tbuckley/cabot-search huggingface dataset:
Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus.
Authors: N M O'Meara, J Sturis, E Van Cauter, K S Polonsky
Journal: Journal of Clinical Investigation (1993)

Normal subjects demonstrate the presence of ultradian oscillations (period 80-150 min) in insulin secretion rate (ISR) tightly coupled to glucose oscillations of similar period. These oscillations appear to be a function of the feedback loop linking glucose and insulin. The present study was undertaken to determine whether the control by glucose of the ultradian oscillations in insulin secretion is altered in impaired glucose tolerance IGT and in non-insulin-dependent diabetes mellitus (NIDDM). Patients with NIDDM (n = 7), IGT (n = 4), and matched nondiabetic controls (n = 5) were studied under three separate protocols that involved administration of glucose at either a constant rate of 6 mg/kg per min for 28 h or in one of two oscillatory patterns at the same overall mean rate. The amplitude of the oscillations was 33% above and below the mean infusion rate, and their respective periods were 144 min (slow oscillatory infusion) or 96 min (rapid oscillatory infusion). Insulin, C-peptide, and glucose were sampled at 10-min intervals during the last 24 h of each study. ISRs were calculated by deconvolution of C-peptide levels. Analysis of the data showed that (a) the tight temporal coupling between glucose and ISR in the nondiabetic controls was impaired in the IGT and NIDDM groups as demonstrated by pulse analysis, cross-correlation analysis, and spectral analysis; (b) the absolute amplitude of the ISR pulses progressively declined with the transition from obesity to IGT to NIDDM; and (c) the absolute amplitude of the ISR oscillations failed to increase appropriately with increasing absolute amplitude of glucose oscillations in the IGT and NIDDM subjects compared with the control group. In conclusion, the present study demonstrates that important dynamic properties of the feedback loop linking insulin secretion and glucose are disrupted not only in established NIDDM but also in conditions where glucose tolerance is only minimally impaired. Further studies are needed to determine how early in the course of beta-cell dysfunction this lack of control by glucose of the ultradian oscillations in insulin secretion occurs and to define more precisely if this phenomenon plays a pathogenetic role in the onset of hyperglycemia in genetically susceptible individuals.
Risk Assessment and Prevention of Pressure Ulcers: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Tanveer P. Mir, Melissa Starkey, Thomas D. Denberg
Journal: Annals of Internal Medicine (2015)

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations based on the comparative effectiveness of risk assessment scales and preventive interventions for pressure ulcers.This guideline is based on published literature on this topic that was identified by using MEDLINE (1946 through February 2014), CINAHL (1998 through February 2014), the Cochrane Library, clinical trials registries, and reference lists. Searches were limited to English-language publications. The outcomes evaluated for this guideline include pressure ulcer incidence and severity, resource use, diagnostic accuracy, measures of risk, and harms. This guideline grades the quality of evidence and strength of recommendations by using ACP's clinical practice guidelines grading system. The target audience for this guideline includes all clinicians, and the target patient population is patients at risk for pressure ulcers.ACP recommends that clinicians should perform a risk assessment to identify patients who are at risk of developing pressure ulcers. (Grade: weak recommendation, low-quality evidence).ACP recommends that clinicians should choose advanced static mattresses or advanced static overlays in patients who are at an increased risk of developing pressure ulcers. (Grade: strong recommendation, moderate-quality evidence).ACP recommends against using alternating-air mattresses or alternating-air overlays in patients who are at an increased risk of developing pressure ulcers. (Grade: weak recommendation, moderate-quality evidence).
Teenage confidence and consent
Authors: D S. Irvine
Journal: BMJ (1985)

The British Medical Journal's legal correspondent summarizes the 1984 Court of Appeal decision in Gillick v. West Norfolk and Wisbech Area Health Authority. Mrs. Gillick, the mother of several daughters under 16, had sued the health authority and the Department of Health and Social Security over the issue of giving contraceptive and abortion advice to minors without notifying their parents and seeking parental consent. The Court ruled that, except in emergencies, the rights and duties of parents are paramount in deciding medical treatment for children under the age of majority. These rights and duties are grounded in British statutory law, and may only be overridden by the courts. In the opinion of the BMJ's correspondent, the Gillick decision's implications are not limited to contraceptive advice and teenage girls, but extend to all medical treatment of minors.
What makes the dyspeptic patient feel ill? A cross sectional survey of functional health status, Helicobacter pylori infection, and psychological distress in dyspeptic patients in general practice
Authors: A O Quartero, M W M Post, M E Numans, R A de Melker, N J de Wit
Journal: Gut (1999)

<h3>BACKGROUND</h3> Dyspepsia is prevalent in about 30% of the general population in Europe, but only 25% of people with complaints consult their general practitioner. <h3>AIMS</h3> To study the relation between the severity of dyspeptic complaints and the health status of patients presenting to the general practitioner; and the relation with patient characteristics, <i>Helicobacter pylori</i>infection, and psychological distress. <h3>METHODS</h3> A cross sectional, general practice based survey of 360 unselected primary care dyspeptic patients from 92 general practices in The Netherlands was conducted. Symptom severity was measured using a validated symptom score,<i>H pylori</i> using a whole blood test, and psychological distress using the GHQ-12 test. Functional health status was assessed using the COOP/Wonca charts. <h3>RESULTS</h3> Symptoms lasting more than three months and presence of relevant psychological distress were both associated with higher levels of dyspepsia.<i>H pylori</i> infection, frequency of symptoms, and age had no influence on dyspepsia severity. Severity of dyspepsia and psychological distress, but not <i>H pylori</i>infection or duration of symptoms, affected health status univariately. Dyspepsia correlated with general health, daily activities, and social activities. In logistic modelling, health status was far better predicted by psychological distress than by dyspepsia severity. <h3>CONCLUSION</h3> The relation between dyspeptic symptom severity and health status is limited.<i>H pylori</i> infection relates neither to functional health status, nor to intensity of dyspepsia. Psychological distress is a major determinant of impaired health of dyspeptic patients in general practice and may be the clue to improvement of health status in many dyspeptic patients.
Anxiety in Major Depression: Relationship to Suicide Attempts
Authors: Giovanni P.A. Placidi, Maria A. Oquendo, Kevin M. Malone, Beth Brodsky, Steven P. Ellis, J. John Mann
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: This study was an examination of the relationship of lifetime panic disorder and anxiety symptoms at index hospitalization to a history of a suicide attempt in patients with a major depressive episode. METHOD: A total of 272 inpatients with at least one major depressive episode, with or without a history of a suicide attempt, were entered into the study. They were given structured diagnostic interviews for axis I and axis II disorders. Suicide attempt history, current psychopathology, and traits of aggression and impulsivity were also assessed. RESULTS: The rates of panic disorder did not differ in the suicide attempters and nonattempters. Agitation, psychic anxiety, and hypochondriasis were more severe in the nonattempter group. A multivariate analysis confirmed that this effect was independent of aggression and impulsivity. CONCLUSIONS: Comorbid panic disorder in patients with major depression does not seem to increase the risk for lifetime suicide attempt. The presence of greater anxiety in the nonattempters warrants further investigation.
Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome
Authors: Christoph Engel, Markus Loeffler, Verena Steinke, Nils Rahner, Elke Holinski-Feder, Wolfgang Dietmaier, Hans K. Schackert, Heike Goergens, Magnus von Knebel Doeberitz, Timm O. Goecke, Wolff Schmiegel, Reinhard Buettner, Gabriela Moeslein, Tom G.W. Letteboer, Encarna Gómez García, Frederik J. Hes, Nicoline Hoogerbrugge, Fred H. Menko, Theo A.M. van Os, Rolf H. Sijmons, Anja Wagner, Irma Kluijt, Peter Propping, Hans F.A. Vasen
Journal: Journal of Clinical Oncology (2012)

Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.Data were pooled from the German and Dutch national Lynch syndrome registries. Seven different cancer types were analyzed: stomach, small bowel, urinary bladder, other urothelial, breast, ovarian, and prostate cancer. Age-, sex- and MMR gene-specific cumulative risks (CRs) were calculated using the Kaplan-Meier method. Sex-specific incidence rates were compared with general population incidence rates by calculating standardized incidence ratios (SIRs). Multivariate Cox regression analysis was used to estimate the impact of sex and mutated gene on cancer risk.The cohort comprised 2,118 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308). All cancers were significantly more frequent than in the general population. The highest risks were found for male small bowel cancer (SIR, 251; 95% CI, 177 to 346; CR at 70 years, 12.0; 95% CI, 5.7 to 18.2). Breast cancer showed an SIR of 1.9 (95% CI, 1.4 to 2.4) and a CR of 14.4 (95% CI, 9.5 to 19.3). MSH2 mutation carriers had a considerably higher risk of developing urothelial cancer than MLH1 or MSH6 carriers.The sex- and gene-specific differences of less common cancer risks should be taken into account in cancer surveillance and prevention programs for patients with Lynch syndrome.
Sulfasalazine sensitises human monocytic/macrophage cells for glucocorticoids by upregulation of glucocorticoid receptor and glucocorticoid induced apoptosis
Authors: R. Oerlemans, J. Vink, B. A C Dijkmans, Y. G Assaraf, M. van Miltenburg, J. van der Heijden, I. Ifergan, W. F Lems, R. J Scheper, G. J L Kaspers, J. Cloos, G. Jansen
Journal: Annals of the Rheumatic Diseases (2007)

Glucocorticoids (GCs) are commonly used in the treatment of (chronic) inflammatory diseases and cancer, but inherent or acquired resistance to these drugs limits their optimal efficacy. The availability of drugs that could modulate GC resistance is therefore of potential clinical interest.To explore the molecular basis of GC sensitisation of GC resistant monocytic/macrophage cells after chronic exposure to sulfasalazine.Human monocytic/macrophage THP1 and U937 cells represent a cell line model system characterised by inherent resistance to the GCs dexamethasone and prednisolone. Both cell lines were chronically exposed in vitro to 0.3-0.6 mM sulfasalazine (SSZ) for approximately 3 months, after which they were characterised for GC sensitivity, expression levels of GC receptor and components of the nuclear factor kappa B (NFkappaB) signalling pathway, and their ability to undergo GC induced apoptosis.Chronic exposure to SSZ markedly sensitised both U937 and THP1 cells to dexamethasone (781-fold and 1389-fold, respectively) and prednisolone (562-fold and 1220-fold, respectively). Restoration of GC sensitivity in cells exposed to SSZ was provoked via GC induced apoptosis, coinciding with inhibition of NFkappaB activation. Moreover, western blot analysis revealed a markedly increased expression of glucocorticoid receptor alpha (GRalpha) in cells exposed to SSZ. Since GRalpha mRNA levels were only marginally increased, these results suggest that an altered post-transcriptional mechanism was operable which conferred a stable GRalpha protein on SSZ exposed cells.These results suggest that chronic targeting of the NFkappaB signalling pathway by SSZ may be exploited as a novel strategy to stabilise GRalpha expression and thereby sensitise primary resistant cells to GCs.
Cancer Stem Cells and Self-renewal
Authors: Catherine Adell O'Brien, Antonija Kreso, Catriona H.M. Jamieson
Journal: Clinical Cancer Research (2010)

The cancer stem cell (CSC) or cancer-initiating cancer (C-IC) model has garnered considerable attention over the past several years since Dick and colleagues published a seminal report showing that a hierarchy exists among leukemic cells. In more recent years, a similar hierarchical organization, at the apex of which exists the CSC, has been identified in a variety of solid tumors. Human CSCs are defined by their ability to: (i) generate a xenograft that histologically resembles the parent tumor from which it was derived, (ii) be serially transplanted in a xenograft assay thereby showing the ability to self-renew (regenerate), and (iii) generate daughter cells that possess some proliferative capacity but are unable to initiate or maintain the cancer because they lack intrinsic regenerative potential. The emerging complexity of the CSC phenotype and function is at times daunting and has led to some confusion in the field. However, at its core, the CSC model is about identifying and characterizing the cancer cells that possess the greatest capacity to regenerate all aspects of the tumor. It is becoming clear that cancer cells evolve as a result of their ability to hijack normal self-renewal pathways, a process that can drive malignant transformation. Studying self-renewal in the context of cancer and CSC maintenance will lead to a better understanding of the mechanisms driving tumor growth. This review will address some of the main controversies in the CSC field and emphasize the importance of focusing first and foremost on the defining feature of CSCs: dysregulated self-renewal capacity.
CHANGES IN BLOOD COAGULATION DURING THE CLEARING OF LIPID EMULSIONS BY LIPOPROTEIN LIPASE
Authors: Robert L. Hirsch, Aaron Kellner, Rosemary Ireland
Journal: The Journal of Experimental Medicine (1960)

The clearing of lipid emulsions by postheparin plasma from rabbits or human beings was accompanied regularly by a sharp reduction in the recalcification time of the plasma. No change in blood coagulation took place when the activity of lipoprotein lipase, the clearing enzyme, was inhibited by means of heat or the action of a surface-active agent. In control studies, the recalcification time of postheparin plasma was not altered by the addition of glycerol, free fatty acids, or the products of hydrolysis of a lipid emulsion. Taken together, the findings indicated that a heat-labile factor was released during the course of clearing which was capable of inactivating reversibly the anti-coagulant properties of heparin.
Myocardial First-Pass Perfusion Magnetic Resonance Imaging
Authors: S.D. Wolff, J. Schwitter, R. Coulden, M.G. Friedrich, D.A. Bluemke, R.W. Biederman, E.T. Martin, A.J. Lansky, F. Kashanian, T.K.F. Foo, P.E. Licato, C.R. Comeau
Journal: Circulation (2004)

MRI can identify patients with obstructive coronary artery disease by imaging the left ventricular myocardium during a first-pass contrast bolus in the presence and absence of pharmacologically induced myocardial hyperemia. The purpose of this multicenter dose-ranging study was to determine the minimally efficacious dose of gadopentetate dimeglumine injection (Magnevist Injection; Berlex Laboratories) for detecting obstructive coronary artery disease.A total of 99 patients scheduled for coronary artery catheterization as part of their clinical evaluation were enrolled in this study. Patients were randomized to 1 of 3 doses of gadopentate dimeglumine: 0.05, 0.10, or 0.15 mmol/kg. First-pass perfusion imaging was performed during hyperemia (induced by a 4-minute infusion of adenosine at a rate of 140 microg x kg(-1) x min(-1)) and then again in the absence of adenosine with otherwise identical imaging parameters and the same contrast dose. Perfusion defects were evaluated subjectively by 4 blinded reviewers. Receiver-operating curve analysis showed that the areas under the receiver-operating curve were 0.90, 0.72, and 0.83 for the low-, medium-, and high-contrast doses, respectively, compared with quantitative coronary angiography (diameter stenosis > or =70%). For the low-dose group, mean sensitivity was 93+/-0%, mean specificity was 75+/-7%, and mean accuracy was 85+/-3%.First-pass perfusion MRI is a safe and accurate test for identifying patients with obstructive coronary artery disease. A low dose of 0.05 mmol/kg gadopentetate dimeglumine is at least as efficacious as higher doses.
Radioimmunotherapy of Experimental Human Metastatic Melanoma with Melanin-Binding Antibodies and in Combination with Dacarbazine
Authors: Ekaterina Revskaya, Artemio M. Jongco, Rani S. Sellers, Robertha C. Howell, Wade Koba, Allan J. Guimaraes, Joshua D. Nosanchuk, Arturo Casadevall, Ekaterina Dadachova
Journal: Clinical Cancer Research (2009)

Melanin has emerged as an attractive target for radioimmunotherapy (RIT) of melanoma, and a radiolabeled monoclonal antibody (mAb) 6D2 to melanin is currently in clinical evaluation. We investigated two approaches to improve the targeting of radiation to tumors using melanin-binding mAbs: (a) the use of an additional mAb to melanin could provide information on whether using antibodies to melanin can serve as a general approach to development of therapeutics for melanoma, and (b) as melanin targeting involves the antibody binding to extracellular melanin released from necrotic melanoma cells, we hypothesized that the administration of a chemotherapeutic agent followed by RIT would facilitate the delivery of radiation to the tumors due to the increased presence of free melanin.We evaluated the therapeutic efficacy of two melanin-binding IgM mAbs labeled with (188)Re (6D2 and 11B11). We compared the efficacy of RIT with (188)Re-6D2 to chemotherapy with dacarbazine (DTIC) and to combined chemotherapy and RIT in human metastatic melanoma-bearing nude mice.Therapeutic efficacy of (188)Re-labeled 6D2 and 11B11 was comparable despite differences in their affinity and binding site numbers. Comparison of chemotherapy with DTIC and RIT revealed that RIT was more effective in slowing tumor growth in mice. Administration of DTIC followed by RIT was more effective than either modality alone.These results provide encouragement for the development of RIT for melanoma with melanin-binding mAbs and suggest that combining chemotherapy and RIT may be a promising approach for the treatment of metastatic melanoma.
Rectus femoris muscle injuries in football: a clinically relevant review of mechanisms of injury, risk factors and preventive strategies
Authors: Jurdan Mendiguchia, Eduard Alentorn-Geli, Fernando Idoate, Gregory D Myer
Journal: British Journal of Sports Medicine (2012)

Quadriceps muscle strains frequently occur in sports that require repetitive kicking and sprinting, and are common in football in its different forms around the world. This paper is a review of aetiology, mechanism of injury and the natural history of rectus femoris injury. Investigating the mechanism and risk factors for rectus femoris muscle injury aims to allow the development of a framework for future initiatives to prevent quadriceps injury in football players.
Hypercholesterolemia in Rats Induces Podocyte Stress and Decreases Renal Cortical Nitric Oxide Synthesis via an Angiotensin II Type 1 Receptor–Sensitive Mechanism
Authors: Diana M. Attia, Olivier Feron, Roel Goldschmeding, Louk H. Radermakers, Nosratola D. Vaziri, Peter Boer, Jean-Luc Balligand, Hein A. Koomans, Jaap A. Joles
Journal: Journal of the American Society of Nephrology (2004)

Podocyte stress precedes proteinuria in hypercholesterolemic rats. Molsidomine, a nitric oxide (NO) donor, prevented podocyte stress and proteinuria in long-term hypercholesterolemia, suggesting that podocyte stress was due to NO deficiency. Podocytes express the angiotensin II type 1 receptor, which influences their function. Because NO counteracts angiotensin II, it was hypothesized that in a setting of impaired renal NO availability, angiotensin II receptor inhibition could prevent podocyte stress. For determining the effect of NO deficiency on podocyte stress, one group of female rats were fed 2% cholesterol and another group the arginine analogue N-omega-nitro-L-arginine (L-NNA; 40 mg/kg food) for 2 wk. Another group of rats that were fed 2% cholesterol also received the NO donor molsidomine (120 mg/L water) for 2 wk before and during cholesterol feeding. For determining the influence of angiotensin II in the setting of decreased renal NO availability, rats that were treated with cholesterol or L-NNA received the angiotensin II type 1 antagonist losartan (200 mg/L water) for 2 wk before and during cholesterol or L-NNA administration. Desmin staining and electron microscopy were used to monitor podocyte activation. Glomerular caveolin was quantified by immunohistochemistry. Renal cortical NO synthesis, NO synthase isoforms, and caveolin-1 protein mass were also measured. Both short-term cholesterol and L-NNA induced podocyte stress as evidenced by enhanced desmin staining and electron-dense fused foot processes. Podocyte stress was prevented by molsidomine in short-term hypercholesterolemia. Furthermore, losartan prevented podocyte stress in rats that were treated with cholesterol or with L-NNA. Finally, hypercholesterolemia decreased renal cortical NO synthase activity and increased caveolin-1 protein mass and glomerular caveolin staining, and these changes were also prevented by losartan. It is suggested that podocyte stress in these models of early injury results from angiotensin II, unopposed by the action of endogenous NO. This underscores the strategic role of angiotensin II blockers in early kidney disease.