tbuckley/cabot-search huggingface dataset:
PTH-251 Bile acid diarrhoea is associated with gallstones
Authors: RN Appleby, JD Nolan, IM Johnston, SS Pattni, JR Walters
Journal: Gut (2015)

<h3>Introduction</h3> Bile acid diarrhoea (BAD) is a common disorder which in the primary, idiopathic form may result from low serum fibroblast growth factor 19 (FGF19) producing impaired regulation of bile acid synthesis. <sup>75</sup>Selenium Homocholic Acid Taurate (SeHCAT) 7day retention is used in diagnosis, predicting faecal bile acid loss and correlating with fasting serum FGF19. Several groups have shown that overweight and obesity are associated with BAD and low FGF19. Reduced FXR target gene expression, of which FGF19 is one, is associated with gallstones. We hypothesised that the two conditions might share pathophysiologic mechanisms and commonly coexist. <h3>Method</h3> SeHCAT 7 day retention values were collected between 2003–2014 in patients being investigated for chronic diarrhoea. Other conditions known to be associated with BAD such as cholecystectomy or Crohn’s disease were recorded. A subset of these patients had fasting FGF19 measured. Retrospectively, gallbladder imaging was added to database following cross-referencing with the NHS trust’s PACS system. Where multiple investigations had been performed, the test nearest to the date of the SeHCAT test was recorded. Imaging reporting gallbladder polyps without gallstones were excluded from the final analysis. <h3>Results</h3> Of 578 SeHCAT values on the database, 303 (52%) were positive with a value &lt;15%. 183 had imaging that reported upon the gallbladder, of which 7 were excluded due to the presence of polyps, leaving 176. Of these 103 (59%) had a positive SeHCAT scan, 47 (27%) had gallstones, 12 (7%) had a cholecystectomy, so 59 (34%) had either gallstones or cholecystectomy. There was no significant difference in the rate of gallstones or cholecystectomy by gender (64% v 72%, p = 0.2), but mean age in the gallstones/cholecystectomy group was higher (50 v 57, p &lt; 0.005). Median SeHCAT for the whole cohort was 11.7%. The median SeHCAT for those with gallstones or cholecystectomy was significantly lower than those without (7.2% v 14%, p &lt; 0.001). With cholecystectomy excluded, the median SeHCAT was still lower for those with gallstones (3.8% v 14%, p &lt; 0.0001). Overall, a SeHCAT value of &lt;15% conferred an increased risk of gallstones or cholecystectomy (OR=2.0, 95% CI 1.04–3.919, p &lt; 0.05) and the presence of primary bile acid diarrhoea was associated with gallstones, although this did not reach statistical significance (OR=1.98, 95% CI 0.65–5.99, p = 0.23). FGF19 was measured in 60 patients with imaging, of whom 15 had gallstones or cholecystectomy. There was no significant difference in the median serum FGF19 between those with gallstones or cholecystectomy and those without (224 v 227 pg/ml, p = 0.7). <h3>Conclusion</h3> Bile acid diarrhoea is associated with gallstones, even when adjusted for cholecystectomy which is a known risk factor for BAD. Bile acid diarrhoea and gallstones may share a pathophysiological mechanism. <h3>Disclosure of interest</h3> None Declared.
When and How to Treat Chronic Lymphocytic Leukemia
Authors: Guillaume Dighiero, Jacques-Louis Binet
Journal: New England Journal of Medicine (2000)

Chronic lymphocytic leukemia (CLL), the most common form of leukemia in adults, is usually recognized first by the patient's primary care physician. When the patient has other medical problems — which is frequently the case, given that the median age at diagnosis is 64 years — the primary care physician collaborates with the hematologist or oncologist in treating the patient. It is often difficult to make decisions about therapy, which can involve subtle factors that are best understood by the patient's own doctor.CLL most commonly arises from a malignant clone of B cells with a characteristic phenotype. It is . . .
Hypersensitivity to Wood Dust
Authors: Abe J. Sosman, Donald P. Schlueter, Jordan N. Fink, Joseph J. Barboriak
Journal: New England Journal of Medicine (1969)

Respiratory disease resulting from prolonged exposure to wood dusts may be due to a hypersensitivity reaction in addition to the nonspecific toxic or irritant effects of the inhaled materials. In four patients the hypersensitivity response was manifested by two clinical patterns, one characterized by immediate onset and rapid reversibility of asthmatic symptoms, and the other by a more delayed onset and more gradual reversibility. In this disease the clinical history and challenge with the suspected offending dust proved to be of greater diagnostic importance than skin testing.
The NCCN Clinical Practice Guidelines on Liver Cancer: Guidelines for All Settings?
Authors: Rodger J. Winn
Journal: Journal of the National Comprehensive Cancer Network (2006)

Rodger J. Winn is the Editorin-Chief of JNCCN. He is Clinical Consultant at the National Quality Forum, and his past positions include Associate Professor of Clinical Medicine at The University of Texas M. D. Anderson Cancer Center. Dr. Winn received his medical degree from Jefferson Medical College of Philadelphia. His postgraduate training includes an internship and residency at Jefferson Medical College, and he also completed a medical oncology fellowship at Memorial Sloan-Kettering Cancer Center in New York. He is board certified in internal medicine and holds subspecialty certification in oncology. The NCCN Clinical Practice Guidelines on Liver Cancer: Guidelines for All Settings?
Prognosis of Childhood Urinary-Tract Infection
Authors: Robert E. Steele, Guy W. Leadbetter, John D. Crawford
Journal: New England Journal of Medicine (1963)

THERE has been increasing awareness of the potential danger that symptomatic and asymptomatic infections of the urinary tract may lead to renal failure and death. This has stimulated the production of new antibacterial drugs and their longer and more carefully supervised administration. Improved diagnostic procedures have also been devised for detection of urinary-tract abnormalities, and new surgical approaches for their correction. Records of long-term results of the new methods of medical and surgical therapy will soon be available. For their evaluation, it will be necessary to have an appraisal of the natural history of urinary-tract infections in the child before . . .
Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis
Authors: S L Taube, L S Kirstein, D R Sweeney, G R Heninger, J W Maas
Journal: American Journal of Psychiatry (1978)

The authors examined the quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the urine of 11 schizophrenic female patients, 14 primary affective disorder (depressed type) female patients, and 10 healthy comparison women. The primary affective disorder patients had significantly less MHPG in their urine than did the comparison subjects. The schizophrenic patients when compared with the healthy subjects or the depressed patients did not excrete significantly different amounts of MHPG in urine. The variance in MHPG in schizophrenic patients was quite large; some had very low urinary MHPG. There was a significant positive correlation between agitation and urinary MHPG for schizophrenic but not depressed patients. The authors discuss theoretical and practical implications of these findings.
Right Ventricular Infarction
Authors: Jack W. Kinch, Thomas J. Ryan
Journal: New England Journal of Medicine (1994)

The description of right ventricular myocardial infarction appeared more than 60 years ago,1 yet for decades it was not considered an important clinical entity, in large part because of studies in animals in which experimentally induced isolated right ventricular damage caused no substantial change in systemic venous pressure, pulmonary pressure, or cardiac output24. Twenty years ago Cohn and coworkers5 published their classic report on right ventricular infarction as a distinct clinical entity. The condition is now recognized to occur in nearly half of all inferior myocardial infarctions.Normal PhysiologyThe right ventricle has the same cardiac output as . . .
Association Between Use of Lipid-Lowering Therapy and Cardiovascular Diseases and Death in Individuals With Type 1 Diabetes
Authors: Christel Hero, Araz Rawshani, Ann-Marie Svensson, Stefan Franzén, Björn Eliasson, Katarina Eeg-Olofsson, Soffia Gudbjörnsdottir
Journal: Diabetes Care (2016)

OBJECTIVE To evaluate the effect of lipid-lowering therapy (LLT) in primary prevention on cardiovascular disease (CVD) and death in type 1 diabetes. RESEARCH DESIGN AND METHODS We used the Swedish National Diabetes Register (NDR) to perform a propensity score–based study. Propensity scores for treatment with LLT were calculated from 32 baseline clinical and socioeconomic variables. The propensity score was used to estimate the effect of LLT in the overall cohort (by stratification). We estimated risk of acute myocardial infarction, stroke, coronary heart disease, and cardiovascular and all-cause mortality in individuals with and without LLT using Cox regression. A total of 24,230 individuals included in 2006–2008 NDR with type 1 diabetes without a history of CVD were followed until 31 December 2012; 18,843 were untreated and 5,387 treated with LLT (97% statins). The mean follow-up was 6.0 years. RESULTS The propensity score allowed balancing of all 32 covariates, with no differences between treated and untreated after accounting for propensity score. Hazard ratios (HRs) for treated versus untreated were as follows: cardiovascular death 0.60 (95% CI 0.50–0.72), all-cause death 0.56 (0.48–0.64), fatal/nonfatal stroke 0.56 (0.46–0.70), fatal/nonfatal acute myocardial infarction 0.78 (0.66–0.92), fatal/nonfatal coronary heart disease 0.85 (0.74–0.97), and fatal/nonfatal CVD 0.77 (0.69–0.87). CONCLUSIONS This observational study shows that LLT is associated with 22–44% reduction in the risk of CVD and cardiovascular death among individuals with type 1 diabetes without history of CVD and underlines the importance of primary prevention with LLT to reduce cardiovascular risk in type 1 diabetes.
Isolation of Two Syngeneic Cell Lines From a Rat Mammary Carcinoma: Growth Factor Production by Neoplastic Epithelial Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Hiragun, Y Yoshida, M Sato, T Tominaga, H Mitsui
Journal: JNCI Journal of the National Cancer Institute (1985)

Two distinctly different clonal cell lines were isolated from a mammary tumor induced by ingestion of 7,12-dimethylbenz[a]anthracene (CAS: 57-97-6) in a SD rat. Cells of one of the clones, RMT-1 clone E4, showed typical epithelial characters; it was concluded that they were derived from neoplastic mammary epithelial cells. The other clone, M2, exhibited characters consistent with its derivation from the normal mammary myoepithelial component. The 2 cell lines had different proliferative responses to growth factors (GF) such as cholera toxin, dexamethasone, and epidermal GF. The epithelioid E4 cells were found to produce potent growth-promoting activity in culture medium that stimulated proliferation of myoepithelial M2 cells as well as that of stromal fibroblasts. The present work provides supporting evidence that the mechanism of "paracrine stimulation" is operative in the mammary tumorigenesis of the rat.
Differences in sites of metastatic disease and outcomes observed in patients with BRAF mutant colorectal cancers.
Authors: B. Tran, S. Kopetz, J. Tie, P. Gibbs, Z. Jiang, C. H. Lieu, A. Agarwal, D. Maru, O. Sieber, J. Desai
Journal: Journal of Clinical Oncology (2010)

3592 Background: It has been hypothesized that BRAF mutant cancers represent a distinct subset of colorectal cancer (CRC), with BRAFV600E mutant metastatic CRC patients appearing to have a significantly poorer survival than the BRAF wild-type population. Resistance to antibodies targeting EGFR may be one contributing factor but this alone does not explain all observed survival differences. This study investigates whether there are differences in sites of metastatic disease between BRAFV600E and wild-type patients, a possible contributor to poorer outcomes. Methods: Data was collected from two major centers using prospective databases supplemented by review of medical records. All patients with known BRAF mutation status were analyzed for sites of metastatic disease and clinical characteristics. Differences in sites of metastases between BRAFV600E and wild-type populations were analyzed using Fisher's exact test. Results: We identified 524 metastatic CRC patients with known BRAF mutation status. BRAFV600E was identified in 57 patients (11%) with the remaining 467 patients all wild-type. BRAFV600E patients trended to older ages (median age 66 v 63, p = 0.175), were more likely to have a right sided primary (67% v 34%, p < 0.0001) and had poorer overall survival (median 10.4 v 34.7 months, p < 0.0001). There was no difference in proportion of liver metastases between the BRAFV600E and wild-type groups (63% v 72%, p = 0.163). However there was a significantly lower incidence of lung metastases (35% v 49%, p = 0.049) and higher incidence of peritoneal metastases (46% v 24%, p = 0.001). Data regarding the rate of CNS metastases suggests a clinically significant but not statistically significant difference (8.8% v 4.7%, p = 0.199). Conclusions: Patients with BRAF mutant CRC appear to have a distinct pattern of metastatic spread. Our data provides further evidence that this population represents a distinct subset of CRC. Further confirmatory data should explore whether BRAF mutant CRC is associated with an increased rate of peritoneal and brain metastases, known adverse prognostic factors in CRC, as this may be one factor contributing to the inferior outcome in this patient subgroup. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche
Neutrophil Activation in Thermal Injury as Assessed by Increased Expression of Complement Receptors
Authors: Francis D. Moore, Carl Davis, Mary Rodrick, John A. Mannick, Douglas T. Fearon
Journal: New England Journal of Medicine (1986)

We studied neutrophil activation in patients with burns by serial immunofluorescent measurement of neutrophil expression of the complement opsonin receptors CR1 and CR3. CR1-dependent fluorescence was initially (days 0 through 5 after the burn) elevated (mean ±SEM, 294±42 vs. 63±6 in the controls; P<0.001) and gradually returned to normal (days 6 through 8, 270±62, P<0.001; days 9 through 13, 185±38, P<0.001; days 14 through 19, 143±27, P<0.001; and days 20 through 50, 93±5, P<0.04). CR3-dependent fluorescence paralleled that of CR1. Neutrophil chemotaxis in response to zymosan-activated serum, a source of C5a, was depressed (days 0 through 5, 77±4 percent of control, P<0.001; days 6 through 8, 70±4 percent, P<0.001; days 9 through 13, 74±3 percent, P<0.001; days 14 through 19, 90±4 percent, P<0.01; and days 20 through 50, 97±3 percent, P not significant) and inversely correlated with CR1and CR3-dependent fluorescence (r = -0.559, P<0.001; and r =-0.709, P<0.001, respectively). Plasma C3a desArg levels were above normal (100±5 ng per milliliter) throughout (days 0 through 5, 305±42; days 6 through 8, 546±69; days 9 through 13, 490±72; days 14 through 19, 409±54; and days 20 through 50, 260±36; all P<0.005). Thus, neutrophils in burned patients were activated as indicated by increased expression of complement receptors. The correlation between this increase and the depression of chemotaxis in response to zymosan-activated serum suggests that C5a is responsible for systemic neutrophil activation, which may contribute to the increased susceptibility to infection of patients with burns. (N Engl J Med 1986;314:948–53.)
Abstract 4869: Validation of a procedure for simultaneous variant calling and differential expression in cancer study
Authors: Gang Feng, Jamie Osman, Sean Leighton, Lynn Carmichael, Yuchen Bai, John Begemann, Richard Mazzarella
Journal: Cancer Research (2015)

Abstract We have designed an integrated RNA-seq pipeline that determines both sequence variants and the differential expression of the transcripts from the same alignment in cancer samples. Comparison with other widely used protocols for RNA-seq data analysis showed that our method was more sensitive for determining subtle phenotypes in studies with large sample size, which frequently occur in compound screening approaches for cancer therapy. This whole transcriptome sequencing technology provides a cost-effective approach to gain understanding into the RNA relative biological events by deciphering RNA sequences. Benefiting from the fast developing technology, the cost of deep RNA-seq is no longer a barrier for current applications. Furthermore, an RNA-seq dataset provides more insight into disease processes than DNA-seq, since single nucleotide variant (SNV) detection in addition to gene and exon level expression and new isoform detection can be garnered from the same information. Based on the recent public data for mixed cancer cell lines and pooled normal human samples in MicroArray Quality Control (MAQC) phase III, also referred to as Sequencing Quality Control (SEQC), we evaluated our method with previous published results by means of different alignment strategies, sequencing depths and replicates numbers. Receiver operating characteristic (ROC) analysis showed our gene expression results agreed with the ones from the SEQC teams. In most cases, our solution has similar performance with other widely used strategies, while our STAR 2 pass based strategy has better true positive and true negative rates in the experiments with large sample size and subtle difference between groups. At the same time, the Genome Analysis Toolkit (GATK) 3 in our pipeline gained a reasonable balance between accuracy and performance. In summary, our new RNA-seq analysis pipeline has good performance and balance between precision and speed. Furthermore, this work also implicitly indicates that our gene expression method generates more accurate results in a large sample size experiment among similar groups. Citation Format: Gang Feng, Jamie Osman, Sean Leighton, Lynn Carmichael, Yuchen Bai, John Begemann, Richard Mazzarella. Validation of a procedure for simultaneous variant calling and differential expression in cancer study. [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 4869. doi:10.1158/1538-7445.AM2015-4869
Uncompensated Care by Hospitals or Public Insurance for the Poor
Authors: Robert J. Blendon, Linda H. Aiken, Howard E. Freeman, Bradford L. Kirkman-Liff, John W. Murphy
Journal: New England Journal of Medicine (1986)

Abstract Results from two recent surveys of access to medical care, one nationwide and the other in Arizona, were analyzed to determine the consequences of reductions in Medicaid coverage for low-income Americans and the accompanying shift of responsibility for their health care to clinics and hospitals that provide uncompensated or subsidized care. The analysis indicated that in 1982, low-income persons received substantially less care from physicians if they resided in states without Medicaid programs or with only limited programs. In Arizona, the only state at the time without a Medicaid program, poor children saw physicians 40 percent less often, and poor rural residents saw physicians 22 percent less often, than poor residents of states with Medicaid programs; the proportion of poor Arizona residents refused care for financial reasons was almost double that in states with Medicaid programs. In addition, poor residents of states with the highest proportions of their low-income populations covered by Medicaid fared better than those in states with less extensive coverage. Moreover, poor elderly Americans were found to have comparable access to health care, regardless of where they lived, as a result of almost universal coverage under Medicare. Thus, this analysis suggests that the growing reliance on uncompensated care provided by hospitals and clinics may not be an effective substitute for public insurance and may adversely affect the health care received by the poor. (N Engl J Med 1986; 314:1160–3.)
Cancer pain education: a call for role models.
Authors: D E Weissman
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.12.1793 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3199165 Cancer pain education: a call for role models. D E WeissmanxD E WeissmanSearch for articles by this author https://doi.org/10.1200/JCO.1988.6.12.1793 PDF "Cancer pain education: a call for role models.." Journal of Clinical Oncology, 6(12), pp. 1793–1794© 1988 by American Society of Clinical Oncology
Effect of adjuvant chemotherapy with docetaxel, cisplatin, and continuous infusion fluorouracil for gastric cancer: A phase II study.
Authors: L. Zhao, H. Ying, X. Ning, J. Zhou, Y. Wang, C. Bai, S. Chen
Journal: Journal of Clinical Oncology (2010)

e14652 Background: In USA, adjuvant chemoradiotherapy is standard treatment for resectable gastric cancer. But compared to the situation in the United States, the standard of care in Asia and many parts of Europe is adjuvant chemotherapy. Many randomized trials have compared adjuvant systemic chemotherapy to surgery alone with variable results. Now there are at least three meta-analyses support adjuvant chemotherapy for a significant survival benefit. A major problem is which regimen is more effective for gastric cancer. DCF regimen (docetaxel plus cisplatin and 5-Fu) has shown improvement of survival in a multicenter TAX-325 trial in advanced gastric cancer. Its value in adjuvant chemotherapy is unclear. Methods: Twenty eight patients with gastric or gastroesophageal junction cancer were enrolled after radical resection. Treatment consisted of docetaxel 60 mg/m2 on Day 1 and cisplatin 12 mg/m2/d on Day 1 to Day 5 plus fluorouracil 2,500mg/m2 continuous infusion for 120 hours, repeated every three weeks. The primary endpoint was DFS. Results: The median age was 50 years (range 32-66). The median performance status (ECOG) was 0. The stages of patients were: stage IB 2 pts (7.1%), stage II 7 pts (25.0%), stage III 15 pts (53.6%) and stage IV with M0 4 pts (14.3%). They received 143 cycles of adjuvant chemotherapy totally. Four patients terminated chemotherapy for grade 3/4 toxicity after 2 cycles' treatment. Eleven patients had got local recurrence or metastases till Dec 31, 2009. The median disease-free-survival was 18.1 months. The estimated DFS rate for 1 year was 63.2% and 2 year 39.9%. Hematologic adverse events were the main toxicities with grade 3/4 neutropenia occurred in 20 pts (71.4%) and febrile neutropenia in 3 pts (10.7%). The frequency of anemia was high with 71.4%, but all of them were grade 1/2. Grade 3/4 thrombocytopenia was recorded only in 1 patient (3.6%). Most frequent nonhematology grade 3/4 adverse events were vomiting (14.3%), diarrhea (10.7%), and syncope (7.1%). There was no chemotherapy related death. Conclusions: Modified DCF regimen as adjuvant chemotherapy in gastric cancer was effective. Although the frequency of hematological toxicity was high, it could be well controlled. No significant financial relationships to disclose.
An albumin-mediated cholesterol design-based strategy for tuning siRNA pharmacokinetics and gene silencing
Authors: Konrad Bienk, Michael Lykke Hvam, Malgorzata Maria Pakula, Frederik Dagnæs-Hansen, Jesper Wengel, Birgitte Mølholm Malle, Ulrich Kragh-Hansen, Jason Cameron, Jens Thostrup Bukrinski, Kenneth A. Howard
Journal: Journal of Controlled Release (2016)