tbuckley/cabot-search huggingface dataset:
Refractory ascites: Modulation of atrial natriuretic factor unresponsiveness by mannitol
Authors: Gilles A. Morali, Sheldon W. Tobe, Karl L. Skorecki, Laurence M. Blendis
Journal: Hepatology (1992)

We have previously shown that unresponsiveness to atrial natriuretic factor is a marker of the severity of ascites. The tubular mechanisms are unknown, but it seems that increased reabsorption of sodium proximal to the main site of action of atrial natriuretic factor (i.e., the inner medullary collecting duct) plays an important role. We attempted to decrease the proximal reabsorption of sodium with mannitol in patients unresponsive to atrial natriuretic factor. The results of mannitol in such a group of patients has previously been conflicting. We studied 10 patients with massive, resistant ascites who were off diuretics and on a 20-mmol/day sodium diet for 7 days. Atrial natriuretic factor unresponsiveness was confirmed by failure of a 2-hr atrial natriuretic factor infusion to induce a natriuresis. The next day all patients received an infusion of 40 gm of mannitol and subsequently a combined infusion of mannitol and atrial natriuretic factor. Proximal reabsorption of sodium and water were evaluated by lithium clearance, and glomerular filtration rate and renal blood flow were evaluated by inulin clearance and p-aminohippurate clearances, respectively. Six patients responded to mannitol alone with an increased diuresis (from 39 ± 7 to 148 ± 35 ml/hr) and natriuresis (from 0.27 ± 0.05 mmol/hr to 1.65 ± 0.53 mmol/hr; p < 0.05) (responders), whereas four did not (nonresponders). The combination of atrial natriuretic factor and mannitol induced a further significant increase in sodium excretion (3.28 ± 0.68 mmol/hr) but not in urine excretion, compared with mannitol alone. Lithium clearance increased in the responders after mannitol infusion, but it did not increase further with ANF plus mannitol. Inulin and p-aminohippurate clearances were equally low in the two groups and did not change during the infusions. The responders had significantly lower plasma renin activity, aldosterone and norepinephrine levels than the nonresponders (plasma renin activity = 1.9 ± 0.7 vs. 7.3 ± 1.5 ng/L/sec; aldosterone = 2,830 ± 1,273 vs. 9,457 ± 3,873 pmol/L; norepinephrine = 2.6 ± 1.6 vs. 8.4 ± 1.6 nmol/L; p < 0.05). We conclude the following: (a) atrial natriuretic factor unresponsiveness in cirrhotic patients is due, in part, to increased reabsorption of sodium proximal to the distal site of atrial natriuretic factor action; (b) increased proximal reabsorption of sodium might be mediated in part by increased renin aldosterone and sympathetic nervous system activity; with moderate as opposed to marked elevation, this effect can be overcome by mannitol; and (c) with increased mannitol-induced distal delivery of sodium, atrial natriuretic factor further increases sodium excretion, indicating that receptor or intracellular signaling of atrial natriuretic factor response remains intact. (HEPATOLOGY 1992;16:42–48.)
MUC5B Is the Major Mucin in the Gel Phase of Sputum in Chronic Obstructive Pulmonary Disease
Authors: Sara Kirkham, Umme Kolsum, Karine Rousseau, Dave Singh, Jørgen Vestbo, David J. Thornton
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Overproduction of mucus is a contributory factor in the progression of chronic obstructive pulmonary disease (COPD). The polymeric mucins are major macromolecules in the secretion. Therefore, we hypothesized that the polymeric mucin composition or properties may be different in the sputum from individuals with COPD and smokers without airflow obstruction.Objectives: To determine the major polymeric mucins in COPD sputum and whether these are different in the sputum from individuals with COPD compared with that from smokers without airflow obstruction.Methods: The polymeric mucin composition of sputum from patients with COPD and smokers without airflow obstruction was analyzed by Western blotting analysis. The tissue localization of the mucins was determined by immunohistochemistry, and their size distribution was analyzed by rate–zonal centrifugation.Measurements and Main Results: MUC5AC and MUC5B were the major mucins. MUC5AC was the predominant mucin in the smoker group, whereas MUC5B was more abundant from the patients with COPD, with a significant difference in the ratio of MUC5B to MUC5AC (P = 0.004); this ratio was correlated with FEV1 in the COPD group (r = 0.63; P = 0.01). The lower-charged glycosylated form of MUC5B was more predominant in COPD (P = 0.012). No significant associations were observed with respect to sex, age, or pack-year history. In both groups, MUC5AC was produced by surface epithelial cells and MUC5B by submucosal gland cells. Finally, there was a shift toward smaller mucins in the COPD group.Conclusions: Our data indicate that there are differences in mucin amounts and properties between smokers with and without COPD. Further studies are needed to examine how this may impact disease progression.
Dose-related effect of inhaled fluticasone on allergen-induced airway changes in rats
Authors: N.J. Vanacker, E. Palmans, R.A. Pauwels, J.C. Kips
Journal: European Respiratory Journal (2002)

To examine whether fluticasone propionate (FP) dose-dependently inhibits inflammatory as well as structural changes, Brown Norway rats were sensitised to ovalbumin (OA) on day 0 and 7. From day 14–28, rats were exposed to aerosolised OA (1%) or phosphate buffered saline every 2 days. Thirty minutes before each allergen exposure, animals were pre-treated with aerosolised placebo or FP (0.1, 1 or 10 mg) or prednisolone 3 mg·kg −1 i.p . At day 29, 0.1 mg FP had no measurable effect, either on inflammatory or structural changes, such as goblet cell hyperplasia and airway wall thickening. The allergen-induced increase in eosinophilic inflammation in bronchoalveolar lavage fluid and in the airway mucosa, as well as increased fibronectin deposition, were inhibited by treatment with FP from a dose of 1 mg onwards. Inhibition of goblet cell hyperplasia and thickening of the airway wall required 10 mg inhaled FP. At this dose, systemic effects were observed. However, for a comparable degree of systemic activity, prednisolone was far less effective at preventing airway changes. The dose of inhaled fluticasone propionate required to inhibit allergen-induced structural alterations was higher than to prevent eosinophil influx, and caused systemic side-effects. However, for a similar systemic activity, prednisolone was ineffective in preventing airway remodelling.
Upper gastrointestinal bleeding in the UK: does a dedicated bleed unit improve outcomes?: Table 1
Authors: Matthew Kurien, Emma Wong, Paraskevi Sakellariou, Reena Sidhu, Alan Lobo, David S Sanders
Journal: Gut (2011)

We read with interest the recent Gut paper by Hearnshaw et al .1 We would like to add to this debate. Our recent audit conducted during a similar time frame obtained comparable data …
Prevention of Blinking Alters Iris Configuration in Pigment Dispersion Syndrome and in Normal Eyes
Authors: Jeffrey M. Liebmann, Celso Tello, Sek-Jin Chew, Henry Cohen, Robert Ritch
Journal: Ophthalmology (1995)

To examine the effect of blinking on iris configuration and aqueous humor distribution between the posterior and anterior chambers in eyes with pigment dispersion syndrome compared with healthy eyes.High-resolution, anterior segment ultrasound biomicroscopy was performed on ten eyes of ten patients with untreated pigment dispersion syndrome and on ten control subjects. Patients were scanned continuously for 15 minutes or until the maximal change in iris configuration occurred. During this time, the eyelids were held open mechanically, and blinking was prevented. Eyes then were rescanned immediately after blinking.Initial iris configuration was concave in all eyes with pigment dispersion syndrome, whereas in control eyes it was concave in four eyes, planar in four eyes, and convex in two eyes. Iridozonular contact occurred in eyes with pigment dispersion syndrome only. Iridolenticular contact was greater in eyes with pigment dispersion syndrome than in control eyes. Analysis of covariance controlling for age, sex, and refractive error showed pigment dispersion syndrome to be a significant predictor of increased iris concavity. During continuous scanning, the mean change in iris position, from most concave to most convex, and mean time to the maximal change in iris configuration were greater for eyes with pigment dispersion syndrome than in control eyes and were related to the degree of initial iris concavity only (analysis of covariance). In six eyes with pigment dispersion syndrome, the eye cup was removed, normal blinking was permitted, and the eye was rescanned. The iris resumed a concave configuration in all eyes.Increased iris concavity in pigment dispersion syndrome appears to be related to increased iridolenticular contact. This creates an anatomic configuration that predisposes to reverse pupillary block. The accumulation of aqueous humor in the posterior chamber, when blinking is prevented, alters iris position in pigment dispersion syndrome and in healthy eyes and increases iridozonular and iridociliary-process distances while minimizing iridolenticular contact. Normal blinking appears to create transient vector forces which promote aqueous humor flow from the posterior to anterior chamber.
Dobutamine Stress–Induced Microparticle Release
Authors: Brandon M. Williams, Julie C. Williams
Journal: Circulation Research (2014)

Figure.Kinetics of microparticle (MP) release and clearance after dobutamine infusion.Schematic representation of MP levels in circulation before, immediately after, and 1 hour after dobutamine stress echocardiogram (DSE) as documented in Augustine et al. 13 CVD indicates cardiovascular disease.
Diagnostic Value of Intraoperative Fiberscopy for Small-intestinal Polyps in Familial Adenomatosis Coli
Authors: M. lida, T. Yao, K. Ohsato, H. Itoh, H. Watanabe
Journal: Endoscopy (1980)

X-ray examination and intraoperative fiberscopy of the small intestine were performed in 20 patients with familial adenomatosis coli. Roentgenographic study detected polypoid lesions in the upper jejunum in 2 patients (10 %), and in the terminal ileum in 9 (45 %). In contrast, endoscopic study revealed polyps in the jejunum in 10 patients (50 %), and in the ileum in 14 (70 %). Polyps in most cases were multiple and small in size (less than 3 mm in diameter). Histology revealed the lesions of the jejunum to be adenomas, and those of the ileum to be lymphoid hyperplasia with or without adenoma. The present study suggests that intraoperative endoscopy is much more valuable than roentgenography in detecting these minute polyps of the small intestine in this disease.
Effects of circuit training as alternative to usual physiotherapy after stroke: randomised controlled trial
Authors: I. G. L. van de Port, L. E. G. Wevers, E. Lindeman, G. Kwakkel
Journal: BMJ (2012)

<b>Objective</b> To analyse the effect of task oriented circuit training compared with usual physiotherapy in terms of self reported walking competency for patients with stroke discharged from a rehabilitation centre to their own home. <b>Design</b> Randomised controlled trial with follow-up to 24 weeks. <b>Setting</b> Multicentre trial in nine outpatient rehabilitation centres in the Netherlands <b>Participants</b> Patients with stroke who were able to walk a minimum of 10 m without physical assistance and were discharged from inpatient rehabilitation to an outpatient rehabilitation clinic. Patients were randomly allocated to circuit training or usual physiotherapy, after stratification by rehabilitation centre, with an online randomisation procedure. <b>Intervention</b> Patients in the intervention group received circuit training in 90 minute sessions twice a week for 12 weeks. The training included eight different workstations in a gym and was intended to improve performance in tasks relating to walking competency. The control group received usual outpatient physiotherapy. <b>Main outcome measures</b> The primary outcome was the mobility domain of the stroke impact scale (SIS, version 3.0). Secondary outcomes were standing balance, self reported abilities, gait speed, walking distance, stair climbing, instrumental activities of daily living, fatigue, anxiety, and depression. Differences between groups were analysed according to the intention to treat principle. All outcomes were assessed by blinded observers in a repeated measurement design lasting 24 weeks. <b>Results</b> 126 patients were included in the circuit training group and 124 in the usual care group (control), with data from 125 and 117, respectively, available for analysis. One patient from the circuit training group and seven from the control group dropped out. Circuit training was a safe intervention, and no serious adverse events were reported. There were no significant differences between groups for the stroke impact scale mobility domain (β=0.05 (SE 0.68), P=0.943) at 12 weeks. Circuit training was associated with significantly higher scores in terms of gait speed (0.09 m/s (SE 0.02), P&lt;0.001), walking distance (20.0 m (SE 7.4), P=0.007), and modified stairs test (−1.6 s (SE 0.7), P=0.015). There were no significant differences between groups for the other secondary outcomes, except for the leisure domain of the Nottingham extended activities of daily living and the memory and thinking domain of the stroke impact scale. With the exception of gait speed (−0.04 m/s (SE 0.02), P=0.040), there were no significant differences between groups at follow-up. <b>Conclusion</b> Task oriented circuit training can safely replace usual physiotherapy for patients with stroke who are discharged from inpatient rehabilitation to the community and need further training in gait and gait related activities as an outpatient. <b>Trial registration</b> Dutch Trial Register (NTR1534).
Overstimulated and ineffective
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

CD4+ T cells become ineffective if repeatedly stimulated through their T cell receptors (TCRs), according to a study by Jelley-Gibbs and colleagues on page 1101. The functional demise of these cells may help explain why persisting pathogens, such as Mycobacterium tuberculosis and HIV, are associated with ineffective CD4+ T cell responses during the chronic phase of infection.

Chronic infections have been shown to induce exhaustion or functional unresponsiveness in cytotoxic CD8+ T cells, but their effect on CD4+ T helper cells has not been well studied. Jelley-Gibbs et al. now show that repeated stimulation of CD4+ T cells generated effector cells that were more activated, based on the expression of activation markers CD69 and CD62L, than cells stimulated only once but that secreted lower levels of the cytokines interferon-γ (IFN-γ) and interleukin-4 (IL-4). These repeatedly stimulated cells could not provide help to antibody-producing B cells, nor could they protect against influenza virus infection when transferred into mice.






Figure 

CD4+ T cells that undergo multiple rounds of stimulation (Th1RS) are unable to protect mice against influenza infection.




The decreased function of these repeatedly stimulated cells could not be explained by the down-regulation of their TCRs, whose levels were only marginally affected by the multiple rounds of stimulation. The authors are now studying chromatin remodeling at the IFNγ and IL-4 loci for possible clues to the decreased cytokine production.
Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia
Authors: Alessandra Carobbio, Elisabetta Antonioli, Paola Guglielmelli, Alessandro M. Vannucchi, Federica Delaini, Vittoria Guerini, Guido Finazzi, Alessandro Rambaldi, Tiziano Barbui
Journal: Journal of Clinical Oncology (2008)

Established risk factors for thrombosis in essential thrombocythemia (ET) include age and previous vascular events. We aimed to refine this risk stratification by adding baseline leukocytosis.We enrolled 657 patients with ET followed for a median of 4.5 years who developed 72 major thrombosis. Cox proportional hazard model was performed to analyze the thrombotic risk and to discriminate ET patients with or without thrombosis, multivariable C statistic index was used. We searched for leukocytes cutoff with the best sensitivity and specificity by a receiver operating characteristic curve.Results confirmed that age and prior events are independent risk factors for thrombosis and showed a gradient between baseline leukocytosis and thrombosis. On the contrary, no significant association was found either for JAK2(V617F) allele burden and for other laboratory parameters, including platelet number. In the model with conventional risk factors alone, C statistic ratio for total thrombosis was 0.63 and when leukocytosis was added, the change was small (C = 0.67). In contrast, in younger and asymptomatic patients (low-risk category), C statistic value indicated an high risk for thrombosis in patients with leukocytosis, similar to that calculated in conventionally defined high-risk group (C = 0.65). The best leukocyte cutoff values for predicting the events was found to be 9.4 (x 10(9)/L).We suggest to include baseline leukocytosis in the risk stratification of ET patients enrolled in clinical trials.
Cell cycle, oncogenic and tumor suppressor pathways regulate numerous long and macro non-protein-coding RNAs
Authors: Jörg Hackermüller, Kristin Reiche, Christian Otto, Nadine Hösler, Conny Blumert, Katja Brocke-Heidrich, Levin Böhlig, Anne Nitsche, Katharina Kasack, Peter Ahnert, Wolfgang Krupp, Kurt Engeland, Peter F Stadler, Friedemann Horn
Journal: Genome biology (2014)

Abstract Background The genome is pervasively transcribed but most transcripts do not code for proteins, constituting non-protein-coding RNAs. Despite increasing numbers of functional reports of individual long non-coding RNAs (lncRNAs), assessing the extent of functionality among the non-coding transcriptional output of mammalian cells remains intricate. In the protein-coding world, transcripts differentially expressed in the context of processes essential for the survival of multicellular organisms have been instrumental in the discovery of functionally relevant proteins and their deregulation is frequently associated with diseases. We therefore systematically identified lncRNAs expressed differentially in response to oncologically relevant processes and cell-cycle, p53 and STAT3 pathways, using tiling arrays. Results We found that up to 80% of the pathway-triggered transcriptional responses are non-coding. Among these we identified very large macroRNAs with pathway-specific expression patterns and demonstrated that these are likely continuous transcripts. MacroRNAs contain elements conserved in mammals and sauropsids, which in part exhibit conserved RNA secondary structure. Comparing evolutionary rates of a macroRNA to adjacent protein-coding genes suggests a local action of the transcript. Finally, in different grades of astrocytoma, a tumor disease unrelated to the initially used cell lines, macroRNAs are differentially expressed. Conclusions It has been shown previously that the majority of expressed non-ribosomal transcripts are non-coding. We now conclude that differential expression triggered by signaling pathways gives rise to a similar abundance of non-coding content. It is thus unlikely that the prevalence of non-coding transcripts in the cell is a trivial consequence of leaky or random transcription events.
Radiology versus Endoscopy of the Small Bowel
Authors: B. Lewis
Journal: Endoscopy (1998)

Since the development of endoscopy, physicians have been comparing radiographic studies with endoscopic examinations. Colonoscopy and upper endoscopy have largely replaced barium enema and upper gastrointestinal series. Unfortunately, many study protocols comparing colonoscopy with barium enema have been retrospective and the radiologic examination is compared with colonoscopy in a cohort group. The greatest difficulty with interpreting results of these studies is the inclusion of clinically insignificant findings in the calculation of the diagnostic yield. For example, in most studies barium enema is more successful than colonoscopy in diagnosing diverticular disease, and inclusion of this clinically insignificant entity increases the overall yield.
Associations of a Polymorphism in the Ornithine Decarboxylase Gene with Colorectal Cancer Survival
Authors: Jason A. Zell, Argyrios Ziogas, Natalia Ignatenko, Jane Honda, Ning Qu, Alexander S. Bobbs, Susan L. Neuhausen, Eugene W. Gerner, Hoda Anton-Culver
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Activity of ornithine decarboxylase (ODC), the first enzyme in polyamine synthesis, is required for normal growth and is elevated in many cancers, including colorectal cancer. We examined associations of the +316 ODC1 single nucleotide polymorphism (SNP) with colorectal cancer–specific survival among colorectal cancer cases, and then investigated its functional significance in colon cancer cells. Experimental Design: The study included 400 incident stage I-III colorectal cancer cases from the population-based University of California Irvine Gene-Environment Study of Familial Colorectal Cancer (diagnosed from 1994 to 1996 with follow-up through March 2008). The primary outcome was colorectal cancer–specific survival dependent on ODC1 (rs2302615) genotype (GG versus GA/AA). In human colon cancer cell lines, ODC1 allele-specific binding of E-box transcription factors was determined via Western blotting and chromatin immunoprecipitation assays. ODC1 allele-specific promoter activity was determined using promoter constructs in combination with vectors expressing either the transcriptional activator c-MYC or the repressor MAD1. Results: Genotype-specific survival differences were observed among colorectal cancer cases: compared with cases with the ODC1 GG genotype (hazards ratio, 1; reference) the adjusted colorectal cancer–specific survival hazards ratio was 2.02 (95% confidence interval, 1.17-3.50) for ODC1 GA/AA cases (P = 0.012). In colon cancer cells, the ODC1 SNP, flanked by two E-boxes, predicts ODC1 promoter activity. The E-box activator c-MYC and repressors MAD1 and MAD4 preferentially bind to ODC1 minor A-alleles, compared with major G-alleles, in cultured cells. Conclusions: These results have implications for conditional regulation of polyamine homeostasis and suggest a model in which the ODC1 SNP may be protective for colon adenoma recurrence and detrimental for survival after colon cancer diagnosis. (Clin Cancer Res 2009;15(19):6208–16)