tbuckley/cabot-search huggingface dataset:
Adjuvant zoledronic acid therapy for patients with early stage breast cancer: an updated systematic review and meta-analysis
Authors: Mingfeng He, Weidong Fan, Xianquan Zhang
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption and has been widely used in bone metastasis malignancies and postmenopausal osteoporosis as a preventive therapy against skeletal-related events. The purpose of this study was to evaluate the clinical outcome of zoledronic acid as an adjuvant therapy for patients with early stage breast cancer. Patients and methods Entries in the PubMed and EMBASE databases up to 12 July 2013 were systematically reviewed. Online abstracts from the proceedings of the Annual Meetings of the American Society of Clinical Oncology (ASCO) (1992–2013) and the San Antonio Breast Cancer Symposium (SABCS) (2004–2013) were also reviewed. Primary endpoints included overall survival (OS) and disease-free survival (DFS), while secondary endpoints included bone metastasis-free survival (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR). Results A total of eight studies including 3,866 subjects and 3,864 controls met our search criteria and were evaluated. The use of zoledronic acid was found to improve OS (relative risk (RR), 0.88; 95% confidence interval (CI), 0.77–1.01; p- value = 0.06) and DMFS (RR, 0.77; 95% CI, 0.60–1.00; p- value = 0.05). Furthermore, statistically significant benefits were associated with BMFS (RR, 0.81; 95% CI, 0.66–0.99; p- value = 0.04) and FFRs (RR, 0.75; 95% CI, 0.61–0.92; p- value = 0.007). In contrast, there was no significant difference in DFS with the application of zoledronic acid (RR, 0.88; 95% CI, 0.72–1.09; p- value = 0.24). Sensitivity analysis further identified the improvement of 5-year OS for the adjuvant zoledronic acid therapy in early stage breast cancer patients (RR, 0.86; 95% CI, 0.75–0.99; p- value = 0.03), while a borderline statistically significant benefit was observed for 5-year DFS (RR, 0.90; 95% CI, 0.81–1.00; p- value = 0.06). Conclusion Zoledronic acid as an adjuvant therapy appears to improve the 5-year OS rate for early stage breast cancer patients, and was associated with a protective effect for the bone metastases and fractures evaluated in more than 7,000 patients. However, further research is needed to confirm our findings, and sub-group analyses according to menopause status or hormone status may provide further insight.
Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia
Authors: Catherine Féart
Journal: JAMA (2009)

Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear.To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons.Prospective cohort study of 1410 adults (> or = 65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall.Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists.Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (beta = -0.006; 95% confidence interval [CI], -0.01 to -0.0003; P = .04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant (adjusted for all factors, for MMSE: beta = -0.03; 95% CI, -0.05 to -0.001; P = .04; for FCSRT: beta = 0.21; 95% CI, 0.008 to 0.41; P =.04). Mediterranean diet adherence was not associated with the risk for incident dementia (fully adjusted model: hazard ratio, 1.12; 95% CI, 0.60 to 2.10; P = .72), although power to detect a difference was limited.Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.
Kinetic analysis of synovial signalling and gene expression in animal models of arthritis
Authors: A. Fukushima, D. L. Boyle, M. Corr, G. S. Firestein
Journal: Annals of the Rheumatic Diseases (2009)

Animal models of arthritis are frequently used to evaluate novel therapeutic agents. However, their ability to predict responses in humans is variable.To examine the time course of signalling molecule and gene expression in two models of arthritis to assist with selection of the model and timing of drug administration.The passive K/BxN serum transfer and collagen-induced arthritis (CIA) models were studied. Activation of MAP kinase and interferon (IFN)-response pathways was evaluated by quantitative PCR and western blot analysis of ankle joints at various time points during the models.The kinetics of gene expression and kinase phosphorylation were strikingly different in passive K/BxN and CIA. All three MAP kinases (ERK, JNK and p38) and upstream kinases were activated within days in passive K/BxN and declined as arthritis severity decreased. Surprisingly, IFN-regulated genes, including IRF7, were not induced in the model. In CIA, activation of ERK and JNK was surprisingly low and p38 phosphorylation mainly peaked late in the disease. IFN-response genes were activated during CIA, with especially prominent peaks at the onset of clinical arthritis.Timing of treatment and selection of CIA or passive K/BxN might have an important impact on therapeutic response. p38, in particular, increases during the late stages of CIA. ERK and JNK patterns are similar in passive K/BxN and rheumatoid arthritis (RA), while IFN-response genes in CIA and RA are similar. The dichotomy between RA and animal models could help explain the poor correlation between efficacy in RA and preclinical studies.
A PECULIAR, PELLAGRA-LIKE SKIN SENSITIZATION TO LIGHT IN STARVING PERSONS
Authors: M. GRZYBOWSKI
Journal: British Journal of Dermatology (1948)

Journal Article A PECULIAR, PELLAGRA‐LIKE SKIN SENSITIZATION TO LIGHT IN STARVING PERSONS Get access M. GRZYBOWSKI, M.D M. GRZYBOWSKI, M.D Professor, Warsaw University Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 60, Issue 12, 1 December 1948, Pages 410–415, https://doi.org/10.1111/j.1365-2133.1948.tb10973.x Published: 01 December 1948
Persistent improvement after coronary bypass surgery: ergometric and angiographic correlations at 5 years.
Authors: M H Frick, P T Harjola, M Valle
Journal: Circulation (1983)

One hundred patients with angina pectoris who fulfilled specific entry criteria were randomly assigned to either medical therapy or bypass surgery. These groups were subjected to annual exercise testing during a 5-year follow-up period. The degree of revascularization was assessed by graft and native vessel angiography at 3 weeks, 1 year and 5 years after the operation. The exercise tolerance of the medical group remained largely unchanged during the follow-up. Eighty-five to 95% of the patients were using beta-blocking compounds at the successive testing situations. The surgical group exhibited a sustained improvement in exercise tolerance: Total work increased by 39-66% (p less than 0.02-0.001) and maximal ergometric load by 23-35% (p less than 0.01-0.001), and maximal ST depression decreased by 39-61% (p less than 0.05-0.001). The use of beta-blocking compounds in the surgical group steadily increased, from 44% at 6 months after operation to 63% of patients at 5 years. Division of the surgical group into subsets of complete and incomplete revascularization revealed that the improvement was confined to complete revascularization. Thus, the improved exercise tolerance after bypass surgery was a result of successful reestablishment of effective coronary perfusion; despite graft attrition (15% in 5 years) and new lesions in the native arteries, this improvement persisted for 5 years with appropriate medical therapy.
Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Authors: Suzanne E. Wahrle, Hong Jiang, Maia Parsadanian, Jungsu Kim, Aimin Li, Amanda Knoten, Sanjay Jain, Veronica Hirsch-Reinshagen, Cheryl L. Wellington, Kelly R. Bales, Steven M. Paul, David M. Holtzman
Journal: Journal of Clinical Investigation (2008)

APOE genotype is a major genetic risk factor for late-onset Alzheimer disease (AD). ABCA1, a member of the ATP-binding cassette family of active transporters, lipidates apoE in the CNS. Abca1–/– mice have decreased lipid associated with apoE and increased amyloid deposition in several AD mouse models. We hypothesized that mice overexpressing ABCA1 in the brain would have increased lipidation of apoE-containing lipoproteins and decreased amyloid deposition. To address these hypotheses, we created PrP-mAbca1 Tg mice that overexpress mouse Abca1 throughout the brain under the control of the mouse prion promoter. We bred the PrP-mAbca1 mice to the PDAPP AD mouse model, a transgenic line overexpressing a mutant human amyloid precursor protein. PDAPP/Abca1 Tg mice developed a phenotype remarkably similar to that seen in PDAPP/Apoe–/– mice: there was significantly less amyloid β-peptide (Aβ) deposition, a redistribution of Aβ to the hilus of the dentate gyrus in the hippocampus, and an almost complete absence of thioflavine S–positive amyloid plaques. Analyses of CSF from PrP-mAbca1 Tg mice and media conditioned by PrP-mAbca1 Tg primary astrocytes demonstrated increased lipidation of apoE-containing particles. These data support the conclusions that increased ABCA1-mediated lipidation of apoE in the CNS can reduce amyloid burden and that increasing ABCA1 function may have a therapeutic effect on AD.
Do Estrogens Reduce Glycemic Levels?
Authors: Peter W F Wilson
Journal: Diabetes Care (1998)

tomy in rats was followed by an increase in insulin resistance, which was determined using euglycemic-hyperinsulinemic clamp techniques. Estrogen replacement, with or without progesterone, restored insulin sensitivity (18). Similarly, estrogen withdrawal augmented fasting and glucose-stimulated insulin levels in juvenile rats that were made insulin resistant and hypertensive with a sucrose diet (19). Hormonal replacement in postmenopausal cynomolgus monkeys has yielded different results: progestins, alone or with estrogens, were associated with greater insulin resistance, which was assessed using the minimal model after a frequently sampled intravenous glucose tolerance test (20). The theme that hyperglycemia is atherogenic and partly androgenic is gaining acceptance, but the metabolic issues are complex. ERT has been associated with lower androgen levels and less insulin resistance in postmenopausal women with type 2 diabetes (21,22). Conversely, total estrogen levels were reported to be increased in postmenopausal women with insulintreated diabetes, and high levels of sex hormone-binding globulin were thought to keep the free fraction of the sex hormone levels within normal limits (23). The polycystic ovary syndrome, typified by high levels of androgens, hyperglycemia, oligomenorrhea, and infertility, represents a condition in which glycemia and androgens foster a milieu that increases the risk for cardiovascular disease (24,25). The estrogen/androgen balance and menstrual irregularity may also be tipped unfavorably by obesity, diabetes, and cigarette smoking before menopause (26-28). It has been suggested that diabetic women taking insulin before menopause may experience shorter periods of fertility and a higher incidence of menstrual disturbances compared with nondiabetic women. The current investigation has limita
Recommendations for the management of patients with obstructive sleep apnoea and hypertension
Authors: Gianfranco Parati, Carolina Lombardi, Jan Hedner, Maria R. Bonsignore, Ludger Grote, Ruzena Tkacova, Patrick Lévy, Renata Riha, Claudio Bassetti, Krzysztof Narkiewicz, Giuseppe Mancia, Walter T. McNicholas
Journal: European Respiratory Journal (2013)

This article is aimed at addressing the current state-of-the-art in epidemiology, pathophysiology, diagnostic procedures and treatment options for appropriate management of obstructive sleep apnoea (OSA) in cardiovascular (in particular hypertensive) patients, as well as for the management of cardiovascular diseases (in particular arterial hypertension) in OSA patients. The present document is the result of work performed by a panel of experts participating in the European Union COST (Cooperation in Scientific and Technological research) Action B26 on OSA, with the endorsement of the European Respiratory Society and the European Society of Hypertension. In particular, these recommendations are aimed at reminding cardiovascular experts to consider the occurrence of sleep-related breathing disorders in patients with high blood pressure. They are also aimed at reminding respiration experts to consider the occurrence of hypertension in patients with respiratory problems at night.
MLL leukemia induction by genome editing of human CD34+ hematopoietic cells
Authors: Corina Buechele, Erin H. Breese, Dominik Schneidawind, Chiou-Hong Lin, Johan Jeong, Jesus Duque-Afonso, Stephen H. K. Wong, Kevin S. Smith, Robert S. Negrin, Matthew Porteus, Michael L. Cleary
Journal: Blood (2015)
Placebo-Controlled Trials of New Drugs: Ethical Considerations
Authors: David Orentlicher
Journal: Diabetes Care (2001)

Much controversy exists regarding the ethics of placebo-controlled trials in which an experimental therapy will compete with an already established treatment (or treatments). In such cases, argue critics, patients in the control arm of the study should receive an accepted therapy rather than a placebo. By using an active and effective drug, the control patients would not be placed at risk for deterioration of their disease, and the study would generate more meaningful results for physicians. The key question, it is said, is not whether a new therapy is better than nothing but whether it is better than the current standard of care (1,2).

In response, say proponents of placebo-controlled trials, critical information cannot always be obtained by giving control patients an existing therapy. For some effective therapies, the drug may perform no better than placebo in a particular trial even though other trials demonstrate the drug’s superiority to placebo. If an experimental agent confers the same benefit as such an existing therapy in a comparative trial, we cannot be certain that the new agent is any better than placebo. We might have one of the trials in which the existing therapy (and therefore the new agent) does no better than placebo, perhaps because of inadequate sample size, perhaps because the outcome measure can vary widely from one patient group to another (3–5). In addition, some new therapies are useful even if they are less effective than existing therapies. Some patients might choose a less effective drug if substantial cost savings or a reduction in side effects would be realized (6). Without a placebo control, however, one cannot always tell whether a new drug that is not as effective as existing therapy is still sufficiently more effective than placebo to justify its use. Finally, not …
Impact of an Exercise Program on Arterial Stiffness and Insulin Resistance in Hemodialysis Patients
Authors: Stefan Mustata, Christopher Chan, Vesta Lai, Judith A. Miller
Journal: Journal of the American Society of Nephrology (2004)

Cardiovascular disease remains the primary cause of mortality in patients who are maintained on hemodialysis. Arterial stiffness and insulin resistance are independent risk factors for cardiovascular mortality in this population. In healthy individuals, higher physical conditioning is associated with reduced arterial stiffness. Exercise reduces insulin resistance and glucose intolerance in sedentary, overweight individuals and diabetic patients. The purpose of this study was to determine the impact of an exercise program on arterial stiffness and insulin resistance in a group of patients on hemodialysis. The effect of exercise training on arterial stiffness and insulin resistance in 11 patients who were on chronic hemodialysis was evaluated. Exercise classes of 1-h duration were conducted twice weekly for 3 mo. Arterial stiffness was assessed using the radial artery pressure waveform analysis. Aerobic exercise improved arterial stiffness from 17 ± 3 u at baseline to 12.2 ± 3 u at the end of the intervention (P = 0.01). After 1 mo of detraining, arterial stiffness reverted to pre-exercise levels (17.3 ± 3 u). Pulse pressure paralleled arterial stiffness changes, and the correlation between them was statistically significant (r = 0.725, P = 0.012). Insulin resistance was calculated using the homeostatic model assessment formula. Exercise at the intensity and duration used in our study had no impact on insulin resistance (P = 0.38). These findings suggest that 3 mo of aerobic exercise training improves arterial stiffness, an independent risk factor for cardiovascular mortality in patients who are on hemodialysis, and has no impact on insulin resistance. The beneficial effect on arterial stiffness dissipates within 1 mo of detraining. To obtain therapeutic benefits, an exercise program for patients who are maintained on hemodialysis should be designed to promote regular long term exercise, >3 h/wk.
A novel peroxisome proliferator-activated receptor (PPAR)γ agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARγ activation
Authors: Takashi Yotsumoto, Takeshi Naitoh, Tatsuro Kanaki, Maho Matsuda, Nobutomo Tsuruzoe
Journal: Metabolism (2003)
Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo
Authors: Kejian Shi, Qian Jiang, Zhushi Li, Lei Shan, Feng Li, JiaJia An, Yang Yang, Caimin Xu
Journal: Journal of Hematology & Oncology (2013)

Abstract Background Previous studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated. Methods The toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting. In situ detection of apoptotic ratio was performed with TUNEL assay. Results Our current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally, in vivo experiments confirmed the in vitro microtubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite. Conclusions Taken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.
Relaxant effect of C-type natriuretic peptide involves endothelium and nitric oxide–cGMP system in rat coronary microvasculature
Authors: F Brunner
Journal: Cardiovascular Research (2001)

Objective: Recent evidence suggests a possible role for nitric oxide (NO) in atrial natriuretic peptide-induced blood pressure effects. We tested the hypothesis that C-type natriuretic peptide (CNP)-mediated relaxation of the rat coronary circulation involves NO and activation of soluble guanylyl cyclase. Methods: Rat hearts (n=6 per group) were perfused in vitro at constant flow and the effect of CNP (0.1–3 μmol/l) on coronary perfusion pressure (a measure of vascular tone) and release of guanosine 3′,5′-cyclic monophosphate (cGMP) was determined in absence and presence of the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine (l-NNA; 0.2 mmol/l) or the natriuretic peptide receptor antagonist HS-142-1 (50 μg/ml). The involvement of Ca2+-gated and ATP-dependent K+ channels in CNP-induced relaxation was tested with iberiotoxin (30 nmol/l) and glibenclamide (1 μmol/l), respectively. Rings of rat aorta (n=12) were tested using the organ bath set-up. Results: CNP reduced perfusion pressure from 134±2 mmHg (baseline) to 71±1 mmHg (−48%) and this effect was significantly attenuated by l-NNA (−37%) or HS-142-1 (−19%). In presence of glibenclamide, CNP reduced perfusion pressure to 92±2 mmHg (−32%), in presence of iberiotoxin to 93±1 mmHg (−30% and in their combined presence to 102±2 mmHg (−23%) (P<0.05 vs. corresponding control). Basal release of cGMP was increased up to 4-fold by CNP and this increase was reduced (−50%) in presence of l-NNA or HS-142-1 (−68%). By contrast, relaxation of rat aortic rings mounted in organ baths was insensitive to inhibition by l-NNA. Conclusion: Relaxation of the coronary resistance vessels of the rat by CNP is partly mediated by the NO–cGMP pathway. These novel data support the existence of an endogenous link between soluble and particulate guanylyl cyclases in the control of natriuretic peptide-mediated coronary resistance vessel function.
Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double‐blind placebo‐controlled trial
Authors: M. Viljanen, E. Savilahti, T. Haahtela, K. Juntunen‐Backman, R. Korpela, T. Poussa, T. Tuure, M. Kuitunen
Journal: Allergy (2004)

Background: Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food‐allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS. Methods: Follow‐up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double‐blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double‐blind placebo‐controlled (DBPC) milk challenge in 120 infants. Results: In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE‐sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, −26.1 vs −19.8 ( P = 0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE‐sensitized subgroup. Conclusion: Treatment with LGG may alleviate AEDS symptoms in IgE‐sensitized infants but not in non‐IgE‐sensitized infants.