tbuckley/cabot-search huggingface dataset:
Electrocardiographic changes suggestive of myocardial ischemia elicited by dipyridamole infusion in acute rejection early after heart transplantation.
Authors: E Picano, G De Pieri, J A Salerno, E Arbustini, A Distante, L Martinelli, A Pucci, C Montemartini, M Viganò, L Donato
Journal: Circulation (1990)

Acute cardiac rejection, syndrome X, and arterial hypertension can induce small vessel damage and, therefore, restriction of coronary reserve in the presence of normal epicardial coronary arteries. A characteristic response pattern to dipyridamole (DIP) infusion has been previously described in syndrome X and arterial hypertension: ST segment depression without any measurable systolic dysfunction. The aim of this study was to establish whether acute cardiac rejection might induce electrocardiographic alterations during DIP infusion. Changes in the 12-lead electrocardiogram and two-dimensional echocardiogram during high-dose DIP infusion (up to 0.84 mg/kg in 10 minutes) were evaluated within 24 hours of endomyocardial biopsy in 14 transplanted patients. A total of 47 biopsy-controlled DIP studies were performed within 5 weeks after cardiac transplantation. For each patient, at least 7 days elapsed between two consecutive studies. Electrocardiographic and echocardiographic tracings were analyzed without prior knowledge of endomyocardial biopsy findings. No remarkable side effects occurred in any case, so that the DIP study could be completed in all patients. A diagnostic (greater than 0.1 mV) ST segment depression was found in 11 studies. The sensitivity and specificity of DIP-induced ST segment depression for the detection of biopsy-proven acute rejection were 72% and 94%, respectively. These data show that DIP stress is feasible and safe in transplanted patients and that acute cardiac rejection can be accompanied by DIP-induced ST segment depression without detectable impairment in systolic function. These changes might provide noninvasive markers for surveillance of rejection.
Lactoferrin–Endothelin-1 Axis Contributes to the Development and Invasiveness of Triple-Negative Breast Cancer Phenotypes
Authors: Ngoc-Han Ha, Vasudha S. Nair, Divijendra Natha Sirigiri Reddy, Prakriti Mudvari, Kazufumi Ohshiro, Krishna Sumanth Ghanta, Suresh B. Pakala, Da-Qiang Li, Luis Costa, Allan Lipton, Rajendra A. Badwe, Suzanne Fuqua, Margaretha Wallon, George C. Prendergast, Rakesh Kumar
Journal: Cancer Research (2011)

Triple-negative breast cancer (TNBC) is characterized by the lack of expression of estrogen receptor-α (ER-α), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). However, pathways responsible for downregulation of therapeutic receptors, as well as subsequent aggressiveness, remain unknown. In this study, we discovered that lactoferrin (Lf) efficiently downregulates levels of ER-α, PR, and HER-2 in a proteasome-dependent manner in breast cancer cells, and it accounts for the loss of responsiveness to ER- or HER-2-targeted therapies. Furthermore, we found that lactoferrin increases migration and invasiveness of both non-TNBC and TNBC cell lines. We discovered that lactoferrin directly stimulates the transcription of endothelin-1 (ET-1), a secreted proinvasive polypeptide that acts through a specific receptor, ET(A)R, leading to secretion of the bioactive ET-1 peptide. Interestingly, a therapeutic ET-1 receptor-antagonist blocked lactoferrin-dependent motility and invasiveness of breast cancer cells. The physiologic significance of this newly discovered Lf-ET-1 axis in the manifestation of TNBC phenotypes is revealed by elevated plasma and tissue lactoferrin and ET-1 levels in patients with TNBC compared with those in ER(+) cases. These findings describe the first physiologically relevant polypeptide as a functional determinant in downregulating all three therapeutic receptors in breast cancer, which uses another secreted ET-1 system to confer invasiveness. Results presented in this article provide proof-of-principle evidence in support of the therapeutic effectiveness of ET-1 receptor antagonist to completely block the lactoferrin-induced motility and invasiveness of the TNBC as well as non-TNBC cells, and thus, open a remarkable opportunity to treat TNBC by targeting the Lf-ET-1 axis using an approved developmental drug.
Expression of programmed death-1 (CD279) in primary cutaneous B-cell lymphomas with correlation to lymphoma entities and biological behaviour
Authors: C. Mitteldorf, M. Bieri, N. Wey, K. Kerl, J. Kamarachev, M. Pfaltz, H. Kutzner, G. Roncador, D. Tomasini, W. Kempf
Journal: British Journal of Dermatology (2013)

Programmed death-1 (PD-1/CD279) is a cell-surface protein expressed in activated T cells and a subset of T lymphocytes including follicular helper T cells (TFH ). The interaction between PD-1 and its ligands plays a role in immune response and evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1-positive lymphocytes is associated with overall survival.To investigate 28 cases of primary cutaneous B-cell lymphoma, including the subtypes PCFCL (n = 10), PCMZL (n = 10) and DLBCL-LT (n = 8) for the number and density of PD-1-positive cells.Immunohistochemical staining and a computerized morphometric analysis for evaluation were applied. The results were correlated with the clinical outcome. To distinguish between activated T cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13 staining. Double staining for PD-1 and PAX-5 was used to investigate whether tumour cells were positive for PD-1.The PD-1-positive cells represented tumour-infiltrating T cells (TILs). Only a minor subset was represented by TFH . Patients with DLBCL-LT had a significantly lower number of PD-1-positive TILs than those with PCMZL (P = 0·012) and PCFCL (P = 0·002) or both (P = 0·001). The difference between PCMZL and PCFCL did not reach significance (P = 0·074). The tumour cells were negative for PD-1.A higher number of PD-1-expressing cells was found in indolent PCMZL and PCFCL than in high-malignant DLBCL-LT. The PD-1-positive cells represented not only TFH , but also other activated T cells as a part of the tumour microenvironment. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression.
Abstract 3542: A novel Hedgehog pathway inhibitor in combination with chemotherapy in mesothelioma cell lines
Authors: Natalie Lui, Hui Li, Hanh Do, Qing Sheng, David Jablons, Biao He
Journal: Cancer Research (2011)

Abstract We tested a novel Hedgehog pathway inhibitor in combination with chemotherapy to determine if there are synergistic effects in mesothelioma cell lines. The Hedgehog signaling pathway has been shown to be activated in many types of cancer. Our laboratory developed a novel Hedgehog pathway inhibitor that has promising characteristics. Several mesothelioma cell lines were treated with this new compound in combination with two standard chemotherapeutic agents, pemetrexed and cisplatin. The cells were seeded in 96-well plates on day 1 and then treated with a matrix of drug dosages on day 2. Cell viability was measured on day 5 using the CellTiter-Glo Luminescent Cell Viability Assay (Promega). The dose-effect relationship was plotted for each drug alone to determine the IC50, the inhibitory concentration at which cell viability was 50%. The IC50 of our Hedgehog inhibitor ranged from 1uM to 10uM for various cell lines. The dose-effect relationship in the combination studies was analyzed using Calcusyn (Biosoft). A combination index less than 0.9, indicating synergy, was found at several dose combinations in multiple cell lines. In summary, a novel Hedgehog pathway inhibitor in combination with chemotherapy showed synergy in multiple mesothelioma cell lines, showing high potential for this new compound to improve standard chemotherapeutic regimens and allow treatment at lower doses with fewer side effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3542. doi:10.1158/1538-7445.AM2011-3542
Response of patients and physicians to mass screening for coronary risk factors.
Authors: W S Aronow, W H Allen, D De Cristofaro
Journal: Circulation (1975)

Qestionnaires were sent to 1,817 adults screened twice for coronary risk factors 10 to 11 months apart and to their physicians. Physician questionnaires returned on 1,764 persons indicated that 359 (20.4%) of the total group and 227 of 1,191 persons (19.1%) with one or more abnormal risk factors during the first screen did not return for follow-up care. Only persons with one or more risk factors were given advice or medication. When the 227 patients that did not return for follow-up are removed from the group with one or more risk factors, the 239 patients who received advice or treatment comprise 24.8% of those who could have been treated. Of the total 1,764 patients, 13.5% recieved treatment or advice. Qestionnaires returned by 1,396 persons who received follow-up care by their physicians confirmed that only those who had one or more risk factors received advice or treatment. Results of the patient questionnaires show that 223 persons received advice or treatment (23.2% of all with risk factors who returned for follow-up; 16.0% of the 1,396 persons). Furthermore, of 116 persons prescribed medication for risk factor control, 60 (51.7%) were not taking this medication. Of 20, persons given advice for reduction of risk factors, 162 (78.9%) were not following this advice. These data indicate physician indifference and patient apathy to reduction of coronary risk factors in asymptomatic individuals.
PWE-090 Management and short term outcomes of malignant colorectal polyps in the North of England
Authors: M D Gill, M D Rutter, S J Holtham
Journal: Gut (2012)

<h3>Introduction</h3> Management of malignant colorectal polyps (MCPs) is contentious with no randomised controlled trials comparing endoscopic with surgical management. This study reviews the management and outcomes of MCPs across a UK region. <h3>Methods</h3> Patients were identified using the NORCCAG (NORthern Colorectal Cancer Audit Group) database between April 2006 and July 2010. All histopathology reports and follow-up procedures were reviewed. <h3>Results</h3> Of 386 patients identified, 165 (42.7%) had the polyp biopsied, 37 (9.6%) a piecemeal excision, 184 (47.7%) a polypectomy. All initial biopsies underwent surgical intervention. 103/221 initial local excisions (46.6%) had follow-up surgery of whom 79 (76.7%) had no residual cancer. Of the 118 managed endoscopically, none had residual cancer on follow-up endoscopy. The 21 (5.4%) Dukes9 C cancers were significantly associated with Kikuchi SM3/Haggitt 4 lesions (χ<sup>2</sup>=10.85, p=0.005) and lesions with an involved/unsure excision margin (χ<sup>2</sup>=7.44, p=0.017). Positive predictors of finding residual tumour at surgery were Kikuchi SM3/Haggitt Level 4 (χ<sup>2</sup>=17.07, p&lt;0.001), and any involved/unsure excision margin (χ<sup>2</sup>=20.45, p&lt;0.001). An excision margin &gt;0 mm was significantly associated with finding no residual tumour (χ<sup>2</sup>=25.21, p&lt;0.001). There was no difference in survival between surgical and endoscopic management (χ<sup>2</sup>=0.634, p=0.426). <h3>Conclusion</h3> Endoscopic management of a subgroup of MCPs appears safe and effective. A clear resection margin (&gt;0 mm) appears sufficient to avoid surgery. Advanced lesions (Kikuchi 3/Haggitt 4) have a greater risk of residual cancer at surgery, and of lymph node metastases. <h3>Competing interests</h3> None declared.
Clinical Experience with Technetium-99m DTPA Aerosol with Perfusion Scintigraphy in Suspected Pulmonary Embolism
Authors: JOHN B. SELBY, JARED J. GARDNER
Journal: Clinical Nuclear Medicine (1987)

To evaluate the clinical value of radioaerosol imaging, 156 patients with suspected pulmonary embolism (PE) were studied. In 25 patients, a preperfusion xenon-133 (Xe-133) study was compared with a postperfusion study using Tc-99m DTPA aerosol. It was found that they were of equal value most of the time (56%), but that the aerosol study was more often helpful. Because of this, and the technical ease of using six standard views with radioaerosol, the series was completed using perfusion scintigraphy followed by radioaerosol images. In 19 patients the perfusion scintigraphy with Tc-99 macroaggregated albumin (Tc-99m MAA) was normal or nearly normal and no aerosol study was required. Tc-99m DTPA aerosol images were satisfactory when the count rate was at least twice and preferably three times that of the previous perfusion study. There were 17 studies (11%) classified as intermediate. There were 26 patients classified as high probability for PE, and angiographic or autopsy correlation was available in 14. All of the 14 proved to have PE. In the 113 patients classified as low probability, there were ten with angiographic or autopsy correlation. In the ten, there was one patient with a small pulmonary embolus found at autopsy. Clinical follow-up for over two months confirmed the absence of PE in the remainder of this group. Aerosol studies have proven technically easier to perform and a satisfactory substitute for xenon imaging in suspected PE.
Comprehensive Comparison of Health-Related Quality of Life After Contemporary Therapies for Localized Prostate Cancer
Authors: John T. Wei, Rodney L. Dunn, Howard M. Sandler, P. William McLaughlin, James E. Montie, Mark S. Litwin, Linda Nyquist, Martin G. Sanda
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Health-related quality-of-life (HRQOL) concerns are pivotal in choosing prostate cancer therapy. However, concurrent HRQOL comparison between brachytherapy, external radiation, radical prostatectomy, and controls is hitherto lacking. HRQOL effects of hormonal adjuvants and of cancer control after therapy also lack prior characterization. PATIENTS AND METHODS: A cross-sectional survey was administered to patients who underwent brachytherapy, external-beam radiation, or radical prostatectomy during 4 years at an academic medical center and to age-matched controls. HRQOL among controls was compared with therapy groups. Comparison between therapy groups was performed using regression models to control covariates. HRQOL effects of cancer progression were evaluated. RESULTS: One thousand fourteen subjects participated. Compared with controls, each therapy group reported bothersome sexual dysfunction; radical prostatectomy was associated with adverse urinary HRQOL; external-beam radiation was associated with adverse bowel HRQOL; and brachytherapy was associated with adverse urinary, bowel, and sexual HRQOL (P ≤ .0002 for each). Hormonal adjuvant symptoms were associated with significant impairment (P < .002). More than 1 year after therapy, several HRQOL outcomes were less favorable among subjects after brachytherapy than after external radiation or radical prostatectomy. Progression-free subjects reported better sexual and hormonal HRQOL than subjects with increasing prostate-specific antigen (P < .0001). CONCLUSION: Long-term HRQOL after prostate brachytherapy showed no benefit relative to radical prostatectomy or external-beam radiation and may be less favorable in some domains. Hormonal adjuvants can be associated with significant impairment. Progression-free survival is associated with HRQOL benefits. These findings facilitate patient counseling regarding HRQOL expectations and highlight the need for prospective studies sensitive to urinary irritative and hormonal concerns in addition to incontinence, sexual, and bowel HRQOL domains.
Polymicrobial septicaemia due to Clostridium difficile and Bacteroides fragilis.
Authors: R C Spencer, S P Courtney, C D Nicol
Journal: BMJ (1984)

<h3>Background</h3> Despite several known risk factors it is still difficult to foresee who will develop a stroke and who will not. Vascular brain damage, visualised with MRI, reflects how the brain tolerates the effects of vascular risk factors and may therefore be relevant in predicting individual stroke risk. <h3>Objective</h3> To examine whether the presence of small vessel disease on brain MRI could improve the prediction of stroke beyond the classic stroke risk factors from the 1991 Framingham Stroke Risk Function. <h3>Methods</h3> 1007 community-dwelling elderly people, free of stroke at baseline were included in the study. Small vessel disease—that is, the presence of silent brain infarcts (SBI) and white matter lesions (WML), was scored on MRI scans obtained in 1995–6. 10-Year stroke risk prediction was assessed by the C statistic and by reclassification adding SBI and WML to a risk model including the classic stroke risk factors. <h3>Results</h3> During 10-years of follow-up 99 strokes occurred. Individual stroke risk prediction significantly improved from 0.73 (95% CI 0.67 to 0.78) to 0.75 (0.69 to 0.80) in men and from 0.69 (0.64 to 0.75) to 0.77 (0.71 to 0.82) in women after inclusion of SBI and periventricular WML to the stroke risk factors. Reclassification occurred mainly in the intermediate stroke risk group (men 26%; women 61% reclassified). <h3>Conclusions</h3> Assessment of small vessel disease with MRI beyond the classic stroke risk factors improved the prediction of subsequent stroke, especially in women with an intermediate stroke risk. These findings support the use of MRI as a possible tool for better identifying people at high risk of stroke.
Inhibition by prostaglandin E1 and E2 of 1,25-dihydroxyvitamin D3 synthesis by synovial fluid macrophages from arthritic joints.
Authors: M.E Hayes, A Rai, R.G Cooper, D Bayley, A.J Freemont, E.B Mawer
Journal: Annals of the Rheumatic Diseases (1992)

Previous work has shown that renal metabolism of 25-dihydroxyvitamin D3 (25(OH)D3) to the active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is stimulated by prostaglandin E2 and inhibited by acetylsalicylate (aspirin). As prostaglandins are primary inflammatory mediators and synovial fluid macrophages are known to synthesise 1,25(OH)2D3 in vitro, the effects of prostaglandin E1, prostaglandin E2, and aspirin on the metabolism of 25(OH)D3 by cells cultured from synovial fluid of patients with inflammatory arthritis were investigated. Most cultures contained non-proliferating macrophages which formed 1,25(OH)2D3; however, two of 13 cultures contained colonies of rapidly proliferating fibroblast-like cells which formed 24,25(OH)2D3 (24,25(OH)2D3). Prostaglandin E1 and prostaglandin E2 (0.01-10 mumol/l) induced marked inhibition of 1,25(OH)2D3 synthesis (up to 94%) in a dose dependent manner after preincubations of 24 hours but not over straightforward six hour incubations. Exposure of macrophages to aspirin (1 mumol/l-1 mmol/l) for 24 hours did not affect 1,25(OH)2D3 synthesis unless the cells had been pretreated with lipopolysaccharides, in which instance 1 mM aspirin increased 1,25(OH)2D3 synthesis. Lipopolysaccharide is a macrophage activating factor which stimulates macrophages to form 1,25(OH)2D3, and it also induces prostaglandin synthesis which would be inhibited by aspirin. Taken together these results suggest that prostaglandin E1 and prostaglandin E2 synthesised by macrophages may act in an autocrine manner to attenuate the ability of macrophage activating factors, such as lipopolysaccharide, to stimulate 1,25(OH)2D3 synthesis. Prostaglandins synthesised by other inflammatory cells may also inhibit 1,25(OH)2D3 synthesis in a paracrine manner. In contrast, prostaglandin E2 and aspirin had limited effects on fibroblast 24,25(OH)2D3 synthesis. This study shows that the effects of prostaglandin E1, prostaglandin E2, and aspirin in macrophages contrast with those previously reported for the renal 25(OH)D3-1alpha-hydroxylase, where prostaglandin E2 stimulated and aspirin inhibited enzyme activity. These results further emphasise that synthesis of 1,25(OH)2D3 in non-renal sites is independently regulated, which is consistent with it having an immunological role at a local level rather than playing a part in systemic calcium homeostasis.
Ventilatory Response to Brief Arousal from Non–Rapid Eye Movement Sleep Is Greater in Men Than in Women
Authors: Amy S. Jordan, Danny J. Eckert, Peter G. Catcheside, R. Doug McEvoy
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Sleep apnea syndromes are more common in men than in women. The ventilatory response to arousal from sleep may be an important determinant of respiratory stability/instability and could contribute to this sex difference. We therefore compared changes in ventilation, end-tidal carbon dioxide (CO2), upper airway resistance, heart rate, and finger photoplethysmogram pulse wave amplitude after both spontaneous and tone-induced arousal from non–rapid eye movement sleep in 13 men and 13 women. At sleep onset, ventilation fell and both upper airway resistance and end-tidal CO2 rose, but these changes were not different between sexes. Spontaneous arousal (duration, 6.6 ± 0.2 seconds) resulted in a biphasic ventilatory response consisting of brief hyperventilation (5 seconds) followed by prolonged hypoventilation (30–40 seconds) on resumption of sleep. The biphasic ventilatory response was greater in men than in women and did not appear to be explained by different wake-to-sleep increments in end-tidal CO2 or upper airway resistance between sexes. Peripheral vasoconstriction with arousal was also greater in men than in women. Ventilatory responses were more marked after tone-induced versus spontaneous arousals and when subjects slept supine compared with the left lateral position. These results suggest that male sex and supine position are associated with greater ventilatory instability after arousal from sleep.
Is Atherosclerosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL Cholesterol or by Decreased HDL Cholesterol?
Authors: Matthias B. Schulze, Kurt Hoffmann
Journal: Diabetes Care (2005)

In the report of Drexel et al. (1), an HDL-related cluster of lipid markers was significantly associated with risk of cardiovascular disease among coronary patients with type 2 diabetes, whereas an LDL-related cluster was not significantly associated. The authors conclude from their observation that “in today’s setting of effective LDL cholesterol lowering with statins, HDL cholesterol, triglycerides, and LDL particle diameter are the predominant lipid risk factors determining the fate of coronary patients with diabetes.”

Although Drexel et al. briefly discuss the issue …