tbuckley/cabot-search huggingface dataset:
Insulin dependent diabetes mellitus in twins
Authors: J. A Davis
Journal: BMJ (1996)

numerical data suggest a plateauing or even slight decrease in the length of unaffected nail in the itraconazole group.In contrast to Buck, however, we think that there is a continuous increase in the terbinafine group.We are confident that our opinion will be supported by the statistical evalua- tion of an additional, blinded 24 week follow up that we have performed in patients with clinical cure or continuous clinical improvement at 52 weeks.Buck's letter gives us the opportunity to com- ment on rates of relapse.De Cuyper recently reported that after 16 weeks' treatment with terbinafine and 32 weeks' follow up 17 patients who had been treated effectively were observed for a further two years; relapse occurred in only three.'This result accords with the 18% recurrence rate 12 months after clinical and mycological cure of the toenails with terbinafine reported by Villars and Jones.2The relatively high proportion of patients with adverse events in our study (40%) should not be overemphasised.In another study of onychomycosis with similar methodological conditions adverse events occurred in 41% of the patients taking placebo for 12 weeks.3In our study more than 90% of the patients and doctors stated that the tolerability of both drugs was good or excellent.We believe that terbinafine provides more than short term benefit for most patients.
Association of Dermatology Consultation With Accuracy of Cutaneous Disorder Diagnoses in Hospitalized Patients
Authors: Daniela Kroshinsky, Jonathan Cotliar, Lauren C. Hughey, Kanade Shinkai, Lindy P. Fox
Journal: JAMA Dermatology (2016)

topical lidocaine cream, 4%, is typically used to produce anesthesia 60 minutes after application. 4,6Our results suggest that the use of microneedle pretreatment can reduce the incubation time to 30 minutes-perhaps even to 10 minutes in more pain-sensitive individuals-to achieve sufficient anesthesia for needle insertion.Our study has several limitations.First, the pain stimulus was needle based and it is not known how laser-or scalpelbased pain would have been altered.Second, our study was limited to men; future studies should include women.Finally, this study evaluated pain on the volar forearms, but pain sensitivity can vary by anatomical site.Because the participants served as their own controls and the anatomical site at each pain assessment had a symmetrically placed control, the role of the site was minimized.The study should be repeated using other anatomical sites.Randomized clinical trials should be conducted with laseror scalpel-based stimuli to simulate other dermatologic procedures.In particular, studies in a pediatric population can help clarify the role of microneedle pretreatment in topical anesthesia before invasive procedures.Regardless, the findings of this study are promising, showing that microneedles offer a minimally painful method of enhancing the effects of topical anesthesia.
Treatment of non-small-cell lung cancer.
Authors: J L Mulshine, E Glatstein, J C Ruckdeschel
Journal: Journal of Clinical Oncology (1986)

The treatment of non-small-cell lung cancer (NSCLC; including squamous, large-cell anaplastic, and adenocarcinoma) is one of the most frustrating areas in oncology. With the exception of the high cure rates for surgical treatment of truly localized disease, the prognosis for patients with NSCLC is grim. Often rancorous debate has ensued about the best means of exploiting the currently available modalities of radiation therapy and chemotherapy. Recognizing that the effectiveness of the current therapeutic modalities is limited, we will review the treatment results from the past few years that help define where specific treatment options should be used or suggest areas in which to focus future trials. We will also review the implications of current findings in the cell biology of lung cancer as they pertain to the therapy of NSCLC.
Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons
Authors: Sofia Söllvander, Elisabeth Nikitidou, Robin Brolin, Linda Söderberg, Dag Sehlin, Lars Lannfelt, Anna Erlandsson
Journal: Molecular Neurodegeneration (2016)

Despite the clear physical association between activated astrocytes and amyloid-β (Aβ) plaques, the importance of astrocytes and their therapeutic potential in Alzheimer's disease remain elusive. Soluble Aβ aggregates, such as protofibrils, have been suggested to be responsible for the widespread neuronal cell death in Alzheimer's disease, but the mechanisms behind this remain unclear. Moreover, ineffective degradation is of great interest when it comes to the development and progression of neurodegeneration. Based on our previous results that astrocytes are extremely slow in degrading phagocytosed material, we hypothesized that astrocytes may be an important player in these processes. Hence, the aim of this study was to clarify the role of astrocytes in clearance, spreading and neuronal toxicity of Aβ. To examine the role of astrocytes in Aβ pathology, we added Aβ protofibrils to a co-culture system of primary neurons and glia. Our data demonstrates that astrocytes rapidly engulf large amounts of Aβ protofibrils, but then store, rather than degrade the ingested material. The incomplete digestion results in a high intracellular load of toxic, partly N-terminally truncated Aβ and severe lysosomal dysfunction. Moreover, secretion of microvesicles containing N-terminally truncated Aβ, induce apoptosis of cortical neurons. Taken together, our results suggest that astrocytes play a central role in the progression of Alzheimer's disease, by accumulating and spreading toxic Aβ species.
Safety and response with nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus erlotinib in patients (pts) with epidermal growth factor receptor mutant (EGFR MT) advanced NSCLC.
Authors: Naiyer A. Rizvi, Laura Quan Man Chow, Hossein Borghaei, Yun Shen, Christopher Harbison, Suresh Alaparthy, Allen C. Chen, Scott N. Gettinger
Journal: Journal of Clinical Oncology (2014)

8022 Background: Erlotinib is FDA-approved for the first-line treatment of EGFR MT NSCLC, with a median progression free survival (PFS) of 10.4 months. Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, demonstrated encouraging safety and survival outcomes as monotherapy in advanced NSCLC pts. Preclinical data support EGFR pathway activation of PD-L1 expression and immune escape in EGFR driven lung tumors. Interim results from a phase I study evaluating nivolumab + erlotinib in an EGFR MT advanced NSCLC cohort are reported. Methods: Stage IIIB/IV EGFR MT chemotherapy-naïve NSCLC pts (EGFR TKI naïve or progression post prior TKI therapy) received nivolumab 3 mg/kg IV Q2W + erlotinib 150 mg PO daily until progression/unacceptable toxicity. Objective response rate (ORR) and PFS were evaluated by RECIST 1.1. Results: All pts (n=21) began study treatment ≥10 months prior to data analysis; only 1 pt was EGFR TKI naïve. Any-grade treatment-related AEs were reported in all 21 pts; treatment-related grade 3–4 AEs (4 pts) were increased AST (n=2) or ALT (n=1), weight decrease and diarrhea (1 pt each); 2 pts discontinued due to treatment-related AEs (grade 3 AST increase and grade 2 nephritis). No pneumonitis (any grade) was observed. ORR was 19% (4/21 pts) and 24 wk PFS rate was 47%; median duration of response (DOR) was not reached (range 6.1+ to 27.1+ wks). Of the 20 pts with acquired erlotinib resistance, 3 (15%) achieved partial response (PR, all ongoing; DOR 6.1+, 16.3+ and 27.1+ wks); 9 pts (45%) had stable disease with 3/9 (33%) ongoing (time to progression/death 9.9+, 15.7, 21, 22.3, 24.4+, 31.1+, 35.9, 52.7 and 53 wks), and 1 pt had an unconventional "immune related" response (ongoing), with 46% reduction in target lesions after progression in non-target lesions. The EGFR TKI-naïve pt achieved PR with DOR 24.3+ wks (ongoing). Conclusions: These interim results suggest that nivolumab + erlotinib may provide durable clinical benefit and an acceptable safety profile in TKI refractory, EGFR MT advanced NSCLC, supporting further evaluation of nivolumab in pts with EGFR MT NSCLC. Additional follow up will be presented. Clinical trial information: NCT01454102.
Abstract 9479: Comparison of European Society of Cardiology and Circulation Criteria for Interpretation of the electrocardiogram in Young Athletes
Authors: Andrea Menafoglio, Marcello Di Valentino, Costanzo Limoni, Patrick Siragusa, Giorgio Moschovitis, Augusto Gallino
Journal: Circulation (2012)

Background: adding ECG to cardiovascular screening of young athletes remains controversial. One of the reasons refers to the false positive rate of ECG requiring subsequent examinations and raising costs. In an attempt to increase specificity, the European Society of Cardiology (ESC) in 2010 and a group of experts in 2011 (Circulation - CIRC) have proposed recommendations for interpretation of ECG in athletes. The purpose of this study is to compare the ESC and the CIRC criteria for interpreting ECG in young athletes. Methods: ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) competitive athletes. ECG was interpreted applying strictly the ESC criteria and the CIRC criteria. The rate of pathologic ECG following both criteria were compared. Results: ECG of 1070 athletes (75 % males, age 19.7 ± 6.3 years) was analysed. ECG was considered pathologic in 211 (19.7 %) athletes following the ESC criteria and in 42 (3.9 %) athletes following the CIRC criteria (p &lt; 0.001). In table 1 are reported the ECG changes in whom there were differences in pathologic ECG applying ESC and CIRC criteria. Conclusions: strictly applying ESC criteria for interpretation of ECG in young athletes, in respect to CIRC criteria, results in a considerably higher proportion of pathologic ECG thus requiring more subsequent examinations. It appears that ESC criteria should be improved toward the best balance between false positive and negative findings.
Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies
Authors: James S. Ware, Jian Li, Erica Mazaika, Christopher M. Yasso, Tiffany DeSouza, Thomas P. Cappola, Emily J. Tsai, Denise Hilfiker-Kleiner, Chizuko A. Kamiya, Francesco Mazzarotto, Stuart A. Cook, Indrani Halder, Sanjay K. Prasad, Jessica Pisarcik, Karen Hanley-Yanez, Rami Alharethi, Julie Damp, Eileen Hsich, Uri Elkayam, Richard Sheppard, Angela Kealey, Jeffrey Alexis, Gautam Ramani, Jordan Safirstein, John Boehmer, Daniel F. Pauly, Ilan S. Wittstein, Vinay Thohan, Mark J. Zucker, Peter Liu, John Gorcsan, Dennis M. McNamara, Christine E. Seidman, Jonathan G. Seidman, Zoltan Arany
Journal: New England Journal of Medicine (2016)

Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin.
Sugar-Sweetened Beverage Consumption Is Associated With Change of Visceral Adipose Tissue Over 6 Years of Follow-Up
Authors: Jiantao Ma, Nicola M. McKeown, Shih-Jen Hwang, Udo Hoffmann, Paul F. Jacques, Caroline S. Fox
Journal: Circulation (2016)

Sugar-sweetened beverage (SSB) intake has been linked to abnormal abdominal adipose tissue. We examined the prospective association of habitual SSB intake and change in visceral adipose tissue (VAT) and subcutaneous adipose tissue.The quantity (volume, cm(3)) and quality (attenuation, Hounsfield Unit) of abdominal adipose tissue were measured using computed tomography in 1003 participants (mean age 45.3 years, 45.0% women) at examination 1 and 2 in the Framingham's Third Generation cohort. The 2 exams were ≈ 6 years apart. At baseline, SSB and diet soda intake were assessed using a valid food frequency questionnaire. Participants were categorized into 4 groups: none to <1 serving/mo (nonconsumers), 1 serving/mo to <1 serving/week, 1 serving/week to 1 serving/d, and ≥ 1 serving/d (daily consumers) of either SSB or diet soda. After adjustment for multiple confounders including change in body weight, higher SSB intake was associated with greater change in VAT volume (P trend<0.001). VAT volume increased by 658 cm(3) (95% confidence interval [CI], 602 to 713), 649 cm(3) (95% CI, 582 to 716), 707 cm(3) (95% CI, 657 to 757), and 852 cm(3) (95% CI, 760 to 943) from nonconsumers to daily consumers. Higher SSB intake was also associated with greater decline of VAT attenuation (P trend=0.007); however, the association became nonsignificant after additional adjustment for VAT volume change. In contrast, diet soda consumption was not associated with change in abdominal adipose tissue.Regular SSB intake was associated with adverse change in both VAT quality and quantity, whereas we observed no such association for diet soda.
ACEIs/ARBs to improve survival in advanced gastric cancer patients receiving S-1 plus cisplatin.
Authors: Yosuke Kumekawa, Takeru Wakatsuki, Hiroki Osumi, TOMOHIRO MATSUSHIMA, Izuma Nakayama, Mariko Ogura, Takashi Ichimura, Daisuke Takahari, Masato Ozaka, Mitsukuni Suenaga, Eiji Shinozaki, Keisho Chin, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2015)

174 Background: Gastric cancer is heterogeneous disease and male predominant incidence is recognized across the world. Interactions between tumor cells and microenvironments, such as cancer-associated fibroblasts (CAFs) and M2 macrophage, play an important role in cancer progression and CAFs and M2 macrophage predict worse outcomes in several types of cancer. Angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are widely used in cardiovascular disease because these drugs reduced cardiovascular events via inhibiting fibroblasts and inflammation. Moreover these drugs improved survival in advanced pancreatic cancer gemcitabine (Br J Cancer, Nakai, 2010). Given that CAFs and M2 macrophage are associated worse outcomes and ACEIs/ARBs may inhibit these factors, we hypothesized that these drugs may improve survival in advanced gastric cancer. Methods: Two-hundred and twenty advanced gastric cancer patients were enrolled between Jan. 2007 and Dec. 2011. These patients were received S-1 plus cisplatin (SP) as the first-line therapy in our institute. We retrospectively analyzed whether ACEIs/ARBs could predict better survival. Primary endpoint was overall survival (OS) and endpoint was estimated using by Kaplan-Meier methods and compared by the log-rank test. Results: Median age was 61 years old and 68.1% of the patients were male. Eighteen of 220 patients took ACEIs and/or ARBs. No significant difference was shown in patient characteristics between two groups. Median survival time (MST) of all patients was 416 days. There was marginal differences between two groups; MST in ACEI/ARB group was 763 days and 412 days in non-ACEI/ARB group, respectively (HR, 0.59 ; 95% CI 0.34-1.05 ; P=0.071). After analyzing according to gender, MST in male was 997 days in ACEI/ARB group vs. 412 days in non-ACEI/ARB group (HR, 0.42 ; 95% CI 0.18-0.97 ; P=0.037); however, no significant difference was found in female (HR, 0.84 ; 95% CI 0.38-1.86 ; P=0.67). Conclusions: ACEIs/ARBs may have a favorable effect in gastric cancer; however, gender difference may be involved in their efficacy. Further clinical validations and molecular correlation analyses are warranted.
Somatic G17V Rhoa Mutation Specifies Angioimmunoblastic T-Cell Lymphoma
Authors: Mamiko Sakata-Yanagimoto, Terukazu Enami, Kenichi Yoshida, Yuichi Shiraishi, Ryohei Ishii, Yasuyuki Miyake, Hideharu Muto, Naoko Tsuyama, Yusuke Okuno, Seiji Sakata, Yuhei Kamada, Rie Nakamoto-Matsubara, Tran Nguyen, Koji Izutsu, Yasunori Ohta, Junichi Furuta, Seiichi Shimizu, Takuya Komeno, Yuji Sato, Takayoshi Ito, Masayuki Noguchi, Emiko Noguchi, Masashi Sanada, Kenichi Chiba, Hiroko Tanaka, Kazumi Suzukawa, Toru Nanmoku, Yuichi Hasegawa, Osamu Nureki, Satoru Miyano, Naoya Nakamura, Kengo Takeuchi, Seishi Ogawa, Shigeru Chiba
Journal: Blood (2013)
Expression of Aberrantly Spliced Oncogenic Ikaros Isoforms in Childhood Acute Lymphoblastic Leukemia
Authors: Lei Sun, Patricia A. Goodman, Carla M. Wood, Mya-Lisa Crotty, Martha Sensel, Harland Sather, Christopher Navara, James Nachman, Peter G. Steinherz, Paul S. Gaynon, Nita Seibel, Alexei Vassilev, Brian D. Juran, Gregory H. Reaman, Fatih M. Uckun
Journal: Journal of Clinical Oncology (1999)

PURPOSE: We sought to determine if molecular abnormalities involving the Ikaros gene could contribute to the development of acute lymphoblastic leukemia (ALL) in children. PATIENTS AND METHODS: We studied Ikaros gene expression in normal human bone marrow, normal thymocytes, normal fetal liver–derived immature lymphocyte precursor cell lines, eight different ALL cell lines, and leukemic cells from 69 children with ALL (T-lineage ALL, n = 18; B-lineage ALL, n = 51). Expression of Ikaros protein and its subcellular localization were examined by immunoblotting and confocal laser-scanning microscopy, respectively. Polymerase chain reaction (PCR) and nucleotide sequencing were used to identify the specific Ikaros isoforms expressed in these cells. Genomic sequencing of splice junction regions of the Ikaros gene was performed in search for mutations. RESULTS: In each of the ALL cases, we found high-level expression of a non–DNA-binding or aberrant DNA-binding isoform of Ikaros with abnormal subcellular compartmentalization patterns. In contrast, only wild-type Ik-1 and Ik-2 isoforms with normal subcellular localization were found in normal bone marrow cells and thymus-derived or fetal liver–derived normal lymphocyte precursors. In leukemic cells expressing the aberrant Ikaros coding sequences with the 30-base-pair deletion, genomic sequence analysis of the intron-exon junctions between exons 6 and 7 yielded the wild-type sequence. We identified a single nucleotide polymorphism (SNP) affecting the third base of the triplet codon for a proline (CCC or CCA) in the highly conserved bipartite activation region (viz, A or C at position 1002 numbering from the translation start site of Ik-1) within our Ikaros clones. Bi-allelic expression of truncated and/or non–DNA-binding isoforms along with wild-type isoforms was observed in leukemic cells, which implicates trans-acting factor(s) affecting splice site recognition. CONCLUSION: Our findings link specific molecular defects involving the Ikaros gene to childhood ALL. Posttranscriptional regulation of alternative splicing of Ikaros RNA seems to be defective in leukemic lymphocyte precursors from most children with ALL. Consequently, leukemic cells from ALL patients, in contrast to normal lymphocyte precursors, express high levels of non–DNA-binding Ikaros isoforms that are reminiscent of the non–DNA-binding Ikaros isoforms that lead to lymphoblastic leukemia in mice.
The Inhibitory Action of Infection and Fever on the Hematopoietic Response in a Case of Pernicious Anemia
Authors: KENNETH C.  SMITHBURN, L. G.  ZERFAS
Journal: Annals of Internal Medicine (1931)

Article1 March 1931The Inhibitory Action of Infection and Fever on the Hematopoietic Response in a Case of Pernicious AnemiaKENNETH C. SMITHBURN, M.D., L. G. ZERFAS, M.D.KENNETH C. SMITHBURN, M.D.Search for more papers by this author, L. G. ZERFAS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-4-9-1108 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the study of more than 150 cases of primary and secondary anemia, it has been frequently observed that fevers and intoxications of various origins have apparently retarded, interrupted, or prevented the hematopoietic response during active treatment. Minot1 has pointed out that the hematopoietic response in cases of pernicious anemia treated with liver extract may be slight or delayed in the presence of complications. Whipple and his associates2 have observed that infections and intoxications may retard the increase in hemoglobin production in experimental anemias.The following patient, who came under our observation, demonstrates in a striking manner the effect of...References1 MINOTMURPHYSTETSON GRWPRP: "The Response of Reticulocytes to Liver Therapy," Am. J. Med. Sc. 125:581 (May) 1928. CrossrefGoogle Scholar2 WHIPPLEROBSCHEIT-ROBBINSWALDEN GHFSGB: "Blood Regeneration in Severe Anemia," Am. J. Med. Sc. 179:628 (May) 1930. CrossrefGoogle Scholar3 ZERFAS LG: "Liver Extract of Pernicious Anemia—Blood Changes During the First Month," Arch. Int. Med. 47:135 (Jan.) 1931. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Indianapolis*Lilly Laboratories for Clinical Research, Indianapolis City Hospital and Department of Medicine, Indiana University. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1931Volume 4, Issue 9Page: 1108-1111KeywordsAnemiaClinical laboratoriesFeversHemoglobinHospital medicineIntoxicationLiverPernicious anemiaResearch laboratories ePublished: 1 December 2008 Issue Published: 1 March 1931 PDF downloadLoading ...
Radiation Protection
Authors: Shields Warren
Journal: New England Journal of Medicine (1961)

ACTIVE research in many aspects of the measurement and distribution of ionizing radiation and its effects on man has led to much new information in recent years. Likewise, public concern over radioactive fallout and progress in the utilization of atomic energy have led to broader awareness of potential exposure to sources of radiation.Radiation is one of many hazards. Although the basic mechanisms of action of ionizing radiation are not known and only sparse information about doseeffect relations is available, there is far more information1 2 3 4 than is available regarding many other hazards such as carcinogenic food additives and noxious substances . . .
Staff in the NHS
Authors: A. Cockcroft, S. Williams
Journal: BMJ (1998)

Concerns about the well being of staff in the NHS are nothing new. Many have blamed the organisation of the NHS in the past decade, especially the purchaser-provider split, and the underfunding of the service. The white paper outlines government plans for the future of the NHS: what does it have to offer staff?

The document is long on rhetoric and short on specifics. It delineates new roles and responsibilities for several groups of staff. General practitioners and community nurses will form primary care groups and be responsible for commissioning services for local patients. Within trusts, doctors, nurses, and other senior professionals will be “much more closely involved” in designing service agreements with commissioners. The commitment to introduce more information technology will require more …
Immunocytochemical localization of fibrinogen on washed human platelets. Lack of requirement for fibrinogen during adenosine diphosphate-induced responses and enhanced fibrinogen binding in a medium with low calcium levels
Authors: H Suzuki, RL Kinlough-Rathbone, MA Packham, K Tanoue, H Yamazaki, JF Mustard
Journal: Blood (1988)
Blocking the ZZ domain of sequestosome1/p62 suppresses myeloma growth and osteoclast formation in vitro and induces dramatic bone formation in myeloma-bearing bones in vivo
Authors: J Teramachi, R Silbermann, P Yang, W Zhao, K S Mohammad, J Guo, J L Anderson, D Zhou, R Feng, K-Z Myint, N Maertz, J H Beumer, J L Eiseman, J J Windle, X-Q Xie, G D Roodman, N Kurihara
Journal: Leukemia (2015)
A Prospective Multicenter Study of Hepatocellular Carcinoma in Italian Hemophiliacs With Chronic Hepatitis C
Authors: F. Tradati, M. Colombo, P.M. Mannucci, M.G. Rumi, C. De Fazio, G. Gamba, N. Ciavarella, A. Rocino, M. Morfini, A. Scaraggi, E. Taioli
Journal: Blood (1998)