tbuckley/cabot-search huggingface dataset:
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: L. Joe Berry, Dorothy S. Smythe
Journal: The Journal of Experimental Medicine (1964)

Cortisone acetate administered to mice at the same time as either the LD50 or 2 x LD50 of endotoxin significantly protected against lethality. Delaying the injection of cortisone to 1, 2, or 4 hours after that of endotoxin resulted in loss of protection with the possible exception of a 1 hour delay with the LD50 of endotoxin. Associated with this loss of protection was the failure of the hormone to induce liver tryptophan pyrrolase. Normal mice given only cortisone showed an increase in enzyme activity nearly three times that of control values when assays were carried out either 4 or 17 hours after the hormone was given. Endotoxin-poisoned mice showed normal levels of enzyme activity with concurrent injection of cortisone but depressed levels of enzyme when the cortisone injection was delayed for only 1 hour or more. Apparently, therefore, enzyme induction (or maintenance) is related to survival in endotoxin poisoning. In line with this hypothesis was the observation that inhibitors of enzyme (protein) synthesis were found to potentiate the lethal action of endotoxin and to prevent the protective effect of cortisone. The inhibitors employed were actinomycin D, ethionine, 2-thiouracil, and 8-azaguanine. Activity of liver tryptophan pyrrolase was lowered by endotoxin and elevated by cortisone. When the two were given concurrently, normal enzyme activity was maintained. Chloramphenicol, an active inhibitor of protein synthesis in microorganisms but with limited effect in mammals, was without observable influence in these respects. Mice 18 hours postinfection with Salmonella typhimurium, strain SR-11, given at a level that caused first deaths on the 3rd day, had a lower than normal activity of liver tryptophan pyrrolase and responded to cortisone induction with a smaller increase in enzyme level than that found in control mice. Each is characteristic of endotoxin poisoning. Animals 42 hours postinfection were free of these signs of endointoxication, an observation in agreement with earlier experiments where other measures of endotoxin were employed.
Cost-effectiveness of the NICE guidelines for screening for latent tuberculosis infection: the QuantiFERON-TB Gold IGRA alone is more cost-effective for immigrants from high burden countries
Authors: A. B. Hardy, R. Varma, T. Collyns, S. J. Moffitt, C. Mullarkey, J. P. Watson
Journal: Thorax (2009)

NICE (National Institute for Health and Clinical Excellence) guidelines for new entrant tuberculosis (TB) screening recommend chest x ray (CXR) for immigrants from countries with TB incidence >40/10(5), and tuberculin skin test (TST) for people with normal CXR from very high TB prevalence countries. A revised screening policy using first-line QuantiFERON-TB Gold (QFT) in high risk immigrants was piloted in 2007. Initially, TST was offered to immigrants from countries with TB incidence 200-339/10(5), and QFT to those from countries with incidence >340/10(5). When increased resources became available, all immigrants from countries with TB incidence >200/10(5) had QFT. Those with positive QFT were invited for CXR. 1336 immigrant were invited for screening, with a 32% attendance rate. 280 patients had QFT, of which 38% were positive, with <2% being indeterminate. Using the NICE approach, the cost of screening these 280 immigrants would be pound 13,346.75 ( pound 47.67 per immigrant) and would identify 83 cases of latent TB infection (LTBI). Using first-line QFT followed by CXR the cost was pound 9781.82 ( pound 34.94 per immigrant) and identified 105 cases of LTBI. The cost to identify one case of LTBI following NICE guidelines would be pound 160.81 and using the present protocol was pound 93.16. For immigrants from high risk countries QFT blood testing followed by CXR is feasible for TB screening, cheaper than screening using the NICE guideline and identifies more cases of LTBI.
Antiviral Treatment of Chronic Hepatitis B Virus Infection: Infectious Virus Cannot Be Detected in Patient Serum after Permanent Responses to Treatment
Authors: George H. Scullard, Harry B. Greenberg, Joseph L. Smith, Peter B. Gregory, Thomas C. Merigan, William S. Robinson
Journal: Hepatology (2007)

Fourteen chimpanzees were inoculated with pre- and posttreatment sera from seven patients with persistent hepatitis B virus infection and chronic hepatitis who had permanent responses of their infection to treatment with interferon and/or adenine arabinoside. Inoculation of pretreatment serum at a dilution of 10−8 from a patient with a Type I response to treatment [disappearance of Dane particle DNA polymerase (DNAP) activity, HBeAg, and HBsAg from serum] resulted in infection, while undiluted posttreatment serum (all markers negative) failed to infect another animal. Pretreatment sera (DNAP, HBeAg, and HBsAg positive) from all of six patients with a Type II response to treatment (disappearance of DNAP activity and HBeAg but not HBsAg from serum) led to infection in six chimpanzees after inoculation of serum dilutions varying between 10−2 and 10−7. Inoculation of undiluted posttreatment sera (HBsAg positive and DNAP and HBeAg negative) from the same six patients produced no evidence of hepatitis B virus infection in another six animals. These results indicate that a Type I or II response to treatment with these antiviral agents reduces the infectivity in the serum of patients with chronic hepatitis B to below the level of detection by this assay. Such changes should be useful in interrupting spread of the infection between individuals. Our findings suggest that the serum of some patients who, without treatment are HBsAg positive and DNAP and HBeAg negative, may also be free of detectable infectious hepatitis B virus.
P9 The evaluation of an improved method of occupational asthma diagnosis from timepoint analysis of serial PEF records
Authors: C. Burge, V. Moore, A. Robertson, C. Pantin, P. Burge
Journal: Thorax (2010)

<h3>Background</h3> The diagnosis of occupational asthma requires objective confirmation. Analysis of serial measurements of Peak Expiratory Flow (PEF) is usually the most convenient first step in the confirmatory process. We previously described a statistical method of analysis comparing mean 2-h values on work and rest days which required the worker to wake at similar times on rest and work days. This was achieved in only 43% of records. We describe a new method of timepoint analysis without this restriction and overcoming a theoretical problem with the original analysis (the assumption that the variance of the waking reading was the same as the variance at other times of the day). <h3>Methods</h3> Workers were asked to measure PEF approximately 2-h from waking to sleeping for 3–4 weeks. 236 PEF records from workers with independently diagnosed occupational asthma, and 320 from asthmatic controls were available. Readings were grouped by the time since waking, in an attempt to correct for changes in diurnal variation induced by changes in shift and waking time. Daily PEF measurements were meaned into matching 2-h time segments. The pooled SD for rest day measurements (excluding waking readings) was obtained from a one-way ANOVA. Timepoints with mean workday PEF statistically lower (at the Bonferroni adjusted 5% level) than the restdays were counted, after adjusting for the number of contributing measurements at each point. <h3>Results</h3> A minimum of four analysable timepoint comparisons per day was needed. 78% of records were suitable for analysis. Records with one or more timepoints statistically worse on workdays gave a sensitivity of 71% against independently diagnosed occupational asthma and a specificity of 93% in non-occupational asthmatics. <h3>Conclusion</h3> The removal the requirement to wake at similar times on work and rest days increased the utility of timepoint analysis for the diagnosis of occupational asthma from 43–78% without compromising sensitivity or specificity. Statistical validity was also improved.
Monomeric C-reactive protein is prothrombotic and dissociates from circulating pentameric C-reactive protein on adhered activated platelets under flow
Authors: Blanca Molins, Esther Peña, Raquel de la Torre, Lina Badimon
Journal: Cardiovascular Research (2011)

AimsWe previously reported that C-reactive protein bioactivity on thrombogenesis was based on loss of its pentameric symmetry, resulting in formation of monomeric C-reactive protein. Our purpose was to provide mechanistic information on the direct effects of C-reactive protein isoforms on platelet activation and provide a C-reactive protein dissociation mechanism in circulating blood.
Pretreatment Attrition in a Comparative Treatment Outcome Study on Panic Disorder
Authors: Stefan G. Hofmann, David H. Barlow, Laszlo A. Papp, Michael F. Detweiler, Susan E. Ray, M. Katherine Shear, Scott W. Woods, Jack M. Gorman
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: Whereas the fact of attrition during the course of treatment is well documented, little is known about the factors that affect sample selection before the beginning of a study ("pretreatment attrition"). The present study reports on the degree and sources of pretreatment attrition at two sites of a multicenter study on panic disorder that compared treatment outcomes for imipramine and cognitive behavior therapy. METHOD: Data were collected at two clinical research sites, one with a pharmacological treatment orientation (N=420) and one with a psychosocial treatment orientation (N=208). RESULTS: The main source of pretreatment attrition was participant refusal. At both research sites, eligible patients most often refused participation because they were either unwilling to start treatment with imipramine (30.6% and 47.4%, respectively) or discontinue their current medication (22.6% and 35.1%, respectively). CONCLUSIONS: Results from comparative treatment outcome studies are limited not only to people who meet the study criteria but also to those who are willing to begin a medication treatment and discontinue their current medication. (Am J Psychiatry 1998; 155:43–47)
Placement of central feeding catheters.
Authors: E M Kiely
Journal: BMJ (1978)

Unusual chromosomal variant in Klinefelter's syndrome Unusual variants of common conditions can be informative about the origins of abnormalities associated with those conditions.Classical cases of Klinefelter's syndrome have a combination of hypogonadism, azoospermia, small testes, tall stature, gynaecomastia, and diminished intelligence.This syndrome is usually associated with the karyotype 47 XXY.We therefore describe a patient with Klinefelter's syndrome in whom one of the X chromosomes is an isochromosome for the long arm, karyotype 47 XXqiY.The patient was of normal stature, had normal male habitus, and was of average intelligence.The pa- tient's chromosome complement thus provided unique information about the influence on development of the individual arms of the X chromosome. Case reportA 36-year-old service engineer was referred to an endocrine clinic because of infertility after four years of marriage.Azoospermia had been documented on two occasions.The patient had been partially impotent for the previous six months.He had grown a beard while in the Merchant Navy and since leaving the Service had shaved dailv.In the past he was said to have suffered from Reiter's syndrome.His height was 164-5 cm.He was of average intelligence, judged by his occupation and his response to investigative procedures.He had a normal male habitus, with normal male distribution of facial and body hair.There was no gynaecomastia.The testes were firm and small, volume 2 ml each.We also obtained the heights of his family: father 165 cm, mother 152 cm, and sisters 162 cm and 150 cm.
Urotensin II Receptor Knockout Mice on an ApoE Knockout Background Fed a High-Fat Diet Exhibit an Enhanced Hyperlipidemic and Atherosclerotic Phenotype
Authors: Nicolas Bousette, Pedro D'Orleans-Juste, Robert S. Kiss, Zhipeng You, Jacques Genest, Wisam Al-Ramli, Salman T. Qureshi, Anthony Gramolini, David Behm, Eliot H. Ohlstein, Stephen M. Harrison, Stephen A. Douglas, Adel Giaid
Journal: Circulation Research (2009)

Expression of the vasoactive peptide Urotensin II (UII) is elevated in a number of cardiovascular diseases.Here, we sought to determine the effect of UII receptor (UT) gene deletion in a mouse model of atherosclerosis.UT knockout (KO) mice were crossed with ApoE KO mice to generate UT/ApoE double knockout (DKO) mice. Mice were placed on a high-fat Western-type diet for 12 weeks. We evaluated the degree of atherosclerosis and hepatic steatosis by histology. In addition, serum glucose, insulin, and lipids were determined. DKO mice exhibited significantly increased atherosclerosis compared to ApoE KO mice (P<0.05). This was associated with a significant increase in serum insulin and lipids (P<0.001) but a decrease in hepatic steatosis (P<0.001). UT gene deletion led to a significant increase in systolic pressure and pulse pressure. RT-PCR and immunoblot analyses showed significant reductions in hepatic scavenger receptors, nuclear receptors, and acyl-CoA:cholesterol acyltransferase (ACAT1) expression in DKO mice. UII induced a significant increase in intracellular cholesteryl ester formation in primary mouse hepatocytes, which was blocked by the MEK inhibitor, PD98059. Hepatocytes of UTKO mice showed a significant reduction in lipoprotein uptake compared to wild-type mice.We propose that UT gene deletion in an ApoE-deficient background promotes downregulation of ACAT1, which in turn attenuates hepatic lipoprotein receptor-mediated uptake and lipid transporter expression. As the liver is the main organ for uptake of lipoprotein-derived lipids, DKO leads to an increase in hyperlipidemia, with a concomitant decrease in hepatic steatosis, and consequently increased atherosclerotic lesion formation. Furthermore, the hypertension associated with UT gene deletion is likely to contribute to the increased atherosclerotic burden.
Essential role of nucleotide diphosphates in nicorandil-mediated activation of cardiac ATP-sensitive K+ channel. A comparison with pinacidil and lemakalim.
Authors: W K Shen, R T Tung, M M Machulda, Y Kurachi
Journal: Circulation Research (1991)

Vasorelaxant agents such as pinacidil, lemakalim, and nicorandil, known as K+ channel openers, can activate the ATP-sensitive K+ channel (KATP channel) in cardiac myocytes. The aim of this study was to elucidate the molecular mechanisms underlying the K+ channel opener-mediated cardiac KATP channel activation by using the inside-out patch-clamp technique in guinea pig ventricular myocytes. Effects of pinacidil, lemakalim, and nicorandil on the KATP channel were examined both before and after channel "run-down". Since nucleotide diphosphates (NDPs) could activate the channel after complete run-down, effects of the drugs on the NDP-induced channel openings were also examined. We made the following observations: 1) Pinacidil (10-100 microM) and lemakalim (300 microM) activated the KATP channel before run-down and after run-down when NDPs were present. 2) Nicorandil (30 microM-1 mM) activated the KATP channel only in the presence of NDPs regardless of the condition of the channel with respect to run-down. 3) None of these K+ channel openers activated the channel after run-down in the absence of NDPs. These observations suggest that NDP binding is essential for nicorandil-mediated activation of the KATP channel and indicate that the molecular mechanisms underlying nicorandil activation are distinct from those of pinacidil and lemakalim activation of the KATP channel. We discuss the possible interactions between the drugs and the KATP channel based on a functional channel model.
Social Determinants and the Decline of Cardiovascular Diseases: Understanding the Links
Authors: Sam Harper, John Lynch, George Davey Smith
Journal: Annual Review of Public Health (2011)

This article reviews the historical declines in cardiovascular mortality and provides an overview of the contribution of social and economic factors to disease change. We document the magnitude of declines in cardiovascular diseases and the major role of changes in conventional risk factors, and we review the contributions of social determinants to changes in disease rates. We conclude by arguing that understanding patterns and trends of social inequalities in cardiovascular disease and its risk factors requires consideration of the specific intersections of health and social exposures acting across the life course in different settings, in both time and place.
Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice
Authors: Robert P. Cornell, Barbara L. Liljequist, Kenneth F. Bartizal
Journal: Hepatology (1990)

A hypothesis has been proposed by this laboratory that endogenous gut–derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ–free euthymic mice that lack the gram–negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ–free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide–resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [ 3 H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ–free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide–resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ–free euthymic, conventional athymic, and conventional lipopolysaccharide–resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ–free euthymic, conventional athymic, and conventional lipopolysaccharide–resistant mice as compared with conventional euthymic controls. The inability to release cytokines in response to gut–derived endotoxin in the three murine strains studied or the paucity of endogenous lipopolysaccharide in germ–free animals may explain the significant depression or delay of liver regeneration as compared with conventional euthymic control mice.(HEPATOLOGY 1990;11:916–922.).
Cytokine gene polymorphisms in psoriasis
Authors: N.M. Craven, C.W. Jackson, B. Kirby, C. Perrey, V. Pravica, I.V. Hutchinson, C.E.M. Griffiths
Journal: British Journal of Dermatology (2001)

Cytokine production is under genetic control, and certain allelic variants of cytokine genes are associated with higher or lower cytokine production in vitro and in vivo. Psoriasis is associated with an overexpression in the involved skin of T-helper cell type 1 (Th1) cytokines, e.g. interferon (IFN) -gamma and tumour necrosis factor (TNF) alpha and relative underexpression of Th2 cytokines, e.g. interleukin (IL) -4 and IL-10. Objective We investigated the hypothesis that allelic variants of genes for a high production of Th1 cytokines or TNF-alpha, or conversely low production of Th2 cytokines might represent a risk factor for developing psoriasis.Genotyping for IFN-gamma, IL-10, IL-4 and TNF-alpha was undertaken for 84 patients with psoriasis and compared with control data on file.Genotype frequencies showed no differences between patients and controls for IFN-gamma, TNF-alpha or IL-4. For IL-10, patients with late onset psoriasis (over 40 years) were more likely to be heterozygous at position - 1082 (P = 0.02), corresponding to intermediate production of IL-10 in vitro and in vivo.Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.
The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity
Authors: Meghana D. Gadgil, Lawrence J. Appel, Edwina Yeung, Cheryl A.M. Anderson, Frank M. Sacks, Edgar R. Miller
Journal: Diabetes Care (2012)

Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat-rich diet (UNSAT; predominantly monounsaturated).This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2-4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations.At baseline, mean (SD) BMI was 30.2 (6.1) kg/m(2), and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB.A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity.