tbuckley/cabot-search huggingface dataset:
Pilot gene expression analysis of inflamed synovium
Authors: F Ponchel, S M Churchman, V Goeb, E A Horner, K Henshaw, P Emery
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> Within the synovial membrane of an rheumatoid arthritis (RA) joint, tissue architecture varies depending on organisation of the infiltrating inflammatory cells (diffuse, aggregates and germinal centres). It has been hypothesised that more organised cell network could represent a true autoimmune phenotype due to better presentation of auto-antigens and higher expression of various cytokines and chemokines, leading to the hypothesis that these differing tissue architectures (TA) could predict response to biologics. The authors designed a customised gene array to pilot the feasibility of gene expression signatures in synovial biopsy. <h3>Methods</h3> Twenty biopsies from 12 RA and 8 OA patients were collected by arthroscopy with scored joint inflammation (VAS). Tissue architecture was classified in three categories; diffuse infiltration, aggregates and germinal centre-like structures. A custom 96 gene Taqman array was designed (including three reference genes) and expression was measured using quantitative real-time (q)PCR. <h3>Results</h3> Of the 93 genes tested, only 1 was below detection and 3 undetected in over 75% of samples. Pilot analysis was performed as the number of samples was not allowing highly significant difference to be found. Analysing samples based on diagnostic criteria showed differential expression of 25 genes between RA and OA including TNFα but not IL-1/6/10/17/18, CD4 (T cell) (p=0.064), but not B/plasma cell lineage markers (CD20/38/138), increased co-stimulation (CTLA4/CD86), chemokines (CXCL13/CCL12), PADI4 for citrullination and HDAC7 for epigenetic modification. Expression of 21 genes was related to local levels of inflammation: CCL21, Ig constant chain and IgG/IgM heavy chains, chemokine CXCL13 and BLIMP1 (rho=0.753, p&lt;0.001) a transcription factor involved in B cell differentiation. Increasing TA complexity was associated with 21 genes including plasma cell (CD38), T cell (CD4), co-stimulation (CD80/86/CTLA4), IL-7 as lymphoid tissue inducer, TNFα and STAT-1/STAT-5 signalling, CCL21 and IgG/IgM heavychains. No difference was observed for the expression of CD68 (macrophages) between diseases, levels of inflammation or TA. CD68 expression was related to TNFα, TGFβ and CD86. CD4 (T cells) was related to IL-6 and STAT5 (rho=0.768, p&lt;0.001). CD20 (B cells) was hardly detected but CD38 (plasma cells) were related to the expression of BLIMP1 (rho=0.900, p&lt;0.001), IKZF-3, CD79, IgM/IgG heavychains, Ig constant-chain and STAT-1. <h3>Conclusion</h3> Altogether, these data suggest that analysis of gene expression using qPCR in synovial biopsy is technically feasible with limited data loss. The analysis of gene expression levels however needs to be closely examined in relation to the expression of cell lineage markers as it is clear that the cellular composition of the biopsy will impact on analysis.
Value of Repeat Lumbar Puncture in the Differential Diagnosis of Meningitis
Authors: Ralph D. Feigin, Penelope G. Shackelford
Journal: New England Journal of Medicine (1973)

THE symptoms and signs of bacterial and aseptic meningitis may be similar, and thus the differential diagnosis usually cannot be made on clinical grounds. A critical determinant in differentiating bacterial from aseptic meningitis is evaluation of the cerebrospinal fluid at the time of initial examination of the patient. When pleocytosis exceeds 1000 cells per cubic millimeter and consists predominantly of polymorphonuclear leukocytes, suspicion of bacterial meningitis is heightened. If, in addition, the cerebrospinal-fluid glucose is less than 40 mg per 100 ml, or less than 66 per cent of a simultaneously obtained blood glucose, and is associated with the presence . . .
Letter by Caruthers and Dorsch Regarding Article, “Dosing of Clopidogrel for Platelet Inhibition in Infants and Young Children: Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial”
Authors: Regine L. Caruthers, Michael P. Dorsch
Journal: Circulation (2008)

Primary Results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) Trial"To the Editor:We appreciate and were excited to read the article by Li et al, 1 which evaluated the pharmacodynamics of clopidogrel in children to determine the dose of clopidogrel necessary to achieve a mean 30% to 50% inhibition of 5-mol/L ADP-induced platelet aggregation.We have concerns, however, about the authors' conclusion that a uniform clopidogrel dose of 0.2 mg • kg Ϫ1 • d Ϫ1 in children between 0 and 24 months of age produces levels of inhibition similar to those observed in adults receiving the standard clopidogrel dose of 75 mg/d.The pharmacokinetic profile of clopidogrel is complex and has yet to be completely elucidated.3][4] The activity of CYP3A4 is highly variable in the first year of life.Lacroix and colleagues 5 reported CYP3A4 activity to be 8% of that seen in adults in the first 24 hours of life, 13% on days 1 to 7, 29% on days 8 to 28, 34% during the second and third month of life, 43% during months 3 through 12, and 108% of adult activity between the ages of 1 and 15 years.In the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial, patients were stratified on the basis of age into 2 groups; this methodology, however, does not take into account developmental and pharmacokinetic differences present in the neonatal period and throughout infancy.Similarly, it raises the question of whether the method of patient stratification impacted the variability observed in the data presented in their Figure 2. Clinical experience with clopidogrel has shown a need for higher doses of clopidogrel to achieve 30% to 50% inhibition of 5-mol/L ADP-induced platelet aggregation in the early years of life.The presentation of subset data, based on age, would be helpful in interpreting and understanding the variability in the data and its impact on the surrogate end points of inhibition of maximum extent and rate of platelet aggregation.It also seems reasonable to start with a dose based on this subset data and then check periodic platelet aggregation based on simple point-ofcare tests to confirm the 30% to 50% inhibition.
Inflammatory F-18 FDG Uptake Secondary to Ruptured Breast Prosthesis
Authors: Peeyush Bhargava, Elizabeth Glass, Munir Ghesani
Journal: Clinical Nuclear Medicine (2006)

We present the FDG PET images of a 60-year-old woman with a history of breast cancer, bilateral mastectomy, and reconstruction 4 years ago who presented for a whole-body scan to evaluate for recurrent and metastatic disease. The images showed inflammatory FDG activity around the ruptured left breast prosthesis likely in response to the leaking prosthesis. The patient underwent surgery for the replacement of the prosthesis, which did not show any evidence of neoplastic disease.
IMPROVED EVALUATION OF CORONARY ARTERY DISEASE BY ADDITION OF A THIRD VIEW TO T1???201 PLANAR IMAGING
Authors: F. L. Murphy, J. Moddohi, A. Becerra, M. Steuer, E. Garcia, A. Kimchi, S. Reisman, A. Rozanski, H. J.C. Swan, D. S. Berman
Journal: Clinical Nuclear Medicine (1982)

Murphy, F. L.; Moddohi, J.; Becerra, A.; Steuer, M.; Garcia, E.; Kimchi, A.; Reisman, S.; Rozanski, A.; Swan, H. J.C.; Berman, D. S. Author Information
Plasminogen activator activity in cultures from human tissues. An immunological and histochemical study
Authors: Maria B. Bernik, Hau C. Kwaan
Journal: Journal of Clinical Investigation (1969)

Human tissues and cells from pre- and postnatal life were cultivated and studied for plasminogen activator activity. Cultures were obtained from kidney, renal blood vessels, ureter, bladder, lung, and heart. Local activator activity of cells was demonstrated by histochemical techniques. Activator released by cells into the supernatant culture media was assayed by fibrin plate techniques and was investigated for immunological identity using specific antisera to an activator of human origin, urokinase (UK). Plasminogen activator was produced in primary cultures where cells retain specific functions and generally reflect the enzyme pattern of the tissues of origin. Cells from fetal and adult sources were found to yield activator antigenically identical to UK, as well as activator activity which differed from that of UK in immunoassays and which may represent tissue type activator. Such activity was released after injury or death of cells while UK was produced in cultures containing live, metabolizing cells. Primary cultures of kidney confirmed that this organ is a rich source of UK and demonstrated, in addition, that UK is produced from the early stages of gestation and in increasing amounts thereafter. However, primary cultures also demonstrated that the ability to produce UK is not limited to the kidney but is a function of cells which are distributed widely in body tissues. Thus, activator antigenically identical to UK accumulated progressively after many refeedings in culture supernates of fetal lung and ureter, as well as in supernates of renal blood vessels of adults. These findings indicate continuous formation of UK by the cultured cells and, furthermore, provide evidence of UK production in blood vessels. In cultures from other tissues, particularly those from fetal heart and adult lung and bladder, investigation of activator was hindered by inhibitory activity which accumulated in the supernates. Such activity was derived from cells in culture and was directed selectively against UK, indicating that inhibitor as well as UK are produced by cells of various organs of the body. Plasminogen activator also was produced by serially propagated cells, diploid and heteroploid. However, only diploid cell lines retained activator activity of the original tissues and continued to produce activator antigenically identical to UK. In contrast, heteroploid line appeared to have lost the ability to form UK by yielded activator activity that differed from that of UK in immunoassays. Serially propagated cells thus provide an additional tool for in vitro study of plasminogen activator and may facilitate investigation of the fibrinolytic system in man.
The majority of postselection CD4+ single-positive thymocytes requires the thymus to produce long-lived, functional T cells.
Authors: R Dyall, J Nikolić-Zugić
Journal: The Journal of Experimental Medicine (1995)

We have previously isolated, and characterized in vitro, two subsets of CD4hi T cell receptor (TCR)hi single positive (SP) thymocytes: CD8- and CD8lo. In this report, we have analyzed phenotypic, functional, and developmental characteristics of these "late" CD4hi SP thymocyte subsets. The TCRhi phenotype and the elimination of T cells expressing TCR V beta segments reactive with endogenous mouse mammary tumor virus (MMTV) products suggested that both subsets had undergone positive and negative selection. CD8-4hi thymocytes were functional, as judged by their ability to: (a) induce lethal graft versus host disease (GVHD); (b) survive and expand in peripheral lymphoid organs; and (c) proliferate, rather than undergo apoptosis, in response to in vitro TCR cross-linking. By contrast, CD8lo4hi cells could not induce GVHD, were unable to expand (and perhaps even survive) in peripheral organs and underwent apoptosis upon TCR cross-linking. However, when reintroduced into the thymus, these cells matured into functional, long-lived CD8-4hi lymphocytes. These results document an obligatory requirement for the thymic microenvironment in the final maturation of the majority of CD4hi SP postselection thymocytes, and demonstrate the existence of a previously unrecognized control point in T cell development.
The IGF-I axis in kidney and skeletal muscle of potassium deficient rats
Authors: Fay W. Hsu, Tanny Tsao, Ralph Rabkin
Journal: Kidney International (1997)

Potassium deficiency in the rat results in growth retardation, muscle wasting and renal hypertrophy. This study tests the thesis that K deficiency leads to tissue distinct changes in the local IGF-I system and cell sensitivity to IGF-I that favors renal enlargement on the one hand and impaired muscle growth on the other. In rats after eight days of K deficiency, compared to pair-fed control rats, food utilization and muscle and body wt gain were attenuated while the kidneys enlarged. In muscle GH receptor and IGF-I gene expression, IGF-I peptide and IGF binding protein-5 (IGFBP) levels were decreased. Together with reduced food utilization, these changes may contribute to the attenuated muscle growth. In the enlarged kidneys despite a fall in IGF-I mRNA level, IGF-I peptide concentration was increased more than twofold. This increase in IGF-I could be caused by the increase in kidney IGFBP-1 gene and protein expression and the decrease in kidney IGF-I degrading activity noted in K deficiency. Treatment with IGF-I failed to induce body or muscle growth, but induced a further increase in kidney size and enlargement of the spleen. Thus, in K deficiency the spontaneous increase in IGF-I levels in the kidney that is IGF-I sensitive may well be a cause of the renal hypertrophy.
TEM8/ANTXR1 Blockade Inhibits Pathological Angiogenesis and Potentiates Tumoricidal Responses against Multiple Cancer Types
Authors: Amit Chaudhary, Mary Beth Hilton, Steven Seaman, Diana C. Haines, Susan Stevenson, Peter K. Lemotte, William R. Tschantz, Xiaoyan M. Zhang, Saurabh Saha, Tony Fleming, Brad St. Croix
Journal: Cancer Cell (2012)
The sensitivity of neutrophil CD64 expression as a biomarker of bacterial infection is low in critically ill patients
Authors: Antoine Gros, Mikael Roussel, Elise Sauvadet, Arnaud Gacouin, Sophie Marqué, Loïc Chimot, Sylvain Lavoué, Christophe Camus, Thierry Fest, Yves Le Tulzo
Journal: Intensive Care Medicine (2012)
Early neurological complications of coronary artery bypass surgery.
Authors: P J Shaw, D Bates, N E Cartlidge, D Heaviside, D G Julian, D A Shaw
Journal: BMJ (1985)

A prospective study of 312 patients undergoing elective coronary artery bypass surgery was undertaken to determine the incidence, severity, and functional impact of postoperative neurological complications. Detailed evaluation of the patients showed that neurological complications after surgery were common, occurring in 191 of the 312 patients (61%). Although such a high proportion of the total developed detectable changes, serious neurological morbidity was rare. Neurological disorders resulted in death in only one patient (0.3%) and severe disability in only four (1.3%). Forty eight patients were mildly disabled during the early postoperative period, and the remaining 138 with neurological signs had no serious functional disability. The postoperative neurological disorders detected included one death from cerebral hypoxic damage. Prolonged depression of conscious level was observed in 10 patients (3%) and definite stroke in 15 (5%); 78 (25%) developed ophthalmological abnormalities and 123 (39%) primitive reflexes; postoperative psychosis was observed in four (1%); and 37 (12%) developed disorders of the peripheral nervous system. The incidence of serious neurological problems such as fatal cerebral damage, stroke, and brachial plexopathy is in accordance with experience elsewhere. Lesser abnormalities, whose detection required detailed neurological examination, were much commoner than expected from previous reports.
Turkish Medical Association calls for help to defend its role
Authors: N. Stafford
Journal: BMJ (2012)

The Turkish Medical Association has issued an appeal for support from the World Medical Association, saying that a decree adopted by the Turkish government to give more authority to the Ministry of Health is threatening its autonomy.

In a letter to the world association the Turkish association says that the decree, adopted in November, has stripped it of several key functions, making it impossible to fulfil some of its chief missions, including “ensuring that [medicine] is practised and promoted in line with public and individual wellbeing and benefit” and protecting the rights of doctors.

Feride Aksu Tanik, secretary general of the Turkish Medical Association, told the BMJ that the government decree has amended laws that affect not just the association but other medicine related organisations and medical schools.

“We deeply believe in the necessity of the self …
Surrogate Decision-Makers' Perspectives on Discussing Prognosis in the Face of Uncertainty
Authors: Leah R. Evans, Elizabeth A. Boyd, Grace Malvar, Latifat Apatira, John M. Luce, Bernard Lo, Douglas B. White
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Many physicians are reluctant to discuss a patient's prognosis when there is significant prognostic uncertainty.
PSYCHIATRY, NATURE AND SCIENCE
Authors: MARTIN HOFFMAN
Journal: American Journal of Psychiatry (1960)

It is a purpose of philosophic analysis to clarify the meaning of concepts used in scientific discourse. An attempt to do so has been made here, with special reference to the value-terms used in psychiatry. Such terms as "mental health," "mental illness," "normal," "abnormal," "neurosis," "psychosis," "perversion," "psychopathic" or "sociopathic" personality have been subject to scrutiny. It has been shown that such terms cannot be defined scientifically. Therefore, it is suggested either that they not be used or that a precise statement of the basis of their use in any given case be made. Such attention to our use of language will bring rewards both in the clarity of our discourse and in the elimination of issues hitherto considered unsolved problems of science.
The Discovery of HIV as the Cause of AIDS
Authors: Robert C. Gallo, Luc Montagnier
Journal: New England Journal of Medicine (2003)

Progress in scientific research rarely follows a straight path. Generally it entails many unexpected meanderings with a mix of good and bad ideas good and bad luck. The discovery of the human immunodeficiency virus (HIV) as the cause of AIDS did not avoid this pattern. The story began in an unfavorable environment: during the late 1970s many people thought that epidemic diseases caused by microbes including viruses no longer posed a threat in industrialized countries. Other prevailing beliefs were that viruses did not cause any human cancers and that there was no such thing as a retrovirus that infected humans. Some of these beliefs were justified since attempts to find tumor viruses and in particular retroviruses in cancers or other diseases in humans had a troubled history and many of the groups that had the greatest expertise in the study of retroviruses had turned their efforts toward research on oncogenes. Luckily and rather amazingly however the conceptual and technical tools arrived in our hands just before the first patients with AIDS were identified in 1981. In addition there remained a few heretical or old-fashioned groups - among which were our two laboratories - that persisted in searching for retroviruses in human cancers particularly breast cancers and leukemias. This search finally paid off with the discovery of human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) the first of which was shown to cause an unusual T-cell leukemia. This discovery was made possible by 15 years of basic research on leukemogenic retroviruses in animals including the design and development of highly sensitive biochemical assays that were based on reverse transcriptase - the enzyme that is present in all retroviruses which was discovered in 1970 by Temin and Baltimore. (excerpt)
The Effect of Isoniazid on Transaminase Levels
Authors: WILLIAM C. BAILEY
Journal: Annals of Internal Medicine (1974)

To determine if something other than isoniazid causes the serum glutamic-oxalacetic transaminase (SGOT) elevations in isoniazid recipients, tuberculin-positive hospital employees receiving the drug were compared, by monthly SGOT measurements, with a comparable group of tuberculin-positive employees not receiving isoniazid. About 12% of the drug recipients developed SGOT levels higher than 100 mU/ml (upper limits of normal, 40 mU/ml). Once the drug had been withdrawn, their SGOT levels declined rapidly. In the control group, no one who had a base-line SGOT level below 100 mU/ml had subsequent values exceeding 100 mU/ml. Those subjects with elevations above 100 mU/ml (mean age, 50.2 years) were, on the average, older than the other isoniazid recipients (mean age, 36.9 years) whose SGOT levels remained below 100 mU/ml during treatment. The base-line mean SGOT level of the control group was slightly higher than in the drug group (excluding the 12% with significant SGOT elevations), but this relation reversed as soon as isoniazid treatment was started. This controlled prospective study shows, without question, that the SGOT elevations noted in the isoniazid recipients are related to the drug, not other factors.
Chronic hepatitis C genotype 2 or 3 short treatment
Authors: Ricardo Moreno-Otero, María Trapero, José A. Moreno-Monteagudo
Journal: Hepatology (2008)

Dalgard et al.1 reported interesting data on 14 versus 24 weeks of combination therapy in patients with hepatitis C virus (HCV) genotype 2 or 3, and they concluded that it is rational to treat those patients with rapid virological response (RVR) for only 14 weeks. Adequate treatment duration is generally considered decisive in order to improve adherence and reduce side effects. At present, the strategy involves adapting therapy to each individualized case instead of adapting the patient to an established regimen.2, 3 Young, white, nonobese patients with low viremia, infected by genotype 2 or 3 HCV, with low fibrosis and RVR could receive shorter treatment.2, 3 However, the point regarding duration may be elusive and, in spite of some studies,4, 5 definite conclusions are still lacking. The current experience of our group is in agreement with the results by Dalgard et al.1 The well-documented case of a patient adds further support to the value of the short regimen in patients with genotype 2 or 3 and RVR. A 34-year-old Spanish woman, with a body mass index of 21 kg/m2, moderate alanine aminotransferase (ALT) serum levels (64 IU/L), HCV-3a genotype infection, HCV RNA 5.7 × 105 IU/mL, and mild chronic hepatitis on biopsy (grade 2, stage 1–2), was initiated treatment with peginterferon α-2a (180 μg/weekly) plus ribavirin (800 mg/daily) on August 29, 2001. At week 4, the patient attained an RVR with normal ALT levels (13 IU/L). The tolerance was excellent but after receiving combination therapy during 10 weeks, she presented with fever and productive cough; chest radiography led to a diagnosis of pulmonary tuberculosis, documented by bacilli culture and sputum smears. Premature withdrawal (November 6, 2001) from antiviral treatment was required. Then, tuberculostatic therapy was started and maintained for 36 weeks with good tolerance. During this time, serum ALT levels were persistently normal and HCV RNA remained negative in three determinations carried out at weeks 12, 24, and 48. A second liver biopsy obtained at year 4 after antiviral withdrawal demonstrated no inflammation (A0) or fibrosis (F0). It can be concluded that: (1) Fewer side effects and their more limited duration are in favor of the short treatment regimen in patients with genotype 2 or 3 and RVR; (2) Short therapy is able to eradicate HCV and cure chronic hepatitis C in these patients; (3) Optimal treatment duration needs to be defined for each individualized patient; and (4) Further studies including customized management and therapeutic regimens based on virological characteristics (genotype and viremia), demographic aspects, liver disease severity, and individual genomic-marker analysis are warranted. Whether all points of this strategy have similar relevance with imminent new therapies remains to be investigated. Ricardo Moreno-Otero M.D.*, María Trapero M.D.*, José A. Moreno-Monteagudo M.D.*, * Digestive Diseases Service and CIBEREHD, University Hospital of La Princesa, Autonomous University of Madrid, Madrid, Spain.