tbuckley/cabot-search huggingface dataset:
Estrogen Receptor–Positive, Progesterone Receptor–Negative Breast Cancer: Association With Growth Factor Receptor Expression and Tamoxifen Resistance
Authors: Grazia Arpino, Heidi Weiss, Adrian V. Lee, Rachel Schiff, Sabino De Placido, C. Kent Osborne, Richard M. Elledge
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Clinical data indicate that estrogen receptor–positive/progesterone receptor–negative (ER + /PR − ) breast cancers are less sensitive to tamoxifen than are ER + /PR + tumors. It has also been reported that tamoxifen may be less effective in tumors that overexpress either HER-2 or HER-1 (epidermal growth factor receptor) and that signaling through these receptors reduces PR expression in experimental models. We hypothesized that ER + /PR − breast tumors are more likely than ER + /PR + breast tumors to have an aggressive phenotype, to express HER-1 and overexpress HER-2, and are less likely to benefit from tamoxifen adjuvant therapy. Methods: Clinical and biological features of 31 415 patients with ER + /PR + tumors were compared with those of 13 404 patients with ER + /PR − tumors. Association between disease-free survival (DFS) and HER-1 and HER-2 status was analyzed in a subset of 11 399 patients receiving adjuvant tamoxifen therapy. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression or Kaplan–Meier analyses, and all statistical tests were two-sided. Results: ER + /PR − tumors were more frequent in older patients, were larger in size, had a higher S-phase fraction, and were more likely to be aneuploid than ER + /PR + tumors. Furthermore, three times as many ER + /PR − tumors as ER + /PR + tumors expressed HER-1 (25% versus 8%; P <.001) and 50% more overexpressed HER-2 (21% versus 14%; P <.001). Among all tamoxifen-treated women, recurrence was higher among women with HER-1–expressing tumors than with HER-1–negative tumors (HR = 1.9, 95% CI = 1.0 to 3.5; P = .05); a stronger association between worse DFS and HER-2 overexpression was observed (HR = 2.3, 95% CI = 1.2 to 4.3; P = .006). However, results varied by PR status. Among tamoxifen-treated women with ER + /PR + tumors, HER-1 or HER-2 status was not associated with worse DFS. Among women with ER + /PR − tumors, however, both HER-1 expression (HR = 2.4, 95% CI = 1.0 to 5.4; P = .036) and HER-2 overexpression (HR = 2.6, 95% CI = 1.1 to 6.0; P = .022) were associated with a higher likelihood of recurrence. Conclusions: ER + /PR − tumors express higher levels of HER-1 and HER-2 and display more aggressive features than ER + /PR + tumors. As in laboratory models, lack of PR expression in ER + tumors may be a surrogate marker of aberrant growth factor signaling that could contribute to the tamoxifen resistance observed in these tumors.
Stress Burden and Diabetes in Two American Indian Reservation Communities
Authors: Luohua Jiang, Janette Beals, Nancy R. Whitesell, Yvette Roubideaux, Spero M. Manson
Journal: Diabetes Care (2008)

To examine the association between psychosocial stress and diabetes in two American Indian reservation communities (Northern Plains and Southwest).The American Indian Services Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project (AI-SUPERPFP), a cross-sectional probability sample survey, interviewed 3,084 randomly selected members of two American Indian tribal groups. Included were a psychiatric epidemiological interview, a physical health problems checklist, and an extensive sociodemographic section.Stress was common in these reservation communities, and the stress burden was greater among those with diabetes. After adjusting for sociodemographic characteristics, early-life interpersonal trauma and community family dysfunction were significantly associated with increased odds of diabetes in the Northern Plains, while discrimination and community addiction problems were significantly associated with increased odds of diabetes in the Southwest.A number of psychosocial stresses were significantly associated with increased odds of self-reported diabetes in these two American Indian communities.
Evaluation of neodymium:yttrium-aluminum-garnet capsulotomies in eyes implanted with AcrySof intraocular lenses 1 1The authors have no financial or proprietary interest in any products mentioned in this paper.
Authors: Josef M Schmidbauer, Luis G Vargas, David J Apple, Marcela Escobar-Gomez, Andrea Izak, Stella N Arthur, Ariadne Golescu, Qun Peng
Journal: Ophthalmology (2002)
Parallel adaptation of the rabbit renal cortical sodium/proton antiporter and sodium/bicarbonate cotransporter in metabolic acidosis and alkalosis.
Authors: T Akiba, V K Rocco, D G Warnock
Journal: Journal of Clinical Investigation (1987)

Recent studies have shown that the bicarbonate reabsorptive capacity of the proximal tubule is increased in metabolic acidosis. For net bicarbonate reabsorption to be regulated, there may be changes in the rate of apical H+ secretion as well as in the basolateral base exit step. The present studies examined the rate of Na+/H+ exchange (acridine orange method) and Na+/HCO3 cotransport (22Na uptake) in apical and basolateral membranes prepared from the rabbit renal cortex by sucrose density gradient centrifugation. NH4Cl loading was used to produce acidosis (arterial pH, 7.27 +/- 0.03), and Cl-deficient diet with furosemide was used to produce alkalosis (arterial pH, 7.51 +/- 0.02). Maximal transport rate (Vmax) of Na+/H+ antiporter and Na+/HCO3 cotransporter were inversely related with plasma bicarbonate concentration from 6 to 39 mM. Furthermore, the maximal transport rates of both systems varied in parallel; when Vmax for the Na+/HCO3 cotransporter was plotted against Vmax for the Na+/H+ antiporter for each of the 24 groups of rabbits, the regression coefficient (r) was 0.648 (P less than 0.001). There was no effect of acidosis or alkalosis on affinity for Na+ of either transporter. We conclude that both apical and basolateral H+/HCO3 transporters adapt during acid-base disturbances, and that the maximal transport rates of both systems vary in parallel during such acid-base perturbations.
Challenges in Systematic Reviews of Complementary and Alternative Medicine Topics
Authors: Paul G. Shekelle
Journal: Annals of Internal Medicine (2005)

The use of complementary and alternative medicine (CAM) continues to grow in the United States. The Agency for Healthcare Research and Quality has devoted a substantial proportion of the Evidence-based Practice Center (EPC) program to systematic reviews of CAM. Such syntheses present different challenges from those conducted on western medicine topics, and in many ways are more difficult. We discuss 3 challenges: identifying evidence about CAM, assessing the quality of individual studies, and addressing rare serious adverse events. We use illustrations from EPC evidence reports to show readers approaches to the 3 areas and then present specific recommendations for each issue.
Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in HIV-infected hospitalised patients
Authors: Jonathan G. Peter, Grant Theron, Richard van Zyl-Smit, Asheen Haripersad, Lynelle Mottay, Sarah Kraus, Anke Binder, Richard Meldau, Anneli Hardy, Keertan Dheda
Journal: European Respiratory Journal (2012)

Lack of point-of-care tests for tuberculosis (TB) result in diagnostic delay, and increased mortality and healthcare-related costs. The urine Determine TM TB-LAM point-of-care strip-test was evaluated in 335 prospectively-recruited hospitalised patients with suspected TB-HIV co-infection (group 1) and from 88 HIV-infected hospitalised patients with non-TB diagnoses (group 2). Cut-off point-specific analyses were performed using: 1) a microbiological reference standard (culture positive versus negative); and 2) a composite reference standard (exclusion of patients with clinical-TB from the culture-negative group). Using the microbiological reference and the manufacturer-recommended grade-1 cut-off point, LAM sensitivity and specificity was 66% (95% CI 57–74%). By contrast, using the composite reference sensitivity was 60% (95% CI 53–67%) and specificity improved to 96% (95% CI 89–100%) (p=0.001). The same pattern was seen when the grade-2 cut-off point was used (specificity 75% versus 96%; p=0.01). In group two patients specificity was poor using the grade-1 cut-off point, but improved significantly when the grade-2 cut-off point was used (90% versus 99%; p=0.009). The grade-2 cut-off point also offered superior inter-reader reliability (p=0.002). Sensitivity was highest in those with a CD4 &lt;200 cells per mL. LAM combined with smear-microscopy was able to rule-in TB in 71% of Mycobacterium tuberculosis culture-positive patients. This preliminary study indicates that the LAM strip-test may be a potentially useful rapid rule-in test for TB in hospitalised patients with advanced immunosuppression. The grade 2, but not the manufacturer-recommended grade 1 cut-off point, offered superior rule-in utility and inter-reader reliability. Larger studies to evaluate cut-off points and diagnostic accuracy are urgently required.
Induction of Skeletal Fluorosis in Two Common Demineralizing Disorders
Authors: Phin Cohen
Journal: JAMA (1966)

THE COMBINATION of fluoride, calcium, and androgen therapy has been shown to induce radiologically obvious fluorosis in four cases of multiple myeloma.<sup>1</sup>The purpose of this report is to show that fluorosis may be induced in two other common types of osteoporosis. <h3>Report of Cases</h3><h3>CASE 1.—</h3> A 59-year-old woman with classical rheumatoid arthritis was seen in 1950. During the next nine years she was treated in another clinic with daily doses of corticosteroids with good control of joint symptoms. In 1959 severe thrombocytopenia developed which was unresponsive to corticosteroids. Splenectomy resulted only in a brief remission, and treatment with prednisone was continued at a dose of 15 mg daily. In 1962, because of severe back pain with vertebral (Fig 1, top<i>left</i>) and pelvic (Fig 1,<i>bottom left</i>) osteoporosis, the prednisone was reduced to 7.5 mg/day and treatment with azathioprine was started at 150 mg/day. This program controlled
Optimising colorectal cancer screening acceptance: a review
Authors: Carlo Senore, John Inadomi, Nereo Segnan, Cristina Bellisario, Cesare Hassan
Journal: Gut (2015)

The study aims to review available evidence concerning effective interventions to increase colorectal cancer (CRC) screening acceptance. We performed a literature search of randomised trials designed to increase individuals9 use of CRC screening on PubMed, Embase, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects. Small (≤100 subjects per arm) studies and those reporting results of interventions implemented before publication of the large faecal occult blood test trials were excluded. Interventions were categorised following the Continuum of Cancer Care and the PRECEDE–PROCEED models and studies were grouped by screening model (opportunistic vs organised). Multifactor interventions targeting multiple levels of care and considering factors outside the individual clinician control, represent the most effective strategy to enhance CRC screening acceptance. Removing financial barriers, implementing methods allowing a systematic contact of the whole target population, using personal invitation letters, preferably signed by the reference care provider, and reminders mailed to all non-attendees are highly effective in enhancing CRC screening acceptance. Physician reminders may support the diffusion of screening, but they can be effective only for individuals who have access to and make use of healthcare services. Educational interventions for patients and providers are effective, but the implementation of organisational measures may be necessary to favour their impact. Available evidence indicates that organised programmes allow to achieve an extensive coverage and to enhance equity of access, while maximising the health impact of screening. They provide at the same time an infrastructure allowing to achieve a more favourable cost-effectiveness profile of potentially effective strategies, which would not be sustainable in opportunistic settings.
Arthur Osman Farquhar Stuart
Authors: H. T Fay
Journal: BMJ (2002)

Among Sierra Leoneans and the wider West African community, Arthur Stuart was known as “the leading physician of his generation.” The weekly magazine West Africa said that “in a country whose perverse politics no longer treats people as people, Dr Stuart was first and last the people's doctor.” He came to England for his medical training, going back to work in the remote parts of his beloved country, and returned to England 10 years later to study at the Liverpool School of Tropical Medicine. But he spent most of his life and career in Sierra Leone's capital, Freetown, where he cared for rich and poor alike. …
Effects of an Angiotensin-converting Enzyme Inhibitor–based Regimen on Pneumonia Risk
Authors: Takayoshi Ohkubo, Neil Chapman, Bruce Neal, Mark Woodward, Teruo Omae, John Chalmers
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Observational studies conducted among Asian populations suggest that the risk of pneumonia is substantially reduced among users of angiotensin-converting enzyme (ACE) inhibitors but not other blood pressure–lowering agents. We conducted analyses of the effects of ACE inhibitor therapy on pneumonia in 6,105 patients with a history of stroke or transient ischemic attack enrolled in a randomized trial conducted in Australasia, Europe, and Asia. Patients were randomly assigned perindopril-based active treatment or placebo. The effects of ACE inhibitors on pneumonia (fatal or nonfatal) were determined from Cox models fitted according to the principle of intention to treat. During a median follow-up of 3.9 years, 261 patients developed pneumonia. Overall, active treatment was associated with a nonsignificant 19% lower risk of pneumonia (95% confidence interval, −3 to 37; p = 0.09) compared with placebo. Active treatment significantly reduced the risk of pneumonia among participants of Asian ethnicity (47%, 14–67%; p = 0.01), with no significant effect among non-Asian participants (5%, −27 to 29%; p = 0.7) (p for homogeneity = 0.04). These findings substantially add to the body of evidence about the effects of these drugs on pneumonia but do not provide the definitive information required to inform clinical decisions about the prevention of pneumonia with ACE inhibitors.
Multifocal osteonecrosis related to steroid treatment in a patient with ulcerative colitis.
Authors: P V Madsen, G Andersen
Journal: Gut (1994)

A case of multifocal steroid related osteonecrosis in a patient with ulcerative colitis is presented. The pathogenesis, diagnosis, natural history, and treatment of the disease is discussed briefly with emphasis on the importance of early diagnosis--preferably by magnetic resonance imaging. Early diagnosis often depends on the gastroenterologist considering the possibility of osteonecrosis.
Haematometra in Right Horn of an Undeveloped Double Uterus, Successfully Treated by Abdominal Section
Authors: F. W. N. Haultain
Journal: BMJ (1900)

CASES of absence of fusion of the Millerian ducts to a greater or less extent are of comparative frequency, and as might be expected give rise to almost endless varieties of anomalous conditions.These are of great interest, not only on account of their anatomical peculiarities but more particularly from a clinical standpoint, as the pathological effects of arrested development tend frequently to extremely grave conse- quences, and at the same time are often surrounded with
State-of-the-Art Therapeutics: Diffuse Large B-Cell Lymphoma
Authors: Bertrand Coiffier
Journal: Journal of Clinical Oncology (2005)

This article is a review of the improvement in the treatment of patients with diffuse large B-cell lymphoma made during the last 10 years. Patients with diffuse large B-cell lymphoma now have a better outcome with longer survival because of two major developments: (1) increasing the dose of active drugs with shortening the time between cycles, resulting in dose-dense and/or dose-intense regimens; and (2) combining rituximab with chemotherapy. Both strategies were associated with higher response rates, lower relapse rates, longer event-free survival, longer time to progression, and longer overall survival, particularly in patients without adverse prognostic parameters. A combination of dose-dense, dose-intense regimens plus rituximab is currently being tested for poor-risk patients with diffuse large B-cell lymphoma. However, much work has to be done for patients with high-risk lymphoma. It may come with a better definition of genetic abnormalities specifically associated with refractoriness to chemotherapy.
Acute lung injury and ventilator associated pneumonia: introduction
Authors: J. Mancebo, J-Y. Fagon
Journal: European Respiratory Journal (2003)

Acute lung injury and ventilator-associated pneumonia are recurrent, never ending issues for critical care physicians.Not astonishing though that the editors of this supplement are interested one in the field of mechanical ventilation, the other in infectious diseases.There is no doubt that these two areas of knowledge, are central pillars of modern critical care medicine.The goal of this supplement is to review the current understanding of the mechanisms behind acute lung injury, strategies for its treatment, and prevention and management of ventilator-associated pneumonia, one of the most worrying complications occurring during mechanical ventilation.What is rare, however, is to have such an equilibrated marriage like this in a single supplement of a scientific journal.When planning the outline of this Supplement, we tried to keep a balance among basic science, pathophysiology, and clinical issues including prevention, diagnosis and treatment.When deciding the topics, we chose a dual approach: the novelty and the essentials.Authors are well known specialists in their respective fields, and have provided state-of-the-art articles which every respiratory physician and intensivist should know.
Mycobacterium tuberculosis DNA facilitates selective autophagy within infected macrophages
Authors: Rawya Ahmed
Journal: Thorax (2012)

Mycobacterium tuberculosis DNA facilitates selective autophagy within infected macrophagesSelective autophagy is a housekeeping energy-generating cytosolic process through which organelles and protein aggregates are tagged within a double-membrane autophagosome and delivered to the lysosome for proteolysis releasing amino acids and generating ATP.The molecular mechanisms underlying protein selection for degradation and ubiquitin complex formation within the cytosol are yet to be elucidated.The authors describe a novel molecular process through a series of experiments using bone marrow-derived macrophages infected with wild-type Mycobacterium tuberculosis (MTB).They demonstrate that MTB possesses a pore-forming enzyme system ESX-1 that exposes the MTB-containing vacuole to the cytosol.The exposure of mycobacterial DNA attracts ubiquitin and ubiquitin-binding cytosolic receptors, p62 and NADP52, through activation of the DNA-sensing STING pathway.This recruits the protein LC3 that forms puncta within the autophagosome marking it for fusion with the lysosome.They were able to demonstrate that this process is driven by MTB DNA, that bacteria targeted are killed within phagolysosomes and that this is essential for in vivo control of MTB infection-demonstrated by a fall in the number of colony-forming units within 6 h and 24 h post-infection.The work sheds new light on the processes through which MTB is cleared within macrophages, adding to the growing interest over the last decade on the cellular mechanisms underlying autophagy.It paves the way for the molecular pathways underlying MTB resistance to be elucidated and in turn identify appropriate targets for therapeutic intervention.
Response of subcutaneous and cutaneous metastases of malignant melanoma to combined cytostatic plus interferon therapy
Authors: M. HAHKA-KEMPPINEN, T. MUHONEN, M. VIROLAINEN, A. JEKUNEN, S. ASKO-SELTAVAARA, S. PYRHÖNEN
Journal: British Journal of Dermatology (2010)

Summary A chemotherapy regimen consisting of dacarbazine (DTIC), vincristine, bleomycin and lomustine (CCNU) was combined with natural leucocyte interferon (IFN) in the treatment of 37 patients with cutaneous and subcutaneous metastases of malignant melanoma. Twenty-five also had concomitant lymph node, visceral, bone or brain metastases. Fifteen patients (41%) experienced complete response (CR) and 10 (27%) partial response (PR) of the superficial lesions. In addition, three patients were rendered surgically tumour-free after PR or disease stabilization during drug therapy. The median overall duration of response was 10.2 months (range 1–53 months). In disseminated disease, the combined therapy produced favourable results, particularly with regard to superficial lesions. It is also possible that this therapy may retard the growth of aggressive subcutaneous metastases in patients who have previously had multiple surgical procedures in an attempt to stabilize their disease. In a small proportion of patients, the long-term complete remission with the drug therapy alone, or in combination with surgery, suggests that this regimen might have been curative.
Understanding and Modulating Mammalian-Microbial Communication for Improved Human Health
Authors: Sridhar Mani, Urs A. Boelsterli, Matthew R. Redinbo
Journal: The Annual Review of Pharmacology and Toxicology (2013)

The fact that the bacteria in the human gastrointestinal (GI) tract play a symbiotic role was noted as early as 1885, well before we began to manage microbial infections using antibiotics. However, even with the first antimicrobial compounds used in humans, the sulfa drugs, microbes were recognized to be critically involved in the biotransformation of these therapeutics. Thus, the roles played by the microbiota in physiology and in the management of human health have long been appreciated. Detailed examinations of GI symbiotic bacteria that started in the early 2000s and the first phases of the Human Microbiome Project that were completed in 2012 have ushered in an exciting period of granularity with respect to the ecology, genetics, and chemistry of the mammalian-microbial axes of communication. Here we review aspects of the biochemical pathways at play between commensal GI bacteria and several mammalian systems, including both local-epithelia and nonlocal responses impacting inflammation, immunology, metabolism, and neurobiology. Finally, we discuss how the microbial biotransformation of therapeutic compounds, such as anticancer or nonsteroidal anti-inflammatory drugs, can be modulated to reduce toxicity and potentially improve therapeutic efficacy.