tbuckley/cabot-search huggingface dataset:
Comparison of Myocardial Perfusion Imaging Using Thallium-201 Between a New Cadmium-Zinc-Telluride Cardiac Camera and a Conventional SPECT Camera
Authors: Bernard Songy, David Lussato, Mohamed Guernou, Mathieu Queneau, Ricardo Geronazzo
Journal: Clinical Nuclear Medicine (2011)

Cadmium zinc telluride (CZT) solid-state detectors have been recently introduced in myocardial perfusion imaging. However, they had not been yet validated with thallium-201. This study compares the clinical performances of the CZT ultrafast camera GE DNM 530c with a conventional SPECT camera (CC) using thallium-201.We prospectively studied with thallium-201 a total of 153 consecutive patients referred for myocardial perfusion imaging at exercise (3-4 mCi) then redistribution (with 1 mCi reinjection). Sequential acquisitions were performed first with a conventional dual-head tomographic Anger camera (CC) in 10 to 15 minutes and then with a CZT camera (CZT) in 5 minutes, in prone position.In all, 9 patients were excluded: 1 for mispositioning, 3 for camera failure, 3 for delayed acquisition after exercise, 1 for nonacceptance of redistribution, 1 for motion. Acquisition was more comfortable with CZT for all patients. Global counts rate was higher with CZT than with CC (3.6±0.57 KCts/s vs. 1.14±0.16). CZT has a 5-fold increased myocardial counts rate compared with CC (448±69 Kcts in 5 minutes vs. 209±40 Kcts in 12.5±1.8 minutes). Quality of CZT images was considered as better in 40%, equal in 56%, and worse in 4% of cases; we found less artifacts with CZT; diagnostic conclusions were the same in 140 of 144 cases (97%); discordances were 2 artifacts with CC and 2 small ischemia (less than 2 segments) missed by CZT.This new dedicated cardiac CZT camera allows with thallium-201 five minutes acquisitions with an increased image quality and a reliable diagnosis quality.
The Use of the Diagnostic Radionuclide Ascites Scan to Facilitate Treatment Decisions for Hepatic Hydrothorax
Authors: DAVID M. SCHUSTER, SRINIVASAN MUKUNDAN, WILLIAM SMALL, WILLIAM A. FAJMAN
Journal: Clinical Nuclear Medicine (1998)

A 44-year-old man had an intractable right-sided pleural effusion due to cirrhosis, despite the absence of abdominal ascites. Instillation of Tc-99m macroaggregated serum albumin under CT guidance into the peritoneal space demonstrated transdiaphragmatic communication. This finding indicated the necessity for decompressing the portal system to treat the hydrothorax. The diagnostic radionuclide ascites scan may play an important role in the treatment approach to such patients.
PWE-174 Proton pump inhibitors (PPI) use and<i>Clostridium difficile</i>infection: guilty or innocent bystander?: Abstract PWE-174 Table 1
Authors: M Srinivas, A Kerrane, S Ahuja, J Hilton, C Hughes, P Basumani, K Bardhan
Journal: Gut (2012)

<h3>Introduction</h3> PPIs have been implicated in predisposing to <i>Clostridium difficile</i> infection by causing hypochlorhydria. A 5–10% asymptomatic toxin burden in the community is also reported. The previously voluntary reporting of <i>C difficile</i> infection in UK became mandatory for all age-groups in April 2007. Aim: To compare the pattern of PPI prescribing &amp; <i>C difficile</i> rates in Rotherham (industrial town in Yorkshire; pop 250k) and England (50mill.) over a 7-year period to identify any association at a community level. <h3>Methods</h3> Retrospective population study of seven consecutive years (2004/2005–2010/2011) on data of annual PPI prescriptions &amp; <i>C difficile</i> incidence (both/100k pop.) in Rotherham primary care trust (PCT) and all England PCTs combined obtained from our microbiology department, Rotherham PCT, NHS Information Centre and UK Health Protection Agency. PPI prescribing trends and <i>C difficile</i> rates (irrespective of PPI use) in each year was compared between the two groups as % difference (Rotherham vs England: + =higher %, − =lower %). <h3>Results</h3> (Abstract PWE-174 table 1) PPI prescription: Prescription rates have risen steadily in both cohorts over the study period. Rotherham had higher rate throughout study period but gap with England in % terms has steadily narrowed. <i>C difficile</i> rates: Rotherham rates were much higher till 2006/2007, reversed dramatically in 2007/2008, continuing to fall for next 2 years. England rates peaked in 2007/2008 and fell steadily from 2008/2009 with hardly any gap in 2010/2011. <h3>Conclusion</h3> Strict hand hygiene in hospital and microbiologist-controlled prudent antibiotic use in hospital and community from 2002/2007 seem to have resulted in a marked fall in <i>C difficile</i> rates in Rotherham from 2007/2008. We presume that similar measures, gradually introduced in the rest of England during 2007, account for the more widespread but less steep fall in the England infection rates from 2008/2009.·The 7-year community level data suggests a mere association rather than true cause-effect relation between <i>C difficile</i> rates and PPI use in the past. Any potential risk from PPI use seems to be offset by rigorously applied hand hygiene (secondary care) and careful antibiotic prescribing (primary and secondary care) as evidenced by falling infection rates, despite rising PPI prescribing, since 2007/2008. <h3>Competing interests</h3> None declared.
Abstract 2896: MEK inhibition controls EGFR level in EGFR-dependent NSCLC cells via deregulated expression of EGF-like ligands
Authors: Marta Milewska, Justin Micah Balko, Esther Penni Black
Journal: Cancer Research (2011)

Abstract Purpose: The aim of the present study is to investigate the molecular mechanism underlying MEK inhibitor-induced EGFR down-regulation in EGFR-dependent NSCLC cell lines. Methods: EGFR protein level in A549 and H1975 cell lysates was explored by Western blot assay. A549 and H1975 cell lysates were prepared and separated on SDS-polyacrylamide gels and blotted on PVDF membranes with antibodies specific for total or phosphorylated forms of EGFR, AKT, and total or phosphorylated ERK1/2. Calnexin or α-tubulin was used as loading control. Analysis of EGFR, HB-EGF and TGFα gene expression was performed using quantitative real time PCR (qPCR). Total RNA was extracted from cells and used for cDNA synthesis. qPCR was performed using Taqman On-Demand assays for EGFR, TGFα, HB-EGF and GAPDH. Relative quantification was applied using normalization to GAPDH. Results: In the present study we observed that activation of the EGFR signaling cascade is attenuated by inhibition of MEK, resulting in down-regulation of EGFR in EGFR-dependent H1975 cells but not in EGFR-independent A549 cells. Interestingly EGFR down-regulation in H1975 cells does not occur at the level of transcription. However, mRNA expression of HB-EGF and TGFα, ligands overexpressed in EGFR-dependent H1975 cell line, decreased when treated with MEK inhibitor (AZD6244, Astra Zeneca). In contrast, no decrease in expression of either of the ligands was observed in the EGFR-independent A549 cell line following AZD6244 treatment. Interrogation of EGFR turnover using both protein degradation inhibitors and neutralizing anti-EGFR and anti-HB-EGF antibodies suggested that MEK inhibition down-regulates EGFR expression by directing EGFR to lysosomal degradation via deregulated EGFR and ligands interactions. Conclusions: Our results suggest that loss of active ERK1/2 does not directly impact EGFR gene transcription and that MEK inhibition eliminates the signal for EGFR recycling and promotes degradation of EGFR. We assert that the MAPK cascade regulates production of EGF-like ligands responsible for maintaining high levels of active EGFR on which the cells depend. The difference in level of HB-EGF and TGFα ligands observed in EGFR-dependent cells indicates that EGFR signaling in these cells is maintained by both overexpression of ligands and maintenance of active ligands for EGFR interaction. Finally, our findings indicate that targeting EGFR ligand expression via the MAPK pathway may provide therapeutic benefit in EGFR-dependent lung cancer harboring resistant mutation to TKIs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2896. doi:10.1158/1538-7445.AM2011-2896
INCREMENTAL VALUE OF THE NOVEL MARKER, “ECHOCARDIOGRAPHIC PULMONARY-LEFT ATRIAL RATIO” FOR NON-INVASIVE DETERMINATION OF THE AETIOLOGY IN PULMONARY HYPERTENSION
Authors: David Platts, Jonathan Hunter, Ryan Maxwell, Jilani Latona, Darryl Burstow, Gregory Scalia
Journal: Journal of the American College of Cardiology (2015)
Phase II trial of sequential bevacizumab (B), erlotinib (E) and chemotherapy for first line treatment of clinical stage IIIB or IV non-small cell lung cancer (NSCLC)
Authors: L. Faoro, E. E. Cohen, R. Govindan, M. F. Kozloff, P. C. Hoffman, M. L. Maitland, K. Verel, L. Szeto, R. Salgia, E. E. Vokes
Journal: Journal of Clinical Oncology (2008)

19130 Background: B improves survival in first-line treatment of selected patients (pts) with NSCLC. The addition of an EGFR inhibitor to B appears promising. Methods: Eligible pts with untreated stage IIIB (pleural effusion) or IV NSCLC and good PS were enrolled. Pts with brain metastasis, squamous histology, or hemoptysis were excluded. Treatment consisted of 3 modules. Module A: up to 4 cycles of B (15 mg/kg) every 21 days and E (150 mg qd). Module B: up to 4 cycles of carboplatin (AUC=6), paclitaxel (200 mg/m2) and B (15 mg/kg) every 21 days. Pts who had SD or any response in module A then continued treatment in module C: B every 21 days and E until PD. This study follows a three- stage design, with a maximum sample of 48 pts. The primary objective was to determine the rate of non-PD after module A. Results: 48 pts have been enrolled. Demographics: 30 males (62%), with a median age of 65 years (35–80). 79.2% (n=38) were Caucasian. ECOG PS was 1 in 60% (n=29). 45 (94%) pts had stage IV disease. 66% (n=32) of pts’ tumors were adenocarcinomas, followed by NSCLC not otherwise specified in 25% (n=12). 70% of pts were heavy smokers. In module A, 63% of pts had 4 cycles (n=30). Lack of progression was seen in 64% (n=31), and 12% had a PR. Treatment-related (TR) grade 3/4 AEs: 12% of pts had rash, 6% neuropathy, 4% diarrhea, 4% bowel perforation. 37 pts were treated on module B, with 36 evaluable for response (1 was taken off study due to thrombosis), resulting in PR in 21% (n=8), SD in 45% (n=17) and PD in 29% (n=11). TR grade 3/4 AEs: 10% of pts had neutropenia, 10% neuropathy, 8% infection. 23 pts were treated on module C (median 7 cycles per pt). 19 pts were evaluated for response: 17% (n=4) had PR, 39% (n=9) had SD and 26% (n=6) had PD. TR grade 3/4 AEs: 10% had thrombosis, 10% diarrhea, 10% neuropathy, one patient each with vomiting, anorexia, weight loss and one required an aneurysmal repair. 10 pts remain on study. Median survival for all pts was 12.9 months (95% CI= 7.1 to 18.6 mo). 1-year survival rate was 49%. Pts who had SD or PR in module A had a median survival of 23.2 mo (versus 6.6 mo, p<0.001). Conclusions: The combination of B and E followed by chemotherapy is feasible in pts with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech
AB0508 Assessment of synovitis using ultrasonography in tocilizumab treated rheumatoid arthritis patients remaining in clinical remission
Authors: A. Sagawa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In rheumatoid arthritis (RA), in order to prevent the progression of joint destruction, it is important to prevent synovitis, primarily in swollen joints. We have already reported that Tocilizumab (TCZ) treatment for 3 months<sup>1)</sup> and 6 months<sup>2)</sup> resulted in rapid improvement in disease activity and synovitis. <h3>Objectives</h3> To evaluate synovitis in patients remaining in clinical remission on TCZ treatment. <h3>Methods</h3> We investigated the 1-year therapeutic efficacy of patients started on TCZ at the same time. Patients received TCZ 8 mg/kg every 4 weeks. Disease activity was assessed using the DAS28-ESR. Maintenance of clinical remission was defined as a mean DAS28 score lower than 2.6 from 24 weeks to 52 weeks after TCZ treatment initiation. Swollen joint count (SJC) was assessed by 28 joints. Synovitis was assessed semi-quantitatively (Grades 0-3) using ultrasonography for hand, wrist, elbow, and knee joints for which the patient complained of symptoms or which exhibited signs of synovitis.<sup>3)</sup> The chi-squared test and the Wilcoxon test were used for the statistical analysis. <h3>Results</h3> We studied 214 assessment joints in 47 patients. The mean age (years) was 53.3±15.3, and the mean disease duration (years) was 10.0±7.1. The mean DAS28-EAR at treatment initiation was 5.19±1.06, the mean SJC was 7.7±4.5, and 66% of the patients had received biological agents in the past. The mean DAS28-ESR at 52 weeks was significantly improved to 2.57±0.85 (p&lt;0.001). There were 17 patients (36.2%) who remained in clinical remission from 24 weeks to 52 weeks after TCZ treatment initiation. Grade 0 in patients remaining in clinical remission was 58.0% (47 of 81 assessment joints) at 24 weeks, and 82.7% (67 of 81 assessment joints) at 52 weeks. Grade 0 in patients remaining in clinical remission and having a mean SJC &lt;2 from 24 weeks to 52 weeks was 74.5% and remained after 52 weeks as well. However, in patients remaining in clinical remission and having a mean SJC ≥2, Grade 0 was only 35.3% at 24 weeks, but achieved 85.3% at 52 weeks.Grade 2 or Grade 3 were observed in total 61.7% in patients remaining in clinical remission and having a mean SJC &lt;2, but improved substantially to 4.3% after 24 weeks. <h3>Conclusions</h3> This study confirms that it is possible to have rapid improvement in synovitis for patients in clinical remission without SJC on TCZ treatment. Patients in clinical remission with SJC also have improvement to the same level on synovitis gradually. <h3>References</h3> A. Sagawa. Ann Rheum Dis. 2010; 69 (Suppl3):539. A. Sagawa. Ann Rheum Dis. 2011; 70 (Suppl3):458. Marcin Szkudlarek et al. Arthritis &amp; Rheumatizm.2003;48(4):955-962 <h3>Disclosure of Interest</h3> None Declared
Bile Acid Pools, Kinetics and Biliary Lipid Composition before and after Cholecystectomy
Authors: Hilton R. Almond, Z. Reno Vlahcevic, C. Cooper Bell, Daniel H. Gregory, Leon Swell
Journal: New England Journal of Medicine (1973)

Bile acid pools, kinetics and biliary lipid composition were determined in 10 patients with cholesterol gallstones before and after cholecystectomy. The determinations of post-cholecystectomy bile acid pools were carried out three to 41 months after surgery. Cholecystectomy had no significant effect on biliary lipid composition, and the bile remained lithogenic after removal of the gallbladder. The total bile acid pool in the patients was small before cholecystectomy (about 1.0 g), and there was no significant change in bile acid pool size after removal of the gallbladder. Cholic and chenodeoxycholic acid synthesis did not change after cholecystectomy. The fractional daily turnover rate of cholic and chenodeoxycholic acid was significantly greater after cholecystectomy. These findings support the view that the gallbladder does not have an important role either in the formation of lithogenic bile or in the reduction of bile acid pool size observed in patients with cholesterol gallstones. (N Engl J Med 289:1213–1216, 1973)
Brave new world of transplant technology
Authors: S. Goldbeck-Wood
Journal: BMJ (1995)

It's Tuesday evening, 945 pm, and a mouse scuttles across the television screen. An unusual mouse, with a human ear growing from its back. This is no science fiction movie: this is Tomorrow's World analysing recent American work on human tissue culture. The protagonist is Dr Charles Vacanti, a tissue engineer from the University of Massachusetts, and the mouse is a “nude” mouse--hairless and without an immune system. This makes it an ideal recipient, modelling transplant behaviour in a rejection free environment. It also makes for controversial television.



Vivienne Parry, “Tomorrow's World” reporter, with the mouse in question



The sight of this bizarre creature on our …
Case 10-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Michael L. Grossbard, Nancy L. Harris
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 37-year-old woman with treated Hodgkin's disease in remission was admitted to the hospital because of a question of idiopathic thrombocytopenic purpura.The patient had been well until seven years earlier, when she was seen at another hospital because of a left supraclavicular mass. Microscopical examination of a biopsy specimen of the mass revealed Hodgkin's disease, nodular-sclerosis type, of stage IIIA. The patient received several cycles of the MOPP regimen (mechlorethamine, vincristine, procarbazine, and prednisone), followed by radiation in a dose of 40 Gy to the retroperitoneum. Thereafter she felt well until two years before entry, when . . .
A4.23 S100 proteins induce canonical WNT signalling, which causes increased expression of MMPS in the synovium
Authors: MH van den Bosch, AB Blom, RP Hoek, RF Schelbergen, SW Suen, AE van Erp, WB van den Berg, PM van der Kraan, PL van Lent
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background/Objectives</h3> Many osteoarthritis (OA) patients show synovial activation, which is thought to be involved in joint destruction. Previously, we found that the alarmins S100A8/A9 and members of the Wnt signalling pathway were increased in the joints during experimental OA. S100A9KO mice showed reduced pathology in experimental OA. Canonical Wnt signalling has been linked to OA, but the role of the synovium in OA under the influence of Wnt signalling is unclear. In this study we investigated whether S100 proteins induce Wnt signalling and whether induction of Wnt signalling led to increased synovial expression of MMPs. <h3>Methods</h3> Pathway analysis of microarray data from synovium of a collagenase-induced OA was done using DAVID. Activation of Wnt signalling was determined with β-catenin immunostaining. Gene expression was analysed by qPCR. Human OA synovial tissue collected from joint replacement surgery and stimulated with members of the Wnt signalling pathway or blocked with the Wnt inhibitors FrzB and DKK-1. <h3>Results</h3> Pathway analysis showed enrichment of Wnt signalling in the synovium during experimental OA. Because upregulation of both S100 and Wnt proteins during experimental OA showed comparable kinetics, we determined if S100 proteins could induce Wnt signalling. We found that injections of S100A8 into mouse knee joints led to increased Wnt16 and WISP1 expression in the synovium and β-catenin accumulation in the joint. Underlining an interrelationship between Wnt signalling and S100A8/9, we found less β-catenin accumulation during experimental OA in S100A9KO mice. To determine the effects of canonical Wnt signalling in the synovium, we overexpressed Wnt8a and 16 in the synovium with adenoviral vectors, which resulted in increased MMP expression in the synovium. To translate this finding to a human situation, we stimulated human OA synovial tissues with Wnt3a, as a model for a canonical Wnt. This led to significantly increased expression of MMP1, MMP9 and MMP13. Next, we hypothesised that if Wnt signalling was increased in OA synovium, we should be able to decrease the expression of MMPs by blocking the Wnt signalling pathway. Inhibition of Wnt signalling by both FrzB, a general Wnt inhibitor, and DKK-1, selectively blocking canonical Wnt signalling, led to significantly decreased expression of various MMPs. <h3>Conclusions</h3> S100 proteins are able to increase Wnt signalling. Stimulation of human OA synovium with Wnts and WISP1 increases the expression of MMPs, whereas blocking Wnt signalling results in decreased expression of MMPs. This underlines synovial Wnt expression to be a potential target for OA therapy.
Abstract 3975: CLIC4 induces a Smad7 variant to enhance TGF-β signaling in keratinocytes
Authors: Anjali Shukla, Yihan Yang, Sara Madanikia, Yan Ho, Stuart H. Yuspa
Journal: Cancer Research (2010)

Abstract CLIC4 (Chloride intracellular channel 4) is a member of a family of intracellular chloride channel proteins that are ubiquitously expressed in multiple tissue types. It is a dimorphic protein that exists in both soluble and membrane-bound forms. CLIC4 is multifunctional, traffics between the cytoplasm and nucleus, and participates in cell cycle control and differentiation in keratinocytes and other cell types. CLIC4 expression is lost in multiple human epithelial cancers. We have recently shown that nuclear CLIC4 enhances transforming growth factor beta (TGF-β) signaling through stabilization of phospho-Smad2/3. The TGF-β signaling pathway is a major growth regulator of multiple cell types, and its regulation is altered in many human cancers suggesting that CLIC4 could participate in altering TGF-β regulation in tumor cells. Here we show that in addition to stabilizing phospho-Smads 2/3, CLIC4 alters Smad7, a feedback inhibitor of the TGF-β pathway. Elevated levels of CLIC4 in primary keratinocytes lead to the expression of a truncated form of Smad7 (Smad7Δ), which is detectable as a PCR product. The Smad7Δ variant contains a missing region of 94bp in exon 4 of Smad7 and appears to be an alternately spliced form. Absence of these 94bp leads to a frameshift mutation and an early protein truncation causing the Smad7Δ variant to lack the MH2 domain of Smad7, the domain responsible for inhibition of TGF-β signaling. While wild-type Smad7 expression inhibits TGF-β signaling, exogenously expressed Smad7Δ variant does not inhibit TGF-β signaling, based upon analysis of TGF-β dependent proliferation, reporter assays and phosphorylation of Smad proteins. Together, these data suggest that CLIC4 regulates TGF-β signaling by multiple mechanisms. In light of this, CLIC4 may serve as a target for modifying TGF-β function in cancer and other conditions where this pathway is involved in pathological changes. 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 3975.