tbuckley/cabot-search huggingface dataset:
Altered Expression of Metastasis-Associated and Regulatory Molecules in Effusions from Breast Cancer Patients
Authors: Ben Davidson, Sophya Konstantinovsky, Søren Nielsen, Hiep Phuc Dong, Aasmund Berner, Mogens Vyberg, Reuven Reich
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The aim of this study was to characterize phenotypic alterations along the progression of breast carcinoma from primary tumor to pleural effusion through analysis of the expression of proteases, laminin receptors (LRs), and transcription factors involved in invasion and metastasis. Experimental Design: The material studied consisted of 60 malignant pleural effusions from breast cancer patients and 68 corresponding solid tumors (37 primary and 31 metastatic tumors). Expression of matrix metalloproteinases [MMPs (MMP-1, MMP-2, MMP-9, and MMP-14)], the MMP inhibitor tissue inhibitor of metalloproteinase-2, the MMP inducer EMMPRIN, the 67-kDa LR, the α6 integrin subunit, and the transcription factors AP-2, Ets-1, and PEA3 was studied using immunohistochemistry, mRNA in situ hybridization, reverse transcription-polymerase chain reaction, zymography, and flow cytometry. Hormone receptor (estrogen receptor and progesterone receptor) status and c-erbB-2 status were also studied. Results: Significantly reduced estrogen receptor (P &amp;lt; 0.001) and progesterone receptor (P = 0.001) expression was seen in effusions compared with primary tumors, with opposite findings for c-erbB-2 (P = 0.003). Tumor cell MMP-2 protein expression in effusions was higher than that in primary tumors (P &amp;lt; 0.001) and lymph node metastases (P = 0.01). In situ hybridization demonstrated higher MMP-2 (P = 0.007), PEA3 (P = 0.038), and EMMPRIN (P = 0.026) mRNA expression in effusions. The time to progression from primary tumor to effusion was significantly shorter for patients whose primary tumors expressed MMP-1 (P = 0.016) and who expressed the 67-kDa LR protein in primary tumor (P = 0.007) and effusion (P = 0.015). Conclusions: Our data provide documented evidence of molecular events that occur during the progression of breast carcinoma from primary tumor to effusion. The coordinated up-regulation of MMP-2 and Ets transcription factors in carcinoma cells in effusions is in full agreement with our previous reports linking these factors to poor prognosis in ovarian cancer. The rapid progression to effusion in cases showing MMP-1 and 67-kDa LR expression in primary tumor cells links aggressive clinical behavior with expression of metastasis-associated molecules in this setting.
Ras Pathway Activation in Malignant Mesothelioma
Authors: Manish R. Patel, Blake A. Jacobson, Arpita De, Sandra P. Frizelle, Pasi Janne, Saritha C. Thumma, Brian A. Whitson, Faris Farassati, Robert A. Kratzke
Journal: Journal of Thoracic Oncology (2007)
The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes
Authors: Richard Kahn, John Buse, Ele Ferrannini, Michael Stern
Journal: Diabetes Care (2006)

Citrome et al. (1) seem to agree with our review (2) of all the shortcomings associated with the metabolic syndrome, yet they claim it is somehow still an aid in identifying risk factors and in the “ongoing education of practitioners,” both of which may improve health care. This seems perplexing because what must occur prior to making the “diagnosis” is knowledge of the components, and thus, a priori, the provider must be familiar with the cardiovascular disease (CVD) risk factors that comprise the concept and that the factors must be monitored. Moreover, many other CVD risk factors (e.g., LDL …
Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause
Authors: E Mouloudi, K Katsanoulas, M Anastasaki, E Askitopoulou, D Georgopoulos
Journal: European Respiratory Journal (1998)

The delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer in mechanically ventilated patients has become widespread practice. However, the various ventilator settings that influence the efficacy of MDI are not well established. Application of an end-inspiratory pause (EIP) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy. To test this, the effect of EIP on the bronchodilation induced by beta2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) was examined. Twelve patients with COPD, mechanically ventilated on volume-controlled mode, were prospectively randomized to receive six puffs of salbutamol (100 microg x puff(-1)) either with or without EIP of 5 s duration. Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer. After a 6 h wash-out, patients were crossed over to receive salbutamol by the alternative mode of administration. Static and dynamic airway pressures, minimum (Rmin) and maximum (Rmax) airflow resistance, the difference between Rmax and Rmin (deltaR), static end-inspiratory respiratory system compliance (Cst,rs) and cardiac frequency (fc) were measured before and at 15, 30 and 60 min after salbutamol administration. Salbutamol caused a significant decrease in dynamic and static airway pressures, Rmin and Rmax. These changes were not influenced by application of EIP and were evident at 15, 30 and 60 min after salbutamol. With and without EIP, Cst,rs,deltaR and fc did not change after salbutamol. In conclusion, salbutamol delivered with a metered-dose inhaler and a spacer device induced significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease, the magnitude of which was not affected by an end-expiratory pause of 5 s. These results do not support the use of end-inspiratory pause when bronchodilators are administered in adequate doses during controlled mechanical ventilation.
Primary demyelination as a nonspecific consequence of a cell-mediated immune reaction.
Authors: H M Wisniewski, B R Bloom
Journal: The Journal of Experimental Medicine (1975)

Primary demyelination occurs in a variety of human and experimental diseases known to be associated with the presence of inflammatory cells. However, the mechanism of demyelination remains unclear. The possibility that myelin can be damaged as a nonspecific consequence of a specific delayed type of hypersensitivity reaction directed at nonnervous tissue antigens was investigated. Guinea pigs were sensitized to tuberculin with Freund's complete adjuvant, and were challenged in the central and peripheral nervous system either with live or killed sonicated tubercle bacilli, Old Tuberculin, or tuberculin purified protein derivative (PPD). Local inflammatory reactions were invariably produced and primary demyelination was a constant feature of the lesions. The morphological picture was rather similar to that observed in human neurotuberculosis and early tuberculoid leprosy, and in experimental allergic encephalomyelitis and distemper encephalitis in animals. The infiltrates consisted predominantly of mononuclear cells with some polymorphonuclear cells as well. Vesicular disruption of the myelin sheath in the immediate vicinity of the inflammatory cells and stripping of the myelin lamellae by the histiocytes without axonal damage were the leading features of the lesion. The results indicate that cell-mediated immune reactions to a variety of nonbrain antigens could be responsible for a component of the demyelination seen in some inflammatory demyelinating conditions, and suggest that this system may serve as a useful model for studying the immunopathology of demyelinating disease.
Children's Factual and Delusional Memories of Intensive Care
Authors: Gillian Colville, Sally Kerry, Christine Pierce
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Delusional memories are significantly associated with post-traumatic stress in adult patients after intensive care.In this study, we attempted to establish whether this relationship was found in children. We also examined the association between factual memory and distress.One hundred two consecutive children, aged between 7 and 17 years, were interviewed about their pediatric intensive care unit (PICU) experience 3 months after discharge from a PICU. Principal measures were the ICU Memory Tool (a checklist of intensive care memories) and an abbreviated version of the Impact of Event Scale (a screen for post-traumatic stress disorder).In total, 64 of 102 (63%) children reported at least one factual memory of their admission and 33 of 102 (32%) reported delusional memories, including disturbing hallucinations. Traumatic brain injury was negatively associated with factual memory (odds ratio, 0.23; 95% confidence interval [CI], 0.09-0.58; P = 0.002). Longer duration of opiates/benzodiazepines was associated with delusional memory (odds ratio, 4.98; 95% CI, 1.3-20.0; P = 0.023). Post-traumatic stress scores were higher in children reporting delusional memories (adjusted difference, 3.0; 95% CI, 0.06-5.9; P = 0.045) when illness severity and emergency status were controlled for. Factual memory was not significantly associated with post-traumatic stress.This study indicates that delusional memories are reported by almost one-third of children and are associated both with the duration of opiates/benzodiazepines and risk of post-traumatic stress. More research is needed on the presence of delusional memories and associated risk factors in children receiving intensive care treatment.
Comparative clinicopathological and immunohistochemical study of ras and p53 in flat and polypoid type colorectal tumours.
Authors: M Yukawa, T Fujimori, S Maeda, M Tabuchi, K Nagasako
Journal: Gut (1994)

Mutations in oncogenes and tumour suppressor genes may have an important oncogenic role. Although flat type tumours have been frequently detected in recent years, ras and p53 expressions have not been studied in these tumours. Using a monoclonal and polyclonal antibody to the ras p21 and p53 product, paraffin wax embedded sections of 98 colorectal tumours (43 cases of the flat type colorectal tumour and 55 cases of polypoid type tumour) were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination. Positive staining rate of ras p21 for the flat type was 0%; for the polypoid type, it was 60% in cancer with submucosal invasion, 82% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The positive staining rate of p53 for the flat type was 50% in submucosal cancer, 9% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. For the polypoid type, it was 40% in submucosal cancer, 12% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The intermediate staining rate of p53 in the polypoid type was 20% in submucosal cancer and 41% in adenoma with high grade dysplasia. It was seen that p53 was commonly expressed in both flat and polypoid lesions, p21 was not expressed in flat lesions, whereas it was commonly expressed in polypoid neoplasms. In the flat type cancer, a genetic change different from that of the polypoid type cancer is suggested.
Transient elastography in chronic viral hepatitis: a critical appraisal
Authors: A.-C. Cardoso, R. J. Carvalho-Filho, P. Marcellin
Journal: Gut (2011)

Even with all the heated discussion about the value of liver biopsy, it remains the gold standard method for the assessment of liver fibrosis and the severity of chronic liver diseases.1 Histological analysis of liver tissue still provides invaluable information about three key issues for the management of patients with liver diseases: diagnosis, prognosis and therapeutic decisions. In the context of chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), evaluation of the stage of liver fibrosis is of major importance. Additional information can also be provided, such as the pattern of liver fibrosis, grading of necroinflammatory activity and the presence of steatosis and hepatic iron overload. These and other histological findings are highly relevant in clinical practice, because they not only allow the clinician to infer on the dynamics of fibrogenesis (whether lesions are ancient or progressive), but also permit the identification of associated liver diseases that can potentially alter the natural history of chronic viral hepatitis and impair the efficacy of therapy.

Nevertheless, liver biopsy is a costly and invasive technique with associated mortality and morbidity, well documented in both retrospective and prospective studies.2 3 A typical biopsy fragment represents only 1/50 000 of the organ and most chronic liver diseases exhibit a heterogeneous distribution of hepatic fibrosis. Therefore, histopathological analysis of liver tissue is susceptible to variability in interpretation, being significantly influenced by the quality of the fragment (adequate length and number of portal tracts) and by the expertise of the pathologist.4 5

In a world with an imperfect gold standard model, several non-invasive approaches have been proposed to estimate liver fibrosis in patients with liver diseases, …
Complete basal cell carcinoma remission with imiquimod in a patient with nevoid basal cell carcinoma syndrome and associated basal cell carcinoma of the scalp and invasive ductal breast cancer
Authors: Sven R. Quist, Ingolf Franke, Marten Helmdach, Cornelia Kraus, André Reis, Ursula G. Froster, Dirk Fehsecke, Harald P. Gollnick, Bernd Bonnekoh
Journal: Journal of the American Academy of Dermatology (2011)
A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--part 10
Authors: S J Stear, L M Castell, L M Burke, N Jeacocke, B Ekblom, C Shing, P C Calder, N Lewis
Journal: British Journal of Sports Medicine (2010)

A–Z of nutritional supplements : dietary supplements, sports nutrition foods and ergogenic aids for health and performance—part                                          10
Local Radiotherapy Induces Homing of Hematopoietic Stem Cells to the Irradiated Bone Marrow
Authors: Carlo Bastianutto, Asim Mian, Julie Symes, Joseph Mocanu, Nehad Alajez, Gillian Sleep, Wei Shi, Armand Keating, Michael Crump, Mary Gospodarowicz, Jeff Medin, Mark Minden, Fei-Fei Liu
Journal: Cancer Research (2007)

Abstract Local breast radiation therapy (RT) is associated with a 3-fold increased risk of secondary acute myeloid leukemia. As a first step in determining the mechanism(s) underlying this observation, we investigated the role of RT in mediating the active recruitment of hematopoietic stem cells (HSC) to the site of RT. Our results show in a mouse model that local RT delivered to the left leg causes preferential accumulation of bone marrow mononuclear cells to the irradiated site, with maximum signal intensity observed at 7 days post-RT. This is associated with a 4-fold higher number of donor-derived HSC present in the left leg, demonstrating recruitment of HSC to the site of RT. SDF-1, matrix metalloproteinase 2 (MMP-2), and MMP-9 expression is significantly increased in the irradiated bone marrow, and their inhibition significantly reduced HSC recruitment to the irradiated bone marrow. Our data show that local RT has significant systemic effects by recruiting HSC to the irradiated bone marrow site, a process mediated by SDF-1, MMP-2, and MMP-9. These results raise the possibility that the exposure of increased numbers of HSC at a local site to fractionated irradiation may increase the risk of leukemogenesis. Our data also suggest some opportunities for leukemia prevention in breast cancer patients undergoing RT. [Cancer Res 2007;67(21):10112–6]
A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012–14): a retrospective cohort study
Authors: Alexander L Greninger, Samia N Naccache, Kevin Messacar, Anna Clayton, Guixia Yu, Sneha Somasekar, Scot Federman, Doug Stryke, Christopher Anderson, Shigeo Yagi, Sharon Messenger, Debra Wadford, Dongxiang Xia, James P Watt, Keith Van Haren, Samuel R Dominguez, Carol Glaser, Grace Aldrovandi, Charles Y Chiu
Journal: The Lancet Infectious Diseases (2015)
Endoscopic Ultrasound in Non–Small Cell Lung Cancer and Negative Mediastinum on Computed Tomography
Authors: Julia K. LeBlanc, Benedict M. Devereaux, Thomas F. Imperiale, Ken Kesler, John M. DeWitt, Oscar Cummings, Donato Ciaccia, Stuart Sherman, Praveen Mathur, Dewey Conces, Joann Brooks, Melissa Chriswell, Lawrence Einhorn, Edith Collins
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Despite technical advances in staging non-small cell lung cancer (NSCLC), accurate staging remains a challenge. Endoscopic ultrasound is useful in staging NSCLC when lymphadenopathy is present on a computed tomography (CT), but its role in the absence of lymphadenopathy on CT has not been well defined. Therefore, we sought to determine the clinical impact of endoscopic ultrasound (EUS) in staging NSCLC in absence of mediastinal lymphadenopathy on CT. Seventy-six patients with NSCLC with absence of mediastinal lymphadenopathy on CT were enrolled and followed prospectively. EUS-guided fine-needle aspiration was performed on sites that were suspicious for metastases. Surgical pathology after thoracotomy was used as the reference standard for assessing accuracy. Sixty-two (86%) patients underwent surgery, and 10 (13%) did not. EUS precluded surgery in 9 patients (12%) and influenced management in 18 (25%) of all patients in this study. EUS detected malignant mediastinal lymphadenopathy more frequently in patients with lower lobe and hilar cancers combined compared with upper lobe cancers (p = 0.004). EUS played a significant role in identifying patients with unresectable (N3) NSCLC when adenopathy was not present on CT imaging and appears to be more sensitive in detecting lymph node metastases in lower lobe and hilar NSCLC compared with upper lobe NSCLC.
P61 BTS MDRTB Clinical Advice Service
Authors: D Cullen, JP Watson, PDO Davies
Journal: Thorax (2012)

Developing an initiative begun by Professor Peter Davies and colleagues in Liverpool in 2008, the BTS has now significantly increased the functionality of this Service to offer an opportunity for genuine on line dialogue between experts and service users on all aspects of the management of patients with MDRTB. Fully operational since July 2011–64 discrete case queries were received in the first year of operation, of which 41 were confirmed as MDRTB; 4 XDRTB; 7 Isoniazid mono-resistant and 1 related to a mycobacterium infection. The remaining 11 cases discussed were never confirmed as MDRTB or were general requests for advice. This represents a 45% increase in case discussion since the BTS unveiled the new Service and the initial post is now regularly being followed by further requests for help as new difficulties in case management emerge. The BTS MDRTB Clinical Advice Forum is accessible via a link on the home page of the BTS website OR directly at the url below: http://forums.brit-thoracic.org.uk/ After an on line registration is approved by the forum administrator, users are prompted to provide anonymised case details according to a pre-set questionnaire template. There is also a free text box and an opportunity to post X-ray and CT images.
Extraction of Pulmonary Vascular Compliance, Pulmonary Vascular Resistance, and Right Ventricular Work From Single-Pressure and Doppler Flow Measurements in Children With Pulmonary Hypertension: a New Method for Evaluating Reactivity
Authors: Craig E. Weinberg, Jean R. Hertzberg, D. Dunbar Ivy, K. Scott Kirby, K. Chen Chan, Lilliam Valdes-Cruz, Robin Shandas
Journal: Circulation (2004)

Current evaluation of pulmonary hypertension (PH) in children involves measurement of pulmonary vascular resistance (PVR); however, PVR neglects important pulsatile components. Pulmonary artery (PA) input impedance and ventricular power (VP) include mean and pulsatile effects and have shown promise as alternative measures of vascular function. Here we report the utility of pulsed-wave (PW) Doppler-measured instantaneous flow and pressure measurements for estimation of input impedance and VP and use this method to develop a novel parameter: reactivity in compliance.An in vitro model of the general pulmonary vasculature was used to obtain impedance and VP, measured by PW Doppler and a reference flow meter. The method was then tested in a preliminary clinical study in subjects with normal PA hemodynamics (n=4) and patients with PH undergoing reactivity evaluation (8 patients; 23 data points). In vitro results showed good agreement between the impedance spectra computed from both flow-measurement methods. Excellent correlation was seen in vitro between actual resistance and the zero-frequency (Z(o)) impedance value (r2=0.984). Excellent agreement was also found between Z(o) and PVR in the clinical measurements (y=1.075x+0.73; r=0.993). Furthermore, total VP and VP/cardiac output increased significantly with hypertension (128.73 to 365.91 mW and 2.42 to 6.69 mW x mL(-1) x s(-1), respectively). The first-harmonic value of impedance (Z1) was used as a measure of compliance reactivity; older patients exhibited markedly less compliance reactivity than did younger patients.Input impedance and VP calculated from Doppler measurements and a single-catheter pressure measurement provide comprehensive characterization of PH and reactivity.
Existence of an Endogenous Circadian Blood Pressure Rhythm in Humans That Peaks in the Evening
Authors: Steven A. Shea, Michael F. Hilton, Kun Hu, Frank A.J.L. Scheer
Journal: Circulation Research (2011)

Blood pressure (BP) usually decreases during nocturnal sleep and increases during daytime activities. Whether the endogenous circadian control system contributes to this daily BP variation has not been determined under appropriately controlled conditions.To determine whether there exists an endogenous circadian rhythm of BP in humans.In 28 normotensive adults (16 men), we assessed BP across 3 complementary, multiday, in-laboratory protocols performed in dim light, throughout which behavioral and environmental influences were controlled and/or uniformly distributed across the circadian cycle via: (1) a 38-hour "constant routine," including continuous wakefulness; (2) a 196-hour "forced desynchrony" with 7 recurring 28-hour sleep/wake cycles; and (3) a 240-hour forced desynchrony with 12 recurring 20-hour sleep/wake cycles. Circadian phases were derived from core body temperature. Each protocol revealed significant circadian rhythms in systolic and diastolic BP, with almost identical rhythm profiles among protocols. The peak-to-trough amplitudes were 3 to 6 mm Hg for systolic BP and 2 to 3 mm Hg for diastolic BP (always P<0.05). All 6 peaks (systolic and diastolic BP in 3 protocols) occurred at a circadian phase corresponding to ≈9:00 pm (ie, the biological evening). Based on substantial phase differences among circadian rhythms of BP and other variables, the rhythm in BP appeared to be unrelated to circadian rhythms in cortisol, catecholamines, cardiac vagal modulation, heart rate, or urine flow.There exists a robust endogenous circadian rhythm in BP. The highest BP occurred at the circadian time corresponding to ≈9:00 pm, suggesting that the endogenous BP rhythm is unlikely to underlie the well-documented morning peak in adverse cardiovascular events.