tbuckley/cabot-search huggingface dataset:
Abstract CSF1-2: Controversies in Screening for Breast Cancer
Authors: LJ Esserman
Journal: Cancer Research (2010)

Abstract Over the last 10 years, we have learned a great deal about breast cancer. We now know that all breast cancers are not the same. Whether defined by receptor status or molecular subtype, we now know that there is a range of growth rates and associated risk of metastases for each breast cancer subtype. It stands to reason then that the impact of screening is likely to be different for each breast cancer subtype. And of course, every woman is not the same, and consideration of both genetic predisposition and the context of competing health risks should play a role in optimizing screening strategies for women. The goal of this talk is to integrate these considerations with the observations on breast cancer incidence over the past 25 years since the advent of screening. The rise in the incidence of early stage disease, particularly for women over the age of 50, has not been accompanied by a commensurate decline in the incidence of regional cancers. Regional or more locally advanced cancers are more likely to present at younger ages, and as interval cancers. On the other hand, indolent disease is more likely to appear in women of older age. This knowledge helps us to understand how to better personalize screening recommendations and better understand the screening trial data and the differential impact by age as well as the US Preventive Services Task Force screening guidelines. The screening trials also reflect an era when systemic treatment was quite different than it is today. Moreover, recent data suggest that the impact of optimal systemic treatment reduces the impact of screening. Finally, we must take into account the fact that screening is more likely to detect indolent cancers (IDLE tumors) when they are present. These insights present opportunities to improve our approach to screening which may in turn reduce the burden of cancer and cancer diagnosis. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr CSF1-2.
P89 The Effect of Sample Handling on Viable Bacterial Community Profiles from Cystic Fibrosis Sputum Samples
Authors: TH Hafiz, LC Cuthbertson, AO Oliver, GB Rogers, KD Bruce, MP Carroll, CV van der Gast
Journal: Thorax (2012)

<h3>Introduction</h3> Obtaining accurate information on the composition of Cystic fibrosis (CF) lung infections is essential for the selection of appropriate therapy and maintenance of respiratory function. Whilst significant advances have been made using molecular techniques to provide such characterisation, there is a pressing need to identify the most appropriate sampling handling protocols. Here, we investigated the relationship between the time period prior to sample freezing and the bacterial community profiles. <h3>Methods</h3> Eleven sputum samples were collected from adult CF patients experiencing acute pulmonary exacerbations. Expectorated sputum was aliquoted into 12 equal portions, with one portion being frozen immediately and others transferred to –80°C at time points over a 72 hour period. Samples were treated with propidium monoazide prior to DNA extraction to limit analysis to viable bacterial cells. The bacterial composition of samples was determined by 16S rRNA gene Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling. Changes in bacterial community composition over the time course were then analysed using ecological statistical tools. <h3>Results</h3> A marked change in the bacterial community composition and abundance was observed within the first hour. Using Bray Curtis similarity index, a 51% similarity change in the bacterial community was observed in the first hour when compared to the sample frozen immediately. Thereafter, the bacterial community remained relatively stable for the following 72 hours (Figure 1A). Species cumulative richness showed an increase of approximately 63 new bacterial species over 72 hours, of which 25/63 (40%) emerged within the first hour. The mean sample richness also showed a significant increase in bacterial species within the first hour (Figure 1B). <h3>Conclusion</h3> The data presented indicates a significant change in sample bacterial composition within the first hour of sample collection. These findings have clear implications for the handling of samples for viable community profiling.
Glomerulopathy Associated with Cytomegalovirus Viremia in Renal Allografts
Authors: Walter P. Richardson, Robert B. Colvin, Sarah H. Cheeseman, Nina E. Tolkoff-Rubin, John T. Herrin, A. Benedict Cosimi, A. Bernard Collins, Martin S. Hirsch, Robert T. McCluskey, Paul S. Russell, Robert H. Rubin
Journal: New England Journal of Medicine (1981)

We investigated the relation between cytomegalovirus (CMV) infection and renal-allograft dysfunction in 14 patients. In seven instances (including two successive transplants in one patient), allograft dysfunction occurred during clinically manifest, viremic CMV infection. In five of these, biopsies revealed little or no tubulointerstitial change but a distinctive, diffuse glomerulopathy characterized by enlargement or necrosis of endothelial cells and accumulation of mononuclear cells and fibrillar material in glomerular capillaries. Two of these allografts recovered their function, both with cessation of high-dose immunosuppression. Biopsies in the other 10 patients revealed predominantly tubulointerstitial changes typical of cellular rejection, and most of these patients did not have viremia. One additional patient, studied prospectively, manifested both forms of allograft injury: tubulointerstitial changes occurring two weeks after transplantation and responding to increased immunosuppression, and CMV-associated glomerulopathy occurring seven weeks after transplantation and responding to decreased immunosuppression. We conclude that viremic CMV infection can cause acute glomerular injury and that recovery may be favored by a decreased in immunosuppressants.
Preliminary pharmacokinetic evaluation of Albuleukin; an interleukin-2 human serum albumin fusion protein, in solid tumor patients
Authors: Blaire L. Osborn, Mili Gu, Krzysztof J. Grzegorzewski, Theodore F. Logan, Kristin Crowder, Geoffrey R. Weiss, Samira Syed, Eric Rowensky, Anthony Tolcher, Sanjiv S. Agarwala, John Kirkwood, Ronald M. Bukowski, Patricia Weiss, Thomas Olencki, Robert Melder
Journal: Cancer Research (2004)

4757  Albuleukin is a novel therapeutic protein generated by the fusion of the human serum albumin and interleukin-2 genes. It was hypothesized that fusion to albumin would combine the short-acting but potent pharmacological activity of interleukin-2 and the favorable pharmacokinetic properties of albumin. Two Phase 1 clinical trials of Albuleukin are ongoing in patients with solid tumors. The objective of these studies is to determine the safety, tolerability, and pharmacokinetics of subcutaneously administered Albuleukin. In the first trial, doses of 2.0, 6.6, 22and 44 μg/kg of Albuleukin have been given every 2 weeks. In the second study, doses of 1.0, 3.3, 11 and 22 μg/kg have been administered weekly. Plasma samples for pharmacokinetic analysis were obtained at times out to one week following dosing. Plasma Albuleukin concentrations following the 1.0 μg/kg dose were below the 2 ng/mL limit of quantitation. Albuleukin was detectable in 4/5 patients given a 2.0 μg/kg dose, and in all patients at higher doses. Absorption of Albuleukin was prolonged with the Cmax occurring approximately 24-48 hours after dosing. The Cmax increased linearly with increasing dose, from a low of 6.4 ± 4.7 ng/mL after a 2.0 μg/kg dose to a high of 149 ± 76 ng/mL following a dose of 44 μg/kg. Plasma concentration curves suitable for calculation of terminal phase parameters were obtained following doses of 11, 22 and 44 μg/kg. The terminal half-life (t1/2) is 14 to 15 hours following the first SC dose of Albuleukin and is considerably longer than the reported 85-minute t1/2 for IV IL-2. The average mean residence time was between 46 and 50 hours. In most patients receiving more than one cycle of treatment, Cmax was 40-80% lower in the second and subsequent courses of Albuleukin than in the first course. Immunogenicity testing showed that subjects had not developed anti-Albuleukin antibodies that could account for the altered PK. Decreases in Cmax following multiple doses of IL-2 have been previously reported in the literature and were associated with increases in soluble IL-2 receptors. Increases in soluble IL-2 receptors have been observed following dosing with Albuleukin. The relationship between the decreased Albuleukin plasma concentrations and increased soluble IL-2 receptors will be further explored as more data become available.
USDA Publishes Parts One and Two of Animal Regulations
Authors: S. Kumar
Journal: JNCI Journal of the National Cancer Institute (1989)

USDA Publishes Parts One and Two of Animal Regulations Seema Kumar Seema Kumar Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 19, 4 October 1989, Page 1443, https://doi.org/10.1093/jnci/81.19.1443 Published: 04 October 1989
Abstract 115: KIR haplotype polymorphism determines innate susceptibility/resistance to childhood leukemia
Authors: Suzanne Samarani, Julie Nocq, Ossama Allam, Rim Marzouk, Richard.L Momparler, Ali Ahmad
Journal: Cancer Research (2012)

Abstract Background: The Killer-cell Immunoglobulin-like Receptor (KIR) genes encode receptors that are expressed on the surface of Natural Killer (NK) cells and a subset of T cells. The receptors regulate functional activities of these immune cells in the body. There exist seventeen distinct KIR genes in humans of which nine encode inhibitory, and six encode activating receptors, while two are pseudo genes. KIR haplotypes show extensive variability with respect to their repertoire of activating KIR genes. Humans may have none or up to six different activating KIR genes. The acquisition of these genes is believed to decrease activation threshold of NK cells in humans, and provide resistance to malignancy. Hypothesis: We hypothesized that the acquisition of activating KIR genes by an individual may protect him/her from childhood leukemia. Methods: We used the candidate gene approach. In a case-control study, we determined the presence or absence of different activating KIR genes using gene-specific primer pairs. The frequencies of each gene were compared between cases and controls using Chi2 test and multivariate logistic regression. Results: Our results show for the first time that the inheritance of activating KIR genes is associated with increased resistance to childhood leukemia (both B-ALL and T-ALL; in adjusted analysis p-values being as low as 1.14x10-7). Interestingly, this resistance increased as the number of activating KIR genes increased in the genome of the individual. Furthermore, we found that that this resistance/susceptibility is differentially modulated by co-inheritance of different inhibitory KIR-MHC class I gene pairs. Conclusions: The inheritance of activating KIR gene-containing haplotypes confers innate resistance to childhood leukemia. These receptors may serve as novel target molecules for therapeutic interventions in childhood leukemia. The study was supported by a research grant (≠2010-700554) from the Canadian Cancer Society Research Institute (CCSRI). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 115. doi:1538-7445.AM2012-115
Today's Trends in Medical Education
Authors: Dwight O'Hara
Journal: New England Journal of Medicine (1950)

YOUR kind invitation to talk this evening about today's trends in medical education was one I was happy to accept — not because I have any pet convictions to fan, but rather because I hoped an attempt to organize my own thoughts on the subject might be profitable. When one spends most of his time in the administrative details of a medical school, the opportunity to come up for air should be seized with gratitude, and I can think of no place in which I would rather come up for air than here in Worcester.Worcester has always been a . . .
AB0004 HLA association of behçet’s disease in HLA-B*51negative german and turkish patients
Authors: A. Kuranov, F. Riewerts, I. Kötter, J. Gamper-Tsigaras, I. Steiert, C.A. Müller
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Behçet’s disease (BD) as systemic vasculitis of unknown etiology is associated with HLA-B*51 in different European and Asian populations. HLA-A*26 was claimed as additional BD susceptibility marker in Japanese and Greek patients independent of HLA-B*51. This study was performed to test for HLA-A associations in German and Turkish BD populations. HLA-B*51 negative BD patients were compared with respective control populations. <h3>Methods</h3> 62 German and 44 Turkish patients lacking HLA-B*51 were analyzed in comparison to healthy German (N=1500) and Turks (N=77) negative for B*51. HLA-A/B genotypes were determined by SSOP (Luminex Corp.) Fisher’s exact test and Odds ratio (OR) were used for statistical evaluation. <h3>Results</h3> HLA-A*26 was significantly more frequent in German patients (14.52% patients vs. 5.9% healthy Germans, chi-square =6,07, OR =2,69, p&lt;0.0137). When individuals carrying a second Bw4+ HLA-B locus allele were excluded from this analysis, HLA-A*26 association with BD was no longer observed. Frequency of HLA-Bw4+ (HLA-A and B alleles) alleles, however, was significantly different in German B*51 negative BD patients versus controls (patients vs. controls: 72.6% vs. 54.5%, chi-square =7,18, OR =2,21, p&lt;0.0058).In addition a significant decrease in the frequency of HLA-A*03 was observed in German BD patients (patients vs. controls: 14.5% vs. 30.1%, chi-square =6,20, OR =0,39, p&lt;0.0127).No significant association of any of the tested HLA-A alleles nor of the HLA-Bw4 determinant in B*51 negative Turkish patients was seen. <h3>Conclusions</h3> Although B*51 negative German BD patients showed an association with HLA-A*26 as in Japanese and Greek, this appeared to reflect a higher frequency of Bw4<sup>+</sup>alleles inherited in linkage. Thus, stronger association with HLA-Bw4 in the B*51 negative Germans may indicate relevance in BD pathogenesis. A protective factor may be inherited in association with HLA-A*03 in Germans. No BD association to HLA-A alleles was detected in Turks, possibly due to the low numbers of patients analyzed. <h3>Disclosure of Interest</h3> A. Kuranov Grant/Research support from: DAAD, F. Riewerts: None Declared, I. Kötter: None Declared, J. Gamper-Tsigaras: None Declared, I. Steiert: None Declared, C. Müller: None Declared
FRI0073 Recent, Common Infections Are Associated with Decreased Risk of Rheumatoid Arthritis
Authors: M.E. Sandberg, L. Klareskog, L. Alfredsson, S. Saevarsdottir
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> A hypothesis has been put forward that infections may trigger the clinical onset of rheumatoid arthritis (RA), although the underlying evidence is sparse. <h3>Objectives</h3> We asked whether recent, common infections affect the risk of RA. <h3>Methods</h3> We used the population-based case-control study EIRA on incident RA, matched for sex, age and county of residence. In total, 6401 participants completed a questionnaire regarding infections during the 2 years before diagnosis. Conditional logistic regression was used to calculate odds ratios (OR), adjusting for smoking and socioeconomic status. <h3>Results</h3> Infections in the gastrointestinal and urogenital tract before clinical onset were associated with a lowered risk of RA: gastroenteritis (OR=0.71 [95%CI: 0.63-0.80]) urinary tract infections (OR=0.78 [95%CI: 0.68-0.90]) and genital infections (OR=0.80 [95%CI: 0.64-1.00]), while a non-significant association of similar magnitude was observed for the less common prostatitis (OR=0.64 [95%CI: 0.38-1.08]). An even lower risk was observed for those who had experienced both gastrointestinal and urogenital infections (OR=0.50 (95%CI:0.32-0.79). In striking contrast, no association was observed for upper respiratory infections (sinusitis, tonsillitis) or infections in the teeth/gum (OR=0.96 [95%CI: 0.82-1.13], 0.99 [95% CI: 0.86-1.14] and 1.10 [95%CI: 0.96-1.26], respectively). Gastroenteritis was significantly associated with a lowered risk of both ACPA-positive and ACPA-negative RA, while the lowered risk associated with urogenital infections, despite no statistically significant interactions, was more pronounced in the ACPA-positive subset. <h3>Conclusions</h3> Gastrointestinal and urogenital infections, but not respiratory infections, are associated with a lowered risk of RA. Thus, our findings do not support the notion that common infections trigger RA onset. Perhaps, this reflects strong immune defenses in RA patients, that make them less vulnerable for infections but prone to develop autoimmune reactions. That fact that the infections are protective speaks against recall bias in the study. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4450
TCTAP C-044 The Reality PF Intervention Cardiologist. How Did I Treat Bifurcation and Chronic Total Occlusion?
Authors: Mohammad Golam Azam, Kazi Md Zafrul Haq, Jafrin Jahan, Md Badiuzzaman, Jatindra Nath Saha
Journal: Journal of the American College of Cardiology (2015)
Quantitative Serologic Tests for Syphilis
Authors: Albert Heyman
Journal: New England Journal of Medicine (1945)

QUANTITATIVE serologic tests for syphilis have become more widely used in recent years following the introduction of intensive methods of syphilotherapy. These tests not only are useful in methods of rapid treatment but are often of considerable value in the management of various problems encountered in the diagnosis of syphilis.1 , 2 It is the purpose of this report to discuss the indications for quantitative serologic testing and to illustrate how these tests, when used judiciously, may aid greatly in the recognition of certain manifestations occurring in syphilitic infection.The quantitative titer of syphilitic serum may be determined by several methods. The . . .
Meeting the Growing Need for Heroin Addiction Treatment
Authors: Richard S. Schottenfeld, Stephanie S. O’Malley
Journal: JAMA Psychiatry (2016)

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Abortion and Maternal Mortality in Africa
Authors: Patrick Thonneau, Nathalie Goyaux, Segbegnon Goufodji, Johanne Sundby
Journal: New England Journal of Medicine (2002)

To the Editor: The World Health Organization (WHO) estimates that 5 million unsafe abortions are performed annually in Africa, resulting in the deaths of an estimated 34,000 women.1 In Africa, abor...
Hepatocellular Carcinoma in Italian Patients with Cirrhosis
Authors: Massimo Colombo, Roberto de Franchis, Ersilio Del Ninno, Angelo Sangiovanni, Cristina De Fazio, Maurizio Tommasini, M. Francesca Donato, Anna Piva, Valerio Di Carlo, Nicola Dioguardi
Journal: New England Journal of Medicine (1991)

Patients with cirrhosis of the liver are recognized as being at risk for hepatocellular carcinoma. The magnitude of the risk, the natural history of this disease, and the possibilities for detecting potentially curable tumors in patients in the Western world are unknown. To address these questions, we examined 447 Italian patients with well-compensated cirrhosis (which was of viral origin in 62 percent of them) from 1985 through 1990, performing serum alpha-fetoprotein assays and real-time ultrasonography every 3 to 12 months.Hepatocellular carcinoma was found in 30 patients (7 percent) at base line and in another 29 patients (7 percent of 417 patients free of tumor at base line) during follow-up periods averaging 33 months (range, 1 to 48). The cumulative hazard of the development of hepatocellular carcinoma during follow-up was higher among patients with persistently elevated serum alpha-fetoprotein levels (12 with tumors among 42 with such levels) than among those with fluctuating levels (11 among 82) or those with consistently normal levels (6 among 255). Only 17 patients had potentially operable tumors. The proportion of potentially operable tumors among those detected during follow-up was significantly lower than the proportion at enrollment (4 of 29 vs. 13 of 30, P = 0.027). The survival at one year of the 12 patients who underwent surgery was 67 percent, and the tumor-recurrence rate was 60 percent. Outcome was not appreciably different for the five patients who refused surgery.In the West, as in Asia, patients with cirrhosis of the liver are at substantial risk for hepatocellular carcinoma, with a yearly incidence rate of 3 percent. Our screening program did not appreciably increase the rate of detection of potentially curable tumors.