bluuebunny/crossref_metadata_2025 huggingface dataset:
Phospho‐STAT5 and phospho‐Akt expression in chronic myeloproliferative neoplasms
Authors: Grimwade Lizz F. , Happerfield Lisa , Tristram Colin , McIntosh Gary , Rees Mark , Bench Anthony J. , Boyd Elaine M. , Hall Marie , Quinn Amy , Piggott Nigel , Scorer Paul , Scott Mike A. , Erber Wendy N.
Published: August 2009

The majority of Myeloproliferative Neoplasms (MPNs) are characterised by mutations in genes encoding molecules or receptors involved in cell signalling, the most common being the JAK2 V617F mutation. This mutation leads to ligand‐independent activation of downstream signalling pathways by constitutive phosphorylation. The signalling pathways affected include the Janus kinase‐signal transducers and activators of transcription (JAK‐STAT) and phosphotidylinositide‐3 kinase (PI3K) pathways, which regulate cell survival and apoptosis respectively. Monoclonal antibodies to phospho‐STAT5 and phospho‐Akt were generated and assessed by immunocytochemistry on bone marrow biopsies of MPN patients with JAK2 V617F, JAK2 exon 12, MPL exon 10 and KIT D816V mutations. JAK2 V617F mutation was associated with significantly increased levels of phosphorylated STAT5 and Akt in haemopoietic cells, most marked in megakaryocytes. In contrast, JAK2 exon 12 and MPL exon 10 mutations did not affect the level of phosphorylation. In systemic mastocytosis with KIT D618V mutation there was significantly increased expression of phosphorylated STAT5 and Akt in neoplastic mast cells although there was no change in the expression in other haemopoietic cells. JAK2 V617F is associated with upregulated phosphorylation of STAT5 and Akt in megakaryocytes, and to a lesser extent in other haemopoietic cells. Immunocytochemistry of bone marrow trephines for these phospho‐proteins can be used as a supplementary diagnostic test with a high negative predictive value.
Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan
Authors: Cappelli Barbara , Chiesa Robert , Evangelio Costanza , Biffi Alessandra , Roccia Tito , Frugnoli Ilaria , Biral Erika , Noè Anna , Fossati Marco , Finizio Valentina , Miniero Roberto , Napolitano Sara , Ferrua Francesca , Soliman Clara , Ciceri Fabio , Roncarolo Maria G. , Marktel Sarah
Published: August 2009

Hepatic veno‐occlusive disease (VOD) is a common complication of haematopoietic stem cell transplantation (HSCT), with reported incidences of 5–40% in children. Recently, defibrotide (DF) has been successfully used as prophylaxis and treatment of VOD. This study reports data on 63 human leucocyte antigen‐matched HSCT performed in 57 children affected by beta thalassemia at very high risk for developing VOD (liver fibrosis, iron overload, hepatitis C virus infections, busulphan‐based conditioning, methotraexate + ciclosporine). All patients received a busulphan‐based conditioning regimen, either orally (four HSCT) or intravenously (59 HSCT). All patients received oral DF (40 mg/kg per day, final dose) as VOD prophylaxis from median day −9 to median day +29. In order to overcome the lack of oral paediatric formulations, a galenic formulation was administered. DF was well tolerated. Only one patient fulfilled Seattle Criteria for VOD diagnosis. This patient had discontinued DF 6 d prior to VOD onset, due to high risk of haemorrhage. We concluded that oral defibrotide prophylaxis and i.v. busulphan safely abated VOD incidence in high‐risk patients who had undergone HSCT. A galenic preparation of oral DF also permits this treatment in low‐weight patients. Costs of DF prophylaxis are acceptable considering the reduced incidence of VOD.
Association studies of erythoid α‐spectrin at the tetramerization site
Authors: Lam Vinh Q. , Antoniou Chloe , Rolius Ramunas , Fung Leslie W.‐M.
Published: August 2009

The functional roles of residues 21–43 and 55–59 in the α‐spectrin N‐terminal region in forming tetramers were determined by the introduction of mutations at each of these positions. We measured association affinities for tetramer formation (Kd), which can be used to predict clinical severity, of these mutants. A total of nine residues critical for association with β‐spectrin were found. The mutations of six of these residues have already been known to cause hereditary elliptocytosis or hereditary pyropoikilocytosis. Clinical symptoms associated with three mutations of residues 23, 57 and 58 have not yet been reported. We suggest that these mutations may also introduce abnormalities to erythrocytes.
Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia
Authors: Blum Kristie A. , Advani Anjani , Fernandez Louis , Van Der Jagt Richard , Brandwein Joseph , Kambhampati Suman , Kassis Jeannine , Davis Melanie , Bonfils Claire , Dubay Marja , Dumouchel Julie , Drouin Michel , Lucas David M. , Martell Robert E. , Byrd John C.
Published: August 2009

MGCD0103, an orally available class I histone deacetylase (HDAC) inhibitor, was examined for pre‐clinical activity in chronic lymphocytic leukaemia (CLL). A phase II clinical trial was performed, starting at a dose of 85 mg/d, three times per week. Dose escalation to 110 mg or the addition of rituximab was permitted in patients without a response after two or more cycles. MGCD0103 demonstrated pre‐clinical activity against CLL cells with a LC50 (concentration lethal to 50%) of 0·23 μmol/l and increased acetylation of the HDAC class I specific target histone H3. Twenty‐one patients received a median of two cycles of MGCD0103 (range, 0–12). All patients had previously received fludarabine, 33% were fludarabine refractory, and 71% had del(11q22·3) or del(17p13·1). No responses according to the National Cancer Institutes 1996 criteria were observed. Three patients received 110 mg and four patients received concomitant rituximab, with no improvement in response. Grade 3–4 toxicity consisted of infections, thrombocytopenia, anaemia, diarrhoea, and fatigue. HDAC inhibition was observed in six out of nine patients on day 8. Limited activity was observed with single agent MGCD0103 in high risk patients with CLL. Future investigations in CLL should focus on broad HDAC inhibition, combination strategies, and approaches to diminish constitutional symptoms associated with this class of drugs.
Clofarabine, cyclophosphamide and etoposide as single‐course re‐induction therapy for children with refractory/multiple relapsed acute lymphoblastic leukaemia
Authors: Locatelli Franco , Testi Anna M. , Bernardo Maria Ester , Rizzari Carmelo , Bertaina Alice , Merli Pietro , Pession Andrea , Giraldi Eugenia , Parasole Rosanna , Barberi Walter , Zecca Marco
Published: August 2009

The safety and efficacy of the combination clofarabine/cyclophosphamide/etoposide were evaluated in children with advanced acute lymphoblastic leukaemia (ALL). The study enrolled 25 paediatric patients (median age 12·5 years) with either refractory (n = 17; 68%) or multiple relapsed (n = 8; 32%) ALL to receive clofarabine 40 mg/m2, cyclophosphamide 400 mg/m2 and etoposide 150 mg/m2, daily for 5 consecutive days. No patient died from treatment‐related complications. The most common adverse events were febrile neutropenia, mucositis and reversible liver toxicity; no case of liver veno‐occlusive disease was reported. The overall remission rate was 56%: 13 patients (52%) achieved complete remission (CR) and one (4%) CR without platelet recovery (CRp). In seven of the 13 (54%) patients achieving CR, remissions were of sufficient duration to allow patients to receive allogeneic haematopoietic stem cell transplantation. The probability of CR/CRp was greater in the 17 patients with B cell precursor ALL than in the eight with T‐ALL (76% vs. 12%, respectively, P < 0·01). The 18‐month overall survival probability was 39% and 0% in patients who did or did not respond to the treatment, respectively (P < 0·01). These data suggest that the clofarabine/cyclophosphamide/etoposide regimen is well tolerated and can induce clinical response in a relevant proportion of children with refractory/multiple relapsed ALL.
Baby swimming: exploring the effects of early intervention on subsequent motor abilities
Authors: Sigmundsson H. , Hopkins B.
Published: August 2009

Aim  The aim of the study was to explore the effects of baby swimming on subsequent motor abilities.

Background  A range of motor abilities was examined in 4‐year‐old children who had previously participated in a programme of baby swimming (n= 19) and compared with a matched group of coevals who had not had this experience (n= 19).

Results  As predicted from the nature of the exercises that comprise the programme, the effects of baby swimming were restricted to abilities associated with prehension and balance.

Conclusions  Suggestions are made as to how the theme of this hypothesis‐generating, demonstration study can be pursued in the future with more rigorous experimental controls and applications to children with disabilities and impairments.
Perspectives of normal child development in rural Malawi – a qualitative analysis to create a more culturally appropriate developmental assessment tool
Authors: Gladstone M. , Lancaster G. , Umar E. , Nyirenda M. , Kayira E. , Van Den Broek N. , Smyth R. L.
Published: August 2009

Background  Child development in developing countries is often evaluated using assessment tools created for ‘Western’ settings. Recent work has demonstrated that, for certain developmental milestones, ‘Western’ tools may be inaccurate as they include items unfamiliar to children of different cultural settings.

Methods  We used qualitative methods to gather information about normal development in an African setting. Ten village and two professional focus group discussions (FGDs) were conducted. We used purposive sampling methods to recruit groups of mothers, grandmothers and men in four areas of Southern Malawi for village FGDs. Separate FGDs were carried out with professionals working in areas relating to child development. A thematic content analysis established main patterns and themes and dissemination of results and continued feedback allowed for respondent validation and reflection of results. The information then gathered was used to create questions for a revised Malawian developmental assessment tool.

Results  Social and gross motor milestones were the main focus of interest for village and professional FGDs with the latter creating new language and fine motor concepts. Social milestones highlighted included ‘duties and chores’, ‘sharing’ and ‘taking up leadership roles’. Language milestones included ‘reporting events’ and ‘shrugging to indicate no’ and fine motor milestones included ‘peeling bananas’, ‘sorting maize’ and ‘making patterns with bottle tops’. Intelligence was described in relation to social and community integrity rather than ‘Western’ concepts of numeracy and literacy.

Conclusions  Concepts, ideas and language relating to normal development in a sub‐Saharan African setting have been gathered in this study. These have been used to create items for a more culturally appropriate developmental assessment tool.
Parental satisfaction with follow‐up services for children with major anatomical congenital anomalies
Authors: Van Dijk M. , Poley M. J. , Gischler S. J. , Mazer P. , IJsselstijn H. , Tibboel D. , Latour J. M.
Published: August 2009

Background  Since 1999 a multidisciplinary follow‐up programme for parents and children with major anatomical congenital anomalies is in place in our hospital, run by a dedicated team. The aim of the present study was to evaluate the services of this team from a parental perspective.

Methods  Parents completed a questionnaire including open and closed questions about satisfaction with the various professional disciplines involved in the follow‐up, statements on usefulness of the follow‐up services and suggestions for improvement.

Results  Four hundred and sixty‐nine surveys were sent out, of which 71% were returned. Non‐responding parents included significantly more parents of non‐Dutch origin (P= 0.038) and parents who never responded to invitations for follow‐up examinations (P < 0.001). Parental satisfaction differed for the various disciplines. Eighty per cent of the parents were (very) satisfied with the social worker, compared with 92% with nurses. More than half of the parents agreed that the follow‐up services give peace of mind. Almost a quarter of parents, however, considered the follow‐up services as redundant. The children of these parents had significantly shorter intensive care unit stay (P= 0.02), were older at the time of the questionnaire (P= 0.04), of higher socio‐economic status (P= 0.001) and less likely to be of non‐Dutch origin (P= 0.008). Sixty‐one per cent of the parents had contacted the 24‐h helpline. Ninety per cent of the parents were satisfied with the intensive care unit, almost 80% with the general ward.

Conclusion  Overall, parents were satisfied with the services of the follow‐up team. Some parents, however, saw room for improvement related to better communication, recognizability of the team and better planning and organization.
Sensory pulpal nerve fibres and trigeminal ganglion neurons express IL‐1RI: a potential mechanism for development of inflammatory hyperalgesia
Authors: Bletsa A. , Fristad I. , Berggreen E.
Published: September 2009

Aim  To localize interleukin‐1 receptor type I (IL‐1RI) in rat dental pulp and trigeminal ganglion (TG) and to test the hypothesis that pulpal inflammation increases neuronal expression of IL‐1RI.

Methodology  Female Wistar rats were subjected to unilateral pulp exposures in the maxillary and mandibular first molars, whereas the contralateral jaws served as untreated controls. Seven days later the animals were transcardiacally perfused and the jaws and the TGs were removed and prepared for immunohistochemistry. Immunoreactivity for IL‐1RI was examined alone (DAB) and together with calcitonin gene‐related peptide (CGRP), neuropeptide Y (NPY), CD31 or CD34 by multiple‐labelling immunofluorescence. Quantification of IL‐1RI‐immunoreactive (‐IR) cells in the maxillary and mandibular division of the ganglion was performed in parasagittal immunoreacted sections of the right and left TGs. Data were analysed with Mann–Whitney Rank Sum test (P < 0.05).

Results  Interleukin‐1 receptor type I was found on sensory (CGRP‐IR) and sympathetic (NPY‐IR) nerve fibres and on blood vessels (CD31‐ and CD34‐IR) in the dental pulp. It was also localized on sensory neurons and axons in the TG. Pulpal inflammation significantly increased the expression of IL‐1RI in the TG (P < 0.001).

Conclusions  The localization of IL‐1RI on sensory nerve fibres and its up‐regulation in TG neurons during pulpal inflammation may imply a direct effect of IL‐1 in pulpal nociception. The presence of IL‐1RI on sympathetic nerve fibres and on blood vessels may indicate a vasoactive role of the same cytokine in the pulp.
Less advanced testicular dysgenesis is associated by a higher prevalence of germ cell neoplasia
Authors: Guminska A. , Oszukowska E. , Kuzanski W. , Sosnowski M. , Wolski J. K. , Walczak‐Jedrzejowska R. , Marchlewska K. , Niedzielski J. , Kula K. , Slowikowska‐Hilczer J.
Published: August 2009

There is a theory that the more evident clinical signs of testicular dysgenesis, the more frequent the neoplastic lesions are. The aim of this study was to relate the incidence of testicular germ cell neoplastic lesions (overt germ cell tumours – GCT or testicular carcinoma in situ) to the intensity of testicular organogenesis disturbances (dysgenesis). Biopsies were taken from 154 testes of the following patients: 23 patients with GCT in the contralateral gonad (CGCT), 41 patients with undescended testes operated in childhood (UDT), 90 with azoo‐/oligozoospermia (A/O) diagnosed because of infertility. Assessment of seminiferous epithelium, number of Leydig cells, areal fraction of intertubular space (IS), morphometric analysis of seminiferous tubules diameter and thickness of tubular wall were performed. Monoclonal antibodies against placental like alkaline phosphatase and cytokeratin 18 were applied. Germ cell neoplastic lesions were detected in 7.1% of testes and were associated with disturbed spermatogenesis. Among testes with disturbed spermatogenesis they were found the most frequently in CGCT (22.2% vs. 11.1% in UDT and 3.8% in A/O), where spermatogenesis had the highest score (5.7 ± 3.8 points vs. 4.2 ± 2.7 in UDT and 4.6 ± 2.9 in A/O). In CGCT, signs of testicular dysgenesis were less advanced: the highest tubular diameter was 164.4 ± 32.3 μm vs. 163.5 ± 28.6 in UDT and 161.4 ± 31.5 in A/O, the lowest thickness of tubular wall was 8.9 ± 3.2 μm vs. 10.2 ± 3.6 in UDT and 10.2 ± 3.2 in A/O, lowest IS was 36.9 ± 14.9% vs. 47.9 ± 18.0 in UDT and 46.5 ± 18.5 in A/O, and the lowest percentage of tubules with immature Sertoli cells was 0.1 ± 0.4% vs. 4.9 ± 7.0 in UDT and 5.2 ± 9.7 in A/O. Results indicate that neoplastic lesions appear only in testes with disturbed spermatogenesis. Worse condition of spermatogenesis is associated by the presence of other dysgenetic features, but neoplastic lesions appear more frequently in testes with the less advanced features of testicular dysgenesis.
Prospective longitudinal studies of salmonid alphavirus infections on two Atlantic salmon farms in Ireland; evidence for viral persistence
Authors: Graham D A , Fringuelli E , Wilson C , Rowley H M , Brown A , Rodger H , McLoughlin M F , McManus C , Casey E , McCarthy L J , Ruane N M
Published: August 2009

Prospective longitudinal studies of two outbreaks of pancreas disease in Atlantic salmon (AS), Salmo salar L., in Ireland were conducted. Both outbreaks occurred during the marine phase of production, with one caused by salmonid alphavirus subtype 1 (SAV1) and the other by SAV4. In addition to screening a range of tissues by real‐time reverse transcriptase polymerase chain reaction (RRT‐PCR), virological, serological and histopathological examinations were performed along with partial genome sequencing and results were related to environmental and production data and farm history. On Farm 1 (marine sampling only), infection was detected within 3 weeks of smolts being placed on the farm, while on Farm 2 (freshwater and marine sampling), infection was first detected 315 days after transfer to sea. In both outbreaks, RRT‐PCR signals were detected in a range of tissues including gill, heart, kidney, pancreas/pyloric caeca, brain and serum. Persistence of signal was longest in gill and heart (≥265 days on both farms) and shortest in serum. Mortalities on the two farms varied from 10.9% to 30%. In both cases, partial genome sequence of the causative viruses were identical to SAV strains detected in previous populations of AS on each of the study farms, including populations with which the study populations overlapped in time and space.
A single‐dose pharmacokinetic study of emamectin benzoate in cod, Gadus morhua L., held in sea water at 9 °C
Authors: Samuelsen O B
Published: August 2009

The pharmacokinetic profile of the antiparasitic agent emamectin benzoate was studied in plasma after intravenous (i.v.) injection and in plasma, muscle and skin following oral (p.o.) administration to cod, Gadus morhua, held in sea water at 9 °C and weighing 100–200 g. Following i.v. injection, the plasma drug concentration‐time profile showed two distinct phases. The plasma distribution half‐life (t1/2α) was estimated as 2.5 h, the elimination half‐life (t1/2β) as 216 h, the total body clearance (ClT) as 0.0059 L kg−1 h−1 and mean residence time (MRT) as 385 h. The volume of distribution at steady state, Vd(ss), was calculated to be 1.839 L kg−1. Following p.o. administration the peak plasma concentration (Cmax) was 15 ng mL−1, the time to peak plasma concentration (Tmax) was 89 h and t1/2β was 180 h. The highest concentration in muscle (21 ng g−1) was measured after 7 days and t1/2β was calculated to be 247 h. For skin, a peak concentration of 28 ng g−1 at 3 days was observed and a t1/2β of 235 h was determined. The bioavailability following p.o. administration was calculated to be 38%.
An experimental vaccine against Aeromonas hydrophila can induce protection in rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: LaPatra S E , Plant K P , Alcorn S , Ostland V , Winton J
Published: August 2009

A candidate vaccine against Aeromonas hydrophila in rainbow trout, Oncorhynchus mykiss, was developed using a bacterial lysate. To test the strength of protection, A. hydrophila challenge models were compared using injection into both the intraperitoneal (IP) cavity and the dorsal sinus (DS) with selected doses of live bacteria washed in saline or left untreated. Unlike the IP route, injection into the DS with either saline washed or unwashed cells resulted in consistent cumulative mortality and a dose response that could be used to establish a standard challenge having an LD50 of approximately 3 × 107 colony forming units per fish. Survivors of the challenge suffered significantly lower mortality upon re‐challenge than naïve fish, suggesting a high level of acquired resistance was elicited by infection. Passive immunization using serum from hyper‐immunized fish also resulted in significantly reduced mortality indicating protection can be transferred and that some portion of resistance may be antibody mediated. Vaccination of groups of rainbow trout with A. hydrophila lysate resulted in significant protection against a high challenge dose but only when injected along with Freund’s complete adjuvant. At a low challenge dose, mortality in all groups was low, but the bacterial lysate alone appeared to offer some protection.
Social information processing in boys with autistic spectrum disorder and mild to borderline intellectual disabilities
Authors: Embregts P. , Van Nieuwenhuijzen M.
Published: August 2009

Background  Children with autistic spectrum disorders (ASD) and mild to borderline intellectual disability (ID) have less adaptive behaviour and more behaviour problems than children with mild to borderline ID. Social information processing appears to be an important mechanism in the explanation of the socially inadequate behaviour of children with mild to borderline ID; however, little is known about the social information processing skills of children with ASD and mild to borderline ID.

Method  In the present study, a total of 136 boys in the age of 10–14 years participated; 26 with ASD (specifically Pervasive Developmental Disorder – Not Otherwise Specified) and mild to borderline ID, 54 with mild to borderline ID without ASD and 56 typically developing boys. They completed the Social Problem Solving Test to measure their social information processing.

Results  The research results show boys with PDD‐NOS and mild to borderline ID to differ from typically developing boys in their encoding of information; they focus on negative and emotional information in the social situation. They differ from boys with mild to borderline ID in response generation, evaluation of inadequate solutions (aggressive and submissive responses) and assertive response decision.

Conclusions  The present study extends our knowledge regarding social information processing of children with ASD (PDD‐NOS) and mild to borderline ID. This knowledge may be helpful in designing and adapting programmes (e.g. social skills training, self‐management training) for the management of behaviour problems and development of adaptive behaviour of children with ASD and mild to borderline ID.
Clinical outcomes of a specialised inpatient unit for adults with mild to severe intellectual disability and mental illness
Authors: Lunsky Y. , White S. E. , Palucka A. M. , Weiss J. , Bockus S. , Gofine T.
Published: August 2009

Background  Limitations of general psychiatric services have led to the development of specialised psychiatric programmes for patients with intellectual disability (ID) and mental health needs. Few studies have examined treatment outcomes of specialised inpatient units, and no studies have explored how the effects of intervention may differ for individuals at varying levels of cognitive ability. The present study examined clinical outcomes of inpatients with mild ID in contrast to inpatients with moderate to severe ID within the same service.

Method  Thirty‐three patients (17 with mild ID and 16 with moderate to severe ID) discharged between 2006 and 2008 from a specialised inpatient unit in Canada for adults with ID and mental illness were studied. In addition to examining change in scores on clinical measures, outcomes with regard to length of stay, diagnostic change, residential change and re‐admission to hospital were explored.

Results  Both groups demonstrated clinical improvement from admission to discharge. However, only patients with mild ID demonstrated improvements on the Global Assessment of Functioning.

Conclusions  This study is one of the first to consider outcomes of higher and lower functioning individuals with ID on a specialised inpatient unit. Results suggest that outcomes may be different for these groups, and some clinical measures may be more sensitive to changes in patients with more severe disabilities.
Self‐reported sleep duration and cognitive functioning in the general population
Authors: KRONHOLM ERKKI , SALLINEN MIKAEL , SUUTAMA TIMO , SULKAVA RAIMO , ERA PERTTI , PARTONEN TIMO
Published: August 2009

This study investigated the relationship between self‐reported sleep factors (sleep duration, insomnia, use of sleeping medicine, probable sleep apnoea and feelings of fatigue and tiredness) with cognitive functioning in 5177 people aged 30 years or older from a cross‐sectional representative sample of the adult population in Finland (The Finnish Health 2000 Survey). Previous studies have indicated a U‐shaped association between increased health risks and sleep duration; we hypothesized a U‐shaped association between sleep duration and cognitive functioning. Objective cognitive functioning was assessed with tasks derived from the Consortium to Establish a Registry for Alzheimer’s Disease test battery (verbal fluency, encoding and retaining verbal material). Subjective cognitive functioning and sleep‐related factors were assessed with questionnaires. Health status was assessed during a health interview. Depressive and alcohol use disorders were assessed with the Composite International Diagnostic Interview. Medication was recorded during the health examination. Short and long sleep duration, tiredness and fatigue were found to be associated with both objectively assessed and self‐reported decreased cognitive functioning. The association was stronger between sleep factors and subjective cognitive function than with objective cognitive tests. These data suggest that self‐reported habitual short and long sleep duration reflect both realization of homeostatic sleep need and symptom formation in the context of the individual’s health status.
Central apnoeas have significant effects on blood pressure and heart rate in children
Authors: O’DRISCOLL DENISE M. , FOSTER ALISON M. , NG MICHELLE L. , YANG JOEL S. C. , BASHIR FARHAT , WONG SHI , NIXON GILLIAN M. , DAVEY MARGOT J. , ANDERSON VICKI , WALKER ADRIAN M. , TRINDER JOHN , HORNE ROSEMARY S. C.
Published: August 2009

Brief central apnoeas (CAs) during sleep are common in children and are not usually considered clinically significant unless associated with oxygen desaturation. CAs can occur spontaneously or following a movement or sigh. The aim of this study was to investigate acute cardiovascular changes associated with CAs in children. Beat‐by‐beat mean arterial pressure (MAP) and heart rate (HR) were analysed across CAs, and spontaneous and movement‐induced events were compared using two‐way analysis of variance with post hoc analyses. Fifty‐three children (28 male/25 female) aged 7–12 years referred for investigation of sleep‐disordered breathing (SDB) and 21 age‐matched healthy controls (8 male/13 female) were studied. Children underwent routine clinical polysomnography with continuous blood pressure (BP) recordings. Movement‐induced, but not spontaneous, CAs were more frequent in children with mild or moderate/severe obstructive sleep apnoea (OSA) compared with healthy controls (P < 0.05 for both). Movement‐induced CAs were associated with significantly larger MAP and HR changes across the event compared with spontaneous CAs. The percentage changes in MAP and HR between late‐event and post‐event were significantly greater for movement‐induced compared with spontaneous CAs (MAP 20.6 ± 2.3 versus 12.2 ± 1.8%, P < 0.01; HR 28.2 ± 2.6 versus 14.7 ± 2.5%, P < 0.001). This study demonstrates that movement‐induced CAs are more common in children with OSA, and are associated with significantly greater changes in HR and BP compared with spontaneous CAs. These data suggest that movement‐induced CAs should be considered when assessing the cardiovascular impact of SDB.
Marked sperm dimorphism in the ground beetle Scarites terricola: a novel type of insect sperm polymorphism
Authors: SASAKAWA KÔJI
Published: August 2009

Sperm polymorphism describes the phenomenon of male ejaculates containing two or more distinct types of sperm. In insects, four types of sperm polymorphism are recognized in species from the orders Diptera, Hemiptera, Hymenoptera, Lepidoptera and Coleoptera. The present study describes dimorphic sperm of the ground beetle Scarites terricola (Coleoptera: Carabidae) as a novel type of sperm polymorphism in insects. Sperm from the spermatophore and male seminal vesicles are examined at the light‐microscopic level, and both display marked dimorphism. One type has sperm formed into bundles, in which the head of numerous spermatozoa are ‘glued’ together, with tails free‐moving. The other type are free as single spermatozoa and have a disproportionately large‐sized head and an elongated tail. Both types are motile in Ringer's solution. The adaptive and phylogenetic importance of these findings is discussed.
The German Haemovigilance System–reports of serious adverse transfusion reactions between 1997 and 2007
Authors: Keller‐Stanislawski B. , Lohmann A. , Günay S. , Heiden M. , Funk M. B.
Published: September 2009

summary.

Data of the German Haemovigilance System were collected from 1997 to 2007 and assessed on the basis of pre‐defined safety standards. Suspected cases of serious adverse reactions following transfusions reported to the Paul‐Ehrlich‐Institut were evaluated on the basis of national criteria, and the definitions of International Society of Blood Transfusion (ISBT) in compliance with defined causality criteria. The suspected cases were rated as confirmed and unconfirmed transfusion reactions. Assessment of causality took into consideration the clinical course of the adverse reaction and, if necessary, information about donation and manufacturing. Of the 5128 suspected serious adverse reactions, 1603 could be confirmed. Referring to the absolute figures, acute transfusion reactions (e.g. allergic reactions, hypotension and dyspnoea) were recorded most frequently, followed by transfusion‐related acute lung injury (TRALI), haemolytic reactions, transfusion‐related bacterial infections and virus infections. The majority of the 52 transfusion‐related fatalities (14 each) were due to TRALI and acute transfusion reactions (mostly severe allergic reactions). Referred to the blood products administered, immune TRALI cases and TRALI‐related fatal courses were most frequently reported after administration of fresh frozen plasma (FFP) (15/106 and 3.5/106 units, respectively), transfusion‐related bacterial infections after administration of platelet concentrates (7/106 units), acute haemolytic transfusion reactions after administration of red blood cell concentrates (2.3/106units) and acute transfusion reactions after administration of red blood cell or platelet concentrates (7.8/106 and 13/106 units, respectively). Despite the high safety standard required for blood products in Germany, there is still room for reducing the frequency of isolated cases of transfusion reactions by targeted action.
Validation of methodologies for quantifying isolated human islets: an islet cell resources study
Authors: Kissler H.J. , Niland J.C. , Olack B. , Ricordi C. , Hering B.J. , Naji A. , Kandeel F. , Oberholzer J. , Fernandez L. , Contreras J. , Stiller T. , Sowinski J. , Kaufman D.B.
Published: August 2009

Kissler HJ, Niland JC, Olack B, Ricordi C, Hering B J, Naji A, Kandeel F, Oberholzer J, Fernandez L, Contreras J, Stiller T, Sowinski J, Kaufman DB. Validation of methodologies for quantifying isolated human islets: an islet cell resources study. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01052.x. © 2009 John Wiley & Sons A/S.

Abstract:  Background:  Quantification of islet mass is a crucial criterion for defining the quality of the islet product ensuring a potent islet transplant when used as a therapeutic intervention for select patients with type I diabetes.

Methods:  This multi‐center study involved all eight member institutions of the National Institutes of Health‐supported Islet Cell Resources Consortium. The study was designed to validate the standard counting procedure for quantifying isolated, dithizone‐stained human islets as a reliable methodology by ascertaining the accuracy, repeatability (intra‐observer variability), and intermediate precision (inter‐observer variability). The secondary aim of the study was to evaluate a new software‐assisted digital image analysis method as a supplement for islet quantification.

Results:  The study demonstrated the accuracy, repeatability and intermediate precision of the standard counting procedure for isolated human islets. This study also demonstrated that software‐assisted digital image analysis as a supplemental method for islet quantification was more accurate and consistent than the standard manual counting method.

Conclusions:  Standard counting procedures for enumerating isolated stained human islets is a valid methodology, but computer‐assisted digital image analysis assessment of islet mass has the added benefit of providing a permanent record of the isolated islet product being evaluated that improves quality assurance operations of current good manufacturing practice.
Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration
Authors: Ulrich Frank , Niedzwiecki Sebastian , Fikatas Panos , Nebrig Maxim , Schmidt Sven C. , Kohler Sven , Weiss Sascha , Schumacher Guido , Pascher Andreas , Reinke Petra , Tullius Stefan G. , Pratschke Johann
Published: August 2009

Ulrich F, Niedzwiecki S, Fikatas P, Nebrig M, Schmidt SC, Kohler S, Weiss S, Schumacher G, Pascher A, Reinke P, Tullius SG, Pratschke J. Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration. Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01073.x © 2009 John Wiley & Sons A/S.

Abstract:  Lymphocele formation is a common complication after kidney transplantation, and laparoscopic surgery has become a widely accepted treatment option. The aim of this retrospective study was to analyze the risk factors of lymphocele development and to assess the treatment outcome after laparoscopic fenestration. We analyzed 426 renal allograft recipients operated between 2002 and 2006 receiving triple immunosuppression with calcineurin inhibitors. The incidence of lymphocele was 9.9%, while 24 (5.6%) patients with symptomatic lymphoceles required laparoscopic surgery. Serum creatinine at diagnosis was significantly higher in patients with lymphoceles treated surgically (3.2 ± 0.7 vs. 1.7 ± 0.6 mg/dL; p < 0.001). After successful laparoscopic intervention, creatinine concentrations recovered until discharge and were comparable to other patients (1.6 ± 0.5 vs. 1.5 ± 0.5 mg/dL; p = NS). While we observed a significant association of lymphocele formation with diabetes, tacrolimus therapy, and acute rejection in univariate testing, only diabetes remained a significant factor after multivariate analysis. Laparoscopic fenestration proved to be a safe and efficient method without any associated mortality and a low recurrence rate of 8.3% (n = 2). We conclude that diabetes is an independent risk factor for lymphocele development, and laparoscopic fenestration should be the treatment of choice for larger and symptomatic lymphoceles, as it is safe and offers a low recurrence rate.
Serum leptin and adiponectin levels correlate with severity of allergic rhinitis
Authors: Hsueh Kai‐Chung , Lin Ying‐Ju , Lin Hsiao Chuan , Lin Ching‐Yuang
Published: August 2009

Hsueh K‐C, Lin Y‐J, Lin HC, Lin C‐Y. Serum leptin and adiponectin levels correlate with severity of allergic rhinitis. Pediatr Allergy Immunol 2010: 21: e155–e159. © 2009 John Wiley & Sons A/S

The aim of this study was to evaluate the roles of leptin and adiponectin, which are adipokines produced by adipose tissue, in childhood allergic rhinitis (AR), and their association with severity of AR, parameters of atopy and pro‐/anti‐inflammatory cytokines. Serum levels of leptin, adiponectin, mite allergen‐specific and total immunoglobulin E, eosinophil cationic protein (ECP), and pro‐ and anti‐inflammatory cytokines were analysed in 97 non‐asthmatic children presenting with persistent AR and in 64 controls. The nasal symptom scores and body mass index were evaluated at the time of blood collection. We found that patients had significantly higher serum levels of leptin and significantly lower serum levels of adiponectin than controls. Furthermore, multivariate logistic regression analysis revealed that leptin and adiponectin were significant predictive factors for AR. Serum levels of leptin and adiponectin were significantly correlated with nasal symptom scores. There was no correlation between levels of pro‐ and anti‐inflammatory cytokines and level of leptin or adiponectin. A significant negative correlation was observed between serum levels of adiponectin and ECP levels in AR children. Our findings suggest that serum leptin and adiponectin levels may serve as predictors of disease severity in childhood AR and both of them appear to be attractive candidates for unmasking or modulating AR.
Urinary nitric oxide excretion in infants with eczema
Authors: Devenney Irene , Norrman Gunilla , Forslund Tony , Fälth‐Magnusson Karin , Sundqvist Tommy
Published: August 2009

Devenney I, Norrman G, Forslund T, Fälth‐Magnusson K, Sundqvist T. Urinary nitric oxide excretion in infants with eczema. Pediatr Allergy Immunol 2010: 21: e229–e234. © 2009 John Wiley & Sons A/S

Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety‐four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 μm (median; IQR) vs. 457; 678 μm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6‐wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.
An evaluation of monitoring possibilities of argatroban using rotational thromboelastometry and activated partial thromboplastin time
Authors: ENGSTRÖM M. , RUNDGREN M. , SCHÖTT U.
Published: August 2009

Background:
Rotational thrombelastometry/thrombelastography with ROTEM® and TEG® is becoming available bedside in an increasing number of intensive care units, where many patients with heparin‐induced thrombocytopenia (HIT) are treated. The study has been performed in an effort to find out whether ROTEM® could be an alternative to activated partial thromboplastin time (aPTT) when argatroban is used for anticoagulation.

Methods:
Argatroban was added in vitro to a series of citrated whole‐blood samples from 10 healthy volunteers to obtain whole‐blood concentrations of 0, 0.125, 0.25, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/l. ROTEM® and whole‐blood aPTT analyses were performed at each argatroban concentration. Correlation analyses were performed using the Spearman correlation analysis.

Results:
There was a significant and strong correlation between argatroban concentrations and clotting time (CT in ROTEM® analysis with INTEM) (P<0.0001 and r=0.98). Also, the ROTEM® time to maximum clot formation velocity (MAXV‐t) appeared to have a very strong and highly significant correlation to argatroban concentrations (P<0.0001 and r=0.95). When we studied the correlation between aPTT and CT, we found a highly significant and strong correlation between these two analyses (P<0.0001 and r=0.97), especially so in the clinically relevant therapeutic range up to 100 s aPTT prolongation for HIT patients.

Conclusion:
A significant and strong correlation was found between argatroban concentrations and several ROTEM® parameters. Rotational thrombelastometry/thrombelastography has a potential role in increasing the safety of argatroban anticoagulation in critically ill patients.
High or low current threshold for nerve stimulation for regional anaesthesia
Authors: STEINFELDT T. , GRAF J. , VASSILIOU T. , MORIN A. , FELDMANN K. , NIMPHIUS W. , DE ANDRES J. , WULF H.
Published: August 2009

Background: The purpose of this study was to determine whether the application of high stimulation current thresholds (SCT) leads to a distant needle to nerve proximity (NNP) compared with low SCT during nerve localization for regional anaesthesia in pigs.

Methods: A minimal motor response to the stimulation of femoral or brachial plexus nerves in 16 anaesthetized pigs was triggered either by a minimal SCT of a low (0.01–0.3 mA) or a high (0.8–1.0 mA) current in a random order. After eliciting a motor response with a predetermined SCT, synthetic resin was injected via the needle. After postmortem dissection of the injection site, the localization of the resin deposition was determined verifying the final position of the needle tip. Depending on the proximity of resin deposition to the nerve epineurium, the needle tip placement was considered either as a close or a distant NNP.

Results: A total of 235 punctures were performed. Ninety‐one punctures were carried out with low SCT and 92 with a high SCT. Fifty‐two punctures served as a control (1.8–2.0 mA). All injectates following both high or low SCT were considered ‘close needle tip to nerve placement’, whereas 27 of 52 injectates of the control group appeared distant to nerve epineurium.

Conclusion: Regardless of the applied SCT, i.e. high or low, all resin deposition was found adjacent to nerve epineurium. These findings suggest that high and low SCT result in equivalent needle tip localization in pigs.
Modafinil reduces patient‐reported tiredness after sedation/analgesia but does not improve patient psychomotor skills
Authors: GALVIN E. , BOESJES H. , HOL J. , UBBEN J. F. , KLEIN J. , VERBRUGGE S. J. C.
Published: August 2009

Background: Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia.

Methods: Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment.

Results: Sixty‐seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05.

Conclusion: Modafinil reduces patient‐reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills.
Comparison of desaturation and resaturation response times between transmission and reflectance pulse oximeters
Authors: CHOI S. J. , AHN H. J. , YANG M. K. , KIM C. S. , SIM W. S. , KIM J. A. , KANG J. G. , KIM J. K. , KANG J. Y.
Published: August 2009

Background: In general, there is a response time between actual arterial hypoxemia and its detection by pulse oximeters. We compared the desaturation and resaturation response times between two types of pulse oximeters, transmission and reflectance pulse oximeters, to find out which oximeter has a more rapid response time.

Methods: Thirty‐three ASA 1 or 2 patients were enrolled in this study. A transmission pulse oximeter was placed on the index finger and a reflectance pulse oximeter was placed on the forehead and monitored simultaneously. After the induction of general anesthesia without pre‐oxygenation, we waited until the oxygen saturation value of any of two pulse oximeters declined to 90%, and then mask ventilation was started with 100% oxygen. Oxygen saturation was recorded at an interval of 2 s during this time.

Results: The desaturation response time of SpO2 to 95% after apnea was 82.0 s (interquartile range: 67.0–98.5 s) vs. 94.0 s (interquartile range: 84.0–106.5 s) (P<0.001) and SpO2 to 90% was 94.0 s (interquartile range: 75.5–109.5 s) vs. 100.0 s (interquartile range: 84.5–114.5 s) (P<0.001) in the reflectance and transmission oximeters, respectively. The resaturation response time from mask ventilation to 100% SpO2 was 23.2±5.6 vs. 28.9±7.6 s (P<0.001) in the reflectance and transmission oximeters, respectively.

Conclusion: In clinical situations in which rapid changes in oxygen saturation are expected, we recommend the forehead reflectance pulse oximeter because it responds more quickly in detecting oxygen desaturation and resaturation compared with the transmission pulse oximeter.