tbuckley/cabot-search huggingface dataset:
Lichen planus pemphigoides. Is it a separate entity?
Authors: R. K. Joshi, D. Natukorala, A. Abanmi, T.Al Awadi
Journal: British Journal of Dermatology (1994)

Journal Article Lichen planus pemphigoides. Is it a separate entity? Get access R. K. Joshi, R. K. Joshi Department of Dermatology, Riyadh Armed Forces Hospital, PO Box 7897.Riyadh 11159, Saudi Arabia Search for other works by this author on: Oxford Academic Google Scholar D. Natukorala, D. Natukorala Department of Dermatology, Riyadh Armed Forces Hospital, PO Box 7897.Riyadh 11159, Saudi Arabia Search for other works by this author on: Oxford Academic Google Scholar A. Abanmi, A. Abanmi Department of Dermatology, Riyadh Armed Forces Hospital, PO Box 7897.Riyadh 11159, Saudi Arabia Search for other works by this author on: Oxford Academic Google Scholar T.Al Awadi T.Al Awadi Department of Dermatology, Riyadh Armed Forces Hospital, PO Box 7897.Riyadh 11159, Saudi Arabia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 4, 1 April 1994, Pages 537–538, https://doi.org/10.1111/j.1365-2133.1994.tb03394.x Published: 01 April 1994
Progress Toward the Healthy People 2010 Goals and Objectives
Authors: Edward J. Sondik, David T. Huang, Richard J. Klein, David Satcher
Journal: Annual Review of Public Health (2010)

Healthy People 2010 is a comprehensive framework for improving the health of Americans, built on the foundation of several decades of predecessor initiatives. Its two overarching goals, to “[i]ncrease the quality and years of healthy life” and “[e]liminate health disparities,” subsume 28 focus areas and comprise 955 objectives and subobjectives. This review evaluates progress toward meeting the Healthy People 2010 program's challenging agenda in the context of leading health indicator (LHI) measures, developed by the Department of Health and Human Services (DHHS), augmented by additional objectives for a total of 31 measures. Our evaluation of progress includes analysis of changes in objective values, including progress toward Healthy People 2010 targets, where appropriate, and analysis of changes in disparities. The Healthy People 2010 LHI measures suggest that although some progress has been made, there is much work to be done toward the Healthy People 2010 targets and both overarching goals.
Postradiation lumbosacral radiculopathy with spinal root cavernomas mimicking carcinomatous meningitis
Authors: François Ducray, Rémy Guillevin, Dimitri Psimaras, Marc Sanson, Karima Mokhtari, Sylvie Delanian, Soledad Navarro, Thierry Maisonobe, Philippe Cornu, Khê Hoang-Xuan, Jean-Yves Delattre, Pierre-François Pradat
Journal: Neuro-Oncology (2008)

Lumbosacral radiculopathy is a rare complication of radiotherapy and may be challenging to differentiate from diagnosis of a tumor recurrence. We reviewed the records of three patients with a past history of cancer and radiotherapy who were referred for suspicion of carcinomatous meningitis on lumbar MRI, but whose final diagnosis was radiation-induced lumbosacral radiculopathy. The three patients developed a progressive lumbosacral radiculopathy at 20, 13, and 47 years after lumbar radiotherapy delivered for renal cancer, Hodgkin's disease, and a seminoma, respectively. MRI showed a diffuse, nodular enhancement of the cauda equina nerve roots on T1 sequences, suggestive of leptomeningeal metastasis. A slowly progressive clinical course over several years and negative cerebrospinal fluid cytologic analysis ruled out the diagnosis of carcinomatous meningitis. Because of the radiologic findings, a biopsy was performed in two patients. In the first, a biopsy limited to the arachnoid excluded a malignant infiltration. In the second, a biopsy of the enhancing lesions demonstrated spinal root cavernomas. These observations, together with three recent case reports in the literature, delineate a syndrome of "radiationinduced lumbosacral radiculopathy with multiple spinal root cavernomas" that mimics carcinomatous meningitis on MRI. Its diagnosis is important in order to avoid inappropriate treatment and useless or dangerous spinal root biopsies.
Early Respiratory Infection Is Associated with Reduced Spirometry in Children with Cystic Fibrosis
Authors: Kathryn A. Ramsey, Sarath Ranganathan, Judy Park, Billy Skoric, Anne-Marie Adams, Shannon J. Simpson, Roy M. Robins-Browne, Peter J. Franklin, Nick H. de Klerk, Peter D. Sly, Steve M. Stick, Graham L. Hall
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Pulmonary inflammation, infection, and structural lung disease occur early in life in children with cystic fibrosis.We hypothesized that the presence of these markers of cystic fibrosis lung disease in the first 2 years of life would be associated with reduced lung function in childhood.Lung function (forced expiratory volume in the first three-quarters of a second [FEV0.75], FVC) was assessed in individuals with cystic fibrosis diagnosed after newborn screening and healthy subjects during infancy (0-2 yr) and again at early school age (4-8 yr). Individuals with cystic fibrosis underwent annual bronchoalveolar lavage fluid examination, and chest computed tomography. We examined which clinical outcomes (pulmonary inflammation, infection, structural lung disease, respiratory hospitalizations, antibiotic prophylaxis) measured in the first 2 years of life were associated with reduced lung function in infants and young children with cystic fibrosis, using a mixed effects model.Children with cystic fibrosis (n = 56) had 8.3% (95% confidence interval [CI], -15.9 to -6.6; P = 0.04) lower FEV0.75 compared with healthy subjects (n = 18). Detection of proinflammatory bacterial pathogens (Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Aspergillus species, Streptococcus pneumoniae) in bronchoalveolar lavage fluid was associated with clinically significant reductions in FEV0.75 (ranging between 11.3 and 15.6%).The onset of lung disease in infancy, specifically the occurrence of lower respiratory tract infection, is associated with low lung function in young children with cystic fibrosis. Deficits in lung function measured in infancy persist into childhood, emphasizing the need for targeted therapeutic interventions in infancy to maximize functional outcomes later in life.
The Effect of Ketoconazole on the Pharmacokinetics and Pharmacodynamics of Ixabepilone: A First in Class Epothilone B Analogue in Late-Phase Clinical Development
Authors: Sanjay Goel, Marvin Cohen, S. Nilgün Çömezoglu, Lionel Perrin, François André, David Jayabalan, Lisa Iacono, Adriana Comprelli, Van T. Ly, Donglu Zhang, Carrie Xu, W. Griffith Humphreys, Hayley McDaid, Gary Goldberg, Susan B. Horwitz, Sridhar Mani
Journal: Clinical Cancer Research (2008)

To determine if ixabepilone is a substrate for cytochrome P450 3A4 (CYP3A4) and if its metabolism by this cytochrome is clinically important, we did a clinical drug interaction study in humans using ketoconazole as an inhibitor of CYP3A4.Human microsomes were used to determine the cytochrome P450 enzyme(s) involved in the metabolism of ixabepilone. Computational docking (CYP3A4) studies were done for epothilone B and ixabepilone. A follow-up clinical study was done in patients with cancer to determine if 400 mg/d ketoconazole (inhibitor of CYP3A4) altered the pharmacokinetics, drug-target interactions, and pharmacodynamics of ixabepilone.Molecular modeling and human microsomal studies predicted ixabepilone to be a good substrate for CYP3A4. In patients, ketoconazole coadministration resulted in a maximum ixabepilone dose administration to 25 mg/m(2) when compared with single-agent therapy of 40 mg/m(2). Coadministration of ketoconazole with ixabepilone resulted in a 79% increase in AUC(0-infinity). The relationship of microtubule bundle formation in peripheral blood mononuclear cells to plasma ixabepilone concentration was well described by the Hill equation. Microtubule bundle formation in peripheral blood mononuclear cells correlated with neutropenia.Ixabepilone is a good CYP3A4 substrate in vitro; however, in humans, it is likely to be cleared by multiple mechanisms. Furthermore, our results provide evidence that there is a direct relationship between ixabepilone pharmacokinetics, neutrophil counts, and microtubule bundle formation in PBMCs. Strong inhibitors of CYP3A4 should be used cautiously in the context of ixabepilone dosing.
Evaluation of ventilation maldistribution as an early indicator of lung disease in children with cystic fibrosis
Authors: P.M. Gustafsson, P. Aurora, A. Lindblad
Journal: European Respiratory Journal (2003)

Many children with cystic fibrosis (CF), receiving modern, aggressive CF care, have normal spirometry results. This study aimed to see if homogeneity of ventilation distribution is impaired early in the course of CF lung disease, and if ventilation inhomogeneity is a more frequent finding than abnormal spirometry in children benefiting from modern CF care. The study compared spirometry findings to two indices of ventilation inhomogeneity (mixing ratio (MR) and lung clearance index (LCI)) from multiple-breath inert gas washout in 43 children with CF, aged 3–18 yrs, and 28 healthy children. In total, 10/43 CF subjects (23%) had reduced forced expiratory volume in one second (FEV 1 ) and 14/34 (41%) showed abnormal maximum expiratory flow at 25% of forced vital capacity (MEF 25 ). In contrast, MR was abnormal in 31/43 (72%) and LCI in 27/43 (63%). MR was abnormal in 22/33 CF subjects with normal FEV 1 , versus 0/28 controls (p&lt;0.001), and abnormal MR was found in 10/20 CF subjects with normal MEF 25 , versus 0/22 controls (p&lt;0.001). Nine of the 10 CF subjects with reduced FEV 1 and 12/14 with abnormal MEF 25 showed abnormal MR. Inert gas washout discloses airway dysfunction in the majority of children with cystic fibrosis with normal lung function judged by spirometry. These findings suggest that multiple-breath inert gas washout is of greater value than spirometry in detecting early cystic fibrosis lung disease.
RTOG 0522: Huge Investment in Patients and Resources and No Benefit With Addition of Cetuximab to Radiotherapy—Why Did This Occur?
Authors: Douglas Adkins, Jessica Ley, Tanya M. Wildes, Loren Michel
Journal: Journal of Clinical Oncology (2015)

TO THEEDITOR: Angetal 1 recentlypresentedRadiationTherapy Oncology Group 0522 (RTOG 0522; Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With Stage III or Stage IV Head and Neck Cancer), a large randomized phase III trial of 940 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) that tested whether the addition of cetuximab to cisplatin and accelerated radiation therapy (RT) improved progression-free survival (PFS) compared with cisplatin and radiation (CRT) alone. 1 It did not. Survival, locoregional failure, and distant metastases end points were not significantly different between the two groups. However, cetuximab plus CRT versus CRT resulted in more interruptions in RT, more treatment-relatedgrade5adverseevents(death),andmoregrade3 to 4 radiation mucositis, rash, fatigue, anorexia, and hypokalemia. These results are extremely disappointing. Should we be surprised? Let us look at prior data that led to the development of RTOG 0522. The rationale for performing RTOG 0522includedphaseIIItrialsshowingimprovedoverallsurvival(OS) with the addition of cetuximab to RT in patients with curable HNSCC 2 andimprovedOSwiththeadditionofcetuximabtochemotherapy in patients with incurable HNSCC. 3 Importantly, one small
Proinflammatory Cytokines, Adiponectin, and Increased Risk of Primary Cardiovascular Events in Diabetic Patients With or Without Renal Dysfunction
Authors: Ben Schöttker, Christian Herder, Dietrich Rothenbacher, Michael Roden, Hubert Kolb, Heiko Müller, Hermann Brenner
Journal: Diabetes Care (2013)

OBJECTIVE Inflammatory processes contribute to both diabetes and cardiovascular risk. We wanted to investigate whether circulating concentrations of proinflammatory immune mediators and adiponectin in diabetic patients are associated with incident cardiovascular events. RESEARCH DESIGN AND METHODS In 1,038 participants with diabetes of the population-based ESTHER study, of whom 326 showed signs of renal dysfunction, Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for the association of increasing concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), IL-18, macrophage migration inhibitory factor (MIF), adiponectin, and leptin with cardiovascular events (myocardial infarction, stroke, or fatal cardiovascular event) during a follow-up period of 8 years. RESULTS During follow-up, 161 subjects with diabetes experienced a primary cardiovascular event. Proinflammatory markers were not associated with a higher risk for primary cardiovascular events in the total study population after adjustment for multiple confounders. However, IL-6 and MIF were associated with cardiovascular events in subjects with renal dysfunction (HR for the comparison of top vs. bottom tertile 1.98 [95% CI 1.12–3.52], P [trend] = 0.10 for IL-6; 1.48 [0.87–2.51], P [trend] = 0.04 for MIF). Adiponectin levels were associated with cardiovascular events in the total population (1.48 [1.01–2.21], P [trend] = 0.03), and the association was even more pronounced in the subgroup with renal dysfunction (1.97 [1.08–3.57], P [trend] = 0.02). CONCLUSIONS In particular, the absence of an association between CRP and a U-shaped association of adiponectin levels with incident cardiovascular events show that associations between circulating immune mediators and cardiovascular risk differ between diabetic patients and subjects of the general population.
Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision
Authors: Cheryl A. London, Phyllis B. Malpas, Stacey L. Wood-Follis, Joseph F. Boucher, Anthony W. Rusk, Mona P. Rosenberg, Carolyn J. Henry, Kathy L. Mitchener, Mary K. Klein, John G. Hintermeister, Philip J. Bergman, Guillermo C. Couto, Guy N. Mauldin, Gina M. Michels
Journal: Clinical Cancer Research (2009)

The purpose of this study was to determine the objective response rate (ORR) following treatment of canine mast cell tumors (MCT) with toceranib phosphate (Palladia, SU11654), a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRbeta. Secondary objectives were to determine biological response rate, time to tumor progression, duration of objective response, health-related quality of life, and safety of Palladia.Dogs were randomized to receive oral Palladia 3.25 mg/kg or placebo every other day for 6 weeks in the blinded phase. Thereafter, eligible dogs received open-label Palladia.The blinded phase ORR in Palladia-treated dogs (n = 86) was 37.2% (7 complete response, 25 partial response) versus 7.9% (5 partial response) in placebo-treated dogs (n = 63; P = 0.0004). Of 58 dogs that received Palladia following placebo-escape, 41.4% (8 complete response, 16 partial response) experienced objective response. The ORR for all 145 dogs receiving Palladia was 42.8% (21 complete response, 41 partial response); among the 62 responders, the median duration of objective response and time to tumor progression was 12.0 weeks and 18.1 weeks, respectively. Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated nonresponders (P = 0.030). There was no significant difference in the number of dogs with grade 3/4 (of 4) adverse events; adverse events were generally manageable with dose modification and/or supportive care.Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine planned treatment breaks. This clinical trial further shows that spontaneous tumors in dogs are good models to evaluate therapeutic index of targeted therapeutics in a clinical setting.
Trastuzumab after Adjuvant Chemotherapy in HER2-Positive Breast Cancer
Authors: Martine J. Piccart-Gebhart, Marion Procter, Brian Leyland-Jones, Aron Goldhirsch, Michael Untch, Ian Smith, Luca Gianni, Jose Baselga, Richard Bell, Christian Jackisch, David Cameron, Mitch Dowsett, Carlos H. Barrios, Günther Steger, Chiun-Shen Huang, Michael Andersson, Moshe Inbar, Mikhail Lichinitser, István Láng, Ulrike Nitz, Hiroji Iwata, Christoph Thomssen, Caroline Lohrisch, Thomas M. Suter, Josef Rüschoff, Tamás Sütő, Victoria Greatorex, Carol Ward, Carolyn Straehle, Eleanor McFadden, M. Stella Dolci, Richard D. Gelber
Journal: New England Journal of Medicine (2005)

Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.
Recent advances in autoimmune pancreatitis: type 1 and type 2
Authors: Terumi Kamisawa, Suresh T Chari, Markus M Lerch, Myung-Hwan Kim, Thomas M Gress, Tooru Shimosegawa
Journal: Gut (2013)

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to steroids. When so defined, AIP can be sub-classified into two subtypes, 1 and 2. Recent international consensus diagnostic criteria for AIP have been developed for diagnosis of both forms of AIP. Type 1 AIP is the pancreatic manifestation of a multiorgan disease, recently named IgG4-related disease. Little is known about the pathogenesis of either form of AIP. Despite frequent association of type 1 AIP with elevated serum IgG4 levels and infiltration with IgG4-positive plasma cells, it is unlikely that IgG4 plays a pathogenic role in AIP. Type 1 AIP responds to steroids, but there needs to be consensus on treatment regimens for induction and therapeutic end points. Relapses are common, but can be reduced by long-term use of low-dose steroids. Recent reports suggest that immunomodulators (azathioprine, 6-mercaptopurine and mycophenolate mofetil), as well biological agents (the antibody to CD20, rituximab) may have a role in maintaining remission in relapsing type 1 AIP. Future studies should clarify the best management options for treatment of relapses and maintenance of remission. Type 2 AIP is a pancreas-specific disorder not associated with IgG4. It presents in younger individuals equally with obstructive jaundice and pancreatitis. The inflammatory process responds to steroid therapy; relapses are uncommon. The clinical spectrum and long-term outcomes of medically treated type 2 AIP are still being evaluated.
A Follow-Up Study of Intensively Treated Chronic Schizophrenic Patients
Authors: MICHEL MESSIER, RICHARD FINNERTY, CONSTANCE S. BOTVIN, LESTER GRINSPOON
Journal: American Journal of Psychiatry (1969)

Two groups of chronic schizophrenic patients were treated with intensive psychotherapy for a period of two years, starting in 1962 and 1964. Half of the patients also took phenothiazines. Control groups at a local state hospital received phenothiazines but no psychotherapy. A follow-up of the groups on three tests of adjustment, administered at the end of 1967, indicated some trends toward better adjustment by patients who had received psychotherapy but there were no statistically significant differences among the groups.
Quantitative T1 mapping of hepatic encephalopathy using magnetic resonance imaging
Authors: Nadim Joni Shah, Heiko Neeb, Maxim Zaitsev, Sven Steinhoff, Gerald Kircheis, Katrin Amunts, Dieter Häussinger, Karl Zilles
Journal: Hepatology (2003)

Changes are shown in the spin-lattice (T1) relaxation time caused by the putative deposition of manganese in various brain regions of hepatic encephalopathy (HE) patients using a novel and fast magnetic resonance imaging (MRI) method for quantitative relaxation time mapping. A new method, T1 mapping with partial inversion recovery (TAPIR), was used to obtain a series of T1-weighted images to produce T1 maps. Imaging of 15 control subjects and 11 patients was performed on a 1.5T MRI scanner. The measurement time per patient with this technique, including adjustments, was approximately 5 minutes. Regions of interest in the globus pallidus, the caudate nucleus, the posterior and anterior limbs of the internal capsule, the putamen, the frontal and occipital white matter, the white matter of the corona radiata, the occipital visual and frontal cortices, and the thalamus were interactively defined in the left hemisphere and analyzed with respect to their T1 values. T1 changes in the brains of HE patients can be determined quantitatively with TAPIR in short, clinically relevant measurement times. Significant correlations between the change in T1 and HE severity have been shown in the globus pallidus, the caudate nucleus, and the posterior limb of the internal capsule. No significant correlation of T1 with grade of HE was found in the putamen, frontal white matter, white matter of the corona radiata, white matter in the occipital lobe, the anterior limb of the internal capsule, visual cortex, thalamus, or frontal cortex. In conclusion, these measurements show that T1 mapping is feasible in short, clinically relevant acquisition times.
Combined adenosine and lidocaine administration limits myocardial reperfusion injury.
Authors: J W Homeister, P T Hoff, D D Fletcher, B R Lucchesi
Journal: Circulation (1990)

The endogenous compound adenosine may play a role in limiting myocardial ischemia-reperfusion injury through its ability to cause vasodilation, modulate cardiac adrenergic responses, inhibit neutrophil function, or modulate energy supply and demand of the myocardium. The local anesthetic lidocaine has been shown to be protective against myocardial ischemia-reperfusion injury, although its mechanism of action remains unresolved. We hypothesized that administration of exogenous adenosine during reperfusion would limit the size of the infarct that results from a period of ischemia and reperfusion only when the animals are treated with lidocaine. Male, mongrel dogs (13.0-20.0 kg) were anesthetized (30 mg/kg i.v. sodium pentobarbital), and a left thoracotomy was performed. The left circumflex coronary artery (LCx) was isolated and instrumented with an electromagnetic flow probe, a 25-gauge nonobstructing intracoronary catheter, and a critical stenosis. The dogs were allocated randomly to one of four groups: 1) control, n = 13, (saline), 2) adenosine, n = 13, (0.15 mg/kg/ml/min i.c. for the first hour of reperfusion), 3) lidocaine, n = 9, (2.0 mg/kg i.v. given immediately before coronary artery occlusion and just before reperfusion), or 4) adenosine plus lidocaine, n = 11. The LCx was occluded for 90 minutes and reperfused for 6 hours. Regional myocardial blood flow (RMBF) was determined (n = 6 per group) at 80 minutes of occlusion and at 45 minutes of reperfusion with radiolabeled microspheres. RMBF determinations revealed an increase in blood flow to the inner two thirds of the myocardium at 45 minutes of reperfusion only in the presence of the combined treatment. Adenosine treatment alone or lidocaine treatment alone did not affect RMBF. Quantification of infarct size (triphenyltetrazolium method) expressed as a percent of the area at risk revealed a significant limitation of infarct size only in the group treated with both adenosine and lidocaine: control, 47.8 +/- 6.6%; adenosine, 45.0 +/- 3.2%; lidocaine, 46.9 +/- 6.0%; and adenosine and lidocaine, 20.8 +/- 5.6%. Statistical analyses were performed with two-way analysis of variance to account for the two individual drug treatments. The findings show that intracoronary administration of exogenous adenosine, at the dose used, is only effective at limiting myocardial infarct size when administered to lidocaine-treated animals.