatinib Plus Dasatinib and/or Nilotinib: 48-Month Update of a Phase 1/2 Study
Authors: Carlo Gambacorti-Passerini, H. Jean Khoury, Hagop M. Kantarjian, Jeffrey H. Lipton, Dong-Wook Kim, Philippe Schafhausen, Ewa M. Matczak, Eric Leip, Kay Noonan, Tim H. Brümmendorf, Jorge E. Cortes
Journal: Blood (2014)
Abstract 3998: Patients on Chronic Warfarin Therapy Who Present With an Acute Coronary Syndrome are High Risk and Receive Delayed and Inadequate Treatment
Authors: Philippe Gabriel Steg, Yves Cottin, Gilles Montalescot, Frans Van de Werf, Dietrich C Gulba, Keith A Fox, Rajendra H Mehta, Didier Tchetche, Rebecca Dedrick, Christopher B Granger, Grace Investigators
Journal: Circulation (2006)
Up-regulation of collagen type V mRNA in a model of systemic sclerosis
Authors: Roberta Gonçalves Marangoni, Ana Paula P. Velosa, Edwin E. Parra, Jymenez de Moraes, Vera L. Capelozzi, Walcy R. Teodoro, Natalino H. Yoshinari
Journal: European Respiratory Journal (2011)

Background: We have described an animal model of systemic sclerosis (SSc) induced by type V collagen (COLV) that resembles the human disease. The aim of this study was to investigate the early disease in the lung of this model with special emphasis on collagen deposition and mRNA collagen synthesis.

Methods: Female rabbits from New Zealand lineage were immunized with COLV plus Freund's adjuvant (FA). Animals immunized only with FA were used as controls. The animals were sacrificed at day-7, day-75 and day-210; and the lungs submitted to immunofluorescence, real-time qPCR and biochemical examination.

Results: The immunolabeling for the COL I, III and V by immunofluorescence showed an intense expression of COLV in the bronchovascular interstitium near the inflammatory infiltrate of COLV-rabbits at day-210. Additionally, morphologic analysis demonstrated that the progressive remodeling of the extracellular matrix observed in this group of animals was characterized by thickened COLV deposition with distorted fibrils. In accordance with these observations, the real-time qPCR revealed markedly up-regulation of COLV mRNA of the COLV-group at day-210 comparing with controls (p<0.001). The content of hydroxyproline was compared for COLV-group and controls at day-7, day-75 and day-210, suggesting that the day-210 group represents an early disease without established fibrosis.

Conclusions: We found an early up-regulation of COLV mRNA in the lung tissue of this experimental model emphasizing the role of this protein in the pathogenesis of SSc. In addition, our results reinforce the importance of this model, emerging promising to study the early stages of pulmonary fibrosis in this severe disease.
Observations on 67 patients who took Erhard Seminars Training
Authors: J Simon
Journal: American Journal of Psychiatry (1978)

The author describes the effects of Erhard Seminars Training (est) on 67 patients--49 who took est during the course of psychotherapy with him and 18 who were seen for evaluation, consultation, or treatment after having taken est. Responsiveness to est was assessed in terms of individually predefined psychodynamics and treatment goals. Of the 49 patients who took est during therapy, 30 were judged to show some positive response and 19 were rated unchanged. The author believes that est often has a strong influence toward psychotherapeutic movement in patients with good ego strength who are motivated to change.
Immunological measures as potential markers of dose
Authors: J. Kleine-Tebbe
Journal: Allergy (2011)

Specific immunotherapy (SIT) induces immunological changes leading to a decrease in allergen-driven symptoms and medication use. However, the use of arbitrary and variable assay formats and units hampers comparisons between SIT studies. The magnitude of IgG response induced by SIT is not directly linked to clinical improvement, so an increase in allergen-specific IgG(4) should be considered a necessary but not sufficient marker of clinical efficacy. Dose-dependent IgG(4) immune responses should be demonstrated by the manufacturer, not by doctors. Symptom and medication scores are essential end-points for immunotherapy studies, but are subjective, so close association with objective assay measurements will be difficult. Nonetheless, blocking antibody assays combining serology and cellular function may provide a solution for relating immunological assay measurements to clinical outcomes.
ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery—executive summary
Authors: Kim A Eagle, Peter B Berger, Hugh Calkins, Bernard R Chaitman, Gordon A Ewy, Kirsten E Fleischmann, Lee A Fleisher, James B Froehlich, Richard J Gusberg, Jeffrey A Leppo, Thomas Ryan, Robert C Schlant, William L Winters, Raymond J Gibbons, Elliott M Antman, Joseph S Alpert, David P Faxon, Valentin Fuster, Gabriel Gregoratos, Alice K Jacobs, Loren F Hiratzka, Richard O Russell, Sidney C Smith
Journal: Journal of the American College of Cardiology (2002)
Sarcopenia and nonalcoholic fatty liver disease: New evidence for low vitamin D status contributing to the link
Authors: Qing Pang, Kai Qu, Chang Liu, Jing‐Yao Zhang, Su‐Shun Liu
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: The Hepatology article by Hong et al.1 showed a strong relationship between sarcopenia and nonalcoholic fatty liver disease (NAFLD). Recently, a larger study further highlighted that individuals with sarcopenia had increased risk of NAFLD and developing hepatic fibrosis after adjusting for obesity or insulin resistance.2 We suggest that this causal association between sarcopaenia and NAFLD may partially be related to the low vitamin D status frequently found in patients with chronic liver diseases. On the one hand, a growing body of evidence has established a close link between vitamin D and sarcopenia. Vitamin D receptors (VDRs) have been successfully isolated from human skeletal muscle, and it has been proposed that vitamin D signaling by VDRs plays important roles in the regulation of myoblast proliferation and differentiation, myogenesis, skeletal muscle growth, and muscle inflammation. Levels of vitamin D were significantly lower in patients with sarcopenia in comparison to controls, regardless of obesity.2 In addition, vitamin D supplement could significantly increase expression of VDRs in skeletal muscle and subsequently rescue sarcopenia as well as suppressed osteoblastic differentiation by osteoglycin.3 On the other hand, the association between vitamin D levels and NAFLD has been increasingly recognized. A meta‐analysis with 17 studies highlighted that, compared to controls, patients with NAFLD had significant lower levels of vitamin D and higher probability of vitamin D deficiency,4 suggesting a potential role of vitamin D in the formation of NAFLD. Additionally, mice with VDR knockout would spontaneously develop hepatic steatosis. Recently, a randomized, clinical trial showed that treatment with vitamin D status could significantly ameliorate serum hs‐C reactive protein and methane dicarboxylic aldehyde in NAFLD patients.5 These findings suggest that vitamin D may be considered as an adjunctive therapy for NAFLD. In conclusion, we believe that vitamin D deficiency, sarcopenia, and NAFLD may be linked together. Given that NAFLD has risen to become the most common form of chronic liver disease in Western countries, further studies are required to fully determine the complex relationships and the therapeutic potentialities of vitamin D for patients with NAFLD, especially those accompanied by sarcopenia.
Increased Risk of Lyme Disease for Cat Owners
Authors: K L Curran, D Fish
Journal: New England Journal of Medicine (1989)

A 2-year prospective study (October 1985-October 1987) was undertaken of sexual transmission of human immunodeficiency virus (HIV) by patients with hemophilia to their partners.  31 patients with hemophilia who were seropositive for HIV and their partners who were seronegative for HIV at entry agreed to attend counseling sessions twice a year and completed the study.  HIV antibody status and the subjects attitudes toward preventive measures were recorded and the data were reviewed in late 1987.  14 couples always used condoms during intercourse and no seroconversion occurred in this group; the 17 other couples did not adhere to the use of condoms and 3 women (17%) seroconverted.  We tested HIV antigen (Abbott Laboratories) in serial serum samples collected during this study from the 17 patients with hemophilia who did not take preventive measures.  3 of the 6 patients who were seropositive infected their partners whereas none of the 11 who were seronegative did so.  These data suggest that active viral replication as evidenced by the presence of HIV antigens in serum may correspond to an increased risk of transmission.  This limited study of heterosexual transmission of HIV in well-educated self-treating patients with hemophilia raises 2 important issues.  The 1st one concerns the risk of HIV transmission by heterosexual contacts.  Among the 17 couples who did not use condoms only 3 female sexual partners where infected during this 2-year follow- up all of them by seropositive partners with hemophilia.  The 2nd issue raised by this study is the relative ineffectiveness of education and counseling in preventing the transmission of HIV:  17 of the 31 couples of which 1 member was an HIV-seropositive man disregarded counseling aimed at preventing HIV transmission.  (full text)