tbuckley/cabot-search huggingface dataset:
Diaphragm Length during Tidal Breathing in Patients with Chronic Obstructive Pulmonary Disease
Authors: Robert B. Gorman, David K. McKenzie, Neil B. Pride, Jane F. Tolman, Simon C. Gandevia
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Diaphragm function is compromised in severe chronic obstructive pulmonary disease (COPD) by hyperinflation, but its ability to shorten and contribute to tidal volume is uncertain. We estimated coronal diaphragm length by measuring zone of apposition length with ultrasound and rib cage diameters with magnetometers, in 10 male patients with severe COPD and 10 age- and sex-matched control subjects. Diaphragm length was 20% shorter in patients at residual volume (413 and 536 mm in patients and control subjects, respectively) and FRC (381 and 456 mm, respectively), but was not different at total lung capacity (312 and 336 mm, respectively). Zone of apposition length was reduced 50% at residual volume and FRC in patients, but was larger at a given absolute lung volume than in control subjects. There were no differences in tidal volume (0.8 L), tidal changes in zone of apposition length (20 mm) and diaphragm length (38 and 42 mm), and tidal volume displaced by the diaphragm (0.6 L), even though mean FRC in patients was similar to predicted total lung capacity. Although the diaphragm is shorter at FRC in patients with COPD, its motion and change in length during tidal breathing is similar to that in control subjects.
Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations.
Authors: M K Whyte, A M Peters, J M Hughes, B L Henderson, G J Bellingan, J E Jackson, E R Chilvers
Journal: Thorax (1992)

Current treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods.Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification.The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80).The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.
Effect of manual percussion on tracheobronchial clearance in patients with chronic airflow obstruction and excessive tracheobronchial secretion.
Authors: C P van der Schans, D A Piers, D S Postma
Journal: Thorax (1986)

The effect of manual percussion of the thorax in nine patients with stable chronic airflow obstruction and excessive tracheobronchial secretion has been studied. Tracheobronchial clearance was measured over 50 minutes on three different days. On the first day manual percussion was applied for 10 minutes. In the period when percussion was applied the mucus clearance was slightly but significantly greater than in the periods when no percussion was applied. On the second day manual percussion was applied in combination with postural drainage, coughing, and breathing exercises for 20 minutes. This resulted in a much greater clearance than on the first day. On the third day postural drainage, coughing, and breathing exercises, but no manual percussion, were carried out for 20 minutes. There was no significant difference between the clearance of days 2 and 3. From this study it is apparent that manual percussion is a relatively ineffective procedure in patients with stable chronic airflow obstruction, but may be useful when the patient is not able to cough and cannot assume the appropriate position for postural drainage.
Foxa3 Induces Goblet Cell Metaplasia and Inhibits Innate Antiviral Immunity
Authors: Gang Chen, Thomas R. Korfhagen, Christopher L. Karp, Soren Impey, Yan Xu, Scott H. Randell, Joseph Kitzmiller, Yutaka Maeda, Hans Michael Haitchi, Anusha Sridharan, Albert P. Senft, Jeffrey A. Whitsett
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Goblet cell metaplasia accompanies common pulmonary disorders that are prone to recurrent viral infections. Mechanisms regulating both goblet cell metaplasia and susceptibility to viral infection associated with chronic lung diseases are incompletely understood.Objectives: We sought to identify the role of the transcription factor FOXA3 in regulation of goblet cell metaplasia and pulmonary innate immunity.Methods: FOXA3 was identified in airways from patients with asthma and chronic obstructive pulmonary disease. We produced transgenic mice conditionally expressing Foxa3 in airway epithelial cells and developed human bronchial epithelial cells expressing Foxa3. Foxa3-regulated genes were identified by immunostaining, Western blotting, and RNA analysis. Direct binding of FOXA3 to target genes was identified by chromatin immunoprecipitation sequencing correlated with RNA sequencing.Measurements and Main Results: FOXA3 was highly expressed in airway goblet cells from patients with asthma and chronic obstructive pulmonary disease. FOXA3 was induced by either IL-13 or rhinovirus. Foxa3 induced goblet cell metaplasia and enhanced expression of a network of genes mediating mucus production. Paradoxically, FOXA3 inhibited rhinovirus-induced IFN production, IRF-3 phosphorylation, and IKKε expression and inhibited viral clearance and expression of genes required for antiviral defenses, including MDA5, RIG-I, TLR3, IRF7/9, and nuclear factor-κB.Conclusions: FOXA3 induces goblet cell metaplasia in response to infection or Th2 stimulation. Suppression of IFN signaling by FOXA3 provides a plausible mechanism that may serve to limit ongoing Th1 inflammation during the resolution of acute viral infection; however, inhibition of innate immunity by FOXA3 may contribute to susceptibility to viral infections associated with chronic lung disorders accompanied by chronic goblet cell metaplasia.
Prevalence of oxygen desaturation and use of oxygen at home in adults at sea level and at moderate altitude
Authors: R. Perez-Padilla, L. Torre-Bouscoulet, A. Muiño, M. N. Marquez, M. V. Lopez, M. M. de Oca, C. Talamo, A. M. B. Menezes
Journal: European Respiratory Journal (2006)

The aim of this study was to determine the prevalence of oxygen desaturation in adults aged ≥40 yrs as altitude above sea level increases. A population-based, cross-sectional study with a multistage cluster sampling of 1,063 subjects from metropolitan Mexico City (Mexico; 2,240 m above sea level), 1,357 from Caracas (Venezuela; 950 m) and 943 from Montevideo (Uruguay; 35 m). The mean of six measurements of arterial oxygen saturation ( S P,O 2 ) was estimated using a pulse oximeter. Mean S P,O 2 decreased with altitude. No subject from Montevideo had a mean S P,O 2 ≤88%. Prevalence of subjects with S P,O 2 ≤88%, a common criterion used for oxygen prescription, was 1.0% in Caracas and 6.0% in Mexico City. Additional predicting factors for hypoxaemia in multiple regression models were age, body mass index and a low forced expiratory volume in one second as a percentage of the predicted value. In Mexico City and Caracas, &lt;10% of the hypoxaemic subjects reported use of domiciliary oxygen, whereas at least half of the subjects reporting use of oxygen at home had a resting S P,O 2 &gt;88%. In conclusion, the prevalence of hypoxaemia was closely related to altitude. Priorities for oxygen prescription must be defined in moderate altitudes because it is unfeasible to provide it to all subjects fulfilling the criteria commonly used.
The Two Faces of Interferon-γ in Cancer
Authors: M. Raza Zaidi, Glenn Merlino
Journal: Clinical Cancer Research (2011)

Abstract Interferon-γ is a cytokine whose biological activity is conventionally associated with cytostatic/cytotoxic and antitumor mechanisms during cell-mediated adaptive immune response. It has been used clinically to treat a variety of malignancies, albeit with mixed results and side effects that can be severe. Despite ample evidence implicating a role for IFN-γ in tumor immune surveillance, a steady flow of reports has suggested that it may also have protumorigenic effects under certain circumstances. We propose that, in fact, IFN-γ treatment is a double-edged sword whose anti- and protumorigenic activities are dependent on the cellular, microenvironmental, and/or molecular context. As such, inhibition of the IFN-γ/IFN-γ receptor pathway may prove to be a viable new therapeutic target for a subset of malignancies. Clin Cancer Res; 17(19); 6118–24. ©2011 AACR.
Adhesion of Staphylococcus aureus to the vessel wall under flow is mediated by von Willebrand factor–binding protein
Authors: Jorien Claes, Thomas Vanassche, Marijke Peetermans, Laurens Liesenborghs, Christophe Vandenbriele, Karen Vanhoorelbeke, Dominique Missiakas, Olaf Schneewind, Marc F. Hoylaerts, Ruth Heying, Peter Verhamme
Journal: Blood (2014)
Well-Being, Cerebral Function, and Physical Fatigue After Nocturnal Hypoglycemia in IDDM
Authors: Paromita King, Marie-France Kong, Heather Parkin, Ian A Macdonald, Robert B Tattersall
Journal: Diabetes Care (1998)

OBJECTIVE This study assessed the effect of nocturnal hypoglycemia on well-being cerebral function, and physical fatigue the next day in 10 subjects with IDDM. RESEARCH DESIGN AND METHODS After an exercise test to determine work-loads corresponding to 30 and 60% VO2max, volunteers were studied twice, 4 weeks apart. Blood glucose was lowered one night to 2.3–2.7 mmol/l for 1 h, and at the control visit, hypoglycemia was avoided. The next morning, well-being was assessed using the minor symptom evaluation profile (MSEP), and cerebral function was assessed with the paced auditory serial addition test, the digit symbol substitution test, trail making part B, four-choice reaction time, and auditory P300 latency. Subjects then exercised at predetermined workloads corresponding to 30% VO2max for 30 min and 60% VO2max until exhaustion. Fatigue was assessed every 10 min using the Borg scale for rating of perceived exertion. RESULTS All three components of the MSEP scored higher (indicating more symptoms) after the hypoglycemic night compared with the control night (P &amp;lt; 0.01 contentment, sleep; P &amp;lt; 0.001 vitality). None of the cerebral function tests performed the next day was affected by hypoglycemia. Exercise capacity was similar at both visits, but subjects were more fatigued after the hypoglycemic night (P &amp;lt; 0.01, analysis of variance). There were no differences in potassium, catecholamine, glucose, or lactate concentrations between visits either before or during exercise. CONCLUSIONS One hour of hypoglycemia at night affects a subject's sense of well-being, but not cerebral function, the next day. The greater fatigue after the hypoglycemic night cannot be explained by the biochemical parameters measured.
Measurement of Glomerular Filtration Rate by Inulin Clearance without Urine Collection
Authors: G. A. Rose
Journal: BMJ (1969)

A continuous infusion method for measuring inulin clearance (and hence glomerular filtration rate) which does not require urine collection has been re-evaluated and found to give satisfactory results. In two non-oedematous and anephric patients the plasma level of inulin became virtually constant four hours after a single intravenous dose, and hence this is the minimum time required for the infusion with this method.
Folic Acid for the Prevention of Colorectal Adenomas
Authors: Bernard F. Cole, John A. Baron, Robert S. Sandler, Robert W. Haile, Dennis J. Ahnen, Robert S. Bresalier, Gail McKeown-Eyssen, Robert W. Summers, Richard I. Rothstein, Carol A. Burke, Dale C. Snover, Timothy R. Church, John I. Allen, Douglas J. Robertson, Gerald J. Beck, John H. Bond, Tim Byers, Jack S. Mandel, Leila A. Mott, Loretta H. Pearson, Elizabeth L. Barry, Judy R. Rees, Norman Marcon, Fred Saibil, Per Magne Ueland, E. Robert Greenberg, for the Polyp Prevention Study Group
Journal: JAMA (2007)

Laboratory and epidemiological data suggest that folic acid may have an antineoplastic effect in the large intestine.To assess the safety and efficacy of folic acid supplementation for preventing colorectal adenomas.A double-blind, placebo-controlled, 2-factor, phase 3, randomized clinical trial conducted at 9 clinical centers between July 6, 1994, and October 1, 2004. Participants included 1021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma.Participants were randomly assigned in a 1:1 ratio to receive 1 mg/d of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/d) or placebo. Follow-up consisted of 2 colonoscopic surveillance cycles (the first interval was at 3 years and the second at 3 or 5 years later).The primary outcome measure was occurrence of at least 1 colorectal adenoma. Secondary outcomes were the occurrence of advanced lesions (> or =25% villous features, high-grade dysplasia, size > or =1 cm, or invasive cancer) and adenoma multiplicity (0, 1-2, or > or =3 adenomas).During the first 3 years, 987 participants (96.7%) underwent colonoscopic follow-up, and the incidence of at least 1 colorectal adenoma was 44.1% for folic acid (n = 221) and 42.4% for placebo (n = 206) (unadjusted risk ratio [RR], 1.04; 95% confidence interval [CI], 0.90-1.20; P = .58). Incidence of at least 1 advanced lesion was 11.4% for folic acid (n = 57) and 8.6% for placebo (n = 42) (unadjusted RR, 1.32; 95% CI, 0.90-1.92; P = .15). A total of 607 participants (59.5%) underwent a second follow-up, and the incidence of at least 1 colorectal adenoma was 41.9% for folic acid (n = 127) and 37.2% for placebo (n = 113) (unadjusted RR, 1.13; 95% CI, 0.93-1.37; P = .23); and incidence of at least 1 advanced lesion was 11.6% for folic acid (n = 35) and 6.9% for placebo (n = 21) (unadjusted RR, 1.67; 95% CI, 1.00-2.80; P = .05). Folic acid was associated with higher risks of having 3 or more adenomas and of noncolorectal cancers. There was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate, or aspirin allocation.Folic acid at 1 mg/d does not reduce colorectal adenoma risk. Further research is needed to investigate the possibility that folic acid supplementation might increase the risk of colorectal neoplasia.clinicaltrials.gov Identifier: NCT00272324.
Chlamydia pneumoniae (Cp)-specific IgE is associated with asthma severity
Authors: David Hahn, Katir Patel, Eduard Drizik, Wilmore Webley
Journal: European Respiratory Journal (2011)

Background: Multiple Cp biomarkers are associated with asthma severity but potential mechanisms are unclear.

Aims: To investigate bacterial allergy as a potential mechanism for Cp-associated asthma.

Methods: Practice-based prevalence study of serum Cp IgE by immunoblotting and whole blood Cp DNA by PCR, and associations with asthma severity and antibiotic treatment outcomes; nested case-control study of asthma cases and non-asthma controls.

Results: We studied 66 asthma subjects (mean age 40.9 years, range 5-75. 59% males, 65% never-smokers, 15% co-existing COPD). Cp IgE was detected in 33 (50%) and Cp DNA in 16 (24%); 88% of Cp DNA pos subjects were Cp IgE pos (P=.0011). 4 (22%) of 18 subjects with intermittent asthma were Cp IgE pos compared to 30 (63%) of 48 with persistent asthma (P=.005). We also found a significant “dose-response” relationship (Table).

View this table:

Cp IgE positivity and asthma severity category





A nested case-control study detected Cp IgE in 10 (53%) of 19 asthma cases and in 15 (75%) of 20 non-asthma controls (P=.15).

Of 31 asthma subjects who elected azithromycin treatment, 26 (84%) reported improvement. Cp IgE was detected in 16 of 26 reporting improvement and in 4 of 5 without improvement (P=.63).

Conclusions: Cp IgE was prevalent (50%) in community asthma patients, and was associated with Cp DNA and asthma severity, but was also common in non-asthma controls and did not predict response to azithromycin. Cp allergy may be one mechanism supporting a causal association of Cp and asthma. However, Cp pathogenesis is likely to be multifactorial.
Are Mastectomy Rates Really Increasing in the United States?
Authors: Elizabeth B. Habermann, Andrea Abbott, Helen M. Parsons, Beth A. Virnig, Waddah B. Al-Refaie, Todd M. Tuttle
Journal: Journal of Clinical Oncology (2010)

After the National Institutes of Health Consensus Statement in 1990, breast-conserving surgery (BCS) became more common while mastectomy rates decreased. However, several recently published single-institution studies have reported an increase in mastectomy rates in the past decade. We conducted a population-based study to evaluate national trends in the surgical treatment of breast cancer from 2000 through 2006.Using the Surveillance, Epidemiology, and End Results database, we conducted a retrospective cohort analysis of women undergoing surgical treatment for breast cancer. We evaluated variation in mastectomy rates by demographic and tumor factors and calculated differences in mastectomy rates across time. We utilized logistic regression to identify time trends and patient and tumor factors associated with mastectomy, testing for significance using two-sided methods.We identified 233,754 patients diagnosed with ductal carcinoma in situ or stage I to III unilateral breast cancer from 2000 to 2006. The proportion of women treated with mastectomy decreased from 40.8% in 2000 to 37.0% in 2006 (P < .001). These patterns were maintained across patient and tumor factors. Although the unilateral mastectomy rate decreased during the study period, the contralateral prophylactic mastectomy rate increased. Women were less likely to receive mastectomy over time (odds ratio, 1.18 for 2000 v 2006; 95% CI, 1.14 to 1.23; P < .0001), after adjusting for patient and tumor factors.In contrast to single-institution studies, our population-based analysis found a decrease in unilateral mastectomy rates from 2000 to 2006 in the United States. Variations in referral patterns and patient selection are potential explanations for these differences between single institutions and national trends.
Lower Concentration of Hippocampal <i>N</i>-Acetylaspartate in Familial Bipolar I Disorder
Authors: Raymond F. Deicken, Mary P. Pegues, Susan Anzalone, Robert Feiwell, Brian Soher
Journal: American Journal of Psychiatry (2003)

Previous studies attempting to identify neuropathological alterations in the hippocampus in bipolar disorder have been inconclusive. The objective of this study was to determine if the concentration of N-acetylaspartate, a neuronal and axonal marker, was lower in subjects with familial bipolar I disorder than in healthy comparison subjects, suggesting possible neuronal loss, neuronal dysfunction, or neuropil reduction in bipolar I disorder.N-acetylaspartate, choline, and creatine in the right and left hippocampus were measured in 15 euthymic male patients with familial bipolar I disorder and 20 healthy male comparison subjects by using proton magnetic resonance spectroscopy ((1)H-MRS).Relative to the comparison group, the patients with bipolar I disorder demonstrated significantly lower concentrations of N-acetylaspartate and creatine but normal choline concentration in both the right and left hippocampus. There were no group or lateralized differences in the percentages of different tissue types within the MRS voxels, suggesting that the hippocampal N-acetylaspartate and creatine alterations were not an artifact of variations in tissue types represented in the voxels. There was also a significant negative correlation between N-acetylaspartate concentration in the right hippocampus and illness duration, after adjustment for the effects of age.This preliminary study provides support for the existence of neuronal loss, neuronal metabolic dysfunction, or interneuronal neuropil reduction in the hippocampal region in male patients with familial bipolar I disorder. The finding of normal hippocampal choline levels in these patients does not provide support for ongoing myelin breakdown or glial cell proliferation in this brain region in familial bipolar I disorder. The significant association between illness duration and N-acetylaspartate concentration in the right hippocampus supports the idea that neuronal pathology may increase with disease progression and that this effect may be lateralized, involving the right but not the left hippocampus.
Phase I Clinical Trial of the Inosine Monophosphate Dehydrogenase Inhibitor Mycophenolate Mofetil (Cellcept) in Advanced Multiple Myeloma Patients
Authors: Naoko Takebe, Xiangfei Cheng, Suhlan Wu, Kenneth Bauer, Olga G. Goloubeva, Robert G. Fenton, Meyer Heyman, Aaron P. Rapoport, Ashraf Badros, John Shaughnessy, Douglas Ross, Barry Meisenberg, Guido Tricot
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Inosine monophosphate dehydrogenase (IMPDH) inhibitors have been used to induce leukemia blast cell differentiation but have not been tested in multiple myeloma for activity. Currently, available IMPDH inhibitor, mycophenolate mofetil (MMF), which is known as an immunosuppressant, was shown to induce apoptosis in myeloma cell lines. On the basis of our preclinical studies, we designed a clinical study to test our hypothesis that MMF has antimyeloma activity. Experimental Design: A Phase I MMF dose escalation study was conducted in relapsed and refractory myeloma patients who had documented disease progression by myeloma markers or bone marrow plasmacytosis to determine the maximum tolerated dose, toxicities, and efficacy of the drug. To assess the activity of IMPDH inhibition in the myeloma cells of patients, we measured intracellular nucleotide triphosphate levels by high-performance liquid chromatography-based analysis and examined the correlation with clinical response. Results: Among the 11 study patients, MMF was generally well tolerated and was administered up to a maximum dose of 5g/day. The most common toxicity was grade 1 fatigue (n = 4, 36%). One patient had a partial response (3g/day), four patients had stable disease, and six patients had progression of disease. There was a statistically significant difference in the intracellular dGTP level changes between the stable disease/partial response group versus progression of disease. Conclusions: MMF at 1 to 5 g/day daily dose is well tolerated by patients with relapsed and refractory multiple myeloma patients. Positive correlation between clinical response and depletion of intracellular dGTP level was shown. Future drug development to target this enzyme maybe useful in treating myelomas.