tbuckley/cabot-search huggingface dataset:
URINARY DIVERSION AND PELVIC SURGERY FOR CANCER
Authors: J. Hartwell Harrison
Journal: JAMA (1968)

Brunschwig and Barber (p 617) have made an important study of secondary and tertiary rediversion of the urinary tract in 72 patients, found among a group of 840 patients who had pelvic exenteration for advanced cancer performed in the last 20 years. They have shown that, if a five-year survival is achieved, the most frequent subsequent cause of death is deterioration of the diverted urinary tract. Also, at various shorter times following the initial exenteration, the diverted urinary tract may be the cause of major and indeed fatal complications, aside from any problem concerned with the cancer itself. This vigorous attack on female pelvic cancer made by Brunschwig at the Memorial Cancer Center represents a unique and brave effort. The specific emphasis on the importance of urinary tract diversion, the careful study of the complications, and the methods used to correct the morbidity deserve special commendation. The common immediate complications
Prognostic Significance of<i>p53</i>and<i>X-ray Repair Cross-complementing Group 1</i>Polymorphisms on Prostate-Specific Antigen Recurrence in Prostate Cancer Post–Radical Prostatectomy
Authors: Shu-Pin Huang, Chao-Yuan Huang, Jyh-Seng Wang, Chia-Chu Liu, Yeong-Shiau Pu, Hong-Jeng Yu, Chia-Cheng Yu, Tony T. Wu, Chun-Hsiung Huang, Wen-Jeng Wu, Yii-Her Chou, Ming-Tsang Wu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The tumor suppressor p53 and DNA repair gene X-ray repair cross-complementing group 1 (XRCC1) are thought to play important roles on prostate cancer susceptibility and tumor development. We investigated the potential prognostic roles of p53 (codon 72) and XRCC1 (codons 194, 280, and 399) polymorphisms in clinical localized prostate cancer after radical prostatectomy. Experimental Design: A total of 126 clinical localized prostate cancer patients undergoing curative radical prostatectomy at the Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital were included in this study. The p53 codon 72 and XRCC1 codons 194, 280 and 399 polymorphisms were determined by the PCR-RFLP method. Their prognostic significance on prostate-specific antigen (PSA) recurrence were assessed using the Kaplan-Meier analysis and Cox regression model. Results: The p53 codon 72 Arg/Arg genotype was associated with increased PSA recurrence risk compared with the Arg/Pro and Pro/Pro genotypes, although the difference did not reach significance (30.3% versus 20.4%, P = 0.247). Of these three XRCC1 polymorphisms, the codon 399 Arg/Gln + Gln/Gn genotypes were significantly associated with higher risk of PSA recurrence after radical prostatectomy compared with the Arg/Arg genotype (34.0% versus 15.1%, P = 0.013) and poorer PSA-free survival (log-rank test, P = 0.0056). After considering for other covariates in a Cox proportional hazard model, the XRCC1 Arg/Gln and Gln/Gln genotypes (hazard ratio, 4.73; 95% confidence interval, 1.61-13.92; P = 0.005) and high Gleason score (Gleason score, 8-10; hazard ratio, 5.58; 95% confidence interval, 1.58-19.71; P = 0.008) were still independent predictors of poor PSA-free survival after radical prostatectomy. The similar significant results were not found in XRCC1 codons 194 and 280. Conclusions: Our results suggest that the XRCC1 codon 399 polymorphism may be a prognostic factor for PSA recurrence after radical prostatectomy.
Treatment of Parkinson's Disease with Aporphines
Authors: George C. Cotzias, Paul S. Papavasiliou, Eduardo S. Tolosa, Jorge S. Mendez, Margaret Bell-Midura
Journal: New England Journal of Medicine (1976)

To avoid the main drawbacks of prolonged treatment with levodopa (involuntary movements and the "on-off" phenomenon), we administered apomorphine by mouth to 14 patients with Parkinson's disease. This treatment caused azotemia, which we circumvented by switching to N-propylnoraporpine, whose nephrotoxic dose (80 mg six times per day) was larger than its therapeutic dose (10 to 15 mg six times per day). Slowly increasing doses induced significant improvement (P less than 0.005) in all 24 patients studied, transitory mental aberrations in seven, and release of growth hormone in three patients tested. In patients previously on prolonged levodopa administration, the dyskinesia and "on-off" phenomenon were almost identical with N-propylnoraporphine, but both drawbacks were reduced or abolished in six patients by coadministration of alpha-methyldopa hydrazine plus levodopa. This coadministration seemed to abolish tachyphylaxis. We conclude that N-propylnoraporphine is very useful in the treatment of Parkinson's disease.
The BMJ should not take the law into its own hands on competing interests
Authors: S. Forsyth
Journal: BMJ (2015)

The case for discriminating against clinicians whose professional interest leads them to collaborate with industry needs to be built on evidence rather than perception.1 Reference is made to two papers, both of which are low response questionnaires to doctors requesting their perception of validity and believability on hypothetical papers that made no declaration of interest, were grant funded, or were funded by a company with which the lead author was financially …
Oxidized Phospholipids Induce Type VIII Collagen Expression and Vascular Smooth Muscle Cell Migration
Authors: Olga A. Cherepanova, Nataliya A. Pidkovka, Olga F. Sarmento, Tadashi Yoshida, Qiong Gan, Eser Adiguzel, Michelle P. Bendeck, Judith Berliner, Norbert Leitinger, Gary K. Owens
Journal: Circulation Research (2009)

Phenotypic switching of vascular smooth muscle cells (VSMCs) is known to play a critical role in the development of atherosclerosis. However, the factors present within lesions that mediate VSMC phenotypic switching are unclear. Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-(5-oxovaleroyl)- sn -glycero-3-phosphorylcholine (POVPC), are active components of minimally modified low density lipoprotein and have been previously shown to induce multiple proatherogenic events in endothelial cells and macrophages, but their effects on VSMCs have been largely unexplored until recently. We previously showed that OxPLs induced phenotypic switching of VSMCs, including suppression of SMC differentiation marker genes. The goal of the present studies was to test the hypothesis that OxPLs alter extracellular matrix production and VSMC migration. Results showed that POVPC activated expression of several extracellular matrix proteins in VSMC. POVPC increased expression of type VIII collagen α1 chain ( Col8a1 ) mRNA in cultured VSMCs and in vivo in rat carotid arteries by 9-fold and 4-fold, respectively. POVPC-induced activation of Col8a1 gene expression was reduced by small interfering RNA–mediated suppression of Krüppel-like factor 4 (Klf4) and Sp1, and was abolished in Klf4- knockout VSMCs. POVPC increased Klf4 binding to the Col8a1 gene promoter both in vivo in rat carotid arteries and in cultured VSMCs based on chromatin immunoprecipitation assays. Moreover, POVPC-induced VSMC migration was markedly reduced in Klf4 - or type VIII collagen–knockout VSMCs. Given evidence that OxPLs are present within atherosclerotic lesions, it is interesting to suggest that OxPL-induced changes in VSMC phenotype may contribute to the pathogenesis of atherosclerosis at least in part through changes in extracellular matrix composition.
Iatrogenic Illness on a General Medical Service at a University Hospital
Authors: Knight Steel, Paul M. Gertman, Caroline Crescenzi, Jennifer Anderson
Journal: New England Journal of Medicine (1981)

We found that 36% of 815 consecutive patients on a general medical service of a university hospital had an iatrogenic illness. In 9% of all persons admitted, the incident was considered major in that it threatened life or produced considerable disability. In 2% of the 815 patients, the iatrogenic illness was believed to contribute to the death of the patient. Exposure to drugs was a particularly important factor in determining which patients had complications. Given the increasing number and complexity of diagnostic procedures and therapeutic agents, monitoring of untoward events is essential, and attention should be paid to educational efforts to reduce the risks of iatrogenic illness.
Evaluation of safety and efficacy of topical prostaglandin E<sub>2</sub>in treatment of vitiligo
Authors: R. Kapoor, M.M. Phiske, H.R. Jerajani
Journal: British Journal of Dermatology (2008)

Prostaglandin E2 (PGE2) has stimulant and immunomodulatory effects on melanocytes and regulates their proliferation.To study the efficacy and safety of topical PGE2 in treating stable vitiligo patches involving <5% body surface area.Fifty-six consecutive patients with clinically diagnosed stable vitiligo of types vulgaris, focal, segmental, lip and genital applied a translucent PGE2 (0.25 mg g(-1)) gel twice daily for 6 months. Evaluation was fortnightly for 3 months and monthly thereafter up to 6 months. Assessment was based on degree of repigmentation in treated patches ranging from 0% (no change) to 100% (complete repigmentation). Overall response was graded as: poor, 1-25% repigmentation; moderate, 26-50%; good, 51-75%; excellent, >75%.Vitiligo vulgaris was the most common type (n=22; 39%), followed by focal and lip vitiligo, with lesions being mostly on the face (25%) and lips. Repigmentation was seen in 40 of 56 patients (71%), with mean onset at 2 months. Patients with disease duration of 6 months or less repigmented best, with face and scalp responding earliest (1-1.5 months). Complete clearance occurred in eight of 40 patients, six of the eight having face lesions. Excellent response was seen in 22 of 40 patients. All neck, scalp and trunk lesions, 33% genital, 29% lip vitiligo, 100% segmental and 63% focal patches showed moderate to excellent response. Incidence of side-effects was 18%, mainly a transient burning sensation especially on the lips.The efficacy and safety of topical PGE2 make it a promising therapy for localized stable vitiligo.
Risk Factors for Complications of Chronic Anticoagulation: A Multicenter Study
Authors: Stephan D. Fihn
Journal: Annals of Internal Medicine (1993)

Objective: To define risk factors for complications that occur during warfarin therapy. Design: Retrospective cohort study. Setting: Five anticoagulation clinics. Patients: Nine hundred twenty-eight consecutive patients receiving 1103 courses of warfarin. Main Outcome Measures: Hemorrhagic and thromboembolic complications. Results: In 1950 patient-years of follow-up, there were 1332 bleeding events (4 were classified as fatal, 31 as life-threatening, 226 as serious, and 1071 as minor). The cumulative incidence of fatal bleeding was 1% at 1 year and 2% at 3 years. The cumulative incidences of first episodes of life-threatening and serious bleeding at 1, 2, 4, and 8 years were 1%, 2%, 5%, and 9% and 12%, 20%, 28%, and 40%, respectively. Of 156 patients who had a serious or life-threatening hemorrhage, 32% suffered a recurrence, typically within 1 year. Independent predictors of a first episode of serious bleeding included a mean prothrombin time ratio (PTR) of 2.0 or more during the course of treatment (relative risk, 3.0; 95% CI, 1.9 to 4.7); recent initiation of warfarin therapy (relative risk during the first 3 months compared with the rest of the first year, the second year, and anytime thereafter, 1.9 [CI, 1.3 to 3.0], 3.0 (CI, 1.8 to 4.8), and 5.9 [CI, 3.8 to 9.3], respectively); variability of the PTR over time (relative risk for the highest compared with the lowest tertile, 1.6 [CI, 1.2 to 2.7]); and the presence of 3 or more comorbid conditions (RR, 1.4 [CI, 1.1 to 2.5]). Age, reason for anticoagulation, use of interfering drugs, and hypertension were not associated with risk for bleeding. The risk for a thromboembolic complication at a PTR of less than 1.3 was 3.6 (CI, 2.1 to 6.4) times higher than at a PTR of 1.3 to 1.5. Conclusions: The incidence of warfarin-associated bleeding may be reduced by attending to modifiable risk factors (that is, highly variable PTRs and values greater than 2.0), frequent monitoring early in treatment, and careful patient selection. Older age, in and of itself, is not a risk factor.
Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy
Authors: Christian M. Lange, Zoltan Kutalik, Kenichi Morikawa, Stéphanie Bibert, Andreas Cerny, Günter Dollenmaier, Jean-François Dufour, Tilman J. Gerlach, Markus H. Heim, Raffaele Malinverni, Beat Müllhaupt, Francesco Negro, Darius Moradpour, Pierre-Yves Bochud
Journal: Hepatology (2011)

Abstract Elevated serum ferritin levels may reflect a systemic inflammatory state as well as increased iron storage, both of which may contribute to an unfavorable outcome of chronic hepatitis C (CHC). We therefore performed a comprehensive analysis of the role of serum ferritin and its genetic determinants in the pathogenesis and treatment of CHC. To this end, serum ferritin levels at baseline of therapy with pegylated interferon-alpha and ribavirin or before biopsy were correlated with clinical and histological features of chronic hepatitis C virus (HCV) infection, including necroinflammatory activity (N = 970), fibrosis (N = 980), steatosis (N = 886), and response to treatment (N = 876). The association between high serum ferritin levels (&gt;median) and the endpoints was assessed by logistic regression. Moreover, a candidate gene as well as a genome-wide association study of serum ferritin were performed. We found that serum ferritin ≥ the sex-specific median was one of the strongest pretreatment predictors of treatment failure (univariate P &lt; 0.0001, odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.34–0.60). This association remained highly significant in a multivariate analysis ( P = 0.0002, OR = 0.35, 95% CI = 0.20–0.61), with an OR comparable to that of interleukin ( IL ) 28B genotype. When patients with the unfavorable IL28B genotypes were stratified according to high versus low ferritin levels, SVR rates differed by &gt;30% in both HCV genotype 1- and genotype 3–infected patients ( P &lt; 0.001). Serum ferritin levels were also independently associated with severe liver fibrosis ( P &lt; 0.0001, OR = 2.67, 95% CI = 1.68–4.25) and steatosis ( P = 0.002, OR = 2.29, 95% CI = 1.35–3.91), but not with necroinflammatory activity ( P = 0.3). Genetic variations had only a limited impact on serum ferritin levels. Conclusion: In patients with CHC, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy. (Hepatology 2012)
Mechanical Stretch Induces Enhanced Expression of Angiotensin II Receptor Subtypes in Neonatal Rat Cardiac Myocytes
Authors: Kazuhisa Kijima, Hiroaki Matsubara, Satoshi Murasawa, Katsuya Maruyama, Yasukiyo Mori, Naohiko Ohkubo, Issei Komuro, Yoshio Yazaki, Toshiji Iwasaka, Mitsuo Inada
Journal: Circulation Research (1996)

Mechanical stress plays a pivotal role in the development of cardiac hypertrophy during hemodynamic overload, and angiotensin (Ang) II secreted from stretched myocytes plays an important role in mechanical stretch-induced hypertrophy. In the present study, we examined stretch-induced expression of Ang II receptors in an in vitro stretch model using 1-day-old rat myocytes. Both Ang II type 1 receptor (AT1-R) and type 2 receptor (AT2-R) mRNA levels were upregulated by myocyte stretching with similar time courses: significant increases were evident 6 hours after stretching, maximal levels (2.8- and 3.3-fold, respectively) were observed at 12 hours, and these were sustained for up to 18 hours. Ang II receptor expression in fibroblast-rich cultures was not affected by stretching. Conditioned medium in which myocytes were stretched for 12 hours significantly downregulated AT1-R and AT2-R mRNA levels in recipient myocytes, and this effect was almost completely blocked by AT1-R antagonists but not AT2-R antagonists. Stretch-induced expression of AT1-R and AT2-R mRNAs was further increased by 27% and 31%, respectively, after pretreatment with AT1-R antagonists, suggesting that Ang II secreted from stretched myocytes downregulates both AT1-R and AT2-R. Western blot and binding assays showed that the number of AT1-Rs and AT2-Rs increased by 2.4- and 2.6-fold, respectively, without affecting receptor affinities. Inositol phosphate response to 0.5 mumol/L Ang II was enhanced 2.1-fold in stretched myocytes. Nuclear runoff assays and treatment with actinomycin D revealed that stretch-induced upregulation of AT1-R was mainly due to increased transcription, whereas that of AT2-R resulted from a stabilizing effect on AT2-R mRNA metabolism. Stretch-induced changes in levels of Ang II receptors were inhibited by genistein but not by H-7, staurosporin, and protein kinase C depletion or by BAPTA-AM. Exposure to cycloheximide did not affect stretch-induced changes. These findings indicate that nonsecretory pathways activated by myocyte stretching upregulate the expression of Ang II receptor subtypes transcriptionally and posttranscriptionally through mechanisms involving stretch-activated tyrosine kinases independently of de novo protein synthesis and that the AT1-R-mediated action of Ang II is functionally enhanced in stretched cardiac myocytes.
931. Inhibition of VEGF Signaling Pathway and Tumor Metastasis
Authors: Yi Lu, Jun Zhang
Journal: Molecular Therapy (2006)

Blocking vascular endothelial growth factor (VEGF) signaling pathway appears to be an effective approach to suppress tumor angiogenesis and metastasis. Because degree of tumor malignancy correlates with the expression of VEGF and the inverse expression of tumor suppressor gene p16, we examined whether restoration of wild-type p16 in cancer cells that lack p16 expression would modulate VEGF expression, and if so, how is the effect of p16 expression on tumor angiogenesis and metastasis. Human breast cancer cell lines MDA-MB-231, MCF-7 and mouse breast cancer cell line JygMC(A) were used as models for this study. To facilitate induction of p16 expression, a replication-defective recombinant adenovirus expressing human wild-type p16 (AdRSVp16) has been generated. Our study showed that adenoviral-mediated p16 expression downregulated VEGF expression at both mRNA and protein levels in breast cancer cells, as well as VEGF receptor activation. By using a chimeric VEGF promoter-reporter gene construct, we demonstrated that p16 downregulated VEGF gene expression at the transcriptional level. A molecular mechanism of how p16 modulates VEGF expression at the transcriptional level is proposed. By comparing with control virus-treated group, AdRSVp16 inhibited breast cancer angiogenesis in dorsal air sac and matrigel plug models, in vitro and in vivo growth of breast cancer cells, and metastasis in a subcutaneous metastasis model. The dual effects of p16's anti-proliferation and anti-angiogenesis were examined by simultaneously analyzing proliferation marker PCNA and neovascularization marker CD31 (immunohistochemistry), and apoptosis (TUNEL) inside the tumors. Our results showed that p16 has combinative effects on breast tumor angiogenesis and proliferation. Taken together, these results demonstrate that p16 downregulates VEGF gene expression at the transcriptional level, inhibits angiogenesis, and suppresses tumor growth and metastasis in breast cancer cells. This study suggests that viral vector-based p16 gene therapy may have a clinical potential to treat breast cancer in conjunction with other therapeutic modalities. This research is supported in part by National Institute of Health (DK65962) and in part by Cancer Research and Prevention Foundation.
Training for What? — Winter of Discontent
Authors: John Lister
Journal: New England Journal of Medicine (1979)

BECAUSE there are still far more suitable applicants than there are medical-school places it is inevitable that the method of selecting medical students should be a matter for continuing debate. Anyone interviewing applicants quickly finds that few of them have any idea about what is involved in the medical curriculum and even fewer have any idea of the many opportunities that will be open to them after they successfully complete the course. The answers to the inevitable question — "What made you decide to apply for a place in medical school?" — are predictable and range from the expression of . . .
THE DANGER OF SMALL-POX
Authors: R. Broadbent
Journal: BMJ (1917)

THE DANGER OF SMALL-POX.SIR,-It mrav not be witlhout interest if I put on record- *wo somewlhat striking cases that occurred in my practice in Leicester.Case 1.-Tweinty years ago a mother broughlt her eldest daughter to me to be vaccinated in order to enable lher to become a teacher.The fathter had been prominen-t in the anti-
The Effect of Funding Source on Outcome Reporting Among Drug Trials
Authors: Erick H. Turner
Journal: Annals of Internal Medicine (2011)

Letters18 January 2011The Effect of Funding Source on Outcome Reporting Among Drug TrialsErick H. Turner, MDErick H. Turner, MDFrom Oregon Health & Science University, Portland, OR 97239.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-2-201101180-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Bourgeois and colleagues' recent article (1) with interest, and I agree with the point made in the rapid responses on www.annals.org about the importance of the differences in sample size. Although this confounding variable was not mentioned in the article's Discussion section, it could have played a major role in generating the outcome observed.As can be seen in the authors' Table 1, the median final sample size for the industry-sponsored trials was 3 times larger than that for the trials funded by nonprofit or nonfederal organizations and 8 times larger than that for the ...References1. Bourgeois FT, Murthy S, Mandl KD. Outcome reporting among drug trials registered in ClinicalTrials.gov. Ann Intern Med. 2010;153:158-66. [PMID: 20679560] LinkGoogle Scholar2. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. New York: Lawrence Erlbaum Associates; 1988. Google Scholar3. Chan AW, Upshur R, Singh JA, Ghersi D, Chapuis F, Altman DG. Research protocols: waiving confidentiality for the greater good. BMJ. 2006;332:1086-9. [PMID: 16675819] CrossrefMedlineGoogle Scholar4. Turner EH. A taxpayer-funded clinical trials registry and results database [Editorial]. PLoS Med. 2004;1:60. [PMID: 15562322] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Oregon Health & Science University, Portland, OR 97239.Disclosures: Dr. Turner was on speakers' bureaus for AstraZeneca, Bristol-Myers Squibb, and Eli Lilly; these activities ceased 5 years ago. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOutcome Reporting Among Drug Trials Registered in ClinicalTrials.gov Florence T. Bourgeois , Srinivas Murthy , and Kenneth D. Mandl The Effect of Funding Source on Outcome Reporting Among Drug Trials Adam Jacobs The Effect of Funding Source on Outcome Reporting Among Drug Trials Deborah A. Zarin and Tony Tse The Effect of Funding Source on Outcome Reporting Among Drug Trials Florence T. Bourgeois , Kenneth D. Mandl , and Srinivas Murthy Metrics Cited BySponsorship and design characteristics of trials registered in ClinicalTrials.gov 18 January 2011Volume 154, Issue 2Page: 137KeywordsClinical trialsConflicts of interestDrugs ePublished: 18 January 2011 Issue Published: 18 January 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...