tbuckley/cabot-search huggingface dataset:
ATPS-23MULTIMODALITY TREATMENT FOR METASTATIC, RECURRENT PINEAL PARENCHYMAL TUMOR OF INTERMEDIATE DIFFERENTIATION: A NOVEL TREATMENT APPROACH
Authors: Juanita Garces, Franklin Berry, Mansour Mathkour, Edison Valle, Ilias Caralopoulos, Lee Roy Morgan, Marcus Ware
Journal: Neuro-Oncology (2015)

INTRODUCTION: Pineal parenchymal tumors of intermediate differentiation (PPTID) represent less than 0.04% of brain tumors. Due to the rarity of this disease, there is no consensus as to appropriate treatment of this tumor. We present a patient with PPTID and our novel approach thereafter. CASE: A 34 year-old male presented with headache, nausea and vomiting, and an MRI showing a 2-cm pineal mass. Biopsy showed PPTID. He underwent whole brain radiation therapy and chemotherapy with carboplatin, bleomycin and VP-16. He showed recurrence after 5-years, after which partial tumor resection was performed and he underwent further treatment with cisplatin/melphalan and radiation. Two years later, MRI showed hydrocephalus and diffuse leptomeningeal spread with several solid tumors, which was treated with a VP shunt. After in-vitro chemosensitivity analysis, the patient was started on temozolamide. He had resolution of symptoms and radiographic masses. Eight months later, patient presented with further symptoms and thrombocytopenia. MRI showed tumor progression and cerebellar hemorrhage. The family elected not to treat and care was withdrawn. METHODS/RESULT: Tumor cells collected from CSF were grown in culture and sensitivity to chemotherapeutic agents was determined. In-vitro chemosensitivity trials showed DM-CHOC-PEN, a novel agent that is currently in phase-2 clinical trials at our institution, and temozolamide each had excellent response with 75% tumor cell death. We elected to treat the patient with temozolamide. CONCLUSION: We took a practical and rational approach of applying several low morbidity treatments to treat this patient's disease. Based off of our chemosensitivity trials, we found excellent results with DM-CHOC-PEN as well as temozolamide. We elected to treat the patient with temozolamide. With this approach, we were able to control this patient's disease for up to 8-years. In cases of rare tumors, we suggest the use of similar rational approaches to individual patients until proven treatment regimens are available.
Abiraterone in Metastatic Salivary Duct Carcinoma
Authors: Damien Urban, Danny Rischin, Christopher Angel, Ieta D’Costa, Benjamin Solomon
Journal: Journal of the National Comprehensive Cancer Network (2015)

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy with limited evidence guiding standard treatment. SDC is known to overexpress the androgen receptor, with only a handful of cases reporting responses to androgen blockade. This report presents a case of SDC responding to multiple lines of androgen blockade, including a rapid response to abiraterone, a CYP17 inhibitor effective in prostate cancer. This case represents the first published report of SDC responding to abiraterone and illustrates that androgen receptor expressing SDC may be treated with multiple lines of androgen blockade, including newer agents such as abiraterone. This case suggests that SDC may continue to be androgen-dependent after progression on androgen deprivation, which is analogous to prostate cancer.
Antiangiogenesis Treatment for Glioblastoma Multiforme: Challenges and Opportunities
Authors: Eric T. Wong, Steven Brem
Journal: Journal of the National Comprehensive Cancer Network (2008)

Angiogenesis is a major hallmark of cancer cells, and glioblastomas are among the most angiogenic tumors. The cascade of angiogenesis is probably initiated by hypoxia, leading to the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Both VEGF and bFGF have paracrine effects on endothelial cells, pericytes, or both, causing the formation of hyperpermeable tumor blood vessels. Advanced MRI techniques, such as dynamic contrast-enhanced, dynamic susceptibility, and arterial spin labeling MRI, have provided semiquantitative measurements of tumor vascular permeability and perfusion. A decrease in vascular permeability and perfusion can be detected after antiangiogenesis drug treatment, either with monoclonal antibody such as bevacizumab that sequesters VEGF, or small-molecule VEGF receptor tyrosine kinase inhibitors. Therefore, antiangiogenesis therapies are being increasingly adopted for treating glioblastomas. However, caution must be exercised because neural stem cells are also sensitive to antiangiogenesis drugs and the combined effect of ionizing radiation. This article summarizes 30 years of laboratory and clinical research on glioblastoma angiogenesis and discusses its underlying biology, clinical trial results, vascular neuroimaging, and the potential side effects of antiangiogenesis treatment.
Contraception and Sterilization
Authors: J A Fust
Journal: New England Journal of Medicine (1971)

To the Editor: In the letter of Jean Buckalew (in the September 2 issue of the Journal) under the caption Feminist Disagreement on Abortion The Last Paragraph refers to All the effective contraceptive measures available to men and  women including voluntary sterilization.  Along with Effectiveness The factors of safety and acceptance injluence use.  The following happens in practice: About 5 per cent of males will use prophylaxis; according to a recent poll of college males 5 per cent would agree to voluntary sterilization (Sterilization is more dangerous and less successful in  females); safe and acceptable contraception for females has not yet been provided by medical science; and it is females who die from the effects of contraceptives abortions childbirth and sterilization (About 2000 per Year in the United States from complications of pregnancy); yet there is not a female on the population control council. (Full Text)
Fatty Acid Metabolic Defects and Right Ventricular Lipotoxicity in Human Pulmonary Arterial Hypertension
Authors: Evan L. Brittain, Megha Talati, Joshua P. Fessel, He Zhu, Niki Penner, M. Wade Calcutt, James D. West, Mitch Funke, Gregory D. Lewis, Robert E. Gerszten, Rizwan Hamid, Meredith E. Pugh, Eric D. Austin, John H. Newman, Anna R. Hemnes
Journal: Circulation (2016)

The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. Abnormalities in fatty acid (FA) metabolism have been described in experimental models of PAH, but systemic and myocardial FA metabolism has not been studied in human PAH.We used human blood, RV tissue, and noninvasive imaging to characterize multiple steps in the FA metabolic pathway in PAH subjects and controls. Circulating free FAs and long-chain acylcarnitines were elevated in PAH patients versus controls. Human RV long-chain FAs were increased and long-chain acylcarnitines were markedly reduced in PAH versus controls. With the use of proton magnetic resonance spectroscopy, in vivo myocardial triglyceride content was elevated in human PAH versus controls (1.4±1.3% triglyceride versus 0.22±0.11% triglyceride, P=0.02). Ceramide, a mediator of lipotoxicity, was increased in PAH RVs versus controls. Using an animal model of heritable PAH, we demonstrated reduced FA oxidation via failure of palmitoylcarnitine to stimulate oxygen consumption in the PAH RV.Abnormalities in FA metabolism can be detected in the blood and myocardium in human PAH and are associated with in vivo cardiac steatosis and lipotoxicity. Murine data suggest that lipotoxicity may arise from reduction in FA oxidation.
University of Michigan Comprehensive Cancer Center Opportunities for Improvement Project
Authors: Tara M. Breslin, Marcy Waldinger, Samuel M. Silver
Journal: Journal of the National Comprehensive Cancer Network (2014)

The University of Michigan Comprehensive Cancer Center (UMCCC) Opportunities for Improvement project involved a detailed patient-level medical record review, feedback to medical providers and clinical leadership, and discussion of potential predictors of discordant or delayed care. The medical record review revealed that reasons for discordant or delayed care were well documented by clinical providers, and medical comorbidity was the most common predisposing factor. Another common theme was the difficulty in obtaining treatment records for patients who received a portion of their care outside UMCCC. The project provided a valuable opportunity to examine established processes of care and data collection and consider how the newly implemented electronic health record might support future efforts aimed at improving efficiency and communication among providers.
Abstract 11013: Resource Utilization for Non-Cardiac Hospital Admissions in Patients With Single Ventricle Congenital Heart Disease
Authors: Ian D Thomas, Michael D Seckeler
Journal: Circulation (2014)

Background: Patients with single ventricle (SV) congenital heart disease (CHD) incur high hospital costs during staged surgical palliation. However, resource utilization for non-cardiac admissions in SV patients has not been reported. This study sought to compare costs for common non-cardiac hospital admissions between SV patients and patients without CHD. Methods: A retrospective review of hospital discharge data from the University HealthSystem Consortium (UHC) from January 2011 through December 2013 was performed. UHC collects discharge data from 120 academic institutions and 302 affiliated hospitals. The database was queried for patients &lt;18 years of age with ICD-9 codes for SV lesions: hypoplastic left heart syndrome (746.7), tricuspid atresia (746.1) or common ventricle (745.3). Neonates (&lt;30 days old) were excluded to eliminate hospitalizations for Stage 1 surgical palliation. Primary diagnosis, direct cost, length of stay (LOS), ICU admission rate and mortality data were obtained. The eight most common non-cardiac admission diagnoses were compared between SV patients and non-CHD patients using t-test and Fisher’s exact test, as appropriate. Results: The non-cardiac admission diagnoses, with ICD-9 codes, and comparisons between SV and non-CHD patients are shown in the Table. Total direct cost, LOS and ICU admission rate were higher for SV patients for all diagnoses with the exception of LOS for failure to thrive, which was not different between groups. Notably, hospital mortality was markedly higher for SV patients admitted for RSV bronchiolitis or pneumonia. Conclusions: Hospital costs for common non-cardiac diagnoses are higher for patients with SV CHD. As long-term survival of SV CHD patients increase they will utilize a disproportionate amount of medical dollars, as our study shows. Further characterization of SV CHD patient costs will be important so steps can be taken to reduce or prevent hospitalization in these patients.
The significance of childhood neurosis for adult mental health: a follow-up study
Authors: S Waldron
Journal: American Journal of Psychiatry (1976)

The author compared the mental health of 42 young adults who had suffered from a neurosis in childhood with that of 20 control subjects. Various aspects of functioning were clinically assessed using the Current and Past Psychopathology Scales and the Health-Sickness Rating Scale. More than 75% of the former patients were at least mildly ill at follow-up, compared with only 15% of the control group. Intergroup differences in diagnoses and symptoms are described. The findings establish the fact that neurotic children require much more effective treatment than they have traditionally received in order to attain a good prognosis for adult mental health.
c‐Jun N‐terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)‐dependent pathway leading to inactivation of intramitochondrial Src
Authors: Sanda Win, Tin Aung Than, Robert Win Maw Min, Mariam Aghajan, Neil Kaplowitz
Journal: Hepatology (2016)

Sustained c‐Jun N‐terminal kinase (JNK) activation has been implicated in many models of cell death and tissue injury. Phosphorylated JNK (p‐JNK) interacts with the mitochondrial outer membrane SH3 homology associated BTK binding protein (Sab, or SH3BP5). Using knockdown or liver‐specific deletion of Sab, we aimed to elucidate the consequences of this interaction on mitochondrial function in isolated mitochondria and liver injury models in vivo . Respiration in isolated mitochondria was directly inhibited by p‐JNK + adenosine triphosphate. Knockdown or liver‐specific knockout of Sab abrogated this effect and markedly inhibited sustained JNK activation and liver injury from acetaminophen or tumor necrosis factor/galactosamine. We then elucidated an intramitochondrial pathway in which interaction of JNK and Sab on the outside of the mitochondria released protein tyrosine phosphatase, nonreceptor type 6 (SHP1, or PTPN6) from Sab in the inside of the mitochondrial outer membrane, leading to its activation and transfer to the inner membrane, where it dephosphorylates P‐Y419Src (active), which required a platform protein, docking protein 4 (DOK4), on the inner membrane. Knockdown of mitochondrial DOK4 or SHP1 inhibited the inactivation of mitochondrial p‐Src and the effect of p‐JNK on mitochondria. Conclusions: The binding to and phosphorylation of Sab by p‐JNK on the outer mitochondrial membrane leads to SHP1‐dependent and DOK4‐dependent inactivation of p‐Src on the inner membrane; inactivation of mitochondrial Src inhibits electron transport and increases reactive oxygen species release, which sustains JNK activation and promotes cell death and organ injury. (H epatology 2016;63:1987‐2003)
Intraoperative intraperitoneal (IP) chemotherapy with cisplatin and escalated dose of epinephrine in patient with recurrent peritoneal carcinomatosis of ovarian cancer: A phase I study
Authors: E. Guardiola, B. Chauffert, D. Delroeux, L. Benoit, S. Causeret, M. Combe, B. Royer, J. Plaza, B. Heyd, X. Pivot
Journal: Journal of Clinical Oncology (2007)

16019 Background: IP epinephrine (E) has been shown to enhance the accumulation and antitumor activity of IP cisplatin in rats with peritoneal carcinomatosis (Duvillard et al. Int J Cancer, 1999). E induces a vasoconstriction of peritoneal vascular bed which limits platin peritoneal leakage and enhances drug penetration into tumor nodules. Results of a phase I study with the association of IP E and IP cisplatin in patient with refractory peritoneal carcinomatosis has been reported (Molucon-Chabrot et al, Anticancer Drugs, 2006). We conducted a phase I study to evaluate intraoperative IP chemotherapy with the association of cisplatin and escalated dose of E. Methods: 18 patients (pts) with recurrent ovarian cancer were enrolled. The median age was 56 years old (range 42–66). After an optimal cytoreductive surgery, IP chemotherapy was performed during surgery by filling twice the peritoneal cavity with 3 liters of an isotonic saline pre heated at 37°C and 90 mg of cisplatin associated with increasing concentrations of E during 1 hour. Results: E was escalated according to the following dosage: 0, 1, 2, 3 mg/L (3 pts by step). No toxicity was observed during and after intraoperative IP chemotherapy in the first 10 patients. The 2 nd patient included in the 3 mg/L level of E experienced a tachycardia ≥ 120/min, ventricular extrasystoles (VES) ≥ 2/min, increase of troponine plasmatic concentration without significant electric sign of cardiac ischemia. The 3 rd patient at this level experienced a tachycardia ≥ 120/min with ventricular VES ≥ 2/min and no increase of troponine concentration or electric sign of cardiac ischemia. According to the protocol design, 6 additional patients were included in the lower dose of 2 mg/L of E and no toxicity occurred. One can consider that the recommended dose of E was established. Conclusion: The combination of IP E with IP cisplatin in intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The limiting toxicity was the cardiovascular effect which occurred with 3 mg/L dose of E. A phase II-III study is planned to investigate if IP chemotherapy adds to a second look surgery for the initial treatment of stage III ovarian carcinoma. No significant financial relationships to disclose.
Timing of Initial Antibiotic Treatment for Febrile Neutropenia in the Emergency Department: The Need for Evidence-Based Guidelines
Authors: Demetrios N Kyriacou, Borko Jovanovic, Olga Frankfurt
Journal: Journal of the National Comprehensive Cancer Network (2014)

Guidelines for the treatment of febrile neutropenia (FN) universally recommend the prompt initiation (<60 minutes) of antibiotic therapy for patients with this complication presenting to medical settings. Unfortunately, administration delays exist in emergency departments where patients with FN frequently seek care. Future guidelines should be based on investigations that clearly indicate the effectiveness of rapid antibiotic therapy. If definitive investigations identify an optimal time period for the initial administration of antibiotics for patients with FN, administrative efforts will be developed to improve the emergency department care of these critically ill patients with cancer.
Cardiac salvage by tweaking with beta-3-adrenergic receptors
Authors: Jean-Luc Balligand
Journal: Cardiovascular Research (2016)

Overstimulation of the orthosympathetic system leads to cardiovascular cell and tissue damage through prolonged activation of β-1-2 adrenergic receptors (BARs). The more recent identification of the third isotype of BAR (B3AR) in cardiac myocytes and endothelial cells with a distinctive coupling and effect on cardiac function and remodelling introduced a new facet to this paradigm. In particular, B3AR is up-regulated in cardiac disease and less prone to homologous desensitization, which may reinforce its influence on the diseased myocardium. Mice with transgenic cardiac-specific expression of the human B3AR are protected from cardiac hypertrophy and fibrosis in response to neurohormonal stimulation. B3AR has also been implicated in cardiac protection after ischaemia-reperfusion and the benefits of exercise on the heart. Many of these salvage mechanisms are mediated by B3AR coupling to nitric oxide synthase (eNOS and nNOS) and downstream cGMP/protein kinase G signalling. Notably, B3AR exerts antioxidant protective effects on these and other signalling elements, which may subserve its protective properties in the setting of chronic heart failure. Additional vasorelaxing properties and paracrine NO-mediated signalling by B3AR in endothelium, together with systemic metabolic effects on beige/brown fat complete the pleiotropic protective properties of this new therapeutic target.
The Mechanism of Low-renin Hypertension : Aldosterone Response to Sodium Restriction and Upright Posture, Angiotensin II, ACTH and Potassium in Patients with Hypertension
Authors: Ikuo Saito, Takao Saruta, Ryuichi Nakamura, Jiro Misumi, Kazuoki Kondo, Shun Matsuki
Journal: Circulation (1976)

Plasma renin activity and aldosterone were measured simultaneously in 67 out-patients with essential hypertension. High aldosterone was more often in patients with high renin, and low levels of aldosterone were usual in those with low or normal renin. In order to study the mechanism by which aldosterone and renin activity are suppressed in low-renin hypertension, 25 patients (13 normal-renin hypertensives, 10 low renin patients including 4 non-responders and two DOC excess hypertensives) were investigated as inpatients. Plasma renin activity, aldosterone and cortisol were determined by the following stimulations with 3 days of sodium restriction and 2 hours of upright posture, angiotensin II infusion (at a dose which increased 20mmHg of diastolic blood pressure), ACTH administration (rapid i.m. injection of 0.25 mg of alpha 1-24 preparation) and potassium infusion (30meq of potassium i.v.). Responses of aldosterone in normal-renin hypertensives to all stimulations were 3-5 fold increases from base line values. Low renin hypertensives except two of four non-responders showed the responses similar to those in normal-renin patients. The responses of two of the non-responders were similar to those in DOC excess hypertensives who showed reduced responses of aldosterone to some of these stimulations. Thus, it seems that low-renin hypertension is a clinical entity caused by a variety of mechanisms, and the mechanism by which low-renin hypertension is induced is not explained by one factor such as an unknown mineralocorticoid.
Imatinib Long-Term Effects Study: Global Independent Assessment of Imatinib in Chronic Myeloid Leukemia: Results At 8 Years,
Authors: Carlo Gambacorti-Passerini, Laura Antolini, Rocco Piazza, François Guilhot, Michael Deininger, Carmen Fava, Arnon Nagler, Enrica Morra, Elisabetta Abruzzese, Anna D'Emilio, Fabio Stagno, Philipp D. le Coutre, Rafael Hurtado Monroy, Valeria Santini, Fabrizio Pane, Pilar Giraldo, Sarit Assouline, Muheez A Durosinmi, Onno Leeksma, Enrico Maria Pogliani, Francesca Pavesi, Miriam Puttini, Christian Rizzo, Ilaria Dilda, Silvia Mori, Dong-Wook Kim, Maria Grazia Valsecchi
Journal: Blood (2011)
Effects of strength training intervention in breast cancer survivors.
Authors: Joanne Monterroso, Kim Dittus, Abigail Crocker, Nathan Kokinda, Patricia O'Brien
Journal: Journal of Clinical Oncology (2015)

9565 Background: Oncology rehabilitation programs provide a potential avenue for improving fitness, function and quality of life. Few studies evaluate how cancer survivors respond to such interventions. Objectives: 1. Compare upper and lower body strength of breast cancer survivors (BCS) to normative data. 2. Evaluate changes in strength after 12 weeks of resistance training. Methods: Participants received a 12 week, 2x per week aerobic and resistance training intervention as part of the University of Vermont Medical Center oncology rehabilitation program. One repetition maximum strength testing of upper and lower body strength was completed before and after the intervention. Strength was compared to American College of Sports Medicine normative values. Pre/post comparisons were completed for participants attending ≥ 25% of sessions. Breast cancer survivors were included in the analysis. Results: Baseline assessments were obtained on 130 participants, 91 completed at least 25% of exercise sessions. 90% completed ≥ 66% of training sessions. Over 90% of BCS had upper extremity strength at < 25th percentile and over 74% had lower extremity strength at < 20th percentile. Upper and lower extremity strength remained < 25thpercentile for the majority of participants after the intervention but percentiles improved 8 and 16 points respectively. For participants completing the intervention, upper extremity strength increased from 57 ± 31lbs to 70 ± 31lbs (p < 0.001). Lower extremity strength increased from 125 ± 45 to 154 42lbs (p < 0.001). There were no significant differences in strength improvement between BCS who did and did not receive chemotherapy. The upper extremity strength of women age ≤ 55 improved to a greater degree than women over age 55 (p = 0.01). Conclusions: Breast cancer survivors entering an oncology rehabilitation program have markedly lower upper and lower body strength compared to normative data. Strength training intervention results in improved strength in this population but strength remains below expected. The benefit of resistance training was seen regardless of age or previous exposure to chemotherapy. Opportunities for breast cancer survivors to participate in resistance training interventions should be encouraged.