tbuckley/cabot-search huggingface dataset:
Intracellular Aggregation of Multimodal Silica Nanoparticles for Ultrasound-Guided Stem Cell Implantation
Authors: Jesse V. Jokerst, Christine Khademi, Sanjiv S. Gambhir
Journal: Science Translational Medicine (2013)

The promises of cardiac stem cell therapy have yet to be fully realized, in part because of poor survival and engraftment efficacy of implanted cells. Cells die after implantation owing to ischemia, inflammation, immune response, as well as mis-injection or implantation into fibrotic tissue. Imaging tools can help implant cells in areas of the heart most receptive to stem cell therapy and monitor the efficacy of treatment by reporting the viability, location, and number of implanted stem cells. We describe a multimodal, silica-based nanoparticle that can be used for cell sorting (fluorescence), real-time guided cell implantation ultrasound, and high-resolution, long-term monitoring by magnetic resonance imaging (MRI). The nanoparticle agent increased the ultrasound and MRI contrast of labeled human mesenchymal stem cells (hMSCs) 700 and 200% versus unlabeled cells, respectively, and allowed cell imaging in animal models for 13 days after implantation. The agent had no significant impact on hMSC cell metabolic activity, proliferation, or pluripotency, and it increased the production of many paracrine factors implicated in cardiac repair. Electron microscopy and ultrasound imaging suggest that the mechanism of action is in vivo aggregation of the 300-nm silica nanoparticles into larger silica frameworks that amplify the ultrasound backscatter. The detection limit in cardiac tissue was 250,000 hMSCs via MRI and 70,000 via ultrasound. This ultrasound-guided cell delivery and multimodal optical/ultrasound/MRI intracardiac cell-tracking platform could improve cell therapy in the clinic by minimizing misdelivery or implantation into fibrotic tissue.
A prospective study comparing rapid assessment of smears and ThinPrep<sup>®</sup> for endoscopic ultrasound-guided fine-needle aspirates
Authors: J. LeBlanc, R. Emerson, J. Dewitt, M. Symms, H. Cramer, L. McHenry, C. Wade, X. Wang, P. Musto, L. Eichelberger, M. Al-Haddad, C. Johnson, S. Sherman
Journal: Endoscopy (2010)

ThinPrep is often used for endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples but the sensitivity of this method is unknown. The objective of the study was to compare sensitivity and accuracy of ThinPrep versus the smear method in pancreas and lymph node samples obtained by EUS-FNA.Patients with suspected malignancy in the pancreas or lymph node underwent EUS-FNA. On-site rapid assessment of all aspirates using the smear method was performed. After rapid assessment, three additional passes from each site were submitted into ThinPrep liquid medium. Cytopathologists interpreting the smear method and ThinPrep slides were blinded to each other. The gold standard was final cytology or pathology results.A total of 130 patients (36 % women, mean age 63 years) underwent EUS-FNA of 139 sites (50 pancreas, 89 lymph node). Malignancy was confirmed in 47 pancreas samples (94 %) and 48 lymph node samples (54 %). Mean +/- SD number of passes made for the smear method was 2.6 +/- 1.3. For pancreatic cancer, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the ThinPrep versus the smear method were: 62 % versus 98 %, 100 % versus 100 %, 100 % versus 100 %, 14 % versus 75 %, and 64 % versus 98 %, respectively. For lymph nodes the values were 67 % versus 92 %, 100 % versus 98 %, 100 % versus 98 %, 72 % versus 72 %, and 82 % versus 94 %, respectively.The smear method is more sensitive and accurate than ThinPrep in detecting malignancy from EUS-FNA samples of the pancreas and lymph nodes. Smear method with on-site rapid assessment should be favored over ThinPrep in suspected malignancy.
New Source of Pseudomonas Aeruginosa in a Nursery
Authors: Miriam G. Wilson
Journal: JAMA (1961)

During routine bacteriological culturing of nursery fomites in a hospital,<i>Pseudomonas aeruginosa</i>was found in sinks and in faucet aerators. Water from these faucets was used to wash hands and to clean equipment, and may have contributed to the difficulty encountered in cleaning incubators free of Pseudomonas. The only other fomites providing a moist environment and culturing Pseudomonas were sink sponges. Handwashing within the room with the contaminated water could easily have transmitted Pseudomonas to susceptible infants. In the nursery for premature infants, one of the 7 infants had a persistent nasopharyngeal culture of Pseudomonas, which was also obtained in pure culture from his lungs after death; the other 6 were not infected. Cultures of the humidifying water, the infant's Isolette, air of his Isolette, and of the room were negative for Pseudomonas.
Boosting with recombinant vaccinia increases HPV-16 E7-Specific T cell precursor frequencies and antitumor effects of HPV-16 E7-Expressing sindbis virus replicon particles
Authors: Cheng-Tao Lin, Chien-Fu Hung, Jeremy Juang, Liangmei He, Ken-Yu Lin, Tae WooKim, T.-C. Wu
Journal: Molecular Therapy (2003)

Immunotherapy using the heterologous prime-boost regimen has emerged as an attractive approach for generating antigen-specific T-cell-mediated immune responses against tumors and infectious diseases. We have previously linked the Mycobacterium tuberculosis heat-shock protein 70 (HSP70) to the HPV-16 E7 antigen creating a chimera, E7/HSP70. We found that nucleic acid vaccines encoding E7/HSP70 can generate strong antitumor immunity. Recently, replication-defective Sindbis virus replicon particle vaccines have been considered as an important vector system for vaccine development. In this study, we assessed whether the combination of E7/HSP70 Sindbis virus replicon particles (SINrep5-E7/HSP70) and E7/HSP70 vaccinia (Vac-E7/HSP70) can further enhance E7-specific immune responses using sequential vaccination. We found that priming with SINrep5-E7/HSP70 and boosting with Vac-E7/HSP70 generated the highest number of E7-specific CD8(+) T cells and best antitumor effect compared to other combinations. Moreover, our data showed that at the dosage and route of immunization used in this study, mice treated with the Sindbis virus replicon particle prime-vaccinia boost regimen generated stronger antitumor responses compared to mice treated with the DNA prime-vaccinia boost vaccine regimen. Our results encourage the use of the Sindbis virus replicon particle prime-vaccinia boost regimen in future clinical trials.
O10.05 * FINAL ANALYSIS OF THE BELOB TRIAL (A RANDOMIZED PHASE II STUDY ON BEVACIZUMAB VERSUS BEVACIZUMAB PLUS LOMUSTINE VERSUS LOMUSTINE SINGLE AGENT IN RECURRENT GLIOBLASTOMA) AND FIRST RADIOLOGY REVIEW RESULTS
Authors: W. Taal, H. M. Oosterkamp, A. M. E. Walenkamp, H. J. Dubbink, L. V. Beerepoot, M. Hanse, J. Buter, A. Honkoop, D. Boerman, F. Y. F. Vos, W. N. M. Dinjens, R. H. Enting, M. J. B. Taphoorn, F. W. P. J. van den Berkmortel, R. Jansen, D. Brandsma, J. E. Bromberg, I. van Heuvel, R. M. Vernhout, B. van der Holt, M. J. van den Bent
Journal: Neuro-Oncology (2014)

INTRODUCTION: Treatment options for recurrent glioblastoma remain limited, with only modest activity of second line chemotherapy. Despite the absence of well controlled trials, bevacizumab is widely used for recurrent glioblastoma. Nonetheless, it remains unclear if the high response rates observed after treatment with bevacizumab translate into an overall survival (OS) benefit. We report the first randomized phase II trial on bevacizumab in recurrent glioblastoma with a control arm without bevacizumab. METHODS: This was multicenter phase II study conducted in 14 Dutch sites. Patients with a first recurrence of a glioblastoma after chemo-irradiation with temozolomide were randomized between treatment with oral lomustine 110 mg/m2 once every 6 weeks, with bevacizumab 10 mg/kg once every 2 weeks intravenously or with the combination lomustine 110 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Response was assessed using the RANO criteria. Primary endpoint was OS at 9 months. A safety analysis was planned after the first ten patients completed two cycles of 6 weeks in the combination arm. RESULTS: 153 patients were randomized, of which 148 were eligible. After the safety analysis the lomustine dosage in the combination arm was reduced to 90 mg/m2 because of thrombocytopenia, resulting in bevacizumab dose delays. After reduction the treatment in the combination arm was well tolerated. The percentage 9 month OS (95% confidence interval) was 43% (29, 57) in the lomustine arm, 38% (25, 51) in the bevacizumab arm, and 59% (43, 72) in the bevacizumab/lomustine 90 arm. Response rates were 35-40% for bevacizumab treated patients, and 5% in the lomustine single agent arm. CONCLUSION: This study does not show a meaningful OS at 9 months after treatment with bevacizumab alone. However, the results of combination therapy of bevacizumab with lomustine met the prespecified criterion for further phase III studies. AKNOWLEDGMENTS: This study was supported by an unrestricted grant from Roche Nederland bv. The study was also supported by grant nr DDHK 2010-4678 from the 'KWF Kankerbestrijding' (Dutch Cancer Society).
Association of Oligomenorrhoea, Hirsuties, and Infertility
Authors: D. Ferriman, A. W. Purdie
Journal: BMJ (1965)

Organo-chlorine Pesticides-Egan et al.MEDICsHL 69 by subcutaneous biopsy, and 19 samples of human breast milk were analysed quantitatively for D.D.E., D.D.T., total B
Single-Dose Azithromycin versus Penicillin G Benzathine for the Treatment of Early Syphilis
Authors: Gabriele Riedner, Mary Rusizoka, Jim Todd, Leonard Maboko, Michael Hoelscher, Donan Mmbando, Eleuter Samky, Eligius Lyamuya, David Mabey, Heiner Grosskurth, Richard Hayes
Journal: New England Journal of Medicine (2005)

Pilot studies suggest that a single, 2-g oral dose of azithromycin may be an alternative to a 2.4-MU intramuscular dose of penicillin G benzathine in the prevention and treatment of syphilis. We evaluated the efficacy of treatment with azithromycin in a developing country.
Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density
Authors: Gudmar Thorleifsson, Hilma Holm, Vidar Edvardsson, G Bragi Walters, Unnur Styrkarsdottir, Daniel F Gudbjartsson, Patrick Sulem, Bjarni V Halldorsson, Femmie de Vegt, Frank C H d'Ancona, Martin den Heijer, Leifur Franzson, Claus Christiansen, Peter Alexandersen, Thorunn Rafnar, Kristleifur Kristjansson, Gunnar Sigurdsson, Lambertus A Kiemeney, Magnus Bodvarsson, Olafur S Indridason, Runolfur Palsson, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2009)
Sodium nitroprusside and renovascular hypertension.
Authors: G I Russell, R F Bing, J D Swales
Journal: BMJ (1978)

abscess fits into this group.Thirdly, true orbital cellulitis or inflam- matory infiltration within the space enclosed by the orbital periosteum and orbital septum; case 3 fits into this group.In Scott's series4 two of the four patients in this group died and three of them developed cavernous sinus thrombosis.In our series two diagnostic points emerged.Firstly, the results of nasal-swab culture may help.In all three patients Staph aureus was grown from the nose, but conjunctival swabs were initially sterile.Secondly, the x-ray view employed is important.Thus the occipitomental sinus x-ray film may not show the ethmoid opacity.In departments where an occipitomental view has become standard an occipitofrontal view should be requested specifically.
Management of breast cancer--Part I
Authors: N. C Turner, A. L Jones
Journal: BMJ (2008)

Breast cancer remains the second most common cause of cancer related death in women in the United Kingdom, with over 12 000 deaths a year.However, substantial progress is being made: deaths from breast cancer in the Western world have fallen by over 25% in the past two decades, 1 reflecting substantial improvements in management (fig 1).Incidence in Great Britain has risen by 50% over the past three decades, reflecting not only changes in population demographics and environmental factors but also an increase in diagnosis as a result of screening.Over a similar time period mortality has fallen.We review here the recent advances in the prevention, screening, and treatment of breast cancer and the recent efforts to individualise treatment.The review is published in two parts; in the second part we will review advances in the systemic treatment of breast cancer and how an increasing understanding of the biology of breast cancer is beginning to change the way we treat the disease.
Apoptosis Induction by a Novel Retinoid-Related Molecule Requires Nuclear Factor-κB Activation
Authors: Lulu Farhana, Marcia I. Dawson, Joseph A. Fontana
Journal: Cancer Research (2005)

Abstract Nuclear factor-κB (NF-κB) activation has been shown to be both antiapoptotic and proapoptotic depending on the stimulus and the specific cell type involved. NF-κB activation has also been shown to be essential for apoptosis induction by a number of agents. The novel retinoid-related molecule 4-[3-Cl-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) activates NF-κB with subsequent apoptosis in a number of cell types. We have found that NF-κB activation is essential for 3-Cl-AHPC–mediated apoptosis. 3-Cl-AHPC activates NF-κB through IKKα kinase activation and the subsequent degradation of IκBα. IKKα kinase activation is associated with IKKα-enhanced binding to HSP90. The HSP90 inhibitor geldanamycin enhances the degradation of IKKα and blocks 3-Cl-AHPC activation of NF-κB and 3-Cl-AHPC–mediated apoptosis. In addition, inhibition of IκBα degradation using a dominant-negative IκBα inhibits 3-Cl-AHPC–mediated apoptosis. NF-κB p65 activation is essential for 3-Cl-AHPC apoptosis induction as evidenced by the fact that inhibition of p65 activation utilizing the inhibitor helenalin or loss of p65 expression block 3-Cl-AHPC–mediated apoptosis. NF-κB has been shown to be antiapoptotic through its enhanced expression of a number of antiapoptotic proteins including X-linked inhibitor of apoptosis protein (XIAP), c-IAP1, and Bcl-XL. Whereas exposure to 3-Cl-AHPC results in NF-κB activation, it inhibits the expression of XIAP, c-IAP1, and Bcl-XL and enhances the expression of proapoptotic molecules, including the death receptors DR4 and DR5 as well as Fas and Rip1. Thus, 3-Cl-AHPC, which is under preclinical development, has pleotrophic effects on malignant cells resulting in their apoptosis.
Colestipol and cholestyramine resin. Comparative effects in familial type II hyperlipoproteinemia
Authors: C. J. Glueck
Journal: JAMA (1972)

Two bile acid-sequestrant anion exchange resins, colestipol (U-26, 597A) and cholestyramine resin (Questran), were given in doses of 20 gm/day for four months each in a 14-month placebo crossover study to 25 patients with familial type II hyperlipoproteinemia. Plasma cholesterol and β-lipoprotein cholesterol were reduced to normal levels in 20 and 22 subjects, respectively, by one or both drugs. Coupled with low cholesterol, low saturated fat, polyunsaturate-rich diet, colestipol and cholestyramine provide parallel and alternative approaches to normalization of cholesterol and β-lipoprotein cholesterol in familial type II hyperlipoproteinemia.
Management of TIAs-Reply
Authors: David Lefkowitz
Journal: JAMA (1985)

<h3>In Reply.—</h3> I appreciate the opportunity to reply to Drs Svoboda and Balaji's comments regarding the management of patients with TIAs. Their letter raises some important issues that could not be addressed in detail in my original response because of limited space in a forum such as QUESTIONS AND ANSWERS. Drs Svoboda and Balaji's major points are all corollaries of their basic thesis that "anything other than a normal [antiographic] study in the implicated carotid should indicate surgical endarterectomy," regardless of the magnitude of the abnormality. I submit that this approach is extreme and inappropriate for reasons I will discuss below. It does, however, explain their recommendation that all TIA patients with acceptable surgical risk undergo arteriography since they would consider even minor abnormalities, which might not be as well visualized by ultrasound, to be surgical lesions. Since I do not share this view, I am more inclined to forego
Toxic epidermal necrolysis: current evidence, practical management and future directions
Authors: T.A. Chave, N.J. Mortimer, M.J. Sladden, A.P. Hall, P.E. Hutchinson
Journal: British Journal of Dermatology (2005)

Toxic epidermal necrolysis (TEN) is a rare disorder characterized by extensive epidermal death. Almost all cases appear to be caused by an idiosyncratic drug reaction. Proposed pathogenic mechanisms are conflicting, and the evidence for the benefits of individual treatments is inadequate, and in some cases contradictory. The mortality rate remains high. We review the literature pertaining to the pathogenesis of TEN and drug reactions in general. The rationale for therapeutic interventions, together with reported evidence of efficacy, are considered. We present a composite model of TEN, based on previous work and suggested pathogeneses of TEN, mechanisms of drug reactions and reported cytotoxic lymphocyte (CTL) cytolytic pathways. In this system, TEN, like some other cutaneous drug eruptions, is an HLA class I-restricted, specific drug sensitivity, resulting in clonal expansion of CD8+ CTLs. Cytotoxicity is mediated by CTL granzyme and possibly death receptor (DR) ligand (DR-L), probably Fas ligand (FasL). Particular to TEN, there is then an amplification sequence involving further DR-L expression. FasL is likely to be particularly important but tumour necrosis factor (TNF) may well contribute, via the TNF receptor 1 (TNF-R1) death pathway. Alternatively, we suggest the possibility of upregulation of an antiapoptotic TNF-R1-nuclear factor kappaB pathway, which would proscribe treatments which downregulate this pathway. None of the published data on individual treatment efficacies is sufficiently strong to suggest a definitive single treatment. Currently a multifaceted regimen appears indicated, targeting various likely intermediary mechanisms, including elimination of residual drug, immunosuppression, inhibition of DR pathways, general antiapoptotic strategies, and aggressive supportive care. Particular attention has been directed at avoiding potential conflicts between different treatments and avoiding agents that theoretically might have a net proapoptotic rather than antiapoptotic effect. Nursing on a specialized unit is of paramount importance.
Open Payments goes live with pharma to doctor fee data: first analysis
Authors: D. Jarvies, R. Coombes, W. Stahl-Timmins
Journal: BMJ (2014)

<h3>Background</h3> Particularly for the less haemolytic antibodies, there is limited evidence to aid management. New Scottish guidelines are in production. To provide evidence for their development, we sought to study over the last 3 years, in a DGH with 4000 deliveries/yr, how effective our existing local management has been and what impact new draft guidelines would have had. <h3>Aims</h3> To identify babies affected by haemolytic disease of the newborn and to establish whether new guidelines could have changed pregnancy or neonatal management. To estimate extra demands on services made by the proposed new guideline. <h3>Methods</h3> All women with red cell antibodies were identified over a three year period. Numbers of ultrasound appointments required and neonatal outcomes were noted and applied to existing management and the proposed guideline. <h3>Results</h3> There were 101 women identified of which 12 had anti-D; 6 anti-c; 6 anti-K; 7 others had titres over 1/32 and 2 others which doubled. Had the new guideline been in place this would have equated to 111 extra ultrasound appointments. With the existing guideline, one baby affected by anti-Jka fetal anaemia required top up transfusion that was not anticipated but would have been with the new guideline. <h3>Conclusions</h3> The new guideline suggests more close screening and intervention than our existing management. The data supports the proposed management for anti-D, c and K but we suggest that MCAPSV screening only should be undertaken for other antibodies if titre &gt;1/64 with no place for extra scans in other situations
Visualization of Cutaneous Hemangioma with Tc-99m Tagged Red Blood Cells
Authors: LEONIE GORDON, IVAN VUJIC, K M SPICER
Journal: Clinical Nuclear Medicine (1981)

Scintigraphy with Tc-99m labeled red blood cells (RBCs) was used to evaluate a patient with a large cutaneous hemangioma. The usefulness of this procedure when combined with arteriography is discussed.
Extrahepatic Biliary Atresia
Authors: Daniel Alagille
Journal: Hepatology (1984)

Extrahepatic biliary atresia is defined as partial or total absence of permeable bile duct between porta hepatis and the duodenum. The incidence varies from 1:8,000 to 1:10,000. Cholestasis is total and permanent. 131I Rose Bengal test and needle liver biopsy allow correct identification of 95% of cases before surgery Before the surgical procedure described by Kasai in 1959, all patients died between 1 and 2 years of age. Through the use of different types of Kasai’s procedures by experienced groups, 30 to 35% of patients are successfully operated on. In our group, 248 infants underwent surgery, 121 before 1977: 44 (36.6%) are alive at least 5 years after surgery. Growth is within normal limits in all children still alive, even in those who presented with numerous and severe episodes of cholangitis during the first two postoperative years. Portal hypertension was progressive in 23 children with splenomegaly and esophageal varices developing between 1 and 2 years of age. Five patients bled profusely between 2 and 4 years of age: portal systemic shunts were performed in 4. Surgical liver biopsies were performed in 20 children, 5 to 8 years old: cirrhosis was present in all and was micronodular in 13 and macronodular in 7. The most impressive histologic change was absence of biliary ducts or ductules. This histologic finding can be related with percutaneous transhepatic cholangiographic pictures. Despite the abnormal appearance of intrahepatic bile ducts and the constant presence of cirrhosis with portal hypertension, all 44 patients who are alive at least 5 years after surgery seem to lead almost normal lives.
Case of Secondary Suture of Ulnar Nerve Six Months after its Division
Authors: H. W. Page
Journal: BMJ (1883)

had been amputated, and in each instance the disease had recurred in the stump.The patient' was admitted into the hospital-under Mr. Heath, and both feet were eventually amputated.A microscopic examination of the nerves from both feet was made by Mr. Priestley (Lamncet, 1883, vol.i, page 452), and in each instance he found well- marked evidence of sclerosis. MFl;In this case, which has now been in progress for six years, and which is still under observation as an out-patient, there has never, from first to last, been any evidence of locomotor ataxy.The changes here found in the peripheral nerves resemble very closely those met with in a case recorded by vol.lxii, Case v, page 378).Almost iden- tical cases have also been described by other writers; so that it appears probable that perforating ulcer may, in some cases, be dependent simply on disease of the peripheral nerves, without any apparent implication of the nerve-centres.Of course, it is quite possible that, in cases of this kind, symptoms of central disease (e.g., of locomotor ataxy) may eventually develop themselves ; but, in Case IV, six years have now elapsed, and as yet no indications of the onset of that condition are present.