tbuckley/cabot-search huggingface dataset:
Lipid lowering and plaque regression. New insights into prevention of plaque disruption and clinical events in coronary disease.
Authors: B G Brown, X Q Zhao, D E Sacco, J J Albers
Journal: Circulation (1993)

The consensus of evidence from angiographic trials demonstrates both coronary artery and clinical benefits from lowering of lipids by a variety of regimens. The findings of reduced arterial disease progression and increased regression have been convincing but, at best, modest in their magnitude. For example, among those treated intensively in FATS, the mean improvement in proximal stenosis severity per patient was &lt; 1% stenosis, and only 12% of all lesions showed convincing regression. In view of these modest arterial benefits, the associated reductions in cardiovascular events have been surprisingly great. For example, coronary events were reduced 75% in FATS; this was entirely a result of a 93% reduction in the likelihood that a mildly or moderately diseased arterial segment would experience substantial progression to a severe lesion at the time of a clinical event. We believe that the magnitude of the clinical benefit is best explained in terms of this observation, according to the following lines of reasoning. Clinical events most commonly spring from lesions that are initially of mild or moderate severity and then abruptly undergo a disruptive transformation to a severe culprit lesion. The process of plaque fissuring, leading to plaque disruption and thrombosis, triggers most clinical coronary events. Fissuring is predicted by a large accumulation of core lipid in the plaque and by a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics constitute only 10-20% of the overall lesion population but account for 80-90% of the acute clinical events. In the experimental setting, normalization of an atherogenic lipid profile substantially decreases the number of lipid-laden intimal macrophages (foam cells) and depletes cholesterol from the core lipid pool. In the clinical setting, intensive lipid lowering virtually halts the progression of mild and moderate lesions to clinical events. Thus, the reduction in clinical events observed in these trials appears to be best explained by the relation of the lipid and foam cell content of the plaque to its likelihood of fissuring and by the effects of lipid-lowering therapy on these "high-risk" features of plaque morphology. The composite of data presented here supports the hypothesis that lipid-lowering therapy selectively depletes (regresses) that relatively small but dangerous subgroup of fatty lesions containing a large lipid core and dense clusters of intimal macrophages. By doing so, these lesions are effectively stabilized and clinical event rate is accordingly decreased.
Maligne Tumoren im Kindesalter
Authors: John G. Raffensperger
Journal: JAMA (1969)

This book comprises original articles on tumors in children. Most of the studies are written in German, but have English summaries at the end. The authors review large numbers of cases and illustrate discussions of pathology, diagnosis, and treatment with case histories and excellent pictures. The primary value of the book lies in the amount of information collected by the authors on some of the very rare tumors of childhood, such as lesions of the spinal cord, oral cavity, and gastrointestinal tract. The two chapters on angiography of tumors are particularly timely and valuable. The papers on neuroblastoma and on Wilms' tumor add nothing to the extensive experience we have had in this country with surgery, radiation, and chemotherapy. Except for Rickham in Live pool, there seems to be worldwide agreement that dactinomycin (actinomycin D) therapy has tremendously improved the survival rates of children with Wilms' tumors. There are several
Health of King Henry VIII.
Authors: M Skoblo, J Leslau
Journal: BMJ (1978)

Further investigation has shown that the incorrect Reflomat result may have resulted from inserting the Reflomat strip into the machine upside down, which can give spurious readings up to 4 0 mmol/l.Incorrect insertion of the strip is, of course, more likely when testing for hypoglycaemia since the test surface fails to show significant colour change in this situation.This problem does not appear to be significant with the more recently available Reflotest-Hypoglycemie strips, though false results may occur.if either of the strips is not fully inserted into the machine.Although all laboratory results should be interpreted in the context of the clinical findings, we should like to alert your readers to this potential cause of error and suggest that the manufacturers alter the colour of the blank reverse side of the strip to obviate this risk.
Indirect assessment of renal dysfunction in patients taking cyclosporin A for autoimmune diseases
Authors: JUNE MASON, L.C. MOORE
Journal: British Journal of Dermatology (1990)

The reliability of increases in serum creatinine and serum urea above initial values in detecting decreases in glomerular filtration rate below initial values was assessed in patients taking cyclosporin A (CyA) for autoimmune diseases. Both serum creatinine and serum urea provided reasonable estimates of the decline in glomerular filtration rate when measured simultaneously and when compared to patients' own baseline values. Combination of both serum creatinine and serum urea improved the assessment of renal dysfunction, partly by reducing the influence of any analytical errors. Frequent measurements, precise baseline evaluation and standardization of procedures can be expected to increase further the precision of assessing renal dysfunction from serum measurements. Hence, careful evaluation of changes in serum creatinine, with the option to include changes in serum urea, can provide a simple and reliable way of monitoring changes in renal function in patients taking CyA for autoimmune diseases.
LINEAR URTICARIA DUE TO LARVA CURRENS-STRONGYLOIDIASIS
Authors: W. J. CUNLIFFE, L. GARCIA E SILVA
Journal: British Journal of Dermatology (1968)

Journal Article LINEAR URTICARIA DUE TO LARVA CURRENS—STRONGYLOIDIASIS Get access W. J. CUNLIFFE, W. J. CUNLIFFE University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne. (Dr. Cunliffe, Registrar; Dr. Garcia e Silva, Research Associate) Search for other works by this author on: Oxford Academic Google Scholar L. GARCIA E SILVA L. GARCIA E SILVA University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne. (Dr. Cunliffe, Registrar; Dr. Garcia e Silva, Research Associate) Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 2, 1 February 1968, Pages 108–110, https://doi.org/10.1111/j.1365-2133.1968.tb12269.x Published: 01 February 1968 Article history Accepted: 14 September 1967 Published: 01 February 1968
Re: Didem Sunay, Melih Sunay, Yasin Aydoğmuş, et al. Acupuncture Versus Paroxetine for the Treatment of Premature Ejaculation: A Randomized, Placebo-Controlled Clinical Trial. Eur Urol 2011;59:765–71
Authors: Xiaojun Wu, Zhansong Zhou
Journal: European Urology (2011)
Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes
Authors: Peng Cui, Feng Ding, Qiang Lin, Lingfang Zhang, Ang Li, Zhang Zhang, Songnian Hu, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2012)

Abstract Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.
CD2+, CD3‐, CD56/NCAM+ malignant lymphoma with TCRβ gene rearrangement: A case report
Authors: Elena Savilo, Ralph M. Meyer, Praniti Soamboonsrup, Linda Sunisloe, George L. Frank, Gerard T. Simon, Peter B. Neame
Journal: American Journal of Hematology (1995)

Abstract A case of CD56/NCAM+ malignant lymphoma is reported. Only a rare malignant lymphoma cell showed azurophilic granules in the cytoplasm of Giesma‐stained preparations, while electron microscopic examination revealed occasional cytoplasmic granules with paracrystalline inclusions. The most common phenotype seen in NK lymphomas, CD2+, CD3‐, CD56+, CD16‐, CD57‐, was present in the case. Cases with this phenotype have been interpreted to represent either true NK lymphoma or T‐cell lymphoma with NK expression. Genotyping, where performed, has shown TCR germline configuration. Our case showed TCRβ rearrangement indicating that the above phenotype can be associated with a peripheral T‐cell lymphoma.
Mechanical ventilation for acute postoperative respiratory failure after surgery for bronchial carcinoma.
Authors: C J Hirschler-Schulte, B S Hylkema, R W Meyer
Journal: Thorax (1985)

From 1978 to 1982 365 patients were treated surgically for bronchial carcinoma. Lobectomy was performed in 250 and pneumonectomy in 115. Sixteen (4.4%) needed mechanical ventilation for acute respiratory failure. Six out of eight with a lobectomy, but only two out of eight with a pneumonectomy, survived initially. Of these eight survivors, five died from recurrent malignancy within a year but three were alive and well at two years. The complications leading to acute respiratory failure were unpredictable in most patients. Improving techniques of mechanical ventilation and intensive care may lead to better results in the future.
Bridging Low-Molecular-Weight Heparin for Temporary Interruption of Warfarin
Authors: Martin J. O'Donnell, Clive Kearon, Alexander G. Turpie
Journal: Annals of Internal Medicine (2007)

Letters6 November 2007Bridging Low-Molecular-Weight Heparin for Temporary Interruption of WarfarinMartin J. O'Donnell, MB, Clive Kearon, MB, PhD, and Alexander G. Turpie, MBMartin J. O'Donnell, MBFrom McMaster University, Hamilton, Ontario L8V 1C3, Canada.Search for more papers by this author, Clive Kearon, MB, PhDFrom McMaster University, Hamilton, Ontario L8V 1C3, Canada.Search for more papers by this author, and Alexander G. Turpie, MBFrom McMaster University, Hamilton, Ontario L8V 1C3, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-9-200711060-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate the opportunity to respond to issues raised by Dr. Shojania. We agree that the therapeutic anti-Xa heparin level range for LMWH has not been rigorously evaluated; however, the high residual anti-Xa heparin activity observed in our study is a cause for concern because it may increase bleeding during surgery. We believe that when physicians stop warfarin therapy before surgery, they do not intend to substitute another anticoagulant during the surgical procedure.The difference in mean anti-Xa heparin levels between our study and the study by Ferreira and colleagues (1) is not surprising because their patient population ...Reference1. Ferreira I, Dos L, Tornos P, Nicolau I, Permanyer-Miralda G, Soler-Soler J. Experience with enoxaparin in patients with mechanical heart valves who must withhold acenocumarol. Heart. 2003;89:527-30. [PMID: 12695457] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From McMaster University, Hamilton, Ontario L8V 1C3, Canada.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBrief Communication: Preoperative Anticoagulant Activity after Bridging Low-Molecular-Weight Heparin for Temporary Interruption of Warfarin Martin J. O'Donnell , Clive Kearon , Judy Johnson , Marlene Robinson , Michelle Zondag , Irene Turpie , and Alexander G. Turpie Bridging Low-Molecular-Weight Heparin for Temporary Interruption of Warfarin A. M. Shojania Metrics 6 November 2007Volume 147, Issue 9Page: 671KeywordsAnticoagulant therapyAnticoagulantsClinical trialsCohort studiesConflicts of interestHemorrhageHeparinSafetySurgery ePublished: 6 November 2007 Issue Published: 6 November 2007 CopyrightCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Helper-Independent sleeping beauty Transposon–Transposase vectors for efficient nonviral gene delivery and persistent gene expression in vivo
Authors: Jacob Giehm Mikkelsen, Stephen R Yant, Leonard Meuse, Zan Huang, Hui Xu, Mark A Kay
Journal: Molecular Therapy (2003)

Transposon-based vectors represent promising new tools for chromosomal transgene insertion and establishment of persistent gene expression in vivo. Here, we report the development of helper-independent transposon-transposase (HITT) vectors, which contain on single plasmids (i) a Sleeping Beauty (SB) transposon containing the transgene and (ii) a SB transposase expression cassette. To obtain an optimal level of transposase expression from HITT vectors, we determined the relative strength of a panel of different promoters in mouse liver and used these promoters to drive transposase expression from injected HITT vectors carrying a human alpha(1)-antitrypsin (hAAT) expression cassette flanked by transposon inverted repeats. By correlating promoter strength with stabilized serum hAAT levels, a narrow expression window supporting high-level transposition in the liver was defined. Peak levels of long-term gene expression were obtained with promoters 30- to 40-fold less active than CMV in mouse liver, whereas reduced stable levels of hAAT were detected with both weaker and stronger promoters. Injected HITT vectors induced transposase-dependent insertion of transposon DNA into the genome of at least 5-6% of transfected hepatocytes, generating levels of persistent hAAT expression that were 2- to 4-fold higher than with an optimized two-plasmid approach. In addition, we show that HITT vectors carrying a human factor IX (hFIX)-containing transposon support (i) long-term hFIX expression in normal mice and (ii) partial phenotypic correction in a mouse model of hemophilia B. SB-based HITT vectors represent a major advance in the establishment of persistent transgene expression from nonviral gene delivery systems and should prove useful for gene transfer to tissues or cell types in which transfection efficiencies are low.
Results in journals often fail to match those on ClinicalTrials.gov, study finds
Authors: M. McCarthy
Journal: BMJ (2014)

Clinical trial results appearing in journals are often inconsistent with those posted on the online registry ClinicalTrials.gov, a new study has found.1

Although the differences were often small and most would probably not meaningfully alter the trial conclusions, the findings suggest neither journal articles nor the registry can be assumed to be accurate sources for trial results, the researchers said.

In the study, the researchers conducted a systematic review of the results of 110 randomly selected phase 3 and 4 clinical trials completed before 2009 whose results appeared in journal publications and were posted on website ClinicalTrials.gov.

Beginning in 2008, summary results of most phase II through IV …
Bismuth Preparations for Diarrhea
Authors: Ray V. McIntyre
Journal: JAMA (1980)

<h3>To the Editor.—</h3> I read the article by DuPont et al (243:237, 1980), describing their experience with the use of subsalicylate bismuth as prophylaxis for traveler's diarrhea. The authors suggest that subsalicylate is the active moiety. Information from Australia may suggest otherwise and add impetus to the authors urging characterization of the dynamics of bismuth absorption. Australian colostomy patients have frequently used bismuth subgallate to make bowel action more predictable and to control fecal odors effectively,<sup>1</sup>actions similar to those seen with the salicylate bismuth. A more important consideration for persons planning to take bismuth for a prolonged period is the risk of neuropsychiatric toxic effects that may be seen with long-term bismuth ingestion. Case reports<sup>1,2</sup>note difficulty in recall, upper and lower limb ataxia, tremor, insomnia, visual disturbances, possible hearing loss, and acute brain syndrome, which has included both auditory and visual hallucinations. In all of these
Bundle-Branch Block and In-Hospital Mortality in Acute Myocardial Infarction
Authors: Alan S. Go
Journal: Annals of Internal Medicine (1998)

Left bundle-branch block (BBB) is considered an important predictor of poor outcome in patients with acute myocardial infarction, but the consequences of right BBB are not well understood.To 1) estimate the prevalence of left and right BBB in patients with myocardial infarction; 2) compare the clinical characteristics of and treatments received by patients with left, right, or no BBB; and 3) determine the independent association of left BBB and right BBB with in-hospital death.Retrospective cohort study.Multicenter registry of 1571 U.S. hospitals.297,832 patients with acute myocardial infarction who had left, right, or no BBB on initial electrocardiography.Presence and type of BBB, clinical characteristics of patients, therapies given, and in-hospital death.Patients with left BBB (n = 19,967; 6.7%) or right BBB (n = 18,354; 6.2%) were older and had more comorbid illness and congestive heart failure than patients with no BBB. Among patients for whom thrombolytic therapy was clearly indicated, fewer patients with left or right BBB (16.6% and 32.0%, respectively) than patients with no BBB (66.5%) received this therapy (P < 0.001). Fewer patients with left or right BBB (60.6% and 67.3%, respectively) than patients with no BBB (75.6%) received aspirin within the first 24 hours (P < 0.001), and fewer patients with left or right BBB (23.9% and 31.8%, respectively) than patients with no BBB (40.4%) received beta-blockers within the first 24 hours (P < 0.001). Unadjusted in-hospital mortality rates were almost twice as high for patients with left or right BBB (22.6% and 23.0%, respectively) as for patients with no BBB (13.1%) (P < 0.001). Compared with no BBB and no ST-segment elevation, left BBB was associated with a 34% increase (odds ratio, 1.34 [95% CI, 1.28 to 1.39]) and right BBB was associated with a 64% increase (odds ratio, 1.64 [CI, 1.57 to 1.71]) in the risk for in-hospital death, after adjustment for potential confounders.In patients with acute myocardial infarction, prevalences of right and left BBB are similar. Patients with BBB have more comorbid conditions, are less likely to receive therapy, and have an increased risk for in-hospital death compared with patients with no BBB. Compared with left BBB, right BBB seems to be a stronger independent predictor of in-hospital death.
p19ARF/p14ARF controls oncogenic functions of signal transducer and activator of transcription 3 in hepatocellular carcinoma
Authors: Doris Schneller, Georg Machat, Alexandra Sousek, Verena Proell, Franziska van Zijl, Gudrun Zulehner, Heidemarie Huber, Markus Mair, Markus K. Muellner, Sebastian M.B. Nijman, Robert Eferl, Richard Moriggl, Wolfgang Mikulits
Journal: Hepatology (2011)

Abstract: Signal transducer and activator of transcription 3 (Stat3) is activated in a variety of malignancies, including hepatocellular carcinoma (HCC). Activation of Ras occurs frequently at advanced stages of HCC by aberrant signaling through growth factor receptors or inactivation of effectors negatively regulating Ras signaling. Here, we addressed the role of Stat3 in Ras-dependent HCC progression in the presence and absence of p19 ARF /p14 ARF . We show that constitutive active (ca) Stat3 is tumor suppressive in Ras-transformed p19 ARF−/− hepatocytes, whereas the expression of Stat3 lacking Tyr 705 phosphorylation (U-Stat3) enhances tumor formation. Accordingly, Ras-transformed Stat3 Δhc /p19 ARF−/− hepatocytes (lacking Stat3 and p19 ARF ) showed increased tumor growth, compared to those expressing Stat3, demonstrating a tumor-suppressor activity of Stat3 in cells lacking p19 ARF . Notably, endogenous expression of p19 ARF in Ras-transformed hepatocytes conveyed oncogenic Stat3 functions, resulting in augmented or reduced HCC progression after the expression of caStat3 or U-Stat3, respectively. In accord with these data, the knockdown of p14 ARF (the human homolog of p19 ARF ) in Hep3B cells was associated with reduced pY-Stat3 levels during tumor growth to circumvent the tumor-suppressive effect of Stat3. Inhibition of Janus kinases (Jaks) revealed that Jak causes pY-Stat3 activation independently of p14 ARF levels, indicating that p14 ARF controls the oncogenic function of pY-Stat3 downstream of Jak. Conclusion: These data show evidence that p19 ARF /p14 ARF determines the pro- or anti-oncogenic activity of U-Stat3 and pY-Stat3 in Ras-dependent HCC progression. (HEPATOLOGY 2011;)
The Expression of Phosphorylated mTOR in Breast Cancer from BRCA1-Mutation Carriers.
Authors: K. Korski, A. Malicka, P. Wysocki
Journal: Cancer Research (2009)

Abstract Background: The mammalian target of rapamycin (mTOR) is a serine-threonine kinase coupling growth stimuli and metabolic signals to cell cycle progression and protein synthesis. mTOR represents also a novel therapeutic target in various types of cancer. The role of mTOR in development and progression of breast cancer is not fully understood. There are studies suggesting that mTOR is responsible for the resistance of breast cancer to tamoxifen, trastuzumab and various chemotherapeutic agents. Since there are no studies evaluating the activation (phosphorylation) of mTOR in breast cancer cells carrying a germinal mutation of BRCA1, we have decided to assess activation of this kinase in tumor specimens in BRCA1-mutation carriers.Materials and methods: Formalin fixed paraffin-embedded tumor samples were obtained from 19 patients carrying BRCA1 germinal mutation and 24 patients with intact BRCA1 gene. All patients have been treated in the Great Poland Cancer Center between 2000-2008. The blocks were retrieved from the archives of the Department of Pathology and immunostained for phospho mTOR (Phospho-mTOR (Ser 2448), rabbit antibody, Cell Signaling).Results: Phosphorylation of mTOR was not detected in any of 19 patients carrying the mutated BRCA1 gene. Most of the BRCA1-mutated cancers were ER and HER2 negative (18 (95%) and 16 (94%), respectively). In the tumors with a wildtype BRCA1 gene, mTOR activation was detected in 12 samples (50%). Lack of mTOR phosphorylation was again observed mostly in ER and HER2 negative tissue samples (10 (83%) and 11 (92%), respectively).Discussion: Our findings have demonstrated differential activation of mTOR between tumors carrying a wild-type and mutated BRCA1 gene. We have also observed a negative correlation between ER and HER2 status and phosphorylation of mTOR. Although our study included a relatively low number of cases, the results indicate that activation of mTOR and probably also of its upstream targets do not play a crucial role in biology of tumors with a BRCA1 mutation or with the triple-negative phenotype. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3144.