bluuebunny/crossref_metadata_2025 huggingface dataset:
Health management for people with intellectual disabilities in primary care; impact on basic physical functions
Authors: Van Schrojenstein Lantman‐de Valk H. , Veenstra M. , Straetmans J. , Metsemakers J. , Curfs L.
Published: October 2008

Background: Health problems are more frequently reported in people with intellectual disabilities (ID) in primary care than in the general population. In this study we aimed to explore the basic health needs in persons with ID in order to promote a more proactive approach to health care in primary care settings. Method: The design was a nested (1:5) case‐control study across 100 practices in the Netherlands. 868 persons with ID were matched with 4305 controls (age, gender, practice). Results: People with ID consulted their GP 1.7 times more often than control participants. Among the presented health problems, sleep problems and other complaints which could not be classified as a disease were the most commonly reported. Prescriptions of laxatives as well as medication for treatment of peptic ulcers were significantly higher among persons with ID. These data indicate a high prevalence of problems in basic physical functions such as sleeping, eating and defecation in people with ID. Conclusion: We intend to further explore these health problems and the way they are addressed. Through focus group interviews of people with ID and their carers, general practitioners, practice nurses, specialist physicians for people with ID and care providers, we intend to develop models for tailoring primary health care to the specific and basic needs of persons with ID. The presentation will cover the evidence base to date and discuss our further research plans.
Molecular karyotyping is important in determining the cause of behavioural phenotypes
Authors: De Ravel T. J. L. , Swillen A. , Willekens D. , Descheemaeker M.‐J. , Govers V. , Borghgraef M. , Vermeesch J. R. , Fryns J.‐P.
Published: October 2008

Background: The cytogenetic delineation and behavioural phenotype of syndromes has evolved from the chromosome level, through FISH (microdeletions syndromes, such as PWS, VCFS, SMS, del1p36) to molecular karyotyping (array CGH). The new syndromes being outlined in recent years account for rarer microdeletions and microduplications, in which the behavioural phenotype is not always well characterized. Method: We have screened by array CGH more than 2000 patients, of which almost 400 have cytogenetic imbalances. We present a subset of these patients, in which the behaviour was an important component of the motivation for molecular karyotyping. Results: Three case studies: 1) A boy with severe feeding problems, speech delay, stereotypic and autistic behaviour. He is dysmorphic and has an intellectual disability. Molecular karyotyping showed a de novo microdeletion of chromosome 15q13.2. 2) A 3‐year old girl with difficult behaviour, including negative vocalizations, aggression and repetitive rocking. She has poor weight gain, difficulty in falling asleep and wakes early. She is dysmorphic, has a developmental IQ of 67, a paternally inherited microdeletion of chromosome 9p21.3 and a de novo microduplication of chromosome 17p11.2. 3) A 5‐year old girl with intellectual disability who participates in interactive play but remains slow in task execution. Her balance is poor when standing and walking, She does not evidence satiety for food and constantly air‐swallows. Molecular karyotyping revealed a de novo microdeletion of chromosome 9qter. Conclusion: The molecular karyotyping results encourage its use in finding the cause of intellectual disability. With the assistance of international collaboration via common databases, such as Decipher, pinpointing and understanding the underlying genes contributing to the overall clinical picture, especially behaviour, will become a reality.
Cognitive‐behavioural and autistic features of children with subtelomeric deletions
Authors: Fisch G. S. , Carey J. , Youngblom J. , Simensen R. , Battaglia A.
Published: October 2008

Background: Cognitive‐behavioural features of children with subtelomeric deletions have, to date, not been systematically assessed. Methods: We examined 29 children with del2q37 [n = 7], del8p23 [n = 7], del11q25 [n = 3], or 4p16 [n = 12], from 9 sites in the US and Europe using a neuropsychological battery to evaluate cognitive ability, adaptive behaviour, emotionality and temperament, attentiveness/hyperactivity, and autistic‐like features. Results: We found 10/29 (34%) of our sample with CARS scores ≥30. That is, more than a third of the sample could be diagnosed as autistic. Cognitive deficits ranged from low‐normal to severe. In addition, each disorder was associated with a distinct cognitive‐behavioural profile. Children with de11q25 had significantly higher cognitive abilities, while those with del4p16 were significantly lower. Adaptive behaviour was significantly higher among children with 11q25. Cognitive ability and adaptive behaviour profiles were also statistically significantly different among the groups. Attention deficits and hyperactivity [ADHD] were also noted in 14/29 [47%] of the sample of children assessed. Conclusions: The study of the behavioural phenotypes associated with subtelomeric deletions is starting to demonstrate behavioural phenotypes for rare genetic disorders.
Genetics of autism
Authors: Freitag C. M.
Published: October 2008

Autism and Autism Spectrum disorders (ASD) are predominately genetically determined. Phenotypically, ASD are heterogeneous disorders, presenting with a broad range of intellectual and language abilities as well as autism specific impairments in communication, social interaction, and stereotyped, repetitive behaviour. Twin studies have shown that the narrow as well as the broad phenotype of ASD are strongly genetically determined. Genetic research has elicited a few monogenic disorders, as well as genetic syndromes, which are known to cause ASD. Several candidate genes have been assessed for association with the disorder. In addition, copy number variations have recently been reported to be more frequent in ASD than in control individuals. The lecture addresses aspects of the ASD phenotype which are relevant for genetic studies, the most important genetic findings and their implication for genetic counselling in ASD.
Non‐syndromal autism: Neuropsychology
Authors: Bolte S.
Published: October 2008

The clinical phenotype of idiopathic autism and associated conditions according to ICD‐10 and DSM‐IV‐TR is defined by deficits in social reciprocity and communication as well as by stereotypic interests and activities. The cognitive phenotype is less understood, but there is robust evidence that it is characterized by attention to detail (local processing, weak central coherence), a pattern of executive dysfunction, problems in theory of (own and other) mind and altered affect processing. Neuroimaging has identified anatomic and functional alterations being likely to underlie cognitive features in autism. In this talk, current psychological approaches to autism spectrum disorders and corresponding neurobiological findings are briefly summarized. Moreover, preliminary results from a controlled longitudinal study on the neural effects of cognitive training (‘Neuropsychotherapy’) are presented.
Is there an increased prevalence of autistic spectrum disorders in people with 22q11 Deletion Syndrome?
Authors: Murphy K. C. , Sundram F.
Published: October 2008

22q11 Deletion Syndrome (22q11DS) is a relatively common interstitial deletion disorder with a minimum prevalence of approximately 1:5000 live births. Although considerable phenotypic variability occurs, common clinical features include a typical dysmorphology, cleft palate, congenital heart defects and a characteristic behavioural phenotype. While much of the literature has focussed on the well documented association between 22q11DS and schizophrenia, there is now increasing attention on the prevalence of autistic spectrum disorders (ASD) in 22q11DS. The current evidence implicating ASD in 22q11DS and the implications for the clinical management of affected individuals will be discussed.
Rett Syndrome and long‐term disorder profile
Authors: Smeets E. , Schrander‐Stumpel C. , Curfs L.
Published: October 2008

Since the identification of mutations in MECP2 in females with clinical Rett syndrome, numerous efforts have been made to understand phenotype‐genotype relationships. Most of these studies were conducted by examining the type and localization of these mutations in the gene in relation to clinical severity. It seemed unsatisfactory, in view of the age range and variable severity, to look only at the type and localization of the mutation in MECP2 in trying to establish a phenotype/genotype relationship. Describing each RTT individual after a long term follow up and grouping females with the same disorder history and same MECP2 mutation is therefore appropriate.

Complete clinical and molecular data were obtained on 103 females. The guidelines for reporting manifestations common in Rett syndrome were used in the evaluation of clinical severity. The individuals were grouped according to similar disorder profiles on long‐term follow up. In a cohort of 103 females clinically diagnosed with Rett syndrome, 91 had a detectable MECP2 mutation. 60% still sit and walk. Hand use is preserved or reduced in 44%. Speech has been lost in the majority (87%). Epilepsy was problematic in about 30%. Scoliosis, severe kyphosis or a combination of both was present in 27%, needing surgery in 13%.

Description of the profile of the disorder and long‐term clinical history facilitated the grouping of females with the same MECP2 mutation and a similar history. This approach will contribute more to the understanding of the ongoing pathology in Rett syndrome relative to the specific character of the involved MECP2 mutation. Some examples of these disorder profiles will be discussed.
Prevalence of myofascial temporomandibular disorder in US community women
Authors: JANAL M. N. , RAPHAEL K. G. , NAYAK S. , KLAUSNER J.
Published: October 2008

Summary  This study estimates the prevalence of the myofascial subtype of temporomandibular disorders (M‐TMD) defined by Research Diagnostic Criteria (RDC), and relates that prevalence to the surveyed report of facial pain. From among 20 000 women selected at random in the NY metropolitan area who completed a telephone survey of facial pain, 2000 were invited for an RDC/TMD examination; 782 examinations were completed. Prevalence was estimated in analyses that were weighted to correct sampling biases. Differences among demographic strata were evaluated with logistic regression. The prevalence of M‐TMD was estimated to be 10·5% (95% CL = 8·5–13·0%). Prevalence was significantly higher among younger women, among women of lower socio‐economic status, among Black women, and among non‐Hispanic women. The report of facial pain in the telephone survey (10·1%) had high specificity for M‐TMD diagnosis (94·7%), but low sensitivity (42·7%). M‐TMD is a fairly common disorder among American women. Among those reporting facial pain during the last month, half met RDC palpation criteria for M‐TMD; thus, a formal physical examination is imperative to establish this diagnosis. Prevalence varies with age, socio‐economic status, race and Hispanic ethnicity. A substantial number of RDC‐diagnosed cases of M‐TMD did not report facial pain in the survey; the reason for this requires further study.
Are patients with chronic fatigue syndrome just ‘tired’ or also ‘sleepy’?
Authors: NEU DANIEL , HOFFMANN GUY , MOUTRIER ROBERT , VERBANCK PAUL , LINKOWSKI PAUL , LE BON OLIVIER
Published: October 2008

It is presently unclear whether chronic fatigue syndrome (CFS) patients exhibit daytime sleepiness in addition to fatigue. Both, fatigue, such as that seen in CFS patients, and excessive daytime sleepiness, such as in sleep apnea–hypopnea syndrome (SAHS), remain poorly understood. Both daytime conditions are generally related to unrefreshing sleep and show affective symptoms. This study’s objective was to contribute to the understanding of the relationship between fatigue and sleepiness in CFS patients not co‐morbid for primary sleep or psychiatric disorders. We compared 16 untreated CFS patients (mean age 32.8, all females) with 13 untreated SAHS (mean age 47.7, all females) patients and 12 healthy controls (mean age 32.2, all females). Objective sleepiness was measured using multiple sleep latency tests (MSLT). Subjective sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Fatigue Severity Scale, respectively. Mean Sleep Latency (SL) on the MSLT was significantly shorter in SAHS patients than in CFS patients and CFS patients showed significantly shorter mean SL than matched controls but within normal range. Subjective sleepiness was greatest in SAHS patients and subjective fatigue was highest in CFS patients. Affective symptoms showed highest intensities in CFS patients. While higher than the control group on all measures, compared to SAHS, the CFS group had higher subjective fatigue and lower subjective and objective sleepiness. Despite possible overlap in symptoms and signs of both daytime conditions, our data indirectly support the clinical distinction between fatigue and sleepiness.
24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat‐psychomotor vigilance task
Authors: CHRISTIE MICHAEL A. , MCKENNA JAMES T. , CONNOLLY NINA P. , MCCARLEY ROBERT W. , STRECKER ROBERT E.
Published: October 2008

A novel animal‐analog of the human psychomotor vigilance task (PVT) was validated by subjecting rats to 24 h of sleep deprivation (SD) and examining the effect on performance in the rat‐PVT (rPVT), and a rat multiple sleep latency test (rMSLT). During a three‐phase (separate cohorts) crossover design, vigilance performance in the rPVT was compared with 24 h SD‐induced changes in sleepiness assessed by polysomnographic evaluation and the rMSLT. Twenty‐four hours of SD was produced by brief rotation of activity wheels at regular intervals in which the animals resided throughout the experiment. In the rPVT experiment, exercise controls (EC) experienced the same overall amount of locomotor activity as during SD, but allowed long periods of undisturbed sleep. After 24 h SD response latencies slowed, and lapses increased significantly during rPVT performance when compared with baseline and EC conditions. During the first 3 h of the recovery period following 24 h SD, polysomnographic measures indicated sleepiness. Latency to fall asleep after 24 h SD was assessed six times during the first 3 h after SD. Rats fell asleep significantly faster immediately after SD, than after non‐SD baseline sessions. In conclusion, 24 h of SD in rats increased sleepiness, as indicated by polysomnography and the rMSLT, and impaired vigilance as measured by the rPVT. The rPVT closely resembles the human PVT test widely used in human sleep research and will assist investigation of the neurobiologic mechanisms that produce vigilance impairments after sleep disruption.
Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs
Authors: ALBARELLOS G. A. , KREIL V. E. , AMBROS L. A. , WAXMAN S. , MONTOYA L. , TARRAGONA L. , QUAINE P. C. , HALLU R. E. , REBUELTO M.
Published: October 2008

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD):AUC(0–∞)4.20 ± 1.66 μg·h/mL;Cmax6.64 ± 1.38 μg/mL; Vz4.80 ± 0.91 L/kg;Clt2.64 ± 0.84 L/h·kg;t½λ1.35 ± 0.40 h andMRT1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD):Cmax, 0.30 ± 0.17 and 0.17 ± 0.09 μg/mL;tmax, 1.75 ± 0.76 and 0.69 ± 0.30 h;t½λ, 2.92 ± 0.79 and 1.53 ± 1.28 h andMRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations aboveMIC90 = 0.5 μg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.
P‐glycoprotein in intestines, liver, kidney and lymphocytes in horse
Authors: TYDÉN E. , TALLKVIST J. , TJÄLVE H. , LARSSON P.
Published: October 2008

P‐glycoprotein (P‐gp) is an important drug transporter, which is expressed in a variety of cells, such as the intestinal enterocytes, the hepatocytes, the renal tubular cells and the intestinal and peripheral blood lymphocytes. We have studied the localization and the gene and protein expression of P‐gp in these cells in horse. In addition we have compared the protein sequence of P‐gp in horse with the protein sequences of P‐gp in several other species. Real time RT‐PCR and Western blot showed gene and protein expression of horse P‐gp in all parts of the intestines, but there was no strict correlation between these parameters. Immunohistochemistry showed localization of P‐gp in the apical cell membranes of the enterocytes and, in addition, staining was observed in the intestinal intraepithelial and lamina propria lymphocytes. Peripheral blood lymphocytes also stained for P‐gp, and gene and protein expression of P‐gp were observed in these cells. There was a high gene and protein expression of P‐gp in the liver, with P‐gp‐immunoreactivity in the bile canalicular membranes of the hepatocytes. Gene and protein expression of P‐gp were found in the kidney with localization of the protein in different parts of the nephrons. Protein sequence alignment showed that horse P‐gp has two amino acid insertions at the N‐terminal region of the protein, which are not present in several other species examined. One of these is a 99 amino acid long sequence inserted at amino acid positions 23–121 from the N‐terminal. The other is a six amino acid long sequence present at the amino acid positions 140–145 from the N‐terminal. The results of the present study indicate that P‐gp has an important function for oral bioavailability, distribution and excretion of substrate compounds in horse.
Multiple oral dosing of valacyclovir in horses and ponies
Authors: GARRÉ B. , BAERT K. , NAUWYNCK H. , DEPREZ P. , DE BACKER P. , CROUBELS S.
Published: October 2008

The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC50‐value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC50‐value of 1.7 μg/mL, i.e. EC50of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC50‐value of 3.0 μg/mL, i.e. EC50of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36–1.17 μg/mL and 0.11–0.23 μg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC50‐value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC50.
Dispositions and residue depletion of enrofloxacin and its metabolite ciprofloxacin in muscle tissue of giant freshwater prawns (Macrobrachium rosenbergii)
Authors: POAPOLATHEP A. , JERMNAK U. , CHAREONSAN A. , SAKULTHAEW C. , KLANGKAEW N. , SUKASEM T. , KUMAGAI S.
Published: October 2008

Fates and residue depletion of enrofloxacin (ER) and its metabolite ciprofloxacin (CP) were examined in giant freshwater prawns, Macrobrachium rosenbergii, following either single oral (p.o.) administration of ER at a dosage of 10 mg/kg body weight (b.w.) or medicated‐feed treatment at the feeding concentration of 5 g/kg of feed for five consecutive days. The concentrations of ER and CP in prawn muscle tissues were measured simultaneously using high‐performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations of ER and CP were below the detection limit (LOD, 0.015 μg/g for ER; 0.025 μg/g for CP) after 360 and 42 h, following single p.o. administration respectively. Peak muscle concentration (Cmax) of ER was 1.98 ± 0.22 μg/g whereas CP was measurable at concentrations close to the detection limit of the analytical method after p.o. administration at a single dosage of 10 mg/kg b.w. The concentration of ER in prawn muscle tissue with respect to time was analyzed with a non‐compartmental pharmacokinetic model. The elimination half‐life and area under the curve of ER were 39.33 ± 7.27 h and 168.7 ± 28.7 μg·h/g after p.o. administration at a single dose of 10 mg/kg·b.w. respectively. In medicated‐feed treated group, ER was detectable in prawn muscle tissue 11 days postdosing at the dose of 5 g/kg of feed for five consecutive days, which is the value corresponding to the maximum residue limit (MRL) of ER in animal products. The maximum concentrations of ER and CP were 2.77 ± 0.91 and 0.06 ± 0.006 μg/g during medicated‐feed treatment and postdosing respectively. The values of elimination half‐life and absorption half‐life of ER after single p.o. administration at a dosage of 10 mg/kg b.w. corresponded well with the values determined from medicated‐feed treated group, showing 41.01 ± 6.62 and 11.36 ± 3.15 h respectively in M. rosenbergii. Based on data derived from this study, to avoid the ER residue in prawn muscle, it should take at least 11 days postcessation of medicated feed containing ER at the dose concentration of 5 g/kg of feed twice a day at a rate of 1% of total body weight for five consecutive days to wash out the drug from the muscle of M. rosenbergii.
Medical students’ attitudes to psychiatric illness in primary care
Authors: Dixon Robert P , Roberts Lesley M , Lawrie Stephen , Jones Lisa A , Humphreys Martin S
Published: October 2008

Context  Previous research has shown that general practitioners (GPs) hold negative attitudes towards patients with schizophrenia, which do not simply reflect the nature or chronic aspects of the illness. This study aimed to describe the attitudes and predicted behaviour of medical students towards patients with mental illness in a primary care setting and to investigate whether these were affected by the students’ level of training.

Methods  A sample of 1239 students from the University of Birmingham Medical School were each given one of four case vignettes, all of which were identical except that the patient involved was described as having a previous diagnosis of, respectively, schizophrenia, depression, diabetes or no illness. Students rated their level of agreement with 12 attitudinal statements relating to the vignette.

Results  A total of 1081 (88%) students responded to the questionnaire. Students were generally less favourable in their responses to patients with either schizophrenia or depression. They would not be as happy to have them on their list, believed they would consume more time and considered they would be less likely to comply with advice and treatment. They expressed more concern about the risk of violence, the potential welfare of children and the possibility of illegal drug and excessive alcohol use. General clinical and psychiatric training had little effect on these reactions.

Conclusions  Patients with mental illness provoke less favourable responses in medical students, which are not altered by furthering education. Undergraduate primary care‐based mental health education should be re‐evaluated to ensure that students develop an empathetic and positive approach to mental health patients and their treatment.
Oculimacula yallundae lifestyle revisited: relationships between the timing of eyespot symptom appearance, the development of the pathogen and the responses of infected partially resistant wheat plants
Authors: Blein M. , Levrel A. , Lemoine J. , Gautier V. , Chevalier M. , Barloy D.
Published: October 2008

Possible relationships between the timing of eyespot symptom appearance, the development of Oculimacula yallundae and the responses of infected wheat plants were investigated. By comparing, for 45 days after inoculation (d.a.i.), eyespot‐ and mock‐inoculated coleoptiles and leaf sheaths of a wheat line carrying the Pch1 partial resistance gene, this study showed that cell death, used as a criterion for symptom appearance, occurred on the first leaf sheath around 30 d.a.i. Monitoring of O. yallundae development by optical and scanning electron microscopy revealed that the fungus colonized the coleoptile within 30 d.a.i. It then attacked the first leaf sheath and underwent morphological and growth modifications. For 30 d.a.i., infected plants responded by local accumulations of H2O2 and callose in coleoptile epidermal cells and by up‐regulation of pathogenesis‐related (PR) genes. From 30 d.a.i., natural browning occurred in the first leaf sheath epidermis and the expression level of PR genes, determined by quantitative PCR, significantly increased in infected plants. These results show that the wheat/O. yallundae interaction is characterized by two distinct phases: the asymptomatic phase and the symptomatic phase. The possibility that O. yallundae should be considered hemibiotrophic rather than necrotrophic is discussed.
Monitoring expression of selected Plasmodiophora brassicae genes during clubroot development in Arabidopsis thaliana
Authors: Siemens J. , Graf H. , Bulman S. , In O. , Ludwig‐Müller J.
Published: October 2008

The expression of 12 cDNAs from Plasmodiophora brassicae, among them two novel sequences, was determined during clubroot development on Arabidopsis thaliana. The aim was to find cDNAs expressed at distinct stages of pathogenesis. The relative amount of infection with active plasmodia could be estimated using PbActin cDNA as an internal standard. Two cDNAs, PbBrip9 and PbCC249, were strongly expressed at stages of disease development corresponding to the occurrence of sporulating plasmodia. Therefore, it should be possible in the future to find more cDNAs which could be used as markers for certain stages of clubroot development.
Diversity of Ralstonia solanacearum causing potato bacterial wilt in Iran and the first record of phylotype II/biovar 2T strains outside South America
Authors: Nouri S. , Bahar M. , Fegan M.
Published: October 2008

The diversity of 40 strains of Ralstonia solanacearum causing bacterial wilt of potato in the major potato‐growing areas of Iran was assessed. Based on rep‐PCR genomic fingerprinting, strains fell into two distinct groups. The first group contained 37 of the 40 strains and the second consisted of three strains from a narrow tropical region in Iran. The three strains from the narrow tropical region were found to be phenotypically and genotypically most similar to R. solanacearum biovar 2T strains, whereas all other strains were phenotypically and genotypically identified as being R. solanacearum biovar 2/race 3. Phylogenetic analysis of endoglucanase gene sequence information of two of the strains from the tropical region revealed that they belonged to phylotype II of the R. solanacearum species complex and had 100% sequence similarity to a biovar 2T strain from potato in Peru. This is the first report of the presence of R. solanacearum phylotype II/biovar 2T in Iran and the first report of the existence of this group of R. solanacearum outside South America.
A new Fusarium lineage within the Gibberella fujikuroi species complex is the main causal agent of mango malformation disease in Brazil
Authors: Lima C. S. , Pfenning L. H. , Costa S. S. , Campos M. A. , Leslie J. F.
Published: October 2008

Mango malformation is a serious disease in tropical and subtropical areas of the world and has been attributed to various Fusarium spp., including F. mangiferae, F. proliferatum, F. sacchari, F. sterilihyphosum and F. subglutinans. Isolates of Fusarium associated with mango malformation from Brazil, Egypt, India, South Africa and the United States were evaluated through amplified fragment length polymorphisms (AFLPs) and partial DNA sequences of the genes encoding β‐tubulin (tub2) and translation elongation factor 1‐α (tef1). These techniques were used to delimit species and to estimate the genetic and phylogenetic relatedness of the isolates. In the AFLP analysis, most of the Brazilian isolates formed a unique cluster. Additionally, one small cluster was formed by isolates of F. sterilihyphosum from Brazil and South Africa, and another by isolates of F. mangiferae from Egypt, India, South Africa and the United States. In the phylogenetic analysis, most of the Brazilian isolates represented a new phylogenetic lineage in the Gibberella fujikuroi species complex, where they formed a sister clade to F. sterilihyphosum. Representatives of both clades were pathogenic to mango (cv. Tommy Atkins) and Koch's postulates were completed for isolates belonging to the new lineage and to F. sterilihyphosum. Thus, most of the mango malformation disease in Brazil is due to a distinct phylogenetic lineage of Fusarium, and to a lesser extent by F. sterilihyphosum. The new phylogenetic lineage identified in this study, together with F. mangiferae and F. sterilihyphosum, are the only known taxa of Fusarium proven to be capable of causing mango malformation.
Differential CXC Receptor Expression in Colorectal Carcinomas
Authors: Rubie C. , Kollmar O. , Frick V. O. , Wagner M. , Brittner B. , Gräber S. , Schilling M. K.
Published: October 2008

In this study, we aimed to assess the expression profile of chemokine receptors CXCR1–4 in inflammatory and malignant colorectal diseases and corresponding hepatic metastases of synchronous and metachronous origin to elucidate their role in colorectal cancer (CRC) progression and metastasis. Chemokine receptor expression was assessed by quantitative real‐time PCR, immunohistochemistry (IHC) and Western blot analysis in resection specimens from patients with ulcerative colitis (UC, n = 25), colorectal adenomas (CRA, n = 8), different stages of CRC (n = 48) as well as colorectal liver metastases (CRLM) along with their corresponding primary colorectal tumours (n = 16). While none of the chemokine receptors were significantly upregulated or downregulated in UC or CRA tissues, CXC receptors 1, 2 and 4 demonstrated a significant increase in expression in all tumour stages of CRC specimens with CXCR4 correlating with tumour grading (P < 0.05). On the other hand, CXCR3 showed no significant upregulation in either tumour stage, but significant overexpression in CRLM. While CXCR4 demonstrated significant upregulation in both tumour entities, IHC analysis revealed that the predominate cell type expressing CXCR4 in CRC is represented by tumour cells, whereas in CRLM the majority of positive CXCR4 signals is due to hepatocytes along the tumour invasion front. In conclusion, our findings show a very differential expression pattern of the four receptors in colorectal carcinomas and their corresponding liver metastases with prominent expression profiles that indicate a potential role in the pathogenesis of CRC.
Adjuvants LT‐K63 and CpG Enhance the Activation of Dendritic Cells in Neonatal Mice
Authors: Hannesdottir S. G. , Olafsdottir T. A. , Giudice G. D. , Jonsdottir I.
Published: October 2008

Dendritic cells (DC) play a major role in the priming of T cells and initiating specific immune responses. We assessed the effects of the adjuvants LT‐K63 and CpG on neonatal DC in vivo and in vitro. Cytokine levels (IL‐10, IL‐12p70 and IL‐12p40/IL‐23p40) were measured and the expression of the activation markers CD86, CD40 and MHCII on CD11c+ DC was analysed by using FACS. The proportion of MHCIIhigh CD11c+ DC was higher in neonatal mice immunized with a pneumococcal conjugate (PncTT) and LT‐K63 or CpG compared with that when PncTT was alone. In vitro stimulation with LT‐K63 enhanced the expression of CD86 more on CD11c+ DC from spleens of mice immunized as neonates than those immunized as adults, whereas in vitro stimulation with CpG enhanced the expression of CD86 and CD40 on CD11c+ DC similarly in both age groups. CpG stimulation in vitro enhanced IL‐10 and IL‐12(p70) production in mice immunized as neonates with PncTT and either adjuvant, but not PncTT alone. The adjuvants LT‐K63 and CpG enhance the activation of CD11c+ DC in mice immunized as neonates and can thereby overcome one of the limiting factors in the initiation of the immune response to conjugate vaccines in early life. The fact that neonatal DC are more susceptible to stimulation with either adjuvant, LT‐K63 or CpG, could imply that neonatal CD11c+ DC are more easily activated than adult CD11c+ DC, and/or be a consequence of the predominance of different DC subsets in neonatal and adult mice.
Post‐partum depression in Kinshasa, Democratic Republic of Congo: Validation of a concept using a mixed‐methods cross‐cultural approach
Authors: Bass Judith K. , Ryder Robert W. , Lammers Marie‐Christine , Mukaba Thibaut N. , Bolton Paul A.
Published: October 2008

Objective  To determine if a post‐partum depression syndrome exists among mothers in Kinshasa, Democratic Republic of Congo, by adapting and validating standard screening instruments.

Methods  Using qualitative interviewing techniques, we interviewed a convenience sample of 80 women living in a large peri‐urban community to better understand local conceptions of mental illness. We used this information to adapt two standard depression screeners, the Edinburgh Post‐partum Depression Scale and the Hopkins Symptom Checklist. In a subsequent quantitative study, we identified another 133 women with and without the local depression syndrome and used this information to validate the adapted screening instruments.

Results  Based on the qualitative data, we found a local syndrome that closely approximates the Western model of major depressive disorder. The women we interviewed, representative of the local populace, considered this an important syndrome among new mothers because it negatively affects women and their young children. Women (n = 41) identified as suffering from this syndrome had statistically significantly higher depression severity scores on both adapted screeners than women identified as not having this syndrome (n = 20; P < 0.0001).

Conclusions  When it is unclear or unknown if Western models of psychopathology are appropriate for use in the local context, these models must be validated to ensure cross‐cultural applicability. Using a mixed‐methods approach we found a local syndrome similar to depression and validated instruments to screen for this disorder. As the importance of compromised mental health in developing world populations becomes recognized, the methods described in this report will be useful more widely.
A significant increase in kdr in Anopheles gambiae is associated with an intensive vector control intervention in Burundi highlands
Authors: Protopopoff Natacha , Verhaeghen Katrijn , Van Bortel Wim , Roelants Patricia , Marcotty Tanguy , Baza Dismas , D’Alessandro Umberto , Coosemans Marc
Published: October 2008

Objectives and Methods  In Burundi, the occurrence of the knock down resistance (kdr) mutation in Anopheles gambiae sensu lato (s.l.) was determined for six consecutive years within the framework of a vector control programme. Findings were also linked with the insecticide resistance status observed with bioassay in An. gambiae s.l. and An. funestus.

Results  The proportion of An. gambiae s.l. carrying the East Leu‐Ser kdr mutation was 1% before the spraying intervention in 2002; by 2007 it was 86% in sprayed valleys and 67% in untreated valleys. Multivariate analysis showed that increased risk of carrying the kdr mutation is associated with spraying interventions, location and time. In bioassays conducted between 2005 and 2007 at five sites, An. funestus was susceptible to permethrin, deltamethrin and DDT. Anopheles gambiae s.l. remained susceptible or tolerant to deltamethrin and resistant to DDT and permethrin, but only when kdr allele carriers reached 90% of the population.

Conclusions  The cross‐resistance against DDT and permethrin in Karuzi suggests a possible kdr resistance mechanism. Nevertheless, the homozygous resistant genotype alone does not entirely explain the bioassay results, and other mechanisms conferring resistance cannot be ruled out. After exposure to all three insecticides, homozygote individuals for the kdr allele dominate among the surviving An. gambiae s.l. This confirms the potential selection pressure of pyrethroids on kdr mutation. However, the high occurrence of the kdr mutation, even at sites far from the sprayed areas, suggests a selection pressure other than that exerted by the vector control programme.
Successful stent placement for hepatic venous outflow obstruction in pediatric living donor liver transplantation, including a case series review
Authors: Sakamoto Seisuke , Ogura Yasuhiro , Shibata Toshiya , Haga Hironori , Ogawa Kohei , Oike Fumitaka , Ueda Mikiko , Egawa Hiroto , Takada Yasutsugu , Uemoto Shinji
Published: October 2008

Abstract: HVOO may lead to graft dysfunction in LDLT. Balloon angioplasty is the first treatment for HVOO. However, some cases with recurrent HVOO need multiple interventions and require stent placement. The authors describe a pediatric case with recurrent HVOO requiring multiple stent placements. Her symptoms related to HVOO finally disappeared after the third stenting. A year later, follow‐up liver biopsy did not show any dramatic change in perivenular fibrosis. From a review of our pediatric cases with HVOO requiring stent placement, the majority of them lost the grafts, because the timing of stent placement was too late to prevent the progression of fibrosis. In conclusion, stent placement should be considered in select cases of HVOO. Serial liver biopsies evaluating the degree of fibrosis are essential in determining the timing of stent placement.
Heart transplantation in infants with idiopathic hypertrophic cardiomyopathy
Authors: Ragni Luca , Biagini Elena , Picchio Fernando M. , Prandstraller Daniela , Leone Ornella , Berardini Alessandra , Perolo Antonella , Grigioni Francesco , Di Diodoro Lara , Gargiulo Gaetano , Arbustini Eloisa , Rapezzi Claudio
Published: October 2008

Abstract:  Whereas it is well known that idiopathic HCM can present in newborns and infants, little information is available on HT in this very young age group. We report a series of 17 infants with idiopathic HCM, including two neonates with rapidly progressive severe HF for whom HT was necessary. When HF manifests in a newborn/infant with idiopathic HCM and extreme cavity size reduction, the possibility of a rapidly progressive clinical course should be anticipated and HT may become the only available therapeutic solution.
Urinary excretion of ganciclovir contributes to improvement of adenovirus‐associated hemorrhagic cystitis after allogeneic bone marrow transplantation
Authors: Nakazawa Yozo , Suzuki Takefumi , Fukuyama Tetsuhiro , Katsuyama Yoshihiko , Tanaka Miyuki , Yanagisawa Ryu , Sakashita Kazuo , Shiohara Masaaki , Koike Kenichi
Published: October 2008

Abstract:  A nine‐yr‐old girl developed AdV‐associated HC after bone marrow transplantation. Intravenous GCV markedly reduced urinary AdV DNA loads and improved clinical findings. This appeared to result partly from a high concentration of GCV in urine. GCV may be effective for AdV‐induced HC without definitive disseminated infection.
Double apheresis of peripheral blood stem cells in a single day in children mobilized by granulocyte colony‐stimulating factor for transplantation
Authors: Okamoto Yasuhiro , Watanabe Tsutomu , Watanabe Hiroyoshi , Onishi Toshihiro , Kawano Yoshifumi
Published: October 2008

Abstract:  Due to the movement of hematopoietic stem cells through the bone marrow environment, it may be possible to effectively harvest peripheral blood stem cells in a second apheresis within a few hours after a first apheresis. In a retrospective analysis, 107 aphereses were performed in consecutive 33 pediatric and six healthy pediatric donors who received granulocyte‐colony stimulating factor at 10 μg/kg/day or 400 μg/m2/day for five days. The median age and weight of cases were seven yr (range 1–19) and 20 kg (range 8–87). The toxicities related to apheresis procedure were minimal in both aphereses. In 22 double aphereses, the average number of CD34‐positive cells per body weight (kg) collected was 5.3 ± 4.2 (range 0.6–16.6) and 4.7 ± 3.1 (range 0.2–10.9) × 106 in the first and second aphereses, respectively (p = 0.569). Multivariate analysis showed that number of CD34‐positive cells collected in the first apheresis (p = 0.008) was an independent factor of increased CD34‐positive cells in the second apheresis. Double apheresis in a single day was feasible and this procedure may be able to lessen the burden of apheresis compared to two consecutive‐day apheresis.
Multidimensional Adherence Classification System: Initial development with adolescent transplant recipients
Authors: Simons Laura E. , Gilleland Jordan , Blount Ronald L. , Amaral Sandra , Berg Alexandra , Mee Laura L.
Published: October 2008

Abstract:  As transplantation has progressively become a more viable option for children with life‐threatening illness, ensuring that adolescents do not lose their new organ secondary to medication non‐adherence is paramount. The first step to addressing non‐adherence is adequate assessment of this construct. In this investigation, we introduce the MACS. The MACS includes self‐report and drug assay levels. Self‐report is a subjective measure with a low false‐positive rate, but is vulnerable to social desirability. Drug assays are an objective measure of drug ingestion, but values suggestive of non‐adherence may be influenced by medical complications and timing. The MACS builds on the strengths of both methods and attempts to contain their weaknesses. The sample in this study consisted of 82 adolescent solid organ transplant recipients. The non‐adherence rate using the MACS in this sample was 61%. Initial data to support this system are promising. The occurrence of rejection episodes and mortality were significantly related to membership in the Genuinely Non‐adherent category. Beyond providing initial support for the MACS, we discuss the clinical implications of this adherence classification system.
Unrelated cord blood transplantation in children with severe congenital neutropenia
Authors: Yesilipek M. Akif , Tezcan Gulsun , Germeshausen Manuela , Kupesiz Alphan , Uygun Vedat , Hazar Volkan
Published: October 2008

Abstract:  SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG‐CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG‐CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA‐matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 × 107/kg and CD34+  cell number was 3, 74 × 105/kg in Case 1. Those cell numbers were 8, 8 × 107/kg and 5, 34 × 105/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post‐transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.
Invasive mold infections in iatrogenically immunocompromised children: An eight‐yr review
Authors: Al‐Rezqi Abdulkader , Hawkes Michael , Doyle John , Richardson Susan E. , Allen Upton
Published: October 2008

Abstract:  IMI are emerging as an important cause of mortality and morbidity among the growing number of immunocompromised children. A retrospective chart review was performed in all patients with a proven diagnosis of IMI over an eight‐yr period (1997–2004) at The Hospital for Sick Children, Toronto, Canada to document the incidence, clinical spectrum, microbiology, treatment, and outcome of pediatric IMI. Twenty‐eight patients developed IMI over the study period (10 cancer, 12 HCT, and six SOT patients). IMI occurred in 0.51%, 2.2% and 3.2% after a median time of 118, 60 and 71 days, among cancer, HCT and SOT recipients, respectively. Aspergillus spp. infection was diagnosed most commonly (23 patients) and the most common site of infection was the lung (21 patients). Patients at increased risk included those with acute myelogenous leukemia, allogeneic unrelated HCT recipients, graft‐versus‐host disease, and lung transplant recipients. The mortality after one yr was 60% among cancer patients, 58% among HCT patients, and 16% among SOT patients.
Infections detected in English surgical bone and deceased donors (2001–2006) and estimated risk of undetected hepatitis B and hepatitis C virus
Authors: Brant L. J. , Davison K. L.
Published: October 2008

Background and Objectives  Infections can be transmitted through donated tissue products, such as femoral heads. Here we describe infections detected through microbiological testing of English surgical bone and deceased donors (2001–2006) and estimate the residual risk of infection.

Materials and Methods  Data on infected tissue donors identified by NHS Blood and Transplant (NHSBT) were collected through the NBS/Health Protection Agency Infection Surveillance programme. The blood donor model for estimating risk was adapted for tissue donors. Incidence among surgical bone donors was derived from new blood donor data and estimates of residual risk presented for surgical bone donors only.

Results  Fifty‐seven surgical bone and four deceased donors were identified with 60 and five infections, respectively, during the 6 years. Syphilis was the most common infection detected, with no human T‐lymphotropic virus infections and one HIV infection in a deceased donor. Hepatitis B virus, hepatitis C virus and syphilis prevalence was higher among surgical bone and deceased donors than new blood donors for the same period. The overall estimated risk of undetected hepatitis B and hepatitis C virus among surgical bone donors (2001–2006) on initial screening was 0·426 and 0·048 per 100 000 donors, respectively. Testing a follow‐up sample made these risks almost negligible.

Conclusion  The prevalence of infections was low among English tissue donors. Risk estimates were higher for surgical bone donors on first screening than among new blood donors. However, the probability of an infectious donation entering the tissue supply became negligible after obtaining a follow‐up sample 6 months post‐donation and were well below that of new blood donors.