486 research outputs found
A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation
We assessed the effectiveness and safety of 3 yr combined GH and GnRH
agonist (GnRHa) treatment in a randomized controlled study in children
with idiopathic short stature (ISS) or intrauterine growth retardation
(IUGR). Gonadal suppression, GH reserve, and adrenal development were
assessed by hormone measurements in both treated children and controls
during the study period. Thirty-six short children, 24 girls (16 ISS/8
IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less
in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to
treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa
(triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of
the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age
was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During
3 yr of study height SD score for chronological age did not change in both
treated children and controls, whereas a decreased rate of bone maturation
after treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15
(0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height SD
score for bone age and predicted adult height increased significantly
after 3 yr of treatment; compared with controls the predicted adult height
gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio
between sitting height/height SD score decreased significantly in treated
children, whereas body mass index was not influenced by treatment. Puberty
was effectively arrested in the treated children, as was confirmed by
physical examination and prepubertal testosterone and estradiol levels.
GH-dependent hormones including serum insulin-like growth factor I and II,
carboxy terminal propeptide of type I collagen, amino terminal propeptide
of type III collagen, alkaline phosphatase, and osteocalcin were not
different between treated children and controls during the study period.
Thus, a GH dose of 4 IU/m(2) seems adequate for stabilization of the GH
reserve and growth in these GnRHa-treated children. We conclude that 3 yr
treatment with GnRHa was effective in suppressing pubertal development and
skeletal maturation, whereas the addition of GH preserved growth velocity
during treatment. This resulted in a considerable gain in predicted adult
height, without demonstrable side effects. Final height results will
provide the definite answer on the effectiveness of this combined
treatment
Prorenin accumulation and activation in human endothelial cells: importance of mannose 6-phosphate receptors
ACE inhibitors improve endothelial dysfunction, possibly by blocking
endothelial angiotensin production. Prorenin, through its binding and
activation by endothelial mannose 6-phosphate (M6P) receptors, may
contribute to this production. Here, we investigated this possibility as
well as prorenin activation kinetics, the nature of the
prorenin-activating enzyme, and M6P receptor-independent prorenin binding.
Human umbilical vein endothelial cells (HUVECs) were incubated with
wild-type prorenin, K/A-2 prorenin (in which Lys42 is mutated to Ala,
thereby preventing cleavage by known proteases), M6P-free prorenin, and
nonglycosylated prorenin, with or without M6P, protease inhibitors, or
angiotensinogen. HUVECs bound only M6P-containing prorenin (K(d) 0.9+/-0.1
nmol/L, maximum number of binding sites [B(max)] 1010+/-50
receptors/cell). At 37 degrees C, because of M6P receptor recycling, the
amount of prorenin internalized via M6P receptors was >25 times B(max).
Inside the cells, wild-type and K/A-2 prorenin were proteolytically
activated to renin. Renin was subsequently degraded. Protease inhibitors
interfered with the latter but not with prorenin activation, thereby
indicating that the activating enzyme is different from any of the known
prorenin-activating enzymes. Incubation with angiotensinogen did not lead
to endothelial angiotensin generation, inasmuch as HUVECs were unable to
internalize angiotensinogen. Most likely, therefore, in the absence of
angiotensinogen synthesis or endocytosis, M6P receptor-mediated prorenin
internalization by endothelial cells represents prorenin clearance
Enlarged NT (≥3.5 mm) in the first trimester - Not all chromosome aberrations can be detected by NIPT
__Background:__ Since non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well.
__Method:__ 362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm). Chromosome aberrations were investigated using QF-PCR, karyotyping and whole genome SNP array.
__Results:__ After invasive testing a chromosomal abnormality was detected in 137/362 (38 %) fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8 %) a susceptibility locus for neurodevelopmental disorders was found. We estimated that in 2-10 % of fetuses with enlarged NT a chromosome aberration would be missed by current NIPT approaches.
__Conclusion:__ Based on our cohort of fetuses with enlarged NT we may conclude that NIPT, depending on the approach, will miss chromosome aberrations in a significant percentage of pregnancies. Moreover all abnormal NIPT results require confirmatory studies with invasive testing, which will delay definitive diagnosis in ca. 30 % of patients. These figures are important for pretest counseling enabling pregnant women to make informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged NT should be investigated to assess the additional diagnostic value of high resolution array testing for this indication
System size dependence of cluster properties from two-particle angular correlations in Cu+Cu and Au+Au collisions at = 200 GeV
We present results on two-particle angular correlations in Cu+Cu and Au+Au
collisions at a center of mass energy per nucleon pair of 200 GeV over a broad
range of pseudorapidity () and azimuthal angle () as a function of
collision centrality. The PHOBOS detector at RHIC has a uniquely-large angular
coverage for inclusive charged particles, which allows for the study of
correlations on both long- and short-range scales. A complex two-dimensional
correlation structure in and emerges, which is
interpreted in the context of a cluster model. The effective cluster size and
decay width are extracted from the two-particle pseudorapidity correlation
functions. The effective cluster size found in semi-central Cu+Cu and Au+Au
collisions is comparable to that found in proton-proton collisions but a
non-trivial decrease of the size with increasing centrality is observed.
Moreover, a comparison between results from Cu+Cu and Au+Au collisions shows an
interesting scaling of the effective cluster size with the measured fraction of
total cross section (which is related to the ratio of the impact parameter to
the nuclear radius, ), suggesting a geometric origin. Further analysis
for pairs from restricted azimuthal regions shows that the effective cluster
size at drops more rapidly toward central
collisions than the size at . The effect of limited
acceptance on the cluster parameters is also addressed, and a correction
is applied to present cluster parameters for full coverage, leading to
much larger effective cluster sizes and widths than previously noted in the
literature. These results should provide insight into the hot and dense medium
created in heavy ion collisions.Comment: 9 pages, 8 figures, Published in Phys. Rev.
Cost-effectiveness of rotavirus vaccination in the Netherlands; the results of a consensus model
Contains fulltext :
96770.pdf (publisher's version ) (Open Access)BACKGROUND: Each year rotavirus gastroenteritis results in thousands of paediatric hospitalisations and primary care visits in the Netherlands. While two vaccines against rotavirus are registered, routine immunisation of infants has not yet been implemented. Existing cost-effectiveness studies showed inconsistent results for these vaccines because of lack of consensus on the impact. We aimed to investigate which factors had a major impact on cost-effectiveness and were primarily responsible for the large differences in previously estimated cost-effectiveness ratios. METHODS: Based on updated data on health outcomes and cost estimates, we re-assessed the cost-effectiveness of routine paediatric rotavirus vaccination within the National Immunization Program for the Netherlands. Two consensus meetings were organised with national and international experts in the field to achieve consensus and resolve potential controversies. RESULTS: It was estimated that rotavirus vaccination in the Netherlands could avert 34,214 cases of rotavirus gastroenteritis in children aged less than 5 years. Notably, 2,779 hospitalisations were averted of which 315 were extensions of existing hospital stays due to nosocomial rotavirus infection. With a threshold varying from 20K euro - 50K euro per QALY and according to the base-case scenario, the full vaccination costs per child leading to cost-effectiveness was euro 57.76 -euro 77.71. Results were sensitive to the inclusion of potential vaccine induced herd protection, QALY losses and number of deaths associated with rotavirus gastroenteritis. CONCLUSIONS: Our economic analysis indicates that inclusion of rotavirus vaccination in the Dutch National Immunization Program might be cost-effective depending on the cost of the vaccine and the impact of rotavirus gastroenteritis on children's quality of life
Nucleon-Gold Collisions at 200 AGeV Using Tagged d+Au Interactions in PHOBOS
Forward calorimetry in the PHOBOS detector has been used to study charged
hadron production in d+Au, p+Au and n+Au collisions at sqrt(s_nn) = 200 GeV.
The forward proton calorimeter detectors are described and a procedure for
determining collision centrality with these detectors is detailed. The
deposition of energy by deuteron spectator nucleons in the forward calorimeters
is used to identify p+Au and n+Au collisions in the data. A weighted
combination of the yield of p+Au and n+Au is constructed to build a reference
for Au+Au collisions that better matches the isospin composition of the gold
nucleus. The p_T and centrality dependence of the yield of this improved
reference system is found to match that of d+Au. The shape of the charged
particle transverse momentum distribution is observed to extrapolate smoothly
from pbar+p to central d+Au as a function of the charged particle
pseudorapidity density. The asymmetry of positively- and negatively-charged
hadron production in p+Au is compared to that of n+Au. No significant asymmetry
is observed at mid-rapidity. These studies augment recent results from
experiments at the LHC and RHIC facilities to give a more complete description
of particle production in p+A and d+A collisions, essential for the
understanding the medium produced in high energy nucleus-nucleus collisions.Comment: 17 pages, 18 figure
Referral patterns of children with poor growth in primary health care
Background. To promote early diagnosis and treatment of short stature, consensus meetings were held in the mid nineteen nineties in the Netherlands and the UK. This resulted in guidelines for referral. In this study we evaluate the referral pattern of short stature in primary health care using these guidelines, comparing it with cut-off values mentioned by the WHO. Methods. Three sets of referral rules were tested on the
Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)
BACKGROUND: Recent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay. The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease. METHODS/DESIGN: The LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate. Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected. DISCUSSION: The LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease
Catch-up growth up to ten years of age in children born very preterm or with very low birth weight
BACKGROUND: Improved survival due to advances in neonatal care has brought issues such as postnatal growth and development more to the focus of our attention. Most studies report stunting in children born very preterm and/or small for gestational age. In this article we study the growth pattern of these children and aim to identify factors associated with postnatal catch-up growth. METHODS: 1338 children born with a gestational age <32 weeks and/or a birth weight of <1500 grams were followed during a Dutch nationwide prospective study (POPS). Subgroups were classified as appropriate for gestational age and <32 weeks (AGA) or small for gestational age (<32 wks SGA and ≥32 wks SGA). Data were collected at different intervals from birth until 10 years for the 962 survivors and compared to reference values. The correlation between several factors and growth was analysed. RESULTS: At 10 years the AGA children had attained normal height, whereas the SGA group demonstrated stunting, even after correction for target height (AGA: 0.0 SDS; SGA <32 wks: -0.29SDS and ≥32 wks: -0.13SDS). Catch-up growth was especially seen in the SGA children with a fast initial weight gain. BMI was approximately 1 SD below the population reference mean. CONCLUSION: At 10 years of age, children born very preterm AGA show no stunting. However, many children born SGA, especially the very preterm, show persistent stunting. Early weight gain seems an important prognostic factor in predicting childhood growth
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