bluuebunny/crossref_metadata_2025 huggingface dataset:
The Public Health Approach to Eliminating Disparities in Health
Authors: Satcher David , Higginbotham Eve J.
Published: January 2008

Reducing and eliminating disparities in health is a matter of life and death. Each year in the United States, thousands of individuals die unnecessarily from easily preventable diseases and conditions. It is critical that we approach this problem from a broad public health perspective, attacking all of the determinants of health: access to care, behavior, social and physical environments, and overriding policies of universal access to care, physical education in schools, and restricted exposure to toxic substances. We describe the historical background for recognizing and addressing disparities in health, various factors that contribute to disparities, how the public health approach addresses such challenges, and two successful programs that apply the public health approach to reducing disparities in health. Public health leaders must advocate for public health solutions to eliminate disparities in health.
ACE2 Deficiency Modifies Renoprotection Afforded by ACE Inhibition in Experimental Diabetes
Authors: Tikellis Chris , Bialkowski Katarzyna , Pete Josepha , Sheehy Karen , Su Qui , Johnston Colin , Cooper Mark E. , Thomas Merlin C.
Published: January 2008

OBJECTIVE— The degradation of angiotensin (Ang) II by ACE2, leading to the formation of Ang 1–7, is an important step in the renin-angiotensin system (RAS) and one that is significantly altered in the diabetic kidney. This study examines the role of ACE2 in early renal changes associated with diabetes and the influence of ACE2 deficiency on ACE inhibitor–mediated renoprotection.

RESEARCH DESIGN AND METHODS— Diabetes was induced by streptozotocin in male c57bl6 mice and ACE2 knockout (KO) mice. After 5 weeks of study, animals were randomized to receive the ACE inhibitor perindopril (2 mg · kg−1 · day−1). Wild-type mice were further randomized to receive the selective ACE2 inhibitor MLN-4760 (10 mg · kg−1 · day−1) and followed for an additional 5 weeks. Markers of renal function and injury were then assessed.

RESULTS— Induction of diabetes in wild-type mice was associated with a reduction in renal ACE2 expression and decreased Ang 1–7. In diabetic mice receiving MLN-4760 and in ACE2 KO mice, diabetes-associated albuminuria was enhanced, associated with an increase in blood pressure. However, renal hypertrophy and fibrogenesis were reduced in diabetic mice with ACE2 deficiency, and hyperfiltration was attenuated. Diabetic wild-type mice treated with an ACE inhibitor experienced a reduction in albuminuria and blood pressure. These responses were attenuated in both diabetic ACE2 KO mice and diabetic mice receiving MLN-4760. However, other renoprotective and antifibrotic actions of ACE inhibition in diabetes were preserved in ACE2-deficient mice.

CONCLUSIONS— The expression of ACE2 is significantly modified by diabetes, which impacts both pathogenesis of kidney disease and responsiveness to RAS blockade. These data indicate that ACE2 is a complex and site-specific modulator of diabetic kidney disease.
Association of NOS1AP Genetic Variants With QT Interval Duration in Families From the Diabetes Heart Study
Authors: Lehtinen Allison B. , Newton-Cheh Christopher , Ziegler Julie T. , Langefeld Carl D. , Freedman Barry I. , Daniel Kurt R. , Herrington David M. , Bowden Donald W.
Published: January 2008

OBJECTIVES—Prolongation of the electrocardiographic QT interval is a risk factor for sudden cardiac death (SCD). Diabetic individuals are at increased risk for prolonged QT interval and SCD. We sought to replicate the finding that genetic variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with QT interval duration in a type 2 diabetes–enriched sample of European ancestry.

RESEARCH DESIGN AND METHODS—Two single nucleotide polymorphisms (SNPs) in NOS1AP were genotyped in 624 European Americans and 127 African Americans from 400 pedigrees enriched for type 2 diabetes. An additive genetic model was tested for each SNP in ancestry-specific analyses in the total sample and the diabetic subset (European Americans, n = 514; African Americans, n = 115), excluding from the analyses individuals taking QT-altering medications.

RESULTS—In European Americans, rs10494366 minor homozygotes had a 9.3-ms-longer QT interval compared with major homozygotes (P = 5.7 × 10−5); rs10918594 minor homozygotes had a 12.5-ms-longer QT interval compared with major homozygotes (P = 1.5 × 10−6). Restricting analyses to the diabetic European Americans strengthened the effect despite the reduction in sample size (11.3-ms difference, P = 5.1 × 10−5; 13.9-ms difference, P = 1.6 × 10−6, respectively). No association between the NOS1AP SNPs and QT interval duration was observed in the limited number of African Americans.

CONCLUSIONS—Two NOS1AP SNPs are strongly associated with QT interval duration in a predominately diabetic European-American sample. Stronger effects of NOS1AP variants in diabetic individuals suggest that this patient subset may be particularly susceptible to genetic variants that influence myocardial depolarization and repolarization as manifest in the QT interval.
Synchronisation of spatiotemporal complex states by incoherent coupling
Authors: Havermann Katharina , Gütlich Björn , Denz Cornelia
Published: January 2008

Synchronisation of spatiotemporal continuous disorder is realised in a Liquid Crystal Light Valve single feedback system with an incoherent, unidirectional master-slave-coupling scheme as excellent model system for synchronisation. Thus, complex states disordered in space and time were completely synchronised by using identical systems as master and slave. Thereby the impeding role of system differences is demonstrated in comparison to former experiments. A novel imaging method is introduced, in which the synchronisation process and effects like a time lag can be more easily characterised.
Differential survival among life stages contributes to co‐dominance of Abies mariesii and Abies veitchii in a sub‐alpine old‐growth forest
Authors: Mori Akira S. , Komiyama Akira
Published: January 2008

Questions: Are there interspecific differences in mortality and recruitment rates across life stages between two shade‐tolerant dominant trees in a sub‐alpine old‐growth forest? Do such differences in demography contribute to the coexistence and co‐dominance of the two species?

Location: Sub‐alpine, old‐growth forest on Mt. Ontake, central Honshu, Japan.

Methods: From 1980 to 2005, we recorded DBH and status (alive or dead) of all Abies mariesii and A. veitchii individuals (DBH ≥ 5 cm) in a 0.44‐ha plot. Based on this 25 year census, we quantified mortality and recruitment rates of the two species in three life stages (small tree, 5 cm ≤ DBH < 10 cm; subcanopy tree, 10 cm ≤ DBH < 20 cm; canopy tree, DBH ≥ 20 cm).

Results: Significant interspecific differences in mortality and recruitment rates were observed in both the small tree and sub‐canopy tree stages. In this forest, saplings (< 5 cm DBH) are mostly buried by snow‐pack during winter. As a consequence, saplings of A. mariesii, which is snow and shade tolerant, show higher rates of recruitment into the small tree stage than do those of A. veitchii. Above the snow‐pack, trees must tolerate dry, cold temperatures. A. veitchii, which can more readily endure such climate conditions, showed lower mortality rate at the subcanopy stage and a higher recruitment rate into the canopy tree stage. This differential mortality and recruitment among life‐stages determines relative dominance of the two species in the canopy.

Conclusion: Differential growth conditions along a vertical gradient in this old forest determine survival of the two species prior to reaching the canopy, and consequently allow co‐dominance at the canopy stage.
Synthesis and Evaluation of Some Xanthone Derivatives for Anti‐Arrhythmic, Hypotensive Properties and Their Affinity for Adrenergic Receptors
Authors: Marona Henryk , Szkaradek Natalia , Kubacka Monika , Bednarski Marek , Filipek Barbara , Cegla Marek , Szneler Edward
Published: January 2008

A series of 2‐, 4‐ or 2‐methyl‐6‐substituted xanthone derivatives 8–17 containing selected piperazine moieties were synthesized and tested for their electrocardiographic, anti‐arrhythmic, and antihypertensive activity, as well as for the α1‐ and β1‐adrenoceptor binding affinities. Of the newly synthesized derivatives, 2‐(2‐hydroxy‐3‐(4‐(2‐phenoxyethyl)piperazin‐1‐yl)propoxy)‐9H‐xanthen‐9‐one dihydrochloride 9, 4‐(2‐hydroxy‐3‐(4‐(2‐phenoxyethyl)piperazin‐1‐yl)propoxy)‐9H‐xanthen‐9‐one dihydrochloride 12, and 4‐(2‐(4‐(pyridin‐2‐yl)piperazin‐1‐yl)ethoxy)‐9H‐xanthen‐9‐one dihydrochloride 15 possessed significant anti‐arrhythmic activity in the adrenaline‐induced model of arrhythmia, with the ED50 values ranging 1.7–7.2 mg/kg. Compound 15 had the lowest ED50 value equaling 1.7 mg/kg, which was comparable with ED50 value of propranolol, which was used in this test as a reference compound. Compound 9 showed also the strongest hypotensive activity, which persisted for 60 minutes at the dose of 2.5 mg/kg. 2‐(2‐(4‐(2‐Phenoxyethyl)piperazin‐1‐yl)ethoxy)‐9H‐xanthen‐9‐one dihydrochloride 8 also significantly lowered blood pressure at a dose of 2.5 mg/kg but much weaker than compound 9. Binding studies are in agreement with our pharmacological results and could explain anti‐arrhythmic effect of compound 15 and anti‐arrhythmic and hypotensive effects of compounds 9 and 12.
Successful treatment of resistant pseudogout with anakinra
Authors: McGonagle Dennis , Tan Ai Lyn , Madden Julie , Emery Paul , McDermott Michael F.
Published: January 2008

We describe herein the case of a 63‐year‐old man with pseudogout affecting multiple joints that was resistant to treatment with allopurinol, steroids, and antiinflammatory drugs. Based on recent data on the molecular mechanism of pseudogout that demonstrated overproduction of interleukin‐1 (IL‐1), we treated the patient with anakinra, an IL‐1 receptor antagonist. The patient responded to treatment with anakinra within 2 weeks, with resolution of the signs and symptoms of pseudogout and normalization of levels of inflammation markers.
Morbidity and mortality in rheumatoid arthritis patients with prolonged therapy‐induced lymphopenia: Twelve‐year outcomes
Authors: Lorenzi Alice R. , Clarke Alexandra M. , Wooldridge Tom , Waldmann Herman , Hale Geoff , Symmons Deborah , Hazleman Brian L. , Isaacs John D.
Published: January 2008

Objective

To assess immunologically relevant outcomes in a cohort of rheumatoid arthritis (RA) patients with prolonged therapy‐induced lymphopenia.

Methods

Morbidity (infection or malignancy) and mortality were assessed in 53 RA patients who were treated with the lymphocytotoxic monoclonal antibody alemtuzumab between 1991 and 1994. Data were obtained by interview, medical record review, and Office for National Statistics mortality monitoring. Lymphocyte subsets were enumerated by flow cytometry. A retrospective, matched‐cohort study of mortality was performed with 102 control subjects selected from the European League Against Rheumatism database of patients with rheumatic disorders.

Results

Lymphopenia persisted in the patients: median CD3+CD4+, CD3+CD8+, CD19+, and CD56+ lymphocyte counts measured at a median followup of 11.8 years from the first administration of alemtuzumab were 0.50 × 109/liter, 0.26 × 109/liter, 0.11 × 109/liter, and 0.09 × 109/liter, respectively. Twenty‐seven of 51 cases and 46 of 101 controls with available data had died, yielding a mortality rate ratio of 1.20 (95% confidence interval 0.72–1.98). Causes of death were similar to those that would be expected in a hospital‐based RA cohort. No opportunistic infections were noted, and only 3 infections were documented following 36 elective orthopedic procedures.

Conclusion

Despite continued lymphopenia 11.8 years after therapy, our patient cohort did not exhibit excess mortality or unusual infection‐related morbidity, and surgery was well tolerated. These data should be reassuring for clinicians and patients who are considering lymphocytotoxic or other immunomodulatory therapy for RA.
Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone
Authors: Sanchez Christelle , Deberg Michelle A. , Bellahcène Akeila , Castronovo Vincent , Msika Philippe , Delcour J. P. , Crielaard J. M. , Henrotin Yves E.
Published: January 2008

Objective

To determine the phenotype of osteoblasts from the sclerotic zones of human osteoarthritic (OA) subchondral bone.

Methods

Human osteoblasts were isolated from sclerotic or nonsclerotic areas of subchondral bone and cultured for 14 days in monolayer. The expression of 14 genes was investigated by real‐time reverse transcription–polymerase chain reaction. The activities of alkaline phosphatase (AP) and transglutaminases (TGases) were quantified by enzymatic assays. C‐terminal type I procollagen propeptide (CPI), interleukin‐1β (IL‐1β), IL‐6, IL‐8, transforming growth factor β1 (TGFβ1), osteocalcin (OC), and osteopontin (OPN) were assayed in the culture medium by immunoassay.

Results

Gene expression levels of matrix metalloproteinase 13, COL1A1 and COL1A2, OPN, tissue‐nonspecific AP, OC, vascular endothelial growth factor, ANKH, TGase 2, factor XIIIA, and dentin matrix protein 1 were significantly up‐regulated in sclerotic osteoblasts compared with nonsclerotic osteoblasts. In contrast, parathyroid hormone receptor gene expression was depressed in sclerotic osteoblasts, but bone sialoprotein levels were unchanged. The activities of AP and TGases were increased in sclerotic osteoblasts, while matrix mineralization, revealed by alizarin red staining, was decreased. In parallel, protein synthesis of CPI, OC, OPN, IL‐6, IL‐8, and TGFβ1 was significantly higher in sclerotic osteoblasts than in nonsclerotic osteoblasts, while IL‐1β production was similar in both groups.

Conclusion

These findings contribute to a better understanding of the mechanisms involved in subchondral bone sclerosis and identify osteoblasts with an altered phenotype as a potential target for future OA therapies.
The HLA–DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture
Authors: Hughes Laura B. , Morrison Dahliann , Kelley James M. , Padilla Miguel A. , Vaughan L. Kelly , Westfall Andrew O. , Dwivedi Harshit , Mikuls Ted R. , Holers V. Michael , Parrish Lezlie A. , Alarcón Graciela S. , Conn Doyt L. , Jonas Beth L. , Callahan Leigh F. , Smith Edwin A. , Gilkeson Gary S. , Howard George , Moreland Larry W. , Patterson Nick , Reich David , Bridges S. Louis
Published: January 2008

Objective

To determine whether shared epitope (SE)–containing HLA–DRB1 alleles are associated with rheumatoid arthritis (RA) in African Americans and whether their presence is associated with higher degrees of global (genome‐wide) genetic admixture from the European population.

Methods

In this multicenter cohort study, African Americans with early RA and matched control subjects were analyzed. In addition to measurement of serum anti–cyclic citrullinated peptide (anti‐CCP) antibodies and HLA–DRB1 genotyping, a panel of >1,200 ancestry‐informative markers was analyzed in patients with RA and control subjects, to estimate the proportion of European ancestry.

Results

The frequency of SE‐containing HLA–DRB1 alleles was 25.2% in African American patients with RA versus 13.6% in control subjects (P = 0.00005). Of 321 patients with RA, 42.1% had at least 1 SE‐containing allele, compared with 25.3% of 166 control subjects (P = 0.0004). The mean estimated percent European ancestry was associated with SE‐containing HLA–DRB1 alleles in African Americans, regardless of disease status (RA or control). As reported in RA patients of European ancestry, there was a significant association of the SE with the presence of the anti‐CCP antibody: 86 (48.9%) of 176 patients with anti‐CCP antibody–positive RA had at least 1 SE allele, compared with 36 (32.7%) of 110 patients with anti‐CCP antibody–negative RA (P = 0.01, by chi‐square test).

Conclusion

HLA–DRB1 alleles containing the SE are strongly associated with susceptibility to RA in African Americans. The absolute contribution is less than that reported in RA among populations of European ancestry, in which ∼50–70% of patients have at least 1 SE allele. As in Europeans with RA, the SE association was strongest in the subset of African American patients with anti‐CCP antibodies. The finding of a higher degree of European ancestry among African Americans with SE alleles suggests that a genetic risk factor for RA was introduced into the African American population through admixture, thus making these individuals more susceptible to subsequent environmental or unknown factors that trigger the disease.
Serum type I interferon activity is dependent on maternal diagnosis in anti‐SSA/Ro–positive mothers of children with neonatal lupus
Authors: Niewold Timothy B. , Rivera Tania L. , Buyon Jill P. , Crow Mary K.
Published: January 2008

Objective

The type I interferon (IFN) pathway is activated in many patients with systemic lupus erythematosus (SLE), and high serum levels of IFN are associated with anti‐SSA/Ro autoantibodies. To investigate the clinical features associated with type I IFN production in vivo, we compared serum IFN activity in individuals with anti‐SSA/Ro antibodies who were asymptomatic with that in individuals with clinical manifestations of SLE or Sjögren's syndrome (SS).

Methods

Antibody‐positive sera from 84 mothers of children with manifestations of neonatal lupus were studied for type I IFN activity, using a functional reporter cell assay. Maternal health status was characterized as asymptomatic, SS, SLE, pauci‐SLE, or pauci‐SS, based on a screening questionnaire, telephone interview, and review of medical records. The prefix “pauci‐” indicates symptoms insufficient for a formal classification of the disease.

Results

Only 4% of asymptomatic mothers had high serum type I IFN activity, compared with 73% with pauci‐SLE (P = 5.7 × 10−5), 35% with SLE (P = 0.011), and 32% of patients with SS (P = 0.032). One of the 4 patients with pauci‐SS had high levels of IFN. The majority of patients for whom longitudinal data were available had stable type I IFN activity over time, and changes in IFN activity were not clearly accompanied by changes in the clinical diagnosis.

Conclusion

Patients with SLE, patients with pauci‐SLE, and patients with SS are more likely to have high serum IFN activity than asymptomatic individuals with SSA/Ro autoantibodies, suggesting that these autoantibodies are insufficient for activation of the type I IFN pathway, and that disease‐specific factors are important for type I IFN generation in vivo.
Treatment of Churg‐Strauss syndrome without poor‐prognosis factors: A multicenter, prospective, randomized, open‐label study of seventy‐two patients
Authors: Ribi Camillo , Cohen Pascal , Pagnoux Christian , Mahr Alfred , Arène Jean‐Pierre , Lauque Dominique , Puéchal Xavier , Letellier Philippe , Delaval Philippe , Cordier Jean‐François , Guillevin Loïc
Published: January 2008

Objective

To assess the efficacy of systemic corticosteroids (CS) alone as first‐line treatment in patients with Churg‐Strauss syndrome (CSS) without poor‐prognosis factors, as defined by the Five‐Factors Score (FFS), and to compare the efficacy and safety of oral azathioprine (AZA) versus intravenous pulse cyclophosphamide (CYC) as adjuvant immunosuppressive therapy for treatment failure or relapse.

Methods

This multicenter, prospective, randomized, open‐label therapeutic trial included 72 patients with newly diagnosed CSS (FFS of 0) treated with CS alone. At treatment failure or relapse, patients were randomized to receive 6 months of oral AZA or 6 pulses of CYC. Analyses were performed according to an intent‐to‐treat strategy.

Results

The mean ± SD followup was 56.2 ± 31.7 months. Among the 72 patients studied, 93% achieved remission with CS therapy alone, and 35% relapsed, mainly during the first year of treatment. Among the 19 patients randomized to additional immunosuppression because of treatment failure or relapse, 5 of 10 receiving AZA and 7 of 9 receiving pulse CYC achieved remission, but the difference was not statistically significant. Survival rates in all patients at 1 and 5 years were 100% and 97%, respectively. At the end of followup, 79% of the patients whose disease was in remission required low‐dose CS therapy, mainly to control respiratory disease. CS‐related adverse events were observed in 31% of the 72 patients.

Conclusion

In CSS patients with an FFS of 0, survival was excellent, confirming the predictive value of the FFS in this disease. First‐line therapy with CS achieved remission in most patients, but relapses were common, and one‐third of them required additional immunosuppressive therapy. AZA or pulse CYC was fairly effective in treating CS‐resistant disease or major relapses. Over the long term, most patients continued to take oral CS, which might explain the high rate of CS‐related adverse events.
Antiinflammatory role of endomorphins in osteoarthritis, rheumatoid arthritis, and adjuvant‐induced polyarthritis
Authors: Straub Rainer H. , Wolff Christine , Fassold Alexander , Hofbauer Rafael , Chover‐Gonzalez Antonio , Richards Louise J. , Jessop David S.
Published: January 2008

Objective

Pain sensitization and the related secretion of neuropeptides from sensory nerve terminals are proinflammatory in osteoarthritis (OA), rheumatoid arthritis (RA), and adjuvant‐induced polyarthritis. In contrast, endogenous opioids such as the recently discovered endomorphins (EMs) are antiinflammatory. However, the role of endogenous EMs such as EM‐1 and EM‐2 has never been investigated in OA and RA.

Methods

We established a highly sensitive radioimmunoassay to detect EM‐1 and EM‐2. In patients with RA and patients with OA, immunohistochemistry for EM‐1 and EM‐2 was performed, and double‐staining was used to identify EM‐positive cells. The effects of EM‐1 and EM‐2 on the secretion of interleukin‐6 (IL‐6) and IL‐8 from human synovial tissue were studied by tissue superfusion, and the therapeutic effects of EM‐1 were tested in a rat model of adjuvant‐induced polyarthritis.

Results

EM‐positive cells were located in the sublining area and vessel walls but were particularly evident in the highly inflamed lining area. Human macrophages, T cells, and fibroblasts stained positive for EMs. The synovial density of EM‐positive cells was higher in patients with OA than in those with RA. EM‐1 inhibited synovial secretion of IL‐6 in patients with RA and secretion of IL‐8 in patients with RA and those with OA (maximum 10−10M). EM‐2 inhibited IL‐8 secretion only from RA tissue (maximum 10−10M). In rats with adjuvant‐induced polyarthritis, thymus, spleen, and synovial tissue contained significantly more EM‐1 than was observed in controls. Rats with adjuvant‐induced polyarthritis benefited from EM‐1 treatment.

Conclusion

EM‐1 had antiinflammatory effects in patients with OA or RA and in a model of adjuvant‐induced polyarthritis. Local enhancement of EM‐1 might be an interesting therapeutic option in different forms of arthritis.
Relapse of hepatitis C virus–associated mixed cryoglobulinemia vasculitis in patients with sustained viral response
Authors: Landau Dan‐Avi , Saadoun David , Halfon Philippe , Martinot‐Peignoux Michelle , Marcellin Patrick , Fois Elena , Cacoub Patrice
Published: January 2008

Objective

To investigate the clinical characteristics, outcomes, and results of hepatitis C virus (HCV) RNA analyses in a group of patients with HCV‐associated mixed cryoglobulinemia (MC) vasculitis who experienced a relapse of vasculitis despite achieving a sustained viral response to treatment with antiviral agents.

Methods

HCV RNA testing was performed by the transcription‐mediated amplification (TMA) method in sera and cryoprecipitates (detection limit 2.5 IU/ml). HCV replication was assessed in peripheral blood mononuclear cells (PBMCs) by a modified real‐time polymerase chain reaction assay (detection limit 15 IU/106 cells).

Results

We identified 8 patients with relapse of HCV‐MC vasculitis despite their having achieved a sustained viral response to treatment. Relapse appeared early after the end of treatment (mean ± SD 2.5 ± 3.5 months) and included mainly purpura (n = 7) and arthralgia (n = 5). Relapse was associated with an increase in serum cryoglobulin levels as compared with end‐of‐treatment levels (mean ± SD 0.3 ± 0.09 gm/liter and 0.08 ± 0.04 gm/liter, respectively; P < 0.01) and a decrease in C4 levels. In most patients, the relapse was brief, and the MC vasculitis manifestations subsided. A search for HCV RNA by TMA was negative in all patients tested (7 of 8 patients), both in sera and in cryoprecipitates. HCV replication was not found in PBMCs from any of the patients tested (6 of 8 patients). In 3 patients, the MC vasculitis symptoms persisted and were associated with elevated cryoglobulin levels. B cell lymphoma was diagnosed in 2 of these 3 patients.

Conclusion

Relapse of MC vasculitis does occur in a few patients with HCV infection, despite achieving a sustained viral response, and this relapse is not related to persistence of virus. Relapse is short‐lived and may be induced by the withdrawal of interferon alfa therapy. However, in patients with persistent MC vasculitis symptoms, a different underlying condition should be considered, especially B cell lymphoma.
Cost‐effectiveness of intensive exercise therapy directly following hospital discharge in patients with arthritis: Results of a randomized controlled clinical trial
Authors: Bulthuis Yvette , Mohammad Sabrina , Braakman‐Jansen Louise M. A. , Drossaers‐Bakker K. Wiepke , van de Laar Martin A. F. J.
Published: January 2008

Objective

To estimate the cost‐utility and cost‐effectiveness of a 3‐week intensive exercise training (IET) program directly following hospital discharge in patients with rheumatic diseases.

Methods

Patients with arthritis who were admitted to the hospital because of a disease activity flare or for elective hip or knee arthroplasty were randomly assigned to either the IET group or usual care (UC) group. Followup lasted 1 year. Quality‐adjusted life years (QALYs) were derived from Short Form 6D scores and a visual analog scale (VAS) rating personal health. Function‐related outcome was measured using the Health Assessment Questionnaire, the McMaster Toronto Arthritis (MACTAR) Patient Preference Disability Questionnaire, and the Escola Paulista de Medicina Range of Motion scale (EPMROM). Costs were reported from a societal perspective. Differences in costs and incremental cost‐effectiveness ratios (ICERs) were estimated.

Results

Data from 85 patients (50 IET and 35 UC) could be used for health‐economic analysis. VAS personal health–based QALYs were in favor of IET. Function‐related outcome showed statistically significant improvements in favor of IET over the first 6 months, according to the MACTAR (P < 0.05) and the EPMROM (P < 0.01). At 1‐year followup, IET was €718 less per patient. The ICER showed a reduction in mean total costs per QALY. In 70% of cases the intervention was cost‐saving.

Conclusion

IET results in better quality of life at lower costs after 1 year. Thus, IET is the dominant strategy compared with UC. This highlights the need for implementation of IET after hospital discharge in patients with arthritis.
The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: Results from a longitudinal, observational, multicenter study
Authors: Heiberg Marte Schrumpf , Koldingsnes Wenche , Mikkelsen Knut , Rødevand Erik , Kaufmann Cecilie , Mowinckel Petter , Kvien Tore K.
Published: January 2008

Objective

To compare the 1‐year retention rates of anti–tumor necrosis factor α (anti‐TNFα) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status.

Methods

Our analyses comprised 847, 172, and 249 anti‐TNFα treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigator's global assessment, and concomitant methotrexate (MTX). Adjusted changes in health‐related quality of life (HRQOL) were compared among the groups.

Results

Unadjusted 1‐year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53–1.07) for PsA versus RA and 0.66 (95% CI 0.47–0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA.

Conclusion

Our results suggest that survival of anti‐TNFα treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.
A followup study of antiphospholipid antibodies and associated neuropsychiatric manifestations in 137 children with systemic lupus erythematosus
Authors: Avčin Tadej , Benseler Susanne M. , Tyrrell Pascal N. , Čučnik Saša , Silverman Earl D.
Published: January 2008

Objective

To determine the prevalence of anticardiolipin antibodies (aCL), anti–β2‐glycoprotein I (anti‐β2GPI) antibodies, and lupus anticoagulant (LAC) in a large cohort of children with systemic lupus erythematosus (SLE), and to evaluate the associations with neuropsychiatric manifestations.

Methods

A single‐center retrospective cohort study with longitudinal followup of antiphospholipid antibodies (aPL) in 137 children with SLE (25 boys and 112 girls, mean age at diagnosis 13.0 years) was performed. Patients were followed up for a mean of 31 months.

Results

At the time of diagnosis, 65% of the children were aCL positive, 41% had anti‐β2GPI antibodies, and 26% were LAC positive. Analysis of the association between presence of aPL and individual neuropsychiatric manifestations at diagnosis showed a statistically significant association of positive LAC with cerebrovascular disease (5 patients; P = 0.015). A persistently positive aCL was observed in 50%, anti‐β2GPI antibodies in 29%, and LAC in 16% of children over time. The prevalence of anti‐β2GPI antibodies, but not aCL and LAC, was found to be statistically significantly higher in children with neuropsychiatric disease compared with those without (P = 0.02). Comparison for specific neuropsychiatric manifestations showed a statistically significant association between a persistently positive LAC and chorea (2 patients; P = 0.02).

Conclusion

The prevalence of anti‐β2GPI antibodies was found to be higher in the group of SLE patients with neuropsychiatric disease compared with those without. Our data suggest an association between LAC and cerebrovascular disease at the time of SLE diagnosis and chorea over the disease course, but not between aPL and other neuropsychiatric manifestations.
The prevalence of foot ulceration in patients with rheumatoid arthritis
Authors: Firth Jill , Hale Claire , Helliwell Philip , Hill Jackie , Nelson E. Andrea
Published: January 2008

Objective

To establish the prevalence of foot ulceration in patients with rheumatoid arthritis (RA) in secondary care.

Methods

A postal survey of all patients with RA (n = 1,130) under the care of rheumatologists in Bradford, West Yorkshire, UK was performed. The prevalence data were validated through clinical examination, case‐note review, and contact with health professionals. The false‐negative rate was investigated in a subsample of patients (n = 70) who denied any history of ulceration.

Results

The postal survey achieved a 78% response rate. Following validation, the point prevalence of foot ulceration was 3.39% and the overall prevalence was 9.73%. The false‐positive rate was initially high at 21.21%, but use of diagrammatic questionnaire data to exclude leg ulceration reduced the rate to 10.76%. The false‐negative rate was 11.76%. The most common sites for ulceration were the dorsal aspect of hammer toes, the metatarsal heads, and the metatarsophalangeal joint in patients with hallux abducto valgus, with 33% of patients reporting multiple sites of ulceration. Patients with open‐foot and healed‐foot ulceration had significantly longer RA disease duration, reported significantly greater use of special footwear, and had a higher prevalence of foot surgery than ulcer‐free patients.

Conclusion

Foot ulceration affects a significant proportion of patients with RA. Further work is needed to establish risk factors for foot ulceration in RA and to target foot health provision more effectively.
Clinical correlates of quality of life in systemic sclerosis measured with the World Health Organization Disability Assessment Schedule II
Authors: Hudson Marie , Thombs Brett D. , Steele Russell , Watterson Rita , Taillefer Suzanne , Baron Murray ,   Canadian Scleroderma Research Group
Published: January 2008

Objective

To identify the clinical characteristics of systemic sclerosis (SSc) that best correlate with the health‐related quality of life (HRQOL) of patients with SSc, using the World Health Organization Disability Assessment Schedule II (WHODAS II) as the measure of HRQOL.

Methods

A cross‐sectional, multicenter study of 337 patients from the Canadian Scleroderma Research Group Registry was conducted. Patients were assessed through detailed clinical histories, medical examination, and the WHODAS II. Hierarchical multiple linear regression was used to assess the relationship between selected clinical variables and HRQOL.

Results

The mean WHODAS II score was 23.7 (range 0–100), with the greatest impairments seen in the subscales measuring life activities, mobility, and participation in society. In multivariate analysis, significant predictors of the WHODAS II were skin scores, shortness of breath, number of gastrointestinal problems, fatigue, pain, and depression. The final model explained 61% of the variance in the WHODAS II scores.

Conclusion

The clinical characteristics identified in this study as significant correlates of HRQOL in SSc should each be targets of intervention in order to improve the HRQOL of patients with this disease.
Communication about depression during rheumatoid arthritis patient visits
Authors: Sleath Betsy , Chewning Betty , de Vellis Brenda M. , Weinberger Morris , de Vellis Robert F. , Tudor Gail , Beard Ashley
Published: January 2008

Objective

To examine whether rheumatologists and rheumatoid arthritis (RA) patients with depressive symptoms communicate about depression.

Methods

The data used in this study came from a randomized controlled trial to improve provider‐patient communication about patients' agendas. The current secondary analysis used data collected at baseline, before any intervention occurred. A total of 200 RA patients from 4 rheumatology clinics participated in the study. Patient medical visits were audiotape recorded and patients were interviewed after their medical visits. Physicians recorded patients' American College of Rheumatology (ACR) functional status after their visits.

Results

Twenty‐one (11%) patients were scored as having moderately severe to severe symptoms of depression. Patients who were rated by their physicians as having worse ACR functional status were more than twice as likely to have moderately severe to severe symptoms of depression (odds ratio 2.23, 95% confidence interval 1.1–4.6). Only 4 (19%) of the 21 patients who were scored as having moderately severe to severe symptoms of depression discussed depression during their medical visits, and patients initiated the discussion each time.

Conclusion

Rheumatologists should consider assessing depressive symptoms among their patients, especially among those with worse functional status.
Online presentations as a source of scientific impact? An analysis of PowerPoint files citing academic journals
Authors: Thelwall Mike , Kousha Kayvan
Published: January 2008

Open‐access online publication has made available an increasingly wide range of document types for scientometric analysis. In this article, we focus on citations in online presentations, seeking evidence of their value as nontraditional indicators of research impact. For this purpose, we searched for online PowerPoint files mentioning any one of 1,807 ISI‐indexed journals in ten science and ten social science disciplines. We also manually classified 1,378 online PowerPoint citations to journals in eight additional science and social science disciplines. The results showed that very few journals were cited frequently enough in online PowerPoint files to make impact assessment worthwhile, with the main exceptions being popular magazines likeScientific AmericanandHarvard Business Review. Surprisingly, however, there was little difference overall in the number of PowerPoint citations to science and to the social sciences, and also in the proportion representing traditional impact (about 60%) and wider impact (about 15%). It seems that the main scientometric value for online presentations may be in tracking the popularization of research, or for comparing the impact of whole journals rather than individual articles.
Are there better indices for evaluation purposes than the h index? A comparison of nine different variants of the h index using data from biomedicine
Authors: Bornmann Lutz , Mutz Rüdiger , Daniel Hans‐Dieter
Published: February 2008

In this study, we examined empirical results on the h index and its most important variants in order to determine whether the variants developed are associated with an incremental contribution for evaluation purposes. The results of a factor analysis using bibliographic data on postdoctoral researchers in biomedicine indicate that regarding the h index and its variants, we are dealing with two types of indices that load on one factor each. One type describes the most productive core of a scientist's output and gives the number of papers in that core. The other type of indices describes the impact of the papers in the core. Because an index for evaluative purposes is a useful yardstick for comparison among scientists if the index corresponds strongly with peer assessments, we calculated a logistic regression analysis with the two factors resulting from the factor analysis as independent variables and peer assessment of the postdoctoral researchers as the dependent variable. The results of the regression analysis show that peer assessments can be predicted better using the factor ‘impact of the productive core’ than using the factor ‘quantity of the productive core.’
Pharmacokinetics of antofloxacin hydrochloride, a new fluoroquinolone antibiotic, after single oral dose administration in Chinese healthy male volunteers
Authors: Xiao Yonghong , Lu Yuan , Kang Zisheng , Zhang Ming , Liu Yan , Zhang Man , Li Tianyun
Published: January 2008

Antofloxacin hydrochloride is a newly developed fluoroquinolone antibacterial in China, which has comparable in vitro and animal pharmacological and toxicological properties to levofloxacin and is worthy of further clinical trial. Human tolerance of single escalating doses from 50 to 500 mg was shown to be safe. The purpose of the present study was to evaluate the pharmacokinetic characteristics of a single oral dose of antofloxacin hydrochloride in Chinese healthy male volunteers. Twelve subjects were randomized for administration of a single dose of 300, 400 and 500 mg antofloxacin hydrochloride in a 3‐way crossover design. High pressure liquid chromatography (HPLC) was used to assay the serum and urine concentrations of antofloxacin in samples collected over a period of 72 h following drug administration. All three dosages were well tolerated. Antofloxacin hydrochloride demonstrated linear pharmacokinetic characteristics with mean pharmacokinetic values varying from 0.09 to 0.10 l/h/kg for CL/F and from 2.75–3.00 l/kg for V/F. The t1/2β was around 20 h and the mean fraction of dose excreted in urine varied from 0.40 to 0.46. Based on these data, 300 mg of antofloxacin hydrochloride administered once daily was selected for further investigation in a multiple dose administration study. Copyright © 2008 John Wiley & Sons, Ltd.
Fetal alcohol syndrome (FAS) in C57BL/6 mice detected through proteomics screening of the amniotic fluid
Authors: Datta Susmita , Turner Delano , Singh Reetu , Ruest L. Bruno , Pierce William M. , Knudsen Thomas B.
Published: January 2008

BACKGROUND:

Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol‐induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high‐risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low‐risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS‐positive and FAS‐negative pregnancies.

METHODS:

B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix‐assisted laser desorption–time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods.

RESULTS:

We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS‐positive litters was confirmed by area under the receiver operating characteristic curve.

CONCLUSIONS:

These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.
No effect of mobile phone‐like RF exposure on patients with atopic dermatitis
Authors: Johansson Amanda , Forsgren Sture , Stenberg Berndt , Wilén Jonna , Kalezic Nebojsa , Sandström Monica
Published: January 2008

This study investigates the effect of exposure to a mobile phone‐like radiofrequency (RF) electromagnetic field on people with atopic dermatitis (AD). Fifteen subjects with AD were recruited and matched with 15 controls without AD. The subjects were exposed for 30 min to an RF field at 1 W/kg via an indoor base station antenna attached to a 900 MHz GSM mobile phone. Blood samples for ELISA analysis of the concentration of substance P (SP), tumor necrosis factor receptor 1 (TNF R1), and brain derived neurotrophic factor (BDNF) in serum were drawn before and after the provocation (exposure/sham). Baseline heart rate and heart rate variability, local blood flow, and electrodermal activity were also recorded. No significant differences between the subject groups were found for baseline neurophysiological data. The cases displayed a serum concentration of TNF R1 significantly higher than the control subjects and a significantly lower serum concentration of BDNF in the baseline condition. For SP there was no difference between groups. However, no effects related to RF exposure condition were encountered for any of the measured substances. As to symptoms, a possible correlation with exposure could not be evaluated, due to too few symptom reports. The result of the study does not support the hypothesis of an effect of mobile phone‐like RF exposure on serum levels of SP, TNF R1, and BDNF in persons with AD. Bioelectromagnetics 29:353–362, 2008. © 2008 Wiley‐Liss, Inc.
Letter to the editor
Authors: Kocabiyik Necdet , Yalcın Bulent , Candlır Nesrin , Ozan Hasan
Published: January 2008

The article to which this Erratum refers was published in Clinical Anatomy 20:709.

In the published version of this article online, Dr. Yalcın's name was transposed. Please find his name given correctly here as Bülent Yalcın. The Publisher regrets this error.
New Redesigned Zinc‐Finger Proteins: Design Strategy and Its Application
Authors: Negi Shigeru , Imanishi Miki , Matsumoto Makoto , Sugiura Yukio
Published: January 2008

The design of DNA‐binding proteins for the specific control of the gene expression is one of the big challenges for several research laboratories in the post‐genomic era. An artificial transcription factor with the desired DNA binding specificity could work as a powerful tool and drug to regulate the target gene. The zinc‐finger proteins, which typically contain many fingers linked in a tandem fashion, are some of the most intensively studied DNA‐binding proteins. In particular, the Cys2His2‐type zinc finger is one of the most common DNA‐binding motifs in eukaryotes. A simple mode of DNA recognition by the Cys2His2‐type zinc‐finger domain provides an ideal framework for designing proteins with new functions. Our laboratory has utilized several design strategies to create new zinc‐finger peptides/proteins by redesigning the Cys2His2‐type zinc‐finger motif. This review focuses on the aspects of design strategies, mainly from our recent results, for the creation of artificial zinc‐finger proteins, and discusses the possible application of zinc‐finger technology for gene regulation and gene therapy.
Total Synthesis of (+)‐Alexine by Utilizing a Highly Stereoselective [3+2] Annulation Reaction of an N‐Tosyl‐α‐Amino Aldehyde and a 1,3‐Bis(silyl)propene
Authors: Dressel Martina , Restorp Per , Somfai Peter
Published: January 2008

A novel route towards the polyhydroxylated pyrrolizidine alkaloid (+)‐alexine has been developed. A key step in this synthesis is a highly stereoselective [3+2] annulation reaction of N‐Ts‐α‐amino aldehyde 7 a (Ts=tosyl) and 1,3‐bis(silyl)propene 8 a for the construction of the polyhydroxylated pyrrolidine subunit of the target molecule. Previous synthetic strategies rely on carbohydrates that require several protecting‐group manipulations, thereby making the total number of steps relatively high. The [3+2] annulation strategy compares favorably with carbohydrate‐based syntheses and constitutes a highly efficient entry to polyhydroxylated alkaloids.
ChemInform Abstract: Theoretical Studies on Structures of Neptunyl Carbonates: NpO2(CO3)m (H2O)nq‐ (m = 1—3, n = 0—3) in Aqueous Solution
Authors: Balasubramanian K. , Cao Zhiji
Published: January 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Rare‐Earth Site Splitting in Sm3MoO7.
Authors: Barrier N. , Gall P. , Gougeon P.
Published: January 2008

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.