tbuckley/cabot-search huggingface dataset:
Association between toluene diisocyanate-induced asthma and DQB1 markers: a possible role for aspartic acid at position 57
Authors: A Balboni, OR Baricordi, LM Fabbri, E Gandini, A Ciaccia, CE Mapp
Journal: European Respiratory Journal (1996)

Toluene diisocyanate (TDI) is the most common cause of occupational asthma in western countries. The aim of this study was to investigate whether genetic factors are involved in toluene diisocyanate-induced asthma. We studied the frequency of human leucocyte antigen (HLA) class II genetic markers in three groups of subjects: 1) subjects with TDI-induced asthma (n = 30); 2) exposed subjects with no history of TDI-induced asthma (n = 12); and 3) normal subjects not exposed to TDI (n = 126). Venous blood samples were collected from the three groups and the polymorphic second exon of DQA and DQB genes was amplified by the polymerase chain reaction (PCR) method. Evaluation of HLA class II gene products in TDI-induced asthma cases showed a positive association with HLA-DQB1 * 0503 and a negative association with HLA-DQB1 * 0501 alleles, which differed at residue 57 for a single amino acid, i.e. aspartic acid in DQB1 * 0503 and valine in DQB1 * 0501. No significant difference was found in the distribution of DQA1 alleles between asthmatics and controls. Our results confirm the hypothesis that HLA-DQB1 * 0503 has a role in conferring susceptibility to TDI-induced asthma and that residue 57 of HLA-DQB1 is a potentially critical location.
The Case for Practical Clinical Trials in Psychiatry
Authors: John S. March, Susan G. Silva, Scott Compton, Mark Shapiro, Robert Califf, Ranga Krishnan
Journal: American Journal of Psychiatry (2005)

Clinical trials in psychiatry frequently fail to maximize clinical utility for practicing clinicians, or, stated differently, available evidence is not perceived by clinicians (and other decision makers) as sufficiently relevant to clinical practice, thereby diluting its impact. To attain maximum clinical relevance and acceptability, researchers must conduct clinical trials designed to meet the needs of clinicians and others who are making decisions about patients' care. The authors present the case for psychiatry's adoption of the practical clinical trials model, which is widely used in research in other areas of medicine.The authors outline the characteristics and scope of practical clinical trials, give examples of practical clinical trials, and discuss the challenges of using the practical clinical trials model in psychiatry, including issues of funding.Practical clinical trials, which are intended to provide generalizable answers to important clinical questions without bias, are characterized by eight key features: a straightforward clinically relevant question, a representative sample of patients and practice settings, sufficient power to identify modest clinically relevant effects, randomization to protect against bias, clinical uncertainty regarding the outcome of treatment at the patient level, assessment and treatment protocols that enact best clinical practices, simple and clinically relevant outcomes, and limited subject and investigator burden.To implement the practical clinical trials model in psychiatry will require stable funding for network construction and maintenance plus methodological innovation in governance and trial selection, assessment, treatment, data management, site management, and data analytic procedures.
Patient-Reported Outcomes and the Evolution of Adverse Event Reporting in Oncology
Authors: Andy Trotti, A. Dimitrios Colevas, Ann Setser, Ethan Basch
Journal: Journal of Clinical Oncology (2007)

Adverse event (AE) reporting in oncology has evolved from informal descriptions to a highly systematized process. The Common Terminology Criteria for Adverse Events (CTCAE) is the predominant system for describing the severity of AEs commonly encountered in oncology clinical trials. CTCAE clinical descriptors have been developed empirically during more than 30 years of use. The method of data collection is clinician based. Limitations of the CTC system include potential for incomplete reporting and limited guidance on data analysis and presentation methods. The Medical Dictionary for Regulatory Activities (MedDRA) is a comprehensive medical terminology system used for regulatory reporting and drug labeling. MedDRA does not provide for severity ranking of AEs. CTC-based data presentations are the primary method of AE data reporting used in scientific journals and oncology meetings. Patient-reported outcome instruments (PROs) cover the subjective domain of AEs. Exploratory work suggests PROs can be used with a high degree of patient engagement and compliance. Additional studies are needed to determine how PROs can be used to complement current AE reporting systems. Potential models for integrating PROs into AE reporting are described in this review. AE reporting methods will continue to evolve in response to changing therapies and growing interest in measuring the impact of cancer treatment on health status. Although integration of PROs into AE reporting may ultimately improve the comprehensiveness and quality of collected data, it may also increase the administrative burden and cost of conducting trials. Therefore, care must be used when developing health outcomes and safety data collection plans.
Predictors of normotension on withdrawal of antihypertensive drugs in elderly patients: prospective study in second Australian national blood pressure study cohort
Authors: M. R Nelson
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives</b>: To identify simple long term predictors of maintenance of normotension after withdrawal of antihypertensive drugs in elderly patients in general practice. <b>Design</b>: Prospective cohort study. <b>Setting</b>: 169 general practices in Victoria, Australia. <b>Participants</b>: 503 patients aged 65-84 with treated hypertension who were withdrawn from all antihypertensive drugs and remained drug free and normotensive for an initial two week period; all were followed for a further 12 months. <b>Main outcome measures</b>: Relative likelihood of maintaining normotension 12 months after drug withdrawal; relative likelihood of early return to hypertension after drug withdrawal. <b>Results</b>: The likelihood of remaining normotensive at 12 months was greater among younger patients (65-74 years), patients with lower "on-treatment" systolic blood pressure, patients on single agent treatment, and patients with a greater waist:hip ratio. The likelihood of return to hypertension was greatest for patients with higher "on-treatment" systolic blood pressure. <b>Conclusions</b>: Age, blood pressure control, and the number of antihypertensive drugs are important factors in the clinical decision to withdraw drug treatment. Because of consistent rates of return to antihypertensive treatment, all patients from whom such treatment is withdrawn should be monitored indefinitely to detect a recurrence of hypertension.
Human leucocyte antigen typing in rheumatoid arthritis/polymyositis overlap syndrome.
Authors: A Sharma, B A Baethge, J R Lisse, S Vaidya, J D Reveille
Journal: Annals of the Rheumatic Diseases (1995)

Relapsing polychondritis and Beh,et's syndrome in a patient with HIV infection Relapsing polychondritis is a systemic disorder characterised by recurrent inflam- matory lesions involving cartilaginous struc- tures, the cardiovascular system, the eyes, and the ears.Connective tissue diseases, dysmyelopoietic and myeloproliferative syn- dromes, ulcerative colitis, and thyroid diseases have been reported in association with relapsing polychondritis.'We present a patient with coexisting relapsing polychon- dritis, Behcet's syndrome, and infection with the human immunodeficiencv virus (HIV).A 25 year old man presented with a six on July 30, 2023 by guest.
Targeted drug delivery by in vivo coupling to endogenous albumin: an albumin-binding prodrug of methotrexate (MTX) is better than MTX in the treatment of murine collagen-induced arthritis
Authors: C Fiehn, F Kratz, G Sass, U Muller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2008)

To examine the effect of an albumin-binding prodrug of methotrexate (MTX) in the treatment of murine collagen-induced arthritis (CIA).The prodrug AWO54 with the formula EMC-d-Ala-Phe-Lys-Lys-MTX binds selectively to the cysteine-34 position of endogenous albumin, which acts as a macromolecular drug carrier for MTX to the site of inflammation. The CIA model was used to evaluate the anti-arthritic effect of the compound after intravenous application.The albumin-bound form of AWO54 was efficiently cleaved by cathepsin B and plasmin, two proteases that are overexpressed in rheumatoid arthritis, and release a MTX lysine derivative. AWO54 suppressed CIA in a dose-dependent manner and was significantly better than MTX. To obtain a similar effect only about 20% of the MTX-equivalent dose of AWO54 had to be given. The efficacy of the drug was tested in two different stages of CIA: while both, MTX and AWO54 inhibited arthritis in an early stage of the disease, in a later stage only AWO54 showed a significant inhibitory effect in comparison with control.Targeted drug delivery by in vivo coupling of a prodrug of MTX to endogenous albumin is better than MTX in the treatment of CIA.
Rcan1 negatively regulates FcɛRI-mediated signaling and mast cell function
Authors: Yong Jun Yang, Wei Chen, Alexander Edgar, Bo Li, Jeffery D. Molkentin, Jason N. Berman, Tong-Jun Lin
Journal: The Journal of Experimental Medicine (2009)

Aggregation of the high affinity IgE receptor (FcɛRI) activates a cascade of signaling events leading to mast cell activation. Subsequently, inhibitory signals are engaged for turning off activating signals. We identified that regulator of calcineurin (Rcan) 1 serves as a negative regulator for turning off FcɛRI-mediated mast cell activation. FcɛRI-induced Rcan1 expression was identified by suppression subtractive hybridization and verified by real-time quantitative polymerase chain reaction and Western blotting. Deficiency of Rcan1 led to increased calcineurin activity, increased nuclear factor of activated T cells and nuclear factor κB activation, increased cytokine production, and enhanced immunoglobulin E–mediated late-phase cutaneous reactions. Forced expression of Rcan1 in wild-type or Rcan1-deficient mast cells reduced FcɛRI-mediated cytokine production. Rcan1 deficiency also led to increased FcɛRI-mediated mast cell degranulation and enhanced passive cutaneous anaphylaxis. Analysis of the Rcan1 promoter identified a functional Egr1 binding site. Biochemical and genetic evidence suggested that Egr1 controls Rcan1 expression. Our results identified Rcan1 as a novel inhibitory signal in FcɛRI-induced mast cell activation and established a new link of Egr1 and Rcan1 in FcɛRI signaling.
Brain Imaging Biomarkers to Predict Relapse in Alcohol Addiction
Authors: Nora D. Volkow, Ruben D. Baler
Journal: JAMA Psychiatry (2013)

The finding that various regions were associated with relapse and craving is consistent with the organization of the brain into functional networks comprising complex connections among multiple regions. It is notable that the regions with the strongest prediction for relapse (vmPFC/ACC and precuneus) are central nodes of the default mode network (DMN), which is involved with the processing of internal states (including selfmonitoring) and deactivated when engaging in various behavioral tasks or when responding to the environment 9 (Figure). Also, the ventral striatum, which is one of the main targets for
Varicocele as a progressive lesion: positive effect of varicocele repair
Authors: D. J. Cozzolino
Journal: Human Reproduction Update (2001)

Varicoceles are the leading correctable cause of infertility in men who present to an infertility clinic for evaluation. Consequently, the surgical correction of a varicocele, known as a varicocelectomy, is the most commonly performed operation for the treatment of male infertility. The current data suggest that an individual with a varicocele, even with a previously normal semen analysis or documentation of previous fertility, is at risk for subsequent loss of testicular function and infertility. Many of these patients will need to be treated because there is convincing evidence that a varicocele may have a progressive toxic effect on the testes that may ultimately result in irreversible infertility if left untreated. Identifying those individuals with varicoceles that will ultimately cause fertility impairment is still beyond our current clinical capabilities. Current investigative modalities, e.g. semen analysis, testicular measurement, serum gonadotrophin determination, gonadotrophin-releasing hormone (GnRH) stimulation test, and testis biopsy analysis, may be employed to detect early changes in testicular physiology produced by a varicocele.
Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer
Authors: Douglas G. McNeel, Edward J. Dunphy, James G. Davies, Thomas P. Frye, Laura E. Johnson, Mary Jane Staab, Dorothea L. Horvath, Jane Straus, Dona Alberti, Rebecca Marnocha, Glenn Liu, Jens C. Eickhoff, George Wilding
Journal: Journal of Clinical Oncology (2009)

Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.Twenty-two patients were treated in a dose-escalation trial with 100 microg, 500 microg, or 1,500 microg plasmid DNA, coadministered intradermally with 200 microg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN gamma-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.
Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus.
Authors: K Iida, R Mornaghi, V Nussenzweig
Journal: The Journal of Experimental Medicine (1982)

This study reports quantitative information on the concentration of complement receptor for C3b and C4b (CR1) on erythrocytes from normal individuals and patients with immune complex disease. The measurements were performed by an immunoradiometric assay using monoclonal antibodies against CR1. The antibody specificity was confirmed by immunoprecipitation of CR1 from extracts of surface-labeled cells, by inhibition of rosette formation between B lymphocytes and the erythrocytes intermediate EAC14oxy23b, and by the characteristic distribution of the antigen among cells of human peripheral blood. The number of CR1 molecules in erythrocytes from 52 normal individuals was estimated as 1,410 +/- 620. No significant differences in CR1 levels were observed when individuals were grouped by sex, age, or blood groups. In patients with SLE and rheumatoid arthritis, the number of CR1 molecules per RBC was significantly lower, i.e., 600 +/- 307 and 903 +/- 417, respectively. CR1 levels were normal in asthmatics undergoing long-term treatment with prednisone. In SLE patients, significant correlations were found between CR1 levels, C4 hemolytic titers, and levels of circulating immune complexes. In two out of four patients with SLE, CR1 levels increased significantly during remission, showing that the deficiency is, at least in part, reversible. The deficiency in CR1 could be genetically controlled or could represent an epiphenomenon caused by the interaction of the receptor with a ligand present in the circulation of patients.
Expression of the matrix receptor CD44v5 on chondrocytes changes with osteoarthritis: an experimental investigation in the rabbit
Authors: C O Tibesku
Journal: Annals of the Rheumatic Diseases (2005)

To evaluate the expression of CD44v5 on chondrocytes of hyaline cartilage during the course of osteoarthritis (OA).In 12 white New Zealand rabbits the anterior cruciate ligament (ACL) was resected to create an anterior instability of the knee. In 12 control rabbits only a sham operation without resection of the ACL was done. Four animals of each group were killed at 3, 6, and 12 weeks. The loadbearing area was evaluated histologically according to Mankin and by immunostaining for CD44v5.In the trial group, histological grades of OA showed a positive linear correlation with the time after surgery. Immunostaining showed an increased expression of CD44v5 in the control group after 3 and 6 weeks, which dropped to normal after 12 weeks. There was no difference between control and trial groups after 3 and 6 weeks, but a difference was seen after 12 weeks. A significant positive correlation between CD44v5 expression and the histological grade of OA was found (r = 0.314).An in vivo increase of expression of the hyaluronan receptor CD44v5 occurs during the course of OA. Further studies are needed to evaluate whether this pattern applies to man and whether new treatment approaches might evolve from this knowledge.
THE ROLE OF ALKALINE PHOSPHATASE IN OSTEOGENESIS
Authors: Robert S. Siffert
Journal: The Journal of Experimental Medicine (1951)

The role of alkaline phosphatase in osteogenesis has been investigated by histochemical techniques with particular attention to its relationship to phosphate metabolism and matrix elaboration. The upper tibial epiphysis mainly, and other epiphyses as well of growing rabbits, and the costochondral junctions of newborn human beings were studied, as were bone grafts in growing rabbits. The findings in the newborn human beings were identical with those in the rabbits. Phosphatase activity and free phosphate localization do not universally coincide. The enzyme appears to be intimately related to preosseous cellular metabolism and to the elaboration of a bone matrix that is chemically calcifiable. It remains possible, however, that phosphatase may be in some way involved in making inorganic salts available to the calcifiable matrix. If this function does exist it is a secondary one, since the elaboration of bone matrix, which is always associated with phosphatase activity, can and does occur in the absence of calcification. Calcification may occur later, in the absence of the enzyme. There is evidence to suggest that cartilage matrix is utilized in the formation of bone matrix. Phosphatase is physiologically active only in the presence of living cells. Where it is demonstrable in the absence of living cells, as in the cartilage remnants of the metaphysis, it appears to be physiologically inactive. Since phosphatase is temporarily inactivated in weakly acid media, and readily reactivated by alkaline solutions it is possible that the enzyme might survive in a physiologically inactive state in weakly acid tissues, and yet remain capable of histochemical demonstration in vitro in an alkaline medium. Phosphatase is not related to the disappearance of chondroitin sulfate.
Efficacy of etanercept in the treatment of acute, severe sciatica: a pilot study
Authors: S Genevay
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To explore the efficacy of a tumour necrosis factor α (TNFα) inhibitor (etanercept, Enbrel) in patients with severe sciatica. <b>Methods:</b> A pilot study of etanercept was conducted in patients admitted to hospital for acute severe sciatica. Ten consecutive patients received three subcutaneous injections of etanercept (25 mg every 3 days) in addition to standard analgesia. Response was evaluated at day 10 (T1) and week 6 (T2) using a visual analogue scale for leg pain (VASL) and for low back pain (VASB), and two validated functional scores: the Oswestry disability index (ODI) and the Roland Morris disability questionnaire (RMDQ). The control group consisted of 10 patients with severe sciatica, who took part in an observational study on IV methylprednisolone. <b>Results:</b> In the etanercept group all variables improved: VASB from 36 to 7; VASL from 74 to 12; RMDQ from 17.8 to 5.8, and ODI from 75.4 to 17.3; all p&lt;0.001. Pain (VASL and VASB: p&lt;0.001) and ODI (p&lt;0.05) were significantly better in the etanercept group than in the methylprednisolone group. <b>Conclusion:</b> In this open, historical group controlled study, patients with severe sciatica had sustained improvement after a short treatment with etanercept that was better than standard care plus a short course of methylprednisolone. These results suggest that inhibition of TNFα is beneficial in the treatment of sciatica and support a pathological role for TNFα in the pathogenesis of sciatica. These results need to be confirmed by a randomised controlled trial.
Preclinical and clinical activity of sunitinib in patients with cisplatin-refractory or multiply relapsed germ cell tumors: a Canadian Urologic Oncology Group/German Testicular Cancer Study Group cooperative study
Authors: K. Oechsle, F. Honecker, T. Cheng, F. Mayer, P. Czaykowski, E. Winquist, L. Wood, M. Fenner, S. Glaesener, J.T. Hartmann, K. Chi, C. Bokemeyer, C. Kollmannsberger
Journal: Annals of Oncology (2011)
The association of tumor necrosis factor α receptor 2 and tumor necrosis factor α with insulin resistance and the influence of adipose tissue biomarkers in humans
Authors: Marie-France Hivert, Lisa M. Sullivan, Peter Shrader, Caroline S. Fox, David M. Nathan, Ralph B. D'Agostino, Peter W.F. Wilson, Emelia J. Benjamin, James B. Meigs
Journal: Metabolism (2009)