tbuckley/cabot-search huggingface dataset:
Nocturnal non-invasive ventilation in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study
Authors: F M Struik, R T M Sprooten, H A M Kerstjens, G Bladder, M Zijnen, J Asin, N A M Cobben, J M Vonk, P J Wijkstra
Journal: Thorax (2014)

<h3>Introduction</h3> The effectiveness of non-invasive positive pressure ventilation (NIV) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure (ARF) remains unclear. We investigated if nocturnal NIV in these patients prolongs the time to readmission for respiratory causes or death (primary endpoint) in the following 12 months. <h3>Methods</h3> 201 COPD patients admitted to hospital with ARF and prolonged hypercapnia &gt;48 h after termination of ventilatory support were randomised to NIV or standard treatment. Secondary outcomes were daytime arterial blood gasses, transcutaneous PCO<sub>2</sub> during the night, lung function, health-related quality-of-life (HRQL), mood state, daily activities and dyspnoea. <h3>Results</h3> 1 year after discharge, 65% versus 64% of patients (NIV vs standard treatment) were readmitted to hospital for respiratory causes or had died; time to event was not different (p=0.85). Daytime PaCO<sub>2</sub> was significantly improved in NIV versus standard treatment (PaCO<sub>2</sub> 0.5 kPa (95% CI 0.04&nbsp;to 0.90, p=0.03)) as was transcutaneous PCO<sub>2</sub> during the night. HRQL showed a trend (p=0.054, Severe Respiratory Insufficiency questionnaire) in favour of NIV. Number of exacerbations, lung function, mood state, daily activity levels or dyspnoea was not significantly different. <h3>Discussions</h3> We could not demonstrate an improvement in time to readmission or death by adding NIV for 1 year in patients with prolonged hypercapnia after an episode of NIV for ARF. There is no reason to believe the NIV was not effective since daytime PaCO<sub>2</sub> and night-time PCO<sub>2</sub> improved. The trend for improvement in HRQL favouring NIV we believe nevertheless should be explored further. <h3>Trial registration number</h3> NTR1100.
A systematic review of patient-reported outcome measures used to assess Achilles tendon rupture management: What's being used and should we be using it?
Authors: Rebecca S Kearney, Juul Achten, Sarah E Lamb, Caroline Plant, Matthew L Costa
Journal: British Journal of Sports Medicine (2011)

Background Currently, there is no consensus regarding the optimal management for patients following an Achilles tendon rupture. To allow comparisons between different treatments, a universally accepted outcome measure is required. However, there are currently a range of these reported within the literature. Objective To recommend the most suitable patient-reported outcome measure for the assessment of patients following an Achilles tendon rupture, based on a systematic review of first what is currently used and second evidence of validity. Methods The electronic databases MEDLINE, EMBASE and AMED were searched up to September 2010. Predefined inclusion and exclusion criteria were applied to identify what outcome measures are reported in the literature. Aspects of validity were defined and a checklist used to determine which aspects have been evaluated. Results Twenty-one outcome measures in 50 research papers were identified. The most commonly used was the American Orthopaedic Foot and Ankle Society hind-foot score. Of the 21 outcome measures, only 4 cited independent validation data. Of these four, only the ‘Achilles tendon Total Rupture Score’ reported evidence to support multiple facets of validity, as defined by a predetermined criteria checklist. Conclusions The Achilles tendon Total Rupture Score was identified as the only outcome measure which has demonstrated multiple facets of validity for use in this patient group. However, even this tool has limitations. Researchers should be aware of the limitations of the available outcome measurement tools and check on their validity before use in clinical research.
Phase II Trial of Temozolomide and Sorafenib in Advanced Melanoma Patients with or without Brain Metastases
Authors: Ravi K. Amaravadi, Lynn M. Schuchter, David F. McDermott, Amy Kramer, Lydia Giles, Kristi Gramlich, Mary Carberry, Andrea B. Troxel, Richard Letrero, Katherine L. Nathanson, Michael B. Atkins, Peter J. O'Dwyer, Keith T. Flaherty
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The combination of the oral alkylating agent temozolomide and the oral multikinase inhibitor sorafenib was evaluated in advanced melanoma patients. Experimental Design: Patients with metastatic melanoma (n = 167) were treated on four arms. All patients received sorafenib at 400 mg p.o. twice daily without interruption. Patients without brain metastases or prior temozolomide were randomized between arm A: extended dosing of temozolomide (75 mg/m2 temozolomide daily for 6 of every 8 weeks) and arm B: standard dosing (150 mg/m2 temozolomide daily for 5 of every 28 days). Patients previously treated with temozolomide were enrolled on arm C: extended dosing of temozolomide. Patients with brain metastases and no prior temozolomide were assigned to arm D: standard dosing. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included response rate, toxicity rates, and the rates of BRAF or NRAS mutations. Results: The 6-month PFS rate for arms A, B, C, and D were 50%, 40%, 11%, and 23%. The median PFS for patients on arm A, B, C, and D was 5.9, 4.2, 2.2, and 3.5 months, respectively. No significant differences were observed between arms A and B in 6-month PFS rate, median PFS, or response rates. Treatment was well tolerated in all arms. No significant differences in toxicity were observed between arms A and B except for more grade 3 to 4 lymphopenia in arm A. Conclusion: Temozolomide plus sorafenib was well tolerated and showed activity in melanoma patients without prior history of temozolomide. The activity of this combination regimen warrants further investigation. (Clin Cancer Res 2009;15(24):7711–8)
The effect of diphenylhydantoin on thyroxine metabolism in man
Authors: P. R. Larsen, A. J. Atkinson, H. N. Wellman, R. E. Goldsmith
Journal: Journal of Clinical Investigation (1970)

The effect of 5,5'-diphenylhydantoin on thyroxine metabolism was examined in five normal volunteers. Intravenous injection of radiothyroxine was followed by a 10-12 day control and subsequent 9-14 day treatment periods. During oral administration of diphenylhydantoin, plasma thyroxine concentration decreased to about 80% of its pretreatment level and the plasma radiothyroxine disappearance rate increased a maximum of 20% over control estimates. These changes were a result of increases in both urinary and fecal excretion of radioisotope.A minimum plasma thyroxine was apparent after 10-12 days of diphenylhydantoin administration. In two of the subjects, treatment was sufficiently prolonged to achieve this new steady state. In these subjects, the decrease in total body thyroxine was balanced by the increase in the fractional turnover rate. As a result, absolute thyroxine degradation during diphenylhydantoin administration was unchanged from the pretreatment values. Plasma ultrafiltration was used to estimate the free thyroxine fraction at regular intervals during the control and treatment periods. During diphenylhydantoin treatment, there was little or no change in this fraction and therefore, absolute free thyroxine decreased. Thyroxine-binding globulin and thyroxine-binding prealbumin capacities remained constant. These results indicate that thyroxine degradation can proceed at a normal rate in subjects receiving diphenylhydantoin despite decreases in plasma free thyroxine concentration. If free thyroxine is the only portion of the hormone available for cellular utilization, then free thyroxine clearance must be increased in these subjects. This increase in clearance could represent either a direct stimulation of peripheral thyroxine metabolism by diphenylhydantoin, or it could reflect the response of intrinsic regulatory systems to a diphenylhydantoin-mediated displacement of thyroxine from thyroxine-binding globulin. Whatever the mechanism for this effect, a decreased free thyroxine value in patients receiving diphenylhydantoin may not imply hypothyroidism.
INSULIN PRODUCTION AND GLUCOSE TOLERANCE IN PATIENTS WITH GRANULOMA ANNULARE
Authors: RICHARD HAMMOND, KIRBY DYESS, ALBERT CASTRO
Journal: British Journal of Dermatology (1972)

Summary.— Ten patients with granuloma annulare were studied for evidence of carbohydrate intolerance. By traditional criteria, 2 had an abnormal glucose tolerance test. Of the remaining 8,3 had an abnormal cortisone-glucose tolerance test. The findings indicate a higher incidence (50%) of glucose intolerance in these patients than is found in the average population. In the cortisone-glucose tolerance test, plasma insulin response to glucose loading was significantly lower in the population of 10 patients with granuloma annulare than in a normal control group. The remaining 4 granuloma annulare patients with normal glucose values in both the standard and cortisone-induced glucose tolerance tests were aiso evaluated by measuring plasma insulin response to glucose loading. These 4 patients, when evaluated as a group, demonstrated also a significantly lower insulin response to glucose than the control population. These results suggest a decreased pancreatic beta cell sensitivity to glucose stimulation in patients with granuloma annulare.
Doctors support biggest local reconfiguration in NHS, says Hunt
Authors: A. O'Dowd
Journal: BMJ (2013)

Ambitious plans to reconfigure nine hospitals across northwest London have the blessing of local doctors, said England’s health secretary, Jeremy Hunt.

Hunt announced on 30 October that he was backing plans to reconfigure health services in northwest London that were presented to him in advice from the Independent Reconfiguration Panel, the group of experts that advises the health secretary on changes to NHS services.

However, the trade union Unite described the plans as a “cause for considerable concern,” especially the downgrading of two accident and emergency departments to urgent care centres and changes planned for another two emergency departments.

The panel was asked to scrutinise proposals made earlier this year by the Shaping a Healthier Future programme led by …
Macrophage Migration Inhibitory Factor Enzymatic Activity, Lung Inflammation, and Cystic Fibrosis
Authors: Huzaifa Adamali, Michelle E. Armstrong, Anne Marie McLaughlin, Gordon Cooke, Edward McKone, Christine M. Costello, Charles G. Gallagher, Lin Leng, John A. Baugh, Günter Fingerle-Rowson, Richard J. Bucala, Paul McLoughlin, Seamas C. Donnelly
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury.Objectives: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF's tautomerase activity in a murine model of Pseudomonas aeruginosa infection.Methods: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif+/+) and in tautomerase-null, MIF gene knockin mice (mif P1G/P1G).Measurements and Main Results: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mifP1G/P1G compared with mif+/+ mice.Conclusions: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine.
COX-2–Dependent Cardiac Failure in Gh/tTG Transgenic Mice
Authors: Zhibing Zhang, Roberta Vezza, Theodore Plappert, Peter McNamara, John A. Lawson, Sandra Austin, Domenico Praticò, Martin St-John Sutton, Garret A. FitzGerald
Journal: Circulation Research (2003)

Gh is a GTP binding protein that couples to the thromboxane receptor (TP), but also functions as tissue transglutaminase II (tTG). A transgenic mouse model was generated in which Gh was overexpressed (GhOE) in ventricular myocytes under the control of the α-myosin heavy chain promoter. Heart rate was elevated and both blood pressure and left ventricular ejection fraction were depressed in GhOEs. Left ventricular mass was increased, consistent with genetic and ultrastructural evidence of hypertrophy. Fibrosis and apoptosis were also augmented. Survival declined disproportionately in older GhOEs. Cardiomyocyte expression of COX-2, thromboxane synthase (TxS), and the receptors for TxA 2 (the TP), PGF 2α (the FP), and PGI 2 (the IP) were upregulated and urinary 8,12- iso -iPF 2α -VI,2,3-dinor-6-keto-PGF 1α and 2,3-dinor-thromboxane B 2 were increased in GhOEs, reflecting increased lipid peroxidation and cyclooxygenase (COX) activation. Selective COX-2 inhibition, TP antagonism, and suppression of lipid peroxidation each rescued the cardiac phenotype. Infusion of an FP agonist exacerbated the phenotype, whereas administration of an IP agonist improved cardiac function. Directed cardiac overexpression of Gh/tTG causes both TG activation and increased TP/Gh-dependent signaling. The COX-2–dependent increase in TxA 2 generation augments cardiac hypertrophy, whereas formation of PGI 2 by the same isozyme ameliorates the phenotype. Oxidant stress may contribute, via regulation of COX-2 expression and/or ligation of the TP and the FP by isoprostanes. Gh/tTG activation regulates expression of COX-2 and its products may differentially modulate cardiomyocyte commitment to cell death or survival.
Association between the Epworth Sleepiness Scale and the Multiple Sleep Latency Test in a Clinical Population
Authors: Selim R. Benbadis
Journal: Annals of Internal Medicine (1999)

Background: Excessive daytime sleepiness can be evaluated with both subjective and objective tests. Objective: To examine the association between Epworth Sleepiness Scale scores and sleep latency on the multiple sleep latency test. Design: Case series. Setting: Referral sleep disorders center. Patients: 102 consecutive patients evaluated for excessive daytime sleepiness. Measurements: Epworth Sleepiness Scale scores and mean sleep latency on the multiple sleep latency test. Results: No significant association was seen between Epworth scores and mean sleep latency (Pearson correlation, −0.17 [95% CI, −0.35 to 0.03]; P = 0.09) (analysis of variance, P = 0.13). The mean Epworth score did not differ in three groups of patients who were defined by mean sleep latency as having normal sleep latency (>10 minutes), moderate sleep latency (5 to 10 minutes), or severe sleep latency (<5 minutes) (analysis of variance, P = 0.13). Conclusions: No statistically or clinically significant association was seen between Epworth scores and mean sleep latency. The subjective Epworth Sleepiness Scale and the objective multiple sleep latency test may evaluate different, complementary aspects of sleepiness.
“Refractory” Eosinophilic Airway Inflammation in Severe Asthma
Authors: Anneke ten Brinke, Aeilko H. Zwinderman, Peter J. Sterk, Klaus F. Rabe, Elisabeth H. Bel
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

It has been suggested that patients with refractory eosinophilic airway inflammation represent a separate “eosinophilic” asthma phenotype associated with increased morbidity and a poor prognosis. To investigate whether persistent eosinophilia in these patients is a fixed feature or can still be modified by treatment, we investigated the effect of high-dose intramuscular corticosteroids on eosinophils in induced sputum. Twenty-two patients with stable severe asthma (15 women, aged 21–73 years) participated in this double-blind, placebo-controlled study. All were using inhaled corticosteroids (⩾ 1,600 μg/day) or chronic oral prednisone. They were included if the percentage of eosinophils in induced sputum was above the upper limit of normal (⩾ 2%). Two weeks after treatment with triamcinolone, but not placebo, sputum eosinophils almost completely disappeared from a median of 12.6–0.2% (p < 0.001). In 82% of patients, no eosinophils could be observed at all. In addition, the rescue medication score decreased...
Leucocyte superoxide dismutase in rheumatoid arthritis.
Authors: A A Youssef, D N Baron
Journal: Annals of the Rheumatic Diseases (1983)

Superoxide dismutase (SOD) activity was measured in polymorphonuclear leucocytes (PMNLs) and mononuclear cells (MNCs) from 60 patients with rheumatoid arthritis (RA) and in 15 controls. In all patients and controls SOD activity (U/mg protein) in MNCs was twice that in PMNLs. SOD activity in PMNLs and in MNCs from patients with RA was significantly higher than that in controls. SOD activity in PMNLs (but not in MNCs) from patients treated with corticosteroids was significantly higher than that from patients treated with nonsteroidal anti-inflammatory drugs. There was no relation between SOD activity in both PMNLs and MNCs and either the patients9 age, sex, duration of disease, serum immunoglobulin concentration, IgM rheumatoid factor, and copper level, or the degree of disease activity.
Management of Infantile Eczema
Authors: J. T. Ingram
Journal: BMJ (1962)

The management of infantile eczema turns upon a correct diagnosis, which is relatively easy, and upon the proper interpretation of the meaning of that diagnosis, which is more difficult. Wise men would not be too dogmatic on this subject, but I fear that the compression of what I have to say into a limited space of time may give an air of dogmatism. I am, however, conscious of the variety of opinions about infantile eczema held by experienced physicians, and I am very conscious of the fact that the problem is always a peculiarly individual one concerning not only the parti cular patient and particular family but also the doctor, and that it has to be assessed on its merits.
SIX CASES OF HYPERTENSIVE CRISIS IN PATIENTS ON TRANYLCYPROMINE AFTER EATING CHICKEN LIVERS
Authors: DAVID L. HEDBERG, MALCOLM W. GORDON, BERNARD C. GLUECK
Journal: American Journal of Psychiatry (1966)

Chicken livers ingested by patients who were receiving the MAO inhibitor, tranylcypromine, gave rise to six serious hypertensive episodes and four moderately severe side reactions. Biochemical analysis of samples of chicken livers ingested by patients who showed adverse reactions showed the presence of approximately 100 µg/gm of tyramine. Further investigation is needed to verify the hypothesis that patients on tranylcypromine and a phenothiazine who ingested liver were free of symptoms as a result of the protection afforded by the phenothiazine when prescribed with the MAO inhibitor at a given milligram ratio.
CONTACT PHOTODERMATITIS DUE TO TRIBROMSALICYLANILTDE
Authors: P. E. OSMUNDSEN
Journal: British Journal of Dermatology (1968)

SUMMARY.— During a period of 3 months contact photoallergy to tribrom‐salicylanilide (TBS) in a toilet soap was diagnosed in 39 patients in Copenhagen. The clinical features are described and the results of photopatch tests are reported. The importance of using long wave UV in photopatch testing is emphasized. Evidence is presented that TBS is a primary photosensitizer with a sensitizelzing potential approximately equal to that of tetrachlorsalicylanilide. The frequency of photosensitization is estimated as 1:1000 users.
T cell receptor for antigen induces linker for activation of T cell–dependent activation of a negative signaling complex involving Dok-2, SHIP-1, and Grb-2
Authors: Shen Dong, Béatrice Corre, Eliane Foulon, Evelyne Dufour, André Veillette, Oreste Acuto, Frédérique Michel
Journal: The Journal of Experimental Medicine (2006)

Adaptor proteins positively or negatively regulate the T cell receptor for antigen (TCR) signaling cascade. We report that after TCR stimulation, the inhibitory adaptor downstream of kinase (Dok)-2 and its homologue Dok-1 are involved in a multimolecular complex including the lipid phosphatase Src homology 2 domain–containing inositol polyphosphate 5′-phosphatase (SHIP)-1 and Grb-2 which interacts with the membrane signaling scaffold linker for activation of T cells (LAT). Knockdown of LAT and SHIP-1 expression indicated that SHIP-1 favored recruitment of Dok-2 to LAT. Knockdown of Dok-2 and Dok-1 revealed their negative control on Akt and, unexpectedly, on Zap-70 activation. Our findings support the view that Dok-1 and -2 are critical elements of a LAT-dependent negative feedback loop that attenuates early TCR signal. Dok-1 and -2 may therefore exert a critical role in shaping the immune response and as gatekeepers for T cell tolerance.
Post-pneumonectomy oesophageal fistula
Authors: J. P. Evans
Journal: Thorax (1972)

The complication of oesophagopleural fistula is described in eight of 1,389 patients (0·5%) who underwent pneumonectomy for carcinoma of the bronchus. All the patients had a right pneumonectomy performed and seven of the eight patients developed a bronchopleural fistula before developing an oesophageal fistula. The complication appeared between two weeks and 22 months after pneumonectomy. All the fistulae occurred on the right side; three were at the level of the bronchial stump and five were within 5 cm below the stump. The cause of the fistula was thought to be the development of a peribronchial abscess which ruptured into the oesophagus. The complication was diagnosed by the presence of food particles on the dressings in those patients with chest drains <i>in situ.</i> It was confirmed by Gastrografin swallow. The size of the fistulae varied between 3 and 8 mm. Successful immediate surgical closure of the fistula was accomplished in three patients. Feeding was continued using a gastrostomy. Five patients unfit for surgery and treated by palliative measures died.