tbuckley/cabot-search huggingface dataset:
Multislice Spiral Computed Tomography for the Evaluation of Stent Patency After Left Main Coronary Artery Stenting
Authors: Carlos A.G. Van Mieghem, Filippo Cademartiri, Nico R. Mollet, Patrizia Malagutti, Marco Valgimigli, Willem B. Meijboom, Francesca Pugliese, Eugene P. McFadden, Jurgen Ligthart, Giuseppe Runza, Nico Bruining, Pieter C. Smits, Evelyn Regar, Willem J. van der Giessen, Georgios Sianos, Ron van Domburg, Peter de Jaegere, Gabriel P. Krestin, Patrick W. Serruys, Pim J. de Feyter
Journal: Circulation (2006)

Background— Surveillance conventional coronary angiography (CCA) is recommended 2 to 6 months after stent-supported left main coronary artery (LMCA) percutaneous coronary intervention due to the unpredictable occurrence of in-stent restenosis (ISR), with its attendant risks. Multislice computed tomography (MSCT) is a promising technique for noninvasive coronary evaluation. We evaluated the diagnostic performance of high-resolution MSCT to detect ISR after stenting of the LMCA. Methods and Results— Seventy-four patients were prospectively identified from a consecutive patient population scheduled for follow-up CCA after LMCA stenting and underwent MSCT before CCA. Until August 2004, a 16-slice scanner was used (n=27), but we switched to the 64-slice scanner after that period (n=43). Patients with initial heart rates &gt;65 bpm received β-blockers, which resulted in a mean periscan heart rate of 57±7 bpm. Among patients with technically adequate scans (n=70), MSCT correctly identified all patients with ISR (10 of 70) but misclassified 5 patients without ISR (false-positives). Overall, the accuracy of MSCT for detection of angiographic ISR was 93%. The sensitivity, specificity, and positive and negative predictive values were 100%, 91%, 67%, and 100%, respectively. When analysis was restricted to patients with stenting of the LMCA with or without extension into a single major side branch, accuracy was 98%. When both branches of the LMCA bifurcation were stented, accuracy was 83%. For the assessment of stent diameter and area, MSCT showed good correlation with intravascular ultrasound ( r =0.78 and 0.73, respectively). An intravascular ultrasound threshold value ≥1 mm was identified to reliably detect in-stent neointima hyperplasia with MSCT. Conclusions— Current MSCT technology, in combination with optimal heart rate control, allows reliable noninvasive evaluation of selected patients after LMCA stenting. MSCT is safe to exclude left main ISR and may therefore be an acceptable first-line alternative to CCA.
Thromboembolism in Hospitalized Neutropenic Cancer Patients
Authors: Alok A. Khorana, Charles W. Francis, Eva Culakova, Richard I. Fisher, Nicole M. Kuderer, Gary H. Lyman
Journal: Journal of Clinical Oncology (2006)

Cancer is associated with thrombosis, but the frequency of thromboembolism in hospitalized cancer patients receiving current chemotherapy regimens is not known. We investigated venous and arterial thromboembolism and associated outcomes in hospitalized cancer patients actively receiving therapy, as identified by neutropenia.We conducted a retrospective cohort study using the discharge database of the University HealthSystem Consortium. This included 66,106 adult neutropenic cancer patients with 88,074 hospitalizations between 1995 and 2002 at 115 medical centers in the United States.Thromboembolism was reported in 5,272 patients (8%), with 5.4% patients developing venous thromboembolism and 1.5% developing arterial thromboembolism during the first hospitalization. Patients with lymphoma and leukemia accounted for one third of venous and nearly one half of arterial events. Clinical variables most frequently associated with thromboembolism were age > or = 65 years; primary site of cancer, including lung, GI, gynecologic, and brain; and comorbidities, including infection, pulmonary and renal disease, and obesity. In-hospital mortality was significantly greater in patients with venous (odds ratio [OR] = 2.01; 95% CI, 1.83 to 2.22) or arterial thromboembolism (OR = 5.04; 95% CI, 4.38 to 5.79). From 1995 to 2002, there was a 36% increase in venous events and a 124% increase in arterial events (P < .0001 for trend).Thromboembolism is frequent in hospitalized neutropenic cancer patients, including in perceived low-risk subgroups such as patients with hematologic malignancies and nonmetastatic disease, and seems to be increasing. Thromboembolism is associated with increased in-hospital mortality. Increased efforts at thromboprophylaxis are warranted.
Proepithelin Promotes Migration and Invasion of 5637 Bladder Cancer Cells through the Activation of ERK1/2 and the Formation of a Paxillin/FAK/ERK Complex
Authors: Giada Monami, Eva M. Gonzalez, Michelle Hellman, Leonard G. Gomella, Raffaele Baffa, Renato V. Iozzo, Andrea Morrione
Journal: Cancer Research (2006)

Abstract The growth factor proepithelin (also known as progranulin, acrogranin, PC-derived growth factor, or granulin-epithelin precursor) is a secreted glycoprotein that functions as an important regulator of cell growth, migration, and transformation. Proepithelin is overexpressed in a great variety of cancer cell lines and clinical specimens of breast, ovarian, and renal cancer as well as glioblastomas. In this study, we have investigated the effects of proepithelin on bladder cancer cells using human recombinant proepithelin purified to homogeneity from 293-EBNA cells. Although proepithelin did not appreciably affect cell growth, it did promote migration of 5637 bladder cancer cells and stimulate in vitro wound closure and invasion. These effects required the activation of the mitogen-activated protein kinase pathway and paxillin, which upon proepithelin stimulation formed a complex with focal adhesion kinase and active extracellular signal-regulated kinase. Our results provide the first evidence for a role of proepithelin in stimulating migration and invasion of bladder cancer cells, and support the hypothesis that this growth factor may play a critical role in the establishment of the invasive phenotype. (Cancer Res 2006; 66(14): 7103-10)
Effects of nicotine on the human nasal mucosa.
Authors: L Greiff, P Wollmer, I Erjefalt, M Andersson, U Pipkorn, C G Persson
Journal: Thorax (1993)

Topical application of nicotine and stimulation of tachykinin containing sensory nerves have been shown to produce mucosal exudation of plasma and derangement of the epithelial lining in guinea pig and rat airways. If this occurred in man these effects might contribute to the pathogenesis of airway disease. This study, performed in healthy volunteers without atopy, examined whether nicotine affects the plasma exudation response and the mucosal absorption permeability of the human nasal airway.The acute effects of increasing topical doses of nicotine (0.08-2.0 mg) were examined (n = 8) on nasal symptoms (pain), mucosal exudation of plasma (albumin), mucosal secretion of mucin (fucose), and mucosal exudative responsiveness (histamine induced mucosal exudation of albumin). A separate placebo controlled study was carried out to determine whether frequent applications of the high dose of nicotine (2.0 mg given eight times daily for nine days) had any deleterious effects on the airway mucosa detectable as altered responses to histamine challenge. Both mucosal exudation of plasma (n = 12) and mucosal absorption of chromium-51 labelled EDTA (n = 8) were thus examined in nasal airways exposed to both nicotine and histamine.Nicotine caused nasal pain and produced dose dependent mucosal secretion of fucose but failed to produce any mucosal exudation of albumin. The exudative responsiveness to histamine was, indeed, decreased when the challenge was performed immediately after administration of acute doses of nicotine, whereas the responsiveness was unaffected when histamine challenges were carried out during prolonged treatment with nicotine. The nasal mucosal absorption of 51Cr-EDTA in the presence of histamine did not differ between subjects receiving either placebo or nicotine treatment for nine days.The results indicate that nicotine applied to the human airway mucosa produces pain and secretion of mucin, but inflammatory changes such as mucosal exudation of plasma and epithelial disruption may not be produced. Neurogenic inflammatory responses, which are so readily produced in guinea pig and rat airways, may not occur in human airways.
A Physiologic Imaging Pilot Study of Breast Cancer Treated with AZD2171
Authors: Kathy D. Miller, Michael Miller, Sanjana Mehrotra, Beamon Agarwal, Bruce H. Mock, Qi-Huang Zheng, Sunil Badve, Gary D. Hutchins, George W. Sledge
Journal: Clinical Cancer Research (2006)

Abstract Background: This pilot study combined physiologic imaging, microcomputed tomography, and histologic tumor evaluation with a xenograft model of breast cancer to identify surrogates likely to correlate with response to AZD2171, an inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinases. Experimental Design: MCF-7 cells transfected with vector (MCF-7neo) or VEGF (MCFVEGF) were implanted in the right and left mammary fat pads of 75 athymic mice. Treatment with AZD2171 (5 mg/kg/d) or vehicle control was initiated once tumors were established. Positron emission tomography with [11C]carbon monoxide to measure blood volume, [18F]fluoromethane to measure perfusion, and [18F]fluorodeoxyglucose to measure glucose utilization was done at baseline, and after 24 hours, 72 hours, and 4 weeks of treatment. After imaging, tumors were analyzed for microvessel density, proliferation, and VEGF expression. Results: AZD2171 induced significant inhibition of tumor growth in established MCF-7neo xenografts and regression of established MCF-7VEGF xenografts. An acute decrease in blood flow was detected in MCF-7VEGF tumors at 24 hours (P = 0.05). Tumor blood volume was increased in the MCF-7VEGF tumors but correlated with tumor size; blood volume did not change with AZD2171 therapy. Glucose utilization correlated with tumor size and did not change with acute or chronic AZD2171 therapy. Unlike blood flow and blood volume, glucose utilization was similar in MCF-7neo and MCF-7VEGF tumors. Microvessel density and proliferation acutely decreased in MCF-7VEGF tumors but returned to baseline during chronic therapy. Conclusions: [18F]Fluoromethane imaging may be a useful surrogate for biological activity of AZD2171 with changes identified within 24 hours of starting therapy.
The Severity of Neural Invasion Is Associated with Shortened Survival in Colon Cancer
Authors: Florian Liebl, Ihsan Ekin Demir, Robert Rosenberg, Alexandra Boldis, Esra Yildiz, Kristina Kujundzic, Timo Kehl, Dominic Dischl, Tibor Schuster, Matthias Maak, Karen Becker, Rupert Langer, Melanie Laschinger, Helmut Friess, Güralp O. Ceyhan
Journal: Clinical Cancer Research (2012)

Neural invasion (NI) is a histopathologic feature of colon cancer that receives little consideration. Therefore, we conducted a morphologic and functional characterization of NI in colon cancer.NI was investigated in 673 patients with colon cancer. Localization and severity of NI was determined and related to patient's prognosis and survival. The neuro-affinity of colon cancer cells (HT29, HCT-116, SW620, and DLD-1) was compared with pancreatic cancer (T3M4 and SU86.86) and rectal cancer cells (CMT-93) in the in vitro three-dimensional (3D)-neural-migration assay and analyzed via live-cell imaging. Immunoreactivity of the neuroplasticity marker GAP-43, and the neurotrophic-chemoattractant factors Artemin and nerve growth factor (NGF), was quantified in colon cancer and pancreatic cancer nerves. Dorsal root ganglia of newborn rats were exposed to supernatants of colon cancer, rectal cancer, and pancreatic cancer cells and neurite density was determined.NI was detected in 210 of 673 patients (31.2%). Although increasing NI severity scores were associated with a significantly poorer survival, presence of NI was not an independent prognostic factor in colon cancer. In the 3D migration assay, colon cancer and rectal cancer cells showed much less neurite-targeted migration when compared with pancreatic cancer cells. Supernatants of pancreatic cancer and rectal cancer cells induced a much higher neurite density than those of colon cancer cells. Accordingly, NGF, Artemin, and GAP-43 were much more pronounced in nerves in pancreatic cancer than in colon cancer.NI is not an independent prognostic factor in colon cancer. The lack of a considerable biologic affinity between colon cancer cells and neurons, the low expression profile of colonic nerves for chemoattractant molecules, and the absence of a major neuroplasticity in colon cancer may explain the low prevalence and impact of NI in colon cancer.
Independent sector treatment centres: how the NHS is left to pick up the pieces
Authors: W Angus Wallace
Journal: BMJ (2006)

T here is no doubt that the expansion of orthopaedic services, provided by the Department of Health through private hospitals and independent sector treatment centres (ISTCs), has been a much needed development, but it has occurred at a price. Admittedly there are many patients who have benefited from the development of ISTCs and are now leading pain free lives as a result of surgery carried out much earlier than would have been possible in the early 1990s, when our health service was grossly underfunded. However, the number of patients we are seeing with problems resulting from poor surgery—incorrectly inserted prostheses, technical errors, and infected joint replacements—is too great.

> The number of patients we are seeing with problems resulting from poor surgery is too great 

Perhaps we should look at the mechanisms through which this whole ISTC exercise has been carried out. Surgeons from overseas have been flown into the United Kingdom to increase the numbers available to provide elective orthopaedic services. They have come from many countries, usually European, and their training and clinical practice at home are quite different from those to which they are exposed in an ISTC.

In Germany, Hungary, and Croatia, for example—countries I know about because I have visited surgical centres in all of them—the junior specialist usually …
The Interplay between the Effects of Lifetime Asthma, Smoking, and Atopy on Fixed Airflow Obstruction in Middle Age
Authors: Jennifer L. Perret, Shyamali C. Dharmage, Melanie C. Matheson, David P. Johns, Lyle C. Gurrin, John A. Burgess, John Marrone, James Markos, Stephen Morrison, Iain Feather, Paul S. Thomas, Christine F. McDonald, Graham G. Giles, John L. Hopper, Richard Wood-Baker, Michael J. Abramson, Eugene H. Walters
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: The contribution by asthma to the development of fixed airflow obstruction (AO) and the nature of its effect combined with active smoking and atopy remain unclear.Objectives: To investigate the prevalence and relative influence of lifetime asthma, active smoking, and atopy on fixed AO in middle age.Methods: The population-based Tasmanian Longitudinal Health Study cohort born in 1961 (n = 8,583) and studied with prebronchodilator spirometry in 1968 was retraced (n = 7,312) and resurveyed (n = 5,729 responses) from 2002 to 2005. A sample enriched for asthma and chronic bronchitis underwent a further questionnaire, pre- and post-bronchodilator spirometry (n = 1,389), skin prick testing, lung volumes, and diffusing capacity measurements. Prevalence estimates were reweighted for sampling fractions. Multiple linear and logistic regression were used to assess the relevant associations.Measurements and Main Results: Main effects and interactions between lifetime asthma, active smoking, and atopy as they relate to fixed AO were measured. The prevalence of fixed AO was 6.0% (95% confidence interval [CI], 4.5–7.5%). Its association with early-onset current clinical asthma was equivalent to a 33 pack-year history of smoking (odds ratio, 3.7; 95% CI, 1.5–9.3; P = 0.005), compared with a 24 pack-year history for late-onset current clinical asthma (odds ratio, 2.6; 95% CI, 1.03–6.5; P = 0.042). An interaction (multiplicative effect) was present between asthma and active smoking as it relates to the ratio of post-bronchodilator FEV1/FVC, but only among those with atopic sensitization.Conclusions: Active smoking and current clinical asthma both contribute substantially to fixed AO in middle age, especially among those with atopy. The interaction between these factors provides another compelling reason for atopic individuals with current asthma who smoke to quit.
A pregnant woman with acute cardiorespiratory failure: dengue myocarditis
Authors: Thuy Duong Bich, Oanh Kieu Nguyet Pham, Duong Ha Thi Hai, Nguyet Minh Nguyen, Hao Nguyen Van, Trung Dinh The, Bridget Wills, Sophie Yacoub
Journal: The Lancet (2015)
Pigmented actinic lichen planus successfully treated with intense pulsed light
Authors: J. Santos-Juanes, A. Mas-Vidal, P. Coto-Segura, J. Sánchez del Río, C. Galache Osuna
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, Actinic lichen planus (ALP) is a rare clinical variant of lichen planus. Pigmented actinic lichen planus (PALP) may constitute the final stage of other ALP variants, or may be a distinctive type of ALP with clinical features similar to those of melasma, but restricted to the face.1 In this study, we present a patient with PALP that was successfully treated with intense pulsed light (IPL). To the best of our knowledge, this therapeutic option has not been previously used. An otherwise healthy 55‐year‐old white woman (Fitzpatrick skin type II) was referred to our department because of a 3‐year history of a facial pigment disorder. The dermatosis started in summer, but no remarkable improvement was noticed during the winter season. The clinical findings worsened during the subsequent sunny seasons. The patient had no history of drug contact or intake. There was no family history of any similar condition. The patient had tried treating the skin condition with 4% hydroquinone preparations applied twice daily, to no avail. On physical examination, asymptomatic, large, symmetrical patches of dark brown colour with irregular borders were present in the cheeks, the chin and the neck, sparing the skin under the chin (Fig. 1, left). No further cutaneous or mucosal lesions were found. The Dermatology Life Quality Index (DLQI) score was 27. Biopsy specimens from the skin of the neck showed orthokeratosis, focal hypergranulosis and jagged epidermal hyperplasia. The patient was treated with acitretin 0·25 mg kg−1 daily for 4 months, and 0·1% methylprednisolone ointment applied twice daily for 1 month. Protection measures against natural ultraviolet (UV) radiation were taken, and she was also instructed to avoid sun exposure. No improvement of lesions was observed during the 4 months of treatment. The patient started taking hydroxychloroquine 200 mg daily, without improvement after 2 months. Afterwards, she was treated with oral ciclosporin 3 mg kg−1 daily for 3 months; after the treatment, the hyperpigmentation remained unchanged. Thus, treatment with IPL was proposed. A Harmony® VL/PL module with Advanced Fluorescence Technology (Alma Lasers, Caesarea, Israel) was used with the following settings: wavelength 540–950 nm; pulse width 12 ms; spot size 40 × 16 mm; pulse repetition rate 1/3 Hz; energy density 12 J cm−2 for the first three sessions and 14 J cm−2 from the fourth to seventh sessions. The patient was instructed to avoid the sun. After the seventh session, the patient showed a good improvement (DLQI = 6; Fig. 1, right).
Update on Sleep and Its Disorders
Authors: Allan I. Pack, Grace W. Pien
Journal: Annual Review of Medicine (2010)

Inadequate sleep and sleep disorders have important adverse consequences on multiple systems. This review covers three areas: (a) Genetic determinants of sleep disorders. Common gene variants with small effects have been identified for both restless legs syndrome and narcolepsy with cataplexy. Rare variants with large effects have been found in familial phase advance syndrome and in subjects with short sleep durations. (b) Obstructive sleep apnea (OSA). OSA is an oxidative stress disorder. Prospective cohort studies show an increased risk of cardiovascular events in patients with untreated severe OSA. (c) The impact of sleep disorders on obesity and diabetes. Inadequate sleep results in changes in insulin resistance and in hormone levels leading to increases in appetite. Hence, inadequate sleep is associated with development of obesity. OSA is also an independent risk factor for insulin resistance; treatment of OSA can improve insulin sensitivity.
Microvascular caliber changes in intramucosal and submucosally invasive esophageal cancer
Authors: E. Santi, H. Inoue, H. Ikeda, A. Yoshida, M. Onimaru, H. Sato, R. Maselli, B.-H. Hayee, S.-E. Kudo
Journal: Endoscopy (2013)

<b>Background and study aim:</b> Intrapapillary capillary loops (IPCLs) show distinct pattern changes corresponding to tumor progression and depth of invasion, important for in vivo characterization of superficial squamous cell carcinoma (SCC). We examined the relation between invasion depth and histopathologic IPCL diameter. <b>Patients and methods:</b> Prospectively, before lesion resection, magnification endoscopy and narrow band imaging were used to identify IPCL patterns of type V1 (corresponding to tumors limited to the mucosa; 10 patients) and type Vn (submucosally invading tumors; 10 patients). Post-resection, IPCL samples (type I [normal mucosa], n = 103; V1, n = 113; Vn, n = 100) were stained with hematoxylin & eosin, CD34, and desmin, and vessel diameter measured using light microscopy. <b>Results:</b> Mean (standard deviation [SD]) histopathologic calibers of IPCLs of types I, V1, and Vn were significantly different, being 7.7 (2.8) µm, 21.9 (7.4) µm, and 65.2 (22.9) µm; type 1 vs. V1, <i>P</i> < 0.001; V1 vs. Vn, <i>P</i> < 0.001. <b>Conclusions:</b> Magnification endoscopy observation of IPCLs allows in vivo discrimination between intramucosal and submucosally invasive cancer.
Serum-dependent transcriptional networks identify distinct functional roles for H-Ras and N-Ras during initial stages of the cell cycle
Authors: Esther Castellano, Carmen Guerrero, Alejandro Núñez, Javier De Las Rivas, Eugenio Santos
Journal: Genome biology (2009)

Using oligonucleotide microarrays, we compared transcriptional profiles corresponding to the initial cell cycle stages of mouse fibroblasts lacking the small GTPases H-Ras and/or N-Ras with those of matching, wild-type controls.Serum-starved wild-type and knockout ras fibroblasts had very similar transcriptional profiles, indicating that H-Ras and N-Ras do not significantly control transcriptional responses to serum deprivation stress. In contrast, genomic disruption of H-ras or N-ras, individually or in combination, determined specific differential gene expression profiles in response to post-starvation stimulation with serum for 1 hour (G0/G1 transition) or 8 hours (mid-G1 progression). The absence of N-Ras caused significantly higher changes than the absence of H-Ras in the wave of transcriptional activation linked to G0/G1 transition. In contrast, the absence of H-Ras affected the profile of the transcriptional wave detected during G1 progression more strongly than did the absence of N-Ras. H-Ras was predominantly functionally associated with growth and proliferation, whereas N-Ras had a closer link to the regulation of development, the cell cycle, immunomodulation and apoptosis. Mechanistic analysis indicated that extracellular signal-regulated kinase (ERK)-dependent activation of signal transducer and activator of transcription 1 (Stat1) mediates the regulatory effect of N-Ras on defense and immunity, whereas the pro-apoptotic effects of N-Ras are mediated through ERK and p38 mitogen-activated protein kinase signaling.Our observations confirm the notion of an absolute requirement for different peaks of Ras activity during the initial stages of the cell cycle and document the functional specificity of H-Ras and N-Ras during those processes.