bluuebunny/crossref_metadata_2025 huggingface dataset:
PROGRESS IN UREMIC TOXIN RESEARCH: Highlights and Hotspots of Protein Glycation in End‐Stage Renal Disease
Authors: Thornalley Paul J. , Rabbani Naila
Published: August 2009

Analysis of tissues, plasma, urine, other body fluids, and dialysate for glycation adducts has revealed the presence of two major forms: glycation adduct residues of proteins and related glycated amino acids—called glycation free adducts. The major effect on protein glycation in uremia is loss of clearance of glycation free adducts and their marked increase in plasma. Changes in glycation adduct residue content of plasma protein in uremia is, in contrast, relatively modest. There is now doubt as to whether the concept of interaction of advanced glycation endproduct (AGE)‐modified proteins with putative AGE receptors can be sustained in vivo. A residual important feature of the receptor for AGEs may be decrease in expression of glyoxalase 1 of the antiglycation defence by S100A12 protein leaving the vasculature vulnerable to dicarbonyl stress and related AGE formation. The dicarbonyl proteome, proteins susceptible to dicarbonyl glycation at functional sites, is the likely mediator of glycation damage in uremia. Glycation of type IV collagen with shedding of endothelial cells and glycation of apolipoprotein B100 with increased atherogenicity of low density lipoprotein are two examples which may link protein glycation to increased risk of cardiovascular disease in end‐stage renal disease.
TRANSCRIPTOMIC ANALYSIS OF GRACILARIA CHANGII (RHODOPHYTA) IN RESPONSE TO HYPER‐ AND HYPOOSMOTIC STRESSES1
Authors: Teo Swee‐Sen , Ho Chai‐Ling , Teoh Seddon , Rahim Raha Abdul , Phang Siew‐Moi
Published: August 2009

Osmotic stress is one of the most significant natural abiotic stresses that occur in the intertidal zones. Seaweeds may physiologically acclimate to changing osmolarity by altering their transcriptome. Here, we investigated the transcriptomic changes of Gracilaria changii (B. M. Xia et I. A. Abbott) I. A. Abbott, J. Zhang et B. M. Xia in response to hyper‐ and hypoosmotic stresses using a cDNA microarray approach. Microarray analysis revealed that 199 and 200 genes from ∼3,300 genes examined were up‐ and down‐regulated by >2‐fold in seaweed samples treated at 50 parts per thousand (ppt) artificial seawater (ASW) compared with those at 30 ppt ASW, respectively. The number of genes that were up‐ and down‐regulated by >2‐fold in seaweed samples treated at 10 ppt ASW compared with those at 30 ppt ASW were 154 and 187, respectively. A majority of these genes were only differentially expressed under hyper‐ or hypoosmotic conditions, whereas 67 transcripts were affected by both stresses. The findings of this study have shed light on the expression profiles of many transcripts during the acclimation of G. changii to hyperosmotic and hypoosmotic conditions. This information may assist in the prioritization of genes to be examined in future studies.
NO MECHANISTIC DEPENDENCE OF PHOTOSYNTHESIS ON CALCIFICATION IN THE COCCOLITHOPHORID EMILIANIA HUXLEYI (HAPTOPHYTA)1
Authors: Leonardos Nikos , Read Betsy , Thake Brenda , Young Jeremy R.
Published: August 2009

There is still considerable uncertainty about the relationship between calcification and photosynthesis. It has been suggested that since calcification in coccolithophorids is an intracellular process that releases CO2, it enhances photosynthesis in a manner analogous to a carbon‐concentrating mechanism (CCM). The ubiquitous, bloom‐forming, and numerically abundant coccolithophorid Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler was studied in nutrient‐replete, pH and [CO2] controlled, continuous cultures (turbidostats) under a range of [Ca2+] from 0 to 9 mM. We examined the long‐term, fully acclimated photosynthesis‐light responses and analyzed the crystalline structure of the coccoliths using SEM. The E. huxleyi cells completely lost their coccosphere when grown in 0 [Ca2+], while thin, undercalcified and brittle coccoliths were evident at 1 mM [Ca2+]. Coccoliths showed increasing levels of calcification with increasing [Ca2+]. More robust coccoliths were noted, with no discernable differences in coccolith morphology when the cells were grown in either 5 or 9 mM (ambient seawater) [Ca2+]. In contrast to calcification, photosynthesis was not affected by the [Ca2+] in the media. Cells showed no correlation of their light‐dependent O2 evolution with [Ca2+], and in all [Ca2+]‐containing turbidostats, there were no significant differences in growth rate. The results show unequivocally that as a process, photosynthesis in E. huxleyi is mechanistically independent from calcification.
ELLIPTOCHLORIS MARINA SP. NOV. (TREBOUXIOPHYCEAE, CHLOROPHYTA), SYMBIOTIC GREEN ALGA OF THE TEMPERATE PACIFIC SEA ANEMONES ANTHOPLEURA XANTHOGRAMMICA AND A. ELEGANTISSIMA (ANTHOZOA, CNIDARIA)1
Authors: Letsch Molly R. , Muller‐Parker Gisèle , Friedl Thomas , Lewis Louise A.
Published: August 2009

Symbiotic green algae from two species of intertidal Pacific sea anemones, Anthopleura elegantissima and Anthopleura xanthogrammica, were collected from the northeastern Pacific coast of North America across the known range of the symbiont. Freshly isolated Anthopleura symbionts were used for both morphological and molecular analyses because Anthopleura symbiont cultures were not available. Light and transmission electron microscopy supported previous morphological studies, showing the symbionts consist of spherical unicells from 5 to 10 μm in diameter, with numerous vesicles, and a single bilobed chloroplast. Pyrenoids were not seen in LM, but a thylakoid‐free area was observed in TEM, consistent with previous findings. Many algal cells extracted from fresh anemone tissue were observed in the process of division, producing two autospores within a maternal cell wall. The morphology of the green symbionts matches that of Elliptochloris Tscherm.‐Woess. Molecular phylogenetic analyses of the nuclear SSU rDNA and the plastid encoded gene for the large subunit of RUBISCO (rbcL) support the monophyly of these green algal symbionts, regardless of host species and geographic origin. Phylogenetically, sequences of the Anthopleura symbionts are nested within the genus Elliptochloris and are distinct from sequences of all other Elliptochloris spp. examined. Given the ecological and phylogenetic distinctions among the green algal symbionts in Anthopleura spp. and the named species of Elliptochloris, we designate the green algal symbionts as a new species, Elliptochloris marina (Trebouxiophyceae, Chlorophyta).
Physical Activity and Executive Function in Aging: The MOBILIZE Boston Study
Authors: Eggermont Laura H. P. , Milberg William P. , Lipsitz Lewis A. , Scherder Erik J. A. , Leveille Suzanne G.
Published: August 2009

OBJECTIVES: To determine the relationship between physical activity and cognition, specifically executive function, and the possible mediating role of factors such as cardiovascular disease (CVD) and CVD risk factors, chronic pain, and depressive symptoms.

DESIGN: Cross‐sectional study.

SETTING: Population‐based study of individuals aged 70 and older in the Boston area.

PARTICIPANTS: Older community‐dwelling adults (n=544; mean age 78, 62% female).

MEASUREMENTS:

Presence of heart disease (self‐reported physician diagnosed), pain, and depressive symptomatology were assessed using interviewer‐administered questions. Blood pressure was measured. Engagement in physical activity was determined using the Physical Activity Scale for the Elderly (PASE). Cognitive function was measured using a battery of neuropsychological tests.

RESULTS: The older adults who engaged in more physical activity had significantly better performance on all cognitive tests, except for Letter Fluency and the memory test of delayed recall, after adjusting for age, sex, education, and total number of medications. With further adjustment for CVD and CVD risk factors (heart disease, diabetes mellitus, stroke, and hypertension), pain, and depressive symptoms, PASE score remained significantly associated with executive function tests.

CONCLUSION: Even after multivariate adjustment, neuropsychological tests that were executive in nature were positively associated with physical activity participation in this cohort of older community‐dwelling adults. In contrast, delayed recall of episodic memory was not associated with physical activity, supporting the idea that the relationship with executive function represents a specific biologically determined relationship.
The Effect of a High‐Intensity Functional Exercise Program on Activities of Daily Living: A Randomized Controlled Trial in Residential Care Facilities
Authors: Littbrand Håkan , Lundin‐Olsson Lillemor , Gustafson Yngve , Rosendahl Erik
Published: August 2009

OBJECTIVES: To evaluate whether a high‐intensity functional weight‐bearing exercise program reduces dependency in activities of daily living (ADLs) in older people living in residential care facilities, focusing on people with dementia.

DESIGN: Randomized, controlled trial.

SETTING: Nine residential care facilities.

PARTICIPANTS: One hundred ninety‐one older people dependent in ADLs and with a Mini‐Mental State Examination score of 10 or greater. One hundred (52.4%) of the participants had dementia.

INTERVENTION: A high‐intensity functional weight‐bearing exercise program or a control activity consisting of 29 sessions over 3 months.

MEASUREMENTS: The Barthel ADL Index; follow‐up at 3 months (directly after the intervention) and 6 months with intention‐to‐treat analyses.

RESULTS: There were no statistically significant differences between the groups regarding overall ADL performance. Analyses for each item revealed that a smaller proportion of participants in the exercise group had deteriorated in indoor mobility at 3 months (exercise 3.5% vs control 16.0%, P=.01) and 6 months (7.7% vs 19.8%, P=.03). For people with dementia, there was a significant difference in overall ADL performance in favor of the exercise group at 3 months (mean difference 1.1, P=.03) but not at 6 months.

CONCLUSION: A high‐intensity functional weight‐bearing exercise program seems to reduce ADL decline related to indoor mobility for older people living in residential care facilities. The program does not appear to have an overall effect on ADLs. In people with dementia, the exercise program may prevent decline in overall ADL performance, but continuous training may be needed to maintain that effect.
Bedrail Use in English and Welsh Hospitals
Authors: Healey Frances M. , Cronberg Alexandra , Oliver David
Published: August 2009

OBJECTIVES: To explore rates of bedrail use, nurses' rationale, and factors related to bedrail use.

DESIGN: An overnight observational study of patient and equipment characteristics related to bedrail use, analyzed using a logistic regression model.

SETTING: A stratified random sample of seven organizations, drawn from 167 organizations providing acute general hospital care in England and Wales during 2006.

PARTICIPANTS: One thousand ninety‐two inpatients on adult inpatient wards observed at night.

MEASUREMENTS: Categorical data on bedrail use related to bed type, mattress type, patient age, nurses' description of patients' mobility and confusion, and nurses' rationale for bedrail use or nonuse.

RESULTS: Approximately one‐quarter of patients had full bedrails raised at night; prevention of falls was the nurses' main rationale. Full bedrail use was much more likely to occur in patients who nurses described as immobile and very or slightly confused. Older patients appeared no more likely to be given bedrails than younger patients after adjusting for individual patient and equipment factors.

CONCLUSION: Bedrail use varied significantly between organizations and could not be explained by differences in nurses' description of patients' mobility and confusion levels, equipment, or policy.
Palliative Access Through Care at Home: Experiences with an Urban, Geriatric Home Palliative Care Program
Authors: Holley Abigail P. H. , Gorawara‐Bhat Rita , Dale William , Hemmerich Joshua , Cox‐Hayley Deon
Published: August 2009

The aging of the U.S. population has resulted in a large number of persons with multiple, chronic illnesses and gradual functional decline. Many older adults with these conditions are homebound and have great difficulty accessing medical care. They are also more likely to suffer from unaddressed symptoms and end‐of‐life care needs. Certain groups, such as African‐American patients and patients with dementia, are even less likely to access palliative care and hospice services. Although the informal caregivers attending to such persons may become overwhelmed without adequate support, palliative care, which covers a broad population, is an optimal way to address many of these needs. This article describes a unique, urban, home‐based geriatrics palliative care program (Palliative Access Through Care at Home (PATCH)) designed to address some of these unmet needs. After 1 year of providing service, a mixed‐methods study consisting of chart review, telephone interviews, and face‐to‐face interviews was conducted to assess caregiver expectations of and satisfaction with the program. Caregivers for the elderly, mostly African‐American patients, more than half of whom had dementia, were overall very satisfied with their experience, despite the large amount of time necessary to provide the care that patients required. Themes extracted during qualitative analysis were the desire to remain at home, the need for easy access to a practitioner specializing in geriatrics and palliative medicine, and the challenges of transitions of care. PATCH was able to address many of these needs and provide high levels of caregiver satisfaction.
Nursing Home Residents and Enrollment in Medicare Part D
Authors: Briesacher Becky A. , Soumerai Stephen B. , Field Terry S. , Fouayzi Hassan , Gurwitz Jerry H.
Published: August 2009

OBJECTIVES: To assess the impact of Medicare Part D in the nursing home (NH) setting.

DESIGN: A population‐based study using 2005/06 prescription dispensing records, Poisson regressions with generalized estimating equations, and interrupted times series estimation with segmented regression methods.

SETTING: Nursing Homes.

PARTICIPANTS: A nationwide sample of long‐stay Medicare enrollees in NHs (N=861,082).

MEASUREMENTS: Probability of Part D enrollment, changes in source of drug payments, changes in average number of monthly prescriptions dispensed per resident.

RESULTS: In 2006, 81.0% of NH residents were enrolled in Part D, 16.1% had other drug coverage, and 3.0% (n=11,000) remained without drug coverage, which was the same rate of no drug coverage as in 2005. NH residents who did not enroll in Part D were the oldest (relative risk (RR)=0.82, P<.001), had no drug coverage in 2005 (RR=0.84, P<.001), and had high comorbidity burden (RR=0.94, P<.001). The proportion of prescription drugs paid out of pocket decreased from 11.0% in 2005 to 8.1% in 2006 (P<.001). Average monthly prescription use per resident in 2006 decreased by half a prescription from 2005 levels (9.6 vs 10.1, P=.003).

CONCLUSION: Part D decreased some out‐of‐pocket drug costs but did not expand drug coverage in the NH population or reach some vulnerable segments. Part D was also associated with some disruption in NH drug use, especially right after implementation.
Evaluation of the persistence and characteristics of indeterminate reactivity against hepatitis C virus in blood donors
Authors: Melve Guro Kristin , Myrmel Helge , Eide Geir Egil , Hervig Tor
Published: August 2009

BACKGROUND: A substantial number of individuals are excluded from blood donation due to indeterminate results in screening tests for hepatitis C virus antibody (anti‐HCV). Disclosure of the characteristics of the indeterminate serologic pattern could optimize the testing and the management and care of blood donors.

STUDY DESIGN AND METHODS: Ninety‐two former blood donors deferred from blood donation due to consistent reactivity in anti‐HCV enzyme immunoassay and indeterminate HCV recombinant immunoblot assay (RIBA) results were retested for anti‐HCV to examine the extent of disappearance of reactivity. In addition, they were screened for selected viral, immunologic, and inflammatory variables to detect possible causes of the test reactivity pattern.

RESULTS: After a median observation time of 75 months, 66 of 92 individuals had persistent indeterminate HCV RIBA results. Reactivity against the nonstructural NS5 antigen was the most frequent finding. A significant association was detected both between indeterminate reactivity in HCV RIBA and against the NS5 antigen independently and detectable antibody against adenovirus. Novel indeterminate reactivity showed increased prevalence during autumn and winter months.

CONCLUSION: Indeterminate HCV RIBA reactivity in blood donors persists over years. Increased prevalence during autumn and winter and association to detection of adenovirus antibody indicate that viral infection and cross‐reactivity are etiologic factors in indeterminate HCV RIBA reactivity. Further prospective studies are needed to confirm the results.
Positive association of DRB1*04 and DRB1*15 alleles with Fya immunization in a Southern European population
Authors: Picard Chistophe , Frassati Coralie , Basire Agnes , Buhler Stephan , Galicher Vital , Ferrera Virginie , Reviron Denis , Zappitelli Jean‐Pierre , Bailly Pascal , Chiaroni Jacques
Published: August 2009

BACKGROUND: Anti‐Fya has been implicated in hemolytic transfusion reactions. However, not all Fy(a−) patients develop anti‐Fya after transfusion with 1 unit of blood [Fy(a+)]. This study was designed to identify HLA‐DRB1 alleles associated with a predisposition to Fya immunization after blood transfusion.

STUDY DESIGN AND METHODS: To identify HLA‐DRB1 alleles prone to immunization after blood transfusion or pregnancy, HLA‐DRB1 genotyping using polymerase chain reaction with sequence‐specific oligonucleotide nonradioactive probe/sequence‐specific priming methods was performed on blood samples from 67 immunized patients and 200 unrelated controls from the same southern European population in a case‐control retrospective study.

RESULTS: Ninety‐six percent of patients with anti‐Fya had at least one HLA‐DRB1*04 or HLA‐DRB1*15 allele compared to 34% of controls (pc < 0.001). Furthermore HLA‐DRB1*04 and HLA‐DRB1*1501 frequencies were significantly increased in Fya‐immunized patients (35% vs. 12%, pc < 0.001; and 30% vs. 19%, pc < 0.001, respectively). Among HLA‐DRB1*04 allelic subtypes, DRB1*0401 and DRB1*0403 alleles were more strongly correlated with Fya immunization (51% vs. 24% and 19% vs. 9%; pc < 0.001, respectively).

CONCLUSIONS: This study indicated that HLA‐DRB1*04 and DRB1*1501 are overrepresented in Fya‐immunized patients. The correlation between these alleles and Fya immunization could be due to a particular presentation of the Fya peptide in HLA‐DRB1 molecules.
The Impact of the Secondary Market on Life Insurers’ Surrender Profits
Authors: Gatzert Nadine , Hoermann Gudrun , Schmeiser Hato
Published: August 2009

Abstract

Life insurers often claim that the life settlement industry reduces their surrender profits and leads to an adverse shift in their portfolio of insured risks; that is, high risks remain in the portfolio instead of surrendering. In this article, we aim to quantify the effect of altered surrender behavior––subject to the health status of an insured––in a portfolio of life insurance contracts on the surrender profits of primary insurers. Our model includes mortality heterogeneity by applying a stochastic frailty factor to a mortality table. We additionally analyze the impact of the premium payment method by comparing results for annual and single premium payments.
Are State Marriage Initiatives Having an Eff ect ?An Initial Exploration of the Impact on Divorce and Childhood Poverty Rates
Authors: Kickham Kenneth , Ford David A.
Published: August 2009

The central question addressed by this article is the effect of state‐level marriage initiatives on divorce and childhood poverty rates. State divorce rates have been problematic for researchers because of variation across states in the way they are compiled. This research takes a different approach, measuring instead the prevalence of divorce rather than the number of divorces granted in a given state or year. The authors use this indicator, derived from Current Population Survey data, as an outcome measure in a test of marriage initiatives, and as an independent variable in a childhood poverty analysis. The quasi‐experimental design employs time‐series and cross‐section regression analysis. Results show a significant negative effect from marriage initiatives on divorce prevalence, and a significant positive association between divorce prevalence and childhood poverty rates.
Wolff‐Parkinson‐White Syndrome and Atrioventricular Nodal Re‐Entry Tachycardia in a Swedish Population: Consequences on Health‐Related Quality of Life
Authors: WALFRIDSSON ULLA , STRÖMBERG ANNA , JANZON MAGNUS , WALFRIDSSON HÅKAN
Published: August 2009

Background: Living with paroxysmal supraventricular tachycardia affects a patient's whole life situation, but few studies have addressed health‐related quality of life (HRQOL) aspects in these patients. The aim was therefore to describe HRQOL in patients with atrioventricular nodal re‐entry tachycardia (AVNRT) or Wolff‐Parkinson‐White (WPW) syndrome, referred for radiofrequency ablation (RF‐ablation), compared to age‐ and gender‐matched Swedish reference groups.

Methods: HRQOL was assessed with SF‐36 and EuroQol (EQ‐5D and EQ‐VAS) and the patients were asked disease‐specific questions.

Results: The 97 patients with AVNRT [53 ± 16 years of age/65 women] and 79 patients with WPW [42 ± 15 years of age/26 women] exhibited significantly lower HRQOL scores in SF‐36 in the same seven of the eight scales: Physical functioning (PF), role‐physical (RP), social functioning (SF), role‐emotional (RE), general health (GH), vitality (VT), and mental health (MH) while there was no difference in bodily pain (BP) compared to their respective age‐ and gender matched Swedish reference group. HRQOL scores were lower for patients with AVNRT compared to WPW in the areas of PF (P < 0.001), BP (P < 0.05), and GH (P < 0.01) in SF‐36, and the same was found in EQ‐VAS (64.8 vs. 71.2, P < 0.05). Occurrence of episodes of tachycardia more often than once a month compared to less frequently than once a month was associated with significantly lower HRQOL in all eight scales in SF‐36 (GH, RE, MH: P < 0.01 and PF, RP, BP, VT, SF: P < 0.001) and EQ‐5D index (P < 0.001) and EQ‐VAS (P < 0.05) Arrhythmia duration longer than one hour compared to patients with shorter duration of the tachycardia‐affected GH in SF‐36 negatively (P < 0.05). Patients who experienced symptoms not only during activity but also at rest scored lower in SF‐36 GH (P < 0.01) and SF (P < 0.05).

Conclusion: Measuring HRQOL in patients with WPW or AVNRT is an important way to evaluate and describe these patients’ life situation. These conditions were found to have a pronounced negative impact on HRQOL. The frequency of arrhythmia occurrence is one important factor to consider when setting priorities for treatment with RF‐ablation.
Response to Cardiac Resynchronization Therapy: Is It Time to Expand the Criteria?
Authors: VERSTEEG HENNEKE , SCHIFFER ANGÉLIQUE A. , WIDDERSHOVEN JOS W. , MEINE MATHIAS M. , DOEVENDANS PIETER A. , PEDERSEN SUSANNE S.
Published: August 2009

Background: Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10–40% of patients do not respond to this treatment and are labeled as nonresponders. Given that there is a lack of consensus on how to define response to CRT, the purpose of this viewpoint is to discuss currently used definitions and their shortcomings, and to provide recommendations as to how an expansion of the criteria for CRT response may be useful to clinicians.

Methods and Results: Analysis of the literature and case reports indicates that the majority of established measures of CRT response, including New York Heart Association functional class and echocardiographic, hemodynamic, and neurohormonal parameters, are poor associates of patient‐reported symptoms and quality of life. Moreover, the potential moderating role of psychological factors in determining health outcomes after CRT has largely been neglected.

Conclusions: It is recommended to routinely assess health status after CRT with a disease‐specific questionnaire in standard clinical practice and to examine its determinants, including psychological factors such as personality traits and depression. This may lead to improved (secondary) treatment and prognosis in CHF patients treated with CRT.
The Carina Angle—New Geometrical Parameter Associated with Periprocedural Side Branch Compromise and the Long‐Term Results in Coronary Bifurcation Lesions with Main Vessel Stenting Only
Authors: GIL ROBERT J. , VASSILEV DOBRIN , FORMUSZEWICZ RADOSLAW , RUSICKA‐PIEKARZ TERESA , DOGANOV ALEXANDER
Published: August 2009

Background:

The two main problems unresolved in coronary bifurcation stenting are periprocedural side branch compromise and higher restenosis at long term. The purpose of this study is to reveal the link between periprocedural side branch compromise and long‐term results after main vessel stenting only in coronary bifurcations.

Methods:

Eighty‐four patients formed the study population. The inclusion criteria were good‐quality angiograms, with maximal between‐branch angle opening, no overlap, permitting accurate angiographic analysis. Carina angle (α)—the distal angle between main vessel (MV) before bifurcation and side branch (SB)—was measured pre‐ and poststenting. Clinical follow‐up 9–12 months was obtained with coronary angiography if needed.

Results:

The patient population was high‐risk with 33% diabetics and 84% two‐ and three‐vessel disease. Ninety‐five stents were implanted in 92 lesions, with three T‐stenting cases. Drug‐eluting stents were implanted in 54%. Kissing‐balloon (KBI) or sequential inflation was performed in 35%. SB functional closure occurred in 17.4%, with independent predictors α < 40° and diameter ratio MB/SB >1.22. After 12±4 months there were five myocardial infarctions (6%) and 13 (15%) target lesion revascularization procedures. Independent predictors of major cardiovascular events were carina angle <40°, MB lesion length >8 mm, negative change of between‐branch angle, DES usage, and KBI.

Conclusions:

Smaller carina angle with straightening of MV—main branch from stent implantation in coronary bifurcations predicted higher SB compromise, restenosis, and MACE rates during follow‐up of 1 year.
Outcomes of Patients with Coronary Artery Perforation Complicating Percutaneous Coronary Intervention and Correlations with the Type of Adjunctive Antithrombotic Therapy: Pooled Analysis from REPLACE‐2, ACUITY, and HORIZONS‐AMI Trials
Authors: DOLL JACOB A. , NIKOLSKY EUGENIA , STONE GREGG W. , MEHRAN ROXANA , LINCOFF A. MICHAEL , CAIXETA ADRIANO , MCLAURIN BRENT , CRISTEA ECATERINA , FAHY MARTIN , KESANAKURTHY VIJAYA , LANSKY ALEXANDRA J.
Published: August 2009

Background:

The lack of a specific counteragent to bivalirudin may complicate the management of patients with coronary artery (CA) perforation during percutaneous coronary intervention (PCI).

Aim:

Assess outcomes of patients with CA perforation from three PCI trials comparing intravenous bivalirudin with provisional glycoprotein (GP) IIb/IIIa inhibition versus unfractionated heparin (UFH) plus GP IIb/IIIa.

Methods:

A pooled analysis of patients treated with PCI in three randomized trials including REPLACE‐2, ACUITY, and HORIZONS‐AMI.

Results:

Among a total of 12,921 patients, CA perforation occurred in 35 patients (0.27%). By multivariable analysis, baseline creatinine clearance was the only independent predictor of CA perforation (per 10 mL/min decrease, odds ratio [95% confidence interval]= 1.28 [1.11, 1.47], P = 0.0007). At 30 days, patients with versus without CA perforation had significantly (all P values ≤0.001) higher rates of 30‐day mortality (11.4% vs. 1.0%), myocardial infarction (MI) [Q wave: 22.9% vs. 5.7%; non‐Q wave: 17.1% vs. 4.9%], target vessel revascularization (TVR) [20.1% vs. 1.8%], and composite end‐point of death/MI/TVR (31.4% vs. 7.8%). Patients assigned to bivalirudin versus UFH plus a GP IIb/IIIa inhibitor had nonsignificantly lower rates of death (0% vs. 18.8%, P = 0.08), similar rates of MI (26.7% vs. 25.0%, P = 0.92), significantly lower rates of TVR (6.7% vs. 37.5%, P = 0.04), and similar rates of the composite end‐point of death/MI/TVR (35.5% vs. 26.7%, P = 0.54).

Conclusion:

In three PCI trials, treatment of patients experiencing CA perforation with adjunctive antithrombotic therapy of bivalirudin monotherapy was not associated with worse outcomes compared to treatment with UFH plus GP IIb/IIIa inhibitors.
No evidence for switching the antidepressant: systematic review and meta‐analysis of RCTs of a common therapeutic strategy
Authors: Bschor T. , Baethge C.
Published: August 2009

Bschor T, Baethge C. No evidence for switching the antidepressant: systematic review and meta‐analysis of RCTs of a common therapeutic strategy.

Objective:  Switching antidepressants is a common strategy for managing treatment‐resistant depressed patients. However, no systematic reviews have been conducted to date.

Method:  We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double‐blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta‐analysis of response + remission rates using a fixed‐effects model.

Results:  A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta‐analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55–1.30) favoring continuing].

Conclusion:  There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies.
Principles and methodology for translation and cross‐cultural adaptation of the Nordic Occupational Skin Questionnaire (NOSQ‐2002) to Spanish and Catalan
Authors: Sala‐Sastre Nohemi , Herdman Mike , Navarro Lidia , De LaPRADA Miriam , Pujol RAMÓN M. , Serra Consol , Alonso Jordi , Flyvholm Mari‐Ann , GIMÉNEZ‐Arnau Ana M.
Published: August 2009

Background: Occupational skin diseases are among the most frequent work‐related diseases in industrialized countries. The Nordic Occupational Skin Questionnaire (NOSQ‐2002), developed in English, is a useful tool for screening of occupational skin diseases.

Objectives: To culturally adapt the NOSQ‐2002 to Spanish and Catalan and to assess the clarity, comprehension, cultural relevance and appropriateness of the translated versions.

Methods: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) principles of good practice for the translation and cultural adaptation of patient‐reported outcomes were followed.

Results: After translation into the target language, a first consensus version of the questionnaire was evaluated in multiple cognitive debriefing interviews. The expert panel introduced some modifications in 39 (68%) and 27 (47%) items in the Spanish and Catalan version, respectively (e.g. addition of examples and definitions, reformulation of instructions and use of direct question format). This version was back translated and submitted to the original authors, who suggested a further seven and two modifications in the Spanish and Catalan versions, respectively. A second set of cognitive interviews were performed. A consensus version of both questionnaires was obtained after final modifications based on comments by the patients.

Conclusions: The final versions of the Spanish and Catalan NOSQ‐2002 questionnaires are now available at www.NRCWE.dk/NOSQ.
Allergens associated with severe symptoms of hand eczema and a poor prognosis
Authors: Hald Marianne , Agner Tove , Blands Jette , Ravn Henrik , Johansen Jean Duus
Published: August 2009

Background: Contact allergy is frequent among persons with hand eczema and may be associated with a poor prognosis.

Objectives: To identify allergens associated with the most severe initial clinical symptoms and the worst prognosis in a cohort of hand eczema patients followed for 6 months.

Methods: The study population comprised 799 consecutive hand eczema patients enrolled during January 2006–February 2007. All patients were patch tested with the European baseline series. Severity assessment of the hand eczema was performed initially and at the 6‐month follow‐up using a validated scoring system (HECSI). With logistic regression analyses, associations of severe hand eczema or a poor prognosis with 15 individual allergens were analysed and adjusted for by sex, age, atopic dermatitis and other allergens.

Results: At baseline, greater severity of hand eczema was associated with a positive patch test to formaldehyde, methyldibromo glutaronitrile, sesquiterpene lactone mix, nickel sulfate and potassium dichromate. A poor prognosis was associated with chromate allergy, odds ratio: 4.18 (95% CI: 1.42–12.28).

Conclusions: Nickel, chromate, formaldehyde, methyldibromo glutaronitrile and sesquiterpene lactone mix were allergens associated with the greatest severity of hand eczema. Patients with chromate allergy had the worst prognosis.
Formaldehyde‐releasers: relationship to formaldehyde contact allergy. Contact allergy to formaldehyde and inventory of formaldehyde‐releasers
Authors: De Groot Anton C , Flyvholm Mari‐Ann , Lensen Gerda , Menné Torkil , Coenraads Pieter‐Jan
Published: August 2009

This is one of series of review articles on formaldehyde and formaldehyde‐releasers (others: formaldehyde in cosmetics, in clothes and in metalworking fluids and miscellaneous). Thirty‐five chemicals were identified as being formaldehyde‐releasers. Although a further seven are listed in the literature as formaldehyde‐releasers, data are inadequate to consider them as such beyond doubt. Several (nomenclature) mistakes and outdated information are discussed. Formaldehyde and formaldehyde allergy are reviewed: applications, exposure scenarios, legislation, patch testing problems, frequency of sensitization, relevance of positive patch test reactions, clinical pattern of allergic contact dermatitis from formaldehyde, prognosis, threshold for elicitation of allergic contact dermatitis, analytical tests to determine formaldehyde in products and frequency of exposure to formaldehyde and releasers. The frequency of contact allergy to formaldehyde is consistently higher in the USA (8–9%) than in Europe (2–3%). Patch testing with formaldehyde is problematic; the currently used 1% solution may result in both false‐positive and false‐negative (up to 40%) reactions. Determining the relevance of patch test reactions is often challenging. What concentration of formaldehyde is safe for sensitive patients remains unknown. Levels of 200–300 p.p.m. free formaldehyde in cosmetic products have been shown to induce dermatitis from short‐term use on normal skin.
Accumulation of FITC near stratum corneum–visualizing epidermal distribution of a strong sensitizer using two‐photon microscopy
Authors: Samuelsson Kristin , Simonsson Carl , Jonsson Charlotte A. , Westman Gunnar , Ericson Marica B. , Karlberg Ann‐Therese
Published: August 2009

Background: The allergenic potency of a hapten is related to its skin penetration properties, but little is known about the distribution of haptens in the skin following topical application.

Objectives: The aim of this study was to investigate the diffusion and epidermal distribution using two‐photon microscopy (TPM) of two fluorescent compounds.

Methods: Sensitizing capacities of fluorescein isothiocyanate (FITC) and fluorescein were investigated using the local lymph node assay. Chemical reactivity of the compounds was analysed, and their distribution in human epidermis was visualized using TPM and confocal microscopy. Also the in vitro diffusion through epidermis of FITC and fluorescein has been examined.

Results: FITC was classified as an extreme sensitizer, whereas fluorescein was non‐sensitizing. TPM and confocal microscopy showed an accumulation of FITC in stratum corneum (SC), whereas fluorescein was more evenly distributed in epidermis. The diffusion of fluorescein through epidermis was three times higher than that of FITC.

Conclusions: TPM, which has never been used in this context before, is a promising tool for visualizing the distribution of fluorescent compounds of varying reactivity in intact skin. The strong allergen FITC is mainly retained in or adjacent to SC, whereas most fluorescein diffused through the epidermis.
Development of lichen sclerosus et atrophicus while receiving a therapeutic dose of imatinib mesylate for chronic myelogenous leukemia
Authors: Skupsky Hadas , Abuav Rachel , High Whitney , Pass Carolyn , Goldenberg Gary
Published: August 2009

Background: Imatinib mesylate (Gleevec®) is a selective Bcr‐Abl protein tyrosine‐kinase inhibitor, and it also inhibits the receptor tyrosine kinases for stem cell factor (c‐kit) and platelet‐derived growth factor (PDGFR). It is being investigated for use in the treatment of sclerosing dermatoses.

Observation: A 44‐year‐old woman with a history of chronic myelogenous leukemia (CML) was referred for the evaluation of a pruritic eruption that developed over 6 months. Examination revealed atrophic plaques confined to the groin, vulva, axillae, inframammary region, trunk, antecubital and popliteal fossae, and posterior thighs bilaterally. A biopsy showed lichen sclerosus et atrophicus (LSetA). At the time of presentation, the patient was receiving imatinib mesylate 400 mg daily for CML.

Conclusion: This is the first report of development of LSetA, a sclerosing dermatosis, while receiving a therapeutic dose of imatinib mesylate, a drug thought to have anti‐sclerotic properties.

Skupsky H, Abuav R, High W, Pass C, Goldenberg G. Development of lichen sclerosus et atrophicus while receiving a therapeutic dose of imatinib mesylate for chronic myelogenous leukemia.
Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) arising on the extremities
Authors: Cham Elaine , Smoller Bruce R. , Lorber David A. , Victor Thomas A. , Cibull Thomas L.
Published: August 2009

Background: Epithelioid hemangioma (EH) is a benign vascular proliferation usually accompanied by a mixed inflammatory infiltrate.

Methods: Skin biopsy specimens from four patients with EH on the extremities were studied. Architecture, extent of vascular proliferation and the presence of epithelioid endothelial cells were evaluated. The features of the inflammatory infiltrate were also assessed, including the distribution, depth, predominant cell type, presence of germinal centers, and distribution and number of CD30+ cells.

Results: All cases showed the typical lobular pattern of small vessels centered about a ‘feeder’ vessel. Larger vessels were lined by epithelioid endothelial cells. The mixed inflammatory infiltrate was nodular, perivascular and periadnexal. Germinal centers were seen in two cases. Large activated CD30+ lymphocytes were seen in all cases.

Conclusions: EH can lead to diagnostic confusion with cutaneous lymphoma and other entities, especially when its mixed inflammatory infiltrate predominates over its vascular component and contains large activated CD30+ lymphocytes. Awareness that the presence of CD30+ activated lymphocytes is not specific for lymphoma and recognition of the vascular component is critical for proper diagnosis of EH.

Cham E, Smoller BR, Lorber DA, Victor TA, Cibull TL. Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) arising on the extremities.
Characterization of cytotoxic immune response in skin and mucosal lesions of paracoccidioidomycosis
Authors: Pagliari Carla , Pereira Naiura Vieira , Kanashiro Luciane , Stegun Felipe Weisshaupt , Croda Julio , Duarte Maria Irma Seixas , Sotto Mirian Nacagami
Published: August 2009

Background: CD8+ T cells and natural killer (NK) cells are involved in the immune response against some pathogens. For this purpose, we investigated the in situ paracoccidioidomycosis (PCM) immune response addressing the participation of NK cells, CD8+ T cells, perforin and granzyme B expression.

Methods: Sixty biopsies of PCM skin and mucosa were classified according to the presence of compact granulomas (G1), poorly organized granulomas (G2) and both kinds in the same lesion (G3). CD8+ T cells, NK cells, perforin and granzyme B were showed by immunohistochemistry.

Results: CD8+ T cells were increased over NK cells in cutaneous G1 and G2 lesions. There was no difference regarding such cells in G3 lesions, although they were abundant in such lesions. In mucosa, CD8+ T cells were increased in number over NK cells in all groups. Granzyme B in skin increased in G2 and G3. The number of granzyme did not differ in mucosal lesions in the three groups.

Conclusions: CD8+ T cells and NK cells play a role in PCM cutaneous and mucosal lesions. The predominance of CD8+ T cells over NK cells may represent an effective response against the fungi. Moreover, the high number of granzyme B expressing cells corroborates this possibility.

Pagliari C, Pereira NV, Kanashiro L, Stegun FW, Croda J, Seixas Duarte MI, Sotto MN. Characterization of cytotoxic immune response in skin and mucosal lesions of paracoccidioidomycosis.
Animal models for autoimmune bullous dermatoses
Authors: Bieber Katja , Sun Shijie , Ishii Norito , Kasperkiewicz Michael , Schmidt Enno , Hirose Misa , Westermann Jürgen , Yu Xinhua , Zillikens Detlef , Ludwig Ralf J.
Published: August 2009

Abstract:  Autoimmune bullous dermatoses are a group of severe diseases, which are clinically characterized by blisters and erosions of skin and/or mucous membranes. In order to investigate the pathogenesis of these potentially life‐threatening diseases and to develop more specific therapeutic approaches, animal models have been developed that aim to reproduce the clinical, histological and immunopathological findings. We here review established and novel animal models of autoimmune skin blistering diseases and discuss their applications and limitations.
Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction
Authors: Mogensen Mette , Jørgensen Thomas Martini , Thrane Lars , Nürnberg Birgit Meinecke , Jemec Gregor Borut Ernst
Published: August 2009

Please cite this paper as: Improved quality of optical coherence tomography imaging of basal cell carcinomas using speckle reduction. Experimental Dermatology 2010; 19: e293–e295.

Background:  Optical coherence tomography (OCT) is a possible imaging method for delineation of non‐melanoma skin cancer. Speckle noise is the dominant noise contribution in OCT images; it limits the ability to identify cellular structures especially skin cancer.

Questions addressed:  This report suggests a method for improving OCT image quality for skin cancer imaging.

Experimental design:  OCT is an optical imaging method analogous to ultrasound. Two basal cell carcinomas (BCC) were imaged using an OCT speckle reduction technique (SR‐OCT) based on repeated scanning by altering the distance between the probe and the surface of the skin.

Results:  SR‐OCT resulted in improved visualisation and more accurate thickness measurements in BCC lesions.

Conclusion:  This OCT speckle reduction method led to improved visualisation and better defined delineations in two BCC lesions. Thus, OCT was improved to a clinically relevant level when imaging BCC lesions.
Stretching stimulates fibulin‐5 expression and controls microfibril bundles in human periodontal ligament cells
Authors: Nakashima K. , Tsuruga E. , Hisanaga Y. , Ishikawa H. , Sawa Y.
Published: August 2009

Background and Objective:  The elastic fiber system comprises oxytalan, elaunin and elastic fibers, differing in their relative microfibril and elastin contents. Human periodontal ligaments contain oxytalan fibers (pure microfibrils). Periodontal ligaments are continuously exposed to various functional forces, such as tooth movement and occlusal loading. We have reported that bundles of microfibrils coalesce in response to mechanical strain in cultured periodontal ligament fibroblasts, as assessed in terms of their positivity for fibrillin‐1 (the major component of microfibrils). However, the mechanism of microfibril coalescence is unclear. We hypothesized that the fibrillin‐1‐binding molecule, fibulin‐5, contributes to oxytalan fiber formation under mechanical strain.

Material and Methods:  We subjected periodontal ligament fibroblasts to stretching in order to examine the effects of fibulin‐5 on the formation of oxytalan fibers in cell/matrix layers. We transfected periodontal ligament cells with small interference RNA for fibulin‐5, then examined oxytalan fibers using immunofluorescence and electron microscopy.

Results:  Immunofluorescence showed that fibrillin‐1‐positive microfibrils coalesced as a result of stretching, compared with cells that were not subjected to stretching. Fibulin‐5 colocalized on fibrillin‐1‐positive microfibrils. Stretching increased fibulin‐5 gene expression and protein deposition. Immunofluorescence and immunogold electron microscopy analysis revealed that fibulin‐5 suppression inhibited the coalescence of microfibrils under stretching conditions.

Conclusion:  These results suggest that fibulin‐5 up‐regulated in response to tension strain may control the formation of microfibril bundles in periodontal ligament.
ORIGINAL ARTICLE: Endogenous Adenosine Down‐Modulates Mid‐Trimester IntraAmniotic Tumor Necrosis Factor‐α Production
Authors: Perni Uma , Sezen Devrim , Bongiovanni Ann Marie , Linhares Iara M. , Skupski Daniel , Witkin Steven S.
Published: August 2009

Problem  To determine whether adenosine in amniotic fluid down‐regulates pro‐inflammatory cytokine production.

Method of study  Mid‐trimester amniotic fluid from 21 women was incubated ex vivo in the presence or absence of human adenosine deaminase, the enzyme that irreversibly degrades adenosine. After 24 hr, supernatants were assayed by ELISA for tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, and IL‐10. Clinical parameters were obtained after completion of laboratory testing.

Results  Inclusion of adenosine deaminase resulted in a median increase in TNF‐α production from 0.9 to 7.3 pg/mL (P = 0.0014). IL‐6 production exhibited a non‐significant median increase from <2.0 to 53.0 pg/mL (P = 0.0780). Median IL‐10 production increased slightly from a median of <0.2 to 1.3 pg/mL. Adenosine deaminase‐stimulated TNF‐α production was proportional to parity and unrelated to gestational age, time of delivery, maternal age or indication for amniocentesis.

Conclusion  Adenosine deaminase treatment increases TNF‐α production by ex vivo‐cultured amniotic fluid. Adenosine contributes to immune modulation in the amniotic cavity.
IMAGING DIAGNOSIS: TRAUMATIC DURAL TEAR DIAGNOSED USING INTRATHECAL GADOPENTATE DIMEGLUMINE
Authors: MUÑOZ ALBERTO , MATEO ISIDRO , LORENZO VALENTINA , MARTÍNEZ JERÓNIMO
Published: August 2009

A dog with traumatic monoplegia had a spinal cord lesion, identified using conventional magnetic resonance imaging. In addition, the intrathecal use of gadopentate dimeglumine allowed identification of two sites of cerebrospinal fluid leakage from the vertebral canal, supporting a diagnosis of brachial plexus avulsion.