tbuckley/cabot-search huggingface dataset:
Evaluation of common breast problems: guidance for primary care providers
Authors: B. Cady, G. D. Steele, M. Morrow, B. Gardner, B. L. Smith, N. C. Lee, H. W. Lawson, D. P. Winchester
Journal: CA A Cancer Journal for Clinicians (1998)

The evaluation of common breast problems requires an assessment of the patient's risks and symptoms and a thorough physical examination. When indicated, appropriate imaging studies should be done, the patient should be referred to a surgeon or a breast specialist, and operative interventions should be used.
Human RecQL4 Helicase Plays Critical Roles in Prostate Carcinogenesis
Authors: Yanrong Su, Jarah A. Meador, Gloria M. Calaf, Luca Proietti De-Santis, Yongliang Zhao, Vilhelm A. Bohr, Adayabalam S. Balajee
Journal: Cancer Research (2010)

Prostate cancer is the second leading cause of cancer-associated deaths among men in the western countries. Here, we report that human RecQL4 helicase, which is implicated in the pathogenesis of a subset of cancer-prone Rothmund-Thomson syndrome, is highly elevated in metastatic prostate cancer cell lines. Increased RecQL4 expression was also detected in human prostate tumor tissues as a function of tumor grade with the highest expression level in metastatic tumor samples, suggesting that RecQL4 may be a potential prognostic factor for advanced stage of prostate cancer. Transient and stable suppression of RecQL4 by small interfering RNA and short hairpin RNA vectors drastically reduced the growth and survival of metastatic prostate cancer cells, indicating that RecQL4 is a prosurvival factor for prostate cancer cells. RecQL4 suppression led to increased poly(ADP-ribose) polymerase (PARP) synthesis and RecQL4-suppressed prostate cancer cells underwent an extensive apoptotic death in a PARP-1-dependent manner. Most notably, RecQL4 knockdown in metastatic prostate cancer cells drastically reduced their cell invasiveness in vitro and tumorigenicity in vivo, showing that RecQL4 is essential for prostate cancer promotion. Observation of a direct interaction of retinoblastoma (Rb) and E2F1 proteins with RecQL4 promoter suggests that Rb-E2F1 pathway may regulate RecQL4 expression. Collectively, our study shows that RecQL4 is an essential factor for prostate carcinogenesis.
Reliability and agreement studies: a guide for clinical investigators
Authors: Ruben Hernaez
Journal: Gut (2015)

On a daily basis, clinicians and researchers face the challenge of measuring multiple outcomes. From responses to therapies and assessments of disease activity, to certainty of diagnoses and innovation of cutting-edge diagnostic tools, it is essential within every field that outcome measurement be valid, reproducible and reliable.1 At first glance, validity, reproducibility, reliability and agreement may seem similar; however, there are fundamental differences among these concepts that are important for study design and execution, and for methodology and statistical analyses. Alvan Feinstein saw that problem and introduced the term clinimetrics, or, “the methodologic discipline focusing on measurement issues in clinical medicine”.2 The concept of clinimetrics is not new; on the contrary, it has been considered a subset of psychometrics.3 Terwee, de Vet, Mokkink and Knol, among others,4 developed tools to assess and evaluate health measurement instruments in clinical medicine. It is, therefore, why the backbone of this paper will rely on the CO nsensus-based S tandards for the selection of health M easurement In struments (COSMIN) initiative.

The COSMIN initiative is a multidisciplinary, international consensus which aimed to create standards to evaluate the methodological quality and design and preferred statistical analyses of a study on measurement properties.5 The initiative primarily focused on Health Related Patient-Reported Outcomes (HR-PRO) due to the complexity of these outcomes measurements; however, these concepts still apply to other type of outcomes and will be followed here.4 For reader clarification, HR-PRO is defined by Mokkink et al 4 as “any aspect of a patient's health status that is directly assessed by the patient, that is, without the interpretation of the patient's responses by a physician or anyone else”; examples include self-administered or computer-administered questionnaires.

The COSMIN taxonomy in the evaluation of a measurement instrument shows three main quality domains: reliability, validity …
Specific Lymphocyte Stimulation by Purified, Heat-inactivated Hepatitis-B Antigen
Authors: G. C. de Gast, B. Houwen, H. O. Nieweg
Journal: BMJ (1973)

The ability of purified, heat-inactivated hepatitis-B antigen (HBAg) to stimulate sensitized lymphocytes in vitro was investigated with the lymphocyte stimulation test on lymphocytes from three groups of individuals. Stimulation was minimal in the lymphocytes of two out of 15 normal controls, whereas lymphocytes from nine out of 12 patients who had recovered from hepatitis B showed stimulation, as did lymphocytes from five out of 12 laboratory technicians who had been regularly exposed to HBAg but who had no history of hepatitis or signs of it in the previous two years. No differences were observed in the responses to phytohaemagglutinin of lymphocytes from persons in the three groups. HBAg and HBAg inactivated by heat were shown in immunodiffusion to be immunologically identical. Inactivated HBAg stimulated antibody production in guinea-pigs. These findings suggest that not only humoral but also cell-mediated immunity might be induced by vaccination with purified, heat-inactivated HBAg.
Risk of Fracture after Androgen Deprivation for Prostate Cancer
Authors: Vahakn B. Shahinian, Yong-Fang Kuo, Jean L. Freeman, James S. Goodwin
Journal: New England Journal of Medicine (2005)

The use of androgen-deprivation therapy for prostate cancer has increased substantially over the past 15 years. This treatment is associated with a loss of bone-mineral density, but the risk of fracture after androgen-deprivation therapy has not been well studied.We studied the records of 50,613 men who were listed in the linked database of the Surveillance, Epidemiology, and End Results program and Medicare as having received a diagnosis of prostate cancer in the period from 1992 through 1997. The primary outcomes were the occurrence of any fracture and the occurrence of a fracture resulting in hospitalization. Cox proportional-hazards analyses were adjusted for characteristics of the patients and the cancer, other cancer treatment received, and the occurrence of a fracture or the diagnosis of osteoporosis during the 12 months preceding the diagnosis of cancer.Of men surviving at least five years after diagnosis, 19.4 percent of those who received androgen-deprivation therapy had a fracture, as compared with 12.6 percent of those not receiving androgen-deprivation therapy (P<0.001). In the Cox proportional-hazards analyses, adjusted for characteristics of the patient and the tumor, there was a statistically significant relation between the number of doses of gonadotropin-releasing hormone received during the 12 months after diagnosis and the subsequent risk of fracture.Androgen-deprivation therapy for prostate cancer increases the risk of fracture.
Impact of Intraoperative Stimulation Brain Mapping on Glioma Surgery Outcome: A Meta-Analysis
Authors: Philip C. De Witt Hamer, Santiago Gil Robles, Aeilko H. Zwinderman, Hugues Duffau, Mitchel S. Berger
Journal: Journal of Clinical Oncology (2012)

Purpose Surgery for infiltrative gliomas aims to balance tumor removal with preservation of functional integrity. The usefulness of intraoperative stimulation mapping (ISM) has not been addressed in randomized trials. This study addresses glioma surgery outcome on the basis of a meta-analysis of observational studies. Methods A systematic search retrieved 90 reports published between 1990 and 2010 with 8,091 adult patients who had resective surgery for supratentorial infiltrative glioma, with or without ISM. Quality criteria consisted of postoperative neurologic examination details and follow-up timing. New postoperative neurologic deficits were categorized on the basis of timing and severity. Meta-analysis with a Bayesian random effects model determined summary event rates of deficits as well as gross total resection rate and eloquent locations. Meta-regression analysis explored heterogeneity among studies. Results Late severe neurologic deficits were observed in 3.4% (95% CI, 2.3% to 4.8%) of patients after resections with ISM, and in 8.2% (95% CI, 5.7% to 11.4%) of patients after resections without ISM (adjusted odds ratio, 0.39; 95% CI, 0.23 to 0.64). The percentages of radiologically confirmed gross total resections were 75% (95% CI, 66% to 82%) with ISM and 58% (95% CI, 48% to 69%) without ISM. Eloquent locations were involved in 99.9% (95% CI, 99.9% to 100%) of resections with ISM and in 95.8% (95% CI, 73.1% to 99.8%) of resections without ISM. Relevant sources of heterogeneity among studies were ISM, continent, and academic setting. Conclusion Glioma resections using ISM are associated with fewer late severe neurologic deficits and more extensive resection, and they involve eloquent locations more frequently. This indicates that ISM should be universally implemented as standard of care for glioma surgery.
Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism.
Authors: P M Barker, M S Nguyen, J T Gatzy, B Grubb, H Norman, E Hummler, B Rossier, R C Boucher, B Koller
Journal: Journal of Clinical Investigation (1998)

Genetic evidence supports a critical role for the epithelial sodium channel (ENaC) in both clearance of fetal lung liquid at birth and total body electrolyte homeostasis. Evidence from heterologous expression systems suggests that expression of the alphaENaC subunit is essential for channel function, whereas residual channel function can be measured in the absence of beta or gamma subunits. We generated mice without gammaENaC (gammaENaC -/-) to test the role of this subunit in neonatal lung liquid clearance and total body electrolyte balance. Relative to controls, gammaENaC (-/-) pups showed low urinary [K+] and high urinary [Na+] and died between 24 and 36 h, probably from hyperkalemia (gammaENaC -/- 18.3 mEq/l, control littermates 9.7 mEq/l). Newborn gammaENaC (-/-) mice cleared lung liquid more slowly than control littermates, but lung water at 12 h (wet/dry = 5.5) was nearly normal (wet/dry = 5.3). This study suggests that gammaENaC facilitates neonatal lung liquid clearance and is critical for renal Na+ and K+ transport, and that low level Na+ transport may be sufficient for perinatal lung liquid absorption but insufficient to maintain electrolyte balance by the distal nephron. The gammaENaC (-/-) newborn exhibits a phenotype that resembles the clinical manifestations of human neonatal PHA1.
Exome Sequencing Reveals Cubilin Mutation as a Single-Gene Cause of Proteinuria
Authors: Bugsu Ovunc, Edgar A. Otto, Virginia Vega-Warner, Pawaree Saisawat, Shazia Ashraf, Gokul Ramaswami, Hanan M. Fathy, Dominik Schoeb, Gil Chernin, Robert H. Lyons, Engin Yilmaz, Friedhelm Hildebrandt
Journal: Journal of the American Society of Nephrology (2011)

In two siblings of consanguineous parents with intermittent nephrotic-range proteinuria, we identified a homozygous deleterious frameshift mutation in the gene CUBN, which encodes cubulin, using exome capture and massively parallel re-sequencing. The mutation segregated with affected members of this family and was absent from 92 healthy individuals, thereby identifying a recessive mutation in CUBN as the single-gene cause of proteinuria in this sibship. Cubulin mutations cause a hereditary form of megaloblastic anemia secondary to vitamin B(12) deficiency, and proteinuria occurs in 50% of cases since cubilin is coreceptor for both the intestinal vitamin B(12)-intrinsic factor complex and the tubular reabsorption of protein in the proximal tubule. In summary, we report successful use of exome capture and massively parallel re-sequencing to identify a rare, single-gene cause of nephropathy.
Correlation Analysis between Single-Nucleotide Polymorphism and Expression Arrays in Gliomas Identifies Potentially Relevant Target Genes
Authors: Yuri Kotliarov, Svetlana Kotliarova, Nurdina Charong, Aiguo Li, Jennifer Walling, Elisa Aquilanti, Susie Ahn, Mary Ellen Steed, Qin Su, Angela Center, Jean C. Zenklusen, Howard A. Fine
Journal: Cancer Research (2009)

Primary brain tumors are a major cause of cancer mortality in the United States. Therapy for gliomas, the most common type of primary brain tumors, remains suboptimal. The development of improved therapeutics will require greater knowledge of the biology of gliomas at both the genomic and transcriptional levels. We have previously reported whole genome profiling of chromosome copy number alterations (CNA) in gliomas, and now present our findings on how those changes may affect transcription of genes that may be involved in tumor induction and progression. By calculating correlation values of mRNA expression versus DNA copy number average in a moving window around a given RNA probe set, biologically relevant information can be gained that is obscured by the analysis of a single data type. Correlation coefficients ranged from -0.6 to 0.7, highly significant when compared with previous studies. Most correlated genes are located on chromosomes 1, 7, 9, 10, 13, 14, 19, 20, and 22, chromosomes known to have genomic alterations in gliomas. Additionally, we were able to identify CNAs whose gene expression correlation suggests possible epigenetic regulation. This analysis revealed a number of interesting candidates such as CXCL12, PTER, and LRRN6C, among others. The results have been verified using real-time PCR and methylation sequencing assays. These data will further help differentiate genes involved in the induction and/or maintenance of the tumorigenic process from those that are mere passenger mutations, thereby enriching for a population of potentially new therapeutic molecular targets.
Rifampin — A Major New Chemotherapeutic Agent for the Treatment of Tuberculosis
Authors: Thomas M. Daniel
Journal: New England Journal of Medicine (1969)

At the twenty-eighth Veterans Administration —Armed Forces Pulmonary Disease Research Conference held in Cleveland, Ohio, January 20 to 22, 1969, four papers described the first American laboratory and clinical studies of rifampin, a new chemotherapeutic agent of great promise in the treatment of tuberculosis. This drug is an agent that may approach or even surpass isoniazid both in its efficacy and in its freedom from toxicity. It has engendered an excitement among those concerned with the chemotherapy of tuberculosis unequaled since the introduction of isoniazid.A semisynthetic derivative of rifamycin, an antibiotic isolated by Italian workers from Streptomyces mediterranei in . . .
Physician Practices in the Prevention of Venous Thromboembolism
Authors: Frederick A. Anderson, H. Brownell Wheeler, Robert J. Goldberg, David W. Hosmer, Ann Forcier, Nilima A. Patwardhan
Journal: Annals of Internal Medicine (1991)

▪Objective: To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. ▪Design: A retrospective medical record review. ▪Setting: A community-wide study in 16 short-stay hospitals in central Massachusetts. ▪Patients: A total of 2017 patients with multiple risk factors for venous thromboembolism. ▪Measurements and Main Results: On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151 349 discharges (25 410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P < 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P < 0.001). ▪Conclusion: Prophylaxis for venous thromboembolism is underused, particularly in nonteaching hospitals.
Suppression of adrenomedullin contributes to vascular leakage and altered epithelial repair during asthma
Authors: S. Hagner, H. Welz, A. Kicic, M. Alrifai, L. M. Marsh, E. N. Sutanto, K.‐M. Ling, S. M. Stick, B. Müller, N. Weissmann, H. Renz
Journal: Allergy (2012)

Abstract Background The anti‐inflammatory peptide, adrenomedullin ( AM ), and its cognate receptor are expressed in lung tissue, but its pathophysiological significance in airway inflammation is unknown. Objectives This study investigated whether allergen‐induced airway inflammation involves an impaired local AM response. Methods Airway AM expression was measured in acute and chronically sensitized mice following allergen inhalation and in airway epithelial cells of asthmatic and nonasthmatic patients. The effects of AM on experimental allergen‐induced airway inflammation and of AM on lung epithelial repair in vitro were investigated. Results Adrenomedullin m RNA levels were significantly ( P &lt; 0.05) reduced in acute ovalbumin ( OVA )‐sensitized mice after OVA challenge, by over 60% at 24 h and for up to 6 days. Similarly, reduced AM expression was observed in two models of chronic allergen‐induced inflammation, OVA ‐ and house dust mite–sensitized mice. The reduced AM expression was restricted to airway epithelial and endothelial cells, while AM expression in alveolar macrophages was unaltered. Intranasal AM completely attenuated the OVA ‐induced airway hyperresponsiveness and mucosal plasma leakage but had no effect on inflammatory cells or cytokines. The effects of inhaled AM were reversed by pre‐inhalation of the putative AM receptor antagonist, AM (22‐52) . AM m RNA levels were significantly ( P &lt; 0.05) lower in human asthmatic airway epithelial samples than in nonasthmatic controls. In vitro , AM dose‐dependently (10 −11 –10 −7 M) accelerated experimental wound healing in human and mouse lung epithelial cell monolayers and stimulated epithelial cell migration. Conclusion Adrenomedullin suppression in T H 2‐related inflammation is of pathophysiological significance and represents loss of a factor that maintains tissue integrity during inflammation.
Waiting for Rounds
Authors: Allison Kolodinsky
Journal: JAMA (1991)

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Cytomegalovirus Pneumonitis Detected by Gallium-67 Scintigraphy With a Negative Diagnostic Chest Computed Tomography
Authors: Wichana Chamroonrat, Gang Cheng, Sabah Servaes, Jianing Li, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2010)

Computed tomography is known to have a high sensitivity in the detection of lung abnormalities caused by cytomegalovirus (CMV) infection. Gallium-67 scintigraphy has long been used in nuclear medicine to evaluate many different infectious processes. A gallium-67 scan was performed to search for the source of the intermittent fever of 2 months’ duration in an 18-year-old immunocompromised man. The gallium-67 images showed diffuse abnormal activity in both lungs while a chest computed tomography was negative. On the basis of gallium scan result and subsequent laboratory results, a diagnosis of CMV pneumonitis was made. The patient received anti-CMV therapy and recovered promptly.
"Burnam's Test" for Formaldehyd: a Question of Priority
Authors: A. C. Croftan
Journal: JAMA (1913)

<h3>To the Editor:</h3> —Hugh Cabot and O. R. T. L'Esperance in an article entitled "The Excretion of Formaldehyd by the Kidneys of Patients Taking Hexamethylenamin, a Study of Burnam's Test" (<i>Boston Med. and Surg. Jour.</i>, Oct. 24, 1912, p. 577), and later B. F. Jeness in an article entitled "Burnam's Test for Formaldehyd in the Urine" (The Journal, March 1, 1913, p. 662) described in detail a method for determining small quantities of formaldehyd in the urine, calling this method, both in the title and in the text, "Burnam's test." This test consists in the use of dilute solutions of phenylhydrazin hydrochlorid, sodium nitroprussid and sodium hydroxid. It is a delicate color reaction, for all practical purposes specific for formaldehyd and very sensitive, revealing the presence of minute quantities of formaldehyd, even in albuminous fluids, such as milk, nephritic urine, etc. This so-called "Burnam's test" was discovered by Rimini (<i>Ann.</i>
Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study
Authors: M.-A. Gall, P. Hougaard, K. Borch-Johnsen, H.-H. Parving
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To evaluate putative risk factors for the development of incipient diabetic nephropathy (persistent microalbuminuria) and overt diabetic nephropathy (persistent macroalbuminuria) in patients with non-insulin dependent diabetes. <b>Design:</b> Prospective, observational study of a cohort of white, non-insulin dependent diabetic patients followed for a median period of 5.8 years. <b>Setting:</b> Outpatient clinic in tertiary referral centre. <b>Subjects:</b> 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria (urinary albumin excretion rate&lt;30 mg/24 h) who attended the clinic during 1987. <b>Main outcome measures:</b> Incipient and overt diabetic nephropathy. <b>Results:</b> Fifteen patients were lost to follow up. Thirty six of the 176 remaining developed persistent microalbuminuria (30-299 mg/24 h in two out of three consecutive 24 hour urine collections) and five developed persistent macroalbuminuria (≥300 mg/24 h in two out of three consecutive collections) during follow up. The five year cumulative incidence of incipient diabetic nephropathy was 23% (95% confidence interval 17% to 30%). Cox9s multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy: increased baseline log urinary albumin excretion rate (relative risk 11.1 (3.4 to 35.9); P&lt;0.0001); male sex (2.6 (1.2 to 5.4); P&lt;0.02); presence of retinopathy (2.4 (1.3 to 4.7); P&lt;0.01); increased serum cholesterol concentration (1.4 (1.1 to 1.7); P&lt;0.01); haemoglobin A 1c concentration (1.2 (1.0 to 1.4); P&lt;0.05); and age (1.07 (1.02 to 1.12); P&lt;0.01). Known duration of diabetes, body mass index, arterial blood pressure, serum creatinine concentration, pre-existing coronary heart disease, and history of smoking were not risk factors. <b>Conclusion:</b> Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non-insulin dependent diabetes.