tbuckley/cabot-search huggingface dataset:
Bone marrow autotransplantation for solid tumors--prospects.
Authors: E Frei, K Antman, B Teicher, P Eder, L Schnipper
Journal: Journal of Clinical Oncology (1989)

Autologous bone marrow transplantation (AuBMT) is in clinical trial for patients with metastatic solid tumors, particularly breast cancer. This review deals with the potential of this approach. AuBMT is curative for the leukemias and lymphomas. Curative cancer chemotherapy has, almost without exception, required combinations of agents wherein dose was well maintained. However, curative chemotherapy strategies for the hematologic neoplasms have not proven successful for the common solid tumors. An important exception is that standard adjuvant chemotherapy can "cure" some micrometastatic tumors. Preclinical studies indicate the effectiveness of alkylating agents in terms of maintained dose effect through multiple logs of tumor cell kill; difficulty in developing drug resistance; general lack of cross resistance; and synergy for alkylating agents used in combination. There is an increasingly effective experimental basis for the construct of intensification regimens employing combinations of alkylating agents. Differing nonmyelosuppressive toxicity for alkylating agents provides a basis for maintaining dose when employed in combination in the autologous marrow situation. The aforementioned studies and cytokinetic analyses of combined intensive alkylating agent therapy for breast cancer support the potential of this approach. Clinical trials indicate a high response rate in refractory breast cancer. Trials involving induction chemotherapy followed by combined alkylating agent intensification have produced substantial complete remission rates. The duration of response has, in most studies, been short. This approach is associated with major toxicity, including mortality, and is expensive. Experimental and preliminary clinical evidence as marshalled in this review indicate that this is a promising area for therapeutic research.
Abstract 11216: Reproducibility and Interobserver Agreement of Global Longitudinal Strain between Novice and Expert during Dobutamine Stress Echocardiography
Authors: Daniel Sathianathan, Akira Yamada, Natalie Kelly, Wei-Lynn Chong, Darryl Burstow, Jonathan Chan
Journal: Circulation (2011)

Background: Wall motion analysis (WMA) during dobutamine stress echocardiography (DSE) is subjective and requires expert training. Global longitudinal strain (GLS) has been shown to have incrementa...
Measuring quality of dermatology care from the patient's perspective: how was it for you?
Authors: A.Y. Finlay
Journal: British Journal of Dermatology (2015)

Unless you ask, you don't find out. It is important to know patients' opinions of their experience using dermatology services. Feedback may be uncomfortable, especially if it is not complimentary to you (or, worse, to me), but absolutely necessary. van Cranenburgh et al.1 in this issue of the BJD should therefore be congratulated for focusing our thinking on this. The patient's experience is not only based on their encounter with the dermatologist. Accompanying a relative to outpatients recently, parking was difficult, in the waiting room we were subjected to a noisy, inane television programme (until I furtively switched it off, to general applause) and the status of the doctor we were to see was unclear. While waiting to have blood taken, we were crammed into an uncomfortably overcrowded waiting room, grimly checking our supermarket deli‐counter style numbered tickets. So the patient's frame of mind at the start of a consultation is already strongly influenced by a wide range of factors: it is clearly in the interests of all that that frame should be positive.
Postremission chemotherapy for adults with acute myelogenous leukemia: improved survival with high-dose cytarabine and daunorubicin consolidation treatment.
Authors: R Champlin, J Gajewski, S Nimer, S Vollset, E Landaw, D Winston, G Schiller, W Ho
Journal: Journal of Clinical Oncology (1990)

Results of postremission chemotherapy for adults with acute myelogenous leukemia (AML) were assessed in two sequential prospective studies involving similar induction therapy and two courses of intensive consolidation treatment. Fifty-six patients achieving remission on the acute leukemia protocol (ALP3) study received high-dose cytarabine and daunorubicin as course one and standard-dose cytarabine and daunorubicin as course two. Results are compared with forty-six patients achieving remission on the ALP2 study who received azacitidine and doxorubicin as consolidation course one and standard-dose cytarabine, daunorubicin, and thioguanine as course two. The ALP3 regimen resulted in a significantly improved 5-year disease-free survival of 32% +/- 19% versus 20% +/- 11% for the ALP2 study (P = .03). Survival from remission was also improved, 40% +/- 14% versus 24% +/- 12% (P less than .01). Favorable prognostic factors for disease-free survival included receiving the ALP3 treatment regimen, absence of a prior preleukemic syndrome, and female sex. These factors and younger patient age were significant for survival following first chemotherapy and survival after achieving remission. Six of 34 patients who relapsed after receiving the ALP3 regimen successfully achieved prolonged second remissions with high-dose cytarabine-based chemotherapy and/or allogeneic bone marrow transplantation (BMT). Overall survival for adults less than or equal to 45 years of age was 58% +/- 19% with the ALP3 postremission chemotherapy regimen, comparable to most studies of BMT for AML in first remission. Actuarial 5-year survival for ALP3 patients greater than 60 years of age was 18% +/- 20% with no improvement compared with ALP2.
Operative Cholangiography — Techniques and Inadequacies
Authors: M E Foster, D R Foster
Journal: Journal of the Royal Society of Medicine (1984)

The effectiveness of three methods of operative cholangiography in outlining biliary anatomy was assessed in 60 patients undergoing routine cholecystectomy for gallbladder calculi. X-rays were scored according to bile duct visualization and an overall score calculated. There were no statistically significant differences between the three groups. However, ductal opacification was inadequate in a majority of patients. It is suggested that closer cooperation with the radiologist and more emphasis on technique are required if cholangiography is used to identify unsuspected calculi.
Combination of Oxaliplatin Plus Irinotecan in Patients With Gastrointestinal Tumors: Results of Two Independent Phase I Studies With Pharmacokinetics
Authors: Ernesto Wasserman, Caroline Cuvier, François Lokiec, François Goldwasser, Salima Kalla, Dominique Méry-Mignard, Mahmoud Ouldkaci, Amine Besmaine, Ghislaine Dupont-André, Mondher Mahjoubi, Michel Marty, Jean-Louis Misset, Esteban Cvitkovic
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Two phase I studies of the oxaliplatin and irinotecan combination were performed in advanced gastrointestinal cancer patients to characterize the safety and pharmacokinetics of the regimen. PATIENTS AND METHODS: Patients with a performance status (PS) of ≤2 and normal hematologic, hepatic, and renal functions received oxaliplatin (2-hour intravenous infusion) followed 1 hour later by irinotecan administered over a 30-minute period, every 3 weeks. Dose levels that were explored ranged from 85 to 110 mg/m 2 for oxaliplatin and 150 to 250 mg/m 2 for irinotecan. Plasma pharmacokinetics of total and ultrafiltrable platinum, irinotecan, SN-38, and its glucuronide, SN-38G, were determined. RESULTS: Thirty-nine patients with gastrointestinal carcinomas (24 with colorectal cancer [CRC], four with pancreas cancer, four with gastric cancer, three with hepatocarcinoma, and four with other) received 216 treatment cycles. Median age was 54 years (range, 21 to 72 years); 95% had PS of 0 to 1; all but six had failed fluorouracil (5-FU) chemotherapy. The maximum-tolerated dose was oxaliplatin 110 mg/m 2 plus irinotecan 200 mg/m 2 in one study and oxaliplatin 110 mg/m 2 plus irinotecan 250 mg/m 2 in the other study. Grade 3 to 4 diarrhea and febrile neutropenia were dose-limiting toxicities; other toxicities included emesis and dose-cumulative neuropathy. Recommended dose for phase II studies is oxaliplatin 85 mg/m 2 and irinotecan 200 mg/m 2 . At this dose (12 patients, 65 cycles), grade 3 and 4 toxicities per patient included the following: emesis in 42% of patients, neutropenia in 33% (febrile episodes in 17%), peripheral neuropathy in 25%, delayed diarrhea in 17%, and thrombocytopenia in 8%. Two patients with Gilbert's syndrome experienced severe irinotecan toxicity. No plasmatic pharmacokinetic interactions were detected. Seven partial responses were observed in 24 CRC patients. CONCLUSION: This combination is feasible, with activity in 5-FU–resistant CRC patients. Phase I studies that explore the every-2-weeks schedule, in addition to phase II studies of this schedule (as well as in combination with 5-FU) as second-line therapy of metastatic CRC, are ongoing.
Noninvasive Computed Tomography–based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial
Authors: Fabien Maldonado, Fenghai Duan, Sushravya M. Raghunath, Srinivasan Rajagopalan, Ronald A. Karwoski, Kavita Garg, Erin Greco, Hrudaya Nath, Richard A. Robb, Brian J. Bartholmai, Tobias Peikert
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification.Objectives: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes.Methods: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival.Measurements and Main Results: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases.Conclusions: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.
Diagnostic luciferase reporter phage assay for active and non-replicating persistors to detect tubercle bacilli from sputum samples
Authors: V.N.A. Dusthackeer, S. Balaji, N.S. Gomathi, N. Selvakumar, V. Kumar
Journal: Clinical Microbiology and Infection (2011)

<h2>Abstract</h2> Diagnosis of latent tuberculosis infection is a myth for want of a simple, direct tool. Simulation of hypoxic environment was done to create a novel hypothetical model for persistence using processed sputum samples. The adaptation of tubercle bacilli to hypoxic environment seems to be influenced by pre-existing clinical status of the patients at the time of sputum collection, resulting in varied growth pattern. Bacilli from 36 samples did not get adapted to latency of which 15 samples were from patients in whom the disease was well established and the tubercle bacilli in them probably did not experience any stress whatsoever. Similarly, 10 of the 37 samples showing the presence of cultivable cells in both aerobic and anaerobic conditions were from patients who had relapsed. The bacilli in these samples had been probably experiencing stress and thus were ready to adapt to the hypoxic environment. Diagnostic luciferase reporter phage assay for non-replicating persistors (DLRPA-NRP) identified 30 additional positives which failed to grow on Lowenstein–Jensen medium. Presence of viable bacilli in these samples was confirmed by reverse transcriptase-PCR (RT-PCR) for 16S rRNA indicating either the improved sensitivity of the assay to detect actively growing bacilli or its ability to detect non-replicating persistors. The utility of LRP assay to detect both dormant and active tubercle bacilli was explored in this work and was optimized using lysis inhibition to diagnose tuberculosis with rapidity, improved sensitivity and specificity. DLRPA-NRP, a rapid growth based assay is thus developed to detect both dormant and actively growing tubercle bacilli.
Abstract 3625: Do Patients Who Meet SCD-HeFT Criteria in Clinical Practice Differ from Patients Enrolled in SCD-HeFT?
Authors: Sana M Al-Khatib, Yongfei Wang, Kerry L Lee, Daniel B Mark, Jeanne E Poole, Gillian D Sanders, Eric Peterson, Jeptha Curtis, Gust H Bardy
Journal: Circulation (2007)

Background: Many studies have demonstrated the lack of generalizability of randomized clinical trials’ findings to clinical practice. We conducted this study to determine whether the baseline characteristics of patients meeting SCD-HeFT criteria in the ACC-NCDR ICD Registry are similar to those of patients enrolled in SCD-HeFT. Methods: Of the 1,438 US hospitals participating in the ICD Registry, 85% submit data on all ICD implants. We identified patients with NYHA class II or III symptoms and an LVEF ≤ 35%. We excluded patients with an MI within 40 days, CABG within 1 month, and PCI within 3 months prior to ICD implantation. We also excluded patients who received an ICD for secondary prevention or an ICD with cardiac resynchronization therapy. Baseline characteristics were compared using the t-test for continuous variables and the chi-square test for categorical variables. Results: Patients in the ICD Registry are significantly older and have more co-morbidities than patients enrolled in SCD-HeFT (Table ). The rates of use of ACE-inhibitors and digoxin were significantly lower in the Registry than in the trial (p &lt;0.01 for both). The rates of use of beta-blockers, aspirin and statins were significantly higher in the Registry than in the trial (p &lt;0.01 for all) Conclusions: The baseline characteristics and medical management of patients who receive an ICD in clinical practice are significantly different from those of patients enrolled in SCD-HeFT. Future studies should investigate whether these differences translate into differences in ICD effectiveness.
GX15–070MS, a synthetic small molecule induces apoptosis in vitro and in vivo in chronic lymphocytic leukemia
Authors: J. E. Castro, C. E. Prada, S. Kitada, D. Contreras, J. Viallet, J. C. Reed, T. J. Kipps
Journal: Journal of Clinical Oncology (2005)

3167 Chronic lymphocytic leukemia (CLL) B cells express high levels of anti-apoptotic proteins of the Bcl-2 family, such as Mcl-1, Bcl-XL, and Bcl-2. These proteins enhance the resistance of CLL cells to spontaneous and/or drug-induced apoptosis primarily by interacting with, and antagonizing the activity of mitochondria membrane pro-apoptotic proteins such as Bax and Bik. These interactions are governed by the binding to anti-apoptotic proteins via the BH3 domains of Bcl-2-family-member proteins. GX15–070MS is a small-molecule antagonist of the BH3-binding groove of the Bcl-2 family of proteins that can inhibit the interactions of Bcl-2 with proapoptotic molecules. We examined the activity of GX15–070MS on CLL cells in vitro and in vivo in a phase I/II clinical study initiated at our institution for patients with intermediate-risk or high-risk disease refractory to alkylating drugs, fludarabine-based regimens, and, in some cases also Alemtuzumab. Patients were treated with the initial escalating doses of 3.5 and 7 mg/m2. Administration of GX15–070 has been well tolerated and patients have not experienced any Grade 3 or Grade 4 toxicity. We have evaluated in vitro and in vivo the pro-apoptotic activity of GX15–070MS. GX15–070MS induced apoptosis in CLL-B cells in a time and dose-dependent manner with an IC50=10nM at 48 hours in culture. GX15–070MS induced apoptosis in CLL B cells independent of IgVH gene mutational status or ZAP-70 expression. In addition, we have analyzed the effect of this compound based on co-immunoprecipitations and Bcl-2/Mcl-1 mitochondrial displacement assays using video-confocal microscopy. These results indicate that GX15–070MS has activity inhibiting Bcl-2 family member proteins and inducing apoptosis in CLL B cells both in vitro and in vivo at dose ranges that are substantially below those estimated to induce toxicity in preclinical animal models. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gemin X
Science funding may be protected in next spending review, minister says:
Authors: Adrian O’Dowd
Journal: BMJ (2015)

Government funding of science could continue to be protected in the next spending review as part of ministers’ determination to make science central to the United Kingdom’s economic recovery, MPs have heard.

The four national academies, however, have raised concerns about UK spending on science and research, which they said was “falling behind” that of other comparable countries. During an evidence session of the House of Commons Science and Technology Committee on 15 July, Jo Johnson, minister for universities and science, told MPs, “We want to make science and research front and centre to our plan to lift the productivity of the British economy.”

As part of the first evidence session for their new …
Does pseudo-ROSE enhance the diagnostic utility for conventional TBNA?
Authors: Andrew Medford, Anilkumar Pillai
Journal: European Respiratory Journal (2012)

Background: Conventional transbronchial needle aspiration (TBNA) is a useful mediastinal diagnostic and staging technique1. It is more accessible and cheaper than endobronchial ultrasound. Some centres use ROSE (rapid on-site evaluation for cytology with a cytopathologist) to improve results but limited by cost and resources. There are less published studies on pseudo-ROSE (a cytotechnician assesses sample adequacy alone).  Hypothesis: Pseudo-ROSE improves diagnostic utility of TBNA.  Methods: 22 consecutive patients underwent pseudo-ROSE-TBNA for investigation of suspected lung cancer (with N2 or N3 disease on CT) in a UK teaching hospital by previously described methods1. Diagnostic utility to detect mediastinal metastases was calculated via contingency table analysis (GraphPad Prism 5).  Results: Pseudo-ROSE-TBNA resulted in 13 true positive cases (59% of cohort) of malignancy (5 small cell, 8 non-small cell) with 7 true negative cases and 2 presumed false negative cases (10mm nodes in stations 10R and 3 on CT but not confirmed). 87% sensitivity, (compared to 78% in a UK non-ROSE study1) 78% negative predictive value, 68% cancer prevalence and 91% accuracy. Pseudo-ROSE-TBNA detected granulomatous disease due to sarcoidosis in 3 of the 7 true negative cases.  Conclusion: Pseudo-ROSE improves the diagnostic utility of conventional TBNA for lymph node metastases in high prevalence cohorts with malignancy. In the absence of endobronchial ultrasound or conventional ROSE, pseudo-ROSE should be used as an effective and inexpensive adjunct to conventional TBNA.  References  1. Medford AR et al. A prospective study of conventional transbronchial needle aspiration: performance and cost utility. Respiration 2010;79(6):482-9.
Mycobacterium avium complex develop resistance to synergistically active drug combinations during infection
Authors: SE Hoffner, N Heurlin, B Petrini, SB Svenson, G Kallenius
Journal: European Respiratory Journal (1994)

Isolates of Mycobacterium avium complex from five patients on longterm (3-5 yrs) anti-mycobacterial drug treatment were collected during the early and late phase of disease, and studied in vitro for their susceptibility to anti-mycobacterial drugs and drug-combinations. All isolates were resistant or moderately resistant to ethambutol, rifampicin and streptomycin when given singly; however, all strains isolated early in the disease were susceptible to the combination of ethambutol with either rifampicin or streptomycin. All late isolates had developed resistance to one or both of these combinations. Three of the patients died within a year after the last isolation of M. avium complex, and the two remaining patients still have severe chronic disease. It is concluded that the susceptibility of M. avium strains to combinations of drugs should be monitored during the course of treatment, in order to guide the selection of effective drug-combinations throughout the infection.
An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas.
Authors: K Antman, J Crowley, S P Balcerzak, S E Rivkin, G R Weiss, A Elias, R B Natale, R M Cooper, B Barlogie, D L Trump
Journal: Journal of Clinical Oncology (1993)

PURPOSE AND METHODS Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin. RESULTS Between 1987 and 1989, 340 eligible patients were randomized. Significantly more myelosuppression, a higher response rate (17% v 32%; P &lt; .002) and longer time to progression (4 v 6 months; P &lt; .02) were observed for patients who received ifosfamide. An overall survival advantage for the two-drug regimen (12 v 13 months; P = .04) was not significant by multivariate analysis. CONCLUSION In all three randomized trials of doxorubicin with and without ifosfamide (Eastern Cooperative Oncology Group [ECOG], European Organization for Research and Treatment of Cancer [EORTC], and this study), the response rate was higher for the ifosfamide-containing arm, significantly so in this and the ECOG studies. An improved response rate may be particularly important for the preoperative management of high-grade, borderline resectable lesions or pulmonary metastases, particularly in younger patients. In older patients, or for low-to intermediate-grade lesions, doxorubicin and DTIC followed by ifosfamide on progression is preferred.
Black grain mycetoma.
Authors: G.H. FINDLAY, H.F. VISMER
Journal: British Journal of Dermatology (1977)

The tissue grain of Madurella mycetomi infection shows a spread of mineral constituents which is somewhat higher than the known values for the dermis, but differs little in relative concentrations. The unique physical resistance of the grain cannot be related to departures in concentration of calcium or of trace elements. Our earlier hypothesis of a tanned protein structure for the grain therefore still holds (Findlay & Vismer, 1974).