tbuckley/cabot-search huggingface dataset:
Abstract 5015: TCR usage analysis in blood reveals different mechanisms of action of CTLA-4 and PD-1 blockade in patients
Authors: Lidia Robert, Christina L. Harview, Ryan Emerson, Stephen Mok, Blanca Homet, Begonya Comin-Anduix, Richard C. Koya, Harlan Robins, Paul C. Tumeh, Antoni Ribas
Journal: Cancer Research (2014)

Abstract Immune-checkpoint blockade therapies are providing long-lasting responses in a subset of patients with malignant metastatic melanoma. In an effort to better understand the underlying mechanism, the T-cell population in peripheral blood mononuclear cells (PBMCs) was characterized. The complementarity determining region 3 (CDR3) of the rearranged T cell receptor variable ß chain genes (TCR Vß) was sequenced. This was performed using gDNA extracted from the PBMCs of twenty-one patients that were treated with antibody to Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) (tremelimumab) and seven patients that were treated with antibody to the Programmed Death-1 (PD-1) blockade (MK-3475) at baseline and at day 30-60 post first treatment. Four healthy donors were also sequenced as controls. Control PBMCs displayed random distribution with three patients showing a decrease and one showing an increase in the number of unique productive sequences (UPS) from baseline to the time after first cycle. In PBMCs from patients receiving the CTLA-4 antibody, two out of 21 samples showed a decrease in total number of UPS, while 19 out of 21samples experienced an increase. In PBMCs from patients receiving PD-1 antibody, the reponse was more similar to healthy donors as 5 out of 7 (71%) displayed a decrease and 2 out 7 (29%) an increase in total UPS from the pre to post timepoint. There was an increase in the absolute lymphocyte count (ALC) after CTLA-4 blockade therapy (p=0.03), but not in the samples from patients treated with PD-1 antibody (p=0.53). A direct correlation between ALC increase and increase in UPS for CTLA-4 blockade was ruled out (p=0.1 Spearman Correlation). When analyzing according to clinical response status, all responders to CTLA-4 blockade (4 out of 19) experienced an increase in the number of circulating clones. However, samples from clinical responders to PD-1 blockade showed an increase (2 out of 5) or decrease (1 out of 2) in the circulating pool. Considering the concerning toxicity profile for CTLA-4-blockade versus the mild toxicity for PD-1 antibodies, this data supports a model where CTLA-4 blockade induces a non-specific systemic expansion of T cells, while PD-1 blockade may have more specific effects directly in the tumor. Citation Format: Lidia Robert, Christina L. Harview, Ryan Emerson, Stephen Mok, Blanca Homet, Begonya Comin-Anduix, Richard C. Koya, Harlan Robins, Paul C. Tumeh, Antoni Ribas. TCR usage analysis in blood reveals different mechanisms of action of CTLA-4 and PD-1 blockade in patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5015. doi:10.1158/1538-7445.AM2014-5015
Pulmonary Embolism by Hepatic Tissue After External Cardiac Massage
Authors: Sang Yon Cho
Journal: JAMA (1976)

<h3>To the Editor.—</h3> A 45-year-old woman who had been anephric by surgery and on hemodialysis three times a week for three years had a terminal respiratory arrest. She received external cardiac massage for one hour, but could not be resuscitated. Autopsy revealed a fracture of T<sub>6</sub>, right hemothorax, left ventricular hypertrophy, and pericarditis. The liver was unremarkable on gross examination. However, microscopic examination revealed pulmonary embolism by hepatic tissue, along with bone marrow and fat emboli (Fig 1 and 2). We speculate that external cardiac massage was instrumental in producing pulmonary embolism by hepatic tissue. To our knowledge, all previously reported cases of pulmonary embolism by hepatic tissue were caused by catastrophic traumatic injuries.<sup>1,2</sup>
Airway inflammation and cough sensitivity in cough‐variant asthma
Authors: A. De Diego, E. Martínez, M. Perpiñá, L. Nieto, L. Compte, V. Macián, L. Senent
Journal: Allergy (2005)

Background: Mechanisms underlying cough and bronchoconstriction in patients with cough‐variant asthma (CVA) are not well established. Differences in location or degree of activation of eosinophils and allergic cytokines have been suggested as the likely causes. To address this issue, we have carried out a comparative study of airway inflammatory markers between patients with CVA and classic asthma (CA). The relationship between these markers with airway hyperresponsiveness (AHR) and cough sensitivity has also been studied. Methods: Twenty‐seven non‐smokers and steroid‐naive patients with CVA (12) and CA (15) were examined. Capsaicin challenge, histamine bronchoprovocation test, nitric oxide levels in exhaled air and sputum induction were performed in all of them. Differential cell sputum recount and supernatant concentrations of eosinophil granule‐derived cationic proteins (ECP), interleukin (IL)5, IL8 and tumour necrosis factor (TNF)‐ α were also measured. Results: There were no significant differences in either the inflammatory pattern of soluble markers or differential cell counts between CA and CVA. Histamine PC20 was correlated with IL‐5 in CVA, whereas it was associated with sputum eosinophilia in CA. Cough sensitivity (log C5) and histamine PC20 were inversely related in CA. Conclusions: Although the pattern of inflammatory sputum markers in patients with asthma and cough‐variant asthma is similar, its relation with bronchial hyperreactivity and cough sensitivity is different in each group.
John Robert Stephen Innes
Authors: M. J. Williams
Journal: BMJ (2012)

John Robert Stephen (“Donny”) Innes was born into a distinguished Aberdeen medical family, his father being a physician and his mother a city GP.

On completing his medical training he enlisted in the Royal Army Medical Corps (RAMC) and served for a period in Germany. On demobilisation he returned to Aberdeen and joined his mother in practice, where he worked …
The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre
Authors: H.Y. Lee, Y.L. Lim, T. Thirumoorthy, S.M. Pang
Journal: British Journal of Dermatology (2013)

Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction with a mortality of 40%. Intravenous immunoglobulin (IVIg) is widely used as a specific treatment for this reaction, although evidence of its benefit is conflicting.We sought to evaluate whether the use of IVIg improved mortality in patients with Stevens-Johnson syndrome (SJS)/TEN overlap and TEN.We retrospectively analysed data for 64 patients with SJS/TEN overlap and TEN who were treated with IVIg at a single referral centre. The primary outcome analysed was in-hospital mortality. Predicted mortality was calculated based on severity-of-illness score for TEN (SCORTEN) values. Secondary analyses of survival based on IVIg dosages and prior corticosteroid exposure were also performed.There were 28 cases of SJS/TEN overlap and 36 cases of TEN, with a mean SCORTEN value of 2·6. The mean dose of IVIg given was 2·4 g kg(-1) and the mean delay from the onset of epidermal detachment to administration of IVIg was 3·2 days. There were 20 deaths (31%) in our cohort. The standardized mortality rate was 1·10 (95% confidence interval 0·62-1·58). Subgroup analysis comparing survivors and nonsurvivors showed a higher SCORTEN in nonsurvivors (3·4 vs. 2·2). There were no differences with regard to the dosage, delay and duration of IVIg administration. When stratified according to dosage, there was no mortality difference between patients who receive high-dose (≥ 3 g kg(-1) ) vs. low-dose (< 3 g kg(-1) ) IVIg.This study shows that the use of IVIg does not yield survival benefits in SJS/TEN overlap and TEN, even when corrected for IVIg dosages.
Identification of microRNA expression patterns and definition of a microRNA/mRNA regulatory network in distinct molecular groups of multiple myeloma
Authors: Marta Lionetti, Marta Biasiolo, Luca Agnelli, Katia Todoerti, Laura Mosca, Sonia Fabris, Gabriele Sales, Giorgio Lambertenghi Deliliers, Silvio Bicciato, Luigia Lombardi, Stefania Bortoluzzi, Antonino Neri
Journal: Blood (2009)
Effect of readmissions on increasing hospital admissions for asthma in children.
Authors: A Senthilselvan
Journal: Thorax (1995)

BACKGROUND--Previous studies have reported increases in the number of hospital admissions for asthma in children. The aim of the present study was to examine the effect of readmissions on these increased hospital admissions and to investigate gender differences in asthma readmissions. METHODS--The Provincial Government of Saskatchewan provides universal health care to its residents. Hospital admissions data for asthma were obtained from the Saskatchewan Health Department for all 134 hospitals in the province between 1980 and 1989. Age-specific and sex-specific hospital admission rates for asthma were calculated for each calendar year using first admissions and all admissions. The ratio between the number of readmissions and all admissions in a year was defined as the readmission rate for that year. RESULTS--Although rates based on all admissions for asthma were greater than rates based on first admissions, trends and sex differences were similar for the two rates. Despite the higher hospital admission rates for boys aged 10-14 years, girls in this age group had higher readmission rates for asthma from 1981 to 1989 (odds ratio (OR) 1.6 for girls; 95% confidence intervals (CI) 1.3 to 1.9). Similar increases were observed in readmission rates for asthma among children aged 5-9 years from 1985 to 1989 (OR 1.3 for girls; 95% CI 1.1 to 1.5). CONCLUSIONS--Readmissions for asthma do not seem to explain the increasing trend in hospital admissions for asthma in children. In children aged 10-14 years girls had higher hospital readmission rates for asthma than boys, and further studies are required to find factors related to the increased readmissions among girls in this age group.
Noninvasive Testing for Fetal Anemia
Authors: George R. Saade
Journal: New England Journal of Medicine (2000)

Despite the introduction of anti-D immune globulin (Rh immunoglobulin) for the prevention of anti-D red-cell alloimmunization, hemolytic disease of the newborn continues to occur because of the lack or failure of prophylaxis or because of maternal alloimmunization against other red-cell antigens for which prophylaxis is not available. The central tenet in the management of pregnancies complicated by red-cell alloimmunization is the detection of fetal anemia and intervention, by either intrauterine transfusion or delivery, before fetal death. Fetal anemia is usually diagnosed in a stepwise fashion, starting with less sensitive but less invasive screening methods (obtaining the reproductive history and measuring . . .
Urban Health In America
Authors: Odin W. Anderson
Journal: JAMA (1976)

The author is demonstrating, in his fact-packed book, that in any time and place, the patterns of disease and mortality are more or less related to environing social and economic circumstances. He has used the concepts of "rural" and "urban" in the United States to illustrate this thesis. The person who brought the concept of disease and mortality patterns to our attention is Rene Dubos, in his book,<i>The Mirage of Health</i>(1959). The author cites Dubos but is distressed by his pessimism regarding mankind's ability to exercise any basic control over his disease patterns. They are mainly tradeoffs, the choice of lesser evils, and there will always be a disease pattern. The author is not yet ready to accept this premise, eg, "We can take courage for the effort from the fact that... past successes in the control of infectious disease have made the modern world safe and liveable
An Alginate-Antacid Formulation Localizes to the Acid Pocket to Reduce Acid Reflux in Patients With Gastroesophageal Reflux Disease
Authors: Wout O. Rohof, Roel J. Bennink, Andre J.P.M. Smout, Edward Thomas, Guy E. Boeckxstaens
Journal: Clinical Gastroenterology and Hepatology (2013)
TNF inhibitor therapy and risk of breast cancer recurrence in patients with rheumatoid arthritis: a nationwide cohort study
Authors: Pauline Raaschou, Thomas Frisell, Johan Askling
Journal: Annals of the Rheumatic Diseases (2014)

Objective To investigate the risk of breast cancer recurrence in rheumatoid arthritis (RA)—patients with tumour necrosis factor inhibitor (TNFi) treatment and a history of breast cancer, taking several breast cancer, comorbidity and RA-related prognostic factors into account. Methods 143 female TNFi-treated patients (1999–2010) with RA and a history of breast cancer before start of TNFi were identified through register linkages, and matched 1:1 from a cohort of 1598 comparable biologics-naive individuals. 120 TNFi-treated and 120 matched biologics-naive individuals with a history of equally recent/distant breast cancer met the eligibility criteria and comprised the final study population. The primary outcome was first recurrence of breast cancer. Through register-linkages and chart review, individuals were followed until 2011. HRs for recurrence were calculated using Cox regression. Results The median time from breast cancer diagnosis until TNFi-treatment/start of follow-up was 9.4 years. Modest differences in breast cancer characteristics and/or treatment among TNFi-treated and biologics-naive individuals were noted at time of breast cancer diagnosis. Median follow-up from TNFi start was 4.9 years (4.6 years among biologics-naive). Among the TNFi-treated, 9 developed a breast cancer recurrence (crude incidence rate 15/1000 person-years) during follow-up, compared with 9 among the matched biologics-naive (16/1000 person-years). The adjusted corresponding HR was 1.1 (95% CI 0.4 to 2.8). Conclusions Among patients with RA and a history of breast cancer, those who started TNFi-treatment did not experience more breast cancer recurrences than patients with RA treated otherwise. The generalisability of our findings to women with a very recent or a poor prognosis of breast cancer remains unknown.
Abstract LB-228: Resistance to BRAF inhibition in BRAF V600E colorectal cancer is associated with PI3K/AKT activation and hypermethylation
Authors: Muling Mao, Lawrence Tsao, Farshid Dayyani, Vashisht Gopal Yennu Nanda, Gordon Mills, Gideon Bollag, Michael Davies, Gary Gallick, Scott Kopetz
Journal: Cancer Research (2011)

Abstract BRAF V600E mutation has been detected in approximately 8% of metastatic colorectal cancers (CRC) and results in constitutive activation of BRAF and the downstream MEK-ERK1/2 pathway. PLX4032, a selective inhibitor of BRAF V600E, has shown meaningful activity in melanoma (greater than 70% response) but only modest activity in BRAF V600E CRC (5%). The resistance of BRAF V600E CRC to BRAF inhibitors has been poorly understood. To explore these differences, BRAF V600E CRC cell lines were compared to BRAF V600E melanoma cell lines by reverse-phase proteomic array, which demonstrated higher levels of phospho-AKT and associated downstream pathway activation in CRC cell lines. Both colorectal cancer cells inherently resistant to PLX4720, an analog of PLX4032, and resistant subclones that were derived from BRAF V600E positive cells, showed increased expression of phospho-AKT and phospho-GSK3β, despite the sustained ability of PLX4720 to effectively inhibit MEK signaling. Silencing of PTEN, which in turn induced AKT activation, desensitized cells to the BRAF inhibitor. Furthermore, combined treatment of PLX4720 with two different PI3K inhibitors, LY294002 and GDC-0941, synergistically inhibited growth in a panel of BRAF V600E cells through both apoptosis and G1 phase arrest. It has been previously shown that BRAF V600E colorectal cancers are commonly associated with the CpG island methylation phenotype (CIMP), which is associated with epigenetically diminished PTEN expression. Combination treatment with the demethylating agent azacitadine and PLX4032 was also synergistic in cell lines with intact but suppressed PTEN, and was associated with PTEN re-expression. This was not seen in non-CIMP or PTEN BRAF V600E cell lines. Thus, colorectal cancer cells appear to escape BRAF targeting through a mechanism of increased PI3K/AKT activity, providing evidence to support investigation of new combination therapies with PI3K/AKT pathway inhibitors or demethylating agents. 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 LB-228. doi:10.1158/1538-7445.AM2011-LB-228
Lymphedema, Lymphocytic Myocarditis, and Sarcoidlike Granulomatosis
Authors: James F. Southern
Journal: JAMA (1989)

A patient with Whipple's disease presented with a long prodromal period characterized by granulomatous lymphadenitis and progressive lymphedema of the extremities. No gastrointestinal tract symptoms were present and a small bowel biopsy sample was normal. His clinical condition deteriorated with the onset of lymphocytic myocarditis. At autopsy, intestinal involvement with macrophages that stained positively with periodic acid—Schiff was limited primarily to the submucosa. Diffuse fibrous effacement of lymph nodes with afferent lymphangiectasia seemed to be the mechanism of diffuse lymphedema, protein-losing enteropathy, and hypoproteinemia. Whipple's disease, therefore, should be considered in the differential diagnosis of patients presenting with granulomatous disease, lymphocytic myocarditis, or unusual lymphedema. (<i>JAMA</i>1989;261:1467-1470)
Triggering of bullous pemphigoid by iodine
Authors: P. Piletta, L. Rieckhoff, J.H. Saurat
Journal: British Journal of Dermatology (1994)

Journal Article Triggering of bullous pemphigoid by iodine Get access P. Piletta, P. Piletta Clinique de Dermatologie, Hôpital Cantonal Universitaire, CH‐1211 Genève 4, Switzerland Search for other works by this author on: Oxford Academic Google Scholar L. Rieckhoff, L. Rieckhoff Clinique de Dermatologie, Hôpital Cantonal Universitaire, CH‐1211 Genève 4, Switzerland Search for other works by this author on: Oxford Academic Google Scholar J.H. Saurat J.H. Saurat Clinique de Dermatologie, Hôpital Cantonal Universitaire, CH‐1211 Genève 4, Switzerland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 1, 1 July 1994, Pages 145–147, https://doi.org/10.1111/j.1365-2133.1994.tb08481.x Published: 01 July 1994
The lipoproteins: predictors, protectors, and pathogens.
Authors: B Lewis
Journal: BMJ (1983)

<b>Background:</b> Adefovir dipivoxil (ADV) is a potent nucleotide analogue against both the wild-type and lamivudine (LMV) resistant hepatitis B virus (HBV). The cumulative incidence of ADV resistant mutations in the nucleoside/-tide treatment naïve chronic hepatitis B patient (CHB) at weeks 48, 96, and 144 was 0, 0.8–3%, and ∼5.9%, respectively. <b>Aims:</b> The aim of this study was to characterise the genotypic and phenotypic mutation profiles to ADV in 67 LMV resistant CHB patients who were treated with ADV. <b>Methods:</b> Serum HBV DNA was quantified by real time polymerase chain reaction. The ADV mutant was detected using matrix assisted laser desorption/ionisation time of flight mass spectrometry based genotyping assays, termed restriction fragment mass polymorphism (RFMP). <b>Results:</b> RFMP analysis revealed that a total of 11 amino acid substitutions developed in the rt domain of the HBV polymerase in nine patients. The cumulative incidence of genotypic ADV resistance at months 12 and 24 was 6.4% and 25.4%, respectively. The rtA181V, rtN236T, and rtA181T mutations were detected in five, four, and two of the 67 patients at treatment months 12–17, 3–19, and 7–20, respectively. Serial quantification of serum HBV DNA revealed that two patients with the rtA181V mutation, with or without the rtN236T mutation, and one patient with the rtA181T mutation displayed HBV DNA rebound. <b>Conclusion:</b> Emergence of the ADV mutation in LMV resistant patients who are treated with ADV appeared to present earlier and more frequently than was reported in previous studies on nucleoside/-tide treatment naïve patients.
The Growing Burden of Chronic Kidney Disease in Pakistan
Authors: Tazeen H. Jafar
Journal: New England Journal of Medicine (2006)

A Pakistani tailor, the sole breadwinner for a family of eight, had received diagnoses of type 2 diabetes and hypertension at 31 years of age. For the next 15 years, although he felt well and visited his primary care practitioner twice a year, his conditions were poorly controlled. When he was 46, he began to notice fatigue and loss of appetite. After several weeks of the gradual progression of these symptoms, the man sought medical attention and was found to have a serum creatinine concentration of 5.2 mg per deciliter (460 μmol per liter), a blood urea nitrogen concentration of . . .
Subclavian Catheters in Cardiac Arrest
Authors: Justin A. Bergman
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Polyethylene subclavian catheters classically have been employed for central venous pressure monitoring or for fluid or blood administration. The surgical staff here has studied the use of such catheters in cardiac arrests. Catheter insertion via the infraclavicular route was accomplished in almost all cases within one to two minutes, without interruption of external cardiac massage or ventilatory resuscitative measures. <h3>Technique.—</h3> The patient was placed nearly in a Trendelenburg position and the head averted. A 14-gauge needle connected to a 1-cc tuberculin syringe was inserted approximately at the mid-clavicular line. The needle was advanced medially, slightly cephalad (ie, in the direction of the suprasternal notch) at a 15° to 20° angle to the long axis of the clavicle. The needle was then advanced to a point beneath the posterior head of the clavicle. The diameter of the tuberculin syringe helped to maintain the needle close to the chest
New Paths to a Growing Problem
Authors: Thomas Parran
Journal: New England Journal of Medicine (1954)

WHEN my long-time friend and colleague, John Gordon, asked me to give the Cutter Lecture this year, he explained that today he would be out of the country working on a project supported by the Rockefeller Foundation. He asked me to discuss the "existing position of public health in the approach to a control of chronic disease"; to "sum up what came out of the meetings themselves" at the Conference on the Care of the Long-Term Patient in Chicago in March, 1954; and to "give an assay of what needs to be done." It will be agreed that this was . . .
A brain-targeted rabies virus glycoprotein-disulfide linked PEI nanocarrier for delivery of neurogenic microRNA
Authors: Do Won Hwang, Sejin Son, Jaeho Jang, Hyewon Youn, Song Lee, Duhwan Lee, Yun-Sang Lee, Jae Min Jeong, Won Jong Kim, Dong Soo Lee
Journal: Biomaterials (2011)