tbuckley/cabot-search huggingface dataset:
Phase II study on lapatinib in advanced EGFR-positive chordoma
Authors: S. Stacchiotti, E. Tamborini, S. Lo Vullo, F. Bozzi, A. Messina, C. Morosi, A. Casale, F. Crippa, E. Conca, T. Negri, E. Palassini, A. Marrari, E. Palmerini, L. Mariani, A. Gronchi, S. Pilotti, P.G. Casali
Journal: Annals of Oncology (2013)
Bilateral chylothorax complicating massive osteolysis (Gorham's syndrome)
Authors: P. Riantawan, S. Tansupasawasdikul, P. Subhannachart
Journal: Thorax (1996)

Abstract Chylothorax may rarely occur in osteolysis. A fatal case of bilateral chylothorax complicating massive osteolysis is described and the pathogenesis and management are discussed.
Early Allogeneic Stem-Cell Transplantation for Young Adults With Acute Myeloblastic Leukemia in First Complete Remission: An Intent-to-Treat Long-Term Analysis of the BGMT Experience
Authors: Eric Jourdan, Jean-Michel Boiron, Nicole Dastugue, Norbert Vey, Gérald Marit, Françoise Rigal-Huguet, Lysiane Molina, Nathalie Fegueux, Arnaud Pigneux, Christian Recher, Jean-François Rossi, Michel Attal, Jean-Jacques Sotto, Dominique Maraninchi, Josy Reiffers, Valerie-Jeanne Bardou, Benjamin Esterni, Didier Blaise
Journal: Journal of Clinical Oncology (2005)

We analyzed the impact of allogeneic stem-cell transplantation (alloSCT) as an early consolidation for young patients with acute myeloblastic leukemia in first complete remission (CR1) through four successive protocols.Of the 472 patients who achieved CR1, 182 (38%) had an HLA-identical sibling (donor group), and alloSCT was performed in 171 patients (94%). Of the 290 patients without donor (no-donor group), 62% received an autologous SCT.In an intent-to-treat analysis based on donor availability, the overall 10-year survival probability was 51% v 43% (P = .11) for the donor and no-donor groups, respectively. A Cox analysis determined that four factors had independent prognostic significance for survival (initial WBC count, French-American-British subtypes, cytogenetic risk, and number of induction courses). This permitted constitution of a simple index that reclassified 21% of the patients compared with usual cytogenetic classification and identified three subpopulations with different outcome and different impact of alloSCT.AlloSCT was associated with a survival advantage for an intermediate-risk group. In other groups, numbers are limited for definitive conclusion. However, early performed alloSCT does not seem to be the optimal treatment of high-risk patients or offer any advantage over intensive chemotherapy in low-risk patients.
Myocardial infarction after aspirin
Authors: S Rachapalli
Journal: Journal of the Royal Society of Medicine (2005)

Dr Fox and his colleagues (January 2004, JRSM1) describe a patient who had a myocardial infarction in the course of a severe allergic reaction to aspirin. They suggest that the observed coronary vasospasm could have been due either to aspirin directly or to massive release of catecholamines during the anaphylactic reaction. In my opinion, the latter explanation is more likely. There are many reports of coronary vasospasm in severe anaphylaxis—for example, in allergic reactions to drugs such as amoxicillin2 and naproxen3 and even after a bee sting.4 Physicians should be cautious in using epinephrine in these circumstances since it can worsen the vasospasm.5
Bone Metastases in Lung Cancer. Potential Novel Approaches to Therapy
Authors: Silvestre Vicent, Naiara Perurena, Ramaswamy Govindan, Fernando Lecanda
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The skeleton is a common site of metastases in lung cancer, an event associated with significant morbidities and poor outcomes. Current antiresorptive therapies provide limited benefit, and novel strategies of prevention and treatment are urgently needed. This review summarizes the latest advances and new perspectives on emerging experimental and clinical approaches to block this deleterious process. Progress propelled by preclinical models has led to a deeper understanding on the complex interplay of tumor cells in the osseous milieu, unveiling potential new targets for drug development. Improvements in early diagnosis through the use of sophisticated imaging techniques with bone serum biomarkers are also discussed in the context of identifying patients at risk and monitoring disease progression during the course of treatment.
Neurogenic bladder due to peripheral neuropathy and a visual disturbance in an elderly man with systemic lupus erythematosus.
Authors: T Wada, H Yokoyama, K Ikeda, N Tomosugi, K Kobayashi
Journal: Annals of the Rheumatic Diseases (1992)

A 63 year old man with central nervous system lupus with a neurogenic bladder and visual disturbance is described. The diagnosis of neurogenic bladder, attributed to peripheral neuropathy, was made on the basis of cystometrography and clinical symptoms. A brain magnetic resonance imaging scan showed gliosis along the cerebral vessels and the optic nerve. This case shows that systemic lupus erythematosus can be accompanied by a peripheral neurogenic bladder and visual disturbance, and that these symptoms may not improve despite the amelioration of other lupus symptoms on treatment with steroids.
Concordance and Discordance in Tumor Genomic Profiling
Authors: Levi A. Garraway
Journal: Journal of Clinical Oncology (2012)

Each year, ASCO organizes a wide array of high-quality meetings that provide educational and scientific programs to advance our understanding of cancer.At each of ASCO's meetings, you can expect an engaging and interactive agenda featuring high-level scientific or clinical abstracts and educational sessions led by world-class faculty.Join us to earn CME credit, network with colleagues, and interact with cancer experts.
Peripheral and respiratory muscles in chronic heart failure
Authors: G Stassijns, R Lysens, M Decramer
Journal: European Respiratory Journal (1996)

It is well-established that in patients with congestive heart failure (CHF), exercise is limited by fatigue and shortness of breath. The poor correlation between the fatigue and indices of central haemodynamic function might indicate that peripheral muscle alterations contribute to impaired exercise capacity. Intrinsic abnormalities of the skeletal muscles have been suggested as a possible explanation. Since the shortness of breath correlates poorly with changes in lung function, changes in the respiratory muscles have been investigated. Studies have demonstrated diaphragmatic myopathy and atrophy similar, in part, to the changes in peripheral skeletal muscles. In CHF, type I (slow twitch) fibre atrophy is seen in respiratory as well as in peripheral muscles. The mechanism of these alterations remains to be elucidated. Studies into the mechanism of muscle dysfunction in congestive heart failure are relevant to the prospect of treatment of the changes in peripheral and respiratory muscles.
Influence of Sex on Toxicity and Treatment Outcome in Small-Cell Lung Cancer
Authors: Simron Singh, Wendy Parulekar, Nevin Murray, Ronald Feld, William K. Evans, Dongsheng Tu, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2005)

Female sex has been shown consistently to be a favorable prognostic factor in small-cell lung cancer (SCLC). Studies have shown that women with other tumor types experience greater treatment toxicity, but there have been few studies of sex-related toxicity in SCLC.This was a sex-based retrospective analysis of four SCLC trials conducted by the National Cancer Institute of Canada Clinical Trials Group between 1987 and 1999. The 1,006 patients (648 males and 358 females) received similar chemotherapy consisting of cyclophosphamide-doxorubicin-vincristine and etoposide-cisplatin. Toxicities examined included myelosuppression, stomatitis, vomiting, and infection. Other end points included dose reductions and omissions, response, and survival.Women experienced significantly more hematologic toxicity than men (grade 3 and 4 anemia, 16.3% v 7.6%, respectively, P < .001; grade 3 and 4 leukopenia, 80.4% v 69.2%, respectively, P = .0001). However, toxic death rates were similar for men and women (1.5% v 1.1%, respectively, P = .58). Women also had significantly more stomatitis and vomiting of all grades. Despite increased toxicity, 76% of females versus 73.4% of males received all six treatment cycles (P = .38), but 52% of females versus 43.4% of males had treatment delayed for 2 weeks or more (P = .022). Only 31.8% of females and 28.2% of males had at least one cycle of chemotherapy dose reduction (P = .23). The overall response rate was 80.3% for females and 66.9% for males (P < .0001), and the median survival time was 1.31 years for females compared with only 0.91 year for males (P < .0001).Women experience more chemotherapy-related toxicity in the treatment of SCLC, but they also have increased response rates and survival.
Beneficial effects of alpha 1-adrenoceptor activity on myocardial stunning in dogs.
Authors: M Kitakaze, M Hori, H Sato, K Iwakura, K Gotoh, M Inoue, A Kitabatake, T Kamada
Journal: Circulation Research (1991)

This study was undertaken to elucidate whether alpha-1 adrenoceptor activity is beneficial to contractile dysfunction during reperfusion after a brief period of ischemia (stunned myocardium) in 54 open-chest dogs. Contractile dysfunction assessed by fractional shortening (FS) was observed 3 hours after the onset of reperfusion following 15 minutes of complete occlusion of the left anterior descending coronary artery. Pretreatment with prazosin (4 micrograms/kg/min i.c.) further deteriorated contractile dysfunction compared with the untreated condition (12.7 +/- 0.6% versus 6.9 +/- 0.4% with prazosin treatment, p less than 0.001). Conversely, alpha 1-adrenoceptor agonists, methoxamine (1.0 microgram/kg/min i.c.) and norepinephrine (0.24 microgram/kg/min i.c.) with rauwolscine and propranolol, significantly attenuated contractile dysfunction (FS in the methoxamine-treated group, 17.3 +/- 0.3%, p less than 0.001 versus the untreated group; FS in the norepinephrine-treated group, 18.0 +/- 0.9%, p less than 0.05 versus 13.6 +/- 1.1% in the propranolol group). Both adenosine release and hyperemic coronary flow response during the early reperfusion period were significantly attenuated in the prazosin-treated group, and both were enhanced in the alpha 1-adrenoceptor stimulation groups. These results suggest that beneficial effects of alpha 1-adrenoceptor activity may be due to the enhanced release of adenosine. To test the cause-effect relation between the extent of adenosine release and contractile dysfunction during reperfusion, 8-phenyltheophylline was infused to block adenosine receptors in the methoxamine-treated group. The treatment with 8-phenyltheophylline completely abolished (FS, 7.4 +/- 0.3%) the beneficial effect of the enhanced adenosine release by alpha 1-adrenoceptor stimulation. Furthermore, in the prazosin-treated group, adenosine (9 micrograms/kg/min) was additionally infused into the left anterior descending coronary artery 5 minutes before and 2 hours after the onset of reperfusion. Both hyperemic coronary flow and contractile dysfunction (FS, 17.3 +/- 0.3%) recovered to the levels of the alpha 1-adrenoceptor stimulation groups. However, treatment with papaverine could not prevent deleterious effects of prazosin despite the fact that comparable hyperemic flow was obtained. Instead, lactate production up to 10 minutes after the onset of reperfusion was significantly larger (p less than 0.01) despite augmented contractile function in the prazosin-treated and the 8-phenyltheophylline with methoxamine-treated groups compared with the untreated group. The electron microscopic examination revealed no irreversible myocardial injury with and without pharmacological interventions. Thus, we conclude that alpha 1-adrenoceptor activity can reduce the magnitude of myocardial stunning and that its cellular mechanism is due to enhanced adenosine release by alpha 1-adrenoceptor activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Knee pain and osteoarthritis in older adults: a review of community burden and current use of primary health care
Authors: G Peat
Journal: Annals of the Rheumatic Diseases (2001)

<h3>BACKGROUND</h3> Osteoarthritis is the single most common cause of disability in older adults, and most patients with the condition will be managed in the community and primary care. <h3>AIM</h3> To discuss case definition of knee osteoarthritis for primary care and to summarise the burden of the condition in the community and related use of primary health care in the United Kingdom. <h3>DESIGN</h3> Narrative review. <h3>METHOD</h3> A literature search identified studies of incidence and prevalence of knee pain, disability, and radiographic osteoarthritis in the general population, and data related to primary care consultations. Findings from UK studies were summarised with reference to European and international studies. <h3>RESULTS</h3> During a one year period 25% of people over 55 years have a persistent episode of knee pain, of whom about one in six in the UK and the Netherlands consult their general practitioner about it in the same time period. The prevalence of painful disabling knee osteoarthritis in people over 55 years is 10%, of whom one quarter are severely disabled. <h3>CONCLUSION</h3> Knee osteoarthritis sufficiently severe to consider joint replacement represents a minority of all knee pain and disability suffered by older people. Healthcare provision in primary care needs to focus on this broader group to impact on community levels of pain and disability.
Polyamines as Mediators of the Effect of Prolactin and Growth Hormone on the Growth of <italic>N</italic>-Nitroso-<italic>N</italic>-methylurea-Induced Rat Mammary Tumor Cultured in Vitro in Soft Agar<xref ref-type="fn" rid="FN1">2</xref>
Authors: Andrea Manni, Carol Wright
Journal: JNCI Journal of the National Cancer Institute (1985)

This study evaluated the role of polyamines in mediating the effect of ovine prolactin (oPRL) and ovine growth hormone (oGH) on the growth of the N-nitroso-N-methylurea [(NMU) CAS: 684-93-5)-induced rat (Sprague-Dawley) mammary cancer cultured in soft agar. oPRL and oGH had a dose-related growth-promoting effect when added to NMU-induced mammary tumors cultured in soft agar in the absence of serum. The effect of oPRL and oGH was blocked by a-difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase, the rate-limiting enzyme of polyamine biosynthesis. Exogenous administration of polyamines reversed the inhibitory effect of DFMO and completely restored the action of oPRL and oGH. Our results indicated that polyamines are essential in mediating the growth of the NMU-induced mammary tumor under these experimental conditions.
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis
Authors: Xiao Mei Wang, Yingze Zhang, Hong Pyo Kim, Zhihong Zhou, Carol A. Feghali-Bostwick, Fang Liu, Emeka Ifedigbo, Xiaohui Xu, Tim D. Oury, Naftali Kaminski, Augustine M.K. Choi
Journal: The Journal of Experimental Medicine (2006)

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder characterized by activation of fibroblasts and overproduction of extracellular matrix (ECM). Caveolin-1 (cav-1), a principal component of caveolae, has been implicated in the regulation of numerous signaling pathways and biological processes. We observed marked reduction of cav-1 expression in lung tissues and in primary pulmonary fibroblasts from IPF patients compared with controls. We also demonstrated that cav-1 markedly ameliorated bleomycin (BLM)-induced pulmonary fibrosis, as indicated by histological analysis, hydroxyproline content, and immunoblot analysis. Additionally, transforming growth factor β1 (TGF-β1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-β1–induced ECM production in cultured fibroblasts through the regulation of the c-Jun N-terminal kinase (JNK) pathway. Interestingly, highly activated JNK was detected in IPF- and BLM-instilled lung tissue samples, which was dramatically suppressed by ad–cav-1 infection. Moreover, JNK1-null fibroblasts showed reduced smad signaling cascades, mimicking the effects of cav-1. This study indicates a pivotal role for cav-1 in ECM regulation and suggests a novel therapeutic target for patients with pulmonary fibrosis.
PTU-073 Comparison Of Sicus Versus Mr-enterography In Patients With Crohn’s Disease
Authors: C Alexakis, V Chhaya, D Tzias, J Pilcher, R Pollok
Journal: Gut (2014)

<h3>Introduction</h3> Small intestinal contrast-enhanced ultrasonography (SICUS) is an emerging radiological technique for the imaging of patients with Crohn’s disease that avoids exposure to diagnostic medical radiation. We have previously demonstrated that SICUS is diagnostically comparable to small bowel barium follow through and computerised tomography in the diagnosis of Crohn’s<sup>.1</sup> MR enterography (MRE) is becoming the gold standard radiological technique for the diagnosis of complications in patients with Crohn’s, but is expensive and access is limited. We aimed to compare the diagnostic sensitivity of SICUS with MRE in routine clinical practice. <h3>Methods</h3> Patients with established Crohn’s disease, who had undergone both SICUS and MRE within 6 months of each other were identified retrospectively from the radiology database at a UK tertiary centre. Imaging and reports were reviewed for both modalities. Kappa coefficient data was calculated for luminal parameters including the presence of strictures, stricture number and location, the presence of abscess/fistulae, mucosal thickening, active mucosal inflammation and fibrotic changes. Reported stricture lengths were compared using paired student’s<i> t-</i>test. Inflammatory markers including platelet levels, where available, were recorded within 2 weeks of each of the imaging modalities as a surrogate marker for active inflammation. <h3>Results</h3> 20 Crohn’s patients were identified (10 male), with a mean age of 30.1 years at time of first investigation. Mean time between modalities was 72.3 days (range 2–147). There was no significant difference between mean platelet counts between the 2 radiological tests. Agreement between the 2 modalities was excellent for the presence of stricturing disease (k=0.92, 95% CI 0.71–1.00), stricture number (k=0.91, 95% CI 0.73–1.00) and stricture location (k=0.91, 95% CI 0.71–1.00). Agreement was good for the presence of fistulae (k=0.74, 95% CI 0.40–1.00) and mucosal thickening (k=0.74, 95% CI 0.40–1.00). Agreement was moderate for the presence of abscess (k=0.46 95% CI 0.14–1.00), acute mucosal inflammatory changes (k=0.55, 95% CI 0.19–0.90) and fibrotic changes (k=0.50, 95% CI 0.04–0.95). There was no significant difference in the mean estimated stricture length between MRE and SICUS. <h3>Conclusion</h3> SICUS compares favourably with MRE in the diagnosis of complications in patients with Crohn’s disease. This imaging technique is particularly useful in patients with stricturing (Montreal B2) disease. SICUS is a useful alternative diagnostic technique to MRE, particularly when access to MR may be limited or is poorly tolerated by the patient. <h3>Reference</h3> Chatu S <i>et al</i>. Diagnostic accuracy of small intestine ultrasonography using an oral contrast agent in Crohn’s disease: comparative study from the UK. <i>Clin Radiol</i>. 2012 Jun;67(6):553-9 <h3>Disclosure of Interest</h3> None Declared.
The Influence of Diagnostic and Therapeutic Laparoscopy on Patients Presenting with an Acute Abdomen
Authors: H J Scott, R D Rosin
Journal: Journal of the Royal Society of Medicine (1993)

The role of laparoscopy in the management of patients presenting to one surgical firm with an acute abdomen is discussed. Sixty-seven laparoscopies have been performed over an 18 month period and it has altered the diagnosis in 19.4% of cases and the management in 13.4% of cases. At laparoscopy the diagnosis of appendicitis was made in 37 patients (81% had attempted laparoscopic appendicectomies); pelvic inflammatory disease in 15 patients; torted fimbrial cyst in two patients; and free pus in the right lower peritoneum as a result of a perforated appendix was seen in two patients. Normal laparoscopy was performed in five patients and four patients who presented with a perforated duodenal ulcer had the diagnosis confirmed at laparoscopy, in three cases the perforation was oversewn laparoscopically. Two laparoscopies were performed on trauma patients; one stabbing and one blunt trauma to the right hypochondrium. It has been demonstrated that diagnostic laparoscopy is a useful adjunct to the general surgeon's armamentarium. It is suggested that the skill of laparoscopy is passed on to junior trainee surgeons who can use this technique to help attain a diagnosis in patients presenting with an acute abdomen.
Ozone-induced mediator release from human bronchial epithelial cells in vitro and the influence of nedocromil sodium
Authors: C Rusznak, JL Devalia, RJ Sapsford, RJ Davies
Journal: European Respiratory Journal (1996)

Although animal and human studies have demonstrated that ozone inhalation leads to airway epithelial inflammation and damage, the underlying mechanisms are not fully understood. We cultured human bronchial epithelial cells as explant cultures and investigated the effect of 6 h of exposure to 0-500 parts per billion (ppb) O3 with or without 10(-5) M nedocromil sodium on: 1) epithelial cell membrane integrity; and 2) release of inflammatory cytokines and soluble intercellular adhesion molecule-1 (sICAM-1), as assessed by enzyme-linked immunosorbent assay (ELISA). O3 exposure led to significant epithelial cell damage at concentrations of 10-500 ppb O3, as indicated by increased release of [51Cr]-labelled sodium chromate. At concentrations of 10-100 ppb, O3 induced maximal release of interleukin-8 (IL-8), granulocyte/macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and sICAM-1. The IL-8 and GM-CSF release increased significantly from 5.64+/-0.58 and 0.04+/-0.03 pg x microg(-1) cellular protein, respectively, from control cells exposed to air, to 20.16+/-2.56 and 0.20+/-0.04 pg x microg(-1) cellular protein, respectively, from cells exposed to 50 ppb O3. 10(-5) M nedocromil sodium significantly attenuated the O3-induced release of both IL-8 and GM-CSF (p&lt;0.01). The TNF-alpha and sICAM-1 increases after exposure to 10-50 ppb O3, were also abrogated by treatment of the cells with 10(-5) M nedocromil sodium (p&lt;0.05). Similarly, the antioxidant, glutathione, at concentrations of 400-600 microM, significantly reduced the O3-induced release of IL-8 (p&lt;0.05). In conclusion, these studies indicate that ambient concentrations of ozone may induce airway inflammation, through release of proinflammatory mediators from airway epithelial cells. This effect may be inhibited both by the anti-inflammatory drug, nedocromil sodium, and the naturally occurring antioxidant glutathione.