tbuckley/cabot-search huggingface dataset:
Impaired Glucose Tolerance in Adolescent Offspring of Diabetic Mothers: Relationship to fetal hyperinsulinism
Authors: Bernard L Silverman, Boyd E Metzger, Nam H Cho, Caroline A Loeb
Journal: Diabetes Care (1995)

OBJECTIVE To test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. RESEARCH DESIGN AND METHODS We enrolled offspring of women with pregestational diabetes (this included insulin-dependent diabetes mellitus. [1DDM] and non-insulin-dependent diabetes mellitus [NIDDM]) and gestational diabetes in a prospective study from 1977 through 1983. Fetal /3-cell function was assessed by measurement of arrmiotic fluid insulin (AF1) at 32–38 weeks gestation. Postnatally, plasma glucose and insulin were measured yearly from 1.5 years of age after fasting and 2 h after 1.75 g/kg oral glucose. Control subjects had a single oral glucose challenge at 10-16 years. RESULTS In offspring of diabetic mothers, the prevalence of impaired glucose tolerance (IGT) (2-h glucose concentration &amp;gt;7.8 mmol/1) was: 1.2% at &amp;lt;5 years, 5.4% at 5–9 years, and 19.3% at 10–16 years. The 88 offspring of diabetic mothers (12.3 ± 1.7 years), when compared with 80 control subjects of the same age and pubertal stage, had higher 2-h glucose (6.8 ±1.4 vs. 5.7 ± 0.9 mmol/1, P &amp;lt; 0.001) and insulin (660 ± 720 vs. 455 ± 285 pmol/1, P &amp;lt; 0.03) concentrations. The 17 subjects with IGT at &amp;gt; 10 years of age (9 boys and 8 girls) include one girl with NIDDM. IGT was not associated with the etiology of the mother's diabetes (gestational versus pregestational) or macrosomia at birth. IGT was found in only 3.7% (1 of 27) of adolescents whose AFI was normal (≥100 pmol/l) and 33.3% (12 of 36) of those with elevated AFI (P &amp;lt; 0.001). Although most of the children with IGT are obese, AFI and obesity are independently associated with IGT by multiple logistic analysis. CONCLUSIONS In confirmation of our original hypothesis, IGT in the offspring is a long-term complication of maternal diabetes. Excessive insulin secretion in utero, as assessed by AFI concentration, is a strong predictor of IGT in childhood.
NCX is an important determinant for premature ventricular activity in a drug-induced model of Andersen–Tawil syndrome
Authors: Przemysław B. Radwański, Steven Poelzing
Journal: Cardiovascular Research (2011)

AimsAndersen–Tawil syndrome (ATS1)-associated ventricular arrhythmias are initiated by premature ventricular activity (PVA) resulting from diastolic Ca2+ (CaD) accumulation. We hypothesized that relatively high Na+–Ca2+ exchanger (NCX) expression coupled with slower Ca2+ uptake may constitute an arrhythmogenic substrate during drug-induced ATS1 (DI-ATS1).
An <i>In vivo</i> Model of Met-Driven Lymphoma as a Tool to Explore the Therapeutic Potential of Met Inhibitors
Authors: Paolo Accornero, Giuseppe Lattanzio, Tony Mangano, Roberto Chiarle, Riccardo Taulli, Francesca Bersani, Paolo E. Forni, Silvia Miretti, Claudio Scuoppo, Walter Dastrù, James G. Christensen, Tiziana Crepaldi, Carola Ponzetto
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Met, the tyrosine kinase receptor for hepatocyte growth factor, is frequently deregulated in human cancer. Recent evidence indicates that Met amplification may confer resistance to treatments directed toward other receptor tyrosine kinases. Thus, there is a need to develop Met inhibitors into therapeutic tools, to be used alone or in combination with other molecularly targeted drugs. Preclinical validation of Met inhibitors has thus far been done in nude mice bearing cancer cells xenogratfs. A far superior model would be a transgenic line developing spontaneous Met-driven tumors with high penetrance and short latency. Experimental Design: To this end, we introduced into the mouse genome TPR-MET, the oncogenic form of MET. The Tpr-Met protein ensures deregulation of Met signaling because dimerization motifs in the Tpr moiety cause ligand-independent activation of the Met kinase. Results: Here, we describe a TPR-MET transgenic line that develops thymic T-cell lymphoma with full penetrance and very short latency. In the tumors, Tpr-Met and its effectors were phosphorylated. Treatment of tumor-derived T lymphocytes with the selective Met inhibitor PHA-665752 at nanomolar concentrations abolished phosphorylation of Met and downstream effectors and led to caspase-mediated apoptosis. I.v. administration of PHA-665752 to transgenic mice bearing lymphomas in exponential growth phase led to a significant decrease in tumor growth and, in some cases, to tumor regression. Conclusions: Our transgenic line, which within 2 months reliably develops Tpr-Met–driven T-cell lymphoma, represents a valuable tool to explore the efficacy and therapeutic potential of Met kinase inhibitors as anticancer drugs.
Effects of sodium pentobarbital anesthesia on left ventricular function and distribution of cardiac output in dogs, with particular reference to the mechanism for tachycardia.
Authors: W T Manders, S F Vatner
Journal: Circulation Research (1976)

Sodium pentobarbital (PB), 30 mg/kg, iv, was administered to 30 conscious dogs instrumented for measurement of cardiac output and regional blood flow distribution, left ventricular (LV) diameter, LV pressure, dP/dt, and dD/dt, i.e., velocity of myocardial fiber shortening. Ventilation was controlled during anesthesia to maintain arterial blood gases at control values for conscious dogs. The anesthetic produced an initial transient, peripheral vasodilation but the steady state effects 15-30 minutes later were characterized by slight reductions in mesenteric flow and cardiac output and increases in mesenteric and systemic resistances, whereas iliac and renal resistances were not significantly different from control. When heart rate rose, PB increased end-systolic diameter and decreased coronary resistance, LV end-diastolic diameter, dP/dt/P (42%), and shortening velocity (36%). When heart rate was controlled, PB still increased end-systolic diameter and decreased shortening velocity and dP/dt/P, as occurred during spontaneous rhythm, but end-diastolic diameter rose instead of falling and coronary resistance did not change. After recovery from bilateral cervical section of both carotid sinus and aortic nerves, PB failed to elicit tachycardia. Thus, PB affects systemic and regional hemodynamics only slightly, but depresses the myocardium markedly. The tachycardia associated with PB anesthesia in intact, trained dogs appears not to be only vagolytic, as previously thought, but is predominantly mediated through the arterial baroreceptor reflex.
Granulocyte colony-stimulating factor exacerbates cardiac fibrosis after myocardial infarction in a rat model of permanent occlusion
Authors: Zhaokang Cheng, Lailiang Ou, Yi Liu, Xiaolei Liu, Fei Li, Bin Sun, Yongzhe Che, Deling Kong, Yaoting Yu, Gustav Steinhoff
Journal: Cardiovascular Research (2008)

AimsControversy exists regarding the effects of granulocyte colony-stimulating factor (G-CSF) on post-infarction remodelling, which is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to investigate the impact of G-CSF administration on cardiac MMP/TIMP ratios and long-term remodelling in a rat model of acute myocardial infarction (MI).
Professor Wallace's reply
Authors: W A. Wallace
Journal: BMJ (1995)

EDITOR,--When I was first asked to examine Paula Dixon she was complaining only of pain in the right forearm. She told me that she had injured her right forearm when she fell off her bike on her way to the airport. I assumed, incorrectly, that she had fallen off a bicycle and had injured the forearm while breaking her fall. It was only later (during …
Central Pulse Pressure and Its Hemodynamic Determinants in Middle-Aged Adults With Impaired Fasting Glucose and Diabetes
Authors: Julio A. Chirinos, Patrick Segers, Thierry C. Gillebert, Marc L. De Buyzere, Caroline M. Van daele, Zubair A. Khan, Umair Khawar, Dirk De Bacquer, Ernst R. Rietzschel
Journal: Diabetes Care (2013)

OBJECTIVE Pulse pressure (PP), a strong predictor of cardiovascular events in type 2 diabetes, is a composite measure affected by several hemodynamic factors. Little is known about the hemodynamic determinants of central PP in type 2 diabetes or whether abnormalities in central pulsatile hemodynamics are already present in individuals with impaired fasting glucose (IFG). In a population-based study, we aimed to compare central PP and its hemodynamic determinants among adults with normal fasting glucose (n = 1654), IFG (n = 240), and type 2 diabetes (n = 33). RESEARCH DESIGN AND METHODS We measured carotid pressure, left ventricular outflow, aortic root diameter, carotid artery flow, and distension in order to measure various structural and hemodynamic arterial parameters. RESULTS IFG was associated with a greater mean arterial pressure (MAP) but was not associated with intrinsic aortic stiffening or abnormal aortic pulsatile indices after adjustment for MAP. After adjustment for age, sex, and MAP, type 2 diabetes was associated with a higher aortic root characteristic impedance (Zc), aortic root elastance-thickness product (Eh), and aortic root pulse wave velocity (but not aortic root diameter), a greater carotid-femoral pulse wave velocity, and lower total arterial compliance and wave reflection magnitude. Carotid size, Zc, distensibility, or Eh did not significantly differ between the groups. CONCLUSIONS Type 2 diabetes, but not IFG, is associated with greater large artery stiffness, without abnormalities in aortic root diameter or carotid stiffness. Subjects with type 2 diabetes demonstrate a decreased reflection magnitude, which may indicate an increased penetration of pulsatile energy to distal vascular beds.
Novel role of Egr-1 in nicotine-related neointimal formation
Authors: Roberto I. Vazquez-Padron, Dania Mateu, Luis Rodriguez-Menocal, Yuntao Wei, Keith A. Webster, Si M. Pham
Journal: Cardiovascular Research (2010)

The aim of this study was to investigate the mechanisms by which nicotine increases vascular smooth muscle cell (VSMC) proliferation and post-injury neointimal formation. Vascular injury was inflicted in the right iliac artery of nicotine-treated and control rats. Nicotine increased post-injury VSMC proliferation (Ki67+ cells) and neointimal formation (neointima/media ratio, 0.42 ± 0.23 vs. 0.14 ± 0.07, P= 0.02). To determine the mechanisms by which nicotine exacerbates VSMC proliferation, cultured cells were exposed to nicotine, and signalling pathways leading to cell proliferation were studied. Nicotine activated extracellular signal-regulated kinase (ERK) 1/2 in a dose- and time-dependent manner. The blockade of this signalling axis abolished nicotine-mediated proliferation. Functional nicotinic acetylcholine receptors and Ca2+ influx were necessary for ERK1/2 activation and nicotine-induced mitogenesis in VSMCs. Downstream to ERK1/2, nicotine induced the phosphorylation of Ets-like gene 1 in a timely co-ordinated manner with the up-regulation of the atherogenic transcription factor, early growth response 1 (Egr-1). The treatment of balloon-injured arteries with a lentivirus vector carrying a short hairpin RNA against Egr-1 abolished the deleterious effect of nicotine on vascular remodelling. Nicotine acts through its receptors in VSMC to activate the ERK–Egr-1 signaling cascade that induces cell proliferation and exacerbates post-injury neointimal development.
Complementation of Der p 2–induced histamine release from human basophils sensitized with monoclonal IgE: Not only by IgE, but also by IgG antibodies directed to a nonoverlapping epitope of Der p 2☆☆☆★★★
Authors: Janine Schuurman, Gerrard J. Perdok, Geoffrey A. Mueller, Rob C. Aalberse
Journal: Journal of Allergy and Clinical Immunology (1998)
A SINGULAR DISTORTION OF TEMPORAL ORIENTATION
Authors: MAX DAHL
Journal: American Journal of Psychiatry (1958)

The subject of this study is the observation that some patients will give the year of their birth and the current year correctly but are unable to give their correct age. Pertinent literature is quoted. Five hundred female patients, chosen at random, were interviewed. The results were tabulated with means and standard deviations. It was found that this symptom occurs only in regressed schizophrenics and that it might be a diagnostic and prognostic aid. An attempt is made to interpret this phenomenon from the psycho-structural frame of reference.
Breast Cancer Risk after Occupational Solvent Exposure: the Influence of Timing and Setting
Authors: Christine C. Ekenga, Christine G. Parks, Aimee A. D'Aloisio, Lisa A. DeRoo, Dale P. Sandler
Journal: Cancer Research (2014)

Abstract Organic solvents are ubiquitous in occupational settings where they may contribute to risks for carcinogenesis. However, there is limited information on organic solvents as human breast carcinogens. We examined the relationship between occupational exposure to solvents and breast cancer in a prospective study of 47,661 women with an occupational history in the Sister Study cohort. Occupational solvent exposure was categorized using self-reported job-specific solvent use collected at baseline. Multivariable Cox regression analyses were used to assess breast cancer risk, adjusting for established breast cancer risk factors. A total of 1,798 women were diagnosed with breast cancer during follow-up, including 1,255 invasive cases. Overall the risk of invasive breast cancer was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence interval (CI), 0.88–1.24]. Parous women who worked with solvents before their first full-term birth had an increased risk of estrogen receptor–positive invasive breast cancer compared with women who never worked with solvents (HR, 1.39; 95% CI, 1.03–1.86). A significantly elevated risk for estrogen receptor–positive invasive breast cancer was associated with solvent exposure among clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07–3.73). Occupational exposure to solvents before first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our findings suggest a need for future studies in this area to focus on exposure time windows and solvent types in different occupational settings. Cancer Res; 74(11); 3076–83. ©2014 AACR.
Adenosine release by the isolated guinea pig heart in response to isoproterenol, acetylcholine, and acidosis: the minimal role of vascular endothelium.
Authors: H Bardenheuer, B Whelton, H V Sparks
Journal: Circulation Research (1987)

The objective of this study was to determine the contribution of endothelial cells to adenosine appearing in venous effluent of isolated perfused guinea pig hearts. The adenine nucleotide pool of endothelial cells was selectively labelled by infusing 3H-adenosine (5 X 10(-8) M) into the heart for 30 minutes. Selective labelling of the endothelial adenine nucleotides was confirmed by measuring the relative specific activities of the nucleotides of coronary endothelial cells (removed from the heart by enzyme treatment). Endothelial ATP, ADP, and AMP had relative specific activities that were 49, 25, and 7 times higher, respectively, than their nucleotide counterparts in total myocardial tissue. Isoproterenol increased the release of both total adenosine and radioactive adenosine, but the relative specific activity of venous adenosine decreased dramatically. Acetylcholine, at a concentration that caused no change in left ventricular pressure but caused a decrease in coronary vascular resistance, increased the release of total adenosine. However, both radioactive adenosine release and the relative specific activity of venous effluent adenosine were decreased with acetylcholine. Infusion of hydrochloric acid caused a sustained reduction in left ventricular pressure and coronary vascular resistance. Total adenosine release fell within one minute and remained reduced during HCl. Radioactive adenosine release was elevated at 15 seconds but fell below control values at 2 minutes and remained reduced during steady-state acidosis. We conclude that the majority of the adenosine released in response to isoproterenol and acetylcholine originates from an unlabelled compartment, most likely the myocytes. Acidosis results in decreased release of adenosine from both the labelled endothelium and the unlabelled cells in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Quality Assessment of Quality Improvement Programs
Authors: W. Dale Overfield
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The article on peer review organization methods by Rubin et al<sup>1</sup>was interesting and its results conform to my empiric observation and bias. It is also my bias that the detection of quality problems on the part of physicians is probably not of value. It is my opinion that most problems are recognized by the physician and self-corrected. It would also be my bias that mistakes occur at a relatively continuous level and that picking up a mistake does not change overall quality of care. I would be interested to know whether there has been any change in overall morbidity or mortality from the period before peer review organization review processes were instituted to the present. I suspect that there has been no substantive change in outcome as a result of peer review organization review processes. This same sort of outcome analysis that is starting to
Transitional care for elderly people
Authors: John R Gladman
Journal: BMJ (2005)

Editor—Crotty et al show that transitional, or intermediate, care facilities can be used to divert older people safely from hospital to a care home setting.1 Our randomised controlled trial had similar findings,2 but we could not exclude the possibility that such transitional care increases long term institutionalisation over a longer period of follow-up (12 months, compared with four months in the study by Crotty et al). Young et al's whole system study in Leeds showed that intermediate care services increased admissions to hospital.3 So, intermediate care can sometimes reduce hospital admission and sometimes it does not. It is not guaranteed to lead to outcomes that are equivalent to those of the services being replaced.

This inconsistency of the evidence base raises the question of whether findings obtained in controlled research studies of services can be generalised to other times and settings. If not, the fears previously raised about the quality of care for older people in intermediate care services4-5 cannot be put to rest simply because some demonstration projects have shown acceptable findings.

We need high quality randomised controlled trials, such as that reported by Crotty et al, to show what is possible, but we also need to establish the conditions that are necessary for success—those conditions that when not met lead to ineffective or unsafe care.

This is likely to require a wide range of descriptive research methods such as systems analyses and case studies undertaken alongside controlled studies. Once these conditions for success have been established, we need a systematic quality assurance exercise to ensure that they are being met.

If we do not do this then we may find ourselves so blinded by policy pressure to keep older people out of hospital that we fail to do our jobs as clinicians as we collude with the provision of substandard care.
Treatment of refractory anterior knee pain using botulinum toxin type A (Dysport) injection to the distal vastus lateralis muscle: a randomised placebo controlled crossover trial
Authors: Barbara J Singer, Peter L Silbert, Swithin Song, John W Dunne, Kevin P Singer
Journal: British Journal of Sports Medicine (2010)

Objectives This randomised controlled crossover trial examined the efficacy of botulinum toxin type A (BoNT-A) injection, plus an exercise programme, to remediate chronic anterior knee pain (AKP) associated with quadriceps muscle imbalance. Methods 24 individuals with refractory AKP received either BoNT-A (500 U Dysport) or the same volume saline injection to the vastus lateralis (VL) muscle and performed home exercises focusing on re-training the vastus medialis (VM) muscle. All subjects were offered open-label injection at 12 weeks. Knee-related disability (anterior knee pain scale; AKPS) and activity-induced pain (10 cm visual analogue scale) at 12 weeks were the primary outcomes. Peak isometric extensor force was recorded and normalised VL:VM ratios were derived from simultaneous surface electromyography. Selfreported pain and disability measures were collected at six time points to a mean of 20±8 months. Results 14 subjects received BoNT-A and 10 placebo injection. Improvement at 12 weeks was significantly greater for BoNT-A compared with placebo-injected subjects for the AKPS (p&lt;0.03), pain on kneeling (p&lt;0.004), squatting (p&lt;0.02) and level walking (p&lt;0.04). At week 12, five placebo subjects crossed over to open-label injection. At 24 weeks, 16 of 19 BoNT-A-injected and two of the remaining five placeboinjected subjects were either satisfied or very satisfied with treatment outcomes. Improvements were maintained in 11 of 14 BoNT-A-injected and two of five placebo subjects available at longer-term follow-up. Conclusion BoNT-A injection produced a greater reduction in pain and disability than placebo injection in carefully selected patients with chronic AKP related to quadriceps muscle imbalance.
A Scan for Human-Specific Relaxation of Negative Selection Reveals Unexpected Polymorphism in Proteasome Genes
Authors: Mehmet Somel, Melissa A. Wilson Sayres, Gregory Jordan, Emilia Huerta-Sanchez, Matteo Fumagalli, Anna Ferrer-Admetlla, Rasmus Nielsen
Journal: Molecular Biology and Evolution (2013)

Environmental or genomic changes during evolution can relax negative selection pressure on specific loci, permitting high frequency polymorphisms at previously conserved sites. Here, we jointly analyze population genomic and comparative genomic data to search for functional processes showing relaxed negative selection specifically in the human lineage, whereas remaining evolutionarily conserved in other mammals. Consistent with previous studies, we find that olfactory receptor genes display such a signature of relaxation in humans. Intriguingly, proteasome genes also show a prominent signal of human-specific relaxation: multiple proteasome subunits, including four members of the catalytic core particle, contain high frequency nonsynonymous polymorphisms at sites conserved across mammals. Chimpanzee proteasome genes do not display a similar trend. Human proteasome genes also bear no evidence of recent positive or balancing selection. These results suggest human-specific relaxation of negative selection in proteasome subunits; the exact biological causes, however, remain unknown.
Serum concentrations of vitamin D metabolites in untreated tuberculosis.
Authors: P D Davies, R C Brown, J S Woodhead
Journal: Thorax (1985)

A prospective study of 50 consecutive patients presenting with tuberculosis has shown that patients have on average lower serum concentrations of 25-hydroxycholecalciferol (25-OHD) than healthy matched controls. No difference was shown in serum 1,25-(OH)2D, 24,25-(OH)2D, or parathyroid hormone. Uncorrected serum calcium was lower in the patient group but identical when correction concentrations were made for albumin. Serum liver enzyme concentrations were significantly higher in the patient population. Low serum vitamin D concentrations may be a consequence of disease. The possibility that low serum 25-OHD concentrations may predispose to tuberculosis infection cannot, however, be excluded. Prolonged treatment with isoniazid or rifampicin, both of which have been shown to reduce serum 25-OHD, may increase the risk of vitamin D deficiency and consequent osteomalacia in groups of patients most at risk, such as those of Indian subcontinental ethnic origin.