tbuckley/cabot-search huggingface dataset:
2D and 3D Nanopatterning of Titanium for Enhancing Osteoinduction of Stem Cells at Implant Surfaces
Authors: Terje Sjöström, Laura E. McNamara, R. M. Dominic Meek, Matthew J. Dalby, Bo Su
Journal: Advanced Healthcare Materials (2013)

The potential for the use of well-defined nanopatterns to control stem cell behaviour on surfaces has been well documented on polymeric substrates. In terms of translation to orthopaedic applications, there is a need to develop nanopatterning techniques for clinically relevant surfaces, such as the load-bearing material titanium (Ti). In this work, a novel nanopatterning method for Ti surfaces is demonstrated, using anodisation in combination with PS-b-P4VP block copolymer templates. The block copolymer templates allows for fabrication of titania nanodot patterns with precisely controlled dimensions and positioning which means that this technique can be used as a lithography-like patterning method of bulk Ti surfaces on both flat 2D and complex shaped 3D surfaces. In vitro studies demonstrate that precise tuning of the height of titania nanodot patterns can modulate the osteogenic differentiation of mesenchymal stem cells. Cells on both the 8 nm and 15 nm patterned surfaces showed a trend towards a greater number of the large, super-mature osteogenic focal adhesions than on the control polished Ti surface, but the osteogenic effect was more pronounced on the 15 nm substrate. Cells on this surface had the longest adhesions of all and produced larger osteocalcin deposits. The results suggest that nanopatterning of Ti using the technique of anodisation through a block copolymer template could provide a novel way to enhance osteoinductivity on Ti surfaces.
Efficacy of the heater probe in peptic ulcer with a non-bleeding visible vessel. A controlled, randomised study.
Authors: J L Jaramillo, C Carmona, C Galvez, M de la Mata, G Mino
Journal: Gut (1993)

A controlled, randomised study was performed to evaluate the efficacy of treatment with heater probe in the prevention of rebleeding from peptic ulcer with a non-bleeding visible vessel. One hundred and one patients were randomised into two groups: patients to be treated by heater probe (n = 51) and controls without active treatment (n = 50). In the heater probe group rebleeding occurred in five patients (10%) v 13 (26%) in the control group (p = 0.03), with a comparative risk of 0.38 in favour of the heater probe group. The difference in proportions of successful treatment for each group was 16.2% in favour of the heater probe (95% CI = 2 to 31%). Haemorrhage directly related to heater probe treatment occurred in four patients. In three of them bleeding was easily controlled by further heater probe pulses. There were no other complications and no death in the heater probe group. One patient in the control group died of pulmonary embolism. No significant differences in the length of stay in hospital, blood transfusions, surgical rates, or death were found; the design of the study, however, precluded an adequate assessment of these variables, because the heater probe was an optional rescue treatment when high surgical risk patients rebled. These results suggest that the heater probe is an effective and safe procedure in the prevention of recurrent haemorrhage in peptic ulcer with a non-bleeding visible vessel.
BILATERAL CHYLOTHORAX AND CHYLOPERITONEUM
Authors: George J. Heppner
Journal: JAMA (1934)

Unilateral chylothorax or chyloperitoneum alone, although not frequently found, has been reported several times. To my knowledge there are no cases in the literature in which chyle has been recovered in the three major cavities of the body. <h3>REPORT OF CASE</h3> G. B., a woman, aged 19, while riding in the rumble seat of an automobile, May 14, 1933, met with an accident which resulted in a transverse fracture of the left humerus in its middle third. Cursory examination showed no other injuries, and a body spica was applied following closed reduction. Roentgenograms revealed excellent position of the fragments. At the end of two and one-half weeks a roentgen recheck showed that the fragments had slipped. A general anesthetic was given and a pin was placed through the olecranon and traction applied. Symptoms of nerve paralysis appeared and accordingly, under a second general anesthetic, an open reduction was performed three
Survival of Patients Receiving a Primary Prevention Implantable Cardioverter-Defibrillator in Clinical Practice vs Clinical Trials
Authors: Sana M. Al-Khatib, Anne Hellkamp, Gust H. Bardy, Stephen Hammill, W. Jackson Hall, Daniel B. Mark, Kevin J. Anstrom, Jeptha Curtis, Hussein Al-Khalidi, Lesley H. Curtis, Paul Heidenreich, Eric D. Peterson, Gillian Sanders, Nancy Clapp-Channing, Kerry L. Lee, Arthur J. Moss
Journal: JAMA (2013)

<h3>Importance</h3>Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown.<h3>Objective</h3>To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n = 742) and SCD-HeFT (n = 829).<h3>Design, Setting, and Patients</h3>Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score–matched patients) or the SCD-HeFT criteria (3352 propensity score–matched patients). Mortality data for the registry patients were collected through December 31, 2009.<h3>Main Outcome Measures</h3>Cox proportional hazards models were used to compare mortality from any cause.<h3>Results</h3>The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II–like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85-1.31; P = .62). Likewise, the survival among SCD-HeFT–like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97-1.38; P = .11).<h3>Conclusions and Relevance</h3>There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice.<h3>Trial Registration</h3>clinicaltrials.gov Identifier: NCT00000609
Surrogate Embryo Transfer Combined With Estrogen-Progesterone Therapy in Monkeys
Authors: Gary D. Hodgen
Journal: JAMA (1983)

The collection of in vivo fertilized monkey embryos by lavage of the normal donor's uterotubal lumens and transfer of these surrogate embryos to the uterotubal environs of long-term castrate female monkeys is described. Sequential estrogen-progesterone replacement therapy that mimics the natural ovarian-menstrual cycle was administered to the recipients, causing the development of proliferative and secretory endometrium to accommodate the perinidatory events leading to successful placentation and embryogenesis. Retrograde irrigation of the uterotubal lumens of 23 normal intact donors was performed three to four days after the estimated time of ovulation, coitus, and fertilization. Of the 17 embryos or eggs collected, some were apparently healthy, as assessed by microscopic inspection, whereas others were obviously degenerating. Eleven surrogate embryos were transferred to steroid-treated, long-term castrate female recipients; four viable pregnancies were detected by measurement of chorionic gonadotropin, all concluding with uneventful deliveries of normal live neonates at term. These findings demonstrate the feasibility of establishing and maintaining normal pregnancy by combining surrogate embryo transfer with an exogenous steroid hormone regimen, even in the complete absence of ovarian function. The clinical implications of these primate studies may be far-reaching because they indicate new potential for childbearing by otherwise infertile or sterile women who have a competent uterus but lack the hormonal milieu provided by ovarian follicular maturation and corpus luteum function in the normal menstrual cycle. (<i>JAMA</i>1983;250:2167-2171)
Fibrosis-dependent mechanisms of hepatocarcinogenesis
Authors: David Y. Zhang, Scott L. Friedman
Journal: Hepatology (2012)

Hepatocellular carcinoma (HCC) is a rising worldwide cause of cancer mortality, making the elucidation of its underlying mechanisms an urgent priority. The liver is unique in its response to injury, simultaneously undergoing regeneration and fibrosis. HCC occurs in the context of these two divergent responses, leading to distinctive pathways of carcinogenesis. In this review we highlight pathways of liver tumorigenesis that depend on, or are enhanced by, fibrosis. Activated hepatic stellate cells drive fibrogenesis, changing the composition of the extracellular matrix. Matrix quantity and stiffness also increase, providing a reservoir for bound growth factors. In addition to promoting angiogenesis, these factors may enhance the survival of both preneoplastic hepatocytes and activated hepatic stellate cells. Fibrotic changes also modulate the activity of inflammatory cells in the liver, reducing the activity of natural killer and natural killer T cells that normally contribute to tumor surveillance. These pathways synergize with inflammatory signals, including telomerase reactivation and reactive oxygen species release, ultimately resulting in cancer. Clarifying fibrosis-dependent tumorigenic mechanisms will help rationalize antifibrotic therapies as a strategy to prevent and treat HCC. (HEPATOLOGY 2012)
Academics question government's policy on open access to study results
Authors: K. Chinthapalli
Journal: BMJ (2013)

Academics at a seminar at the Royal Society have raised concerns over the forthcoming open access policy developed by the government and Research Councils UK.

Frederick Friend, honorary director of scholarly communication at University College London, who spoke at the event on 5 February, said “The UK government’s hasty decision to prioritise open access through the payment [by authors] of article processing charges rather than through long established repositories leaves the UK in an isolated position vis-a-vis open access developments in other countries and with an extra bill for the taxpayer in a time of austerity. 

“The UK taxpayer has also lost out through the additional payments to the high profit publishers for …
Are community mental health teams providing an equitable service? Comparison of source of referrals with inpatient care
Authors: R. Laugharne, S. Fleminger
Journal: BMJ (1996)

Some researchers have suggested that community mental health teams may have policies that result in those most in need not receiving priority for services and may thus not provide an equitable service.1 2 Referral practices of general practitioners have been suggested as a source of inequity.3 4 We investigated the factors affecting which patients are referred to a community mental health team by comparing the demographic characteristics of people referred to one community team with those of patients being admitted to hospital and also with the general population.

and results

The community mental health team serves a multiethnic population of 52 059 (of whom 32 783 are aged 15-64) in a deprived inner city area. It …
Theme issue for patients: Negative stereotypes are becoming ingrained in national psyche
Authors: R. McConvey
Journal: BMJ (2003)

EDITOR–I found the patients' issue thoroughly depressing.1 As a doctor in training, I am presented, on a daily basis, with evidence implying that doctors are, variously, self serving, arrogant, poor communicators, unconcerned with their patients, lazy, insufficiently expert, dangerous, negligent, in the pay of big business, reactionary, Luddite, …
Variant of Hepatitis B Virus with Primary Resistance to Adefovir
Authors: Oliver Schildgen, Hueseyin Sirma, Anneke Funk, Cynthia Olotu, Ulrike C. Wend, Heinz Hartmann, Martin Helm, Jürgen K. Rockstroh, Wulf R. Willems, Hans Will, Wolfram H. Gerlich
Journal: New England Journal of Medicine (2006)

The reverse-transcriptase inhibitor lamivudine (Zeffix, GlaxoSmithKline) is often used to treat chronic infection with hepatitis B virus (HBV) until resistance develops. Treatment may then be switched to the reverse-transcriptase inhibitor adefovir (Hepsera, Gilead), which has a lower frequency of resistance. Here, we describe three cases of primary adefovir resistance that were sensitive to tenofovir (Viread, Gilead). All three cases involved a rare HBV variant with a valine at position 233 of the reverse-transcriptase domain instead of isoleucine (rtI233V), as in the wild-type virus. This HBV variant also displayed resistance to adefovir and sensitivity to tenofovir in vitro.
Dextroamphetamine-Sulfate-Induced Dyskinesias
Authors: Richard H. Mattson
Journal: JAMA (1968)

Dyskinesia developed in four patients soon after the administration of therapeutic doses of dextroamphetamine sulfate. The movements were tic-like, dystonic, and similar to those occasionally produced by phenothiazines, and they promptly disappeared when the use of the drug ceased. They probably represented idiosyncratic reactions rather than extension of the pharmacologic effects of amphetamines. It is possible that the dextroamphetamine unmasked a subclinical extrapyramidal disorder in these patients.
Abstract 5128: Incidence of Stroke Among Patients With Paroxysmal Supraventricular Tachycardia
Authors: Béatrice Brembilla-Perrot, Pierre Yves Zinzius, Etienne Aliot, Hugues Blangy, Laurent Groben, Lucian Muresan, Sonia Magalhaes, Daniel Beurrier
Journal: Circulation (2009)

Background : Atrial fibrillation (AF) is a major cause of embolic event, but the significance of other arrhythmias remains unknown. The purpose of study was to assess the significance of unexplained stroke in patients who had apparently only supraventricular tachycardia (SVT). Population : Unexplained stroke was noted in 27 patients (group I) admitted for palpitations and electrophysiological study (EPS); they were issued from a population of 1007 patients with normal ECG in sinus rhythm, palpitations or tachycardia and with inducible SVT at EPS; 980 pts had no history of stroke (group II). Methods : EPS consisted of atrial pacing and programmed atrial stimulation in control state and if necessary after infusion of isoproterenol. Clinical and electrophysiological data of both groups were studied. Patients with stroke had a normal carotid ultrasound study and transcranial Doppler ultrasonography. Results : Patients with unexplained stroke represent 2.6 % of population with SVT. They were older than remaining patients without stroke (65±10 vs 50±19 years) (0.001). They have more frequently associated heart disease (8/27, 30 % vs 37/980, 4 %) (p &lt; 0.001). Male gender was more frequent in group I (16/27, 59 %) than in group II (361/980, 37 %) (p&lt; 0.05). Typical AV node re-entrant tachycardia was noted in 17 group I patients (65 %) and 695 group II patients (68 %) (NS); AV re-entrant tachycardia associated with a concealed accessory pathway was noted in 2 group I patients (7 %) and 169 group II patients (17 %) (NS); atypical AV node re-entrant tachycardia was more frequent in group I (7/27, 26 %) than in group II (115/980, 12 %) (p&lt;0.05). AF induction was more frequent in group I (7/27, 26 %) than in group II (36/980, 4 %) (p&lt; 0.001). Ablation was performed in 6 group I patients; one of them died from another stroke; another one died suddenly; another one developed a permanent AF. Conclusions : Unexplained stroke was a rare event in patients with paroxysmal SVT, noted in 2.6 % of this population. Old age, male gender, associated heart disease, and induction of atrial fibrillation were significant factors associated with the history of stroke in patients with SVT. They have a risk of adverse events during the follow-up.
Companies still breaking milk marketing code
Authors: J. Wise
Journal: BMJ (1998)

The International Baby Food Action Network recently released a report entitled "Breaking the Rules, Stretching the Rules 1998." This report indicates that producers of infant formula and other breast milk substitutes are failing to comply with the World Health Assembly's international code of marketing of breast milk substitutes. The Network cited violations in nearly all of 31 countries surveyed, with many occurring in health facilities. Most companies have ceased direct media advertising of infant formula in developing countries and have switched their emphasis to "follow on" formula for older babies and formula milk for mothers. Companies now send the message that breast milk is best for newborns but that the infant will soon need a "follow on" formula. The laws in 21 countries are actually tougher than the code requirements and incorporate recent World Health Assembly resolutions. Such laws are pending in an additional 22 countries.
Abstract P6-04-24: Overexpression of protein kinase C alpha differentially activates transcription factors in T47D breast cancer cells in the presence of 17β-estradiol both in the 2D and 3D environments.
Authors: TND Pham, S Asztalos, MS Weiss, LD Shea, DA Tonetti
Journal: Cancer Research (2012)

Abstract Background: Our lab has previously shown that overexpression of protein kinase C alpha (PKCα) results in a hormone independent, tamoxifen resistant phenotype in the T47D:A18 breast cancer cell line. Moreover, 17β-estradiol (E2) inhibits colony formation of T47D/PKCα in 3D Matrigel and tumor growth in vivo but not in the 2D environment (Zhang et al, Mol. Cancer Res, 2009). Differential transcriptional activation may account for the phenotypic changes observed in T47D/PKCα cells. In this study, we sought to identify transcription factors (TF) differentially activated in T47D:A18/neo versus T47D:A18/PKCα grown in 3D Matrigel in the presence and absence of E2, and compare these TFs with those activated in the 2D environment using a high-throughput screening (HTS) technology. Methods: A system for rapid, non-invasive, large scale, dynamic quantification of TF activity was developed (Weiss et al, PLoS ONE, 2010). Reporter constructs were created containing a TF binding site that preceeds a basal promoter to produce firefly luciferase (Fluc) using a lentiviral backbone. The control construct contained only the basal promoter and was used for normalization. T47D/PKCα and T47D/neo cells were infected with lentiviral reporter constructs. Cells were seeded either on top of Matrigel or without Matrigel in 384 well plates in E2-free media. After 3 days, cells were treated with either E2 (10–9M) or vehicle (0.1% ethanol). Fluc activity was assessed by bioluminescence imaging at 24, 48 and 72 hours following treatment using Xenogen IVIS Spectrum imaging system. Results: Initial findings showed differential transcriptional activities between the parental T47D/neo and T47D/PKCα cell lines at the basal level (without E2 treatment) in the 3D environment. Specifically, TFs involved in tumorigenesis (such as ETS1, STAT5) or the EMT process (such as SNAI1) were more highly activated in T47D/PKCα cells. Furthermore, E2 has a modulating effect on the activities of TFs in the two cell lines over time; observed both in the 2D and 3D environments. In particular, some TFs, such as Oct4, ETS1, and Stat5; were modulated (either induced or suppressed) by E2 only in T47D/PKCα cells. Conclusion: These findings suggest that overexpression of PKCα alters TF activity in T47D breast cancer cells both basally and in response to E2. This HTS technology allowed us to reveal the dynamic regulation of TF activation in PKCα overexpressing T47D breast cancer cells. We are now beginning to understand the mechanism whereby PKCα may mediate differential response to E2 dependent on the microenvironment. This HTS approach is likely to lead to the identification of new therapeutic targets. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-24.
Abstract 711: VEGF121/rGel inhibits prostate cancer-induced osteoblastogenesis by targeting osteoblasts and tumor neovasculature
Authors: Khalid A. Mohamedali, Zhi Gang Li, Michael W. Starbuck, Xinhai Wan, Jun Yang, Sehoon Kim, Wendy Zhang, Nora M. Navone, Michael G. Rosenblum
Journal: Cancer Research (2010)

Abstract Prostate cancer metastasis to bone usually produces bone-forming lesions although an osteolytic component is present in most cases. We have previously shown excellent efficacy against prostate cancer growth in bone in an osteolytic model (PC-3) with VEGF121/rGel, a chimeric fusion toxin of VEGF121 and the plant toxin gelonin (rGel) that targets VEGFR-1 and VEGFR-2. In the current study, we demonstrate that VEGF121/rGel systemic administration is also effective in a model of prostate cancer that displays the bone-forming phenotype when growing in the femurs of immunodeficient mice. Both murine osteoblast precursor (MC3T3) cells and primary mouse osteoblasts (PMOs) were shown to express VEGFR-1 but not VEGFR-2. VEGFR-1 mRNA expression was shown to down-regulate during osteoblast (MC3T3) differentiation. In vitro, treatment with VEGF121/rGel showed cytotoxicity against osteoblast precursor cells (IC50 = 15 nM) that was substantially reduced (IC50 &amp;gt; 1000 nM) after MC3T3 had been allowed to undergo differentiation. This suggests that the effect of VEGF121/rGel is specifically mediated by VEGFR-1. Furthermore, immunofluorescence microscopy showed that internalization of VEGF121/rGel into PMOs is VEGF121-receptor driven. In an ex vivo model of osteoblastic disease, 100 nM VEGF121/rGel significantly inhibited prostate cancer-mediated new bone formation in neonatal mouse calvaria. In vivo, systemic (iv, tail vein) administration of VEGF121/rGel significantly inhibited growth of the osteoblastic prostate cancer cell line MDA PCa 118b growing intrafemorally. Only 25% of VEGF121/rGel-treated mice showed the development of osteoblastic lesions compared to 90% of saline-treated mice. Micro-CT (µCT) analysis of isolated femurs demonstrated that intrafemoral growth of MDA PCa118b tumors caused a dramatic increase in bone volume and that treatment with VEGF121/rGel restored the bone volume fraction to normalized levels with no changes to the uninvolved contralateral femurs. H&amp;E results confirmed that the osteoblastic growth of 118b cells was severely impeded. Our results clearly demonstrate that VEGF121/rGel administration may suppress the eventual development of skeletal prostate tumors and may have significant therapeutic effect against prostate cancer-mediated osteoblastic lesions in bone. Research conducted, in part, by the Clayton Foundation for Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 711.
Long-term effects of octreotide therapy: A somatostatin analog, on in-stent restenosis
Authors: Hurkan Kursaklioglu, Atila Iyisoy, Sedat Kose, Turgay Celik, Cem Barcin, Basri Amasyali, Nadir Barindik, Ertan Demirtas
Journal: Journal of the American College of Cardiology (2003)