tbuckley/cabot-search huggingface dataset:
Response to Letter Regarding Article, “Delayed Coverage in Malapposed and Side-Branch Struts With Respect to Well-Apposed Struts in Drug-Eluting Stents: In Vivo Assessment With Optical Coherence Tomography”
Authors: Juan Luis Gutiérrez-Chico, Evelyn Regar, Takayuki Okamura, Joanna Wykrzykowska, Patrick W. Serruys, Eveline Nüesch, Peter Jüni, Carlo di Mario, Stephan Windecker, Gerrit-Anne van Es, Pierre Gobbens
Journal: Circulation (2012)

We appreciate the interest shown by Dr Pe ´rez de Prado and colleagues in our article. 1Nonapposed side-branch struts have been excluded from most optical coherence tomography (OCT) studies, probably not because they were deemed "unsuitable to be covered," but because incorporating nonapposed side-branch struts into the standard analysis increases its complexity and cost.Not surprisingly, experimental models and clinical OCT studies coincide to report that most nonapposed side-branch struts are covered as well-apposed struts, but the former are in disadvantage with respect to the latter to get covered.However, the coverage of nonapposed side-branch struts might not "come necessarily from circulating endothelial progenitor cells."Still, the main mechanism for reendothelialization is cellular proliferation starting from the noninjured margins and spreading on the strut surface until endothelial continuity is restored, thus resulting in conformal coating of the detached mesh.Nonapposed side-branch struts are not "floating," indeed, as a 2-dimensional cross-section might tempt us to think, but are part of a 3-dimensional structure in close contact with the vessel wall.OCT has been instrumental in our gaining insight into the neointimal healing of detached struts because of its ability for sequential in vivo assessment even of the abluminal side (in translucent polymers).Different manuscripts summarizing our findings in this regard are currently under review and will certainly answer some of the specific questions raised by Dr Pe ´rez de Prado and colleagues.Scientists (not to mention clinicians) are used to pushing the boundaries of knowledge using tools with sensitivity and specificity Ͻ100%.OCT is not an exception, so hypercriticism should not lead us to neglect the enormous potential and the seminal lessons learned from this technology.OCT has been validated in the estimation of neointimal coverage, 2,3 although the logarithmic signal analysis cannot discern the material covering the struts (specificity Ͻ100%).This caveat becomes an issue at very early phases, when the prevalence of struts covered by fibrin or granulation tissue is high; 1 to 3 days after implantation, struts are completely covered with fibrin, resulting in false coverage rates of 45% to 76% in OCT. 2 At later phases, however, when the prevalence of fibrin-covered struts is low, the impact is minimal. 1 Finally, neither experimental nor clinical studies have reported a single case of side-branch embolism in the bioresorbable scaffold.This could be explained by faster resorption in the middle of the lumen than in the regions closer to the vessel wall, thus preventing fracture and embolism, but further studies are warranted.
High mutation detection rate in the COL4A5 collagen gene in suspected Alport syndrome using PCR and direct DNA sequencing.
Authors: P Martin, N Heiskari, J Zhou, A Leinonen, T Tumelius, J M Hertz, D Barker, M Gregory, C Atkin, U Styrkarsdottir, H Neumann, J Springate, T Shows, E Pettersson, K Tryggvason
Journal: Journal of the American Society of Nephrology (1998)

Approximately 85% of patients with Alport syndrome (hereditary nephritis) have been estimated to have mutations in the X chromosomal COL4A5 collagen gene; the remaining cases are autosomal with mutations in the COL4A3 or COL4A4 genes located on chromosome 2. In the present work, the promoter sequence and previously unknown intron sequences flanking exons 2 and 37 of COL4A5 were determined. Furthermore, intron sequences flanking the other 49 exons were expanded from 35 to 190 to facilitate mutation analysis of the gene. Using this information, all 51 exons and the promoter region were PCR-amplified and sequenced from DNA of 50 randomly chosen patients with suspected Alport syndrome. Mutations were found in 41 patients, giving a mutation detection rate of 82%. Retrospective analysis of clinical data revealed that two of the cases might be autosomal. Although it could not be determined whether the remaining seven cases (14%) were autosomal or X chromosome-linked, it is likely that some of them were autosomal. It is concluded that PCR amplification and direct DNA sequencing of the promoter and exons is currently the best procedure to detect mutations in COL4A5 in Alport syndrome.
An HLA-D region restriction fragment length polymorphism associated with celiac disease.
Authors: M D Howell, R K Austin, D Kelleher, G T Nepom, M F Kagnoff
Journal: The Journal of Experimental Medicine (1986)

This study is the first to describe a molecular marker that distinguishes the celiac disease HLA-D region haplotype from a serologically identical haplotype in unaffected controls. Using a DQ beta chain cDNA probe and the restriction endonuclease Rsa I, we have detected a polymorphic 4.0 kb fragment which, in DQw2 individuals, is associated with a 40-fold increased relative risk of developing celiac disease. This finding should permit the identification of the celiac disease susceptibility gene(s) in the HLA-D region and facilitate a more precise dissection of the molecular and immunogenetic mechanisms involved in the pathogenesis of that disease.
Sildenafil: a definitive NO in COPD
Authors: Anton Vonk-Noordegraaf, Bart G. Boerrigter
Journal: European Respiratory Journal (2013)

Several studies have shown that chronic obstructive pulmonary disease (COPD) patients have a low stroke volume at rest and an impaired stroke volume response during exercise [1, 2]. As a consequence, oxygen delivery to the tissues is impaired. Since oxygen delivery is critical for maintenance and growth of muscles, the systemic effects of COPD might, in part, be attributed to the lowered stroke volume. Therefore, restoring the stroke volume response would not only improve oxygen delivery capacity, but may also have beneficial effects at the muscle level. Improving muscle strength may, in turn, enhance exercise tolerance by reducing negative feedback from lower limb sensory muscle afferents and by reducing ventilatory responses and dyspnoea during exercise [3].

Since increased right ventricular afterload is considered the most likely explanation for the impaired stroke volume response, reducing pulmonary artery pressure is the key to restore stroke volume. Although pulmonary hypertension is present in 50% of the patients with severe COPD, pulmonary hypertension is usually mild-to-moderate [4]. However, exercise will induce a steep increase in pulmonary artery pressure in these patients [5, 6 …
OC-085 Circulating tumour markers can discriminate between patients with and without oesophageal neoplasia: Abstract OC-085 Table 1
Authors: R J Mead, M Duku, I Cree, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> Oesophageal cancer is the fastest rising cause of gastro-intestinal cancer in the UK, and associated with a poor prognosis. Early diagnosis represents the best opportunity for cure, but early disease is often asymptomatic. Current surveillance programs improve outcome, but rely on two yearly endoscopic screening of previously identified Barrett9s oesophagus patients. This has limited sensitivity and acceptability to patients. New endoscopic treatments for oesophageal dysplasia can avoid major surgery, but discriminating between patients with and without invasive disease can be challenging. A discriminating diagnostic blood test may offer improved patient outcome. <h3>Methods</h3> In this study, we optimised a series of promising diagnostic markers utilising circulating free DNA (cfDNA), with a preparation method allowing small DNA fragments to be purified. cfDNA was isolated from 115 patients including a “normal” population of 44 patients (Barrett9s oesophagus or normal endoscopic findings). Twenty-five patients had high grade dysplasia (HGD) or intra-mucosal cancer (IMC), and 46 patients had invasive cancer. In each case real time quantitative polymerase chain reaction (RT-PCR) was performed for Line 1 79 bp (quantitative total DNA marker), Line 1 300 bp, Alu 115 bp, Alu 247 bp and mitochondrial primers. Each marker was analysed for differences between normal, HGD and IMC, and invasive cancer populations using Mann–Whitney U tests and ROC curves. The best performing were analysed in combination by logistic regression. A Bonferroni correction was applied. <h3>Results</h3> The average age of the normal population group was 56.1 years, the HGD and IMC population group 70.0 years, and the cancer population group 68.9 years. The mean total DNA (ng/ml) was 10.8, 14.1, and 19.2 respectively. Mean DNA marker levels ng/ml. Analysing total DNA, mitochondrial DNA and Line 1 300bp fragment DNA levels, there were highly significant differences between the normal group vs all dysplastic and cancerous patients (p ≤ 0.003). <h3>Conclusion</h3> The combination DNA marker was able to discriminate the normal population from all dysplasia and cancer patients with a ROC curve of 0.778. This may offer the prospect of a simple blood test to stratify patients and improve surveillance for dysplasia and early cancer. The same model was able to discriminate the normal population from invasive cancer patients with a ROC curve of 0.847. This may help in the rapid identification of patients who require surgery. <h3>Competing interests</h3> None declared.
Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 and -2 in Type 2 Diabetes
Authors: Muzahir H. Tayebjee, H. Sern Lim, Robert J. MacFadyen, Gregory Y.H. Lip
Journal: Diabetes Care (2004)

Cardiovascular risk reduction therapy in diabetic patients reduces vascular events (1) by retarding atherosclerosis and improving vascular reactivity. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) are integral to the vascular changes of atheroma, and MMP-9 and TIMP-1 are raised in diabetes (2). We hypothesized that global risk reduction of intensified diabetes and cardiovascular risk management in type 2 diabetes would be associated with reductions in circulating markers of extracellular matrix turnover, namely MMP-9, TIMP-1, and TIMP-2.

### Cross-sectional study

Eighty-six patients with type 2 diabetes (3) and treated hypertension with serum creatinine <120 mmol/l were recruited from local clinics (Table 1). Of these, 46% ( n = 36) had a clinical history of cardiovascular disease. Data from these patients were compared with 49 healthy control subjects. Ethical approval and informed consent were obtained.

### Interventional study

Sixty-five of the recruited diabetic patients (of whom 36 had cardiovascular disease) consented to intensified diabetes and cardiovascular risk management therapy. This consisted of 3 monthly consultations, lifestyle advice, and adjusting oral hypoglycemia therapy to achieve HbA 1c   25 kg/m 2 or added second-line in lean patients, who received initial treatment with gliclazide MR (30 mg o.d.) and vice versa. Insulin could be started if HbA 1c  remained >7.0% despite …
Clinical trials are bureaucratic, opaque, and offputting to researchers and patients, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2013)

<h3>Introduction</h3> Venous sinus stenting has become increasingly accepted as an acceptable treatment for idiopathic intracranial hypertension (IIH) in selected patients who fail medical treatment and in whom a hemodynamically significant stenosis and pressure gradient can be measured. Technical challenges may include navigating past the jugular bulb or area of stenosis without prolapsing the supporting catheter into the heart and the fact that all carotid stenting systems use a 0.014” wire, which often does not provide adequate support in tortuous venous anatomy. <h3>Methods</h3> We review our initial experience using a peripheral vascular stent using brachial or jugular access, which is delivered over a 0.035" wire. In addition, we review the clinical features and angiographic outcomes of these patients. <h3>Results</h3> Three patients were available with at least 6 month angiographic follow-up. One patient presented with typical IIH symptoms, one with failure of medical and endovascular treatment for sinus thrombosis, and one with acute severe vision loss, intracranial hypertension and sinus stenosis without obvious thrombus. All patients had documented papilledema and the two acute patients also had bilateral 6th cranial nerve palsies. All patients had venous pressure gradients &gt;20 mmHg across the stenotic segment. All stents were deployed across the target segment from either brachial or cervical venous access with a 6F short sheath and a 0.035" Rosen or glide wire. All stents were 10mm diameter, flexible, open cell stents (LifeStar: Bard PV: Tempe, AZ). One patient required two stents and the remainder required only one. Delayed imaging showed patency of all stents without stenosis (range 6–15 months.) Anti-platelet medications were used in all patients_one with aspirin only, two with aspirin and clopidogrel. All patients had improvement of clinical and ophthalmological symptoms. <h3>Conclusions</h3> Venous sinus stenting is a promising treatment for restoration of sinus patency and improvement of clinical symptoms in selected patients. Cervical access and the support of a 0.035” wire makes delivery of the device simpler compared to use of standard carotid stents. <h3>Disclosures</h3> A. Carlson: None. A. Delu: None. C. Taylor: None.
Postremission therapy in older patients with de novo acute myeloid leukemia: a randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine
Authors: Richard M. Stone, Deborah T. Berg, Stephen L. George, Richard K. Dodge, Paolo A. Paciucci, Philip P. Schulman, Edward J. Lee, Joseph O. Moore, Bayard L. Powell, Maria R. Baer, Clara D. Bloomfield, Charles A. Schiffer
Journal: Blood (2001)
Reply to C.D. Atkins
Authors: Smita Bhatia, Javier G. Blanco, Wendy Landier, Mary V. Relling
Journal: Journal of Clinical Oncology (2012)

One of the values that Journal of ClinicalOncology brings to clinicians is the collection of content from different fields.Although I do not treat children with cancer, I make it a habit to peruse articles about pediatric oncology in the event that one of them might resonate with something of importance to my practice.Reviewing the May 1 issue of the Journal while pursuing this habit, I was rewarded by finding articles by Visscher et al 1 and Blanco et al 2 along with an accompanying editorial by Davies 3 discussing the role of single nucleotide polymorphisms in predicting cardiotoxicity after anthracycline-based chemotherapy for childhood cancer.The editorial by Davies 3 is an intelligent, balanced synthesis of the data presented in the two original articles and gives an excellent summary of their importance to the management of childhood cancer.However, the potential implications for adult cancer are entirely missed.Whereas anthracyclines may be an integral part of treatment for those childhood malignancies in which it is used, the situation is different in adults, most glaringly in breast cancer.Anthracyclines are commonly used for adjuvant therapy in early breast cancer, but the survival advantage over nonanthracycline-containing regimens is small (3% to 4% at 8-10 years of follow-up) and limited to higher-dose or prolonged treatment regimens. 4If we could predict which patients will develop anthracycline-induced cardiotoxicity, the risk/benefit ratio of the drugs can be more clearly conveyed to our patients.
Lung function and short-term outcome in young asthmatic children
Authors: B Klug, H Bisgaard
Journal: European Respiratory Journal (1999)

The aims of this study were to investigate lung function in 2-5-yr-old stable asthmatic children consecutively referred from general practitioners and to analyse the outcome on the basis of their requirement for antiasthmatic treatment and symptoms after 1.6-4.5 yrs. Lung function was measured in 110 children with a mean+/-SD age of 3.8+/-1.0 yrs using the interruptor technique (resistance assessed using the interruptor technique (Rint)), whole body plethysmography (specific airway resistance (sRaw) and respiratory resistance (Rrs,5)and reactance at 5 Hz (Xrs,5) using the impulse oscillation technique. Rint, sRaw, Xrs,5 and Rrs,5 were suggestive of impaired lung function in 44%, 14%, 11% and 7.5% of the children, respectively, with a predominance of children aged 2-3 yrs. Sixty-five per cent were treated with inhaled steroids, and 35% were treated only with beta2-agonists as needed; lung function was not significantly different between these two groups. Outcome after 2.9+/-0.7 yrs was not significantly different between children with Rint measurements above and those children with Rint measurements within the reference range at enrolment. Of these children, 58 and 59% were currently on antiasthmatic treatment, and 40% and 49% had current symptoms, respectively. Impairment of lung function may be a common finding in stable young asthmatic children, but apparently this is not a risk factor for persistence of asthmatic symptoms.
MANAGEMENT OF PATIENTS WITH INTERMEDIATE-THICKNESS MELANOMA
Authors: Marshall M. Urist, M.D
Journal: Annual Review of Medicine (1996)

▪ Abstract It is important to understand the management of patients with melanoma because of a rising incidence of this cancer in the United States. The most important prognostic factor is tumor thickness. Patients with early melanoma (thickness &lt;1.0 mm) have an excellent prognosis and are effectively treated with narrow local excision (1-cm radius). Those with advanced melanomas (tumor thickness &gt;4.0 mm) have a high risk of metastases and are treated with a wider local excision (2–3 cm). Controversies surrounding the management of patients with intermediate-thickness melanoma (thickness 1–4 mm) center on the issues of local excision and management of regional lymph nodes. Randomized trials have shown that a 2-cm radius of excision will minimize the risk for local recurrence. Although retrospective analyses have indicated a survival advantage for elective regional lymph node dissection, two randomized trials have not shown a benefit for the early removal of lymph nodes. Two more randomized trials are in progress. Techniques are now available to identify the sentinel lymph node, which will help to limit lymph node dissections to those patients with nodal metastases. Postoperative surveillance for recurrence is most effectively performed with a combination of patient self-examination and regular physician examinations rather than frequent X-rays and laboratory tests. Adjuvant therapy has not been proven effective for melanoma patients; however, many investigational trials are available.
Antiangiogenic Treatment with Three Thrombospondin-1 Type 1 Repeats versus Gemcitabine in an Orthotopic Human Pancreatic Cancer Model
Authors: Xuefeng Zhang, Eric Galardi, Mark Duquette, Jack Lawler, Sareh Parangi
Journal: Clinical Cancer Research (2005)

Abstract Purpose: In this study, we investigated the antitumor efficacy of thrombospondin-1 three type 1 repeats (3TSR), the antiangiogenic domain of thrombospondin-1, in comparison and in combination with gemcitabine, in an orthotopic pancreatic cancer model. Experimental Design: Human pancreatic cancer cells were injected into the pancreas of severe combined immunodeficient mice. The animals were treated with 3TSR, gemcitabine, 3TSR plus gemcitabine, or vehicle for 3 weeks. Subsequently, the effects of 3TSR and/or gemcitabine on tumor growth, tumor necrosis, microvessel density, cancer cell proliferation, apoptosis, and endothelial cell apoptosis were analyzed. Results: After 3 weeks of treatment, 3TSR reduced tumor volume by 65%, and gemcitabine by 84%. Tumor volume was not statistically different between gemcitabine group and combinatorial treatment group. Extensive necrotic areas were observed in tumors from 3TSR-treated mice, whereas tumors from gemcitabine and combinatorially treated mice were less necrotic than control tumors. 3TSR reduced tumor microvessel density and increased tumor blood vessel endothelial cell apoptosis. In contrast, gemcitabine induced apoptosis and inhibited proliferation of cancer cells. Conclusion: 3TSR, the antiangiogenic domain of thrombospondin-1, showed comparable antitumor efficacy to gemcitabine in a human pancreatic cancer orthotopic mouse model. No synergistic effect was found when the two drugs were combined and possible reasons are discussed in detail. A delicate balance between normalization and excessive regression of tumor vasculature is important when initiating alternative combinatorial regimens for treatment of patients with pancreatic cancer.
Expiratory valves used for home devices: experimental and clinical comparison
Authors: F Lofaso, P Aslanian, JC Richard, D Isabey, T Hang, E Corriger, A Harf, L Brochard
Journal: European Respiratory Journal (1998)

A bench study followed by a clinical trial were performed to evaluate the mechanical characteristics of five (commercially available) expiratory valves used for home ventilators, as well as the potential clinical impact of differences between these valves. In the in vitro study, expiratory valve resistance was evaluated under unvarying conditions, whereas dynamic behaviour was evaluated by calculating the imposed expiratory work of breathing during a simulated breath generated by a lung model. Differences in resistance and imposed expiratory work of up to twofold and 150%, respectively, were found across valves. We then conducted a randomized crossover clinical study to compare the effects of the least resistive (Bennett) and most resistive expiratory valves (Peters) in 10 intubated patients receiving pressure support ventilation. There were no significant differences regarding blood gases or respiratory parameters except for the oesophageal pressure-time product (PTPoes), which was significantly increased by the Peters valve (236+/-113 cmH2O x s x min(-1) versus 194+/-90 cmH2O x s x min(-1)). An analysis of individual responses found that the Peters valve induced substantial increases in intrinsic positive end-expiratory pressure (PEEP), PTPoes, and expiratory activity in those patients with the greatest ventilatory demand. In conclusion, differences between home expiratory valve resistances may have a clinically relevant impact on the respiratory effort of patients with a high ventilatory demand.