tbuckley/cabot-search huggingface dataset:
Effect of a volumatic spacer and mouth rinsing on systemic absorption of inhaled corticosteroids from a metered dose inhaler and dry powder inhaler.
Authors: O Selroos, M Halme
Journal: Thorax (1991)

High doses of inhaled corticosteroids are absorbed systemically and may cause long term side effects. As rinsing the mouth out after use and inhaling through a spacing device may reduce systemic absorption this has been further investigated.Three crossover studies were carried out to assess the effect of budesonide given by dry powder inhaler (Turbuhaler) with and without mouth rinsing and beclomethasone dipropionate given by metered dose inhaler with or without a spacing device (Volumatic) on serum cortisol concentrations and urinary cortisol excretion in patients with asthma taking an inhaled corticosteroid. Each treatment period was two weeks with in a two week washout period. Serum cortisol concentrations at 0800 hours on day 14 and the 24 hour urinary excretion of cortisol were measured. In study 1 24 patients taking beclomethasone dipropionate 500 micrograms twice a day inhaled with (n = 10) or without (n = 14) a Volumatic spacing device were switched to a budesonide dry powder inhaler, 600 micrograms to be taken twice a day without mouth rinsing. In study 2 10 patients took budesonide 800 micrograms twice a day with and without mouth rinsing and without swallowing the rinsing water. In study 3 17 patients took budesonide 800 micrograms twice daily with mouth rinsing and beclomethasone dipropionate 500 micrograms twice daily with the spacing device and mouth rinsing.In study 1 no difference was seen between budesonide without mouth rinsing and beclomethasone dipropionate without a spacer: beclomethasone with spacer caused less suppression of cortisol (mean (SD) serum cortisol concentration: beclomethasone and spacer 487(148), budesonide 368(145) nmol/l). In study 2 mouth rinsing caused less suppression of morning serum cortisol concentrations (rinsing 440(63), no rinsing 375(56) nmol/1). In study 3 there was no difference in serum or urinary cortisol concentrations between twice daily beclomethasone dipropionate 500 micrograms inhaled by Volumatic spacer or budesonide by Turbuhaler 800 micrograms twice daily, both with mouth rinsing. Individual serum cortisol values were within the normal range in all patients except one in study 1.Systemic absorption of a corticosteroid inhaled from a metered dose inhaler is reduced by using a spacing device and that from a dry powder inhaler by mouth rinsing.
Tannic acid in plant dust causes airway obstruction
Authors: D Taubert
Journal: Thorax (2005)

Occupational or environmental exposure to plant dusts has been shown to increase the risk of obstructive lung diseases, primarily by non-immunological activity.1 However, the causative agents and the underlying mechanisms have not been established. We have recently suggested that the polyphenolic fraction of hydrolysable tannins in plant derived dusts, with tannic acid (TA) as the main constituent, may contribute to airway constriction.2 Here we present experimental evidence that TA causes acute airway obstruction by non-competitive inhibition of the constitutive endothelial isoform of nitric oxide synthase (eNOS) in the tracheobronchial epithelium, which is reported to provoke airway hyperresponsiveness and bronchoconstriction.3

Organ bath experiments were performed using the trachea and main bronchi of non-sensitised guinea pigs. The tracheobronchial tree was dissected out of CO2 sacrificed guinea pigs of either sex weighing 300–450 g and cut into rings of 3–4 cartilage segments wide. Isometric contractions were recorded as described previously.4 Briefly, individual rings were mounted in organ baths containing 10 ml carbogen aerated Tyrode solution (pH 7.4, 37°C), kept at a preload of 25 mN, left to equilibrate for 60 minutes, and precontracted by addition of 25 μmol/l prostaglandin F2α to 30–40% of their individual isometric maximum (100%).

NO release was determined in real time by an amperometric microsensor as described elsewhere.4 Briefly, …
Nonsteroidal anti-inflammatory drugs for preventing post-ERCP pancreatitis: why rectal and not intramuscular?
Authors: B. Elmunzer
Journal: Endoscopy (2014)

Eight randomized, controlled trials (RCTs) and several meta-analyses have demonstrated that rectal nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) by about 50 % [1] [2]. Rectal indomethacin and diclofenac also reduce the severity of PEP [3], appear to be effective in both high- and average-risk cases [1] [2], and are recommended (as a grade A recommendation) by the European Society of Gastrointestinal Endoscopy for almost all patients undergoing ERCP [4]. Although the recent uptake of these medications in clinical practice has been rapid and widespread, there does appear to be some apprehension surrounding the rectal mode of administration.
GMC’s reply
Authors: Graeme Catto
Journal: BMJ (2008)

The open letter to me from Wheatley makes several statements about the case of David Southall.1 Southall has appealed to the High Court, and it would be inappropriate for me to comment on the case at this stage.

But I am very concerned about Wheatley’s conclusion that paediatricians will not be fairly dealt with by the General Medical Council (GMC). This is wrong, and it is not borne out by the facts. It is important that he and those …
Exploring the interaction between SNP genotype and postmenopausal hormone therapy effects on stroke risk
Authors: Ying Huang, Dennis G Ballinger, Renee Stokowski, Erica Beilharz, Jennifer G Robinson, Simin Liu, Randal D Robinson, Victor W Henderson, Jacques E Rossouw, Ross L Prentice
Journal: Genome Medicine (2012)

Genome-wide association studies have identified several genomic regions that are associated with stroke risk, but these provide an explanation for only a small fraction of familial stroke aggregation. Genotype by environment interactions may contribute further to such an explanation. The Women's Health Initiative (WHI) clinical trial found increased stroke risk with postmenopausal hormone therapy (HT) and provides an efficient setting for evaluating genotype-HT interaction on stroke risk. We examined HT by genotype interactions for 392 SNPs selected from candidate gene studies, and 2,371 SNPs associated with changes in blood protein concentrations after hormone therapy, in analyses that included 2,045 postmenopausal women who developed stroke during WHI clinical trial and observational study follow-up and one-to-one matched controls. A two-stage procedure was implemented where SNPs passing the first stage screening based on marginal association with stroke risk were tested in the second stage for interaction with HT using case-only analysis. The two-stage procedure identified two SNPs, rs2154299 and rs12194855, in the coagulation factor XIII subunit A (F13A1) region and two SNPs, rs630431 and rs560892, in the proprotein convertase subtilisin kexin 9 (PCSK9) region, with an estimated false discovery rate <0.05 based on interaction tests. Further analyses showed significant stroke risk interaction between these F13A1 SNPs and estrogen plus progestin (E+P) treatment for ischemic stroke and for ischemic and hemorrhagic stroke combined, and suggested interactions between PCSK9 SNPs with either E+P or estrogen-alone treatment. Genotype by environment interaction information may help to define genomic regions relevant to stroke risk. Two-stage analysis among postmenopausal women generates novel hypotheses concerning the F13A1 and PCSK9 genomic regions and the effects of hormonal exposures on postmenopausal stroke risk for subsequent independent validation.
Improved Survival and Reduced Phenotypic Severity Following AAV9/MECP2 Gene Transfer to Neonatal and Juvenile Male Mecp2 Knockout Mice
Authors: Kamal KE Gadalla, Mark ES Bailey, Rosemary C Spike, Paul D Ross, Kenton T Woodard, Sahana Nagabhushan Kalburgi, Lavanya Bachaboina, Jie V Deng, Anne E West, R Jude Samulski, Steven J Gray, Stuart R Cobb
Journal: Molecular Therapy (2012)

Typical Rett syndrome (RTT) is a pediatric disorder caused by loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. The demonstrated reversibility of RTT-like phenotypes in mice suggests that MECP2 gene replacement is a potential therapeutic option in patients. We report improvements in survival and phenotypic severity in Mecp2-null male mice after neonatal intracranial delivery of a single-stranded (ss) AAV9/chicken β-actin (CBA)-MECP2 vector. Median survival was 16.6 weeks for MECP2-treated versus 9.3 weeks for green fluorescent protein (GFP)-treated mice. ssAAV9/CBA-MECP2-treated mice also showed significant improvement in the phenotype severity score, in locomotor function, and in exploratory activity, as well as a normalization of neuronal nuclear volume in transduced cells. Wild-type (WT) mice receiving neonatal injections of the same ssAAV9/CBA-MECP2 vector did not show any significant deficits, suggesting a tolerance for modest MeCP2 overexpression. To test a MECP2 gene replacement approach in a manner more relevant for human translation, a self-complementary (sc) adeno-associated virus (AAV) vector designed to drive MeCP2 expression from a fragment of the Mecp2 promoter was injected intravenously (IV) into juvenile (4-5 weeks old) Mecp2-null mice. While the brain transduction efficiency in juvenile mice was low (~2-4% of neurons), modest improvements in survival were still observed. These results support the concept of MECP2 gene therapy for RTT.
The renal glomerulus in hypoxic cor pulmonale.
Authors: J L Campbell, P M Calverley, D Lamb, D C Flenley
Journal: Thorax (1982)

We measured the mean capillary tuft area by a custom-built semi-automatic technique in postmortem sections from the kidneys of 16 patients with "blue and bloated" chronic bronchitis and emphysema and in seven patients of similar age who were free of respiratory and renal disease at death. Nine bronchitic patients had received domiciliary oxygen treatment while seven had not. The mean glomerular tuft area in these treated bronchitic patients (14 200 microns2) was not significantly different from that of the untreated patients (16 900 microns2) but the tuft area in the bronchitic subjects was significantly larger than that of the non-bronchitic controls (12 100 microns2, p less than 0 . 02). There was no reduction in glomerular cellularity to suggest passive venous distension, and glomerular size was not correlated with clinical or pathological indices of cor pulmonale (including red cell mass). The arterial oxygen tension (Po2), however, was correlated with glomerular size (r = 0 . 68, p less than 0 . 01) if allowance was made for the higher Po2 of the patients receiving oxygen. The percentage of glomeruli with an identifiable juxtaglomerular apparatus also increased with increasing glomerular size. These structural changes in the kidneys of patients with severe chronic bronchitis and emphysema may reflect changes in renal salt and water handling that are potentially reversible by oxygen treatment.
Simulated descent v dexamethasone in treatment of acute mountain sickness: a randomised trial
Authors: H.-R. Keller, M. Maggiorini, P. Bartsch, O. Oelz
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: Evaluation and comparison of the therapeutic efficacy of a portable hyperbaric chamber and dexamethasone in the treatment of acute mountain sickness. <b>Design</b>: Randomised trial during the summer mountaineering season. <b>Setting</b>: High altitude research laboratory in the Capanna Regina Margherita at 4559m above sea level (Alps Valais). <b>Subjects</b>: 31 climbers with symptoms of acute mountain sickness randomly assigned to different treatments. <b>Interventions</b>: One hour of treatment in the hyperbaric chamber at a pressure of 193 mbar or oral administration of 8mg dexamethasone initially, followed by 4 mg after 6 hours. <b>Main outcome measures</b>: Symptoms of acute mountain sickness (Lake Louise score, clinical score, and AMS-C score) before one and about 11 hours after beginning the different methods of treatment. Permitted intake of mild analgesics before treatment and in the follow up period. <b>Results</b>: After one hour of treatment compression with 193mbar caused a significantly greater relief of symptoms of acute mountain sickness than dexamethasone (Lake Louise score: mean (SD) -4.6 (1.9) v -2.5 (1.8); clinical score: -4.0 (1.2) v -1.5 (1.4); AMS-C score: -1.24 (0.51) v -0.54 (0.59)). In contrast after about 11 hours subjects treated with dexamethasone suffered from significantly less severe acute mountain sickness than subjects treated with the hyperbaric chamber (-7.0 (3.6) v -1.6 (3.0); -4.1 (1.9) v -1.0 (1.5); -1.78 (0.73) v -0.75 (0.82) respectively). Intake of analgesics was similar in both groups. <b>Conclusion</b>: Both methods were efficient in treatment of acute mountain sickness. One hour of compression with 193mbar in the hyperbaric chamber, corresponding to a descent of 2250m, led to short term improvement but had no long term beneficial effect. On the other hand, treatment with dexamethasone in an oral dose of 8mg initially followed by 4mg every 6 hours resulted in a longer term clinical improvement. For optimal efficacy the two methods should be combined if descent or evacuation is not possible. <h3>Key messages</h3> Key messages Simulated descent in a hyperbaric chamber quickly relieves symptoms but the effect is short lived The drug dexamethasone takes longer to work but the effect is longer lasting A combination of the two methods may be the treatment of choice when the subject cannot be transported to lower altitudes
Secular trends in antibiotic consumption in the adult population in Emilia-Romagna, Italy, 2003–2009
Authors: A. Pan, R. Buttazzi, M. Marchi, C. Gagliotti, D. Resi, M.L. Moro
Journal: Clinical Microbiology and Infection (2011)

Antibiotic resistance is closely related to antibiotic use and Italy is a country with high levels of both antibiotic use and antimicrobial resistance. We analysed the trend in antibiotic use in the community among adults (≥15 years) and elderly, in the period 2003-2009, in Emilia-Romagna, Italy, a region with over 4 000 000 inhabitants. Data regarding antibiotic use were obtained from the regional public health system databases. Between 2003 and 2009 the antibiotic consumption increased from 15.4 to 18.7 defined daily doses/1000 inhabitants per day (DID) (+21.4%, p <0.0001). The prescription rate in 2009 was 2.19 prescriptions/1000 inhabitants per day, an increase of 13.8% compared with 2003. The highest increase in antibiotic use was observed among persons aged 20-59 years (+24.7%). The proportion of inhabitants receiving at least one antibiotic treatment was 36.4% in 2003 and 39.7% in 2009, and the proportions receiving at least three antibiotic treatments were 3.5% and 4.2%, respectively. The H1N1 pandemic was associated, in October and November 2009, with a 37-90% increase in antibiotic use among the 15-19-year and 20-59-year age groups compared with 2007 and 2008. No other difference was observed in any other age group. The analysis per antibiotic class showed increases for penicillin + beta-lactamase inhibitor (from 3.6 to 6.3 DID), quinolones (from 2.6 to 3.0 DID) and macrolides (from 3.1 to 3.7 DID), whereas cephalosporin use was stable (1.4 DID). A steady increase in antibiotic use in the adult population has been observed in the Emilia-Romagna: public health interventions are mandatory to counteract this trend.
Nonimmune and Immune Surveillance. I. Growth of Tumors and Normal Fetal Tissues Grafted Into Newborn Mice
Authors: Svetlana N. Zinzar, George J. Svet Moldavsky, Natalia V. Karmanova
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Nonimmune and Immune Surveillance. I. Growth of Tumors and Normal Fetal Tissues Grafted Into Newborn Mice Get access Svetlana N. Zinzar, Svetlana N. Zinzar Search for other works by this author on: Oxford Academic PubMed Google Scholar George J. Svet Moldavsky, M.D., George J. Svet Moldavsky, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Natalia V. Karmanova Natalia V. Karmanova Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 1, July 1976, Pages 47–55, https://doi.org/10.1093/jnci/57.1.47 Published: 01 July 1976 Article history Received: 17 July 1975 Accepted: 21 November 1975 Published: 01 July 1976
Lung Stress and Strain during Mechanical Ventilation
Authors: Alessandro Protti, Massimo Cressoni, Alessandro Santini, Thomas Langer, Cristina Mietto, Daniela Febres, Monica Chierichetti, Silvia Coppola, Grazia Conte, Stefano Gatti, Orazio Leopardi, Serge Masson, Luciano Lombardi, Marco Lazzerini, Erica Rampoldi, Paolo Cadringher, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Unphysiologic strain (the ratio between tidal volume and functional residual capacity) and stress (the transpulmonary pressure) can cause ventilator-induced lung damage.Objectives: To identify a strain–stress threshold (if any) above which ventilator-induced lung damage can occur.Methods: Twenty-nine healthy pigs were mechanically ventilated for 54 hours with a tidal volume producing a strain between 0.45 and 3.30. Ventilator-induced lung damage was defined as net increase in lung weight.Measurements and Main Results: Initial lung weight and functional residual capacity were measured with computed tomography. Final lung weight was measured using a balance. After setting tidal volume, data collection included respiratory system mechanics, gas exchange and hemodynamics (every 6 h); cytokine levels in serum (every 12 h) and bronchoalveolar lavage fluid (end of the experiment); and blood laboratory examination (start and end of the experiment). Two clusters of animals could be clearly identified: animals that increased their lung weight (n = 14) and those that did not (n = 15). Tidal volume was 38 ± 9 ml/kg in the former and 22 ± 8 ml/kg in the latter group, corresponding to a strain of 2.16 ± 0.58 and 1.29 ± 0.57 and a stress of 13 ± 5 and 8 ± 3 cm H2O, respectively. Lung weight gain was associated with deterioration in respiratory system mechanics, gas exchange, and hemodynamics, pulmonary and systemic inflammation and multiple organ dysfunction.Conclusions: In healthy pigs, ventilator-induced lung damage develops only when a strain greater than 1.5–2 is reached or overcome. Because of differences in intrinsic lung properties, caution is warranted in translating these findings to humans.
Inhibition of calcitriol-induced monocyte CD14 expression by uremic toxins
Authors: G Glorieux, C H Hsu, R de Smet, A Dhondt, J van Kaer, P Vogeleere, N Lameire, R Vanholder
Journal: Journal of the American Society of Nephrology (1998)

End-stage renal disease is associated with a defect in immunologic functions. Previous studies have demonstrated that uremic ultrafiltrate (UUF) contains factors that suppress calcitriol synthesis and its biological actions. In the present study, the effect of UUF on basal and calcitriol-induced membrane bound CD14 expression of monocytes activated by phorbol 12-myristate 13-acetate was evaluated. CD14 acts as a receptor for the complexes of lipopolysaccharide and lipopolysaccharide-binding protein. Monocytes isolated from normal donors were used for the assay of monocyte CD14 expression. A calcitriol induced rise in monocyte CD14 expression (1966+/-423 to 2421+/-436 fluorescence intensity) was found. However, UUF not only suppressed basal CD14 expression of monocytes (from 1966+/-423 to 1240+/-203, P < 0.05) but also significantly blunted calcitriol-induced CD14 expression (from 2421+/-436 to 1744+/-229, P < 0.05). HPLC fractionated UUF collected from 8 to 16 min (fraction 1, F1) and from 25 to 40 min (fraction 3, F3) also significantly suppressed the expression of CD14. Because purine derivatives coeluted within F1, their effect on monocyte CD14 expression was also tested. Uric acid, xanthine, and hypoxanthine was found to suppress basal as well as calcitriol-induced CD14 expression of monocytes in a dose-dependent manner. In conclusion, UUF contains factors that impair calcitriol activated function of monocytes.
Anticipatory Socialization for Psychotherapy: Method and Rationale
Authors: MARTIN T. ORNE, PAUL H. WENDER
Journal: American Journal of Psychiatry (1968)

There is a strong positive relationship between a patient's perception of psychotherapy and its ultimate success. Some patients who appear to lack motivation for treatment may be capable of profiting from psychotherapy if they are taught what to expect— if they understand the "rules of the game." A clinical procedure for introducing such patients to psychotherapy is outlined by the authors, who also present excerpts from a hypothetical socialization interview.
"Food deserts"---evidence and assumption in health policy making
Authors: S. Cummins
Journal: BMJ (2002)

Assertions can be reported so often that they are considered true ("factoids").They may sometimes even be used to determine health policy when empirical information is lacking.Steven Cummins and Sally Macintyre use the claimed existence of "food deserts"-poor urban areas where residents cannot buy affordable, healthy food-to illustrate why policy makers need to look more critically at the facts In December 2001 a cross party motion on food poverty signed by 198 UK MPs gained its first reading in parliament.The Food Poverty (Eradication) Bill is now waiting to be read for a second time. 1 Though this bill is a laudable attempt to introduce a policy designed to improve the nutrition of those with the lowest incomes and in the poorest places, it is an example of how some ideas become accepted as fact though they may not be true.They become "factoids": assumptions or speculations reported and repeated so often that they are popularly considered true; they are simulated or imagined facts. 2 This paper illustrates how, if the social climate is right, facts about the social world can be assumed and hence used as the basis for health policy in the absence of much empirical information.
Dendritic cells that have interacted with antigen are targets for natural killer cells.
Authors: P D Shah, S M Gilbertson, D A Rowley
Journal: The Journal of Experimental Medicine (1985)

Natural killer (NK) cells (poly I:C induced, x-ray resistant, nonadherent, Thy-1-, Ly-1.1-, Ly-2.1-, anti-asialo GM1-positive, and cytotoxic for YAC-1) suppressed T lymphocyte proliferation in mixed lymphocyte reaction (MLR) and autologous MLR cultures. Dendritic cells (DC) were required for proliferation of lymphocytes in both responses. The question whether lymphocytes or DC were the targets for NK cells was resolved by taking advantage of the fact that NK cells, but not DC, lose activity after 24 h in culture. Three findings indicate that DC, not lymphocytes, are targets for NK cells. First, responses suppressed by NK cells were fully restored by adding small numbers of DC to cultures 24 h after NK cells had been added. Second, DC incubated alone with NK cells and antigen for 24 h did not stimulate proliferation of lymphocytes. Third, lymphocytes incubated alone with NK cells for 24 h proliferated normally when DC were added. Additional experiments showed that DC became targets only after interaction with antigen. Thus, we suggest that NK cells may regulate lymphocyte proliferation by monitoring antigen presentation by DC.