tbuckley/cabot-search huggingface dataset:
Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use
Authors: None Mrowietz, None Christophers, None Altmeyer For The German Fumaric Aci
Journal: British Journal of Dermatology (1999)

Fumaric acid ester (FAE) therapy has proved to be safe and effective in patients with severe psoriasis vulgaris. This treatment was introduced nearly 30 years ago, but is only now gaining renewed interest among dermatologists. FAE therapy is licensed in Germany and registration is pending in many European countries. Multicentre trials have confirmed the beneficial effect of FAE in psoriasis and have defined the spectrum of its adverse effects. Although the mode of action of FAEs in the treatment of psoriasis is not fully understood, recent experimental data point towards a skewing of the Th1-dominated T-cell response in psoriasis to a Th2-like pattern, and inhibition of proliferation of keratinocytes. This article reviews the experimental and clinical information on FAEs in psoriasis and provides guidelines for the clinical use of FAEs derived from a consensus meeting of leading experts.
Semiquantitative Epstein-Barr Virus (EBV) Polymerase Chain Reaction for the Determination of Patients at Risk for EBV-Induced Lymphoproliferative Disease After Stem Cell Transplantation
Authors: Kenneth G. Lucas, Robert L. Burton, Sarah E. Zimmerman, Jinghong Wang, Kenneth G. Cornetta, Kent A. Robertson, Chao H. Lee, David J. Emanuel
Journal: Blood (1998)
Notch1 Activation or Loss Promotes HPV-Induced Oral Tumorigenesis
Authors: Rong Zhong, Riyue Bao, Pieter W. Faber, Vytautas P. Bindokas, John Bechill, Mark W. Lingen, Michael T. Spiotto
Journal: Cancer Research (2015)

Abstract Viral oncogene expression is insufficient for neoplastic transformation of human cells, so human papillomavirus (HPV)–associated cancers will also rely upon mutations in cellular oncogenes and tumor suppressors. However, it has been difficult so far to distinguish incidental mutations without phenotypic impact from causal mutations that drive the development of HPV-associated cancers. In this study, we addressed this issue by conducting a functional screen for genes that facilitate the formation of HPV E6/E7–induced squamous cell cancers in mice using a transposon-mediated insertional mutagenesis protocol. Overall, we identified 39 candidate driver genes, including Notch1, which unexpectedly was scored by gain- or loss-of-function mutations that were capable of promoting squamous cell carcinogenesis. Autochthonous HPV-positive oral tumors possessing an activated Notch1 allele exhibited high rates of cell proliferation and tumor growth. Conversely, Notch1 loss could accelerate the growth of invasive tumors in a manner associated with increased expression of matrix metalloproteinases and other proinvasive genes. HPV oncogenes clearly cooperated with loss of Notch1, insofar as its haploinsufficiency accelerated tumor growth only in HPV-positive tumors. In clinical specimens of various human cancers, there was a consistent pattern of NOTCH1 expression that correlated with invasive character, in support of our observations in mice. Although Notch1 acts as a tumor suppressor in mouse skin, we found that oncogenes enabling any perturbation in Notch1 expression promoted tumor growth, albeit via distinct pathways. Our findings suggest caution in interpreting the meaning of putative driver gene mutations in cancer, and therefore therapeutic efforts to target them, given the significant contextual differences in which such mutations may arise, including in virus-associated tumors. Cancer Res; 75(18); 3958–69. ©2015 AACR.
Current maintenance treatment of chronic obstructive pulmonary disease in China
Authors: Kewu Huang, Chen Wang, Jiangna Han, Jinping Zheng, Lu Dai, Intact Study Investigators
Journal: European Respiratory Journal (2014)

Background:  Treatment with long-acting bronchodilators is recommended to control symptoms, reduce exacerbations and improve quality of life in COPD, according to the GOLD 2011 recommendations. In China, the patterns of pharmacological treatment in COPD patients are not known yet.   Aims: We investigated the current status of COPD maintenance treatments in China.   Methods:  1,634 patients with spirometry diagnosis of COPD from 83 hospitals covering 17 provinces in China have so far been enrolled in the ongoing INTACT study (Indacaterol on Chronic Obstructive Pulmonary Disease maintenance treatment in China). The participants had extensive interviews concerning clinical and demographic data, symptoms as assessed by the mMRC and the CAT, exacerbation history, physician-diagnosed comorbidities, and maintenance medications used at home. Patients were assigned to the GOLD December 2011 groups A, B, C, and D.   Results:  10.3% of the overall population was GOLD A; 21% B; 8.4% C and 60.3% D. The current status of COPD maintenance treatments in China are shown below. In GOLD A and GOLD B, 47.6% and 48.5% patients were on ICS/LABA; 23.1% and 25.4% patients triple.   Conclusions:  COPD treatment in this sample did not follow the GOLD 2011 recommendations, particularly in A, B, and C patients.
The Growing Burden of Chronic Obstructive Pulmonary Disease and Lung Cancer in Women
Authors: Sigal Ben-Zaken Cohen, Peter D. Paré, S. F. Paul Man, Don D. Sin
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Smoking-related lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer are growing epidemics in women in the United States and elsewhere. Although some of this disturbing trend in women can be attributed to changing smoking habits, there is emerging evidence that women may be biologically more susceptible to the harmful effects of cigarette smoke than are men. Estrogen and related compounds may up-regulate the expression of cytochrome P450 (CYP) enzymes in lungs and liver, which are involved in the metabolism of various constituents of cigarette smoke. Although metabolism of foreign substances is usually beneficial in eliminating potential toxins from the body, in some instances the metabolic process can transform harmless substances into toxic chemicals through a process called metabolic bioactivation. One important xenobiotic substrate for CYP enzymes in cigarette smoke is polycyclic aromatic hydrocarbon, which in its native form is relatively harmless in small doses but upon bioactivation by CYP enzymes, can become very toxic substances for the lungs. In this article, we explore CYP and other related pathways as potential mechanisms and targets of future research and novel discoveries to curb the growing epidemic of COPD and lung cancer in women.
Subclinical Hypothyroidism Overdiagnosis in Pregnant Women
Authors: Tim. I. M. Korevaar, Marco Medici, Robin P. Peeters
Journal: JAMA Internal Medicine (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b: results of a multicentric Italian study.
Authors: F Boccardo, D Cannata, A Rubagotti, D Guarneri, A Decensi, L Canobbio, A Curotto, G Martorana, C Pegoraro, F Selvaggi
Journal: Journal of Clinical Oncology (1994)

PURPOSE Interferons have shown a definite activity in the intravesical treatment of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of the present study was to investigate the efficacy of interferon alfa-2b (IFN) as prophylactic treatment of superficial bladder cancer. PATIENTS AND METHODS Two hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial bladder cancer, following complete transurethral resection (TUR), were randomly allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8 weeks. RESULTS MIT-C was superior to IFN treatment with respect to time to recurrence, relative recurrence rate, recurrence rate per 100 patients per month, and recurrence tumor rate per 100 patients per month. This difference was particularly evident in patients with pTa G2 tumors. After multivariate analysis, the number of primary tumors and tumor grade were the best predictors of recurrence, while allocated treatment had only a moderate effect. Intravesical treatment was well tolerated in both arms. However, more local toxicity was experienced by patients treated with MIT-C. On the other hand, fever occurred significantly more frequently in patients treated with IFN. CONCLUSION IFN was less effective, although locally better tolerated, than MIT-C as prophylactic treatment of primary superficial bladder cancer.
HER-2-PET imaging with <sup>89</sup>Zr-trastuzumab in metastatic breast cancer patients
Authors: T. Oude Munnink, E. Dijkers, M. Lub-de Hooge, J. Kosterink, A. Brouwers, J. de Jong, G. van Dongen, E. de Vries
Journal: Journal of Clinical Oncology (2009)

1045 Background: Non-invasive diagnostic tools can optimize and evaluate HER2 directed therapy in HER2 positive breast cancer patients. HER2 imaging with 111 In-trastuzumab SPECT showed promising results (Perik et al, J Clin Oncol. 2006). To further optimize HER2 imaging, we developed 89 Zr-trastuzumab for high resolution, quantitative and sensitive PET imaging. A feasibility study was performed to determine optimal conditions (tracer dose and scans) for visualization HER2 positive lesions. Methods: Trastuzumab was labeled with 89 Zr according to Verel et al. (J Nucl Med. 2003). HER-2 positive metastatic breast cancer patients received 37 MBq 89 Zr-trastuzumab at 3 protein doses of trastuzumab: 1) 10 mg, or 2) 50 mg trastuzumab, or 3) 10 mg trastuzumab when on trastuzumab treatment. Patients underwent 2 or 3 PET-scans during 1–7 days post tracer injection. Images were analyzed visually and the relative tissue or tumor uptake was calculated as the ratio tissue/tumor to whole body uptake. Results: Fourteen patients were included. Optimal time point to assess 89 Zr-trastuzumab tumor uptake was 4–5 days post injection. The tracer dose of 10 mg was sufficient for patients on trastuzumab treatment, while best imaging results in trastuzumab naive patients were obtained with the 50 mg dose as 10 mg resulted in rapid tracer clearance. In trastuzumab naive patients, 89 Zr-trastuzumab clearance was not only dose-dependent but also clearly influenced by tumor burden, indicating a need for individualization of therapy. 89 Zr-trastuzumab PET-imaging detected not only known tumor lesions in the liver, lung, bone and brain but also unknown brain and bone lesions were detected. The mean relative tumor uptake(± SD) in liver, bone and brain lesions was respectively 13.0±5.2, 4.2±1.5 and 3.5±4.2, while mean relative tissue uptake in normal liver, spleen, kidneys and brain was respectively 6.1±2.3, 2.7±0.8, 3.8±1.0 and 0.19±0.11. Conclusions: HER2-PET imaging with 89 Zr-trastuzumab shows excellent tumor tracer uptake and can be used to detect HER2 positive breast cancer metastases and to quantify 89 Zr-trastuzumab uptake, non-invasively. Patients on trastuzumab can be imaged with 37 MBq 89 Zr-trastuzumab at a protein dose of 10 mg trastuzumab while trastuzumab naive patients require 50 mg. No significant financial relationships to disclose.
Abstract 110: Anesthetic Preconditioning and Mitochondrial Slo K <sup>+</sup> Channel Activity Require <i>Slo2.1</i>
Authors: Andrew P Wojtovich, C O Smith, Sergiy M Nadtochiy, William R Urciuoli, Xiao-Ming Xia, Elizabeth Jonas, Christopher J Lingle, Keith Nehrke, Paul S Brookes
Journal: Circulation Research (2014)

Introduction: Volatile anesthetic preconditioning (APC) protects the heart from ischemia-reperfusion (IR) injury. APC elicits evolutionarily-conserved protective signaling pathways that converge at the mitochondrial level, where the Slo family of K + channels is thought to mediate protection through an unknown mechanism. Recent work in C. elegans has focused attention on the Slo2 gene product as a transducer of APC effects on hypoxic survival. In mammals, Slo2 has diverged into two paralogs, Slo 2.1 (KCNT2; Slick) and Slo2.2 (KCNT1; Slack). These genes code for Na + -activated K + channels and are highly expressed in brain, but their function in cardiomyocytes and/or mitochondria is unknown. Methods: The contribution of Slo channels to cardiac physiology was characterized using knockout mice, including Slo1 and two novel Slo2.x alleles. APC was assessed through ex-vivo cardiac IR injury. Isolated mitochondrial K + channel activity was assessed using a Tl + flux assay, and by patch-clamp of cardiac mitoplasts. Electron microscopy was used to assess mitochondrial morphology in primary cardiomyocytes and Seahorse extracellular flux analysis used to assess bioenergetics. Results: The Slo2.x ( double KO ) and the Slo2.1 single KO mice could not be protected from cardiac IR injury by APC. Physiologic approaches demonstrated that Slo2.1 is present in mitochondria and Slo2.1 -dependent mitochondrial K + transport can be triggered directly by volatile anesthetics. Cardiomyocytes from Slo2.x dKO mice exhibited profound metabolic remodeling and electron microscopy revealed that Slo2.1 knockouts had enlarged circular mitochondria. In contrast, Slo1 KO mice responded normally to APC and exhibited wild type mitochondrial physiology. Conclusion: Slo2.1 activation protects against cardiac IR, and is required for APC. Slo2.1 also contributes to mitochondrial metabolic homeostasis. As a molecular target for APC, identification of Slo2.1 may facilitate development of targeted therapeutic molecules that can protect the heart and minimize the side effects of volatile anesthetics.
Beneficial cardiovascular risk factor modification observed in patients with obstructive sleep apnoea following maxillomandibular advancement surgery
Authors: Shofiq Islam, Christopher Taylor, Ian Ormiston
Journal: European Respiratory Journal (2014)

Background: Obstructive sleep apnoea (OSA) is known as an independent risk factor associated with cardiovascular disease. Resistant hypertension is prevalent amongst OSA sufferers and this increases the risk of adverse cardiovascular events.  Aims: We studied a group of patients who had undergone Maxillomandibular advancement (MMA) surgery for their OSA assessing what benefit, if any, would be observed with regard to blood pressure control.  Methods: A retrospective study was performed on consecutive patients with OSA who had MMA between 2002 and 2012. All patients had failed first line CPAP. Pertinent data were retrieved from medical records; focusing upon blood pressure and mean arterial pressure (MAP). Pre-operative results were compared with those observed 6 months following surgery.  Results: 51 patients underwent surgery for their OSA. Blood pressure data were available in 45 cases. There was a significant fall in mean systolic blood pressure at 6 months post-surgery (131 +/- 12 compared with 127 +/- 12 mmHg, p  Conclusions: Our analysis showed a statistically significant fall in blood pressure in patients who had undergone MMA for their OSA. This is likely to be clinically beneficial to these patients given the significant cardiovascular morbidity that is associated with untreated OSA.
Heart Disease
Authors: Cynthia L. Henderson, Rigobert Lapu-Bula
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A prospective randomized trial of adjuvant brachytherapy in the management of low-grade soft tissue sarcomas of the extremity and superficial trunk.
Authors: P W Pisters, L B Harrison, J M Woodruff, J J Gaynor, M F Brennan
Journal: Journal of Clinical Oncology (1994)

PURPOSE This study was designed to evaluate the impact of adjuvant brachytherapy (BRT) on local and systemic recurrence rates in patients with low-grade sarcoma. PATIENTS AND METHODS Forty-five patients with histologic low-grade, completely resected soft tissue sarcomas of the extremity or superficial trunk were entered onto this trial. Following resection of all gross disease, patients were randomized to the BRT arm (n = 22) or to the no-BRT arm (n = 23). On the fifth or sixth postoperative day, catheters were loaded with iridium 192 to deliver a dose of 45 Gy to the tumor bed over 4 to 6 days. RESULTS The two groups were evenly distributed with respect to the distribution of presentation status (primary v recurrent), tumor site (trunk v extremity, proximal v distal extremity), tumor size (&lt; 5 cm v &gt; or = 5 cm), tumor depth (superficial v deep), and microscopic tumor margins (positive v negative). The predominant histopathologic diagnosis in each group was liposarcoma (BRT, 13 of 22 [59%]; no BRT, 14 of 23 [61%]) with other histopathologic subtypes evenly distributed between the two groups. The median follow-up duration among the ongoing survivors is 67 months. One patient in the BRT group developed systemic disease and died of progressive disease. Local recurrence occurred in five of 23 patients (22%) in the no-BRT group and six of 22 patients (27%) in the BRT group (P = .60). CONCLUSION Adjuvant radiation in the form of BRT does not appear to decrease local recurrence rates following complete resection of low-grade extremity and superficial trunk soft tissue sarcomas. Other adjuvant approaches, such as external-beam radiotherapy, are required to have a significant impact on local recurrence rates in this group of patients.
Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study.
Authors: C W Taylor, S Green, W S Dalton, S Martino, D Rector, J N Ingle, N J Robert, G T Budd, J C Paradelo, R B Natale, J D Bearden, J A Mailliard, C K Osborne
Journal: Journal of Clinical Oncology (1998)

To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy.Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed. Patients were randomly assigned to goserelin (3.6 mg subcutaneously every 4 weeks; (n = 69) versus surgical ovariectomy (n = 67). The study was initially designed as an equivalence trial with 80% power to rule out a 50% improvement in survival due to ovariectomy. However, accrual was slow and the study was terminated early, which resulted in a final power of 60% for the alternative hypothesis of equal survival distributions.FFS and OS were similar for goserelin and ovariectomy. The goserelin/ovariectomy death hazards ratio was .80 and the associated 95% confidence interval (CI) was .53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P = .006. Goserelin lowered serum estradiol to postmenopausal levels. Hot flashes (75% v 46%) and tumor flare (16% v 3%) were more common with goserelin.Goserelin and ovariectomy resulted in similar FFS and OS. We can rule out a moderate advantage for ovariectomy. Goserelin was safe and well tolerated.
Morbidity and Mortality Associated With Elective or Emergency Paraesophageal Hernia Repair
Authors: Jennifer A. Kaplan, Samuel Schecter, Matthew Y. C. Lin, Stanley J. Rogers, Jonathan T. Carter
Journal: JAMA Surgery (2015)

Morbidity and Mortality Associated With Elective or Emergency Paraesophageal Hernia RepairFor decades, the standard of care for a paraesophageal hiatal hernia (PEH) was surgical repair after diagnosis, irrespective of symptoms.This standard of care was based on the reported high risk of acute gastric volvulus, strangulation, bleeding, or obstruction associated with untreated PEH and on the high mortality associated with emergency repair. 1,2A paradigm shift occurred in 2002, when Stylopoulos et al, 3 using Markov analysis, found that watchful waiting was superior to elective repair for patients older than 65 years of age with a minimally symptomatic PEH.As a result, many patients with a PEH deferred surgery and opted for watchful waiting.A predictable consequence of watchful waiting has been an increase in the number of patients presenting with an acute PEH, sometimes with catastrophic outcomes. 4We characterized outcomes of emergency PEH repair in the modern era compared with elective repair using data from the American College of Surgeons National Surgical Quality Improvement Program. Methods |We reviewed all PEH repairs reported to the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2012.Inclusion criteria were an age of 18 years or older at the time of surgery, an International Classification of Diseases, Ninth Revision (ICD-9) primary diagnosis code of diaphragmatic hernia (ie, ICD-9 code 551.3, 552.3, or 553.3), and a primary Current Procedural Terminology code indicating repair, as described by Mungo et al. 5 Demographic data, comorbidities, and preoperative laboratory values were reviewed.The primary outcome was 30-day mortality.Secondary outcomes were hospital length of stay and serious morbidity (defined as return to the operating room, cardiac complication, sepsis, shock, ventilation >48 hours, unplanned reintubation, or cerebrovascular accident or stroke).Because this research involves only deidentified patient information, it did not require institutional review board approval from the University of California, San Francisco.Predictors of serious morbidity and 30-day mortality were identified in univariate logistic regression.Multivariate predictors were identified using backward-stepwise logistic regression.