bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous iron therapy: well‐tolerated, yet not harmless
Authors: Sengölge G. , Hörl W. H. , Sunder‐Plassmann G.
Published: October 2005

In the majority of patients with chronic renal failure, it is essential to substitute erythropoietic agents and iron to maintain a haemoglobin level above 11 g dL−1. Intravenous iron is more effective than oral iron. Substitution of intravenous iron is mainly performed using iron(III)‐hydroxide–sucrose complex (iron sucrose) and iron(III)–sodium‐gluconate in sucrose (iron gluconate), and is, in general, well‐tolerated. Nonetheless, intravenous iron therapy has effects on endothelial cells, polymorphonuclear leucocytes and cytokines which are most likely related to non‐transferrin bound labile iron. These effects suggest a role of iron in infection or atherosclerosis. Yet, not all available data support the association of iron with infection and atherosclerosis. A recent trial showed that iron sucrose is safe when given as treatment for iron deficiency or for maintenance of iron stores. Nevertheless, iron therapy should be handled with cautiousness but its use should not be feared whenever indicated.
Sex, haemoglobin and kidney disease: new perspectives
Authors: Duncan J. A. , Levin A.
Published: October 2005

Anaemia is recognized as a common complication of chronic kidney disease with significant associated morbidity and mortality. Published data document the negative impact of anaemia on cardiovascular disease outcomes, progression of chronic kidney disease (CKD), hospitalizations, rehabilitation and quality of life, among others. Gender differences have been identified in many of these areas as well as, and importantly, in cardiovascular and chronic kidney disease outcomes. Female gender is associated with lower risk of cardiovascular morbidity and mortality as well as slower progression of chronic kidney disease. Interestingly, there are some well‐described physiological adaptations to anaemia in women, which include shifting of the haemoglobin oxygen dissociation curve to reduce oxygen affinity secondary to higher levels of 2,3‐diphosphoglycerate. However, the complex physiology underlying the impact of anaemia or gender on patients with chronic kidney disease is not well‐characterized to date. Furthermore, there has been little examination of the potential interaction between anaemia and gender on cardiac or kidney outcomes.

In this paper, we review the documented impact of anaemia and gender on outcomes, and explore the interaction of anaemia and gender in patients with CKD. We also present data that describe the potential importance of considering gender when targeting specific levels of haemoglobin. The value of a new perspective on haemoglobin and gender in kidney disease is important from both a physiological and an economical perspective.
The epidemiology and control of anaemia among pre‐ESRD patients with chronic kidney disease
Authors: McClellan W. M. , Jurkovitz C. , Abramson J.
Published: October 2005

Anaemia is a common condition among pre‐end‐stage renal disease (pre‐ESRD) patients with chronic kidney disease (CKD). Indeed, data from clinical studies indicate that anaemia may be present in as many as two‐thirds of such patients. Use of recombinant human erythropoietin (EPO) provides an effective means of correcting anaemia in CKD patients and helps to reduce the risk of renal disease progression and related problems. Unfortunately, EPO therapy is underutilized in these persons. Consequently, anaemia remains a major problem in the pre‐ESRD CKD population. Evidence suggests that anaemia in the presence of CKD can lead to an increased risk of a number of adverse outcomes, including mortality, progression of kidney disease, coronary heart disease, stroke, hospitalization, and decreases in quality of life. Anaemia's association with these adverse outcomes suggests that effective treatment of anaemia in pre‐ESRD CKD patients is of great importance and that substantial efforts should be made to ensure that these patients receive appropriate therapy to correct anaemia.
Hormonal adjuvants for the treatment of renal anaemia
Authors: Deicher R. , Hörl W. H.
Published: October 2005

Hormonal adjuvants, besides being erythropoietic agents, broaden the spectrum of therapeutic options for the treatment of the anaemia of chronic kidney disease (CKD). Lowering elevated parathyroid hormone levels by oral calcium supplementation and phosphate restriction, by varying dialysate calcium concentrations, by administration of vitamin D3 derivatives and, in the near future, by treatment with calcimimetics may prove efficient in some patients to fight extensive requirements of erythropoietic agents. Clinical evidence for a principal role of secondary hyperparathyroidism in resistance to erythropoietin, however, is lacking. Active vitamin D3 derivatives, in addition to their beneficial effects on secondary hyperparathyroidism, appear to exert a direct, stimulatory action on erythroid precursor cells and possibly also an inhibitory action on collagen synthesis by bone marrow stromal cells. Growth hormone (GH) induces insulin‐like growth factor (IGF)‐1, which in turn counteracts apoptosis similarly to erythropoietin, and fosters proliferation of burst‐ and colony‐forming units‐erythroid (BFU‐E, CFU‐E). If erythropoietic agents improve survival of CKD patients, a similar benefit should apply for strategies that increase synthesis and bioavailabilty of IGF‐1. The latter appears to be reduced in CKD patients, and zinc supplementation potentially enhances it via an increase in free IGF‐1. Finally, androgens also exert anti‐anaemic effects. Nandrolone decanoate constitutes the only androgen currently applicable for selected male dialysis patients over the age of 50 years. It should not be given to women, however, because of serious side effects. Collectively, hormonal interventions offer the potential to reduce requirements of erythropoietic agents, and some may also improve physical performance.
Anaemia after renal transplantation
Authors: Lorenz M. , Winkelmayer W. C. , Hörl W. H. , Sunder‐Plassmann G.
Published: October 2005

Anaemia is a frequent complication among long‐term renal transplant recipients. A prevalence of approximately 40% has been reported in several studies. If renal function declines to stage 5 kidney disease, the prevalence of anaemia in kidney transplants is even higher. A positive correlation between haemoglobin concentration and creatinine clearance has been reported, which is a function of endogenous erythropoietin production by the functioning graft. Inflammation related to a retained kidney graft may cause hypo‐responsiveness to erythropoietic agents once kidney transplant recipients return to dialysis. Furthermore, the use of azathioprine, mycophenolate mofetil and sirolimus may be associated with post‐transplant anaemia. Along with erythropoietin deficiency, depletion of iron stores is one of the major reasons for anaemia in the kidney transplant population. The proportion of hypochromic red blood cells appears to be a useful parameter to measure iron supply and utilization as well as to estimate mortality risks in kidney transplant recipients. While anaemia is an important cardiovascular risk‐factor after transplantation, our data suggest that anaemia is not associated with mortality and graft loss. Nevertheless, inadequate attention is paid so far to the management of anaemia after renal transplantation. A promising future aspect for risk reduction of cardiovascular disease includes the effect of erythropoietic agents on endothelial progenitor cells.
Erythropoietin‐induced, antibody‐mediated pure red cell aplasia*
Authors:   The Pure Red Cell Aplasia Global Scientific Advisory Board (GSAB)
Published: October 2005

Pure red cell aplasia (PRCA) is a rare haematological condition that is characterized by severe aregenerative anaemia due to an almost complete cessation of red blood cell production. While antibody‐mediated PRCA was extremely rare before 1998, the incidence of this disorder increased sharply after 1998 in patients receiving subcutaneous epoetin alfa produced by Ortho‐Biotech and marketed outside the USA. The diagnosis of antibody‐mediated PRCA relies mostly on the results of bone marrow biopsy or aspirate, which shows an absence of erythroid precursors and/or red cell maturation arrest while counts of white cell and platelet precursors are normal, and on the identification of circulating anti‐erythropoietin antibodies. Retrospective analysis of PRCA cases has shown that immunosuppressive therapy can induce a disappearance of anti‐erythropoietin antibodies in most patients.
VEGF‐A, VEGF‐D and VEGF‐DΔNΔC induced intimal hyperplasia in carotid arteries
Authors: Bhardwaj S. , Roy H. , Heikura T. , Ylä‐Herttuala S.
Published: October 2005

Background  The role of vascular endothelial growth factors (VEGFs) in intimal hyperplasia and atherogenesis remains unknown. Several studies have suggested that some members of the VEGF family reduce intimal hyperplasia, but others have proposed that VEGFs accelerate restenosis and atherosclerosis. This investigation conducted a comparative study with adenoviruses encoding different VEGFs in a rabbit carotid artery collar model of intimal hyperplasia in order to analyze the role of VEGFs in the formation of intimal hyperplasia.

Materials and methods  Intimal hyperplasia was induced in the carotid arteries of cholesterol fed New Zealand White rabbits using a silastic collar. Adenoviral vectors encoding VEGF‐A, VEGF‐B, VEGF‐C, VEGF‐CΔNΔC, VEGF‐D and VEGF‐DΔNΔC were delivered to the adventitia using the collar as a gene delivery device. Adeno‐LacZ was used as a control.

Results  A significant (P < 0·01) increase in the intima/media ratio was observed in the arteries transduced with VEGF‐A, VEGF‐D and VEGF‐DΔNΔC. There was a significant increase in the number of proliferating cells in the adventitia, media and intima of the VEGF‐A, VEGF‐D and the VEGF‐DΔNΔC transduced arteries. The majority of medial smooth muscle cells in these arteries had a synthetic phenotype. The presence of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 in the VEGF‐A, VEGF‐D and the VEGF‐DΔNΔC transduced arteries was significantly increased. A significant positive correlation was observed between adventitial angiogenesis and intimal hyperplasia.

Conclusions  Adventitial delivery of adenoviruses encoding VEGF‐A, VEGF‐D and VEGF‐DΔNΔC increased intimal hyperplasia in the rabbit collar model. Adventitial angiogenesis correlated positively with the intimal hyperplasia. These results indicated that efficient adventitial production of VEGF‐A, VEGF‐D and VEGF‐DΔNΔC can cause thickening of the inner layer of the artery in rabbits.
Erythrocyte transport efficacy of human blood: a rheological point of view
Authors: Bogar L. , Juricskay I. , Kesmarky G. , Kenyeres P. , Toth K.
Published: October 2005

Background  Large‐scale epidemiological studies have demonstrated that both anaemia and polycytaemia are independent cardiovascular risk factors. This was substantiated by the Framingham study, which demonstrated a U‐shaped relation between haemoglobin concentration and mortality. It was previously noted that delineating the corresponding haematocrit/blood viscosity ratios in the function of haematocrit provided a distribution of an inverted U‐shaped curve. The peak appeared physiologically important because it denotes a healthy balance between a relatively high oxygen binding capacity and a moderately low blood viscosity. It was the aim of this study to examine the mathematical relationship between the haematocrit and haematocrit/blood viscosity ratio.

Methods  In a retrospective study, the haemorheological data of 32 healthy controls, 52 outpatients with hyperlipidaemia and 120 outpatients with Raynaud's disease were analyzed. Whole blood viscosity was measured with Hevimet 40 capillary viscometer at 37·0 °C and at shear rates of 10 s−1, 90 s−1 and 200 s−1.

Results  Haematocrit/blood viscosity ratios in the function of haematocrit values showed a Gaussian association in the healthy subjects, hyperlipidaemic and Raynaud's disease outpatient groups. Peak values (i.e. the rheologically optimal haematocrit) were shear‐rate and group dependent and were found at 44·3%, 43·5% and 38·3% in controls, hyperlipidaemic and Raynaud's disease patients, respectively, at a shear rate of 90 s−1.

Conclusions  This is one of the first reports in which a theoretically optimal haematocrit value was determined using the haematocrit/blood viscosity ratio. Further studies are needed to examine the potential clinical usefulness of this approach.
Severely impaired IL‐12/IL‐18/IFNγ axis in patients with hyper IgE syndrome
Authors: Netea M. G. , Kullberg B. J. , van Der Meer J. W. M.
Published: October 2005

Background  Hyperimmunoglobulin E syndrome (HIES) is an inborn disorder characterized by recurrent skin and respiratory tract infections, skeletal abnormalities, chronic eczema and elevated serum IgE. The nature of the host defence defect has yet to be established. The aim of this study was to investigate whether activation of the interleukin‐12/interleukin‐18/interferon‐γ axis, known to be crucial for the activation of cellular immune responses, is impaired in patients with HIES.

Materials and methods  Cytokine production capacity of seven HIES patients and seven healthy controls was investigated in whole‐blood cultures stimulated with heat‐killed Staphylococcus aureus, Candida albicans, or a combination of interleukin (IL)‐12/IL‐18.

Results  Interferon (IFN)γ production, in addition to IFNγ/IL‐10 ratios, was 10–30‐fold lower in the HIES patients compared with the healthy volunteers. In contrast TNF, IL‐1β and IL‐8 production was normal.

Conclusions  These data revealed a severe dysbalance towards a Th2 phenotype in HIES patients which is likely to contribute to the specific pattern of infection susceptibility characteristic to HIES.
Comparison of monoclonal antibody (P504S) and polyclonal antibody to alpha methylacyl‐CoA racemase (AMACR) in the work‐up of prostate cancer
Authors: Kunju L P , Chinnaiyan A M , Shah R B
Published: October 2005

Aim : Studies using a monoclonal (P504S) and a polyclonal antibody (p‐AMACR) to α‐methylacyl‐CoA racemase (AMACR) have shown variable expression in prostate cancer (PCa). The goal is to compare the sensitivity of both antibodies in PCa and evaluate their utility in the work‐up of atypical prostate needle biopsies (NBXs).

Methods and results : A tissue microarray (TMA) with 248 samples of benign prostate, high‐grade prostatic intraepithelial neoplasia (HGPIN) and PCa samples, 20 NBXs with minute PCa and 32 NBXs with ‘atypical’ foci were stained with P504S and p‐AMACR. Ninety percent of PCa (76/76 TMA, 16/20 NBXs) showed predominantly strong p‐AMACR expression while 87% (65/69 TMA, 16/20 NBXs) showed variable P504S expression (sensitivity 90% versus 87%, P = 0.10). In HGPIN, P504S and p‐AMACR were positive in 77% and 91% of samples, respectively. In the ‘atypical’ NBXs group, 53% were classified as PCa, 12% benign and 35% atypical, suspicious for PCa, after review of the basal marker. Of atypical, suspicious for PCa, P504S/p‐AMACR helped convert the diagnosis to PCa in 5/11 (45%) cases, where, despite negative basal cell markers, morphology was less than optimal.

Conclusions : Differences between P504S and p‐AMACR appear marginal and clinically insignificant. AMACR is negative in a subset of unequivocal minute PCa with both antibodies. However, when utilized in proper context, AMACR may offer significant advantage in converting an ‘atypical’ diagnosis to PCa where morphology and basal markers are less than optimal in resolving the diagnosis.
Gene clusters involved in anaerobic benzoate degradation of Geobacter metallireducens
Authors: Wischgoll Simon , Heintz Dimitri , Peters Franziska , Erxleben Anika , Sarnighausen Eric , Reski Ralf , Van Dorsselaer Alain , Boll Matthias
Published: October 2005

The degradation of aromatic compounds follows different biochemical principles in aerobic and anaerobic microorganisms. While aerobes dearomatize and cleave the aromatic ring by oxygenases, facultative anaerobes utilize an ATP‐dependent ring reductase for the dearomatization of the activated key intermediate benzoyl‐coenzyme A (CoA). In this work, the aromatic metabolism was studied in the obligately anaerobic model organism Geobacter metallireducens. The gene coding for a putative carboxylic acid‐CoA ligase was heterologously overexpressed and the gene product was characterized as a highly specific benzoate‐CoA ligase catalysing the initial step of benzoate metabolism. However, no evidence for the presence of an ATP‐dependent benzoyl‐CoA reductase as observed in facultative anaerobes was obtained. In a proteomic approach benzoate‐induced proteins were identified; the corresponding genes are organized in two clusters comprising 44 genes. Induction of representative genes during growth on benzoate was confirmed by reverse transcription polymerase chain reaction. The results obtained suggest that benzoate is activated to benzoyl‐CoA, which is then reductively dearomatized to cyclohexa‐1,5‐diene‐1‐carbonyl‐CoA, followed by β‐oxidation reactions to acetyl‐CoA units, as in facultatively anaerobic bacteria. However, in G. metallireducens the process of reductive benzene ring dearomatization appears to be catalysed by a set of completely different protein components comprising putative molybdenum and selenocysteine containing enzymes.
Iron‐reducing bacteria unravel novel strategies for the anaerobic catabolism of aromatic compounds
Authors: Carmona Manuel , Díaz Eduardo
Published: October 2005

Although the aerobic degradation of aromatic compounds has been extensively studied in many microorganisms, the anaerobic mineralization of the aromatic ring is a more recently discovered microbial capacity on which very little information is available from facultative anaerobic bacteria. In this issue of Molecular Microbiology, Wischgoll and colleagues use proteomic and reverse‐transcription polymerase chain reaction (PCR) approaches to identify for the first time the gene clusters involved in the central pathway for the catabolism of aromatic compounds in Geobacter metallireducens, a strictly anaerobic iron‐reducing bacterium. This work highlights that the major difference in anaerobic benzoate metabolism of facultative and strictly anaerobic bacteria is the reductive process for dearomatization of benzoyl‐CoA. The authors propose that a new type of benzoyl‐CoA reductase, comprising molybdenum‐ and selenocysteine‐containing proteins, is present in strictly anaerobic bacteria. This work paves the way to fundamental studies on the biochemistry and regulation of this new reductive process and provides the first genetic clues on the anaerobic catabolism of benzoate by strict anaerobes.
Release of the type I secreted α‐haemolysin via outer membrane vesicles from Escherichia coli
Authors: Balsalobre Carlos , Silván Jose Manuel , Berglund Stina , Mizunoe Yoshimitsu , Uhlin Bernt Eric , Wai Sun Nyunt
Published: October 2005

The α‐haemolysin is an important virulence factor commonly expressed by extraintestinal pathogenic Escherichia coli. The secretion of the α‐haemolysin is mediated by the type I secretion system and the toxin reaches the extracellular space without the formation of periplasmic intermediates presumably in a soluble form. Surprisingly, we found that a fraction of this type I secreted protein is located within outer membrane vesicles (OMVs) that are released by the bacteria. The α‐haemolysin appeared very tightly associated with the OMVs as judged by dissociation assays and proteinase susceptibility tests. The α‐haemolysin in OMVs was cytotoxically active and caused lysis of red blood cells. The OMVs containing the α‐haemolysin were distinct from the OMVs not containing α‐haemolysin, showing a lower density. Furthermore, they differed in protein composition and one component of the type I secretion system, the TolC protein, was found in the lower density vesicles. Studies of natural isolates of E. coli demonstrated that the localization of α‐haemolysin in OMVs is a common feature among haemolytic strains. We propose an alternative pathway for the transport of the type I secreted α‐haemolysin from the bacteria to the host cells during bacterial infections.
Mucin–Pseudomonas aeruginosa interactions promote biofilm formation and antibiotic resistance
Authors: Landry Rebecca M. , An Dingding , Hupp Joseph T. , Singh Pradeep K. , Parsek Matthew R.
Published: October 2005

Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in people suffering from cystic fibrosis (CF). In CF airways, P. aeruginosa forms surface‐associated communities called biofilms. Compared with free‐swimming cultures, biofilms resist clearance by the host immune system and display increased resistance to antimicrobial agents. In this study we developed a technique to coat surfaces with molecules that are abundant in CF airways in order to investigate their impact on P. aeruginosa biofilm development. We found that P. aeruginosa biofilm development proceeds differently on surfaces coated with the glycoprotein mucin compared with biofilm development on glass and surfaces coated with actin or DNA. Biofilms formed on mucin‐coated surfaces developed large cellular aggregates and had increased tolerance to the antibiotic tobramycin compared with biofilms grown on glass. Analysis of selected mutant backgrounds in conjunction with time‐lapse microscopy revealed that surface‐associated motility was blocked on the mucin surface. Furthermore, our data suggest that a specific adhesin–mucin interaction immobilizes the bacterium on the surface. Together, these experiments suggest that mucin, which may serve as an attachment surface in CF airways, impacts P. aeruginosa biofilm development and function.
Characterization of the putative operon containing arylamine N‐acetyltransferase (nat) in Mycobacterium bovis BCG
Authors: Anderton Matthew C. , Bhakta Sanjib , Besra Gurdyal S. , Jeavons Peter , Eltis Lindsay D. , Sim Edith
Published: October 2005

Mycobacterium bovis BCG and Mycobacterium tuberculosis possess a single arylamine N‐acetyltransferase whose gene is predicted to occur within a six‐gene operon. Deletion of the nat gene caused an extended lag phase in M. bovis BCG and a cell morphology associated with an altered pattern of cell wall mycolates. Analysis of cDNA from M. bovis BCG shows that during in vitro growth all the genes in the putative nat operon are expressed and the open reading frames are contiguous, supporting the existence of an operon. Two genes in the operon, Mb3599c and Mb3600c, are predicted to encode homologues of enzymes annotated as a 2,3‐dihydroxybiphenyl 1,2‐dioxygenase (bphC5) and a 2‐hydroxy‐6‐oxo‐6‐phenylhexa‐2,4‐dienoate hydrolase (bphD2), respectively, in Rhodococcus RHA1. As predicted, M. bovis BCG cell lysates metabolized the BphC substrate 2,3‐dihydroxybiphenyl (2,3‐DHB) to 2‐hydroxy‐6‐oxo‐6‐phenylhexa‐2,4‐dienoic acid (HOPDA), a BphD substrate, which was subsequently hydrolysed. Immunoprecipitation of the BphD homologue from these lysates led to an accumulation of HOPDA. M. bovis BCG growth on both solid and liquid media was inhibited with either 2,3‐DHB or an inhibitor of BphC, 3‐chlorocatechol (3‐CC). In addition, incubation with 2,3‐DHB affects the lipid composition of the cell wall resulting in a diminished level of mycolates and an altered cell morphology similar to the Δnat strain. We propose the enzymes encoded by the putative operon have a similar endogenous role to that of the NAT enzyme and are part of a pathway important for cell wall synthesis.
Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis
Authors: Dahl R. , Stender A. , Rak S.
Published: October 2005

Background:  The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75 000 SQ‐T (Grazax®Phleum pratense, ALK‐Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co‐exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis.

Methods:  A randomized, double‐blind, placebo‐controlled, multicentre trial was performed 10–14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc.

Results:  Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 μg) was scored 2]. No serious adverse events were reported.

A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002).

Conclusions:  Self‐administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.
CD4+CD30+ T cells perpetuate IL‐5 production in Dermatophagoides pteronyssinus allergic patients
Authors: Garfias Y. , Ortiz B. , Hernández J. , Magaña D. , Becerril‐Angeles M. , Zenteno E. , Lascurain R.
Published: October 2005

Background:  Airway allergic diseases are regulated by interleukin (IL)‐5, which causes infiltration of eosinophils into the bronchial epithelium, and by IL‐4 which increases serum immunoglobulin E (IgE) production and promotes CD30 expression on Th cells. CD30 generates a costimulatory signal involved in apoptosis or cell proliferation, depending on the microenvironment. Our aims were: (i) to analyze if CD4+CD30+ T cells from allergic patients proliferate in response to Dermatophagoides pteronyssinus, and (ii) if upon stimulation this cell population produces IL‐4 and IL‐5.

Methods:  Peripheral blood mononuclear cell (PBMC) from 17 allergic rhinitis and mild allergic asthma patients and 12 healthy nonallergic individuals were stimulated with allergen in the presence or absence of anti‐IL‐4, anti‐IL‐5 or anti‐IL‐4Rα monoclonal antibodies (mAbs). TdT‐mediated dUTP nick end‐labeling (TUNEL) assay, 7‐aminoactinomycin‐D (7‐AAD) intercalation, and flow cytometry were used to determine the CD4+CD30+ blasts percentage, cell proliferation, apoptosis, and intracellular cytokines after 7 culture days.

Results:  Cell proliferation induced with allergen showed that 90% of the allergen‐stimulated blasts were CD4+, 50% of which were CD30+. Allergen‐stimulated PBMC showed a progressive increase (mean: from 7% to 23%) of CD4+CD30+IFN‐γ+ and CD4+CD30+IL‐4+ blasts which diminished (mean: 6%) after 5 culture days. In contrast, CD4+CD30+IL‐5+ blasts showed a continuous progression (from 12% to 24%) that maintained after 7 culture days. The vast majority of CD4+CD30+ blasts were negative to 7‐AAD or TUNEL. Additionally, a significant decrease (34%) was observed in the number of CD4+CD30+ blasts when IL‐4 was neutralized.

Conclusions:  These data suggest that specific allergen stimulation of PBMC isolated from allergic patients generates a nonapoptotic CD4+CD30+ blast subset that produces IL‐5.
Malassezia sympodialis differently affects the expression of LL‐37 in dendritic cells from atopic eczema patients and healthy individuals
Authors: Agerberth B. , Buentke E. , Bergman P. , Eshaghi H. , Gabrielsson S. , Gudmundsson G. H. , Scheynius A.
Published: October 2005

Background:  Atopic eczema (AE) is a multifactorial disease, which has increased in prevalence. The skin‐colonizing yeast Malasezzia sympodialis can induce IgE‐ and T‐cell reactivity in patients with AE. LL‐37 is an endogenous peptide antibiotic belonging to the cathelicidin family. The aim of this study was to examine whether exposure to M. sympodialis would affect the expression of LL‐37 in dendritic cells.

Methods:  The presence of LL‐37 was analyzed in monocyte‐derived dendritic cells (MDDCs) generated from healthy individuals and patients with AE by Western blotting and the corresponding cDNA by real‐time quantitative RT‐PCR. Antibacterial activity was measured with an inhibition zone assay in fractions after reverse phase chromatography.

Results:  For the first time we here present data, showing that LL‐37 is produced by MDDCs. Notably, the secretion of LL‐37 was substantially enhanced in M. sympodialis‐exposed MDDCs generated from patients with a high degree of eczema, as measured by SCORAD, compared to healthy controls and patients with a low SCORAD. The relative expression of LL‐37 transcript in MDDCs generated from patients was up‐regulated after 1 h of exposure to M. sympodialis and declined gradually at the time points analyzed, whereas the transcription was unaffected in the MDDCs of healthy controls.

Conclusions:  Our results suggest that M. sympodialis can trigger the innate immune response differently in patients with AE and healthy individuals. The enhanced LL‐37 secretion from the MDDCs in the patients with AE may reflect the severity of their inflammatory response to M. sympodialis.
Motivation, recruitment and retention of voluntary non‐remunerated blood donors: a survey‐based questionnaire study
Authors: Misje A. H. , Bosnes V. , Gåsdal O. , Heier H. E.
Published: October 2005

Background and Objectives  The aim of this study was to establish which motivational and socio‐demographic factors are important for the development of a long‐term commitment as a voluntary, non‐remunerated blood donor.

Study Design and Methods  A cross‐sectional sample survey of active blood donors in Oslo, Norway, was conducted. Donors filled in a self‐administered questionnaire during donation. Data on motivation were analysed using factor analysis.

Results  The blood donors’ socio‐demographic characteristics were found to be similar to those of the population as a whole. The single, most important, recruitment channel was the influence of active blood donors. Five dimensions of blood‐donor motivation were identified with factor analysis. These were: altruism and empathy; social reasons (such as the influence of friends and family); strengthening of one's self‐esteem; positive experiences associated with donation; and a moral obligation to donate. Support for statements on altruistic motives for donation was strong and similar in long‐time and short‐time donors. In contrast, short‐time donors were more likely to be motivated by factors related to self‐esteem than were long‐term donors.

Conclusion  The ‘good habit’ of continued blood donation seems not to be exclusively linked to a high degree of reported other‐regarding (‘altruistic’) reasons, but also to a combination of motives, including some modestly self‐regarding motives.
Optimal sampling time after preparation of platelet concentrates for detection of bacterial contamination by quantitative real‐time polymerase chain reaction
Authors: Mohammadi T. , Pietersz R. N. I. , Scholtalbers L. A. H. , Vandenbroucke‐Grauls C. M. J. E. , Savelkoul P. H. M. , Reesink H. W.
Published: October 2005

Background and Objectives  A universal quantitative real‐time polymerase chain reaction (PCR), based on bacterial 16S rDNA, to detect bacterial contamination of platelet concentrates (PCs), was developed previously and compared with automated culturing. In the present study, this real‐time PCR method was evaluated to determine the optimal sampling time for screening of bacterial contamination in PCs.

Materials and Methods  Routinely prepared PCs were spiked with suspensions of Escherichia coli, Bacillus cereus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Propionibacterium acnes to 1, 10 and 100 colony‐forming units (CFU)/ml and stored at room temperature for 7 days. The presence of bacteria in these PCs was monitored by quantitative real‐time PCR. As a reference method (additional control), BacT/Alert automated culturing was used. For PCR, 1‐ml aliquots were drawn from all (spiked) PCs on days 0, 1, 2, 3, 6 and 7 of storage. As a control, triplicate samples (10 ml) were inoculated into aerobic and anaerobic BacT/Alert culture bottles immediately after spiking (day 0) and after storage for 1, 2, 3, 6 or 7 days.

Results  With quantitative real‐time PCR, all bacterial species tested were reproducibly detected on day 1 after spiking at original concentrations of 10 and 100 CFU/ml. Bacteria were also detected on day 1 from PCs spiked with an initial concentration of 1 CFU/ml, except for E. coli, which was detected in only one of the three samples and P. aeruginosa, for which analysis was not performed on day 1. With the reference method, bacteria were detected in culture bottles (inoculated on day 0) within a mean time of 20·1 h, with the exception of P. acnes which was detected at a mean time of 102·3 and 49·3 h (for original spiking concentrations of 10 and 100 CFU/ml respectively).

Conclusions  PCR enables the rapid detection of low initial numbers of bacteria in PCs. For reliable detection, our results support that sampling of PCs for real‐time PCR screening should not be carried out earlier than 1 day after preparation (48 h after blood collection). Importantly, the real‐time PCR approach has the potential to be used before the release of PCs from the blood centre or shortly before they are transfused in the hospital.
Mutual suffering: A nurse's story of caring for the living as they are dying
Authors: Graham Iain W , Andrewes Tanya , Clark Lisa
Published: October 2005

The aim of this study was to uncover the meaning of the lived experience of mutual suffering in relation to the care of a dying patient. The study took place within an acute medical ward in a district general hospital on the south coast of England as part of a reflective practice development programme. Parse's human becoming theory provided a framework for the study and Parse's research methodology was adopted. Understanding the nature of human relationships within nursing practice is central to nursing work, enabling patients and their health‐professional carers to live and work healthily in the context of human becoming. Illuminating mutual suffering through reflection enables nursing and health‐care professionals to acknowledge the paradoxes of practice and, thus, create new strategies for the provision of care and the improvement of practice, so that quality of life is maximized for the patient and for themselves.
‘They first killed his heart (then) he took his own life’. Part 1: A review of the context and literature on mental health issues for refugees and asylum seekers
Authors: Procter Nicholas G
Published: October 2005

This is the first in a two‐part series of papers examining mental health issues for refugees and asylum seekers. Beginning with the suicide of an asylum seeker in Scotland, the paper emphasizes mental health issues for adult and child asylum seekers, stress and memory, suicide, self‐harm, risk and protective factors, compulsory health treatments and the prevention of mental illness. It sets the scene for the second paper by drawing implications for nursing practice in the community. Although most literature on refugee and asylum seeker mental health exists outside of nursing scholarship, a majority of the issues reviewed in this paper are mutual challenges for all in the health and helping professions. Nurses interested in refugee and migration issues face two intertwined challenges: that of how to assist migrants with their diverse mental health needs and how, at the same time, to contribute to a society that can promote mental health for all by taking on both the difficulties and opportunities posed by cultural diversity.
Extending the Box–Cox Transformation to the Linear Mixed Model
Authors: Gurka Matthew J. , Edwards Lloyd J. , Muller Keith E. , Kupper Lawrence L.
Published: October 2005

For a univariate linear model, the Box–Cox method helps to choose a response transformation to ensure the validity of a Gaussian distribution and related assumptions. The desire to extend the method to a linear mixed model raises many vexing questions. Most importantly, how do the distributions of the two sources of randomness (pure error and random effects) interact in determining the validity of assumptions? For an otherwise valid model, we prove that the success of a transformation may be judged solely in terms of how closely the total error follows a Gaussian distribution. Hence the approach avoids the complexity of separately evaluating pure errors and random effects. The extension of the transformation to the mixed model requires an exploration of its potential effect on estimation and inference of the model parameters. Analysis of longitudinal pulmonary function data and Monte Carlo simulations illustrate the methodology discussed.
The effect of low‐dose ritonavir monotherapy on fasting serum lipid concentrations
Authors: Shafran SD , Mashinter LD , Roberts SE
Published: October 2005

Objectives

Ritonavir (RTV) at doses of 400 mg twice a day (bid) or higher adversely affects serum lipids. However, the effect of RTV 100 mg bid on serum lipids is unknown. We conducted a study to evaluate the effect of RTV 100 mg bid on fasting serum lipid profiles in HIV‐negative healthy volunteers.

Methods

Ritonavir 100 mg bid was administered for 14 days to 20 healthy HIV‐seronegative adults with normal serum lipids. After a 7‐day washout, lopinavir/ritonavir (LPV/RTV) 400/100 mg bid was administered for 14 days. Fasting serum lipid parameters were measured twice at baseline, after 14 days of RTV, and after 14 days of LPV/RTV, and comparisons were made at each time‐point for levels of total cholesterol, low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol, the total/HDL cholesterol ratio and triglycerides.

Results

After 14 days of RTV 100 mg bid, total cholesterol level increased by 10.2% (P<0.001), LDL cholesterol level increased by 16.2% (P<0.001), triglyceride levels increased by 26.5% (P<0.001), HDL cholesterol level decreased by 5.4% (P<0.01) and the total/HDL cholesterol ratio increased by 17.3% (P<0.001). The addition of LPV 400 mg bid to RTV 100 mg bid resulted in no significant further changes in LDL cholesterol or triglyceride level or total/HDL cholesterol ratio, but there were significant increases in both total cholesterol (8.0% increase; P=0.007) and HDL cholesterol levels (6.7% increase; P=0.008).

Conclusions

Ritonavir dosed at 100 mg bid significantly increased the concentration of total cholesterol, LDL cholesterol, total/HDL cholesterol ratio and triglycerides and reduced HDL cholesterol concentration. The addition of LPV 400 mg bid to RTV 100 mg bid further increased both total and HDL cholesterol levels without affecting the total/HDL ratio.
Validation of a simple model for predicting liver fibrosis in HIV/hepatitis C virus‐coinfected patients
Authors: Al‐Mohri H , Cooper C , Murphy T , Klein MB
Published: October 2005

Objectives

Recently, several models incorporating laboratory measurements have been validated for use as surrogate markers for liver fibrosis in hepatitis C virus (HCV) mono‐infection, the simplest of these being the aspartate aminotransferase (AST) to platelet ratio index (APRI). We evaluated how well the APRI predicts significant hepatic fibrosis in patients with HIV/HCV coinfection.

Methods

Forty‐six HIV/HCV‐coinfected patients who underwent liver biopsy and had concomitant laboratory measurements (±3 months) were included in the study. Significant fibrosis was defined as F2–F4 using Batt and Ludwig scoring (=3 Ishak). APRI=[(AST/upper limit of normal)/platelet count (109/L)] × 100. We used sas proc logistic (SAS Institute, Cary, NC) to calculate the area under the receiver operating curve (ROC) (AUC). Sensitivities, specificities, positive predictive value (PPV) and negative predictive value (NPV) were compared using cut‐offs previously identified in the literature.

Results

Thirty‐three of 46 patients (72%) had significant fibrosis on biopsy. For significant fibrosis, the area under the ROC for the APRI was 0.847±0.057. APRI scores >1.5 (the higher cut‐off) were 100% specific and 52% sensitive; PPV was 100% and NPV 45%. Scores <0.5 (the lower cut‐off) were 82% sensitive and 46% specific in ruling out significant fibrosis (PPV 79%; NPV 50%).

Conclusions

A simple model incorporating readily available laboratory data is highly predictive of significant fibrosis in HIV/HCV coinfection and could serve as a biopsy‐sparing measure, thus making treatment more accessible for this population.
Consumer credit, household financial management, and sustainable consumption
Authors: Cohen Maurie J.
Published: October 2005

Over the past decade, sustainable consumption has emerged as an issue of growing international prominence. Policy initiatives to facilitate more environmentally and socially preferable household provisioning have typically emphasized materials and energy efficiency. While this approach holds the prospect for some notable short‐term gains, experience suggests that longer‐term improvements are likely to fall short of expectations and trigger unanticipated rebound effects. Effective policy programs need to acknowledge the social and financial dimensions of consumer decision making and become more attentive to the role of households as catalysts of production. From this perspective, consumer payment systems take on special significance. In particular, the prevalence of credit cards and the accumulation of consumer debt in the USA and other advanced countries have been important drivers of economic growth in recent years. This paper highlights the linkages between consumer credit and sustainable consumption and discusses the structural changes in lending practices that account for the popularity of this payment system. While unsatisfactory conceptual models and inadequate data make it difficult to advance any definitive assessment of this relationship, it is possible to outline the basic elements of a research agenda in this area.
In Vivo Conditioning of Tissue‐engineered Heart Muscle Improves Contractile Performance
Authors: Birla Ravi K. , Borschel Gregory H. , Dennis Robert G.
Published: October 2005

Abstract:  The ability to engineer cardiac tissue in vitro is limited by the absence of a vasculature. In this study we describe an in vivo model which allows neovascularization of engineered cardiac tissue. Three‐dimensional cardiac tissue, termed “cardioids,” was engineered in vitro from the spontaneous delamination of a confluent monolayer of cardiac cells. Cardioids were sutured onto a support framework and then implanted in a subcutaneous pocket in syngeneic recipient rats. Three weeks after implantation, cardioids were recovered for in vitro force testing and histological evaluation. Staining for hematoxylin and eosin demonstrated the presence of viable cells within explanted cardioids. Immunostaining with von Willebrand factor showed the presence of vascularization. Electron micrographs revealed the presence of large amounts of aligned contractile proteins and a high degree of intercellular connectivity. The peak active force increased from an average value of 57 µN for control cardioids to 447 µN for explanted cardioids. There was also a significant increase in the specific force. There was a significant decrease in the time to peak tension and half relaxation time. Explanted cardioids could be electrically paced at frequencies of 1–5 Hz. Explanted cardioids exhibited a sigmoidal response to calcium and positive chronotropy in response to epinephrine. As the field of cardiac tissue engineering progresses, it becomes desirable to engineer larger diameter tissue equivalents and to induce angiogenesis within tissue constructs. This study describes a relatively simple in vivo model, which promotes the neovascularization of tissue‐engineered heart muscle and subsequent improvement in contractile performance.
End‐point Temperature of Rewarming After Hypothermic Cardiopulmonary Bypass in Pediatric Patients
Authors: Kim Won Gon , Yang Ji Hyuck
Published: October 2005

Abstract:  In an attempt to find an adequate end‐point rewarming temperature after hypothermic cardiopulmonary bypass (CPB), 50 pediatric patients who underwent cardiac surgery were randomly assigned for the end‐point rectal rewarming temperature at either 35.5 (Group 1) or 37.0°C (Group 2). The patients’ rectal temperature, with heart rate and blood pressure, was measured 0.5, 1.0, 4.0, 8.0, and 16.0 h after the arrival in the intensive care unit. For all patients, nonpulsatile perfusion with a roller pump and a membrane or bubble oxygenator was used for oxygenation. Age, sex, body surface area, total bypass time, and rewarming time were comparable in both groups. No afterdrop and no statistical differences in the rectal temperatures between the two groups were observed. Also, no statistical differences were observed between the two groups with respect to the heart rate and blood pressure. No shivering was noted in all patients. In conclusion, with the restoration of rectal temperature above 35.5°C at the end of CPB in pediatric patients, the present study found no afterdrop.
Correlation Between Function and Structure in “Epileptic” Human Hippocampal Tissue Maintained In Vitro
Authors: Urban Laszlo , Aitken Peter G. , Grain Barbara J. , Friedman Allan H. , Somjen George G.
Published: October 2005

Summary: Intracellular and extracellular recordings were obtained from the CA1 region and gyrus dentatus of human hippocampi that had been surgically removed for treatment of intractable seizures. Pathologic diagnoses were obtained, and electrophysiologic results were correlated with degree of principal cell loss (sclerosis) in the regions studied. Extracellular field potentials were absent or smaller in amplitude, with abnormal characteristics, in sclerotic regions. In all regions, regardless of the degree of sclerosis, individual pyramidal or granule cells could be penetrated. These neurons showed apparently normal electrophysiologic characteristics and intact excitatory synaptic input. No signs of hyperexcitability were observed.
Anticonvulsant Action of Oxcarbazepine, Hydroxycarbamazepine, and Carbamazepine Against Metrazol‐Induced Motor Seizures in Developing Rats
Authors: Kubová Hana , Maresš Pavel
Published: October 2005

Summary: Antimetrazol effects of carbamazepine (CBZ, 5, 12.5, 25, or 50 mg/kg), oxcarbazepine (OCBZ, 5, 10, 30, or 60 mg/kg), and hydroxycarbamazepine (HCBZ, the main human metabolite of OCBZ, 10, 30, or 60 mg/kg) were studied in 7–, 12–, 18–, 25–, and/or 90‐day‐old laboratory rats. No drug tested affected the incidence of minimal (clonic) metrazol seizures (mMs) in animals aged ≥18 days; in rats aged 7 or 12 days in which mMs are rare under control conditions, the incidence of mMs was increased by lower doses of CBZ and HCBZ. All drugs tested specifically abolished the tonic phase of major generalized tonic‐clonic seizures (MMs) in a dose‐dependent manner. In addition, CBZ and OCBZ were able to suppress all phases of MMs in the two youngest groups (7‐and 12‐day‐old). There were no marked differences among the three drugs tested (CBZ, OCBZ, and HCBZ) on their action against metrazol‐induced seizures during ontogenesis of rats; i.e., all these drugs appeared to possess an identical profile of anticonvulsant action.
Vigabatrin (γ‐Vinyl‐GABA): Neuropathologic Evaluation in Five Patients
Authors: Sivenius J. , Paljärvi L. , Vapalahti M. , Nousiainen U. , Riekkinen P. J.
Published: October 2005

Summary: We performed neuropathologic examination of cerebral cortex specimens from 4 patients who underwent epilepsy surgery and the brain of 1 patient who died suddenly. All had severe epilepsy and had received γ‐vi‐nyl‐GABA (GVG, vigabatrin) for 3–5.5 years. Neither the surgically resected temporal lobe specimens nor the frontal and temporal lobes autopsy specimens showed abnormal white matter vacuolation.