tbuckley/cabot-search huggingface dataset:
Prevalence of exacerbation in COPD patients with chronic bronchitis and association with elevated serum inflammatory biomarkers
Authors: Theerasuk Kawamatawong, Karoon Lueprasitsakul
Journal: European Respiratory Journal (2014)

Background : Chronic bronchitis phenotype is associated with COPD exacerbation. Mechanisms are enhanced local and systemic inflammation. We hypothesized whether chronic bronchitis is associated with exacerbation and increased inflammatory biomarkers.   Methods : Stable COPD patients were enrolled in 2103. The presence of chronic bronchitis and exacerbations in the past year were reviewed. Serum hsCRP, fibrinogen and total leukocytes (WBC) were measured.   Results:  Total 58 COPD patients having mean FEV 1  72.5 % were classified as GOLD A, B, C and D (27.6%, 53.5%, 3.5% and 15.5%). Chronic bronchitis was noted in 43% and exacerbation in the past year was noted in 29.3% of patients. There was no association between chronic bronchitis and COPD exacerbation history (p 0.12). Regarding chronic bronchitic COPD, their WBC, hsCRP and fibrinogen were 6943± 1642 cells /mm 3 , 7.4±10.7 mcg/ml and 318±85.2 mg/dl respectively. There was no difference of inflammatory biomarkers between COPD with and without chronic bronchitis. Furthermore, WBC, hsCRP and fibrinogen of COPD patients with history of exacerbations were 7678± 2226 cells /mm 3 , 10.9±20.3 mcg/ml and 330±91.9 mg/dl respectively. There was no difference of biomarkers between COPD with or without exacerbation history. Additionally, the presence of leukocytosis (WBC> 10,000 cells/mm 3 ), increased hsCRP (>3 mcg/ml), increased fibrinogen (>400 mg/dl) were not associated with exacerbation in the past year.   Conclusion : Chronic bronchitis was not associated with history of exacerbations. There was no association between abnormal biomarkers in COPD with exacerbation history and chronic bronchitis.
Global Patterns of Human DNA Sequence Variation in a 10-kb Region on Chromosome 1
Authors: Ning Yu, Z. Zhao, Y.-X. Fu, N. Sambuughin, M. Ramsay, T. Jenkins, E. Leskinen, L. Patthy, L. B. Jorde, T. Kuromori, W.-H. Li
Journal: Molecular Biology and Evolution (2001)

Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A ∼10-kb region on chromosome 1, which contains only four small exons (each <155 bp), was sequenced for 61 humans (20 Africans, 20 Asians, and 21 Europeans) and for 1 chimpanzee, 1 gorilla, and 1 orangutan. We found 52 polymorphic sites among the 122 human sequences and 382 variant sites among the human, chimpanzee, gorilla, and orangutan sequences. For the introns sequenced (8,991 bp), the nucleotide diversity (π) was 0.058% among all sequences, 0.076% among the African sequences, 0.047% among the Asian sequences, and 0.045% among the European sequences. A compilation of data revealed that autosomal regions have, on average, the highest π value (0.091%), X-linked regions have a somewhat lower π value (0.079%), and Y-linked regions have a very low π value (0.008%). The lower polymorphism in the present region may be due to a lower mutation rate and/or selection in the gene containing these introns or in genes linked to this region. The present region and two other 10-kb noncoding regions all show a strong excess of low-frequency variants, indicating a relatively recent population expansion. This region has a low mutation rate, which was estimated to be 0.74 × 10 per nucleotide per year. An average estimate of ∼12,600 for the long-term effective population size was obtained using various methods; the estimate was not far from the commonly used value of 10,000. Fu and Li's tests rejected the assumption of an equilibrium neutral Wright-Fisher population, largely owing to the high proportion of low-frequency variants. The age of the most recent common ancestor of the sequences in our sample was estimated to be more than 1 Myr. Allowing for some unrealistic assumptions in the model, this estimate would still suggest an age of more than 500,000 years, providing further evidence for a genetic history of humans much more ancient than the emergence of modern humans. The fact that many unique variants exist in Europe and Asia also suggests a fairly long genetic history outside of Africa and argues against a complete replacement of all indigenous populations in Europe and Asia by a small Africa stock. Moreover, the ancient genetic history of humans indicates no severe bottleneck during the evolution of humans in the last half million years; otherwise, much of the ancient genetic history would have been lost during a severe bottleneck. We suggest that both the “Out of Africa” and the multiregional models are too simple to explain the evolution of modern humans.
Immediate and one-year safety of intracoronary ultrasonic imaging. Evaluation with serial quantitative angiography.
Authors: F J Pinto, F G St Goar, S Z Gao, A Chenzbraun, T A Fischell, E L Alderman, J S Schroeder, R L Popp
Journal: Circulation (1993)

BACKGROUND Intracoronary ultrasound (ICUS) has the ability to quantitatively evaluate vessel wall morphology and is well suited for serial studies of coronary artery disease regression and progression. However, the potential risk for catheter-induced endothelial damage and accelerated atherosclerosis in instrumented vessels is a concern. The acute effects as well as the 1-year safety of ICUS regarding its impact on the atherosclerotic process were assessed. METHODS AND RESULTS The acute studies include 240 intracoronary studies performed in 170 cardiac transplant recipients. Patients were systematically heparinized. Only vessels &gt; or = 2 mm in diameter were visualized. Coronary arteries of 38 patients were measured by quantitative coronary angiography in matched angiograms at an interval of 1 year after the initial ICUS examination was performed to assess long-term effects. The angiographic measurements in the previously instrumented and noninstrumented vessels were compared. Forty-nine vessels that had been imaged (IM) in these 38 patients with a 5F ICUS catheter were compared with 61 vessels not previously imaged (NIM) in the same patients. Absolute and percentage change in angiographically measured mean vessel diameters in the ICUS imaged and nonimaged segments were compared. Despite pretreatment with nitroglycerin, 20 patients (8.3%) had angiographically evident coronary spasm. In all cases, this was reversed by giving nitroglycerin. One year after the original imaging study, no difference was noted between imaged and nonimaged vessels in change in absolute vessel diameter (IM, -0.11 +/- 0.28 mm vs NIM, -0.07 +/- 0.22 mm; P = .49) or in percentage change in diameter (IM, -5 +/- 11% vs NIM, -3 +/- 7%; P = .32). CONCLUSIONS Intracoronary ultrasound in cardiac transplant recipients was associated with no clinical morbidity and a low incidence of vessel spasm in large and medium-size coronary arteries. It does not accelerate progression of angiographically quantifiable coronary artery disease. This study suggests that ICUS can be safely used even in coronary arteries not undergoing interventions.
Changes in cardiovascular and adrenal cortical responses to angiotensin III induced by sodium deprivation in the rat.
Authors: M J Peach, C A Sarstedt, E D Vaughan
Journal: Circulation Research (1976)

The restriction of dietary sodium intake is known to depress the cardiovascular responses to angiotensin II and increase the sensitivity of the adrenal zona glomerulosa to this steroidogenic octapeptide. In sodium-repleted animals, angiotensin III is a weak pressor substance and a potent stimulant of aldosterone biosynthesis. The effect of a low sodium diet on vascular and steroidogenic responses to angiotensin II and angiotensin III was investigated. In nephrectomized rats, angiotensin III had one-third of the pressor activity relative to angiotensin II when either normal or sodium-deprived animals were compared. When administered subcutaneously (sc) to rats, angiotensin II and III induced comparable steroidogenic responses, whereas only angiotensin II significantly elevated blood pressure. The comparison of cell suspensions from control adrenals with suspensions of adrenals from sodium-deprived animals showed that the zona glomerulosa from rats on low sodium diets had increased wet weight (20%), cell protein (25%), and basal steroidogenic rats (45%). Adrenocorticotropic hormone (ACTH)-induced responses in adrenal cells from low sodium animals were about twice the responses of cells from normal adrenals. Angiotensin II and III stimulated the cortex at a threshold concentration of 5 X 10(-10) M and induced a maximum response at about 5 X 10(-8) M in cells prepared from normal rat adrenals. In cells dispersed from adrenal capsules of sodium-deprived rats, the maximal steroidogenic response to angiotensin II occurred at 3 X 10(-8) M, whereas angiotensin III was maximal at 1 X 10(-9) M. Aldosterone synthesis induced by both peptides was increased approximately 45% in adrenal cells from low salt rats. At 0.9 mumol/kg, sc, Sar-1, Ile-8-angiotensin II antagonized cardiovascular responses to angiotensin II and did not alter aldosterone in the sodium-deprived rat. In contrast, treatment with Ile-7-angiotensin III blocked the adrenal cortex but not the vascular actions of angiotensin II. These data are consistent with a role for angiotensin III in the renin-angiotensin-aldosterone response to sodium deprivation.
Drug-induced Sweet's syndrome in acne caused by different tetracyclines: case report and review of the literature
Authors: B. Khan Durani, U. Jappe
Journal: British Journal of Dermatology (2002)

Sweet's syndrome was first described in 1964. It is characterized by an acute onset of non-pruritic, painful reddish nodules on the head and neck, chest and/or the upper limbs, mostly accompanied by fever, general malaise and leucocytosis. Histopathological examination shows a diffuse dermal neutrophilic infiltrate. The pathogenesis is still not fully understood, and different diseases have been shown to be associated with this syndrome. However, although still very rare, there is an increase of reports on Sweet's syndrome induced by drugs. We describe a 30-year-old man who experienced acute neutrophilic dermatosis after systemic treatment with minocycline. Additionally, there is a strong possibility that the same patient developed a drug-induced Sweet's syndrome after oral administration of tetracycline and doxycycline.
Effect of changes in blood pH on the vascular resistance of the normal and hypoxic cat lung
Authors: G. R. Barer, J. R. McCurrie, J. W. Shaw
Journal: Cardiovascular Research (1971)

Journal Article Effect of changes in blood pH on the vascular resistance of the normal and hypoxic cat lung Get access Gwenda R. Barer, Gwenda R. Barer From the Department of Medicine, University of Sheffield, The Royal Hospital, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar Janice R. McCurrie, Janice R. McCurrie 1 From the Department of Medicine, University of Sheffield, The Royal Hospital, Sheffield 1J.R.M. is in receipt of a personal grant from the Medical Research Council of Great Britain. The Medical Research Council and The Sheffield University Research Fund provided funds for apparatus. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Shaw J. W. Shaw From the Department of Medicine, University of Sheffield, The Royal Hospital, Sheffield Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue 4, October 1971, Pages 490–497, https://doi.org/10.1093/cvr/5.4.490 Published: 01 October 1971
Improving Diabetes Care Among Patients Overdue for Recommended Testing: A Randomized Controlled Trial of Automated Telephone Outreach
Authors: Steven R. Simon, Connie Mah Trinacty, Stephen B. Soumerai, John D. Piette, James B. Meigs, Ping Shi, Arthur Ensroth, Dennis Ross-Degnan
Journal: Diabetes Care (2010)

OBJECTIVE The study's objective was to assess the effects of automated telephone outreach with speech recognition (ATO-SR) on diabetes-related testing. RESEARCH DESIGN AND METHODS We identified 1,200 health plan members who were overdue for diabetes-related testing and randomly allocated 600 to ATO-SR and 600 to usual care (no intervention). The intervention included three interactive calls encouraging recommended testing. The primary outcome was retinopathy testing, since this was the health plan's principal goal. Tests for glycemia, hyperlipidemia, and nephropathy were secondary outcomes. RESULTS In total, 232 participants (39%) verbally responded to the calls. There was no difference between the intervention and the usual care groups in the primary outcome (adjusted hazard ratio 0.93 [95% CI 0.71–1.22]) and no effect of the intervention on any of the secondary outcomes. CONCLUSIONS Fewer than 40% of the patients randomized to ATO-SR interacted verbally with the system. The intervention had no effect on the study's outcomes.
AAV-mediated Overexpression of Human α7 Integrin Leads to Histological and Functional Improvement in Dystrophic Mice
Authors: Kristin N Heller, Chrystal L Montgomery, Paul ML Janssen, K Reed Clark, Jerry R Mendell, Louise R Rodino-Klapac
Journal: Molecular Therapy (2013)

Duchenne muscular dystrophy (DMD) is a severe muscle disease caused by mutations in the DMD gene, with loss of its gene product, dystrophin. Dystrophin helps link integral membrane proteins to the actin cytoskeleton and stabilizes the sarcolemma during muscle activity. We investigated an alternative therapeutic approach to dystrophin replacement by overexpressing human α7 integrin (ITGA7) using adeno-associated virus (AAV) delivery. ITGA7 is a laminin receptor in skeletal and cardiac muscle that links the extracellular matrix (ECM) to the actin skeleton. It is modestly upregulated in DMD muscle and has been proposed to be an important modifier of dystrophic symptoms. We delivered rAAV8.MCK.ITGA7 to the lower limb of mdx mice through isolated limb perfusion (ILP) of the femoral artery. We demonstrated ~50% of fibers in the tibialis anterior (TA) and extensor digitorum longus (EDL) overexpressing α7 integrin at the sarcolemma following AAV gene transfer. The increase in ITGA7 in skeletal muscle significantly protected against loss of force following eccentric contraction-induced injury compared with untreated (contralateral) muscles while specific force following tetanic contraction was unchanged. Reversal of additional dystrophic features included reduced Evans blue dye (EBD) uptake and increased muscle fiber diameter. Taken together, this data shows that rAAV8.MCK.ITGA7 gene transfer stabilizes the sarcolemma potentially preserving mdx muscle from further damage. This therapeutic approach demonstrates promise as a viable treatment for DMD with further implications for other forms of muscular dystrophy.
Tositumomab and Iodine-131 Tositumomab Produces Durable Complete Remissions in a Subset of Heavily Pretreated Patients With Low-Grade and Transformed Non-Hodgkin’s Lymphomas
Authors: Richard I. Fisher, Mark S. Kaminski, Richard L. Wahl, Susan J. Knox, Andrew D. Zelenetz, Julie M. Vose, John P. Leonard, Stewart Kroll, Stanley J. Goldsmith, Morton Coleman
Journal: Journal of Clinical Oncology (2005)

This study is an integrated efficacy analysis of the five clinical trials of tositumomab and iodine-131 tositumomab in patients with relapsed or refractory low-grade, follicular, or transformed low-grade non-Hodgkin's lymphoma (NHL) that resulted in the regulatory approval of the iodine-131 tositumomab by the US Food and Drug Administration.This integrated analysis included 250 patients. Patients received a single course of iodine-131 tositumomab. Responses were assessed by an independent panel of radiologists and oncologists.Response rates in the five trials ranged from 47% to 68%; complete response rates ranged from 20% to 38%. With a median follow-up of 5.3 years, the 5-year progression-free survival was 17%. Eighty-one (32%) of 250 patients had a time to progression of > or = 1 year (termed durable response population). For the durable response population, 44% had not progressed at > or = 2.5 to > or = 9.5 years and had a median duration of response of 45.8 months. The median duration of complete response was not reached. The durable response population had many poor prognostic characteristics, including bone marrow involvement (41%), bulky disease > or = 5 cm (49%), and transformed histology (23%). Forty-three percent of the patients had been treated with more than four prior therapies and 36% had not responded to their most recent therapy.The tositumomab and iodine-131 tositumomab therapeutic regimen produces high response rates in patients with relapsed or refractory low-grade, follicular, and transformed low-grade NHL, with a sizable subgroup of patients achieving long-term durable responses.
Unbalanced oxidant-induced DNA damage and repair in COPD: a link towards lung cancer
Authors: G. Caramori, I. M. Adcock, P. Casolari, K. Ito, E. Jazrawi, L. Tsaprouni, G. Villetti, M. Civelli, C. Carnini, K. F. Chung, P. J. Barnes, A. Papi
Journal: Thorax (2011)

<h3>Background</h3> Chronic obstructive pulmonary disease (COPD) is characterised by oxidative stress and increased risk of lung carcinoma. Oxidative stress causes DNA damage which can be repaired by DNA-dependent protein kinase complex. <h3>Objectives</h3> To investigate DNA damage/repair balance and DNA-dependent protein kinase complex in COPD lung and in an animal model of smoking-induced lung damage and to evaluate the effects of oxidative stress on Ku expression and function in human bronchial epithelial cells. <h3>Methods</h3> Protein expression was quantified using immunohistochemistry and/or western blotting. DNA damage/repair was measured using colorimetric assays. <h3>Results</h3> 8-OH-dG, a marker of oxidant-induced DNA damage, was statistically significantly increased in the peripheral lung of smokers (with and without COPD) compared with non-smokers, while the number of apurinic/apyrimidinic (AP) sites (DNA damage and repair) was increased in smokers compared with non-smokers (p=0.0012) and patients with COPD (p&lt;0.0148). Nuclear expression of Ku86, but not of DNA-PKcs, phospho-DNA-PKcs, Ku70 or γ-H2AFX, was reduced in bronchiolar epithelial cells from patients with COPD compared with normal smokers and non-smokers (p&lt;0.039). Loss of Ku86 expression was also observed in a smoking mouse model (p&lt;0.012) and prevented by antioxidants. Oxidants reduced (p&lt;0.0112) Ku86 expression in human bronchial epithelial cells and Ku86 knock down modified AP sites in response to oxidative stress. <h3>Conclusions</h3> Ineffective DNA repair rather than strand breakage per se accounts for the reduced AP sites observed in COPD and this is correlated with a selective decrease of the expression of Ku86 in the bronchiolar epithelium. DNA damage/repair imbalance may contribute to increased risk of lung carcinoma in COPD.
Sirolimus-Eluting Stent or Paclitaxel-Eluting Stent vs Balloon Angioplasty for Prevention of Recurrences in Patients With Coronary In-Stent Restenosis
Authors: Adnan Kastrati, Julinda Mehilli, Nicolas von Beckerath, Alban Dibra, Jörg Hausleiter, Jürgen Pache, Helmut Schühlen, Claus Schmitt, Josef Dirschinger, Albert Schömig, for the ISAR-DESIRE Study Investigators
Journal: JAMA (2005)

In patients with de novo coronary lesions, drug-eluting stents have drastically reduced restenosis risk compared with bare metal stents and conventional balloon angioplasty. It is less clear whether drug-eluting stents are superior to conventional balloon angioplasty for the treatment of patients with in-stent restenosis.To assess if drug-eluting stents are a more effective treatment of in-stent restenosis than conventional balloon angioplasty, and to assess the relative merits of 2 drug-eluting stents, a sirolimus-eluting stent and a paclitaxel-eluting stent.Randomized, open-label, active-controlled trial conducted among 300 patients with angiographically significant in-stent restenosis in 2 tertiary German centers from June 1, 2003, to October 20, 2003.After pretreatment with 600 mg of clopidogrel for at least 2 hours before intervention, all patients were randomly assigned to 1 of 3 treatment groups: sirolimus stent, paclitaxel stent, or balloon angioplasty (100 patients in each group).Primary end point: angiographic restenosis (diameter stenosis > or =50%) at 6-month follow-up angiography based on "in-segment" analysis. Primary analysis was comparison between stent groups and balloon angioplasty groups; a secondary analysis compared sirolimus and paclitaxel stents.Follow-up angiography was performed in 275 (92%) of 300 patients. The incidence of angiographic restenosis was 44.6% (41/92) in the balloon angioplasty group, 14.3% (13/91) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 21.7% (20/92) in the paclitaxel stent group (P = .001 vs balloon angioplasty). When compared with balloon angioplasty, receiving a sirolimus stent had a relative risk (RR) of angiographic restenosis of 0.32 (95% confidence interval [CI], 0.18-0.56); a paclitaxel stent had an RR of 0.49 (95% CI, 0.31-0.76). The incidence of target vessel revascularization was 33.0% (33/100) in the balloon angioplasty group, 8.0% (8/100) in the sirolimus stent group (P<.001 vs balloon angioplasty), and 19.0% (19/100) in the paclitaxel stent group (P = .02 vs balloon angioplasty). The secondary analysis showed a trend toward a lower rate of angiographic restenosis (P = .19) and a significantly lower rate of target vessel revascularization (P = .02) among sirolimus stent patients compared with paclitaxel stent patients.In patients with in-stent restenosis, a strategy based on sirolimus- or paclitaxel-eluting stents is superior to conventional balloon angioplasty for the prevention of recurrent restenosis. Sirolimus-eluting stents may be superior to paclitaxel-eluting stents for treatment of this disorder.
Systematic review of the efficacy of nasal CPAP
Authors: N. J Douglas
Journal: Thorax (1998)

Continuous positive airway pressure (CPAP) therapy has been regarded for more than a decade by those in the field as the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS). Nevertheless, two recent systematic reviews1 2 have appropriately pointed out that there is a shortage of robust evidence that CPAP benefits medium and long term outcomes in SAHS. However, the striking aspect of the two reviews is their diametrically opposed conclusions about the efficacy of CPAP, one concluding from the evidence that CPAP was indicated in patients with more than 20 apnoeas + hypopnoeas per hour of sleep plus daytime sleepiness,1 whereas the other concluded that “the studies do not provide sufficiently robust evidence for the effectiveness of CPAP”.2 There are differences in the design of these reviews which may account for this disparity.

Systematic review should be impartial. The review by Wright and colleagues3 was funded, at least in the initial stages, by purchasing authorities concerned about the increasing costs of provision of sleep services and CPAP. Sackett has commented that there is a “fear that evidence based medicine may be hijacked by purchasers and managers to cut the costs of healthcare”.4 The study by Wright et al 2 would appear to be one such example. In contrast, the Australasian study1 was commissioned by the Australian Medical Research Council and the New Zealand Ministry of Health.

Evidence based medicine has been defined as “integrating individual clinical expertise with the best available external clinical evidence from systematic research”, where clinical expertise is “the proficiency and judgement that individual clinicians acquire through clinical experience and clinical practice”.4 Wright and colleagues2 did not …