tbuckley/cabot-search huggingface dataset:
Elevated Cyclooxygenase-2 Expression Is Associated with Altered Expression of p53 and SMAD4, Amplification of HER-2/neu, and Poor Outcome in Serous Ovarian Carcinoma
Authors: Tiina-Liisa Erkinheimo, Heini Lassus, Patrik Finne, Bastiaan P. van Rees, Arto Leminen, Olavi Ylikorkala, Caj Haglund, Ralf Butzow, Ari Ristimäki
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: Cyclooxygenase-2 (COX-2) is frequently expressed in human adenocarcinomas and inhibition of COX-2 suppresses tumor formation in various animal models of carcinogenesis. We analyzed expression of COX-2 protein in human serous ovarian carcinomas by immunohistochemistry (n = 442) and by Western blotting (n = 12) and COX-2 mRNA by reverse transcriptase PCR (n = 12). COX-2 immunoreactivity was correlated to clinicopathological variables and to expression of p53 and SMAD4 as detected by immunohistochemistry and to amplification of HER-2/neu as detected by in situ hybridization. Results: COX-2 mRNA expression was detected in 75% (9 of 12) and COX-2 protein in 42% (5 of 12) of the serous ovarian adenocarcinoma specimens as detected by reverse transcriptase-PCR and Western blot analysis, respectively. Moderate to strong (elevated) immunoreactivity for COX-2 was detected in 70% (310 of 442) of the tumors. Elevated COX-2 expression associated with reduced disease-specific survival (P = 0.0011), high histological grade (P &amp;lt; 0.0001), residual tumor size &amp;gt; 1 cm (P = 0.0111), and age &amp;gt; 57 years (P = 0.0099). Tumors with altered immunostaining pattern for p53 or SMAD4 expressed more frequently elevated levels of COX-2 when compared with the tumors with normal staining pattern of these tumor suppressor genes (P &amp;lt; 0.0001 and P = 0.0004, respectively). In addition, elevated COX-2 expression associated with amplification of HER-2/neu oncogene (P = 0.0479). Conclusions: Our results suggest that elevated expression of COX-2 associates with reduced survival in serous ovarian carcinomas and that expression of COX-2 may be induced in these tumors by loss of tumor suppressor genes such as p53and SMAD4and by amplification of HER-2/neuoncogene.
A Case of Episodic Flushing and Organic Psychosis: Reversal by Opiate Antagonists
Authors: DANIEL J. GOLDSTEIN
Journal: Annals of Internal Medicine (1983)

A woman had episodic attacks of flushing associated with severe skin, bone, and abdominal pain, accompanied by mood alterations and anxiety, and followed by an organic psychosis. These symptoms and signs could be induced by small doses of clonidine, L-5-hydroxytryptophan, pentagastrin, insulin, epinephrine, compound 48/80, methacholine, morphine, histamine, or d-tubocurarine. Skin testing showed abnormally sensitive mast cells and an exaggerated axon flare. Cimetidine initially prevented the attacks but became less effective after 18 months. Thyrotropin-releasing hormone stopped the skin pain whereas neurotensin reproduced the burning sensation in the skin without inducing the attack. Both the flush and the organic psychosis were reversed entirely by naloxone or naltrexone, and the hallucinosis could be reversed by vasodilators.
Raised respiratory rate in elderly patients: a valuable physical sign.
Authors: J P McFadden, R C Price, H D Eastwood, R S Briggs
Journal: BMJ (1982)

Measurements of respiratory rate in 82 long-stay patients aged 67-101 years yielded a normal range of 16-25 breaths a minute. In a prospective study of 60 consecutive acute admissions to a geriatric unit, 19 out of 21 patients diagnosed as lower respiratory tract infections had respiratory rates above the upper limit of normal on the day of diagnosis; the rise in respiratory rate preceded the clinical diagnosis. All eight patients who were diagnosed on admission as having a lower respiratory tract infection had a respiratory rate greater than 26, with a mean of 29.7 breaths a minute. Patients admitted for other conditions-for example, urinary tract infection-rarely had respiratory rates outside the normal range. Accurate measurement of respiratory rate is a valuable diagnostic aid in elderly patients.
Methodological Aspects of the Evaluation of Psychotherapies
Authors: G. Leresche, J.F. Ballif
Journal: Psychotherapy and Psychosomatics (1980)

With the aim of methodically examining the evaluation of short-term psychotherapies, the authors study the conditions of setting up and applying Osgood's semantic differential. For an ad hoc selection of the inducive words, an in-depth study of the parametrization of bipolar scales based on new premises is undertaken, after which the semantic space is reconstructed. These stages are carried out, on the one hand, on a sample of patients under treatment at a psychiatric policlinic, and on the other hand, on a sample drawn from the general population. The results are compared step for step. In addition, correspondence analyses between the inducive words and the scales shed new light on the stability of Osgood's semantic differential.
The future for trainee doctors
Authors: Martin Marshall
Journal: BMJ (2007)

The Tooke report has identified the challenges, now the profession must respond

Medicine has always been a highly competitive career option, attracting some of the brightest and best of each generation. For those who succeed, the rewards go beyond job satisfaction and social standing. Few careers guarantee the same level of income and security of employment. Fewer still offer the same high odds of getting to the top of the professional ladder by becoming a consultant or principal in general practice. After years of good fortune, these benefits are seen by most doctors almost as a right. Other professions must look on with envy.

The fallout from the current reforms of postgraduate medical training, Modernising Medical Careers (MMC), is shaking these expectations to the core. The tacit understanding that some specialty training programmes were more popular than others has now been turned into the hard reality of competition ratios.1 In 2007, there were 53.2 applicants for each post in the third year of specialist training in cardiothoracic surgery, whereas fewer than one person applied per post for a similar number of jobs in clinical immunology. Next year is likely to be even more competitive, …
Long-Term Administration of Second-Line Chemotherapy with S-1 and Gemcitabine for Platinum-Resistant Non-small Cell Lung Cancer: A Phase II Study
Authors: Yuichi Takiguchi, Takashi Seto, Yukito Ichinose, Naoyuki Nogami, Tetsu Shinkai, Hiroaki Okamoto, Koichi Minato, Nobuhiko Seki, Kenji Eguchi, Kazuma Kishi, Masanori Nishikawa, Koshiro Watanabe
Journal: Journal of Thoracic Oncology (2010)
Effect of Synchronized, Systolic, Lower Body, Positive Pressure on Hemodynamics in Human Septic Shock: A Pilot Study
Authors: John P. Gunter, Bennett P. deBoisblanc, Brad S. Rust, William D. Johnson, Warren R. Summer
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The pathophysiologic disturbance observed in volume-resuscitated patients with septic shock is primarily that of hyperdynamic circulation with a markedly reduced systemic vascular resistance. We hypothesized that external, mechanically applied, phasic lower body positive pressure could increase systemic vascular resistance and, thus, blood pressure in patients with refractory septic shock. A total of nine studies were performed on seven patients with septic shock refractory to volume resuscitation and vasopressors. All pre-existing therapies were continued unaltered during the study period. Phasic lower body positive pressure was produced by rapid synchronized inflation of pneumatic fabric cuffs fitted around each lower extremity. The cuffs were inflated for 200 ms to a pressure of 150 mm Hg, and the timing of inflation was adjusted to coincide with the peak systolic arterial pressure. Hemodynamic measurements were obtained at baseline and after 15 min of phasic lower body positive pressure. This off-on cycle was repeated twice for each study. Phasic lower body positive pressure increased mean arterial pressure by 12% and cardiac index by 14% (p = 0.01) over baseline (p ≤ 0.001). Heart rate, central venous pressure, pulmonary capillary wedge pressure, arterial pH, arterial pO2, and mixed venous pO2 were unchanged. Synchronized external systolic compression of the lower extremities increased mean arterial pressure and cardiac output in seven patients with refractory septic shock. This hemodynamic improvement was independent of changes in calculated systemic vascular resistance.
THE EMERGENCE OF PSEUDOTUBERCULOSIS IN RATS GIVEN CORTISONE
Authors: Charles LeMaistre, Ralph Tompsett
Journal: The Journal of Experimental Medicine (1952)

The emergence of a severe infection in albino rats during cortisone administration is reported. Evidence is present that the causative agent of the disease was Corynebacterium pseudotuberculosis murium, a microbial species not demonstrably a part of the usual bacterial flora of the host. It has been possible to reproduce the disease in rats by a relatively large infecting inoculum of this strain of Corynebacterium, but the susceptibility of normal rats to infection has been found to be low. The disease occurred in 41 of 50 rats given cortisone and in 28 of 30 instances in which isolation of the etiologic agent was attempted, this strain of Corynebacterium was recovered. The disease was characterized by widespread necrotizing lesions, with multiple coalescent lesions occurring in the lungs, and similar, though smaller lesions of the pericardium, pleurae, liver, and kidneys. In its gross appearance the pulmonary disease was similar to that of a disseminated, far advanced tuberculous process. The histologic appearance of the lesions, however, was sufficiently distinctive so that they could be readily differentiated from the lesions characteristically produced by Mycobacterium tuberculosis. Moreover, the host-parasite relationship established by the experimental infection with avian tubercle bacilli, was not markedly altered by the factors which led to the emergence of the pseudotuberculosis. In contrast to the high frequency of pseudotuberculosis in rats given cortisone, no instance of this disease has been encountered in a similar group of animals given large quantities of corticotropin.
East-West mortality divide and its potential explanations: proposed research agenda
Authors: M. Bobak, M. Marmot
Journal: BMJ (1996)

There is a sharp divide in mortality between eastern and western Europe, which has largely developed over the past three decades and is caused mainly by chronic diseases in adulthood. The difference in life expectancy at birth between the best and worst European countries in this respect is more than 10 years for both sexes. The reasons for these differences in mortality are not clear and data currently available permit only speculation. The contributions of medical care and pollution are likely to be modest; health behaviour, diet, and alcohol consumption seem to be more important; smoking seems to have the largest impact. There is also evidence that psychosocial factors are less favourable in eastern Europe. Available data show socioeconomic gradients in all cause mortality within eastern European countries similar to those in the West. Determinants of the mortality gap between eastern and western Europe are probably related to the contrast in their social environments and may be similar to those underlying the social gradients in mortality within countries.
Corneal Confocal Microscopy Detects Neuropathy in Subjects With Impaired Glucose Tolerance
Authors: Omar Asghar, Ioannis N. Petropoulos, Uazman Alam, Wendy Jones, Maria Jeziorska, Andrew Marshall, Georgios Ponirakis, Hassan Fadavi, Andrew J.M. Boulton, Mitra Tavakoli, Rayaz A. Malik
Journal: Diabetes Care (2014)

Impaired glucose tolerance (IGT) represents one of the earliest stages of glucose dysregulation and is associated with macrovascular disease, retinopathy, and microalbuminuria, but whether IGT causes neuropathy is unclear.Thirty-seven subjects with IGT and 20 age-matched control subjects underwent a comprehensive evaluation of neuropathy by assessing symptoms, neurological deficits, nerve conduction studies, quantitative sensory testing, heart rate variability deep breathing (HRVdb), skin biopsy, and corneal confocal microscopy (CCM).Subjects with IGT had a significantly increased neuropathy symptom profile (P < 0.001), McGill pain index (P < 0.001), neuropathy disability score (P = 0.001), vibration perception threshold (P = 0.002), warm threshold (P = 0.006), and cool threshold (P = 0.03), with a reduction in intraepidermal nerve fiber density (P = 0.03), corneal nerve fiber density (P < 0.001), corneal nerve branch density (P = 0.002), and corneal nerve fiber length (P = 0.05). No significant difference was found in sensory and motor nerve amplitude and conduction velocity or HRVdb.Subjects with IGT have evidence of neuropathy, particularly small-fiber damage, which can be detected using skin biopsy and CCM.
Physician Evaluation and Management of Nursing Home Residents
Authors: Joseph G. Ouslander
Journal: Annals of Internal Medicine (1994)

The diverse goals of nursing home care, the heterogeneity of nursing home residents, and the varied circumstances under which physicians care for them make their evaluation and care complex and challenging.When evaluating and caring for nursing home residents, physicians must address many issues besides treatment of multiple chronic diseases (including impairments in cognitive and physical functioning, sensory deficits, depression, and behavioral disorders associated with dementia) and concerns of family members. The physician should be integrated with an interdisciplinary team composed of nurses, rehabilitation therapists, social workers, and others. Recently implemented federal rules for nursing home care, which include the Minimum Data Set and Resident Assessment Protocols, provide a useful framework for interdisciplinary assessment and care planning and should improve the care nursing home residents receive. Better data are needed on the most cost-effective strategies for evaluating and caring for nursing home residents. Reimbursement for physician services, availability of nurse practitioners and physician assistants, and overall quality of nursing home care must be improved so physicians can better achieve the recommendations outlined.
"Polypill" to fight cardiovascular disease: Now who's playing God?
Authors: S. Taylor
Journal: BMJ (2003)

EDITOR—The implications of Wald and Law's paper are truly monumental.1 Although they are scientifically brilliant and Nobelian in their relevance, they are simultaneously unsettling and alarming.

The impact of such a low cost initiative on individual and population based health parameters is potentially enormous. But having, at a stroke (to coin a phrase), slashed the risk of cardiovascular disease—what then …
Mental problems in rheumatoid arthritis.
Authors: A J Rowe
Journal: BMJ (1969)

cancer discovered by miniature mass radio- graphy.Of course, mass radiography has widened its scope since its introduction in the early1940s.It has become a service, a tool for presymptomatic diagnosis.X-ray depart- ments in hospitals are neither meant nor equipped to do this.To destroy such a service without even taking regional differences and problems into consideration is a retrograde step.-Iam, etc.,
Silicone Breast Implants and Atypical Autoimmune Disease
Authors: Eugene H. Ryan
Journal: Annals of Internal Medicine (1993)

Letters15 November 1993Silicone Breast Implants and Atypical Autoimmune DiseaseEugene H. Ryan, MD and Walter J. Moore, MDEugene H. Ryan, MDSearch for more papers by this author and Walter J. Moore, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-10-199311150-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Bridges and associates [1] have provided timely documentation of clinical and immunologic features in women with rheumatologic complaints after silicone augmentation mammoplasty. Human adjuvant disease is a connective tissue disorder that sometimes meets American College of Rheumatology criteria for the diagnosis of systemic lupus erythematosus, rheumatoid arthritis, progressive systemic sclerosis, mixed connective tissue disease, or unclassified rheumatic syndromes [1-5] and occurs 6 to 15 years after implantation mammoplasty [1-5]. We describe a 39-year-old white woman who had augmentation mammoplasty in 1982 and revision of a ruptured left implant in 1989 and who developed a skin rash and ...References1. Bridges AJ, Conley C, Wang G, Burns PE, Vasey FB. A clinical and immunological evaluation of women with silicone breast implants and symptoms of rheumatic disease. Ann Intern Med. 1993; 118:929-36. Google Scholar2. Spiera H. Scleroderma after silicone augmentation mammoplasty. JAMA. 1988; 260:236-8. Google Scholar3. Brozena SJ, Fenske NA, Cruse CW, Espinoza CG, Vasey FB, Germain BF, et al. Human adjuvant disease following augmentation mammoplasty. Arch Dermatol. 1988; 124:1383-6. Google Scholar4. Weisman MH, Vecchione TR, Albert D, Moor LT, Mueller MR. Connective tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg. 1988; 82:626-30. Google Scholar5. Varga J, Jimenez S. Augmentation mammoplasty and scleroderma. Arch Dermatol. 1990; 126:1220-2. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPneumonitis caused by silicone gel following breast implant ruptureSilicone breast implants 15 November 1993Volume 119, Issue 10Page: 1053-1054KeywordsInflammationLesionsLupus erythematosusMixed connective tissue diseaseRashesResearch laboratoriesRheumatoid arthritisRheumatologySclerodermaSystemic lupus erythematosus Issue Published: 15 November 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 2269: Metformin prolongs survival in a K-rasLA2 lung cancer mouse model by inhibiting cancer stem cells and tumor growth.
Authors: Hiroshi Kitagawa, Matthew Dallos, Brendan Quinn, Ajaikumar Kunnumakkara, Irem Dogan, Christine M. Hollander, Phillip A. Dennis
Journal: Cancer Research (2013)

Abstract Mutations in K-Ras are characteristic of human lung cancers and occur almost exclusively in smokers. Metformin, which is widely prescribed for the treatment of type II diabetes mellitus, may reduce lung cancer incidence in diabetics. We previously showed that metformin prevents K-Ras-mediated lung tumorigenesis in mice exposed to tobacco-carcinogen in an AMPK-independent manner. To elucidate further mechanisms of tumor prevention and estimate the survival impact of metformin on mutant K-Ras-mediated-lung tumorigenesis, we treated mutant K-Ras transgenic mice (K-RasLA2), with oral metformin. Metformin reduced tumor multiplicity by 48.9% and increased overall survival by 34% (median survival 191 days (control) vs 257 days (metformin); HR=0.27; 95% CI 0.11-0.68; p=0.009). Metformin decreased the number of bronchioloalveolar cells (BASCs), which are recognized as the cells of origin for lung adenocarcinomas initiated by oncogenic K-ras, as well as expression of cancer stem cell markers such as OCT4 and SOX2. Markers of cellular proliferation such as cyclin D1 and Ki67 were also decreased in lung tumors from metformin-treated mice. Metformin inhibited activation of multiple receptor tyrosine kinases as well as Ras-Raf signaling. Collectively, these data confirm that metformin inhibits K-Ras-induced lung tumorigenesis and identifies tumor-initiating cells as targets of metformin whose inhibition may underlie the ability of metformin to prolong survival. Clinical chemoprevention trials using metformin are warranted for high-risk populations likely to develop K-Ras mutations such as current or former smokers. Citation Format: Hiroshi Kitagawa, Matthew Dallos, Brendan Quinn, Ajaikumar Kunnumakkara, Irem Dogan, Christine M. Hollander, Phillip A. Dennis. Metformin prolongs survival in a K-rasLA2 lung cancer mouse model by inhibiting cancer stem cells and tumor growth. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2269. doi:10.1158/1538-7445.AM2013-2269
Elevated serum uric acid levels following heart transplantation predict all‐cause and cardiac mortality
Authors: Satish Arora, Pål Aukrust, Thor Ueland, Kaspar Broch, Svein Simonsen, Einar Gude, Arnt E. Fiane, Odd Geiran, Ragnhild Wergeland, Arne K. Andreassen, Lars Gullestad
Journal: European Journal of Heart Failure (2009)
Dolutegravir plus Abacavir–Lamivudine for the Treatment of HIV-1 Infection
Authors: Sharon L. Walmsley, Antonio Antela, Nathan Clumeck, Dan Duiculescu, Andrea Eberhard, Felix Gutiérrez, Laurent Hocqueloux, Franco Maggiolo, Uriel Sandkovsky, Catherine Granier, Keith Pappa, Brian Wynne, Sherene Min, Garrett Nichols
Journal: New England Journal of Medicine (2013)

Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen.We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance.A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group.Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015 .).
TCTAP A-195 The Impact of Multi-vessel Spasm on 3-year Clinical Outcomes Compared with Single Vessel Spasm as Assessed by Intracoronary Acetylcholine Provocation Test
Authors: Ji Young Park, Seung-Woon Rha, Byoung Geol Choi, Jae Woong Choi, Sung Kee Ryu, Se Yeon Choi, Yoonjee Park, Akkala Raghavender Goud, Hu Li, Sunki Lee, Ji Bak Kim, Sung Il Im, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2014)