tbuckley/cabot-search huggingface dataset:
Expression of insulin-like growth factors and their binding proteins by bronchoalveolar cells from children with and without interstitial lung disease
Authors: K Chadelat, M Boule, S Corroyer, B Fauroux, B Delaisi, G Tournier, A Clement
Journal: European Respiratory Journal (1998)

The involvement of the insulin-like growth factor (IGF) system in lung growth and repair following injury is sustained by a number of studies. Based on this knowledge, the aim of the present work was to document the expression of the IGFs and their binding proteins by alveolar cells obtained by bronchoalveolar lavage (BAL). Two groups were investigated: a control group of five children and a group of 11 children referred to the department for exploration of interstitial lung disease (ILD). Components of the IGF system studied included IGF-I, IGF-II and IGF-binding proteins (IGFBP). Expression of these factors was analysed at the level of messenger ribonucleic acid (mRNA) (by semi-quantitative reverse transcription polymerase chain reaction techniques), and of protein for the IGFBPs. In addition, expression of two major cytokines associated with the inflammatory process, tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), was also documented. In children without parenchymal disease, the growth factor expressed was IGF-I, in association with the presence of mRNA for IGFBP-2 in all cases. In children with ILD, expression of IGF-I was observed in nine patients and of IGF-II in three patients, and the presence of IGFBP-2 was found in all extracts analysed (mRNA and proteins). Evaluation of IGFBP-2 expression indicated an increase in the group of children with ILD. Interestingly, a significant association was observed between the increase in IGFBP-2 expression and TGF-beta expression. The present data emphasize the presence on insulin-like growth factor-binding protein-2 in the BAL of all patients, and suggest that this protein may be an important factor of the injury/repair processes during the progression of alveolar inflammation.
Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development
Authors: Bianca Rocca, Lisa M. Spain, Ellen Puré, Robert Langenbach, Carlo Patrono, Garret A. FitzGerald
Journal: Journal of Clinical Investigation (1999)

Prostaglandin G and H synthases, or cyclooxygenases (COXs), catalyze the formation of prostaglandins (PGs). Whereas COX-1 is diffusely expressed in lymphoid cells in embryonic day 15.5 thymus, COX-2 expression is sparse, apparently limited to stromal cells. By contrast, COX-2 is predominant in a subset of medullary stromal cells in three- to five-week-old mice. The isozymes also differ in their contributions to lymphocyte development. Thus, experiments with selective COX-1 inhibitors in thymic lobes from normal and recombinase-activating gene-1 knockout mice support a role for this isoform in the transition from CD4–CD8– double-negative (DN) to CD4+CD8+ double-positive (DP). Concordant data were obtained in COX-1 knockouts. Pharmacological inhibition and genetic deletion of COX-2, by contrast, support its role during early thymocyte proliferation and differentiation and, later, during maturation of the CD4 helper T-cell lineage. PGE2, but not other PGs, can rescue the effects of inhibition of either isoform, although it acts through distinct EP receptor subtypes. COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development.
Platelet count and survival of patients with compensated cirrhosis and small hepatocellular carcinoma treated with surgery
Authors: Edoardo G. Giannini, Vincenzo Savarino
Journal: Hepatology (2013)

We read with great interest the article by Roayaie et al. evaluating the 5-year outcome and the main prognostic factors after resection of single, tiny (≤2-cm) hepatocellular carcinoma (HCC) in patients with compensated chronic liver disease (CLD).1 Analyzing 132 patients from two Western tertiary referral centers, they found that the presence of satellites and a platelet count <150 × 109/L were the independent prognostic factors for survival. However, despite the indubitable prognostic relevance of satellites, even in these patients with very early HCC, from a practical standpoint it should be noted that (1) their presence cannot be documented by imaging techniques before surgery (as clearly demonstrated in the study), (2) they were observed in only 12% of these patients, (3) they did not retain their prognostic meaning in the subset of patients with cirrhosis.1 On the contrary, platelet count is a bed-side obtainable, inexpensive, routinely assessed parameter that resulted in being significantly associated with survival, regardless of the presence of cirrhosis.1 However, the identification of platelet count as a prognostic parameter in patients with well-compensated cirrhosis should not be regarded as a marker of the presence of portal hypertension (PH) alone.2, 3 In fact, in patients with CLD, other factors, such as decreased liver production of thrombopoietin, may be responsible for decreased platelet count.4 Thus, when patients with a similar stage of liver disease are evaluated, as in the study by Roayaie et al., thrombocytopenia may be a parameter able to pinpoint patients with subtle decrease in liver function and therefore with a worse prognosis. Indeed, in the Roayaie et al. series, the survival of patients with low platelet counts started to diverge late (>2 years) after resection, thus suggesting that low platelet count may herald late clinical problems, rather than perioperative risks. In this regard, it is interesting to note that surgical resection of HCC—despite the presence of thrombocytopenia—was not associated with an increased early perioperative mortality and that, in one of the two centers involved in the study, liver resection was allowed even in patients with small esophageal varices and platelet count below 100 × 109/L, pending the presence of an indocyanine green retention <20%. The data by Roayaie et al. further add to the role of platelet count as a prognostic marker in patients with cirrhosis and HCC and indirectly disclose potential meanings that are not limited to the association of this hematological parameter with PH. Edoardo G. Giannini, M.D., Ph.D., FACG Vincenzo Savarino, M.D. Dipartimento di Medicina Interna Unità di Gastroenterologia IRCCS-Azienda Ospedaliera Universitaria San Martino-ISTUniversità di Genova Genova, Italy
A phase II trial of capecitabine and docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) as preoperative treatment in women with stage II/III breast cancer
Authors: H. Jinno, M. Sakata, T. Hayashida, M. Takahashi, M. Mukai, T. Ikeda, Y. Kitagawa
Journal: Annals of Oncology (2009)
New TB vaccines: is there a requirement for CD8+ T cells?
Authors: W Henry Boom
Journal: Journal of Clinical Investigation (2007)

MHC class I–restricted CD8+ T cells are necessary to mount an immune response against Mycobacterium tuberculosis. M. tuberculosis antigens can enter MHC class I cross-processing pathways through a number of different mechanisms, including via the uptake of antigen-containing apoptotic vesicles released by infected cells. A study in this issue of the JCI by Hinchey and colleagues shows that M. tuberculosis inhibits host cell apoptosis and thus may interfere with optimal cross-priming and action of CD8+ T cells (see the related article beginning on page 2279). M. tuberculosis genetically modified to induce apoptosis is shown to be more effective in priming CD8+ T cells in vivo and therefore may be a more effective vaccine against tuberculosis than the currently utilized M. bovis BCG vaccine.
Air Pollution and Respiratory Health among Children with Asthmatic or Cough Symptoms
Authors: KIRSI LIISA TIMONEN, JUHA PEKKANEN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

During the winter of 1994, the association between daily changes in air pollution and in the respiratory health of children 7 to 12 yr of age were studied in Kuopio, Finland. Seventy-four children with asthmatic symptoms and 95 children with cough only, living either in urban or suburban areas, were followed for 3 mo. During the study period, the mean daily concentration of particulate air pollution (PM10) was 18 μ g/m3 in the urban area and 13 μ g/m3 in the suburban area. Lagged concentrations of PM10, black smoke, and NO2 were significantly associated with declines in morning peak expiratory flow (PEF) among asthmatic children. The regression coefficient ( × 10) for a 2-d lag of PM10 was − 0.911 (SE, 0.386) in the urban and − 1.05 (0.596), in the suburban area. Among children with cough only, PM10, black smoke, and NO2 were not significantly associated with PEF. In the urban area, there was a significant association between SO2 and morning and evening PEF and incidence of upper respiratory symptoms among children who cough only. No other associations between air pollution and evening PEF or respiratory symptoms were observed. This study suggests that particulate air pollution is associated with respiratory health, especially among children with asthmatic symptoms.
Combination of folinic acid, 5-fluorouracil bolus and infusion, and cisplatin (LV5FU2-P regimen) in patients with advanced gastricor gastroesophageal junction carcinoma
Authors: E. Mitry, J. Taïeb, P. Artru, V. Boige, J.-N. Vaillant, M.-C. Clavero-Fabri, M. Ducreux, P. Rougier
Journal: Annals of Oncology (2004)
Extracellular Signal–Regulated Kinase Inhibition Slows Disease Progression in Mice with Polycystic Kidney Disease
Authors: Sayu Omori, Mariko Hida, Hisayo Fujita, Hisahide Takahashi, Susumu Tanimura, Michiaki Kohno, Midori Awazu
Journal: Journal of the American Society of Nephrology (2006)

The expression of mitogen-activated protein kinases (MAPK) in DBA/2-pcy/pcy (pcy) mice, a murine model of polycystic kidney disease was investigated. Proliferating cell nuclear antigen-positive cells were recognized in cyst epithelium from embryonic day 14.5 to 25 wk of age. Extracellular signal-regulated kinase (ERK) was expressed in the renal tubules of control and pcy mice, but stronger immunostaining was observed in cyst epithelium. Phosphorylated ERK was detected only in pcy mice and was localized predominantly in the cysts. p38 MAPK (p38) was no longer expressed after birth in controls but was detected in the cyst epithelium and in occasional tubular cells of pcy mice at all stages examined. c-Jun N-terminal kinase (JNK) was expressed in all tubular segments of controls after neonatal day 7, whereas in pcy kidneys, tubules became positive for JNK after 8 wk, and the cysts expressed little JNK. Administration of an oral MAP/ERK kinase inhibitor, PD184352, 400 mg/kg per d, to 10-wk-old pcy mice daily for the first week and then every third day for 6 additional weeks significantly decreased BP, kidney weight, serum creatinine level, and water intake and significantly increased urine osmolality. The cystic index and expression of phosphorylated ERK and ERK were significantly lower in PD184352-treated pcy mice. These results demonstrate that the expression of MAPK is dysregulated in cyst epithelium and that inhibition of ERK slowed the progression of renal disease in pcy mice.
HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER
Authors: G. H. Whipple, F. S. Robscheit-Robbins
Journal: The Journal of Experimental Medicine (1933)

Human liver tissue has been assayed to determine the concentration of hemoglobin production factors in normal and abnormal states. Standardized dogs made anemic by bleeding have been used in this biological assay and the human liver tissue compared with control animal tissue. Normal human liver tissue (external trauma) contains much more of these hemoglobin production factors than the normal control animal liver-the ratio being 162 to 100. In this form of biological assay 42 gm. of animal liver or 26 gm. of human liver represent 1 gm. of potential hemoglobin. A second group (Table 2) in which the viscera were practically normal except for atrophy, the cases presenting a good deal of arteriosclerosis and senile changes, shows a lower content of these hemoglobin production factors. The ratio of human to control here is 117 to 100. This is certainly the low limit of normal. Acute fulminant infections reduce somewhat the store of these potent hemoglobin production factors in the human liver (Table 3). The average value is 117 as compared with 100 control but the more acute cases show the lower values. Chronic intoxications show values which are close to the human normal-151 per cent. The liver content of hemoglobin producing factors shows very wide fluctuations in cases of thyrotoxicosis. Diabetes may be associated with rather low values. There may be complete dissociation of the organic iron content and the concentration of hemoglobin production factors in the liver.
Effect of Rosuvastatin Therapy on Coronary Artery Stenoses Assessed by Quantitative Coronary Angiography
Authors: Christie M. Ballantyne, Joel S. Raichlen, Stephen J. Nicholls, Raimund Erbel, Jean-Claude Tardif, Sorin J. Brener, Valerie A. Cain, Steven E. Nissen
Journal: Circulation (2008)

Previous studies using quantitative coronary angiography have demonstrated that statin therapy slows the progression of coronary stenoses in proportion to average low-density lipoprotein cholesterol levels during therapy. However, no major statin monotherapy study has demonstrated either halted progression or regression of angiographic disease. A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) assessed whether rosuvastatin could regress coronary atherosclerosis by intravascular ultrasound and quantitative coronary angiography. Intravascular ultrasound showed atheroma volume regression in a single coronary artery with <50% angiographic luminal narrowing.ASTEROID treated 507 coronary disease patients with rosuvastatin 40 mg/d for 24 months. Blinded quantitative coronary angiography analyses of percent diameter stenosis and minimum lumen diameter were performed for up to 10 segments of coronary arteries and major branches with >25% diameter stenosis at baseline. For each patient, the mean of all matched lesions at baseline and study end was calculated. There were 292 patients with 613 matched stenoses. Rosuvastatin reduced low-density lipoprotein cholesterol by 53.3% to 61.1+/-20.3 mg/dL and increased high-density lipoprotein cholesterol by 13.8% to 48.3+/-12.4 mg/dL. Mean+/-SD percent diameter stenosis decreased from 37.3+/-8.4% (median, 35.7%; range, 26% to 73%) to 36.0+/-10.1% (median, 34.5%; range, 8% to 74%; P<0.001). Minimum lumen diameter increased from 1.65+/-0.36 mm (median, 1.62 mm; range, 0.56 to 2.65 mm) to 1.68+/-0.38 mm (median, 1.67 mm; range, 0.76 to 2.77 mm; P<0.001).Rosuvastatin treatment for 24 months to average low-density lipoprotein cholesterol levels well below 70 mg/dL, accompanied by significant increases in high-density lipoprotein cholesterol, produced regression by decreasing percent diameter stenosis and improving minimum lumen diameter as measured by quantitative coronary angiography in coronary disease patients.
One month treatment with the once daily oral beta 2-agonist bambuterol in asthmatic patients
Authors: G Persson, A Baas, A Knight, B Larsen, H Olsson
Journal: European Respiratory Journal (1995)

Bambuterol is a new long-acting oral bronchodilator for once daily use in patients with asthma. It is a prodrug of terbutaline, designed to be slowly metabolized to terbutaline. Results from comparative studies have shown that it has similar clinical efficacy to other oral bronchodilators, but less side-effects. The present study was aimed at verifying the 24 h effect duration of bambuterol, 10 and 20 mg in comparison with placebo during a one month treatment period. The study was conducted as a double-blind, randomized, parallel group placebo-controlled, multicentre trial. It started with a one week run-in period with placebo, when oral bronchodilators were withdrawn. At the end of this reference period, the patients were randomized to one of three treatments: placebo, bambuterol 10 mg, or bambuterol 20 mg, once daily in the evening. The treatment period lasted for 4 weeks. Four hundred and eighty seven patients with a mean age of 45 yrs were included. Mean baseline forced expiratory volume in one second (FEV1) and FEV1% of predicted were 2.05 l and 62%, respectively. Administration of 10 mg bambuterol resulted in a significant 24 h effect duration, expressed as an increase in mean daily morning and evening peak expiratory flow (PEF) (+11 l.min-1, adjusted means) throughout the study, as compared with placebo. Bambuterol, 20 mg, gave a significant 24 h effect duration in both FEV1 and morning and evening PEF as compared with placebo. Furthermore, the adverse events observed during the study were relatively few and mild.(ABSTRACT TRUNCATED AT 250 WORDS)
Evidence-based Gastroenterology and Hepatology, 2nd Edn
Authors: S Ghosh
Journal: Gut (2006)

Edited by J W D McDonald, A K Burroughs, B G Feagan. London: BMJ Books, 2004, £125, pp 624. ISBN 072791751X

 “Facts are stubborn things; and whatever may be our wishes, our inclinations, or the dictates of our passions, they cannot alter the state of facts and evidence” , John Adams  

We owe it to our patients to know the facts and implement them accurately for improving their quality of lives. This obligation imposes formidable challenges to a modern practicing physician often struggling with information overload, demands of revalidation, and a maze of regulatory requirements. The second edition of this very successful and well known volume is a superb way of updating gastroenterology and hepatology evidence and facts encapsulated within one …
Increased Water Intake Decreases Progression of Polycystic Kidney Disease in the PCK Rat
Authors: Shizuko Nagao, Kazuhiro Nishii, Makoto Katsuyama, Hiroki Kurahashi, Tohru Marunouchi, Hisahide Takahashi, Darren P Wallace
Journal: Journal of the American Society of Nephrology (2006)

Renal enlargement in polycystic kidney disease (PKD) is caused by the proliferation of mural epithelial cells and transepithelial fluid secretion into the cavities of innumerable cysts. Arginine vasopressin (AVP) stimulates the proliferation of human PKD cells <i>in vitro via</i> cAMP-dependent activation of the B-Raf/MEK (MAPK/ERK kinase/extracellular signal–regulated kinase (ERK) pathway. ERK activity is elevated in cells that line the cysts in animals with PKD, and AVP receptor antagonists reduce ERK activity and halt disease progression. For suppression of the effect of AVP physiologically, water intake was increased in PCK rats, a model of PKD, and the effect on renal morphology, cellular mechanism, and function was determined. The addition of 5% glucose in the drinking water increased fluid intake approximately 3.5-fold compared with rats that received tap water. In PCK rats, increased water intake for 10 wk reduced urinary AVP excretion (68.3%), and urine osmolality fell below 290 mOsmol/kg. High water intake was associated with reduced renal expression of AVP V2 receptors (41.0%), B-Raf (15.4%), phosphorylated ERK (38.1%), and proliferating cell nuclear antigen–positive renal cells (61.7%). High water intake reduced the kidney/body weight ratio 28.0% and improved renal function. Taken together, these data demonstrate that water intake that is sufficient to cause persistent water diuresis suppresses B-Raf/MEK/ERK activity and decreases cyst and renal volumes in PCK rats. It is suggested that limiting serum AVP levels by increased water intake may be beneficial to some patients with PKD.
First influenza season after the 2009 pandemic influenza: characteristics of intensive care unit admissions in adults and children in Vall d'Hebron Hospital
Authors: G. Poulakou, J. Souto, J. Balcells, M. Pérez, C. Laborda, O. Roca, T. Tórtola, M. Pujol, M. Palomar, J. Rello
Journal: Clinical Microbiology and Infection (2011)
The effect of nitrous oxide on the measurement of single-breath transfer factor
Authors: CL Phillips, R Simmul, AI Smith, N Berend
Journal: European Respiratory Journal (1997)

One hour after a bone marrow biopsy and inhalation of Entonox gas (50% nitrous oxide (N2O) and 50% oxygen), a patient had a markedly reduced transfer factor of the lung for carbon monoxide (TL,CO). Three hours after Entonox, the patient had a normal TL,CO. Since carbon monoxide (CO) and N2O have similar spectral wavelengths, it was proposed that residual N2O in the lungs was interfering with the infra-red analysers used to detect CO concentrations. Experiments were performed to verify the "interference" effect and its duration. Five healthy volunteers performed serial triplicate TL,CO measurements over 3 h on two randomized days (Control vs N2O). The first triplicate TL,CO on each day served as a baseline measurement. Following the baseline measurement on the N2O day, each subject inhaled Entonox for 10 min. To serve as a control for the infrared effect, the identical protocol was repeated using a gas chromatography method for TL,CO determination. The infra-red method showed a marked reduction (&gt; 50%) in TL,CO 30 min after N2O inhalation. This reduction did not return to baseline levels for at least 2 h. In comparison, the gas chromatography method showed no significant reduction in TL,CO. In a group of healthy nonsmoking subjects, N2O markedly affected the measurement of the transfer factor of the lungs for carbon monoxide using infra-red analysers. The time course over which the measurement was reduced was at least 2 h for a 10 min inhalation period. The effect was entirely due to a measurement error associated with infra-red technology.
Monitoring without metacognition
Authors: Peter Carruthers
Journal: Behavioral and Brain Sciences (2003)

Smith et al. present us with a false dichotomy in explaining their uncertainty data: Either the animals' responses are "under the associative control of stimulus cues," or the animals must be responding "under the metacognitive control of uncertainty cues." There is a third alternative to consider: one that is genuinely cognitive, neither associative nor stimulus driven, but purely first-order in character. On this alternative the metacognitive reports of humans in these situations reflect states that are interpretative rather than causal in character.
Parasympathetic Control of Coronary Blood Flow in Dogs
Authors: ERIC O. FEIGL
Journal: Circulation Research (1969)

The role of the vagus in the control of coronary blood flow was studied in chloralose-anesthetized dogs with open chests. Propranolol, 1.0 mg/kg iv, was used for beta-receptor blockade. Heart rate was maintained at a constant level with atrial and ventricular pacing. Left circumflex coronary artery blood flow was measured with an electromagnetic flowmeter. The experimental design accounted for the four major determinants of coronary blood flow: (1) aortic pressure, (2) myocardial systolic compression, (3) alterations in myocardial oxygen tension and metabolism secondary to changes in contractile force, (4) neural control. Efferent stimulation of the cut cervical vagi (30 Hz, 2 msec, 8-10 v) resulted in decreased aortic blood pressure and increased coronary blood flow. Late diastolic coronary artery resistance fell to 58% of the control value after 5 seconds of vagal stimulation. Atropine, 0.5 mg/kg iv, blocked these effects. It is concluded that direct parasympathetic coronary vasodilation results from vagal stimulation, which is independent of vagal chronotropic and inotropic effects.