tbuckley/cabot-search huggingface dataset:
Role of the Major Histocompatibility Complex Class I Antigens in Tumor Growth and Metastasis
Authors: K Tanaka, T Yoshioka, C Bieberich, G Jay
Journal: Annual Review of Immunology (1988)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Direct anti-HCV agents
Authors: Xingquan Zhang
Journal: Acta Pharmaceutica Sinica B (2015)

Unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir (Sovaldi), simeprevir (Olysio), and fixed combination medicines Harvoni and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the "cure HCV" goal has become a reality. Concerns remain about drug resistance mutations and the high cost of these drugs. The investigation of new HCV drugs is progressing rapidly; fixed dose combination medicines in phase III clinical trials include Viekirax, asunaprevir+daclatasvir+beclabuvir, grazoprevir+elbasvir and others.
GMSC's advice on intrapartum care
Authors: L. Zander
Journal: BMJ (1996)

Training for overseas doctors may not be appropriate EDITOR,-James Owen Drife highlights the inappropriateness of much medical work that takes place in the developing world.'Regrettably, Britain contributes much to this.Many of the doctors who attended the congress in India about which Drife writes will have received much of their medical training in Britain.How helpful was this training in addressing the real health needs (obstetric and others) in these doctors' own country?The curricula vitae of overseas doctors applying for positions in Britain often mention the doctors' desire for "subspecialty training."The attendance at the seminar on in vitro fertilisation in India reflects this attitude.As long as we continue to train overseas doctors in Britain as if they were returning to situations similar to those in western Europe and as long as the royal colleges seem to pursue the same agenda, Drife's experiences will continue.
<scp>CAR</scp><scp>T</scp>‐cells merge into the fast lane of cancer care
Authors: Noelle V. Frey, David L. Porter
Journal: American Journal of Hematology (2015)

Chimeric antigen receptors (CARs) can be introduced into T-cells redirecting them to target specific tumor antigens. CAR-modified T cells targeting CD19 have shown remarkable activity against CD19+ malignancies including B cell acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphomas (NHL). Complete remission rates as high as 90% have been observed for patients with relapsed and refractory ALL and greater than 50% response rates have been seen in heavily pre-treated CLL and NHL. Excitingly, some remissions have been durable without any additional therapy, a finding which correlates with in-vivo T-cell persistence and B-cell aplasia. The major treatment related toxicities include B-cell aplasia, neurologic toxicities, and a potentially severe cytokine release syndrome. This review summarizes outcomes for patients treated with CD19-CAR T-cells while exploring the field's challenges and future directions.
Role of Covalent and Noncovalent Interactions in Cell Toxicity: Effects on Proteins
Authors: J A Hinson, D W Roberts
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Since the spread of tobacco from the Americas hundreds of years ago, tobacco cigarettes and, more recently, alternative tobacco products have become global products of nicotine addiction. Within the evolving alternative tobacco product space, electronic ...Read More
Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.
Authors: W P Mason, A Grovas, S Halpern, I J Dunkel, J Garvin, G Heller, M Rosenblum, S Gardner, D Lyden, S Sands, D Puccetti, K Lindsley, T E Merchant, B O'Malley, L Bayer, M M Petriccione, J Allen, J L Finlay
Journal: Journal of Clinical Oncology (1998)

PURPOSE To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, &gt;44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.
Human Energy Metabolism: What Have We Learned from the Doubly Labeled Water Method?
Authors: D A Schoeller, C R Fjeld
Journal: Annual Review of Nutrition (1991)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for locally advanced head and neck cancer: a clinical and pharmacologic analysis.
Authors: E E Vokes, R L Schilsky, R R Weichselbaum, M F Kozloff, W R Panje
Journal: Journal of Clinical Oncology (1990)

Both cisplatin and leucovorin (LV) interact with fluorouracil (5-FU) by increasing intracellular reduced folate levels and thereby the inhibition of thymidylate synthase. Therefore, the addition of LV to cisplatin and 5-FU (PFL) may increase the activity of that combination in head and neck cancer. We treated 31 patients with locally advanced head and neck cancer with two cycles of neoadjuvant PFL consisting of 100 mg/m2 of cisplatin on day 1 followed by a 5-day continuous infusion of 5-FU at 1,000 mg/m2/day and oral LV at 100 mg administered every 4 hours during the entire duration of chemotherapy infusion. Two patients died during neoadjuvant chemotherapy of sudden death and sepsis, respectively, and were not evaluated for response. Of 29 evaluable patients, nine had a complete response (CR), 17 had a partial response (PR), and three had stable disease. Toxicities consisted of mild to moderate myelosuppression and moderate to severe mucositis, necessitating reduction of 5-FU on cycle 2 to less than or equal to 80% of the intended dose in 22 of 29 patients. Administration of LV by repeated oral dosing resulted in total reduced folate plasma concentrations of 5.3 (+/- 2.9) and 6.7 (+/- 3.4) mumol on days 2 and 4 of the 5-FU infusion. The sum of 1-LV and its metabolite 5-CH3-tetrahydrofolate exceeded the concentration of d-LV, consistent with selective absorption of the biologically active 1-stereoisomer from the gastrointestinal tract.
Observations on Suprapubic Prostatectomy
Authors: T. Stoker
Journal: BMJ (1904)

ber glove for the rectum, and this lessens the delicacy of @b$ erbatiotuS manipulation.During this examination the surgeon must determine ON whether one or both sides of the gland require removal, and SUPRAPUBIC PROSTATECTOMY.whether some myomatous outgrowth may not have been the cause of obstruction and its removal suffice to open the BY SIR THORNLEY STOKER, M.D.
Follicular large cell lymphoma: analysis and prognostic factors in 62 patients.
Authors: H M Kantarjian, P McLaughlin, L M Fuller, D O Dixon, B M Osborne, F F Cabanillas
Journal: Journal of Clinical Oncology (1984)

Sixty-two patients with follicular large cell lymphoma were treated between 1973 and 1981. The overall median survival was 78 months with a five-year survival of 62%. The complete remission rate was 76%, with a median relapse-free interval of 72 months for responders. Complete remission produced a significantly longer survival than partial response and failure. Patients who tolerated therapy with an intensive doxorubicin-containing regimen had a significantly longer relapse-free interval and survival. Patients with stage I-II disease treated with radiation therapy alone had a higher relapse rate than those treated with radiation and combination chemotherapy. The addition of radiation therapy to combination chemotherapy in stage III-IV disease decreased the incidence of relapse at irradiated sites, but did not translate into improved survival. Pretreatment prognostic factors associated with poor response were thrombocytosis and stage III-IV disease; those associated with shortened survival were thrombocytosis, elevated lactic dehydrogenase level, stage III-IV disease, and bulky abdominal disease. Follicular large cell lymphoma is an aggressive lymphoma. Treatment should be curative in intent, and should include intensive combination chemotherapy even in stage I-II disease. Knowledge of important prognostic factors can be useful for analysis of future trials and planning therapeutic strategies.
Time is muscle ... even after reperfusion: EXPERT'S PERSPECTIVE
Authors: M. Ovize
Journal: Cardiovascular Research (2012)

This editorial refers to an article by H. Kin et al . [ 3 ][1] published in Cardiovascular Research in 2004. It is accompanied by a retrospective editorial by one of the authors of that original article, J. Vinten-Johansen, pp. 183–187, this issue, as part of this Spotlight on Landmark Papers in Cardiovascular Research . 

It has long been known that time is a major determinant of tissue damage following a prolonged ischaemic insult. This holds true for all organs in all experimental models. The seminal experimental studies by Reimer et al. 1 have clearly identified the wavefront progression of cardiomyocyte death as a function of the duration of ischaemia. This knowledge has been translated into clinical practice where considerable efforts have been made to limit the duration of ischaemia duration and hasten reperfusion therapy in acute myocardial infarction (MI) patients. As a consequence, the prognosis of ST elevation myocardial infarction (STEMI) patients has improved, and the specific ‘management of time’ represents indeed a wonderful example of a successful transfer from bench to bedside.

Importantly, the crucial importance of ‘time management’ during acute MI is not limited to the ischaemic period. Following his landmark description of the postconditioning phenomenon, Vinten-Johansen's group completed a second study which clearly identified one major limitation of this protection against lethal reperfusion injury.2,3 Kin et al. …

 [1]: #ref-3
Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts
Authors: C. Macdonald-Wallis, R. J. Silverwood, B. L. de Stavola, H. Inskip, C. Cooper, K. M. Godfrey, S. Crozier, A. Fraser, S. M. Nelson, D. A. Lawlor, K. Tilling
Journal: BMJ (2015)

<b>Study question</b> Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? <b>Methods</b> This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women's Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. <b>Study answer and limitations</b> The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. <b>What this study adds</b> The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. <b>Funding, competing interests, data sharing</b> UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests.
Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular Abnormalities: Task Force 8: Coronary Artery Disease
Authors: Paul D. Thompson, Robert J. Myerburg, Benjamin D. Levine, James E. Udelson, Richard J. Kovacs
Journal: Circulation (2015)

A therosclerotic coronary artery disease (ASCAD) is the leading cause of sudden cardiac death (SCD) and acute myocardial infarction (AMI) in adult athletes, variously defined as people older than age 30, 35, or 40 years. 1 ASCAD can occur in younger athletes who have inherited hyperlipidemia.For many adults, SCD or AMI is the first manifestation of ASCAD, because most of these acute events are caused by coronary plaque disruption and acute coronary thrombosis in plaques that were previously not sufficiently narrowed to have caused ischemia, even during intense exercise. 1There is universal agreement that vigorous exercise, such as athletic competition, acutely, albeit transiently, increases the risk of SCD and AMI in previously healthy people. 1 Vigorous exercise also transiently increases the risk for SCD and AMI in people with diagnosed ASCAD.These events may be caused by plaque disruption, but SCD in these patients may also be produced by malignant arrhythmias caused by demand ischemia or originating in areas of myocardial scar. 1 In addition to ASCAD, other coronary conditions such as coronary vasospasm, myocardial bridging, and coronary dissection, as well as infection such as Kawasaki disease, vasculitis, and cardiac transplant vasculopathy, may also cause acute cardiac events during exercise.The present section makes recommendations on how to evaluate patients with disease of the coronary arteries and make appropriate recommendations for athletic competition.Anomalous coronary arteries are considered in the Task Force 4 report. 2e searched PubMed for English language articles reporting exercise-related issues related to coronary diseases.This search produced no clinical trials examining how competitive athletes with coronary artery diseases should be advised regarding vigorous exercise in general or athletic competition in particular.Consequently, the following recommendations are based on case series, case reports, and consensus among the committee members.
Seroprevalence and risk factors for human herpes virus 8 (Kaposi’s sarcoma-associated herpes virus) in African-Caribbean women in Tobago
Authors: Alicia McDonald, Camille Ragin, Victor Wheeler, Jaquie Wilson, Clareann Bunker, Frank Jenkins
Journal: Cancer Research (2007)

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

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Human Herpes Virus 8 (HHV-8) is endemic in Tobago men and seropositivity has been associated with prostate cancer risk, 39.9% in prostate cancer cases and 22.9% in non-cases. For endemic populations, sexual and asexual transmission have been shown as probable modes of transmitting this virus. In Tobago, mode of HHV-8 transmission is unknown and the seroprevalence in Tobago women is unknown. Our study examined HHV-8 seropositivity in Tobago women and whether certain sexual practices are associated with increased risk for acquiring this oncogenic virus.

A cross-sectional study was conducted in 215 African-Caribbean Tobago women, aged 18-65, who participated in the Tobago Cervical and Oral Cancer Screening Study. Questionnaires were administered to ascertain demographic and sexual behavior information. HHV-8 seropositivity was determined by monoclonal antibody-enhanced immunofluorescent assay (IFA). Age-specific HHV-8 seropositivity rates were examined. Logistic regression analyses, adjusting for age, were performed to determine the association between HHV8 seropositivity and sexual behavior.

HHV-8 seroprevalence was 14.5%. Age-specific rates did not increase across agegroups. HHV-8 antibody titers ranged from 100 to 6400 (median = 400, 25-75% percentile = 200-800). Tobago women who were diagnosed with a sexually transmitted disease (STD) were more likely to be HHV-8 seropositive than women who were not diagnosed with an STD (OR= 2.4, 95% C.I.= .84-6.74). Age < 17 at first sexual intercourse was significantly associated with HHV-8 seropositivity (OR=2.4, 95% C.I.= 1.06-5.41).

We demonstrated a moderate rate of HHV-8 infections in Tobago women. Data suggest there is little HHV-8 transmission during the adult years. Prior to 18 years of age, the frequency of asexual and sexual transmissions remains unclear. Further studies are needed to evaluate HHV-8 infection and transmission in high-risk cancer populations.
Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry
Authors: Marco Matucci-Cerinic, Thomas Krieg, Loic Guillevin, Barbara Schwierin, Daniel Rosenberg, Peter Cornelisse, Christopher P Denton
Journal: Annals of the Rheumatic Diseases (2015)

Digital ulcers (DUs) occur in up to half of patients with systemic sclerosis (SSc) and may lead to infection, gangrene and amputation with functional disability and reduced quality of life. This study has elucidated the burden of SSc-associated DUs through identification of four patient categories based on the pattern of DU recurrence over a 2-year observation period.Patients with SSc-associated DUs enrolled in the Digital Ulcers Outcome Registry between 1 April 2008 and 19 November 2013, and with ≥2 years of observation and ≥3 follow-up visits during the observation period were analysed. Incident DU-associated complications were recorded during follow-up. Work and daily activity impairment were measured using a functional assessment questionnaire completed by patients after the observation period. Potential factors that could predict incident complications were identified in patients with chronic DUs.From 1459 patients, four DU occurrence categories were identified: 33.2% no-DU; 9.4% episodic; 46.2% recurrent; 11.2% chronic. During the observation period, patients from the chronic category had the highest rate of incident complications, highest work impairment and greatest need for help compared with the other categories. Independent factors associated with incident complications included gastrointestinal manifestations (OR 3.73, p=0.03) and previous soft tissue infection (OR 5.86, p=0.01).This proposed novel categorisation of patients with SSc-associated DUs based on the occurrence of DUs over time may help to identify patients in the clinic with a heavier DU burden who could benefit from more complex management to improve their functioning and quality of life.
Afamelanotide for Erythropoietic Protoporphyria
Authors: Janneke G. Langendonk, Manisha Balwani, Karl E. Anderson, Herbert L. Bonkovsky, Alexander V. Anstey, D. Montgomery Bissell, Joseph Bloomer, Chris Edwards, Norbert J. Neumann, Charles Parker, John D. Phillips, Henry W. Lim, Iltefat Hamzavi, Jean-Charles Deybach, Raili Kauppinen, Lesley E. Rhodes, Jorge Frank, Gillian M. Murphy, Francois P.J. Karstens, Eric J.G. Sijbrands, Felix W.M. de Rooij, Mark Lebwohl, Hetanshi Naik, Colin R. Goding, J.H. Paul Wilson, Robert J. Desnick
Journal: New England Journal of Medicine (2015)

Erythropoietic protoporphyria is a severe photodermatosis that is associated with acute phototoxicity. Patients with this condition have excruciating pain and a markedly reduced quality of life. We evaluated the safety and efficacy of an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease pain and improve quality of life.We conducted two multicenter, randomized, double-blind, placebo-controlled trials of subcutaneous implants containing 16 mg of afamelanotide. Patients in the European Union (74 patients) and the United States (94 patients) were randomly assigned, in a 1:1 ratio, to receive a subcutaneous implant containing either afamelanotide or placebo every 60 days (a total of five implants in the European Union study and three in the U.S study). The type and duration of sun exposure, number and severity of phototoxic reactions, and adverse events were recorded over the respective 180-day and 270-day study periods. Quality of life was assessed with the use of validated questionnaires. A subgroup of U.S. patients underwent photoprovocation testing. The primary efficacy end point was the number of hours of direct exposure to sunlight without pain.In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04). In the European Union study, the duration of pain-free time after 9 months was also longer in the afamelanotide group than in the placebo group (median, 6.0 hours vs. 0.8 hours; P=0.005), and the number of phototoxic reactions was lower in the the afamelanotide group (77 vs. 146, P=0.04). In both trials, quality of life improved with afamelanotide therapy. Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug.Afamelanotide had an acceptable side-effect and adverse-event profile and was associated with an increased duration of sun exposure without pain and improved quality of life in patients with erythropoietic protoporphyria. (Funded by Clinuvel Pharmaceuticals and others; ClinicalTrials.gov numbers, NCT01605136 and NCT00979745.).