tbuckley/cabot-search huggingface dataset:
Predicting peak cycle work rate from the six-minute walk test in COPD
Authors: Rahizan Zainuldin, Martin Mackey, Nia Luxton, Jennifer Alison
Journal: European Respiratory Journal (2011)

Equations predicting peak work rate (W peak ) on an incremental cycle test (ICT) from a six-minute walk test (6MWT) have been developed but often overestimate W peak . Since peak oxygen consumption (VO 2 ) from the 6MWT and ICT have been shown to be equivalent in moderate to severe COPD, it may be possible to use VO 2  as the common measure between 6MWT and ICT to improve the accuracy of the predictive equations. The study aimed to develop equations to estimate the W peak  of an ICT from a 6MWT using VO 2  as the common link. In a prospective study, 50 participants with COPD (mean [SD] FEV 1  = 57 [18]%predicted) performed an ICT and two 6MWTs. Data from the better 6MWT were used for analysis. Gas exchange during exercise tests was measured by a portable gas analyser. The analyses performed were: 1) Stepwise multiple regression analysis with independent variables of gender, age, height, FEV 1  and 6MWwork (product of 6MWdistance and weight) used to develop an equation predicting peak VO 2  (VO 2peak(ICT) ); 2) The slopes and intercepts of the relationship between VO 2(ICT)  and work rate for each participant were averaged to create an equation relating VO 2(ICT)  and work rate. The mean peak VO 2  measured in the 6MWT and ICT were not significantly different. From the stepwise analysis, the regression equation was VO 2peak(ICT)  = 0.018$*$6MWwork + 7.57$*$Ht – 737.3 (r=0.77). A linear relationship between VO 2(ICT)  and work rate was found, thus an equation to predict peak work rate was developed as: W peak  = (VO 2peak(ICT)  – 429)/10.2. The calculation of a W peak(ICT)  from a clinically available 6MWT via these equations may aid prescription of cycle training intensity when an ICT is unavailable.
Reserpine and Carcinogenesis: Inhibition of Carcinoma Formation in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Lupulescu
Journal: JNCI Journal of the National Cancer Institute (1983)

Long-term administration of reserpine, an alkaloid, significantly retarded the induction of squamous cell carcinomas by a chemical carcinogen, 3-methylcholanthrene (MCA) in Swiss male albino mice. The incidence and development of carcinomas in mice simultaneously treated with reserpine and MCA was notably lowered as compared to those occurring in mice treated with MCA alone at any time interval. DNA synthesis and the percentage of labeled cells with [3H]thymidine was also significantly decreased in the nuclei of tumor cells following reserpine and MCA administration as compared to the findings for cells treated with MCA alone (18.50 and 39.00%, respectively). Electron microscopic and cytologic observations of tumors revealed the predominance of large areas of cytolysis and disintegration with an increase of lysosomes, myelin figures, and a decrease of mitochondria and polyribosome populations in tumor cells treated with reserpine and MCA, as compared to those results after treatment with MCA only. These findings demonstrate that reserpine significantly inhibited the carcinoma induction by a chemical carcinogen (MCA) in mice, possibly by inducing an advanced cytolysis and decreasing DNA synthesis in mouse tumor cells.
Less pain without pain-killers?
Authors: Vasile Grigorie, Cornel Savu, Radu Posea, Boris Coman, Cornel Petreanu, Dan Avramescu, Nicolae Galie
Journal: European Respiratory Journal (2012)

OBJECTIVES  To assess if the mode of closing the thoracothomy may have an influence over the post-operative pain.  MATHERIAL AND METODS  Prospective study, with 2 groups of patients, 15 cases each. Group A – for this patients, the stiches used to close the thoracothomy were passed between the rib and intercostal nerve (in this cases the nerve wasn9t compressed against the rib when the stich was tightened). Group B – the stiches were passed in classic fashion, inferior to intercostal nerve and when the thoracotomy was closed, the pressure of the stiches compressed the nerve against the rib. All patients had lateral thoracotomy, 3 stiches were used for all patients, no peridural/paravertebral catheter was used and regular analgesia (consisted in Paracetamol, Tramadol and NSAID) was used for all patients. For assessing the pain, we used a scale from 0-10, 0 = no pain, 10 = pain intensity was the biggest ever felt by the patient. We assess the pain in the first 48 h post-op and after 21 days.  RESULTS  Group A – only 2 patients alleged pain score 10 in first 48 hours post op, 1 patient – score 9, the rest of the group pain was 8 or less. Group B – 13 patients alleged pain score 10 post-op, 1 patient – score 8 and 1- score 7. Pain assessed 3 weeks after: group A pain score range from 0 to 7, and in group B from 0 to 10.  DISCUSSIONS  Pain is difficult to assess preciselly because the threshold and perception is different from person to person. According with this study, it seems that involvement of the intercostal nerve in the closure of thoracotomy increase the post-operative pain, especially in the first 48 hours.
Blood gas measurement during exercise: a comparative study between arterialized earlobe sampling and direct arterial puncture in adults
Authors: I Fajac, J Texereau, V Rivoal, JF Dessanges, AT Dinh-Xuan, J Dall'Ava-Santucci
Journal: European Respiratory Journal (1998)

Sampling arterialized earlobe blood is thought to be easier and less painful than direct arterial puncture, and to allow measurement of blood gas values during exercise without the need to insert an arterial cannula. However, arterialized earlobe oxygen tension (PO2) often underestimates arterial PO2 at rest, and is not fully validated during exercise. We have therefore conducted a prospective study to compare values of PO2 and carbon dioxide tension (PCO2) and the discomfort experienced by adult subjects undergoing the two methods of blood sampling during exercise. Seventy consecutive adult patients were studied. Blood samples were drawn simultaneously from the radial artery and arterialized earlobe of each patient during the last minute of an 8 min exercise. Values of PO2 and PCO2 were measured by means of blood gas electrodes. The correlation coefficients between the two samples were 0.92 for PO2 and 0.91 for PCO2. However, the bias and the limits of agreement between the two methods were wide for PO2 (mean+/-2SD of the differences between the two methods: 0.63+/-1.50 kPa (4.7+/-11.2 mmHg)). The bias and the limits of agreement were smaller for PCO2. Patients felt that the earlobe method was not associated with less discomfort than radial artery puncture. We conclude that arterialized earlobe blood oxygen tension is not a good substitute for arterial oxygen tension during exercise, and should not be used to assess arterial oxygen tension in adults during exercise.
B16 Melanoma Cell Variants: Irreversible Inhibition of Growth and Induction of Morphologic Differentiation by Anthracycline Antibiotics&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: Avraham Raz
Journal: JNCI Journal of the National Cancer Institute (1982)

The interaction of doxorubicin and N-trifluoroacetyladriamycin-14-valerate (AD32) with B16 melanoma cell variants that exhibit distinct metastatic properties was explored. The addition of the two drugs to cell monolayers at noncytolytic concentrations for 16 hours resulted in irreversible inhibition of proliferation of tumor cells and loss of their tumorigenicity after injection into inbred C57BL/6 mice. Cessation of melanoma cell proliferation was accompanied by cellular and nuclear hypertrophy and the development of axon-like processes. As assessed by drug-specific cytofluorescence, after 16-hour exposure of the cells to doxorubicin and AD32, the drugs were localized in the nuclei. Incubation of drug-treated cell monolayers for 6 additional days in drug-free culture medium led to the complete disappearance of nuclear stain. The highly metastatic B16-F10-B2 cell line was the most sensitive to the drugs' effects, whereas the other two malignant melanoma cell lines, although differing in their metastatic capabilities, exhibited similar sensitivities to the drugs' effects. Doxorubicin was notably more potent than AD32 in its growth inhibitory effect on the three tested melanoma cell variants. The possible mutagenic effect of anthracycline drugs on tumor cells was discussed.
Characterization of <sup>89</sup>Zr-trastuzumab for clinical HER2 immunoPET imaging
Authors: E. Dijkers, M. N. Lub-de Hooge, J. G. Kosterink, P. L. Jager, A. H. Brouwers, L. R. Perk, G. A. van Dongen, E. G. de Vries
Journal: Journal of Clinical Oncology (2007)

3508 Background: SPECT imaging with 111 In-DTPA-trastuzumab has recently identified new tumor lesions, undetected with conventional staging, in 13/15 patients with HER2++ breast cancers (Perik et al., J Clin Oncol 2006). The aim of this study was to develop an immunoPET label, suitable for clinical use, which would allow excellent detection of HER2 positive tumor lesions and quantification of HER2 expression levels in vivo. Methods: Trastuzumab has essentially been radiolabeled as described by Verel et al. (J Nucl Med 2003). Radiochemical purity (rcp) and stability were determined by SEC-HPLC, immunoreactivity with a Lindmo assay. Biodistribution was performed in nude mice bearing HER2 positive (SKOV3) or HER2 negative (GLC4) xenografts. Five animals per group were co-injected with 111 In-ITC-DTPA-trastuzumab and 89 Zr-trastuzumab, imaged on a microPET (Focus 220) and sacrificed 144 hours post injection. Results: The immunoreactive fraction of 89 Zr-trastuzumab was 0.96, labeling efficiency &gt; 90% and rcp &gt; 95%. 89 Zr-trastuzumab was stable for 7 days in buffer at 4 °C and in human serum at 37 °C. MicroPET imaging showed excellent tumor uptake and could easily detect metastases with a size approximating the spatial resolution of the microPET scanner. 89 Zr- and 111 In-ITC-DTPA-trastuzumab showed similar biodistribution. Highest uptake was found in HER2 positive tumors at 144 hours post injection (40% ID/g tissue for 89 Zr-trastuzumab and 47% ID/g for 111 In-ITC-DTPA-trastuzumab) compared to 8% ID/g tissue in HER2 negative control tumors. Liver uptake was low (8–12% ID/g tissue). Preliminary results in HER2 positive breast cancer patients show excellent tumor tracer uptake and a resolution unapproachable by 111 In-DTPA-trastuzumab. Conclusions: 89 Zr-trastuzumab is stable, shows excellent and specific tumor uptake and is suitable for clinical use. Minimal aspecific tracer uptake in the liver allows detection of abdominal metastases. No significant financial relationships to disclose.
Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment
Authors: L J van Doorn, P M Schneeberger, N Nouhan, A P Plaisier, W G Quint, W A de Boer
Journal: Gut (2000)

Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment.To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome.121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively.DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation.Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains.The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.
Controversies in the Evaluation and Management of Atypical Melanocytic Proliferations in Children, Adolescents, and Young Adults
Authors: Damon Reed, Ragini Kudchadkar, Jonathan S. Zager, Vernon K. Sondak, Jane L. Messina
Journal: Journal of the National Comprehensive Cancer Network (2013)

The rising incidence of melanoma in children has brought increased attention to the clinical and pathologic diagnosis of pigmented lesions in the pediatric age group. Although melanoma in infancy and early childhood is often associated with large congenital nevi, in older children and teenagers it is most often sporadic, occurring in patients with a low skin phototype and substantial sun exposure. The rarity of this potentially fatal disorder demands astute clinical attention and a high index of suspicion for atypical lesions in pediatric patients. The challenges include the difficult decision of whether to biopsy and an often equivocal pathologic diagnosis. These diagnostically challenging and equivocal lesions lead to a degree of uncertainty regarding additional workup, prognosis, potential therapy, and follow-up plans. Consultation with a specialty dermatopathologist can be very helpful, and advanced molecular diagnostic techniques may be used in selected circumstances. Although still controversial, good evidence exists to justify a role for sentinel lymph node biopsy. Patients with atypical melanocytic proliferations have a high rate of positive sentinel lymph nodes; however, their outcomes are clearly better than in similarly staged adults with conventional melanoma. With the multiple variables involved and the relative lack of prospectively derived evidence, clinical decision-making is challenging and patients and families may experience considerable stress. This article provides data and weighs the pros and cons of a rationale for decision-making in pediatric and young adult patients with diagnostically challenging melanocytic lesions.
PtdIns(3,4,5)<i>P</i>3-Dependent Activation of the mTORC2 Kinase Complex
Authors: Pengda Liu, Wenjian Gan, Y. Rebecca Chin, Kohei Ogura, Jianping Guo, Jinfang Zhang, Bin Wang, John Blenis, Lewis C. Cantley, Alex Toker, Bing Su, Wenyi Wei
Journal: Cancer Discovery (2015)

mTOR serves as a central regulator of cell growth and metabolism by forming two distinct complexes, mTORC1 and mTORC2. Although mechanisms of mTORC1 activation by growth factors and amino acids have been extensively studied, the upstream regulatory mechanisms leading to mTORC2 activation remain largely elusive. Here, we report that the pleckstrin homology (PH) domain of SIN1, an essential and unique component of mTORC2, interacts with the mTOR kinase domain to suppress mTOR activity. More importantly, PtdIns(3,4,5)P3, but not other PtdInsPn species, interacts with SIN1-PH to release its inhibition on the mTOR kinase domain, thereby triggering mTORC2 activation. Mutating critical SIN1 residues that mediate PtdIns(3,4,5)P3 interaction inactivates mTORC2, whereas mTORC2 activity is pathologically increased by patient-derived mutations in the SIN1-PH domain, promoting cell growth and tumor formation. Together, our study unravels a PI3K-dependent mechanism for mTORC2 activation, allowing mTORC2 to activate AKT in a manner that is regulated temporally and spatially by PtdIns(3,4,5)P3.The SIN1-PH domain interacts with the mTOR kinase domain to suppress mTOR activity, and PtdIns(3,4,5)P3 binds the SIN1-PH domain to release its inhibition on the mTOR kinase domain, leading to mTORC2 activation. Cancer patient-derived SIN1-PH domain mutations gain oncogenicity by loss of suppressing mTOR activity as a means to facilitate tumorigenesis.
Tuberculosis elimination in the countries of Europe and other industrialized countries
Authors: L Clancy, H L Rieder, D A Enarson, S Spinaci
Journal: European Respiratory Journal (1991)

The working group summarized the conclusions of the workshop with the intention of providing a guide for the preparation of national plans for tuberculosis elimination. The basic strategies that appear consistently effective are: 1. Direct government responsibility for diagnosis, treatment and prevention of tuberculosis (the government is responsible by law for assuring that tuberculosis is identified early, and that cure of the patients is achieved). 2. Maintenance (or development) of properly designed disease surveillance and a programme monitoring system. 3. Availability of specialized tuberculosis personnel at regional and provincial level, responsible for close monitoring of the diagnostic skills and patient prioritization in general health institutions. Regarding research it was felt that no immediate practical applications of new techniques in the diagnosis of mycobacterial diseases, in treatment, or in vaccination can be recommended, but that further basic research in the field of mycobacteria should be pursued and supported.
Detection of hepatopulmonary syndrome in patients with liver cirrhosis using 3D contrast echocardiography
Authors: Rania Gaber, Dina H. Ziada, Nesreen A. Kotb, Gehan H. Abo El-Magd, Manal Hamisa
Journal: European Respiratory Journal (2014)

Background and study aims: Hepatopulmonary syndrome (HPS) is characterised by triad of advanced liver disease, hypoxaemia and intrapulmonary vascular dilatation (IPVD). This study aimed to evaluate HPS in patients with liver cirrhosis and the role of 3D contrast echocardiography in detection of this syndrome.  Patients and methods: 78 chronic liver disease patients fulfilled the criteria for this study; were subjected to clinical examination, arterial blood gases, pulmonary function tests, upper gastrointestinal endoscopy, 3D contrast echocardiography and CT pulmonary angiography.  Results: According to 3D contrast echocardiography results, we divided the patients into positive group (26) in which patients showed delayed appearance of contrast in left heart chambers and negative group (52). Among 26 patients of positive group, 9 had hypoxaemia were diagnosed as having HPS, the other 17 had shown echocardiographic evidence of IPVDs but without hypoxaemia were diagnosed as subclinical HPS. This study showed significant correlation between positive echocardiography and duration of liver disease, Child score, cyanosis, clubbing, orthodeoxia, portal vein diameter and oesophageal varices. No significant correlation was found between 3D contrast echocardiography and age, sex, spider naevi and pulmonary function tests. Multivariate logistic regression showed that cyanosis, clubbing, orthodeoxia, Child score and portal vein diameter are independent predictors of HPS.  Conclusion: Cyanosis, clubbing and platypnoea-orthodeoxia are suggestive indicators of HPS, which can be easily detected by 3D contrast echocardiography which can replace trans-oesophageal echocardiogram in cirrhotic patients.
Pathophysiology and treatment of posttransplant hypertension.
Authors: R G Luke
Journal: Journal of the American Society of Nephrology (1991)

Post-renal transplant hypertension remains a common problem. The most frequent causes now are chronic rejection and cyclosporine-induced hypertension. Before the development of cyclosporine, renin-dependent hypertension was the dominant pathophysiological mechanism but now, with the widespread use of cyclosporine, a salt-dependent mechanism is the major one. In severe "inappropriate" hypertension, potentially surgically remediable causes such as renal artery stenosis of the allograft artery or renin release from the native kidneys should be considered. Cyclosporine causes hypertension in normal subjects and in all solid organ transplants. The most likely mechanism is renal vasoconstriction with subtle retention of sodium chloride together with systemic vasoconstriction. The vasoconstriction, as yet, is not associated with any specific vasoconstricting agent nor does there appear to be a specific antagonist. Indeed, increased sensitivity to many different vasoconstrictors has been demonstrated. The major site of vasoconstriction appears to be in the afferent arteriole, and optimum antihypertensive therapy is probably provided by calcium channel blockers if the hypertension is due to cyclosporine. Because post-renal transplant hypertension is often multifactorial in origin, however, it is not surprising that the use of combined antihypertensives is often necessary.
Diagnostic contribution of cell block obtained through endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)
Authors: Natalia Fouz Rosón, Estefanía Luque Crespo, María Pavón Masa, Andrés Humberto Vega Arias, Concepción Romero Muñoz, Teodoro Montemayor Rubio
Journal: European Respiratory Journal (2014)

Introduction:   Conventional smear samples, obtained by EBUS-TBNA, have been useful for diagnosing lung cancer and other benign conditions including sarcoidosis. However, the contribution of cell-block analysis has not been clearly established.   Aims:   -A descriptive analysis of patients referred to the respiratory unit who underwent EBUS-TBNA.  -Evaluate the cell-block contribution to the diagnostic yield in the referred patients.   Methods and Materials:   All the patients who underwent EBUS-TBNA (Feb2009-Oct2013) were included, not only for those with staging or suspected lung cancer but also the ones with adenopathies found in the computed tomography.  The procedure was carried out with local anaesthesia (lidocaine) and under conscious sedation (intravenous midazolam).  Smear samples adequacy was assessed by a pathologist using “rapid on-site evaluation” (ROSE).   Results:   244 patients were included (82% men); mean age: 60,19±13,3.  The final diagnosis was obtained by EBUS-TBNA in 54,4% of the cases(n=131). In 92,6% of the cases ROSE was performed, being positive in 55,7%.  Cell-blocks were obtained in 105 patients, of which 70,5%(n=74) were useful for diagnosis. Additional diagnostic information in 15 patients who had a negative result in the smear samples was provided by the cell-block (44,1%) of which 10 cases were cancer, being adenocarcinoma the most common.  No relationship between the number of punctures performed and the cell-block obtention was found.   Conclusions:   The cell-block provides additional pathologic information in patients with negative smear samples confirming its utility for lung cancer diagnosis and other benign diseases.
Concussion history is not a predictor of computerised neurocognitive performance
Authors: S P Broglio, M S Ferrara, S G Piland, R B Anderson
Journal: British Journal of Sports Medicine (2006)

Background: The long term effects of self reported concussion on neurocognitive functioning have been found to be variable. Objectives: To evaluate cognitive performance on the Headminder concussion resolution index (CRI) and ImPACT assessment tests of subjects with and without a history of self reported concussion. Methods: A retrospective analysis was completed on 235 Headminder CRI baseline assessments and 264 ImPACT baseline assessments. Participants were divided into four groups on the basis of reported number of concussions (zero, one, two, or three). Multivariate analysis of variance was used to evaluate differences between the concussion history groups on the two computer based concussion assessment programs. Results: Multivariate analysis of variance indicated no significant difference between those with and without a history of concussion on the CRI (Λ = 0.963, F (15, 627.05) = 0.57, p = 0.898). It also revealed no significant differences between groups on the ImPACT test (Λ = 0.951, F (12, 672.31) = 1.07, p = 0.381). Conclusions: The results suggest that either long term cognitive decrements may not be associated with a history of concussion or the decrements may be subtle and undetectable by these computer programs.