tbuckley/cabot-search huggingface dataset:
Utility scores in patients with oxygen-dependent COPD: A case-control study
Authors: Yves Lacasse, Sarah Bernard, FranÃ§ois Maltais
Journal: European Respiratory Journal (2013)

Background : The comparison of health-related quality of life among patients with different chronic health conditions is essential to the prioritization of limited health resources from cost-effectiveness analyses . To do so, utility measures summarize the health-related quality of life of an individual using a single number usually between 0 (death) and 1 (full health) and are useful to quantify the benefits of health care interventions in terms on quality-adjusted life years (QALYs).

Objective: To determine utility scores in patients with oxygen-dependent COPD to be used in cost-utility analyses.

Methods: 68 patients with oxygen-dependent COPD (the cases) were matched, on a 1:1 basis, to controls according to gender, age (± 5 years) and FEV1 (±5% predicted). Utility scores were obtained from the SF-6D, a measure derived from the SF-36.

Results: 68 oxygen-dependent patients (42 men; mean age: 71 years; mean FEV1: 36% predicted) were successfully matched with as many controls. We found a clinically and statistically significant difference in mean utility scores between cases (0.59 ± 0.07) and controls (0.62 ±0.08; p = 0.004). The same differences were observed in men and women.

Conclusion : Oxygen-dependence adds to the burden of disease in terms of quality of life. These utility scores can be used in cost-utility analyses involving patients with oxygen-dependent COPD.
Prospective randomized trial of one-hour sequential versus simultaneous methotrexate plus 5-fluorouracil in advanced and recurrent squamous cell head and neck cancer.
Authors: G P Browman, S D Archibald, J E Young, W M Hryniuk, R Russell, K Kiehl, M N Levine
Journal: Journal of Clinical Oncology (1983)

Results from experimental systems suggest that the combination of methotrexate (MTX) and 5-fluorouracil (5-FU) produces synergistic cytotoxic effects that are dependent on the sequence of drug administration. Biochemical studies have demonstrated plausible mechanisms of a synergistic effect when MTX precedes 5-FU. A variety of phase I and phase II studies have employed this sequential combination with promising but inconclusive results. In this study, 79 evaluable patients with squamous cell head and neck cancer were randomized to receive MTX (200 mg/m2 IV) and 5-FU (600 mg/m2 IV) either simultaneously or sequentially with MTX preceding 5-FU by one hour. All patients were ambulatory and patients were stratified as to whether they presented with primary disease or with recurrence after prior radiation and/or surgical therapy. The overall response rate was superior for simultaneous therapy (62%) compared with sequential therapy (38%) (p less than 0.06). Among patients with primary head and neck cancer, the stage of the disease influenced the response rate. Eight of nine stage III patients who received simultaneous therapy responded while none of the four patients who received sequential therapy responded (p less than 0.01). This study demonstrates that one-hour sequential MTX plus 5-FU is not superior to simultaneous treatment in patients with squamous cell head and neck cancer.
Randomized phase III trial of sorafenib versus placebo in patients with advanced hepatocellular carcinoma (HCC)
Authors: J. Llovet, S. Ricci, V. Mazzaferro, P. Hilgard, J. Raoul, S. Zeuzem, M. Poulin-Costello, M. Moscovici, D. Voliotis, J. Bruix
Journal: Journal of Clinical Oncology (2007)

LBA1 Background: HCC is the 3rd cause of cancer death globally with most deaths occurring within 1 year of diagnosis. No standard therapy exists for advanced HCC. Sorafenib (Sor) is a multikinase inhibitor with anti-angiogenic, pro-apoptotic and Raf kinase inhibitory activity, with clinical activity in a phase II HCC trial. This large, multicenter, randomized, placebo-controlled phase III trial evaluated the efficacy and safety of Sor vs placebo (P) in pts with HCC. Methods: Patients with advanced measurable HCC, no prior systemic treatment, ECOG PS 0–2 and Child-Pugh status A received Sor 400 mg bid or P. Primary efficacy endpoints were overall survival (OS) and time to symptomatic progression (TTSP). Time to progression (TTP) and disease control rate (DCR; CR+PR+SD for at least 2 cycles) were secondary endpoints.Treatment arms were compared for OS and TTSP using a 1-sided log-rank test [overall a of 0.02 (OS) and 0.005 (TTSP)] stratified by region, ECOG PS and tumor burden. An O’Brien-Fleming-type error spending function determined criteria for early stopping for efficacy. Results: 602 pts (Sor n=299; P n=303) were randomized. Baseline characteristics were similar for Sor vs P: median age (67 vs 68 y), male (87% vs 87%), ECOG PS 0 (54% vs 54%), Child-Pugh A (95% vs 98%), and BCLC stage C (82% vs 83%). Based on 321 deaths (Sor n=143; P n=178), the hazard ratio (HR) for OS (Sor/P) was 0.69 (95% CI: 0.55, 0.87; p=0.0006), representing a 44% improvement in OS vs P which met early stopping criteria. Median OS was 10.7 vs 7.9 mos (Sor vs P). Primary TTSP analysis demonstrated no statistically significant difference for Sor vs P. HR for TTP (independent assessment) was 0.58 (95% CI: 0.45, 0.74; p=0.000007). Median TTP was longer (5.5 vs 2.8 mos) and DCR was higher (43% vs 32%) with Sor vs P. Incidence of serious adverse events was similar for Sor vs P (52% vs 54%). The most frequent grade 3/4 events were diarrhea (11% vs 2%), hand-foot skin reaction (8% vs 1%), fatigue (10% vs 15%), and bleeding (6% vs 9%) for Sor vs P. Conclusions: Sorafenib was well tolerated and is the first agent to demonstrate a statistically significant improvement in OS for pts with advanced HCC. This effect is clinically meaningful and establishes sorafenib as first-line treatment for these pts. [Table: see text]
Adrenocortical tumors in children: The Brazilian experience in a single institution
Authors: P. F. Hirose, A. M. Cappellano, A. Oliveira, M. Mastellaro, I. Cardinalli, L. Zambaldi, S. Brandalise, S. Aguiar
Journal: Journal of Clinical Oncology (2005)

8506 Background: Adrenocortical Tumors (ACT) are a rare entity in pediatric oncology population, occurring in less than 0,2% of all pediatric cancer. The incidence of this tumor in Brazil, however is highest, specially in north of Paraná and São Paulo. Methods: Seventy eight patients (pts) with diagnosis of ACT were admitted to CIB between 1980 and 2004 and were retrospectively reviewed to identify epidemiological and genetic factors that may contribute to these frequency. Results: The children’s age ranged from 2 to 210 months (median of 26 months), 51(65,4%) of them being girls. Clinical presentation consisted in virilization in 56 pts (71,8%), Cushing‘s Syndrome in 5 pts (6,4%) and both in 9 pts (11,5%). Only 8 pts (10,3%) had no symptoms. Concerning to stage, 64 pts (82,1%) were stage I and II and 14 pts (17,9%) were stage III and IV. In 87,2% of the patients, complete tumor resection was performed. Pathology results were 7 Adenomas and 71 (91%) Adrenal Carcinoma (AC), according to Weiss and Medeiros criteria. Twenty of 71 pts with AC had p53 analysis with 100% of positivity (R337H). Chemotherapy was performed in all stage III and IV, after surgery. The overall survival were 76,6% in 10 years. Conclusions: The incidence of ACT in Southern Brazil is 10 to 15 times highest, when compared to incidence in US pediatric cancer population. Genetic factors, predisposing the appearance of ACT was observed in 100% of the 20 pts analyzed, as specific germ line point of mutation in p53 encoding an R337H amino acid substitution in these children. Although, the natural history and best chemotherapy regimen for ACT is not well establish, early diagnosis and surgery in an oncology institution is the best approach to improve the prognosis. No significant financial relationships to disclose.
Modulation by theophylline and enprofylline of the excitatory non-cholinergic transmission in guinea-pig bronchi
Authors: J Barlinski, A Lockhart, N Frossard
Journal: European Respiratory Journal (1992)

The mechanism of action of xanthines in asthma remains controversial. Since sensory innervation may play a role in the pathogenesis of asthma, we investigated whether xanthines were capable of reducing the contractile response of the bronchi to nerve stimulation. In guinea-pig bronchi in vitro, electrical field stimulation (EFS: 40 V, 16 Hz, 0.2 ms during 10 s) induces a rapid cholinergic contraction followed by a long-lasting contraction due to a local release of neuropeptides from C-fibre endings. We measured isometric neuronally-mediated contractions of bronchial smooth muscle and studied the effects of increasing concentrations of two xanthine derivatives, theophylline, an antagonist of adenosine receptors, and enprofylline, which has no effect on adenosine receptors. Both enprofylline (1-50 microM) and theophylline (10-100 microM) inhibited, in a concentration-dependent manner, the peptidergic contraction, an effect which was more marked with enprofylline than theophylline (EC50 = 9.6 +/- 0.7 microM and 62.0 +/- 4.7 microM, respectively). Conversely, the cholinergic response was unaffected. Contractions induced by exogenous substance P (0.03-3 microM) were also unaffected by theophylline and enprofylline at the above mentioned EC50s. Our results suggest that concentrations of theophylline, similar to those used therapeutically, reduce the release of sensory neuropeptides from C-fibre endings. This effect is unrelated to adenosine receptor blockade, since enprofylline had a similar inhibitory effect.
Renal dysfunction due to an arteriovenous fistula in a transplant recipient.
Authors: K L Harrison, H V Nghiem, D M Coldwell, C L Davis
Journal: Journal of the American Society of Nephrology (1994)

Arteriovenous fistulae (AVF) occur after percutaneous renal biopsy in up to 18% of patients. Fistulae may remain asymptomatic or lead to hematuria, hypertension, and/or renal insufficiency. The identification of an AVF has traditionally been made with angiography; however, ultrasonography, which is less invasive and nonnephrotoxic, has become a valuable tool in the localization of a postbiopsy fistula. Most postbiopsy AVF are asymptomatic and close spontaneously. Conversely, AVF may enlarge and become symptomatic, requiring embolization to reverse or prevent complications. A case of renal insufficiency in a renal transplant recipient due to a postbiopsy AVF is presented. Spontaneous closure of the AVF resulted in the resolution of renal insufficiency. One must suspect an AVF when renal insufficiency occurs in an allograft after biopsy. Further study is needed to identify ultrasound characteristics that will predict the natural history of postbiopsy AVF.
Chemoprotective Effect of Progesterone on Carcinoma Formation in Mice and Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Lupulescu
Journal: JNCI Journal of the National Cancer Institute (1985)

The protective effect of progesterone on the development of chemically induced carcinomas (squamous cell carcinomas in mice and basal cell carcinomas in rats) by 3-methylcholanthrene [(MCA) CAS: 56-49-5] was studied. Progesterone administration decreased the average number, size, and weight of carcinomas by 45-50% as compared to those of tumors treated with MCA alone at any time interval. DNA radioactivity and autoradiographic studies with the use of [3H]thymidine showed an inhibition of DNA synthesis in the neoplastic cell nuclei following a concomitant administration of progesterone and MCA (18.4%) as compared to the DNA synthesis following administration of MCA alone (35.0%). Electron microscopic and cytologic observations revealed salient ultrastructural findings following progesterone administration, with advanced cytolysis, tumefied mitochondria, large populations of secondary lysosomes, and autophagic formations; also, cell differentiation tended to be of a glandular-adenomatoid type following progesterone and MCA administration as compared to the characteristic squamous cell and basal cell carcinomas after treatment with MCA alone. In addition, scanning electron microscopic observations revealed advanced cytolytic areas with several disintegrated neoplastic cells and cell debris intermingled with red blood cells, following progesterone and MCA administration. The present findings demonstrate that progesterone in pharmacologic doses exerts important chemoprotective effects on carcinoma formation, possibly by interfering with MCA metabolism and inhibiting DNA synthesis in the epidermal neoplastic cells, and thus plays an important role in tumorigenesis.
Recombinant Human Interleukin-11 Directly Promotes Megakaryocytopoiesis In Vitro
Authors: Nadine S. Weich, Anlai Wang, Michael Fitzgerald, Tamlyn Yee Neben, Debra Donaldson, JoAnn Giannotti, Joanne Yetz-Aldape, Robert M. Leven, Katherine J. Turner
Journal: Blood (1997)
GP is struck off for dishonestly providing sick notes for children
Authors: Clare Dyer
Journal: BMJ (2015)

A now retired GP has been struck off the medical register for dishonestly providing sick notes for two schoolchildren over a three year period and giving diagnoses that were not clinically indicated, without examining the children or recording the notes in their records.

Therese Shortall, who qualified in 1970, had no previous history with the General Medical Council, and the Medical Practitioners Tribunal Service panel said that it gained “no satisfaction from removing …
Five minutes with . . . Chaand Nagpaul
Authors: Gareth Iacobucci
Journal: BMJ (2016)

GPs in the UK held a crisis summit on Saturday 30 January to debate how to tackle the current crisis facing the profession.1 The chairman of the BMA’s General Practitioners Committee, who gave an impassioned keynote talk to the conference, told <i>The BMJ</i> what he thinks should happen next
Volatile organic compounds in exhaled breath of patients with COPD ± lung cancer and their correlation with FEV1-values
Authors: Michael Westhoff, Patric Litterst, H. Sommer, Betram Bödecker, Jörg-Ingo Baumbach
Journal: European Respiratory Journal (2014)

Introduction   Ion mobility spectrometry (MCC/IMS) is currently evaluated for exhaled breath analysis in different pulmonary diseases. The relevance of different specific volatile organic compounds (VOC) and their potential relations to FEV1 still remain unknown. We wondered if patients with COPD ± lung cancer exhale different VOCs and if there is a relation to FEV1 resp. FEV1/VC.   Methods   In 61 patients with COPD and lung cancer, 23 with COPD and 32 healthy controls exhaled breath was analysed with an IMS coupled to a multi capillary column (MCC/IMS). Discrimination between the subgroups was made by a decision-tree-model.   Results   102 different peaks were found. 29 showed a 99 % significance level, including 2-Methylfurane, 2-Methylpentane, 1-Butanole, Butanal, Cyclohexanole, Propanal, 1-Hexanole, n-Nona, 2-Heptanole, 3-Pentanone, Phenylacetylene, 2-Butanone and Isoprene. A decision tree starting with 2-Methylpentane showed the decision power in two steps. Sensitivity of 100 % and specificity of 97 % was calculated. 3-Pentanone Dimer and 1-Hexanole differentiated the LC/COPD group from healthy control, with a specificity of 94 %. Finally, the groups COPD, LC/COPD and healthy control were differenciated using a 2-step decision tree starting with 1-Hexanole and Acetone. Correlations between analyte concentrations and FEV1 were found for the following analytes: increasing e.g. Ammonia, decreasing e.g. 1-Octanole.   Conclusions   Some VOCs in exhaled air of patients with COPD ± lung cancer and healthy controls allowed the separation of these group. Ffunctional impairment seems to influence the concentration of some analytes; this has to be taken into account in further analysis.
Effects of Pyrazole and 3-Amino-1,2,4-triazole on the Metabolism and Toxicity of Dimethylnitrosamine in the Rat 2
Authors: John C. Phillips, Brian G. Lake, Sharat D. Gangolli, Paul Grasso, Alun G. Lloyd
Journal: JNCI Journal of the National Cancer Institute (1977)

Pretreatment of rats with pyrazole or 3-amino-1,2,4-triazole (3-AT) known inhibitors of alcohol metabolism, profoundly inhibited the metabolism of dimethylnitrosamine (DMN), both in terms of [14C]CO2 excretion and of the decline in the blood concentration. Additionally, 4-methylpyrazole, tetraethylthiuram disulfide (disulfiram), methanol, and ethanol inhibited the metabolism of DMN in the whole animal. In parallel experiments with [14C]aminopyrine, no substantial inhibitory effect was found with pyrazole, 3-AT, or disulfiram pretreatment. Investigations into the effects of pyrazole and 3-AT pretreatment on the acute toxicity and hepatotoxicity of DMN showed that pyrazole significantly increased the median lethal dose (LD50) of DMN and provided substantial protection against the hepatotoxicity of DMN, in that centriblobular necrosis was not seen at dose levels of DMN up to 25 mg/kg and early histochemical changes indicative of liver injury were not observed at a dose level of 15 mg DMN/kg. In contrast, 3-AT pretreatment did not affect the LD50 of DMN or provide any protection against the hepatotoxicity of DMN. Further, although both inhibitors delayed the incorporation of radioactivity from [14C]DMN into hepatic subcellular organelles, pyrazole was significantly more effective than was 3-AT.
Prospective evaluation of liposomal doxorubicin (LD) in patients with metastatic breast cancer previously treated with conventional anthracyclines
Authors: D. Bernardi, D. Errante, M. Stefani, M. Ramello, A. Bianco, L. Salvagno
Journal: Journal of Clinical Oncology (2008)

12025 Background: The treatment of pts with MBC, who failed previous chemotherapy regimens and whose favourable Performance Status justifies further treatment, represents a significant challenge. In MBC the use of conventional anthracyclines is limited by cumulative cardiac toxicity and myelosuppression, despite long anthracycline-free intervals in many pts. In these cases LD may represent an attractive option. Methods: 15 pts with MBC already treated with different therapeutic strategies and previously exposed to conventional anthracyclines (epirubicin, EPI, in 9 pts and doxorubicin, DOX, in 6 pts), were treated with LD 60 mg/m2 every 3 weeks. Results: Median age was 54 years. Median time from conventional anthracycline exposure was 40 months. Median previous dose of EPI was 440 mg/m2 and of DOX was 240 mg/m2. All pts had a LVEF>50% at baseline. The median number of previous chemotherapy regimens was 4. The median number of cycles of LD administered was 4. G3-G4 hematologic occurred in 6 pts. A delay or reduction of chemotherapy was necessary in 3 pts. There were 3 pts with asymptomatic cardiologic events (>20% reduction in LVEF in 1 pt after 10 cycles, 10% reduction in LVEF in 2 pt after 5 and 6 cycles, respectively). These pts received a median previous dose of anthracyclines of 350 mg/m2 and were previously exposed to RT and trastuzumab (2 out of 3). A congestive heart failure was registered in 1 pt after 6 cycles, an adjuvant dose of doxorubicin of 240 mg/m2 and RT for metastatic disease. Partial Response was achieved in 3 pts and Stable Disease in 1 (i.e. clinical benefit in 4 patients). Median duration of the clinical benefit was 6.5 months, median overall survival was 5 months. Conclusions: LD appears to be effective even in pts with MBC heavily pre-treated, with manageable hematologic toxicity. Nevertheless, cardiac function should be monitored carefully especially in pts treated for long periods of time. No conclusion on survival can be made. However, the median survival time of 5 months compares favourably with the median survival reported in the literature suggesting that LD monotherapy should be considered as a valuable treatment option in heavily pre-treated pts. No significant financial relationships to disclose.
Abstract A2-44: Stellaris® RNA fluorescence in situ hybridization (RNA FISH) for the detection of long non coding RNA biomarkers
Authors: Arturo V. Orjalo, Hans E. Johansson
Journal: Cancer Research (2015)

Abstract Long non-coding RNAs (lncRNAs) play important roles in all the central aspects of the gene expression cascade with wide ranging effects on cell proliferation and differentiation. As such, lncRNAs are highly promising additions to many cancer biomarkers portfolios and enable more precise diagnostic staging. This, in turn, provides a clearer prognosis and treatment options of different cancers. Direct visualization and quantification of lncRNAs in single cells and in tissue are thus emerging as essential tools for both basic and clinical research. Interestingly, studies have demonstrated that transcript levels are more strongly correlated to clinical traits than the corresponding protein levels. Because RNA biomarkers have the potential to contribute to the development of targeted cancer therapies, there is also an obvious need for a robust and dependable methodology to discover and validate these RNAs. RNA fluorescence in situ hybridization (RNA FISH) provides a powerful means to detect RNA biomarkers in single cells, while still maintaining tissue morphology. Significant advances in RNA FISH technology, such as the hybridization of pools of singly labeled fluorescent 20-mer oligonucleotides to the RNA target, now afford specific and sensitive multiplex detection of RNA to yield information on the RNA's distinct spatial distribution within cells and tissue. Data is presented on the design of probe sets against multiple disease relevant pre-lncRNAs and against the introns of their precursors, as well as on the simultaneous dual-channel imaging of the pre-lncRNAs and mature lncRNAs. Because the absolute majority of post-transcriptional processing, including splicing of mRNAs and lncRNAs, occurs co-transcriptionally, the location of introns can be used as a proxy nuclear location for the encoding gene. We find mature lncRNAs to locate at or close to the site of transcription, but also well away from it. Next, we present data on emerging non-coding RNA biomarkers in breast and prostate cancer tissue and in cell lines utilizing RNA FISH. In summary, the results and tools presented here will contribute to advancing the current capabilities of the detection and treatment of specific cancers, as well as in the continued discovery and development of cancer drug candidates. Citation Format: Arturo V. Orjalo, Jr., Hans E. Johansson. Stellaris® RNA fluorescence in situ hybridization (RNA FISH) for the detection of long non coding RNA biomarkers. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-44.