tbuckley/cabot-search huggingface dataset:
Evaluation of prognosis of squamous cell carcinoma of the oesophagus by endoscopic ultrasonography
Authors: M Shinkai
Journal: Gut (2000)

For pretherapeutic staging of squamous cell carcinoma of the oesophagus, endoscopic ultrasonography (EUS) is considered the most profitable modality because it can provide cross sectional imaging of the tumour. The aim of this study was to evaluate the relation between prognosis and EUS findings, especially tumour area, in squamous cell carcinoma of the oesophagus.A total of 113 patients with squamous cell carcinoma of the oesophagus underwent EUS for pretherapeutic examination at Nagoya University Hospital. We compared EUS findings, histological results, and outcome. In addition, we measured the area of the tumour on EUS images (n=113) and evaluated if EUS area correlated with volume of the tumour on histological findings (n=50).The overall accuracy rate of EUS was 83.2% (94/113) for depth of tumour invasion and 67.6% (69/102) for perioesophageal lymph node metastasis. The EUS area increased in proportion to the development of tumour infiltration, and patients with lymph node metastasis had a larger EUS area than patients without lymph node metastasis. There was a close correlation between EUS area and volume of the tumour on histological findings. If EUS area of the tumour was less than 50 mm(2), the five year survival rate was 100%. As EUS area increased, the survival rate decreased.Measurement of EUS area of the tumour is reliable for quantification of the tumour and prediction of prognosis in patients with squamous cell carcinoma of the oesophagus.
Soluble interleukin-2 receptor retains prognostic value in patients with diffuse large B-cell lymphoma receiving rituximab plus CHOP (RCHOP) therapy
Authors: D. Ennishi, M. Yokoyama, Y. Terui, H. Asai, S. Sakajiri, Y. Mishima, S. Takahashi, H. Komatsu, K. Ikeda, K. Takeuchi, M. Tanimoto, K. Hatake
Journal: Annals of Oncology (2008)
Disabling ossification of the patellar tendon.
Authors: R Lagier, J C Gerster
Journal: Annals of the Rheumatic Diseases (1991)

Diffuse CREST ControlsSystemic sclerosis Plasma von Wilebrandfactor antigen concentrations.Each point represents one patient or control.The bar is the median value.of a higher von Willebrand factor antigen in patients with diffuse disease suggests endothe- lial cell damage may be more extensive and active in this group.The extent of vascular injury as shown by von Willebrand factor antigen concentrations may be regarded as a prognostic marker in these disorders.
Studies on the spray dried lactose as carrier for dry powder inhalation
Authors: Linna Wu, Xu Miao, Ziyun Shan, Ying Huang, Lu Li, Xin Pan, Qinghe Yao, Ge Li, Chuanbin Wu
Journal: Asian Journal of Pharmaceutical Sciences (2014)

The purpose of this study was to investigate the spray dried lactose as carrier for dry powder inhalation (DPI). The lactose particles were prepared by spray drying, then the particle size, shape and crystal form were characterized by laser diffraction, scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The spray dried lactose particles were spherical and amorphous, but would transfer to crystal form when storage humidity was above 32%. Thus, the humidity of the storage environment should be controlled below 30% strictly in order to maintain the amorphous nature of spray dried lactose which is a great benefit to DPI development.
Inhibition of Myogenic MicroRNAs 1, 133, and 206 by Inflammatory Cytokines Links Inflammation and Muscle Degeneration in Adult Inflammatory Myopathies
Authors: Robert W. Georgantas, Katie Streicher, Steven A. Greenberg, Lydia M. Greenlees, Wei Zhu, Philip Z. Brohawn, Brandon W. Higgs, Meggan Czapiga, Christopher A. Morehouse, Anthony Amato, Laura Richman, Bahija Jallal, Yihong Yao, Koustubh Ranade
Journal: Arthritis & Rheumatology (2013)

Objective The molecular basis of inflammatory myopathies such as dermatomyositis (DM), polymyositis, and inclusion body myositis, which share the characteristics of chronic muscle inflammation and skeletal muscle wasting, are poorly understood. As such, effective targeted treatments for these diseases are lacking, resulting in critical unmet medical needs for these devastating diseases. The purpose of this study was to identify possible new targets for drug development by exploring the mechanism by which inflammation may play a role in the pathology of the inflammatory myopathies. Methods We compared expression levels of inflammatory cytokines and microRNAs (miRNAs) between muscle biopsy samples from patients with inflammatory myopathies and those from donors without myositis. In vitro human and mouse model systems were then used to characterize the role of these cytokines and microRNAs on myoblast‐to‐myocyte differentiation. Results We observed increased expression of inflammatory cytokines, including tumor necrosis factor α (TNFα), interferon‐α (IFNα), IFNβ, and interleukin‐1β, in different subtypes of inflammatory myopathies. We observed decreased expression of microRNA‐1 (miR‐1), miR‐133a, and miR‐133b in all of the inflammatory myopathy subtypes we evaluated, as well as decreased expression of miR‐206 in DM; these miRNAs are essential for adult skeletal muscle differentiation and maintenance. TNFα was significantly inversely correlated with decreased myogenic miRNA expression in the inflammatory myopathy subtypes. In mechanistic studies, TNFα inhibited the expression of myogenic miRNAs and suppressed the differentiation of C2C12 myoblasts to myocytes/myotubes in an NF‐κB–dependent manner. This block in differentiation by TNFα was relieved by overexpression of miR‐1, miR‐206, or miR‐133a/b. Conclusion Taken together, these results provide a new mechanistic link between the action of proinflammatory cytokines and the degenerative pathology of inflammatory myopathies, and suggest therapeutic approaches for these diseases.
A Randomized 4–Arm Multicenter Study of Interferon Alfa-2B Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis C Not Responding to Interferon Alone
Authors: Giorgio Saracco, Alessia Ciancio, Alda Olivero, Antonina Smedile, Luigi Roffi, Guido Croce, Cosimo Colletta, Giuseppe Cariti, Massimo Andreoni, Alberto Biglino, Guido Calleri, Giovanni Maggi, Gian Franco Tappero, Pier Giulio Orsi, Natalia Terreni, Antonio Macor, Angelo Di Napoli, Enrico Rinaldi, Giovannino Ciccone, Mario Rizzetto
Journal: Hepatology (2001)

To determine whether a higher dosage of interferon (IFN) associated with ribavirin and/or prolonged time of administration may improve therapeutic efficacy, we conducted a 4–arm randomized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy. Group 1 (n = 139) received 3 million units (MU) IFN–α2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151) received 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hepatitis C virus (HCV)–RNA clearance at the end of 6–month follow–up. HCV–RNA was negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of group 4 (group 2 vs. group 3, P = .04). Among patients with genotypes 1 and 4, sustained response was significantly higher in group 2 vs. group 3 (18% vs. 7%, P = .03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affected by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30%, group 4 = 35%, P = NS). In conclusion, about 23% of nonresponders to IFN monotherapy may achieve a sustained response if re–treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 year. Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.
Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial
Authors: Alan K. Burnett, Robert K. Hills, Donald W. Milligan, Anthony H. Goldstone, Archibald G. Prentice, Mary-Frances McMullin, Andrew Duncombe, Brenda Gibson, Keith Wheatley
Journal: Journal of Clinical Oncology (2009)

To optimize treatment for younger patients with acute myeloid leukemia and high-risk myelodysplastic syndrome by comparing induction options and the number of consolidation courses and whether consolidation should include transplantation.We randomly assigned 1,658 patients younger than age 60 years to receive mitoxantrone/cytarabine/etoposide versus cytarabine/daunorubicin/etoposide and subsequently 1,193 patients to daunorubicin/cytarabine/thioguanine (DAT) where the cytarabine dose was standard (S-DAT) versus double the standard dose (H-DAT). Patients in this randomization were randomly assigned to all-trans-retinoic acid or not. In consolidation, 992 patients were randomly assigned between a total of four courses versus five courses, and 324 patients who were not good risk were randomly assigned to transplantation or chemotherapy as the final course.Complete remission (CR) was achieved in 74% of patients and CR without recovery was achieved in an additional 11%; overall survival (OS) at 8 years was 38%. No differences in CR, relapse-free survival, relapse, or OS were seen between any of the induction randomizations except for a reduction in relapse risk (RR) on the mitoxantrone arm, which was offset by increased myelosuppression and deaths in CR. The addition of a fifth course did not improve OS and may be detrimental in older patients. Although transplantation reduced RR, it did not improve OS for the intermediate-risk group but was probably of benefit in high-risk patients.Several chemotherapy schedules achieved similar remission rates and OS. Four courses of chemotherapy are adequate, but the addition of transplantation as a final course does not improve OS. New agents are required to enhance conventional chemotherapy.
A randomized phase III trial of stereotactic radiosurgery (SRS) versus observation for patients with asymptomatic cerebral oligo-metastases in non-small-cell lung cancer
Authors: S.H. Lim, J.Y. Lee, M.-Y. Lee, H.S. Kim, J. Lee, J.-M. Sun, J.S. Ahn, S.-W. Um, H. Kim, B.S. Kim, S.T. Kim, D.L. Na, J.Y. Sun, S.H. Jung, K. Park, O.J. Kwon, J.-I. Lee, M.-J. Ahn
Journal: Annals of Oncology (2014)
Use of Transdermal Nicotine in a State-Level Prescription Plan for the Elderly
Authors: C. Tracy Orleans
Journal: JAMA (1994)

To assess transdermal nicotine use patterns and outcomes in a population of low-income older smokers.A 6-month telephone follow-up survey of smokers filling prescriptions for transdermal nicotine in the first 3 months of 1992.Pennsylvania's Pharmaceutical Assistance Plan for the Elderly, the nation's largest state-level prescription plan for the elderly.A total of 1070 noninstitutionalized male and female smokers aged 65 through 74 years.Self-reported physician/pharmacist advice and adjunctive treatments, concomitant smoking, and 6-month smoking abstinence.Respondents were predominantly long-term heavy smokers. They used nicotine patches for an average of 5 weeks, with few reporting use beyond 3 months or recalling bothersome side effects. Most of those with previous quit attempts rated quitting with the patch "easier." The 29% self-reported 6-month quit rate observed is encouraging. However, compliance with patch use guidelines was far from ideal in this high-risk population: only 54% of respondents received any initial advice or materials from their physicians or pharmacists, fewer than 2% took part in a formal clinic or one-to-one treatment program, and almost half (47%) smoked while using the patch, including 20% who smoked every day. Concomitant smoking was strongly associated with failure to achieve abstinence (P < .001). More frequent contact with physicians and/or pharmacists was associated with less concomitant smoking (P < .001) and higher quit rates (P = .005).This survey offers an important first look at problems and prospects for nicotine patch therapy in older adults, with implications for other groups as well. Prospective studies are needed to clarify optimal treatment regimens and adjuncts.
Abstract 1025: Antitumor activity of nintedanib (BIBF 1120), a triple angiokinase inhibitor, in combination with gemcitabine in experimental pancreatic cancer
Authors: Niranjan Awasthi, Stefan Hinz, Rolf A. Brekken, Margaret A. Schwarz, Roderich E. Schwarz
Journal: Cancer Research (2014)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the United States with extremely poor prognosis. Gemcitabine (Gem), the standard of care agent over the past 15 years, has limited clinical benefits. There is an urgent requirement for novel therapeutic strategies to improve overall survival of patients with pancreatic cancer. Angiogenesis, an essential process for tumor growth and metastasis, remains a sensible target for PDAC therapy. VEGF, PDGF, FGF and their receptors are all overexpressed and have been correlated with poor prognosis in human PDAC. Nintedanib (BIBF 1120, Nin) is a triple angiokinase inhibitor that targets VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β signaling. Nintedanib is currently under clinical investigation for several solid tumors. The present study investigated the combination treatment benefits of gemcitabine and nintedanib in experimental PDAC. Cell proliferation, migration and protein expression were analyzed by WST-1 assay, wound healing assay and Western blotting. Tumor growth and animal survival experiments were performed in murine xenografts. Percent inhibition of cell proliferation in the Gem, Nin and Gem+Nin groups was 22%, 25% and 53% (AsPC-1 PDAC cells, Gem 50 nM, Nin 100 nM); 55%, 11% and 80% (endothelial cells HUVECs, Gem 100 nM, Nin 100 nM); 91%, 68% and 94% (fibroblast WI-38 cells, Gem 100 nM, Nin 100 nM). Nintedanib increased apoptosis, indicated by the cleavage of caspase-3 protein in all three cell-types tested. In PDAC cells, antitumor activity was accompanied by higher level of cell cycle inhibitor protein p27. Nintedanib (10 μM) inhibited in vitro wound closure by 84% in endothelial cells. In a heterotopic PDAC model, compared to the percent net local tumor growth in controls (100±29), a reduced growth of 60.8±10.5 (p=0.02) was observed in the Gem group, while a net reduction of -2.1±9.9 (p=0.0001) and -12.4±16.2 (p=0.0001) was observed in Nin and Gem+Nin groups, respectively. Compared with controls (16 days) in an AsPC-1 intraperitoneal model, median animal survival in Gem, Nin and Gem+Nin treatment groups was 25 days, 31 days and 38 days. The strong antitumor activity of nintedanib in experimental PDAC supports the potential of nintedanib-controlled mechanisms as targets for improved clinical PDAC therapy. Citation Format: Niranjan Awasthi, Stefan Hinz, Rolf A. Brekken, Margaret A. Schwarz, Roderich E. Schwarz. Antitumor activity of nintedanib (BIBF 1120), a triple angiokinase inhibitor, in combination with gemcitabine in experimental pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1025. doi:10.1158/1538-7445.AM2014-1025
Catecholamine Release–Inhibitory Peptide Catestatin (Chromogranin A <sub>352–372</sub> )
Authors: Fangwen Rao, Gen Wen, Jiaur R. Gayen, Madhusudan Das, Sucheta M. Vaingankar, Brinda K. Rana, Manjula Mahata, Brian P. Kennedy, Rany M. Salem, Mats Stridsberg, Kenneth Abel, Douglas W. Smith, Eleazar Eskin, Nicholas J. Schork, Bruce A. Hamilton, Michael G. Ziegler, Sushil K. Mahata, Daniel T. O’Connor
Journal: Circulation (2007)

Chromogranin A, coreleased with catecholamines by exocytosis, is cleaved to the catecholamine release-inhibitory fragment catestatin. We identified a natural nonsynonymous variant of catestatin, Gly364Ser, that alters human autonomic function and blood pressure.Gly364Ser heterozygotes and controls underwent physiological and biochemical phenotyping, including catecholamine production, chromogranin A precursor, and its catestatin product. Case-control studies replicated effects of the gene on blood pressure in the population. Gly364Ser displayed diminished inhibition of catecholamine secretion from cultured neurons. Gly/Ser heterozygotes displayed increased baroreceptor slope during upward deflections (by approximately 47%) and downward deflections (by approximately 44%), increased cardiac parasympathetic index (by approximately 2.4-fold), and decreased cardiac sympathetic index (by approximately 26%). Renal norepinephrine excretion was diminished by approximately 26% and epinephrine excretion by approximately 34% in Gly/Ser heterozygotes. The coalescent dated emergence of the variant to approximately 70,000 years ago. Gly364Ser was in linkage disequilibrium with 1 major Chromogranin A promoter haplotype, although promoter haplotypes did not predict autonomic phenotypes. The 364Ser variant was associated with lower diastolic blood pressure in 2 independent/confirmatory groups of patients with hypertension; genotype groups differed by approximately 5 to 6 mm Hg, and the polymorphism accounted for approximately 1.8% of population diastolic blood pressure variance, although a significant gene-by-sex interaction existed, with an enhanced effect in men.The catestatin Gly364Ser variant causes profound changes in human autonomic activity, both parasympathetic and sympathetic, and seems to reduce risk of developing hypertension, especially in men. A model for catestatin action in the baroreceptor center of the nucleus of the tractus solitarius accounts for these actions.
Evolution of medical treatment for endometriosis: back to the roots?
Authors: Fritz Wieser, Misha Cohen, Andrew Gaeddert, Jie Yu, Carla Burks-Wicks, Sarah L. Berga, Robert N. Taylor
Journal: Human Reproduction Update (2007)

Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.
Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses.
Authors: A M Kruisbeek, M L Davis, L A Matis, D L Longo
Journal: The Journal of Experimental Medicine (1984)

The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells.
Examining Transcranial Direct-Current Stimulation (tDCS) as a Treatment for Hallucinations in Schizophrenia
Authors: Jerome Brunelin, Marine Mondino, Leila Gassab, Frederic Haesebaert, Lofti Gaha, Marie-Françoise Suaud-Chagny, Mohamed Saoud, Anwar Mechri, Emmanuel Poulet
Journal: American Journal of Psychiatry (2012)

Objective: Some 25%–30% of patients with schizophrenia have auditory verbal hallucinations that are refractory to antipsychotic drugs. Outcomes in studies of repetitive transcranial magnetic stimulation suggest the possibility that application of transcranial direct-current stimulation (tDCS) with inhibitory stimulation over the left temporo-parietal cortex and excitatory stimulation over the left dorsolateral prefrontal cortex could affect hallucinations and negative symptoms, respectively. The authors investigated the efficacy of tDCS in reducing the severity of auditory verbal hallucinations as well as negative symptoms. Method: Thirty patients with schizophrenia and medication-refractory auditory verbal hallucinations were randomly allocated to receive 20 minutes of active 2-mA tDCS or sham stimulation twice a day on 5 consecutive weekdays. The anode was placed over the left dorsolateral prefrontal cortex and the cathode over the left temporo-parietal cortex. Results: Auditory verbal hallucinations were robustly reduced by tDCS relative to sham stimulation, with a mean diminution of 31% (SD=14; d=1.58, 95% CI=0.76–2.40). The beneficial effect on hallucinations lasted for up to 3 months. The authors also observed an amelioration with tDCS of other symptoms as measured by the Positive and Negative Syndrome Scale (d=0.98, 95% CI=0.22–1.73), especially for the negative and positive dimensions. No effect was observed on the dimensions of disorganization or grandiosity/excitement. Conclusions: Although this study is limited by the small sample size, the results show promise for treating refractory auditory verbal hallucinations and other selected manifestations of schizophrenia.