tbuckley/cabot-search huggingface dataset:
CHOLERA; ITS NATURE AND ITS CURE.
Authors: HENRY RAYMOND ROGERS
Journal: JAMA (1893)

"We have no better means of combating the cholera to-day than at any time since it became known to civilization, a thousand years ago," said a distinguished physician in a recent number of the<i>Review of Reviews</i>. The medical profession therefore stands confronted with the appalling fact that hitherto all theories of this disease have been so misleading, and all forms of treatment have proved so worthless, that longer to trust them would be little less than criminal. Better theories and practice are urgently demanded. The bacillus theory of Dr. Robert Koch, which was so eagerly grasped at, is now found to be fallacious. Dr. Koch himself admits that comma-shaped germs are found in the common diarrheas of summer everywhere, and he tells us: "Water, from whatever source, very frequently, not to say invariably, contains comma-shaped organisms." He is not ignorant of the fact that these bacilli are found in
Bortezomib, Paclitaxel, and Carboplatin as a First-Line Regimen for Patients with Metastatic Esophageal, Gastric, and Gastroesophageal Cancer: Phase II Results from the North Central Cancer Treatment Group (N044B)
Authors: Aminah Jatoi, Shaker R. Dakhil, Nathan R. Foster, Cynthia Ma, Kendrith M. Rowland, Dennis F. Moore, Anthony J. Jaslowski, Sachdev P. Thomas, Mark D. Hauge, Patrick J. Flynn, Philip J. Stella, Steven R. Alberts
Journal: Journal of Thoracic Oncology (2008)
SHORT AND LONG-TERM PROGNOSTIC SIGNIFICANCE OF ST-SEGMENT ELEVATION IN LEAD AVR IN PATIENTS WITH NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME
Authors: Nevio Taglieri, Antonio Marzocchi, Francesco Saia, Cinzia Marrozzini, Stefania Rosmini, Laura Cinti, Caterina Villani, Laura Alessi, Fabio Vagnarelli, Pamela Gallo, Tullio Palmerini, Giovanni Melandri, Paolo Ortolani, Angelo Branzi, Claudio Rapezzi
Journal: Journal of the American College of Cardiology (2011)
Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib
Authors: Timothy P. Hughes, Jeffrey H. Lipton, Nelson Spector, Francisco Cervantes, Ricardo Pasquini, Nelma Cristina D. Clementino, Pedro Enrique Dorlhiac Llacer, Anthony P. Schwarer, Francois-Xavier Mahon, Delphine Rea, Susan Branford, Das Purkayastha, LaTonya Collins, Tomasz Szczudlo, Brian Leber
Journal: Blood (2014)
Effects of hydrophobic core components in amphiphilic PDMAEMA nanoparticles on siRNA delivery
Authors: Shangcong Han, Qiang Cheng, Yidi Wu, Junhui Zhou, Xingwen Long, Tuo Wei, Yuanyu Huang, Shuquan Zheng, Jianhua Zhang, Liandong Deng, Xiaoxia Wang, Xing-Jie Liang, Huiqing Cao, Zicai Liang, Anjie Dong
Journal: Biomaterials (2015)
Abstract 5604: Modulation of Stat3 in the tumor microenvironment enhances adoptive T cell therapy
Authors: Maciej Kujawski, Chunyan Zhang, Andreas Herrmann, Karen L. Reckamp, Anna Scuto, Michael Jensen, Robert Figlin, Hua Yu
Journal: Cancer Research (2010)

Abstract Adoptive T cell transfer has shown promise in several malignancies. However, the need to expand antigen-specific T cells for prolonged periods ex vivo and the immunosuppressive effects of the tumor microenvironment severely limit its antitumor efficacy. To overcome these challenges, we tested the feasibility of stimulating and expanding transferred T cells in vivo by targeting Stat3, an oncogenic transcription factor critical for mediating tumor immunosuppression. In contrast to Stat3+/+ CD8+ T cells, transferred naïve CD8+ T cells with genetic Stat3 inhibition, effectively infiltrated tumors where they proliferated robustly, resulting in increased tumor antigen-specific CD8+ T cell activity and tumor growth inhibition. To facilitate the clinical translation of these findings, we further tested sunitinib, an FDA-approved tyrosine kinase inhibitor that has been shown to block Stat3 in several cell types. Sunitinib treatment combined with adoptive T cell transfer of Stat3−/− CD8+ T cells resulted in significant tumor growth inhibition in both immunosuppressed and immunocompetent hosts. Furthermore, sunitinib enhanced tumor T cell infiltration, dendritic cell activation and decreased tumor conversion of T regulatory cells. Targeting Stat3 in tumor cells and immune cells with sunitinib represents a novel approach to overcoming the obstacles that currently face adoptive T cell transfer therapy, which can be translated for immediate use in the clinic for treating cancer. Supported by R01CA146092-01, K12 CA 01727, Kure It Kidney Cancer Research Fund and the Richard and Nancy Bloch Research Fund. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5604.
Alcohol Consumption and Risk for Congestive Heart Failure in the Framingham Heart Study
Authors: Craig R. Walsh, Martin G. Larson, Jane C. Evans, Luc Djousse, R. Curtis Ellison, Ramachandran S. Vasan, Daniel Levy
Journal: Annals of Internal Medicine (2002)

Although excessive alcohol consumption can promote cardiomyopathy, little is known about the association between alcohol consumption and risk for congestive heart failure in the community.To determine the relation between alcohol consumption and risk for congestive heart failure in the community.Community-based, prospective observational study.Framingham, Massachusetts.Participants in the Framingham Heart Study who were free of congestive heart failure and coronary heart disease.Self-reported alcohol consumption; sex-specific rates of congestive heart failure per 1000 person-years of follow-up by level of alcohol consumption.In men, 99 cases of congestive heart failure occurred during 26 035 person-years of follow-up. In women, 120 cases of congestive heart failure occurred during 35 563 person-years of follow-up. After adjustment for multiple confounders, risk for congestive heart failure was lower among men at all levels of alcohol consumption compared with men who consumed less than 1 drink/wk. The hazard ratio for congestive heart failure was lowest among men who consumed 8 to 14 drinks/wk (0.41 [95% CI, 0.21 to 0.81]) compared with those who consumed less than 1 drink/wk. In women, the age-adjusted hazard ratio for congestive heart failure was lowest among those who consumed 3 to 7 drinks/wk (0.49 [CI, 0.25 to 0.96]) compared with those who consumed less than 1 drink/wk. However, after adjustment for multiple predictors of congestive heart failure, this association was no longer statistically significant.In the community, alcohol consumption is not associated with increased risk for congestive heart failure, even among heavy drinkers (> or = 15 drinks/wk in men and > or = 8 drinks/wk in women). To the contrary, when consumed in moderation, alcohol appears to protect against congestive heart failure.
Optimizing Photodynamic Therapy:<i>In vivo</i>Pharmacokinetics of Liposomal<i>meta</i>-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma
Authors: Julia Buchholz, Barbara Kaser-Hotz, Tania Khan, Carla Rohrer Bley, Katja Melzer, Reto A. Schwendener, Malgorzata Roos, Heinrich Walt
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer. Experimental Design: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography. Results: None of the liposomal m-THPC–treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were ∼3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy. Conclusions: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.
Treatment Strategies for Patients With Ischemic Chest Pain-Reply
Authors: Peter H. Stone
Journal: JAMA (1996)

In Reply.  —The purpose of our registry of patients with unstable angina and non—Q-wave MI was to identify the clinical management strategies and outcomes among patients categorized by age, race, and sex. The study was designed to identify the practice patterns used in these groups of patients, not to investigate the explanations underlying the practice patterns or to investigate causal relationships between practice patterns and clinical outcomes. We observed that elderly patients received less aggressive treatment than younger patients, had more severe coronary disease, and experienced worse clinical outcomes.  We welcome Dr Algazy's comments in the debate concerning optimal care for the elderly with unstable angina and non—Q-wave MI. However, he appears to have misinterpreted our main conclusions, since we stated in the last line of the article that aggressive strategies should be directed to those patients with the greatest likelihood to benefit. As Algazy correctly notes, adverse outcomes may result from
The Elderly in the Wrong Unit
Authors: A. G. Mezey, H. M. Hodkinson, G. J. Evans
Journal: BMJ (1968)

Patients over 65 admitted from an area of North London forming the overlapping part of the catchment areas of a geriatric unit and a psychiatric unit were studied, with particular reference to misplacement in the inappropriate hospitals service and its consequences.The incidence of misplacement found was much lower than previously reported. In the geriatric unit 2.2% of admissions were definitely and 6.0% were probably misplaced. In the psychiatric unit 6.2% were definitely and a further 8.4% were probably misplaced. Misplacement did not materially affect the outcome. The striking differences that were found between the patterns of death and discharge in the geriatric and psychiatric units were determined principally by the type of illness leading to admission.The frequent coexistence of mental and physical disorders in the elderly patient, which this study confirms, indicates the need for further development of effective liaison at a local level between the geriatric, psychiatric, and social services.
Childhood cancer incidence rates and hazardous air pollutants in California: an exploratory analysis.
Authors: Peggy Reynolds, Julie Von Behren, Robert B Gunier, Debbie E Goldberg, Andrew Hertz, Daniel F Smith
Journal: Environmental Health Perspectives (2002)

Hazardous air pollutants (HAPs) are compounds shown to cause cancer or other adverse health effects. We analyzed population-based childhood cancer incidence rates in California (USA) from 1988 to 1994, by HAP exposure scores, for all California census tracts. For each census tract, we calculated exposure scores by combining cancer potency factors with outdoor HAP concentrations modeled by the U.S. Environmental Protection Agency. We evaluated the relationship between childhood cancer rates and exposure scores for 25 potentially carcinogenic HAPs emitted from mobile, area, and point sources and from all sources combined. Our study period saw 7,143 newly diagnosed cancer cases in California; of these, 6,989 (97.8%) could be assigned to census tracts and included in our analysis. Using Poisson regression, we estimated rate ratios (RRs) adjusted for age, race/ethnicity, and sex. We found little evidence for elevated cancer RRs for all sites or for gliomas among children living in high-ranking combined-source exposure areas. We found elevated RRs and a significant trend with increasing exposure level for childhood leukemia in tracts ranked highest for exposure to the combined group of 25 HAPs (RR = 1.21; 95% confidence interval, 1.03, 1.42) and in tracts ranked highest for point-source HAP exposure (RR = 1.32; 95% confidence interval, 1.11, 1.57). Our findings suggest an association between increased childhood leukemia rates and high HAP exposure, but studies involving more comprehensive exposure assessment and individual-level exposure data will be important for elucidating this relationship.
Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure.
Authors: S Lopez-Hilker, T Galceran, Y L Chan, N Rapp, K J Martin, E Slatopolsky
Journal: Journal of Clinical Investigation (1986)

Hypocalcemia is the main factor responsible for the genesis of secondary hyperparathyroidism in chronic renal disease. Studies with parathyroid cells obtained from uremic patients indicate that there is a shift in the set point for calcium-regulated hormone (parathyroid hormone [PTH] secretion. Studies were performed in dogs to further clarify this new potential mechanism. Hypocalcemia was prevented in uremic dogs by the administration of a high calcium diet. Initially, ionized calcium was 4.79 +/- 0.09 mg/dl and gradually increased up to 5.30 +/- 0.05 mg/dl. Despite a moderate increase in ionized calcium, immunoreactive PTH (iPTH) increased from 64 +/- 7.7 to 118 +/- 21 pg/ml. Serum 1,25(OH)2D3 decreased from 25.4 +/- 3.8 to 12.2 +/- 3.6 pg/ml. Further studies were performed in two other groups of dogs. One group received 150-200 ng and the second group 75-100 ng of 1,25(OH)2D3 twice daily. The levels of 1,25(OH)2D3 increased from 32.8 +/- 3.5 to a maximum of 69.6 +/- 4.4 pg/ml. In the second group the levels of serum 1,25(OH)2D3 after nephrectomy remained normal during the study. Amino-terminal iPTH did not increase in either of the two groups treated with 1,25(OH)2D3. In summary, the dogs at no time developed hypocalcemia; however, there was an 84% increase in iPTH levels, suggesting that hypocalcemia, per se, may not be the only factor responsible for the genesis of secondary hyperparathyroidism.
Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis
Authors: T Hiratsuka
Journal: Thorax (2003)

<b>Background:</b> Human β-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of β-defensins in cystic fibrosis, suggesting that β-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by <i>Pseudomonas aeruginosa</i>. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. <b>Methods:</b> The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. <b>Results:</b> High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1β. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against <i>P aeruginosa</i>. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. <b>Conclusions:</b> These results indicate that β-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.
Clusters of Comorbidities Based on Validated Objective Measurements and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease
Authors: Lowie E. G. W. Vanfleteren, Martijn A. Spruit, Miriam Groenen, Swetlana Gaffron, Vanessa P. M. van Empel, Piet L. B. Bruijnzeel, Erica P. A. Rutten, Jos Op ’t Roodt, Emiel F. M. Wouters, Frits M. E. Franssen
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: Comorbidities contribute to disease severity and mortality in patients with chronic obstructive pulmonary disease (COPD). Comorbidities have been studied individually and were mostly based on self-reports. The coexistence of objectively identified comorbidities and the role of low-grade systemic inflammation in the pathophysiology of COPD remain to be elucidated.Objectives: To cluster 13 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical outcomes and systemic inflammation.Methods: A total of 213 patients with COPD (FEV1, 51 ± 17% predicted; men, 59%; age, 64 ± 7 yr) were included prospectively. Comorbidities were based on well-known cut-offs identified in the peer-reviewed English literature. Systemic inflammatory biomarkers were determined in all patients. Self-organizing maps were used to generate comorbidity clusters.Measurements and Main Results: A total of 97.7% of all patients had one or more comorbidities and 53.5% had four or more comorbidities. Five comorbidity clusters were identified: (1) less comorbidity, (2) cardiovascular, (3) cachectic, (4) metabolic, and (5) psychological. Comorbidity clusters differed in health status but were comparable with respect to disease severity. An increased inflammatory state was observed only for tumor necrosis factor (TNF) receptors in the metabolic cluster (geometric mean [lower and upper limit]; TNF-R1, 2,377 [1,850, 3,055] pg/ml, confidence, 98.5%; TNF-R2, 4,080 [3,115, 5,344] pg/ml, confidence, 98.8%) and only for IL-6 in the cardiovascular cluster (IL-6, 3.4 [1.8, 6.6] pg/ml; confidence, 99.8%).Conclusions: Multimorbidity is common in patients with COPD, and different comorbidity clusters can be identified. Low-grade systemic inflammation is mostly comparable among comorbidity clusters. Increasing knowledge on the interactions between comorbidities increases the understanding of their development and contributes to strategies for prevention or improved treatment.
DUAL CONTRAST CARDIAC MRI FOR EVALUATION OF TELMISARTAN AND AMLODIPINE COMBINATION THERAPY IN THE DIABETIC MURINE MYOCARDIAL INJURY MODEL
Authors: Paul Kim, Yongquan Gong, Phillip Harnish, Ildiko Toma, Rajesh Dash, Robert Robbins, Phillip Yang
Journal: Journal of the American College of Cardiology (2013)
Tobacco Liability and Public Health Policy
Authors: Larry O. Gostin
Journal: JAMA (1991)

IN MARCH 1991, the US Supreme Court agreed to hear the case of<i>Cipollone v Liggett Group</i>,<sup>1</sup>a tobacco liability suit. The<i>Cipollone</i>case gained notoriety in 1988 when it became the first instance in which a jury awarded damages to a plaintiff to compensate harms caused by the use of cigarettes. Since the 1950s, more than 300 such suits had been filed, few had come to trial, and none had been victorious prior to the<i>Cipollone</i>case.<sup>2,3</sup>The Supreme Court will decide whether the federally mandated warning labels on cigarette packages preempt tort actions claiming that manufacturers failed to adequately warn or misled consumers about the health hazards of smoking. The Court's decision is likely to have profound implications not only for tobacco use and policy in the United States, but for the impact of product liability law on fundamental issues of public health and social policy.
Abstract 1784: Comparing genetically engineered T cells for chimeric TCR versus CD16 + Herceptin for adoptive immunotherapy against HER2 positive breast carcinomas
Authors: Sandrine Valsesia-Wittmann, Béatrice Clemenceau, Anne-Catherine Jallas, Jenny Valladeau, Raphael Rousseau, Jean-Yves Blay, Christophe Caux, Henri Vie
Journal: Cancer Research (2011)

Abstract The HER2 receptor is overexpressed in 25% of breast cancers and is associated with poor prognosis. Herceptin, a monoclonal antibody targeting HER2 has been demonstrated to improve survival of HER2 overexpressing metastatic breast cancer. However, majority of patients who initially respond to Herceptin develop resistance within one year of treatment initiation, and in the adjuvant setting 15% of patients relapse after 5 years despite Herceptin-based therapy. The goal of this project is to develop and compare efficiency of two adoptive immunotherapy approaches by genetically engineered T cells to overcome this resistance. For the first approach, we developed T lymphocytes armed with an anti-HER2 chimaeric TCR (CAR-CTL) to directly kill the HER2 positively cells. For the second approach, we developed T lymphocytes armed with a high affinity IgG FcR (FcγRIIIα, CD16) linked to its transduction chain FC∈RIγ (CD16/γ). In this latter case, the HER2 antigen is pre-targeted by Herceptin Ab to induce a “two step killing” through Antibodies Dependant Cellular Cytotoxicity (ADCC). Results obtained in vitro demonstrated the high direct killing efficiency of anti-HER2 chimaeric TCR CTL against HER2 amplified breast carcinoma cells BT474 or SKBR3 (&amp;gt;75%). However, abnormal reactivity of these CTL against cells with low to undetectable HER2 expression was observed (15 to 30% of lysis). This constitutive non specific activation of chimaeric TCR might represent an important limitation point for clinical use. On the other hand, “two step killing” with CD16/γ-CTL demonstrated a very specific cytotoxicity against HER2 positive cells through ADCC only in the presence of Herceptin. We demonstrated that efficacy of specific lysis is linked to levels of CD16/γ expression and appeared independent of HER2 targeted antigen level. We are comparing in vivo efficacy of both approaches (“one step” TCR vs “two step”ADCC) to induce regression of HER2 + or – breast carcinoma xenograft in immunodeficient mice model NOD-SCID mβ2-/-. Our last results will be presented. Because the alteration of ADCC mechanisms during Herceptin treatment is one rational explanation for the acquired resistance, improving effectors might represent a safe adjuvant treatment to prevent resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1784. doi:10.1158/1538-7445.AM2011-1784