tbuckley/cabot-search huggingface dataset:
Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data
Authors: H. Ali, B. Donovan, H. Wand, T. R. H. Read, D. G. Regan, A. E. Grulich, C. K. Fairley, R. J. Guy
Journal: BMJ (2013)

<b>Objective</b> To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. <b>Design</b> Trend analysis of national surveillance data. <b>Setting</b> Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. <b>Participants</b> Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. <b>Main outcome measure</b> Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). <b>Results</b> Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period—from 11.5% in 2007 to 0.85% in 2011 (P&lt;0.001) and from 11.3% in 2007 to 3.1% in 2011 (P&lt;0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period—from 12.1% in 2007 to 2.2% in 2011 (P&lt;0.001) and from 18.2% in 2007 to 8.9% in 2011 (P&lt;0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. <b>Conclusions</b> The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.
Five-Year Safety and Efficacy of Belatacept in Renal Transplantation
Authors: Flavio Vincenti, Gilles Blancho, Antoine Durrbach, Peter Friend, Josep Grinyo, Philip F. Halloran, Jurgen Klempnauer, Philippe Lang, Christian P. Larsen, Ferdinand Mühlbacher, Björn Nashan, Jean-Paul Soulillou, Yves Vanrenterghem, Thomas Wekerle, Mamta Agarwal, Sheila Gujrathi, Jinshan Shen, Rebecca Shi, Robert Townsend, Bernard Charpentier
Journal: Journal of the American Society of Nephrology (2010)

Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.
A NEW METHOD FOR THE ENUMERATION OF ANTIGEN-REACTIVE CELLS RESPONSIVE TO A PURIFIED PROTEIN ANTIGEN
Authors: W. D. Armstrong, E. Diener
Journal: The Journal of Experimental Medicine (1969)

A new technique for the enumeration of antigen-reactive cells (ARC) responsive to the polymer antigen of S. adelaide flagellin (POL) is described for two strains of mice. Foci have been shown to be antibody dependent, may be mimicked by IgM as well as IgG antibodies, and contain specific antibody-forming cells (AFC). The use of POL offers a system unencumbered by relatively high numbers of background foci which, when present, appear to be basically different from those found using the SRBC antigen. The response of 1 antigen-reactive cell (ARC) focus/1 x 10(6) CBA(T6T6) mouse spleen cells is linearly related to the injected number between 1 x 10(6)-3 x 10(6) donor spleen cells and since 5% of injected cells remain in the spleen, there are an estimated 2400 ARC/spleen. The number of ARC foci does not increase significantly after the 5th postantigen day, and by the 8th day the AFC progeny of ARC have reached the maximum mean of 280 AFC/ARC focus. In response to increasing antigen concentrations, an initial rise in the number of AFC as well as ARC is observed, resulting in a relatively constant AFC/ARC ratio. This suggests that the number of ARC stimulated determines the total number of AFC produced under these conditions rather than a variable mitotic rate of the ARC offspring. The main significance of this technique is that it will allow a study of the kinetics of the ARC in the primary and secondary immune response as well as in immunological tolerance.
AMPHETAMINE SULFATE IN ABORTING THE ACUTE ALCOHOLIC CYCLE
Authors: MICHAEL M. MILLER
Journal: American Journal of Psychiatry (1944)

1. Fifty-six patients were treated with amphetamine sulfate during the early post-intoxication period of the acute alcoholic cycle. The cycle was interrupted in 49 cases, with 7 patients failing to respond satisfactorily. The cycle was not interrupted in the control group treated with placebos. 2. It was found that physical and mental "hangover effects" were markedly reduced by amphetamine sulfate in doses of 10 milligrams. 3. A marked improvement in awareness, sensory perception and activity drive was observed soon after treatment. 4. Mood and rapport were improved, patients demonstrating greater cooperation, increased accessibility and decreased negativism, thus facilitating the initiation of a rehabilitative program.
Sulodexide Fails to Demonstrate Renoprotection in Overt Type 2 Diabetic Nephropathy
Authors: David K. Packham, Rory Wolfe, Anne T. Reutens, Tomas Berl, Hiddo Lambers Heerspink, Richard Rohde, Sara Ivory, Julia Lewis, Itamar Raz, Thomas B. Wiegmann, Juliana C.N. Chan, Dick de Zeeuw, Edmund J. Lewis, Robert C. Atkins
Journal: Journal of the American Society of Nephrology (2011)

Sulodexide, a mixture of naturally occurring glycosaminoglycan polysaccharide components, has been reported to reduce albuminuria in patients with diabetes, but it is unknown whether it is renoprotective. This study reports the results from the randomized, double-blind, placebo-controlled, sulodexide macroalbuminuria (Sun-MACRO) trial, which evaluated the renoprotective effects of sulodexide in patients with type 2 diabetes, renal impairment, and significant proteinuria (>900 mg/d) already receiving maximal therapy with angiotensin II receptor blockers. The primary end point was a composite of a doubling of baseline serum creatinine, development of ESRD, or serum creatinine ≥6.0 mg/dl. We planned to enroll 2240 patients over approximately 24 months but terminated the study after enrolling 1248 patients. After 1029 person-years of follow-up, we did not detect any significant differences between sulodexide and placebo; the primary composite end point occurred in 26 and 30 patients in the sulodexide and placebo groups, respectively. Side effect profiles were similar for both groups. In conclusion, these data do not suggest a renoprotective benefit of sulodexide in patients with type 2 diabetes, renal impairment, and macroalbuminuria.
Successful Hyperlipemic Pregnancy
Authors: Susan L. Sanderson
Journal: JAMA (1991)

Women with hypertriglyceridemia are prone to gestational pancreatitis, a condition carrying substantial maternal and fetal risk. We describe a 33-year-old woman with familial hypertriglyceridemia who had recurrent hyperlipidemic abdominal crises during previous pregnancies despite dietary fat restrictions. A fifth pregnancy was carried to term without complications after aggressive dietary therapy and intermittent intravenous feeding, administered whenever her triglyceride levels exceeded an arbitrarily selected threshold concentration of 28 mmol/L. The efficacy of this approach may be explained by the published observation that low-fat (high-carbohydrate) isocaloric diets elevate serum triglyceride levels by the oral, but not the intravenous, route in normal individuals. Reduction of this patient's serum triglyceride concentrations by interrupting oral intake and administering intravenous glucose appeared to prevent late-pregnancy pancreatitis and culminated in uncomplicated full-term delivery.
Can HLA-DR expression help in the routine diagnosis of malignant melanomas?
Authors: K.P. WEST, P. PRIYAKUMAR, R. JAGJIVAN, P.S. COLLOBY
Journal: British Journal of Dermatology (1989)

Two monoclonal antibodies, TAL‐1B5 and LN3, directed at epitopes of HLA‐DR were applied to a variety of benign naevi and malignant melanomas. Of the 31 naevi examined, 28 were completely unreactive. Weak staining was confined to a few cells in two intradermal naevi and there was more widespread reactivity in a halo naevus. Seven of the 25 primary cutaneous malignant melanomas were reactive with one or both of the antibodies and this reactivity was more marked in the deeper lesions. These positive cases were not felt to present diagnostic difficulties and it was concluded that TAL‐1B5 and LN3 were not of use in distinguishing between benign and malignant melanocytic proliferations.
Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study
Authors: Anne M McIntosh, Jacinta McMahon, Leanne M Dibbens, Xenia Iona, John C Mulley, Ingrid E Scheffer, Samuel F Berkovic
Journal: The Lancet Neurology (2010)

Pertussis vaccination has been alleged to cause an encephalopathy that involves seizures and subsequent intellectual disability. In a previous retrospective study, 11 of 14 patients with so-called vaccine encephalopathy had Dravet syndrome that was associated with de-novo mutations of the sodium channel gene SCN1A. In this study, we aimed to establish whether the apparent association of Dravet syndrome with vaccination was caused by recall bias and, if not, whether vaccination affected the onset or outcome of the disorder.We retrospectively studied patients with Dravet syndrome who had mutations in SCN1A, whose first seizure was a convulsion, and for whom validated source data were available. We analysed medical and vaccination records to investigate whether there was an association between vaccination and onset of seizures in these patients. Patients were separated into two groups according to whether seizure onset occurred shortly after vaccination (vaccination-proximate group) or not (vaccination-distant group). We compared clinical features, intellectual outcome, and type of SCN1A mutation between the groups.Dates of vaccination and seizure onset were available from source records for 40 patients. We identified a peak in the number of patients who had seizure onset within 2 days after vaccination. Thus, patients who had seizure onset on the day of or the day after vaccination (n=12) were included in the vaccination-proximate group and those who had seizure onset 2 days or more after vaccination (n=25) or before vaccination (n=3) were included in the vaccination-distant group. Mean age at seizure onset was 18.4 weeks (SD 5.9) in the vaccination-proximate group and 26.2 weeks (8.1) in the vaccination-distant group (difference 7.8 weeks, 95% CI 2.6-13.1; p=0.004). There were no differences in intellectual outcome, subsequent seizure type, or mutation type between the two groups (all p values >0.3). Furthermore, in a post-hoc analysis, intellectual outcome did not differ between patients who received vaccinations after seizure onset and those who did not.Vaccination might trigger earlier onset of Dravet syndrome in children who, because of an SCN1A mutation, are destined to develop the disease. However, vaccination should not be withheld from children with SCN1A mutations because we found no evidence that vaccinations before or after disease onset affect outcome.
Expression of Neutrophil Collagenase (Matrix Metalloproteinase-8) in Human Atheroma
Authors: Michael P. Herman, Galina K. Sukhova, Peter Libby, Norbert Gerdes, Nga Tang, Daniel B. Horton, Meagan Kilbride, Roger E. Breitbart, Miyoung Chun, Uwe Schönbeck
Journal: Circulation (2001)

Background Loss of interstitial collagen, particularly type I collagen, the major load-bearing molecule of atherosclerotic plaques, renders atheroma prone to rupture. Initiation of collagen breakdown requires interstitial collagenases, a matrix metalloproteinase (MMP) subfamily consisting of MMP-1, MMP-8, and MMP-13. Previous work demonstrated the overexpression of MMP-1 and MMP-13 in human atheroma. However, no study has yet evaluated the expression of MMP-8, known as “neutrophil collagenase,” the enzyme that preferentially degrades type I collagen, because granulocytes do not localize in plaques. Methods and Results Transcriptional profiling and reverse transcription–polymerase chain reaction analysis revealed inducible expression of MMP-8 transcripts in CD40 ligand–stimulated mononuclear phagocytes. Western blot analysis demonstrated that 3 atheroma-associated cell types, namely, endothelial cells, smooth muscle cells, and mononuclear phagocytes, expressed MMP-8 in vitro upon stimulation with proinflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, or CD40 ligand. MMP-8 protein elaborated from these atheroma-associated cell types migrated as 2 immunoreactive bands, corresponding to the molecular weights of the zymogen and the active molecule. Extracts from atherosclerotic, but not nondiseased arterial tissue, contained similar immunoreactive bands. Moreover, all 3 cell types expressed MMP-8 mRNA and protein in human atheroma in situ. Notably, MMP-8 colocalized with cleaved but not intact type I collagen within the shoulder region of the plaque, a frequent site of rupture. Conclusions These data point to MMP-8 as a previously unsuspected participant in collagen breakdown, an important determinant of the vulnerability of human atheroma.
Another new tool for the diagnostic bronchoscopist
Authors: R. C. Rintoul, M. G. Slade
Journal: Thorax (2011)

Solitary pulmonary nodules (SPNs), defined as rounded lesions <3 cm completely surrounded by an aerated lung, are increasingly identified by modern chest radiography and thoracic CT. As CT screening studies report and the debate over the place of national lung cancer screening programmes intensifies, the need for algorithms to efficiently investigate SPNs will become even more important.1

Peripheral pulmonary lesions can be biopsied by various techniques. The most commonly used approach in the UK is transthoracic needle aspiration or core biopsy usually performed under CT guidance. The diagnostic sensitivity for malignancy exceeds 90% in experienced hands but up to 44% of biopsies in benign disease are non-diagnostic.2 While generally safe, it is not without complications; in a large UK-based survey, pneumothorax occurred in 20.5% of cases and intercostal tube drainage was required in 3%.3

Flexible bronchoscopes can be used to approach peripheral lesions but the reported diagnostic sensitivity rates are considerably lower than for CT-guided needle biopsy. Sensitivity has been shown to be dependent upon the size of lesion, the distance from the hilum and the presence of a bronchus leading to the lesion on CT (the CT bronchus sign). A systematic review found that the diagnostic yield was 33% for lesions <2 cm in the outer third of the lung.2 Historically, the approach taken has been to use a thin bronchoscope and perform a combination of bronchial washings, brushings and transbronchial biopsy targeting the appropriate segmental or subsegmental bronchus sometimes with the assistance of fluoroscopy. More recently, several groups have reported their experience of using radial endobronchial ultrasound (EBUS) to guide biopsy of peripheral lesions. Radial EBUS provide 360° images of …
Gene Therapy for Wiskott-Aldrich Syndrome—Long-Term Efficacy and Genotoxicity
Authors: Christian Jörg Braun, Kaan Boztug, Anna Paruzynski, Maximilian Witzel, Adrian Schwarzer, Michael Rothe, Ute Modlich, Rita Beier, Gudrun Göhring, Doris Steinemann, Raffaele Fronza, Claudia Regina Ball, Reinhard Haemmerle, Sonja Naundorf, Klaus Kühlcke, Martina Rose, Chris Fraser, Liesl Mathias, Rudolf Ferrari, Miguel R. Abboud, Waleed Al-Herz, Irina Kondratenko, László Maródi, Hanno Glimm, Brigitte Schlegelberger, Axel Schambach, Michael Heinrich Albert, Manfred Schmidt, Christof von Kalle, Christoph Klein
Journal: Science Translational Medicine (2014)

Wiskott-Aldrich syndrome gene therapy is feasible, but γ-retroviral vectors contribute a substantial risk of leukemogenesis.
Evaluation of the <i>ETS</i>-Related Gene mRNA in Urine for the Detection of Prostate Cancer
Authors: Kevin R. Rice, Yongmei Chen, Amina Ali, Eric J. Whitman, Amy Blase, Mona Ibrahim, Sally Elsamanoudi, Stephen Brassell, Bungo Furusato, Norbert Stingle, Isabell A. Sesterhenn, Gyorgy Petrovics, Siobhan Miick, Harry Rittenhouse, Jack Groskopf, David G. McLeod, Shiv Srivastava
Journal: Clinical Cancer Research (2010)

Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients. Because diverse genomic fusion events lead to ERG overexpression in prostate cancer, we reasoned that it may be more practical to capture such alterations using an assay targeting ERG sequences retained in such gene fusions. This study evaluates the potential of an assay quantitating ERG mRNA in post-digital rectal exam (DRE) urine for improving prostate cancer detection.Patients scheduled to undergo transrectal ultrasound-guided needle biopsy of the prostate were prospectively enrolled. On the day of biopsy, patients provided a urine sample immediately following a DRE. Urine ERG mRNA was measured and normalized to urine prostate-specific antigen (PSA) mRNA using the DTS 400 system. Demographic traits, clinical characteristics and biopsy results were analyzed for association with urine ERG score.The study was conducted on 237 patients. Prostate cancer was shown on biopsy in 40.9% of study subjects. A higher urine ERG score associated significantly with malignancy on biopsy (P = 0.0145), but not with clinical stage or Gleason score. Urine ERG score performed best in Caucasians and in men with a PSA of <or=4 ng/mL (area under the curve = 0.8).A higher urine ERG score in post-DRE urine is associated with the diagnosis of prostate cancer on biopsy. Urine ERG score performed particularly well in men with a PSA of <or=4.0 ng/mL, a segment of the screening population in which further diagnostic markers are needed to determine in whom biopsy should be done.
Changes in 18F-FDG tumor metabolism after a first course of neoadjuvant chemotherapy in breast cancer: influence of tumor subtypes
Authors: O. Humbert, A. Berriolo-Riedinger, J.M. Riedinger, B. Coudert, L. Arnould, A. Cochet, C. Loustalot, P. Fumoleau, F. Brunotte
Journal: Annals of Oncology (2012)
Head-to-Head Comparison of Three-Dimensional Navigator-Gated Magnetic Resonance Imaging and 16-Slice Computed Tomography to Detect Coronary Artery Stenosis in Patients
Authors: Joëlle Kefer, Emmanuel Coche, Gabin Legros, Agnès Pasquet, Cécile Grandin, Bernard E. Van Beers, Jean-Louis Vanoverschelde, Bernhard L. Gerber
Journal: Journal of the American College of Cardiology (2005)
High Specificity of Quantitative <b> <i>Excision Repair Cross-Complementing 1</i> </b> Messenger RNA Expression for Prediction of Minor Histopathological Response to Neoadjuvant Radiochemotherapy in Esophageal Cancer
Authors: Ute Warnecke-Eberz, Ralf Metzger, Futoshi Miyazono, Stephan E. Baldus, Susanne Neiss, Jan Brabender, Hartmut Schaefer, Walter Doerfler, Elfriede Bollschweiler, Hans P. Dienes, Rolf P. Mueller, Peter V. Danenberg, Arnulf H. Hoelscher, Paul M. Schneider
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The excision repair cross-complementing 1 (ERCC1) gene is coding for a nucleotide excision repair protein involved in the repair of radiation- and chemotherapy-induced DNA damage. We examined the potential of quantitative ERCC1 mRNA expression to predict minor or major histopathological response to neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, and 36 Gy of radiation) followed by transthoracic en bloc esophagectomy in patients with locally advanced esophageal cancer (cT2–4, Nx, M0). Experimental Design: Tissue samples were collected by endoscopic biopsy before treatment. RNA was isolated from biopsies, and quantitative real-time reverse transcriptase PCR assays were performed to determine ERCC1 mRNA expression. Relative mRNA levels (tumor/normal ratios) were calculated as (ERCC1/β-actin in tumor)/(ERCC1/β-actin in paired normal tissue). ERCC1 expression levels were correlated with the objective histopathological response in resected specimens. Histomorphological regression was defined as major response when resected specimens contained &amp;lt;10% of residual vital tumor cells or in case a pathologically complete response was achieved. Results: Twelve of 36 tumors showed a major histopathological response, and 24 of 36 showed a minor histopathological response. Relative expression levels of ERCC1 of &amp;gt;1.09 were not associated with a major histopathological response (sensitivity, 62.5%; specificity, 100%) and 15 of 24 patients with minor histopathological response to the delivered neoadjuvant radiochemotherapy could be unequivocally identified. This association of dichotomized relative ERCC1 mRNA expression and histopathological response was statistically significant (P &amp;lt; 0.001). Conclusions: Relative expression levels of ERCC1 mRNA determined by quantitative real-time reverse transcriptase-PCR appear highly specific to predict minor response to our neoadjuvant radiochemotherapy protocol in patients with locally advanced esophageal cancer and could be applied to prevent expensive, noneffective, and potentially harmful therapies in a substantial number (42%) of patients.