tbuckley/cabot-search huggingface dataset:
Pulmonary aspergilloma: Therapeutic challenge
Authors: Ikbel Khalfallah, Hanène Smadhi, Amani Ben Mansour, Ines Akrout, Dorra Greb, Hela Hassan, Hajer Benabdelghaffar, Leila Fekih, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2014)

Introduction : Aspergilloma (fungus ball, mycetoma) is the clinical form of Aspergillus developing in patients with pre-existing pulmonary cavities or areas of infarction or necrosis.

Aim: To study the clinical profile, indications, post-operative complications and long term outcome of patients having pulmonary aspergilloma.

Methods: We retrospectively evaluated 26 cases with pulmonary aspergilloma in our department between January 1990 and January 2014.

Results : The group consisted of 20 men and 6 women with a mean age of 47 years. The underlying lung diseases were tuberculosis (65%), bronchiectasis (15%) and hydatid cysts operated (12%). The mean body mass index was 16. Hemoptysis was the most frequent symptom (85%). In one patient, concomitant ruptured lung hydatid cyst and an aspergilloma was present. Three patients have concomitant tuberculosis and aspergilloma (11%). Seventeen patients were operated with a good outcome. Lobectomy was the most frequent surgical procedure (76%). There was no post-operative mortality. The post operative complications included bronchopleural fistula (11%), empyema (11%) and pneumothorax (6%). Medical treatment was prescribed for patients with poor respiratory reserve.Embolization was done on 1 patient with massive hemoptysis. In 2 patients radiotherapy was indicated for recurrent hemoptysis

Conclusion: Surgery has until now been the treatment of choice for massive bleeding from aspergilloma. Unfortunately, many patients are unsuitable for surgery because of their poor respiratory reserve.
Phase I clinical and pharmacokinetic study of topotecan administered by a 24-hour continuous infusion.
Authors: L J van Warmerdam, W W ten Bokkel Huinink, S Rodenhuis, I Koier, B E Davies, H Rosing, R A Maes, J H Beijnen
Journal: Journal of Clinical Oncology (1995)

To determine the maximum-tolerable dose (MTD) and to investigate the pharmacokinetics and pharmacodynamics of topotecan in a phase I study. Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. Broad preclinical activity rationalized further clinical evaluation.In this phase I trial, topotecan was administered by 24-hour continuous infusion every 21 days to patients with solid malignant tumors.A total of 25 eligible patients, of whom 22 were pretreated, entered the study. They received the following dosages of topotecan: 2.5, 3.75, 5.60, 8.4, and 10.5 mg/m2 by 24-hour infusion. Reversible leukopenia and thrombocytopenia were dose-limiting, with mild anemia occurring regularly. Other toxicities, such as alopecia, mucositis, nausea, and vomiting were sporadic and mild. Responses were not observed. However, eight patients had stable disease. The plasma concentration-time curves were not compatible with standard linear pharmacokinetic models, and indications were found for the occurrence of nonlinear (saturation) kinetics at the dosages studied.The recommended dose for phase II studies is 8.4 mg/m2 when administered as a 24-hour infusion, which is well tolerated. Further studies will be necessary to account for the putative nonlinear behavior of the drug.
Extrarenal potassium homeostasis with maximal exercise in end-stage renal disease.
Authors: B A Clark, C Shannon, R S Brown, E V Gervino
Journal: Journal of the American Society of Nephrology (1996)

Serum potassium levels rise substantially during vigorous exercise as a result of the release of potassium from contracting muscle cells. Widespread use of erythropoietin has allowed for increased exercise capacity in patients with ESRD, raising the concern for severe exertional hyperkalemia. The aim of this study was to determine whether ESRD is associated with alterations in potassium and the neurohumoral mediators of extrarenal potassium disposal with maximal exercise. Eight stable hemodialysis patients (aged 37 +/- 16 yr, mean +/- SE) and eight healthy control subjects (aged 44 +/- 13 yr) exercised to exhaustion, using a graded cycle ergometer. There were no significant differences in exercise performance between groups as assessed by peak work rate, maximal oxygen consumption, and rate pressure product. Although the baseline potassium level was higher in the dialysis group (5.0 +/- 0.2 mEq/L) than in control subjects (4.5 +/- 0.1 mEq/L), both groups had a similar pattern of increase during exercise (with an increment of approximately 1 mEq/L) and a similar return to baseline after exercise. However, the dialysis patients had higher basal norepinephrine levels (820 +/- 104 versus 441 +/- 56 pg/mL, P < 0.01) and a greater response to exercise (3122 +/- 429 versus 1696 +/- 424 pg/mL, P < 0.01), higher basal insulin levels (11 +/- 1 versus 7 +/- 1 microU/mL, P < 0.05), higher insulin post-exercise levels (19 +/- 3 versus 11 +/- 1 microU/mL, P < 0.05), and higher basal aldosterone levels (621 +/- 250 versus 109 +/- 13 pg/mL, P < 0.05) with an increase response to exercise (1100 +/- 350 versus 350 +/- 17 pg/mL, P < 0.05). In summary, despite higher basal potassium, dialysis patients have normal potassium responses to maximal exercise. More vigorous insulin, catecholamine, and aldosterone levels may contribute to the maintenance of extrarenal potassium homeostasis in ESRD.
The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis
Authors: Junsong Zhou, Yi Wu, Lu Wang, Lubica Rauova, Vincent M. Hayes, Mortimer Poncz, David W. Essex
Journal: Journal of Clinical Investigation (2015)

Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (Mx1-Cre Pdifl/fl mice) and transgenic mice harboring PDI that lacks a functional C-terminal CGHC motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition and platelet accumulation in laser-induced cremaster arteriole injury, and PDI(ss-oo) mice had attenuated platelet accumulation in FeCl3-induced mesenteric arterial injury. These defects were rescued by infusion of recombinant PDI containing only a functional C-terminal CGHC motif [PDI(oo-ss)]. PDI infusion restored fibrin formation, but not platelet accumulation, in eptifibatide-treated wild-type mice, suggesting a direct role of PDI in coagulation. In vitro aggregation of platelets from PDI(ss-oo) mice and PDI-null platelets was reduced; however, this defect was rescued by recombinant PDI(oo-ss). In human platelets, recombinant PDI(ss-oo) inhibited aggregation, while recombinant PDI(oo-ss) potentiated aggregation. Platelet secretion assays demonstrated that the C-terminal CGHC motif of PDI is important for P-selectin expression and ATP secretion through a non-αIIbβ3 substrate. In summary, our results indicate that the C-terminal CGHC motif of PDI is important for platelet function and coagulation.
Do co-morbidities in patients with chronic obstructive pulmonary disease affect outcomes?
Authors: Maryam Ahmed, Karen Leech, Barbara Rickard, Carol Lynch, Gill Owen, Wayne Kempson, Martin Allen
Journal: European Respiratory Journal (2014)

Background:  Acute exacerbation of chronic obstructive pulmonary disease (COPD) make up a significant proportion of hospital admissions. Addressing factors that may affect length of stay and re-admissions are important for improving care and reducing costs.   Aim:  We have evaluated the association between chronic co-morbidities and length of stay, exacerbation frequency and re-admission rates in a cohort of patients with COPD.   Methods:  Prospective review of patients admitted with acute COPD exacerbation from July 2012 to March 2013. Data was collated on co-morbidities, length of stay (LOS), number of exacerbations and hospital re-admissions in the preceding 12 months by patient questioning and review of medical records. The co-morbidities specifically evaluated for this study were Ischaemic heart disease, Heart failure, Hypertension, Diabetes and Osteoporosis.   Results:  201 patients were included in the study. 86 (43%) were male, 119 (59%) ex-smokers, 81 (40%) current smokers. Patients were grouped in relation to their number of co-existing co-morbidities. 68 patients (33.8%) had no known co-morbidities, 19 (9.5%) had more than three. [Table 1] shows the relationship between co-morbidities and the factors evaluated  .   Conclusion:  Patients with COPD who have three or more co-morbidities had more exacerbations and hospital re-admissions. Identifying this group of patients has implications on care, both in terms of acute hospital management and strategies to prevent hospital admissions.
Book review: Health, risk and the news
Authors: Michael Fitzpatrick
Journal: Journal of the Royal Society of Medicine (2008)

Now that the MMR–autism scare is receding into history, we can reflect on the role played by the media. Tammy Boyce, researcher in media studies at Cardiff, focuses on a six-month period in 2002 when the controversy was at its height. She has examined the content of newspaper, radio and television reports, consulted national audience surveys, conducted focus groups and interviewed key sources and journalists.

Dr Boyce readily acknowledges that the media had a major impact and that it tended to favour the anti-MMR cause. She found that the repeated association of MMR with autism and the promotion of single vaccines as an alternative ‘resonated with the audience'. Dr Boyce asks some important questions: why was media coverage so sympathetic to the campaigners against MMR, and why did those supporting MMR appear relatively ineffectual?

Dr Boyce shows how the media's formal commitment to balance is ‘not always the most effective or honest way of reporting a story'. Thus an objective account of the MMR controversy ‘would not have been balanced, because, in reality, the evidence was not balanced'. An objective account would have to indicate that, on the one hand there was a vast amount of evidence confirming the safety and efficacy of the MMR vaccine, whilst on the other, there was much speculation but very little evidence for the MMR–autism link. Dr Boyce found much ‘over-balancing’ of stories, giving the misleading impression of an equivalence of evidence, and creating ‘a charade of objectivity’.

There was a similar problem of balancing sources. Though anti-MMR scientists and health professionals were in a tiny minority, they were often presented on equal terms with pro-MMR experts. Furthermore, pro-MMR experts were often challenged by parents who blamed MMR for making their children autistic, elevating emotion over reason and confusing expertise and experience.

Supporters of Andrew Wakefield, the former Royal Free researcher who led the campaign against MMR, often claim that he is a victim of a conspiracy uniting the medical establishment, Big Pharma and the government. An irony that emerges from Dr Boyce's study is that if there was any conspiracy over MMR it was on the other side. Dr Wakefield collaborated with lawyers and parent campaigners, cultivated contacts with compliant (and scientifically naive) journalists and was advised by a leading PR firm. Meanwhile supporters of MMR were fragmented and lacking any coherent media strategy, always in the position of reacting to the latest initiative from the Wakefield campaign. Medical authorities were inclined to leave matters to the Department of Health, but, on the defensive in face of mounting public distrust and wary of exacerbating parental anxieties, government officials were inclined to keep a low profile.

Dr Boyce shows how the politicization of the MMR controversy in the wake of the BSE scandal had a major influence on media coverage, to the detriment of public discussion about science and, ultimately, to the detriment of public health.
The impact of open colectomy on resection of colorectal liver metastases.
Authors: Stuart Michael Robinson, Lucas Arlott, Gourab Sen, Jeremy J. French, Richard M. Charnley, Derek M. Manas, Steve A. White
Journal: Journal of Clinical Oncology (2015)

783 Background: Laparoscopic liver resection (LLR) is increasingly utilized in the management of patients with metastatic colorectal cancer. The aim of this study was to determine the impact of ope...
Phase III Trial Comparing Two Dose Levels of Epirubicin Combined With Cyclophosphamide With Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer
Authors: Martine J. Piccart, Angelo Di Leo, Marc Beauduin, Anita Vindevoghel, Jacques Michel, Christian Focan, Alain Tagnon, Fernand Ries, Philippe Gobert, Claude Finet, Marie T. Closon-Dejardin, Jean P. Dufrane, Joseph Kerger, Françoise Liebens, Sylvie Beauvois, Sylvie Bartholomeus, Stella Dolci, Jean P. Lobelle, Marianne Paesmans, Jean M. Nogaret
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare a full-dose epirubicin-cyclophosphamide (HEC) regimen with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy and with a moderate-dose epirubicin-cyclophosphamide regimen (EC) in the adjuvant therapy of node-positive breast cancer. PATIENTS AND METHODS: Node-positive breast cancer patients who were aged 70 years or younger were randomly allocated to one of the following treatments: CMF for six cycles (oral cyclophosphamide); EC for eight cycles (epirubicin 60 mg/m 2 , cyclophosphamide 500 mg/m 2 ; day 1 every 3 weeks); and HEC for eight cycles (epirubicin 100 mg/m 2 , cyclophosphamide 830 mg/m 2 ; day 1 every 3 weeks). RESULTS: Two hundred fifty-five, 267, and 255 eligible patients were treated with CMF, EC, and HEC, respectively. Patient characteristics were well balanced among the three arms. One and three cases of congestive heart failure were reported in the EC and HEC arms, respectively. Three cases of acute myeloid leukemia were reported in the HEC arm. After 4 years of median follow-up, no statistically significant differences were observed between HEC and CMF (event-free survival [EFS]: hazards ratio [HR] = 0.96, 95% confidence interval [CI], 0.70 to 1.31, P = .80; distant-EFS: HR = 0.97, 95% CI, 0.70 to 1.34, P = .87; overall survival [OS]: HR = 0.97, 95% CI, 0.65 to 1.44, P = .87). HEC is more effective than EC (EFS: HR = 0.73, 95% CI, 0.54 to 0.99, P = .04; distant-EFS: HR = 0.75, 95% CI, 0.55 to 1.02, P = .06; OS HR = 0.69, 95% CI, 0.47 to 1.00, P = .05). CONCLUSION: This three-arm study does not show an advantage in favor of an adequately dosed epirubicin-based regimen over classical CMF in the adjuvant therapy of node-positive pre- and postmenopausal women with breast cancer. Moreover, this study confirms that there is a dose-response curve for epirubicin in breast cancer adjuvant therapy.
Mapping B cell epitopes in Goodpasture's disease.
Authors: J B Levy, A Coulthart, C D Pusey
Journal: Journal of the American Society of Nephrology (1997)

The target antigen of the pathogenic autoantibodies in Goodpasture's disease is the noncollagenous domain of the alpha 3 chain of type IV collagen. A panel of membrane-bound peptides was used to identify antibody-binding regions within the protein, and the significance of the binding by inhibition studies using soluble peptides, and by a structural analysis of the antigen, was confirmed. A total of 117 overlapping 12-mer peptides spanning the entire antigen was simultaneously synthesized as individual spots on a cellulose membrane. All nine patients' sera bound to the membrane, with a conserved pattern of peptides recognized by all sera. Inhibition studies were performed using a panel of overlapping 20-mer peptides, also spanning the entire antigen. Peptides from the regions that bound IgG were able to inhibit the binding of autoantibodies to native antigen. Predictions of the secondary structure of the noncollagenous domain of the alpha 3 chain of type IV collagen were performed by a conventional hydropathy plot and by multiple alignment of homologous alpha chains of type IV collagen and comparison with a structural data base. The core peptides binding and inhibiting Goodpasture's antibodies were predicted to be surface exposed and antigenic. Thus, the conformational epitope(s) of the Goodpasture antigen can be mapped using linear peptides.
Drug points: Hearing loss and tinnitus with carbimazole
Authors: D Hill, H Whittet, H Simspon
Journal: BMJ (1994)

A 26 year old woman pre- sented 17 months after the birth of her second child for some temporary help with the breast feeding of her nephew.The breast feeding of her child had been intermittent after 6-8 months and ceased at 15 months.Lactogenesis had continued with minimal milk expressed.A 28-32 day menstrual cycle had returned by 12 months post partum.A progestogen only pill (levonorgestrel 30 ,ug) had been used since 15 months.A synthetic oxytocin spray (Synto- cinon; Sandoz) was used on day 17 of
P6 Acupressure Reduces Morning Sickness
Authors: J W Dundee, F B R Sourial, R G Ghaly, P F Bell
Journal: Journal of the Royal Society of Medicine (1988)

A prospective study was designed to test the efficacy of pressure at the P6 (Neiguan) acupuncture point, in preventing morning sickness. Three groups of patients in early pregnancy recorded the severity and frequency of sickness over a period of 4 consecutive days following daily pressure at P6 point, pressure at a point near the right elbow and with no treatment. Troublesome sickness was significantly less in both the genuine (23/119) and dummy (41/112) pressure groups as compared with the control series (67/119). When the data are adversely ‘weighted’ to compensate for the lower incidence of fully completed returns in the active treatment groups, only the P6 group show a significant reduction in sickness. No side effects occurred in either group and while anticipation of benefit may offer a partial explanation for the findings, pressure at the Neiguan point appears to have a specific therapeutic effect.
MDCT in tracheal stetosis assessment
Authors: S.Y. Kim, E.A. Chernova, T.N. Galyan, V.V. Khovrin, V.D. Parshin, R.D. Sharipzhanova, V.A. Sandrikov
Journal: European Respiratory Journal (2012)

Purpose. MDCT assessment of the degree and extent of tracheal cicatricial stenosis (CST) in comparison to the results of endoscopic examination and intraoperative data.

Materials and methods. The research included 36 patients with postintubation CST who underwent MDCT from the larynx to the carina levels. Stenosis degree determination based on measurements performed at the level of maximal tracheal stenosis, levels above and below it. By accepted classification of the stenosis degree Grade1 CST with narrowing of the lumen at 1\3 of the diameter in 2 cases, Grade 2 (1\3 to 2\3 of the diameter) in 17, Grade 3 (more than 2\3) in 17. The distance from the proximal to distal intact tracheal wall was defined as the length of the stenosis. According to the accepted classification limited stenosis (up to 2 cm) was detected in 10 cases, extended (more than 2 cm) in 26 cases.

Results: A comparative analysis showed significant coincidence in MDCT (considering the average values and deviations for groups MDCT 3,17±1,37) and intraoperative data (3,48±1,33), and difference in MDCT (3,17±1,37) and fibreoptic data (2,81±1,28). As a result, in the degree of the stenosis extent assessment the correlation coefficient between MSCT and intraoperative studies was r-0,3 with p=0,32; between MSCT and fibrobronchoscopy was r=0,36 with p=0,25. In the stenosis degree assessment the correlation coefficient between MSCT and fibreoptic was r=1,22, with p=0,06 (p=ns); between MSCT and intraoperative data was r=1,58, with p=0,02 (p<0,05). The method gave sensitivity of 100%.

Conclusions: MDCT with 3D-reconstruction images provides indispensable information on the degree and extent of tracheal stenosis and has higher diagnostic value compared with endoscopic examination.
Reproducibility data of breath analysis through a gas sensors array and comparison to spirometry in COPD patients
Authors: Simone Scarlata, Giorgio Pennazza, Domenica Chiurco, Marco Santonico, Arnaldo D'amico, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2011)

Background: There is insufficient information on reproducibility and intra observer variability of breath analysis, a technique proved to have classificatory and discriminative properties in respiratory diseases. Aim of this study is therefore to compare variance over time of breath analysis and global spirometry in elderly patients with COPD.

Materials and methods: Data refer to the 9 COPD patients so far recruited. Patient underwent breath analysis and respiratory function study 3 times along a period of 3 weeks. The gas sensors array (based on 6 Quartz Microbalances (QMB) covered with different metalloporphyrins) used for this study was fabricated by Tor Vergata University, Rome. The reproducibility of sensors measurements and spirometry data were then compared.

Results: Results are summarized in figure 1 with panels A, B and C respectively representing the frequency shifts registered by the six QMB sensors (A) and twelve parameters obtained by global spirometry (B and C). Variance, mean value, confidence interval and outliers of a set of data are graphically depicted.

![Figure][1] 

Figure 1





Conclusions: Spirometric values show a smaller variance respect to the QMB frequency shifts. However, the reproducibility of selected sensor data seems fair enough to allow follow up COPD patients.

 [1]: pending:yes
Role of plasma membrane calcium ATPase (PMCA) in colon cancer
Authors: Cho Aung, Sarah Roberts-Thomson, Gregory Monteith
Journal: Clinical Cancer Research (2007)

A35  The plasma membrane calcium ATPase (PMCA) is an important calcium transporter in all cells and plays a crucial role in maintaining low intracellular Ca2+ levels through the active transport of calcium across the plasma membrane. PMCA is encoded by 4 genes (PMCA1-4), with PMCA1 and 4 expressed in colon epithelial cells. In this study, we examined the expression of PMCA4 in human colon cancer tissue and surrounding normal tissue using real time RT-PCR, and we have observed significant reduction of PMCA4 mRNA in some colon cancers. This is consistent with our previous findings of increased PMCA4 mRNA transcription and protein expression in a human colon cancer cell line (HT-29) during differentiation. To evaluate the possible role of altered PMCA4 expression in colon cancer, small interfering RNA (siRNA) technology was used to silence PMCA4 gene expression in HT-29 cells and the functional consequences of PMCA4 knock down on calcium homeostasis was investigated. Our results suggest that alterations in PMCA4 are likely to have functional consequences on calcium homeostasis and cell signaling in colon cancer.