tbuckley/cabot-search huggingface dataset:
Treatment of VHL patients with sunitinib: Clinical outcomes and translational studies.
Authors: S. F. Matin, I. E. McCutcheon, D. S. Gombos, S. Waguespack, N. M. Tannir, S. Wen, D. W. Davis, L. A. Smith, G. Fuller, E. Jonasch
Journal: Journal of Clinical Oncology (2010)

3040 Background: Von Hippel Lindau (VHL) disease induces vascular neoplasms in multiple organs. We evaluate the safety and efficacy of targeted molecular intervention in VHL patients (pts) and examine activation of various candidate receptors in endothelial and tumor tissue. Methods: Pts with genetically confirmed VHL were enrolled. Inclusion criteria: hemangioblastomas (HBs) at least 5mm dia, renal cell carcinoma (RCC) 1 to 3 cm and pancreatic neuroendocrine tumors (NETs) 1 to 3 cm. Pts received sunitinib 50mg/day 28 days/14 days off for 4 cycles. Primary endpoint was toxicity: study to be stopped early if P (toxicity > 0.3 μ g) > 90% treatment terminating toxicity. Modified RECIST used for efficacy assessment. A separate set of 20 HBs and 20 RCCs were used for laser scanning cytometry (LSC) analysis of total and phospho-vascular endothelial growth factor receptor (pVEGFR), phospho-platelet derived growth factor receptor (pPDGFR), Tie-2, fibroblast growth factor receptor 3 (FGFR3), and phospho-FRS2 (pFRS2) levels in tumor endothelium and neoplastic cells. Protein expression was analysed using Wilcoxon's rank test. Results: Fifteen pts were treated. 11/15 had RCCs, 9/15 HBs, and 3/15 NETs. Grade 3 toxicities included 5/15 pts with fatigue, 2/15 with nausea and 2/15 with hand foot syndrome. 2/15 pts came off study for toxicity. 5/21 RCC lesions achieved PR (p=0.022), 2/21 PD, and 14/21 SD. 2/23 HB lesions achieved PD, and the remaining 21/23 demonstrated SD. 5/5 pancreatic NETs showed SD. LSC analysis revealed the mean (SD) of pVEGFR levels in log-transformation was 11.27 (0.49) and 11.75 (0.37) for HB and RCC endothelium respectively (p = 0.003). There was no significant difference in Tie2 expression, but pFRS2 levels in HB endothelium were 12.5 (0.49) vs. 11.91 (0.99) (p=0.059) in RCC, and 11.45 (0.26) HB vs. 11.26 (0.089) RCC in the neoplastic cells (p=0.003). Conclusions: This is the largest reported study of sunitinib-treated VHL pts. We confirm consistent response in RCC but not HBs or pancreatic NETs. Differential dependence on VEGFR activation in RCC vs. HB endothelium may explain this finding. Increase of pFRS2 in HB tissue relative to RCC suggests treatment with FGF pathway blocking agents may show utility in patients with HBs. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Book: MASH: An Army Surgeon in Korea
Authors: R. N Villar
Journal: BMJ (1998)

Otto F Apel, Pat Apel University Press of Kentucky, £23.75, pp 240 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> ISBN 0 8131 2070 5 ——————— Few truly realise the damage that war can create. The media offer a fireside version of conflict, as if it is taking place in a distant land without any involvement by the observer. Real life is so different, as this book capably shows. MASH is written by a father and … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Theft in Shops — Medicolegal Aspects
Authors: Hugh L'etang
Journal: Journal of the Royal Society of Medicine (1984)

included retailers, security executives, police officers, magistrates, lawyers, justices of the peace, occupational medical officers, psychiatrists, one member of parliament, and the chairman of crisis counselling for alleged shoplifters.The chair was taken by the Baroness Phillips .p,director, Association for Prevention of Theft in Shops.In opening the proceedings Sir James Watt stated that shoplifting had reached epidemic proportions, referred to decreasing standards of honesty, integrity and moral accountability, but
Fluorouracil: biochemistry and pharmacology.
Authors: H M Pinedo, G F Peters
Journal: Journal of Clinical Oncology (1988)

Fluorouracil (5FU) is still considered the most active antineoplastic agent in the treatment of advanced colorectal cancer. The drug needs to be converted to the nucleotide level in order to exert its effect. It can be incorporated into RNA leading to interference with the maturation of nuclear RNA. However, its conversion to 5-fluoro-2'deoxy-5' monophosphate (FdUMP) leading to inhibition of thymidylate synthase (TS) and subsequently of DNA synthesis, is considered to be its main mechanism of action. In the presence of a folate cofactor a covalent ternary complex is formed, the stability of which is the main determinant of the action of 5FU. Resistance against 5FU can be mainly attributed to aberrations in its metabolism or to alterations of TS, eg, gene amplification, altered kinetics in respect to nucleotides or folates. Biochemical modulation of 5FU metabolism can be applied to overcome resistance against 5FU. A variety of normal purines, pyrimidines, and other antimetabolites have been studied in this respect, but only some of them have been clinically successful. Delayed administration of uridine has recently been shown to "rescue" mice and patients from toxicity, while pretreatment with leucovorin is the most promising combination to enhance the therapeutic efficacy. 5FU is frequently administered in an intravenous (IV) injection, and shows a rapid distribution and a triphasic elimination. The nonlinearity of 5FU pharmacokinetics is related to saturation of its degradation. Continuous infusion of 5FU led to different kinetics. Regional administration, such as hepatic artery infusion, offers a way to achieve higher drug concentrations in liver metastases and is accompanied by lower systemic concentration. The current status of the biochemical and pharmacokinetic data is reviewed.
H1- and H56- subunit vaccines against TB - an overview of the clinical development
Authors: Morten Ruhwald, Else Marie Agger, Søren T. Hoff, Peter L. Andersen
Journal: European Respiratory Journal (2014)

Despite a very effective worldwide vaccination program, BCG vaccination has proven to be insufficient to provide protection against TB disease, and a better vaccine is urgently needed. Statens Serum Institut has developed two TB vaccine candidates, H1:IC and its improved successor H56:IC. Both candidates are currently being tested in human clinical trials although H1:IC development will end in 2014 as H56:IC program will take over. These vaccines candidates are intended to be used in adolescents and young adults, and are designed to be effective in both M. tuberculosis - uninfected and latently infected persons.

Being a subunit vaccine, the H1 consists of a recombinant fusion protein of two secreted mycobacterial antigens, Ag85B and ESAT-6, and to this core H56 adds a third antigen - the latency antigen Rv2660c. Both vaccines are adjuvated with the IC31 adjuvant

This presentation summarize results from preclinical studies in rodents and non-human primates to five clinical trials of the H1:IC and H56:IC vaccines.

In preclinical studies, H56:IC provides superior protection against TB disease compared to BCG alone both pre- and post- infection with M.tb. In human trials, H1:IC has been shown to be safe and to induce long term immune responses characterized by T cells with sustained regenerative potential. Latest, this has been shown in HIV infected patients with latent infection in Tanzania and South Africa. Furthermore, a large dose- and schedule trial including 240 adolescents is currently ongoing in South Africa. Recently H56:IC proved similar safety and immunogenicity profile as H1:IC in a small first-in-man trial. These clinical data provides the groundwork for further clinical development of H56:IC.
How does aerodynamic peculiarities of upper airways influence heart rhythm in severe COPD patients
Authors: Yuri Feshchenko, Liudmyla Iashyna, Viktoria Ignatieva, Svitlana Moskalenko, Inna Zvol, Irina Chumak
Journal: European Respiratory Journal (2013)

The aim : to study the interrelation between aerodynamic peculiarities of upper airways and 24-hour Holter monitoring data in severe COPD patients.

Patients and methods : 60 patients (45 male and 15 female aged 41 - 79) with severe COPD (Post BD FEV1– (41,6 ± 2,1)%) were examined with active anterior rhinomanometry, spirometry (Master Screen PFT, Cardinal Health (Germany), 24-hour EC Holter monitoring («EC2H» “Labtech” (Hungary), statistic data.

Results of the study : in 49 patients (81,7 %) vasomotor rhinitis was diagnosed. In 44 (73,3 %) patients it was complicated by hypertrophy of lower rhino bone and in 30 (50,0 %) patients - complicated by deviated septum. After the correlation analysis the statistically reliable feedback of middle rate was found between total nasal expiratory flow (TNEF) and ventricular contractions (per cent of night ones) – (r = – 0,449, p < 0,05), between TNEF and supraventricular extrasystoles (per cent of night ones) – (r = – 0,474, p < 0,05). The following correlation was observed: the lower TNEF index was, the more frequent night heart rhythm failure occurred.

Conclusion: presence of chronic vasomotor rhinitis with hypertrophy of lower rhino bone and deviated septum in severe COPD patients led to aerodynamic violation of upper airways on expiratory flow and to impact on the occurrence and frequency of the night heart rhythm failure.
Abstract 14054: ‘Call 911’ from STEMI Referral Facilities to STEMI Receiving Centers Reduced Times to Treatment in Patients Receiving Primary Percutaneous Coronary Intervention in Los Angeles County
Authors: Terrance Baruch, William Koenig, Alisa Rock, Paula Rashi, William J French
Journal: Circulation (2011)

Background Primary PCI (PPCI) is the preferred method of reperfusion for STEMI, but only if performed in a timely manner (D2B ≤ 90 minutes) by an experienced interventional cardiologist at a high v...
Cytoplasmic Localization of a Functionally Active Fanconi Anemia Group A–Green Fluorescent Protein Chimera in Human 293 Cells
Authors: Frank A.E. Kruyt, Quinten Waisfisz, Lonneke M. Dijkmans, Mario A.J.A. Hermsen, Hagop Youssoufian, Fré Arwert, Hans Joenje
Journal: Blood (1997)
Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: First results from STAMPEDE (MRC PR08, CRUK/06/019), a randomized controlled trial.
Authors: Nicholas David James, Matthew Robert Sydes, Malcolm David Mason, Noel W Clarke, John Anderson, David Paul Dearnaley, John Dwyer, Gordana Jovic, Alastair SW Ritchie, J. Martin Russell, Karen Sanders, George Thalmann, Gianfilippo Bertelli, Alison J Birtle, Joe M. O'Sullivan, Andrew Protheroe, Denise Sheehan, Narayanan Srihari, Mahesh Parmar
Journal: Journal of Clinical Oncology (2012)

26 Background: Long-term hormone therapy (HT) alone is standard of care for men with metastatic or high-risk non-metastatic prostate cancer (PCa). STAMPEDE investigates whether early use of additional therapies improves overall survival. It is an international randomised controlled trial ( NCT00268476 ) using novel multi-arm, multi-stage methods to assess adding 1 or 2 of three agents (docetaxel, zoledronic acid (ZA), celecoxib) in 5 research arms in men with PCa starting long-term HT for the first time. Methods: HT was given as per standard care. Celecoxib was planned as 400mg bid until the sooner of 1 year or disease (including PSA) progression. The trial has 3 intermediate activity stages (I-III) where the outcome measure (OM) is failure-free survival (FFS) and 1 final efficacy stage (IV) with overall survival as primary OM. At the end of each stage, research arms are compared pairwise to the control arm. Accrual of further patients is discontinued early for any research arm either showing (a) safety concerns or (b) insufficient evidence of activity (lack-of-benefit) where the treatment effect on FFS is compared against a pre-defined stopping guideline. The interim activity “hurdle” becomes increasingly stringent stage-by-stage. Results: From Oct-2008 to Feb-2011, 2114 patients were consented and randomised, including 875 in this comparison. With 205 control FFS events, there was evidence of insufficient activity for HT+celecoxib over HT-alone: HR 0.98 (95%CI 0.90-1.06). The Independent Data Monitoring Committee recommended stopping accrual to this arm; stopping celecoxib was also recommended for patients currently on treatment. (Accrual was also stopped to HT+celecoxib+ZA but data are not disclosed.) There was no evidence of differences in toxicity: 25% and 23% of patients reporting grade ≥3 toxicities or adverse events with or without celecoxib. Control arm FFS was 51% at 2 years, in line with expectations. Conclusions: Celecoxib shows no evidence of activity in this setting. Accrual continues seamlessly to the other research arms. Follow-up of all arms is ongoing. Support: MRC, Cancer Research UK, Novartis, Sanofi-Aventis, Pfizer.
Burden, seasonal pattern and symptomatology of acute respiratory illnesses with different viral aetiologies in children presenting at outpatient clinics in Hong Kong
Authors: L. Wei, K.-H. Chan, D.K.M. Ip, V.J. Fang, R.O.P. Fung, G.M. Leung, M.J.S. Peiris, B.J. Cowling
Journal: Clinical Microbiology and Infection (2015)
Abstract 1414: Pim-1 Stimulates Cardiac Progenitor Cell Proliferation And Asymmetric Division
Authors: Christopher T Cottage, Savilla Tuck, Kimberlee Fischer, Natalie Gude, John Muraski, Mark A Sussman
Journal: Circulation (2008)

Cardiac progenitor cells (CPCs) blunt cardiomyopathic damage and increase survival following adoptive transfer into hearts subjected to myocardial infarction (MI), but the initial survival, persistence, and long term engraftment of the donated cell population remains problematic. Previous studies from our group have demonstrated that transgenes driven by the α -myosin heavy chain gene promoter are expressed in the CPC population allowing for enhanced proliferation and survival. This study details a genetic engineering strategy to augment the salutary effects of CPCs through the use of a serine/threonine kinase named Pim-1 that promotes cellular proliferation and survival. Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 activity in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using BrdU or Ki-67 markers relative to non-transgenic (NTG) controls. However, CPC population number was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge, suggesting that Pim-1 expression promotes asymmetric division resulting in maintenance of the CPC pool as well as expansion of the cardiomyocyte population. Localization and quantitation of cell fate determinants Numb and α -adaptin by confocal microscopy were employed to assess levels of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in NTG hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform α -adaptin staining indicative of symmetrically dividing CPCs, with in 36% of the CPCs versus vs. 73% in NTG sections. These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase in the myocardial lineage cells.
How <scp>I</scp> treat newly diagnosed chronic myeloid leukemia in 2015
Authors: Carlo Gambacorti‐Passerini, Rocco Piazza
Journal: American Journal of Hematology (2014)

The initial treatment for chronic myeloid leukemia in chronic phase (CP‐CML) represents a complex process, which includes a prompt and precise diagnosis, the choice among three available tyrosine kinase inhibitors (TKIs), and the initial management of care for these patients, which will protract over a very long period of time. This manuscript summarizes different data on activity, side effects, and supportive measures available for each TKI, the need for particular care in the logistical organization of CML management, the scenario which will be opened by the future availability of generic imatinib. The opinion of the authors is that imatinib remains the first‐line treatment for CP‐CML; this strategy, accompanied by intensive monitoring and possible dose modification/drug switch after the initial 3–12 months of treatment presently assures a normal life expectancy to the population of newly diagnosed patients with CP‐CML. Am. J. Hematol. 90:156–161, 2015. © 2014 Wiley Periodicals, Inc.
Incremental midazolam versus midazolame/rentanyl sedation during flexible bronchoscopy. Safety and tolerance in relation to the complexity of intervention
Authors: Grigoris Stratakos, Ioannis Kokkonouzis, Penny Moraitaki, Philip Emmanouil, Nikos Koufos, Evangelia Stoubi, Dimitra Tsiboura, Filomila Zikopoulou, Fotis Sampsonas, Manos Alchanatis, Nikolaos Koulouris
Journal: European Respiratory Journal (2012)

Background: Sedation during flexible bronchoscopy (FB) is undisputed. Although suggested, benzodiazepines and opiates combination is underused due to fear of complications.  Aim: To prospectively compare safety and tolerance of FB sedation using incremental midazolam (M) versus combined midazolam/fentanyl (MF) administration.  Methods: Consecutive patients referred for FB were enrolled. After administration of 2% lidocaine aerosol, sedation with midazolam (1-5 mg) alone or combined with fentanyl (0.025-.005mg) was given. Decision relied on clinical parameters (fear,anxiety,cough and restlessness) and on staff judgment regarding performed interventions.Nurses took active role estimating sedation need. Patients completed verbal analogue scales (VAS) and overall tolerance questionnaires.Bronchoscopists completed tolerance VAS and complications questionnaires.  Results: 68 patients (53 males, aged 65 ±12) enrolled.31 received only M (mean 2.23 mg) while 37 received combined sedation (mean 2.74mg M and 0.033 mg F).No sedation related complications were reported.Increased duration of FB and interventional procedures (EBUS, TBNA, Electro-Cryotherapy) were associated with combined MF sedation and increased M dosage (p  8/10).Discomfort and adverse effect scores were equally minimal.  Conclusion:Both regimens are safe and effective in reducing anxiety and cough while increasing FB tolerance. Selection can be based on prolonged duration and need for interventional modalities. Trained endoscopy nurses are effective in incrementing sedation during bronchoscopy in an “as needed” basis.
Patients with hepatocellular carcinoma (HCC) listed for liver transplantation (LTX) outside the MELD system: Outcome of a multicenter eurotransplant series
Authors: M. Adler, F. De Pauw, A. Fancello, P. Vereerstraeten, G. Bonduel, E. De Gendt, Frederik Nevens, JD de Goyet, R. Troisi, O. Detry, P. Michielsen
Journal: Hepatology (2005)
Triple 0 - A new respiratory syndrome?
Authors: Marta Drummond, Ana Santos, Tiago Pinto, Miguel Gonçalves, Anabela Marinho, Maria Sucena, Joao Almeida, Joao Winck
Journal: European Respiratory Journal (2012)

Introduction- There is a growing number of patients needing nocturnal ventilatory support, presenting with O besity-Hypoventilation Syndrome (OHS), Chronic O bstructive Pulmonary Disease (COPD) and O bstructive Sleep Apnea (OSA). As these three comorbidities seem so prevalent together and, as these patients, in the light of their demographic characteristics and ventilatory needs, seem different from those with only one or two of the pathologies, a new respiratory syndrome can be emerging-The Triple O Syndrome (TOS).

Objective- To characterize TOS patients and compare their demographic characteristics and ventilatory needs with OHS patients.

Materials and Methods- Forty-four patients with obesity (BMI> 30 kg/m2), COPD (FEV1/FVC   5/h) were included. Exclusion criteria were pulmonary diseases others than COPD, α-1-AT deficit, bronchiectasis, Cheyne-Stokes Breathing, Complex OSA and Central Sleep Apnea. These patients were compared to 46 OHS patients. Both groups started ventilatory support between 2009 and 2011.

Results- TOS patients: mean age 69.4 ± 9.1 years, 84.1% were male, mean BMI 35.8 ± 4.5 Kg/m2, mean Epworth 11.4 ± 4.8, mean FEV1 57.9%±19.5% predicted, median AHI 36.3/h , median PaCO2 47.2 mmHg, median IPAP 18.0 cmH20, median EPAP 10.0 cmH20, median RR 14 cycles per minute, 23.3% needed oxygen complement.

When compared to OHS patients, TOS patients were older, leaner, the percentage of male gender was higher, had less severe OSA and lower RR when adapted to ventilatory support.

Conclusions- Triple O patients seem to be an individualized group, with different demographic characteristics when compared to OHS patients. The ventilatory needs were similar between both groups, but the RR and the mask used, mainly nasal, in TOS patients.
Abstract 3022: Symptoms After Stenting are Unrelated to Symptoms Before or During Stenting
Authors: Deborah K Zimmerman, James C Blankenship, Kimberly A Skelding
Journal: Circulation (2007)

Background : Despite successful PCI, many patients (pts) with chronic chest pain continue to experience pain. The etiology of this is not clear. Objective: To determine whether characteristics of pre-PCI symptoms or intra-PCI symptoms predict relief of symptoms after PCI. We hypothesized that compared to pts with atypical angina, more pts with typical angina pre-PCI would have symptoms reproduced by PCI and would have relief of these symptoms after successful PCI. Methods: We studied 98 consecutive pts with chronic chest pain in whom PCI provided complete revascularization. Pts were excluded if they had unsuccessful PCI, or prior myocardial infarction or wall motion abnormalities in (or collaterals to) the territory undergoing PCI. During PCI, the first balloon (or stent) inflation was prolonged until 3 minutes or until the pt experienced any discomfort. Pts were asked at the time to characterize intra-PCI symptoms. At phone interview 1 month later, pts were queried regarding chest pain. Patients were divided into groups based on pre-PCI symptoms being typical versus atypical for angina versus mixed, and on whether symptoms during PCI did or did not reproduce pre-PCI symptoms Results: Pts presented with unstable angina (25%), chronic outpatient angina (65%), and positive stress tests for ischemia (63%). All target vessels were successfully treated with PCI. At 1 month followup there were no deaths, myocardial infarction, or recurrent PCI. Patients with typical angina more frequently had reproduction of symptoms during PCI (76%) compared to those with atypical symptoms (43%) or patients with mixed symptoms (64%, p = 0.009). However, pain at 1 month after PCI did not correlate with pre-PCI symptoms (typical 26%, atypical 26%, mixed 40%, p = NS). Also, reproduction of pre-PCI symptoms during PCI was similar in patients with pain 1 month later (50%) compared to those without pain 1 month later (65%, p = .24). Conclusions: Chronic typical angina symptoms are more often reproduced during PCI than are atypical symptoms. However, typical and atypical symptom pts are equally likely to have relief of symptoms after complete revascularization. Reproduction of pre-PCI symptoms during PCI does not predict their relief after PCI.
Comparative performance of Thin Layer Agar and Löwenstein–Jensen culture for diagnosis of tuberculosis
Authors: T. Battaglioli, N. Rintiswati, A. Martin, K.R. Palupi, G. Bernaerts, B. Dwihardiani, R.A. Ahmad, F. Matthys, Y. Mahendradhata, P. Van der Stuyft
Journal: Clinical Microbiology and Infection (2013)