tbuckley/cabot-search huggingface dataset:
Where Is the Popular Mandate?
Authors: Vicente Navarro
Journal: New England Journal of Medicine (1982)

Current policies of the federal government include substantial cuts in government health expenditures and dismantling government regulations in the health and medical-care sectors. These policies are being pursued under an assumed popular mandate. The existence of such a mandate is also assumed among large sectors of the political, medical, and academic establishments in this country. There is, indeed, a belief among many leaders of medical academic and healthcare institutions that there is a popular mandate to cut government health expenditures, with particular emphasis on those that affect the poor and the elderly; and an anti-government mood in the country, with . . .
AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival
Authors: Rigel J. Kishton, Carson E. Barnes, Amanda G. Nichols, Sivan Cohen, Valerie A. Gerriets, Peter J. Siska, Andrew N. Macintyre, Pankuri Goraksha-Hicks, Aguirre A. de Cubas, Tingyu Liu, Marc O. Warmoes, E. Dale Abel, Allen Eng Juh Yeoh, Timothy R. Gershon, W. Kimryn Rathmell, Kristy L. Richards, Jason W. Locasale, Jeffrey C. Rathmell
Journal: Cell Metabolism (2016)
P50 Apolipoprotein E and low-density, apolipoprotein B associated lipoviral particles in chronic hepatitis C infection: evidence for genotype-specific modulation of lipid pathways
Authors: S. Bridge, D. Sheridan, D. Felmlee, M. Crossey, H. Thomas, S. Taylor-Robinson, G. Toms, D. Neely, M. Bassendine
Journal: Gut (2011)

<h3>Introduction</h3> Hepatitis C virus (HCV) co-opts the VLDL assembly, maturation, degradation, and secretory machinery of hepatocytes. Infectious low density particles have been termed lipoviral particles (LVP). LVPs in vivo are triglyceride (TG) rich and contain at least viral RNA, HCV core protein and the VLDL components apolipoprotein B (apoB) and apoE. ApoE is a constituent of infectious HCV particles produced in cell culture, and production of infectious particles is dramatically impaired from cells in which apoE expression has been genetically silenced. <h3>Aim</h3> To examine the relationship between LVP and apoE in vivo. <h3>Method</h3> Fasting plasma samples were obtained from 39 chronic HCV genotype (G) three patients and 51 HCV G1 patients. LVP were measured using iodixanol density gradient ultracentrifugation as recently described.1 ApoE levels were determined by an automated immunonephlometric method. Demographic data were recorded and liver biochemical tests, lipid profiles and HOMA-IR were measured in all patients. <h3>Results</h3> The mean LVP in HCV G3 was 5.2 log10 IU/ml with a mean LVP ratio of 0.286, but showed wide variation (0.03–0.96). This was not significantly different to LVP variation in HCV G1 we have previously reported.1 In HCV G1 we found a strong positive correlation of LVP HCV RNA with apoE levels (r=0.488, p=0.001) and also with LVP ratio (r=0.428, p=0.001). In contrast in HCV G3 we found a significant negative correlation of LVP HCV RNA with apoE levels (r=−0.428, p=0.013), suggesting different utilisation of lipoprotein pathways. We also found a negative correlation of LVP in HCV G3 with HDL cholesterol (r= −0.468, p=0.003) and its structural lipoprotein apoA1 (r= −0.479, p=0.002) whereas we have reported no correlation of LVP in cHCVG1 with HDL or apoA1.1 Furthermore in HCV G3 we found low TG levels compared to G1 (1.00±0.71 vs 1.35±0.76) and no correlation of LVP with TG or HOMA-IR, again contrasting to G1 infection1. <h3>Conclusion</h3> This study suggests that while serum apoE quantity is a positive determinant for LVP quantity in HCV G1 infection, it is a negative determinant in HCV G3 infection. Furthermore, LVP quantity in HCV G3 is largely based on the paucity of HDL quantity and their components, rather than the parameters associated with TRL levels as in HCV G1. These differences highlight that interaction with host lipoprotein metabolism is important for HCV infection in different genotypes, but in genotype specific ways.
Finally, a Randomized, Controlled Trial of Epilepsy Surgery
Authors: Jerome Engel
Journal: New England Journal of Medicine (2001)

In all of modern medicine, few generally accepted therapeutic interventions are as underutilized as surgical treatment for epileptic seizures. More than 2 million people in the United States have epilepsy, and 400,000 to 600,000 of them have seizures that cannot be controlled by antiepileptic drugs.1 As many as one quarter to one half of these people are potential candidates for surgical treatment, yet a 1990 survey revealed that only 1500 therapeutic surgical procedures for epilepsy were performed in the United States in that year and that the rate of use of surgery for epilepsy was equally low in other industrialized . . .
The Marfan Syndrome: Diagnosis and Management
Authors: Reed E. Pyeritz, Victor A. McKusick
Journal: New England Journal of Medicine (1979)

THE Marfan syndrome is classified as a heritable disorder of connective tissue because clinical and pathological alterations involve supporting elements. It long has been assumed that an inborn error of protein metabolism, particularly in collagen or elastin, accounts for the Marfan syndrome, but conclusive evidence is not yet available. Moreover, the extent of biochemical variability in structural proteins associated with health and disease is for the most part unknown, one result being that the prevalence and clinical importance of all the heritable disorders of connective tissue are inadequately appreciated. On the basis of recent experience, the prevalence of what we . . .
The Epidemiology and Genetics of Atopic Allergy
Authors: David G. Marsh, Deborah A. Meyers, Wilma B. Bias
Journal: New England Journal of Medicine (1981)

STUDIES of atopic allergy ("allergy") have provided new insight in defining the epidemiologic and genetic basis for the human immune response.1 , 2 Allergy is characterized by the development of antibody responses of a unique immunoglobulin — IgE3 — after exposure to inhaled, ingested, or injected antigens (usually termed "allergens"). Under conditions of natural exposure to extremely low doses (usually less than 1 μg per year),4 atopic persons have IgE-antibody responses toward an array of environmental allergens present in pollens, fungal spores, animal danders, and similar substances. Synthesis of IgE is favored by natural immunization through inhalation, since antigens come directly into . . .
Hemorrhage Risk in Antibiotic-Induced Thrombocytopenia: Rethinking Priorities
Authors: Uri Goldberg, Madhumati Kalavar, Minhaj Musa, Yirgalem Tiruneh, Kalpana Panigrahi, Grace Shyh, MaryAnn Aziz, Hoang Nhu Hua, Roya Mukhtarzad
Journal: Blood (2014)
Efficacy of brachytherapy for prostate cancer in organ transplant patients
Authors: K. Hertzfeld, R. Shirazi, K. Redmond, W. Barrett
Journal: Journal of Clinical Oncology (2005)

4797 Background: It has been shown that there is a 3 to 7-fold increase in cancer incidence in organ transplant recipients.1 Evaluation of the natural history of carcinoma in transplant recipients has shown that these cancers behaved more aggressively than expected.2 The purpose of this study is to compare the biochemical response to prostate brachytherapy in immunosuppressed patients compared to non-immunosuppressed patients. Methods: Between 1994 and 2002, 158 patients were treated at our institution with Iodine-125 seed implantation for presumed localized prostate adenocarcinoma (stage T1a through T2c). All patients had pretreatment evaluation including PSA level, DRE, and biopsies to determine Gleason score. The prescribed dose was 16,000 cGy to the periphery of the prostate determined by endorectal ultrasound. Patients were evaluated for biochemical failure determined by the ASTRO consensus definition, and for achieving and maintaining a PSA level of ≤ 1.0, ≤ 0.5, and ≤ 0.2 ng/ml. Results: The mean pretreatment PSA level was 6.7 ng/ml for the control group, and 6.5 ng/ml for the study group. The mean Gleason score was 6.05 for the control group, and 5.25 for the study group. All of the study patients experienced freedom from biochemical failure according to the ASTRO consensus definition, compared with 88.3% of the control group. PSA nadir of ≤ 1.0 was achieved in 88.3% of control patients and 100.0% of study patients; PSA nadir of ≤ 0.5 was achieved in 82.5% of control patients and 75% of study patients; and PSA nadir of ≤ 0.2 was achieved in 70.1% of control patients and 50% of study patients. Conclusions: Patients who are immunosuppressed are known to have increased rates of cancer and to have worse prognosis compared to non-immunocompromised patients. Although the number of immunocompromised patients in this series is small, our experience is suggestive that brachytherapy is no less efficacious in immunosuppressed patients. Table 1: Characteristics of Immunosuppressed Patients No significant financial relationships to disclose.
Association of Antenatal Corticosteroids With Mortality, Morbidity, and Neurodevelopmental Outcomes in Extremely Preterm Multiple Gestation Infants
Authors: Nansi S. Boghossian, Scott A. McDonald, Edward F. Bell, Waldemar A. Carlo, Jane E. Brumbaugh, Barbara J. Stoll, Abbot R. Laptook, Seetha Shankaran, Michele C. Walsh, Abhik Das, Rosemary D. Higgins
Journal: JAMA Pediatrics (2016)

Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples.To examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples.Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables.Antenatal corticosteroids.In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment.A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01).Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.
Oxaliplatin/5-FU chemotherapy without leucovorin in metastatic colorectal cancer
Authors: B. Y. Shim, H. J. Cho, J. M. Yang, H. J. Kim, J. K. Kim, H. K. Kim
Journal: Journal of Clinical Oncology (2004)

3734 Background: Oxaliplatin, 5-FU and leucovorin combination chemotherapy is one of effective regimen for metastatic colorectal cancer, even in patients who received 5-FU previously. But, in this regimen, the role of ( high dose) leucovorin in patients who previously received 5-FU and leucovorin is unknown. And the response rate of oxaliplatin/5-FU without leuconvorin given as the first regimen is almost similar to that of with leucovorin. We evaluated the effect of oxaliplatin and 5-FU without leucovorin in patients with metastatic colorectal cancer. Methods: Twenty four patients with metastatic colon(n=15), rectal (n=9) cancer were enrolled in this study. There were 9 male and 15 female patients and their median age was 63(range 37–74). Seventeen patients were received 5-FU and leucovorin previously. All patients received oxaliplatin 85mg/m2 on day 1 and, 5-FU bolus infusion 400mg/m2 on day 1 and continous infusion 600mg/m2/22hrs on days 1 and 2. The chemotherapy was repeated every 3 weeks. Response rate and toxicity were evaluated according to WHO criteria and NCI toxicity criteria respectively. Results: The median cycles of chemotherapy was 6(range1–9). Three were not evaluable. There were 6 partial responses with 25% response rate. In previously treated and untreated patients, the response rate were 23.5% (4/17) and 28.5%(2/7) respectively. The median survival time was 18 months(range 4–32). There was no grade III or IV toxicity except one grade 3 anemia. Conclusions: Oxaliplatin/5-FU combination chemotherapy without leucovorin showed good response and very tolerable toxicity. No significant financial relationships to disclose.
Case 23-2002
Authors: William P. Docken, Eugene J. Mark
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 73-year-old man was admitted to the hospital because of leg pains, occipital headaches, and night sweats.He had been in good health until two months earlier, when he began to experience episodes that began with a sensation of “cold feet,” followed by a right-sided occipital headache and then by bilateral knee, calf, and ankle pain with “throbbing” in the affected bones. The headache was dull and was relieved by acetaminophen (650 mg) after 15 minutes. At that point, he would fall asleep, only to awaken 45 minutes later with sweating that was profuse on most nights, . . .
Expression analysis of α-smooth muscle actin and tenascin-C in the periodontal ligament under orthodontic loading or in vitro culture
Authors: Hui Xu, Ding Bai, L-Bruno Ruest, Jian Q Feng, Yong-Wen Guo, Ye Tian, Yan Jing, Yao He, Xiang-Long Han
Journal: International Journal of Oral Science (2015)

α-smooth muscle actin (α-SMA) and tenascin-C are stress-induced phenotypic features of myofibroblasts. The expression levels of these two proteins closely correlate with the extracellular mechanical microenvironment. We investigated how the expression of α-SMA and tenascin-C was altered in the periodontal ligament (PDL) under orthodontic loading to indirectly reveal the intrinsic mechanical microenvironment in the PDL. In this study, we demonstrated the synergistic effects of transforming growth factor-β1 (TGF-β1) and mechanical tensile or compressive stress on myofibroblast differentiation from human periodontal ligament cells (hPDLCs). The hPDLCs under higher tensile or compressive stress significantly increased their levels of α-SMA and tenascin-C compared with those under lower tensile or compressive stress. A similar trend was observed in the tension and compression areas of the PDL under continuous light or heavy orthodontic load in rats. During the time-course analysis of expression, we observed that an increase in α-SMA levels was matched by an increase in tenascin-C levels in the PDL under orthodontic load in vivo. The time-dependent variation of α-SMA and tenascin-C expression in the PDL may indicate the time-dependent variation of intrinsic stress under constant extrinsic loading.
Case 31-1982
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Daniel Tarsy, Edward P. Richardson, Nancy L. Harris
Journal: New England Journal of Medicine (1982)

Presentation of Case First admission. A 52-year-old woman was admitted to the hospital because of a question of herpes simplex encephalitis.She was well until four weeks previously, when she became ataxic, with slurred speech. Fatigue, somnolence, and vomiting developed, and several days later she was taken to another hospital. Physical examination showed that the temperature was 35°C, and the blood pressure was 160/100 mm Hg. Ataxia and left facial weakness were found, with profuse diaphoresis. X-ray films of the skull and a computed tomographic (CT) scan of the brain were normal. A lumbar puncture showed normal cerebrospinal fluid. . . .
The Community Blood Program
Authors: Donald E. Brown
Journal: New England Journal of Medicine (1956)

THE usual community blood program consists of three major components: the hospital blood bank; the community blood bank; and walking donors. If the program is to function smoothly and efficiently, the responsibilities and limitations of each component must be clearly delineated. Failure to do so results in friction, and administrative friction, like its mechanical counterpart, produces dissipation of energy and varying degrees of heat.A blood bank, as defined by the American Association of Blood Banks, is "a medical facility designed, equipped, and staffed to procure, draw, process, store, and distribute human whole blood or its derivatives." There may be . . .
Cytokine Pathways and Joint Inflammation in Rheumatoid Arthritis
Authors: Ernest H.S. Choy, Gabriel S. Panayi
Journal: New England Journal of Medicine (2001)

Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that cannot be cured and that has substantial personal, social, and economic costs. The long-term prognosis is poor: 80 percent of affected patients are disabled after 20 years,1 and life expectancy is reduced by an average of 3 to 18 years.2 The medical cost of rheumatoid arthritis averages $5,919 per case per year in the United States3 and approximately £2,600 per case per year in the United Kingdom.4 Current slow-acting antirheumatic drugs have limited efficacy and many side effects. Moreover, they do not improve the long-term prognosis of rheumatoid arthritis. . . .
A Grade 6 Systolic Murmur
Authors: D H Spodick, A T Pezzella
Journal: New England Journal of Medicine (1999)

Figure 1. A 30-year-old man who had been treated for staphylococcal endocarditis superimposed on a prolapsing mitral valve had a residual grade 6 mitral systolic murmur that was easily audible without a stethoscope. A two-dimensional echocardiogram showed prolapsing flail mitral leaflets with attached material resulting from the endocarditis (Panel A). AML denotes anterior mitral leaflet, and PML posterior mitral leaflet. Attached material from vegetations and prolapse is evident on an M-mode echocardiogram (Panel B) obtained through the mitral valve shown in Panel A. The arrows indicate coarse oscillations coincident with the grade 6 mitral systolic murmur.
ATPS-05CHARACTERIZATION OF THE ACTIVITY OF AT13387, A NOVEL SECOND GENERATION HSP90 INHIBITOR AGAINST GLIOMAS
Authors: Alessandro Canella, Jihong Xu, Ji Young Yoo, Balveen Kaur, Prabakaran Nagarajan, Dyvia Kesanakurti, Vinay K. Puduvalli
Journal: Neuro-Oncology (2015)

Heat shock protein 90 (Hsp90) is a molecular chaperone that regulates folding and stabilization of several key regulatory client proteins. In cancer, elevated Hsp90 activity is implicated in maintenance of high levels of aberrantly expressed proteins such as kinases and transcription factors making it an attractive target for treatment of several malignancies. Hsp90 inhibitors (Hsp90i) have demonstrated preclinical activity against several tumors including gliomas through downregulation of key oncoproteins inducing growth arrest and tumor cell death. AT13387 is a novel second generation orally bioavailable HSP90i which is in early phase clinical trials; however, its potential for activity against gliomas has not been studied to date. We examined the preclinical efficacy of AT13387 both alone and in combination with temozolomide (TMZ) in glioma cell lines and glioma stem-like cells (GSC). AT13387-treated glioma cells and GSC showed decreased proliferation, reduced invasion and induction of apoptosis. AT13387-treated glioma cells showed downregulation of EGFR, Akt, S6 and MAPK, key regulators of survival pathways and proliferation in gliomas. In GSC, AT13387 promoted stem cell markers downregulation and induced cell death. Of note, AT13387 treatment resulted in downregulation of MSH2, a protein of the DNA mismatch repair complex involved in TMZ-resistance and showed synergistic activity in combination with TMZ in vitro effect against glioma cells. Additionally, preliminary studies in an in vivo mouse model demonstrated that AT13387 crosses the intact blood-brain barrier. These results provide the first evidence for the activity of AT13387 against glioma both singly and in combination with TMZ and support the potential of Hsp90 inhibition as a therapeutic strategy against malignant gliomas.
Abstract 20180: Erroneous Diagnosis of Brugada Syndrome: Advanced Multi-Modality Coronary Evaluation to Establish an Ischemic Etiology for Recurrent Ventricular Arrhythmia
Authors: Erin E Flatley, Andrew D Beaser, Husam H Balkhy, Sandeep Nathan, Joshua D Moss
Journal: Circulation (2014)

Introduction: Rapid diagnosis of ST-segment elevation (STE) myocardial infarction is mandatory for optimal treatment, but standard coronary angiography may occasionally result in misdiagnosis. Case presentation: A 54-year-old man was referred for second opinion on treatment of recurrent ventricular tachycardia (VT) and chest pain. Three years prior, he suffered a cardiac arrest requiring AED shock. Initial EKG showed 5-10 mm STE in leads V2-V6. Emergent coronary angiography at another facility reportedly showed non-obstructive disease, and STE resolved spontaneously. Procainamide challenge during a subsequent electrophysiology study elicited changes diagnosed as Brugada syndrome, and an ICD was implanted. Over the next several years, he had frequent episodes of VT, often associated with chest pain and terminated with anti-tachycardia pacing. Multiple antiarrhythmic drugs were ineffective, and VT ablation was recommended. Based on the history and original EKG, we proceeded with multi-modality coronary evaluation and provocative testing for coronary vasospasm. An indistinct proximal LAD lesion was further evaluated with fractional flow reserve (FFR) testing, showing a baseline FFR of 0.90 that decreased to 0.67 after administration of intracoronary adenosine. Optical coherence tomography (OCT) revealed 90% eccentric ostial LAD stenosis (see Figure). Given the location and severity of the lesion, he underwent successful robotic totally endoscopic beating heart LIMA-LAD bypass grafting. Post-operatively, both chest pain and episodes of VT resolved. Conclusions: The differential diagnosis of transient STE includes several non-coronary etiologies. However, in the setting of dramatic STE across the precordium and recurrent ventricular arrhythmias, a comprehensive, multi-modality coronary evaluation should be employed to identify lesions that may be otherwise equivocal via angiography or sites of significant vasospasm.