tbuckley/cabot-search huggingface dataset:
The Risk of In-Transit Melanoma Metastasis Depends on Tumor Biology and Not the Surgical Approach to Regional Lymph Nodes
Authors: Timothy M. Pawlik, Merrick I. Ross, John F. Thompson, Alexander M.M. Eggermont, Jeffrey E. Gershenwald
Journal: Journal of Clinical Oncology (2005)

Although the majority of patients newly diagnosed with cutaneous melanoma present with clinically negative regional nodal basins, many of these patients harbor occult regional lymph node metastases. Historically, the initial treatment strategy for patients with clinically negative regional lymph nodes has been controversial. Treatments have included elective dissection, the goal of which was improved survival, and observation followed by dissection when clinical relapse developed. A more rational selective approach, involving lymphatic mapping and sentinel lymph node biopsy (SLNB), has now been widely adopted. SLNB is a minimally invasive technique for identifying the approximately 20% of patients who harbor occult metastatic disease and who may therefore benefit from comple
Ultrasound may promote fracture healing but this does not necessarily accelerate return of function
Authors: Louella O'Herlihy, Mark R Elkins
Journal: British Journal of Sports Medicine (2013)

▸  Busse JW , Kaur J, Mollon B, et al. BMJ , 2009; 338 :b351.

Bone fractures are common, affecting about six million people in North America annually1 with associated pain, loss of function and socioeconomic expenditure. Although spontaneous union of uncomplicated fractures is typically described as occurring within 6–8 weeks, the duration of fracture healing varies by the site and type of fracture.2–4 Bone mineral density, smoking and underlying disease can further affect the healing time.5–7 While most fractures unite spontaneously, 5–10% of long-bone fractures having delayed healing or do not unite, although again the characteristics of the fracture and the patient can influence this.8 ,9 Delayed and non-union exacerbate the morbidity, dependence and lost productivity associated with fractures.

Regardless of the predicted healing time for individual patients, stimulation of bone formation at the fracture site may reduce the healing time and the risk of non-union. Furthermore, it could reduce the total duration for which distraction osteogenesis needs to be performed.10 Many interventions have been proposed as potential stimulators of bone formation including medication, growth hormone, electric currents, magnetic fields, shockwave therapy and ultrasound.11–14 Ultrasound might induce fracture healing by applying mechanical forces at the fracture site.15

This systematic review was performed to determine the effect of low-intensity-pulsed ultrasound for healing of fractures.

Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and HealthSTAR were searched using terms for fracture healing , callus , remodelling …
Cell-Signaling Evidence for Adenosine Stimulation of Coronary Smooth Muscle Proliferation via the A <sub>1</sub> Adenosine Receptor
Authors: Jianzhong Shen, Stephen P. Halenda, Michael Sturek, Peter A. Wilden
Journal: Circulation Research (2005)

For decades, it has been thought that adenosine is exclusively antimitogenic on vascular smooth muscles via the A2-type adenosine receptor. Recently, we have demonstrated that adenosine stimulates proliferation of porcine coronary artery smooth muscle cells (CASMC) through the A1 adenosine receptor. However, the cell-signaling mechanisms underlying A1 receptor-mediated CASMC proliferation in response to adenosine have not been defined. Here, we show that in cultured CASMC, adenosine stimulates phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK), and AKT in a concentration- and time-dependent manner. This effect is fully mimicked by NECA (nonselective agonist), largely mimicked by CCPA (A1-selective agonist), weakly mimicked by 2-Cl-IB-MECA (A3-selective agonist), but not by CGS21680 (A2A-selective agonist), indicating that adenosine signals strongly via the A1 receptor to these mitogenic signaling pathways. This interpretation is supported by the finding that adenosine- and CCPA-induced phosphorylation of ERK, JNK, and AKT are inhibited by pertussis toxin (inactivator of Gi proteins) and by DPCPX (A1-selective antagonist), but not by SCH58261, MRS1706, and VUF5574 (A2A-, A2B-, and A3-selective antagonists, respectively). In addition, adenosine- and CCPA-induced phosphorylation of ERK, JNK, and AKT is inhibited, respectively, by U0126, PD98059 (mitogen-activated protein kinase kinase inhibitors), SP600125 (JNK kinase inhibitor), and wortmannin (phosphatidylinositol 3-kinase inhibitor). Furthermore, these kinase inhibitors abolish or diminish adenosine- and CCPA-induced increases in the rate of cellular DNA synthesis, bromodeoxyuridine incorporation, protein synthesis, and cell number. We conclude that adenosine activates the ERK, JNK, and phosphatidylinositol 3-kinase/AKT pathways primarily through the A1 receptor, leading to CASMC mitogenesis.
Contribution of free play towards physical activity guidelines for New Zealand primary school children aged 7-9 years
Authors: S E McGall, M R McGuigan, C Nottle
Journal: British Journal of Sports Medicine (2009)

the objectives of this study were to investigate children's physical activity patterns to gain comparisons between home and school and to determine whether the current physical activity guidelines of 60 min of moderate to vigorous physical activity (MVPA) daily were being met.participants were recruited from two New Zealand primary schools (60 children, mean age (SD) 8.3 (0.7) years). Physical activity was measured for seven consecutive days using Actigraph accelerometers. Total activity and average counts were determined for school playtime, after school and weekends. Differences between average counts for these intervals were compared using the t statistic. Time and percentage of time spent were categorised into the activity thresholds: sedentary (<100), light (101-299), moderate (3000-5200) and vigorous (>5200). Total activity for each day was also determined.no child met the recommended 60 min of MVPA daily during the investigation. Compared to school playtime, activity counts were lower by 36% (CI 25% to 45.5%, p<0.001, effect size (ES)=-1.29) after school, 50.1% (CI 37% to 60.5%, p<0.001, ES=-2.01) on Saturday and 57.4% (CI 46.3% to 66.3%, p<0.001, ES=-2.47) on Sunday. Mean results showed children spent 91-96% of their time engaged in light or sedentary activities. Even during school playtime, where the children were most active, only 8 of 80 min were spent engaged in MVPA.this study found activity levels were considerably lower than the recommended guidelines, and children were more active during school playtime compared to after school and weekends.
Implantation of Bone Marrow Mononuclear Cells Into Ischemic Myocardium Enhances Collateral Perfusion and Regional Function via Side Supply of Angioblasts, Angiogenic Ligands, and Cytokines
Authors: Hiroshi Kamihata, Hiroaki Matsubara, Takashi Nishiue, Soichiro Fujiyama, Yoshiaki Tsutsumi, Ryozo Ozono, Hiroya Masaki, Yasukiyo Mori, Osamu Iba, Eriko Tateishi, Atsushi Kosaki, Satoshi Shintani, Toyoaki Murohara, Tsutomu Imaizumi, Toshiji Iwasaka
Journal: Circulation (2001)

Background Bone marrow implantation (BMI) was shown to enhance angiogenesis in a rat ischemic heart model. This preclinical study using a swine model was designed to test the safety and therapeutic effectiveness of BMI. Methods and Results BM-derived mononuclear cells (BM-MNCs) were injected into a zone made ischemic by coronary artery ligation. Three weeks after BMI, regional blood flow and capillary densities were significantly higher (4.6- and 2.8-fold, respectively), and cardiac function was improved. Angiography revealed that there was a marked increase (5.7-fold) in number of visible collateral vessels. Implantation of porcine coronary microvascular endothelial cells (CMECs) did not cause any significant increase in capillary densities. Labeled BM-MNCs were incorporated into ≈31% of neocapillaries and corresponded to ≈8.7% of macrophages but did not actively survive as myoblasts or fibroblasts. There was no bone formation by osteoblasts or malignant ventricular arrhythmia. Time-dependent changes in plasma levels for cardiac enzymes (troponin I and creatine kinase-MB) did not differ between the BMI, CMEC, and medium-alone implantation groups. BM-MNCs contained 16% of endothelial-lineage cells and expressed basic fibroblast growth factor≫vascular endothelial growth factor&gt;angiopoietin 1 mRNAs, and their cardiac levels were significantly upregulated by BMI. Cardiac interleukin-1β and tumor necrosis factor-α mRNA expression were also induced by BMI but not by CMEC implantation. BM-MNCs were actively differentiated to endothelial cells in vitro and formed network structure with human umbilical vein endothelial cells. Conclusions BMI may constitute a novel safety strategy for achieving optimal therapeutic angiogenesis by the natural ability of the BM cells to secrete potent angiogenic ligands and cytokines as well as to be incorporated into foci of neovascularization.
Abraham (“Abe”) Guz: a life devoted to breathing and breathlessness
Authors: Kian Fan Chung, Martyn Partridge, Terry D. Tetley
Journal: European Respiratory Journal (2014)

It is with great sadness that we inform you that Abe Guz passed away on April 11, 2014 at the age of 84. Abe Guz was Professor of Medicine at the Charing Cross Hospital Medical School in London, UK between 1973 and 1982, and subsequently became Professor and Head of the Department of Medicine of the joint Charing Cross and Westminster Medical School, University of London until September 1994. He will be remembered for his contribution to our understanding of breathing control and of breathlessness.

Abe Guz was born in 1929 in East London to Russian Jewish parents who came to England in the 1920s. In 1947, he attended Charing Cross Hospital Medical School where he was a brilliant student, winning the Gold Medal of the School and graduating with the highest honours in medicine and surgery. After serving in the army for 2 years as part of National Service as Chief Medical Officer in Germany, Abe returned to London as a senior house officer at the Hammersmith Hospital. Like many budding clinical scientists of the time, he shortly left for the USA to become a Research Fellow at Harvard University and then Senior Fellow at the Cardiovascular Research Institute (CVRI), University of California San Francisco. He trained under Julius Comroe whom he said taught him to “think” and whom he described as someone who had “the great facility of summarising what was not known”. At the CVRI, he collaborated with Julien Hoffman, a paediatric cardiologist, to develop methods of measuring blood flow and cardiac output.

Abe returned to the UK in 1961, as Assistant Lecturer in the newly created Department …
Tyrosine Kinase Inhibitor Enhances the Bioavailability of Oral Irinotecan in Pediatric Patients With Refractory Solid Tumors
Authors: Wayne L. Furman, Fariba Navid, Najat C. Daw, M. Beth McCarville, Lisa M. McGregor, Sheri L. Spunt, Carlos Rodriguez-Galindo, John C. Panetta, Kristine R. Crews, Jianrong Wu, Amar J. Gajjar, Peter J. Houghton, Victor M. Santana, Clinton F. Stewart
Journal: Journal of Clinical Oncology (2009)

Purpose To assess the maximum-tolerated dosages (MTDs), and dose-limiting toxicities (DLTs) of the epidermal growth factor receptor inhibitor gefitinib and of intravenous (IV) irinotecan when administered together in children with refractory solid tumors. To assess the effect of gefitinib on the pharmacokinetics of IV irinotecan and on the bioavailability of a single oral dose of irinotecan. Patients and Methods IV irinotecan (15 or 20 mg/m 2 ) was given daily for 5 days of 2 consecutive weeks. Oral gefitinib (150 or 112.5 mg/m 2 ) was concomitantly given daily for 12 or 21 days. A single oral dose of irinotecan was given on day 9 of course 2 to allow pharmacokinetic analysis. Results The study enrolled 29 patients with recurrent solid tumors. The 21-day regimen of oral gefitinib with irinotecan was not tolerated. Diarrhea was the most common DLT. The MTD of the combination regimen was 15 mg/m 2 /d of IV irinotecan for 5 days of 2 consecutive weeks and 112.5 mg/m 2 /d of gefitinib given for 12 days. Gefitinib increased the bioavailability of oral irinotecan by four-fold over that observed in historical controls (median, 0.09 v 0.42; P &lt; .000001), reducing the apparent clearance (an inverse measure of exposure) of irinotecan and SN-38 by 37% and 38%, respectively (P &lt; .0001). A partial response was observed in a patient with refractory Ewing sarcoma. Conclusion IV irinotecan given with 12 days of oral gefitinib is well tolerated in children. We observed one partial response. Gefitinib significantly enhances the bioavailability of oral irinotecan. This combination warrants further investigation, particularly with orally administered irinotecan.
Cardiorespiratory strain of a five day jogging relay.
Authors: J Oksa, S Rissanen, V Martikkala
Journal: British Journal of Sports Medicine (1995)

The heart rates of 14 voluntary subjects (seven male and seven females) participating in a 5 d jogging relay were recorded. The jogging speed was controlled at 3.0 m.s-1 on average. The heart rate measurements were related to cardiorespiratory responses obtained during VO2max test on a treadmill. The mean (s.d.) VO2max values were 53(2) and 48(2) ml.kg-1.min-1 and the anaerobic threshold was 42(1) and 38(2) ml.kg-1.min-1 for male and female subjects respectively. During the relay the mean(s.d) heart rate values of male and female subjects were 150(1), and 167(3) beats.min-1 (P < 0.001), corresponding to 68(1) and 76(2)% VO2max (P < 0.01) as calculated from the individual HR/VO2 regression equations. The jogging time above anaerobic threshold heart rate level was 9(3)% for the males and 43(7)% for the females (P < 0.001) of the total jogging time. The results indicate that even in a leisure oriented jogging event, cardiorespiratory strain can be rather high and that the strain can be significantly higher for female than for male subjects. The determination of the anaerobic threshold as well as VO2max is important when quantifying the level of cardiorespiratory strain of exercise.
Comment on Tesfaye et al. Mechanisms and Management of Diabetic Painful Distal Symmetrical Polyneuropathy. Diabetes Care 2013;36:2456–2465
Authors: D. Scott Nickerson
Journal: Diabetes Care (2014)

The excellent discussion by Tesfaye et al. (1) of management of diabetic sensorimotor polyneuropathy (DSPN) pain fails to include mention of any alternatives for the large minority of cases that do not respond to or cannot tolerate available pharmacological interventions. Riazi et al. (2) and others (3) have pointed out that ultrasonographic nerve enlargement is present in these neuropathy cases and might actually be used as a bedside diagnostic tool. Meta-analyses (4,5) have reviewed the favorable response of DSPN patients to nerve decompression (ND) by surgical external neurolysis at the several fibro-osseous tunnel …
Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data
Authors: A D. Edwards, P. Brocklehurst, A. J Gunn, H. Halliday, E. Juszczak, M. Levene, B. Strohm, M. Thoresen, A. Whitelaw, D. Azzopardi
Journal: BMJ (2010)

<b>Objective</b> To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. <b>Design</b> A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. <b>Data sources</b> Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. <b>Review methods</b> Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. <b>Results </b>We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months’ follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P&lt;0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). <b>Conclusions</b> In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.
Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial
Authors: Robert A Byrne, Franz-Josef Neumann, Julinda Mehilli, Susanne Pinieck, Britta Wolff, Klaus Tiroch, Stefanie Schulz, Massimiliano Fusaro, Ilka Ott, Tareq Ibrahim, Jörg Hausleiter, Christian Valina, Jürgen Pache, Karl-Ludwig Laugwitz, Steffen Massberg, Adnan Kastrati
Journal: The Lancet (2012)
How Do We Reduce the Number of Cases of Missed Postpartum Diabetes in Women With Recent Gestational Diabetes Mellitus?
Authors: Ute M. Schaefer-Graf, Silke Klavehn, Reinhard Hartmann, Helmut Kleinwechter, Norbert Demandt, Marianne Sorger, Siri L. Kjos, Klaus Vetter, Michael Abou-Dakn
Journal: Diabetes Care (2009)

OBJECTIVE Up to 30% of women with recent gestational diabetes mellitus (GDM) remain glucose intolerant after delivery. However, the rate of postpartum oral glucose tolerance tests (ppOGTTs) is low. Our aim in this study was to develop a model for risk assessment to target women with high risk for postpartum diabetes. RESEARCH DESIGN AND METHODS In 605 Caucasian women with GDM, antenatal obstetrical and glucose data and the glucose data of the ppOGTTs performed 13 weeks (median) after delivery were prospectively collected. RESULTS A total of 132 (21.8%) women had an abnormal ppOGTT (2.8% impaired fasting glucose, 13.6% impaired glucose tolerance, and 5.5% diabetes). Independent risk factors were BMI ≥30 kg/m2 (prevalence of abnormal ppOGTT 36.0 vs. 17.3%), gestational age at diagnosis &amp;lt;24 weeks (32.4 vs. 18.0%), 1-h antenatal value &amp;gt;200 mg/dl (11.1 mmol/l) (35.2 vs. 14.8%), and insulin therapy (30.3 vs. 14.5%). The prevalence of an abnormal ppOGTT was assessed according to the number of risk factors: 0, 9.2% (14 of 153); 1, 13.4% (25 of 186); 2, 28.5% (43 of 151); 3, 45.6% (26 of 57); and 4, 68.4% (13 of 19). Subjects were divided according to a significant increase of prevalence and risk for a ppOGTT: low risk (59.9% of subjects), &amp;lt;2 risk factors, 11.6%, odds ratio 1.3; intermediate risk, 2 risk factors, 28.5%, 4.0; and high risk, &amp;gt;2 risk factors, 51.3%, 10.5. The intermediate/high-risk group included 86.6% of those with diabetes and 67% of all those with abnormal ppOGTTs. CONCLUSIONS Women with ≥2 risk factors have a high risk for an abnormal ppOGTT, and 86% of postpartum diabetes is diagnosed within this group. Targeting women for ppOGTTs based on a risk assessment using available antenatal risk factors might reduce the number of missed cases of postpartum diabetes.
Pentoxifylline Attenuates Tubulointerstitial Fibrosis by Blocking Smad3/4-Activated Transcription and Profibrogenic Effects of Connective Tissue Growth Factor
Authors: Shuei-Liong Lin, Ruey-Hwa Chen, Yung-Ming Chen, Wen-Chih Chiang, Chun-Fu Lai, Kwan-Dun Wu, Tun-Jun Tsai
Journal: Journal of the American Society of Nephrology (2005)

Pentoxifylline (PTX) is a potent inhibitor of connective tissue growth factor (CTGF), but its underlying mechanism is poorly understood. Here, it was demonstrated that PTX inhibited not only TGF-beta1-induced CTGF expression but also CTGF-induced collagen I (alpha1) [Col I (alpha1)] expression in normal rat kidney fibroblasts (NRK-49F) and alpha-smooth muscle actin expression in normal rat kidney proximal tubular epithelial cells (NRK-52E). Furthermore, PTX attenuated tubulointerstitial fibrosis, myofibroblasts accumulation, and expression of CTGF and Col I (alpha1) in unilateral ureteral obstruction kidneys. The mechanism by which PTX reduced CTGF in NRK-49F and NRK-52E was investigated. Activation of Smad3/4 was essential for TGF-beta1-induced CTGF transcription, but PTX did not interfere with TGF-beta1 signaling to Smad2/3 activation and association with Smad4 and their nuclear translocation. However, PTX was capable of blocking activation of TGF-beta1-induced Smad3/4-dependent reporter as well as CTGF promoter, suggesting that PTX affects a factor that acts cooperatively with Smad3/4 to execute transcriptional activation. It was found that PTX increased intracellular cAMP and caused cAMP response element binding protein phosphorylation. The protein kinase A antagonist H89 abolished the inhibitory effect of PTX on Smad3/4-dependent CTGF transcription, whereas dibutyryl cAMP and forskolin recapitulated the inhibitory effect. In conclusion, these results indicate that PTX inhibits CTGF expression by interfering with Smad3/4-dependent CTGF transcription through protein kinase A and blocks the profibrogenic effects of CTGF on renal cells. Because of the dual blockade, PTX potently attenuates the tubulointerstitial fibrosis in unilateral ureteral obstruction kidneys.
Induction of Apoptosis and Down-Regulation of Bcl-XL in Cancer Cells by a Novel Small Molecule, 2[ [3-(2,3-Dichlorophenoxy)propyl]amino]ethanol
Authors: Shuhong Wu, Hongbo Zhu, Jian Gu, Lidong Zhang, Fuminori Teraishi, John J. Davis, Dietmar A. Jacob, Bingliang Fang
Journal: Cancer Research (2004)

Abstract In a search for new anticancer agents, we identified that 2[[3-(2,3-dichlorophenoxy) propyl]amino]ethanol (2,3-DCPE) induced apoptosis more effectively in various cancer cells than in normal human fibroblasts. We further evaluated the cell-killing effects of this compound in vitro in several human cancer cell lines and normal human fibroblasts. A cell viability assay showed that IC50s for human colon cancer cell lines LoVo and DLD-1, for human lung cancer cell lines H1299 and A549, and for normal human fibroblasts were 0.89, 1.95, 2.24, 2.69, and 12.6 μm, respectively. Subsequent studies revealed that 2,3-DCPE could cause cleavage of caspase-8, caspase-3, caspase-9, and poly(ADP-ribose) polymerase and release of cytochrome c in cancer cells but not in normal human fibroblasts. Our data also showed that 2,3-DCPE attenuated the protein level of Bcl-XL and that apoptosis induction by 2,3-DCPE could be blocked by enforced overexpression of Bcl-XL. Our results suggest that 2,3-DCPE might be a potential new anticancer agent.