tbuckley/cabot-search huggingface dataset:
Sclerosing cholangitis and biliary tract calculi--primary or secondary?
Authors: C S Pokorny, G W McCaughan, N D Gallagher, W S Selby
Journal: Gut (1992)

The clinical features of 61 patients with sclerosing cholangitis were reviewed. This group included 23 patients with biliary tract calculi, commonly considered as excluding the diagnosis of primary sclerosing cholangitis. The aim of this study was to compare these 23 patients (group A) with 38 patients with sclerosing cholangitis free of calculi (group B). Both groups had the following features in common: (i) age at presentation, (ii) incidence of inflammatory bowel disease, (iii) extent of radiological disease, (iv) prevalence of HLA-B8 and DR3 haplotype, (v) incidence of cholangiocarcinoma, and (vi) progression to hepatic transplantation (mean follow up 49.9 months). All patients in group A were symptomatic at diagnosis compared with 23 of the 38 patients (61%) in group B. Recurrent ascending cholangitis occurred in 12 patients in group A (52%) and two patients (5%) in group B. The similarity between the two groups was maintained when the nine patients in group A who developed calculi after sclerosing cholangitis was diagnosed were excluded. It is concluded that choledocholithiasis is part of the spectrum of primary sclerosing cholangitis and that it is not necessary to invoke choledocholithiasis as the initial lesion of the bile ducts in such patients.
Particulate Air Pollution and Risk of ST-Segment Depression During Repeated Submaximal Exercise Tests Among Subjects With Coronary Heart Disease
Authors: Juha Pekkanen, Annette Peters, Gerard Hoek, Pekka Tiittanen, Bert Brunekreef, Jeroen de Hartog, Joachim Heinrich, Angela Ibald-Mulli, Wolfgang G. Kreyling, Timo Lanki, Kirsi L. Timonen, Esko Vanninen
Journal: Circulation (2002)

Background— Daily variations in ambient particulate air pollution have been associated with cardiovascular mortality and morbidity. We therefore assessed the associations between levels of the 3 main modes of urban aerosol distribution and the occurrence of ST-segment depressions during repeated exercise tests. Methods and Results— Repeated biweekly submaximal exercise tests were performed during 6 months among adult subjects with stable coronary heart disease in Helsinki, Finland. Seventy-two exercise-induced ST-segment depressions &gt;0.1 mV occurred during 342 exercise tests among 45 subjects. Simultaneously, particle mass &lt;2.5 μm (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC 0.01–0.1 ]) and accumulation mode particles (100 to 1000 nm [NC 0.1–1 ]) were monitored at a central site. Levels of particulate air pollution 2 days before the clinic visit were significantly associated with increased risk of ST-segment depression during exercise test. The association was most consistent for measures of particles reflecting accumulation mode particles (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC 0.1–1 and 2.84; 95% CI, 1.42 to 5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95% CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO 2 and CO were associated with an increased risk for ST-segment depressions. No consistent association was observed for coarse particles. The associations tended to be stronger among subjects who did not use β-blockers. Conclusions— The present results suggest that the effect of particulate air pollution on cardiovascular morbidity is at least partly mediated through increased susceptibility to myocardial ischemia.
Dexamethasone-induced healing of chronic leg ulcers in a patient with defective organization of the extracellular matrix of fibronectin
Authors: G. De Panfilis, A. Ghidini, S. Graifemberghi, S. Barlati, N. Zoppi, M. Colombi
Journal: British Journal of Dermatology (2000)

Previous investigations have shown that skin fibroblasts derived from patients affected by Ehlers–Danlos syndrome (EDS) lack an organized extracellular matrix (ECM) of fibronectin (FN). As retarded wound healing is a sign of EDS, we hypothesized that a young healthy man suffering from chronic recalcitrant leg ulcers might be affected by a defect of FN–ECM organization similar to that observed in EDS. Immunofluorescence of cultured skin fibroblasts obtained from skin biopsies from the patient and a control demonstrated that the patient’s fibroblasts lacked FN–ECM organization, in contrast with those of the control; this was restored by 10−7 mol/L dexamethasone (DEX) in vitro. DEX treatment of the patient was associated with healing of his leg ulcers. In conclusion, DEX may be effective in reversing impaired wound healing associated with a lack of FN–ECM organization
Resting Energy Expenditure and Subsequent Mortality Risk in Peritoneal Dialysis Patients
Authors: Angela Yee-Moon Wang, Mandy Man-Mei Sea, Nelson Tang, John E. Sanderson, Siu-Fai Lui, Philip Kam-Tao Li, Jean Woo
Journal: Journal of the American Society of Nephrology (2004)

Cardiovascular disease is the leading cause of death in ESRD patients and is strongly associated with malnutrition. The mechanism of malnutrition is not clear, but hypermetabolism is suggested to contribute to cardiac cachexia. This study examined resting energy expenditure (REE) in relation to the clinical outcomes of ESRD patients who receive continuous ambulatory peritoneal dialysis (CAPD) treatment. A prospective observational cohort study was performed in 251 CAPD patients. REE was measured at study baseline using indirect calorimetry together with other clinical, nutritional, and dialysis parameters. Patients were followed up for a mean ± SD duration of 28.7 ± 14.3 mo. REE was 39.1 ± 9.6 and 40.1 ± 9.0 kcal/kg fat-free edema-free body mass per day for men and women, respectively (<i>P</i> = 0.391). Using multiple regression analysis, fat-free edema-free body mass–adjusted REE was negatively associated with residual GFR (<i>P</i> &lt; 0.001) and serum albumin (<i>P</i> = 0.046) and positively associated with diabetes (<i>P</i> = 0.002), cardiovascular disease (<i>P</i> = 0.009), and C-reactive protein (<i>P</i> = 0.009). At 2 yr, the overall survival was 63.3, 73.6, and 95.9% (<i>P</i> &lt; 0.0001), and cardiovascular event-free survival was 72.3, 84.6, and 97.2% (<i>P</i> = 0.0003), respectively, for patients in the upper, middle, and lower tertiles of REE. Adjusting for age, gender, diabetes, and cardiovascular disease, patients in the upper and middle tertiles showed a 4.19-fold (95% confidence interval, 2.15 to 8.16; <i>P</i> &lt; 0.001) and a 2.90-fold (95% confidence interval, 1.49, 5.63; <i>P</i> = 0.002) respective increase in the risk of all-cause mortality compared with those in the lower tertile. However, the significance of REE in predicting mortality was gradually reduced when additional adjustment was made for C-reactive protein, serum albumin, and residual GFR in a stepwise manner. In conclusion, a higher REE is associated with increased mortality and cardiovascular death in CAPD patients and is partly related to its close correlations with residual kidney function, cardiovascular disease, inflammation, and malnutrition in these patients.
Commentary: Methotrexate and ciclosporin in the treatment of severe eczema in children
Authors: A.D. Irvine
Journal: British Journal of Dermatology (2014)

Funding sources: None. Conflicts of interest: None declared. Severe and persistent childhood atopic dermatitis (AD) has a dramatic impact on quality of life. If AD remains poorly controlled after appropriate and well‐adhered‐to topical regimens have been exhausted, including assessment of immediate and delayed allergies and infective aggravations (bacterial, viral and fungal pathogens),1 what is the next option on the treatment menu? Narrowband phototherapy is often an attractive option. When other treatments have been exhausted, paediatric dermatologists not infrequently find themselves offering advice and choices to families considering systemic therapy. Clearly, any treatment offered must be both effective and safe, not just in the immediate term but, especially in a paediatric population, in the long term too. What evidential basis do we have to inform and guide parental and child choice? The truth is that direct evidence is hard to find, as primary data from properly conducted clinical trials of systemic therapies in severe childhood AD are very few, and thus we often must extrapolate backwards from adult studies or from the use of these drugs in childhood for other indications. Neither situation is ideal: in the first instance due to the very different pharmacokinetic and dynamic considerations in children, and in the second for the obvious disease‐specific variations in response to therapy. As a subspecialty, paediatric dermatology has not succeeded in exploring, in a robust and systematic way, the best options in this clinical scenario. In this setting any new evidence is very welcome and is worth examining closely to see whether it can substantiate a change in clinical practice. Current therapeutic choices in this situation include ciclosporin, azathioprine and methotrexate. Ciclosporin is licensed for use in over 16 year olds and remains the systemic therapy of first choice in most of Europe.2 Azathioprine has been widely used in the U.K., but recent reports of late side‐effects with this drug have understandably given cause for concern on safely grounds;3 these include skin cancer, hepatosplenic T‐cell lymphoma and progressive multifocal leucoencephalopathy, albeit in other disease settings and often in conjunction with other immune‐modifying drugs.
A MECHANICAL MEASURING INSTRUMENT FOR STERILE LIQUIDS
Authors: Frederick L. Gates
Journal: The Journal of Experimental Medicine (1921)

An instrument is described by which aliquot portions of a liquid may be mechanically measured and delivered. It was devised especially for use in immunological experiments, to take the place of a graduated pipette in setting up serum tests. The instrument may be set for any quantity within its capacity and measures sterile liquids without danger of contamination. It may therefore find a wider application in other procedures requiring sterile measurements of small amounts of liquid.
Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis
Authors: G C Riise, B Andersson, S Ahlstedt, I Enander, M Söderberg, O Löwhagen, S Larsson
Journal: European Respiratory Journal (1996)

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.
Abstract 517: Anti-glycan IgM and IgG antibodies as new biomarkers for serous ovarian cancers
Authors: Brian WC Tse, Francis Jacob, Tatiana Pochechueva, Sheri Nixdorf, Andre Fedier, Margaret Huflejt, Nicolai Bovin, Daniel A. Fink, Neville F. Hacker, Viola A. Heinzelmann-Schwarz
Journal: Cancer Research (2012)

Abstract Introduction: Patients with advanced-stage serous cancers (ovarian, peritoneal and tubal) often develop ascites, a protein-rich fluid within the peritoneal cavity which causes significant morbidity and is associated with a poor prognosis. Aberrant glycosylation is a common feature of these cancers and this may impact on the humoral immune response. We hypothesized that serous cancer patients and healthy women have different profiles of anti-glycan antibodies in plasma and ascites. Method: Matched pairs of plasma and ascites were collected from 11 patients with advanced stage disease. A custom-made printed glycan array (PGA) allowed the simultaneous detection of anti-glycan antibodies (AGAs) to 203 chemically synthesised glycans, including some tumour-associated carbohydrate antigens. Identified candidate AGAs were additionally detected using a suspension array in an independent patient cohort of 230 patients. Candidates were selected by their discriminatory power between cancer and healthy controls. One top candidate was further analyzed for its biological behavior using ovarian cancer cell lines. Results: Using PGA, we detected a multitude of AGAs in both plasma and ascites. Levels of AGAs in serum and ascites correlated independent of ascites volume. Serous cancer patients had significantly different levels of plasma IgM to 31 glycans when compared to plasma of 14 healthy control patients, with IgM levels being lower in the cancer group. Significant differences in IgG plasma levels were found for 4 glycans. The trisaccharide P1, part of the P blood group system, was selected for further analyses. Plasma expression of P1 was found independent of cohort and method used. The human serous ovarian cancer cell line, IGROV1, was shown to express P1 and was subsequently sorted into P1-high, P1-low, and P1-negative subpopulations. We found that IGROV1/P1-expressing cells correlated with faster tumor cell migration and invasion. Treatment with a human anti-P1 IgM (clone P3NIL100) inhibited the proliferation of these tumour cells in vitro. Conclusion: P1 expression can be detected in ovarian cancer patients in independent of cohorts. P1 seems to be involved in cancer migration and invasion, and is therefore a potential target for ovarian cancer diagnosis and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 517. doi:1538-7445.AM2012-517
Ataluren (PTC124) Induces Cystic Fibrosis Transmembrane Conductance Regulator Protein Expression and Activity in Children with Nonsense Mutation Cystic Fibrosis
Authors: Isabelle Sermet-Gaudelus, Kris De Boeck, Georges J. Casimir, François Vermeulen, Teresinha Leal, Agnès Mogenet, Delphine Roussel, Janine Fritsch, Laurence Hanssens, Samit Hirawat, Nilsen L. Miller, Scott Constantine, Allen Reha, Temitayo Ajayi, Gary L. Elfring, Langdon L. Miller
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) in approximately 10% of patients. Ataluren (PTC124) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein.Objectives: To evaluate ataluren activity, safety, and pharmacokinetics in children with nonsense mutation CF.Methods: Patients were assessed in two 28-day cycles, comprising 14 days on and 14 days off ataluren. Patients took ataluren three times per day (morning, midday, and evening) with randomization to the order of receiving a lower dose (4, 4, and 8 mg/kg) and a higher dose (10, 10, and 20 mg/kg) in the two cycles.Measurements and Main Results: The study enrolled 30 patients (16 male and 14 female, ages 6 through 18 yr) with a nonsense mutation in at least one allele of the CFTR gene, a classical CF phenotype, and abnormal baseline nasal epithelial chloride transport. Ataluren induced a nasal chloride transport response (at least a −5-mV improvement) or hyperpolarization (value more electrically negative than −5 mV) in 50% and 47% of patients, respectively, with more hyperpolarizations at the higher dose. Improvements were seen in seven of nine nonsense mutation genotypes represented. Ataluren significantly increased the proportion of nasal epithelial cells expressing apical full-length CFTR protein. Adverse events and laboratory abnormalities were infrequent and usually mild. Ataluren pharmacokinetics were similar to those in adults.Conclusions: In children with nonsense mutation CF, ataluren can induce functional CFTR production and is well tolerated.Clinical trial registered with www.clinicaltrials.gov (NCT 00458341).
Intra-Arrest Transnasal Evaporative Cooling
Authors: Maaret Castrén, Per Nordberg, Leif Svensson, Fabio Taccone, Jean-Louise Vincent, Didier Desruelles, Frank Eichwede, Pierre Mols, Tilmann Schwab, Michel Vergnion, Christian Storm, Antonio Pesenti, Jan Pachl, Fabien Guérisse, Thomas Elste, Markus Roessler, Harald Fritz, Pieterjan Durnez, Hans-Jörg Busch, Becky Inderbitzen, Denise Barbut
Journal: Circulation (2010)

Background— Transnasal evaporative cooling has sufficient heat transfer capacity for effective intra-arrest cooling and improves survival in swine. The aim of this study was to determine the safety, feasibility, and cooling efficacy of prehospital transnasal cooling in humans and to explore its effects on neurologically intact survival to hospital discharge. Methods and Results— Witnessed cardiac arrest patients with a treatment interval ≤20 minutes were randomized to intra-arrest cooling with a RhinoChill device (treatment group, n=96) versus standard care (control group, n=104). The final analysis included 93 versus 101 patients, respectively. Both groups were cooled after hospital arrival. The patients had similar demographics, initial rhythms, rates of bystander cardiopulmonary resuscitation, and intervals to cardiopulmonary resuscitation and arrival of advanced life support personnel. Eighteen device-related adverse events (1 periorbital emphysema, 3 epistaxis, 1 perioral bleed, and 13 nasal discolorations) were reported. Time to target temperature of 34°C was shorter in the treatment group for both tympanic (102 versus 282 minutes, P =0.03) and core (155 versus 284 minutes, P =0.13) temperature. There were no significant differences in rates of return of spontaneous circulation between the groups (38% in treated subjects versus 43% in control subjects, P =0.48), in overall survival of those admitted alive (44% versus 31%, respectively, P =0.26), or in neurologically intact survival to discharge (Pittsburgh cerebral performance category scale 1 to 2, 34% versus 21%, P =0.21), although the study was not adequately powered to detect changes in these outcomes. Conclusions— Prehospital intra-arrest transnasal cooling is safe and feasible and is associated with a significant improvement in the time intervals required to cool patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00808236.
Factors affecting uptake of antenatal HIV testing in London: results of a multicentre study
Authors: D. M Gibb, S. E MacDonagh, R. Gupta, P. A Tookey, C. S Peckham, A E Ades
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To measure the uptake of antenatal HIV testing and determine its relation to risk of HIV and to screening practices. <b>Design:</b> Multicentre prospective questionnaire study. <b>Subjects:</b> Pregnant women attending six maternity units. <b>Setting:</b> Inner London, 1995-6. <b>Main outcome measures:</b> Uptake of testing by risk factors for HIV, ethnicity, and factors about the antenatal interview. <b>Results:</b> All units had a "universal offer" policy for HIV testing. In five units forms were completed for 18 791 (88%) of 21 247 pregnant women. The sixth unit, where the response rate was too low to assess uptake, was excluded from the analysis. Uptake ranged from 3.4% to 51.2% (overall 22.9%), in parallel with detection of previously undiagnosed infection in pregnant women (4.9-60%). Controlling for unit, uptake was higher among the 7% who disclosed risk factors. Among those at low risk, uptake varied by ethnic group (South Asian women 9%; Latin American and Mediterranean women 33%). The relation between uptake and HIV risk category varied greatly across units. Despite increased HIV seroprevalence in black African women, uptake was similar in this group to that among women at low risk (24%). Uptake increased 2.1-fold if HIV transmission was discussed. Midwives reported spending 7 (2–15) minutes discussing HIV issues. <b>Conclusions:</b> Uptake of HIV testing was unacceptably low in all units, with maternity unit the strongest predictor. New approaches to antenatal HIV testing are urgently required and uptake should be audited routinely. <h3>Key messages</h3> In five major maternity units in inner London, all with "universal offer" policies, fewer than 1 in 4 women were tested for HIV during pregnancy in 1995-6 Maternity unit was the most important factor determining uptake of HIV testing, which ranged from 3% to 51%, in parallel with detection of previously undiagnosed infection during pregnancy Maternity units with the lowest uptake of antenatal HIV testing had the largest differences in uptake between groups of women with different risk factors for HIV Uptake of testing among women exposed in Africa was no higher than among women with no disclosed risk, despite much higher HIV seroprevalence in the former group New approaches to antenatal HIV testing are urgently required; ongoing routine audit of the uptake of antenatal HIV testing is essential if higher uptake rates are to be achieved and maintained
Some observations on the pharmacology of 'deep-heat', a topical rubifacient.
Authors: A J Collins, L J Notarianni, E F Ring, M P Seed
Journal: Annals of the Rheumatic Diseases (1984)

A topically applied rubifacient delivered by aerosol (Deep-Heat) was studied. After spray application to the forearms of volunteers, without massage, the erythema produced was measured by thermography and correlated with the concentration of 2 salicylate components of the mixture found in local and systemic venous blood. Maximum erythema occurred at about 30 minutes, while blood salicylate levels were maximal between 20 and 30 minutes after application. Methyl salicylate was absorbed before ethyl salicylate. Over the time period of the erythematous response oxygen levels in local venous blood were raised. Finally, platelets collected from venous blood draining from the sprayed site, when induced to clump by the addition of arachidonic acid in an aggregometer, showed increased resistance to clumping when compared with control cells. The mechanism of these observed phenomena and the mode of action of the constituents of Deep-Heat are discussed.