tbuckley/cabot-search huggingface dataset:
Informed Consent by Proxy
Authors: John W. Warren, Jeffery Sobal, James H. Tenney, J. Michael Hoopes, Dorothy Damron, Steven Levenson, Bruce R. DeForge, Herbert L. Muncie
Journal: New England Journal of Medicine (1986)

Abstract The need for clinical study of patients in nursing homes is growing as this population grows; yet many of these patients are mentally incompetent to give informed consent for such research, and the decision must therefore be left to family members or other proxies. We studied the decisions by the proxies for 168 patients in nursing homes about whether to permit the patients' participation in a study involving minimal risk. The proxies were family members in all but one case, and 78 of 168 (46 percent) refused consent. Refusal was significantly associated (P<0.001) with the views that research should not be done in nursing homes, that the study would disturb the patient, that the patient, if able, would refuse to participate in the study, and that the proxy would refuse to participate in such a study if asked. Of the 55 proxies who believed that the patient would refuse consent, however, 17 (31 percent) gave consent, in apparent opposition to the patient's wishes. We conclude that refusal by family members to allow incompetent elderly patients to participate in studies may be an important obstacle to research among the elderly. Both the selection of proxies and the bases for their decisions require further study and definition. (N Engl J Med 1986;315:1124–8.)
Responses to Colchicine Therapeutic Trial in Rheumatoid Arthritis
Authors: Jack Zuckner
Journal: New England Journal of Medicine (1962)

IMPROVEMENT from colchicine therapy in patients with arthritic symptoms has always been accepted as indicative of gout.1 2 3 Other arthritides supposedly have not responded satisfactorily to this medication. A diagnostic test designated as the colchicine therapeutic trial has consequently been employed to differentiate gout from other rheumatic diseases. The colchicine therapeutic trial consists of administration of colchicine orally in doses of 0.6 mg. (1/100 gr.) every hour or every two hours until improvement ensues or until gastrointestinal complaints necessitate curtailment of the drug. If improvement results, the diagnosis is considered to be gout.This test has had an important role in . . .
Prolactin-Stimulating Effect on 3H-Thymidine Incorporation in 3-Methylcholanthrene- Induced Cervical Carcinomas in Normal and Estrogenized Mice2
Authors: John-Gunnar Forsberg, Liv Stray-Breistein, Egil Lingaas
Journal: JNCI Journal of the National Cancer Institute (1974)

Neonatal female NMRI mice were given injections of 5μ estradiol in olive oil or olive oil onlyfor the first 5 days after birth. When the animals were 6–9 weeksold, a thread impregnated with 3-methylcholanthrene was inserted into the uterine cervix. When palpable cervical tumors were identified, the animals were killed and the tumors used for organ culture experiments. The incubation medium contained 5μ ovine prelactln/m! or a corresponding volume of Parker 199 medium (controls). Prolactin significantly stimulated 3H-thymidine (3H_TDR) incorporation in tumors from the animals given olive oil neonatally. There was a probable effect in tumors from estrogenized animals (given estradiol neonatally). Prolactin stimulated the 3H-TDR incorporation in monolayer cultures from normal neonatal cervical epithelium.
Propagation of a Human Herpesvirus from AIDS-Associated Kaposi's Sarcoma
Authors: Kimberly E. Foreman, Jacques Friborg, Wing-pui Kong, Clive Woffendin, Peter J. Polverini, Brian J. Nickoloff, Gary J. Nabel
Journal: New England Journal of Medicine (1997)

Although unique DNA sequences related to gammaherpesviruses have been found in Kaposi's sarcoma lesions, it is uncertain whether this DNA encodes a virus that is able to reproduce.
Salicylate-Induced Injury of Pyruvate-Kinase-Deficient Erythrocytes
Authors: Bertil E. Glader
Journal: New England Journal of Medicine (1976)

Salicylate is known to uncouple mitochondrial oxidative phosphorylation. Since the viability of pyruvate-kinase-deficient reticulocytes depends on ATP generated by mitochondrial metabolism, this study examined the effects of salicylate on erythrocytes deficient in pyruvate kinase. When deficient erythrocytes from patients with severe hemolysis were incubated with salicylate (2 to 30 mg per deciliter), there was a marked decrease (25 to 75 percent) in ATP. In addition, this drug-induced ATP depletion produced cell potassium and water loss, and the normal oxidant responsiveness of the hexose-monophosphate shunt was blunted. Since these cellular abnormalities are associated with accelerated hemolysis in vivo, the data suggest that aspirin therapy may aggravate hemolysis in patients with pyruvate kinase deficiency whose erythrocyte manifest sensitivity to salicylate in vitro.
Primary Care in the United States — The Best of Times, the Worst of Times
Authors: Kevin Grumbach
Journal: New England Journal of Medicine (1999)

Until relatively recently, primary care was a neglected facet of the modern U.S. health care system, obscured by the shadows of the citadels of specialty medicine. These lofty icons of American culture were richly furnished with the latest technology that an affluent society could afford, that a public entranced by biomedicine could desire, and that imaginative, well-intentioned physicians could devise. Between 1950 and 1990, the number of specialists per capita tripled in the United States, while the supply of primary care physicians declined.1 The humble general practitioner in fraying tweeds became a second-class citizen. Subspecialists such as invasive cardiologists, slipping . . .
P259 Central Nervous System Tuberculosis: Diagnostic Difficulties
Authors: L Macpherson, R Cuthbert, J Potter, V White, N Jayasera, H Kunst
Journal: Thorax (2015)

<h3>Introduction</h3> Central nervous system (CNS) tuberculosis (TB) is difficult to diagnose. There is often a delay in diagnosis and a lack of robust diagnostic criteria. <h3>Methods</h3> We conducted a retrospective study of all patients treated at our institution for CNS TB from 2009–2014 excluding those with HIV co-infection. Data including demographics, symptoms, microbiological and radiological features was recorded. <h3>Results</h3> 55 cases of CNS TB were identified. The mean age was 36 (4 months – 81 years). Most patients were from the Indian Subcontinent (70.9%), 10.8% were from South East Asia, 1.8% from Africa, 10.9% were UK born and 5.5% were unknown. Symptoms and signs at presentation included headache (67.3%), fever (49%), confusion (34.5%), focal neurological deficit (27.3%), weight loss (27.3%), night sweats (23.6%), altered GCS (23.6%) and seizures (20%). 29% of patients also had pulmonary TB, 11% had TB lymphadenopathy and 11% had miliary TB. 89% of patients had a CT head, of which 42.8% were reported normal, 28.5% reported tuberculomas, 14.2% hydrocephalus and 20.4% exhibited other abnormalities. 87% had an MRI head, of which 10% were normal, 39.6% reported tuberculomas, 33% meningeal enhancement, 6% hydrocephalus, and 23% demonstrated other abnormalities. Lumbar puncture (LP) was performed in 73% of cases, and CSF protein was elevated in 73% of these. The WCC was elevated in 60% with 63% having a predominant lymphocytosis. CSF Glucose was documented in 80% of cases and levels were low (&lt;2.5 mmol/L) in 47%. TB PCR was performed on 15 samples (38%), 2 (13%) were positive. Five CSF samples were not sent for AFB or culture. No samples were smear positive, 26% of CSF samples were culture positive; one was Isoniazid resistant. 7 patients died (one death attributed to TB chemotherapy), 3 became fully dependent for all activities of daily living and 6 patients had significant cognitive or neurological deficit. <h3>Conclusions</h3> CNS TB causes significant morbidity and mortality. CSF examination should always be performed if feasible. Imaging by MRI should be considered in all patients with suspected TB meningitis in view of the much higher diagnostic yield compared to CT.
Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009–2010
Authors: Naila Khalil, Aimin Chen, Miryoung Lee, Stefan A. Czerwinski, James R. Ebert, Jamie C. DeWitt, Kurunthachalam Kannan
Journal: Environmental Health Perspectives (2015)

Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S.Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health.The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009-2010.The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p < 0.001) except for PFNA. In both sexes, serum PFOS concentrations were inversely associated with FNBMD (p < 0.05). In women, significant negative associations were observed for natural log (ln)-transformed PFOS exposure with TFBMD and FNBMD, and for ln-transformed PFOA exposure with TFBMD (p < 0.05). In postmenopausal women, serum PFOS was negatively associated with TFBMD and FNBMD, and PFNA was negatively associated with TFBMD, FNBMD, and LSBMD (all p < 0.05). With one log unit increase in serum PFOA, PFHxS, and PFNA, osteoporosis prevalence in women increased as follows: [adjusted odds ratios (aORs)] 1.84 (95% CI: 1.17, 2.905), 1.64 (95% CI: 1.14, 2.38), and 1.45 (95% CI: 1.02, 2.05), respectively. In women, the prevalence of osteoporosis was significantly higher in the highest versus the lowest quartiles of PFOA, PFHxS, and PFNA, with aORs of 2.59 (95% CI: 1.01, 6.67), 13.20 (95% CI: 2.72, 64.15), and 3.23 (95% CI: 1.44, 7.21), respectively, based on 77 cases in the study sample.In a representative sample of the U.S. adult population, serum PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases.Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, Kannan K. 2016. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009-2010. Environ Health Perspect 124:81-87; http://dx.doi.org/10.1289/ehp.1307909.
A phase III double-blind placebo-controlled trial of methylnaltrexone (MNTX) for opioid-induced constipation (OIC) in advanced medical illness (AMI)
Authors: J. Thomas, A. Lipman, N. Slatkin, G. Wilson, M. Moehl, C. Wellman, D. Zhukovsky, R. Stephenson, N. Stambler, R. J. Israel
Journal: Journal of Clinical Oncology (2005)

LBA8003 Background: Constipation is a common and distressing side effect of opioid treatment. Patients with AMI commonly experience severe OIC unresponsive to laxatives which can significantly complicate pain management. MNTX is a quaternary derivative of the pure opioid antagonist naltrexone formed by the addition of a methyl group to the ring nitrogen. MNTX does not cross the blood-brain barrier; hence it has the potential to antagonize the peripheral effects of opioids while sparing centrally mediated analgesia. MNTX has been shown to reverse OIC in chronic methadone users and we have previously reported positive results of a phase II trial of MNTX for relief of OIC in hospice patients without evidence of withdrawal or worsened pain (Thomas, et al. ProcASCO, 2003). The present phase III study was initiated to confirm the findings of phase II and assess the safety and efficacy of MNTX in treating OIC in patients with AMI. Methods: This is a multi-center, double-blind, randomized, placebo-controlled study of subcutaneous MNTX for OIC in AMI patients in hospice or palliative care programs. Patients must have a life expectancy of 1 to 6 months, no laxation for 48 hours, on stable opioids for pain and stable laxatives. Patients are randomized to either placebo, MNTX 0.15 mg/kg, or MNTX 0.30 mg/kg. 24 hours after a single subcutaneous dose of study drug, patients may receive open label MNTX, as needed over the next 4 weeks, titrated to effect and tolerability. Total accrual will be approximately 150 patients (50 per group). The primary endpoint is the efficacy of single-dose MNTX (0.15 mg/kg or 0.30 mg/kg vs. placebo) to induce laxation within 4 hours of dosing. We will also measure laxation over 24 hours and adverse events, pain scores, and opioid withdrawal symptoms. The primary analysis will be intent-to-treat and include all randomized patients using a Cochran-Mantel-Haenszel test of placebo against each MNTX dose level. Results: 150 patients have been enrolled as of 12/2/04 and enrollment will be closed on 12/15/04. Analysis of the primary and secondary endpoints and a summary of the demographics will be presented for all patients. Conclusions: To be reached after data becomes available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Progenics Progenics Progenics
General Characteristics of Brazilian Children and Adolescents with Cow's Milk Protein Allergy before Starting Oral Tolerance Induction (OIT)
Authors: Fabio C. Kuschnir, Jose Luiz M. Rios, Alfredo A. Neto, Mary A. da Venda, Flavia C. Loyola, Bruno B. Souto, Joao B.M. Rios
Journal: Journal of Allergy and Clinical Immunology (2016)
Heterozygous Expression of X-Linked Mental Retardation and X-Chromosome Marker Fra(X)(Q27)
Authors: Gillian Turner, Ross Brookwell, Art Daniel, Mark Selikowitz, Michael Zilibowitz
Journal: New England Journal of Medicine (1980)

Males affected by one form of X-linked retardation possess the X-chromosomal marker fra(X)(q27) and are physically normal except for macro-orchidism. To relate possession of the marker X to phenotypic expression in female heterozygotes, we investigated 128 mildly retarded (IQ, 55 to 75) schoolgirls in Sydney, New South Wales, Australia. Seventy-two girls had no physical abnormalities and of these, five (7 per cent) carried the marker X. Investigation of relatives revealed retarded males in four of the five families. Pedigree and chromosomal analysis identified a further 18 heterozygotes; six were regarded as intellectually or educationally retarded. We conclude that expression of the X-linked mutation in female carriers contributes to mild mental retardation of girls, that those who are physically normal should be screened for the marker X, and that their relatives should be investigated in order to identify additional females with a high risk of conceiving affected males. (N Engl J Med. 1980; 303:662–4.)
Adrenocorticotrophic-Hormone Deficiency in Chronic Myelogenous Leukemia after Treatment
Authors: Mark S. Tobin, Kyung-Suk Kim, Warren A. Kossowsky
Journal: New England Journal of Medicine (1970)

Two patients with the diagnosis of chronic myelogenous leukemia failed to undergo satisfactory remissions with busulfan therapy or splenic irradiation and were treated with 6-mercaptopurine and allopurinol. Under treatment with these drugs, symptoms, signs and biochemical evidence of adrenal insufficiency developed in both. This defect was not caused by a primary adrenal disturbance but rather by a selective, Central-nervous-system failure in production or release of adrenocorticotrophic hormone.
Expression of a Functional N-Methyl-d-Aspartate–Type Glutamate Receptor by Bone Marrow Megakaryocytes
Authors: Paul G. Genever, David J.P. Wilkinson, Amanda J. Patton, Nicky M. Peet, Ying Hong, Anthony Mathur, Jorge D. Erusalimsky, Tim M. Skerry
Journal: Blood (1999)
Attitudes Toward and Use of Cancer Management Guidelines in a National Sample of Medical Oncologists and Surgeons
Authors: Reshma Jagsi, Grace Huang, Kent Griffith, Brian J. Zikmund-Fisher, Nancy K. Janz, Jennifer J. Griggs, Steven J. Katz, Sarah T. Hawley
Journal: Journal of the National Comprehensive Cancer Network (2014)

Physician attitudes toward and lack of familiarity with guidelines have been identified as potential barriers to adherence in general, but little is known about their attitudes toward and use of cancer management guidelines specifically. This study surveyed 1500 surgeons and medical oncologists drawn from the AMA Masterfile in 2012. This report describes and compares the attitudes of medical oncologists and surgeons who treat patients with breast cancer regarding guidelines in general and the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) in particular, and their familiarity, use, and compliance with these guidelines. Of 896 respondents, responses were analyzed from the 766 who had seen at least one new patient with breast cancer in the past year. Mean participant age was 52 years; 25% worked in a teaching setting. Attitudes toward guidelines were generally favorable. Medical oncologists were more likely than surgeons to be aware that NCCN issues guidelines for cancer management (100% vs 74%; P<.001) and more likely to state that these guidelines generally influence their decisions (96% vs 70%; P<.001). Among those aware of NCCN Guidelines, 96% reported that they often agreed with NCCN recommendations, and 75% reported that almost all of their breast cancer treatment recommendations were consistent with these guidelines. Still, most providers (77%) also reported that they refer one-fourth or fewer of their patients with breast cancer to the NCCN Guidelines for Patients. Attitudes toward physician-directed cancer management guidelines are generally positive, and they are frequently used. However, existing guidelines seem to have greater visibility to the medical oncology audience than to surgeons, and patient versions are infrequently recommended.
Conko-006: a Randomized Double-Blinded Phase Iib-Study of Adjuvant Therapy with Gemcitabine + Sorafenib/Placebo for Patients with R1-Resection of Pancreatic Cancer
Authors: M. Sinn, T. Liersch, K. Gellert, H. Riess, P. Stübs, D.T. Waldschmidt, U. Pelzer, J. Stieler, J.K. Striefler, M. Bahra, B. Dörken, H. Oettle
Journal: Annals of Oncology (2014)
Altered Expression of the Retinoblastoma Gene Product in Human Sarcomas
Authors: William G. Cance, Murray F. Brennan, Marie E. Dudas, Chun-Ming Huang, Carlos Cordon-Cardo
Journal: New England Journal of Medicine (1990)

The retinoblastoma-susceptibility (Rb) gene is a prototype tumor-suppressor gene originally isolated from patients with heritable retinoblastoma. This gene encodes a nuclear phosphoprotein whose expression is altered in several types of human tumors.
Viability of Red Cells of ACD Blood Aseptically Separated from Plasma in a Closed Plastic System
Authors: John G. Gibson, John C. Pond, Thomas J. McManus
Journal: New England Journal of Medicine (1960)

THE clinical indications for the use of separated components of blood are now well established.1 Whole-blood transfusions are indicated only to augment a depleted blood volume due to acute blood loss, shock or conditions associated with intractable capillary bleeding. Secondary anemia from any cause is usually a normovolemic condition in which the administration of whole blood may impose an overload sufficient to produce circulatory failure. This is particularly true in debilitated patients or those with chronic cardiorenal disease and in infants. Separated red cells can safely be given in such cases in quantities sufficient to restore oxygen-carrying capacity without the . . .
Abstract 1035: An angiogenic role of E-cadherin-positive exosomes in ovarian cancer
Authors: Maggie K. S. Tang, Alice Sze Tsai Wong
Journal: Cancer Research (2015)

Abstract Angiogenesis, the induction of vasculature, is a vital step for metastasis. Loss of E-cadherin is a well-established marker for tumor metastasis. In ovarian cancer, a highly metastatic tumor that is rapidly lethal, we and others have previously shown the deregulated pattern of E-cadherin and its close association with tumor progression. Although E-cadherin is synthesized as a transmembrane molecule, it can be shed from the cell surface (sE-cad) which accounts for a rapid removal of functional E-cadherin. Here, in addition to ectodomain shedding, we show for the first time that sE-cad can be actively released from ovarian cancer cells in the form of exosomes. These sE-cad-positive exosomes play a critical role in angiogenesis which stimulated the migration, permeability, and tubulogenesis of human umbilical vein endothelial cells in vitro, and promoted functional neovascularization in vivo. In search of the underlying mechanisms by which sE-cad-positive exosomes might regulate angiogenic endothelial cells, which lack E-cadherin, we showed that a novel heterophilic crosstalk between sE-cad and VE-cadherin. Moreover, such angiogenic effect was mediated through activation of the phosphatidylinositol 3-kinase/Akt-beta-catenin signaling cascade. These results uncover a new angiogenic function for sE-cad and a novel paradigm for sE-cad production which may have potential clinical implications (This study was supported by RGC grant HKU781013). Citation Format: Maggie K. S. Tang, Alice Sze Tsai Wong. An angiogenic role of E-cadherin-positive exosomes in ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1035. doi:10.1158/1538-7445.AM2015-1035
OP0039 Evidence of the intracellular cytokines in peripheral blood mononuclear cells of patients with systemic sclerosis
Authors: C Naclerio, K Esposito, A Farzati, G Cuomo, G Valentini, B Farzati
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Systemic sclerosis (SSc) is currently considered aTh2 disease. The studies underlying such assumption have been mainly carried out on tissues. At present, no data has addressed this topic in the peripheral blood at a cellular level. <h3>Objectives</h3> To investigate the activation of Th1 and Th2 cells in the peripheral blood of SSc patients. <h3>Methods</h3> Peripheral blood mononuclear cells (PBMC) from 15 patients with SSc and 15 sex and age-matched healthy controls were investigated for intracellular IL-2, IL-4, IFN-γ. The assays were carried out on both unstimulated and PMA-activated PBMC incubated in the presence of 1 μg/ml of ionomycin and 10 μg/ml of brefeldin-A. Subsequently, samples were incubated with anti-citokines antibodies and stained cells were analysed on a FACScan flow cytometer. <h3>Results</h3> In basal conditions (i.e. unstimulated cells), 10 out of the 15 SSc patients versus 1 out of the 15 controls presented a significantly higher percentages (i.e. &gt; m ± 2 SD detected in controls) of IL-2 positive cells; 6 patients and 1 control of IL-4 positive cells and 7 patients and 0 control of IFN-γ positive cells. Six patients presented increased percentages of both IL-2 and IL-4 and IFN-γ (i.e. they had both Th1 and Th2 activation), 4 of IL-2 positive cells and 1 IFN-γ only (isolated Th1 activation). After PMA stimulation 6 patients presented increased percentages of IFN-γ positive cells; 1 of IL-4 and 0 patient of IL-2 positive cells. <h3>Conclusion</h3> Our study demonstrates that Th1 activation occurs in peripheral blood of SSc patients. The role, if any, of such activation must be investigated.