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1.
Clin Nutr ; 43(3): 781-786, 2024 03.
Article in English | MEDLINE | ID: mdl-38340410

ABSTRACT

BACKGROUND: Enteral nutrition is necessary when nutritional status is poor and oral intake is insufficient or impossible. Although it has been suspected to reduce spontaneous oral feeding, no study has formally assessed the influence of enteral nutrition on pediatric oral intake. The present study aimed to evaluate variation in oral feeding intake after enteral nutrition initiation, and to identify factors influencing oral feeding. METHODS: This retrospective cohort study included 149 pediatric patients from two French tertiary care hospitals, who received home enteral nutrition from 2009 to 2022. The patients were aged 2 months to 17 years (median age 3 years, interquartile range 1.3-9.2). Oral and enteral intakes were assessed when enteral nutrition was initiated (M0), and again at M3 (n = 123), M6 (n = 129), and M12 (n = 134) follow-ups, based on dieticians' and home services' reports. Oral feeding and body mass index z score variations during follow-ups were evaluated using a linear mixed regression model, including "time" as a fixed effect and "patient" as a random effect. Factors associated with oral feeding changes were assessed using a model interaction term. RESULTS: Oral intake did not vary significantly (P = 0.99) over time and accounted for 47.4% ± 27.4%, 46.9% ± 27.4%, 48.4% ± 28.2%, and 46.6% ± 26.9% of the ideal recommended daily allowance (calculated for the ideal weight for height) at M0, M3, M6, and M12, respectively. Delivery method (nasogastric tube versus gastrostomy), prematurity, underlying disease, history of intrauterine growth retardation, and speech therapy intervention did not influence oral intake. Administration (i.e., exclusively continuous nocturnal infusion versus daytime bolus) led to different oral intake development, although oral intake also differed at M0. CONCLUSIONS: Enteral nutrition, although increasing total energy intake, does not alter oral feeding during the first year of administration. Only the mode of administration might influence oral intake.


Subject(s)
Enteral Nutrition , Nutritional Support , Humans , Child , Child, Preschool , Retrospective Studies , Gastrostomy , Nutritional Status
2.
Behav Brain Res ; 353: 236-241, 2018 11 01.
Article in English | MEDLINE | ID: mdl-29481811

ABSTRACT

BACKGROUND: Behavioral testing provides an essential approach in further developing our understanding of brain structure and function. The aim of our study was to outline a more expanded approach to cognition- and anxiety-related behavior in the rabbit. METHODS: Twenty-one 70-day old rabbits (13 female, 8 male) were exposed to open field test, dark-light box test and object recognition testing with variations in inter-trial-interval, olfactory recognition and object location testing. Independent T-tests were used to compare data by individual baseline characteristics, i.e. birth weight, weight at testing, sex, litter #, litter size. RESULTS: In the open field test, median time spent in the center was 3.64 s (0.84-41.36) for the 9 rabbits who entered the center; median distance moved in the arena was 874.42 cm (54.20-3444.83). In the dark light box test, 12 rabbits entered the light compartment. In the object recognition task, rabbits spent significantly less time exploring the familiar object compared to the novel (0.40 s [0-2.8] vs. 3.17 s [1.30-32.69]; P = 0.003) when using a 30-min inter-trial interval, as well with a 90-min inter-trial interval: 0.87 s [0-7.8] vs. 7.65 s [0-37.6] (P = 0.008). However, recognition was lost when using a 24-h inter-trial interval (time spent exploring the familiar object: 3.33 [0-10.90]; novel object:3.87 [1.15-48.53]; n.s). In the object location task and in olfactory object recognition task, median discrimination indexes were 0.69 (-1 to 1) and 0.37 (-0.38 to 0.78) respectively, higher than level expected by chance (P < 0.001). Litter size >3 during the neonatal period was associated with increased explorative behavior in the dark light box test (P = 0.046) and in the visual object recognition task (P = 0.005), whereas body weight and sex were not. CONCLUSIONS: Settings and outcome measures for multiple behavioral tests, providing reference values and considerations for future developmental studies are reported. Discrimination and memory in the rabbit appear to relate to litter characteristics, although a larger sample size is needed to confirm our findings.


Subject(s)
Exploratory Behavior , Litter Size , Recognition, Psychology , Animals , Behavior Rating Scale , Discrimination, Psychological , Female , Male , Motor Activity , Olfactory Perception , Rabbits , Research Design
3.
J Crohns Colitis ; 11(5): 519-526, 2017 May 01.
Article in English | MEDLINE | ID: mdl-28453757

ABSTRACT

BACKGROUND AND AIMS: Very-early-onset inflammatory bowel disease [VEO-IBD] is a form of IBD that is distinct from that of children with an older onset. We compared changes over time in the incidence and phenotype at diagnosis between two groups according to age at IBD diagnosis: VEO-IBD diagnosed before the age of 6 years, and early-onset IBD [EO-IBD] diagnosed between 6 and 16 years of age. METHODS: Data were obtained from a cohort enrolled in a prospective French population-based registry from 1988 to 2011. RESULTS: Among the 1412 paediatric cases [< 17 years], 42 [3%] were VEO-IBD. In the VEO-IBD group, the incidence remained stable over the study period. In contrast, the incidence of EO-IBD increased from 4.4/105 in 1988-1990 to 9.5/105 in 2009-2011 [+116%; p < 10-4]. Crohn's disease [CD] was the most common IBD, regardless of age, but ulcerative colitis [UC] and unclassified IBD were more common in VEO-IBD cases [40% vs 26%; p = 0.04]. VEO-IBD diagnosis was most often performed in hospital [69% vs 43%; p < 10-3]. Rectal bleeding and mucous stools were more common in patients with VEO-IBD, whereas weight loss and abdominal pain were more frequent in those with EO-IBD. Regarding CD, isolated colonic disease was more common in the VEO-IBD group [39% vs 14%; p = 0.003]. CONCLUSIONS: In this large population-based cohort, the incidence of VEO-IBD was low and stable from 1988 to 2011, with a specific clinical presentation. These results suggest a probable genetic origin for VEO-IBD, whereas the increase in EO-IBD might be linked to environmental factors.


Subject(s)
Inflammatory Bowel Diseases/epidemiology , Adolescent , Age of Onset , Child , Child, Preschool , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/pathology , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Crohn Disease/pathology , Female , France/epidemiology , Humans , Incidence , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/pathology , Male , Phenotype , Prospective Studies , Registries
4.
Infect Immun ; 85(6)2017 06.
Article in English | MEDLINE | ID: mdl-28396323

ABSTRACT

Mycoplasma gallisepticum, known primarily as a respiratory pathogen of domestic poultry, has emerged since 1994 as a significant pathogen of the house finch (Haemorhousmexicanus) causing severe conjunctivitis and mortality. House finch-associated M. gallisepticum (HFMG) spread rapidly and increased in virulence for the finch host in the eastern United States. In the current study, we assessed virulence in domestic poultry with two temporally distant, and yet geographically consistent, HFMG isolates which differ in virulence for house finches-Virginia 1994 (VA1994), the index isolate of the epidemic, and Virginia 2013 (VA2013), a recent isolate of increased house finch virulence. Here we report a significant difference between VA1994 and VA2013 in their levels of virulence for chickens; notably, this difference correlated inversely to the difference in their levels of virulence for house finches. VA1994, while moderately virulent in house finches, displayed significant virulence in the chicken respiratory tract. VA2013, while highly virulent in the house finch, was significantly attenuated in chickens relative to VA1994, displaying less-severe pathological lesions in, and reduced bacterial recovery from, the respiratory tract. Overall, these data indicate that a recent isolate of HFMG is greatly attenuated in the chicken host relative to the index isolate, notably demonstrating a virulence phenotype in chickens inversely related to that in the finch host.


Subject(s)
Chickens/microbiology , Finches/microbiology , Mycoplasma Infections/epidemiology , Mycoplasma gallisepticum/isolation & purification , Mycoplasma gallisepticum/pathogenicity , Animals , Female , Mycoplasma Infections/microbiology , Mycoplasma Infections/veterinary , Phenotype , Phylogeny , Virginia , Virulence
5.
Gut ; 66(11): 1912-1917, 2017 11.
Article in English | MEDLINE | ID: mdl-27489240

ABSTRACT

OBJECTIVE: Natural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC. PATIENTS AND METHODS: All patients with UC diagnosed <17 years from 1988 to 2004, and followed during >2 years have been extracted from a population-based registry. UC location was defined according to the Paris classification. Cumulative risks for use of immunosuppressants (IS), anti-tumour necrosis factor alpha (TNF-α) therapy, colonic extension and colectomy were described using Kaplan-Meier method. Risk factors for colonic extension were assessed using Cox proportional hazards models. RESULTS: 158 patients with paediatric-onset UC (91 females) with a median age at diagnosis of 14.5 years (Q1: 11.4-Q3: 16.1) have been identified and followed during a median of 11.4 years (8.2-15.8). Among them, 25% had UP (E1) at diagnosis and 49% of them presented a colonic extension at maximal follow-up. In these children, the cumulative risk for colonic extension was 10% at 1 year, 45% at 5 years and 52% at 10 years. No parameter at diagnosis was associated with colonic extension in the UP (E1 group). IS use was significantly lower in patients with UP than in those with E2, E3 or E4 location (p=0.049). For the UP cohort, the cumulative risk for colectomy was 3% at 1 year, 10% at 5 years, 13% at 10 years and 13% at 15 years. Risks for colonic extension, treatment with anti-TNF-α and colectomy did not differ between the E1 group and the E2-E3-E4 group. CONCLUSIONS: UP is frequent in paediatric-onset UC and should not be considered as a minor disease. Compared with more extensive UC locations, risks for colonic extension, anti-TNF-α therapy and colectomy were similar in UP, whereas the risk for use of IM was lower.


Subject(s)
Colitis, Ulcerative/diagnosis , Proctitis/diagnosis , Adolescent , Child , Colectomy , Colitis, Ulcerative/physiopathology , Colitis, Ulcerative/therapy , Disease Progression , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/therapeutic use , Kaplan-Meier Estimate , Male , Phenotype , Proctitis/physiopathology , Proctitis/therapy , Prognosis , Proportional Hazards Models , Registries , Retrospective Studies , Risk Factors
6.
Clin Neuroradiol ; 27(3): 335-343, 2017 Sep.
Article in English | MEDLINE | ID: mdl-26699192

ABSTRACT

PURPOSE: In recent years, flow diverters have provided a promising alternative to treat complex intracranial aneurysms. In this study, we compare a second-generation flow-diverting device (Derivo Embolization Device) with its prototype flow diverter, in the treatment of elastase-induced aneurysms in New Zealand white rabbits. METHODS: The Derivo Embolization Device is a self-expanding stent consisting of 48 nitinol wires. The device was implanted across the necks of 17 elastase-induced aneurysms in New Zealand white rabbits. One additional device was implanted in the abdominal aorta of each animal covering the origin of lumbar arteries. Follow-up was performed after 3 months (n = 8) and 6 months (n = 9) under continuous double antiplatelet therapy. Statuses of angiographic and histological aneurysm occlusion as well as patency of branch arteries and neointimal growth were evaluated and compared with its prototype flow diverter. RESULTS: The Derivo Embolization Device provided advanced visibility and flexibility, which led to more accurate navigation and placement. Complete aneurysm occlusion rates were noted in 15 cases (88 %), respectively, compared with 5 cases (28 %) with the first-generation device (p = 0.001). Neointimal growth and diameter stenosis were significantly less with the Derivo Embolization Device and declining after 6 months follow-up in the abdominal aorta. Extreme device oversizing led to distal occlusion of the parent vessel in three cases. Covered branch arteries remained patent throughout the entire period of observation. CONCLUSIONS: The Derivo Embolization Device provides excellent occlusion of elastase-induced aneurysms while preserving branch arteries.


Subject(s)
Embolization, Therapeutic , Intracranial Aneurysm/therapy , Animals , Cerebral Angiography , Embolization, Therapeutic/instrumentation , Embolization, Therapeutic/methods , Female , Germany , Pancreatic Elastase , Rabbits , Stents , Treatment Outcome
8.
Vet Pathol ; 50(2): 291-8, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22903399

ABSTRACT

Three wild American black vultures (Coragyps atratus) were presented to rehabilitation centers with swelling of multiple joints, including elbows, stifles, hocks, and carpal joints, and of the gastrocnemius tendons. Cytological examination of the joint fluid exudate indicated heterophilic arthritis. Radiographic examination in 2 vultures demonstrated periarticular soft tissue swelling in both birds and irregular articular surfaces with subchondral bone erosion in both elbows in 1 bird. Prolonged antibiotic therapy administered in 2 birds did not improve the clinical signs. Necropsy and histological examination demonstrated a chronic lymphoplasmacytic arthritis involving multiple joints and gastrocnemius tenosynovitis. Articular lesions varied in severity and ranged from moderate synovitis and cartilage erosion and fibrillation to severe synovitis, diffuse cartilage ulceration, subchondral bone loss and/or sclerosis, pannus, synovial cysts, and epiphyseal osteomyelitis. No walled bacteria were observed or isolated from the joints. However, mycoplasmas polymerase chain reactions were positive in at least 1 affected joint from each bird. Mycoplasmas were isolated from joints of 1 vulture that did not receive antibiotic therapy. Sequencing of 16S rRNA gene amplicons from joint samples and the mycoplasma isolate identified Mycoplasma corogypsi in 2 vultures and was suggestive in the third vulture. Mycoplasma corogypsi identification was confirmed by sequencing the 16S-23S intergenic spacer region of mycoplasma isolates. This report provides further evidence that M. corogypsi is a likely cause of arthritis and tenosynovitis in American black vultures. Cases of arthritis and tenosynovitis in New World vultures should be investigated for presence of Mycoplasma spp, especially M. corogypsi.


Subject(s)
Arthritis/veterinary , Bird Diseases/microbiology , Bird Diseases/pathology , Mycoplasma Infections/veterinary , Mycoplasma/genetics , Tenosynovitis/veterinary , Animals , Arthritis/microbiology , Arthritis/pathology , Base Sequence , Birds , DNA, Ribosomal Spacer/genetics , Female , Male , Molecular Sequence Data , Mycoplasma Infections/pathology , Polymerase Chain Reaction/veterinary , Sequence Analysis, DNA/veterinary , Tenosynovitis/microbiology , Tenosynovitis/pathology , United States
9.
Tissue Antigens ; 80(4): 317-21, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22823586

ABSTRACT

Extensive research has shown that aberrant expression of microRNAs (miRNAs) plays an important role in innate and adaptive immune responses. The rs2910164 polymorphism has been identified as a functional variant, which affects the transcription and expression level of miR-146a and, thereby, contributes to the pathogenesis of several inflammatory and autoimmune diseases. To investigate whether the rs2910164 G/C polymorphism was associated with asthma, systemic lupus erythematosus (SLE) or juvenile rheumatoid arthritis (JRA), we performed an association study in a pediatric Mexican cohort. We included 979 pediatric patients (asthma: 402, SLE: 367 and JRA: 210) and 531 control subjects without inflammatory or immune diseases. Genotyping was performed using the 5' exonuclease technique. The genotype distribution of the rs2910164 polymorphism was in Hardy-Weinberg equilibrium in each group. No significant differences were detected in the distribution of this polymorphism between cases and controls (P = 0.108, 0.609 and 0.553 for subjects with asthma, JRA and SLE, respectively). However, stratification by gender showed a statistically significant difference between asthmatic and control females, where the C allele was significantly associated with protection to asthma (odds ratio = 0.694, 95% confidence interval 0.519-0.929, P = 0.0138). Our results provide evidence that rs2910164 may play a role in the susceptibility to childhood-onset asthma, but not SLE or JRA in Mexicans. Further association studies may contribute to determining the role of miR-146a single-nucleotide polymorphisms in immune-mediated diseases.


Subject(s)
Arthritis, Juvenile/epidemiology , Asthma/epidemiology , Asthma/genetics , Lupus Erythematosus, Systemic/epidemiology , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Age of Onset , Alleles , Arthritis, Juvenile/genetics , Arthritis, Juvenile/immunology , Asthma/immunology , Case-Control Studies , Child , Child, Preschool , Female , Gene Expression , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Male , Mexico/epidemiology , MicroRNAs/immunology , Risk Factors , Sex Factors
10.
Microbiology (Reading) ; 158(Pt 8): 2073-2088, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22628486

ABSTRACT

Mycoplasma gallisepticum, a significant respiratory and reproductive pathogen of domestic poultry, has since 1994 been recognized as an emergent pathogen of the American house finch (Carpodacus mexicanus). Epizootic spread and pathognomonic characteristics of house finch-associated Mycoplasma gallisepticum (HFMG) have been studied as a model of an emergent to endemic pathogen in a novel host. Here we present comparative analysis of eight HFMG genomes, including one from an index isolate and seven isolates separated spatially and temporally (1994-2008) across the epizootic, and notably having differences in virulence. HFMG represented a monophyletic clade relative to sequenced poultry isolates, with genomic changes indicating a novel M. gallisepticum lineage and including unique deletions of coding sequence. Though most of the HFMG genome was highly conserved among isolates, genetic distances correlated with temporal-spatial distance from the index. The most dramatic genomic differences among HFMG involved phase-variable and immunodominant VlhA lipoprotein genes, including those variable in presence and genomic location. Other genomic differences included tandem copy number variation of a 5 kbp repeat, changes in and adjacent to the clustered regularly interspaced short palindromic repeats, and small-scale changes affecting coding potential and association of genes with virulence. Divergence of monophyletic isolates from similar time/space in the epizootic indicated local diversification of distinct HFMG sublineages. Overall, these data identify candidate virulence genes and reveal the importance of phase-variable lipoproteins during the evolution of M. gallisepticum during its emergence and dissemination in a novel host in nature, likely mediating an important role at the interface between pathogen virulence and host immunity.


Subject(s)
Bacterial Proteins/genetics , Bird Diseases/microbiology , Evolution, Molecular , Genetic Variation , Lipoproteins/genetics , Mycoplasma Infections/veterinary , Mycoplasma gallisepticum/genetics , Passeriformes/microbiology , Animals , Bacterial Proteins/metabolism , Base Sequence , Genome, Bacterial , Genomics , Lipoproteins/metabolism , Molecular Sequence Data , Mycoplasma Infections/microbiology , Mycoplasma gallisepticum/classification , Mycoplasma gallisepticum/isolation & purification , Mycoplasma gallisepticum/pathogenicity , Phylogeny , Virulence , Zoonoses/microbiology
11.
J Evol Biol ; 23(8): 1680-8, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20561136

ABSTRACT

Host genetic diversity can mediate pathogen resistance within and among populations. Here we test whether the lower prevalence of Mycoplasmal conjunctivitis in native North American house finch populations results from greater resistance to the causative agent, Mycoplasma gallisepticum (MG), than introduced, recently-bottlenecked populations that lack genetic diversity. In a common garden experiment, we challenged wild-caught western (native) and eastern (introduced) North American finches with a representative eastern or western MG isolate. Although introduced finches in our study had lower neutral genetic diversity than native finches, we found no support for a population-level genetic diversity effect on host resistance. Instead we detected strong support for isolate differences: the MG isolate circulating in western house finch populations produced lower virulence, but higher pathogen loads, in both native and introduced hosts. Our results indicate that contemporary differences in host genetic diversity likely do not explain the lower conjunctivitis prevalence in native house finches, but isolate-level differences in virulence may play an important role.


Subject(s)
Bird Diseases/microbiology , Finches/genetics , Host-Pathogen Interactions/genetics , Mycoplasma Infections/veterinary , Mycoplasma gallisepticum/pathogenicity , Animals , Bird Diseases/epidemiology , Finches/immunology , Genetic Variation , Immunocompetence/immunology , Microsatellite Repeats/genetics , Mycoplasma Infections/epidemiology , Mycoplasma Infections/microbiology , Mycoplasma gallisepticum/isolation & purification , Prevalence , Time Factors
12.
Acta Paediatr ; 99(4): 502-8, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19878131

ABSTRACT

UNLABELLED: Evidence is accumulating that one of the strongest predictors of retinopathy of prematurity (ROP), in addition to low gestational age, is poor weight gain during the first weeks of life. In infants born preterm, the retina is not fully vascularised. The more premature the child, the larger is the avascular area. In response to hypoxia, vascular endothelial growth factor (VEGF) is secreted. For appropriate VEGF-induced vessel growth, sufficient levels of insulin-like growth factor I (IGF-I) in serum are necessary. IGF-I is a peptide, related to nutrition supply, which is essential for both pre- and post-natal general growth as well as for growth of the retinal vasculature. In prematurely born infants, serum levels are closely related to gestational age and are lower in more prematurely born infants. At preterm birth the placental supply of nutrients is lost, growth factors are suddenly reduced and general as well as vascular growth slows down or ceases. In addition, the relative hyperoxia of the extra-uterine milieu, together with supplemental oxygen, causes a regression of already developed retinal vessels. Postnatal growth retardation is a major problem in very preterm infants. Both poor early weight gain and low serum levels of IGF-I during the first weeks/months of life have been found to be correlated with severity of ROP. CONCLUSION: This review will focus on the mechanisms leading to ROP by exploring factors responsible for poor early weight gain and abnormal vascularisation of the eye of the preterm infant.


Subject(s)
Infant, Premature/growth & development , Infant, Premature/metabolism , Retinopathy of Prematurity/metabolism , Humans , Infant, Newborn , Neonatal Screening/methods , Weight Gain
13.
Ultrasound Obstet Gynecol ; 34(3): 288-96, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19705404

ABSTRACT

OBJECTIVES: To describe the outcome of growth-restricted fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks. METHODS: Between 1998 and 2004, 42 fetuses with intrauterine growth restriction (IUGR) and ARED in the umbilical artery were delivered liveborn by Cesarean section on fetal indication before 30 gestational weeks. The median gestational age at delivery was 27 + 1 (range, 24 + 4 to 29 + 5) weeks. An additional four fetuses died in utero at a median gestational age of 24 + 2 (range, 23 + 5 to 25 + 4) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared with those in two control groups: all 371 liveborn infants delivered at < 30 weeks during the corresponding time period (Group A) and a subset of these, 42 matched infants without IUGR (Group B). RESULTS: Thirty-two fetuses (76%) [corrected] were delivered within 48 h of the occurrence of ARED (25 absent, seven reversed end-diastolic flow). The remaining 10 fetuses (five absent, five reversed end-diastolic flow) were monitored for a median of 6.5 (range, 3-18) days before delivery. One infant died in the neonatal period and three during the first year of postnatal life (2-year survival 90%). The incidence of chronic lung disease was higher in the ARED Group than in Control Groups A and B (P = 0.001 and P = 0.03, respectively). There were no differences between the groups in the occurrence of necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of the index group compared with 11% and 17% of Control Groups A and B (P > 0.05). CONCLUSIONS: Very preterm growth-restricted fetuses with umbilical artery ARED delivered on fetal indication, in most cases before the occurrence of severe changes in the ductus venosus velocity waveforms and/or fetal heart rate tracings, showed high 2-year survival and low morbidity.


Subject(s)
Fetal Growth Retardation/physiopathology , Fetal Heart/physiopathology , Umbilical Arteries/physiopathology , Adult , Blood Flow Velocity/physiology , Female , Fetal Growth Retardation/diagnostic imaging , Fetal Growth Retardation/mortality , Fetal Heart/diagnostic imaging , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Small for Gestational Age , Male , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal , Umbilical Arteries/diagnostic imaging , Young Adult
14.
Br J Pharmacol ; 157(6): 1085-96, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19438510

ABSTRACT

BACKGROUND AND PURPOSE: The effect of age on the distribution of morphine and morphine-3-glucuronide (M3G) across the blood-brain barrier (BBB) was studied in a sheep model utilizing intracerebral microdialysis. The effect of neonatal asphyxia on brain drug distribution was also studied. EXPERIMENTAL APPROACH: Microdialysis probes were inserted into the cortex, striatum and blood of 11 lambs (127 gestation days) and six ewes. Morphine, 1 mg x kg(-1), was intravenously administered as a 10 min constant infusion. Microdialysis and blood samples were collected for up to 360 min and analysed using liquid chromatography-tandem mass spectrometry. The half-life, clearance, volume of distribution, unbound drug brain : blood distribution ratio (K(p,uu)) and unbound drug volume of distribution in brain (V(u,brain)) were estimated. KEY RESULTS: Morphine K(p,uu) was 1.19 and 1.89 for the sheep and premature lambs, respectively, indicating that active influx into the brain decreases with age. Induced asphyxia did not affect transport of morphine or M3G across the BBB. Morphine V(u,brain) measurements were higher in sheep than in premature lambs. The M3G K(p,uu) values were 0.27 and 0.17 in sheep and premature lambs, indicating a net efflux from the brain in both groups. CONCLUSIONS AND IMPLICATIONS: The morphine K(p,uu) was above unity, indicating active transport into the brain; influx was significantly higher in premature lambs than in adult sheep. These results in sheep differ from those in humans, rats, mice and pigs where a net efflux of morphine from the brain is observed.


Subject(s)
Aging/physiology , Blood-Brain Barrier/metabolism , Morphine Derivatives/metabolism , Morphine/metabolism , Age Factors , Aging/drug effects , Animals , Blood-Brain Barrier/drug effects , Brain/drug effects , Brain/physiology , Female , Male , Morphine/pharmacology , Morphine Derivatives/pharmacology , Sheep , Tissue Distribution/drug effects , Tissue Distribution/physiology
15.
Ultrasound Obstet Gynecol ; 29(6): 614-8, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17523158

ABSTRACT

OBJECTIVE: Intrauterine growth restriction (IUGR) is a recognized risk factor for neurological deficits later in life. Abnormal fetal blood flow in the presence of IUGR helps to distinguish fetuses with true growth impairment from those that are small but normally grown. This study aimed to evaluate the influence of IUGR with abnormal fetal blood flow on cognitive function and psychological development in young adults. METHODS: Cognitive capacity (Wechsler adult intelligence scale-III (WAIS-III)) and psychological development (symptom check-list and Wender Utah rating scale) were evaluated at 18 years of age in 19 subjects who had had IUGR (abnormal fetal blood flow in the descending aorta and birth weight small-for-gestational age) and in 23 control subjects who had had normal fetal aortic blood flow and birth weight appropriate-for-gestational age (AGA). School grades at 16 years of age were also recorded. RESULTS: The IUGR subjects had significantly lower results at 18 years of age in the combined subtests of the WAIS-III measuring executive cognitive functions (P = 0.03) and lower school grades at 16 years of age (P = 0.03) compared with the AGA group. IUGR subjects did not exhibit significantly more psychological distress symptoms. CONCLUSION: IUGR with abnormal fetal blood flow is associated with impaired executive cognitive function in young adults.


Subject(s)
Cognition Disorders/diagnosis , Fetal Growth Retardation , Infant, Small for Gestational Age/physiology , Adolescent , Adult , Aorta, Thoracic/physiopathology , Blood Flow Velocity , Child , Cohort Studies , Female , Fetal Growth Retardation/physiopathology , Follow-Up Studies , Gestational Age , Humans , Infant, Newborn , Male , Pregnancy , Pregnancy Trimester, Third , Prospective Studies , Ultrasonography, Doppler , Ultrasonography, Prenatal
16.
Acta Paediatr ; 96(6): 830-6, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17465986

ABSTRACT

BACKGROUND: Foetal inflammation is associated with an increased risk of brain damage in preterm infants whereas IGF-I is essential for cerebral development and exhibits anti-apoptotic properties. AIM: To assess levels of IGF-I and IGF binding proteins at very preterm birth and to evaluate their relationship with foetal pro-inflammation and cerebral damage. METHODS: Levels of IGF-I, IGF binding protein 3 (IGFBP-3), high- (hp) and low-phosphorylated (lp) IGFBP-1 in cord blood and neonatal blood at 72 h after delivery were analysed in relation to levels of cytokines and cerebral damage as detected by ultrasound in 74 inborn infants [mean gestational age (GA) 27.1 weeks]. Evaluation was performed separately according to birth weight for GA. RESULTS: In cord blood of infants appropriate for gestational age (AGA) higher levels of IL-6 and IL-8 were associated with lower IGF-I (r =-0.38, p = 0.008 and r =-0.36, p = 0.014). Higher levels of IL-6, IL-8 and TNF-alpha were associated with both higher levels of lpIGFBP-1 (r = 0.54, p < 0.001, r = 0.50, p < 0.001 and r = 0.13, p = 0.012, respectively) and hpIGFBP-1 (r = 0.55, p < 0.001, r = 0.45, p = 0.002 and r = 0.32, p = 0.026, respectively). Infants with intraventricular haemorrhage grade III (n = 5) had higher levels of lp/hpIGFBP-1 in cord blood (p = 0.001 and 0.002, respectively). CONCLUSION: Pro-inflammation at birth is associated with changes in the IGF-system. This may be of importance for development of brain damage in preterm infants.


Subject(s)
Brain Injuries/blood , Infant, Small for Gestational Age/blood , Inflammation/blood , Biomarkers/blood , Brain/enzymology , Brain/immunology , Fetal Blood/chemistry , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Inflammation/diagnosis , Insulin-Like Growth Factor Binding Protein 1/blood , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/analysis , Interleukin-6/blood , Interleukin-8/blood , Linear Models , Prospective Studies
17.
Acta Paediatr ; 96(5): 650-4, 2007 May.
Article in English | MEDLINE | ID: mdl-17381469

ABSTRACT

OBJECTIVE: Norepinephrine (NE) is elevated in pregnancies complicated by preeclampsia (PE). Specific uptake of NE by the NE transporter (NET) plays a central role as regulator of NE levels. Expression of NET is reduced in placentas from PE pregnancies. To study adverse fetal effects of reduced NET expression on the placental buffering capacity, the NET was pharmacologically blocked by a specific uptake inhibitor reboxetine. STUDY DESIGN: We evaluated the effect of NE uptake inhibition on maternal and fetal arterial blood pressure responses to increasing maternal doses of NE in 10 chronically prepared fetal sheep. Arterial blood pressure was monitored continuously during increasing doses of i.v. NE. RESULTS: NET inhibition increased both fetal and maternal mean arterial blood pressure (p < 0.001, respectively). CONCLUSION: Reuptake by NET appears to be a mechanism protecting the fetus from NE. A reduced uptake capacity in preeclamptic pregnancies due to reduced NE uptake may lead to increased fetal arterial blood pressure.


Subject(s)
Blood Pressure/drug effects , Fetus/physiology , Norepinephrine Plasma Membrane Transport Proteins/drug effects , Norepinephrine/metabolism , Norepinephrine/pharmacology , Adrenergic Uptake Inhibitors/pharmacology , Animals , Female , Morpholines/pharmacology , Pregnancy , Reboxetine , Sheep
18.
Circulation ; 111(20): 2623-8, 2005 May 24.
Article in English | MEDLINE | ID: mdl-15883208

ABSTRACT

BACKGROUND: Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence. METHODS AND RESULTS: In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta, and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (P=0.003 and P=0.002, respectively), with a similar trend in the CCA (P=0.09). A higher resting heart rate was observed in the IUGR group (P=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups. CONCLUSIONS: IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health.


Subject(s)
Adolescent Development , Blood Vessels/growth & development , Fetal Growth Retardation/physiopathology , Adolescent , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/physiopathology , Blood Vessels/diagnostic imaging , Carotid Arteries/diagnostic imaging , Carotid Arteries/physiopathology , Case-Control Studies , Endothelium, Vascular , Female , Fetal Growth Retardation/epidemiology , Fetus/blood supply , Heart Rate , Humans , Placenta/blood supply , Popliteal Artery/diagnostic imaging , Popliteal Artery/physiopathology , Prospective Studies , Ultrasonography , Vasodilation
19.
Avian Dis ; 48(3): 562-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15529978

ABSTRACT

Mycoplasma gallisepticum was isolated from several turkey flocks at different locations in the United States that were clinically affected with respiratory disease. Five of these isolates from four series of outbreaks had patterns similar to the 6/85 vaccine strain of M. gallisepticum by random amplified polymorphic DNA (RAPD) analysis using three different primer sets, whereas with a fourth primer set (OPA13 and OPA14), only two of the isolates were similar to 6/85. Results obtained by sequencing portions of the pvpA, gapA, and mgc2 genes and an uncharacterized surface lipoprotein gene indicated that the field isolates had DNA sequences that ranged from 97.6% to 100%, similar to the 6/85 results. In some of the outbreaks there was an indirect association with the presence of commercial layers in the area that had been vaccinated with this vaccine strain, but there was no known close association with vaccinated birds in any of the outbreaks. Turkeys were challenged with two of the field isolates and with 6/85 vaccine strain. Turkeys challenged with the field isolates developed respiratory disease with airsacculitis and a typical M. gallisepticum antibody response, whereas birds challenged with 6/85 developed no respiratory signs or lesions and developed only a weak antibody response. Although these isolates were very similar to the 6/85 vaccine strain, it was not possible to prove that they originated from the vaccine strain-it is possible that they could be naturally occurring field isolates.


Subject(s)
Mycoplasma Infections/veterinary , Mycoplasma gallisepticum/genetics , Poultry Diseases/immunology , Poultry Diseases/microbiology , Turkeys/microbiology , Adhesins, Bacterial/genetics , Animals , Antibodies, Bacterial/blood , Base Sequence , DNA Primers , Molecular Sequence Data , Mycoplasma Infections/immunology , Random Amplified Polymorphic DNA Technique , Sequence Analysis, DNA , Trachea/pathology , United States
20.
Ultrasound Obstet Gynecol ; 23(4): 363-8, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15065186

ABSTRACT

OBJECTIVE: To compare fractional moving blood volume (FMBV) estimation using power Doppler ultrasound (PDU) with blood flow estimation using radioactive microspheres (RMS) for evaluation of fetal organ blood perfusion. METHODS: Blood flow was measured in the adrenal gland of nine exteriorized fetal lambs. Five fetal lambs underwent total umbilical cord occlusion in order to induce changes in the adrenal blood flow (asphyxia group). Four lambs were used as sham controls (control group). Three RMS injections, with coincident PDU recordings of the adrenal gland, were performed in each lamb. In the asphyxia group, measurements were taken before the cord occlusion, 5 min later and when the mean blood pressure decreased below 25 mmHg. In the control group, the measurements were done with an interval of 5 min. FMBV normalized for attenuation of PDU signals, and mean pixel intensity (MPI) were estimated offline. After completion of the study, adrenal blood perfusion was calculated according to the reference sample microsphere technique, using the isotope activity and expressed in mL/min/100 g. The correlation between RMS and FMBV and MPI, respectively, was analyzed individually for each lamb. RESULTS: In the asphyxia group, all lambs showed a marked reduction in the adrenal blood perfusion towards the third RMS injection. In the control group, the adrenal perfusion showed small variations throughout the experiment. In the total material, there was a higher correlation between FMBV and RMS (median, r = 0.90; range, 0.43-0.99) than between MPI and RMS (median, r = 0.55; range, -0.53 to 0.99). CONCLUSION: The FMBV method of quantifying PDU signals correlates highly with blood flow perfusion estimation using RMS in the fetal lamb adrenal gland.


Subject(s)
Fetus/blood supply , Ultrasonography, Doppler/methods , Adrenal Glands/blood supply , Adrenal Glands/diagnostic imaging , Animals , Asphyxia/diagnostic imaging , Blood Flow Velocity/physiology , Blood Volume Determination/methods , Female , Models, Animal , Pregnancy , Sheep
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