tbuckley/cabot-search huggingface dataset:
AN ALL HUMAN 3D IN VITRO MODEL OF THE BLOOD BRAIN BARRIER IN NANOPARTICLE DELIVERY AND CANCER METASTASIS STUDIES
Authors: G. J. Pilkington, Z. Maherally, S. Jassam, E. Barbu, H. Fillmore
Journal: Neuro-Oncology (2014)

BACKGROUND: The blood-brain barrier (B-BB) is a dynamic functional unit consisting of endothelial cells, astrocytic endfeet and pericytes embedded in a specialized basement membrane. Most in vitro studies examine the ability of therapeutics to cross the B-BB using monolayer cultures or mixed species co-cultures and rely on Trans-Endothelial Electrical Resistance (TEER) measurements without verification of tight-junction (TJ) formation. More reliable high throughput in vitro models are therefore essential in brain tumour drug delivery and metastatic tumour behavioural studies. We are developing and testing a 3-dimensional in vitro model incorporating aspects of known B-BB in vivo characteristics. METHODS: A 3D model of the B-BB was constructed using human brain endothelial cells (hCMEC/D3), human astrocytes (SC-1800/UP010) and human brain vascular pericytes (HBVP) in mono-, co-, tri- cultures. TEER values were measured using a cell monitoring system- cellZscope®. TJ proteins (ZO-1 and occludin) were examined by Western blotting and immunocytochemistry. Effects of extracellular matrix (ECM) molecules (laminin, fibronectin, collagen type IV, agrin, perlecan) were assessed on endothelial cell proliferation, adhesion and TEER changes using an Electric Cell-Substrate Impedance Sensing (ECIS) system. Modified chitosyme nanoparticles and metastatic lung cancer cells were tested for effects on B-BB integrity. RESULTS: Co-cultures and tri-cultures resulted in significantly higher TEER values compared to endothelial cells alone (p < 0.05). TEER values for co-culture of ECs and astrocytes were 4620 Ω/cm2, and for tri-cultivation including pericytes, 4141.50 Ω/cm2 compared to single EC cultures (2244 Ω/cm2). Western blot revealed higher expression of ZO-1 and occludin in co- and tri-cultures. The individual optimal ECM concentrations for highest and longest TEER values differed depending on ECM molecule and concentration. Cell adhesion (%) correlated with TEER values. Recovery time of B-BB integrity following chitosyme nanoparticle/metastatic cell treatment, differed in mono-, co-, tri-cultures. CONCLUSIONS: Astrocytes contribute to B-BB formation in this in vitro model. Motile pericytes may positively or negatively influence barrier formation or TJ tightness. ECM has varied and profound effects on TEER values. Multiple measures are needed to confirm TJ formation in addition to TEER values as these may not reflect ‘true’ B-BB integrity. Using compounds with known low B-BB penetration and analysing TJ protein expression in combination with novel therapeutics will aid in providing meaningful data to bridge the gap between drug discovery and pre-clinical studies. In addition, our brain metastatic research group utilizes this model to test effect of CD15 knockdown in lung metastatic cells on endothelial cell adhesion and B-BB passage. SECONDARY CATEGORY: Tumor Biology.
Fraud in breast cancer trial shakes US
Authors: J. Roberts
Journal: BMJ (1994)

Evidence that data from the largest trial of treatments for breast cancer in the US were, falsified has shaken both the public and the scientific community. The national surgical adjuvant breast and bowel project studied more than 5000 patients in 485 academic and community hospitals. When it reported in the New England Journal of Medicine in 1985 that lumpectomy plus radiotherapy was as effective as mastectomy it was influential in the move away from mastectomy as the operation of choice for women with breast cancer.

But this month the Chicago Tribune reported that about 16% of the patients came from St Luc's Hospital, a small centre in Montreal, and that Dr Roger Poisson there had included ineligible patients. Within 24 hours telephone lines at the American Cancer Society were jammed by women who had had lumpectomies …
Ulcerative Colitis and Diffuse Interstitial Lung Disease: Rare Association or Complete Coincidence?
Authors: M. L. Janower
Journal: JAMA (1989)

To the Editor. —  The article by Balestra et al 1 that reports a case of diffuse interstitial lung disease that developed 14 months after total colectomy for ulcerative colitis is of interest, but I think that the authors have exercised poetic license in making the assumption that the lung disease was related to the ulcerative colitis. A probable and much more reasonable assumption is that the patient who had had ulcerative colitis subsequently developed unrelated lung disease one year after surgery. Both ulcerative colitis and interstitial lung disease are quite common. Rarely, the diseases will occur in the same patient but this does not necessarily imply any relationship. To establish a definite relationship, one would have to show that there was an increased incidence of interstitial lung disease in patients with ulcerative colitis or that there was an increased incidence of ulcerative colitis in patients with interstitial lung disease.
BCVPP Chemotherapy for Advanced Hodgkin's Disease: Evidence for Greater Duration of Complete Remission, Greater Survival, and Less Toxicity Than with a MOPP Regimen
Authors: RICHARD F. BAKEMEIER
Journal: Annals of Internal Medicine (1984)

Two chemotherapy regimens for treatment of patients with advanced Hodgkin's disease, BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone) and MOPP (mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone), were compared in a randomized prospective study. Two hundred ninety-three patients were evaluable in the induction phase of this study. The complete remission rate with BCVPP was 76% (112/147) and with MOPP, 73% (106/146) (p = 0.51). The duration of complete remissions for previously untreated patients given BCVPP was significantly longer than that for previously untreated patients given MOPP (p = 0.02). Although hematologic toxicities were similar, BCVPP caused less gastrointestinal (p = 0.0001) and neurologic toxicity (p = 0.01) than MOPP. Previously untreated patients achieving complete remission with BCVPP survived significantly longer than those receiving MOPP (p = 0.03). As primary induction chemotherapy for advanced Hodgkin's disease, BCVPP is an effective alternative to MOPP, having equal or greater therapeutic benefit with less toxicity.
The Mechanism of Syncope Associated with Chronic Auricular Fibrillation without Evidence of Organic Heart Disease
Authors: Charles K. Friedberg, Morton H. Edelman
Journal: New England Journal of Medicine (1953)

THE unusual opportunity of observing a patient with long-standing auricular fibrillation during an episode of syncope and of studying the possible mechanism responsible for the syncopal attack impels us to report the following case. Syncope or faintness is not unusual in patients with paroxysmal auricular fibrillation at the onset of the arrhythmia due to tachycardia or the sudden change in rhythm.1 2 3 4 However, it is not a part of the clinical picture of established auricular fibrillation with relatively slow and unchanged ventricular rate in the patient with organic heart disease. Although syncope is often listed as one of the possible symptoms . . .
Ten-year Recovery from Chronic Lymphocytic Leukaemia
Authors: M. Schott
Journal: BMJ (1955)

BICLJH 877 granulocytes and producing rapid reduction of spleno- megaly and a marked clinical improvement in six of eight such treated cases.The disadvantage of many other agents such as myleran in producing thrombocytopenia and aplastic anaemia was not seen in cases of chronic myeloid leukaemia treated with colcemid.The effects of colcemid on myelofibrosis are con- sidered.Colcemid would seem to be contraindicated in the treatment of chronic lymphatic leukaemia, and evidence suggests that it may even produce an acute change.Colcemid has little or no beneficial effects on acute myeloblastic leukaemia.This work has been done during the tenure by one of us (B.
Pneumococcal Infections After Human Bone-Marrow Transplantation
Authors: DREW J. WINSTON
Journal: Annals of Internal Medicine (1979)

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.
Auditory System: Clinical and Special Topics
Authors: R. W. Cantrell
Journal: JAMA (1977)

This is the last of a three-volume series dealing with the auditory system in the<i>Handbook of Sensory Physiology</i>. Keidel and Neff deserve credit for merely attempting such a monumental task. To have completed the job is laudatory; to have done it so well is commendable. Volume V/1 dealt with anatomy and physiology of the ear; V/2 with physiology of the CNS, behavioral studies, and psychoacoustics. This final volume, dealing with clinical and special topics, is cast in the same mold as the first two: scholarly, well-written chapters with extensive bibliographies on topics ranging from sensorineural deafness and loudness recruitment to community response to noise. Two chapters are devoted to electrical stimulation of the ear, one in man and the other in animals. Blair Simmons' chapter on electrical stimulation of the ear in man is especially timely considering the work of House, Michelson, and others who are now implanting various
INTRAPERITONEAL INJECTION OF CITRATED BLOOD
Authors: David M. Siperstein
Journal: JAMA (1923)

<h3>To the Editor:</h3> —There is no doubt that the intraperitoneal method of giving citrated blood is unnecessary for some men. For the same reason, I very much doubt the ability of the average man successfully to expose and utilize the median cephalic vein in the new-born. The mere fact that Helmholz recommends the sinus route; Robertson, the internal saphenous vein; Falls, the jugular vein; and Sidbury, the umbilical vein shows that difficulties have been encountered. The method was not intended as a substitute for Dr. Lewisohn's excellent pioneer work, but only as an addition of possible merit. I have never used the intraperitoneal route in hemophilia neonatorum, for I have found whole blood intramuscularly a satisfactory therapeutic agent. However, it is felt that this means of approach may be used. I know of no scientific reason why citrated blood in the peritoneal cavity should be dangerous, "especially in the new-born
Indices of lower airway inflammation in children monosensitized to house dust mite after nasal allergen challenge
Authors: A. Inal, S. G. Kendirli, M. Yilmaz, D. U. Altintas, G. B. Karakoc, S. Erdogan
Journal: Allergy (2008)

Background: There are few available data assessing the united airway disease and its systemic aspects in children. With this study, we aimed to investigate the inflammation markers of upper and lower airways before and after nasal allergen challenge in mite sensitive children with different clinical expression of the allergic disease. Methods: Four study groups were formed: rhinitis only, without bronchial hyper‐responsiveness (R, n = 10), rhinitis with asthma (R + A, n = 22), atopic asymptomatics (AA, n = 8) and nonallergic healthy controls (C, n = 10). Blood eosinophils, nasal and sputum eosinophils, sputum eosinophil cationic protein (ECP) and cys‐LTs, and serum ECP levels were measured before and 24 h after nasal allergen challenge. Results: The groups were comparable in terms of age and gender. Cumulative symptom scores recorded during and 1 h after nasal challenge were not significantly different between patients with R, R + A and AA groups. At T 24 , the children belonging to R, R + A and AA showed significant increases in nasal eosinophils ( P &lt; 0.01, P &lt; 0.001, and P = 0.01, respectively), sputum eosinophils ( P = 0.01, P &lt; 0.001, and P &lt; 0.05, respectively) and blood eosinophils ( P &lt; 0.01, P &lt; 0.001, and P &lt; 0.05, respectively). Similarly, increases in sputum ECP ( P &lt; 0.01, P &lt; 0.001, and P = 0.07, respectively) and sputum cys‐LT levels ( P = 0.07, P &lt; 0.001, and P &lt; 0.05, respectively) were detected in children belonging to these three groups at T 24 . Sputum eosinophils significantly correlated with blood eosinophils ( r = 0.54, P &lt; 0.001) and sputum ECP ( r = 0.58, P &lt; 0.001) at T 24 . Conclusions: This study showed that nasal allergen challenge increased markers of eosinophilic inflammation in both upper and lower airways of children monosensitized to mites, even before the onset of clinical symptoms.
Cardiac resynchronization therapyhomogenizes myocardial glucosemetabolism and perfusion in dilatedcardiomyopathy and left bundle branch block
Authors: Bernd Nowak, Anil M Sinha, Wolfgang M Schaefer, Karl-Christian Koch, Hans-Juergen Kaiser, Peter Hanrath, Udalrich Buell, Christoph Stellbrink
Journal: Journal of the American College of Cardiology (2003)
Anesthesia in Emphysema
Authors: Samuel Berkowitz
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In the article, "Chronic Obstructive Emphysema: The Thoracic Surgeon's Position" (<i>JAMA</i><b>192</b>:365-367 [May 3] 1965), Minas Joannides, Jr., MD, dictates anesthetic management, "Anesthesia should be given through a negative phase respirator." Anesthetists have learned that a negative phase in a mechanical ventilator is far from effective from a ventilatory aspect; resistance increases from bronchiolar collapse, and compliance may decrease with decrease in lung volume. Bronchial obstruction will consequently increase in obstructive emphysema which is characterized by resistance to air flow. Both hypercarbia and hypoxia should be exaggerated. For anesthesia in a patient with obstructive emphysema, positive pressure respiration both during inspiration and expiration with sufficient decrease during the latter phase to permit adequate venous return is the most desirable technique.
Management of Pain in Elderly Patients With Cancer
Authors: Roberto Bernabei
Journal: JAMA (1998)

Context.—Cancer pain can be relieved with pharmacological agents as indicated by the World Health Organization (WHO). All too frequently pain management is reported to be poor.Objective.—To evaluate the adequacy of pain management in elderly and minority cancer patients admitted to nursing homes.Design.—Retrospective, cross-sectional study.Setting.—A total of 1492 Medicare-certified and/or Medicaid-certified nursing homes in 5 states participating in the Health Care Financing Administration's demonstration project, which evaluated the implementation of the Resident Assessment Instrument and its Minimum Data Set.Study Population.—A group of 13625 cancer patients aged 65 years and older discharged from the hospital to any of the facilities from 1992 to 1995. Data were from the multilinked Systematic Assessment of Geriatric Drug Use via Epidemiology (SAGE) database.Main Outcome Measures.—Prevalence and predictors of daily pain and of analgesic treatment. Pain assessment was based on patients' report and was completed by a multidisciplinary team of nursing home personnel that observed, over a 7-day period, whether each resident complained or showed evidence of pain daily.Results.—A total of 4003 patients (24%, 29%, and 38% of those aged ≥85 years, 75 to 84 years, and 65 to 74 years, respectively) reported daily pain. Age, gender, race, marital status, physical function, depression, and cognitive status were all independently associated with the presence of pain. Of patients with daily pain, 16% received a WHO level 1 drug, 32% a WHO level 2 drug, and only 26% received morphine. Patients aged 85 years and older were less likely to receive either weak opiates or morphine than those aged 65 to 74 years (13% vs 38%, respectively). More than a quarter of patients (26%) in daily pain did not receive any analgesic agent. Patients older than 85 years in daily pain were also more likely to receive no analgesia (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73). Other independent predictors of failing to receive any analgesic agent were minority race (OR, 1.63; 95% CI, 1.18-2.26 for African Americans), low cognitive performance (OR, 1.23; 95% CI, 1.05-1.44), and the number of other medications received (OR, 0.65; 95% CI, 0.5-0.84 for 11 or more medications).Conclusions.—Daily pain is prevalent among nursing home residents with cancer and is often untreated, particularly among older and minority patients.
NONPROTEIN NITROGENOUS CONSTITUENTS OF BLOOD IN ECLAMPSIA AND ALLIED CONDITIONS
Authors: E. D. PLASS
Journal: JAMA (1924)

During recent years, we have accumulated considerable data on the general question of nitrogen retention in the blood during the late toxemias of pregnancy; and, in view of the divergent opinions that prevail concerning the value of such determinations in the differential diagnosis and prognosis of these conditions, it seems that they should be recorded. Our investigations have led us to believe that blood chemical studies are at present of little or no practical assistance in the clinical management of these cases, and that the older methods of examination—urinalysis, blood pressure readings and ophthalmoscopy—yield the most valuable information concerning the patient's condition. Previous workers (Folin,<sup>1</sup>Caldwell and Lyle,<sup>2</sup>Killian and Sherwin,<sup>3</sup>de Wesselow<sup>4</sup>and others) have demonstrated that the substances studied (total non protein nitrogen, urea and uric acid) occur in normal concentrations in the blood during normal gestation. They have, moreover, pointed out that there
47 METABOLIC REPROGRAMMING OF LIPID METABOLISM BY THE SIDE-CHAIN MODIFIED BILE ACID, 24-NORURSODEOXYCHOLIC ACID, RESTORES INFLAMMATION-DRIVEN LIVER INJURY AND ABERRANT PROLIFERATION IN ABCB4−/− MICE
Authors: T. Moustafa, P. Fickert, C. Magnes, S. Frank, D. Kratky, F. Sinner, J. Gumhold, D. Silbert, S. Halsegger, M. Trauner
Journal: Journal of Hepatology (2010)
Economic model of a birth cohort screening program for hepatitis C virus
Authors: Lisa J. McGarry, Vivek S. Pawar, Hemangi R. Panchmatia, Jaime L. Rubin, Gary L. Davis, Zobair M. Younossi, James C. Capretta, Michael J. O'Grady, Milton C. Weinstein
Journal: Hepatology (2011)

Abstract Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. Conclusion: Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds. (Hepatology 2012)
Lengthy Tale of Varicella Vaccine Development Finally Nears a Clinically Useful Conclusion
Authors: Charles Marwick
Journal: JAMA (1995)

THE VICISSITUDES that have delayed the licensing of a vaccine against varicella-zoster virus are finally ending. The manufacturer has indicated that this vaccine will shortly become available, although the Food and Drug Administration (FDA) does not comment on pending license applications.   are fairly comfortable with the clinical data. We believe they have been analyzed as carefully as they can be, Philip Krause, MD, an FDA senior research investigator, told a meeting in January of the Vaccines and Related Biological Products Advisory Committee to the FDA. However, he added, we're still awaiting answers to questions regarding manufacturing and establishment issues.  Almost from the beginning, problems with manufacturing, efficacy, and safety have plagued this biological agent. Since critics of the FDA are currently charging the agency with undue delays in product licensing and approval procedures, it may be instructive to consider briefly the experience of the past decade and a half
Immunohistological reactivity pattern of the anti-cutaneous T-cell lymphoma antibody BE2
Authors: ELISABETH RALFKIAER, K.C. GATTER, GUNHILD LANGE WANTZIN, K. THOMSEN, D.Y. MASON
Journal: British Journal of Dermatology (1986)

Journal Article Immunohistological reactivity pattern of the anti‐cutaneous T‐cell lymphoma antibody BE2 Get access ELISABETH RALFKIAER, ELISABETH RALFKIAER Department of Pathology, The Finsen Institute, University of Copenhagen, Denmark Dr E. Ralfkiaer, Department of Pathology, The Finsen Institute, University of Copenhagen, 49 Strandboulevarden, DK‐2100 Copenhagen Ø, Denmark. Search for other works by this author on: Oxford Academic Google Scholar K.C. GATTER, K.C. GATTER Department of Dermatology, The Finsen Institute, University of Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar GUNHILD LANGE WANTZIN, GUNHILD LANGE WANTZIN Department of Dermatology, The Finsen Institute, University of Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar K. THOMSEN, K. THOMSEN Department of Dermatology, The Finsen Institute, University of Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar D.Y. MASON D.Y. MASON Nuffield Department of Pathology, John Radcliffe Hospital, University of Oxford, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 114, Issue 6, 1 June 1986, Pages 677–684, https://doi.org/10.1111/j.1365-2133.1986.tb04875.x Published: 01 June 1986 Article history Accepted: 17 January 1986 Published: 01 June 1986