tbuckley/cabot-search huggingface dataset:
Laetrile for Cancer
Authors: Thomas H. Jukes
Journal: JAMA (1976)

ANOTHER chapter is being written in the melancholy history of cancer quackery. This chapter, entitled "Laetrile," follows the outline of its predecessors. First, a remedy is introduced resulting from a novel "strange idea." Next, its promoters become so dedicated to advocating the remedy that they cannot retreat from a position which becomes untenable as a result of exposure of the worthlessness of the remedy. Third, the promoters are reinforced in their fraudulence by champions of the "underdog" against the "establishment," and by the surviving relatives of the deceased victims of cancer. These relatives, because of feelings of guilt, cling to their belief that treatment with the "remedy" was the best possible therapy. Finally, vast sums of money and amounts of time are wasted on elaborate tests of the "remedy" by qualified scientists who should be doing something useful. These tests are usually undertaken because of coercion by legislators and other
Endogenous oncogenic Nras mutation initiates hematopoietic malignancies in a dose- and cell type-dependent manner
Authors: Jinyong Wang, Yangang Liu, Zeyang Li, Zhongde Wang, Li Xuan Tan, Myung-Jeom Ryu, Benjamin Meline, Juan Du, Ken H. Young, Erik Ranheim, Qiang Chang, Jing Zhang
Journal: Blood (2011)
Somatic Mutations and Immunotherapy Outcome with CTLA-4 Blockade in Melanoma
Authors: Vassiliki A. Boussiotis
Journal: New England Journal of Medicine (2014)

One of the greatest challenges in the study and treatment of cancer has been that the disease is too heterogeneous: too many tissue types, too many etiologic factors, too much genetic diversity. After the discovery of oncogenes, it was thought that a limited number of genes, the proto-oncogenes, might turn a normal cell into a cancerous one. But soon it was discovered that tumor-suppressor genes antagonize the action of oncogenes, thus increasing genetic diversity in the context of cancer pathogenesis. To date, about 140 genes have been identified that can drive cancer growth when genetically altered.1 The discovery that driver . . .
Comparison of two repositioning schedules for the prevention of pressure ulcers in patients on mechanical ventilation with alternating pressure air mattresses
Authors: Francisco Manzano, Manuel Colmenero, Ana María Pérez-Pérez, Delphine Roldán, María del Mar Jiménez-Quintana, María Reyes Mañas, María Angustias Sánchez-Moya, Carmen Guerrero, María Ángeles Moral-Marfil, Emilio Sánchez-Cantalejo, Enrique Fernández-Mondéjar
Journal: Intensive Care Medicine (2014)
Polymicrobial infection in campylobacter enteritis.
Authors: I Melamed, Y Bujanover, Z Spirer, D Schwartz, N Conforty
Journal: BMJ (1985)

showed a haemoglobin concentration of 124 g 1; white cell count 2-4x 109/1 (76°,' neutrophils, 20",, lymphocytes, 4",, monocvtes); platelet count 200 x 109 1; sedimentation rate 44 mm in first hour; normal urea and electro- lytes and liver function values; antinuclear factor titre positive at 1/1280; rheumatoid arthritis haemagglutination titre positive at 1 80; and double stranded deoxyribonucleic acid (DNA) binding 94 U ml (normal 25 U'ml).She was a slow acetylator and her HLA type was Al AW24 B7 B17 DR2, DR3.Chest x ray appearances were normal.In view of the polvarthritis, cutaneous vasculitis, pleurisy, leucopenia, positive antinuclear factor titre, and raised DNA binding value, a diagnosis of carbamazepine induced systemic lupus erythematosus was made.The carbamazepine was withdrawn but the phenobarbitone continued.Predisolone 30 mg daily was added.The patient improved rapidly and prednisolone was stopped after six months.Subsequently she remained well for 12 months.The DNA binding returned to normal but her antinuclear factor titre remained positive at 1160.As the colitis resolved clinically so did the oral problem.
Bullying in school: are short pupils at risk? Questionnaire study in a cohort
Authors: L. D Voss
Journal: BMJ (2000)

To address the challenges related to the interconnectivity between vial container closure systems and vial transfer devices, pharmaceutical, elastomer, and transfer device manufacturers have formed a working group under the Product Quality Research Institute (PQRI) to establish best practices for the evaluation of the assembly of vial transfer devices and vial systems. As part of the project, the first activity was to quantify the nature and frequency of issues (complaints). To this end, the working group conducted a survey with questionnaires related to categories and numbers of complaints, regions/countries where complaints were received, and the nature of the manufacturers who received the complaints. The survey was distributed to the 16 companies participating in the working group, and 11 companies submitted a response. Besides quantifying and ranking the frequency of issues, the survey determined what issues are common across all companies and what issues may be product-specific or specific by manufacturer. In this article, the analysis and outcomes of the survey will be presented, and the next steps will be discussed.
Mechanisms underlying transition from acute glomerular injury to late glomerular sclerosis in a rat model of nephrotic syndrome.
Authors: S Anderson, J R Diamond, M J Karnovsky, B M Brenner
Journal: Journal of Clinical Investigation (1988)

Functional and morphologic measurements were performed in Munich-Wistar rats after a single central venous injection of puromycin aminonucleoside (PA) or saline vehicle (sham). During phase I, PA rats exhibited overt nephrotic syndrome and impaired glomerular filtration, primarily due to a reduction in the glomerular capillary ultrafiltration coefficient. The morphologic counterpart of the latter consisted of effacement of glomerular epithelial cell foot processes and decrease in the number of filtration slit diaphragms. Administration of the angiotensin I converting enzyme inhibitor (CEI) enalapril to PA rats did not ameliorate glomerular dysfunction. During phase II, PA rats exhibited spontaneous resolution of proteinuria, impaired function, and morphologic abnormalities. However, PA rats now demonstrated marked glomerular capillary hypertension and continued, albeit lesser, reductions in the ultrafiltration coefficient. Concurrent CEI administration modestly lowered systemic arterial pressure, and normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. Additional rats were studied during phase III, 70 wk after injection. In PA rats, prior glomerular hypertension was associated with development of recurrent proteinuria and extensive glomerular sclerosis, whereas concurrent CEI administration limited these parameters to values comparable to those in sham rats. Glomerular hypertension thus may explain the development of glomerular sclerosis and renal failure long after an episode of acute glomerular injury.
A Transcriptomic Network Identified in Uninfected Macrophages Responding to Inflammation Controls Intracellular Pathogen Survival
Authors: Lynette Beattie, Micely d’El-Rei Hermida, John W.J. Moore, Asher Maroof, Najmeeyah Brown, Dimitris Lagos, Paul M. Kaye
Journal: Cell Host & Microbe (2013)

Intracellular pathogens modulate host cell function to promote their survival. However, in vitro infection studies do not account for the impact of host-derived inflammatory signals. Examining the response of liver-resident macrophages (Kupffer cells) in mice infected with the parasite Leishmania donovani, we identified a transcriptomic network operating in uninfected Kupffer cells exposed to inflammation but absent from Kupffer cells from the same animal that contained intracellular Leishmania. To test the hypothesis that regulated expression of genes within this transcriptomic network might impact parasite survival, we pharmacologically perturbed the activity of retinoid X receptor alpha (RXRα), a key hub within this network, and showed that this intervention enhanced the innate resistance of Kupffer cells to Leishmania infection. Our results illustrate a broadly applicable strategy for understanding the host response to infection in vivo and identify Rxra as the hub of a gene network controlling antileishmanial resistance.
When to Perform Biopsies of Enlarged Lymph Nodes in Young Patients-Reply
Authors: Gail B. Slap
Journal: JAMA (1985)

In Reply.—  We agree with Drs Abemayor and Mickel and recognize the potential problems accompanying premature cervical biopsy in older patients. We did not mean to imply that biopsy for these patients should precede or replace a thorough examination for primary head and neck cancer, but rather that this evaluation should begin early in presentation. As noted in our original article, the model we described was developed and tested in a 9- to 25-year-old population. We again must emphasize that it should not be applied to either younger or older patient populations.
Ventilator-Associated Pneumonia
Authors: Marin H. Kollef
Journal: JAMA (1993)

To identify factors associated with the development of ventilator-associated pneumonia (VAP) and to examine the incidence of VAP in different intensive care unit (ICU) populations.An inception cohort study.Barnes Hospital, St Louis, Mo, an academic tertiary care center.A total of 277 consecutive patients required mechanical ventilation for longer than 24 hours from a medical ICU (75 patients), surgical ICU (100 patients), or cardiothoracic ICU (102 patients).Prospective patient surveillance and data collection.Ventilator-associated pneumonia and ICU mortality.Ventilator-associated pneumonia occurred in 43 patients (15.5%). Stepwise logistic regression analysis identified four factors to be independently associated with VAP (P < .05): an organ system failure index of 3 or greater (adjusted odds ratio [AOR] = 10.2; 95% confidence interval [CI], 4.5 to 23; P < .001); patient age of 60 years or older (AOR = 5.1; 95% CI, 1.9 to 14.1; P = .002); prior administration of antibiotics (AOR = 3.1; 95% CI, 1.4 to 6.9; P = .004); and supine head positioning during the first 24 hours of mechanical ventilation (AOR = 2.9; 95% CI, 1.3 to 6.8; P = .013). Ventilator-associated pneumonia occurred more often in cardiothoracic patients (21.6%) compared with medical patients (9.3%) (P = .03). Patients with VAP also had a higher mortality (37.2%) than those without VAP (8.5%) (P < .001). An organ system failure index of 3 or greater (AOR = 16.1; 95% CI, 6.1 to 42; P < .001), a premorbid lifestyle score of 2 or greater (AOR = 3.1; 95% CI, 1.3 to 7.3; P = .012), and supine head positioning during the first 24 hours of mechanical ventilation (AOR = 3.1; 95% CI, 1.2 to 7.8; P = .016) were independently associated with mortality.These data suggest potential interventions that might affect the incidence of VAP or outcome associated with VAP. Additionally, they indicate that different ICU populations may have different incidences of VAP.
THE STAGES IN CALCIFICATION OF THE RAT KIDNEY AFTER THE ADMINISTRATION OF URANIUM NITRATE
Authors: Lewis K. Dahl
Journal: The Journal of Experimental Medicine (1953)

The anatomical and histochemical alterations in rat kidneys after the parenteral administration of uranium nitrate [UO2(NO3)2·6H2O] have been studied. The histological effects produced by this agent over a wide range of dose levels were nearly identical in character and differed principally in their speed of evolution. The deposition of calcium always began at foci in the cytoplasm of the cells of the proximal convoluted tubules of the inner cortex. It remained intracellular until the cell boundaries were destroyed. Deposits of calcium could be found before any other cellular damage could be demonstrated by histological examination. Later, when degeneration and necrosis were present, the foci of calcification were imperfectly related to them in location or degree. In contrast, the amount of calcification was correlated with the dose of uranium nitrate, being greatest in the kidneys of rats that received 20 mg./kg., next greatest in the 30 mg./kg. rats, less in the 10 mg./kg. rats, and slight in those that received 2 mg./kg. Histochemical stains for ferric and ferrous iron, chondroitinsulfate, and polysaccharides gave results that were negative or unrelated to the deposits of calcium, thus making it unlikely that these substances held any appreciable amount of calcium in the tissue. Yet it is clear that some anion other than phosphate must be combined with part of the calcium; the results with the alizarin and von Kóssa stains confirmed an earlier result (1) in showing that the first deposits of calcium are formed without comparable accumulations of phosphate.
Outcome of breech delivery at term
Authors: A. Farkas
Journal: BMJ (1992)

assessment of the mode of delivery.Another group at potentially higher risk are primigravid patients, a subgroup not considered in the report but presumably identifiable from the database.The critical question therefore remains: is a carefully planned and managed trial of vaginal delivery any less safe for the fetus than an elective caesarean section?The uncertainty is in itself an argument in favour of elective caesarean section for all breech presentations at term since this reduces the opportunity for errors of judgment.
Fusarium--A New Culprit in the Contact Lens Case
Authors: Todd P Margolis, John P Whitcher
Journal: JAMA (2006)

Eduardo C. Alfonso, MD; Jorge Cantu-Dibildox, MD;
Wuqaas M. Munir, MD; Darlene Miller, DHSc, MPH; Terrence P. O’Brien,
MD; Carol L. Karp, MD; Sonia H. Yoo, MD; Richard K. Forster, MD; William W.
Culbertson, MD; Kendall Donaldson, MD; Jill Rodila, MD; Yunhee Lee, MDObjective: To describe the clinical presentation
and course of patients who developed keratitis due to Fusarium while wearing nontherapeutic soft contact lenses.Methods: A retrospective review of microbiologic
records from January 1, 2004, through April 15, 2006, was performed, identifying
all patients with corneal ulceration and a culture positive for Fusarium species. Medical records of 34 patients were reviewed for
clinical characteristics, treatment regimens, and microbiologic features.Results: The most common antimicrobial medications
administered prior to Fusarium diagnosis were antibacterials
in 31 of 34 patients. No distinct preponderance of any one brand of either
contact lens or solution was identified. The microbiologic cultures found Fusarium oxysporum in 20 cases, Fusarium
solani in 3 cases, Fusarium species not further
identifiable in 10 cases, and no growth in 1 case. Patients with a delayed
onset of treatment had a tendency for prolonged treatment until cure.Conclusions: Fusarium has
previously been an unusual organism in the etiology of infectious keratitis
in the setting of nontherapeutic soft contact lens wear. A delay in proper
diagnosis and intervention may contribute to a prolonged treatment course.
The microbial spectrum of contact lens–related keratitis may be evolving
with higher participation of Fusarium species compared
with prior reports.
Chronic Obstructive Pulmonary Disease Stage and Health-Related Quality of Life
Authors: Montserrat Ferrer
Journal: Annals of Internal Medicine (1997)

Background: The American Thoracic Society recently recommended that chronic obstructive pulmonary disease be staged on the basis of the percentage of predicted FEV1. Objective: To examine 1) the relation between the American Thoracic Society system for staging chronic obstructive pulmonary disease and health-related quality of life and 2) the effect of self-reported comorbid conditions on health-related quality of life. Design: Cross-sectional study. Setting: Outpatient clinics of respiratory department of four hospitals and one primary health care center in Spain. Patients: 321 consecutive male patients with chronic obstructive pulmonary disease. Measurements: Functional respiratory impairment, FEV1, respiratory symptoms, and health-related quality of life. Respiratory symptoms and health-related quality of life were measured by using the Spanish version of the St. George's Respiratory Questionnaire and the Nottingham Health Profile. Results: Patient scores on the St. George's Respiratory Questionnaire were moderately to strongly associated with disease staging (r = 0.27 to 0.51). Compared with reference values, values for health-related quality of life for patients with stage I disease were substantially higher on the St. George's Respiratory Questionnaire (6 and 34; P < 0.001) and values for impairment were significantly greater in stage I patients with comorbid conditions (19 and 36; P = 0.001). At least one concomitant chronic condition was found in 84% of study patients. Comorbid conditions only partly influenced the observed pattern of deterioration of health-related quality of life with worsening stages of disease. Conclusion: Staging criteria for chronic obstructive pulmonary disease based on percentage of predicted FEV1 separated groups of patients with varying degrees of impairment in health-related quality of life. Contrary to expectations, even patients with mild disease showed substantially compromised health-related quality of life. Comorbid conditions influenced the relation between chronic obstructive pulmonary disease and health-related quality of life.
The Excretion of Tritiated Digoxin in Normal Human Volunteers Before and After Unilateral Nephrectomy
Authors: JAMES E. DOHERTY, WILLIAM J. FLANIGAN, RODNEY M. PATTERSON, GLENN V. DALRYMPLE, Jacquelyn Gammill, Joyce Sherwood
Journal: Circulation (1969)

Six normal human volunteers as renal transplant donors were given 3 H-digoxin before and again after unilateral nephrectomy. The serum digoxin concentration was modestly increased following nephrectomy, the serum digoxin half-time was slightly prolonged, and total digoxin excretion for the group was reduced by only 6.4% during a 7-day study. Four of the six patients studied before and after unilateral nephrectomy exhibited no important reduction in digoxin excretion after nephrectomy; two patients excreted only 66% and 64% as much of the administered dose of digoxin as they had excreted compared to the control study. The removal of one kidney from an individual whose remaining kidney is normal does not usually cause significant reduction in the excretion of tritiated digoxin, and one may conclude that in such instances nephrectomy should not in itself prompt a change in digoxin dosage provided the remaining kidney achieves its expected increased functional capacity. The adequacy of renal function determines digoxin excretion and the dosage of digoxin in these patients.
Expression levels of interleukin-17a, interleukin-17f and their receptors in synovium of patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis: a target validation study
Authors: L G M van Baarsen, M C Lebre, D van der Coelen, D M Gerlag, P P Tak
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Accumulating evidence suggests an important role for interleukin (IL)-17 in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA). IL-17A has been well studied in models of arthritis, but little is known about the relative expression and cellular source(s) of IL-17A, IL-17F, and their receptors in human synovial tissue. <h3>Objective</h3> To determine the origin and expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in synovial tissues of patients with RA, psoriatic arthritis (PsA) and inflammatory osteoarthritis (OA). <h3>Methods</h3> Synovial biopsy specimens were obtained by arthroscopy from patients with RA (n=13), PsA (n=15) and inflammatory OA (n=14). For comparison synovial tissues from non-inflammatory controls (n=7) were included. Immunohistological analysis was performed on frozen sections using monoclonal antibodies specific for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. Immunofluorescence analysis was used to determine which cells in the synovium produce IL-17A and IL-17F using antibodies specific for T cells (CD4, CD8), neutrophils (CD15), macrophages (CD68, CD163), B cells (CD19), endothelial cells (CD31, Von Willebrand Factor, PNAd), lymphatics (Lyve-1) and mast cells (mast cell tryptase). Stained sections were evaluated by confocal microscopy. <h3>Results</h3> Levels of IL-17A, IL-17F, IL-17RA and IL-17RC were abundantly present in synovial tissues of all patient groups and highly variable between patients. Whereas IL-17RA was mostly present in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant increase of IL-17A but not of IL-17F, IL-17RA and IL-17RC in patients with arthritis compared to non-inflamed control tissues, while the expression of IL-17A, IL-17F and IL-17RA was similar between the different patient groups. Expression of IL-17RC in the intimal lining layer was significantly increased in PsA compared to OA patients. IL-17A was found to be expressed by CD4 and CD8 positive cells, while CD15, CD19 and mast cell tryptase (MCT) positive cells were negative. IL-17F was not expressed by CD15 positive cells and only occasionally by CD4, CD8 and MCT positive cells in the synovial tissues of arthritic patients. Interestingly, IL-17A and IL-17F staining was also observed in some macrophages as well as in endothelial cells and lymphatics.. <h3>Conclusions</h3> Increased expression of IL-17A is not restricted to synovial tissues of RA patients but also observed in other forms of inflammatory arthritis. In inflamed synovium various cell types contribute to the production of IL-17A and IL-17F.