tbuckley/cabot-search huggingface dataset:
Surgical treatment of cervical cord compression in rheumatoid arthritis.
Authors: H A Crockard, W K Essigman, J M Stevens, J L Pozo, A O Ransford, B E Kendall
Journal: Annals of the Rheumatic Diseases (1985)

Cervical myelopathy is a rare but potentially dangerous complication of rheumatoid arthritis and presents considerable therapeutic problems. A conservative approach carries high mortality and surgical intervention is not without serious risks. Reduction of subluxation and posterior fusion is widely practised but may require prolonged bed rest and continuous skull traction, sometimes for many weeks. When anterior decompression has been attempted prolonged immobilisation and external fixation have created problems. In this series 23 rheumatoid patients with cervical myelopathy were investigated over a four-year period. Seventeen underwent anterior decompression of the cervical cord, of whom 14 had a transoral removal of the odontoid peg and pannus and posterior occipitocervical fusion during the same anaesthetic without mortality or serious postoperative complications; all but one have improved. The authors believe that early mobilisation after a combined cord decompression and internal fixation has reduced the mortality and morbidity. Management of cervical myelopathy in rheumatoid arthritis and indications for operation are discussed.
Body Mass Index Is a Stronger Predictor than the Metabolic Syndrome for Future Asthma in Women. The Longitudinal CARDIA Study
Authors: Nour Assad, Clifford Qualls, Lewis J. Smith, Alex Arynchyn, Bharat Thyagarajan, Mark Schuyler, David R. Jacobs, Akshay Sood
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

It is hypothesized that the metabolic syndrome explains the association between body mass index (BMI) and asthma in adults.
Suppression of tumour-specific CD4<sup>+</sup>T cells by regulatory T cells is associated with progression of human colorectal cancer
Authors: Gareth Betts, Emma Jones, Syed Junaid, Tariq El-Shanawany, Martin Scurr, Paul Mizen, Mayur Kumar, Sion Jones, Brian Rees, Geraint Williams, Awen Gallimore, Andrew Godkin
Journal: Gut (2011)

<h3>Background</h3> There is indirect evidence that T cell responses can control the metastatic spread of colorectal cancer (CRC). However, an enrichment of CD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Tregs) has also been documented. <h3>Objective</h3> To evaluate whether CRC promotes Treg activity and how this influences anti-tumour immune responses and disease progression. <h3>Methods</h3> A longitudinal study of Treg activity on a cohort of patients was performed before and after tumour resection. Specific CD4<sup>+</sup> T cell responses were also measured to the tumour associated antigens carcinoembryonic antigen (CEA) and 5T4. <h3>Results</h3> Tregs from 62 preoperative CRC patients expressed a highly significant increase in levels of Foxp3 compared to healthy age-matched controls (p=0.007), which returned to normal after surgery (p=0.0075). CD4<sup>+</sup> T cell responses to one or both of the tumour associated antigens, CEA and 5T4, were observed in approximately two-thirds of patients and one third of these responses were suppressed by Tregs. Strikingly, in all patients with tumour recurrence at 12 months, significant preoperative suppression was observed of tumour-specific (p=0.003) but not control CD4<sup>+</sup> T cell responses. <h3>Conclusion</h3> These findings demonstrate that the presence of CRC drives the activity of Tregs and accompanying suppression of CD4<sup>+</sup> T cell responses to tumour-associated antigens. Suppression is associated with recurrence of tumour at 12 months, implying that Tregs contribute to disease progression. These findings offer a rationale for the manipulation of Tregs for therapeutic intervention.
Effect of Intensive Insulin Therapy Using a Closed-Loop Glycemic Control System in Hepatic Resection Patients
Authors: Takehiro Okabayashi, Isao Nishimori, Hiromichi Maeda, Koichi Yamashita, Tomoaki Yatabe, Kazuhiro Hanazaki
Journal: Diabetes Care (2009)

OBJECTIVE Intensive insulin therapy (IIT) reduces morbidity and mortality in patients in surgical intensive care units. The aim of this study is to assess the effect of IIT using a closed-loop system in hepatectomized patients. RESEARCH DESIGN AND METHODS Patients were randomly assigned to receive IIT using a closed-loop system: an artificial pancreas (AP group) or conventional insulin therapy using the sliding-scale method (SS group). RESULTS The incidence of surgical-site infection in the AP group was significantly lower than that in the SS group. The length of hospitalization required for patients in the AP group was significantly shorter than that in the SS group. CONCLUSIONS Total hospital costs for patients in the AP group were significantly lower than for patients in the SS group. IIT using a closed-loop system maintained near-normoglycemia and contributed to a reduction in the incidence of SSI and total hospital costs due to shortened hospitalization.
Liver dysfunction in patients with IBD under immunosuppressive treatment: do we need to fear?
Authors: L. Beaugerie, A. L. Gerbes
Journal: Gut (2010)

There is an ineluctable trend in the treatment of inflammatory bowel disease (IBD) towards an extensive use of immunosuppressive drugs. These agents are prescribed earlier in the disease,1 in an increased proportion of patients (reaching one-third in some European countries2) and for prolonged periods since their impact on the disease course is unfortunately only suspensive.3 As a consequence, clinicians have less to do with the well-known direct complications of IBD, but there are growing preoccupations regarding established or uncertain safety concerns related to immunosuppressive treatment. IBD specialists are living in slow motion the cultural revolution brutally experienced by HIV specialists with the arrival of efficient combined antiviral treatment: these clinicians had to turn from infectious disease specialists into experts in drug management (observance, viral resistance) and drug complications (lipodystrophy, cardiovascular problems).

Immunosuppressive drugs for IBD can be deleterious through direct toxicity on organs, and promotion of serious infections or cancers. Regarding the liver, direct toxicity of anti-tumour necrosis factor (TNF) appears anecdotal4 and that of methotrexate well circumscribed and largely preventable through the experience of rheumatologists.5 Direct liver toxicity of thiopurines is more problematic, representing the most frequent cause of liver injury, together with fatty liver disease, in tertiary care IBD centres.6 Concordant data suggest that the prevalence and annual incidence of 6-mercaptopurine- and azathioprine-induced hepatotoxicity are low (3% and 1.4%, respectively)7), and that dose adaptation is most cases is sufficient to resolve the problem.6 8 However, a safety signal of thiopurine-induced injury of endothelial cells, essentially nodular regenerative hyperplasia, came from the use of …
Autologous peripheral blood stem cell transplantation for acute myeloid leukemia
Authors: Edo Vellenga, Wim van Putten, Gert J. Ossenkoppele, Leo F. Verdonck, Matthias Theobald, Jan J. Cornelissen, Peter C. Huijgens, Johan Maertens, Alois Gratwohl, Ron Schaafsma, Urs Schanz, Carlos Graux, Harry C. Schouten, Augustin Ferrant, Mario Bargetzi, Martin F. Fey, Bob Löwenberg
Journal: Blood (2011)
The Inflammatory Cytokine Tumor Necrosis Factor-α Generates an Autocrine Tumor-Promoting Network in Epithelial Ovarian Cancer Cells
Authors: Hagen Kulbe, Richard Thompson, Julia L. Wilson, Stephen Robinson, Thorsten Hagemann, Rewas Fatah, David Gould, Ayse Ayhan, Frances Balkwill
Journal: Cancer Research (2007)

Abstract Constitutive expression of the inflammatory cytokine tumor necrosis factor-α (TNF-α) is characteristic of malignant ovarian surface epithelium. We investigated the hypothesis that this autocrine action of TNF-α generates and sustains a network of other mediators that promote peritoneal cancer growth and spread. When compared with two ovarian cancer cell lines that did not make TNF-α, constitutive production of TNF-α was associated with greater release of the chemokines CCL2 and CXCL12, the cytokines interleukin-6 (IL-6) and macrophage migration-inhibitory factor (MIF), and the angiogenic factor vascular endothelial growth factor (VEGF). TNF-α production was associated also with increased peritoneal dissemination when the ovarian cancer cells were xenografted. We next used RNA interference to generate stable knockdown of TNF-α in ovarian cancer cells. Production of CCL2, CXCL12, VEGF, IL-6, and MIF was decreased significantly in these cells compared with wild-type or mock-transfected cells, but in vitro growth rates were unaltered. Tumor growth and dissemination in vivo were significantly reduced when stable knockdown of TNF-α was achieved. Tumors derived from TNF-α knockdown cells were noninvasive and well circumscribed and showed high levels of apoptosis, even in the smallest deposits. This was reflected in reduced vascularization of TNF-α knockdown tumors. Furthermore, culture supernatants from such cells failed to stimulate endothelial cell growth in vitro. We conclude that autocrine production of TNF-α by ovarian cancer cells stimulates a constitutive network of other cytokines, angiogenic factors, and chemokines that may act in an autocrine/paracrine manner to promote colonization of the peritoneum and neovascularization of developing tumor deposits. [Cancer Res 2007;67(2):585–92]
Intermittent negative pressure ventilation in the treatment of hypoxic hypercapnic coma in chronic respiratory insufficiency.
Authors: A Corrado, E De Paola, M Gorini, A Messori, G Bruscoli, S Nutini, D Tozzi, R Ginanni
Journal: Thorax (1996)

In recent years non-invasive ventilatory techniques have been used successfully in the treatment of acute on chronic respiratory failure (ACRF), but careful selection of patients is essential and a comatose state may represent an exclusion criterion. The aim of this retrospective and uncontrolled study was to evaluate whether a non-invasive ventilatory technique such as the iron lung could also be used successfully in patients with hypoxic hypercapnic coma, thus widening the range for application of non-invasive ventilatory techniques.A series of 150 consecutive patients with ACRF and hypoxic hypercapnic coma admitted to our respiratory intensive care unit were evaluated retrospectively. The most common underlying condition was chronic obstructive pulmonary disease (79%). On admission a severe hypoxaemia (Pao2 5.81 (3.01) kPa) and hypercapnia (Paco2 14.88 (2.78) kPa) associated with a decompensated acidosis (pH 7.13 (0.13)) were present, the Glasgow coma score ranged from 3 to 8, and the mean APACHE II score was 31.6 (5.3). All patients underwent intermittent negative pressure ventilation with the iron lung. The study end point was based on a dichotomous classification of treatment failure (defined as death or need for endotracheal intubation) versus therapeutic success.There were 45 treatment failures (30%) and 36 deaths (24%). Nine patients (6%) required intubation because of lack of airway control. The median total duration of ventilation was 27 hours per patient (range 2-274). The 105 successfully treated cases recovered consciousness after a median of four hours (range 1-90) of continuous ventilatory treatment and were discharged after 12.1 (9.0) days.These results show that, in patients with acute on chronic respiratory failure and hypoxic hypercapnic coma, the iron lung resulted in a high rate of success. As this study has the typical limitations of all retrospective and uncontrolled studies, the results need to be formally confirmed by controlled prospective studies. Confirmation of these results could widen the range of application of non-invasive ventilatory techniques.
Bone marrow Th17 TNFα cells induce osteoclast differentiation and link bone destruction to IBD
Authors: Uta Syrbe, Britta Siegmund
Journal: Gut (2014)

Osteoporosis in IBD has long been attributed to impaired bone formation caused by malabsorption and consequent vitamin D and calcium deficiency or to long-term steroid therapy. However, systemic bone loss is not restricted to chronic inflammatory conditions of the intestine such as IBD or coeliac disease, but is also found in non-intestinal chronic inflammatory conditions including rheumatoid arthritis, ankylosing spondylitis and psoriatric arthritis.1 In a groundbreaking paper in 1999, rheumatologists started to shed light on the process of inflammation-induced bone loss.2 In this work by Kong and colleagues, the initial evidence indicated that T cells affect maturation of osteoclasts, the primary bone-resorbing cells. They showed in an arthritis model that systemically activated T cells are sufficient to induce receptor activator of NF-κB ligand (RANKL), which binds to its corresponding receptor RANK on osteoclast precursor cells, which ultimately induces their differentiation into osteoclasts. Hence, this work suggested a novel role for T cells in bone pathology. In the same year, the osteoclastogenic function of interleukin (IL)-17, at this time a newly discovered T-cell-derived cytokine, was first described. It was shown that IL-17 induces RANKL expression by osteoblasts, which further promotes osteoclast maturation. The presence of high levels of IL-17 in the synovial fluid of patients with rheumatoid arthritis led the authors to conclude that IL-17 is a crucial cytokine for osteoclastogenic bone resorption in …
Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction
Authors: Mehdi Alizadeh, Marc Bernard, Bruno Danic, Charly Dauriac, Brigitte Birebent, Christine Lapart, Thierry Lamy, Pierre-Yves Le Prisé, Alain Beauplet, Dominique Bories, Gilbert Semana, Erwann Quelvennec
Journal: Blood (2002)
Preventing sports injuries at the national level: time for other nations to follow New Zealand’s remarkable success
Authors: John W Orchard
Journal: British Journal of Sports Medicine (2008)

Imagine yourself reading an editorial in Traffic Injury Prevention about the best system for preventing and managing traffic accidents. The editorial suggests that it is wrong for national governments to take an interest in preventing and managing road trauma. It argues that competition among car manufacturers, local governments and trauma hospitals can be relied upon to ensure road safety. It asserts that driving a motor vehicle is an inherently risky activity and that motor vehicle users should not expect non-driving taxpayers to help fund national government involvement.

As you read that editorial you disagree vehemently, perhaps even feeling outrage. You are aware that the countries in which national government bodies are dedicated to preventing and managing traffic accidents have excellent records at lowering mortality and have lower rates of injury than those countries without organised systems.1 You appreciate that the editorial mounts an argument that may sound good in theory, but in the real world it has been proven wrong. The laissez-faire (“do nothing”) approach to traffic injuries costs countries like India (which lack necessary government infrastructure) thousands of deaths per year compared with countries that have nationwide systems dedicated to lowering traffic injuries.2

Now imagine a similar editorial about sports injuries in the British Journal of Sports Medicine . Very few countries have a national government body taking responsibility for sports injuries. Generally, countries rely on the general health …
Prof. Andrzej Szczeklik, 1938–2012: aspirin-induced asthma and much more: Figure 1–
Authors: Sven-Erik Dahlén, Barbro Dahlén, Klaus F. Rabe
Journal: European Respiratory Journal (2012)

2012: aspirin-induced asthma and much moreWe were sad to learn that Andrzej Szczeklik died on February 3, 2012 after a short period of cardiac illness.We seek comfort in his many achievements that remain and which will continue to inspire and guide future generations of scientists and clinicians.Among respiratory physicians and allergologists, Szczeklik will certainly be remembered as the world-leading authority on aspirin-induced asthma.At this juncture it is somewhat ironic that he, outside our field, is known because of a number of key basic and clinical findings relating to diagnosis and treatment of thrombosis and cardiovascular disease.In fact, the Polish Nobel Laureate in Literature, Czeslaw Milosz, who wrote the foreword to Szczeklik's book Catharsis [1], described Szczeklik as a world famous cardiologist.That book, incidentally, showed yet another side of Szczeklik, the reflecting author providing a personal and very scholarly perspective on history, society and, above all, the moral and ethical issues that challenge us as human beings.Szczeklik's career as a doctor scientist was formed by strong gene-environment interactions.He was born in Cracow, Poland, in 1938 as the son of the eminent Polish Professor of Internal Medicine, Edward Szczeklik.It may, thus, be more than coincidental that young Andrzej, mostly known as Andrew outside Poland, developed a deep commitment to the improvement of the health of his fellow humans.This heritage was most likely further inspired by the hardships of his countrymen that he observed growing up in the immediate post-war era.
Ustekinumab improves psoriasis-related gene expression in noninvolved psoriatic skin without inhibition of the antimicrobial response
Authors: E.M. Baerveldt, A.J. Onderdijk, D. Kurek, M. Kant, E.F. Florencia, A.S. Ijpma, P.J. van der Spek, J. Bastiaans, P.A. Jansen, J.W.J. van Kilsdonk, J.D. Laman, E.P. Prens
Journal: British Journal of Dermatology (2012)

Ustekinumab is a fully human anti-p40 monoclonal antibody which neutralizes interleukin (IL)-12 and IL-23, thereby interfering with T-helper (Th)1/Th17 pathways and keratinocyte activation, and is highly effective in the treatment of psoriasis. During ustekinumab treatment, some of our patients noticed reduced koebnerization of noninvolved skin and less new plaque formation.To determine whether ustekinumab improves psoriasis-related gene expression and tape-strip responses in noninvolved skin.Before and 4 weeks after ustekinumab treatment, noninvolved skin was tape-stripped. After 5 h, biopsies were taken from untouched and tape-stripped skin. The mRNA expression of psoriasis-related markers such as NGF, GATA3 and IL-22RA1, and several antimicrobial peptides (AMP) was quantified. Leucocyte counts and a broad range of inflammatory serum proteins were analysed to gain insight into the systemic alterations.Four weeks following a single ustekinumab injection, NGF showed a significant decrease, whereas GATA3 and IL-22RA1 expression increased, indicative of reduced responsiveness to epidermal triggering. This was accompanied by an increase of the inflammation-related serum proteins GPNMB, MST1 and TRADD. The baseline and tape-strip-induced mRNA expression of the AMP human β-defensin-2 (hBD-2), S100A7 and LL-37 remained unaltered. Clinically, after 4 weeks, eight out of 11 patients showed a 50% psoriasis area and severity index (PASI) improvement, which was accompanied by a significant reduction in serum hBD-2 levels. No changes were noted in total leucocytes, C-reactive protein and erythrocyte sedimentation rate.These findings indicate that ustekinumab reduces psoriasis-related gene expression in noninvolved psoriatic skin, making it more resistant to exogenous triggering, without disturbing its antimicrobial response. In parallel, ustekinumab modulates important circulating inflammation-related proteins.
Complement-mediated adipocyte lysis by nephritic factor sera.
Authors: P W Mathieson, R Würzner, D B Oliveria, P J Lachmann, D K Peters
Journal: The Journal of Experimental Medicine (1993)

Recent data indicate a previously unsuspected link between the complement system and adipocyte biology. Murine adipocytes produce key components of the alternative pathway of complement and are able to activate this pathway. This suggested to us an explanation for adipose tissue loss in partial lipodystrophy, a rare human condition usually associated with the immunoglobulin G(IgG) autoantibody nephritic factor (NeF) which leads to enhanced alternative pathway activation in vivo. We hypothesized that in the presence of NeF, there is dysregulated complement activation at the membrane of the adipocyte, leading to adipocyte lysis. Here we show that adipocytes explanted from rat epididymal fat pads are lysed by NeF-containing sera but not by control sera. A similar pattern is seen with IgG fractions of these sera. Adipocyte lysis in the presence of NeF is associated with the generation of fluid-phase terminal complement complexes, the level of which correlates closely with the level of lactate dehydrogenase, a marker of cell lysis. Lysis is abolished by ethylenediaminetetraacetic acid, which chelates divalent cations and prevents complement activation, and reduced by an antibody to factor D, a key component of the alternative pathway. These data provide an explanation for the previously obscure link between NeF and fat cell damage.
Clonal analysis of B cells in the osteoarthritis synovium
Authors: S Shiokawa
Journal: Annals of the Rheumatic Diseases (2001)

Cellular and humoral immunity to collagen and cartilage proteoglycan were shown in patients with osteoarthritis (OA). Inflammatory infiltration containing T and B lymphocytes and macrophages, which are HLA-DR positive, is often seen in the synovial membrane of patients with OA. An analysis of the DNA restriction enzyme patterns of T lymphocytes from the OA synovium showed an oligoclonal pattern of T cell receptor beta chain gene rearrangements. No similar studies of B cell clonality have previously been performed. This study aimed at determining the clonal characteristics of the B cells in the OA synovium.A reverse transcriptase-polymerase chain reaction of the immunoglobulin transcripts of B cells in the synovial membranes from six patients with OA was performed and the products were analysed by a single strand conformation polymorphism analysis.Several dominant bands were seen in all samples and some of the dominant bands were common among the two or three separate regions of each synovial sample.Infiltrated B cells are oligoclonal, and an antigen driven immune response may play a part in the progression of the disease process in OA.