tbuckley/cabot-search huggingface dataset:
Adenoviral-delivered angiopoietin-1 reduces the infarction and attenuates the progression of cardiac dysfunction in the rat model of acute myocardial infarction
Authors: Kazuhiro Takahashi, Yoshinori Ito, Masayuki Morikawa, Masayoshi Kobune, Jianhua Huang, Masaru Tsukamoto, Katsunori Sasaki, Kiminori Nakamura, Hironari Dehari, Katsuya Ikeda, Hiroaki Uchida, Sachie Hirai, Tomio Abe, Hirofumi Hamada
Journal: Molecular Therapy (2003)

In acute myocardial infarction (AMI), prognosis and mortality rate are closely related to the infarct size and the progression of postinfarction cardiac failure. Angiogenic gene therapy has presented a new approach for the treatment of AMI. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that gene therapy using Ang1 for AMI might promote angiogenesis cooperatively with intrinsic VEGF, since high concentrations of circulating VEGF have been reported in AMI. To evaluate our hypothesis, we employed a rat AMI model and adenoviral Ang1 (HGMW-approved gene symbol ANGPT1) gene transfer to the heart. A significant increase in capillary density and reduction in infarct sizes were noted in the infarcted hearts with adenoviral Ang1 gene treatment compared with control infarcted hearts treated with saline or adenoviral vector containing the β-galactosidase gene. Furthermore, the Ang1 group showed significantly higher cardiac performance in echocardiography (55.0% of ejection fraction, P < 0.05 vs control) than the saline or adenoviral controls (36.0 or 40.5%, respectively) 4 weeks after myocardial infarction. The adenoviral delivery of Ang1 during the acute phase of myocardial infarction would be feasible to attenuate the progression of cardiac dysfunction in the rat model.
Comparison of PAM50 Risk of Recurrence Score With Onco<i>type</i> DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy
Authors: Mitch Dowsett, Ivana Sestak, Elena Lopez-Knowles, Kalvinder Sidhu, Anita K. Dunbier, J. Wayne Cowens, Sean Ferree, James Storhoff, Carl Schaper, Jack Cuzick
Journal: Journal of Clinical Oncology (2013)

Purpose Risk of distant recurrence (DR) among women with estrogen receptor (ER) –positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes. Patients and Methods mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67. Results ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ 2 = 33.9; P &lt; .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group. Conclusion ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.
Improving Epinephrine Responses in Hypoglycemia Unawareness With Real-Time Continuous Glucose Monitoring in Adolescents With Type 1 Diabetes
Authors: Trang T. Ly, Jacqueline Hewitt, Raymond J. Davey, Ee Mun Lim, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2010)

OBJECTIVE To determine whether real-time continuous glucose monitoring (CGM) with preset alarms at specific glucose levels would prove a useful tool to achieve avoidance of hypoglycemia and improve the counterregulatory response to hypoglycemia in adolescents with type 1 diabetes with hypoglycemia unawareness. RESEARCH DESIGN AND METHODS Adolescents with type 1 diabetes with hypoglycemia unawareness underwent hyperinsulinemic hypoglycemic clamp studies at baseline to determine their counterregulatory hormone responses to hypoglycemia. Subjects were then randomized to either standard therapy or real-time CGM for 4 weeks. The clamp study was then repeated. RESULTS The epinephrine response during hypoglycemia after the intervention was greater in the CGM group than in the standard therapy group. CONCLUSIONS A greater epinephrine response during hypoglycemia suggests that real-time CGM is a useful clinical tool to improve hypoglycemia unawareness in adolescents with type 1 diabetes.
Thou shalt not strive officiously
Authors: S L H. Smith
Journal: BMJ (1982)

case reported from this centre3 has highlighted the value of sigmoidoscopy in these circumstances.Visualisation of the characteristic pseudomembranes enabled immediate diagnosis, and treatment with vancomycin was started without waiting for stool or toxin assay.Rapid resolution of toxicity and mega- colon ensued.Sigmoidoscopy is considered hazardous in toxic megacolon because of the risks of perforation.Proctoscopy alone, however, may not show pseudomembranes, because of rectal sparing.4I would suggest that careful sigmoidoscopy with minimal insufflation performed in all cases of toxic megacolon may avoid delay in diagnosing the few cases so amenable to non-operative management.
Low circulating soluble interleukin 2 receptor level predicts rapid response in patients with refractory rheumatoid arthritis treated with infliximab
Authors: A Kuuliala
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> Treatment with infliximab induces a rapid therapeutic response in most patients with active rheumatoid arthritis. Factors predicting good response are not well known. <b>Objective:</b> To study the predictive value of baseline level of soluble interleukin 2 receptor (sIL2R), a marker of lymphocyte activation, on the treatment response. <b>Methods:</b> 24 patients with active rheumatoid arthritis received intravenous infusions of infliximab at study entry, at two weeks, at six weeks, and at eight week intervals thereafter. Outcome was evaluated at six weeks and 22 weeks. Clinical assessment and standard laboratory tests were made and the DAS28 disease activity score was calculated. Serum sIL2R level at entry was measured by automated immunoassay analyser (Immulite®). The mean change in DAS28 score from entry to six weeks and 22 weeks was calculated and related to sIL2R level using baseline adjusted robust regression analysis. <b>Results:</b> Baseline level of serum sIL2R (mean (SD), 621 (325) U/ml) did not correlate with baseline DAS28 score (<i>r</i> = 0.24 (95% confidence interval, −0.18 to 0.58)). At six weeks DAS28 scores improved, with a mean change of −2.53 (−3.08 to −1.98) (p&lt;0.001). This change was predicted by low baseline sIL2R level (regression coefficient per 100 U/ml: 0.205 (0.003 to 0.407) (p = 0.047)). At 22 weeks the DAS28 scores improved, with a mean change of −2.26 (−2.75 to −1.77) (p&lt;0.001). The change was not predicted by baseline sIL2R level. <b>Conclusions:</b> Low baseline sIL2R level may predict a rapid clinical response in patients with refractory rheumatoid arthritis treated with infliximab.
Identification of COPD patients reaching last year of life; a survey of South-West (SW) clinicians' perceptions of personal ability & barriers to identification
Authors: Marianne Tinkler, Mark Gillam, Tobenna Onyirioha
Journal: European Respiratory Journal (2013)

The identification of COPD patients reaching last year of life is recommended.  A questionnaire was e-mailed to West Country Chest Society members for self assessment.  Response rate was 30% (55/185). 53% consultants, 32% SpR’s, 8% COPD Nurses, and 6% GP’s. 87% saw patients daily.  93% clinicians felt experienced & capable in undertaking end of life discussions however only 22% felt they did it well.  Barriers identified were:  DISCUSSION  SW respiratory clinicians feel experienced in identification but only 22% felt it is done well. Time is a significant limitation identified. Awareness of the importance of psychosocial support is needed as quality of life in the year before death has been reported as very low. Respiratory physicains have an important role in generalist palliative care therefore facilitation to improve identification is vital.
ISOLATION OF HERPES SIMPLEX VIRUS FROM HUMAN TRIGEMINAL GANGLIA, INCLUDING GANGLIA FROM ONE PATIENT WITH MULTIPLE SCLEROSIS
Authors: KennethG. Warren, DonaldH. Gilden, S. Moira Brown, Mary Devlin, Zofia Wroblewska, J. Subak-Sharpe, Hilary Koprowski
Journal: The Lancet (1977)
Association Between Metabolic Syndrome and Depressive Symptoms in Middle-Aged Adults
Authors: Tasnime N. Akbaraly, Mika Kivimäki, Eric J. Brunner, Tarani Chandola, Michael G. Marmot, Archana Singh-Manoux, Jane E. Ferrie
Journal: Diabetes Care (2008)

Although it is possible that the association between depression and the metabolic syndrome is a "two-way street," the metabolic syndrome as a predictor of depression has been little investigated. We examined whether the metabolic syndrome is associated with the onset of depressive symptoms in a cohort of middle-aged British civil servants.Analyses included 5,232 participants (41-61 years of age) from the Whitehall II prospective cohort study. Depressive symptoms were assessed in 1991-1993 and again 6 years later using the depression subscale from the 30-item General Health Questionnaire. Metabolic syndrome was assessed in 1991-1993, according to National Cholesterol Education Program criteria.Presence of the metabolic syndrome was associated with an increased risk of future depressive symptoms, odds ratio 1.38 (95% CI 1.02-1.96) after adjustment for potential confounders. Of the five components, only central obesity, high triglyceride levels, and low HDL cholesterol levels predicted depressive symptoms. These components explained most of the association between the metabolic syndrome and the onset of depressive symptoms.Our results suggest that the metabolic syndrome, in particular the obesity and dyslipidemia components, is predictive of depressive symptoms.
Role of Na <sup>+</sup> /H <sup>+</sup> Exchanger During Ischemia and Preconditioning in the Isolated Rat Heart
Authors: Xiao-Hui Xiao, David G. Allen
Journal: Circulation Research (1999)

Abstract —The role of the Na + /H + exchanger in ischemia, reperfusion, and preconditioning was investigated in isolated perfused rat hearts. Contractile function, [Na + ] i , and pH i were measured; ischemic damage was assessed by the recovery of developed pressure (DP) on reperfusion. After 30 minutes of ischemia, DP recovered to only 14±4% of preischemic control. In contrast, after preconditioning (3×5-minute periods of ischemia) followed by 30 minutes of ischemia, DP recovered to 75±4%. Hearts treated with the Na + /H + exchange inhibitor 5-( N -methyl- N -isobutyl)amiloride (MIA) also showed an enhanced recovery after ischemia (DP 62±9%). Treatment with a low concentration of tetrodotoxin (TTX, 100 nmol/L), which blocks the persistent component of the Na + current, had a small beneficial effect on recovery (DP 37±8%). Thirty minutes of ischemia caused a small [Na + ] i rise (3.2±0.9 mmol/L); reperfusion resulted in a further [Na + ] i increase (+11.9±2.5 mmol/L), which partially recovered over 30 minutes. Preconditioning did not change the [Na + ] i rise during ischemia but abolished the large [Na + ] i rise on reperfusion, and [Na + ] i instead fell (−3.6±1.3 mmol/L). In the presence of MIA, the [Na + ] i rise was unchanged from ischemia only; on reperfusion, [Na + ] i fell (−3.7±0.9 mmol/L), similar to the preconditioned hearts. TTX abolished the [Na + ] i rise during ischemia (+0.3±0.7 mmol/L), and the increase on reperfusion was similar to ischemia only. We conclude that the rise of [Na + ] i during ischemia is caused by Na + entry through persistent Na + channels. The rise of [Na + ] i on reperfusion is caused by activation of the Na + /H + exchanger and is blocked by MIA and by preconditioning. It is known that the Na + /H + exchanger is inhibited during ischemia; the present result suggests that this inhibition is prolonged into the early part of reperfusion by preconditioning. To test this hypothesis, we measured the time course of pH i recovery after ischemia and preconditioning. Preconditioning slowed the rate of pH i recovery after ischemia, providing further support for the hypothesis that preconditioning inhibits the Na + /H + exchanger during early reperfusion. This inhibition of the Na + /H + exchanger during reperfusion prevents Na + entry, and therefore Ca 2+ loading, and is part of the protective pathway involved in preconditioning.
Head and Neck Cancer in 1994: a Change in the Standard of Care
Authors: C. Jacobs
Journal: JNCI Journal of the National Cancer Institute (1994)

In this issue of the Journal, Paccagnella et al. (7) report improved survival in patients with inoperable head and neck cancer who received neoadjuvant chemotherapy. Their results, as well as those of several other recent trials (2-4), make us contemplate whether standard therapy should be altered for these patients. In the last two decades, there have been significant strides in the field of head and neck oncology, and the role of chemotherapy in combined modality treatment has been studied extensively (5,6). The primary goal of these trials has been to increase curability of advanced disease by adding chemotherapy either prior to standard treatment, concurrently with radiotherapy, or following standard therapy. The two most commonly studied populations have been patients with advanced resectable and unresectable disease. In the 1970s, multiple induction regimens were tested, most using cisplatin, bleomycin, or methotrexate. Pilot trials (5,7) demonstrated few intraoperative and postoperative complications, tolerable toxicity, and response rates that ranged from 50% to 70%, with up to 20% complete responses. Randomized trials (5,7) followed, but all of these early trials gave negative results, which led some head and neck oncologists to abandon the idea of induction chemotherapy. Others believed that these trials were somewhat conservative and sought to develop more effective regimens. One of the most widely used regimens was cisplatin plus fluorouracil (5-FU). This combination achieved 93% overall response (complete response + partial response) and 54% complete response rates after three cycles (8). Several other effective regimens were designed, and a new series of randomized trials (7) followed, again none of which demonstrated improved survival. These studies made several important observations, however. First, a few trials showed significant reduction in metastatic rate from a range of 17%-30% to 9%-15% for patients who received neoadjuvant and/or adjuvant chemotherapy. These trials included the Head and Neck Contracts Program (9), in which one cycle of neoadjuvant cisplatin plus bleomycin and 6 months of adjuvant cisplatin were given; the Southwest Oncology Group trial (10), in which three cycles of cisplatin, methotrexate, and bleomycin
Effects of GLP-1 on Forearm Vasodilator Function and Glucose Disposal During Hyperinsulinemia in the Metabolic Syndrome
Authors: Manfredi Tesauro, Francesca Schinzari, Angelo Adamo, Valentina Rovella, Francesca Martini, Nadia Mores, Angela Barini, Dario Pitocco, Giovanni Ghirlanda, Davide Lauro, Umberto Campia, Carmine Cardillo
Journal: Diabetes Care (2012)

Patients with the metabolic syndrome (MetS) have impaired insulin-induced enhancement of vasodilator responses. The incretin hormone glucagon-like peptide 1 (GLP-1), beyond its effects on blood glucose, has beneficial actions on vascular function. This study, therefore, aimed to assess whether GLP-1 affects insulin-stimulated vasodilator reactivity in patients with the MetS.Forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in MetS patients before and after the addition of GLP-1 to an intra-arterial infusion of saline (n = 5) or insulin (n = 5). The possible involvement of oxidative stress in the vascular effects of GLP-1 in this setting was investigated by infusion of vitamin C (n = 5). The receptor specificity of GLP-1 effect during hyperinsulinemia was assessed by infusing its metabolite GLP-1(9-36) (n = 5). The metabolic actions of GLP-1 were also tested by analyzing forearm glucose disposal during hyperinsulinemia (n = 5).In MetS patients, GLP-1 enhanced endothelium-dependent and -independent responses to ACh and SNP, respectively, during hyperinsulinemia (P < 0.001 for both), but not during saline (P > 0.05 for both). No changes in vasodilator reactivity to ACh and SNP were seen after GLP-1 was added to insulin and vitamin C (P > 0.05 for both) and after GLP-1(9-36) was given during hyperinsulinemia (P > 0.05 for both). Also, GLP-1 did not affect forearm glucose extraction and uptake during hyperinsulinemia (P > 0.05 for both).In patients with the MetS, GLP-1 improves insulin-mediated enhancement of endothelium-dependent and -independent vascular reactivity. This effect may be influenced by vascular oxidative stress and is possibly exerted through a receptor-mediated mechanism.
Payment by Colour
Authors: A. S. Truswell
Journal: BMJ (1972)

<h3>Abstract</h3> Neurostimulation applied from deep brain stimulation (DBS) electrodes is an effective therapeutic intervention in patients suffering from intractable drug-resistant epilepsy when resective surgery is contraindicated or failed. Inhibitory DBS to suppress seizures and associated epileptogenic biomarkers could be performed with high-frequency stimulation (HFS), typically between 100 –165Hz, to various deep-seated targets such as for instance the Mesio-temporal lobe (MTL) which leads to changes in brain rhythms, specifically in the hippocampus. The most prominent alterations concern high-frequency oscillations (HFOs), namely increase in ripples, a reduction in pathological Fast Ripples (FRs), and a decrease in pathological interictal epileptiform discharges (IEDs). In the current study, we use Temporal Interference stimulation to provide a non-invasive focal DBS (130 Hz) of the MTL, specifically the hippocampus, which increases physiological ripples, and decreases the number of FRs and IEDs in a mouse model of epilepsy. Similarly, we show the inability of 130 Hz transcranial current stimulation (TCS) to achieve similar results. The method could potentially revolutionize how DBS, certainly in epilepsy, is performed, and we therefore further demonstrate the translatability to human subjects via measurements of the TI stimulation vs TCS in human cadavers. Results show the better penetration of TI fields into the human hippocampus as compared with TCS. Finally, we provide evidence of the efficacy of the specific form of Pulse-width Modulated TI (PWM-TI), implemented with square waves, which is used in this study. <h3>One Sentence Summary</h3> A non-invasive deep brain stimulation applied via temporal interference achieves the suppression of biomarkers of epilepsy in mice and is scaled to humans.
Prospective validation of the Barcelona Clinic Liver Cancer staging system
Authors: Umberto Cillo, Alessandro Vitale, Francesco Grigoletto, Fabio Farinati, Alberto Brolese, Giacomo Zanus, Daniele Neri, Patrizia Boccagni, Nela Srsen, Francesco D'Amico, Francesco Antonio Ciarleglio, Alessio Bridda, Davide Francesco D'Amico
Journal: Journal of Hepatology (2006)
Quantification of Regulatory T Cells Enables the Identification of High-Risk Breast Cancer Patients and Those at Risk of Late Relapse
Authors: Gaynor J. Bates, Stephen B. Fox, Cheng Han, Russell D. Leek, José F. Garcia, Adrian L. Harris, Alison H. Banham
Journal: Journal of Clinical Oncology (2006)

Purpose To assess the clinical significance of tumor-infiltrating FOXP3-positive regulatory T cells (T R ) in breast cancer patients with long-term follow-up. Patients and Methods FOXP3-positive T R were detected by immunohistochemistry with our new, extensively characterized FOXP3 monoclonal antibody, 236A/E7. Numbers of FOXP3-positive lymphocytes in tissue microarray cores from pure ductal carcinoma in situ (DCIS; n = 62), invasive breast cancer (n = 237) or from comparable areas of normal terminal duct lobular breast tissue (n = 10) were determined. A median cutoff of ≥ 15 defined patients with high numbers of T R . Results T R numbers were significantly higher in in situ and invasive breast carcinomas than in normal breast; invasive tumors have significantly higher numbers than DCIS (P = .001). High numbers of FOXP3-positive T R identified patients with DCIS at increased risk of relapse (P = .04) and patients with invasive tumors with both shorter relapse-free (P = .004) and overall survival (P = .007). High T R numbers were present in high-grade tumors (P ≤ .001), in patients with lymph node involvement (P = .01), and in estrogen receptor (ER) –negative tumors (P = .001). Importantly, high numbers of T R within ER-positive tumors identified high-risk patients (P = .005). Unlike conventional clinicopathologic factors, high numbers of FOXP3-positive T R can identify patients at risk of relapse after 5 years. Conclusion These findings indicate that quantification of FOXP3-positive T R in breast tumors is valuable for assessing disease prognosis and progression, and that T R are an important therapeutic target for breast cancer. FOXP3-positive T R represent a novel marker for identifying late-relapse patients who may benefit from aromatase therapy after standard tamoxifen treatment.
Nephrotic Syndrome Caused by Immune-Mediated Acquired LCAT Deficiency
Authors: Satoshi Takahashi, Keiju Hiromura, Mayuko Tsukida, Yuko Ohishi, Hiroko Hamatani, Noriyuki Sakurai, Toru Sakairi, Hidekazu Ikeuchi, Yoriaki Kaneko, Akito Maeshima, Takashi Kuroiwa, Hideaki Yokoo, Takeo Aoki, Michio Nagata, Yoshihisa Nojima
Journal: Journal of the American Society of Nephrology (2013)

Lecithin-cholesterol acyltransferase (LCAT) is an enzyme involved in maintaining cholesterol homeostasis. In familial LCAT deficiency (FLD), abnormal lipid deposition causes renal injury and nephrotic syndrome, frequently progressing to ESRD. Here, we describe a 63-year-old Japanese woman with no family history of renal disease who presented with nephrotic syndrome. The laboratory data revealed an extremely low level of serum HDL and undetectable serum LCAT activity. Renal biopsy showed glomerular lipid deposition with prominent accumulation of foam cells, similar to the histologic findings of FLD. In addition, she had subepithelial electron-dense deposits compatible with membranous nephropathy, which are not typical of FLD. A mixing test and coimmunoprecipitation study demonstrated the presence of an inhibitory anti-LCAT antibody in the patient's serum. Immunohistochemistry and immunofluorescence detected LCAT along parts of the glomerular capillary walls, suggesting that LCAT was an antigen responsible for the membranous nephropathy. Treatment with steroids resulted in complete remission of the nephrotic syndrome, normalization of serum LCAT activity and HDL level, and disappearance of foam cell accumulation in renal tissue. In summary, inhibitory anti-LCAT antibody can lead to glomerular lesions similar to those observed in FLD.