tbuckley/cabot-search huggingface dataset:
Phase I and pharmacologic study of sequences of paclitaxel and cyclophosphamide supported by granulocyte colony-stimulating factor in women with previously treated metastatic breast cancer.
Authors: M J Kennedy, M L Zahurak, R C Donehower, D A Noe, S Sartorius, T L Chen, K Bowling, E K Rowinsky
Journal: Journal of Clinical Oncology (1996)

PURPOSE Pacltaxel is active in metastatic breast cancer, but limited information is available on combinations of this agent with other cytotoxic agents. Study aims were to determine the maximum-tolerated doses (MTDs) of paclitaxel (24-hour infusion) and cyclophosphamide (1-hour infusion) administered every 21 days with granulocyte colony-stimulating factor (G-CSF, filgrastim) to determine the effect of drug sequence on toxicity and pharmacology and to evaluate the activity of this combination in women with anthracycline-resistant disease. PATIENTS AND METHODS Thirty-seven women with metastatic breast cancer were treated. Starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2, with filgrastim 5 microG/kg/d subcutaneously beginning 24 hours after chemotherapy. Four patients were treated at each dose level. The sequence of drug administration was alternated between sequential patients, and with subsequent courses of therapy in each patient, to enable evaluation of effects of drug sequence on toxicity and pharmacology. Patients were treated every 21 days and disease status was reevaluated every two courses. RESULTS Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 is the MTD for this combination on this schedule. The hematopoietic toxicity of therapy was sequence-dependent. Paired analysis of toxicity data indicated more severe toxicity in courses in which paclitaxel was administered first. Sequence-dependent pharmacologic effects did not account for this phenomenon. Responses were noted in 29% of patients with anthracycline-resistant disease. CONCLUSION Paclitaxel 200 mg/m2 and cyclophosphamide 1,250 mg/m2 with filgrastim administered every 21 days are the doses recommended for further study.
Smoke or Fire? Acute Pancreatitis and the Liraglutide Trials
Authors: Edwin A.M. Gale
Journal: Diabetes Care (2015)

Over the past few years, substantial clinical data have been presented showing that incretin-based therapies are effective glucose-lowering agents. Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy comparable to insulin treatment with minimal hypoglycemia and have favorable effects on body weight. Thus, many of the unmet clinical needs noted from prior therapies are addressed by these agents. However, even after many years of use, many continue to raise concerns about the long-term safety of these agents and, in particular, the concern with pancreatitis. This clearly remains a complicated topic. Thus, in this issue of Diabetes Care, we continue to update our readers on this very important issue by presenting two studies evaluating incretin-based medications and risk of pancreatitis. Both have undergone significant revisions based on peer review that provided significant clarification of the data. We applaud both author groups for being extremely responsive in providing the additional data and revisions requested by the editorial team. As such, because of the critical peer review, we feel both articles achieve the high level we require for Diabetes Care and are pleased to now present them to our readers. In keeping with our aim to comprehensively evaluate this topic, we asked for additional commentaries to be prepared. In the narrative outlined below, Prof. Edwin A.M. Gale provides a commentary on the report that focuses on clinical trials of liraglutide in the treatment of diabetes. In the narrative that follows Prof. Gale’s contribution, Dr. Laurent Azoulay provides a commentary about the remaining uncertainty in this area and also discusses the results from a nationwide population-based case-control study. From the journal’s perspective, both of the articles on pancreatitis and incretin-based therapies reported in this issue have been well vetted, and we feel both of the commentaries are insightful. —William T. Cefalu Editor in Chief, Diabetes Care
Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support.
Authors: F R Dunphy, G Spitzer, A U Buzdar, G N Hortobagyi, L J Horwitz, J C Yau, J A Spinolo, S Jagannath, F Holmes, R O Wallerstein
Journal: Journal of Clinical Oncology (1990)

We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.
Suppressive Effect of 3-Methylcholanthrene on Phagocytic Activity of Mouse Peritoneal Macrophages for &lt;italic&gt;Torulopsis glabrata&lt;/italic&gt;&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R P Tewari, J P Balint, K A Brown
Journal: JNCI Journal of the National Cancer Institute (1979)

The effect of 3-methylcholanthrene (MCA) on the phagocytic activity of mouse peritoneal macrophages for Torulopsis glabrata was investigated. Macrophages were maintained in glass scintillation vials or on cover slips in Leighton tubes with the use of Hanks' balanced salt solution plus 30% horse serum. Graded amounts of MCA were incorporated into the medium and the macrophages were parasitized with viable cells of T. glabrata. Macrophages from C3H mice, a strain highly susceptible to MCA carcinogenesis, were more prone to the suppressive effect of MCA than were the macrophages from CFW mice, a relatively resistant strain. Significant suppressive effect on phagocytosis of macrophages from C3H mice was observed with 5 micrograms MCA/ml, whereas up to 50 micrograms MCA/ml did not alter the phagocytic activity of CFW macrophages. However, 100 micrograms MCA/ml also suppressed the phagocytosis of CFW macrophages. Suppression in phagocytosis of C3H macrophages was observed after 6 hours' exposure to MCA, whereas a similar effect on CFW macrophages was seen after 12 hours. Treatment with 100 micrograms MCA/ml imparied the fungicidal activity of both C3H and CFW macrophages. These results indicate a correlation between the suppressive effect of MCA on macrophage activity and the strain susceptibility of mice to chemical carcinogenesis.
Digital Radiology in Skeletal Trauma: Assessment of Casualty Officers' Performance
Authors: J H Gillard, C Hubbard, R Das, H Sherriff
Journal: Journal of the Royal Society of Medicine (1998)

Radiographic images can now be produced without the requirement of film processing and development, and can be displayed rapidly on a computer monitor. We assessed junior doctors' performance in interpreting images from 25 patients being investigated for possible fracture and also compared the diagnostic abilities of casualty officers with those of radiology specialist registrars. For interpretation of images viewed at a workstation or as filmed laser images, respectively, sensitivities were 75% and 78%, and specificities were 65% and 76%. These differences were not significant. There was a tendency for radiology specialist registrars to be less specific when reviewing images at a workstation. The demonstration that there is no loss in diagnostic quality when casualty officers interpret fracture images in a purely digitally acquired and viewed format forms a robust basis for economic evaluation of the technology.
Antineoplastic Activity of Cannabinoids2
Authors: A. E. Munson, L. S. Harris, M. A. Friedman, W. L. Dewey, R. A. Carchman
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Antineoplastic Activity of Cannabinoids Get access A. E. Munson, A. E. Munson Search for other works by this author on: Oxford Academic PubMed Google Scholar L. S. Harris, L. S. Harris Search for other works by this author on: Oxford Academic PubMed Google Scholar M. A. Friedman, M. A. Friedman Search for other works by this author on: Oxford Academic PubMed Google Scholar W. L. Dewey, W. L. Dewey Search for other works by this author on: Oxford Academic PubMed Google Scholar R. A. Carchman R. A. Carchman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 55, Issue 3, September 1975, Pages 597–602, https://doi.org/10.1093/jnci/55.3.597 Published: 01 September 1975 Article history Received: 26 December 1974 Accepted: 30 May 1975 Published: 01 September 1975
Abstract 13205: Mitochondrial Inhibitor of Division 1 (Mdivi-1) Improves Myocardial Hemodynamics and Return of Spontaneous Circulation in a Murine Model of Cardiac Arrest
Authors: Williard W Sharp, Yong H Fang, Mei Han, Hannah J Zhang, Stephen L Archer, David G Beiser
Journal: Circulation (2013)

Introduction: Mitochondrial fission following ischemia/reperfusion injury (IR) is an important determinant of reactive oxygen species (ROS) generation and cellular apoptosis but its role in cardiac...
Peripheral airway function in COPD assessed by Sacin and Scond using SF6 and He multiple breath washout
Authors: Maria Ström, Paul Robinson, Emilia Viklund, Sanna Kjellberg, Per Gustafsson
Journal: European Respiratory Journal (2011)

Background:  Peripheral airways, particularly acinar airways, are involved in COPD. Sacin for SF6 reflects ventilation inhomogeneity deep inside the acinus, while Sacin for He reflects inhomogeneity proximally in the acinus, and Scond indicates inhomogeneity in the small conducting airways. We tested the hypothesis that Sacin and Scond are greater for SF6 vs. He in COPD.   Methods:  Multiple breath SF6 and He washout, using a mass spectrometer, was performed at baseline and post bronchodilator (BD, 400 mcg salbutamol and 80 mcg ipratropium pMDI) prior to spirometry and DLCO: 41 COPD subjects (17M/24F), 45-66 yrs, smoking history 10-75 pack yrs. Reference values for Sacin and Scond were obtained in 46 non-smoking healthy subjects aged 19-71 yrs. Local spirometry and DLCO reference equations were used [1,2]. Results were expressed as median (range) z-scores, and wilcoxon rank sum test used for paired comparisons.   Results:  SF6 Sacin and Scond z scores were greater than He indices both at baseline and post BD in COPD subjects (p   Conclusions:  COPD was characterized by greater ventilation inhomogeneity in the distal vs. the proximal acinar portion. The degree of ventilation inhomogeneity found in COPD within the acinus is greater than in the conducting airway zone.   References:   1Hedenstrom et al. Bull Eur Physiopatol Respir. 1985;21:551-7.  2Hedenstrom et al. Upsala J Med Sci. 1986;91: 299-310.
THE TOXIC ACTIONS OF PYRROLIZIDINE (SENECIO) ALKALOIDS
Authors: ELIZABETH K. McLEAN
Journal: Pharmacological Reviews (1970)

The pyrrolizidine alkaloids give rise to a large number of toxic effects, many of them apparently unconnected with each other. They were for a long time regarded principally as liver poisons. In the past 10 years it has become clear that they also have a severe toxic action on the lung. The importance of making a systematic investigation of lesions in some other tissues has been stressed. Only one paper (42) deals with a possible autoimmune element among the toxic reactions. This aspect has been neglected and might repay investigation.

There are repeated, separate, reports of a protective effect of cysteine and methionine. Again, systematic investigation might turn these into a useful tool for investigating toxic mechanisms.

In assessing the veterinary problems and the results of feeding experiments with plants it is necessary to remember that plants can contain more than one toxin. Some plants containing pyrrolizidine alkaloids have been shown to contain a neurolathyrogen (19) and toxic levels of nitrites (127).

The study of the effects of the alkaloids upon cell division in mammals has now reached a point where it could profitably be linked up with the more detailed knowledge of DNA metabolism in bacteria. An investigation of the effects of the alkaloids and the pyrrolizidine pyrroles on DNA metabolism in Escherichia coli would be worthwhile.

According to the current evidence, it seems that these alkaloids present a hazard to man only in special circumstances. As a veterinary hazard, they remain important wherever pasture is poor or forage crops are likely to be heavily contaminated with the appropriate weeds. As tools for the student of biological mechanisms they are becoming increasingly interesting.
Thirty‐Day Hospital Readmissions in Systemic Lupus Erythematosus: Predictors and Hospital‐ and State‐Level Variation
Authors: Jinoos Yazdany, Ben J. Marafino, Mitzi L. Dean, Naomi S. Bardach, Reena Duseja, Michael M. Ward, R. Adams Dudley
Journal: Arthritis & Rheumatology (2014)

Objective Systemic lupus erythematosus (SLE) has one of the highest hospital readmission rates among chronic conditions. This study was undertaken to identify patient‐level, hospital‐level, and geographic predictors of 30‐day hospital readmissions associated with SLE. Methods Using hospital discharge databases from 5 geographically dispersed states, we studied all‐cause readmission of SLE patients between 2008 and 2009. We evaluated each hospitalization as a possible index event leading up to a readmission, our primary outcome. We accounted for clustering of hospitalizations within patients and within hospitals and adjusted for hospital case mix. Using multilevel mixed‐effects logistic regression, we examined factors associated with 30‐day readmission and calculated risk‐standardized hospital‐level and state‐level readmission rates. Results We examined 55,936 hospitalizations among 31,903 patients with SLE. Of these hospitalizations, 9,244 (16.5%) resulted in readmission within 30 days. In adjusted analyses, age was inversely related to risk of readmission. African American and Hispanic patients were more likely to be readmitted than white patients, as were those with Medicare or Medicaid insurance (versus private insurance). Several clinical characteristics of lupus, including nephritis, serositis, and thrombocytopenia, were associated with readmission. Readmission rates varied significantly between hospitals after accounting for patient‐level clustering and hospital case mix. We also found geographic variation, with risk‐adjusted readmission rates lower in New York and higher in Florida as compared to California. Conclusion We found that ∼1 in 6 hospitalized patients with SLE were readmitted within 30 days of discharge, with higher rates among historically underserved populations. Significant geographic and hospital‐level variation in risk‐adjusted readmission rates suggests potential for quality improvement.
Reticular Neoplasms Induced in DBA/2 and CBA Mice by Intraperitoneal Injections of Mineral Oil2
Authors: R. Rask-Nielsen, P. Ebbesen
Journal: JNCI Journal of the National Cancer Institute (1965)

A total of 1.5 ml of mineral oil, Primol D, was given in 3 intraperitoneal injections into 36 DBA/2 and 12 CBA female mice, most of which survived for more than 15 months. Small granulomatous nodules containing oil droplets developed intraperitoneally in all mice. Oil droplets were also found in the liver, spleen, and lungs. Of the 36 DBA/2 mice, 15 (42%) developed reticulosarcomatous growths of Type A of Dunn in some of the peritoneal nodules. In addition, leukemic infiltrations of varying degrees of severity were found in the liver and less frequently in other organs. Only one mouse had a definite myeloid leukemia; 2 mice showed incipient myeloid leukemia (or myeloid hyperplasia), one associated with plasma cellular infiltrations. Three mice developed plasma cell leukemia with some admixture of myeloid cells, and 2 developed lymphocytic leukemia, the latter considered spontaneous. Thus, a total of 21 of 36 DBA/2 mice (58%) responded in some way or other to the deposited mineral oil. In the 12 CBA animals one reticulum cell sarcoma, probably of Type B of Dunn and one most likely spontaneous lymphocytic leukemia were found. Successful transplantations from 3 reticulum cell sarcomas and from the myeloid leukemia maintained the morphology of the primary hosts. The results are compared with those obtained with injection of mineral oil into BALB/c mice, and the importance of the genetic constitution of the mice is emphasized. The multicentric development of the reticulosarcomatous growths in the peritoneal nodules and the potentiality of the hepatic perivascular reticulum to transform into various types of reticular cells under the influence of the mineral oil are suggested.
Identification of Malassezia species from patient skin scales by PCR-RFLP
Authors: G. Gaitanis, A. Velegraki, E. Frangoulis, A. Mitroussia, A. Tsigonia, A. Tzimogianni, A. Katsambas, N.J. Legakis
Journal: Clinical Microbiology and Infection (2002)
Descending necrotizing mediastinitis: A 10-year surgical experience
Authors: Kalliopi Athanassiadi, Ilias Samiotis, Dimitris Lioumpas, Vassili Karameri, Konstantina Sotiriou
Journal: European Respiratory Journal (2013)

OBJECTIVE: Early diagnosis and aggressive surgical drainage are very important for successful treatment of descending necrotizing mediastinitis. We report our 10-year experience of managing this devastating disease, focusing on the multidisciplinary management.  METHODS: Between January2003 and January 2013, we retrospectively reviewed 11 patients with descending necrotizing mediastinitis due to odontogenic abscess or retropharyngeal or parapharyngeal abscess, who were treated by a single surgeon. Four women and 7 men were included in this study. The mean age was 59.7 +/- 15.2 years. Cervical drainage was performed in the involved area in all patients. Combined surgical and massive antibiotic treatment according to the bacteriological findings was carried out. The methods for mediastinal drainage included transcervical in all cases along with thoracotomy with radical surgical debridement of the mediastinum and excision of necrotic tissue only in 3 cases where the mediastinitis was extending below T4 in the CT scan. Permanent suction drainage and lavage of the abscess cavities were used. In cervical phlegmonas the surgical wounds were left open against anaerobic infection.  RESULTS: Mortality raised to 18%. Two patients with uncontrolled sepsis at the time of presentation died after a prolonged stay at the ICU.  CONCLUSION: Descending mediastinitis is still a life-threatening complications. The great importance of the early surgical treatment of neck infections, the use of antibiotics covering both aerobic and anaerobic bacterial spectrum and the good coordination between otolaryngologists, surgeons, reanimators and microbiologists is manadatory to the outcome of these patients.
Clinical impact of anaemia in patients with chronic obstructive pulmonary disease: Results from ECLIPSE study
Authors: Mitja Lainscak, Lisa Edwards, Stefan Anker, Courtney Crim, Stephen Rennard, Emiel Wouters, William MacNee
Journal: European Respiratory Journal (2012)

Anaemia is common in chronic diseases, associated with poor outcomes. In COPD, data on the effects of anaemia are scarce and inconclusive. We assessed the prevalence, incidence and clinical impact of anaemia in the ECLIPSE study,a large well characterised COPD cohort.

Methods. We included patients with haemoglobin (Hb) value at baseline and at least one measurement during 3-years follow-up. Anaemia was defined as Hb <13g/L in men and <12 g/L in women.

Results. In 2097 COPD patients (63±7years, 65% men, postbronchodilator FEV1 48±16%) anaemia was recorded at baseline in 123 patients (6%, Hb 120.9±49.9 g/dl), who were older (67±7 vs 63±7 years, p<0.001), and had greater functional limitation as assessed by 6-minute walking distance, mMRC dyspnoea score, SGRQ and BODE index (p<0.05), than those without anaemia. They had greater cardiovascular, diabetes, peptic ulcer comorbidities (p<0.05) and had higher systemic levels of inflammatory markers (p<0.01). During follow-up, more patients with anaemia died (24% vs 9%, p<0.001),with no significant differences in FEV1 decline, exacerbation rates or hospitalizations compared to those without anaemia. New onset anaemia developed in 285/1974 (14%) of patients during follow up. These patients had a similar pattern of functional limitation, comorbidity and systemic inflammation as patients with anaemia at baseline, but had higher exacerbation rates and hospitalizations (p<0.05), but a similar proportion of deaths (9%).

Conclusions . In the ECLIPSE COPD cohort, anaemia was present or developed in 19% of patients and was associated with functional limitations and poor outcomes.

Supported by GlaxoSmithKline (SCO104960, [NCT00292552][1]).

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00292552&atom=%2Ferj%2F40%2FSuppl_56%2FP211.atom
Many faces of neursarcoidosis
Authors: Nelson Marçal, Margarida Aguiar, Joana Pimentel, Inês Claro, Ana Cristina Mendes, Antonio Bugalho de Almeida
Journal: European Respiratory Journal (2011)

Nervous system infiltration occurs in approximately 5% of patients with sarcoidosis; it is associated with a less favorable course and accounts for a disproportionate amount of disability.  Our aim was to evaluate clinical manifestations of patients with neurosarcoidosis, their demographics, and form of presentation, extra-neurological involvement and therapy.  We performed a retrospective analysis of 23 patients9 clinical records (5,1%) out of a total of 450 with biopsy proven or high clinical suspicion of sarcoidosis with neurological involvement. Five males, 20 caucasian, mean age of 47,8±9,9 years with mean follow-up of 10,4±8,2 years (min. 1 and max. 23 years). At presentation, in 10 patients, neurologic symptoms. Twenty-one patients had further involvement of at least a second organ and 18 also had pulmonary compromise.  Most patients (n=15) had III, IV, VI or VII cranial nerve palsy conditioning dysarthria and diplopia. Three patients had peripheral neuropathy conditioning mainly paresthesia, two had headache, one had spastic paraparesis and one had extensive optic chiasm involvement conditioning almost total blindness. One of these patients had osmotic receptor dysregulation conditioning high sodium levels, a condition never yet reported in sarcoidosis and another presented with a rapidly progressive dementia  All patients except for 3 were submitted to steroid therapy and 5 still required the association of a second imunosupressor. Three patients were treated with Infliximab, 2 with total resolution of neurological symptoms.  In conclusion, most patients had localized disease affecting essentially the base of the brain however sarcoidosis9 neurologic manifestations can be diverse and disabling, conditioning an aggressive approach.