tbuckley/cabot-search huggingface dataset:
Chronic angiotensin IV treatment reverses endothelial dysfunction in ApoE-deficient mice
Authors: Antony Vinh, Robert E. Widdop, Grant R. Drummond, Tracey A. Gaspari
Journal: Cardiovascular Research (2007)

Endothelial dysfunction is considered a surrogate marker for cardiovascular disease. Angiotensin II, the principal hormone of the renin angiotensin system, is known to promote atherogenesis. However, other angiotensin peptide fragments such as angiotensin IV possess biological activity that may in fact counter-regulate the actions of angiotensin II. Therefore, we investigated the role of angiotensin IV on the development of endothelial dysfunction in apolipoprotein E-deficient (ApoE−/−) mice. In contrast to their wild-type control, ApoE−/− mice that were fed a high-fat diet had exacerbated endothelial dysfunction, evidenced by impaired endothelium-dependent vasodilation. Chronic infusion of angiotensin IV (1.44 mg/kg per day) in ApoE−/− mice for 2 weeks resulted in significant improvements in endothelial function. Angiotensin IV treatment markedly decreased superoxide levels (dihydroethidium staining fluorescence and L-012 chemiluminescence) and increased endothelial nitric oxide synthase expression (immunoreactivity and western blotting) in aortic tissue. Co-treatment of angiotensin IV with either AT4 receptor antagonist divalinal-Ang IV or AT2 receptor antagonist PD123319 attenuated these changes, indicating involvement of both the AT4 and the AT2 receptors. Chronic angiotensin IV treatment in ApoE−/− mice evoked a marked vasoprotective effect that appeared to be mediated by improved NO bioavailability as a result of AT4 and/or AT2 receptor stimulation.
Idiosyncratic Personal Explanations for Blood Glucose Events Are Associated With Poorer Self-Management and Glycemic Control in Adult Patients With Long-Standing Type 1 Diabetes
Authors: Alison J. Wearden, Kathryn Hynd, Helen Smith, Rob Davies, Nicholas Tarrier
Journal: Diabetes Care (2006)

To examine whether spontaneous causal attributions for blood glucose events were associated with blood glucose control (HbA(1c) [A1C]), self-management, and adjustment to diabetes.A total of 62 adults (31 female) with type 1 diabetes, recruited from a diabetes specialist clinic, with a mean age of 42.3 years and a mean illness duration of 19.6 years, were interviewed about the onset, history, course, and management of their diabetes. Spontaneous causal attributions for fluctuations in blood glucose level were extracted from the interviews and coded in accordance with the Leeds Attributional Coding System. Participants completed questionnaire measures of anxiety, depression, and appraisal of diabetes. Glycemic control (A1C) at the time of interview and 1 year later was extracted from notes.Participants who made proportionally more personal, or idiosyncratic, explanations for blood glucose fluctuations or events (such as hypoglycemic episodes) had higher A1C levels at time 1 and 1 year later and were judged to manage their diabetes less well. Furthermore, the association between personal attributions and A1C was partly accounted for by self-management behavior. Participants who made personal and stable attributions appraised their diabetes more negatively.Clinicians should be sensitive to patients' causal explanations for blood glucose events. Helping patients consider alternative explanations may produce benefits in terms of better management and control of diabetes.
Clinical Trial of Low-Fat, High-Carbohydrate Diet in Subjects With Mammographic Dysplasia: Report of Early Outcomes
Authors: N. F. Boyd, M. Cousins, M. Beaton, E. Fishell, B. Wright, E. Fish, V. Kriukov, G. Lockwood, D. Tritchler, W. Hanna, D. L. Page
Journal: JNCI Journal of the National Cancer Institute (1988)

Despite evidence that dietary fat intake may influence breast cancer risk, there is little information about the effects of dietary fat on the human breast. We have studied the effects of dietary fat on the breast by examining the influence of dietary fat reduction on mammographic dysplasia (nodular or sheetlike areas of radiological density). Subjects with mammographic dysplasia were randomly allocated to a control group, in which they received advice about maintaining a balanced diet (36% of calories as fat), or an intervention group, in which they were taught to reduce dietary fat to a target of 15% of calories. A total of 295 patients consented to randomization, and after 1 year, 20% of the intervention group and 5% of the control group had dropped out (failed to keep appointments and provide nutrient data). The remaining patients closely adhered to the dietary goals of the study as assessed by food records, chemical analysis of duplicate meals, and serum cholesterol measurements. Comparison of mammograms before and after 1 year of dietary fat reduction shows no significant influence on the extent or density of mammographic dysplasia. Surgical biopsies performed in subjects after entry in the study showed five cancers in the control group and two cancers in the intervention group; this total of seven cancers is four times the number expected. These data show that clinical trials of the effects of dietary fat reduction on breast cancer risk are feasible and that long-term compliance with a low-fat diet can be achieved, and they confirm that the patients selected because they had mammographic dysplasia had increased risk of breast cancer.
Plasma Metallothionein Antibody, Urinary Cadmium, and Renal Dysfunction in a Chinese Type 2 Diabetic Population
Authors: Liang Chen, Lijian Lei, Taiyi Jin, Monica Nordberg, Gunnar F. Nordberg
Journal: Diabetes Care (2006)

It has been reported that diabetes may increase the risk of cadmium-induced kidney damage. The presence of metallothionein antibody (MT-Ab) increased the susceptibility for tubular damage among cadmium workers. This study focused on the relationships between levels of MT-Ab, urinary cadmium, and kidney function in a Chinese type 2 diabetic population.A cross-sectional study was performed on 229 type 2 diabetic patients (92 men and 137 women) who were recruited from two community centers in one district of Shanghai City in China. Information was obtained from interviews, health records, and blood and urine samples.Levels of the tubular biomarker beta2-microglobulin increased significantly when the levels of MT-Ab and urinary cadmium were elevated in male and female subjects; in contrast, the levels of urinary albumin, a glomerular biomarker, did not display such a pattern. After adjusting for potential confounding covariates, logistic regression showed that the odds ratios (ORs) of tubular dysfunction increased upon 1) increasing the MT-Ab concentration from a low to high level (OR 5.56 [95% CI 2.25-13.73]) and 2) increasing the level of urinary cadmium from <1 to >or=1 microg/g creatinine (3.34 [1.17-9.53]); the OR of patients currently smoking was 3.51 (1.14-10.80) relative to that of those who had never smoked.This study proves that the presence of MT-Ab can potentiate tubular dysfunction among diabetic subjects and that patients with high MT-Ab levels are more prone to development of tubular damage.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Hans Klaus Kaiser, W. Barry Wood
Journal: The Journal of Experimental Medicine (1962)

Determination of the dose-response curve for rabbit leucocytic pyrogen reveals a hyperthermic "ceiling" at which there is a marked insensitivity to dosage. This finding has important implications in relation to the quantitative assay of leucocytic pyrogen. Polymorphonuclear leucocytes separated from normal rabbit blood possess the capacity to produce less than 5 per cent of the pyrogen generated by the same number of rabbit granulocytes collected from acute peritoneal exudates. Blood granulocytes, separated in the cold from the buffy coat, contain no detectable preformed pyrogen. The amount of preformed pyrogen within exudate granulocytes represents but a small fraction of the pyrogen which the cells are capable of generating when incubated in normal saline at 37 degrees C. It is suggested that the active pyrogen is formed from an inactive precursor within the cells. Under the conditions tested, cell fragments of rabbit granulocytes fail to produce endogenous pyrogen. The fact that the production of pyrogen is blocked at 4 degrees C is in keeping with the hypothesis that it involves metabolic reactions within the cell.
Atlas-Based Neuroinformatics via MRI: Harnessing Information from Past Clinical Cases and Quantitative Image Analysis for Patient Care
Authors: Susumu Mori, Kenichi Oishi, Andreia V. Faria, Michael I. Miller
Journal: Annual Review of Biomedical Engineering (2013)

With the ever-increasing amount of anatomical information radiologists have to evaluate for routine diagnoses, computational support that facilitates more efficient education and clinical decision making is highly desired. Despite the rapid progress of image analysis technologies for magnetic resonance imaging of the human brain, these methods have not been widely adopted for clinical diagnoses. To bring computational support into the clinical arena, we need to understand the decision-making process employed by well-trained clinicians and develop tools to simulate that process. In this review, we discuss the potential of atlas-based clinical neuroinformatics, which consists of annotated databases of anatomical measurements grouped according to their morphometric phenotypes and coupled with the clinical informatics upon which their diagnostic groupings are based. As these are indexed via parametric representations, we can use image retrieval tools to search for phenotypes along with their clinical metadata. The review covers the current technology, preliminary data, and future directions of this field.
In Regard to Lassman et al.
Authors: E. Weltman, S. M. Fleury Malheiros
Journal: Neuro-Oncology (2012)

In Regard to Lassman et al. Neuro-Oncol. 2011;13:649–659.

The treatment of patients with anaplastic oligodendroglial tumors remains controversial. Initial treatment with radiation therapy associated or not with concomitant and/or sequential procarbazine, lomustine, and vincristine (PCV) chemotherapy is historically the most frequent approach to treat this disease.1 Radiation therapy has been reported for the treatment of the oligodendrogliomas since the 1960s2 and has been established as an effective treatment for increasing these patients’ probability of surviving 5 years after subtotal tumor resection since the 1980s.3

From the RTOG 94024 and EORTC 269515 well-designed phase III trials, we have the information that patients presenting with anaplastic oligodendroglial tumors with 1p19q codeletion have better prognosis and response to treatment, either radiation or chemotherapy. The early addition of chemotherapy in these trials improved the progression-free survival but not overall survival. In addition, the neurologic function was not assessed; thus, the real impact of this approach was not fully evaluated.

The strength of this article is based on an impressive number of patients, with the retrospective analysis of >1000 patients with anaplastic olidendroglial tumors. However, the 3 initial treatment groups (chemotherapy, radio-chemotherapy, and radiation therapy) were too heterogeneous. Most received combined radio-chemotherapy as the first treatment, demonstrating the preference of the clinicians for this approach. Seventy-three percent of the patients who received chemotherapy as the first treatment and had a known 1p19q status had a codeleted status, compared with  85% in the chemotherapy and radiation therapy arm, compared with <75% in the radiation therapy arm.

Assuming the limitations of this retrospective study, we may observe that there is significant bias in the presented data. Therefore, the authors must be cautious to suggest that “… initial treatment with chemotherapy alone may be a reasonable option for patients with 1p19q codeleted tumors …” Considering that this is not an evidence-based conclusion, they should not stimulate this approach to treatments off protocol.
Peer review must stay as guarantee of quality, research leaders tell MPs
Authors: A. O'Dowd
Journal: BMJ (2011)

The quality of scientific research can be guaranteed only by the continued use of peer review by journals, research leaders have told an inquiry by MPs.

Peer review, although not a perfect system, was the best option available, MPs on the parliamentary science and technology select committee heard on 8 June as part of their inquiry into peer review ( BMJ 2011;342:d3046, doi:10.1136/bmj.d3046).

The committee’s chairman, Andrew Miller, Labour MP for Ellesmere Port and Neston, said that the research charity the Wellcome Trust had highlighted in its written evidence to the committee a “common criticism” that the peer review system could sometimes be slow and limit the emergence of new ideas that challenged established norms. Mr Miller asked the witnesses for …
Quantitative Trait Loci Modulate Renal Cystic Disease Severity in the Mouse bpk Model
Authors: LISA M. GUAY-WOODFORD, CHRISTOPHER J. WRIGHT, GERD WALZ, GARY A. CHURCHILL
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Numerous mouse models of polycystic kidney disease (PKD) have been described in which the mutant phenotypes closely resemble human PKD with regard to morphology, cyst localization, and disease progression. As in human PKD, genetic background affects the disease phenotype in mouse PKD models. Using experimental crosses, these modifying effects can be dissected into discrete genetic factors referred to as quantitative trait loci. The locus for the mouse bpk model was recently mapped to chromosome (Chr) 10. In the course of these studies, marked variability was observed in the renal cystic disease expressed in F2 bpk/bpk homozygotes of a (BALB/c-+/ bpk × CAST/Ei)F1 intercross. The current study was undertaken to further characterize the renal cystic disease as quantitative trait in this F2 cohort and to map the genetic modifiers that modulate this phenotype. Whole-genome scans revealed a CAST-derived locus on distal Chr 6, near D6Mit14 , that affects renal cystic disease severity. Additional analyses identified loci on Chr 1, Chr 2, and Chr 4, as well as a possible interaction between the Chr 6 locus and a locus on distal Chr 1, near D1Mit17 . Interestingly, the gene encoding RGS7, a regulator of G protein signaling that binds to polycystin-1, was mapped to the same Chr 1 interval. It is concluded that the severity of the bpk renal cystic disease phenotype is modulated by multiple loci and possibly by epistatic interaction among them. It is hypothesized that the gene encoding the polycystin-binding partner RGS7 is a candidate for the Chr 1 genetic modifier.
Working Memory Deficits and Levels of<i>N</i>-Acetylaspartate in Patients With Schizophreniform Disorder
Authors: Alessandro Bertolino, Domenico Sciota, Flora Brudaglio, Mario Altamura, Giuseppe Blasi, Antonello Bellomo, Nicola Antonucci, Joseph H. Callicott, Terry E. Goldberg, Tommaso Scarabino, Daniel R. Weinberger, Marcello Nardini
Journal: American Journal of Psychiatry (2003)

The authors used proton magnetic resonance spectroscopic imaging ((1)H-MRSI) to assess potential reductions of N-acetylaspartate (a marker of neuronal integrity) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophreniform disorder. In addition, they assessed the relationship between N-acetylaspartate levels and working memory deficits.Twenty-four patients with DSM-IV schizophreniform disorder and 24 healthy subjects were studied. Subjects underwent (1)H-MRSI and were given the N-back working memory test.The schizophreniform disorder patients had selective reductions of N-acetylaspartate ratios in the hippocampal area and the dorsolateral prefrontal cortex, and a positive correlation was seen between N-acetylaspartate ratios in the dorsolateral prefrontal cortex and performance during the 2-back working memory condition.Similar to findings reported in schizophrenia studies, N-acetylaspartate reductions in the hippocampal area and the dorsolateral prefrontal cortex were seen in patients with schizophreniform disorder. Moreover, the results support other evidence that neuronal pathology in the dorsolateral prefrontal cortex accounts for a proportion of working memory deficits already present at illness outset.
Time Dependence of Myocardial Contractility in the Human Left Ventricle
Authors: E. L. Fallen, R. Gorlin
Journal: Cardiovascular Research (1968)

The timing of intrinsic contractile events has been studied in the human heart. Time to peak force averaged 69 msec in the normal heart as compared with 98 msec in patients with aortic stenosis. Contractile element velocity increased following peak force in both groups, although maintained for different durations before an abrupt deceleration occurred, probably representing decay of maximum active state.
Work and common psychiatric disorders
Authors: M Henderson, SB Harvey, S Øverland, A Mykletun, M Hotopf
Journal: Journal of the Royal Society of Medicine (2011)

Psychiatric disorders are now the most common reason for long-term sickness absence. The associated loss in productivity and the payment of disability benefits places a substantial burden on the economies of many developed countries. The occupational dysfunction associated with psychiatric disorders can also lead to poverty and social isolation. As a result the area of work and psychiatric disorders is a high priority for policymakers. There are two main agendas: for many researchers and clinicians the focus is on the need to overcome stigma and ensure people with severe psychiatric disorders have meaningful work; however the public health agenda predominantly relates to the more common disorders such as depression and anxiety, which contribute a greater burden of disability benefits and pensions. In this review we attempt to address this second agenda. The relatively sparse evidence available reveals a complex field with significant interplay between medical, psychological social and cultural factors. Sick leave can be a ‘process’ as well as an ‘event’. In this review we propose a staged model where different risk and protective factors contribute to the onset of psychiatric disorders in the working population, the onset of short-term sickness absence, and the transition from short- to long-term absence. We also examine strategies to manage psychiatric disorder in the workforce with a view towards returning the employee to work. Our aim in this review is to highlight the complexity of the area, to stimulate debate and to identify important gaps in knowledge where further research might benefit both patients and wider society.
Standardised criteria improve accuracy of ECG interpretation in competitive athletes: a randomised controlled trial
Authors: Daniel J Exeter, C Raina Elley, Mark L Fulcher, Arier C Lee, Jonathan A Drezner, Irfan M Asif
Journal: British Journal of Sports Medicine (2014)

Screening to prevent sudden cardiac death remains a contentious topic in sport and exercise medicine. The aim of this study was to assess whether the use of a standardised criteria tool improves the accuracy of ECG interpretation by physicians screening athletes.Design: Randomised control trial. Study Population: General practitioners with an interest in sports medicine, sports physicians, sports medicine registrars and cardiologists from Australia and New Zealand were eligible to participate. Outcome Measures: Accuracy, sensitivity, specificity and false-positive rates of screening ECG interpretation of athletes. Intervention: A two-page standardised ECG criteria tool was provided to intervention participants. Control participants undertook 'usual' interpretation.62 physicians, with a mean duration of practice of 16 years, were randomised to intervention and control. 10 baseline and 30 postrandomisation athlete ECGs were interpreted by the participants. Intervention participants were more likely to be correct: OR 1.72 (95% CI 1.31 to 2.27, p<0.001). Correct ECG interpretation was higher in the intervention group, 88.4% (95% CI 85.7% to 91.2%), than in the control group, 82.2% (95% CI 78.8% to 85.5%; p=0.005). Sensitivity was 95% in the intervention group and 92% in the control group (p=0.4), with specificity of 86% and 78%, respectively (p=0.006). There were 36% fewer false positives in the intervention group (p=0.006).ECG interpretation in athletes can be improved by using a standardised ECG criteria tool. Use of the tool results in lower false-positive rates; this may have implications for screening recommendations.ACTRN12612000641897.
Molecular Markers in Low-Grade Gliomas: Predictive or Prognostic?
Authors: Christian Hartmann, Bettina Hentschel, Marcos Tatagiba, Johannes Schramm, Oliver Schnell, Clemens Seidel, Robert Stein, Guido Reifenberger, Torsten Pietsch, Andreas von Deimling, Markus Loeffler, Michael Weller
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To investigate whether TP53 mutation, 1p/19q codeletions, O6-methylguanylmethyltransferase (MGMT) promoter methylation, and isocitrate dehydrogenase 1 (IDH1) mutation predict natural course of disease or response to radiotherapy or chemotherapy or both in low-grade glioma patients. Experimental Design: Cohort A consisted of 89 patients with diffuse astrocytoma World Health Organization (WHO) grade II (n = 40), oligoastrocytoma (n = 23), or oligodendroglioma (n = 26) who did not receive radiotherapy or chemotherapy after first operation and were monitored until progression [progressive disease (PD); n = 59] and beyond or until the end of follow-up (n = 30). Cohort B consisted of 50 patients with WHO grade II gliomas who received radiotherapy or chemotherapy at diagnosis. Tumors were analyzed for TP53 mutations, 1p/19q codeletions, MGMT promoter methylation, and IDH1 mutations. Results: Median progression-free survival (PFS) in cohort A was 4.1 years (95% CI: 3.1–5.1). No molecular marker was prognostic for PFS after surgery alone, using multivariate adjustment for histology, age, and extent of resection. IDH1 mutations were associated with prolonged survival from the diagnosis of PD in oligoastrocytomas (OA II)/oligodendrogliomas (O II) and with overall survival (OS) in all tumors. 1p/19q codeletion and IDH1 mutation were prognostic for PFS and OS in cohort B. Conclusions: None of the parameters are sensitive prognostic biomarkers in WHO grade II glioma patients who do not receive radiotherapy or chemotherapy after surgery. Limitations of this study include the selection of patients with favorable outcome, the nonrandomized allocation of treatment, and the insufficient sample size to distinguish between effects of radiotherapy versus chemotherapy. Regardless of histology, IDH1 mutation status is the strongest prognostic marker for OS. Clin Cancer Res; 17(13); 4588–99. ©2011 AACR.