tbuckley/cabot-search huggingface dataset:
Noninvasive ventilation during walking in patients with severe COPD: a randomised cross-over trial
Authors: M. Dreher, J. H. Storre, W. Windisch
Journal: European Respiratory Journal (2007)

It was hypothesised that noninvasive positive-pressure ventilation (NPPV) applied during walking prevents exercise-induced hypoxaemia and improves exercise performance in severe chronic obstructive pulmonary disease (COPD) patients already receiving long-term NPPV. A total of 20 COPD patients (mean± sd age 65.1±8.7 yrs, forced expiratory volume in one second 27±8% predicted and total lung capacity 116±27% pred) reporting dyspnoea, even during mild exertion, underwent two 6-min walking tests with a rollator and supplemental oxygen (2.1±0.9 L·min −1 ) in a randomised cross-over design: with and without pressure-limited NPPV as used at home (inspiratory:expiratory pressure 2.9±0.44:0.4±0.1 kPa (29±4:4±1 mbar), respiratory frequency 20±2 breaths·min −1 ). The arterial oxygen tension significantly increased by 1.39±1.43 kPa (95% confidence interval (CI) 0.71–2.07 kPa) after walking with NPPV, but significantly decreased by 1.43±1.06 kPa (95% CI −1.92 – −0.94 kPa) without NPPV. Dyspnoea, as assessed by the Borg dyspnoea scale, significantly decreased from 6 (interquartile range (IQR) 4.5–10) to 4 (1.5–4.5) and walking distance significantly increased from 209 (IQR 178–279) to 252 (203–314) m when walking was NPPV-aided. In chronic hypercapnic chronic obstructive pulmonary disease, high-intensity noninvasive positive-pressure ventilation can also be administered during walking with unchanged ventilator settings compared with settings used at rest, thus resulting in improved oxygenation, decreased dyspnoea and increased walking distance. Therefore, noninvasive positive-pressure ventilation during walking could prevent hypoxia-induced complications and could, in future, play a role in palliative care.
New Strategies for Protein Crystal Growth
Authors: J. M. Wiencek
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract Protein crystallization is the most difficult and time-consuming step in the determination of a protein’s atomic structure. As X-ray diffraction becomes a commonly available tool in structural biology, the necessity for rational methodologies and protocols to produce single, high-quality protein crystals has come to the forefront. The basics of protein crystallization conform to the classical understanding of crystallization of small molecules. Understanding the effect of solution variables such as pH, temperature, pressure, and ionicity on protein solubility allows the proper evaluation of the degree of supersaturation present in protein crystallization experiments. Physicochemical measurements such as laser light scattering, X-ray scattering, X-ray diffraction, and atomic force microscopy provide a clearer picture of protein crystal nucleation and growth. This ever deepening knowledge base is generating rational methods to produce protein crystals as well as means to improve the diffraction quality of such protein crystals. Yet, much remains unclear, and the protein crystallization research community will be quite active for many years to come.
Role of cyclooxygenases 1 and 2 in the modulation of neuromuscular functions in the distal colon of humans and mice
Authors: M Fornai
Journal: Gut (2005)

<b>Background:</b> Cyclooxygenase isoforms (COX-1, COX-2) may exert differential regulatory actions on enteric motor functions under normal or pathological conditions. <b>Aims:</b> To examine the occurrence and functions of COX-1 and COX-2 in the neuromuscular compartment of normal distal colon using human and murine tissue. <b>Methods:</b> Gene expression (human, mouse), protein expression (human), gene deletion (mouse), and the effects of dual and isoform specific COX inhibitors on in vitro motility (human, mouse) were investigated. <b>Results:</b> Reverse transcription-polymerase chain reaction (RT-PCR) showed mRNA expression of COX-1 and COX-2 in human and wild-type mouse colonic muscle whereas only COX-2 or COX-1 was detected in COX-1 or COX-2 knockout animals. Immunohistochemistry localised both isoforms in neurones of myenteric ganglia, COX-1 in circular layer myocytes, and COX-2 in longitudinal muscle. Indomethacin (COX-1/COX-2 inhibitor), SC-560 (COX-1 inhibitor), or DFU (COX-2 inhibitor) enhanced atropine sensitive electrically induced contractions of human longitudinal muscle. The most prominent actions were recorded with indomethacin or SC-560 plus DFU. These results were confirmed under pharmacological blockade of non-cholinergic nerves. Atropine sensitive contractions evoked by carbachol in the presence of tetrodotoxin were enhanced by indomethacin or DFU but not by SC-560. In wild-type mice, contractile responses to electrical stimulation were enhanced by indomethacin, SC-560, or DFU. SC-560 potentiated electrically induced contractions in COX-2, but not COX-1, knockout mice. In contrast, DFU enhanced the contractions elicited by electrical stimuli in COX-1, but not in COX-2, knockout mice. <b>Conclusions:</b> These results indicate that COX-1 and COX-2 are expressed in the neuromuscular compartment of normal human colon where they modulate cholinergic excitatory control of colonic motility at prejunctional and postjunctional sites, respectively.
Measuring airway dimensions during bronchoscopy using anatomical optical coherence tomography
Authors: J. P. Williamson, J. J. Armstrong, R. A. McLaughlin, P. B. Noble, A. R. West, S. Becker, A. Curatolo, W. J. Noffsinger, H. W. Mitchell, M. J. Phillips, D. D. Sampson, D. R. Hillman, P. R. Eastwood
Journal: European Respiratory Journal (2009)

Airway dimensions are difficult to quantify bronchoscopically because of optical distortion and a limited ability to gauge depth. Anatomical optical coherence tomography ( a OCT), a novel imaging technique, may overcome these limitations. This study evaluated the accuracy of a OCT against existing techniques in phantom, excised pig and in vivo human airways. Three comparative studies were performed: 1) micrometer-derived area measurements in 10 plastic tubes were compared with a OCT-derived area; 2) a OCT-derived airway compliance curves from excised pig airways were compared with curves derived using an endoscopic technique; and 3) airway dimensions from the trachea to subsegmental bronchi were measured using a OCT in four anaesthetised patients during bronchoscopy and compared with computed tomography (CT) measurements. Measurements in plastic tubes revealed a OCT to be accurate and reliable. In pig airways, a OCT-derived compliance measurements compared closely with endoscopic data. In human airways, dimensions measured with a OCT and CT correlated closely. Bland–Altman plots showed that a OCT diameter and area measurements were higher than CT measurements by 7.6% and 15.1%, respectively. Airway measurements using a OCT are accurate, reliable and compare favourably with existing imaging techniques. Using a OCT with conventional bronchoscopy allows real-time measurement of airway dimensions and could be useful clinically in settings where knowledge of airway calibre is required.
A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma
Authors: Daniel M Geynisman, Yuanyuan Zha, Rangesh Kunnavakkam, Mebea Aklilu, Daniel VT Catenacci, Blase N Polite, Cara Rosenbaum, Azadeh Namakydoust, Theodore Karrison, Thomas F Gajewski, Hedy L Kindler
Journal: Journal for ImmunoTherapy of Cancer (2013)

CEA is expressed in >90% of pancreatic cancers (PC) and may be an appropriate immunotherapy target. CEA is poorly immunogenic due to immune tolerance; CAP1-6D, an altered peptide ligand can help bypass tolerance. We conducted a pilot randomized phase I trial in PC patients to determine the peptide dose required to induce an optimal CD8(+) T cell response.Patients with a PS 0-1, HLA-A2+ and CEA-expressing, previously-treated PC were randomized to receive 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C) of CEA peptide emulsified in Montanide and GM-CSF, given every 2 weeks until disease progression.Sixty-six patients were screened and 19 enrolled of whom 14 received at least 3 doses of the vaccine and thus evaluated for the primary immunologic endpoint. A median of 4 cycles (range 1-81) was delivered. Median and mean peak IFN-γ T cell response by ELISPOT (spots per 10(4) CD8(+) cells, Arm A/B/C) was 11/52/271 (A vs. C, p = 0.028) for medians and 37/148/248 (A vs. C, p = 0.032) for means. T cell responses developed or increased in 20%/60%/100% of pts in Arms A/B/C. Seven of the 19 patients remain alive at a minimum 32 months from trial initiation, including three with unresectable disease.The T cell response in this randomized phase I trial was dose-dependent with the 1 mg CEA peptide dose eliciting the most robust T cell responses. A signal of clinical benefit was observed and no significant toxicity was noted. Further evaluation of 1 mg CEA peptide with stronger adjuvants, and/or combined with agents to overcome immune inhibitory pathways, may be warranted in PC pts.ClinicalTrials.gov NCT00203892.
The action spectrum in polymorphic hght eruption
Authors: W. FRAIN-BELL, A. DICKSON, JOYCE HERD, I. STURROCK
Journal: British Journal of Dermatology (1973)

Journal Article The action spectrum in polymorphic hght eruption Get access W. FRAIN‐BELL, W. FRAIN‐BELL Department of Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar A. DICKSON, A. DICKSON Department of Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar JOYCE HERD, JOYCE HERD Department of Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar I. STURROCK I. STURROCK Department of Dermatology, University of Dundee Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 3, 1 September 1973, Pages 243–249, https://doi.org/10.1111/j.1365-2133.1973.tb02971.x Published: 01 September 1973 Article history Accepted: 12 February 1973 Published: 01 September 1973
Role of Lipoprotein (a) and TGF-β1 in Atherosclerosis of Hemodialysis Patients
Authors: MASAHISA FUJISAWA, REIKO HARAMAKI, HIROSHI MIYAZAKI, TSUTOMU IMAIZUMI, SEIYA OKUDA
Journal: Journal of the American Society of Nephrology (2000)

Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-beta 1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 +/- 1.62 mg/ml) and non-HD-CRF patients (25.0 +/- 8.4 mg/ml) than in control subjects (10.9 +/- 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0. 377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-beta 1 significantly increased in HD (119.8 +/- 53.5 ng/ml) and non-HD-CRF patients (93.2 +/- 25.0 ng/ml) compared with control subjects (17.7 +/- 6.4 ng/ml), whereas the plasma level of mature (active) TGF-beta1 did not differ among the groups. When plasma TGF-beta 1 and supernatant TGF-beta 1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-beta 1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-beta 1 and IMT or plaque score, between mature TGF-beta 1 and IMT or plaque score, or between mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.
Prevalence of Cognitive Impairment without Dementia in the United States
Authors: Brenda L. Plassman
Journal: Annals of Internal Medicine (2008)

Background: Cognitive impairment without dementia is associated with increased risk for disability, increased health care costs, and progression to dementia. There are no population-based prevalence estimates of this condition in the United States. Objective: To estimate the prevalence of cognitive impairment without dementia in the United States and determine longitudinal cognitive and mortality outcomes. Design: Longitudinal study from July 2001 to March 2005. Setting: In-home assessment for cognitive impairment. Participants: Participants in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older drawn from the nationally representative HRS (Health and Retirement Study). Of 1770 selected individuals, 856 completed initial assessment, and of 241 selected individuals, 180 completed 16- to 18-month follow-up assessment. Measurements: Assessments, including neuropsychological testing, neurologic examination, and clinical and medical history, were used to assign a diagnosis of normal cognition, cognitive impairment without dementia, or dementia. National prevalence rates were estimated by using a population-weighted sample. Results: In 2002, an estimated 5.4 million people (22.2%) in the United States age 71 years or older had cognitive impairment without dementia. Prominent subtypes included prodromal Alzheimer disease (8.2%) and cerebrovascular disease (5.7%). Among participants who completed follow-up assessments, 11.7% with cognitive impairment without dementia progressed to dementia annually, whereas those with subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of 17% to 20%. The annual death rate was 8% among those with cognitive impairment without dementia and almost 15% among those with cognitive impairment due to medical conditions. Limitations: Only 56% of the nondeceased target sample completed the initial assessment. Population sampling weights were derived to adjust for at least some of the potential bias due to nonresponse and attrition. Conclusion: Cognitive impairment without dementia is more prevalent in the United States than dementia, and its subtypes vary in prevalence and outcomes.
PUVA therapy of chronic actinic dermatitis
Authors: C. HINDSON, J. SPIRO, A. DOWNEY
Journal: British Journal of Dermatology (1985)

Four men with long‐standing chronic actinic dermatitis were treated with a modified PUVA regime which initially included generalized applications of topical steroids given immediately after PUVA exposure. All patients are now free of rash, no longer need protection from UV radiation, and are being maintained on twice monthly PUVA therapy (10 J/cm2).
Delayed allergic reactions to betalactams
Authors: J. M. Vega, M. Blanca, M. J. Carmona, J. Garcia, A. Claros, C. Juarez, M. C. Moya
Journal: Allergy (1991)

We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin. The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated. In two patients these findings were supported by histopathological studies. Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients. The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams.
New Utility of an Old Marker: Serial α-Fetoprotein Measurement in Predicting Radiologic Response and Survival of Patients With Hepatocellular Carcinoma Undergoing Systemic Chemotherapy
Authors: Stephen L. Chan, Frankie K.F. Mo, Philip J. Johnson, Edwin P. Hui, Brigette B.Y. Ma, Wing M. Ho, Kwok C. Lam, Anthony T.C. Chan, Tony S.K. Mok, Winnie Yeo
Journal: Journal of Clinical Oncology (2008)

There are limitations in using radiologic evaluation to assess the treatment outcome of patients with hepatocellular carcinoma (HCC). The use of serial alpha-fetoprotein (AFP) in monitoring response has not been rigorously evaluated. We aimed to study the clinical value of AFP trend in an attempt to validate AFP as a surrogate serologic end point.Participants from a phase III randomized trial of systemic chemotherapy in HCC were studied. Serum AFP was prospectively collected in parallel with clinical and radiologic outcome. AFP response was defined as a decrease in AFP of more than 20% after a minimum of two cycles of chemotherapy. We studied the relationship between AFP response and treatment outcome in terms of radiologic response and overall survival.Of 188 patients, 117 patients with elevated serum AFP (> 20 microg/L) and documented radiologic evaluation had received at least two cycles of chemotherapy. A total of 47 AFP responders were identified. AFP responders had better survival than nonresponders (13.5 v 5.6 months, respectively; P < .0001), and AFP response was strongly associated with radiologic response (P < .0001). Multivariate analysis suggested that AFP response was significantly associated with survival (hazard ratio, 0.413; 95% CI, 0.273 to 0.626; P < .0001). AFP responses were frequently observed in patients with radiologically stable disease (SD) and tended to identify a subgroup of SD patients with better survival.Serial AFP measurement is useful in prognostication and monitoring treatment response in HCC patients undergoing systemic chemotherapy. Incorporation of AFP response into the criteria evaluating treatment outcome should be considered in clinical practice and clinical trials of novel agents in HCC.
How identical would cloned children be? An understanding essential to the ethical debate
Authors: R G Edwards, H K Beard
Journal: Human Reproduction Update (1998)

The ban on human cloning in many countries worldwide is founded on an assumption that cloned children will be identical to each other and to their nuclear donor. This paper explores the scientific basis for this assumption, considering both the principles and practice of cloning in animals and comparing genetic and epigenetic variation in potential human clones with that in monozygotic twins.
Consolidation Therapy With Autologous Bone Marrow Transplantation in Adults With Acute Myeloid Leukemia: A Meta-analysis
Authors: P. C. Nathan, L. Sung, M. Crump, J. Beyene
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The optimal consolidation therapy for adults who are in first remission of acute myeloid leukemia after induction chemotherapy and who do not have a histocompatible donor is poorly established. We conducted a meta-analysis to compare the efficacy of autologous bone marrow transplantation with that of non-myeloablative chemotherapy alone (or no further treatment). Methods: Eligible studies were identified by searching electronic databases and by examining the reference lists of relevant studies and review articles. Eligible studies were those that prospectively enrolled adults with acute myeloid leukemia and randomly assigned patients who were in first remission and who did not have a matched sibling donor to one of the two consolidation therapies. Two reviewers independently assessed all studies for relevance and validity. We used a fixed-effects model to calculate the ratio of probabilities for disease-free and overall survival at 48 months or at the nearest recorded assessment point for each study and for all studies combined. All statistical tests were two-sided. Results: We identified 587 potentially relevant studies, 36 of which were retrieved for detailed evaluation. In the six studies eligible for this meta-analysis, a total of 1044 patients were randomly assigned to receive autologous bone marrow transplantation or non-myeloablative chemotherapy (five studies) or autologous bone marrow transplantation or no further treatment (one study). Compared with patients who received chemotherapy or no further treatment, patients who received autologous bone marrow transplantation had a better disease-free survival (ratio of disease-free survival probabilities = 1.24, 95% confidence interval [CI] = 1.06 to 1.44; P = .006) but a similar overall survival (ratio of overall survival probabilities = 1.01, 95% CI = 0.89 to 1.15; P = .86). Conclusion: Our results do not support the routine use of autologous bone marrow transplantation in adult acute myeloid leukemia patients in first remission.
Credentialing Complementary and Alternative Medical Providers
Authors: David M. Eisenberg
Journal: Annals of Internal Medicine (2002)

Since the late 19th century, state legislatures and professional medical organizations have developed mechanisms to license physicians and other conventional nonphysician providers, establish standards of practice, and protect health care consumers by establishing standardized credentials as markers of competence. The popularity of complementary and alternative medical (CAM) therapies presents new challenges. This article describes the current status of, and central issues in, efforts to create models for health care credentialing of chiropractors, acupuncturists, naturopaths, massage therapists, and other CAM practitioners. It also suggests a strategy of CAM provider credentialing for use by physicians, health care administrators, insurance companies, and national professional organizations. The credentialing debate reflects fundamental questions about who determines which providers and therapies will be accepted as safe, effective, appropriate, and reimbursable. More nationally uniform credentialing mechanisms are necessary to ensure high standards of care and more generalizable clinical research. However, the result of more uniform licensure and credentialing may be excessive standardization and a decrease in individualization of services. Thus, increased standardization of credentialing for CAM practitioners may alter CAM practice substantially. Furthermore, even credentialed providers can deliver ineffective therapy. The suggested framework balances the desire to protect the public from dangerous practices against the wish to grant patients access to reasonably safe and effective therapies.