tbuckley/cabot-search huggingface dataset:
THE OUTDOOR TEEATMENT OF TUBERCULOSIS.
Authors: F. E. WAXHAM
Journal: JAMA (1902)

Few medical men will now dispute the fact that our great remedies in the treatment of tuberculosis are pure air, rest and food. The more abundantly the former can be given the greater and faster will be the progress towards recovery. Pure air in greatest abundance can best be secured by tent life. It is a pleasure to witness the rapid improvement when this mode of life is inaugurated. The sleep becomes more restful and refreshing, the appetite is improved and the vigor and vitality greatly increased. Tent life does not mean or should not mean roughing it, as many suppose. The same watchful care should be exercised, as good food given, as comfortable a bed, as much rest, as would be obtained in the most luxurious home or the best equipped closed sanitarium. The unfortunate results arising from mistaken notions in this regard has been most forcibly emphasized by
P182Involvement of ephrin-A1 in the migration and proliferation of endothelial cells
Authors: E Wiedemann, S Jellinghaus, G Ende, A Augstein, R Sczech, RH Strasser, D M Poitz
Journal: Cardiovascular Research (2014)

The Eph-family, consisting of Eph-receptors and ephrin-ligands represents the largest class of receptor tyrosine-kinases. The role of Eph/ephrins in elementary physiological processes as re-endothelialisation is still not well understood. The aim of the present study was to investigate the regulation of the ligand ephrin-A1 and its potential impact on proliferation and migration of human umbilical venous (HUVEC) and arterial endothelial cells (HUAEC). Initially, it could be shown, that ephrin-A1 expression was positively correlated with the density of the endothelial cells. Thus, a significant induction of ephrin-A1 in endothelial cells was observed after contact inhibition. The impact of ephrin-A1 on endothelial proliferation and migration was studied using siRNA and adenoviral overexpression. The siRNA-mediated silencing of ephrin-A1 in HUVEC increased the proliferation. In contrast, adenoviral overexpression of ephrin-A1 decreased the proliferation, suggesting an involvement of ephrin-A1 in endothelial proliferation. To study the role of ephrin-A1 in processes associated with an endothelial defect, a wound healing assay was performed. Ephrin-A1-silenced HUVEC showed a faster gap area closure in comparison to cells transfected with a scrambled control siRNA. Interestingly, ephrin-A1-overexpressing endothelial cells showed a faster gap area closure compared to lacZ-control as well. Using live cell imaging it could be visualized that the silencing of ephrin-A1 influences the direction of the migration of HUVEC resulting in disorientation and a missing polarization of the cells. Overexpression of ephrin-A1 leads to a straight forward and faster migration compared to the controls. By using baculoviral expression of actin-GFP and talin-RFP accordingly both the silencing and the overexpression of ephrin-A1 resulted in an increased number of endothelial focal adhesions which also influenced the actin-cytoskeleton in endothelial cells. A migration assay was established to investigate endothelial response to contact with an ephrin-A1-coated surface. A temporary stop of migration was observed after surface coating with ephrin-A1-Fc. Taken together, these results show that ephrin-A1-expression depends on cell-density and is a critical determinant of endothelial proliferation. Furthermore, ephrinA1 is involved in the regulation of migration of cells, by modulating the speed of migration and more importantly the direction of migration. These results show, that ephrinA1 is highly involved in the process of wound healing which is amongst others of great importance for re-endothelialisation.
When should clinical guidelines be updated?
Authors: P. Shekelle, M. P Eccles, J. M Grimshaw, S. H Woolf
Journal: BMJ (2001)

Considerable resources are being expended internationally on the development of clinical practice guidelines.1 Although consensus is increasing about methods for developing evidence based guidelines,2 less attention has been paid to the process for assessing when guidelines should be updated. The most common advice is for guidelines to include a scheduled review date. This could result in wasted resources, however, if a full update is undertaken prematurely in a slowly evolving field, or in guidelines in a rapidly evolving field becoming out of date before the scheduled review. Some guidelines state that they should be updated when new information becomes available. It is unclear, however, how this should be done, and we are unaware of any systematic attempts to devise a method. In this paper we propose a set of principles and a pragmatic model for assessing whether guidelines need to be updated.

#### Summary points

Changes in evidence, the values placed on evidence, the resources available for health care, and improvements in current performance are all possible reasons for updating clinical guidelines

The need for an efficient mechanism for identifying when guidelines require updating is urgent

A possible model for assessing validity of guidelines is based on a combination of multidisciplinary expert opinion and limited literature searches

### Changes in evidence on the existing benefits and harms of interventions

New information about the magnitude of benefits and harms may make the pre-existing guideline invalid. The surgical risk of carotid endarterectomy, for example, has fallen substantially over the past 30 years, altering the risk-benefit ratio in favour of performing the operation for selected patients with symptomatic, high grade carotid stenosis.3–5

### Changes in outcomes considered important

New evidence may identify as important outcomes that were previously unappreciated or wholly unrecognised. Quality of life, for example, an end point often not considered in earlier research and guidelines, is receiving increasing …
Propranolol Again: Order out of Chaos?
Authors: Lawrence R. Krakoff
Journal: New England Journal of Medicine (1976)

Readers of the Journal have been witness to a remarkable series of articles over the past four years dealing with the effect of propranolol as an antihypertensive agent in patients representing various sub species of the genus renin. In brief recapitulation, Bühler and his associates described a direct relation between the reduction of plasma renin activity (PRA) and arterial pressure by propranolol alone in a spectrum of patients classified as having low, normal and high levels of PRA.1 About one third of those patients had renal-artery stenosis. In a later publication by the same group rather good correlation was observed . . .
Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers
Authors: Alexander J.V. Thompson, Tin Nguyen, David Iser, Anna Ayres, Kathy Jackson, Margaret Littlejohn, John Slavin, Scott Bowden, Edward J. Gane, William Abbott, George K.K. Lau, Sharon R. Lewin, Kumar Visvanathan, Paul V. Desmond, Stephen A. Locarnini
Journal: Hepatology (2010)

Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo . In all, 149 treatment-naïve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA ( r = 0.69, 0.71, 0.76, P &lt; 0.01). HBeAg correlated with serum HBV DNA ( r = 0.60, P &lt; 0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA ( r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. Conclusion: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker. (Hepatology 2010)
Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes
Authors: Daniel Gordin, Carol Forsblom, Nicolae M. Panduru, Merlin C. Thomas, Mette Bjerre, Aino Soro-Paavonen, Nina Tolonen, Niina Sandholm, Allan Flyvbjerg, Valma Harjutsalo, Per-Henrik Groop
Journal: Diabetes Care (2014)

Osteopontin (OPN) is a multifunctional protein suggested to be a player in the arterial disease of patients with type 2 diabetes. However, its role for complications in patients with type 1 diabetes (T1D) is unknown. We therefore investigated the associations between OPN and diabetic vascular complications and all-cause mortality in patients with T1D.Serum OPN was measured in 2,145 adults with T1D without end-stage renal disease (ESRD; dialysis or transplantation) as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Data on renal status, cardiovascular disease (CVD), and all-cause mortality during follow-up were verified from medical files, hospital discharge registries, and the Finnish National Death Registry, respectively. The median follow-up time was 10.5 (interquartile range 8.9-11.8) years.Serum OPN was higher at baseline in patients who developed incident microalbuminuria (16.0 ± 0.9 vs. 14.1 ± 0.2 µg/L; P = 0.04), progressed to ESRD (28.3 ± 1.7 vs. 15.4 ± 0.2 µg/L; P < 0.001), suffered an incident CVD event (20.2 ± 1.2 vs. 15.5 ± 0.2 µg/L; P < 0.001), or died (23.3 ± 1.4 vs. 15.8 ± 0.2 µg/L; P < 0.001) during follow-up. In multivariate Cox regression analysis, OPN was independently associated with the development of incident microalbuminuria, an incident CVD event, and death, after adjustments for associated risk factors. Even after calculating reclassification indexes, OPN was predictive of CVD and all-cause mortality beyond the Framingham risk score covariates and hs-CRP.Serum OPN is a strong predictor of incipient diabetic nephropathy, a first-ever CVD event, and all-cause mortality in patients with T1D. Serum OPN may be of clinical significance for the risk prediction of CVD events in patients with T1D.
INJURY OF THE RECTUM CAUSED BY THE FAULTY ADMINISTRATION OF AN ENEMA
Authors: H. H. Rayner
Journal: BMJ (1932)

<h3>OBJECTIVE</h3> To investigate the expression of Coxsackie and Adenovirus receptor (CAR) in renal-cell carcinoma and the relationship of the CAR to the biological behavior of the carcinomas. <h3>METHODS</h3> The immunohistochemical SP method was used to detect the expression of Coxsackie and Adenovirus receptor in 48 cases of renal- cell carcinoma and in 12 cases of normal renal tissue 2 cm away from the tumor tissue. <h3>RESULTS</h3> The positive rates of CAR were 100% in 12 cases of para-tumor normal renal tissue and 35.4% in 48 cases of renal-cell carcinoma respectively. The difference of CAR expression between them was significant (P&lt;0.05). The grades of the tumor were as follows: 22 in Grade I, 17 in Grade II and 9 in Grade III with the CAR positive rate being 54.5%, 23.5% and 11.1%, respectively. There was a negative correlation between CAR expression and tumor grading (P&lt;0.05). In addition, the number of the cases in stages I to IV were 19, 13, 11 and 5 respectively, with the respective positive rates being 57.9%, 30.8%, 18.2% and 0.0%, i.e. there also was a negative relationship between CAR expression and the stage (P&lt;0.05). <h3>CONCLUSION</h3> CAR expression is down-regulated in renal-cell carcinoma compared with normal tissue. The level of CAR may be a sensitive predictor of differentiation, invasion and metastasis. Loss of CAR expression correlates with the invasive phenotype in our analysis of renal-cell carcinoma.
Graft-versus-host disease-like immunophenotype and apoptotic keratinocyte death in paraneoplastic pemphigus
Authors: None Reich, None Brinck, None Letschert, None Blaschke, None Dames, None Braess, None Wörmann, None Rünger, None Neumann
Journal: British Journal of Dermatology (1999)

Paraneoplastic pemphigus (PP) is an autoimmune disease, which is frequently associated with non-Hodgkin's lymphoma. Autoantibodies against components of the cytoplasmic plaque of epithelial desmosomes are usually present in the sera and are believed to play a major pathogenic part in acantholysis and suprabasal epidermal blistering. However, another typical histological feature of PP, interface dermatitis with keratinocyte dyskeratosis, is shared with skin diseases that involve epithelial damage mediated by T cells. Here, we present the detailed characterization of the cutaneous T-cell response in a patient with PP and demonstrate a selective epidermal accumulation of activated CD8+ T cells together with an increased local production of interferon-gamma and tumour necrosis factor-alpha, and a strong expression of HLA-DR and ICAM-1 on keratinocytes. Apoptosis was identified as a key mechanism of keratinocyte death, and appeared independent of the FAS/FAS ligand (FAS-L) pathway, as epidermal expression of FAS was not increased compared with normal skin, and FAS-L was undetectable on the protein and mRNA level. Triple therapy with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins reduced levels of pemphigus-like autoantibodies and reversed the cutaneous inflammatory reaction leading to long-standing clinical remission. Our findings support the concept of a major contribution of cytotoxic T lymphocytes to the immunopathology of paraneoplastic pemphigus.
First detection of the Anaplasma phagocytophilum groEL-A genotype in man
Authors: Elisabeth Haschke-Becher, Rainer Bernauer, Anna-Maria Walleczek, Petra Apfalter, Shahrzad Afazel-Saeedi, Joerg Kraus, Gunther Ladurner, Peter Strasser
Journal: Journal of Infection (2009)
NECESSITY OF EXAMINATION OF THE SPUTUM IN THE DIAGNOSIS OF PULMONARY TUBERCULOSIS.
Authors: C. M. WOOD
Journal: JAMA (1900)

It has been wisely said that failure to make use of the well-recognized means of clinical investigation leads to more errors in diagnosis than does ignorance. The laity sometimes neglect to take advantage of the wonderful discovery of Jenner, and we wonder at their apathy. What shall we say of the physician who, in so serious a matter as the diagnosis of phthisis, neglects to make use of the simple and beautiful staining methods of Koch? The typical consumptive is a deplorably familiar spectacle. The layman thinks that he can recognize the disease at sight, but let no physician make this mistake. Of the 1400 patients supposed to be in the advanced stages of pulmonary tuberculosis and sent to the Cook County Hospital for Consumptives from the various hospitals and physicians of Cook county, 120, or 8.5 per cent., have proved, after thorough investigation and prolonged observation, to be non-tuberculous.
Optimizing therapy: tazarotene in combination with phototherapy
Authors: None LOWE
Journal: British Journal of Dermatology (1999)

Phototherapy is often used in combination with other antipsoriatic treatments in an attempt to improve efficacy and reduce patients' cumulative exposure to radiation. Although this aim has been achieved with some combinations, the additional therapies often introduce a potential risk of other tolerability and safety problems. The efficacy of tazarotene reported in clinical trials to date suggest that this drug may help to improve the efficacy of phototherapy, and perhaps reduce the ultraviolet light exposure required without introducing additional, clinically significant problems. Preliminary results from the first 10 patients in a clinical trial investigating such combination therapy are reported here. They demonstrate that the addition of tazarotene to UVB phototherapy increases the percentage of patients achieving treatment success (≥ 50% global improvement in psoriasis) from 60% to 100% at Day 81. The UVB plus tazarotene combination achieved consistently greater reductions in the elevation and scaling of difficult‐to‐treat psoriatic plaques than UVB phototherapy alone or UVB phototherapy plus vehicle gel. The tazarotene combination therapy also achieved initial treatment success in less than half the time needed with phototherapy alone (median of 32 vs. 67 days). Combining UVB phototherapy with tazarotene treatment appears to offer a valuable therapeutic option that is more efficacious and faster than UVB phototherapy alone.
A Manual of Tropical Medicine
Authors: Dwight Kuhns
Journal: JAMA (1960)

This book is the work of 32 collaborators. The first edition was prepared during World War II to meet the need of the Armed Forces in the tropics. The concise presentation of essential, practical aspects of the more important tropical diseases, and diseases of similar nature occurring in the temperate zones, has resulted in its acceptance, not only by those interested in this field but also by medical students and non-military personnel in medicine, public health, and allied fields. The primary objective of the manual is concise presentation of the cause, epidemiology, pathology, clinical characteristics, diagnosis, treatment, and prophylaxis of certain diseases of tropical and temperate climates. As pointed out in the preface to this third edition, bacterial, parasitic, viral, rickettsial, mycotic, and nutritional diseases constitute significant problems in the practice of medicine in any clime. The authors have compiled pertinent information about the major infectious diseases, nutritional disorders, and
Gefilte Fish Does Not Transmit Diphyllobothriasis
Authors: Erhard Groll
Journal: JAMA (1983)

ABSTRACT To the Editor.— The idea of chipping the fish tapeworm to death sounds reasonable (1982;247:1566 and 1982; 248:30), but, alas, it is not the adult tapeworm you might find in raw fish dishes like Gefilte Fish, it is the plerocercoid, the larva. Man is the most important final host of Dipylidium latum. In fish, larvae of D latum might occur in small numbers or in hundreds.An adult specimen of D latum can be up to 20 m in length, and this would require a lot of chopping if this parasite occurred in fish. The fish would need to be one of the larger specimens to accommodate such a large tapeworm. However, man is the principal final host.
The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model
Authors: Rob J.B. Klemans, Dianne Otte, Mirjam Knol, Edward F. Knol, Yolanda Meijer, Frits H.J. Gmelig-Meyling, Carla A.F.M. Bruijnzeel-Koomen, André C. Knulst, Suzanne G.M.A. Pasmans
Journal: Journal of Allergy and Clinical Immunology (2012)
Carbonic Oxide in Tobacco Smoke
Authors: H. E. Armstrong
Journal: BMJ (1922)

WHEN recently thet carboni'o oxid scare a wa's rais-ed in the p ress,thee danger we incur, evenv in the streetss'' r fhro cs nstant dischlarge' of 'the exhaut gas froni buts and mo tor carengines was a mattersca'ee comment.Soo 'us, knowing the secrets.fofcombustion, were, moved to suggest to tobacco.usingfriends that the'y were risky compaaiions.Tllie subjjct -of cigarette smoking wasdidiscussed in tee''s-c'lumns inoeNobveinbear last* by my friend'Professor W. E. Dixon, F.R.S. Ilearn frromhiiim'tlihat' he-hlia' tegaarided the pernicious result' of excessive cigarette smoking as an effect of carbonic oxide but tlat 113 is inclinedto.attribute the obvious effects' Of cigar smokinig'rathert to' theinfluenice of nicoinie, if notL to othler basic products of the de'strucive dis till'ition of tile noxiou's weed.Appaetiently tle gases from thle burningcigar have no be'en specially exiamined for carbonic oxdde .Discussingithe matter With my neigibbor, Mr.
Viral IL-10-Mediated Immune Regulation in Pancreatic Islet Transplantation
Authors: Jeffrey D. Carter, Justin D. Ellett, Meng Chen, Kellie M. Smith, Lawrence B. Fialkow, Marcia J. McDuffie, Kenneth S. Tung, Jerry L. Nadler, Zandong Yang
Journal: Molecular Therapy (2005)

Protection of transplanted pancreatic islet grafts in recipients with autoimmune diabetes depends on the suppression of autoimmune recurrence and allogeneic rejection. The aim of this study was to investigate the efficiency of viral IL-10 gene delivery in the prevention of autoimmune recurrence following islet transplantation. We evaluated the effectiveness of a systemically delivered adeno-associated viral vector (AAV vIL-10) carrying viral IL-10 in protecting islet engraftment. We observed significant prolongation of graft survival after treatment with AAV vIL-10 when using islets from donors lacking autoimmunity. We found that the mechanism of vIL-10-mediated protection was associated with suppression of T cell activation and that donor immune cells that were simultaneously transferred with the islet grafts could induce autoimmune recurrence. AAV vIL-10 gene transfer suppressed previously activated T cells and protected grafted islets from autoimmune-mediated destruction. We conclude that vIL-10 can regulate autoimmune activity and that transfer of its gene may have potential for therapeutic islet transplantation.
Angiopoietin-2: An Attractive Target for Improved Antiangiogenic Tumor Therapy
Authors: Damien Gerald, Sudhakar Chintharlapalli, Hellmut G. Augustin, Laura E. Benjamin
Journal: Cancer Research (2013)

Abstract Anti-VEGF pathway therapies primarily target immature blood vessels in tumors. However, emerging approaches to combine with targeted therapies impacting the later stages of remodeling and vessel maturation are expected to improve clinical efficacy by expanding the target vessel population. The angiopoietin/Tie ligand/receptor system is a prototypic regulator of vessel remodeling and maturation. Angiopoietin-2 (Ang2) appears to be a particularly attractive therapeutic target. In fact, the experimental proof-of-concept showing improved efficacy when VEGF and Ang2-targeting therapies are combined has been solidly established in preclinical models, and several Ang2-targeting drugs are in clinical trials. However, rational development of these second-generation combination therapies is hampered by a limited understanding of the biological complexity that is generated from agonistic and antagonistic Ang/Tie signaling. This review discusses recent mechanistic advances in angiopoietin signaling, particularly in light of the recent study published on REGN910 and summarizes the status quo of Ang2-targeting therapies. In light of the clarified partial agonist function of Ang2, we propose that clarity on the expression profile of the angiopoietin ligands and Tie1 and Tie2 receptors in subsets of cancer vessels and cancer cells will provide clearer hypotheses for more focused rational clinical trials to exploit this seminal pathway and improve current antiangiogenic therapies. Cancer Res; 73(6); 1649–57. ©2013 AACR.