tbuckley/cabot-search huggingface dataset:
A problem-oriented approach to liver disease in oncology patients
Authors: G B McDonald, D Frieze
Journal: Gut (2008)

> Man sieht nur das , was man weiss – You only see what you know. (J.W. von Goethe, 1808)

The disciplines of oncology, clinical pharmacology, and hepatology have seen rapid growth in their respective literatures that deal with new anti-tumour agents; pharmacokinetics, pharmacodynamics and pharmacogenomics of cancer therapies; and the liver as a key organ in metabolism of these therapies as well as a frequent target of toxicity. The challenge for physicians caring for oncology patients is to integrate an understanding of this literature with practical considerations of how to prevent, diagnose and treat hepatobiliary problems that arise in the midst of therapy.

> An ounce of prevention is worth a pound of cure. (Henry De Bracton, c . 1240)

Many underlying hepatobiliary problems become manifest only after anti-cancer therapy has begun. While the lack of recognition of underlying liver disease at baseline is perhaps understandable, some post-therapy liver problems can be prevented with forethought.

### Hepatitis B infection

Patients with haematological malignancy, especially those treated with monoclonal antibodies that deplete lymphocytes (eg, rituximab and alemtuzumab), are at risk for fulminant hepatic failure caused by HBV if they habour HBV at baseline.1–4 Some patients with chronic HBV infection may have underlying fibrosis and portal hypertension, making them vulnerable to sepsis and decompensated liver disease. Baseline testing for HBV (HBsAg, anti-HBc, anti-HBs) should be routine, with polymerase chain reaction (PCR) for HBV DNA reserved for patients who are positive for these markers of HBV infection. There is a hierarchy of risk of fulminant hepatitis B after chemotherapy in the absence of antiviral drugs: high-titre viraemia at baseline > low level viraemia > surface antigenaemia > anti-core positivity > anti-surface antigen positivity (if acquired naturally) > birthplace in an HBV endemic area. Anti-HBc is a marker of prior HBV infection and latent virus; ∼4% …
Acidity at different sites in the proximal duodenum of normal subjects and patients with duodenal ulcer.
Authors: J Rhodes, C J Prestwich
Journal: Gut (1966)

EDITORIAL COMMENT The gradient of acidity from stomach to distal duodenum is of considerable physcological interest and this paper presents the results of the first extensive experimental investigation of this gradient.Rhodes, Apsimon, and Lawrie (1966) have recently measured pH in the duodenal bulb for long periodsl* using two glass electrodes.By this method it is possible to maintain the distal electrode within the duodenal bulb for long periods but its exact position in the bulb cannot be determined.Over short _.... periods of time, however, the electrode can be located accurately by radiological methods.In this paper we describe the results of short-term observations on duodenal pH in normal subjects and patients with duodenal ulcer. SUBJECTSEleven normal subjects and 13 with duodenal ulcer were studied.They were all adult males, and their ages are given in Table I.The normal subjects had no history of 3 epigastric discomfort.All the subjects with ulcer had had recent barium meals which showed a duodenal ulcer, the ulcer being in the duodenal bulb in all except one subject (D.U.13) who had a post-bulbar ulcer; they were all
Hemoglobin A1c Versus Oral Glucose Tolerance Test in Postpartum Diabetes Screening
Authors: María José Picón, Mora Murri, Araceli Muñoz, José Carlos Fernández-García, Ricardo Gomez-Huelgas, Francisco J. Tinahones
Journal: Diabetes Care (2012)

To determine the usefulness of measuring hemoglobin A(1c) (A1C), alone or combined with the fasting glucose test, compared with the oral glucose tolerance test (OGTT) for the reassessment of the carbohydrate metabolism status in postpartum women with a history of gestational diabetes mellitus (GDM).We evaluated the status of carbohydrate metabolism by performing the OGTT and fasting glucose and A1C tests in 231 postpartum women with prior GDM 1 year after delivery.The prevalence of abnormal carbohydrate metabolism was 45.89% by the OGTT criterion, 19.05% by the A1C test criterion, 38.10% by the fasting glucose test criterion, and 46.75% by the A1C-fasting glucose test criteria. Using the OGTT as the gold standard, abnormal carbohydrate metabolism according to the A1C test criterion had 22.64% sensitivity and 54.55% positive predictive value; abnormal carbohydrate metabolism by the fasting glucose criterion had 83.02% sensitivity and 100% positive predictive value. The A1C-fasting glucose test criteria classified 18 women with normal carbohydrate metabolism as having abnormal carbohydrate metabolism. Abnormal carbohydrate metabolism by the A1C-fasting glucose test criteria had 83.02% sensitivity and 81.48% positive predictive value.Our results seem to indicate that the A1C test criterion alone or in combination with fasting glucose test criterion does not provide a sensitive and specific diagnosis of abnormal carbohydrate metabolism in women who have had GDM.
Effect of Pioglitazone on Energy Intake and Ghrelin in Diabetic Patients
Authors: Corby K. Martin, Alok K. Gupta, Steven R. Smith, Frank L. Greenway, Hongmei Han, George A. Bray
Journal: Diabetes Care (2010)

OBJECTIVE To measure ghrelin and energy intake in the laboratory after pioglitazone treatment. RESEARCH DESIGN AND METHODS This was a parallel, three-arm study with 51 obese diabetic subjects randomized to either 1) pioglitazone plus a portion-controlled diet (Pio+PC), 2) pioglitazone plus American Diabetes Association (ADA) dietary advice (Pio+ADA), or 3) metformin plus ADA advice (Met+ADA). Energy intake and the suppressive response of a meal on ghrelin were measured at weeks 0 and 16. Mixed models tested if changes from week 0 to 16 differed by group. RESULTS The Pio+ADA group had a significantly larger increase (P &amp;lt; 0.05) in energy intake ([adjusted means ± SE] 207 ± 53 kcal) compared with the Pio+PC (50 ± 46 kcal) and Met+ADA (52 ± 49 kcal) groups. Change in restraint and disinhibition (variables associated with eating behavior) mediated weight change. Ghrelin suppression increased in the Pio+ADA group, which gained weight. CONCLUSIONS A portion-controlled diet attenuated the increase in energy intake after pioglitazone. Ghrelin responded to weight change not pioglitazone exposure.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Chi-Jen Lee, Rene Dubos
Journal: The Journal of Experimental Medicine (1972)

The effects of neonatal infection, perinatal malnutrition, and crowding on the metabolism of brain catecholamine were studied in specific pathogen-free mice. Metabolic turnover of catecholamine was determined by measuring the incorporation of precursor tyrosine-(14)C into brain tissue, catabolic activity of norepinephrine-(3)H at various times after intracisternal injection, and tissue levels of dopamine and norepinephrine. The rate of tyrosine incorporation was decreased by neonatal infection but was increased by perinatal malnutrition and crowding. There was no difference in catabolic activity of norepinephrine between infected, crowded, and control groups. In the malnourished group, however, the total radioactivity from norepinephrine was significantly higher than in the control group (1/2) and 2 hr after injection. The brain contents of dopamine and norepinephrine were depressed in the malnourished group. There was no significant difference in catecholamine levels between infected, crowded, and control groups. In the malnourished group, treatment of the mothers with growth hormone prevented almost completely weight loss during lactation, and also resulted in higher fetal weight. Hormone treatment restored to normal the levels of brain catecholamine and the enzymatic activity of brain tyrosine hydroxylase in progeny of malnourished mothers.
Horseshoe Kidney Simulation by Paraaortic Metastases from a Testicular Tumor
Authors: H W GRAY
Journal: Clinical Nuclear Medicine (1987)

Following a debulking laparotomy, a 37-year-old male had unresectable secondary testicular tumour around his right kidney. Tc-99m MDP imaging revealed soft tissue uptake in the interrenal area resembling a horseshoe kidney. Specific renal imaging excluded a congenital anomaly. The diagnosis of a horse-shoe kidney should not be made on evidence from bone imaging alone.
Mechanosensitive Cation Channels in Arterial Smooth Muscle Cells Are Activated by Diacylglycerol and Inhibited by Phospholipase C Inhibitor
Authors: Kyoung Sun Park, Yangmi Kim, Young-Ho Lee, Yung E. Earm, Won-Kyung Ho
Journal: Circulation Research (2003)

Mechanosensitive cation channels may be involved in the development of the myogenic tone of arteries. The molecular identity of these channels is not clear, but transient receptor potential channels (TRPCs) are good candidates. In the present study, we searched for mechanosensitive channels at the single-channel level in arterial smooth muscle cells using the patch-clamp technique and investigated the channel properties in the light of properties of TRPCs. With 140 mmol/L CsCl in the pipette solution, application of negative pressures to the back of the pipette induced the activation of channels the open probability of which increased with the amount of negative pressure. The current-voltage relationship was linear in symmetrical ionic conditions, and the single-channel conductances for Cs + , K + , and Na + were 30, 36, and 27 pS, respectively. When NMDG + was substituted for Cs + in the pipette solution, inward currents were abolished, whereas outward currents remained active, indicating that the channels were nonselective to cations. The channel activity was blocked by intracellular Gd 3+ and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid and increased by diacylglycerol and by cyclopiazonic acid. Phospholipase C inhibitor (U73122) inhibited not only channel activity but also the development of myogenic tone induced by stretching of the basilar arteries. These results suggest that the ion channel responsible for the development of myogenic tone is the 30-pS mechanosensitive cation channel that exhibits properties similar to those of TRPCs.
Inhibition of hamster melanoma growth by estrogen.
Authors: Schleicher Rl, Hitselberger Mh, Beattie Cw
Journal: Cancer Research (1987)

A malignant hamster melanoma cell line HM-1 derived from the heterogenous malignant hamster melanoma MM1 contains a specific, high affinity binding protein for estrogens. Partial purification of the binding protein with ammonium sulfate (40% saturation) increased mean binding content (3.1 +/- 1.2 (SD) fmol/mg protein) 15-fold without any change in affinity (10(10) M-1). The binding protein sedimented at 8-9S on 10-30% low salt sucrose gradients and 9-10S in the presence of 20 mM molybdate ion. Addition of 0.4 M KCl shifted the 8S peak to 4S. Binding was specific, saturable, and indicative of a single class of high affinity sites over a concentration range of 0.01-10.0 nM [3H]estradiol. Estradiol produced a dose related inhibition of HM-1 growth in vitro without altering the growth of an additional line (HM-2) which did not bind estrogen. The antiestrogen tamoxifen (10(-7) M) also significantly inhibited HM-1 melanoma growth in vitro, which was reversed by the addition of estradiol (10(-9) M). HM-1 xenografts grew faster in female BALB/c-nu/nu mice than male mice while there was no sex difference in HM-2 growth. Pharmacological doses of estradiol and the antiestrogen nafoxidine significantly inhibited HM-1 growth without altering tumor incidence or latency. Our observations suggest that HM-1 cell lines bind estrogens specifically and with high affinity and that hamster melanoma cells positive for this binding protein respond to estrogen.
Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial
Authors: Richard Dodel, Axel Rominger, Peter Bartenstein, Frederik Barkhof, Kaj Blennow, Stefan Förster, Yaroslav Winter, Jan-Philipp Bach, Julius Popp, Judith Alferink, Jens Wiltfang, Katharina Buerger, Markus Otto, Piero Antuono, Michael Jacoby, Ralph Richter, James Stevens, Isaac Melamed, Jerome Goldstein, Stefan Haag, Stefan Wietek, Martin Farlow, Frank Jessen
Journal: The Lancet Neurology (2013)
Relationship Between Neck Circumference and Cardiometabolic Parameters in HIV-Infected and non–HIV-Infected Adults
Authors: Kathleen V. Fitch, Takara L. Stanley, Sara E. Looby, Alison M. Rope, Steven K. Grinspoon
Journal: Diabetes Care (2011)

OBJECTIVE Upper body fat is associated with increased cardiometabolic risk. More recently, neck circumference (NC) and/or neck fat have been associated with hyperlipidemia, impaired glucose homeostasis, and hypertension. The objective of this study was to determine whether this relationship is evident in HIV-infected individuals, who often exhibit changes in relative fat distribution, and to determine whether NC is independently associated with carotid intima-media thickness (cIMT) in HIV and non–HIV-infected patients. RESEARCH DESIGN AND METHODS Body composition, including anthropometrics, visceral adipose tissue assessment by CT, and metabolic parameters, including lipids, cIMT, and oral glucose tolerance test, were measured in 174 men and women with HIV infection and 154 non–HIV-infected subjects. NC was measured in triplicate inferior to the laryngeal prominence. RESULTS In univariate analysis, NC was significantly and positively related to blood pressure, hemoglobin A1c, glucose, and insulin and significantly and negatively related to HDL cholesterol in HIV-infected individuals and HIV-negative control subjects. NC was significantly associated with cIMT in univariate regression analysis among HIV-infected (r = 0.21, P = 0.006) and non–HIV-infected (r = 0.31, P = 0.0001) patients. This relationship remained significant among non–HIV-infected patients (R2 = 0.45, P &amp;lt; 0.001) but not HIV-infected patients in multivariate modeling controlling for age, sex, race, smoking hypertension, glucose, and lipids. CONCLUSIONS Among both HIV and non–HIV-infected patients, increased NC is strongly associated with decreased HDL and impaired glucose homeostasis. Among non–HIV-infected subjects, NC also predicts increased cIMT when controlling for traditional risk factors.
The Haves, the Have-Nots, and the Health of Everyone: The Relationship Between Social Inequality and Environmental Quality
Authors: Lara Cushing, Rachel Morello-Frosch, Madeline Wander, Manuel Pastor
Journal: Annual Review of Public Health (2015)

A growing body of literature suggests that more unequal societies have more polluted and degraded environments, perhaps helping explain why more unequal societies are often less healthy. We summarize the mechanisms by which inequality can lead to environmental degradation and their relevance for public health. We review the evidence of a relationship between environmental quality and social inequality along the axes of income, wealth, political power, and race and ethnicity. Our review suggests that the evidence is strongest for air- and water-quality measures that have more immediate health implications; evidence is less strong for more dispersed pollutants that have longer-term health impacts. More attention should be paid in research and in practice to links among inequality, the environment, and health, including more within-country studies that may elucidate causal pathways and points of intervention. We synthesize common metrics of inequality and methodological considerations in an effort to bring cohesion to such efforts.
Radiosensitivity Enhancement by Celecoxib, a Cyclooxygenase (COX)-2 Selective Inhibitor, via COX-2–Dependent Cell Cycle Regulation on Human Cancer Cells Expressing Differential COX-2 Levels
Authors: You Keun Shin, Ji Sun Park, Hyun Seok Kim, Hyun Jung Jun, Gwi Eon Kim, Chang Ok Suh, Yeon Sook Yun, Hongryull Pyo
Journal: Cancer Research (2005)

Abstract To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib ± radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib ± radiation. Prostaglandin E2 (PGE2) was applied to medium after treatment with celecoxib ± radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2–expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib ± radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2–overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G2-M arrest in the COX-2–overexpressing cells but further enhanced the radiation-induced G2-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2–overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.
N-methylpurine DNA glycosylase and DNA polymerase β modulate BER inhibitor potentiation of glioma cells to temozolomide
Authors: Jiang-bo Tang, David Svilar, Ram N. Trivedi, Xiao-hong Wang, Eva M. Goellner, Briana Moore, Ronald L. Hamilton, Lauren A. Banze, Ashley R. Brown, Robert W. Sobol
Journal: Neuro-Oncology (2011)

Temozolomide (TMZ) is the preferred chemotherapeutic agent in the treatment of glioma following surgical resection and/or radiation. Resistance to TMZ is attributed to efficient repair and/or tolerance of TMZ-induced DNA lesions. The majority of the TMZ-induced DNA base adducts are repaired by the base excision repair (BER) pathway and therefore modulation of this pathway can enhance drug sensitivity. N-methylpurine DNA glycosylase (MPG) initiates BER by removing TMZ-induced N3-methyladenine and N7-methylguanine base lesions, leaving abasic sites (AP sites) in DNA for further processing by BER. Using the human glioma cell lines LN428 and T98G, we report here that potentiation of TMZ via BER inhibition [methoxyamine (MX), the PARP inhibitors PJ34 and ABT-888 or depletion (knockdown) of PARG] is greatly enhanced by over-expression of the BER initiating enzyme MPG. We also show that methoxyamine-induced potentiation of TMZ in MPG expressing glioma cells is abrogated by elevated-expression of the rate-limiting BER enzyme DNA polymerase β (Polβ), suggesting that cells proficient for BER readily repair AP sites in the presence of MX. Further, depletion of Polβ increases PARP inhibitor-induced potentiation in the MPG over-expressing glioma cells, suggesting that expression of Polβ modulates the cytotoxic effect of combining increased repair initiation and BER inhibition. This study demonstrates that MPG overexpression, together with inhibition of BER, sensitizes glioma cells to the alkylating agent TMZ in a Polβ-dependent manner, suggesting that the expression level of both MPG and Polβ might be used to predict the effectiveness of MX and PARP-mediated potentiation of TMZ in cancer treatment.
Man's best friend? The effect of pet ownership on house dust microbial communities
Authors: Kei E. Fujimura, Christine C. Johnson, Dennis R. Ownby, Michael J. Cox, Eoin L. Brodie, Suzanne L. Havstad, Edward M. Zoratti, Kimberley J. Woodcroft, Kevin R. Bobbitt, Ganesa Wegienka, Homer A. Boushey, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2010)
Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas
Authors: DuyKhanh Pham, Mark G. Kris, Gregory J. Riely, Inderpal S. Sarkaria, Tiffani McDonough, Shaokun Chuai, Ennapadam S. Venkatraman, Vincent A. Miller, Marc Ladanyi, William Pao, Richard K. Wilson, Bhuvanesh Singh, Valerie W. Rusch
Journal: Journal of Clinical Oncology (2006)

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (&lt; 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit &lt; 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P &lt; .001) or stopped smoking less than 25 years ago (P &lt; .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.
Investigating and managing suspected pulmonary embolism in an outpatient setting: the Leicester experience
Authors: Y. Vali, R. Ladwa, E. Bailie, J. Bennett, C. Free
Journal: Thorax (2014)

Having established an ambulatory service for patients with suspected and proven PE, we reviewed our outcomes. All patients referred from June 2010 to May 2012 were analysed. Of 971 patients referred, 905 underwent complete assessment (66 admitted as ineligible). 754 (77.7%) patients were discharged and required no follow-up. 96 (10.6%) patients had PE confirmed of whom 70 (72.9%) were managed as outpatients. 14 (1.6%) patients have died since attending the clinic; no death was related to PE. This audit shows that ambulatory investigation and management of selected low risk patients with suspected PE is safe and reduces hospital admissions.
Pulmonary Tumors in Strain A Mice Given Injections of Aflatoxin B&lt;sub&gt;1&lt;/sub&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. Wieder, G. N. Wogan, Michael B. Shimkin
Journal: JNCI Journal of the National Cancer Institute (1968)

Aflatoxin B1 injected intraperitoneally in 12 thrice-weekly doses, for a total dose of 5.6 mg, produced an average of 5.6 primary pulmonary tumors in all of 14 strain A mice. The pulmonary tumor response is a useful quantitative bioassay method for studies on carcinogenesis with aflatoxins and related agents.