tbuckley/cabot-search huggingface dataset:
Polymorphisms in DNA Repair Genes, Smoking, and Pancreatic Adenocarcinoma Risk
Authors: Robert R. McWilliams, William R. Bamlet, Julie M. Cunningham, Ellen L. Goode, Mariza de Andrade, Lisa A. Boardman, Gloria M. Petersen
Journal: Cancer Research (2008)

Base excision repair and nucleotide excision repair are vital responses to multiple types of DNA damage, including damage from tobacco exposure. Single-nucleotide polymorphisms (SNP) in these pathways may affect DNA repair capacity and therefore influence risk for cancer development. We performed a clinic-based, case-control study comprising 481 consecutive patients with confirmed pancreatic adenocarcinoma and 625 healthy controls. Allele and genotype frequencies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared after adjusting for age, sex, and smoking history. Subgroup analysis by sex and smoking history was performed. Carriers of one or two XPF/ERCC4 minor alleles at R415Q had decreased risk of pancreatic adenocarcinoma compared with those who had two major alleles [odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40-0.85]. Heavy smokers (>40 pack-years) had increased risk for cancer if they were carriers of at least one minor allele for XPD/ERCC2 at D312N (OR, 2.78; 95% CI, 1.28-6.04) or D711D (OR, 2.19; 95% CI, 1.01-4.73). No other significant differences in risk were identified. Minor alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreatic cancer.
Patient-Reported Outcomes and Survivorship in Radiation Oncology: Overcoming the Cons
Authors: Farzan Siddiqui, Arthur K. Liu, Deborah Watkins-Bruner, Benjamin Movsas
Journal: Journal of Clinical Oncology (2014)

Although patient-reported outcomes (PROs) have become a key component of clinical oncology trials, many challenges exist regarding their optimal application. The goal of this article is to methodically review these barriers and suggest strategies to overcome them. This review will primarily focus on radiation oncology examples, will address issues regarding the "why, how, and what" of PROs, and will provide strategies for difficult problems such as methods for reducing missing data. This review will also address cancer survivorship because it closely relates to PROs.Key articles focusing on PROs, quality of life, and survivorship issues in oncology trials are highlighted, with an emphasis on radiation oncology clinical trials. Publications and Web sites of various governmental and regulatory agencies are also reviewed.The study of PROs in clinical oncology trials has become well established. There are guidelines provided by organizations such as the US Food and Drug Administration that clearly indicate the importance of and methodology for studying PROs. Clinical trials in oncology have repeatedly demonstrated the value of studying PROs and suggested ways to overcome some of the key challenges. The Radiation Therapy Oncology Group (RTOG) has led some of these efforts, and their contributions are highlighted. The current state of cancer survivorship guidelines is also discussed.The study of PROs presents significant benefits in understanding and treating toxicities and enhancing quality of life; however, challenges remain. Strategies are presented to overcome these hurdles, which will ultimately improve cancer survivorship.
Phase I Clinical Trial of Ds-7423, an Oral Pi3K/Mtor Dual Inhibitor, in Japanese Patients with Advanced Solid Tumors
Authors: T. Yokota, T. Tsushima, H. Kenmotsu, J. Watanabe, M. Endo, Y. Hirashima, T. Takahashi, H. Murakami, T. Naito, T. Taira, A. Ono, K. Wakuda, A. Todaka, K. Kunieda, T. Jikoh, Y. Nakao, R. Shiga, H. Yasui
Journal: Annals of Oncology (2014)
The dual action of ozone on the skin
Authors: G. Valacchi, V. Fortino, V. Bocci
Journal: British Journal of Dermatology (2005)

The aim of this brief review is to summarize the recent literature on the effect of ozone (O3) on cutaneous tissues. Recently it has been reported that a chronic contact with O3 can be deleterious for the skin. Our group and others have shown a progressive depletion of antioxidant content in the stratum corneum and this can then lead to a cascade of effects resulting in an active cellular response in the deeper layers of the skin. Using an in vivo model we have shown an increase of proliferative, adaptive and proinflammatory cutaneous tissue responses. On the other hand the well known activity of O3 as a potent disinfectant and oxygen (O2) donor has been also studied for therapeutic use. Two approaches have been described. The first consists of a quasi-total body exposure in a thermostatically controlled cabin. This treatment has proved to be useful in patients with chronic limb ischaemia. The second approach is based on the topical application of ozonated olive oil in several kinds of skin infection (from soreness to diabetic ulcers, burns, traumatic and surgical wounds, abscesses and skin reactions after radiotherapy). We and other authors have observed a striking cleansing effect with improved oxygenation and enhanced healing of these conditions. It is now clear that, on the skin, O3, like other drugs, poisons and radiation, can display either a damaging effect from a long exposure or a beneficial effect after a brief exposure to O2 and O3 or to the application of ozonated oil to chronic wounds.
A SCID-hu in vivo model of human Waldenström macroglobulinemia
Authors: Pierfrancesco Tassone, Paola Neri, Jeffery L. Kutok, Olivier Tournilhac, Daniel Ditzel Santos, Evdoxia Hatjiharissi, Vidit Munshi, Salvatore Venuta, Kenneth C. Anderson, Steven P. Treon, Nikhil C. Munshi
Journal: Blood (2005)
Custodianship of Genetic Information: Clinical Challenges and Professional Responsibility
Authors: Annette R. Patterson, Linda D. Robinson, Elizabeth Z. Naftalis, Barbara B. Haley, Gail E. Tomlinson
Journal: Journal of Clinical Oncology (2005)

A 34-year-old patient was diagnosed with breast cancer during her second trimester of pregnancy. Her mother had died of ovarian cancer, diagnosed at age 49 years, after surviving breast cancer diagnosed at age 31 years. The patient was originally seen by genetic specialists during treatment, but opted to defer testing for possible mutation of BRCA1 or BRCA2 until a later date. Hospitalized 1 year later with rapidly progressing metastases, the patient then requested genetic testing for the future benefit of her two children, then 8 months and 5 years old. Testing revealed a deleterious mutation in the BRCA1 gene, which greatly increases the risk of developing breast and ovarian cancer in women, and is inherited in an autosomal dominant fashion. The patient died before receiving results.
Inability to Predict Mammary Tumorigenesis in Strain A Mice From Presence of Mammary Tumor Virus or Antigen in the Milk
Authors: W E Heston, W T Hall, G Vlahakis, J Charney, D H Moore
Journal: JNCI Journal of the National Cancer Institute (1970)

Strain A females were milked and their milk was tested for mammary tumor virus (MTV) by the hyperplastic alveolar nodule test and for MTV antigen by microimmunodiffusion. An attempt was made to correlate these results with later occurrence of mammary tumors in the females. There was not full agreement between the results of the test for the presence of the MTV and those of the test for MTV antigen, and from these results it was impossible to predict accurately whether a specific female would later develop a tumor. It is concluded that, in this strain, factors other than the MTV can be the determinant in whether the individual female will develop a tumor.
Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study
Authors: Meletios Dimopoulos, David S Siegel, Sagar Lonial, Junyuan Qi, Roman Hajek, Thierry Facon, Laura Rosinol, Catherine Williams, Hilary Blacklock, Hartmut Goldschmidt, Vania Hungria, Andrew Spencer, Antonio Palumbo, Thorsten Graef, Joseph E Eid, Jennifer Houp, Linda Sun, Scott Vuocolo, Kenneth C Anderson
Journal: The Lancet Oncology (2013)
Abdominal Visceral Adiposity in the First Trimester Predicts Glucose Intolerance in Later Pregnancy
Authors: Aisling Mary Martin, Howard Berger, Rosane Nisenbaum, Andrea Y. Lausman, Sharon MacGarvie, Carrie Crerar, Joel G. Ray
Journal: Diabetes Care (2009)

To assess whether abdominal adiposity in early pregnancy is associated with a higher risk of glucose intolerance at a later gestational stage.Subcutaneous and visceral fat was measured with ultrasonography at approximately 12 weeks' gestation. A 50-g glucose challenge test (GCT) was performed between 24 and 28 weeks' gestation. The risk of having a positive GCT (>or=7.8 mmol/l) was determined in association with subcutaneous and visceral adipose tissue depths above their respective upper-quartile values relative to their bottom three quartile values.Sixty-two women underwent GCTs. A visceral adipose tissue depth above the upper quartile value was significantly associated with a positive GCT in later pregnancy (adjusted odds ratio 16.9 [95% CI 1.5-194.6]). No associations were seen for subcutaneous adipose tissue.Measurement of visceral adipose tissue depth in early pregnancy may be associated with glucose intolerance later in pregnancy.
An Exponential Dispersion Model for the Distribution of Human Single Nucleotide Polymorphisms
Authors: W. S. Kendal
Journal: Molecular Biology and Evolution (2003)

An analysis of 1.42 million human single nucleotide polymorphisms (SNPs), mapped by the International SNP Map Working Group, revealed an apparent power function relationship between the estimated variance and mean number of SNPs per sample bin. This relationship could be explained by the assumption that a scale invariant Poisson gamma (PG) exponential dispersion model could describe the distribution of SNPs within the bins. In this model the sample bins would contain random (Poisson distributed) numbers of identical by descent genomic segments, each with independently distributed and gamma distributed numbers of SNPs. This model was both qualitatively and quantitatively consistent with the conventional coalescent model. It agreed with the empirical cumulative distribution functions derived from the SNP maps as well as with simulated data. The model was used to estimate the heterozygosity π, and the mean number and size of haplotype blocks for each chromosome. These estimates were consistent with measurements from conventional studies. This PG model thus provides an alternative to Monte Carlo simulation for description of the distribution of SNPs.
Prognostic Value of Dobutamine-Atropine Stress Myocardial Perfusion Imaging in Patients With Diabetes
Authors: Arend F.L. Schinkel, Abdou Elhendy, Ron T. van Domburg, Jeroen J. Bax, Eleni C. Vourvouri, Fabiola B. Sozzi, Roelf Valkema, Jos R.T.C. Roelandt, Don Poldermans
Journal: Diabetes Care (2002)

OBJECTIVE—Exercise tolerance in patients with diabetes is frequently impaired due to noncardiac disease such as claudication and polyneuropathy. This study assesses the prognostic value of dobutamine stress myocardial perfusion imaging in patients with diabetes. RESEARCH DESIGN AND METHODS—A total of 207 consecutive diabetic patients who were unable to undergo exercise stress testing underwent dobutamine-atropine stress myocardial perfusion imaging. Follow-up was successful in 206 of 207 (99.5%) patients. A total of 12 patients underwent early (&amp;lt;60 days) revascularization and were excluded from the analysis. End points during follow-up were hard cardiac events, defined as cardiac death and nonfatal myocardial infarction. RESULTS—Abnormal myocardial perfusion was detected in 125 (64%) patients. During 4.1 ± 2.4 years of follow-up, 73 (38%) deaths occurred, 36 (49%) of which were due to cardiac causes. Nonfatal myocardial infarction occurred in 7 (4%) patients, and 45 (23%) patients underwent late coronary revascularization. Cardiac death occurred in 2 of 69 (3%) patients with normal myocardial perfusion and in 34 of 125 (27%) patients with perfusion abnormalities (P &amp;lt; 0.0001). A multivariable Cox proportional hazard model demonstrated that, in addition to clinical and stress test data, an abnormal scan had an incremental prognostic value for prediction of cardiac death (hazard ratio 7.2, 95% CI 1.7–30). The summed stress score was an important predictor of cardiac death; the hazard ratio was 1.2 (95% CI 1.07–1.34) per one-unit increment. CONCLUSIONS—Dobutamine-atropine stress myocardial perfusion imaging provides additional prognostic information incremental to clinical data in patients with diabetes who are unable to undergo exercise stress testing.
Carcinoma of the lung in Lancashire coalminers.
Authors: G B Rooke, F G Ward, A N Dempsey, J B Dowler, C J Whitaker
Journal: Thorax (1979)

The prevalence at death of carcinoma of the lung in miners and ex-miners has been compared in those with and without pneumoconiosis at necropsy. The prevalence of 11.4% in the group as a whole is no greater than that in the male population in North-west England. Carcinoma of the lung was present in 62 (13.1%) of those without pneumoconiosis and in 52 (9.8%) of those with pneumoconiosis. The mean age at death of those with pneumoconiosis was 71.3 years so that they cannot be said to have died before the age at which they would have developed carcinoma. Those with progressive massive fibrosis whose mean age at death was 72 years had the lowest prevalence of carcinoma of the lung at all ages--8.4%. For reasons stated in the text this is inevitably a biased sample. The number of those without pneumoconiosis is probably lower than the true figure because the deaths of miners and ex-miners in whom there is no suspicion of lung disease may not have been reported to the coroner or to the pneumoconiosis medical panel. There appears to be no positive link between carcinoma of the lung and pneumoconiosis. There is a surprisingly high number of smokers and ex-smokers among these miners, and this appears to have more relevance to the prevalence of carcinoma of the lung than does pneumoconiosis.
STUDIES ON THE COLLAGEN AND ELASTIN CONTENT OF THE HUMAN LUNG*†
Authors: John A. Pierce, Joe B. Hocott
Journal: Journal of Clinical Investigation (1960)

Connective tissues are important to the struc- ture of all organs.Because ventilation imposes mechanical stress, the lungs are perhaps more de- pendent on connective tissue proteins for the main- tenance of normal structure than are other vital organs.Surprisingly, the quantities of fibrous proteins in the lungs had not been measured un- til recently (1, 2).The purpose of this study was to determine the collagen and elastin content of human lungs.Variations in the age and sex of the subjects have been correlated with the findings. MATERIAL AND METHODSThe right middle lobe was studied because it is an easily identified and complete unit of lung, and its size is convenient.The specimens were obtained at autopsy from subjects who did not die of diseases primarily in- volving the lungs.The right middle lobe bronchus was transected just proximal to its initial bifurcation leaving minimal hilar material attached to the specimen.Lobes were rejected if obvious parenchymal disease was present or if there was gross thickening of the pleura.The samples were stored at -40 C.Measurements of collagen and elastin followed the tech- nique of Lowry, Gilligan and Katersky (3).In brief, this procedure is gravimetric and depends upon the insolu- ble nature of the fibrous proteins.Finely divided tissue is extracted at room temperature in 0.1 N sodium hy- droxide solution, alcohol-ether and ether.The con- stant dry weight of residue is obtained after separation in the centrifuge.Collagen is then converted to a solu- ble form with heat in the presence of water.The insolu- ble residue is again separated and dried to constant weight.Extraction is then carried out in 0.1 N sodium hydroxide solution in a boiling water bath.The residual material (elastin) is washed and its dry weight obtained.It has been necessary to modify this method for use with lung tissue.Instead of being finely minced, the tissue
Hepatitis D virus RNA in acute delta infection: Serological profile and correlation with other markers of hepatitis D virus infection
Authors: Maria Buti, Rafael Esteban, Michael Roggendorf, Juan Fernandez, Rosendo Jardi, Rudolf Rashofer, Helena Allende, Juan Genesca, Juan Ignacio Esteban, Jaime Guardia
Journal: Hepatology (1988)

To evaluate the profile of hepatitis D virus replication and the corresponding immunoresponse after acute hepatitis D virus infection, sera from 50 patients with acute hepatitis D (36 with acute hepatitis B virus-hepatitis D virus coinfection and 14 HBsAg carriers with hepatitis D virus superinfection) were investigated for the presence of hepatitis D virus RNA and other serological hepatitis D virus markers. During the first week after onset of symptoms, hepatitis D virus RNA was detected by spot hybridization with a similar frequency among patients with coinfection (64%) and those with super-infection (71%). The presence of hepatitis D virus RNA in the first serum sample correlated with that of circulating hepatitis D antigen in both groups of patients. The presence of hepatitis D virus RNA was transient and its clearance paralleled that of serum hepatitis D antigen among patients with coinfection, so that 1 month after the onset of symptoms serum hepatitis D virus RNA was no longer detectable in any of these patients. Conversely, serum hepatitis D virus RNA was still present in 78% of those with superinfection, all of whom developed chronic liver disease, thus suggesting that the persistence of hepatitis D virus RNA in the serum for more than 4 weeks might indicate progression to chronicity. In nine of the 14 patients (64%) with hepatitis D virus superinfection progressing to chronicity, hepatitis D virus RNA was persistently detected throughout the follow-up, whereas in five patients it was detected occasionally. In four superinfected patients hepatitis D virus RNA and hepatitis B virus DNA were detected simultaneously in serial samples, thus suggesting that, at least during early stages of chronic hepatitis D virus infection, both viruses may replicate at the same time.
Improved Response in High-Risk Neuroblastoma With Protracted Topotecan Administration Using a Pharmacokinetically Guided Dosing Approach
Authors: Victor M. Santana, Wayne L. Furman, Catherine A. Billups, Fredric Hoffer, Andrew M. Davidoff, Peter J. Houghton, Clinton F. Stewart
Journal: Journal of Clinical Oncology (2005)

To estimate the response rate and toxicity associated with intravenous topotecan when it is administered on a protracted schedule according to a pharmacokinetically guided dosing approach to treat childhood high-risk neuroblastoma.In this prospective phase II trial, topotecan was administered intravenously daily for 5 days for each of 2 consecutive weeks for two cycles. On the basis of topotecan systemic clearance, doses were individualized to attain a single-day topotecan lactone area under the plasma concentration-time curve (AUC) of 80 to 120 ng/mL . h. Patients subsequently received standard treatment.Both cycles were administered to 28 (93%) of the 30 enrolled patients (median age, 3.1 years). Target topotecan AUCs were achieved in 92 (72%) of the 127 measurements conducted after pharmacokinetically guided adjustment; the median dosage required to achieve target AUCs was 2.7 mg/m(2) (range, 0.95 to 3.8 mg/m(2)). The response rate was 60% (95% CI, 41% to 77%); there were one complete and 17 partial responses. No patient experienced disease progression during initial topotecan therapy. Primary tumor volumes decreased (median decrease, -58.2%; range, -95.1% to -4.9%) in the 26 patients with available size data. Homovanillic acid levels in 16 (89%) of 18 patients and vanillylmandelic acid levels in 14 (78%) of 18 patients were lower (P = .002 and P = .018, respectively) after topotecan therapy. Reversible grade 4 myelosuppression occurred in all patients, but no deaths occurred as a result of infection or toxicity.Topotecan is active against neuroblastoma when it is administered on a protracted schedule and targeted systemic exposure is achieved.
Near-infrared fluorescence tumor imaging using nanocarrier composed of poly(l-lactic acid)-block-poly(sarcosine) amphiphilic polydepsipeptide
Authors: Akira Makino, Shinae Kizaka-Kondoh, Ryo Yamahara, Isao Hara, Tatsuya Kanzaki, Eiichi Ozeki, Masahiro Hiraoka, Shunsaku Kimura
Journal: Biomaterials (2009)
Urgent endoscopy in lower gastrointestinal bleeding
Authors: J L H WONG
Journal: Gut (2001)

<b><i>Objective:</i></b> To evaluate whether the major histocompatibility complex contains susceptibility genes for carbamazepine hypersensitivity. Carbamazepine hypersensitivity is immune-mediated, although factors determining its occurrence and severity are unknown. <b><i>Methods:</i></b> Using PCR in 60 carbamazepine-hypersensitive patients, 37 with nonserious (Group I) and 23 with serious (Group II) reactions, and 313 control subjects (63 patients on carbamazepine without adverse effects and 250 healthy volunteers), the association with polymorphisms in the promoter region of the tumor necrosis factor α (TNFα) gene (positions −308 and −238), and with HLA-DR3 and -DQ2 was determined. <b><i>Results:</i></b> The frequency of the variant allele (<i>TNF2</i>) at the −308 position was increased in Group II but not Group I carbamazepine-hypersensitive patients compared with all control subjects (<i>p</i> = 0.01; OR = 2.4), as was the frequency of HLA-DR3 (<i>p</i> = 0.01; OR = 3.3), HLA-DQ2 (<i>p</i> = 0.04; OR = 2.7), and the TNF2-DR3-DQ2 haplotypes (<i>p</i> = 0.02; OR = 3.2). None of the alleles were independently associated with serious carbamazepine hypersensitivity. For the −238 polymorphism, there was a difference in the genotype, but not in the allelic, frequencies between Group II hypersensitive patients and all control subjects. <b><i>Conclusions:</i></b> The <i>TNF2</i> allele was associated with severe, but not nonserious, carbamazepine hypersensitivity reactions, suggesting that hypersecretion of tumor necrosis factor α may be a determinant of the severity of tissue damage. However, the association of the <i>TNF2</i> allele with carbamazepine hypersensitivity was not independent of HLA-DR3 and -DQ2, and therefore the possibility that it constitutes a passive component of the TNF2-DR3-DQ2 haplotype cannot be excluded.
Vitamin D deficiency is common in patients with RA and linked to disease activity, but circulating levels are unaffected by TNFα blockade: results from a prospective cohort study
Authors: Paul Welsh, Mike J L Peters, Iain B McInnes, Willem F Lems, Paul T Lips, Gayle McKellar, Susan Knox, A Michael Wallace, Ben A C Dijkmans, Michael T Nurmohamed, Naveed Sattar
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Abstract</h3> <b>Objective</b> To determine the validity of two written screening questions for depression with the addition of a question inquiring if help is needed. <b>Design</b>Cross sectional validation study. <b>Setting</b> 19 general practitioners in six clinics in New Zealand. <b>Participants</b> 1025 consecutive patients receiving no psychotropic drugs. <b>Main outcome measures</b> Sensitivity, specificity, and likelihood ratios of the two screening questions, the help question, combinations of the screening and help questions, and diagnosis by general practitioners. <b>Results</b> The help question alone had a sensitivity of 75% (95% confidence interval 60% to 85%) and a specificity of 94% (93% to 96%). The positive likelihood ratio for the help question was 13.0 (9.5 to 17.8) and the negative likelihood ratio was 0.27 (0.17 to 0.44). The likelihood ratio for patients wanting help today was 17.5 (11.8 to 31.9). The general practitioner diagnosis had a sensitivity of 79% (65% to 88%) and a specificity of 94% (92% to 95%). <b>Conclusion</b> Adding a question inquiring if help is needed to the two screening questions for depression improves the specificity of a general practitioner diagnosis of depression.