tbuckley/cabot-search huggingface dataset:
Uremic Cardiomyopathy — Effect of Hemodialysis on Left Ventricular Function in End-Stage Renal Failure
Authors: Joseph Hung, Philip J. Harris, Roger F. Uren, David J. Tiller, David T. Kelly
Journal: New England Journal of Medicine (1980)

Left ventricular ejection fraction was measured by radionuclide left ventriculography before and immediately after hemodialysis in 20 uremic patients, 11 of whom presented with congestive heart failure. Ejection fraction and contraction were normal in 15 patients (Group A), six of whom had signs of congestive failure; they were abnormal in five patients (Group B), all of whom were in clinical heart failure. Mean arterial pressure and body weight decreased by a similar amount after dialysis in both groups, and heart rate did not change. In Group A ejection fraction was unchanged by dialysis (0.63±0.06 before vs. 0.62±0.09 after) (mean ±S.D.), but in Group B it was improved significantly (0.32±0.04 before vs. 0.44±0.08 after) (P<0.01). In three patients in Group B cardiomegaly and ejection fraction returned to normal with long-term hemodialysis. In end-stage renal failure, radionuclide left ventriculography can separate patients with circulatory congestion due to fluid overload from patients with left ventricular dysfunction in whom hemodialysis can provide immediate and long-term improvement. (N Engl J Med. 1980; 302:547–51.)
RTRB-04STEREOTACTIC RADIOSURGERY FOR RECURRENT HIGH-GRADE GLIOMAS: PATIENT SELECTION AND THE ROLE OF BEVACIZUMAB
Authors: John Boyle, Frances McSherry, James Herndon, Annick Desjardins, John Sampson, Katherine Peters, Junzo Chino, Karen Allen, Alvin Cabrera, Grace Kim, Henry Friedman, John Kirkpatrick
Journal: Neuro-Oncology (2015)

RTRB-04. STEREOTACTIC RADIOSURGERY FOR RECURRENT HIGH-GRADE GLIOMAS: PATIENT SELECTION AND THE ROLE
Repair and Complications of Esophageal Atresia and Tracheoesophageal Fistula
Authors: Orvar Swenson, Richard Lipman, John H. Fisher, Frank G. DeLuca
Journal: New England Journal of Medicine (1962)

ESOPHAGEAL atresia and tracheoesophageal fistula are congenital anomalies that, until twenty years ago, had a very grave prognosis. Leven1 and Ladd,2 using a multiple-stage procedure, were among the first to repair the anomaly successfully, and Haight and Towsley3 performed the first successful primary anastomosis a short time later. The etiology, incidence and much other pertinent material have been reviewed by Haight.4 As summarized in Figure 1, there are five varieties of the anomaly in the following order of frequency: Type 1 consists of esophageal atresia with a fistula from the lower segment to the trachea; Type 2 has simple esophageal atresia . . .
Abstract IA33: Regulation of self-renewal in cancer stem cells.
Authors: Maria Vittoria Verga Falzacappa, Alessandra Insinga, Pier Giuseppe Pelicci
Journal: Clinical Cancer Research (2015)

Abstract We showed that extended self-renewal of leukemia stem-cells (LSCs) is the consequence of the constitutive activation of the cell-cycle inhibitor p21. The pool of LSCs is markedly reduced in p21-/- APLs, and the residual LSCs hyperproliferate and accumulate massive DNA-damage (DD). Notably, p21 is indispensable to maintain the pool of LSCs in PML-RAR leukaemias (PML-RAR – p21-/- leukaemias are not transplantable in syngenic mice). It is not known whether p21 extends the self-renewal of LSCs by activating DD repair, restricting the cell-cycle or regulating their survival. Preliminary results from our lab showed that p21-/- APLs re-acquire the ability to initiate leukemogenesis when transplanted into immunodeficient mice (RAG) or syngeneic mice after γ-irradiation. In these conditions, the growing leukemias are indistinguishable from primary WT APLs and can be re-transplanted into immunodeficient, but not syngeneic mice, suggesting that expansion of p21-/- LSCs is controlled by the host immune-system. Further experiments suggested that p21-/- LSCs are cleared by T-cells since p21-/- APLs: i) initiate leukemias when transplanted into RAG1-/- mice (which lack B, T and NKT cells), but not in JHT mice (lacking only B-cells), and ii) do not grow in NOD/SCID mice when the recipients are injected with a T cell population primed with p21-/- blasts (e.g. obtained from the spleen of WT mice injected with p21-/- APLs), but not with non-primed T cells or T cells primed with WT blasts. T-cells primed with p21-/- blasts are also able to suppress the in vivo growth of wt APLs, but not of T-ALLs. We hypothesize that the immune-surveillance contributes to the elimination of DNA-damaged SCs, and that DNA-damaged LSCs have developed evasion strategies based on p21 activation. Citation Format: Maria Vittoria Verga Falzacappa, Alessandra Insinga, Pier Giuseppe Pelicci. Regulation of self-renewal in cancer stem cells. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr IA33.
Goiter Due to Lymphocytic Thyroiditis (Hashimoto's Struma)
Authors: Donald Gribetz, Nathan B. Talbot, John D. Crawford
Journal: New England Journal of Medicine (1954)

IT has long been thought that in preadolescent children most nontoxic goiters not due to carcinoma were of the simple colloid variety. The present report describes observations made on 6 children with goiters that on histologic examination exhibited changes consistent with chronic lymphocytic thyroiditis of the Hashimoto type. The frequency with which this diagnosis has been made in this clinic may be of interest in view of the supposed rarity of this condition in patients under twenty years of age. Only 11 cases occurring in children could be found in the literature.1 2 3 4 5 6 7 8 9 ¶Clinical, laboratory and pathological findings are presented below . . .
ATPS-90EFFICACY OF NON-VIRAL ENGINEERED ADIPOSE MESENCHYMAL STEM CELLS FOR BRAIN TUMOR THERAPY
Authors: Antonella Mangraviti, Stephany Tzeng, David Gullotti, Kristen Kozielski, Jennifer Kim, Michael Seng, Sara Abbadi, Paula Schiapparelli, Rachel Sarabia-Estrada, Henry Brem, Betty Tyler, Alessandro Olivi, Jordan Green, Alfredo Quinones-Hinojosa
Journal: Neuro-Oncology (2015)

Human adipose derived mesenchymal stem cells (hAMSCs) display high anti-glioma tropism and have been found to be effective as delivery vehicles for targeting brain tumors. Their application, however, has been limited by safety concerns regarding genetic modifications associated with the use of viral vectors. This study developed non-viral, biodegradable nanoparticles to transfect hAMSCs safely and efficiently. We evaluated their efficacy to deliver a bone morphogenetic protein 4 (BMP4), a therapeutic human Brain Tumor Initiating Cells (BTIC)-targeting gene that reduces the clonogenic ability of glioma stem cells, in a human primary malignant glioma model. We optimized a poly (beta-amino ester) (PBAE) polymer structure to transfect hAMSCs with a BMP4-expressing plasmid (NP-hAMSCs), having a transfection efficacy and safety profile superior (p < 0.0001) to Lipofectamine™ 2000. NP-hAMSCs engineered with the PBAE polymer to produce BMP4 (BMP4/NP-hAMSCs) maintained their multi-potency as well as their migration and invasion capacities significantly better than hAMSCs transduced with lentivirus (p = 0.005). Moreover, NP-hAMSC producing BMP4 maintained its pro-differentiation effect on BTICs and significantly inhibited their oncosphere-forming capacity (p < 0.0001). In vivo imaging and histological analyses were conducted to monitor NP-AMSCs administered locally and systemically into the brain of rodents bearing orthotopic human tumors. Intranasal, intravenous, and local delivery of luciferase- and GFP-expressing NP-hAMSCs showed successful migration to the brain and effective transgene expression in the tumor after both systemic and local administration. Finally, twenty-four athymic rats were inoculated with primary BTICs and treated with BMP4-producing NP-AMSCs via intranasal administration and intravenous administration. The animals treated with intranasal administration showed a significant benefit in survival (p = 0.02 vs. control). This study highlights a safe and effective alternative to viral transduction for stem cell-based gene therapies. NP-engineered hAMSCs represents a novel nanomedicine approach to produce and deliver BTIC-targeting genes for brain tumor treatment.
Autophagy as a therapeutic target in cancer treatment.
Authors: V. Karantza, R. A. Moss, J. M. Mehnert, M. N. Stein, E. Poplin, B. Saraiya, J. Aisner, A. R. Tan, E. White, R. S. DiPaola
Journal: Journal of Clinical Oncology (2010)

TPS343 Background: Autophagy is a catabolic cellular process whereby cytoplasm, proteins and organelles are sequestered in double- membrane vesicles, the autophagosomes, and are delivered to and degraded in lysosomes. Autophagy is induced under stress, such as nutrient deprivation. In tumors, autophagy is activated in hypoxic areas and in response to anticancer drugs, providing a survival mechanism that counteracts endogenous and treatment-induced metabolic stress. As such, autophagy prolongs tumor cell survival and is a treatment resistance mechanism. Preclinical studies showed that autophagy inhibition concurrently with chemotherapy preferentially sensitized tumor cells to treatment by depriving them of a critical prosurvival function. Thus, autophagy inhibition in combination with chemotherapy is expected to increase therapeutic efficacy in cancer treatment. Methods: Several phase I/II studies involving autophagy modulation by hydroxychloroquine (HCQ) in combination with chemotherapy for the treatment of different cancers, including breast, colon, prostate and NSCLC, are currently accruing patients at the Cancer Institute of New Jersey. As an example, for patients with metastatic breast cancer who have received no more than 3 prior regimens, we are conducting a phase I/II study of ixabepilone given every 3 weeks with daily HCQ. The phase I portion will determine the MTD. The endpoints for phase II are to assess antitumor activity and time to progression, determine change in CTCs upon treatment, evaluate pharmacodynamic markers for autophagy detection in tumor specimens and characterize the effects of drug treatment on autophagy in PBMCs as a surrogate tissue. The autophagy potential of breast tumors prior to treatment is evaluated by IHC for the autophagy regulators Beclin 1 and LC3, for p62, which accumulates upon autophagy inhibition, and for PTEN and phospho-Akt, as both PTEN loss and Akt activation suppress autophagy. Ixabepilone is given alone on Day 1 of Cycle 1 (HCQ is started on Day 3), and PBMCs are examined for autophagy induction by monitoring Beclin 1, p62 and LC3 levels, as well as LC3 cleavage, by WB at 24 and 48 hours. The same assays are performed in Cycle 2, when both drugs are started on Day 1. No significant financial relationships to disclose.
Overall survival (OS) of metastatic renal cell carcinoma (mRCC) patients corrected for crossover using inverse probability of censoring weights (IPCW) and rank preserving structural failure time (RPSFT) models: Two analyses from the RECORD-1 trial.
Authors: P. Korhonen, E. Malangone, S. Sherman, R. Casciano, R. J. Motzer, J. Baladi, T. Haas, E. Zuber, A. C. Kay, D. E. Lebwohl
Journal: Journal of Clinical Oncology (2010)

4595 Background: The phase III, double-blind, placebo-controlled RECORD-1 trial (NCT00410124) evaluated everolimus (EVE) in VEGF receptor-tyrosine kinase inhibitor (VEGFr-TKI) refractory mRCC. An updated intent-to-treat OS analysis favored EVE (hazard ratio [HR]=0.87, 95% CI: 0.65- 1.15, p=0.162), but was likely null biased as a result of crossover of ∼80% of placebo (PLB) patients to EVE treatment. These 2 validated and independentmethods were used to correct OS for crossover and estimate true survival benefit of a therapy vs PLB had there been no crossover. Methods: RPSFT postulates a structural model where each day on EVE (whether randomized to EVE or after crossover) prolongs survival by a multiplicative factor. The RPSFT method respects randomization and provides a crossover-corrected estimate. The weighted marginal structural IPCW Cox proportional hazards model uses pooled logistic regressions to estimate weights equal to the inverse probability of not crossing over (ie, the probability of PLB patients remaining not censored) and applies these to the final Cox model, resulting in a HR measure of effect. Multiple models were examined using alternate methods to segment time to identify baseline and time-dependent covariates for inclusion. Results: RPSFT estimated survival time was 1.9-fold longer (95% CI: 0.5-8.5) with EVE vs PLB (ie, hypothetical PLB without crossover). A corrected PLB Kaplan-Meier curve estimated OS at 10.0 mo (observed was 14.4 mo). OS for patients randomized to EVE was 14.8 mo. OS HR estimates from multiple IPCW Cox models were robust and indicated a benefit for EVE. Estimated HRs ranged from 0.44-0.55 and most estimated treatment effects were statistically significant. Point estimates from the RPSFT and IPCW methods are intuitively comparable as the former suggests a roughly 2 times longer survival on EVE and the latter suggest a roughly 50% reduction in death risk. Conclusions: Both independent crossover correction methods suggest that EVE was associated with an OS benefit in VEGFr-TKI refractory mRCC patients in RECORD-1. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Analytica International, Novartis Analytica International, Novartis Novartis, sanofi-aventis Wyeth GlaxoSmithKline, Novartis, Pfizer
AB0655 Cross-Cultural Adaptation and Validation of The Behçet's Syndrome Activity Score (BSAS) to Brazilian Portuguese Language: Strong Correlation with Brazilian Behçet's Disease Current Activity form (BR-BDCAF)
Authors: O.G. Colman, L.L. Prado, C.G.S. Saad, M. Levy-Neto, C.R. Gonçalves
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Assessment of Behçet9s Syndrome (BS) activity has been a concern since a treat-to-target strategy may improve disease outcome. The Brazilian Behçet9s Disease Current Activity Form (BR-BDCAF) is currently validated for Brazilian Portuguese, however, it is completed by the physician. Developed originally in English, the Behçet9s Syndrome Activity Score (BSAS) is the first patient-reported assessment tool, which would be useful in clinical routine use and clinical trial evaluations. <h3>Objectives</h3> To perform a cross-cultural adaptation of the BSAS to Brazilian Portuguese language and to evaluate its reliability in a population of Brazilian patients with BS, comparing to BR-BDCAF as a gold standard pattern. <h3>Methods</h3> Brazilian Portuguese version of the BSAS, named BR-BSAS, was obtained according to established guidelines. Fifty-five BS patients, diagnosed according to the International Study Group for Behçet9s Disease criteria, were requested to complete the BR-BSAS. A rheumatologist performed the BR-BDCAF on the same visit. Fifteen patients were selected for a second visit two weeks later, and completed the BR-BSAS once again. Descriptive statistics, intraclass correlation coefficient, internal consistency were calculated to assess reliability and validity of BR-BSAS. Also, we used Pearson coefficient to analyze correlation between the two questionnaires (BR-BSAS and BR-BDCAF). <h3>Results</h3> In this study group, 65.3% were females, with a mean age of 45.6 (SD 13.0) years and a mean disease duration of 15.9 (SD 13.0) years. The test-retest reliability of BSAS presented a good level (ICC=0.839, 95% CI [0.596-0.943]). Internal consistency was also acceptable, with a Cronbach9s alpha of 0.773. Mean BR-BSAS score (range 0-100) was 31,29 (SD 24,54) and mean BR-BDCAF score (range 0-12) was 3,41 (SD 2,34). A strong correlation between BR-BSAS and BR-BDCAF scores was found (r=0.750). <h3>Conclusions</h3> BR-BSAS may be used to assess disease activity in Brazilian BS patients, with a strong correlation between BR-BSAS and BR-BDCAF scores. As a self-reported measure, BR-BSAS may easier to use in clinical practice, adding a patient-derived outcome that may help to improve therapy management decision. <h3>Disclosure of Interest</h3> None declared
Sensitization of Rh-Negative Daughters by Their Rh-Positive Mothers
Authors: Jane Frances Taylor
Journal: New England Journal of Medicine (1967)

THE prediction of immunologic tolerance by Burnett and Fenner1 suggested that tolerance to the Rh antigen might be induced in Rh-negative girls born of Rh-positive mothers.2 Immunologic tolerance was considered possible because maternal red cells cross the placenta to the fetus in at least some pregnancies.3 4 5 6 A contrary opinion held that the few authenticated cases of hemolytic disease, in first-born infants of mothers who had received no known stimulus, might be due to sensitization acquired by the mother in utero.7 , 8 This study was undertaken to determine whether Rh-positive mothers induce immunologic tolerance or primary sensitization in their Rh-negative daughters . . .
Prophylactic effect of lithium and imipramine in unipolar and bipolar II patients: a preliminary report
Authors: F Quitkin, A Rifkin, J Kane, J R Ramos-Lorenzi, D F Klein
Journal: American Journal of Psychiatry (1978)

Relapse rates of the first 35 unipolar and bipolar II manic-depressive patients who entered the controlled phase of a continuing evaluation of the prophylactic value of lithium alone or in combination with imipramine were analyzed. Lithium had a prophylactic effect in unipolar patients and possibly in bipolar II patients. Imipramine did not have a prophylactic effect in either group of patients.
Critical Congenital Aortic Stenosis with Minimal Electrocardiographic Changes
Authors: James L. Reynolds, Alexander S. Nadas, Abraham M. Rudolph, Robert E. Gross
Journal: New England Journal of Medicine (1960)

CONGENITAL aortic stenosis has been regarded in the past as a relatively benign condition in childhood.1 2 3 However, sudden death from this lesion has been emphasized in more recent publications, and in reported series sudden death has occurred in 4 to 18 per cent of the cases.4 5 6 7 8 9 10 Since surgical relief of aortic stenosis is currently available, it becomes of paramount importance to select for operation the patient whose life may be in jeopardy. The criteria for such selection, however, are not well defined. Data from catheterization of the left side of the heart will identify the patient with severe stenosis, but . . .
Care of the caregiver: Transitions at the end of life.
Authors: Margaretta Page, Idonah M. Molina, Judy Patt, Susan Marina Chang
Journal: Journal of Clinical Oncology (2014)

152 Background: Transitions of care can be particularly stressful on cancer patients and caregivers when goals of care are changing, especially at the time when active specialty care shifts to hospice. There are common caregiver issues at the end of life for the brain tumor patient as for any cancer patient however there are a subset of challenging problems unique to the disease. One of the goals of the UCSF caregiver program is to provide information on effective care at home and at the end of life to the caregiver when faced with a family member with a progressive, life threatening brain tumor. Methods: The caregiver program at UCSF sought to overcome the major caregiver challenges of the brain tumor patient at the end of life in two ways. First, caregivers of patients at the terminal phase in the illness trajectory were proactively contacted by a member of the caregiver team to offer informational and emotional support around end-of-life issues. The team also makes contact with the hospice agency in order to provide information about specifics regarding symptoms, family dynamics, or any relevant history. Second, in collaboration with the palliative care service, a palliative care and end of life handbook for brain tumor patients was planned. Results: Since June 2013, 70 caregivers of patients have been identified as “high risk” for distress because of disease progression or transition to hospice care. In addition to providing support to the caregiver at the end of life, the palliative care handbook was produced and distributed. The handbook provided general information on the role of hospice, advance care planning, and bereavement and more importantly incorporates specific sections that highlight the unique challenges regarding neurological symptoms that include cognitive and behavioral changes, language difficulties, corticosteroid use and the inability of oral intake that can significantly affect anti-seizure medication administration. Conclusions: Additional focus to ease transitions for caregivers of brain tumor patients at end of life is needed. Future projects involve creating a handbook to provide resources to hospice professionals caring for brain tumor patients that will highlight common symptoms expected, (ie. seizures) and options for management.
The Relation between Estrogen Receptors and Response Rate to Cytotoxic Chemotherapy in Metastatic Breast Cancer
Authors: Marc E. Lippman, Joseph C. Allegra, E. Brad Thompson, Richard Simon, Audrey Barlock, Linda Green, Karen K. Huff, Hoan My T. Do, Susan C. Aitken, Robert Warren
Journal: New England Journal of Medicine (1978)

In a retrospective study we determined the relation between estrogen receptors and the response rate to cytotoxic chemotherapy in 70 patients with metastatic breast cancer. Thirty-four of 45 patients with low or absent estrogen-receptor values (less than 10 fmol per milligram of cytoplasmic protein) had objective responses to chemotherapy, whereas only three of 25 patients with higher values (greater than 10 fmol per milligram of cytoplasmic protein) responded (P less than 0.0001). There were no statistically significant differences between the two groups in age, menopausal status, disease-free interval, Karnofsky index or prior therapy. Differences in sites of involvement or type of chemotherapy did not account for the increased response rate in receptor-negative patients. We conclude that estrogen-receptor values are an important predictor of response to cytotoxic chemotherapy in metastatic breast cancer.
Hospital patients need open access echocardiography
Authors: J. Zarifis, D G. Beevers, G. Y H Lip
Journal: BMJ (1995)

EDITOR,--We agree with C M Francis and colleagues that echocardiography is useful in patients with heart failure and that an open access service may be used successfully by general practitioners.1 Heart failure is also common among patients admitted to hospital,2 but we have noted a reluctance to use echocardiography in such patients.

To investigate this further we recently …