tbuckley/cabot-search huggingface dataset:
Trebananib (AMG 386) in Combination With Sunitinib in Patients With Metastatic Renal Cell Cancer: An Open-Label, Multicenter, Phase II Study
Authors: Michael B. Atkins, Gwenaelle Gravis, Kazimierz Drosik, Tomasz Demkow, Piotr Tomczak, Shirley S. Wong, M. Dror Michaelson, Toni K. Choueiri, Benjamin Wu, Lynn Navale, Douglas Warner, Alain Ravaud
Journal: Journal of Clinical Oncology (2015)

Trebananib, an investigational recombinant peptide-Fc fusion protein, neutralizes the receptor-ligand interaction between Tie2 and angiopoietin-1/2. This phase II study was conducted to evaluate trebananib plus sunitinib, a vascular endothelial growth factor receptor inhibitor, in patients with metastatic clear cell renal cell carcinoma.Adults with metastatic renal cell carcinoma were enrolled sequentially onto two cohorts that received sunitinib 50 mg once per day for 4 weeks on and 2 weeks off and intravenous trebananib once per week at a dose of 10 mg/kg in cohort A or 15 mg/kg in cohort B. The primary end points were incidences of adverse events (AEs) and dose interruptions of sunitinib during the first 12 weeks of treatment. Secondary end points included objective response rate and progression-free survival.Eighty-five patients were enrolled: 43 in cohort A, and 42 in cohort B. During the first 12 weeks of treatment, 58% and 57% of patients in cohorts A and B, respectively, had sunitinib dose interruptions (dose decrease, withholding, or withdrawal). The most frequent AEs were diarrhea (cohort A, 74%; cohort B, 67%), mucosal inflammation (cohort A, 49%; cohort B, 60%), and hypertension (cohort A, 52%; cohort B, 45%). AEs of grade 3 or greater occurred in 58% of patients in cohort A and in 69% of patients in cohort B. The objective response rate was 58% and 63% in cohorts A and B, respectively. The median progression-free survival time was 13.9 months (95% CI, 10.4 to 19.2) and 16.3 months (95% CI, 13.1 to 21.4) in cohorts A and B, respectively. The median overall survival time was 36 months (95% CI, 25.2 to not estimable) in cohort A and was not estimable (median follow-up, 25 months) in cohort B.Trebananib plus sunitinib seemed to increase toxicity at the tested doses. Efficacy results suggest a potential benefit for the addition of trebananib to sunitinib.
Asking the Obvious Questions Regarding Patient Burden
Authors: Jeff Sloan
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.1.4 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11773146 Asking the Obvious Questions Regarding Patient Burden Jeff SloanxJeff SloanSearch for articles by this author Show More Cancer Center Statistics, Mayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.2002.20.1.4 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Wild-Type Gross Leukemia Virus. II. Influence of Immunogenetic Factors on Natural Transmission and on the Consequences of Infection&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Tadao Aoki, Edward A. Boyse, Lloyd J. Old
Journal: JNCI Journal of the National Cancer Institute (1968)

To determine the influence of host genotype and other factors on the transmission of wild-type Gross virus and on the subsequent course of infection, mice of various inbred, F1 hybrid, and segregating populations were tested individually for the presence of Gross soluble antigen (GSA) or Gross (G) natural antibody in the blood. GSA was invariably present in mice of strains with a high incidence of leukemia. Among the hybrid progeny of various crosses between G+ and G− strains the proportion of mice with GSA in the plasma was influenced by a) the genotype contributed by the G− parent (whether resistant or sensitive to Passage A Gross virus) and b) the direction of the cross (whether G+♀ × G−♂ or G−♀ × G+♂). Naturally occurring G antibody was most frequent in C57BL/6 mice, which are highly resistant to Passage A Gross virus, and in the progeny of hybrids with C57BL/6. G antibody was rare in C3Hf/Bi mice, a G− strain that is sensitive to Gross virus, and in C3Hf/Bi hybrids. In populations segregating for H-2 antigens, the genotype H-2k favored the occurrence of GSA, indicating immunological tolerance, and H-2b, the occurrence of G antibody, indicating lack of tolerance.
ROLE OF L-DOPA DECARBOXYLASE IN THE BIOSYNTHESIS OF CATECHOLAMINES IN NERVOUS TISSUE AND THE ADRENAL MEDULLA
Authors: P. Holtz
Journal: Pharmacological Reviews (1959)

The role played by L-dopa decarboxylase in the biosynthesis of catecholamines depends on the organ in which the primary product of its action, i.e., dopamine, is formed.

In the suprarenal medulla the biosynthesis proceeds via noradrenaline to the methylated end-product, adrenaline. Dopamine is the precursor of the hormones.

In nervous tissue, the biosynthesis stops at the noradrenaline level. Here dopamine is the precursor of the transmitter, and besides this probably an effector substance of its own.

In lungs, intestine and liver dopamine itself is the end-product of the biosynthesis. Here it may act as a local hormone.
General Practitioner Referral of Patients with Lower Gastrointestinal Symptoms
Authors: R G Springall, I P Todd
Journal: Journal of the Royal Society of Medicine (1988)

Of 500 consecutive patients with symptoms of colorectal disease referred to a specialist hospital for outpatient assessment, 305 were studied. There was a low incidence of examination by the general practitioner; less than half the patients had a rectal examination and 31% had no examination at all. In cases where GPs made a diagnosis, this was correct in half, which both demonstrates the potential for dangerous misdiagnosis and confirms the fact that many anorectal conditions can be identified by the history alone. It is suggested that direct-access clinics in a colorectal unit would minimize delay in accurate diagnosis. The resource implications for such a system would be limited in terms of special investigations and additional clinic facilities.
Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial
Authors: Karen Kelly, John Crowley, Paul A. Bunn, Cary A. Presant, Patra K. Grevstad, Carol M. Moinpour, Scott D. Ramsey, Antoinette J. Wozniak, Geoffrey R. Weiss, Dennis F. Moore, Valerie K. Israel, Robert B. Livingston, David R. Gandara
Journal: Journal of Clinical Oncology (2001)

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization. PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m 2 /wk and cisplatin 100 mg/m 2 /d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m 2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months. RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002) and neutropenia (P = .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P = .001, P = .007), and grade 3 peripheral neuropathy was higher on the PC arm (P &lt; .001). More patients on the VC arm discontinued therapy because of toxicity (P = .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs. CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non–small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.
Sustained Treatment Effect of Spinal Cord Stimulation in Painful Diabetic Peripheral Neuropathy: 24-Month Follow-up of a Prospective Two-Center Randomized Controlled Trial
Authors: Maarten van Beek, Rachel Slangen, Nicolaas C. Schaper, Catharina G. Faber, Elbert A. Joosten, Carmen D. Dirksen, Robert T. van Dongen, Alfons G.H. Kessels, Maarten van Kleef
Journal: Diabetes Care (2015)

Spinal cord stimulation (SCS) has been demonstrated to serve as a successful second-line treatment modality for painful diabetic peripheral neuropathy (PDPN), as documented in two randomized clinical trials (RCTs) (1,2). Besides the fact that these two RCTs demonstrate a pain-relieving effect for a period of 6 months after the start of SCS treatment, only small observational studies suggest a long-term sustained effect in PDPN (3–5). In this article, we present the 24-month follow-up data of our recently published RCT in Diabetes Care (1).

Thirty-six patients were enrolled in this study, and after randomization, 22 patients with PDPN in the lower limbs (15 male, mean age 57.1 years [SD 12.4], years of PDPN 6.0 [SD 5.1]) were assigned to the SCS group. A 2-week trial stimulation was performed to evaluate sufficient pain relief. After 6 …
Microsomal Epoxide Hydrolase Expression as a Predictor of Tamoxifen Response in Primary Breast Cancer: A Retrospective Exploratory Study With Long-Term Follow-Up
Authors: Peter Fritz, Thomas E. Mürdter, Michel Eichelbaum, Isabel Siegle, Matthias Weissert, Ulrich M. Zanger
Journal: Journal of Clinical Oncology (2001)

PURPOSE: It has been suggested that estrogen receptor–independent high-affinity binding sites for antiestrogens could limit their local bioavailability and response. Microsomal epoxide hydrolase (mEH) was recently shown to be a component of the antiestrogen binding site complex. We investigated whether mEH expression in primary breast tumors is related to disease outcome and to the efficacy of tamoxifen treatment. PATIENTS AND METHODS: Expression of mEH was semiquantitatively assessed by immunohistochemistry in sections prepared from archival paraffin blocks of primary breast cancers from 179 patients with a mean follow-up time of 81 months. RESULTS: Expression of mEH was correlated with poor disease outcome in all patients (P &lt; .01; n = 179) and in patients receiving tamoxifen (P &lt; .01; n = 78), but not in patients not treated with tamoxifen. Moreover, mEH was an independent prognostic factor by Cox regression analysis. CONCLUSION: The results of this first exploratory study suggest that mEH expression in primary breast cancer could be of predictive value for response to tamoxifen treatment and/or may be a novel independent prognostic factor for survival. The results are in agreement with the model that mEH participates in an estrogen receptor–independent tamoxifen- binding complex.
A Poxvirus of Primates. II. Immunology&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A H Nicholas
Journal: JNCI Journal of the National Cancer Institute (1970)

OrTeCa poxvirus shares antigens with Yaba virus, as evidenced by two-way crossreactions in complement-fixation and neutralization tests. Antibodies produced by vaccinia and monkeypox viruses showed weak complement-fixation reactions with OrTeCa viral antigen, but neutralization reactions were negative and cross protection in vivo was not demonstrated. OrTeCa and Yaba virus antisera both contained complement-fixing and neutralizing antibodies against swinepox virus, but swinepox antiserum had no antibodies to any other poxvirus. Long-lasting immunity to the OrTeCa pox disease was produced in monkeys and man by spontaneous infection or vaccination with OrTeCa poxvirus. Complement-fixing antibody titers could be measured in convalescence, but tended to drop to low levels or disappear thereafter. In contrast, neutralizing antibody titers remained high for 3 years, and monkeys that were challenged with OrTeCa virus were refractory to a second infection.
Surface Antigens on Transplantable Tumor Cell Lines Producing Mouse Type C Viruses
Authors: Tadao Aoki, Ronald B. Herberman, Janet W. Hartley, Margaret Liu, Mary Jane Walling, Myrthel Nunn
Journal: JNCI Journal of the National Cancer Institute (1977)

A variety of transplantable mouse tumor lines were shown to contain murine type C viruses and virus-associated antigens. The type of virus isolated and antigens detected could not invariably be correlated with the original method of tumor induction, but testing of the majority of tumor lines for infectious virus at various levels of in vivo or in vitro passage yielded isolates that were consistent in tissue culture host range for each tumor. In contrast, during the course of in vivo transplantation, some of the lines underwent considerable change in the pattern of virus-associated cell-surface antigens. When the transplanted tumor lines were placed into culture, all showed some alteration in the detectable surface antigens. Upon retransplantation and passage of the cultured cells in mice, the surface antigens gradually returned to the original in vivo patterns and occasionally acquired additional type C virus-associated antigens not detected in the original tumor line. To test for association of antigens with infectious virus, appropriate tissue culture cell lines were infected with the viruses isolated from the tumors. In these infected indicator cells, some new virus-associated cell-surface and virion evelope antigens were detected, but the complete array of antigens found in the original tumor lines was not acquired. These findings indicated the presence of several different type C viruses in long transplanted cell lines and demonstrated that environmental and host cell factors may have major influences on expression of virus-associated antigens.
Usefulness of C-reactive protein and procalcitonin levels in pulmonary tuberculosis
Authors: Jihen Ben Amar, Bouthaina Ben Safta, Khehna Bouzid, Besma Dhahri, Mohamed Ali Baccar, Saloua Azzabi, Hichem Aouina, Hend Bouacha
Journal: European Respiratory Journal (2014)

Pulmonary tuberculosis (PTB) and community-acquired pneumonia (CAP) are common causes of lower respiratory tract infections and may have similar clinical and radiological features.We investigated the utility of serum C-reactive protein (CRP) and procalcitonin (PCT) for differentiating pulmonary tuberculosis from bacterial CAP.

METHODS:We conducted a prospective study, enrolling 102 participants with suspected CAP in pulmonary department. We assessed serum PCT in consecutive patients diagnosed with pulmonary tuberculosis or community-acquired pneumonia (CAP) on admission to discriminate between PTB and CAP, and examined the value of prognostic factors in PTB.

RESULTS:

Of the patients, 72 had bacterial CAP and 30 had pulmonary TB. The median age of the bacterial CAP and pulmonary TB groups was 43,58years (range, 18 to 81) and 47,88 years (range, 25 to 67), respectively.

The median CRP concentration was 138,36mg/L (range 44to 486) in patients with bacterial CAP and 43,39 mg/L (range, 7 to 156) in those with pulmonary TB (p<0.001). The median PCT level was 6,65 ng/mL (range, 0.05 to 27.47) with bacterial CAP and 0.215 ng/mL (range, 0.05 to 1,27) with pulmonary TB (p<0.001).). Pulmonary TB patients had significantly lower

WBC count than CAP patients (6908 versus 15076 cells/ml-1; p<0.01) No difference was detected in the discriminative values of CRP and PCT.

CONCLUSIONS:

The concentrations of CRP and PCT differed significantly in patients with pulmonary TB and bacterial CAP. The high sensitivity and negative predictive value for differentiating pulmonary TB from bacterial CAP suggest a supplementary role of CRP and PCT in the diagnostic exclusion of pulmonary TB from bacterial CAP.
Correction
Authors: Richard O Day, Garry G Graham
Journal: British Journal of Sports Medicine (2013)

A 70 year old obese woman asks if more can be done for her knee and low back pain, due to osteoarthritis. She used to smoke and has type 2 diabetes. Her orthopaedic surgeon does not consider the clinical presentation and radiographic changes in her knees severe enough for surgery. Her height is 160 cm, weight 85 kg, blood pressure 130/80 mm Hg, with normal renal function, plasma cholesterol concentration 5.5 mmol/L, and HDL cholesterol concentration 0.9 mmol/L. Her present drug treatment is paracetamol (4 g daily) and metformin.

NSAIDs act by inhibiting cyclo-oxygenase-1 (COX-1) and COX-2 enzymes, which are involved in prostaglandin synthesis, resulting in their analgesic, anti-inflammatory, and antipyretic effects (figure⇓). Although the boundary is blurred, there are two broad groups of NSAIDs—the older, traditional, non-selective NSAIDs that inhibit both COX-1 and COX-2 and the newer, selective COX-2 inhibitors that predominantly inhibit COX-2 (figure⇓). The non-selective NSAID aspirin is used primarily for its antiplatelet effect, thus reducing the risk of myocardial re-infarction and stroke.



Arachidonic acid is metabolised by the cyclo-oxygenase isoenzymes COX-1 and COX-2 to intermediate prostaglandins (PGG2, then PGH2), which are then converted to other prostaglandins that are mediators of pain, inflammation, and fever, and are gastroprotective. Thromboxane A2 causes platelet aggregation, and prostacyclin produces vasodilation. By blocking COX enzymes, NSAIDs inhibit the synthesis and thus the effects of prostaglandins, prostacyclin, and thromboxane A2. The clinical effects of NSAIDs depend largely on their selectivity for these enzymes. Aspirin works by irreversibly inhibiting COX-1 mediated synthesis of thromboxane A2, and is used to inhibit platelet aggregation



Table 1⇓ shows the indications and effectiveness of the various NSAIDs. There is little difference in their mean efficacy, although a review of individual patient data indicates that patients vary in …
A career forged in iron
Authors: Lawrie W. Powell
Journal: Hepatology (2014)

1The Center for the Advancement of Clinical Research, Royal Brisbane and Women's Hospital, and The University of Queensland Center for Clinical ResearchBrisbaneQueenslandAustralia *Address reprint requests to: Lawrie W. Powell, M.D., Ph.D., Center for the Advancement of Clinical Research, Level 4, UQCCR Building, Royal Brisbane and Women's Hospital, Herston Campus, Brisbane, QLD 4029, Australia. E‐mail: [email protected]; fax: +617 36462355.
Does measuring pre or post bronchodilator FEV1 influence the level of asthma control in patients with controlled or partially controlled asthma as measured by GINA scale
Authors: Marcelino Vieira, Marcia Pizzichini, Cristiane Rocha, Emilio Pizzichini
Journal: European Respiratory Journal (2013)

Background: GINA guidelines indicate that patients with controlled asthma (CA) must have a FEV1 ≥ 80% and the “FEV1 to be used is without bronchodilator (BD) on treatment”. Because of this cut point, minor changes in FEV1 may alter asthma control (AC) from CA to partially controlled asthma (PCA) and vice versa.

Objective: To determine if establishing AC according to GINA using pre or post BD FEV1 withholding or not IC+LABA alters AC level in patients with CA or PCA.

Methods: We enrolled 51 asthmatics [CA (n=22), PCA (n=29)]. All were stable on treatment for at least three months. Spirometry was performed withholding or not IC+LABA for 12 hours.

Results: The mean (SD) pre BD FEV1 on IC+LABA differed from post BD FEV1 expressed in liters [2.9 (0.9)L vs. 3.0 (0.9)L, p <0.001] or in % from predicted [84.5 (14.7)% vs. 86.9 (14.3)%, p<0.001]. When off IC+LABA the pre BD FEV1 also differ from the post BD FEV1 expressed in liters [2.7 (0.9)L vs. 2.9 (1.0)L] or % predicted [80.2 (15.7)% vs. 84.5 (15.3)]. Using pre or post BD FEV1 on IC+LABA did not influence AC level. However, measuring the pre-BD FEV1 withholding IC+LABA changed AC level in 5(22%) subjects with CA and in 4(13.8%) with PCA while the post BD FEV1 changed AC only in 3 (13.6%) patients with CA.

Conclusion: Both pre or post BD FEV1 on IC+LABA treatment can be used to establish AC. Despite the small changes, the pre BD FEV1 whitholding IC+LABA altered AC in one of each five patients with CA. These results provide an opportunity to investigate benefits of withholding IC+LABA to establish control in these patients.
Geinofote: Safety and Activity Analysis of the Use of Fotemustine (Ft) in Different Schedules in Progressive Glioblastoma (Gb) in Spain
Authors: P. Perez Segura, R.A. Manneh, I. Ceballos, A. Garcia Castaño, M. Benavides, J. Fuster, J.M. Cano, M.A. Vaz, J.P. Berros, M. Covela, V. Moreno, T. Quintanar, J.M. Garcia-Bueno, I. Fernández Perez, O. Gallego, P. Ramirez Daffós, J. Espinos Jimenez, S. Gonzalez, S. Del Barco, S. Ros
Journal: Annals of Oncology (2014)
Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis
Authors: Mikael Rydén, Mehmet Uzunel, Joanna L. Hård, Erik Borgström, Jeff E. Mold, Erik Arner, Niklas Mejhert, Daniel P. Andersson, Yvonne Widlund, Moustapha Hassan, Christina V. Jones, Kirsty L. Spalding, Britt-Marie Svahn, Afshin Ahmadian, Jonas Frisén, Samuel Bernard, Jonas Mattsson, Peter Arner
Journal: Cell Metabolism (2015)
Placebos and placebo effects in medicine: historical overview
Authors: Anton J M De Craen, Ted J Kaptchuk, Jan G P Tijssen, J Kleijnen
Journal: Journal of the Royal Society of Medicine (1999)

some experimental intervention. Although the most frequently used placebo is the 'sugar pill' in drug trials, placebos can be and have been used for all kinds of interventions, ranging from placebo ultrasound in the treatment of pressure ulcers and placebo surgery in the treatment of osteoarthritis to sham traction in the treatment of low back pain and placebo oestrogen implants in the prevention of menopause symptoms.
Alternative surgical treatment for tuberculous cavern grafted by micosis
Authors: Ovidiu Burlacu, Calin Tunea, Voicu Voiculescu, Gabriel Cozma, Ioan Petrache, Alexandru Nicodin
Journal: European Respiratory Journal (2013)

INTRODUCTION  The surgical treatment of tuberculous caverns populated by mycosis is dominated by lung resections, be they anatomical or wedge resections. There are some patients who have co-morbidities or limited functional respiratory status that make these types of surgery impossible. Our aim is to present an alternative surgical procedure to treat this patient category.  MATERIAL AND METHODS  An alternative for surgical treatment with a lower impact for the patient is to fill the cavern with a vascular axis pedicle muscle flap. We took into account patients with ASA risk class higher than 3, with FEV and FVC lower than 40%. We applied this treatment to 7 patients that met the criteria for the patient lot.  RESULTS  For the 7 patients, after thoracotomy, cavernotomy, excision of the micetoma, the suture of the bronchial fistulae, we used to fill the cavities the following muscles: pectoris major – 2 cases, intercostal muscle – 4 cases and latissimus dorsi – 1 case. The immediate outcome was favorable in all cases except one for whom we had to re-operate for bleeding. In all cases the viability of the transposed muscle was not affected.  CONCLUSIONS  The aim of the surgical treatment is to evacuate the micetoma, but wedge or anatomical resections for these cases have major complications. We can consider various techniques for thoracoplasty but the scale of the intervention and the duration make us reluctant. Our experience is limited by the number of cases, but in these critical cases the usage of muscle flaps gave us satisfaction.
Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL
Authors: M. Federico, A. Frassoldati, T. Lamparelli, R. Foà, M. Brugiatelli, L. Annino, L. Baldini, G. Capnist, T. Chisesi, P.F. di Celle, R. Invernizzi, F. Lauria, M. Truini, L. Resegotti, V. Silingardi, E.E. Damasio
Journal: Annals of Oncology (1994)