tbuckley/cabot-search huggingface dataset:
Perseveration as a sign of diffuse and focal brain damage. I.
Authors: R. S. Allison
Journal: BMJ (1966)

Che called " asymbolie."This was in a man of 43 years who had been a heavy drinker, and who, when first seen, was in a state of stupor and later in delirium.As the level of con- sciousness rose it was observed that he was slightly dysphasic.At no time, however, did he show any signs of hemiplegia, sensory impairment, visual-field defect, agnosia, or apraxia.The crux of the residual disability lay in his faulty responses to impressions (Eindriicken) (Aulg.Z. Psychiat., 1895).
Total homocysteine in patients with type 1 diabetes.
Authors: C Pavía, I Ferrer, C Valls, R Artuch, C Colomé, M A Vilaseca
Journal: Diabetes Care (2000)

OBJECTIVE: Our aim was to study the presence of moderate hyperhomocysteinemia, a risk factor for premature cardiovascular disease, its modifying vitamin factors (folates, vitamins B12 and B6), and lipid risk factors in juvenile type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 91 patients with type 1 diabetes (46 girls and 45 boys) were studied, with ages ranging from 11 to 18 years, a duration of diabetes from 1 to 15 years, and in pubertal development (stages III, IV, V). In all patients, cholesterol, triglycerides, HDL and LDL cholesterol, lipoprotein(a), folates, cobalamin, vitamin B6, and total homocysteine were determined by specific assays. Microalbuminuria, defined as a ratio of albumin/creatinine &amp;gt;3 mg/mmol creatinine, was analyzed in the first morning specimen. RESULTS: Plasma total homocysteine (tHcy) concentrations were not different in the 91 diabetic children (median [range]) (11-15 years, 6.1 micromol/l [3.2-9.6]; 16-18 years, 7.3 micromol/l [3.9-12]) compared with the control group (11-15 years, 6.6 micromol/l [4.4-10.8]; 16-18 years, 8.1 micromol/l [4.6-11.3]). No significant differences were found in tHcy values in relation to the metabolic control of the disease as assessed by glycohemoglobin values, the duration of disease, alterations in fundus oculi, or presence of lymphocytic thyroiditis. A positive correlation was found between tHcy and plasma creatinine in type 1 diabetic patients that might be related with the increase in muscle mass. There was a negative correlation between tHcy and serum folate (P&amp;lt;0.001) and vitamin B12 (P&amp;lt;0.05), but not with vitamin B6 levels. No significant correlations were found between tHcy and the lipid parameters. CONCLUSIONS: Hyperhomocysteinemia was not detected in adolescents with type 1 diabetes.
Patients With Acute Coronary Syndrome Show Oligoclonal T-Cell Recruitment Within Unstable Plaque
Authors: Raffaele De Palma, Francesco Del Galdo, Gianfranco Abbate, Massimo Chiariello, Raffaele Calabró, Lavinia Forte, Giovanni Cimmino, Maria Francesca Papa, Maria Giovanna Russo, Giuseppe Ambrosio, Claudio Giombolini, Isabella Tritto, Salvatore Notaristefano, Liberato Berrino, Francesco Rossi, Paolo Golino
Journal: Circulation (2006)

Background— Recent studies indicate that T-cell activation may play an important role in the pathophysiology of acute coronary syndromes (ACS). However, although those studies detected T-cell expansion in peripheral blood cells, demonstration of specific T-cell expansion within the plaque of patients with ACS is lacking. The present study aims to address whether a specific, immune-driven T-lymphocyte recruitment occurs within the unstable plaque of patients with ACS. Methods and Results— We simultaneously examined the T-cell repertoire using CDR3 size analysis both in coronary plaques (obtained by directional atherectomy) and in peripheral blood of patients with either ACS (n=11) or chronic stable angina (n=10). Unstable plaques showed a 10-fold increase in T-cell content by quantitative PCR. Using spectratyping analysis, we found several specific T-cell clonotype expansions only in unstable plaque from each patient with ACS, indicating a specific, antigen-driven recruitment of T cells within unstable lesions. Conclusions— For the first time, T-cell repertoire was investigated directly into coronary plaques; using this approach, we demonstrate that coronary plaque instability in the setting of ACS is associated with immune-driven T-cell recruitment, specifically within the plaque.
Surgical Management of Aortic Valve Disease in the Elderly
Authors: W. Gerald Austen
Journal: JAMA (1970)

Forty patients over the age of 70 years, with an average age of 74.6 years, have undergone aortic valve surgery at the Massachusetts General Hospital in the past eight years. Thirty-eight patients had calcific aortic stenosis, and two had aortic insufficiency. Debridement of the aortic valve was performed early in our experience in the surgical treatment of aortic stenosis in four patients, three of whom survived. Two of these patients as well as the other thirty-six underwent prosthetic aortic valve replacement. In this group of 40 patients, 32 of whom were in cardiac class IV, there were eight hospital deaths (20%) and three late deaths (7.5%). The 29 survivors are all much improved, and some spectacularly so. These results justify an aggressive approach to aortic valve replacement in the elderly, if the patient's general status warrants it.
Predictors of long-term compliance with continuous positive airway pressure
Authors: M. Kohler, D. Smith, V. Tippett, J. R. Stradling
Journal: Thorax (2010)

There are very few data on objectively assessed long-term compliance with continuous positive airway pressure (CPAP). No single factor has been consistently identified as predictive of continued CPAP use.Adherence to and associations with objective CPAP use were examined in 639 of 3900 patients in whom CPAP treatment was started between 1994 and 2005. Kaplan-Meier survival analyses were used to estimate the proportion of patients still on CPAP. Cox regression models were used to explore the effects of covariates on continued use of CPAP.The median (IQR) follow-up time after initiating CPAP therapy was 3.9 (1.5-6.9) years and the average use of CPAP was 6.2 (4.5-7.3) h/night. The percentage of patients adherent to CPAP after 5 and 10 years was 81% and 70%, respectively. Multivariate analysis, including gender, age, neck circumference, Epworth Sleepiness Score, oxygen desaturation index (ODI) and research study participation, indicated that ODI was the only clinical variable independently associated with long-term adherence to CPAP (HR per 1 event=0.97, p<0.001, 95% CI 0.96 to 0.98). ODI categories were significantly associated with the risk for stopping CPAP in multivariate analysis (using ODI group 0-15/h as reference, HR for ODI group >15-30/h=0.68, p=0.100, 95% CI 0.43 to 1.08; for ODI group >30-60/h=0.37, p<0.001, 95% CI 0.22 to 0.60; and for ODI group >60/h=0.17, p=0.001, 95% CI 0.06 to 0.48).The majority of patients with sleep-disordered breathing are using CPAP in the long term and the severity of sleep-disordered breathing rather than sleepiness determines long-term adherence to CPAP therapy.
Coronary and Systemic Hemodynamic Effects of Sustained Inhibition of Nitric Oxide Synthesis in Conscious Dogs
Authors: Louis Puybasset, Marie-Luce Béa, Bijan Ghaleh, Jean-François Giudicelli, Alain Berdeaux
Journal: Circulation Research (1996)

Sustained inhibition of NO synthesis ( N ω -nitro- l -arginine [L-NNA], 20 mg·kg −1 ·d −1 , 7 days) was investigated at rest and during exercise in conscious dogs. At rest, L-NNA did not alter mean arterial blood pressure but markedly increased total peripheral resistance (+ 73±14%, P &lt;.01). Exaggerated hypertension was observed during exercise (+132±5 mm Hg after L-NNA versus +113±5 mm Hg before L-NNA, P &lt;.01). L-NNA decreased the resting coronary artery diameter by 6±1% and suppressed its exercise-induced dilation but had no effect on coronary blood flow and resistance. L-NNA decreased flow repayment volumes during reactive hyperemia, but corresponding flow debt volumes remained unchanged. The cyclooxygenase inhibitor diclofenac (10 mg/kg) had no effect on reactive hyperemia parameters before L-NNA but reduced flow repayment volumes, durations, and corresponding debt-to-repayment ratios in L-NNA–treated dogs (all P &lt;.05). In vitro, indomethacin blunted the residual relaxation to bradykinin of large coronary arteries taken from L-NNA–treated, but not from control, dogs. Bradykinin-induced increase in 6-ketoprostaglandin F 1α production was greater in coronary arteries taken from L-NNA–treated dogs (+179±41 pg/mm 2 ) than from control dogs (+66±18 pg/mm 2 ) ( P &lt;.05). These results indicate that (1) NO is of major importance in the control of systemic but not coronary resistance vessels at rest and during exercise, and (2) after L-NNA, the cyclooxygenase pathway is involved in myocardial reactive hyperemia and in the residual relaxation to bradykinin of isolated coronary arteries. Thus, in conscious dogs, the cyclooxygenase pathway might act as a protective mechanism of the coronary circulation when endothelial nitric oxide synthesis is altered.
Leveraging Exploratory Investigational New Drug Studies to Accelerate Drug Development
Authors: David Jacobson-Kram, George Mills
Journal: Clinical Cancer Research (2008)

In 2006, the U.S. Food and Drug Administration published its guide on exploratory investigational new drug (IND) studies with the goal of making the approach to early-stage, pilot clinical trials more flexible within the context of current regulations. The exploratory IND allows sponsors to initiate clinical trials of limited scale with reduced preclinical requirements. These studies may be important vehicles for the conduct of proof-of-principle pharmacodynamic investigations of highly potent molecules, for bioavailability studies that require only a single drug dose to be administered, and for imaging trials that permit critical dosimetry and biodistribution investigations of new molecules. These trials were done with no therapeutic intent and must be followed by traditional dose-escalation investigations that are supported by standard preclinical toxicologic and pharmacologic studies. To the extent that they allow early evaluations of essential drug characteristics that can only be obtained in humans, exploratory IND trials have the potential to limit the cost and improve the development times of new agents.
Enhanced cell-volume regulation in cyclosporin A cardioprotection
Authors: Roberto J. Diaz, Kelly Fernandes, Yuliya Lytvyn, Krista Hawrylyshyn, Kordan Harvey, Taneya Hossain, Alina Hinek, Gregory J. Wilson
Journal: Cardiovascular Research (2013)

Cyclosporin A (CsA) has been shown to protect against ischaemia/reperfusion injury presumably by its inhibition of mitochondrial permeability transition pore opening through cyclophilin D inhibition. We examine if CsA cardioprotection involves a cell-volume regulatory mechanism. To address this issue, cultured rabbit cardiomyocytes were subjected to the following protocols: (i) cardiomyocytes were treated with 200 nM CsA either given for 10 min followed by 10 min of washout prior to 30 min hypo-osmotic stress (200 mOsm) or administered throughout 75 min simulated ischaemia/60 min simulated reperfusion. Cell necrosis and cell swelling were determined by trypan blue staining and cell-volume measurements, respectively; (ii) SPQ(6-methoxy-N-(3-sulfopropyl)quinolinium) dye loaded cardiomyocytes were treated with 200 nM CsA for 10 min followed by 10 min washout and intracellular Cl− concentration measured (Cl− efflux); (iii) 5,5′,6,6′-tetrachloro-1,1′,3,3′- tetraethylbenzimi-dazolylcarbocyanine iodide(JC-1) loaded cardiomyocytes were treated with 200 nM CsA to inhibit mitochondrial membrane potential (ΔΨm) dissipation (an index of mitochondria permeability transition pore opening) by either valinomycin (2 μM) or ischaemia/reperfusion injury. Cl− channels were blocked by indanyloxyacetic acid 94 (IAA-94, 50 μM). CsA not only significantly (P < 0.001) reduced the % of dead cells following simulated ischaemia/reperfusion but it also triggered an efflux of Cl−, hence enhancing cardiomyocyte cell-volume regulatory response. CsA protection against cell necrosis and its effect on Cl− transport/volume regulation were all blocked by IAA-94. IAA-94 had no effect on ΔΨm. These data indicate that CsA protects against cell necrosis at least in part by enhancing cardiomyocyte volume regulation, and not simply by inhibiting MPTP opening.
Host genetics and diet, but not immunoglobulin A expression, converge to shape compositional features of the gut microbiome in an advanced intercross population of mice
Authors: Larry J Leamy, Scott A Kelly, Joseph Nietfeldt, Ryan M Legge, Fangrui Ma, Kunjie Hua, Rohita Sinha, Daniel A Peterson, Jens Walter, Andrew K Benson, Daniel Pomp
Journal: Genome biology (2014)

Abstract Background Individuality in the species composition of the vertebrate gut microbiota is driven by a combination of host and environmental factors that have largely been studied independently. We studied the convergence of these factors in a G 10 mouse population generated from a cross between two strains to search for quantitative trait loci (QTLs) that affect gut microbiota composition or ileal Immunoglobulin A (IgA) expression in mice fed normal or high-fat diets. Results We found 42 microbiota-specific QTLs in 27 different genomic regions that affect the relative abundances of 39 taxa, including four QTL that were shared between this G 10 population and the population previously studied at G 4 . Several of the G 10 QTLs show apparent pleiotropy. Eight of these QTLs, including four at the same site on chromosome 9, show significant interaction with diet, implying that diet can modify the effects of some host loci on gut microbiome composition. Utilization patterns of IghV variable regions among IgA-specific mRNAs from ileal tissue are affected by 54 significant QTLs, most of which map to a segment of chromosome 12 spanning the Igh locus. Despite the effect of genetic variation on IghV utilization, we are unable to detect overlapping microbiota and IgA QTLs and there is no significant correlation between IgA variable pattern utilization and the abundance of any of the taxa from the fecal microbiota. Conclusions We conclude that host genetics and diet can converge to shape the gut microbiota, but host genetic effects are not manifested through differences in IgA production.
A perfluoropolyether corneal inlay for the correction of refractive error
Authors: Margaret D.M. Evans, Ruby K. Prakasam, Pravin K. Vaddavalli, Timothy C. Hughes, Warren Knower, John S. Wilkie, Keith M. McLean, Graham Johnson, Gail A. McFarland, Ruo Zhong Xie, Deborah F. Sweeney
Journal: Biomaterials (2011)
Direct Effects of Interleukin-13 on Signaling Pathways for Physiological Responses in Cultured Human Airway Smooth Muscle Cells
Authors: JOHANNE C. LAPORTE, PAUL E. MOORE, SIMONETTA BARALDO, MARIE-HÉLÈNE JOUVIN, TRUDI L. CHURCH, IGOR N. SCHWARTZMAN, REYNOLD A. PANETTIERI, JEAN-PIERRE KINET, STEPHANIE A. SHORE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Numerous studies have suggested an important role for the Th2 cytokines interleukin (IL)-13 and IL-4 in the development of allergic asthma. We tested the hypothesis that IL-13 and IL-4 have direct effects on cultured airway smooth muscle cells (HASM). Using RT-PCR, we showed that HASM cells express transcripts for IL-4alpha, IL-13RalphaI, and IL-13RalphaII, but not for the common IL-2Rgamma chain. We then analyzed the capacity of the two cytokines to activate signaling pathways in HASM cells. Both IL-13 and IL-4 caused STAT-6 phosphorylation, but the time course was different between the two cytokines, with peak effects occurring 15 min after addition of IL-4 and 1 h after addition of IL-13. Effects on signaling were observed at cytokine concentrations as low as 0.3 ng/ml. IL-4 and IL-13 also caused phosphorylation of ERK MAP kinase. As suggested by the signaling studies, the biological responses of the two cytokines were also different. We used magnetic twisting cytometry to measure cell stiffness of HASM cells and tested the capacity of IL-4 and IL-13 to interfere with the reductions in cell stiffness induced by the beta-agonist isoproterenol (ISO). IL-13 (50 ng/ml for 24 h), but not IL-4, significantly reduced beta-adrenergic responsiveness of HASM cells, and the MEK inhibitor U0126 significantly reduced the effects of IL-13 on ISO-induced changes in cell stiffness. We propose that these direct effect of IL-13 on HASM cells may contribute at least in part to the airway narrowing observed in patients with asthma.
Development and evaluation of a real-time PCR assay for detection of Pneumocystis jirovecii DNA in bronchoalveolar lavage fluid of HIV-infected patients
Authors: J F Huggett, M S Taylor, G Kocjan, H E Evans, S Morris-Jones, V Gant, T Novak, A M Costello, A Zumla, R F Miller
Journal: Thorax (2007)

<h3>Background:</h3> <i>Pneumocystis</i> pneumonia (PCP) is conventionally diagnosed by identifying <i>Pneumocystis jirovecii</i> in lower respiratory tract samples using cytochemical stains. Molecular diagnosis of PCP is potentially more sensitive. <h3>Methods:</h3> A study was undertaken to use an extensively optimised real-time polymerase chain reaction (PCR) using primers designed to hybridise with the <i>P jirovecii</i> heat shock protein 70 (HSP70) gene to quantify <i>P jirovecii</i> DNA in bronchoalveolar lavage (BAL) fluid from HIV-infected patients with and without PCP, and to compare this assay with conventional PCR targeting the <i>P jirovecii</i> mitochondrial large subunit rRNA gene sequence (mt LSU rRNA). <h3>Results:</h3> Sixty-one patients had 62 episodes of PCP (defined by detection of <i>P jirovecii</i> in BAL fluid by cytochemical stains and typical clinical presentation). Quantifiable HSP70 DNA was detected in 61/62 (range ∼13–18 608 copies/reaction; median ∼332) and was detectable but below the limit of quantification (∼5 copies/reaction) in 1/62. Seventy-one other patients had 74 episodes with alternative diagnoses. Quantifiable HSP70 DNA was detectable in 6/74 (8%) episodes (range ∼6–590 copies/reaction; median ∼14) and detectable but below the limit of quantification in 34/74 (46%). Receiver-operator curve analysis (cut-off &gt;10 copies/reaction) showed a clinical sensitivity of 98% (95% 91% to 100%) and specificity of 96% (95% CI 87% to 99%) for diagnosis of PCP. By contrast, clinical sensitivity of mt LSU rRNA PCR was 97% (95% CI 89% to 99%) and specificity was 68% (95% CI 56% to 78%). <h3>Conclusion:</h3> The HSP70 real-time PCR assay detects <i>P jirovecii</i> DNA in BAL fluid and may have a diagnostic application. Quantification of <i>P jirovecii</i> DNA by real-time PCR may also discriminate between colonisation with <i>P jirovecii</i> and infection.
Isolation of Bone Marrow Stromal Cell–Derived Smooth Muscle Cells by a Human SM22α Promoter
Authors: Yuji Kashiwakura, Youichi Katoh, Kenji Tamayose, Hakuoh Konishi, Norihide Takaya, Senji Yuhara, Masanori Yamada, Koichi Sugimoto, Hiroyuki Daida
Journal: Circulation (2003)

Bone marrow stromal cells (BMSCs) have many characteristics of mesenchymal stem cells that can differentiate into smooth muscle cells (SMCs). However, there have been few studies closely following the cell development of smooth muscle lineage among BMSCs.To investigate the possible existence of a cell population committed to the SMC lineage among bone marrow adhesion cells, we tried to detect and follow the in vitro differentiation of such a cell type by using a promoter-sorting method with a human SM22alpha promoter (-480 bp)/green fluorescent protein (GFP) construct. The construct was transfected to adhesion cells that appeared 5 days after the seeding of mononuclear cells from bone marrow. GFP was first detectable 5 days after the transfection in a cell population [Ad(G) cells], which expressed PDGF-beta but neither mature (calponin) nor immature (SMemb) SMC-specific proteins at that time. However, the cells were eventually grown into individual clones that expressed SMC-specific proteins (alpha-smooth muscle actin, calponin, and SM-1), suggesting that Ad(G) cells have partly at least progenitor properties. Because early studies have reported that PDGF-beta signaling plays pivotal roles in the differentiation of mesenchymal smooth muscle progenitor cells, Ad(G) cells might be putative mesenchymal smooth muscle progenitors expressing PDGF-beta.We demonstrated the presence of a cell population fated to become SMCs and followed their differentiation into SMCs among BMSCs.
Psychological Interventions for Psychosis: A Meta-Analysis of Comparative Outcome Studies
Authors: David Trevor Turner, Mark van der Gaag, Eirini Karyotaki, Pim Cuijpers
Journal: American Journal of Psychiatry (2014)

After six psychological interventions for psychosis were compared across 48 outcome trials, some small but reliable differences in efficacy were found. Cognitive-behavioral therapy was more successful than befriending, cognitive remediation, psychoeducation, and supportive counseling in treating positive symptoms, but not as effective as social skills training for negative symptoms.
The A4 Study: Stopping AD Before Symptoms Begin?
Authors: Reisa A. Sperling, Dorene M. Rentz, Keith A. Johnson, Jason Karlawish, Michael Donohue, David P. Salmon, Paul Aisen
Journal: Science Translational Medicine (2014)

A new secondary prevention trial in older people with amyloid accumulation at high risk for Alzheimer’s disease dementia should provide insights into whether anti-amyloid therapy can delay cognitive decline.
Training and "work" for the unemployed.
Authors: R Smith
Journal: BMJ (1986)

9 Boorse C. On the distinction between disease and illness. Philosophy and Public Affairs 1975;5 (l):49-68. 10 Culver CM, Gert B. Philosophy in medicine. New York and Oxford: Oxford University Press, 1982:64-125. 11 Feinstein AR. Clinical judgment. Baltimore: Williams and Wilkins, 1967:145-8. 12 ten Have H, Sporken P. Heroin addiction, ethics and philosophy of medicine. J Med Ethics 1985;11:173-7. 13 Anonymous. Heroin, health and disease [Editorial]. JMedEthics 1985;11:171-2.
Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-α targeting: first in-human results
Authors: Gooitzen M van Dam, George Themelis, Lucia M A Crane, Niels J Harlaar, Rick G Pleijhuis, Wendy Kelder, Athanasios Sarantopoulos, Johannes S de Jong, Henriette J G Arts, Ate G J van der Zee, Joost Bart, Philip S Low, Vasilis Ntziachristos
Journal: Nature Medicine (2011)
Effect of SCH55700, a Humanized Anti-Human Interleukin-5 Antibody, in Severe Persistent Asthma
Authors: Johan C. Kips, Brian J. O'Connor, Stephen J. Langley, Ashley Woodcock, Huib A. M. Kerstjens, Dirkje S. Postma, Mel Danzig, Francis Cuss, Romain A. Pauwels
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.