[Statistical tricks. Can a proband be minus 2 years old?].
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Bias↗
Biomedical subjects
O Butenandt
Publications and source records attributed to O Butenandt.
Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus.
BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2-51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP.
Adaptation, Physiological↗
[Lymphedema. In Ullrich-Turner syndrome it is congenital].
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Child↗
Persistent papilledema in Ullrich-Turner syndrome treated with growth hormone.
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Child↗
GH therapy in juvenile chronic arthritis: results of a two-year controlled study on growth and bone.
Disturbance of growth frequently occurs in children suffering from juvenile chronic arthritis (JCA). Recognition of growth impairment is important because reduced final height is one of the permanent consequences. The aim of this study was to evaluate the efficacy and safety of human GH (hGH) in growth-retarded prepubertal children with JCA. Thirty-five children were tested for GH deficiency (GHD) and randomly assigned to a study and an untreated control group; five were GH deficient and were part of the GHD group. All received glucocorticoids. The study group was treated with 1 IU/kg BW.wk hGH; the GHD group was given 0.5 IU. During 2 yr of hGH treatment growth velocity and height SD score increased compared with baseline values. There was a marked increase in growth velocity in the treated groups, but also some increase in the control group. Plasma levels of IGF-I and IGF-binding protein-3 increased with GH treatment. These results suggest that hGH might be useful in the treatment of growth impairment in JCA. GH may counteract the adverse effects of glucocorticoid therapy, but its effect is dependent on the disease activity. Long-term controlled studies are needed to determine the risks and benefits of GH therapy in JCA.
Arthritis, Juvenile↗
[Measles. A viral illness with risk of permanent damage].
Measles is a highly contagious exanthematous disease. After an incubation period of almost two weeks, catarrhal prodromic, associated with initial attacks of fever appear. Typical manifestations are Koplik's spots. The exanthema appears together with the second rise in temperature. The illness confers lifelong immunity. In individual cases, an encephalitis resulting in permanent neurological deficits must be expected. Every effort should be made to prevent this condition from arising. To this end, immunization with a combination measles, mumps, rubella (MMR) vaccine is recommended.
Adolescent↗
Growth retardation in Turner syndrome: aneuploidy, rather than specific gene loss, may explain growth failure.
The etiology of short stature (SST) in Turner syndrome (TS) is still a subject of speculation. A variety of hypotheses have been put forward, from SST as a result of increased intrauterine tissue pressure after fetal lymphedema to haploinsufficiency of a specific growth gene(s). These hypotheses have various statistical-auxological implications on the growth distribution in TS. Empirical research has provided no clear evidence for any of these theories, but the well known correlation between patients' and midparental height (MPH) could be established. The influence of undetected mosaic status has often been cited as a major problem in the investigation of growth in TS. However, an assessment of mosaic status (simultaneous analysis of karyotype and phenotype) and its effect on growth with inclusion of MPH has been not yet carried out for a large sample. The aim of this study was to evaluate growth and its complex relationship to mosaic status and MPH in TS. In a mixed cross-sectional and longitudinal study we retrospectively analyzed the auxological and clinical data of 447 patients with a pure loss of X-chromosomal material (n = 381 with 45,X0; n = 66 mosaics). The 447 patients were selected from a series of 609 consecutive patients with TS. To assess the effect of mosaic status on growth, we computed a bifactorial analysis of variance (phenotype, karyotype), including MPH as a covariate. In line with the mosaic hypothesis, we found a correlation between individual loss of X-chromosomal material and phenotypical expressivity. In contrast, no correlation was found with respect to growth. With respect to MPH, we found growth retardation (GR) even in those patients with "normal" height above the third percentile (-2 or more SD score). The interindividual variance of GR in TS (comparable to growth variance in the normal population) seems to be unrelated to other TS-specific factors (e.g. mosaic status or single gene loss). Instead, both interindividual variance and the global growth shift distribution are best explained by the presence of an unspecific aneuploidic effect. Furthermore, consideration of patient height in relation to MPH should lead to a better understanding of the nature of GR in TS than the commonly used, strictly qualitative definition of SST.
Adolescent↗
Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators.
OBJECTIVE: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). DESIGN: Included were 223 patients who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. RESULTS: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. CONCLUSIONS: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest.
Body Height↗
Childhood onset of GH deficiency: reassessment of GH status and effects of substitution.
The final height of 77 patients with growth hormone (GH) insufficiency of childhood onset was analysed. Patients were treated between 1968 and 1996 for 1-15 years. The mean final height in patients with severe GH deficiency was 163.9 cm (males) or 151.1 cm (female patients). In patients with partial GH insufficiency, the mean final heights were 166.2 and 157.7 cm, respectively, and in patients with GH deficiency caused by intracerebral tumours, 175.9 or 160.2 cm, respectively. Late established diagnosis, lack of (pituitary) GH during the time prior to 1980 or low frequency of injections per week were related to the fact that final height was often below the target height range. In four of 51 retested patients with childhood onset GH deficiency, a normal response of the pituitary gland to pharmacological testing was found, whereas all other patients still suffered from GH insufficiency. An increased amount of fat and a decreased amount of lean body mass as well as low bone mineral density (12 out of 15 patients) could be demonstrated at re-evaluation.
Adolescent↗
Oesophageal atresia, VACTERL association: Fanconi's anaemia related spectrum of anomalies.
Oesophageal atresia usually occurs without any genetic background. Three cases associated with Fanconi's anaemia are reported. One neonate had growth retardation and numerous malformations including oesophageal atresia and four other components of the VACTERL association. In the two others, oesophageal atresia was isolated. In patients with such malformations an early diagnosis of Fanconi's anaemia may have important genetic and therapeutic implications.
Esophageal Atresia↗
Auxological and endocrinological evaluation of children with hydrocephalus and/or meningomyelocele.
UNLABELLED: Short stature and precocious puberty are frequently found in children with hydrocephalus and/or meningomyelocele (MMC). However, aetiology and pathophysiology have not been well characterized. In this study, 108 patients aged between 3 and 17.8 years were evaluated. Growth was documented on the basis of arm span measurements. Short arm span was found in 47 (43.5%) children with hydrocephalus and/or MMC. Mean arm span was -2.0 standard deviation score (SDS) (-6.4 to +0.8) in 43 girls and -14 SDS (-5.6 to +1.3) in 65 boys. When growth deficiency (more than -2.0 SDS) was diagnosed by arm span measurement (24 F, 23 M) or when early sexual maturation was found (6 F, 9 M), endocrine evaluation followed. Levels of serum insulin-like growth factor and insulin-like growth factor binding protein-3 were low in 22 of 62 (33.8%) patients. In 9 of 62 (14.5%) patients, insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were found to be increased. Growth hormone (GH) deficiency was diagnosed by means of two different stimulation tests (clonidine and arginine) in 7 of 62 (11.3%) patients. In another 3 of 62 (4.8%) children, 12 h night time GH sampling showed low maximum peak levels and decreased area under the curve values, suggesting neurosecretory GH dysfunction. Precocious puberty or early onset of puberty associated with elevated luteinising hormone and follicle stimulating hormone concentrations after stimulation with luteinising hormone releasing hormone was found in 13 of 108 (12.0%) patients (age 7-9 years). Free thyroxine was abnormally low in 2 of 62 (3.2%) patients. Cortisol was within the normal range in all 62 (100%) tested patients. CONCLUSIONS: Short arm span in children with hydrocephalus and/or MMC is frequently accompanied by GH deficiency or neurosecretory GH dysfunction. Early onset of puberty is another frequent finding. Both hormonal disorders may be the consequence of damage to the hypothalamus or the pituitary gland caused by increased intracerebral pressure or increased mass of cerebrospinal fluid.
Adolescent↗
Growth hormone treatment of short children born small for gestational age: reappraisal of the rate of bone maturation over 2 years and metanalysis of height gain over 4 years.
A minority of children born small for gestational age (SGA) fail to achieve sufficient catch-up growth during infancy and remain short throughout childhood, apparently without being growth hormone (GH) deficient. A previous metanalysis of four trials revealed that GH treatment over a period of 2 years induced a dose-dependent acceleration of linear growth and, to a lesser extent, of the rate of bone maturation in short, prepubertal children born SGA. The rate of bone maturation and the change in height SDS for bone age from the previous 2-year metanalysis have been re-analysed according to chronological age (two prepubertal age groups: group A, 3.0-5.9 years old; group B, 6.0-8.9 years old). The rate of bone maturation was slower in younger than in older prepubertal children; this difference was more marked in children receiving high-dose (0.2 or 0.3 IU/kg/day) GH treatment (p < or = 0.01). Accordingly, the change in height SDS for bone age was increased by high-dose GH treatment in both age groups (p < or = 0.01), and was more pronounced in younger than in older children (1.45 +/- 0.28 versus 0.63 +/- 0.20; p < or = 0.01). Height SDS data from 100 short, prepubertal children born SGA have been analysed over 4 years. The change in height SDS appeared to be related to the average dose of GH. A mean GH dose of 0.1 IU/kg/day over 4 years was administered either as 0.1 IU/kg/day for 4 years (continuous) or as 0.2 IU/kg/day for 2 years, followed by 2 years without GH treatment (discontinuous). After 4 years of treatment, the increase in height SDS for the continuous and discontinuous treatment schedules was similar, being 1.42 +/- 0.10 SDS and 1.58 +/- 0.17 SDS, respectively. In a second regimen, a mean GH dose of 0.2 IU/kg/day over 3 years was administered either as 0.2 IU/kg/day for 3 years (continuous) or as 0.3 IU/kg/day for 2 years, followed by 1 year without GH treatment (discontinuous). After 3 years, the increase in height SDS with the continuous and discontinuous treatment schedules was similar, being 2.01 +/- 0.18 SDS and 2.22 +/- 0.16 SDS, respectively. GH administration was well tolerated in all treatment groups. In conclusion, the rate of bone maturation in short, prepubertal children born SGA treated with GH appeared to depend not only on the dose of GH, but also on the age of the child. GH treatment resulted in a prolonged increase in height SDS, the magnitude of the rise being dependent on the average GH dose rather than on the continuous or discontinuous mode of GH administration.
Body Height↗
Growth hormone treatment induces a dose-dependent catch-up growth in short children born small for gestational age: a summary of four clinical trials.
In the present study, data from 230 short children born small for gestational age, who were participating in four clinical trials, were pooled and analysed. At the start of GH treatment, median age and height SDS were 5.3 years and -3.2 SDS, respectively. A dose-dependent increase in height SDS was observed following 2 years of GH treatment: 1.1, 1.7 and 2.5 SDS for the three GH treatment groups (0.1, 0.2 and 0.3 IU/kg/day, respectively), compared with an increase of 0.14 SDS in the control group. In a multiple regression analysis, four variables were found to correlate independently with the gain in height SDS following 2 years of GH treatment. These are given below in order of importance: gain in height SDS = 7.7 x dose of GH (IU/kg/day) -0.11 x age (years) -0.08 x parental-adjusted height SDS + 0.05 x birth length SDS (SD = 0.5; r2 = 0.64). At the end of the 2-year study period, a total of 48%, 66% and 90% of patients in the groups given GH at 0.1, 0.2 and 0.3 IU/kg/day, respectively, had a parental-adjusted height greater than -1.0 SDS.
Body Height↗
[Diphtheria. An illness, which many physicians no longer see in personal experience].
Diphtheria is one of those diseases that the rigorous application of vaccination has rendered very rare in Western countries. However, as a result of being re-introduced from Eastern Europe, it may re-establish itself in the West. The incubation period is two to five days, and in the unprotected, infection may take place via a carrier who himself is not ill. The most feared form is the laryngeal form (croup) and the exotoxin-induced complications: myocarditis with arrhythmias and paresis affecting the muscles of the palate, throat and respiratory system. Once it is clinically suspected, antibiotic treatment and antitoxin therapy should be initiated without delay.
Adolescent↗
[Growth hormone therapy in childhood. Growth hormone therapy in small children without growth hormone deficiency].
The availability of unlimited amounts of recombinant human growth hormone (rhGH) has now made it possible to investigate its growth-promoting effect in children in whom growth hormone production is not deficient. In girls suffering from the Ullrich Turner syndrome, treatment with rhGH increases final height by some 6 to 8 cm. An increase in growth rate has also been observed in children with renal insufficiency, and in children with intrauterine growth retardation. Favourable results have also been reported in children receiving glucocorticoids for such chronic conditions as rheumatoid arthritis, and in youngsters with hypochondroplasia. In a further group of children with various disorders an improvement in the growth rate has been observed, although nothing can yet be said about the outcome in terms of final height. To achieve an increase in growth rate, pharmacological doses of growth hormone higher than those used in children with growth hormone deficiency are necessary. For this reason, the risk of unwanted side effects might be higher than in the latter.
Adolescent↗
Opposite regulation of IGF-I and IGF-I receptor mRNA and concomitant changes of GH receptor and IGF-II/M6P receptor mRNA in human IM-9 lymphoblasts.
Human IM-9 lymphoblasts synthesize IGF-I and express IGF-I receptors, IGF-II/M6P receptors and GH receptors. We have studied the regulation of mRNA expression of IGF-I, IGF-I receptors, IGF-II/M6P receptors and GH receptors in IM-9 cells upon serum-withdrawal and re-addition of serum. IM-9 cells were cultured in RPMI-1640 medium with or without serum for various periods of time. RNA was prepared using guanidinium thiocyanate and CsCl. Antisense riboprobes for human IGF-I, IGF-I receptor, IGF-II/M6P receptor, GH receptor and for comparison for human beta-actin were synthesized and labeled with 32P. Protected fragments of 379 bases and of 420 and 350 bases with the IGF-I receptor and with the IGF-I probe respectively and protected fragments of 670 bases and of 51 and 121 bases with the GH receptor and with the beta-actin probe were detected. For the human IGF-II/M6P receptor probe protected fragments of 260 bases were visualized in RNA samples. The amount of mRNA present in each lane (10 microgram total RNA) was determined by computed densitometry. The amount of IGF-mRNA expressed by IM-9 cells decreased rapidly (within two hours) and dramatically (more than 120%) after the withdrawal of serum and increased significantly (220%) after the re-addition of serum. This increase of IGF-I mRNA preceded the increase in cell number that was seen after 48 h of medium change. Conversely, the expression of IGF-I receptor mRNA and beta-actin mRNA increased by more than 250% after the withdrawal of serum within 2 and 8 h respectively, while GH receptor mRNA fell within 2-4 h. The expression of IGF-II/M6P receptor mRNA continued to increase throughout the duration of the cell culture experiment. We conclude that IGF-I and IGF-I receptor mRNAs are regulated in an opposite direction in serum-deprived IM-9 lymphoblasts. In addition, GH receptor mRNA expression parallels IGF-I mRNA expression.
Actins↗
Endocrine disorders in septo-optic dysplasia (De Morsier syndrome)--evaluation and follow up of 18 patients.
UNLABELLED: Septo-optic dysplasia (SOD) is characterized by hypoplasia of the optic nerve, various types of forebrain defects and hormonal deficiencies. We have studied the clinical and endocrinological characteristics of 18 such patients retrospectively to: (1) better define the endocrine abnormalities in children with SOD; and (2) to find approaches for the interdisciplinary long-term care of children with SOD. The children were seen at the Children's Hospital of the University of Munich from 1976 to 1992 (8 boys, 10 girls; age at initial presentation: 1 day-13 years of age, mean 1.9 years). Unilateral hypoplasia of the optic nerve was found in 7 cases, bilateral hypoplasia in 11. Sonographic, CCT or MRI yielded the following results: 4 of the patients had a cavum septum pellucidum, 3 patients had hypoplasia of the cerebellum, 1 aplasia of the corpus callosum and 1 aplasia of the fornix. An empty sella with or without an ectopic pituitary was seen in 4 cases. Height standard deviation score (SDS) at time of diagnosis was -4.0 to +0.4, mean -2.92. Endocrine deficiencies were present in all 11 patients who had undergone endocrinological investigations. Seven patients suffered from isolated growth hormone (GH) deficiency or multiple hypopituitarism. One had diabetes insipidus centralis, 2 had hypogonadotropic hypogonadism, 1 had hypothyroidism and 2 adrenal insufficiency. Hypothalamic testing was performed only in a subset of patients: in 5 of 11 children tested a thyrotropin releasing hormone (TRH test), in two out of nine a gonadotropin releasing hormone (GnRH) test, and in three out of six GH releasing hormone (GHRH) test yielded abnormal results. High prolactin levels were measured in two out of five patients. CONCLUSION: SOD is characterized by optic nerve hypoplasia and a variety of endocrine deficiencies. In addition, forebrain malformations are present in most SOD patients. Hormonal disorders are present in some SOD patients which may be of hypothalamic origin and need to be investigated systematically.
Adolescent↗
Left ventricular volume and mass in children on growth hormone therapy compared with untreated children.
The myotropic effects of growth hormone (GH) have long been known. An excess of GH as in acromegaly, causes various problems within the circulatory system including cardiac hypertrophy. Although the latter has not been reported as a complication of GH therapy in children, we assessed this possibility in 54 children. Ninety-six echocardiographic studies were performed, in which bisectional images were analysed by Simpson's rule to determine left ventricular volume and mass. Of special interest were 47 results obtained from girls with Ullrich-Turner-syndrome (UTS) treated with supraphysiological doses of GH. Our results showed a significant increase of the myocardial mass in children on GH therapy compared with untreated children, as well as a dose related effect of GH on cardiac mass in girls and cardiac volume in boys. No cardiac hypertrophy, however, could be observed; the increase in muscular mass merely amounting to a normalization of previously low values.
Adolescent↗