tbuckley/cabot-search huggingface dataset:
The Consult Guys - CHADS, SHMADS: What's All This About Anticoagulation?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2016)

Web Exclusives16 February 2016The Consult Guys - CHADS, SHMADS: What's All This About Anticoagulation?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W16-0002 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Consult Guys bring a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations.For more videos from and information on The Consult Guys, visit www.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: The Consult Guys - A Real Headache: Anticoagulation and a Subdural HematomaBreast Cancer Screening 16 February 2016Volume 164, Issue 4Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelines ePublished: 16 February 2016 Issue Published: 16 February 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Evaluation of pharmacokinetics underlies the collaborated usage of lamivudine and oxymatrine in beagle dogs
Authors: Zhenbao Li, Lei Shang, Chang Liu, Panqin Ma, Chunnuan Wu, Wenjuan Zhang, Yinghua Sun, Yongjun Wang, Xiaohong Liu, Jin Sun
Journal: Asian Journal of Pharmaceutical Sciences (2016)

Combinational therapy of lamivudine and oxymatrine has been employed in the battle against hepatitis B virus in clinical setting. However, the pharmacokinetic behavior of the drug or active metabolism in intravenous/oral co-administration regime is poorly investigated. Herein, we evaluated the pharmacokinetic characteristic through a tailor-designed 3 way crossover-Latin square experiment in adult male beagle dogs. Six dogs were randomly treated by intravenous administration of lamivudine (2.5 mg/kg), oxymatrine (15 mg/kg) and combinational dosage, named as intravenous regime. Meanwhile the other six dogs were orally administrated with lamivudine (2.5 mg/kg), oxymatrine (15 mg/kg) and combinational dosage, named as oral regime. The pharmacokinetic feature in simultaneous oral treatment appeared to have no significant difference when compared with individual administration, even including matrine, the active metabolite of oxymatrine. In intravenous regime, the main pharmacokinetic parameters of simultaneous administration were nearly consistent with intravenous regime remedy. The collaborated application of lamivudine and oxymatrine contributed to non-distinctive pharmacokinetic fluctuations of beagle dogs in intravenous/oral regime, compared with individual employment, which established a vital base for the clinical co-administration against hepatitis B. Furthermore, the present study demonstrated that the determination of pharmacokinetics between combinational and individual therapy might assist in the development of drug compatibility in clinical therapy.
Concurrent chemoradiation with and without adjuvant chemotherapy in advanced stage nasopharyngeal carcinoma: A retrospective analysis
Authors: J. Y. Hsiang, K. Liu, S. Iganej, J. Kaptein, J. G. Hsiang, J. M. Hwang, M. Tome
Journal: Journal of Clinical Oncology (2004)

5619 Background: Randomized trials have reported improved outcome by adding chemotherapy to radiation, but none have examined concurrent chemoradiation with and without adjuvant chemotherapy. This retrospective analysis seeks to review our experience. Methods: Records of 29 consecutively treated patients from 1997 to 2002 were reviewed; these included stage IIII(n=8) and stage IV(n=21) patients with a median age of 49years. All patients received concurrent chemoradiation with the majority (82.8%) receiving at least three courses of cisplatin(100mg/m2;days1,22,43). Seventeen patients received adjuvant chemotherapy with cisplatin(80mg/m2;day1) and fluorouracil(1000mg/m2/d;days1–4) every 4 weeks, with a majority(82.4%) receiving at least three courses. Twelve patients did not receive adjuvant chemotherapy. All patients received radiotherapy in 1.8–2.0 Gy/d fractions to 7020Gy median total dose. Results: After a median follow-up of 39.6 months, seven of 29 patients had recurrent(n=6)/persistent disease(n=1). At last follow-up, six patients had died (four of disease, one treatment related, one of intercurrent death). Four patients developed distant metastases: three had no other sites of relapse and one had recurred locally first. Three of the four patients with distant metastases had adjuvant chemotherapy. The median time to relapse was 15.4 months. The 3-year disease-free survival (DFS) and overall survival (OS) for the 29 patients were 77% and 83% respectively. The 3-year DFS for those with and without adjuvant chemotherapy was 78% and 82%(p=0.5), while OS was 85% and 92%(p=0.8), respectively. Patients with adjuvant chemotherapy more frequently had significant weight loss and xerostomia. Conclusions: Our data suggests that concurrent chemoradiation with or without adjuvant chemotherapy provide similar outcomes. However patients with adjuvant chemotherapy are more likely to develop significant weight loss and xerostomia, and they may be at increased risk of treatment-related deaths. Randomized trials are needed to confirm these findings. No significant financial relationships to disclose.
Multimodality therapy for locally advanced esophageal cancer.
Authors: Nitesh N. Paryani, Stephen Ko, Corey James Hobbs, Kristin Kowalchik, Elizabeth Johnson, Siyong Kim, Laura Vallow, Jennifer Layton Peterson, Katherine S. Tzou, Steven J. Buskirk
Journal: Journal of Clinical Oncology (2015)

211 Background: The current standard of care for locally advanced esophageal cancer includes chemoradiotherapy with or without surgery. Radiation is usually delivered via a 3D technique. IMRT has been utilized in the treatment of multiple tumors and demonstrated similar efficacy while offering the possibility of decreased toxicity. Methods: Thirty-six patients were treated with IMRT and chemotherapy. Twenty-one patients underwent surgical resection. Eleven underwent open surgery and the remainder underwent minimally invasive surgery. Chemotherapy consisted primarily of 5-FU with oxaliplatin or cisplatin. All but two patients received 50.4 Gy; one patient received 41.4 Gy without surgery and one patient discontinued treatment after 25.2 Gy. Eleven patients required a treatment break during radiotherapy. The median age was 69 (range 46-87). Approximately two-thirds of tumors were adenocarcinomas located in the lower thorax. Two thirds of patients were staged as T3 and had positive lymph nodes. The median tumor size was 5 cm (range 2-13). Results: With a median follow-up of 21.3 months (range 2.4-44.8) and 33.9 months for survivors (range 3.7-44.8), overall survival at 24 months was 55%. The 24 month overall survival was 75% vs 24% for surgical and non-surgical patients, respectively. Seven patients had a complete pathologic response. Twenty-four patients experienced grade 3 or higher acute toxicity and there was one grade 5 toxicity. Acute toxicity was similar between surgery and non-surgery patients. Fourteen patients experienced grade 3 or higher late toxicity; 9 surgery and 5 non-surgery patients. The most frequent late toxicity was grade 3 stricture (21%). On multivariate analysis, advanced age (RR [10 year increase] 2.01, p=0.032) and heart maximum dose &gt;55 Gy (RR 3.73, p=0.011) were associated with decreased survival. Conclusions: Patients who undergo surgery after chemoradiotherapy demonstrate improved survival; however, this may be related to underlying comorbidities that preclude surgery. IMRT appears to be a reasonable treatment option that may reduce complications from radiotherapy. Careful attention should be given to heart dose during treatment planning.
Autologous Bone Marrow Transplantation in Acute Leukemia&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: N C Gorin
Journal: JNCI Journal of the National Cancer Institute (1986)

Autologous bone marrow transplantation (ABMT), which was developed in the past decade, is currently under investigation for the treatment of leukemias, lymphomas, and a few solid tumors. It consists of engrafting a patient, after ablative chemotherapy and/or total-body irradiation (TBI), with marrow taken from the patient at a propitious time in the history of the disease and usually cryopreserved. This technique has two major consequences: ABMT by reducing the length and variability of posttreatment aplasia can be considered a super hematologic support. It allows the use of chemotherapeutic agents and/or TBI at doses that surpass the dose for effecting the threshold of myelotoxicity. Therefore, a greater tumor cell kill can be expected at a reasonably low cost in terms of toxicity. In patients with acute leukemia (AL), however, the contribution of ABMT may go far beyond. In the initial trials (1974-79), the marrow of patients with AL was collected during complete remission and cryopreserved, with the idea of preserving "the remission status." At relapse this marrow was re-infused after high-dose chemotherapy and/or TBI, for achieving another complete remission. The result could be considered a chronologic chimera; the autograft, which had stem cells younger than those of the organism, reproduced, over the course of a few months or years, the evolution of the remission during which it was collected. As predicted, however, all patients who received this treatment eventually relapsed. For a more aggressive technique, some teams gave autografts to patients earlier, during remission, to allow ablative therapy in the consolidation mode; the whole procedure, including the pretransplant cytoreductive regimen, was modeled on that of allografting. Because allogeneic bone marrow transplantation currently offers the best chance of long-term survival but remains severely restricted, by age and availability of an HLA-identical donor, to less than 10% of the patients, ABMT may be considered an alternative source of stem cells to the other patients. In addition, ABMT avoids the risks of graft-versus-host disease with its associated immunosuppression. However, one major impediment to effective ABMT may be the persistence of leukemia cells in the marrow autograft, although the marrow was collected during earlier remission. The recent development of numerous techniques to cleanse the marrow prior to ABMT has considerably increased the possibility of ABMT becoming a major tool in the cure of leukemia. This report reviews the early data and essentially focuses on recent results of ABMT effected in or done in remission with use of cleansed and uncleansed marrow.
Phase II trial of meloxicam, a COX-2 inhibitor, and interferon alfa in patients with metastatic renal cell carcinoma
Authors: N. Shinohara, T. Abe, A. Sazawa, K. Nonomura
Journal: Journal of Clinical Oncology (2008)

16003 Background: Cyclooxygenase (COX)-2 plays a major role in the development of cancer through numerous mechanisms. We have previously confirmed that COX-2 has an important role in tumorigenesis and angiogenesis of renal cell carcinoma (RCC) (Int J Cancer 2004). Some preclinical studies suggest that a selective COX-2 inhibitor may augment the antitumor effects of immunotherapeutic agents. In view of potential additive or synergistic effects of COX-2 inhibitor and interferon (IFN)-alfa, we conducted a phase II trial to characterize the efficacy and toxicity of the combination of meloxicam, an oral COX-2 inhibitor, and IFN-alfa 2a for the treatment of patients with metastatic RCC. Methods: Eligible patients had metastatic RCC, no prior systemic therapy, performance status 0–2, measurable disease. Patients received IFN 3–5MIU 3x/week and meloxicam 10mg orally once daily continuously. Primary end point was RECIST response rate. Secondary endpoints were time to progression, overall survival and toxicity. Results: Patients characteristics of 43 patients entered included: median age 63 years (44–78), male/female: 34/9, PS 0/1/2: 26/12/5, prior nephrectomy: 32 (74%). Evaluable lesions were lung only in 19 patients and others in 24. MSKCC prognostic categories were good/intermediate/poor: 11(26%)/22 (51%)/10 (23%). A median follow-up was 14 months (range 3–41+). Based on the RECIST criteria, complete response (CR) was observed in 3 patients (7%) and partial response (PR) in 10 (23%), yielding an overall response rate of 30%. An additional 17 patients (40%) had stable disease. Response rates were 7 of 33 patients (21%) in good- or intermediate-risk group and 6 of 10 (60%) in poor-risk group. Median time to progression for 43 patients was 13.7 months (1–41+). Overall survival at 2 years was 71.7%. Fatigue, depression, anorexia were the most common toxicities. Grade 3 toxicities were uncommon but included liver dysfunction, duodenal ulcer, arthralgia and fatigue. Conclusions: In patients with metastatic RCC, the combination of meloxicam and IFN-alfa has enhanced antitumor activity in comparison with IFN alone reported previously, and displays an acceptable safety profile. Further investigation with this combination is warranted. No significant financial relationships to disclose.
Two common genetic variants increase susceptibility to breast cancer in the Spanish population
Authors: E. Millastre, R. Andres, J. Lambea, S. Serrano, M. Tobeña, M. J. Vidal Eduardo Polo, B. Saez, J. Godino, A. Tres, J. I. Mayordomo
Journal: Journal of Clinical Oncology (2008)

11092 Background: Breast cancer is the most common cause of death by cancer in women in Spain. Epidemiology clearly shows that genetic factors are significant components of risk even in women without detectable BRCA1 or BRCA2 germline mutations. We aim to detect genetic variants associated with breast cancer susceptibility in Spain. Methods: Within a multinational genome-wide association study conducted in collaboration with Decode genetics, including 4,554 consenting patients diagnosed with breast cancer and 17,577controls, Spain contributed with 455 patients and 1,002 controls. >300,000 polymorphisms have been assessed with the Infinium II method (Illumina platform). Results: Two common genetic variants associated to breast cancer have been identified. One of them (rs 13387042A) is located in 2q35. Frequency in Spain (cases/controls/relative risk/2-tailed p) is 58.1%/53.3%/1.21/0.01. In the whole multinational study, relative risk/2-tailed p is 1.20/1.3×10–13. A second variant is located in 16q12 (rs3803662T). Frequency in Spain (cases/controls/relative risk/2-tailed p) is 34.8%/30.8%/1.20/0.03. In the whole multinational study, relative risk/2-tailed p is 1.28/5.9×10–19. Taken together, the estimated populational attributtable risk is 25.4%. The second variant is located adjacent to the TNRC9 gene. Both variants are associated with estrogen-positive breast cancer. The implications of these findings will be presented. Conclusions: Two frequent genetic variants are associated with susceptibility to estrogen receptor positive breast cancer in the Spanish population. They are involved in 25.4% of all cases of this neoplasm in Spain. No significant financial relationships to disclose.
Reactivity of Lung Cancer Patients in Leukocyte Migration Inhibition Assays to 3-M Potassium Chloride Extracts of Fresh Tumor and Tissue-Cultured Cells Derived From Lung Cancer2
Authors: J. L. McCoy, L. F. Jerome, G. B. Cannon, J. L. Weese, R. B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1977)

Direct capillary tube, leukocyte migration inhibition (LMI) assays were performed to determine whether lung cancer patients display cell-mediated immunity (CMI) against tumor-associated antigens. The sources of antigen were allogeneic 3-m KCI extracts of a tissue-cultured squamous cell lung tumor cell line (CaLu-1) and a fresh pleural effusion (7661) from a patient with adenocarcinoma of the lung. A total of 40167 (60%) lung cancer patients reacted to 7661 as compared to 4/40 (10%) normal donors. A similar pattern of reactivity [21/38 (55%) lung cancer patients and 1116 (6%) normal donors] was obtained with the CaLu-1 extract. Furthermore, some weak cross-reactivity was observed with lung carcinoma antigens and patients with breast carcinoma and Ewing'S sarcoma. Although the reactivity was largely lung cancer associated, no restriction was found of LMI reactivity to patients with tumors of histologic types homologous to the extracts. With the CaLu-1 extract, 7117 (47%) lung cancer patients with squamous cell tumor reacted, as did 7113 (54%) with adenocarcinomas, 315 (60%) with anaplastic tumors, and 213 (66%) with oat cell carcinoma. With the 7661 extract, 17128 (61%) lung cancer patients with a squamous cell tumor reacted, as did 12117 (71 %) with adenocarcinoma, 418 (50%) with anaplastic cancer, and 417 (57%) with oat cell tumors. Reactivity in LMI did not seem to be related to stage of disease or to extent of tumor burden at the time of testing. Lung cancer patients with the following stages of disease reacted with the 7661 and CaLu-1 extracts, respectively: stages I and II, combined, 15120 (75%) and 9116 (56%); stage III, 19136 (52%) and 9118 (50%). Patients were also LMI-positive during relapse and within 1 month of death. The results indicate that most patients with carcinoma of the lung had CMI against a common lung tumor-associated antigen not restricted to a given histologic type of lung carcinoma. Furthermore, data also demonstrated that lung cancer patients displayed a similar Incidence of LMI reactivity, regardless of the magnitude of their tumor burden.
Association of Rat Virus and Moloney Leukemia Virus in Tissues of Inoculated Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Kilham, Lawrence, Moloney, John B.
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Association of Rat Virus and Moloney Leukemia Virus in Tissues of Inoculated Rats Get access Lawrence Kilham, Lawrence Kilham Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire, and Laboratory of Viral Oncology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar John B. Moloney John B. Moloney Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire, and Laboratory of Viral Oncology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 32, Issue 2, February 1964, Pages 523–531, https://doi.org/10.1093/jnci/32.2.523 Published: 01 February 1964 Article history Received: 10 September 1963 Published: 01 February 1964
Transformation of Cell Cultures as an Indication of the Carcinogenic Potential of Chemicals2
Authors: Aaron E. Freeman, Elizabeth K. Weisburger, John H. Weisburger, Ronald G. Wolford, Jean M. Maryak, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Transformation of Cell Cultures as an Indication of the Carcinogenic Potential of Chemicals Get access Aaron E. Freeman, Aaron E. Freeman Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth K. Weisburger, Elizabeth K. Weisburger Search for other works by this author on: Oxford Academic PubMed Google Scholar John H. Weisburger, John H. Weisburger Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald G. Wolford, Ronald G. Wolford Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean M. Maryak, Jean M. Maryak Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Huebner Robert J. Huebner Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 799–808, https://doi.org/10.1093/jnci/51.3.799 Published: 01 September 1973 Article history Received: 29 January 1973 Accepted: 07 May 1973 Published: 01 September 1973
LAV/HTLV-III Seroconversion and Disease in Hemophiliacs Treated in France
Authors: D Mathez, J Leibovitch, Y Sultan, P Maisonneuve
Journal: New England Journal of Medicine (1986)

The emergence of antibodies to lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III) in French patients with hemophilia coincided with the onset of the acquired immunodeficiency syndrome (AIDS) epidemic in 1984.  The prevalence of antibodies to LAV/HTLV-III in a sample of 63 French hemophiliacs (55 with hemophilia A and 8 with hemophilia B) was 0/8 in 1981 2/13 in 1982 6/33 in 1983 and 27/49 in 1984.  At the end of the 1st trimester of 1985 the cumulated seropositivity prevalence was 60%.  7 patients had received only fractions prepared from plasma obtained in France in the 6-month period preceding documented seroconversion and 2 had received only imported factor VIII concentrates.  20 other antibody positive patients had been treated with both local and international plasma derivatives.  1 patient treated exclusively with French-made products seroconverted in late 1982.  Clinical symptoms of LAV/HTLV-III-related disease developed in 9 of 37 seropositive patients 1-30 months after maximally estimated seroconversion time.  Blood T4 lymphocyte counts of less than 500/ml or T4/T8 ratios less than 0.5 were present in another 3 asymptomatic hemophiliacs.  Thus among the seropositive subjects the overall prevalence of symptoms compatible with LAV/HTLV-III infection was 33% indicating that live retroviruses contaminated the batches of factor concentrates.  This rate is lower than that noted among US hemophiliacs perhaps because the spread of LAV/HTLV-III in France lags 2 years behind that in the US.
Paralogous origin of the red- and green-sensitive visual pigment genes in vertebrates.
Authors: S Yokoyama, W T Starmer, R Yokoyama
Journal: Molecular Biology and Evolution (1993)

The nucleotide sequence of the red-sensitive visual pigment gene, R007Af, in the fish Astyanax fasciatus, from the initiation codon to the stop codon of this gene, including introns, is 1,592 bp, making it the shortest visual pigment gene known in vertebrates. Analysis of this and other homologous sequence data suggests that vertebrates initially had two duplicate genes and that each ancestor of Astyanax, human, and chicken independently duplicated the gene in the process of developing their red-green color vision. Furthermore, many extant red-green colorblind organisms may be explained simply by the failure of achieving very specific nucleotide substitutions at the three codon positions 180, 277, and 285, rather than by the lack of duplicate loci.