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Biomedical subjects

M Craen

Publications and source records attributed to M Craen.

At least 19 recordsLinked to original sources
PubMed1999

Early, discontinuous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years.

Most children born small for gestational age (SGA) normalize their size through spontaneous catch-up growth within the first 2 yr after birth. Some SGA children fail to do so and maintain an abnormally short stature throughout childhood. We have previously reported that high dose GH treatment (66 or 100 microg/kg x day s.c. over 2 yr; age at start, 2-8 yr; n = 38) induces pronounced catch-up growth in short children born SGA, thereby normalizing their height and weight in childhood. Here, we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early, high dose GH treatment. Of the 38 treated children, none developed precocious puberty, and 22 remained prepubertal. Mean age of the latter at start of GH was 4.4 yr, height was -3.7 SD score, and height after adjustment for midparental height was -2.9 SD score. Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD, respectively, during the first and second year after GH withdrawal. Subsequently, when stature was not extremely short at the start (mean adjusted height SD score, -2.7; n = 13), no further GH treatment was given, and the adjusted height was stabilized around -1.0 SD score; when stature was very short at the start (mean adjusted height, -3.3 SD score; n = 9), a second course of GH treatment (66 microg/kg x day s.c.) was initiated either 2 yr (n = 5) or 3 yr (n = 4) after initial GH withdrawal. This second course was associated with renewed catch-up growth and also resulted in a mean adjusted height of -1.0 SD score. In each subgroup, the pattern of the weight course paralleled that of the height course; GH treatment was well tolerated. In conclusion, early, discontinuous, high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children. It remains to be examined whether the normalized stature will be maintained during pubertal development, either with or without further GH treatment.

Blood Cell Count↗
PubMed1998

Age-related perception of stature, acceptance of therapy, and psychosocial functioning in human growth hormone-treated girls with Turner's syndrome.

This study evaluated the perception of stature, acceptance of therapy, and psychosocial functioning in relation to age at onset and time on treatment during 2 yr of GH therapy in 31 girls with Turner's syndrome grouped by age (group A: 3.7-5.8 yr, n = 9; group B: 7.2-11.8 yr, n = 13; group C: 12.5-16.4 yr, n = 9). The growth response after 2 yr was significant in the 3 groups when calculated in terms of growth norms for untreated Turner girls (mean increase in height SD score: +1.2, +1.5, and +1.1, respectively). The effect was less marked in terms of growth norms for normal girls, particularly in group B (+0.5 SD score). Height was perceived as a problem by most patients, except in the youngest girls at the start of treatment (group A) and in the majority of the adolescents after 2 yr of GH therapy (group C), without evidence of relation to growth response during therapy. The GH injections were fairly well accepted by all patients, except those younger than 6 yr. In all patients, expected adult height was unrealistic and became more realistic with age, whereas no consistent changes were observed in relation to growth response to GH therapy. The Child Behavior Checklist revealed elevated mean scores at the behavioral subscales of attention problems (group A and B), social problems, withdrawal, and anxiety-depression (most obviously in group B). No significant changes were seen during GH therapy. In group C, an elevated mean social problem score at the Youth Self Report and a low mean social self-esteem score at the Self-Esteem Inventory were observed before therapy and showed a significant improvement during 2 yr of GH treatment. These results, however, might be biased due to an increase in social desirability during therapy. We conclude that the perception of height, acceptance of GH therapy, and psychosocial functioning in girls with Turner's syndrome show important differences between age groups, with only slight changes observed during GH therapy.

Adolescent↗
PubMed1997

Characterisation of two different nonsense mutations, C6792A and C6792G, causing skipping of exon 37 in the NF1 gene.

Neurofibromatosis type 1 (NF1), characterised by peripheral neurofibromas, café-au-lait spots and iris Lisch nodules, is one of the most common inherited disorders. We have analysed exons 35 to 49 in 21 unrelated NF1 patients using reverse transcription-polymerase chain reaction and protein truncation analysis. In two unrelated patients we found skipping of exon 37 at the cDNA level. Sequence analysis of genomic DNA revealed the presence of a C6792A transversion in one patient and a C6792G transversion in a second patient; both transversions change the codon for tyrosine to a nonsense codon. Sequencing of the exonic sequences as well as the branch sites, and the 3' and 5' splice sites of exons 36, 37 and 38 did not reveal any additional sequence abnormality. This is the first report showing that nonsense mutations in the NF1 gene can induce the skipping of a constitutive exon.

Alleles↗
PubMed1997

Longitudinal study of behavioral and affective patterns in girls with central precocious puberty during long-acting triptorelin therapy.

The aim of the present study was to evaluate the behavioral and affective characteristics and the changes in psychosocial functioning resulting from precocious puberty in 15 girls with central precocious puberty treated for 2 y using the GnRH agonist long-acting triptorelin, and in 5 untreated girls. After diagnosis of precocious puberty at 6.6-10.4 y of age, height, weight and pubertal development were evaluated at 3-month intervals over 2 y. Semi-structured interviews were carried out with the patient, the parents and the pediatric endocrinologists at 1, 8, 16 and 24 months after diagnosis. Standardized questionnaires (Child Behavior Checklist, Self-esteem Inventory) were administered at 1 and 24 months or 16 and 24 months, respectively. There was a mean 1.5-y delay between the observation of signs of puberty as reported by the parents and the diagnosis of precocious puberty at the first consultation of a pediatric endocrinologist. Before follow-up, all 20 girls were very concerned about physical differences from peers, particularly breast development. During therapy, breast regression to minimal or absent development occurred in 5/15 treated patients, who then no longer felt embarrassed about pubertal development in contrast to the other patients. Fear of sexuality remained obvious throughout the study in most patients. Feelings of loneliness and exemplary behavior were observed and tended to decrease in the treated patients and to increase in the untreated patients. Elevated scores of withdrawal, anxiety/depression and somatic complaints at Child Behavior Checklist were still observed after 2 y. These changes in behavioral and affective characteristics appeared to be related neither to height and weight, nor to development of pubic hair, which progressed in most patients. After 2 y, the physical differences remained a concern for 13 girls and the risk of short adult stature for 6. In summary, some behavioral and affective characteristics and particularities in psychosocial functioning are observed in girls with precocious puberty. During treatment with long acting triptorelin, problematic behavior and functioning decrease slightly, particularly in the few girls showing breast regression to minimal or absent development.

Affect↗
PubMed1997

Growth hormone therapy in pre-pubertal children with Noonan syndrome: first year growth response and comparison with Turner syndrome.

We studied the growth-promoting effect of treatment with recombinant human growth hormone in 23 pre-pubertal children with Noonan syndrome, aged between 5.4 and 14.3 y, and all with a height < 1.4 SD for Tanner standards. The growth response and skeletal maturation after 1 y of recombinant human growth hormone treatment (0.15 U/kg/day given by daily injection) in the Noonan syndrome patients was compared with the auxological changes observed in a group of 17 girls with Turner syndrome with a comparable age and height deficit who were treated with recombinant human growth hormone in a similar way. During 1 y of treatment, the mean +/- SD height velocity increased by 4.0 +/- 1.6 cm/y in the Noonan syndrome group and by 3.6 +/- 1.3 cm/y in the Turner syndrome group. Height SDS for chronological age in the Noonan syndrome group increased by 0.53 +/- 0.46 (p < 0.001). In the Noonan syndrome patients the changes in height velocity were positively related to birthweight (r = 0.48, p < 0.05). The changes in height velocity or height SDS were not related to the age, height deficit or a delay in bone age maturation at start of treatment. In neither the patients with Noonan syndrome nor Turner syndrome was an acceleration of bone maturation found. We conclude that treatment with recombinant human growth hormone in pre-pubertal NS patients induces an increase in height velocity and height SDS comparable to that observed in Turner syndrome girls.

Adolescent↗
PubMed1996

Abnormal circulating pancreatic enzyme activities in more than twenty-five percent of recent-onset insulin-dependent diabetic patients: association of hyperlipasemia with high-titer islet cell antibodies. Belgian Diabetes Registry.

Pancreatic amylase and lipase activities were measured in sera of 307 Caucasian insulin-dependent diabetes mellitus patients (IDDM) at clinical onset, 303 nondiabetic siblings of registered patients, and 207 control subjects under age 40 years. In all subject groups lipasemia and pancreatic (but not salivary) amylasemia increased with age and were significantly correlated. Using age-dependent reference ranges, reduced pancreatic enzyme levels were measured in 18% of patients, 6% of siblings, and only 2% of control subjects (p < 0.001). Increased lipase levels were noted in 10% of patients and in only 3% of siblings and 2% of control subjects (p < 0.001). Using both univariate and multivariate statistical analysis, elevated lipase activities at clinical onset were associated with higher titers of autoantibodies against islet cell cytoplasmic antigens and glucagon, but not against insulin or the 65-kDa isoform of glutamic acid decarboxylase (GAD65-Ab), or with markers of genetic predisposition or metabolic dysregulation. These findings indicate the presence of modest, but statistically significant, variations in circulating pancreatic enzyme levels in 28% of IDDM patients at clinical onset (p < 0.001 vs. 5% in control subjects). Increased lipase levels may express a form or a stage of the disease with exocrine cell damage; their association with higher titers of islet cell and glucagon autoantibodies is not yet explained. Lower lipase and isoamylase levels are thought to result from the reduced acinar cell function in the vicinity of insulin-depleted islets. It must be tested whether pancreatic enzyme activities in serum can also be altered during the preclinical stage and can thus be considered as an additional marker for the disease process in the pancreas.

Adolescent↗
PubMed1996

High-dose growth hormone treatment of short children born small for gestational age.

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.

Age Determination by Skeleton↗
PubMed1996

Reduced decrease of peripheral vascular resistance during exercise in young type I diabetic patients.

OBJECTIVE: In normal subjects, peripheral vascular resistance decreases during dynamic exercise. We studied blood pressure and peripheral vascular resistance responses to dynamic exercise in young normotensive type I diabetic patients. RESEARCH DESIGN AND METHODS: Thirty adolescent diabetic patients (9-19 years of age) underwent a maximal exercise test on a cycle ergometer. In a subset of 14 patients, cardiac output was measured by a CO2 rebreathing method and peripheral vascular resistance was calculated. Twenty-four normal individuals, age and sex matched, served as control subjects. RESULTS: Diastolic blood pressure was significantly higher in diabetic patients at intermediate workload (77 +/- 2 vs. 71 +/- 1 mmHg) and peak exercise (86 +/- 2 vs. 73 +/- 2 mmHg). Peripheral vascular resistance was significantly higher in diabetic patients at intermediate workload (17.0 +/- 1.1 vs. 12.6 +/- 0.5 mmHg.l-1.min-1.m-2) and peak exercise (16.3 +/- 1.3 vs. 11.4 +/- 0.5 mmHg.l-1.min-1.m-2). There were no significant correlations with the patient's age, diabetes duration, or diabetes control. CONCLUSIONS: We observed the decrease of vasodilator response during dynamic exercise in normotensive young type I diabetic patients.

Adolescent↗
PubMed1995

Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome.

We report on a girl with the kabuki makeup syndrome, including short stature, premature thelarche and partial growth hormone deficiency of hypothalamic origin, without stalk interruption. Treatment with recombinant human growth hormone resulted in an increase of annualized growth velocity from 3.6 to 11.2 cm. The kabuki makeup syndrome may be associated with hypothalamopituitary dysfunction.

Abnormalities, Multiple↗
PubMed1994

Direct transmission of a tandem duplication in the short arm of chromosome 8.

A family is described in which a mother and her two children carry a tandem duplication of the short arm of chromosome 8. Their phenotypes are similar and characterised by distinct facial dysmorphism, small stature and mild mental retardation. This is one of the first cases of direct familial transmission of a partial duplication of an autosomal chromosome segment.

Adult↗
PubMed1994

Variations in pituitary-gonadal suppression during intranasal buserelin and intramuscular depot-triptorelin therapy for central precocious puberty. Belgian Study Group for Pediatric Endocrinology.

This study evaluated pubertal development, growth and pituitary-gonadal suppression in 21 patients with central precocious puberty treated with buserelin intranasally and switched after a mean of 2.1 yr to depot-triptorelin given im for 1 year. Arrest or regression of puberty was observed in 12 patients while progression of puberty during therapy was seen in 9 patients (6 on buserelin, 2 on triptorelin and 1 on both therapies). The increment in serum LH and FSH concentrations after sc injection of short-acting triptorelin was greater on buserelin than on triptorelin therapy, particularly in patients with evidence of progression of puberty. Height velocity during therapy showed a reduction which paralleled the decelerating phase of the normal pubertal growth spurt. The rate of bone maturation during therapy was inversely related to pretreatment bone age. Predicted final height showed marked individual variations which were inversely related to predicted adult height before therapy. These data indicate that differences in the nature and route of administration of Gn-RH agonist therapy for central precocious puberty can be of importance for inhibition of pituitary gonadotropin secretion and development of secondary sex characteristics. Height velocity and bone maturation are age-related and the change in predicted adult height depends on pretreatment level.

Administration, Intranasal↗
PubMed1994

Growth hormone therapy in Turner's syndrome: one versus two daily injections.

In 44 girls with Turner's syndrome, aged 4.0-15.3 yr, the effects of biosynthetic GH (25 U/m2.week) given as once daily or twice daily injections were compared. During 1 yr of treatment, the growth rate increased similarly by 3.5 +/- 1.3 cm/yr in the once daily group and 2.7 +/- 1.8 cm/yr in the twice daily group. Although pretreatment height velocity was negatively related to age, the increase in height velocity during therapy was not. The mean progression in bone age (TW2-RUS method), during therapy was 1.3 yr in both groups. No significant change in the median insulin secretory response to an oral glucose tolerance test was found. Serum cholesterol and triglyceride concentrations did not change significantly throughout the study in either treatment group. Thyroid hormone concentrations remained within normal limits. Normal increments in left ventricular wall thickness and left ventricular mass for age and body surface were observed after 1 yr of GH treatment. We conclude that division of the daily GH dose given to Turner's syndrome patients into two injections does not result in either a significantly different growth response or different side-effects from once daily treatment during the first year of therapy.

Adolescent↗
PubMed1993

On the variability of the Brachmann-de Lange syndrome in seven patients.

The results of the clinical and radiographic study of 7 patients support the view of a unimodal and rather narrow phenotypic spectrum in the Brachmann-de Lange syndrome (BDLS) and reject the existence of a "classic" type of patient and a "mild phenotype" without upper limb defects who survive with moderate to severe mental retardation. Similarity among all patients is greater than their phenotypic differences. Strict clinical definition of the syndrome warrants easier access to the still unknown cause, most probably a single gene mutation with autosomal dominant inheritance.

Arm↗
PubMed1993

Effects of human growth hormone therapy on melanocytic naevi.

Melanocytic naevi may grow more rapidly during human growth hormone (hGH) therapy. With standardised skin photographs, the growth rate of the naevi was two-fold greater in 14 hypopituitary and 5 Turner's syndrome girls treated with hGH than in untreated patients or controls. HMB-45 immunoreactivity, a marker of stimulated melanocytes, was absent in naevi from 18 of 19 individuals not treated with hGH, including 5 Turner's syndrome patients studied 2-43 months after stopping hGH. In naevi from 39 hGH-treated patients, 22 showed unusual HMB-45 reactivity in dermal naevocytes. During administration of hGH, melanocytic naevi grow faster and there is reversible stimulation of naevocytes.

Adolescent↗
PubMed1993

Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome.

OBJECTIVE: The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH. PATIENTS AND DESIGN: The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradiol orally in 17 girls requesting pubertal development and with a bone age of at least 11 'years' (Group 3). RESULTS: During the first year of rhGH therapy height velocity increased significantly in all patients. Mean +/- SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age-matched girls with Turner's syndrome without puberty (8.9 +/- 1.2 vs 7.4 +/- 1.2 cm/year; P < 0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradiol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm. CONCLUSIONS: The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as possible.

Adolescent↗
PubMed1993

Gender difference in aerobic capacity in adolescents after cure from malignant disease in childhood.

The aim of this study was to document gender difference in aerobic capacity after cure from malignant disease in childhood. We studied 18 males and 17 females aged 11-19 years and 10-18 years, respectively. They had all completed their treatment at least two years previously. Twelve males and 11 females received anthracyclines in comparable doses (range 150-500 mg/m2). Maximal exercise tests were performed on a cycle ergometer. Maximal oxygen consumption (ml/min/kg) was significantly (p < 0.001) lower only in females when compared to their controls. We postulate two causes: girls are smaller than their controls, possibly related to their higher vulnerability to cranial irradiation than boys; and girls were less involved than boys in sports. The influence of anthracycline treatment on aerobic capacity was only observed in males and not in females. This could be related to the higher exercise level in boys than in girls.

Adolescent↗