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Pseudoparalysis of the Right Arm in a 6-Week- Old Infant

Pseudoparalysis of the Right Arm in a 6-Week- Old Infant

Holt, R., Børresen, M. L. & Hoffmann, T. 31 aug. 2018 I : The Pediatric infectious disease journal.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Neonatal pyogenic liver abscess is rare and potentially lethal. We present a six-week-old infant with pseudoparalysis of the right arm.

OriginalsprogEngelsk
TidsskriftThe Pediatric infectious disease journal
ISSN0891-3668
DOI
StatusE-pub ahead of print - 31 aug. 2018
Hepatitis B virus suppresses the secretion of insulin-like growth factor binding protein 1 to facilitate anti-apoptotic IGF-1 effects in HepG2 cells

Hepatitis B virus (HBV) infection is a major global health burden as chronic hepatitis B (CHB) is associated with the development of liver diseases including hepatocellular carcinoma (HCC). To gain insight into the mechanisms causing HBV-related HCC, we investigated the effects of HBV replication on global host cell gene expression using human HepG2 liver cells. By microarray analysis, we identified 54 differentially expressed genes in HBV-replicating HepG2 cells. One of the differentially-expressed genes was insulin-like growth factor binding protein 1 (IGFBP1) which was downregulated in HBV-replicating cells. Consistent with the gene expression data, IGFBP1 was suppressed at both the cellular and secreted protein levels in the presence of HBV replication. Transient transfection experiments with an inducible plasmid encoding the HBV X protein (HBx) revealed that HBx alone was sufficient to modulate IGFBP1 expression. Small interference RNA (siRNA)-mediated loss of function studies revealed that knockdown of IGFBP1 reduced apoptosis induced by either thapsigargin (TG) or staurosporine (STS). Treatment of cells with recombinant insulin-like growth factor 1 (IGF-1) decreased both TG- or STS-induced apoptosis. Interestingly, addition of recombinant IGFBP1 reversed the anti-apoptotic effect of IGF-1 on TG-induced, but not STS-induced, apoptosis. In conclusion, our results suggest an anti-apoptotic autocrine function of HBV-mediated downregulation of IGFBP1 in HepG2 cells. Such an effect may contribute to the development of HBV-mediated HCC by increasing pro-survival and anti-apoptotic IGF-1 effects.

OriginalsprogEngelsk
TidsskriftExperimental Cell Research
ISSN0014-4827
DOI
StatusE-pub ahead of print - 1 aug. 2018
The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies

The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies

Larnkjær, A., Ong, K. K., Carlsen, E. M., Ejlerskov, K. T., Mølgaard, C. & Michaelsen, K. F. 1 aug. 2018 I : Hormone research in paediatrics. s. 1-11

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I).

METHODS: Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected.

RESULTS: At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I.

CONCLUSIONS: Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin.

OriginalsprogEngelsk
TidsskriftHormone research in paediatrics
Sider (fra-til)1-11
ISSN1663-2818
DOI
StatusE-pub ahead of print - 1 aug. 2018
The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis

The sensitivity of fecal calprotectin in predicting deep remission in ulcerative colitis

Carlsen, K., Riis, L. B., Elsberg, H., Maagaard, L., Thorkilgaard, T., Sørbye, S. W., Jakobsen, C., Wewer, V., Florholmen, J., Goll, R. & Munkholm, P. 3 jul. 2018 I : Scandinavian journal of gastroenterology. s. 1-6 6 s.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

BACKGROUND: Mucosal healing is proposed as treat-to-target in ulcerative colitis (UC), even though the definition of mucosal healing remains contested as it has been suggested to be assessed by either endoscopy, histology or both. However, all definitions require an endoscopic evaluation of the mucosa. As endoscopies are invasive and uncomfortable to the patient we aimed to calibrate noninvasive predictors of mucosal inflammatory status defined by both endoscopy and histology.

METHODS: UC patients (n = 106) undergoing a sigmoid-/colonoscopy were prospectively included. Feces (fecal calprotectin, FC), blood samples (hemoglobin, C-reactive protein, orosomucoid, erythrocyte sedimentation rate, albumin) and symptom scores (Simple Clinical Colitis Activity Index, SSCAI) were collected and analyzed. The colonic mucosa was assessed by the Mayo endoscopic sub score and biopsies were obtained for a histologic grading by Geboes score. Predictive cutoff values were analyzed by receiver operating characteristics (ROC). A combined endoscopic and histologic assessment defined deep remission (Mayo =0 and Geboes ≤1) and activity (Mayo ≥2 and Geboes >3).

RESULTS: Only FC showed a significant ROC curve (p < .05). We suggest FC (mg/kg) cutoffs for detection of following: Deep remission: FC ≤25; Indeterminate: FC 25-230 - an endoscopy is recommended if a comprehensive status of both endoscopic and histologic assessed activity is needed; Active disease: FC >230. The complete ROC data is presented, enabling extraction of an FC cutoff value's sensitivity and specificity.

CONCLUSIONS: FC predicts endoscopic and histologic assessed deep remission and inflammatory activity of colon mucosa. Neither the markers in blood nor the SCCAI performed significant ROC results.

OriginalsprogEngelsk
TidsskriftScandinavian journal of gastroenterology
Sider (fra-til)1-6
Antal sider6
ISSN0036-5521
DOI
StatusE-pub ahead of print - 3 jul. 2018
Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model

Chronic hepatitis B (CHB) infection increases the risk of developing severe liver disease including cirrhosis and hepatocellular carcinoma (HCC). As microRNAs may modulate host - virus interactions, we here investigated if hepatitis B virus (HBV) infection modulate microRNA expression using an in vitro HepG2 cell model system with inducible HBV replication. We found that HBV replication was associated with upregulation of miR-192-5p, miR-194-5p and miR-215-5p, of which miR-192-5p and miR-215-5p have identical seed sequences. Bioinformatics analyses revealed a significant enrichment of potential target genes involved in apoptosis signaling of all three microRNAs. In line with this, transfection with a mimic of miR-192-5p suppressed the protein level of pro-apoptotic BIM and reduced endoplasmic reticulum (ER) stress-induced apoptosis in HepG2 cells. In contrast, transfection with a mimic of miR-194-5p downregulated the anti-apoptotic proteins SODD and cFLIP, and sensitized HepG2 cells to both ER stress- and cytokine-induced apoptosis. In conclusion, our study suggests that HBV upregulates the expression of miR-192-5p and miR-194-5p in the host cell. These microRNAs target important apoptosis-regulatory proteins, and may thus contribute to the development of HBV-related liver disease.

OriginalsprogEngelsk
TidsskriftExperimental Cell Research
ISSN0014-4827
DOI
StatusE-pub ahead of print - 1 jul. 2018
Live-Born Major Congenital Heart Disease in Denmark: Incidence, Detection Rate, and Termination of Pregnancy Rate From 1996 to 2013

Live-Born Major Congenital Heart Disease in Denmark: Incidence, Detection Rate, and Termination of Pregnancy Rate From 1996 to 2013

Lytzen, R., Vejlstrup, N., Bjerre, J., Petersen, O. B., Leenskjold, S., Dodd, J. K., Jørgensen, F. S. & Søndergaard, L. 1 jul. 2018 I : JAMA Cardiology.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Importance: The occurrence of major congenital heart disease (CHD) is affected by several variables. Determining the development of the true incidence is critical to the establishment of proper treatment of these patients.

Objective: To evaluate time trends in incidence, detection rate, and termination of pregnancy (TOP) rate of major CHD in fetuses in Denmark and assess the influence of the introduction of general prenatal screening in 2004.

Design, Setting, and Participants: Nationwide, population-based, retrospective observational study in Denmark from 1996 to 2013 that included a consecutive sample of 14 688 live-born children and terminated fetuses diagnosed as having CHD. Patient records on TOP and children with major CHD were reviewed to validate the diagnoses. Major CHD included univentricular heart, transposition of the great arteries, congenitally corrected transposition of the great arteries, truncus arteriosus, interrupted aortic arch, atrioventricular septal defects, double outlet right ventricle, coarctatio of the aorta, Ebstein anomaly, pulmonary atresia with ventricular septal defect, pulmonary atresia with intact ventricular septum, and tetralogy of Fallot. Data were analyzed between January 2017 and March 2018.

Main Outcomes and Measures: Temporal changes in incidence, detection rate, and TOP of major CHD.

Results: Of 14 688 children and fetuses diagnosed with CHD, 2695 (18.4%; 95% CI, 17.8-19.1) had major CHD. A total of 7131 boys (1304 with major CHD) and 6926 girls (920 with major CHD) were included, with a median age of 11 years (interquartile range, 6-15 years). During the study period, the live-birth incidence of CHD was constant at 1.22% (95% CI, 1.18-1.26), whereas it decreased for major CHD. When including TOP, the incidence of major CHD did not change over time. The detection rate of major CHD increased from 4.5% (95% CI, 1.2-7.8) to 71.0% (95% CI, 63.3-78.7) (P < .001). At the end of the study, all cases of double outlet right ventricle, Ebstein anomaly, congenitally corrected transposition of the great arteries, and pulmonary atresia with ventricular septal defect were detected prenatally, whereas coarctation of the aorta had the lowest detection rate (21.7%; 95% CI, 3.5-40.0). The TOP rate increased from 0.6% (95% CI, -0.6 to 1.9) to 39.1% (95% CI, 30.9-47.4) (P < .001) among all major CHD. For prenatally diagnosed major CHD, 57.8% of cases were terminated and the proportion did not change significantly throughout the study. Diagnoses leading to TOP included all major CHD diagnoses.

Conclusions and Relevance: Detection rates of major CHD improved during the study. This has led to increased TOP rates, with a subsequent 39% decrease in the live-birth incidence of major CHD.

OriginalsprogEngelsk
TidsskriftJAMA Cardiology
ISSN2380-6583
DOI
StatusE-pub ahead of print - 1 jul. 2018
Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study

Introduction: Orchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk.

Materials and methods: We included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur®) 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent's choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing.

Results: Two out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S). Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not.

Conclusion: Based on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure of adjuvant LHRH. However, to avoid repeat surgery with biopsy, some parents may choose biopsy for cryopreservation at time of the initial bilateral orchiopexy, well informed that the procedure may only be truly indicated in 22 and 36% of the cases.

OriginalsprogEngelsk
TidsskriftFrontiers in Endocrinology
Vol/bind9
Tidsskriftsnummer299
ISSN1664-2392
DOI
StatusUdgivet - 1 jun. 2018
Impaired serum inhibin-B and number of germ cells in boys with cryptorchidism following heavily gestational maternal smoking

PURPOSE: A meta-analysis including 11,900 cases showed that maternal gestational smoking was associated with increased risk of cryptorchidism. The aim of study was to investigate whether a hormone profile of cryptorchid boys and a supplementing histopathological evaluation of testicular biopsies could add detailed knowledge to the impact of maternal gestational smoking on pathogenesis of cryptorchidism.

METHODS: 601 cryptorchid boys aged 4 months to 14 years old were included. Because normal hormones have a pronounced age dependency, we compared results from boys whose mothers had smoked heavily (>10 cigarettes/day) during pregnancy with age matched cryptorchid controls of nonsmoking mothers (1:6). We studied: birthweight, germ-cell number/tubular cross section, frequency of germ cells positive for placental-like alkaline phosphatase (PLAP), gonadotropins and inhibin-B.

RESULTS: 501 boys were sons of nonsmokers, 72 boys of intermittent smokers and 28 boys of heavy smokers. 39%, 44% and 61% respectively had bilateral cryptorchidism. Compared to age-matched cryptorchid controls of nonsmoking mothers, sons of heavy smokers had lower birthweight (p = 0.006), germ-cell number/tubular cross section (p = 0.009), frequency of germ cells positive for PLAP (p = 0.037) and inhibin-B (p = 0.042).

CONCLUSIONS: All findings could be associated with placental dysfunction with altered human chorionic gonadotropin production well described in women smoking during pregnancy.

TYPE OF STUDY: Prognosis study (prospective cohort study with >80% follow-up).

LEVEL OF EVIDENCE: Level 1.

OriginalsprogEngelsk
TidsskriftJournal of pediatric surgery
ISSN0022-3468
DOI
StatusE-pub ahead of print - 1 maj 2018
The Expression of Markers for Intratubular Germ Cell Neoplasia in Normal Infantile Testes

The Expression of Markers for Intratubular Germ Cell Neoplasia in Normal Infantile Testes

Kvist, K., Clasen-Linde, E., Langballe, O., Hansen, S. H., Cortes, D. & Thorup, J. 2018 I : Frontiers in Endocrinology. 9, s. 286

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Background: Positive immunohistochemical expression of testicular cancer markers is often reported beyond 12 months of age in cryptorchid testes, which is assumed to indicate delayed maturation of the fetal germ cells, or neoplastic changes. These findings allowed for questions as to the extent of positive reaction in normal testes. The aim of the study was to clarify the expression of these markers in a normal material up to 2 years.

Methods: Testicular material from 69 boys aged 1-690 days, who died of causes with no association of testicular pathology. Histology sections were incubated with primary antibodies including anti-placental-like alkaline phosphatase (PLAP), anti-C-Kit, anti-D2-40, and anti-Oct3/4. The mean germ cell number per tubular transverse section (G/T) was calculated based on the G/T of both testes of every boy.

Results: The mean G/T declined through the 690 days. PLAP appeared stably expressed throughout the ages studied. The likelihood of a positive reaction for C-Kit waned with increasing age within the study period. Positive staining for D2-40 and Oct3/4 was demonstrated up to 6 and 9 months respectively.

Conclusion: Up to 1 or 2 years of age, normal infantile testes contain germ cells positive for the immunohistochemical markers commonly utilized to aid in the detection of testicular cancer. This finding supports the concept of germ cells undergoing a continuous maturational process in a heterogeneous fashion, and that this process is not complete by 2 years of age.

OriginalsprogEngelsk
TidsskriftFrontiers in Endocrinology
Vol/bind9
Sider (fra-til)286
ISSN1664-2392
DOI
StatusUdgivet - 2018
Parent perspectives of neonatal tele-homecare: A qualitative study

Parent perspectives of neonatal tele-homecare: A qualitative study

Garne Holm, K., Brødsgaard, A., Zachariassen, G., Smith, A. C. & Clemensen, J. 2018 I : Journal of Telemedicine and Telecare. s. 1357633X18765059

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Introduction Neonatal homecare for preterm infants is a method of supporting families and monitoring infant growth in the home setting. Telehealth may be used to deliver specialist neonatal care remotely, using online communication methods. This study explored parental experiences with neonatal tele-homecare (NTH). Methods Semi-structured interviews were conducted with 49 parents whose preterm infants had received NTH from a neonatal intensive care unit (NICU) in Denmark. Interview transcripts were analysed using Malterud's systematic text condensation. Results Parents experienced NTH as a personalised method for linking to specialist staff in the NICU. NTH promoted the parent's role as the primary care provider, further strengthening the parent-infant relationship. Discussion From the perspective of parents with preterm infants requiring specialist care, NTH is a useful method of supporting families in the home. Telehealth provides effective communication links with NICU specialists and encourages family-centred care.

OriginalsprogEngelsk
TidsskriftJournal of Telemedicine and Telecare
Sider (fra-til)1357633X18765059
ISSN1357-633X
DOI
StatusE-pub ahead of print - 2018

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