| 1. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
-
Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency
- 2008
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:11, s. 4342-4350
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH).OBJECTIVE: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls.DESIGN AND SETTING: A randomized, controlled, long-term multicenter trial was conducted in Sweden.INTERVENTION: Two doses of GH (Genotropin) were administered, 33 or 67 microg/kg.d; control subjects were untreated.SUBJECTS: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (AllITT) population, and 108 in the per protocol (AllPP) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population.MAIN OUTCOME MEASURES: We measured FH sd score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in heightSDS.RESULTS: After 5.9+/-1.1 yr on GH therapy, the FHSDS in the AllPP population treated with GH vs. controls was -1.5+/-0.81 (33 microg/kg.d, -1.7+/-0.70; and 67 microg/kg.d, -1.4+/-0.86; P<0.032), vs. -2.4+/-0.85 (P<0.001); the diff MPHSDS was -0.2+/-1.0 vs. -1.0+/-0.74 (P<0.001); and the gain in heightSDS was 1.3+/-0.78 vs. 0.2+/-0.69 (P<0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations.CONCLUSION: GH treatment significantly increased FH in ISS children in a dose-dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls.
|
|
| 2. |
- Albertsson-Wikland, Kerstin, 1947, et al.
(författare)
-
Growth hormone dose-dependent pubertal growth : a randomized trial in short children with low growth hormone secretion
- 2014
-
Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 82:3, s. 158-170
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i. e. idiopathic isolated GH deficiency.Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH(33) mu g/kg/day for >= 1 year. They were randomized to receive 67 mu g/kg/day (GH(67)) given as one (GH(67x1); n = 35) or two daily injections (GH(33x2); n = 36), or to remain on a single 33 mu g/kg/day dose (GH(33x1); n = 40). Growth was assessed as height SDS gain for prepubertal, pubertal and total periods, as well as AH SDS versus the population and the midparental height.Results: Pubertal height SDS gain was greater for patients receiving a high dose (GH(67), 0.73) than a low dose (GH(33x1), 0.41, p < 0.05). AH(SDS) was greater on GH(67) (GH(67x1), -0.84; GH(33x2), -0.83) than GH(33) (-1.25, p < 0.05), and height SDS gain was greater on GH(67) than GH(33) (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height SDS.Conclusion: Pubertal height SDS gain and AH SDS were dose dependent, with greater growth being observed for the GH(67) than the GH(33) randomization group; however, there were no differences between the once-and twice-daily GH(67) regimens. (C) 2014 S. Karger AG, Basel.
|
|
| 3. |
- Broström, Eva W., et al.
(författare)
-
Gait in children with achondroplasia – a cross-sectional study on joint kinematics and kinetics
- 2022
-
Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Children with achondroplasia have extreme short stature due to short limbs, as well as several other clinical features that may affect their gait. The purpose of this cross-sectional study was to provide a detailed description of gait in children with achondroplasia compared to age-matched controls. Methods: Between the years 2007 and 2010, 16 children with achondroplasia [mean age 9.6 years (range 5–16; six female)] with no previous history of orthopaedic lower limb surgery and 19 age-matched controls conducted three-dimensional (3D) gait analysis at one occasion. The gait analysis rendered pelvis and lower limb joint kinematics and kinetics, and time and distance data. Descriptive statistics, independent samples t-tests, and Fisher’s exact test were used to describe the cohort including gait data and participant characteristics. Results: Children with achondroplasia had kinematic gait pattern deviations in all three planes, especially in the sagittal plane, when compared to the control group. Peak anterior pelvic tilt and peak ankle dorsiflexion were found to be increased. Increased knee flexion was noted at initial contact and again at terminal stance. During stance, children with achondroplasia had a higher peak hip abduction angle and a higher peak knee varus angle in the frontal plane. In the sagittal plane, kinetic gait pattern deviations were found at the hip, knee, and ankle, consistent with a flexion pattern. Compared to the control group, children with achondroplasia walked with reduced walking speed and step length, and increased cadence. There was no difference in walking speed when leg length was taken into account. Normalised step length and normalised cadence, on the other hand, were found to be increased in children with achondroplasia. Conclusions: The observed gait characteristics in children with achondroplasia are related to anatomical attributes and strategies to increase step length, and hence walking speed.
|
|
| 4. |
- Carlsson, A., et al.
(författare)
-
Prevalence of coeliac disease in Turner syndrome
- 1999
-
Ingår i: Acta Pædiatrica. - 1651-2227 .- 0803-5253. ; 88, s. 933-
-
Tidskriftsartikel (refereegranskat)abstract
- This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA- antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA- positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.
|
|
| 5. |
- Ekvall, Sara, et al.
(författare)
-
Co-Occurring SHOC2 and PTPN11 Mutations in a Patient With Severe/Complex Noonan Syndrome-Like Phenotype
- 2011
-
Ingår i: American Journal of Medical Genetics Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 155:6, s. 1217-1224
-
Tidskriftsartikel (refereegranskat)abstract
- Noonan syndrome (NS) is a heterogeneous disorder caused by activating mutations in the RAS-MAPK signaling pathway. It is associated with variable clinical expression including short stature, congenital heart defect, unusual pectus deformity, and typical facial features and the inheritance is autosomal dominant. Here, we present a clinical and molecular characterization of a patient with Noonan-like syndrome with loose anagen hair phenotype and additional features including mild psychomotor developmental delay, osteoporosis, gingival hyperplasia, spinal neuroblastoma, intrathoracic extramedullary hematopoiesis, and liver hemangioma. Mutation analysis of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1, MEK2, NRAS, and SHOC2 was conducted, revealing a co-occurrence of two heterozygous previously identified mutations in the index patient. The mutation SHOC2 c.4A> G; p.Ser2Gly represents a de novo mutation, whereas, PTPN11 c. 1226G>C; p.Gly409Ala was inherited from the mother and also identified in the brother. The mother and the brother present with some NS manifestations, such as short stature, delayed puberty, keratosis pilaris, cafe-au-lait spots, refraction error (mother), and undescended testis (brother), but no NS facial features, supporting the notion that the PTPN11 p. Gly409Ala mutation leads to a relatively mild phenotype. We propose that, the atypical phenotype of the young woman with NS reported here is an additive effect, where the PTPN11 mutation acts as a modifier. Interestingly, co-occurrence of RAS-MAPK mutations has been previously identified in a few patients with variable NS or neurofibromatosis-NS phenotypes. Taken together, the results suggest that co-occurrence of mutations or modifying loci in the RAS-MAPK pathway may contribute to the clinical variability observed among NS patients.
|
|
| 6. |
- Grigelioniene, Giedre, et al.
(författare)
-
Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia
- 2000
-
Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 89:9, s. 1072-1076
-
Tidskriftsartikel (refereegranskat)abstract
- Hypochondroplasia is characterized by a disproportionate short stature with rhizomelic shortening of the limbs. Amino acid substitutions Asn540Lys, Asn540Thr and Ile538Val in the fibroblast growth factor receptor 3 (FGFR3) are considered to cause hypochondroplasia. In this study we examined the FGFR3 gene for the previously described hypochondroplasia mutations and the phenotype of 23 probands with clinically and radiologically diagnosed hypochondroplasia. For the phenotype comparison, the patients were divided into two groups: Group 1: hypochondroplasia with Asn540Lys substitution; Group 2: hypochondroplasia with no mutations identified so far. A three-generation family negative for the known hypochondroplasia mutations was examined with polymorphic markers flanking the FGFR1, FGFR2 and FGFR3 genes. Nine (39%) of 23 probands were found to be heterozygous for the Asn540Lys substitution. The individuals positive for the Asn540Lys substitution were significantly more disproportionate than the individuals without this mutation. In this respect, a genotype-phenotype correlation was found in our patients. However, some individuals belonging to the group without mutations identified so far showed similarly abnormal proportions. Genotyping/haplotyping in the three-generation family with hypochondroplasia showed that FGFR1, FGFR2 and FGFR3 genes were not linked to the hypochondroplasia phenotype in this family, thus further confirming the genetic heterogeneity of hypochondroplasia. CONCLUSION: Individuals with hypochondroplasia heterozygous for the Asn540Lys substitution are significantly more disproportionate than individuals without this mutation. Our study further confirms the clinical and genetic heterogeneity of hypochondroplasia.
|
|
| 7. |
- Grigelioniene, Giedre, et al.
(författare)
-
Mutations in short stature homeobox containing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia
- 2000
-
Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 107:2, s. 145-149
-
Tidskriftsartikel (refereegranskat)abstract
- Dyschondrosteosis (DCO) and hypochondroplasia (HCH) are common skeletal dysplasias characterized by disproportionate short stature. The diagnosis of these conditions might be difficult to establish especially in early childhood. Point mutations and deletions of the short stature homeobox containing gene (SHOX) are detected in DCO and idiopathic short stature with some rhizomelic body disproportion, whereas mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are found in 40-70% of HCH cases. In this study, we performed mutational analysis of the coding region of the SHOX gene in five DCO and 18 HCH patients, all of whom tested negative for the known HCH-associated FGFR3 mutations. The polymorphic CA-repeat analysis, direct sequencing and Southern blotting were used for detection of deletions and point mutations. The auxological and radiological phenotype of these patients was carefully determined. Three novel mutations in DCO patients were found: (1) a deletion of one base (de1272G) (according to GenBank accession nos. Y11536, Y11535), resulting in a premature stop codon at position 75 of the amino acid sequence; (2) the transversion C485G resulting in the substitution Leu132Val; and (3) the transversion G549T causing an Arg153Leu substitution. These substitutions segregate with the DCO phenotype and affect evolutionarily conserved homeodomain residues, based on a comparison of homeobox containing proteins in 13 species. Moreover, these changes were not found in 80 unrelated, unaffected individuals. This strongly suggests that these mutations are pathogenic. The phenotype of our patients with DCO and HCH varied from mild to severe shortness and body disproportion. These results further support clinical and genetic heterogeneity of dyschondrosteosis and hypochondroplasia.
|
|
| 8. |
- Gröndal, Staffan, et al.
(författare)
-
Steroid profile in urine : a useful tool in the diagnosis and follow-up of adrenocortical carcinoma
- 1990
-
Ingår i: Acta Endocrinologica. - : Oxford University Press (OUP). - 0001-5598 .- 0804-4643 .- 1479-683X. ; 122:5, s. 656-663
-
Tidskriftsartikel (refereegranskat)abstract
- The urinary steroid profile was determined in 24 patients with adrenocortical carcinoma. Seventeen of the patients had Cushing's syndrome, virilization or feminization, and 7 had no signs of endocrine disease. Seven of the 11 patients still alive are free of disease, after a follow-up period of 5-75 months. The steroid profile varied widely between the patients with adrenocortical carcinoma. Patients with Cushing's syndrome had increased levels of cortisol metabolites and those with virilism had raised excretion of androgen metabolites. Six of the patients with adrenocortical carcinoma showed normal values of these metabolites. In 23 of the 24 patients the excretion of 3 beta-hydroxy-5-ene steroids and/or metabolites of cortisol precursors, such as tetrahydro-11-deoxycortisol, were significantly increased, compared with healthy controls or patients with adrenal adenomas. These findings suggest a relative deficit or low activity of 3 beta-hydroxysteroid dehydrogenase/delta isomerase and/or 11 beta-hydroxylase in tumour tissue. In the single patient where the steroid profile failed to indicate malignancy, hypercortisolism was seen and the tumour mass was small. The steroid excretion normalized after radical surgery and decreased in patients responding to chemotherapy. During recurred disease the metabolites of 3 beta-hydroxy-5-ene steroids and/or cortisol precursors increased, but in some patients the excretory pattern then was different from that seen before treatment
|
|
| 9. |
|
|
| 10. |
- Hagenäs, Per
(författare)
-
Positioning with supported GPS, A simulation study
- 1995
-
Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The satellite based on positioning system GPS has a very high potential in accuracy and general performance. It has also low cost, low weight and low power consumption.However, among all good proprieties there exist some bad ones. The most serious disadvantages of GPS are that the satellite signal is often disturbed by other electromagnetic signals and that it is shaded by physical obstacles. This diminishes accuracy and reliability, especially when GPS data is used in real time.To decrease this uncertainly, the GPS system should be supported by a complementary sensor. For this supported GPS system the following questions are raised:-how should this positioning system look like and what mathematical methods should be used to get most accurate estimate of the navigation parameters?-how should the achieved accuracy be estimated?-how could erroneous observations be sorted out?This report suggests several methods to solve these problems. Some of these are tested with for this purpose developed software called GPSlab. The main idea is that this is an optimization problem that should be common for all types of sensors to be integrated. A realization of the solution of these problems as software, is here called “A Navigation core”Suggestions presented in this report are:-an optimal estimate of parameters should be carried out on the row data level. This has the advantage to preserve the position information content,-with help of a supporting device it is possible to use several epochs to calculate a more accurate point solution,-if the ambiguities are solved to a number of satellites, also if the number is less than four, a new adjustment of the coordinates should BE Carried out. In this adjustment the observations with solved ambiguities are given a high weight and the pseud oranges are given a low.-a kalman filter could be used on the raw data level. It could detect deviations in the observations such as malfunctions, multipath, cycle slips and other significant errors,- a calibration of the supporting device should be performed when the ambiguities to observed satellites are solved.-it is proposed that Förstner’s method could be used to estimate the proper weights-a method is proposed to detect large errors-the accuracy of the solved parameters is estimated with the help of an optimal weighted point solution, with or without the solved ambiguity-a method to decrease the search volume of possible solutions for ambiguity is proposed,- a method to integrate sensors with different properties is suggested. The simulations show that with the used positioning method, it seems likely to solve the ambiguities, with the support of an Medium Accuracy Navigation System. It also seems possible to solve the ambiguities with the support of an odometer as the only supporting sensor. In that case, however, there have to be at least six satellites, good satellite geometry, small height variations and small errors in the odometer.Furthermore, the azimuth information of the GPS should be used and the observations should be weighted. This system must be initialized with at least five satellites when the receiver is not moving and with at least, probably 7-8 satellites that the receiver moves.
|
|
