tbuckley/cabot-search huggingface dataset:
Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies
Authors: Nancy L Bartlett, Robert Chen, Michelle A Fanale, Pauline Brice, Ajay Gopal, Scott E Smith, Ranjana Advani, Jeffrey V Matous, Radhakrishnan Ramchandren, Joseph D Rosenblatt, Dirk Huebner, Pamela Levine, Laurie Grove, Andres Forero-Torres
Journal: Journal of Hematology & Oncology (2014)

Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. United States registry and results database ClinicalTrials.gov NCT00947856 .
Steatosis affects chronic hepatitis C progression in a genotype specific way
Authors: Rubbia-Brandt L, Fabris P, Paganin S, Leandro G, Male Pj, Giostra E, Carlotto A, Bozzola L, Smedile A, Negro F
Journal: Gut (2004)

Liver steatosis is frequent in chronic hepatitis C, particularly in patients infected with hepatitis C virus (HCV) genotype 3. The aim of this study was to determine the relationship between steatosis and fibrosis in chronic hepatitis C as a function of viral genotype.A multivariable logistic regression analysis was carried out in 755 chronic hepatitis C patients (mean body mass index (BMI) 24.11 kg/m(2); 178 with genotype 3), consecutively admitted to three referral hospitals. Liver histology showed steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78 compensated and 109 decompensated).Steatosis was independently associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression analysis was repeated on patients divided according to viral genotype (that is, 3 v non-3) to identify type specific risk factors, steatosis was associated with ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype infected patients and with Metavir activity (p = 0.044) only in genotype 3 infected patients. Similarly, fibrosis was associated with steatosis only in genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p = 0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected patients.Steatosis influences chronic hepatitis C progression in a genotype specific way. Patients infected with genotype 3 and histologically confirmed steatosis should not be deferred from effective antiviral therapy.
Initial Choice of Oral Glucose-Lowering Medication for Diabetes Mellitus
Authors: Seth A. Berkowitz, Alexis A. Krumme, Jerry Avorn, Troyen Brennan, Olga S. Matlin, Claire M. Spettell, Edmund J. Pezalla, Gregory Brill, William H. Shrank, Niteesh K. Choudhry
Journal: JAMA Internal Medicine (2014)

Although many classes of oral glucose-lowering medications have been approved for use, little comparative effectiveness evidence exists to guide initial selection of therapy for diabetes mellitus.To determine the effect of initial oral glucose-lowering agent class on subsequent need for treatment intensification and 4 short-term adverse clinical events.This study was a retrospective cohort study of patients who were fully insured members of Aetna (a large national health insurer) who had been prescribed an oral glucose-lowering medication from July 1, 2009, through June 30, 2013. Individuals newly prescribed an oral glucose-lowering agent who filled a second prescription for a medication in the same class and with a dosage at or above the World Health Organization's defined daily dose within 90 days of the end-of-day's supply of the first prescription were studied. Individuals with interim prescriptions for other oral glucose-lowering medications were excluded.Initiation of treatment with metformin, a sulfonylurea, a thiazolidinedione, or a dipeptidyl peptidase 4 inhibitor.Time to addition of a second oral agent or insulin, each component separately, hypoglycemia, other diabetes-related emergency department visits, and cardiovascular events.A total of 15 516 patients met the inclusion criteria, of whom 8964 (57.8%) started therapy with metformin. In unadjusted analyses, use of medications other than metformin was significantly associated with an increased risk of adding a second oral agent only, insulin only, and a second agent or insulin (P < .001 for all). In propensity score and multivariable-adjusted Cox proportional hazards models, initiation of therapy with sulfonylureas (hazard ratio [HR], 1.68; 95% CI, 1.57-1.79), thiazolidinediones (HR, 1.61; 95% CI, 1.43-1.80), and dipeptidyl peptidase 4 inhibitors (HR, 1.62; 95% CI, 1.47-1.79) was associated with an increased hazard of intensification. Alternatives to metformin were not associated with a reduced risk of hypoglycemia, emergency department visits, or cardiovascular events.Despite guidelines, only 57.8% of individuals began diabetes treatment with metformin. Beginning treatment with metformin was associated with reduced subsequent treatment intensification, without differences in rates of hypoglycemia or other adverse clinical events. These findings have significant implications for quality of life and medication costs.
Dangerous Spectacle Frames
Authors: W. J. Ferraby
Journal: BMJ (1965)

Cerebral damage which renders the preferred arm useless may lead patients to use their non-preferred arm for everyday tasks including writing. In these circumstances, mirror writing and other mirror movements may occur. The present study on 10 formerly right-handed patients was carried out to determine whether similar phenomena occurred when serious damage to the right arm itself had occurred, cerebral function remaining intact or any damage being coincidental and non-focal. The patients were asked to describe the events that had occurred when they started using their left hand, to carry out a number of writing tests, and to undertake two graphic tasks to assess directional motor preferences. Seven patients had executed mirror reversal of letters, and eight had experienced mirror phenomena when carrying out everyday tasks with their left hand; brief case histories are cited. No patient exhibited mirror writing on formal testing, and there was no evidence of alteration in the expected preference of direction in which graphic tasks were undertaken. The practical and theoretical implications of these observations are discussed.
Urinary excretion of the hydroxypyridinium cross links of collagen in patients with rheumatoid arthritis.
Authors: D Black, M Marabani, R D Sturrock, S P Robins
Journal: Annals of the Rheumatic Diseases (1989)

Values for urinary hydroxypyridinium cross links of collagen measured by high performance liquid chromatography in a group of 19 seropositive patients with rheumatoid arthritis (RA) were compared with 19 controls matched for age and sex. The amounts of pyridinoline, expressed relative to creatinine, were significantly higher in the RA group, but there was no significant increase in a bone specific analogue, deoxypyridinoline. There were significant positive correlations between pyridinoline excretion and both C reactive protein and erythrocyte sedimentation rate, whereas there was an inverse relation with grip strength. The data indicated that pyridinoline concentrations in urine are strongly associated with disease activity in patients with RA.
A Comparative Synteny Map of Burkholderia Species Links Large-Scale Genome Rearrangements to Fine-Scale Nucleotide Variation in Prokaryotes
Authors: Chi Ho Lin, Guillaume Bourque, Patrick Tan
Journal: Molecular Biology and Evolution (2007)

Genome rearrangement events, including inversions and translocations, are frequently observed across related microbial species, but the impact of such events on functional diversity is unclear. To clarify this relationship, we compared 4 members of the Gram-negative Burkholderia family (Burkholderia pseudomallei, Burkholderia mallei, Burkholderia thailandensis, and Burkholderia cenocepacia) and identified a core set of 2,590 orthologs present in all 4 species (metagenes). The metagenes were organized into 255 synteny blocks whose relative order has been altered by a predicted minimum of 242 genome rearrangement events. Functionally, metagenes within individual synteny blocks were often related. The molecular divergence of metagenes adjacent to synteny breakpoints (boundary metagenes) was significantly greater compared with metagenes within blocks, suggesting an association between breakpoint locations and local fine-scale nucleotide alterations. This phenomenon, referred to as boundary element associated divergence, was also observed in Pseudomonas and Shigella, suggesting that this is a common phenomenon in prokaryotes. We also observed preferential localization of species-specific genes and insertion sequence element to synteny breakpoints in Burkholderia. Our results suggest that in prokaryotes, genome rearrangements may influence functional diversity through the enhanced divergence of boundary genes and the creation of foci for acquiring and deleting species-specific genes.
Unintentional Home Injuries Across the Life Span: Problems and Solutions
Authors: Andrea C. Gielen, Eileen M. McDonald, Wendy Shields
Journal: Annual Review of Public Health (2015)

Home injuries cause more than 30,000 deaths and 12 million nonfatal injuries annually in the United States. They generate an estimated $222 billion in lifetime costs annually. Despite some data limitations in documenting home as the location of an injury, much progress has been made in identifying effective prevention strategies that reduce injury or mitigate risk behaviors. The current interest in public health in the role of housing in health offers unparalleled opportunities for injury prevention professionals concerned with home injuries. Sharing the science of injury prevention with the wide array of professionals-such as architects, home builders, home visitors, and fire and emergency medical services providers-who create home environments and interact with residents could be a useful approach. A collaborative national effort to reduce the burden of home injuries is needed.
Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo
Authors: D. Kovacs, G. Cardinali, N. Aspite, C. Cota, F. Luzi, B. Bellei, S. Briganti, A. Amantea, M.R. Torrisi, M. Picardo
Journal: British Journal of Dermatology (2010)

Background Cutaneous pigmentation is regulated by a complex melanogenic network in which both keratinocytes and fibroblasts synthesize growth factors and cytokines. Solar lentigo (SL) is characterized by hyperpigmented lesions occurring on photodamaged skin areas. Despite the association of SL to ultraviolet (UV) exposure, the mechanisms underlying the development of these spots are not completely defined. Objectives To analyse the involvement of the fibroblast-derived growth factors, hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and stem cell factor (SCF) in SL hyperpigmentation; to evaluate whether the photoageing process occurring in fibroblasts could be responsible for the altered expression of these cytokines; and to investigate a new possible role of KGF in regulating pigmentation through the specific induction of melanogenic cytokines by keratinocytes. Methods We performed immunohistochemical analysis of HGF, KGF and SCF on SL biopsies. We analysed the mRNA expression of these cytokines using an in vitro model of photoageing induced on fibroblasts. Finally, we evaluated the effects of KGF on the expression of melanogenic cytokines at the mRNA and protein levels on keratinocytes. Results We found positive staining for HGF, KGF and SCF in the upper dermis of SL lesions and a significant induction of the three cytokines in photoaged fibroblasts. We also demonstrated the contribution of KGF to pigmentation, showing its ability specifically to modulate the expression of SCF in keratinocytes. Conclusions Fibroblasts may be persistently activated by UV exposure to release melanogenic growth factors; this inducible cytokine network acts both directly and indirectly through keratinocytes and may contribute to the hyperpigmentation of SL.
Establishing maximal oxygen uptake in young people during a ramp cycle test to exhaustion
Authors: A R Barker, C A Williams, A M Jones, N Armstrong
Journal: British Journal of Sports Medicine (2009)

Objectives This study tested the hypotheses that (1) secondary criteria (respiratory exchange ratio (RER), heart rate, blood [lactate]) traditionally used to verify the determination of maximum oxygen uptake (V̇O 2max ) in children can result in the acceptance of a ‘submaximal’ V̇O 2max or falsely reject a ‘true’ V̇O 2max and (2) the V̇O2 peak recorded during a ramp test in children is comparable to the V̇O 2peak achieved during supramaximal testing. Methods Thirteen children (9–10 years) completed a ramp cycle test to exhaustion to determine their V̇O 2peak . After 15 min of recovery, the participants performed a supramaximal cycle test to exhaustion at 105% of their ramp test peak power. Results Compared with the V̇O 2peak during the ramp test, a significantly lower V̇O 2 was recorded at a RER of 1.00 (1.293 litre/min (SD 0.265) vs 1.681 litre/min (SD 0.295), p&lt;0.001, n=12), at a heart rate of 195 beats/min (1.556 litre/min (SD 0.265) vs 1.721 litre/min (SD 0.318), p&lt;0.001, n=10) and at 85% of age-predicted maximum (1.345 litre/min (SD 0.228) vs 1.690 litre/min (SD 0.284), p&lt;0.001, n=13). Supramaximal testing yielded a V̇O 2peak that was not significantly different from the ramp test (1.615 litre/min (SD 0.307) vs 1.690 litre/min (SD 0.284), p=0.090, respectively). Conclusions The use of secondary criteria to verify a maximal effort in young people during ramp cycling exercise may result in the acceptance of a submaximal V̇O 2max . As supramaximal testing elicits a V̇O 2peak similar to the ramp protocol, thus satisfying the plateau criterion, the use of such tests is recommended as the appropriate method of confirming a ‘true’ V̇O 2max with children. Keywords Children, Aerobic Fitness, Fitness Testing, Supramaximal Exercise.
Rapamycin-induced alteration of the DC maturation process sustains their capacity to induce regulatory T cells
Authors: J. Quentin, L.-M. Charbonnier, D. Martire, A.-L. Mausset-Bonnefont, C. Jorgensen, P. Louis-Plence
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Dendritic cells (DC) are professional antigen-presenting cells which have unique properties to steer the outcome of immune responses. The authors previously demonstrated that repetitive injection of immature DC (iDC) was able to protect mice from collagen-induced arthritis (CIA). Rapamycin (Rapa) is a macrolide antibiotic with potent immunosuppressive properties that have been ascribed primarily to its inhibitory effects on T cells. More recently the effect of rapamycin on differentiation, antigen uptake and the immunostimulatory capacity of human DC were examined. In the present study the authors investigated the effect of rapamycin on the phenotype as well as the immunogenicity of iDC, and evaluated the tolerogenic potential of such rapamycin-treated DC in CIA. <h3>Methods</h3> Bone marrow-derived DCs were generated in the presence of 10 ng/ml of rapamycin during 6 days. Maturation of DCs was induced or not by addition of lipopolysaccharides ± interferon or interleukin 12 (IL-12). Phenotype of iDC and mature DC were characterised by FACS analysis and their cytokinic secretions were quantified by ELISA. Repetitive injections of 5×10<sup>5</sup> rapamycin-treated DC were performed in naïve mice and regulatory populations were monitored in various lymphoïd organs. In the CIA mouse model, injections of DCs were performed at days 21, 23 and 25 after immunisation. <h3>Results</h3> The addition of rapamycin has an impact on the basal and induced expression of major histocompatibility complex class II and co-stimulatory molecules, with a major impact on CD86 expression. These results suggest that the rapamycin alters the maturation process of murine DC. The secretion profiles of the mDCs were also altered by the addition of rapamycin. The decrease of the immunogenicity and antigen-presentation abilities of rapamycin-treated DCs were confirmed in mixed lymphocyte reaction and antigen presentation assays respectively. In vivo, the repetitive injections of rapamycin-treated or control DCs were able to induce the expansion of IL-10-secreting CD4 CD49b regulatory T cells, but not FoxP3<sup>+</sup>CD25 Treg cells in naïve mice. To evaluate the tolerogenic potential of rapamycin-treated DCs, they were repetitively injected in arthritic mice. The authors observed that mice vaccinated only with Rapa-iDC were protected from arthritis whereas those that received CTL-DC showed highest severity. A specific decrease of IgG2a antibody response was observed in the sera as well as an expansion of IL-10 secreting CD4 CD49b regulatory T cells in the liver of the protected mice. <h3>Conclusion</h3> This results suggest that the DC maturation is altered by Rapamycin, improving their tolerogenic potential in vivo. The therapeutic potential of such a cell-based immuno-modulatory strategy might be assessed in rheumatoid arthritis.
Interaction of phentolamine and noradrenaline on myocardial contractility and adenyl cyclase activity
Authors: B. RABINOWITZ, W. W. PARMLEY, G. BONNORIS, L. CHUCK, M. KLIGERMAN
Journal: Cardiovascular Research (1974)

Journal Article Interaction of phentolamine and noradrenaline on myocardial contractility and adenyl cyclase activity Get access BABETH RABINOWITZ, BABETH RABINOWITZ 2 From the Departments of Cardiology and Biochemistry, Cedars-Sinai Medical Center, Los Angeles, California, USA 2This work was done under the tenure of a Fellow of the Los Angeles Heart Association. Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLIAM W. PARMLEY, WILLIAM W. PARMLEY From the Departments of Cardiology and Biochemistry, Cedars-Sinai Medical Center, Los Angeles, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar GEORGE BONNORIS, GEORGE BONNORIS From the Departments of Cardiology and Biochemistry, Cedars-Sinai Medical Center, Los Angeles, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar LEONARD CHUCK, LEONARD CHUCK From the Departments of Cardiology and Biochemistry, Cedars-Sinai Medical Center, Los Angeles, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar MIRIAM KLIGERMAN MIRIAM KLIGERMAN From the Departments of Cardiology and Biochemistry, Cedars-Sinai Medical Center, Los Angeles, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 2, March 1974, Pages 243–248, https://doi.org/10.1093/cvr/8.2.243 Published: 01 March 1974
Day Treatment Versus Enhanced Standard Methadone Services for Opioid-Dependent Patients: A Comparison of Clinical Efficacy and Cost
Authors: S. Kelly Avants, Arthur Margolin, Jody L. Sindelar, Bruce J. Rounsaville, Richard Schottenfeld, Susan Stine, Ned L. Cooney, Robert A. Rosenheck, Shou-Hua Li, Thomas R. Kosten
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services—a day treatment program and enhanced standard care—for the treatment of opioid-dependent patients maintained on methadone hydrochloride. METHOD: A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master’s-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. RESULTS: Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups’ use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. CONCLUSIONS: Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.
MATERNAL SERUM α-FETOPROTEIN—A MARKER OF FETAL APLASTIC CRISIS DURING INTRAUTERINE HUMAN PARVOVIRUS INFECTION
Authors: D Carrington, M.J Whittle, A.A.M Gibson, T Brown, A.M Field, D.H Gilmore, D Aitken, W.J.A Patrick, E.O Caul, J.P Clewley, B.J Cohen
Journal: The Lancet (1987)