tbuckley/cabot-search huggingface dataset:
The Philosophy of Nosology
Authors: Peter Zachar, Kenneth S. Kendler
Journal: Annual Review of Clinical Psychology (2017)

Many scholars believe that psychiatric nosology is undergoing a crisis of confidence. Some of the issues up for debate hark back to the introduction of the natural history approach to classification in the seventeenth century. Natural histories map sameness and difference rather than speculate about causes. In contrast, the natural classification approach aspires to carve nature at the joints by demarcating classifications by causes. Natural classifications are more ideal scientifically, but speculation about causality has had a poor track record in psychiatric nosology. A natural classification of psychiatric disorders may have the added burden of requiring normative assumptions in addition to the discovery of fact. In the natural classification tradition, the epistemic iteration perspective, the Research Domain Criteria (RDoC) initiative, and dimensional models offer different views about the criteria of naturalness (or validity). Also in this tradition, some thinkers believe that causes can be empirically indexed by latent variable models, especially if the latent variables are moderately heritable, but these assumptions may be neither statistically nor genetically warranted.
Abstract 3459: Human Atrial Natriuretic Peptide (ANP) Gene Is Associated With Metabolic Syndrome In The French Population
Authors: Ronan Roussel, Suliya Maimaitiming, Frederic Fumeron, Samy Hadjadj, Roberte Aubert, Beverley Balkau, Michel Marre
Journal: Circulation (2007)

Background: ANP is important in hemodynamics, but also in lipolysis, particularly in overweight. Its plasmatic concentration is related to number of metabolic syndrome components. Its gene, NPPA, was considered as a candidate for susceptibility to metabolic disorders. Aims-Methods: We assessed the effect of 3 Hapmap-tagged haplotypes-defining NPPA SNPs, G664A (rs5063), 708C&gt;T (rs5064) and 2238T&gt;C (rs5065) on metabolic parameters levels and metabolic syndrome and their interaction with overweight in a cohort study included 2,576 men and 2,636 women from the general population, followed for 9 years. Results: In the whole population, there was a significant effect of the 708C&gt;T SNP on waist girth (CC: 83.5 ± 0.1cm, CT: 83.1 ± 0.2 and TT: 81.2 ± 0.9, p=0.04) and HDL-C (CC: 1.63 ± 0.01 mM CT: 1.63 ± 0.01 and TT: 1.77 ± 0.03, p=0.04). The 708C&gt;T SNP interacted with overweight on triglycerides (TG) and waist girth (p=0.002 and p=0.03 respectively for interaction) and in overweight subjects, was associated with TG (CC: 1.51 ± 0.03mM, CT: 1.37 ± 0.07 and TT: 1.13 ± 0.31, p=0.009) and waist girth (CC: 93.1 ± 0.2cm, CT: 92.1 ± 0.4 and TT: 89.1 ± 1.8, p=0.009). The 2238T&gt;C SNP interacted with overweight on waist girth (p=0.08 for interaction) and in overweight subjects, was associated with waist girth (TT: 93.1 ± 0.2cm, TC: 92.4 ± 0.3 and CC: 91.1 ± 0.9, p=0.03). The overweight 708TT carriers and 2238CC carriers had a lower risk of metabolic syndrome (MS) during the 9-year follow-up (rare allele OR=0.74, p=0.043 and 0.75, p=0.017 respectively). No association was found with 664G&gt;A. Haplotype GTC (carrying the minor allele of 708C&gt;T) was significantly associated with lower waist girth level (p=0.007) and TG (p=0.02) in overweight subjects, and with a lower risk of developing MS during follow-up (p=0.02) in overweight subjects. Conclusion: NPPA tagged SNPs and haplotypes are associated with cardiovascular risk in the general French population through association with lipids, waist girth levels and with incidence of MS in particular in overweight subjects.
An indirect comparison of everolimus and sorafenib therapy in sunitinib-refractory mRCC patients.
Authors: R. Casciano, E. Malangone, S. Sherman, J. Baladi, A. C. Kay, D. Kim, C. A. Garay, N. Hollaender, J. Wang
Journal: Journal of Clinical Oncology (2010)

4611 Background: Everolimus is currently the only approved second-line therapy in VEGF-TKI (sunitinib or sorafenib) refractory mRCC patients following recent findings from the RECORD-1 clinical trial in which everolimus was compared with best supportive care. There is, however, a lack of data comparing everolimus to other second line therapies in this setting. This study aims to compare sorafenib and everolimus for second-line treatment of sunitinib-refractory mRCC patients. Methods: An indirect comparison was employed by examining everolimus patients who had failed prior sunitinib treatment from the RECORD-1 trial and sorafenib patients from the recently published phase II study of sunitinib-refractory mRCC patients in Italy (Di Lorenzo, 2008). While most baseline characteristics were similar in the two study populations, there was a significant difference in baseline MSKCC score (77% vs. 28% low risk for sorafenib and everolimus patients, respectively). A ranuni function in SAS was used to match the two populations on risk score distributions. OS and PFS estimates were compared between treatment arms and the instantaneous hazard rates for each treatment arm were calculated and defined as the rate per patient per day. A 6-year Markov cohort simulation model was also used to estimate the difference in total life-years (LY) for patients treated with everolimus vs sorafenib for potential use in cost-effectiveness (CE) analysis. Results: The final study population consisted of 46 everolimus patients and 52 sorafenib patients with equivalent distributions of MSKCC score. The estimated incremental LY gained for failed sunitinib patients treated with everolimus versus with sorafenib was 1.135 years. Conclusions: In sunitinib-refractory mRCC patients there may be a PFS and OS benefit with the use of everolimus compared to sorafenib. It would be valuable to examine the necessary cost to achieve the additional LY gained through CE analysis. PFS and OS by treatment Median PFS (weeks) Median OS (weeks) Progression hazard rate Death hazard rate Everolimus (N=46) 40.8 78 0.0024 0.0013 Sorafenib (N=52) 17.7 32 0.0056 0.0031 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
The Clinical Toxicity of Terramycin
Authors: Frank L. Miller, Rhey Walker
Journal: New England Journal of Medicine (1953)

FOR four months during 1951 and 1952, 5 gm. of Terramycin was given by mouth daily to a group of 70 tuberculous patients at Fitzsimons Army Hospital. Terramycin was used in combination with 2 gm. of streptomycin every third day primarily to study its effect on the rate of emergence of tubercle bacilli resistant to streptomycin. Streptomycin and Terramycin resistance did not occur in any patient receiving the full dosage schedule during or after the treatment period of one hundred and twenty days.1 With the increasing use of Terramycin in the antimicrobial field, it was believed that a brief review . . .
Androgenic Adrenal Hyperfunction in Acromegaly
Authors: Nicholas Y. Lim, Joseph F. Dingman
Journal: New England Journal of Medicine (1964)

CLINICAL differentiation of active from inactive acromegaly is often difficult. At the present time a diagnosis of active disease is often based on the tenuous correlation of certain signs and symptoms and several inconsistent chemical indexes of growth-hormone excess. Of the latter, hyperphosphatemia is extremely variable, and often absent,1 and plasma growth-hormone assays have not shown consistent elevations in active cases.2 In a recent publication Hamwi et al.3 reported that adrenal function was normal in acromegaly. This conclusion was based on measurement of basal steroid excretion and the glucocorticoid response to ACTH. These workers, however, did not describe or comment . . .
Case 40-2002
Authors: Michelle Ng Gong, Eugene J. Mark
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 56-year-old man was admitted to the hospital because of rapidly progressive dyspnea and pulmonary abnormalities.The patient had been well until about two weeks earlier, when he stopped smoking because he “felt like it”; he had a 100-pack-year history of cigarette smoking. One week later, he began to experience substernal heaviness without radiation, sweating, or nausea and had increasing dyspnea on slight exertion, with a progressive, nonproductive cough. The findings on a chest radiograph were abnormal, and he was admitted the same day to the hospital.The patient had a history of diabetes mellitus with nonketotic . . .
The Value of Lowering Cholesterol after Myocardial Infarction
Authors: Jacques E. Rossouw, Barry Lewis, Basil M. Rifkind
Journal: New England Journal of Medicine (1990)

CURRENT recommendations for lowering the cholesterol level to prevent coronary heart disease have focused largely on primary prevention and have paid less attention to the issue of lowering cholesterol in patients who already have coronary disease.1 2 3 4 5 6 It remains a common conception that in survivors of infarction the extent of myocardial damage is the prime determinant of outcome and serum cholesterol is not a major risk factor.7 The opposing view is that the modifiable risk factors after a myocardial infarction are the same as those before and merit treatment.8 , 9 In current practice, it appears that most patients with coronary disease do . . .
Estrogen and Endometrial Carcinoma
Authors: Jack Gordon, James W. Reagan, William D. Finkle, Harry K. Ziel
Journal: New England Journal of Medicine (1977)

Initial evidence suggested that estrogen therapy increases the risk of endometrial carcinoma. It was then suggested that some studies may have exaggerated the hazard of estrogen therapy by including patients with atypical endometrial hyperplasia among those having endometrial carcinoma. Three internationally recognized pathologists reviewed the histology slides available from the Ziel and Finkle study, which originally reported a risk ratio of 7.6 for estrogen users. At least one of the pathologists concurred with the original diagnosis in all but one case. Furthermore, all pathologists aggreed that 74 per cent (66/89) were correctly diagnosed. In the 66 patients with unanimous diagnosis, 61 per cent (40/66) had used conjugated estrogens, versus 57 per cent (54/94) in the original study. On the basis of 66 patients and 132 matched controls, the revised risk-ratio estimate is 8.1 (with a one-sided 95 per cent lower confidence limit of 4.5), validating the original estimate.
A Controlled Trial of Scheduled Replacement of Central Venous and Pulmonary-Artery Catheters
Authors: David K. Cobb, Kevin P. High, Robert G. Sawyer, Carole A. Sable, Reid B. Adams, Dwight A. Lindley, Timothy L. Pruett, Karen J. Schwenzer, Barry M. Farr
Journal: New England Journal of Medicine (1992)

The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection. It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site.
Successful Homotransplantation of the Kidney between Nonidentical Twins
Authors: John P. Merrill, Joseph E. Murray, J. Hartwell Harrison, Eli A. Friedman, James B. Dealy, Gustave J. Dammin
Journal: New England Journal of Medicine (1960)

IN 1955, we reported the successful transplantation of a kidney from a healthy twenty-three-year-old man to his monozygotic twin who was terminally ill with chronic renal failure. At that time we concluded: "Tissue transplantation including that of a functioning kidney appears to be a feasible procedure in identical twins but to date successful permanently functioning homografts appear to be limited to such individuals."1 It is the purpose of this paper to report the functional survival of a transplanted kidney whose donor was a fraternal, not an identical, twin.Since 1955 in this laboratory, kidneys have been successfully transplanted between 9 . . .
Cohort Study of Internal Malignancy in Genetic Hemochromatosis and Other Chronic Nonalcoholic Liver Diseases&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R A Bradbear, C Bain, V Siskind, F D Schofield, S Webb, E M Axelsen, J W Halliday, M L Bassett, L W Powell
Journal: JNCI Journal of the National Cancer Institute (1985)

The risk of hepatocellular carcinoma (HCC) and other internal malignancies was examined in patients with genetic hemochromatosis (GH) by following 208 patients from the time of diagnosis to June 1983 and by comparing the numbers of cancers they developed with expected values constructed from cancer registry incidence data by means of actuarial methods. In addition, cancers occurring in a comparison group of 148 subjects with other chronic nonalcoholic liver diseases (CLD) were determined. Among the GH group, 16 new cases of HCC occurred subsequent to the diagnosis of GH, together with 8 other malignancies. The 16 cases of HCC reflect a 200-fold excess risk, which from all indications represents the first quantitation of the risk of this tumor in GH. There appears to be no increased risk of other malignancies in this disease. Among the CLD group only 1 HCC and 1 other malignancy occurred.
Loffler's Endocarditis
Authors: T Imaizumi, K Aibara
Journal: New England Journal of Medicine (1994)

Figure 1. Loffler's Endocarditis. A transverse slice of the heart from a 65-year-old man with Loffler's endocarditis shows large mural thrombi (T) surrounding the thickened endocardium in both ventricles. Loffler's endocarditis is characterized by hypereosinophilia and endocardial thickening, which typically causes restrictive cardiomyopathy.
IMCT-15PILOT STUDY OF T CELLS REDIRECTED TO EGFRvIII WITH A CHIMERIC ANTIGEN RECEPTOR IN PATIENTS WITH EGFRvIII+ GLIOBLASTOMA
Authors: Donald O'Rourke, Arati Desai, Jennifer Morrissette, Maria Martinez-Lage, MacLean Nasrallah, Steven Brem, Eileen Maloney, Angela Shen, Suyash Mohan, Sumei Wang, Gaurav Verma, Simon Lacey, Jan Melenhorst, Jean-Marc Navenot, Zhaohui Zheng, Bruce Levine, Hideho Okada, Carl June, Marcela Maus
Journal: Neuro-Oncology (2015)

We have initiated a first-in-human pilot study of intravenous delivery of autologous T cells re-directed to the EGFR variant III mutation by means of a lentiviral vector encoding a chimeric antigen receptor (CAR). Patients with recurrent or incompletely resected glioblastoma (GBM) have their tumors screened for the presence of the EGFRvIII mutation by a next-generation sequencing based assay. Eligible patients undergo leukapheresis for collection of autologous T cells, which are then manufactured to form CART-EGFRvIII T cell products. We report preliminary results on the first six patients we have treated. We targeted a challenging subset of GBM patients, with multi-focal recurrent, residual, progressive disease refractory to standard and experimental therapies, including chemotherapy, radiation, bevacizumab and prior immunotherapy. To date, we have found that infusion of CART-EGFRvIII cells is safe, without evidence of off-tumor toxicity such as cross-reactivity to wild type EGFR. No clinical or laboratory signs of systemic cytokine release syndrome have been observed. One patient developed a seizure and non-convulsive status epilepticus nine days after CART-EGFRvIII infusion. Seizures resolved with anti-epileptic medications, and the patient was treated with steroids and anti-IL6 cytokine therapy. All patients have had significant expansion of CART-EGFRvIII cells as measured by flow cytometry and quantitative PCR in peripheral blood samples, despite the use of steroids in two patients. In one of two patients who had operative resection of presumed residual tumor, pathologic evaluation demonstrated inflammation, T cell infiltration, and EGFRvIII antigen loss. In total, two of six heavily pretreated patients are clinically stable three months post-CART infusion. These findings provide preliminary evidence that CART-EGFRvIII cells are safe, without evidence of off-target toxicity and without evidence of cytokine release syndrome, and that these are active T cell products that expand in the blood.
Penicillin Aerosolization in the Treatment of Serious Respiratory Infections
Authors: Maurice S. Segal, Claire MacIntyre Ryder
Journal: New England Journal of Medicine (1945)

AEROSOLS may be defined as suspensions of liquids or solids in air or oxygen. The use of bronchodilator, vasoconstrictor and chemotherapeutic agents by continuous aerosolization with streams of oxygen or compressed air has been employed in patients with asthma,1 2 3 4 5 6 7 8 9 10 pulmonary emphysema,4 , 5 pneumonia,11 12 13 14 gas poisoning15 16 17 and other types of bronchopulmonary disease.13 , 14, 18 19 20 21 22 23 24 25 26 27 The value of such therapy can be appreciated if one recalls that the inner surface of the lung has an area five hundred times as great as the body surface and absorbs so rapidly as to give an effect similar to that of an intravenous injection. Furthermore, Krueger et . . .
Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome reveals regulatory effects at interferon-induced genes
Authors: Juliana Imgenberg-Kreuz, Johanna K Sandling, Jonas Carlsson Almlöf, Jessica Nordlund, Linnea Signér, Katrine Braekke Norheim, Roald Omdal, Lars Rönnblom, Maija-Leena Eloranta, Ann-Christine Syvänen, Gunnel Nordmark
Journal: Annals of the Rheumatic Diseases (2016)

Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls. Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed. We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed. Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.
Renal Insufficiency after Oral Administration of a Double Dose of a Cholecystographic Medium
Authors: Robert M. Rene, Sherman M. Mellinkoff
Journal: New England Journal of Medicine (1959)

IN the last several years iopanoic acid (3-[3-amino-2,4,6-tri-iodophenyl]-2-ethyl propanoic acid) has been widely used orally in cholecystography, providing excellent x-ray contrast and minimal toxicity. The usual dose is 6 tablets (3.0 gm.) taken ten to twelve hours before the scheduled cholecystogram. Side reactions, generally infrequent, are mild, and consist largely of nausea, vomiting, diarrhea and dysuria.1 , 2 Double doses are usually administered when there is poor or no visualization after the usual dose, and to delineate more clearly the biliary-duct system.The purpose of this paper is to report 2 cases of renal insufficiency, each of which followed the administration of . . .
Better air quality reduces respiratory symptoms among children in southern California
Authors: Jacqui Wise
Journal: BMJ (2016)

Improvements in air quality over the past 20 years in southern California, USA, were linked to statistically significant decreases in bronchitic symptoms in children with and without asthma, a longitudinal study published in JAMA has found.1

Southern California has historically reported high levels of ambient air pollution, but air quality has significantly improved since 1992 owing to a range of policies and strategies.

The study included three cohorts that were followed from 1993 to 2001, 1996 to 2004, and 2003 to 2012. The cohorts included a total of 4602 children from eight communities …
Prothrombin: A Critique of Methods for Its Determination and Their Clinical Significance
Authors: Benjamin Alexander, Andre de Vries, Robert Goldstein
Journal: New England Journal of Medicine (1949)

AS A result of the widespread use of dicumarol in the prevention and treatment of thromboembolism, clinicians have become increasingly interested in the role of prothrombin in blood coagulation. Investigators are aware that present technics for prothrombin estimation have their limitations. Failure to recognize them may prevent accurate diagnosis, obstruct effective therapy or even invite disaster. It is the purpose of this paper to delineate these limitations and to scrutinize current analytical procedures in the light of recent advances in knowledge of blood coagulation.General ConsiderationsBy chemical isolation and purification Seegers et al.1 have defined the plasma protein component . . .
Celiac disease and chemotherapy
Authors: S. I. Robinson, J. Murray, R. R. McWilliams
Journal: Journal of Clinical Oncology (2007)

19561 Background: Diarrhea is a common side effect of chemotherapy (CT). At times, often unpredictably, patients develop profound diarrhea during CT. Though the clinical diagnosis of celiac disease (CD) is relatively rare, (1/ 2000), the serologic prevalence is much higher (1/ 133), suggesting a large number of undiagnosed cases. Latent CD may be unmasked by stressors, such as CT. We hypothesized that undiagnosed CD may account for some cases of severe diarrhea from CT. Methods: We performed a retrospective chart review at the Mayo Clinic (1980–2006) for patients with diagnoses of cancer and CD that received CT at our center. CD cases were confirmed by biopsy (n= 25) or serologic studies. Data analyzed included severe (grade ≥ 3,) diarrhea while on CT, site of primary cancer, diagnosis of CD prior to or after CT, and specific CT agents received. Results: We identified 27 patients with CD and cancer (12 lymphoma, 6 gastrointestinal, 2 leukemia, 2 breast, 1 brain, bladder, lung, uterine, sarcoma) who received CT at our center. Fifteen were diagnosed with CD prior to receiving CT and 12 after, with the former group presumably on a gluten-free diet. One patient was excluded for lack of clinical data. Five of remaining 14 patients (35%) managed for their CD prior to CT had diarrhea, though 4 of these 5 had only mild diarrhea (gr. 1). One patient suffered gr. 3 diarrhea, though was reported to be poorly compliant with his diet. Three patients received treatment with 5- fluorouracil (5FU), and 2 had gr. 1 diarrhea. Five of the 12 patients (42%) with celiac disease undiagnosed prior to CT were reported to have diarrhea during treatment (3 gr. 4; 2 gr. 1). Of those receiving 5FU, 3 out of 4 had severe (gr. 4) diarrhea. The small numbers of patients precluded meaningful statistical analysis. Conclusion: Patients with known CD compliant with a gluten-free diet tolerated CT well. However, in a subset of undiagnosed patients, severe diarrhea developed during CT, most notably with 5FU-based regimens. We propose that when patients have diarrhea disproportionate to other effects, CD should be considered. Also, in malignancies with a high incidence of CD such as lymphoma and small bowel cancer, underlying CD should be considered before CT is given. No significant financial relationships to disclose.