tbuckley/cabot-search huggingface dataset:
Selective Internal Radiation Therapy (SIRT) plus systemic chemotherapy with Irinotecan. A phase I dose escalation study
Authors: D. Goldstein, G. van Hazel, N. Pavlakis, I. Olver
Journal: Journal of Clinical Oncology (2005)

3701 Background: Irinotecan is an active chemotherapeutic agent in first line and refractory colorectal cancer and has shown an additive effect when used with radiation. SIRT involves hepatic artery injection of SIR-Spheres (Sirtex Medical Limited, Sydney, Australia) and has been shown to increase response rates to both hepatic artery and systemic 5-Fluourouracil. The goals of this study are to evaluate the maximum tolerated dose (MTD) and safety profile of Irinotecan given in combination with SIRT in patients with liver dominant metastatic colorectal cancer. Secondary endpoints include standard efficacy parameters. Methods: 25 patients who had failed previous chemotherapy but were Irinotecan naïve have been entered into the study. Irinotecan was given weekly twice every 3 weeks starting the day before SIRT for a maximum of 9 cycles. Irinotecan dose was escalated from 50 to 100 mg/m2 to assess safety, tolerability and identify a MTD. If no grade 3/4 toxicity was experienced after 2 cycles patients could escalate to 75 and then 100 mg/m2. Results: Early stage acute and self-limiting nausea, vomiting and liver pain were experienced by most patients. Mild lethargy and anorexia was also common. Grade 3/4 toxic events were seen in 4/6 pts at 50 mg/m2 (jaundice 1, ascites 1, thrombocytopenia 1, elevated ALP 1), 4/13 at 75 mg/m2 (ascites 1, thrombocytopenia 1 abdominal pain 1 and fatigue 1) and 2/6 so far at 100 mg/m2 (DVT 1, abdominal pain 1). Partial responses were seen in 9/17 pts, median time to liver progression was 7.5 months and median survival was 12 months. Conclusions: The use of SIRT in combination with Irinotecan is, to date, associated with acceptable toxicity. MTD remains to be identified but recommended dose will probably be 100 mg/m2. Protocol chemotherapy is concluding and first line trials with Irinotecan and 5-fluorouracil/folinic acid combinations are also underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sirtex Medical
Long-term survivorship in patients with metastatic renal cell cancer (mRCC) managed with metastasectomy: A retrospective study from the MD Anderson Cancer Center (MDACC).
Authors: Amishi Yogesh Shah, Matthew T. Campbell, Kirtan Das Nautiyal, Neda Hashemi, Surena F. Matin, Ara A. Vaporciyan, Laurence D Rhines, Bryan Moon, Valerae O. Lewis, Patrick P. Lin, Sujit S. Prabhu, Ganesh Rao, Paul Gettys Corn, Lance C. Pagliaro, Reza J. Mehran, Christopher G. Wood, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2015)

504 Background: Overall survival (OS) in mRCC has improved with targeted therapy; however, metastasectomy is still an important tool in select patients. This study evaluated outcomes of patients managed with metastasectomy ± systemic therapies. Methods: After IRB approval, we retrospectively reviewed records of mRCC patients who were treated at MDACC between 1/1/2001 and 12/31/2008 and report on those who survived &gt;4 years with metastatic disease. OS was calculated from diagnosis of metastatic disease to death or last follow-up. Descriptive statistics were used. Results: 168 long-term survivors were identified; 101 patients were treated with metastasectomy at some point (total 205 resections). 42 patients had single metastasectomy; 59 had multiple resections (most common in lung and bone). 12 patients underwent serial metastasectomy alone (no systemic therapy), and 8 remain alive (range 4.6-12.9 years from met diagnosis). Conclusions: Patients with mRCC selected for metastasectomy had a significantly longer OS than those who received systemic therapies only. Whether this reflects tumor biology, therapeutic effect, or selection bias is unknown in this retrospective study. However, the prolonged survival in this group supports continued use of metastasectomy in carefully selected patients. [Table: see text] [Table: see text] [Table: see text]
Space Medical Research
Authors: Hubertus Strughold, Otis O. Benson
Journal: New England Journal of Medicine (1959)

SPACE medicine, today, can look back upon a ten-year history. It came officially into being in February, 1949, with the foundation of a special department of space medicine at the School of Aviation Medicine, Randolph Air Force Base, Texas, by its commandant, Major General Harry G. Armstrong. At about the same time preparations for animal experiments in rockets were started at the Aero Medical Laboratory, Wright–Patterson Air Force Base, Dayton, Ohio. Facilities available for these grand-scale experiments, at Holloman Air Force Base, New Mexico, later became an independent institution under the name of Aero Medical Field Laboratory.At that time . . .
Antibiotics and<i>Clostridium difficile</i>
Authors: Sherwood L. Gorbach
Journal: New England Journal of Medicine (1999)

It is hard to remember a time in the past decades when Clostridium difficile was not a scourge in our hospitals. As a house officer in the early 1960s, I recall seeing only one patient with hospital-acquired colitis, which we called staphylococcal colitis. On the basis of what in retrospect was probably a false diagnosis, we treated the infection successfully with bacitracin, which fortuitously is active against C. difficile. Recognition of the current disease began in the early 1970s with a few isolated reports of a severe, and even lethal, colitis characterized by the formation of pseudomembranous plaques. Because of . . .
Factors related to tardive dyskinesia
Authors: G Chouinard, L Annable, A Ross-Chouinard, J N Nestoros
Journal: American Journal of Psychiatry (1979)

The authors found a 31% incidence of tardive dyskinesia among 261 schizophrenic outpatients treated with neuroleptics. Multiple linear logistic regression analysis revealed a higher incidence of tardive dyskinesia among elderly patients, those with longer records of hospitalization, those for whom neuroleptic medication had little therapeutic effect, and those treated with fluphenazine. Patients manifesting tardive dyskinesia tended to have fewer parkinsonian symptoms than those without the disorder, especially when tremors and akathisia were excluded from consideration. Multiple linear regression analysis indicated that brain-damaged patients and male patients were more susceptible to severe forms of the disorder, even though these factors were not implicated in its initial appearance.
The Contributions of George Richards Minot to Experimental Medicine
Authors: William B. Castle
Journal: New England Journal of Medicine (1952)

BY ESTABLISHING the George Richards Minot Memorial Lectures, the Section on Experimental Medicine and Therapeutics of the American Medical Association has chosen to commemorate the achievements of a physician whose discovery of a successful treatment for pernicious anemia has resulted in the preservation of thousands of lives. Moreover, Dr. George R. Minot's work stands as a landmark in the notable progress in clinical research of the past thirty years. Indeed, it may properly be described as being a major factor in changing the clinical study of blood dyscrasias from a largely passive and descriptive to an active and critically experimental . . .
P0840 : Safety and effectiveness of sofosbuvir-based regimens for the treatment of hepatitis C genotype 3 and 4 infections: Interim analysis of a prospective, observational study
Authors: S. Alqahtani, S. Zeuzem, M. Manns, A. Kuo, A.M. Di Bisceglie, R. Reddy, M. Mailliard, J. O’Leary, P. Pockros, P.Y. Kwo, J.K. Lim, H.E. Vargas, M.W. Fried, D. Nelson, M.S. Sulkowski
Journal: Journal of Hepatology (2015)
Antibody to Cardiolipin as a Predictor of Fetal Distress or Death in Pregnant Patients with Systemic Lupus Erythematosus
Authors: Michael D. Lockshin, Maurice L. Druzin, Stephanie Goei, Tasneem Qamar, Margret S. Magid, Lois Jovanovic, Michael Ferenc
Journal: New England Journal of Medicine (1985)

During a prospective study of pregnancies in women with systemic lupus erythematosus, we examined the relation between antibody to cardiolipin, measured by the enzyme-linked immunosorbent assay, and midpregnancy fetal distress, identified by abnormal results of antepartum fetal heart-rate testing or by fetal death. All of nine patients with lupus and this complication had abnormally high antibody levels (mean, 212.3 +/- 55.3 units), as compared with values in normal nonpregnant women (28.2 +/- 10.1 units). None of 12 pregnant patients with lupus but without this complication had antibody levels above 50 units (mean, 27.5 +/- 3.4 units; P less than 0.005 vs. women with lupus and fetal distress); 4 of 12 pregnant subjects without lupus had antibody levels above 50 units (mean, 42.5 +/- 11.0), and fetal death occurred in the subject with the highest level. The mean antibody level in 12 nonpregnant patients with lupus was 117.4 +/- 35.0 units. Two patients who had lupus anticoagulant but not clinical lupus, both with histories of prior fetal death, also had high antibody levels; fetal death occurred in one, and spontaneous fetal bradycardia in the other. Antibody to cardiolipin was loosely linked to a history, but not the simultaneous presence, of demonstrable lupus anticoagulant or thrombocytopenia, and could be detected as early in pregnancy as either anticoagulant or thrombocytopenia. We conclude that measurement of antibody to cardiolipin is the most sensitive assay to predict fetal distress or death in patients with systemic lupus erythematosus and may be of pathogenetic importance in this syndrome.
Arteriography in the Management of Hemorrhage from Pelvic Fractures
Authors: Michael N. Margolies, Ernest J. Ring, Arthur C. Waltman, Walter S. Kerr, Stanley Baum
Journal: New England Journal of Medicine (1972)

Localization of the source of massive hemorrhage from pelvic fractures is not often made clinically, and the results of expectant management or of hypogastric artery ligation are frequently unsatisfactory. Three patients with pelvic fractures and rapid blood loss were examined by transfemoral aortography. In all of them, bleeding originated from obturator artery branches In the vicinity of fractures involving the pubic rami. In two of these patients, hemorrhage was controlled by selective catheterization of the anterior division of the hypogastric artery, followed by injection of autologous clotted blood. Arterial bleeding from pelvic fractures may be more common than has previously been supposed. Arteriographic localization of the bleeding site should improve selection of patients for surgical exploration, when the described method of hemostasis fails.
P9 Nintedanib for the treatment of Idiopathic Pulmonary Fibrosis – initial clinical experience in a UK cohort
Authors: SV Fletcher, MG Jones, E Renzoni, H Parfrey, R Hoyles, K Spinks, M Kokosi, A Kwok, C Warburton, V Titmuss, T Maher, F Chua, A Wells, L Richeldi, LG Spencer
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Nintedanib (OFEV®) is the second drug licensed for the treatment of Idiopathic Pulmonary Fibrosis (IPF). Evidence from the INPULSIS study demonstrated that it reduced annual FVC decline by approximately 50%. Nintedanib has been available in the UK from October 2014 through the Individual Patient Supply Programme (IPSP); initially for those with FVC &gt;50% predicted, latterly available for all with a diagnosis of IPF regardless of FVC. We present preliminary findings of clinical experience with nintedanib in routine UK clinical practice. <h3>Methods</h3> A multi-centre, cohort review was undertaken across 6 NHS Trusts. Data were collected from clinical records of individuals receiving nintedanib for the treatment of IPF from October 2014 to July 2015. <h3>Results</h3> 210 patients (161 male) had consented to nintedanib IPSP by July 2015. Mean age (±S. D.) at diagnosis was 70.0 ± 7.7 years. Reasons for starting nintedanib included ineligibility for pirfenidone (FVC &gt;80% predicted: 67 (31.9%) and FVC &lt;50% predicted: 12 (5.7%)), intolerance to pirfenidone 63 (30%), patient preference 54 (25.7%), and clinical progression on pirfenidone 8 (3.8%). Pre-treatment lung function was FVC 72.2 ± 19.0% and DL<sub>CO</sub> 40.1 ± 17.2% predicted (Domiciliary oxygen was administered to 66 (31.4%) of the cohort. Mean duration of treatment was 2.4 months (range 0 – 8 months) and 78 patients had completed 3-month follow up. Of these 14/78 patients (17.9%) had discontinued nintedanib due to diarrhoea (5 patients), other GI side effects (3), death/lung transplant (2/1), miscellaneous reasons (3). The commonest potential adverse drug reaction (ADR) was diarrhoea occurring in 21/78 (26.9%), which required a dose reduction in 11 patients. Other common ADRs included nausea 11/78 (14.1%), abdominal pain 11/78 (14.1%), decreased appetite 7/78 (9.0%), and weight loss 5/78 (6.4%). <h3>Conclusions</h3> These data demonstrate that at 3 months follow up, Nintedanib is generally well tolerated when used in routine UK practice in patients with IPF across a wide range of FVC’s. The incidence of diarrhoea at 3 months is much lower than the 12 month reported rate in the INPULSIS study. Ongoing longitudinal follow up of this cohort will further inform our understanding of the use of nintedanib for the treatment of IPF.
S19 Interventions for the management of malignant pleural effusions
Authors: AO Clive, HE Jones, R Bhatnagar, NJ Preston, NA Maskell
Journal: Thorax (2015)

<h3>Aims</h3> Malignant pleural effusion (MPE) is a common clinical problem and a number of treatment options are available to manage these patients. We undertook a systematic review of the literature and meta-analysis in order to ascertain the optimal management strategy for adults with symptomatic MPE. <h3>Methods</h3> We searched CENTRAL, MEDLINE, EMBASE, CINAHL; SCI-EXPANDED and SSCI (ISI Web of Science) databases to May 2015. We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE. Two review authors independently extracted the data and assessed the studies’ risk of bias. The primary outcome measure was pleurodesis failure rate. Secondary outcome measures were adverse effects and complications, patient reported control of breathlessness, quality of life, cost, mortality, duration of inpatient stay and patient acceptability. We performed network meta-analysis with random effects to analyse the primary outcome data and those secondary outcomes with enough data. If this was not possible, we reported the results by narrative synthesis. <h3>Results</h3> Of the 1888 records identified, 62 randomised trials, including a total of 3428 patients, were eligible for inclusion. All studies were at high risk of bias for at least one domain and the majority were unblinded. Network meta-analysis evaluating the rate of pleurodesis failure suggested Talc Poudrage to be the most effective method (estimated rank 1 [95% CI 1, 4]). The estimated ranks of the other evaluated methods are shown in the Figure. The estimates were imprecise as evidenced by the wide credible intervals. Both statistical and clinical heterogeneity was high. The secondary outcomes were inconsistently reported. Network meta-analysis was only performed for pain, fever and mortality and minimal evidence was obtained suggesting differences between treatments for these outcomes. Indwelling pleural catheters were examined in two RCTs, both reporting improved breathlessness when compared to Talc Slurry pleurodesis, despite lower pleurodesis success rates. <h3>Conclusions</h3> Based on the available evidence, Talc Poudrage may be the optimal method for obtaining a pleurodesis in MPE. However, there is minimal evidence to suggest large differences between the next most effective methods. Global experience of these agents and their adverse events must also be considered when selecting a sclerosant.
Parallel <i>In Vivo</i> Assessment of Drug Phenotypes at Various Time Points during Systemic BRAF Inhibition Reveals Tumor Adaptation and Altered Treatment Vulnerabilities
Authors: Oliver Jonas, Madeleine J. Oudin, Tatsiana Kosciuk, Matthew Whitman, Frank B. Gertler, Michael J. Cima, Keith T. Flaherty, Robert Langer
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Treatment of BRAF-mutated melanoma tumors with BRAF inhibitor–based therapy produces high response rates, but of limited duration in the vast majority of patients. Published investigations of resistance mechanisms suggest numerous examples of tumor adaptation and signal transduction bypass mechanisms, but without insight into biomarkers that would predict which mechanism will predominate. Monitoring phenotypic response of multiple adaptive mechanisms simultaneously within the same tumor as it adapts during treatment has been elusive. Experimental Design: This study reports on a method to provide a more complete understanding of adaptive tumor responses. We simultaneously measured in vivo antitumor activity of 12 classes of inhibitors, which are suspected of enabling adaptive escape mechanisms, at various time points during systemic BRAF inhibition. We used implantable microdevices to release multiple compounds into distinct regions of a tumor to measure the efficacy of each compound independently and repeated these measurements as tumors progressed on systemic BRAF treatment. Results: We observed varying phenotypic responses to specific inhibitors before, during, and after prolonged systemic treatment with BRAF inhibitors. Our results specifically identify PI3K, PDGFR, EGFR, and HDAC inhibitors as becoming significantly more efficacious during systemic BRAF inhibition. The sensitivity to other targeted inhibitors remained mostly unchanged, whereas local incremental sensitivity to PLX4720 declined sharply. Conclusions: These findings suggest redundancy of several resistance mechanisms and may help identify optimal constituents of more effective combination therapy in BRAF-mutant melanoma. They also represent a new paradigm for dynamic measurement of adaptive signaling mechanisms within the same tumor during therapy. Clin Cancer Res; 22(24); 6031–8. ©2016 AACR.
A phase I trial of RX-0201 (AKT anti-sense) in patients with an advanced cancer
Authors: J. Marshall, J. Posey, J. Hwang, S. Malik, R. Shen, K. Kazempour, L. R. White, K. M. Fraser, C. G. Chang, C. H. Ahn
Journal: Journal of Clinical Oncology (2007)

3564 Background: Akt-1, a proto-oncogene, plays a vital role in cancer progression by stimulating proliferation and inhibiting apoptosis of cancer cells. RX-0201, a 20-mer oligonucleotide with sequence complementary to Akt-1 mRNA, is designed to inhibit the expression of Akt-1 within cancer cells in cancer patients (pts). Non-clinical studies conducted on RX-0201 demonstrated that RX-0201 bears significant in vitro and in vivo anti-cancer activities with favorable safety. Purposes: The aims of the current phase I trial were to determine the maximum tolerated dose (MTD) and to establish pharmacokinetic (PK) and safety profiles of RX-0201 in pts with an advanced cancer. Methods: RX-0201 was administered to pts with an advanced cancer by up to 2 cycles of continuous infusion; each cycle of infusion lasted for 14 days which was followed by a 7-day rest. Rapid dose escalation had been used until at least a grade (G) 2 toxicity was observed, and then a traditional dose escalation followed. Entry criteria included Karnofsky Performance Status score =70, advanced cancer, tumor accessible for paired biopsy, and signed informed consent. 17 pts were enrolled and treated at a dose level ranging from 6 to 315 mg/m 2 /d on D1–14, repeated q 21 d. Results: G 3 fatigue was observed in two pts at the 315 mg/m 2 /d dose; three pts dosed at 250 mg/m 2 /d were not noted with any G 3 toxicity, which make this dose (250 mg/m 2 /d) the recommended phase II trial dose. No other significant, compound-related, adverse events were observed in those 17 pts participated. Pts PK profiles of RX-0201 and AKT-1 immunohistochemistry results on pts’ tumor biopsy samples will also be presented. Conclusion: MTD of RX-0201 is 315 mg/m 2 /d in pts with an advanced cancer when the compound is administered in the current continuous infusion regimen. No significant financial relationships to disclose.
Interviews should be structured or semistructured
Authors: M. Boohan, R. W Stout
Journal: BMJ (1996)

EDITOR,—Sandra Goldbeck-Wood refers to the fact that using A level results allows medical schools to attenuate “numbers sufficiently to make individual interviews practicable.”1 This suggests that the interview is an appropriate technique to augment other selection procedures. There are, however, numerous problems associated with using the interview as a selection tool. Most of these problems pertain to interviewer bias, which results in low validity and interrater reliability coefficients. The sources …
ATPS-64PRECLINICAL STUDIES USING NATIVIS VOYAGER RFE SYSTEM, A NOVEL NON-INVASIVE, LOW ENERGY, NON-THERMAL, NON-IONIZING RADIOFREQUENCY ENERGY (RFE) DEVICE IN GLIOBLASTOMA MOUSE MODELS
Authors: Rajesh Mukthavaram, Pengfei Jiang, Natsuko Nomura, Sandeep Pingle, John Butters, Bennett Butters, Santosh Kesari
Journal: Neuro-Oncology (2015)

BACKGROUND: Cancer treatment using radiofrequency energy (RFE) devices have been used in the past and have recently shown benefit in clinical trials of glioblastoma. Here we report a proof-of-concept application using the Nativis Voyager RFE System, which provides specific, low energy, non-invasive, non-thermal and non-ionizing oscillating electromagnetic signals. These signals inhibit in vitro glioblastoma tumor cell proliferation via an anti-mitotic effect. METHODS: We tested the ability of Voyager RFE System signals to inhibit tumor growth in both immunocompromised and immunocompetent mouse models. The immunocompetent model study, using white noise signal compared to control showed no difference in growth in the two groups. After establishing this, in the immunocompromised model, we implanted human U87 cells subcutaneously into 6-8 week old nude mice. In the immunocompetent model, we implanted mouse GL261 cells subcutaneously into 6-8 week old C57/BL6 mice. Voyager RFE signal was started ∼10-14 days after cells were implanted, when there were small, measurable tumors. There were two treatment groups (N = 10 tumors each group). The control group was housed in a separate room and was not treated with any RFE signal. The treatment group was treated with Voyager RFE signal 24 hours daily. Voyager RFE signal was applied using a rectangular 40mG coil placed under the cage. Tumors were measured ∼weekly. RESULTS: In the immunocompromised U87 model, tumor growth was significantly delayed in Voyager RFE signal group compared to control group (at day 39; p < 0.0001). Moreover, in the immunocompetent GL261 model, tumor growth was significantly delayed in Voyager RFE signal group compared to control group (at day 28; p < 0.0001). CONCLUSIONS: We show that Nativis Voyager RFE System signal delays glioblastoma tumor growth in SQ immunocompromised and immunocompetent mouse models.
Molecular Heterogeneity of C2 Deficiency
Authors: Charles A. Johnson, Peter Densen, Rick A. Wetsel, F. Sessions Cole, Nancy E. Goeken, Harvey R. Colten
Journal: New England Journal of Medicine (1992)

The most common of the complement deficiencies in populations of European origin is a genetic deficiency of the second component of complement (C2).1 Rheumatologic disorders such as systemic lupus ...