tbuckley/cabot-search huggingface dataset:
Comparison of Oral Fluconazole and Itraconazole for Progressive, Nonmeningeal Coccidioidomycosis
Authors: John N. Galgiani
Journal: Annals of Internal Medicine (2000)

Background: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis. Objective: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections. Design: Randomized, double-blind, placebo-controlled trial. Setting: 7 treatment centers in California, Arizona, and Texas. Patients: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections. Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily. Measurements: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline. Results: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, −2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated. Conclusions: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.
Thromboxane A <sub>2</sub> -Induced Inhibition of Voltage-Gated K <sup>+</sup> Channels and Pulmonary Vasoconstriction
Authors: Angel Cogolludo, Laura Moreno, Lisardo Bosca, Juan Tamargo, Francisco Perez-Vizcaino
Journal: Circulation Research (2003)

Voltage-gated K+ channels (KV) and thromboxane A2 (TXA2) play critical roles in controlling pulmonary arterial tone under physiological and pathological conditions. We hypothesized that TXA2 might inhibit KV channels, thereby establishing a link between these two major pathogenic pathways in pulmonary hypertension. The TXA2 analogue U46619 inhibited IK(V) (Emax=56.1+/-3.9%, EC50=0.054+/-0.019 micromol/L) and depolarized pulmonary artery smooth muscle cells via activation of TP receptors. In isolated pulmonary arteries, U46619 simultaneously increased intracellular Ca2+ concentration and contractile force, and these effects were inhibited by nifedipine or KCl (60 mmol/L). U46619-induced contractions were not altered by the inhibitors of tyrosine kinase genistein or Rho kinase Y-27632 but were prevented by the nonselective protein kinase C (PKC) inhibitors staurosporine and calphostin C. Furthermore, these responses were sensitive to Gö-6983 but insensitive to bisindolylmaleimide I and Gö-6976. Based on the specificity of these drugs, we suggested a role for an atypical PKC in U46619-induced effects. Thus, treatment with a PKCzeta pseudosubstrate inhibitor markedly prevented the vasoconstriction, the inhibition of IK(V), and the depolarization induced by U46619. Western blots showed a transient translocation of PKCzeta from the cytosolic to the particulate fraction on stimulation with U46619. These results indicate that TXA2 inhibits IK(V), leading to depolarization, activation of L-type Ca2+ channels, and vasoconstriction of rat pulmonary arteries. We propose PKCzeta as a link between TP receptor activation and KV channel inhibition.
Phase I Study of Bryostatin 1: Assessment of Interleukin 6 and Tumor Necrosis Factor Induction In Vivo
Authors: P. A. Philip, D. Rea, P. Thavasu, J. Carmichael, N. S. A. Stuart, H. Rockett, D. C. Talbot, T. Ganesan, G. R. Pettit, F. Balkwill, A. L. Harris
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : Many oncogenes have been shown to code for growth factor receptors that are involved in regulation of cell growth and proliferation and can activate transcription via protein kinase C. Bryostatin 1, a partial agonist of protein kinase C, has demonstrated potent antitumor activity in vitro and in vivo in human tumor xenografts. Purpose : The aim of this phase I study was to determine the optimal dosage and toxicity profile of bryostatin 1 and its influence on cytokine release in vivo. Methods : Three successive cohorts consisting of 35 patients with various malignant tumors were treated with bryostatin 1 by intravenous infusion over 1 hour as follows: cohort A—35 μg/m 2 (three patients) or 50 μg/m 2 (eight patients) once every 2 weeks; cohort B—25 μg/m 2 once a week (eight patients); and cohort C—25 μg/m 2 once a week for 3 weeks, with no treatment during the 4th week (16 patients). Plasma levels of tumor necrosis factor a (TNF-α) and interleukin 6 (IL-6) were measured by immunoradiometric assay and by radioimmunoassay, respectively. Results : The dose-limiting toxicity was grade 3 or 4 myalgia in four of 11 patients in cohort A, in two of wight in cohort B, and in none of 16 in cohort C. Occurrence of myalgia was dose related. There was no significant myelosuppression, apart from a small and transient fall in platelet count. Six patients experienced acute but transient skin flushing, dyspnea, hypotension, and bradycardia, probably related to the bryostatin 1 vehicle. TNF-α and IL-6 were detected in plasma at 2 and 24 hours after treatment, respectively, and the levels were dose related (P =.02). Two patients with metastatic malignant melanoma had partial remission after three or four cycles of therapy; remission lasted 6 weeks and 10+ months, respectively. Conclusions : The dose-limiting toxicity of bryostatin 1 was myalgia. Plasma IL-6 and TNF-α concentrations were increased within 24 hours of therapy. Antitumor activity against malignant melanoma was observed early in the course of treatment. Implications : The recommended dosage of bryostatin 1 for phase II studies is 25 μg/m 2 by intravenous infusion for 1 hour once a week for 3 weeks, with no treatment in the 4th week. IL-6 and TNF-α plasma concentrations may be useful in monitoring biological activity of bryostatin 1. Future studies should explore use of this drug with other conventional immune modulators and conventional cytotoxic drugs. [J Natl Cancer Inst 85: 1812–1818, 1993]
Isotretinoin Exposure and Risk of Inflammatory Bowel Disease
Authors: Shadi Rashtak, Shahryar Khaleghi, Mark R. Pittelkow, Joseph J. Larson, Brian D. Lahr, Joseph A. Murray
Journal: JAMA Dermatology (2014)

IMPORTANCE Isotretinoin is the standard treatment for refractory severe nodulocystic acne.A true association between prior isotretinoin use and development of inflammatory bowel disease (IBD) is uncertain. Addressing the reality of this association is important in decision making for both the clinician and the patient when isotretinoin treatment is indicated.OBJECTIVE To assess the risk of IBD mainly in patients with acne with and without isotretinoin exposure.DESIGN, SETTING, AND PARTICIPANTS In this retrospective, single-center study, the electronic medical records of patients who were primarily seeking acne treatment were reviewed for isotretinoin exposure. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to search for IBD diagnosis. participants included 1078 patients from 1995 to 2011,with isotretinoin referenced in their medical records, and who had ongoing local medical care defined as having had a serum sample collected between 2006 to 2011 for any reason while an Olmsted County, Minnesota, resident at the time of serum sample collection.EXPOSURES The exposed group included the patients with confirmed prior isotretinoin exposure (n = 576), and the nonexposed group were defined as patients who never received isotretinoin or received it after the diagnosis of IBD (n = 502).MAIN OUTCOMES AND MEASURES Risk of IBD among isotretinoin-exposed vs non exposed patients.RESULTS Both groups were comparable by race, prior systemic antibiotic use, and systemic tetracycline use. Inflammatory bowel disease developed less frequently in the isotretinoin-exposed group vs the nonexposed group (0.9%vs 2.6%; P = .03; unadjusted odds ratio [OR], 0.33; 95%CI, 0.12-0.93; P = .04). The negative association between isotretinoin exposure and IBD remained after adjusting for sex (OR, 0.28; 95%CI, 0.10-0.80;P = .02) and for sex and non acne indication (OR, 0.28; 95%CI, 0.10-0.79; P = .02).CONCLUSIONS AND RELEVANCE Our study did not show an increased risk of IBD with prior isotretinoin use. If anything, the risk seemed to be decreased. Although these results may be due to chance given the small number of IBD cases, the anti-inflammatory and immune-modulating effects of isotretinoin may be worth exploring.
Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus: A Scientific Statement From the American Heart Association and the American Diabetes Association
Authors: Antonio Nicolucci, Giorgia De Berardis, Michele Sacco, Gianni Tognoni
Journal: Diabetes Care (2007)

The recent American Diabetes Association/American Heart Association statement recommends the use of low doses of aspirin as a strategy for primary prevention of cardiovascular diseases in all individuals with diabetes aged >40 years or who have additional risk factors (1). Like in previous recommendations (2), only selected pieces of evidence are mentioned to support this statement. The data used to sustain the efficacy of aspirin come from the Early Treatment Diabetic Retinopathy Study, the only study specifically conducted in diabetic patients with and without previous cardiovascular disease (3). In this trial, treatment with 650 mg aspirin for 5 years was associated with a nonsignificant 9% reduction in the primary end …
Neutrophil cytoplasmic autoantibodies after liver transplantation in patients with primary sclerosing cholangitis
Authors: E.B. Haagsma, A.H.L. Mulder, A.S.H. Gouw, G. Horst, L. Meerman, M.J.H. Slooff, C.G.M. Kallenberg
Journal: Journal of Hepatology (1993)
Autoantibodies to neurofibrillary tangles and brain tissue in Alzheimer's disease. Establishment of Epstein-Barr virus-transformed antibody-producing cell lines.
Authors: F Gaskin, B S Kingsley, S M Fu
Journal: The Journal of Experimental Medicine (1987)

Multiple EBV-transformed B cell lines were established from five patients with a clinical diagnosis of Alzheimer's disease (AD) and six age-matched controls. The supernatants were screened for antibody activity against SDS-treated isolated neurofibrillary tangles (NFT). Reactive supernatants were identified from both the AD and control group. The frequencies of anti-NFT antibody-secreting lines were 6.3 and 1.6% for the AD and the control groups, respectively. A proportion of these supernatants also stained NFT in situ and neurons and/or glia in sections of the frontal and the temporal cortexes of autopsied AD and normal brains, as well as cells from three cell lines (HeLa, fibroblast, and neuroblastoma). Several patterns of staining were revealed by these supernatants, indicating different reactive antigens. One supernatant stained NFT and astrocytes in sections from AD brains. It did not stain sections from two normal brains. This cell line is the result of the immortalization of a circulating B cell making antibody specific for an antigen in AD. The present approach may provide new insights in the pathogenesis of AD.
The management of gastric polyps
Authors: A. F. Goddard, R. Badreldin, D. M. Pritchard, M. M. Walker, B. Warren
Journal: Gut (2010)

Gastric polyps are important as some have malignant potential. If such polyps are left untreated, gastric cancer may result. The malignant potential depends on the histological type of the polyp. The literature base is relatively weak and any recommendations made must be viewed in light of this.Gastric polyps are sessile or pedunculated lesions that originate in the gastric epithelium or submucosa and protrude into the stomach lumen.Depending on histological type, some gastric polyps (adenomas and hyperplastic polyps) have malignant potential and are precursors of early gastric cancer. They may also indicate an increased risk of intestinal or extra-intestinal malignancy.
Pulmonary fibrosis deaths in the United States, 1979-1991. An analysis of multiple-cause mortality data.
Authors: D M Mannino, R A Etzel, R G Parrish
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We sought to describe pulmonary fibrosis mortality in the United States from 1979 through 1991 by analyzing death certificate reports compiled by the National Center for Health Statistics. Of the 26,866,600 people who died during the study period, 107,292 had a diagnosis of pulmonary fibrosis listed on their death certificates. Among men, age-adjusted mortality rates increased from 48.6 per 1,000,000 in 1979 to 50.9 per 1,000,000 in 1991 and, among women, these rates increased from 21.4 per 1,000,000 in 1979 to 27.2 per 1,000,000 in 1991. Among both men and women rates were higher in older age strata than in younger age strata. Age-adjusted mortality rates were consistently higher among whites and people of races than blacks. The frequency with which pulmonary fibrosis was listed as the underlying cause of death increased from 40% in 1979 to 56% in 1991. Age-adjusted mortality rates varied by state, with lowest rates in the Midwest and Northeast, and the highest rates in the West and Southeast. We conclude that the age-adjusted rate of pulmonary fibrosis among decedents in the United States increased, and pulmonary fibrosis was listed as the underlying cause of death with increasing frequency, over the study period. We cannot determine whether the differences we detected between regions, sexes, and races are related to characteristics of the disease or problems in death certification and coding.
Altered lung developmental pathways during the phase of alveogenesis in mice lacking superoxide dismutase 3, extracellular (SOD3)
Authors: Koustav Ganguly, Timothy M. Martin, Vincent J. Concel, Leema George, Ankita Mitra, Tania A. Thimraj, Louis J. Vuga, Cheryl Fattman, Naftali Kaminski, George D. Leikauf
Journal: European Respiratory Journal (2014)

Background: Previously we detected impaired lung function in gene targeted Sod3(-/-) mice and associated two functional SOD3 single nucleotide polymorphisms to decreased forced expiratory volume in 1s and maximal expiratory flow at 25% volume in children. Decreased lung SOD3 levels and activity were detected in JF1/Msf mice (poor lung function) compared to C3H/HeJ mice (higher lung function) with the greatest difference during postnatal (P) days 14- P28 ie. alveogenesis phase. In this work we studied the global lung transcript profile in Sod3(-/-) mice during alveogenesis. Methods: Lung transcript levels were measured by microarray analysis comparing female P14 and P28 Sod3 (-/-) with matched S od3 (+/+) mice (n=4-16). Significantly altered transcripts (≥2-fold decreased or increased) were analyzed for enriched pathways/categories using Database for Annotation, Visualization, and Integrated Discovery (DAVID), Gene Ontogeny (GO) molecular function, GO biological process, GO cell component, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Results: The GO/KEGG categories for decreased transcripts at P14 (n=1793) and P28 (n= 1047) in S od3 (-/-) mouse lung included Wnt signaling, developmental process, respiratory system development, lung development, MTOR, MAPK, and VEGF signaling. Noteworthy transcripts in these categories include Sftpd, Sftpa1, Wnt4, Wnt1 Wisp1 , Chi3l1, Klf15, Fgfbp1, Spry4, Stk3, and Fgfr4 . Discussion: Our preliminary data indicates altered regulation of key lung developmental pathways during the peak alveogenesis phase in mice lacking SOD3 that may have contributed in impaired lung function development in Sod3(-/-) mice.
Aneurysm of the Abdominal Aorta
Authors: G. Sianos, E. Vourvouri, K. Nieman, J. M.R. Ligthart, A. Thury, P. J. de Feyter, P. W. Serruys, J. R.T.C. Roelandt
Journal: Circulation (2001)

A 76-year-old man was admitted to the intensive care unit with unstable angina pectoris of Braunwald class IIIB. He was known to have hypertension, which was poorly controlled with medication. Physical examination revealed a pulsating mass in the lower abdomen that was suggestive of an aortic aneurysm. An echocardiographic study with a small, hand-held ultrasound device (SonoHeart, SonoSite Inc) showed an abdominal aortic aneurysm containing thrombotic material (Figure 1). His troponin T level was elevated, and he underwent coronary arteriography, which showed a high-grade stenosis at the bifurcation of left anterior descending artery and the first diagonal branch. The lesion was dilated during the same session, with direct stenting of both branches. 



Figure 1. Transverse image of the aneurysm of the abdominal aorta (56 mm in diameter), which contains a large thrombus (TR). The …
Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer
Authors: T. Sakakibara, A. Inoue, S. Sugawara, M. Maemondo, T. Ishida, K. Usui, T. Abe, M. Kanbe, H. Watanabe, Y. Saijo, T. Nukiwa
Journal: Annals of Oncology (2009)
Comparison of health status in stable patients with bronchiectasis due to common variable immune deficiency (CVID), and idiopathic bronchiectasis
Authors: Lorraine Ozerovitch, Samantha Prigmore, Winston Banya, Robert Wilson, Noel Snell, Peter Kelleher, Jillian Riley
Journal: European Respiratory Journal (2011)

Background:  Patients with CVID develop bronchiectasis (bx) due to damage caused by lung infections. Bx is associated with impaired health status (Wilson C  et al  Am J Respir Crit Care Med 1997; 156: 536-541). Improved treatment for CVID+bx has led to fewer infections but little is known about impact on health status.   Methods:  Patients undertook a Shuttle Walking Test (SWT) and completed the St George9s Respiratory Questionnaire (SGRQ). Scores were compared with data from a previous study of idiopathic bx (Ozerovitch L  et al  Am J Respir Crit Care Med 2004; 169: A330).   Results:  22 patients participated; 9 male (41%); mean age 45 (range 17-67); 20 (91%) on immunoglobulin (Ig) therapy. Patients with CVID+bx had better scores for all SGRQ domains, and better SWT, both of which were clinically relevant; SGRQ >4 point difference (Jones P, Eur Respir J 2002; 19: 398-404); SWT 60-115m (Pepin V et al, Thorax 2011;66:115-120), although neither attained statistical significance.  There were no significant correlations between SWT and activity component or SGRQ Total Score (r= -0.45, p>0.05; r= -0.43, p>0.05) in the CVID with bx group.   Conclusion:  Patients with bx due to CVID have impaired health status and SWT; scores were generally better than for demographically similar historical controls with idiopathic bx, possibly as a result of specific therapy (Ig replacement) in the majority of these patients.
Vascular Endothelial Growth Factor-C and C-C Chemokine Receptor 7 in Tumor Cell–Lymphatic Cross-talk Promote Invasive Phenotype
Authors: Amine Issa, Thomas X. Le, Alexander N. Shoushtari, Jacqueline D. Shields, Melody A. Swartz
Journal: Cancer Research (2008)

Abstract Most carcinomas spread to distant sites through lymphatic vessels. Several preclinical and clinical studies have shown a positive correlation between the incidence of lymph node metastasis and secretion of the lymphatic growth factor vascular endothelial growth factor-C (VEGF-C) by tumor cells, suggesting tumor lymphangiogenesis as an escape mechanism. However, recent evidence has shown VEGF receptor-3 (VEGFR-3) expression on tumor cells and autocrine signaling, which increase metastatic potential. Furthermore, there is growing evidence implicating lymphatic-homing chemokine receptors, particularly C-C chemokine receptor 7 (CCR7), in lymph node metastasis. We report here that expressions of VEGF-C and CCR7 by tumor cells act synergistically to promote their invasion toward lymphatics. First, VEGF-C acts to increase lymphatic secretion of CCL21, which in turn drives CCR7-dependent tumor chemoinvasion toward lymphatics. Second, VEGF-C acts in an autocrine fashion to increase tumor invasiveness by increasing the proteolytic activity and motility of tumor cells in a three-dimensional matrix. Both of these effects are VEGFR-3 dependent and evident only in three-dimensional environments. We further verified that VEGF-C induces lymphatic CCL21 up-regulation in vivo by direct injection of VEGF-C protein intradermally in the mouse. Taken together, these results bridge the prometastatic functions of CCR7 and VEGF-C in tumors and show that, beyond lymphangiogenesis, VEGF-C promotes tumor invasion toward lymphatics by both autocrine and CCR7-dependent paracrine signaling mechanisms, which may be a significant cause of lymph node metastasis. [Cancer Res 2009;69(1):349–57]
Therapy of Advanced Established Murine Breast Cancer with a Recombinant Adenoviral ErbB-2/<i>neu</i> Vaccine
Authors: Jong Myun Park, Masaki Terabe, Jason C. Steel, Guido Forni, Yoshio Sakai, John C. Morris, Jay A. Berzofsky
Journal: Cancer Research (2008)

ErbB-2 (HER-2/neu) is a transforming oncogene expressed by a substantial fraction of breast cancers, and monoclonal antibody therapy directed toward this antigen is an established treatment modality. However, not all tumors respond, and with a monoclonal antibody directed to a single epitope, there is always the risk of tumor escape. Furthermore, passive antibody therapy requires continual treatment. Whereas cancer vaccines have prevented the growth of tumors, it has been far more difficult to treat large established tumors. Here, we show that vaccination with a recombinant adenovirus expressing a truncated ErbB-2 antigen can cure large established subcutaneous ErbB-2-expressing breast cancers in mice, and can also cure extensive established lung metastatic disease. We also show that the mechanism of protection involves antibody-mediated blockade of ErbB-2 function, independent of Fc receptors. We conclude that a vaccine inducing antibodies to a functional oncogenic receptor could have tremendous therapeutic potential against cancers overexpressing such molecules.
Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon–mediated immunity
Authors: Adrian Tun-Kyi, Greg Finn, Alex Greenwood, Michael Nowak, Tae Ho Lee, John M Asara, George C Tsokos, Kate Fitzgerald, Elliot Israel, Xiaoxia Li, Mark Exley, Linda K Nicholson, Kun Ping Lu
Journal: Nature Immunology (2011)