tbuckley/cabot-search huggingface dataset:
Phase I trial of oral topotecan (OT) and radiotherapy (XRT) in rectal cancer (RCA)
Authors: T. Yeatman, C. M. Rocha Lima, J. Barthel, D. Calvin, C. Garret, W. R. Dinwoodie, S. Mayfield, M. Wright, R. Lush, D. Sullivan
Journal: Journal of Clinical Oncology (2004)

3743 Background: OT and XRT are synergistic in the laboratory. Methods: To define the MTD, DLT, and PKs (blood samples at time 0 - immediately after taking OT - and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, and 8 hrs after). The amount and subcellular location of DNA topoisomerase (topo) I and IIα - by intensity of fluorescence using monoclonal and polyclonal antibodies and gene expression by oligonucleotide microarray, were studied in RCA biopsies before and during (after 2 weeks) OT and XRT. Eligible pts had locally advanced, M0, RCA staged by EUS, CT scan +/- PET scan, good PS, and good organ function. OT escalated in cohorts of 3 to 6 pts taken at least 3 hrs prior to 1.8 Gy/fraction XRT to a total of 45Gy (standard pelvic fields), Monday through Friday. All post OT + XRT patients had curative, rectal-sparing surgery. 5-FU-based chemotherapy in the adjuvant setting was offered off protocol. Results: 13 patients enrolled (table). The median age was 69 years (range 38–90). M:F=11:2. ECOG PS: 0 (70%), 1 (30%). Baseline Stage T3N0 (10 pts) and T3N1 (3pts). The prescribed XRT was completed in all patients. The grade III AST/ALT happened in patient with hx chronic hepatitis C. Prolonged grade III ANC with no other complication occurred in a 90 yo pt. 10 out of 13 pts were downstaged; pathologic complete response (PCR) (n = 3), microscopic disease (n = 1), Ca in-situ (n = 1), T1N0 (n = 1) and T2N0 (n = 4). One upstaged from T3N0 to T4N0. All 13 pts had sphyncter preservation. PKs. Topo I/IIα, and gene expression were obtained from all pts. Analysis for relationships to response data will be presented. Enrollment continues at the expanded cohort 3. Conclusion: This preoperative OT/XRT regimen has been well tolerated. Despite the phase I nature of this trial, OT and XRT have resulted in significant downstaging and attractive pathological response rates. A phase II study is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Glaxo Glaxo Glaxo Glaxo
Testicular lymphoma: late relapses and poor outcome despite doxorubicin-based therapy.
Authors: N Touroutoglou, M A Dimopoulos, A Younes, M Hess, W Pugh, J Cox, F Cabanillas, A H Sarris
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine the significance of the International Prognostic Index (IPI) score in adults with testicular lymphoma treated with doxorubicin-based regimens. PATIENTS AND METHODS Untreated adults with testicular lymphoma who presented between 1969 and 1993 were studied. Those with Ann Arbor stages III and IV were included if they had a testicular mass at presentation. RESULTS We identified 22 patients, 21 with intermediate-grade and one with high-grade lymphoma. All 10 patients with an IPI score &lt; or = 1 had Ann Arbor stage I disease, whereas the 12 with an IPI score more than 1 had Ann Arbor stage II to IV disease. Complete remission (CR) was achieved in 73% of patients. At 153 months, 22% of all complete responders and 40% and 0% of those with IPI scores &lt; or = 1 and more than 1, respectively, remained in CR (P = .01). With a median follow-up time of 113 months for survivors, the failure-free survival (FFS) rate at 153 months was 16% for all patients or 32% and 0% for those with IPI scores &lt; or = 1 and more than 1, respectively (P = .02). The CNS or contralateral testis were involved in all patients who failed to respond to primary therapy and in 50% of those who relapsed from CR. CONCLUSION The prognosis of patients with testicular lymphoma appears poor despite doxorubicin-based chemotherapy. On the basis of failures in the CNS and contralateral testis, we recommend prophylactic intrathecal chemotherapy and scrotal radiotherapy for all patients. Those with an IPI score &lt; or = 1 can be treated with conventional doxorubicin-based regimens, but those with an IPI score more than 1 should be considered for investigational systemic therapy.
The role of interferon-γ release assay (IGRA) testing in a UK teaching hospital
Authors: Martina Mason, Jennifer Dickens, Diana Aguilar, Gail Hardingham, Russell Phillips
Journal: European Respiratory Journal (2011)

Background: IGRAs including T-SPOT (T-SPOT.TB®) have recently been adopted for the diagnosis of latent (LTBI) infection with Mycobacterium tuberculosis (MTB). They may also have a role in ruling out active tuberculosis; however a recent meta-analysis has suggested that its specificity may not be high enough to exclude active disease [1].

Aims and objectives: The aim of this study was to retrospectively evaluate the use of the T-SPOT assay at a UK University Teaching Hospital to determine i) the indications for which it is being utilised and ii) whether its use led to any change in management.

Methods: Patients having T-SPOT performed between 09/2008 and 02/2010 were retrospectively identified from our TB database. Information regarding test indication, patient demographics and imaging results was collected from case notes and picture archiving and communications system (PACS). Change in patient management as a result of the T-SPOT was noted (as judged by two clinicians).

Results: 

View this table:



Forty-three (45%) of T-SPOT tests were performed to exclude LTBI and 53 (55%) to exclude active disease. The T-SPOT result led to a change in management in 42 (44%) of cases. To the best of our knowledge no patients with a negative T-SPOT result were subsequently diagnosed with active MTB infection.

Conclusion: In addition to excluding LTBI, T-SPOT can be a useful investigative tool in helping clarify the clinical picture in cases of suspected active TB.

Reference: 

*   1. M. Sester et al . Eur Respir J 2011;37:100-11
Treatment of patients with advanced colorectal carcinomas with fluorouracil alone, high-dose leucovorin plus fluorouracil, or sequential methotrexate, fluorouracil, and leucovorin: a randomized trial of the Northern California Oncology Group.
Authors: F H Valone, M A Friedman, P S Wittlinger, T Drakes, P D Eisenberg, M Malec, J F Hannigan, B W Brown
Journal: Journal of Clinical Oncology (1989)

We compared the effectiveness of fluorouracil (5-FU) alone (arm A), high-dose leucovorin plus 5-FU (arm B), and sequential methotrexate, 5-FU, and leucovorin (arm C) for treatment of patients with advanced colorectal carcinomas who had not received prior chemotherapy. Arm A consisted of infusions of 5-FU at 12 mg/kg/d intravenously (IV) for 5 days followed by weekly infusions of 5-FU at 15 mg/kg; arm B consisted of leucovorin infusions at 200 mg/m2/d IV plus infusions of 5-FU at 400 mg/m2/d IV on days 1 through 5 of a 28-day cycle; arm C consisted of methotrexate at 50 mg/m2 orally every 6 hours for five doses followed by infusions of 5-FU, 500 mg/m2 IV, and leucovorin, 10 mg/m2 orally, every 6 hours for five doses every other week. A total of 265 patients were entered into the trial, of whom 249 (94%) were fully evaluable. The objective response rate (complete [CR] plus partial [PR] responses) was 17.3% on arm A, 18.8% on arm B, and 19.8% on arm C (log-rank test, P greater than .4). The median time to failure was 138 days on arm A, 166 days on arm B, and 182 days on arm C (log-rank test, P values of arm A v B = .06; arm A v arm C = .04). Median survival was 345 days on arm A, 324 days on arm B, and 356 days on arm C (log-rank test, P greater than .4). Treatment with 5-FU alone was significantly more dose intensive and more toxic than either of the experimental combinations. The rates of grade 3 or greater nonhematologic toxicity were 42.3% on arm A, 24.3% on arm B, and 14.3% on arm C. Hematologic toxicity was milder but had the same pattern. This study indicates that these regimens of high-dose leucovorin plus 5-FU and sequential methotrexate, 5-FU, and leucovorin are not more effective than is 5-FU alone for treatment of patients with colorectal carcinomas when 5-FU is administered at high-dose intensity.
Nerve Growth Factor Expression Correlates With Perineural Invasion and Pain in Human Pancreatic Cancer
Authors: Zhaowen Zhu, Helmut Friess, Fabio F. diMola, Arthur Zimmermann, Hans U. Graber, Murray Korc, Markus W. Büchler
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The reasons for the high frequency of perineural invasion and the presence of pain in pancreatic cancer are still not clear. Nerve growth factor (NGF) and its high-affinity receptor TrkA are involved in stimulating epithelial cancer cell growth and perineural invasion, as well as in pain generation in chronic benign disorders. PATIENTS AND METHODS: NGF and TrkA were examined by Northern blot analysis, in situ hybridization, and immunohistochemistry in 27 normal and 37 pancreatic cancer tissue samples. The molecular findings were correlated with the degree of perineural invasion, pain, and histopathologic tumor characteristics. RESULTS: Northern blot analysis indicated that NGF and TrkA mRNA levels were increased 2.7-fold and 5.6-fold, respectively (P &lt; .05 and P &lt; .05), in pancreatic cancer tissues compared with the normal pancreas tissue. As shown by in situ hybridization and immunohistochemistry, NGF was strongly present in the cytoplasm of pancreatic cancer cells. TrkA was intensely present in the perineurium of pancreatic nerves but not in the cancer cells. There was no difference in NGF and TrkA expression between early (stages I and II) and advanced (stage III) tumor stages and between well-/moderately differentiated (grades 1 and 2) and poorly differentiated (grade 3) tumors. However, tumors with high NGF/TrkA expression levels exhibited more frequent perineural invasion (P &lt; .01). Furthermore, increased NGF/TrkA expression levels were associated with a higher degree of pain (P &lt; .01). CONCLUSION: Enhanced expression of the NGF/TrkA system may influence perineural invasion and may contribute to the pain syndrome in human pancreatic cancer.
Prevalence of antibiotic resistance of Helicobacter pylori isolates in Estonia during 1995–2000 in comparison to the consumption of antibiotics used in treatment regimens
Authors: K. Lõivukene, H.-I. Maaroos, H. Kolk, I. Kull, K. Labotkin, M. Mikelsaar
Journal: Clinical Microbiology and Infection (2002)
Abstract 2389: Clinical and Prognostic Value of Advanced Glycation End-products (AGEs) in Chronic Heart Failure
Authors: Jasper W Hartog, Adriaan A Voors, Casper G Schalkwijk, Jean Scheijen, Tom D Smilde, Kevin Damman, Stephan J Bakker, Andries J Smit, Dirk J van Veldhuisen
Journal: Circulation (2007)

tk;2 Introduction: Advanced glycation end-products (AGEs) have been proposed as a novel factor involved in the development and progression of chronic heart failure (CHF). Hypothesis: We assessed th...
Anticoagulation in venous Thrombosis
Authors: Sam Schulman
Journal: Journal of the Royal Society of Medicine (1996)

Major studies addressing various aspects of the treatment of deep vein thrombosis are reviewed. It has lately been demonstrated that heparin should be dosed according to body weight and is preferably given as subcutaneous injections twice daily. Alternatively, low-molecular-weight heparins may be given in a fixed dose once daily, which does not require monitoring. Oral anticoagulation should be started concomitantly with heparin and targeted at an international normalized ratio of 2.0-3.0. This treatment should continue for a longer duration than previously accepted, in many cases for 6 months. For patients with contraindications to oral anticoagulation, secondary prophylaxis with a low-molecular-weight heparin is also effective and safe.
Relationship and responsiveness of muscular function and functional tests in patients with COPD
Authors: Andre Nyberg, Britta Lindström, Anna Törnberg, Karin Wadell
Journal: European Respiratory Journal (2014)

Background:  The relationship between, and responsiveness of, performance in functional tests and muscular strength in patients with chronic obstructive pulmonary disease (COPD) has been established. However with regard to peripheral muscular endurance less is known.   Aim: To determine the relationship between and responsiveness of upper and lower limb muscular strength and endurance to functional tests in patients with COPD   Methods:  The study was a secondary analysis of a randomized controlled trial. Twenty-two patients with COPD (FEV 1  58.7% predicted), randomized to an 8-week resistance training regimen were included. The 6-minute walk test (6MWT), 6-minute pegboard and ring test, unsupported upper limb exercise test (UULEX), and isokinetic shoulder flexion and knee extension muscular strength and endurance were assessed. Spearman rank correlation (r) and standardized response means (SRM) were used.   Results:  Both knee strength (r=.53, p=.011) and knee endurance (r=.74, p   Conclusions:  These results indicate that muscular endurance may be more related to functional capacity than muscular strength in patients with COPD. Included tests ware demonstrated to be responsive to a resistance training regimen.
Who benefits most from non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease
Authors: David Miller, Kimberly Scott, Iain Murray, Gillian Thain, Graeme Currie
Journal: European Respiratory Journal (2012)

Introduction:  Non-invasive ventilation (NIV) has revolutionised the management of hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD). We wished to evaluate factors related to its overall success in the real-life setting.   Methods:  A retrospective analysis of patients receiving NIV for a hypercapnic exacerbation of COPD was performed. Demographics, laboratory data, blood gases and outcomes (hospital discharge or in-patient death) were extracted and subsequently analysed to identify factors relating to its overall success or failure.   Results:  Over 6 years, 240 patients (mean age 70 years), received NIV with mean pH and pCO2 prior to NIV 7.24 and 10.4kPa respectively; of these, 167 survived to hospital discharge with a median age (70 vs. 74; p=0.02) lower than non-survivors. Absolute values of pH and pCO2 (higher and lower respectively) prior to NIV and at 1 hour were both associated with successful hospital discharge. An improvement (p=0.02) in pH within an hour of receiving NIV - but not pCO2 - was associated with surviving to hospital discharge. Of all laboratory data assessed, only baseline urea was significantly (p=0.021) associated with a successful outcome.   Conclusion:  Younger patients with a lower urea, higher pH and lower pCO2 at baseline and who demonstrate an improvement in pH within 1 hour, are more likely to have a successful outcome when given NIV for a hypercapnic exacerbation of COPD on an unselected basis.
Comprehensive cytochrome P450 CYP1A2 gene analysis in French caucasian patients with familial and sporadic porphyria cutanea tarda
Authors: D. Tchernitchko, A.M. Robréau, T. Lefebvre, J. Lamoril, J.C. Deybach, H. Puy
Journal: British Journal of Dermatology (2011)

Porphyria cutanea tarda (PCT), the most frequent type of porphyria, results from decreased uroporphyrinogen decarboxylase (UROD) activity. Two forms of PCT have been described: a familial form (fPCT) characterized by the inherited decrease of UROD activity in all tissues and a sporadic form (sPCT) characterized by decreased UROD activity in the liver. Cytochrome P450 CYP1A2 plays a major role in triggering experimental uroporphyria in rodents. It has been suggested that the highly inducible -163A/A genotype of the CYP1A2 gene could confer a heightened risk of PCT in patients.To examine the impact of CYP1A2 polymorphisms on the clinical course of PCT.We performed an extensive CYP1A2 gene analysis in 96 (48 fPCT and 48 sPCT) unrelated French caucasian patients with PCT and in 99 healthy volunteers of similar ethnic origin. Results We did not observe any difference in CYP1A2 allele distribution, including a novel and rare CYP1A2 c.1063C>T (p.R355W) single nucleotide polymorphism. In addition, we compared the frequency of the -163A highly inducible allele both in patients with symptomatic fPCT (n = 48) and in asymptomatic UROD gene mutations carrier relatives (n=54). This variant was not over-represented in patients with PCT vs. either healthy volunteers or asymptomatic UROD gene mutation carriers.The CYP1A2 genotype does not appear to be a major susceptibility factor in the development of fPCT or sPCT in the French population.
Effect of flutamide on survival in patients with pancreatic cancer
Authors: S. Bramhall, J. Buckels, S. J Wigmore, K. C H Fearon, O J. Garden, H S Wasan, B. A Greenway
Journal: BMJ (1999)

Deprivation and emergency admissions for cancersOther possible explanations for findings need to be explored Editor-The reasons for Pollock and Vickers's findings about the relation between deprivation and emergency admissions for cancers remain speculative. 1To impute the differences in care to failures of primary care seems unfair at this stage.The authors discuss a range of possible explanations, but many other could also be relevant.Day case treatment may require a certain level of facilities at home that are less commonly available in deprived areas.The presence of another adult at home may also be a prerequisite.Single people may be more likely to live in deprived areas; patients from deprived areas may be more likely to have a working partner who cannot afford to take time off work or who has a job where such absences would be unacceptable.Patients with lung cancer due to smoking (more common in areas where smoking is more prevalent) may be less likely to have an operable malignancy because of concomitant disease related to smoking.The authors mention this in their discussion, but limiting the study to inpatient finished consultant episodes with a primary diagnosis of any of the three cancers of interest does not give any information about comorbidity.I hope further research will be carried out to help elucidate the reasons behind the apparently inequitable access and treatment decisions that Pollock and Vickers have found.Both qualitative and quantitative research methods could be used to study patients' and professionals' experiences as patients pass through the system.Perhaps allocation of blame should wait until such results are available.
A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer
Authors: N. Colombo, S. McMeekin, P. Schwartz, J. Kostka, C. Sessa, P. Gehrig, R. Holloway, P. Braly, D. Matei, M. Einstein
Journal: Journal of Clinical Oncology (2007)

5516 Background: There are few effective therapies for women with advanced or recurrent endometrial cancer. Targeted therapies such as AP23573, a novel mTOR inhibitor, may result in clinical benefit with fewer side effects. Preliminary results of a trial of single agent AP23573 in patients with progressive endometrial cancer who may have had up to 2 prior regimens of cytotoxic chemotherapy are reported. Methods: The trial is an open-label, Simon 2-stage, single-arm study enrolling patients who have advanced endometrial cancer with documented progression in the 3 months prior to entry. Patients receive 12.5mg AP23573 QDx5 as a 30-min. intravenous infusion every other week for 28-day cycles. The primary efficacy endpoint is Clinical Benefit Response (CBR), defined as a complete or partial response or prolonged stable disease (= 16 weeks) by modified RECIST guidelines. Results: Seven of the first 19 patients achieved CBR, allowing expansion to the second stage. Enrollment is now complete (45 patients). Demographic data are available for 35 (median 66 yrs.; range 46–89) patients who received treatment: 23 adenocarcinomas, 5 carcinosarcomas, 6 papillary serous carcinomas (UPSC) and 1 clear cell carcinoma. Thirty-four patients had prior chemotherapy including doxorubicin, taxanes or platinum agents. Fourteen of the 26 patients with available history had prior pelvic radiotherapy. Nine of 27 (33%) patients evaluable for response had CBRs, including 2 partial responses (PRs). One CBR had UPSC, the remaining patients, including the PRs, had adenocarcinomas. Seven of the patients achieving CBR are still on treatment. Eighteen of the 27 patients discontinued treatment before 4 cycles because of progressive disease (14), consent withdrawal (1) or unrelated adverse events (3). Adverse event data are available for 27 patients. The most common adverse events are fatigue, anemia (33% each), mouth sores and nausea/vomiting (30% each). There have been 16 grade 3/ 4 treatment related adverse events (2 hyperglycemia, 14 separate events similar to those reported in other AP23573 trials). Conclusions: AP23573 shows encouraging single-agent activity in pretreated patients with advanced, progressive endometrial cancer and is well tolerated. No significant financial relationships to disclose.
A functional update of the Escherichia coliK-12 genome
Authors: Margrethe H Serres, Shuba Gopal, Laila A Nahum, Ping Liang, Terry Gaasterland, Monica Riley
Journal: Genome biology (2001)

Since the genome of Escherichia coli K-12 was initially annotated in 1997, additional functional information based on biological characterization and functions of sequence-similar proteins has become available. On the basis of this new information, an updated version of the annotated chromosome has been generated.The E. coli K-12 chromosome is currently represented by 4,401 genes encoding 116 RNAs and 4,285 proteins. The boundaries of the genes identified in the GenBank Accession U00096 were used. Some protein-coding sequences are compound and encode multimodular proteins. The coding sequences (CDSs) are represented by modules (protein elements of at least 100 amino acids with biological activity and independent evolutionary history). There are 4,616 identified modules in the 4,285 proteins. Of these, 48.9% have been characterized, 29.5% have an imputed function, 2.1% have a phenotype and 19.5% have no function assignment. Only 7% of the modules appear unique to E. coli, and this number is expected to be reduced as more genome data becomes available. The imputed functions were assigned on the basis of manual evaluation of functions predicted by BLAST and DARWIN analyses and by the MAGPIE genome annotation system.Much knowledge has been gained about functions encoded by the E. coli K-12 genome since the 1997 annotation was published. The data presented here should be useful for analysis of E. coli gene products as well as gene products encoded by other genomes.
Heterocyclic Cationic Gemini Surfactants: A Comparative Overview of Their Synthesis, Self‐assembling, Physicochemical, and Biological Properties
Authors: Vishnu Dutt Sharma, Marc A. Ilies
Journal: Medicinal Research Reviews (2012)

Abstract Gemini surfactants ( GS ) are presently receiving substantial attention due to their special self‐assembling properties and unique interfacial activity. This comprehensive review is focused on positively charged heterocyclic GS , presenting their major synthetic access routes and examining the impact of structural elements on physicochemical and aggregation properties of this class of amphiphiles. Interaction of geminis surfactants with cells and their biological properties as novel transfection agents are emphasized through a detailed structure–activity relationship analysis. Throughout the review we have also presented the properties of selected ammonium GS , simple surfactants and lipid congeners, in order to emphasize the advantages conferred by using heterocyclic polar heads in GS design.