tbuckley/cabot-search huggingface dataset:
Genetic Deficiency of Inducible Nitric Oxide Synthase Reduces Atherosclerosis and Lowers Plasma Lipid Peroxides in Apolipoprotein E–Knockout Mice
Authors: Peter J. Kuhlencordt, Jiqiu Chen, Fred Han, Joshua Astern, Paul L. Huang
Journal: Circulation (2001)

Inducible nitric oxide synthase (iNOS) is expressed by leukocytes and smooth muscle cells in atherosclerotic lesions. To test whether NO produced by iNOS deficiency affects atherosclerosis, we studied apoE/iNOS-double knockout (dKO) and apoE-knockout (KO) control animals fed a "Western-type" diet.After 16 weeks of Western-type diet, the aortic lesion area in apoE/iNOS-dKO males and females was significantly reduced, by 22% and 21%, respectively, compared with apoE-KO males and females. This effect was more pronounced after 24 weeks of Western-type diet, after which lesion formation in male and female dKO mice was reduced by 38% and 40%, respectively. Plasma levels of lipoperoxides in apoE/iNOS-dKO mice (2.0+/-0.23 micromol/L) were significantly lower than in apoE-KO control animals (3.2+/-0.44 micromol/L; P=0.02). To test whether substrate deficiency plays a role in the proatherogenic actions of iNOS, we administered L-arginine to apoE-KO animals for 16 and 24 weeks. L-Arginine treatment did not affect lesion formation in apoE-KO animals fed a Western-type diet.Genetic deficiency of iNOS decreases diet-induced atherosclerosis and lowers plasma levels of lipoperoxides, a marker for oxidative stress, in apoE-KO animals. Reduction in iNOS-mediated oxidative stress could partly explain protection from lesion formation in dKO animals. L-Arginine supplementation did not change lesion area in apoE-KO mice, indicating that substrate deficiency is not a likely cause for iNOS-mediated injury in this model of atherosclerosis.
Mechanism of action of factor D of the alternative complement pathway.
Authors: P H Lesavre, H J Müller-Eberhard
Journal: The Journal of Experimental Medicine (1978)

Factor D (C3 proactivator convertase) of human serum has been shown to be absolutely necessary for alternative pathway function, for activation of the C3/C5 convertase of that pathway and not to be a subunit of this enzyme. Factor D was found to be present in human plasma in active form only, at a concentration of 2 microgram/ml, and not to be controlled by plasma protease inhibitors or by spontaneous decay. Unlike trypsin, factor D cleaves and activates factor B only when it is in Mg++-dependent complex with C3b, has no esterolytic activity, and is unable to cleave the B chain of insulin. The alleged functional and antigenic relationship of factor D to alpha-thrombin could not be verified. The results of this study led to the description of the mechanism of action of factor D in terms of the cryptic site hypothesis.
Drug information services.
Authors: K Lawday
Journal: BMJ (1978)

had a stillbirth rate of 10 1 per 1000.A decline in the hospital stillbirth rate for this minimalrisk group from 117 to 101 per 1000 is rela- tively less than that achieved outside, from 4 2 to 34-hardly an impressive vindication of the current policy of moving towards hospitalisation for all.Thus the more recent evidence on stillbirths fails to support the conclusion drawn by Mrs Fedrick and Professor Butler from 1958 data.The need for further research is as great as ever.
Increased numbers of IgG-containing cells in rectal lamina propria of patients with ankylosing spondylitis.
Authors: M A Stodell, R C Butler, V A Zemelman, K Henry, D A Brewerton
Journal: Annals of the Rheumatic Diseases (1984)

Using an indirect immunoperoxidase technique we found the numbers of IgG-containing cells in the rectal lamina propria to be increased in patients with ankylosing spondylitis compared with controls, but not in patients with acute anterior uveitis or rheumatoid arthritis, or in the first-degree relatives of patients with ankylosing spondylitis. No differences between diagnostic groups were detected in the numbers of cells containing IgA, IgM, IgD, or IgE. The total numbers of plasma cells in the rectal lamina propria were not significantly increased. Similar increases of IgG-containing cells were not found in the duodenal lamina propria of patients with ankylosing spondylitis.
Lyme Carditis Evaluation by Ga-67 and MRI
Authors: P VELUVOLU, A A BALIAN, R GOLDSMITH, T E GALLANT, L BARTHEL, H J VIDAILLET, J W MELSKI
Journal: Clinical Nuclear Medicine (1992)

The authors describe abnormal Ga-67 and magnetic resonance imaging in a 12-year-old boy with Lyme carditis.
Bacteriuria and Urinary-Tract Infections in Hospitalized Patients
Authors: Alan L. Kaitz, Elizabeth J. Williams
Journal: New England Journal of Medicine (1960)

SIGNIFICANT bacteriuria, defined as more than 100,000 pathogenic bacteria per milliliter of urine, has been a surprisingly frequent finding in surveys of ward and clinic patients of a city hospital in the absence of symptomatic infection of the urinary tract.1 , 2 An association of asymptomatic bacteriuria with pyelonephritis has been considered.2 The correlation of bacteriuria in bladder urine with unsuspected, active pyelonephritis at autopsy3 and the finding of asymptomatic bacteriuria before acute pyelonephritis of pregnancy4 suggest asymptomatic bacteriuria and pyelonephritis are related.Quantitative urine cultures are now performed in many hospital laboratories to assist the physician in the detection of bacteriuria. . . .
A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.
Authors: M. E. Price, S. P. Fisher-Hoch, R. B. Craven, J. B. McCormick
Journal: BMJ (1988)

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother9s chance of survival.
Problems in pregnancy
Authors: T. Nicholson, D. Zehnder, A. Short, A. Ferraro
Journal: BMJ (2011)

A 19 year old woman attended antenatal clinic at 16 weeks’ gestation (gravida 2, para 0+1). Routine urine dipstick testing identified blood (+++) and protein (++). Similar findings had been recorded three weeks earlier. She described tiredness and occasional painless minor haemoptysis. She had a history of chlamydial infection and a spontaneous miscarriage two years earlier. She occasionally smoked marijuana but did not drink alcohol. Her body mass index was 32.2. She had no family history of note. Examination was unremarkable except for bilateral renal angle tenderness. Sequential urine specimens were culture negative.



### 1 What is the differential diagnosis?

#### Short answer

Once infection has been excluded, haematoproteinuria identified by dipstick analysis is indicative of glomerulonephritis; coexistent haemoptysis makes multisystem autoimmune disease a strong possibility that needs urgent investigation.

#### Long answer

Asymptomatic bacteriuria is present in 2-10% of women. At least 1% of women of childbearing age have chronic kidney disease, depending on the definition used.1 Some asymptomatic disease will be identified through pregnancy related screening. Glomerular disease is a possibility when haematoproteinuria is present and urine cultures are sterile, but substantial proteinuria should raise suspicions of underlying glomerular disease even in the presence of urine infection. In this patient, the presence of haemoptysis raises particular clinical suspicion and concern. The differential diagnosis for coexisting haemoptysis and haematoproteinuria is primarily anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis and anti-glomerular basement membrane disease (anti-glomerular basement membrane disease; also known as Goodpasture’s syndrome when lung and kidney are both involved). Although rare diseases, with a combined incidence of around 20 per million population per year, both can cause rapidly …
Who's (still) afraid of talc?
Authors: M. Noppen
Journal: European Respiratory Journal (2007)

Any pulmonologist who has ever visited a pleural disease or pneumothorax session at a major international conference or symposium, has heard the famous exclamation of my good friend Prof. Richard Light, one of the “popes” of pleural disease. Prof. Light is an exponent of the (mainly North American) school of pulmonologists who do not like talc as a pleurodesis agent. These pulmonologists do not like it to be used in malignant effusion, and they certainly do not like it to be used in young people with benign diseases, such as spontaneous pneumothorax!

The main reason for this is fear. Fear that talc is not safe. Fear that talc induces acute respiratory distress syndrome (ARDS). Fear that talc induces death. Fear that talc excludes eventual pulmonary surgery or transplantation. Fear that talc induces impaired lung function. Fear that talc causes mesothelioma or cancer. Fear that talc makes surgeons angry (now that is one I can understand!). Fear, however, is a bad advisor; knowledge is a much better one. Let us see what is known about talc safety.

Although some authors have observed respiratory failure, ARDS and even death after talc pleurodesis 1, 2, others have not, even in large series 3–5. In any case, these serious complications …
P335 DYSFUNCTIONAL GUT MICROBIOTA IN ILEO-COLONIC MUCOSA AND STOOL IN ALCOHOLIC CIRRHOSIS IS ASSOCIATED WITH ENDOTOXEMIA: IMPLICATIONS FOR BACTERIAL TRANSLOCATION
Authors: J.S. Bajaj, D. Heuman, P. Hylemon, M. Sikaroodi, J. Ridlon, W.M. Pandak, M. Schubert, M. Fuchs, M. White, K. Daita, P. Gillevet
Journal: Journal of Hepatology (2014)
THE INCIDENCE OF HEMORRHAGE IN PERFORATED GASTRIC AND DUODENAL ULCERS
Authors: MOSES BEHREND
Journal: JAMA (1930)

<h3>Protocol.</h3> —Perforated ulcers rarely bleed. Bleeding ulcers rarely perforate. Ulcers of the stomach and duodenum manifest themselves in various ways. They are selective in their location, their time of perforation and their incidence of hemorrhage. The varying degrees of morbidity caused by them depend to a large degree on their location. In searching for ulcers, physicians know from previous experience that the most likely site for their formation is the stomach and duodenum. Particularly are they prevalent along the lesser curvature of the stomach, the pylorus and the first portion of the duodenum. Ulcers that perforate are usually found in these places, but those that produce hemorrhage have not always the definite locations referred to. The reasons for these variations in the genesis of ulcers have never been definitely determined. Again, the fact that some ulcers may exist for years and never perforate or produce hemorrhage, but simply result in
Efficacy of Simple Short-Term <i>in Vitro</i> Assays for Predicting the Potential of Metal Oxide Nanoparticles to Cause Pulmonary Inflammation
Authors: Senlin Lu, Rodger Duffin, Craig Poland, Paul Daly, Fiona Murphy, Ellen Drost, William MacNee, Vicki Stone, Ken Donaldson
Journal: Environmental Health Perspectives (2008)

There has been concern regarding risks from inhalation exposure to nanoparticles (NPs). The large number of particles requiring testing means that alternative approaches to animal testing are needed.We set out to determine whether short-term in vitro assays that assess intrinsic oxidative stress potential and membrane-damaging potency of a panel of metal oxide NPs can be used to predict their inflammogenic potency.For a panel of metal oxide NPs, we investigated intrinsic free radical generation, oxidative activity in an extracellular environment, cytotoxicity to lung epithelial cells, hemolysis, and inflammation potency in rat lungs. All exposures were carried out at equal surface area doses.Only nickel oxide (NiO) and alumina 2 caused significant lung inflammation when instilled into rat lungs at equal surface area, suggesting that these two had extra surface reactivity. We observed significant free radical generation with 4 of 13 metal oxides, only one of which was inflammogenic. Only 3 of 13 were significantly hemolytic, two of which were inflammogenic.Potency in generating free radicals in vitro did not predict inflammation, whereas alumina 2 had no free radical activity but was inflammogenic. The hemolysis assay was correct in predicting the proinflammatory potential of 12 of 13 of the particles examined. Using a battery of simple in vitro tests, it is possible to predict the inflammogenicity of metal oxide NPs, although some false-positive results are likely. More research using a larger panel is needed to confirm the efficacy and generality of this approach for metal oxide NPs.
Dynamics of atrial peptide secretion in the coronary circulation of the conscious dog.
Authors: T H Hintze, J Wang, M Patel, M Schustek, M Ochoa, R Dean, F Chiruzzo, G Zeballos
Journal: Circulation Research (1990)

The secretion of atrial natriuretic peptide by the heart is not simply the arterial-coronary sinus concentration difference times coronary blood flow, because only a small fraction of total coronary blood flow passes through the atria. We measured coronary sinus and arterial plasma atrial natriuretic factor (ANF) concentrations and blood flow to each part of the heart using the radioactive microsphere technique. Before acute volume expansion, the arterial-coronary sinus ANF difference was 305 +/- 23 pg/ml and rose to 1,009 +/- 220 pg/ml during volume expansion, whereas total coronary blood flow rose from 167 to 465 ml/min. Atrial blood flow rose from 2.9% to 4.6% of total coronary blood flow during volume expansion. ANF secretion rate increased from 51 to 469 ng/min. When divided by atrial weight, ANF secretion rate increased from 4.0 +/- 0.3 to 56 +/- 12 ng/min/g atrial tissue-in other words, from 0.3% to 3.7% of tissue ANF content each minute. Dividing by atrial blood flow indicated that the concentration of ANF leaving atrial tissue was 10,000 to 29,651 pg/ml, and the additional secretion of ANF was determined by the increase in coronary blood flow. Therefore, at least two mechanisms are responsible for altering coronary sinus ANF and circulating ANF: the release rate from atrial myocytes and the washout via changes in atrial blood flow.
Meta-analysis: Noninvasive Coronary Angiography Using Computed Tomography Versus Magnetic Resonance Imaging
Authors: Georg M. Schuetz
Journal: Annals of Internal Medicine (2010)

Background: Two imaging techniques, multislice computed tomography (CT) and magnetic resonance imaging (MRI), have evolved for noninvasive coronary angiography. Purpose: To compare CT and MRI for ruling out clinically significant coronary artery disease (CAD) in adults with suspected or known CAD. Data Sources: MEDLINE, EMBASE, and ISI Web of Science searches from inception through 2 June 2009 and bibliographies of reviews. Study Selection: Prospective English- or German-language studies that compared CT or MRI with conventional coronary angiography in all patients and included sufficient data for compilation of 2 × 2 tables. Data Extraction: 2 investigators independently extracted patient and study characteristics; differences were resolved by consensus. Data Synthesis: 89 and 20 studies (comprising 7516 and 989 patients) assessed CT and MRI, respectively. Bivariate analysis of data yielded a mean sensitivity and specificity of 97.2% (95% CI, 96.2% to 98.0%) and 87.4% (CI, 84.5% to 89.8%) for CT and 87.1% (CI, 83.0% to 90.3%) and 70.3% (CI, 58.8% to 79.7%) for MRI. In studies that included only patients with suspected CAD, sensitivity and specificity of CT were 97.6% (CI, 96.1% to 98.5%) and 89.2% (CI, 86.0% to 91.8%). Covariate analysis yielded a significantly higher sensitivity for CT scanners with more than 16 rows (98.1% [CI, 97.0% to 99.0%]; P < 0.050) than for older-generation scanners (95.6% [CI, 94.0% to 97.0%]). Heart rates less than 60 beats/min during CT yielded significantly better values for sensitivity than did higher heart rates (P < 0.001). Limitations: Few studies investigated coronary angiography with MRI. Only 5 studies were direct head-to-head comparisons of CT and MRI. Covariate analyses explained only part of the observed heterogeneity. Conclusion: For ruling out CAD, CT is more accurate than MRI. Scanners with more than 16 rows improve sensitivity, as do slowed heart rates. Primary Funding Source: None.
Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy
Authors: Elisa Giannetta, Andrea M. Isidori, Nicola Galea, Iacopo Carbone, Elisabetta Mandosi, Carmine D. Vizza, Fabio Naro, Susanna Morano, Francesco Fedele, Andrea Lenzi
Journal: Circulation (2012)

Background— cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy. Methods and Results— Fifty-nine diabetic men (60.3±7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [σ], −12.6±3.1; increased left ventricular [LV] torsion [θ], 18.4±4.6°; and increased ratio of LV mass to volume, 2.1±0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro–B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (Δθ: sildenafil, −3.89±3.11° versus placebo, 2.13±2.35°; P &lt;0.001) and strain (Δσ: sildenafil, −3.30±1.86 versus placebo, 1.22±1.84; P &lt;0.001). Sildenafil-induced improvement of LV contraction was accompanied by consistent changes in chamber geometry and performance, with a 6.5±11 improvement in mass-to-volume ratio over placebo ( P =0.021). Monocyte chemotactic protein-1 and transforming growth factor-β were the only markers affected by active treatment (Δmonocyte chemotactic protein-1: −75.30±159.28 pg/mL, P =0.032; Δtransforming growth factor-β: 5.26±9.67 ng/mL, P =0.009). No changes were found in endothelial function, afterload, or metabolism. Conclusions— The early features of diabetic cardiomyopathy are LV concentric hypertrophy associated with altered myocardial contraction dynamics. Chronic phosphodiesterase type 5 inhibition, at this stage, has an antiremodeling effect, resulting in improved cardiac kinetics and circulating markers. This effect is independent of any other vasodilatory or endothelial effects and is apparently exerted through a direct intramyocardial action. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00692237.
Until safety and benefit are proved, better not to rush
Authors: A. D. Weeks
Journal: BMJ (2011)

<h3>Abstract</h3> Plants are more susceptible to high temperature stress during reproductive development, which can cause drastic yield loss of fruit and seed crops. Unfortunately, the underlying mechanism remains largely unknown. Here we suggest that m<sup>6</sup>A RNA methylation level increases in the reproductive tissues of <i>Arabidopsis</i> and negatively regulates gene expression variability. It has been suggested that stochasticity of gene expression can be advantageous to fitness of living organisms under environmental challenges. Indeed, reduced gene expression variability in flowers was associated with compromised transcriptional activation of heat-responsive genes. Importantly, disruption of an RNA demethylase <i>AtALKBH10B</i> led to lower gene expression variability, hypo-responsiveness of heat-activated genes, and strong reduction of plant fertility. Overall, our work proposes a novel mechanism that m<sup>6</sup>A RNA modification mediates the bet-hedging strategy of plants challenged by heat stress.
Wheezing, Allergy, and Parasite Infection in Children in Urban and Rural Ethiopia
Authors: Damtew Dagoye, Zegaye Bekele, Kifle Woldemichael, Hailu Nida, Meselech Yimam, Andy Hall, Andrea J. Venn, John R. Britton, Richard Hubbard, Sarah A. Lewis
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Epidemiological studies in developing countries suggest that intestinal parasite infection may reduce the risk of asthma. Because this evidence is all derived from adults and older children, we have investigated the relation between parasite infection, wheezing, and allergen skin sensitization in nested case-control studies drawn from a survey of 7,155 children aged 1 to 4 years living in urban and rural areas of Jimma, Ethiopia. Infection with parasites was common, predominantly with Trichuris (54%), Ascaris (38%), and hookworm (10%). Wheezing in the past year was significantly more prevalent in urban (4.4%) than rural children (2.0%), and was less prevalent in those infected with Ascaris (age, sex, and urban/rural adjusted odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9), particularly in relation to high-intensity infection. Similar, although nonsignificant, associations were found for hookworm (adjusted odds ratio, 0.6; 95% confidence interval, 0.2 to 1.8), but there was no suggestion of any relation to Trichuris infection. Dermatophagoides pteronyssinus and cockroach (Blattella germanica) skin sensitization was more prevalent in rural than urban children, and was unrelated to wheeze. We conclude that Ascaris and possibly hookworm infection protects against wheeze in young Ethiopian children, and that this effect is not mediated by inhibition of allergen sensitization.
The Soda Crush
Authors: Harlan A. Payne
Journal: JAMA (1989)

7b the Editor.—  I read the article by Dr Cosio 1 concerning the soda pop vending machine injuries with great interest. The article states that a force of 81.6 kg (179.5 lb) needs to be exerted to tip a low-weight soda pop machine past the point of equilibrium so that it could conceivably fall on an individual.  Since such a force is not a trivial amount and therefore must be exerted with foresight, it would seem that soda pop machines as described in the article are not inherently unstable or dangerous. Rather than recommend redesign of the machines, it would seem more cost-effective merely to continue to remind people of the obvious.  Perhaps a warning label could be attached to the soda pop machines: Push this machine hard enough and it will tip over and squash you like a bug!