tbuckley/cabot-search huggingface dataset:
FRI0358 Contribution of the Adhesion Receptor DNAX Accessory Molecule-1 (DNAM-1) in the Development of Experimental Arthritis
Authors: M. Elhai, G. Chiocchia, F. Lager, Y. Allanore, J. Avouac
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is a frequent disease leading to joint destruction, deformity, and loss of function. Its pathogenesis results from the combination of genetic susceptibility genes and environmental factors. Recently, a non-synonymous single nucleotide polymorphism Gly307Ser (rs763361) in the <i>CD226</i> gene, encoding the DNAX accessory molecule 1 (DNAM-1), has been associated with different autoimmune diseases including RA. Moreover, the functional role of DNAM-1 has been demonstrated <i>in vivo</i> in animal models of multiple sclerosis and dermal fibrosis. <h3>Objectives</h3> We aimed to determine the impact of DNAM-1 in the development of arthritis <i>in vivo</i> in a widely used mouse model: the collagen-induced arthritis (CIA) model, using two complementary approaches: a targeted molecular approach with neutralizing anti-DNAM-1 monoclonal antibody (mAb) and a gene inactivation strategy using mice lacking DNAM-1 (dnam1-/-). <h3>Methods</h3> CIA was induced in DBA/1 mice, treated in parallel with a DNAM-1 neutralizing monoclonal antibody, a control IgG and PBS, respectively. CIA was also induced in dnam1-/-mice and control dnam-1+/+ mice on a C57/BL6 background. Mice were monitored for clinical and ultrasound signs of arthritis. Histological analysis was performed to evaluate inflammatory infiltrates and erosions. <h3>Results</h3> Clinical evidence of arthritis was observed in 5/7 (71%) mice treated with anti-DNAM-1 mAb, 6/7 (86%) mice treated with control IgG, and 7/7 (100%) mice injected with PBS (p=0.1). There was also a non-significant trend for lower clinical, ultrasound and histological scores in mice receiving anti-DNAM-1 mAb. Although not significant, our results suggested a trend toward a less arthritic phenotype in mice treated with anti-DNAM-1 mAb. However, molecular targeted strategy is characterized by an incomplete blockade of the pathway targeted, unlike the gene inactivation strategy. Therefore to better assess the effect of DNAM-1 inhibition for the prevention of CIA, we performed a gene inactivation strategy using dnam1-/- mice. In all, 7/7 (100%) dnam1+/+ versus 4/5 (80%) dnam1-/- mice developed clinical arthritis (p=0.2). Clinical, ultrasound and histological scores were similar in dnam1+/+ and dnam1-/- mice. Collagen antibodies levels were similar in all mice, confirming immunization with collagen. <h3>Conclusions</h3> These complementary approaches failed to demonstrate the implication of DNAM-1 in the development of CIA. These findings do not confirm the results of the genetic studies on the role of DNAM-1 in RA. Further studies are now needed to confirm or not the contribution of DNAM-1 in other autoimmune conditions. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4931
Return to Albania
Authors: A. Cameron
Journal: BMJ (1995)

“Acountry within sight of Italy about which less is known than the interior of America.” Edward Gibbon's comment of 200 years ago still applies to Albania, Europe's poorest nation. The country's economic and intellectual isolation was imposed by Enver Hoxha, its xenophobic, paranoid, Marxist dictator. After his death in 1985 minor liberalisation was attempted, but pressure for change became unstoppable. Many fled the country—especially to Italy. Finally, in 1992 the Democracy party, led by a cardiologist, established a fragile government.

I had visited Albania as a tourist in 1990 when it was still controlled by the Party of Labour, but during the trip met some doctors and wrote about the experience in a personal view (BMJ 1991;302:1088). I never expected to return, but had an opportunity to revisit in 1994. Changes in the four years were staggering. Gone were the statues of Hoxha and the party slogans and the red flags. Roadside stalls were everywhere, satellite dishes sprouted from every building, and huge numbers of ancient cars roared along the ill kept roads—private cars had been banned by the regime as bourgeois.

People looked poorer; clearly the move to a market economy had benefited a few, but the majority were worse off. Factories were devastated and land untilled. With the loss of state authority law and order had broken down and crime was rampant. Unemployment was at least 50% and there was an air of menace in the crowded streets. There may have been some advantages in the previous regime; at least everybody was …
Pulmonary artery compliance: its role in right ventricular-arterial coupling
Authors: P. R Fourie, A. R Coetzee, C. T Bolliger
Journal: Cardiovascular Research (1992)

The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension.Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary arterial elastance (Ea), applying the Windkessel parameters of the pulmonary arterial input impedance. Coupling between the ventricle and its load could be determined in terms of Ees and Ea. Acute pulmonary hypertension was induced by injecting glass microspheres into the pulmonary vascular bed until a mean pulmonary arterial pressure of more than 35 mm Hg had been reached. Experimental subjects were Landras/Large white pigs (n = 11), studied under general anaesthesia. Ees was obtained by normalising the right ventricle pressure-diameter equivalent of Ees to stroke volume. The lumped element parameters of the Windkessel analogue were calculated from the pulmonary artery pressure and blood flow. Stroke work was calculated from the pressure-volume loop and oxygen consumption derived from the pressure-volume area. Efficiency was taken to be the ratio between stroke work and oxygen consumption.Ea increased significantly as mean pulmonary artery pressure rose, while Ees remained linear and constant. Stroke work, as well as efficiency, increased, with the maximum of the stroke work curve lying to the right of the efficiency maximum. At the control step (before pulmonary artery hypertension), Ees = 1.71 Ea (n = 11).Under control conditions, the right ventricle operates at maximum efficiency and submaximal work output. Compliance of the pulmonary artery is a significant factor in decoupling the right ventricle from its vascular load. As the compliance decreases with acute pulmonary hypertension, the maximum stroke work against load point shifted in such a manner that the right ventricle changed its operational status from a flow to a pressure pump, resulting in a decreased stroke volume.
Endoscopic submucosal dissection for duodenal tumors: a single-center experience
Authors: S. Matsumoto, H. Miyatani, Y. Yoshida
Journal: Endoscopy (2012)

The indications for endoscopic submucosal dissection (ESD) for duodenal tumors have not yet been established. We reviewed our experience of ESD performed for duodenal tumors. We analyzed the data of a total of 13 patients with 14 duodenal lesions (excluding papillary lesions) comprising 2 early cancers, 5 adenomas, and 7 neuroendocrine tumors, who were treated by ESD between 2005 and 2011. The mean tumor diameter was 12.7 ± 14.8 mm. En bloc resection was achieved in 85.7 % of the cases. The procedure time was 89.1 ± 64.6 minutes. Intraoperative perforation occurred in three cases. The mean length of postoperative hospitalization was 8.4 ± 2.4 days. Because ESD for duodenal lesions was associated with a higher incidence of perforation than ESD for lesions in other locations (stomach, esophagus, and colon) reported previously, its use for duodenal lesions should be considered with caution.
Liver in ulcerative colitis: obstructive jaundice due to bile duct carcinoma.
Authors: J G Rankin, A P Skyring, S J Goulston
Journal: Gut (1966)

SYNOPSIS In a series of 441 patients with ulcerative colitis, three patients were found to have bile duct carcinoma.The frequency of the association of the two diseases in this and other series suggests a specific relationship, the basis of which is still undetermined.
Magnesium in acute myocardial infarction
Authors: K. L Woods, D B Barnett
Journal: BMJ (1995)

91 93 Year Life expectancy among males at birth in European republics of former Soviet Union (sources World Health Organisation, Unicef, and V Shkolnikov (personal com- munication)).Data for 1983-4 not available for some republics.vested interests, not least in the Ministry of Finance, that opposed it.2Although alcohol consumption began to increase again in the late 1980s, especially as a result of illicit production and diversion from state trading organisations, alcohol is unlikely to explain all the recent deterioration in life expectancy.5As Ryan notes, much high quality epidemiological research is now being undertaken in the former Soviet Union, although there is little evidence that it is being acted on by policymakers either there or in the West.What is needed is a mechanism for bringing this work to a wider audience in both regions.
Gynaecomastia induced by phenytoin in men with epilepsy.
Authors: J P Monson, D F Scott
Journal: BMJ (1987)

immersion in cold water causes bradycardia.4These effects may occur during burial in an avalanche of snow.Hypothermia often.occurs in burial in an avalanche.The face is often the only area unprotected by clothing and in direct contact with the snow, which may be important as it is the face that triggers the diving reflex.This is unlike immersion in cold water, when cooling is more uniform.During immersion water may enter the nasopharynx, causing cooling of the brain, or may be inhaled, causing rapid cooling of the heart and brain before circulation stops.Although this would not occur during burial in snow, snow has been found packed in the mouth and nose and may be inhaled, possibly with similar effects (N J MacDonald, personal observations).
Thallium-201 Uptake in Myositis Ossificans Potential Pitfall in Diagnosis
Authors: FIRAT GUNGOR, MUHARREM YAZICI, IBRAHIM EGEHAN, ARIF ENGIN DEMIRQALI, MURATHAN SAHIN, SABAN QAKIR, YESIM ELGIN, ZEYNEP BURAK, IREM BERNAY
Journal: Clinical Nuclear Medicine (1995)

Myositis ossificans is primarily a disorder of adolescents or adults, whereby an area of muscle mass undergoes progressive ossification. Its radiographic and sclntigraphic appearances have been well documented. In this paper, a case of histopathologically demonstrated myositis ossificans in the proximal thigh with unexpected TI-201 accumulation was presented.
Cardiovascular Birth Defects and Antenatal Exposure to Female Sex Hormones
Authors: Olli P. Heinonen, Dennis Slone, Richard R. Monson, Ernest B. Hook, Samuel Shapiro
Journal: New England Journal of Medicine (1977)

In a cohort of 50,282 pregnancies 19 children with cardiovascular defects were born to 1042 women who received female hormones during early pregnancy (18.2 per 1000). Among 49,240 children not exposed in utero to these agents there were 385 with cardiovascular malformations (7.8 per 1000). Six children with cardiovascular defects were born to a sub-group of 278 women who used oral contraceptives during early pregnancy (21.5 per 1000). After the data were controlled for a wide variety of potentially confounding factors by multivariate methods, the association between in utero exposure to female hormones and cardiovascular birth defects was statistically significant.
Asthma symptoms in rural living Tanzanian children; prevalence and the relation to aerobic fitness and body fat
Authors: S. Berntsen, K. C. Lødrup Carlsen, R. Hageberg, A. Aandstad, P. Mowinckel, S. A. Anderssen, K.‐H. Carlsen
Journal: Allergy (2009)

To determine the prevalence of asthma symptoms in children from a rural district in North-Tanzania, and their relationship to aerobic fitness and body fat.In Manyara region in Tanzania, children (aged 9-10 years) were randomly selected to participate in the present cross-sectional study. Hundred and seventy two participants completed a video questionnaire showing the symptoms and signs of asthma. Lung function was measured by maximum forced expiratory flow-volume curves. Aerobic fitness was estimated from a standardized indirect maximal cycle ergometer test and sum of three skinfolds reflected body fat.Twenty four per cent reported asthma symptoms last year. Severe wheezing attacks last year were reported in 5% of the participants. Thirty seven per cent of the participants were underweight. Underweight children had significantly lower (P < 0.02) lung function (per cent of predicted). Lower body fat was associated with higher occurrence of asthma symptoms (odds ratio and 95% CI; 0.45 (0.22-0.95; P = 0.04). Aerobic fitness was not associated with asthma symptoms.More than every fifth 9-10 year old child from a rural district in North-Tanzania reported asthma symptoms. Lower body fat was associated with higher occurrence of asthma symptoms, but aerobic fitness was not associated with asthma symptoms.
Hemodynamic and Renal Excretory Effects of Human Brain Natriuretic Peptide Infusion in Patients With Congestive Heart Failure
Authors: Lee S. Marcus, Douglas Hart, Milton Packer, Madeline Yushak, Norma Medina, Robert S. Danziger, Daniel F. Heitjan, Stuart D. Katz
Journal: Circulation (1996)

Background The pharmacological effects of infusion of human brain natriuretic peptide (hBNP) in patients with severe congestive heart failure have not been characterized previously. Methods and Results Twenty patients with severe congestive heart failure were randomized in a double-blind, placebo-controlled, crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01, 0.03, and 0.1 μg/kg per minute) or placebo on 2 consecutive days. At the highest completed dose of the hBNP, mean pulmonary artery pressure decreased from 38.3±1.6 to 25.9±1.7 mm Hg; mean pulmonary capillary wedge pressure decreased from 25.1±1.1 to 13.2±1.3 mm Hg; mean right atrial pressure decreased from 10.9±1 to 4.8±1.0 mm Hg; mean arterial pressure decreased from 85.2±2.0 to 74.9±1.7 mm Hg; and cardiac index increased from 2.0±0.1 to 2.5±0.1 L/min per square meter (all P &lt;.01 versus placebo). Urine volume and urine sodium excretion increased significantly during hBNP infusion when compared with placebo infusion (90±38 versus 67±27 mL/h and 2.6±2.4 versus 1.4±1.2 mEq/h, respectively, both P &lt;.05 versus placebo), whereas creatinine clearance and urinary potassium excretion did not change. Conclusions Infusion of incremental doses of hBNP is associated with favorable hemodynamic and natriuretic effects in patients with severe congestive heart failure. (Circulation. 1996;94:3184-3189.)
French surgeons descend on England to protest about pay
Authors: Brad Spurgeon
Journal: BMJ (2005)

French surgeons last week carried out a threat made last summer to visit England to protest about low pay and high insurance premiums after saying that the government failed to honour an agreement made last August.

Although nearly 2000 surgeons had been expected to take part in the protest trip (originally planned for September), in the end only 350 did. Led by a group called Surgeons of France, the surgeons spent four days at Pontin's holiday camp in Camber Sands, Sussex, where they planned a new …
Activity testing of alveolar macrophages and changes in surfactant phospholipids after irradiation in bronchoalveolar lavage: experimental and clinical data.
Authors: F Steinberg, B Rehn, R Kraus, K Quabeck, J Bruch, D W Beelen, U W Schaefer, C Streffer
Journal: Environmental Health Perspectives (1992)

This study presents results of bronchoalveolar lavage (BAL) after irradiation to the lungs in mice as well as clinical data. The number of BAL cells, mainly macrophages, lymphocytes, and granulocytes, changed in a time-dependent manner. The phagocytic activity of the macrophages measured as the phagocytosis of microbeads and measured as the esterase activity also showed a strong time-dependent increase during the acute phase up to 21 days after irradiation. The contents of surfactant phospholipids (SF) and sphingomyelin (SPH; as a parameter for cell death) were quantified by HPLC. Both were significantly changed between day 2 and 21 after irradiation. Three BALs of a patient with idiopathic interstitial pneumonitis, who had received an allogenic bone marrow graft after total body irradiation with 10 Gy, showed similar effects in the cellular and surfactant parameters. These data indicate that there are positive interactions between the number of different BAL cells, macrophage activity, and SF and SPH content in the preclinical model of the mouse as well as in the clinical situation after lung irradiation.
Lymphatics of the Mitral Valve of the Dog
Authors: ALBERT J. MILLER, RUTH PICK, LOPIS N. KATZ
Journal: Circulation Research (1961)

Thin-walled vessels have been visualized histologically in the mitral valve of the dog; these vessels were increased in number and caliber in animals with chronic impairment of cardiac lymph flow. Injection of diluted India ink into the free edge of the anterior mitral leaflet of the beating heart revealed extensive networks of vessels, grossly visible on the atrial surface of the valve. Histological study showed the India ink to be within thin-walled channels. Thus, there is compelling evidence that the visualized vessels are lymphatics and that their size and number increase when the cardiac lymphatic drainage is chronically impaired. The possible significance of the presence of lymphatic capillaries in the mitral valve is discussed.
68 Independent prospective multicenter validation of biochemical markers (fibrotest-actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C
Authors: P HALFON, M BOURLIERE, R DEYDIER, I PORTAL, C RENOU, J BERTRAND, A TRAN, A ROSENTHAL, M ROTILY, A SATTONET
Journal: Hepatology (2003)
T cell control of the gut IgA response against commensal bacteria
Authors: N A BOS, H-Q JIANG, J J CEBRA
Journal: Gut (2001)

The immunoglobulin A (IgA) is produced to defend mucosal surfaces from environmental organisms, but host defenses against the very heavy load of intestinal commensal microorganisms are poorly understood.The IgA against intestinal commensal bacterial antigens was analyzed; it was not simply "natural antibody" but was specifically induced and responded to antigenic changes within an established gut flora.In contrast to IgA responses against exotoxins, a significant proportion of this specific anti-commensal IgA induction was through a pathway that was independent of T cell help and of follicular lymphoid tissue organization, which may reflect an evolutionarily primitive form of specific immune defense.
A STUDY OF THE GASTRIC ULCERS FOLLOWING REMOVAL OF THE ADRENALS
Authors: Frank C. Mann
Journal: The Journal of Experimental Medicine (1916)

Acute ulcers of the gastric mucosa are found in a large percentage of dogs and cats dying after adrenalectomy. These ulcers seem to develop during the moribund period. They are apparently peptic ulcers forming at the site of local hemorrhages in the gastric mucosa. They are true acute ulcers, usually penetrating to the muscularis mucosa with a total loss of epithelium. They develop in the absence of pancreatic secretion and bile. However, they appear to develop only in an acid medium.
Augmented bicarbonate reabsorption by both the proximal and distal nephron maintains chloride-deplete metabolic alkalosis in rats.
Authors: D E Wesson
Journal: Journal of Clinical Investigation (1989)

Whether augmented bicarbonate reabsorption by renal tubular epithelium contributes to the maintenance of chloride-deplete metabolic alkalosis is not clear. This study used free-flow micropuncture to investigate bicarbonate reabsorption by surface nephron segments in a rat model of diuretic-induced alkalosis compared to control. The proximal and distal nephron of the alkalotic animals had higher values for both delivered load to and absolute reabsorption from these segments. The proximal tubules of alkalotic and control animals had similar values for the slopes of the linear regression of delivered load vs. reabsorption and for the bicarbonate tubular fluid to plasma (TF/P) ratio at the late proximal tubule. By contrast, the corresponding analysis for the distal segment of alkalotic animals revealed a greater slope (0.98 vs. 0.81, P less than 0.003) and a smaller bicarbonate TF/P ratio at the late distal tubule (0.10 vs. 0.16, P less than 0.006). The data indicate that augmented bicarbonate reabsorption by both the proximal and distal nephron contributes to maintaining the alkalosis of this model. The data suggest primary stimulation of bicarbonate reabsorption in the distal nephron and load-dependent reabsorption in the proximal tubule.
Mutations in SEC63 cause autosomal dominant polycystic liver disease
Authors: Sonia Davila, Laszlo Furu, Ali G Gharavi, Xin Tian, Tamehito Onoe, Qi Qian, Airong Li, Yiqiang Cai, Patrick S Kamath, Bernard F King, Pablo J Azurmendi, Pia Tahvanainen, Helena Kääriäinen, Krister Höckerstedt, Olivier Devuyst, Yves Pirson, Rodolfo S Martin, Richard P Lifton, Esa Tahvanainen, Vicente E Torres, Stefan Somlo
Journal: Nature Genetics (2004)

Mutations in PRKCSH, encoding the β-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum (ER), cause autosomal dominant polycystic liver disease. We found that mutations in SEC63, encoding a component of the protein translocation machinery in the ER, also cause this disease. These findings are suggestive of a role for cotranslational protein-processing pathways in maintaining epithelial luminal structure and implicate noncilial ER proteins in human polycystic disease.
Diagnostic Performance of Noninvasive Myocardial Perfusion Imaging Using Single-Photon Emission Computed Tomography, Cardiac Magnetic Resonance, and Positron Emission Tomography Imaging for the Detection of Obstructive Coronary Artery Disease
Authors: Caroline Jaarsma, Tim Leiner, Sebastiaan C. Bekkers, Harry J. Crijns, Joachim E. Wildberger, Eike Nagel, Patricia J. Nelemans, Simon Schalla
Journal: Journal of the American College of Cardiology (2012)
New advice to hospitals on declaring "major incidents" sparks row in parliament
Authors: G. Iacobucci
Journal: BMJ (2015)

<b>Background:</b> Functional capacity is an important outcome in rheumatoid arthritis and is generally measured using the Health Assessment Questionnaire disability index (HAQ). Functional limitation incorporates both activity and damage. Because irreversible damage increases over time, the HAQ may be less likely to show improvement in late than in early rheumatoid arthritis. <b>Objective:</b> To determine the relation between sensitivity to change of the HAQ and duration of rheumatoid arthritis in reports of clinical trials. <b>Methods:</b> Data were pooled from clinical trials that measured responses of HAQ scores at three or six months. The effect size of the HAQ was calculated and linear regression used to predict the effect size by duration of rheumatoid arthritis at group level. Treatment effect was adjusted for by including the effect sizes of pain scores and of tender joint counts as additional independent variables in separate models. Subgroup analysis employed contemporary regimens (methotrexate, leflunomide, combination therapies, and TNF inhibitors) only. <b>Results:</b> 36 studies with 64 active treatment arms and 7628 patients (disease duration 2.5 months to 12.2 years) were included. The effect sizes of the HAQ decreased by 0.02 for each additional year of mean disease duration using all trials, and by 0.04/year in the subgroup analysis (p⩽0.01 for both analyses, except for pain adjusted models at three months). <b>Conclusions:</b> In individual trials, less improvement in the HAQ might be expected in late than in early rheumatoid arthritis. Comparison of changes in HAQ among rheumatoid arthritis trials should take into consideration the disease stage of the treated groups.