tbuckley/cabot-search huggingface dataset:
Addition of Oxaliplatin to Continuous Fluorouracil, <scp>l</scp>-Folinic Acid, and Concomitant Radiotherapy in Rectal Cancer: The Lyon R 97-03 Phase I Trial
Authors: Gilles Freyer, Nadine Bossard, Pascale Romestaing, Françoise Mornex, Olivier Chapet, Véronique Trillet-Lenoir, Jean-Pierre Gérard
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS: Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m 2 2-hour infusion on day 1 followed by l-folinic acid 100 mg/m 2 /d intravenous bolus, and 5-FU 350 mg/m 2 /d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/− brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.
Fluorescence-Guided Surgery of Pancreatic Patient-Derived Orthotopic Xenograft(Pdox) with a Portable Imaging System
Authors: Robert M. Hoffman, Yukihiko Hiroshima, Ali Maawy, Fuminari Uehara, Shinji Miwa, Shuya Yano, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo
Journal: Annals of Oncology (2014)
Backward Masking in Unmedicated Schizophrenic Patients in Psychotic Remission: Possible Reflection of Aberrant Cortical Oscillation
Authors: Michael Foster Green, Keith H. Nuechterlein, Bruno Breitmeyer, Jim Mintz
Journal: American Journal of Psychiatry (1999)

Patients with schizophrenia consistently show performance deficits on measures of visual backward masking, but the nature of these deficits is not well understood. Performance deficits on backward masking tasks may indicate an underlying predisposition instead of the presence of illness, because deficits are present in unaffected first-degree relatives. Performance deficits in remitted patients would constitute converging support for this hypothesis.Eleven patients with recent-onset schizophrenia who were in a period of no medication use during remission of psychosis were compared with a matched normal group on three visual masking conditions. These conditions included target identification tasks with a high-energy mask, a low-energy mask, and a blurred target.Patients in psychotic remission showed significant deficits across all conditions. In addition, trend analyses revealed significant group differences in the shape of the masking functions: the comparison group showed an oscillating performance pattern across all masking conditions, whereas the patients did not exhibit this pattern on any condition.These data from patients in well-documented psychotic remission add converging support for the hypothesis that deficits on backward masking procedures are indicators of vulnerability to schizophrenia. Because visual masking procedures may reflect underlying neural oscillations of 30 to 70 Hz in the visual cortex, the pattern of results is consistent with the theory that visual masking deficits in schizophrenia stem from an underlying failure to establish cortical oscillations.
CT diagnosis of bronchiectasis (BCT) - Casuistic report of a tertiary hospital
Authors: José Meireles, Sara Silva, Vital Domingues, Daniel Pereira, João Neves, Pedro Leuschner
Journal: European Respiratory Journal (2013)

Background: A wide spectrum of diseases can cause BCT; the definition is radiological and the significance of incidental findings is unknown.  Objective: Characterize an adult population with BCT found on chest CT (CT)  Methods: Computerized database search for CT reports performed between 2008-10 mentioning BCT. Classification was adapted from ERS Monograph (Eur Respir Mon 2011. 52, 1–10). BCT were characterized and clinical files reviewed for symptoms, demographic data and etiologic investigation. Symptomatic BCT were defined by use of inhaled medication/oxygen or admission due to respiratory disease.  Results: Of the 1371 reports retrieved, 682 were excluded. There was a slight male predominance (52,4%). Mean age at diagnosis was 66 years (1-94, SD ±14,8); 174 were deceased when the file was reviewed. 31,2% (n=215) had a previous diagnosis of cancer. 79,5% of the patients were considered symptomatic. 26,6% associated with infections, 11,3% obstructive airways disease, 7,1% systemic diseases and 6,0% immunodeficiency; n=14 were idiopathic. In 37,1% etiology wasn9t determined. Most were and found in only one lobe (50,8%), and morphology was varicose (34,5%), cylindrical (29,9%), cystic (8,3%) or mixed (18,6%). 72,4% presented other CT findings. No predictors of mortality were found but there was a trend towards increased mortality in symptomatic patients.  Conclusions: BCT are a relatively common finding in CT and are often symptomatic. Etiologic investigation is insufficient in a great number of patients. The apparent association with cancer may be due to selection bias. Significance in asymptomatic patients is unknown, prospective studies are needed to evaluate natural history in those patients.
Activin-A expression is increased in severe asthma and is involved in tissue angiogenesis
Authors: Konstantinos Samitas, Eleftherios Zervas, Nikolaos Poulos, Maria Semitekolou, Stelios Vittorakis, Harsha Kariyawasam, Vily Panoutsakopoulou, Georgina Xanthou, Mina Gaga
Journal: European Respiratory Journal (2012)

Background : Our recent studies show that Activin-A (Act-A), a cytokine belonging to the TGF-β superfamily, suppresses mouse allergic responses; however its effects on human asthma remain unknown.   Objectives : To determine Act-A expression in healthy controls (CTRL) and asthmatics, identify its cellular sources and signaling mediators, and examine correlations with disease severity and airway remodelling.   Methods : Serum samples were obtained from 46 mild-to-moderate asthmatics (MMA), 27 severe asthmatics (SA) and 41 CTRL. 55 subjects (18 CTRL, 18 MMA, 19 SA) underwent bronchoscopy with endobronchial biopsy and BALF collection. Act-A levels in the serum/BALF were examined. Expression of Act-A and its principal signaling mediator ALK4 in the bronchial tissue were assessed by confocal microscopy. Basement membrane thickness, goblet cell hyperplasia and angiogenesis (vessels/mm2) were also determined.   Results : Act-A levels were significantly increased in MMA in the serum and in MMA and SA in BALF. Serum Act-A was further increased during asthma exacerbation. Bronchial tissue Act-A expression was significantly increased in asthmatics, especially in the subepithelium in SA, while ALK-4 expression decreased with disease severity. Act-A was mainly expressed by mast cells, neutrophils, macrophages and smooth muscle cells. Act-A and ALK-4 were also localized in endothelial cells, particularly in SA. Subepithelial Act-A expression correlated with angiogenesis and disease severity.   Conclusions : Our data suggest that Act-A plays a crucial role in asthma inflammation and participates in the regulation of angiogenesis in SA. Ongoing in vitro studies will further elucidate its specific role.
Some Observations on the Reversibility of Methotrexate Toxicity in Normal Proliferating Tissues2
Authors: J. A. Straw, D. C. Talbot, G. A. Taylor, K. R. Harrap
Journal: JNCI Journal of the National Cancer Institute (1977)

Thymidine, in the absence of hypoxanthine, failed to protect normal mice from the acute toxicity of methotrexate, though tumor-bearing animals could be protected with thymidine alone, probably as a result of the availability of DNA degradation products released from drug-sensitive tumor cells. Although metrotrexate induced an early purine deficiency in gut cells, this effect was not detected in bone marrow. Later, purine deficiency became apparent in the gut and bone marrow of methotrexate-treated animals.
Determination and comparison of ventilatory parameters in anaerobic threshold and the critical load
Authors: Vivian Maria Arakelian, Renata Gonçalves Mendes, Daniela Bassi Dutra, Nuno Manuel Frade de Sousa, Danilo Bertucci, Camila do Vale Gomes Gatto, Vilmar Baldissera, Audrey Borghi-Silva
Journal: European Respiratory Journal (2013)

Background: The anaerobic threshold (AT) and critical power (CP) (Hill,2002; 2004) are tools that can be used in the prescription of aerobic training, but they are not applied for resistance exercises (RE), especially in special populations such as the elderly. Furthermore, little is known of the relationship between these parameters and maximum workload (1RM) in RE and the ventilatory behavior during the execution of these intensities. Objectives: to determine the AT and the critical load (CL) for exercise on leg press and compare the behavior of ventilation (VE) and oxygen consumption (VO2) during these intensities in healthy elderly. Methods: We studied healthy men (69±4 years), who underwent: 1) a 1 repetition maximum (1RM) test on Leg Press and, 2) the crescent test for determining the AT through VE, 3) the constant load test in the AT, 4) on different days, three high-intensity resistance exercise constant load tests (60%, 75% and 90% 1RM) in order to obtain CL by linear regression: load X reverse of time (duration of exercise until fatigue) and 5) the constant in the test CL. Results: On average, it was determined that the value of AT was ∼ 30% 1RM and CP ∼ 52%1RM. Regarding the execution of each intensity was obtained (on average) that VE reached 32.7 l/min in the AT, while in the CP was 41.6 l/min (p <0.05). As for the VO2, was obtained 1.1 l/min in the AT and 0.99 l/min in CL (p <0.05). Conclusion: These findings demonstrate that VE increases as the intensity is increased, but the VO2 exhibit the opposite behavior. Thus, it can be concluded that both tools can be determined in the RE, and should be used as training objective.Financial Support: 2009/01842-0.
Scleredema associated with paraproteinaemia treated by extracorporeal photopheresis
Authors: G.I. Stables, P.C. Taylor, A.S. Highet
Journal: British Journal of Dermatology (2000)

Scleredema is a rare disease characterized by extensive cutaneous woody, non‐pitting induration that spreads throughout the body. We describe a patient with scleredema associated with paraproteinaemia who was successfully treated by extracorporeal photopheresis.
Malignant ventricular arrhythmia during treatment with terfenadine and itraconazole: A pharmacokinetic study
Authors: Olivier Lortholary, Nathalie Rizzo, Michel Tod, Jean-Yves Artigou, Johann Beaudreuil, Yves Cohen, Philippe Casassus, Olivier Petitjean
Journal: Clinical Microbiology and Infection (1996)
Biological and Morphological Characteristics of Mammary Tumors in GR Mice
Authors: Robertha van Nie, Anna Dux
Journal: JNCI Journal of the National Cancer Institute (1971)

Mammary tumor incidence was studied in virgins, in females bearing 1, 4, or 8 pituitary isografts, in ovariectomized females treated with estrone, and in force-bred mice of the GR/A strain. The frequency of mammary tumors was high in all groups of mice. The tumors appeared with significant acceleration in mice bearing pituitary grafts and in mice treated with estrone. Four pituitary grafts had more effect than one graft. Eight pituitary grafts had no further effect. The average age at development of tumor in force-bred females was much lower than that in mice of any other group. Over 80% of the force-bred mice had mammary tumors at the end of the first pregnancy. Of the tumors in force breeders, 98% regressed after breeding was stopped. Nearly all tumors in the mice of the other groups grew progressively. After transplantation, all 13 tumors derived from force breeders retained their hormone dependency, whereas only 3 of the 25 tumors from mice of the other groups retained their hormone dependency. Nearly all tumors in the force breeders had distinct morphological features and were classified as a separate group, mammary tumor type P. Type P was very rare in the other groups, in which adenocarcinoma types A and B predominated. Another type of tumor was frequently observed; it was classified as pale cell carcinoma, which has not been described extensively before. The relation of the hormone dependency and the morphology of the tumors is discussed.
Lack of Adherence With the Analgesic Regimen: A Significant Barrier to Effective Cancer Pain Management
Authors: Christine Miaskowski, Marylin J. Dodd, Claudia West, Steven M. Paul, Debu Tripathy, Peter Koo, Karen Schumacher
Journal: Journal of Clinical Oncology (2001)

To evaluate oncology outpatients' level of adherence to their analgesic regimen during a 5-week period.A random sample of 65 adult oncology outpatients with a Karnofsky performance status score of >or= 50, an average pain intensity score of >or= 2.5, and radiographic evidence of bone metastasis were recruited for this longitudinal study from seven outpatient settings. On a daily basis, patients rated their level of pain intensity and recorded pain medication intake. Adherence rates for opioid analgesics prescribed on an around-the-clock (ATC) and on an as-needed (PRN) basis were calculated on a weekly basis.Overall adherence rates for ATC opioid analgesics ranged from 84.5% to 90.8% and, for PRN analgesics, from 22.2% to 26.6%. No significant differences over time were found in either of these adherence rates.One factor that seems to contribute to ineffective cancer pain management is poor adherence to the analgesic regimen.
Obstructive sleep apnoea and signal averaged electrocardiogram
Authors: S Andreas, B von Breska, A Schaumann, BD Gonska, H Kreuzer
Journal: European Respiratory Journal (1995)

Patients with obstructive sleep apnoea demonstrate an increased rate of ventricular arrhythmias. The present study was designed in order to investigate whether these arrhythmias may be related to myocardial injury, since myocardial injury of various aetiologies has been observed to change the signal averaged electrocardiogram (ECG). Signal averaged ECG was registered in 23 patients with obstructive sleep apnoea diagnosed by polysomnography (apnoea index 43 +/- 20 events.h-1, age 55 +/- 10 yrs). QRS duration, root mean square voltage of the last 40 ms of QRS, and low amplitude (< 40 mV) signal duration were determined from the vector magnitude of the QRS, high-pass filtered at 40 Hz. Patients with coronary heart disease or bundle branch block were excluded. No patient showed an abnormal signal averaged ECG. Mean duration of the filtered QRS complex was 96 +/- 9 ms, root mean square voltage 38 +/- 18 microV and low amplitude signal duration 26 +/- 8 ms. These results were not significantly different from 14 snoring subjects with an apnoea/hypopnoea index < 10. Four patients showed no ventricular arrhythmias and six patients had Lown III or IVa in the Holter ECG. Echocardiography revealed increased left atrial (43.7 +/- 4.1 mm) and interventricular septal diameters (11.3 +/- 1.4 mm). In conclusion, obstructive sleep apnoea does not generate a substrate for late potentials in the signal averaged ECG.
Acute Anti-inflammatory Effects of Inhaled Budesonide in Asthma
Authors: PETER G. GIBSON, NICHOLAS SALTOS, KELLIE FAKES
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing, suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma. This study aimed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma, and to examine whether the mechanism of clearance of eosinophils was by apoptosis. A randomized, double-blind, placebo-controlled, crossover study was conducted. At the screening visit, adults with stable asthma (n = 41) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia (> or = 7%) were randomized (n = 26) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler, on two separate study days. Symptoms and lung function were followed for 6 h, then sputum was induced and airway responsiveness to hypertonic saline determined. Sputum eosinophils (mean, SE) were significantly lower 6 h after budesonide (25%, 4.5), compared with placebo (37%, 6.2, p < 0.05). There was a 2.2-fold (95% CI 1.45 to 3.33) improvement in airway responsiveness with budesonide. No significant difference was seen on mast cells, apoptotic eosinophils, symptoms, or lung function. In conclusion, a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing. This may be clinically useful as therapy during mild exacerbations of asthma.
Dimethylnitrosamine-Induced Hepatic Cell Carcinoma in Rainbow Trout&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Laurence M. Ashley, John E. Halver
Journal: JNCI Journal of the National Cancer Institute (1968)

Liver neoplasms (adenomas and adenocarcinomas) were induced in rainbow trout by feeding dimethylnitrosamine [(DMN) N-nitrosodimethylamine] at levels ranging from 7.5–1920 mg/100 g dry test diet for 9 months or longer. Neoplasms were grossly and histologically similar to those reported by various authors for rats and other mammals. Hemorrhagic ascites, commonly observed in hepatomatous mammals, was largely absent from hepatomatous DMN-fed trout. Metastases seldom occurred in these trout within the 20-month period of the experiments, but direct spread of neoplasms from liver to visceral fascia and to pancreatic adipose tissue sometimes occurred. Extensive proliferation of bile ducts or ductules was rare in DMN-fed trout in contrast to prevalence of such proliferations in several species of DMN-fed mammals. Cystic areas in some of the trout neoplasms appeared to arise from acinous-like formations not related to bile-duct proliferations. Central necrosis and hemorrhage in the larger neoplasms usually spread peripherally until most of the primary neoplastic tissue was destroyed. Control fish fed the complete test diet for similar periods had none of the above pathological anomalies.
Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study
Authors: Donald H. Mahoney, Jonathan J. Shuster, Ruprecht Nitschke, Stephen Lauer, C. Philip Steuber, Bruce Camitta
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine whether early intensification with 12 courses of intravenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 12 courses of IV MTX alone for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction therapy. Patients were randomized to receive intensification with IV MTX 1,000 mg/m 2 plus IV MP 1,000 mg/m 2 (regimen A) or IV MTX 1,000 mg/m 2 alone (regimen C). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and triple intrathecal therapy every 12 weeks for 2 years. RESULTS: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The estimated 4-year overall continuous complete remission for patients treated with regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or race. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. CONCLUSION: Intensification with 12 courses of IV MTX is an effective therapy for prevention of relapse in children with B-precursor ALL who are at lower risk for relapse but may be associated with an increased risk for neurotoxicity. Prolonged infusions of MP combined with IV MTX did not provide apparent advantage.
Abstract 1448: Serine 21 Phosphorylation of GSK-3{alpha} Mediates Myocyte Proliferation through CyclinD1/E2F Pathway under Pressure Overload
Authors: Takahisa Matsuda, Peiyong Zhai, Chull Hong, Shumin Gao, Bin Tian, Kazumichi Goto, Mimi Tamamori-Adachi, Hiromitsu Takagi, Junichi Sadoshima
Journal: Circulation (2008)

Serine(S)21/S9 phosphorylation of glycogen synthase kinase-3α (GSK-3α) and GSK-3β, respectively, by upstream kinases, such as Akt, inhibits GSK-3. In order to elucidate the role of S21/S9 phosphory...
Etiology and treatment of chemotherapeutic agent extravasation injuries: a review.
Authors: R Rudolph, D L Larson
Journal: Journal of Clinical Oncology (1987)

While extravasation from intravenous (IV) lines is common and usually benign, leakage of certain drugs can cause severe skin ulceration. These ulcerogenic drugs can be conveniently divided into two categories, depending on whether they bind to DNA. Chemotherapeutic agents such as doxorubicin, which bind to DNA, are especially prone to cause severe extravasation skin ulcers. These ulcers are often chronic and progressive. Neither clinical nor experimental studies have shown an antidote to doxorubicin extravasation, which is best prevented by careful technique. If extravasation is suspected, the infusion should be immediately stopped. In the event of extravasation, elevation and ice are the currently recommended treatment. While small ulcerations may on occasion heal, large ulcerations require surgical excision for relief of pain and salvage of underlying tissues.
Attitudes to organ donation among South Asians in an English high street
Authors: Wasim Ahmed, Susie Harris, Edwina Brown
Journal: Journal of the Royal Society of Medicine (1999)

In the UK, people of South Asian origin are at more than twice the risk of end-stage renal failure encountered in the Caucasian population but are under-represented among organ donors. Difficulties with matching mean that few donated kidneys are suitable for transplantation to South Asian recipients. A survey of attitudes in 100 South Asian adults was conducted in the main street of Southall, Middlesex. 90 of those questioned were aware of organ transplantation and 69 had heard about donor cards. However, the 16% who carried a donor card was lower than the 28% reported in the general population. The main reason for the low organ donation rate by South Asians seemed to be lack of knowledge, and this could be remedied by more targeting of information in the Asian media.