tbuckley/cabot-search huggingface dataset:
Definitive treatment of intermediate stage laryngeal squamous cell (SCC/L) cancer with chemotherapy (CT)
Authors: M. S. Kies, J. S. Lewin, E. M. Diaz, A. M. Gillenwater, B. S. Glisson, L. E. Ginsberg, G. L. Clayman, S. Taylor, K. A. Gillaspy, F. R. Khuri
Journal: Journal of Clinical Oncology (2004)

5533 Background: Surgery and/or radiotherapy (RT) are definitive local treatment modalities for intermediate stage SCC/L. Methods: We have evaluated paclitaxel (T) 175/mg/m2 day 1, ifosfamide (I) 1000mg/m2/days 1–3 (with mesna), and cisplatin (P) 60mg/m2 day 1 for previously untreated patients (pts) with SCC/L, stage T2 –4, N0 –1, M0. To be eligible, the primary tumor had to be considered resectable with conservation laryngeal surgery. After TIP x 3, pts achieving partial disease regression (PR) proceeded to surgery. Patients achieving a histologic complete response (CR) received an additional 3 CT cycles and no local treatment. A preliminary report was provided previously (FRK Proc ASCO #906, 2002). This is a report of more mature results with focus on CR patients treated with chemotherapy alone. Results: From 10/97 until 8/03, 29 patients (20 M, 9 F; median age 58 years, range 20–79) were entered. Tumor stage ranged from T2 N0 - T4 N1; median follow up is 36 months. Ten pts (34%) achieved CR and 17 (59%) PR after CT. CR patients were monitored monthly. Videostroboscopy will show tumor shrinkage, normalization of mucosa, and dramatic improvement in phonatory approximation in 5 of 5 pts with true vocal cord involvement. Two of 10 CR patients have developed local recurrence, with one living and disease-free after RT. Eight pts are alive and recurrence-free. Of the entire group of 29, 6 pts have developed recurrence (6 local/regional and 1 distant). Two patients have required total laryngectomy and 3 RT. Twenty-four of 29 pts are alive and disease-free. One patient died of a second primary cancer. Conclusions: Systemic chemotherapy for intermediate stage SCC/L provides durable disease remission in some pts. This favorable early experience suggests that SCC/L is potentially curable with systemic therapy. However, treatment of larynx cancer with chemotherapy as a single modality remains highly experimental. No significant financial relationships to disclose.
Trends in chemotherapy and biologic treatment of U.S. metastatic colorectal cancer patients
Authors: K. M. Foley, P. F. Wang, S. Long, B. Barber, E. Bagalman, Z. Zhao
Journal: Journal of Clinical Oncology (2009)

6553 Background: Several long-standing chemotherapy regimens are available to treat metastatic colorectal cancer (mCRC) including: oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (FOLFOX); and Irinotecan plus 5-FU and leucovorin (FOLFIRI). More recently, new biologic therapies were approved for use in mCRC. This cohort study examines trends in first-line chemotherapy treatments for newly diagnosed mCRC patients after the introduction of capecitabine (CAP) in 2001 and the biologic therapies in 2004. Methods: Using a large, US-based administrative medical claims database of a national commercially insured population, patients with newly diagnosed mCRC were identified from 2001 to 2005. At least 6-months of patient history prior to mCRC diagnosis were required to confirm patients were newly diagnosed. Patients were followed from initial mCRC diagnosis to death, disenrollment, or 12/31/2006. Results: Total of 3,781 newly diagnosed mCRC patients were identified between 2001–2005. On average over the 5 years, 58% of patients (with annual variation ± 4% points) received chemotherapy/biologic treatment in the year following their mCRC diagnosis; mean days to initiation of chemotherapy treatment decreased from 135 to 62 between 2001–2005. In 2001, FOLFIRI (40%), 5-FU (30%), and CAP (20%) were the most prevalent first-line treatments. In 2005, first-line treatment regimens were more diverse: FOLFOX plus bevacizumab (35%), FOLFOX alone (15%), 5-FU (15%), and CAP (15%) were the most prevalent, while 33% of patients used other treatment combinations. Among mCRC patients diagnosed in 2005, 63% were treated with at least one biologic therapy in the first year after diagnosis (57% received bevacizumab; 26% received cetuximab). Conclusions: While rates of chemotherapy use remained relatively constant between 2001–2005, patients initiated chemotherapy treatment sooner after their initial diagnosis and the standard course of therapy shifted from being FOLFIRI-based to FOLFOX-based. A rapid uptake in biologic therapies occurred. The majority of newly diagnosed mCRC patients were users of biologic therapy within one year following their introduction. [Table: see text]
Late-Replicating Chromosomal Segments in Aneuploid Chinese Hamster Cell Lines as Determined by Autoradiography
Authors: Alexander F. Zakharov, Natalia A. Egolina, Eugenia S. Kakpakova
Journal: JNCI Journal of the National Cancer Institute (1966)

Chromosome duplication in aneuploid karyotypes of 9 Chinese hamster cell lines with the modal chromosome numbers 19 to 27 was studied by autoradiography with the use of H3-thymidine. All of the aneuploid karyotypes had characteristic and invariable replicational patterns different from the normal ones. Despite their differences, all lines studied could be divided by replicational patterns into groups that correlated with grouping of lines by chromosomal changes. The hypodiploid karyotypes (3 lines with 19, 20, and 21 chromosomes) were characterized by the maintenance of the normal X1X2 chromosomes, and the presence of much additional late-replicating material in the marker subtelocentrics. The striking feature of the pseudodiploid and hyperdiploid karyotypes (6 lines with 22, 23, 24, and 27 chromosomes) was the lack of one (X2) or both (X1 and X2) typical sex elements and the appearance of some additional late-labeling elements. Most late-replicating markers could be considered as products of translocations and had late-labeled distal segments. Two alternatives are proposed to explain the origin of additional late-labeling chromosomal segments. The first is that they are material from heterochromatic arms of the X chromosomes; the second, that they are excess autosomal segments rendered genetically inactive by positive heteropyknosis. No appreciable alteration in the chronology of deoxyribonucleic acid replication was observed in those chromosomes, which were indistinguishable from their normal counterparts and were not in excess.
Recombinant human eotaxin induces oxygen radical production, Ca(2+)- mobilization, actin reorganization, and CD11b upregulation in human eosinophils via a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding protein
Authors: K Tenscher, B Metzner, E Schopf, J Norgauer, W Czech
Journal: Blood (1996)
The NHS, the private sector, and the virtual asylum
Authors: P. A Sugarman
Journal: BMJ (2002)

Emergency response to 999 calls Alternatives to the emergency 999 response can be seen in EuropeEditor-Snooks et al point out that the current 999 emergency response system has problems: increasing demand from the public and ever shorter response time targets. 1 They find a lack of evidence on alternative systems and responses in the English medical literature.By restricting their search, they overlook live examples only a few miles from these shores.France, since the mid-1960s, has had a system which incorporates many of the alternatives quoted by the authors: the Service d'Aide Medical Urgente (SAMU). 2 Calls to the control room are logged by trained telephone operators and then passed on to a "medical dispatcher": a doctor in emergency medicine, trained by the service.Medical dispatchers may simply provide medical advice to the caller, or they may decide to use one of a range of other responses to a call.These are referral to, or the dispatch of, a primary care doctor; arranging nonurgent transport by a private ambulance; urgent transport by pompiers (emergency technicians working through the fire service); or sending out a mobile intensive care unit with a doctor trained in emergency medicine.Medical dispatchers also coordinate the deployment of additional resources and decide on the most appropriate destination for a patient.In 2001 the service covering Paris received 300 000 calls (about 820 calls per day).Only 6% of the calls (50 per day) resulted in the dispatch of a mobile intensive care unit.In 16% of cases (130 per day) a primary care doctor was called.Altogether 205 calls per day were managed by the pompiers, by a private ambulance, or by giving medical advice.The remainder were
T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression
Authors: Scott J. Patterson, Anne M. Pesenacker, Adele Y. Wang, Jana Gillies, Majid Mojibian, Kim Morishita, Rusung Tan, Timothy J. Kieffer, C. Bruce Verchere, Constadina Panagiotopoulos, Megan K. Levings
Journal: Journal of Clinical Investigation (2016)

T regulatory cells (Tregs) control immune homeostasis by preventing inappropriate responses to self and nonharmful foreign antigens. Tregs use multiple mechanisms to control immune responses, all of which require these cells to be near their targets of suppression; however, it is not known how Treg-to-target proximity is controlled. Here, we found that Tregs attract CD4+ and CD8+ T cells by producing chemokines. Specifically, Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells, as Tregs from Ccl3–/– mice, which are also deficient for CCL4 production, did not promote migration. Moreover, CCR5 expression by target T cells was required for migration of these cells to supernatants conditioned by Tregs. Tregs deficient for expression of CCL3 and CCL4 were impaired in their ability to suppress experimental autoimmune encephalomyelitis or islet allograft rejection in murine models. Moreover, Tregs from subjects with established type 1 diabetes were impaired in their ability to produce CCL3 and CCL4. Together, these results demonstrate a previously unappreciated facet of Treg function and suggest that chemokine secretion by Tregs is a fundamental aspect of their therapeutic effect in autoimmunity and transplantation.
Abstract P267: Hemoglobin and Hematocrit Levels are Determinant for Exercise Tolerance in Patients with Class I to III Obesity
Authors: Agatha C Matheus, Antônio R Gagliardi, Ana E Oliveira, Evandro F Sperandio, Matheus B Nascimento, Miriane Barboza, Rodrigo P Silva, Vinicius T Lauria, Marcelo Romiti, Rodolfo L Arantes, Victor Z Dourado
Journal: Circulation (2015)

Introduction: Considerable proportion of patients with obesity presents exercise intolerance (EI) and are not able to reach maximum values of heart rate (HR) and gas exchange. This has been mainly attributed to the severity of obesity. Hypothesis: We tested the hypothesis that hematologic variables are crucial for EI in these patients, regardless of body mass index (BMI). Objective: To evaluate the associations between haematological variables and EI and cardiorespiratory fitness (CRF) in patients with classes I to III obesity. Methods: We retrospectively evaluated 103 patients with obesity (50 men, 39 ± 5 kg/m2) who underwent cardiopulmonary exercise test on a treadmill in a ramp protocol. The physiological responses were continuously monitored during the test using a gas analyzer. Oxygen uptake (V’O2), CO2 production, minute ventilation, and HR were measured. The EI was considered in the case of peak V’O2 < 83% of predicted value. Red blood cells (RBC), hemoglobin concentration (Hb), hematocrit (Ht), me...
Hypertonic saline in children with bronchiolitis
Authors: Yulia Gorinova, Olga Simonova, Yulia Lashkova, Maya Bakradze
Journal: European Respiratory Journal (2014)

Background. Acute viral bronchiolitis is the most frequent infectious disease of the lower airways in the first year of life with hospitalisation rates of about 2%. It is caused by respiratory syncitial virus in 90%. The clinical syndrome is characterized by rales, expiratory wheezing, tachypnoea, retractions, and hyperinflation. Awakening interest on treating these children with hypertonic saline has recently been observed.  Methods. 15 children (mean age 10,25 ±7 month, range 3-24 months) with wheezing were enrolled in this study: 7 patients were hospitalized on first week of disease (group 1) and 8 patients- on second (group 2). All patients were prescribed oxygen therapy, bronchodilators, inhalation steroids, antibiotics if needed and 4 ml of Hypertonic Saline (HS) 3% 2 times a day. Duration of treatment with HS was 14 days. Oxygen saturation, breathe frequency and duration of staying in department were regarded as main outcomes.  Results. Early inclusion (first week) of HS in treatment of wheezing was followed by more quick normalization of O2 saturation (p   Conclusion. Using HS inhalations at early stage promotes more quick recovery in children with wheezing.
RAP-011 improves erythropoiesis in zebrafish model of Diamond-Blackfan anemia through antagonizing lefty1
Authors: Jason Ear, Haigen Huang, Tianna Wilson, Zahra Tehrani, Anne Lindgren, Victoria Sung, Abderrahmane Laadem, Thomas O. Daniel, Rajesh Chopra, Shuo Lin
Journal: Blood (2015)
Studies on the Carcinogenic Activity of Protein-Denaturing Agents: Hepatocarcinogenicity of Dioxane&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Mary F. Argus, Joseph C. Arcos, Cornelia Hoch-Ligeti
Journal: JNCI Journal of the National Cancer Institute (1965)

The carcinogenic activity of diethylformamide, diethylacetamide, N,N′-dimethyl-N,N′-dinitrosophthalamide, heptylamine, and dioxane, compounds selected both because of their potency to denature proteins and their structural resemblance to nitrosamine derivatives, was investigated. Dioxane, when administered orally, was found to be a hepatic carcinogen, producing hepatomas in 6 of 26 rats. Diethylacetamide ingestion produced a transitional cell carcinoma of the kidney in 1 of 30 rats. Dioxane, diethylacetamide, and N,N′-dimethyl-N,N′-dinitrosoph-thalamide caused severe kidney damage. The possible relationship between the carcinogenic activity of dioxane and its capacity to alter cellular metabolic control sites by virtue of its protein-denaturing ability is discussed.
Growth in Continuous Culture, and in Hamsters, of Cells From a Neoplasm Associated With Acanthosis Nigricans
Authors: Clyde J. Dawe, William G. Banfield, Willie D. Morgan, Marilyn S. Slatick, Helen O. Curth
Journal: JNCI Journal of the National Cancer Institute (1964)

A continuous culture cell line (AN3CA) was established from a uterine neoplasm associated with the clinical syndrome of malignant acanthosis nigricans. The cells proliferated rapidly in vitro from the beginning of isolation, without entering a static or decline phase prior to continuous growth. They showed a tendency to attach poorly to glass, and often exhibited a marked “bubbling” activity (zeiosis) of the cytoplasm during interphase. The characteristics of the bubbling cytoplasm are described as seen in fixed preparations with the light microscope, in time-lapse, phase-contrast cinematography, and with the electron microscope. The activity resembled that occurring in anaphase and telophase of mitosis, in Rous virus-infected cells in culture, and in cells under a variety of other special conditions. It did not signify impending death. Tumors histologically similar to the original neoplasm grew in cheek pouches of cortisone-treated hamsters inoculated with AN3CA culture cells. These tumors were serially transplanted in 13 hamsters, representing 5 serial passages. Tumor-bearing hamsters did not show skin changes suggestive of acanthosis nigricans. Tests for production of melanocyte-stimulating hormone by culture cells were also negative. It is concluded that, if neoplasms associated with acanthosis nigricans produce a substance inducing the skin lesions, the methods used did not provide the conditions necessary to demonstrate such a substance.
Maintenance and reliever combination budesonide/formoterol therapy in asthma patients at risk of severe exacerbations: A randomised controlled trial
Authors: Mitesh Patel, Janine Pilcher, Dominick Shaw, Mark Weatherall, Richard Beasley
Journal: European Respiratory Journal (2013)

Background  The Single budesonide/formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations,but it is uncertain whether it increases risk of adverse effects due to high corticosteroid and beta-agonist doses with both short-term & cumulative exposure.  Aim  To determine the efficacy & safety of the SMART regimen in asthma patients at risk of severe exacerbations.  Methods  A 24-week,open-label,multicentre RCT randomised 303 asthma patients with a recent exacerbation to budesonide/formoterol according to SMART or a fixed-dose regimen with salbutamol as reliever (‘Standard’),with electronic monitoring of inhaler use. The primary outcome was the proportion of participants with ≥1 high beta-agonist use episode (>12 actuations/day budesonide/formoterol in SMART or >16 actuations/day salbutamol in Standard).  Results  There was no significant difference between groups in the primary outcome: SMART 84/151 (56%)  v  Standard 68/152 (45%) participants; Relative risk (95% CI) 1.24 (0.99-1.56). Days with high use [5  v  9 days/patient, Relative rate (RR) 0.58 (0.39-0.88)] & days with high use without medical review [9  v  18 days/high use patient, RR 0.49 (0.31-0.75)] favoured SMART. SMART resulted in higher ICS exposure,but reduced oral corticosteroid exposure,with no difference in composite systemic corticosteroid exposure [ratio of means 1.03 (0.86-1.22)]. SMART participants had fewer severe asthma exacerbations [35  v  66, RR 0.54 (0.36-0.82)].  Conclusion  The SMART regimen has a favourable risk/benefit profile in patients at risk of severe asthma exacerbations.  Funding  The Health Research Council of New Zealand.
NHS “winter” pressure could become norm in summer, experts warn
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The typically poorer level of performance of the NHS in England in winters will soon be normal in summer months if current trends continue, a new analysis has concluded.

The study by the health charities the Nuffield Trust and the Health Foundation analysed data from the past five years to assess the root causes of the “winter pressures” that have left the NHS struggling to cope.1

The researchers observed that problems that usually occur only in winter such as slow ambulance response times and long waits for admission to a ward were increasingly occurring at other times of year. They said that this caused the service to enter last winter (2014-15) from a historically poor starting point, and they warned that the trend could cause a “downward spiral” in NHS performance if it continued.

Despite the mild weather conditions in winter 2014-15, the report said that that winter was …
Abstract 197: Overexpression of the Na+/K+ ATPase a2 But Not a1 Isoform Attenuates Pathological Cardiac Hypertrophy and Remodeling
Authors: Robert N Correll, Petra Eder, Adam R Burr, Sanda Despa, Jennifer Davis, Donald M Bers, Jeffery D Molkentin
Journal: Circulation Research (2013)

The Na+/K+ ATPase (NKA) directly regulates intracellular Na+ levels, which indirectly regulate Ca2+ levels by controlling flux through the Na+/Ca2+ exchanger (NCX1). Elevated Na+ levels have been reported during heart failure, which permits some degree of reverse mode Ca2+ entry through NCX1 and less efficient Ca2+ clearance. To determine if lower intracellular Na+ levels would enhance forward-mode Ca2+ clearance and prevent reverse-mode Ca2+ entry through NCX1 as a protective measure, we generated cardiac-specific transgenic mice overexpressing either the NKA-α1 or α2 isoform and subjected them to pressure overload hypertrophic stimulation. We found that while increased expression of the NKA-α1 isoform had no protective effect, overexpression of NKA-α2 significantly decreased cardiac hypertrophy after pressure overload at 2, 10 and 16 weeks of stimulation. Remarkably, total NKA protein expression was not altered in either of these 2 transgenic models, as increased expression of one isoform led to a concomitant decrease in the other endogenous isoform. While total NKA ATPase activity and intracellular Na+ levels were unchanged in either overexpression model, and both showed reduced Ca2+ transient amplitudes and sarcoplasmic reticulum Ca2+ load, only NKA-α2 overexpression led to faster removal of bulk Ca2+ from the cytosol in a manner requiring NCX1 activity. This increased NCX1 activity, though correlated with improved outcome after pressure overload, did not affect signaling through Ca2+-sensitive signaling pathways such as calcineurin/nuclear factor of activated T-cells, Ca2+/calmodulin-dependent kinase II, or protein kinase Cα. Overexpression of NKA-α2 did, however, result in reduced expression of phospholemman (PLM), an inhibitor of NKA activity (when dephosphorylated) and NCX1 activity (when phosphorylated). Our results suggest that the protective effect produced by increased expression of NKA-α2 after pressure overload is likely due to: 1) Na+ regulation in a unique signaling microdomain distinct from NKA-α1, and 2) downregulation of PLM expression that removes a negative regulator of NCX1 activity, both leading to preservation of forward-mode NCX1 activity during disease, in association with optimized cardiac function.
Effect of tumor necrosis factor on the human fibrinolytic system.
Authors: P Silverman, G H Goldsmith, T R Spitzer, E H Rehmus, N A Berger
Journal: Journal of Clinical Oncology (1990)

We report the effects on the fibrinolytic system of intravenous (IV) recombinant tumor necrosis factor-alpha (rTNF-alpha) infusions in patients with advanced cancers. During a phase I clinical trial of rTNF-alpha, the plasma fibrinolytic system was closely monitored, measuring tissue-type plasminogen activator (tPA) antigen, plasminogen activator (PA) inhibitor activity, and plasma fibrinolytic activity. Thirteen patients with refractory malignancies received 40, 80, or 160 micrograms/m2 rTNF-alpha as 2-hour IV infusions. After a 1-week rest, the same dose was repeated daily for 5 days every 3 weeks for a maximum of four courses. The serum rTNF-alpha levels peaked at the completion of the IV infusion and rapidly declined thereafter, becoming unmeasurable within 1 hour in all patients. rTNF-alpha infusion markedly alters the plasma fibrinolytic system. During the 2-hour infusion, significant increases in the tPA antigen and plasma fibrinolytic activity were seen. After the infusion, PA inhibitor activity increased, neutralizing the plasma fibrinolytic activity. The increase in PA inhibitor activity was maximal 6 hours after the onset of the rTNF-alpha infusion. Fibrinolytic properties returned to pretreatment values within 24 hours. Daily rTNF-alpha infusions caused changes in plasma tPA antigen and PA inhibitor similar to those of single infusions. We conclude from these observations that the administration of rTNF-alpha in vivo to cancer patients causes profound alterations of endothelial cell-derived components of the fibrinolytic system.