tbuckley/cabot-search huggingface dataset:
Disease activity assessment in childhood vasculitis: development and preliminary validation of the Paediatric Vasculitis Activity Score (PVAS)
Authors: Pavla Dolezalova, Fiona E Price-Kuehne, Seza Özen, Susanne M Benseler, David A Cabral, Jordi Anton, Jürgen Brunner, Rolando Cimaz, Katheleen M O'Neil, Carol A Wallace, Nicholas Wilkinson, Despina Eleftheriou, Erkan Demirkaya, Marek Böhm, Petra Krol, Raashid A Luqmani, Paul A Brogan
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Rare chronic childhood vasculitides lack a reliable disease activity assessment tool. With emerging new treatment modalities such a tool has become increasingly essential for both clinical practice and therapeutic trials to reproducibly quantify change in disease state. <h3>Objective</h3> To develop and validate a paediatric vasculitis activity assessment tool based on modification of the Birmingham Vasculitis Activity Score (BVASv.3). <h3>Methods</h3> A paediatric vasculitis registry was reviewed to identify clinical features missing in the BVASv.3. A modified nominal group technique was used to develop a working version of the Paediatric Vasculitis Activity Score (PVAS). Prospective validation provided tool reliability, reproducibility and responsiveness to change. Training of assessors was done according to the BVAS principles. <h3>Results</h3> BVAS items were redefined (n=22) and eight paediatric items added in Cutaneous (n=4), Cardiovascular (n=3) and Abdominal (n=1) sections. The final PVAS has 64 active items in nine categories. The principles of new/worse and persistently active disease were retained as were the overall score and weighting of categories. The median PVAS in 63 children with systemic vasculitis was 4/63 (0–38/63). There was a high interobserver agreement for the overall as well as for subsystem scores (linear-weighted-κ ≥0.87). PVAS correlated with physician9s global assessment (p&lt;0.01); treatment decision (p=&lt;0.01) and erythrocyte sedimentation rate (ESR) (p=0.01). In response to treatment, 15/19 patients assessed demonstrated a significant fall in PVAS (p=0.002), with good agreement among assessors for this change. <h3>Conclusions</h3> The PVAS validity in children with systemic vasculitis was demonstrated. Like the BVAS, we anticipate that the PVAS will provide a robust tool to objectively define disease activity for clinical trials and future research.
The Diagnosis and Treatment of Major Depressive Disorder in Childhood
Authors: Joaquim Puig-Antich, Burt Weston
Journal: Annual Review of Medicine (1983)

The authors review the evidence supporting the hypothesis of similarity or identity of prepubertal and adult major depressive disorders and give a state-of-the-art account of current assessment techniques, diagnosis, and treatment methods of prepubertal major depression. This is an area of child psychiatry where recent psychobiological research advances are fueling profound changes in traditional nosology and therapeutics. In addition, further understanding of early onset major depression is likely to throw considerable light on the nature and pathophysiology of depressive illness across ages.
Aldosterone in Chronic Kidney and Cardiac Disease
Authors: Thomas H. Hostetter, Hassan N. Ibrahim
Journal: Journal of the American Society of Nephrology (2003)

Eberhard Ritz Regulatory systems, which are normally involved in homeostasis, can take on maladaptive roles. This paradoxical situation has been convincingly demonstrated in heart failure. The evidence is strongest with respect to the beneficial effects of sympathetic and renin-angiotensin-
Genome-Wide Association Study of Major Recurrent Depression in the U.K. Population
Authors: Cathryn M. Lewis, Mandy Y. Ng, Amy W. Butler, Sarah Cohen-Woods, Rudolf Uher, Katrina Pirlo, Michael E. Weale, Alexandra Schosser, Ursula M. Paredes, Margarita Rivera, Nicholas Craddock, Mike J. Owen, Lisa Jones, Ian Jones, Ania Korszun, Katherine J. Aitchison, Jianxin Shi, John P. Quinn, Alasdair MacKenzie, Peter Vollenweider, Gerard Waeber, Simon Heath, Mark Lathrop, Pierandrea Muglia, Michael R. Barnes, John C. Whittaker, Federica Tozzi, Florian Holsboer, Martin Preisig, Anne E. Farmer, Gerome Breen, Ian W. Craig, Peter McGuffin
Journal: American Journal of Psychiatry (2010)

Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders.Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEP] study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Génotypage on the Illumina Human610-Quad BeadChip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry.Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungenotyped markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1.This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.
Allergic inflammation in the unified airway: start with the nose
Authors: B. J Lipworth
Journal: Thorax (2000)

It has long been recognised that there is an association between allergic inflammation in the upper airway (that is, allergic rhinitis) and in the lower airway (that is, allergic bronchitis or asthma). Indeed, up to 40% of patients with asthma have allergic rhinitis and vice versa.1 Both conditions have similar immunological mechanisms and underlying pathogenesis2 3 and, since one will affect the other, neither condition should be treated in isolation.

Many theories have been postulated as to the link between allergic rhinitis and asthma. Given that the upper and lower airways do, after all, have the same epithelial lining, it is perhaps hardly surprising that each shows similar reactions to inhalant allergens and irritants. Another important factor is that patients with a blocked nose breathe through their mouth and consequently lose the air conditioning effect of normal nose breathing. Mouth breathing is normal only during speech and exercise. Asthmatic patients who mouth breathe are therefore exposing their tracheobronchial tree to cold dehumidified air which may aggravate bronchial hyperresponsiveness.

The link between upper airway inflammation and asthma is not just confined to allergic rhinitis. Patients with nasal polyps are often non-atopic but commonly have associated asthma. Nasal polyposis, for example, occurs in 1% of the population but its frequency in patients with intrinsic asthma is 13% and in those with aspirin intolerance it has been shown to be 36%.4 Patients with allergic rhinitis or polyps who do not have overt symptoms of asthma often exhibit underlying bronchial hyperresponsiveness, bronchial eosinophilia, or increased exhaled levels of nitric oxide.5-8 

It has been shown in several studies that treating allergic airway inflammation in the nose with topical corticosteroids may be associated with a commensurate improvement in bronchial hyperresponsiveness and asthma control.9-13 In one study delivery of a 400 μg nominal …
An Official American Thoracic Society Systematic Review: Influence of Psychosocial Characteristics on Workplace Disability among Workers with Respiratory Impairment
Authors: Christopher G. Slatore, Philip Harber, Margaret C. Haggerty
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Psychosocial characteristics likely play an important role in the severity of workplace disability for workers with a respiratory impairment.We performed a systematic review of the available literature to examine the impact of psychosocial characteristics on workplace disability among workers with a respiratory impairment.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations, we searched Medline and other published and unpublished sources using the PubMed and Cochrane Central Register of Controlled Clinical Trials (CENTRAL) search engines from January 1, 1990 through March 8, 2013 for quantitative studies that examined the association of psychosocial characteristics with workplace disability among workers with a respiratory impairment. We also searched related citations and the bibliographies of selected studies and relevant review articles. One investigator abstracted data about study design and quality, psychosocial characteristics, and outcome measures.Of 5,746 potentially relevant studies, 20 met eligibility criteria and were included. Studies reported heterogeneous outcomes among heterogeneous samples of workers that precluded a quantitative synthesis. In general, mental illness was associated with increased workplace disability among workers with respiratory impairments. Few studies adjusted for disease severity, so the independent association of psychosocial characteristics and workplace disability is unclear. Most studies were cross-sectional, so the direction of the association could not be determined. We found only one trial of targeted therapy for the psychosocial condition, which was not effective at reducing disability.Psychosocial characteristics likely influence workplace disability in workers with respiratory impairments. The impact of targeted therapies is unclear and warrants further study.
Primary and secondary prophylaxis for Pneumocystis carinii related complications in HIV patients
Authors: M Held, FD Goebel
Journal: European Respiratory Journal (1996)

At the beginning of the acquired immune deficiency syndrome (AIDS) era, nearly 15 yrs ago, Pneumocystis carinii pneumonia (PCP) was the most common human immunodeficiency virus (HIV)-related complication. PCP represented about 60% of the initial case-defining events of AIDS patients [1]. Almost 80% of HIV and AIDS patients experienced at least one episode of PCP in the course of their HIV infection [2, 3]. Thanks to secondary prophylaxis, the number of relapses of PCP has recently declined. But PCP is still the most commonly reported AIDS-associated diagnosis amongst HIV-infected individuals in Western industrialized countries [4]. Mortality was high, as the disease was not recognized early enough in many cases and the benefits of systemic steroids were not known at that point of time [5, 6]. Increased risks for PCP are: a CD4+ count  12 months of inhalation time) failure, and found no difference between these two groups. Presentation with upper lobe infections was also a radiographic pattern of late failures. EDELSTEIN and MCCABE [30] first described this atypical presentation in 1990 and, in contrast to EWIG et al. [28], they observed complicated courses, such as cavities and pneumothoraces. Lung cavitation in PCP may also occur without inhaled pentamidine prophylaxis [31]. EDITORIAL
Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report
Authors: Michihide Tokuhira, Kyoko Hanzawa, Reiko Watanabe, Yasunobu Sekiguchi, Tomoe Nemoto, Yasuo Toyozumi, Jun-ichi Tamaru, Shinji Itoyama, Katsuya Suzuki, Hideto Kameda, Shigehisa Mori, Masahiro Kizaki
Journal: Journal of Hematology & Oncology (2009)

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA.
Viable Malignant Cells After Primary Chemotherapy for Disseminated Nonseminomatous Germ Cell Tumors: Prognostic Factors and Role of Postsurgery Chemotherapy—Results From an International Study Group
Authors: Karim Fizazi, Sergei Tjulandin, Roberto Salvioni, José R. Germà-Lluch, Jeannine Bouzy, David Ragan, Carsten Bokemeyer, Arthur Gerl, Aude Fléchon, Johann S. de Bono, Sally Stenning, Alan Horwich, Jörg Pont, Peter Albers, Ugo De Giorgi, Mark Bower, Anatoly Bulanov, Giorgio Pizzocaro, Jorge Aparicio, Craig R. Nichols, Christine Théodore, Jörg Thomas Hartmann, Hans-Joachim Schmoll, Stanley B. Kaye, Stéphane Culine, Jean-Pierre Droz, Cedric Mahé
Journal: Journal of Clinical Oncology (2001)

To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy.The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients.The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group.A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.
The abnormal exercise electrocardiogram in apparently healthy men: a predictor of angina pectoris as an initial coronary event during long-term follow-up.
Authors: P L McHenry, J O'Donnell, S N Morris, J J Jordan
Journal: Circulation (1984)

A group of 916 apparently healthy men between the ages of 27 and 55 years (mean 37) were followed up with serial medical and exercise test evaluations for a period of 8 to 15 years (mean 12.7) to determine (1) the prevalence and specific types of new coronary events observed in subjects with and without abnormal ST segment responses to exercise and (2) the predictive value of a serial conversion to an abnormal ST segment response to exercise for new coronary events. During the initial evaluation there were 23 subjects (2.5%) with an abnormal ST segment response to exercise. During follow-up there were nine (39%) coronary events in this group: eight cases of angina and one of sudden death. With serial testing, an additional 38 subjects (5.1%) experienced conversion to an abnormal ST segment response to exercise. During follow-up there were 12 (32%) coronary events in this group: 10 cases of angina, one of myocardial infarction, and one other. There were 833 subjects with normal ST segment responses to exercise with all tests. In this group there were 44 (5.3%) coronary events: 25 cases of myocardial infarction, seven of sudden death, and 12 of angina. We conclude that in apparently healthy middle-aged men an abnormal ST segment response to exercise is predictive of angina pectoris but not of myocardial infarction or sudden cardiac death as an initial coronary event.
Androgens Regulate Protein Kinase Cδ Transcription and Modulate Its Apoptotic Function in Prostate Cancer Cells
Authors: M. Veronica Gavrielides, Anatilde M. Gonzalez-Guerrico, Natalia A. Riobo, Marcelo G. Kazanietz
Journal: Cancer Research (2006)

Abstract Activation of protein kinase Cδ (PKCδ), a member of the novel PKC family, leads to apoptosis in several cell types. Although the molecular bases of PKCδ activation are being unfolded, limited information is available on the mechanisms that control its expression. Here, we report that in prostate cancer cells PKCδ is tightly regulated by androgens at the transcriptional level. Steroid depletion from the culture medium causes a pronounced down-regulation of PKCδ protein and mRNA in androgen-sensitive LNCaP prostate cancer cells, an effect that is rescued by the androgen R1881 in an androgen receptor (AR)–dependent manner. Analysis of the PKCδ promoter revealed a putative androgen responsive element (ARE) located 4.7 kb upstream from the transcription start site. Luciferase reporter assays show that this element is highly responsive to androgens, and mutations in key nucleotides in the AR-binding consensus abolish reporter activity. Furthermore, using chromatin immunoprecipitation assays, we determined that the AR binds in vivo to the PKCδ ARE in response to androgen stimulation. Functional studies revealed that, notably, androgens modulate phorbol 12-myristate 13-acetate (PMA)–induced apoptosis in LNCaP cells, an effect that is dependent on PKCδ. Indeed, androgen depletion or AR RNA interference severely impaired the apoptotic function of PKCδ or the activation of p38, a downstream effector of PKCδ in LNCaP cells—effects that can be rescued by restoring PKCδ levels using an adenoviral delivery approach. Our studies identified a novel hormonal mechanism for the control of PKCδ expression via transcriptional regulation that fine-tunes the magnitude of PKCδ apoptotic responses. (Cancer Res 2006; 66(24): 11792-801)
Case number 34: Relapse of polyarteritis nodosa presenting as isolated and localised lower limb periostitis
Authors: P Carron
Journal: Annals of the Rheumatic Diseases (2005)

A 59 year old woman presented with progressively increasing pain and swelling over the right lower limb that had started at the end of 2001. No systemic manifestations such as fever, weight loss, arthralgia, myalgia, or rash were present. Upon examination we noticed a painful swelling localised over the middle one third of the right tibia without cutaneous alterations. There were no other pathological clinical signs. At that time, she was taking no drugs.

Her medical history disclosed systemic polyarteritis nodosa (PAN) in 1991, at which time she presented with pain and swelling at the knees and ankles as well as cutaneous nodules over the medial side of the left ankle. This clinical presentation, together with the inflammatory biology, the absence of autoantibodies, …
Natural History of Osteonecrosis of the Jaw in Patients With Multiple Myeloma
Authors: Ashraf Badros, Evangelos Terpos, Eirini Katodritou, Olga Goloubeva, Efstathios Kastritis, Evgenia Verrou, Kostas Zervas, Maria R. Baer, Timothy Meiller, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2008)

To evaluate the natural history of bisphosphonate-related osteonecrosis of the jaw (ONJ) in patients with multiple myeloma.Ninety-seven patients with myeloma from the United States (n = 37) and Greece (n = 60) were observed prospectively for a minimum 3.2 years after ONJ. Patients characteristics were similar with regard to age, bisphosphonate use, and myeloma therapy, except more autologous transplantations were performed on patients in the United States than in Greece (73% v 28%; P < .0001).ONJ resolved in 60 patients (62%), resolved and recurred in 12 patients (12%), and did not heal in 25 patients (26%). Dental procedures preceded ONJ in 46 patients (47%) and were more common in those with single episodes (35 of 60, 58%) than recurrent or nonhealing (11 of 37, 30%; P = .007). Recurrent ONJ followed reinitiation of bisphosphonates in six of 12 patients. Greek patients had more bone pain than United States patients (60% v 30%, P = .001) and were less likely to restart bisphosphonates (5% v 35%, P < .0002). Myeloma relapses were more common in patients with recurrent/nonhealing than single-episode ONJ (84% v 62%; P = .02). Median overall survival from myeloma diagnosis was 10.8 years (95% CI; 9.3 years to not reached) and did not differ between patients with single, recurrent, and nonhealing ONJ (P = .2).ONJ healed in 75% of patients. Patients with spontaneous ONJ have a higher risk of nonhealing and recurrence. Reinitiating bisphosphonates after healing of ONJ is a reasonable option in patients experiencing relapse who are at risk of skeletal complications. Further studies of the pathogenesis and healing of ONJ are needed.