tbuckley/cabot-search huggingface dataset:
Fatigue in primary Sjogren's syndrome
Authors: P J Barendregt, M R M Visser, E M A Smets, J H M Tulen, A H van den Meiracker, F Boomsma, H M Markusse
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To assess fatigue in relation to depression, blood pressure, and plasma catecholamines in patients with primary Sjögren's syndrome (SS), in comparison with healthy controls and patients with rheumatoid arthritis. <h3>METHODS</h3> For the assessment of fatigue the Multidimensional Fatigue Inventory (MFI) was used, a 20 item questionnaire, covering the following dimensions: general fatigue, physical fatigue, mental fatigue, reduced motivation, and reduced activity. Furthermore, the Zung depression scale was used to quantify aspects of depression. Forty nine female primary SS patients, 44 female patients with rheumatoid arthritis (RA), and 32 healthy women filled in both questionnaires. In addition, supine values of blood pressure and plasma catecholamines were measured in the patients with primary SS. <h3>RESULTS</h3> Primary SS patients were more fatigued compared with the healthy controls on all the five dimensions of the MFI. When the analyses were repeated using depression as a covariate, group differences disappeared for the dimensions of reduced motivation and mental fatigue. In the primary SS patients, significant positive correlations between depression and the dimensions of reduced motivation and mental fatigue were found. Comparing patients with primary SS with those with RA, using depression as covariate, no statistically significant differences were found between these groups. No relation between fatigue and blood pressure was found, but a negative correlation was observed between the general fatigue subscale of the MFI and plasma noradrenaline. <h3>CONCLUSION</h3> Patients with primary SS report more fatigue than healthy controls on all the dimensions of the MFI and when controlling for depression significant differences remain on the dimensions of general fatigue, physical fatigue, and reduced activity. The negative correlations between levels of noradrenaline and general fatigue in patients with primary SS may imply the involvement of the autonomic nervous system in chronic fatigue.
Neurotoxicity From Oxaliplatin Combined With Weekly Bolus Fluorouracil and Leucovorin As Surgical Adjuvant Chemotherapy for Stage II and III Colon Cancer: NSABP C-07
Authors: Stephanie R. Land, Jacek A. Kopec, Reena S. Cecchini, Patricia A. Ganz, H. Samuel Wieand, Linda H. Colangelo, Kate Murphy, J. Philip Kuebler, Thomas E. Seay, Burton M. Needles, James D. Bearden, Lauren K. Colman, Keith S. Lanier, Eduardo R. Pajon, David Cella, Roy E. Smith, Michael J. O'Connell, Joseph P. Costantino, Norman Wolmark
Journal: Journal of Clinical Oncology (2007)

Purpose The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments. Patients and Methods Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up. Results A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P &lt; .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, “quite a bit” of cold-induced hand/foot pain 26% FLOX v 2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group. Conclusion Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.
Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis
Authors: Ida K Haugen, Barbara Slatkowsky Christensen, Pernille Bøyesen, Sølve Sesseng, Désirée van der Heijde, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To explore whether changes of MRI-defined synovitis and bone marrow lesions (BMLs) are related to changes in joint tenderness in a 5-year longitudinal study of the Oslo hand osteoarthritis (OA) cohort. Methods We included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and contrast-enhanced synovitis in the distal and proximal interphalangeal joints were evaluated on 0–3 scales in n=69 and n=48 patients, respectively. Among joints without tenderness at baseline, we explored whether increasing/incident synovitis and BMLs were associated with incident joint tenderness using generalised estimating equations. Among joints with tenderness at baseline, we explored whether decreasing or resolution of synovitis and BMLs were associated with loss of joint tenderness. We adjusted for age, sex, body mass index, follow-up time and changes in radiographic OA. Results Among joints without tenderness at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220 (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant associations to incident joint tenderness were found for increasing/incident synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58) independent of structural progression. We found a trend that resolution of synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but these associations were non-significant. Conclusions The Oslo hand OA cohort is the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were significantly associated with incident joint tenderness, whereas no significant associations were found for decreasing or loss of synovitis and BMLs.
The Effect of Previous Alcohol Abuse on Cognitive Function in HIV Infection
Authors: Jill E. Green, Radu V. Saveanu, Robert A. Bornstein
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors’ goal was to study the potential effect on cognitive function of an interaction of HIV infection and a history of alcohol abuse. METHOD: The subjects were 30 HIV-negative and 50 HIV-positive men with and without a past history of alcohol abuse. Thirty-three of the men (12 HIV negative and 21 HIV positive) had a past history of alcohol abuse, and 47 (18 HIV negative and 29 HIV positive) had never abused alcohol. Each subject’s history of alcohol use was obtained by using a syndromal approach based on the Structured Clinical Interview for DSM-III-R and a quantitative approach. Each subject was given a battery of neuropsychological tests assessing verbal reasoning, reaction time, intelligence, memory, and dexterity. The subjects were then compared on a summary neuropsychological impairment rating. RESULTS: There were no significant differences in CD4 level, age, education, depression, anxiety, or other drug abuse history between the HIV-positive and HIV-negative groups with and without a history of alcohol abuse. Significant effects on cognitive function were found for past alcohol abuse and HIV infection, with significant interactions in verbal reasoning, auditory processing, and reaction time. This demonstrates that HIV infection and a history of alcohol abuse have independent effects on some aspects of higher cognitive function but may have synergistic effects on other cognitive domains. In the HIV-negative subjects there were no differences in cognitive function between subjects with and without a history of alcohol abuse. Among the HIV-positive subjects, those with a history of alcohol abuse performed more poorly on tests of verbal IQ, verbal reasoning, and reaction time. CONCLUSIONS: There are both additive and interactive effects of previous alcohol abuse and HIV infection on cognition. Individuals with a history of past alcohol abuse may be at greater risk for cognitive dysfunction in the context of HIV infection.
THE CORRELATION OF FUNCTION: WITH SPECIAL REFERENCE TO THE ORGANS OF INTERNAL SECRETION AND THE REPRODUCTIVE SYSTEM: A British Medical Association Lecture Delivered before the Preston Division on May 21st, 1920
Authors: W. B. Bell
Journal: BMJ (1920)

FIFTY years ago specialists were composed of a body of ,men who had been carried by tiheir scientific bias to limit ;their practical work, as far as possible, but rarely com- pletely, to medicine, surgery, or midwifery; andI venture .tothink that mien whio slhot over tlle rouglh before attempt- .ing to brizng down driven partridges and rocketing plheasanits ,inade specialists whlo lhad a wider outlook and greater ipower of practical deduction tlhan would lhave been the .caselhad they been fed on 'high game from the cradle.Yet, with the tremendous and rapidly accumulatinig knowledge-that camie like an avalanche at the end of tle 'Yictorian era, and has continued ever siince, it became 'inevitable that, unless the brain of the practitioner of -nedicine expanded proportionately, sone must devote
Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control
Authors: Z. Huang
Journal: Journal of Clinical Investigation (2005)

Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80 years ago, the precise identity and mechanism of the oxygen sensor and mediators of vasodilation remain uncertain. In support of a possible role for hemoglobin (Hb) as a sensor and effector of hypoxic vasodilation, here we show biochemical evidence that Hb exhibits enzymatic behavior as a nitrite reductase, with maximal NO generation rates occurring near the oxy-to-deoxy (R-to-T) allosteric structural transition of the protein. The observed rate of nitrite reduction by Hb deviates from second-order kinetics, and sigmoidal reaction progress is determined by a balance between 2 opposing chemistries of the heme in the R (oxygenated conformation) and T (deoxygenated conformation) allosteric quaternary structures of the Hb tetramer--the greater reductive potential of deoxyheme in the R state tetramer and the number of unligated deoxyheme sites necessary for nitrite binding, which are more plentiful in the T state tetramer. These opposing chemistries result in a maximal nitrite reduction rate when Hb is 40-60% saturated with oxygen (near the Hb P50), an apparent ideal set point for hypoxia-responsive NO generation. These data suggest that the oxygen sensor for hypoxic vasodilation is determined by Hb oxygen saturation and quaternary structure and that the nitrite reductase activity of Hb generates NO gas under allosteric and pH control.
Application of Tracheal Gas Insufflation to Acute Unilateral Lung Injury in an Experimental Model
Authors: LLUIS BLANCH, THOMAS E. VAN der KLOOT, A. MELYNNE YOUNGBLOOD, GASTON MURIAS, ALBERTO NAVEIRA, ALEX B. ADAMS, PABLO V. ROMERO, AVI NAHUM
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until PaO2 /Fi O2 fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H2O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved PaO2 /Fi O2 from 212 ± 43 to 301 ± 38 mm Hg (p < 0.01) while PaCO2 and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml / kg while keeping EELV constant, normalized PaCO2 , did not affect PaO2 /Fi O2 , and decreased end-inspiratory plateau pressure from 16.6 ± 1.0 to 11.9 ± 0.5 cm H2O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.
Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function.
Authors: A Moretta, G Pantaleo, M C Mingari, L Moretta, J C Cerottini
Journal: The Journal of Experimental Medicine (1984)

In an attempt to define the requirement of T8, T4, and T3 surface molecules in functional interactions occurring between human cytolytic T lymphocytes (CTL) and specific target cells, we have analyzed a large number of CTL clones derived from primary mixed lymphocyte culture (MLC) T cell populations for their susceptibility to inhibition by monoclonal antibodies (mAb) directed against these surface antigens. In most experiments, MLC T cells were stained with B9.4 (anti-T8) or OKT4 (anti-T4) mAb, separated into positive and negative cells using a fluorescence-activated cell sorter (FACS) and cloned under limiting conditions. While the lytic activity of the majority of T8+ CTL clones was inhibited by B9.4 mAb, approximately 15% of these clones were unaffected even in the presence of excess antibody. Flow cytofluorometric analysis of T8 antigen in individual clones did not show any correlation between the amount of T8 antigen expressed, the magnitude of cytolytic activity and the susceptibility (or lack thereof) to inhibition by B9.4 mAb. Of the 16 T4+ CTL clones analyzed, 7 were resistant to inhibition by OKT4 mAb even at doses 10-fold higher than that sufficient for complete inhibition of susceptible clones. Again, no correlation was found between the amount of T4 antigen expressed and the susceptibility to inhibition by the corresponding antibody. The same sets of T8+ and T4+ CTL clones were also analyzed for their susceptibility to inhibition by OKT3 mAb. Although all of the clones expressed the T3 surface antigen, only 15/23 T8+ clones and 9/14 T4+ clones were inhibited by anti-T3 mAb. To further document this clonal heterogeneity, we selected two T3+ T4- T8+ CTL clones that had no concomitant NK-like activity. One clone was resistant to inhibition by OKT3 mAb, whereas the other was highly susceptible. Incubation with OKT3 mAb resulted in modulation of the T3 molecules in both clones. Following modulation, however, the cytolytic activity of the resistant clones was unaffected, whereas the lytic activity of the susceptible clone was abrogated. These results thus indicate extensive clonal heterogeneity in the requirement for T3, T4, and T8 molecules in CTL function. Moreover, it appears that T3 molecules are not always physically and functionally linked to CTL receptor structures.
Genome Medicine: past, present and future
Authors: Charles Auffray, Timothy Caulfield, Muin J Khoury, James R Lupski, Matthias Schwab, Timothy Veenstra
Journal: Genome Medicine (2011)

e field of genomic medicine continues to expand, driven by the efforts of numerous researchers around the world.To celebrate Genome Medicine's 2nd anniversary, we asked our Section Editors what they felt were the most exciting breakthroughs in research in the past 2 years and what the future of genomic medicine might hold.
Electrostatic charge on a plastic spacer device influences the delivery of salbutamol
Authors: JH Wildhaber, SG Devadason, MJ Hayden, R James, AP Dufty, RA Fox, QA Summers, PN LeSouef
Journal: European Respiratory Journal (1996)

The aim of this study was to determine whether electrostatic charge on a plastic spacer decreases the delivery of salbutamol from a pressurized metered-dose inhaler (pMDI) and, if so, to find an optimal and practical treatment to remove the charge. Ten single actuations from a salbutamol pMDI were drawn through different Volumatic spacers at a constant flow of 60 L.min-1. The efficacies of different methods of removing charge were tested, including detergent coating of the spacers. A multistage liquid impinger was used to determine the particle size distribution of the output of the pMDI through the Volumatic spacers. The electrostatic charge on the inner surface of the spacers was measured both quantitatively with an electrometer, and qualitatively by the attraction of a thin strip of cellulose membrane to the wall of the spacer. Each experiment was repeated four times. Ionic detergent coating of the spacers removed the charge for at least 24 h. This resulted in an increase of 55-70% in small particle (&lt; 6.8 microns) delivery compared to delivery from new spacers with high charge. We have demonstrated that electrostatic charge plays a major role in the delivery of salbutamol through plastic spacers. Adequate treatment with ionic detergent removes the charge and improves drug delivery.
Macrophage Polarization in Pancreatic Carcinoma: Role of Heparanase Enzyme
Authors: Esther Hermano, Amichay Meirovitz, Karen Meir, Gabriel Nussbaum, Limor Appelbaum, Tamar Peretz, Michael Elkin
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundTumor microenvironment, and particularly tumor-associated macrophages (TAMs), represent a key contributing factor in pancreatic ductal adenocarcinoma (PDAC) pathogenesis. Here we report that heparanase (predominant enzyme degrading heparan sulfate, the main polysaccharide found at the cell surface and extracellular matrix) directs tumor-promoting behavior of TAM in PDAC.
Artery Wall Electrolytes in Renal and Dca hypertension1
Authors: Louis Tobian, John Binion
Journal: Journal of Clinical Investigation (1954)

Renal HypertensionIn an earlier study it was found that the renal artery of necropsied hypertensive subjects con- tained abnormally large amounts of sodium and water (1).The present study deals with the elec- trolyte composition of the aorta in rats with renal hypertension.After these aortas have been stripped of adventitia, at least two-fifths of the total area in tissue sections is occupied by smooth mus- cle cells.The remainder is largely connective tis- sue.The rat aorta thus provides for analysis a tissue rich in arterial smooth muscle.Moreover, the smooth muscle cells in the aorta are continuous with and have many of the pharmacological reac- tions of similar cells in the smaller arteries and ar- terioles (2).It seemed likely that any chemical alteration occurring in the aorta would give a clue to similar changes in the smooth muscle of arteri- oles.Technical difficulties have so far prevented us from analyzing the electrolyte content in the walls of arterioles. METHODSHypertension was produced by compressing one kid- ney of 250 gm.male rats with a figure-of-eight ligature and removing the other kidney six days later.All the rats were fed rat chow 3 (.3 per cent sodium and 1.2 per cent potassium) and water ad lib.Eight weeks or longer after the second operation, blood pressure was deter- mined and the rats were sacrificed for tissue analysis.The aortas were dissected, stripped of adventitia, blotted free of blood, and placed in weighing bottles.In one series of rats, tissues were dried, defatted, and extracted with 0.75N HNO, according to the method of Lowry and Hastings (3).Sodium and potassium concentrations
P175 Home Mechanical Ventilation (HMV): an expanding service in acute hospitals
Authors: CA Lynch, O O'Sullivan, N Santana-Vaz, K Morley, B Beauchamp, A Oakes, R Mukherjee
Journal: Thorax (2013)

<h3>Background</h3> HMV/domiciliary non-invasive ventilation (NIV) is being increasingly used to treat chronic ventilatory failure, particularly due to obesity and neuromuscular conditions. In patients attending an acute hospital, most domiciliary NIVs are set up at the end of an acute episode of admission with hypercapnic acidotic respiratory failure but over time, as more at-risk patients come under surveillance for respiratory failure, we hypothesised that a unit supervising domiciliary NIV/HMV is expected to do more elective set-ups. <h3>Methods</h3> Comparison of the volume of new domiciliary NIV set-ups and the elective NIV set-up rate over three 12-month periods: Apr 2005-Mar 2006 (period 1), Apr 2011-Mar 2012 (period 2) and Apr 2012-Mar 2013 (period 3) in a dedicated 11-bedded ward-based NIV unit (established: Aug 2004) in a 1000-bedded central England teaching hospital trust, providing domiciliary NIV support to over 260 patients with over 392 under surveillance for respiratory failure. <h3>Results</h3> The volume more than doubled from 19 new domiciliary NIV set-ups in period 1 to 39 new domiciliary NIV set-ups in period 2; to 64 set- ups in period 3. The elective domiciliary NIV set-up rate increased from 7/19 (36.8%) to 19/39 (48.7%) to 30/64 (46.9%) for periods 1, 2 and 3 respectively [Figure 1]. <h3>Discussion</h3> We have previously shown that the elective set-up rate for new HMV has gone up in our unit. In this survey we have shown that this increase in 9elective set-up rate9 is associated with a consistent increase in volume of HMV set-ups. This is most likely to be due to an increased number of people at risk of respiratory failure coming under the unit9s surveillance. HMV is well known to improve quality of life and reduce unscheduled care utilisation when started at the appropriate timepoint in chronic ventilatory failure through surveillance. Comparison of data between centres supervising domiciliary NIV/HMV, e.g 9elective set-up rates9, is warranted in this rapidly evolving field. <h3>References</h3> Agarwal S <i>et al</i>. <i>Thorax</i> 2012;<b>67</b>:A163. (doi:10.1136/thoraxjnl-2013-204457.327