tbuckley/cabot-search huggingface dataset:
Food Iron Absorption Measured by an Extrinsic Tag
Authors: J. D. Cook, M. Layrisse, C. Martinez-Torres, R. Walker, E. Monsen, C. A. Finch
Journal: Journal of Clinical Investigation (1972)

The paper describes the use of an extrinsic tag of inorganic radioiron to determine the total absorption of nonheme iron from a complete meal. The method was developed by measuring the iron absorbed from vegetable foods containing biosynthetically incorporated 55Fe (intrinsic tag) and from 59Fe added as a small dose of inorganic iron to the same meal (extrinsic tag). In studies with maize, black bean, and wheat, a consistent extrinsic: intrinsic radioiron absorption ratio averaging 1.10 was observed. Similar results were obtained with either ferrous or ferric iron as the extrinsic tag, and with doses of the latter ranging from 0.001 to 0.5 mg iron added to a test meal containing 2-4 mg of food iron. Adding the radioiron at different stages in preparation of the test meal also had little effect. Separate administration of the extrinsic tag was less satisfactory when small portions of a single food were employed, but with a complete meal, the separate dose was preferable. The extrinsic tag provided a valid measure of absorption despite marked differences in the iron status of the subject, and with wide changes in absorption imposed by adding desferrioxamine or ascorbic acid to the test meal. These findings indicate that there is a common pool of nonheme iron, the absorption of which is influenced by various blocking or enhancing substances present in the meal.
The Role of Podocalyxin in Health and Disease
Authors: Julie S. Nielsen, Kelly M. McNagny
Journal: Journal of the American Society of Nephrology (2009)

Podocalyxin, a sialomucin most closely related to CD34 and endoglycan, is expressed by kidney podocytes, hematopoietic progenitors, vascular endothelia, and a subset of neurons; aberrant expression has recently been implicated in a range of cancers. Through interactions with several intracellular proteins and at least one extracellular ligand, podocalyxin regulates both adhesion and cell morphology. In the developing kidney, podocalyxin plays an essential role in the formation and maintenance of podocyte foot processes, and its absence results in perinatal lethality. Podocalyxin expression in the hematopoietic system correlates with cell migration and the seeding of new hematopoietic tissues. In addition, it is abnormally expressed in subsets of breast, prostate, liver, pancreatic, and kidney cancer as well as leukemia. Strikingly, it is often associated with the most aggressive cases, and it is likely involved in metastasis. Thus, a thorough investigation of the normal activities of podocalyxin may facilitate the development of new cancer treatment strategies.
Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data
Authors: K. J L Bell, A. Hayen, P. Macaskill, L. Irwig, J. C Craig, K. Ensrud, D. C Bauer
Journal: BMJ (2009)

<b>Objective:</b> To assess the value of monitoring response to bisphosphonate treatment by means of measuring bone mineral density. <b>Design</b> Secondary analysis of trial data using mixed models. <b>Data source</b> The Fracture Intervention Trial, a randomised controlled trial that compared the effects of alendronate and placebo in 6459 postmenopausal women with low bone mineral density recruited between May 1992 and May 1993. Bone density measurements of hip and spine were obtained at baseline and at one, two, and three years after randomisation. <b>Main outcome measures</b> Between-person (treatment related) variation and within-person (measurement related) variation in hip and spine bone mineral density. <b>Results</b> The mean effect of three years’ treatment with alendronate was to increase hip bone mineral density by 0.030 g/cm<sup>2</sup>. There was some between-person variation in the effects of alendronate, but this was small in size compared with within-person variation. Alendronate treatment is estimated to result in increases in hip bone density ≥0.019 g/cm<sup>2</sup> in 97.5% of patients. <b>Conclusions:</b> Monitoring bone mineral density in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading. Routine monitoring should be avoided in this early period after bisphosphonate treatment is commenced.
Acute Nonspecific Pericarditis
Authors: DAVID B. CARMICHAEL, HOWARD B. SPRAGUE, STANLEY M. WYMAN, EDWARD F. BLAND
Journal: Circulation (1951)

Acute nonspecific pericarditis has been recognized with increasing frequency in recent years although there is reason to believe that it was considered distinct from rheumatic pericarditis almost 100 years ago. The authors have been able to secure follow-up information on 50 cases seen between 1930 and 1949. A few have shown persistent electrocardiographic changes, and calcification of the pericardium occurred in 1 case. In general the prognosis appears excellent and we have not observed constrictive pericarditis as a sequela.
Physiological and clinical effects of diurnal noninvasive ventilation in hypercapnic COPD
Authors: O. Díaz, P. Bégin, M. Andresen, M. E. Prieto, C. Castillo, J. Jorquera, C. Lisboa
Journal: European Respiratory Journal (2005)

To assess the clinical impact of noninvasive mechanical ventilation (NIMV) on stable hypercapnic chronic obstructive pulmonary disease, changes in exercise capacity, dyspnoea and simple physiological parameters were evaluated. The time course of these effects during treatment and recovery was also assessed. Patients were randomly allocated to NIMV (n = 27) or sham-NIMV (n = 15), applied 3 h·day −1 , 5 days a week, for 3 weeks. A 6-min walking distance (6MWD), arterial blood gases, spirometry, pattern of breathing, mouth occlusion pressure ( P 0.1 ), and respiratory system impedance (P 0.1 /tidal volume ( V T )/inspiratory time ( t I )) were measured weekly during treatment and 2 weekly during follow-up. Transition dyspnoea index (TDI) was also measured. During NIMV, carbon dioxide arterial tension decreased progressively, concomitantly with a slow deep pattern of breathing, a proportional increase in the forced expiratory volume in one second (FEV 1) , the forced vital capacity and significant reductions of P 0.1 and P 0.1 / V T / t I . The 6MWD improved by a mean of 76 m after NIMV, and by 73 m and 61 m 1 and 2 weeks, respectively, after treatment. Dyspnoea improved with a mean TDI of three points. Changes in 6MWD were highly related to TDI and to a lesser extent to changes in FEV 1 (r = 0.60). The current authors conclude that noninvasive mechanical ventilation has significant and sustained clinical impact in stable hypercapnic chronic obstructive pulmonary disease.
Management of stable chronic obstructive pulmonary disease in primary and secondary care: summary of updated NICE guidance
Authors: J. O'Reilly, M. M. Jones, J. Parnham, K. Lovibond, M. Rudolf
Journal: BMJ (2010)

Over three million people in the United Kingdom are estimated to have chronic obstructive pulmonary disease (COPD), of whom more than two million remain undiagnosed, representing the so called "missing millions" alluded to in the draft national strategy for COPD.1 2 3 This article summarises the most recent recommendations from the National Institute for Health and Clinical Excellence (NICE) on the management of stable chronic obstructive pulmonary disease in primary and secondary care,4 which update the COPD guidelines first published by NICE in 2004.5 The summary contains the most important recommendations relating to new diagnostic criteria for COPD, changes to the classification of severity of airflow obstruction, the need for multidimensional severity assessment, a new algorithm for inhaled drug treatments (figure⇓), and the value of early pulmonary rehabilitation. Algorithm for use of inhaled therapies NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the updated recommendations are given in italic in square brackets. ### Diagnosing COPD
Glomerular Permselectivity at the Onset of Nephropathy in Type 2 Diabetes Mellitus
Authors: KEVIN V. LEMLEY, KRISTINA BLOUCH, ISHA ABDULLAH, DEREK B. BOOTHROYD, PETER H. BENNETT, BRYAN D. MYERS, ROBERT G. NELSON
Journal: Journal of the American Society of Nephrology (2000)

The development of microalbuminuria in individuals with type 2 diabetes mellitus is associated with a 10-fold increase in the risk of progression to overt nephropathy and eventual end-stage renal failure. The present study reports long-term (up to 8 yr) follow-up of 43 Pima Indians with type 2 diabetes detected on screening to have microalbuminuria. The natural history of albuminuria in these individuals included progression to overt proteinuria (urinary albumin excretion > or = 300 mg/d) in half of the participants by 7 yr of follow-up. The size selectivity of the glomerular barrier was also investigated using dextran sieving and pore theory. Whereas a comparison group of macroalbuminuric Pima Indians had an excess of large pores that served as a macromolecular "shunt," individuals with microalbuminuria had a shunt size no different from long-term diabetic, normoalbuminuric control subjects. An abrupt transition from little or no relationship to a highly significant and positive relationship between increasing albuminuria and shunt size occurred at an albumin-to-creatinine ratio of approximately 3000 mg/g. Shunt size in macroalbuminuric individuals correlated with the extent of foot process broadening. Podocyte foot processes in microalbuminuric participants were not different from those in control subjects. In conclusion, although microalbuminuria in type 2 diabetic Pima Indians often heralds progressive glomerular injury, it is not the result of defects in the size permselectivity of the glomerular barrier but rather of changes in either glomerular charge selectivity or tubular handling of filtered proteins or of a combination of these two factors.
Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
Authors: Stephanie Humblet-Baron, Blythe Sather, Stephanie Anover, Shirly Becker-Herman, Debora J. Kasprowicz, Socheath Khim, Thuc Nguyen, Kelly Hudkins-Loya, Charles E. Alpers, Steve F. Ziegler, Hans Ochs, Troy Torgerson, Daniel J. Campbell, David J. Rawlings
Journal: Journal of Clinical Investigation (2007)

Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell activation. Patients with WAS exhibit both immunodeficiency and a marked susceptibility to systemic autoimmunity. We investigated whether alterations in Treg function might explain these paradoxical observations. While WASp-deficient (WASp(-/-)) mice exhibited normal thymic Treg generation, the competitive fitness of peripheral Tregs was severely compromised. The total percentage of forkhead box P3-positive (Foxp3(+)) Tregs among CD4(+) T cells was reduced, and WASp(-/-) Tregs were rapidly outcompeted by WASp(+) Tregs in vivo. These findings correlated with reduced expression of markers associated with self-antigen-driven peripheral Treg activation and homing to inflamed tissue. Consistent with these findings, WASp(-/-) Tregs showed a reduced ability to control aberrant T cell activation and autoimmune pathology in Foxp3(-/-)Scurfy (sf) mice. Finally, WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient with a spontaneous revertant mutation, indicating that altered Treg fitness likely explains the autoimmune features in human WAS.
A five-year series on the use of noninvasive ventilation as a weaning tool from invasive ventilation
Authors: Adrian Kee, Jason Phua, Yiqing Huang, Eleanor Dela Pena, Erlinda Santiago, Juliet Santos, Sunitha Palani, Rolando Capistrano, Joy Dizon, T.K. Lim
Journal: European Respiratory Journal (2011)

Data from randomised-controlled trials suggest that use of noninvasive ventilation (NIV) as a weaning tool decreases mortality, length of stay (LOS) and duration of invasive ventilation. We aimed to evaluate if increased use of NIV after high-risk extubation over time was associated with improvement in outcomes in the clinical setting.  In this prospective cohort study of all invasively ventilated patients (n=2316) in our medical intensive care unit (ICU) between 2006-2010, we performed time-trend analyses using simple logistic and linear regression to determine temporal changes in post-extubation NIV use, ventilator days, ICU LOS, reintubation rates, and ICU mortality. During this time we had gradually implemented the use of NIV post-extubation in patients with risk factors for extubation failure.  The proportion of patients receiving NIV post-extubation increased from 2006-2010: 21.1%, 22.0%, 28.4%, 34.6% and 32.8% respectively (OR 1.20 with each passing year, 95% CI 1.12-1.29). The commonest indication for NIV was high-risk extubation despite a successful spontaneous breathing trial (79.1%). Increased NIV use was associated with temporal decreases in invasive ventilator days and ICU LOS but these were neither statistically nor clinically significant. There were significant associated decreases in overall reintubation rates (OR 0.87 per year, 95% CI 0.76-0.99) and ICU mortality (OR 0.82 per year, 95% CI 0.76-0.87).  Although greater use of NIV post-extubation did not reduce ventilator days and ICU LOS in a general medical ICU population, there were associated improvements in reintubation rates and mortality. Confounders included a heterogeneous population and sedation protocols.
The Effect of Keto-analogues of Essential Amino Acids in Severe Chronic Uremia
Authors: Mackenzie Walser, A. Will Coulter, Shrikant Dighe, Frank R. Crantz
Journal: Journal of Clinical Investigation (1973)

Alpha keto-analogues of valine, leucine, isoleucine, methionine, phenylalanine, and (in one instance) tryptophan and histidine, along with the remaining essential amino acids, were administered orally to 10 patients with severe chronic uremia fed a diet low in protein but adequate in calories. Ketoacid dosage varied from 6 to 14 g daily, as sodium or calcium salts. Net nitrogen intake, calculated as intake minus urinary protein nitrogen, averaged 1.8 g/day. The urea space was either estimated or measured with [(14)C]urea and daily changes in the body urea pool were calculated. Urea appearance was measured as the sum of urea excretion and the change in urea pool. If these ketoacids were converted to amino acids and utilized for protein synthesis, a fall in urea nitrogen appearance should occur. In five subjects, ketoacids were given for 15-18 days and then withdrawn. Urea nitrogen appearance increased 1.55 g/day on withdrawing ketoacids, and corrected nitrogen balance decreased by 1.73 g/day. In two other subjects ketoacid administration was followed, on two occasions each, by a period of administration of nine essential amino acids. In three of these four instances, urea appearance rose significantly with amino acids. In four patients studied at high blood urea levels, ketoacid treatment was relatively ineffective; two of these patients responded more favorably when studied again after peritoneal dialysis. One of these improved enough clinically to be managed as an out-patient for short intervals, despite virtual anuria. No accumulation of ketoacids in plasma or urine could be detected, and no toxicity was identified.
Comparison of high and low intensity training in well controlled rheumatoid arthritis. Results of a randomised clinical trial.
Authors: C H van den Ende, J M Hazes, S le Cessie, W J Mulder, D G Belfor, F C Breedveld, B A Dijkmans
Journal: Annals of the Rheumatic Diseases (1996)

To investigate the benefit of intensive dynamic exercises in comparison to range of motion (ROM) and isometric exercises in rheumatoid arthritis.100 consecutive rheumatoid arthritis patients on stable medication were randomly assigned to (1) intensive dynamic group exercises which included full weight bearing exercises and conditioning exercises on a stationary bicycle while the heart rate was maintained at 70-85% of the age predicted maximum heart rate, (2) range of motion (ROM) exercises and isometric exercises in a group, (3) individual isometric and ROM exercises, and (4) home instructions for isometric and ROM exercises. Variables of physical condition, muscle strength, joint mobility, daily functioning (HAQ), and disease activity were assessed before and after the 12 week exercise course, and 12 weeks thereafter. An intention to treat analysis was performed.Increases in aerobic capacity (n = 77), muscle strength, and joint mobility in the high intensity exercise programme were respectively 17%, 17% and 16% and differed significantly from the changes in aerobic capacity, muscle strength, and joint mobility in the other exercise groups. No deterioration of disease activity was observed. Twelve weeks after discontinuation of the exercise course the gain in physical capacity had disappeared.Intensive dynamic training is more effective in increasing aerobic capacity, joint mobility, and muscle strength than ROM exercises and isometric training in rheumatoid arthritis patients with well controlled disease.
Clinicopathologic characteristics and treatment outcome of the addition of rituximab to chemotherapy for CD5-positive in comparison with CD5-negative diffuse large B-cell lymphoma
Authors: N. Niitsu, M. Okamoto, J.-i. Tamaru, T. Yoshino, N. Nakamura, S. Nakamura, K. Ohshima, H. Nakamine, M. Hirano
Journal: Annals of Oncology (2010)
Long-term follow-up on effectiveness and safety of etanercept in juvenile idiopathic arthritis: the Dutch national register
Authors: F H M Prince, M Twilt, R ten Cate, M A J van Rossum, W Armbrust, E P A H Hoppenreijs, M van Santen-Hoeufft, Y Koopman-Keemink, N M Wulffraat, L W A van Suijlekom-Smit
Journal: Annals of the Rheumatic Diseases (2008)

<b>Introduction:</b> Twelve percent of our domiciliary NIV patients (n=278)* develop skin issues associated with mask use. We now wish to engage mask users and their carers to help design future research to improve the incidence of skin issues for those using domiciliary NIV. <b>Objectives:</b> To engage patients and their carers who use domiciliary NIV to identify what are the most important questions to include in future research. <b>Methods:</b> We invited patients and their carers who use domiciliary NIV and have a diagnosis of MND or COPD to take part in a Patient and Public Involvement (PPI) focus group. Open questions were used to facilitate a discussion around what users and their carers felt were the most relevant issues for future research. <b>Results:</b> 12 adults (3 MND, 9 COPD) using domiciliary NIV and their carers took part. 8 patients had previous skin issues associated with NIV mask use. Recommendations for future research included: the need for clearer and innovative advice platforms for skin care and mask cleaning; improving the comfort and fit for both masks and straps by individual moulding and via innovative materials; improving the ease of putting a mask on, particularly at night when there is low light and poor vision; development of warm weather mask/straps designs to minimise skin irritation through sweating; improving peer support via social media. <b>Conclusion:</b> Our PPI group identified a number of key areas for our future research. Using a PPI, focus group approach has enabled us to design future research based on patient-identified priority areas. <i>*Ewles S et al. Eur Respir J 2018 (52) suppl 62; PA2372.</i>
Meta-analysis of the risk of mortality with salmeterol and the effect of concomitant inhaled corticosteroid therapy
Authors: M Weatherall, M Wijesinghe, K Perrin, M Harwood, R Beasley
Journal: Thorax (2009)

There is concern that long-acting beta agonist (LABA) drugs may increase the risk of asthma mortality.A meta-analysis was conducted of asthma deaths in randomised controlled clinical trials from the GlaxoSmithKline database that compared salmeterol with a non-LABA comparator treatment in asthma. The Peto one-step method was used to determine the risk overall (all studies) and in derived datasets based on inhaled corticosteroid (ICS) use.There were 35 asthma deaths in 215 studies with 106,575 subjects. Two studies (SMART and SNS) contributed 30/35 (86%) asthma deaths, the overall findings largely reflecting the characteristics of these studies. The odds ratio for risk of asthma mortality with salmeterol was 2.7 (95% CI 1.4 to 5.3). In 54 placebo controlled studies the risk of death from asthma in patients not prescribed ICS was 7.3 (95% CI 1.8 to 29.4). In 127 studies in which patients were prescribed ICS, the risk of asthma death was 2.1 (95% CI 0.6 to 7.9). In 63 studies in which patients were randomised to receive the combination salmeterol/fluticasone propionate inhaler or ICS, there were no asthma deaths among 22,600 patients.Salmeterol monotherapy in asthma increases the risk of asthma mortality and this risk is reduced with concomitant ICS therapy. There is no evidence that combination salmeterol/fluticasone propionate therapy is associated with an increased risk of asthma mortality, although this interpretation is limited by the low statistical power of available studies.
Biochemical Correlates of Cardiac Hypertrophy: III. CHANGES IN DNA CONTENT; THE RELATIVE CONTRIBUTIONS OF POLYPLOIDY AND MITOTIC ACTIVITY
Authors: David Grove, K. G. Nair, Radovan Zak
Journal: Circulation Research (1969)

DNA concentration in the left ventricle of 3-month-old rats 3 to 12 days after aortic constriction was similar to the values obtained in sham-operated litter mates (1.38 ± 0.03 µg/mg wet weight). The total DNA content of the heart was thus increased proportionally to its enlargement. In chronic hypertrophy (2 to 4 months after aortic constriction), the DNA content was increased to a significantly less extent than in short-term hypertrophy. The percentage of polyploid nuclei in 12- to 13-week-old rats increased 1 to 3 weeks after aortic constriction from a normal value of 1.8% to 4.2%. In 17- to 18-week-old rats, polyploidy was present in 3.9% of the nuclei 10 days after banding as compared with 1.6% in normal rats. Mitotic figures were localized almost exclusively outside muscle cells. Mitotic indices in hypertrophied hearts were ten times higher than in controls during the first 3 weeks after aortic constriction.