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Biomedical subjects

J M Wit

Publications and source records attributed to J M Wit.

At least 127 records · Page 7Linked to original sources
PubMed1995

Impaired social status of growth hormone deficient adults as compared to controls with short or normal stature. Dutch Growth Hormone Working Group.

OBJECTIVES: In adults with growth hormone deficiency (GHD) social problems have been reported, but so far the relative contributions of GHD, additional pituitary deficiencies and short stature have not been distinguished. We therefore compared social data from GHD patients with social data from controls with short or normal stature. Furthermore we investigated whether social problems are caused solely by the deficiency of GH or also by the associated absence of other pituitary hormones. DESIGN: A questionnaire was sent to patients and controls with items on education, profession, income, partner and living situation. PATIENTS: Two hundred and ten GHD patients treated in childhood but not in adulthood with GH (93 isolated GHD (IGHD), 111 patients with multiple pituitary deficiency (MPD)) were compared with 53 short controls (height in childhood < third percentile for population) and 39 normal stature controls. RESULTS: There were no differences between short and normal controls. There were also no differences between IGHD and MPD patients in any of the investigated items. GHD patients did not differ from controls on education level, but scored lower on the profession scale, had a lower income and had a partner less often; if they had a partner they less often had children; also, more of them lived with their parents. CONCLUSION: Since patients with multiple pituitary deficiency did not differ from patients with isolated growth hormone deficiency, this suggests that the lower scores on the social parameters are the result of the growth hormone deficiency itself. Since short stature controls had higher scores than patients with growth hormone deficiency and did not differ from normal stature controls in any of the aspects investigated, it seems unlikely that the problems of the patients with growth hormone deficiency can be attributed to short stature.

Adult↗
PubMed1995

Long-term results of growth hormone therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group.

BACKGROUND AND OBJECTIVE: Growth hormone treatment in children with idiopathic short stature (ISS) leads to growth acceleration in the first years, but the effect on final height is still poorly documented. We therefore studied the long-term effect of GH therapy in children with idiopathic short stature. DESIGN: We have treated 27 prepubertal children with ISS with recombinant human GH (rhGH) in an initial dosage of 2 IU/m2 body surface/day subcutaneously, which was doubled either after the first year if the height velocity increment was less than 2 cm/year, or thereafter if height velocity fell below the P50 for bone age. Growth and bone maturation of the treatment group (ISS group, n = 21) were compared to those of an untreated control group with ISS (ISS controls, n = 27) and of a group of rhGH treated children with isolated GH deficiency (GHD group, n = 7). RESULTS: In 9 patients of the ISS group still on treatment, height standard deviation score (HSDS) for chronological age increased from -3.8 +/- 0.7 to -2.3 +/- 0.9 (mean +/- standard deviation) over 6 years, while in matched ISS controls HSDS for age did not change. HSDS for age in the GHD group increased from -3.9 +/- 0.6 to -1.8 +/- 0.7 after 4 years, significantly more than the ISS group. Bone maturation was accelerated in the ISS and GHD groups. HSDS for bone age and predicted adult height did not change in either group. Final height in 12 children of the ISS group was -2.6 +/- 1.0 SDS. In the untreated controls final height was similar. A low integrated GH concentration over 24 hours, a low GH peak to provocative stimuli, and minimal initial BA delay predicted a favourable outcome. CONCLUSION: rhGH treatment in this group of children with idiopathic short stature did not increase average final height. Part of the heterogeneity of the response can be attributed to the variation in endogenous GH secretion and initial bone age delay.

Body Height↗
PubMed1995

A special case of congenital adrenal hypoplasia and acute bilateral infantile striatal necrosis.

Isolated mineralocorticoid deficiency is described in a 5-week-old boy. The deficiency progressed to general adrenal insufficiency during the boy's first year of life. The family history suggested X-linked inheritance. At 18 months of age the patient developed acute bilateral infantile striatal necrosis, which might suggest a possible relationship between both entities.

Adrenal Insufficiency↗
PubMed1995

Catch-up growth in early treated patients with growth hormone deficiency. Dutch Growth Hormone Working Group.

Catch-up growth of 26 children with growth hormone deficiency during four years of growth hormone treatment, which was started young (< 3 years), was compared with that of 16 children with coeliac disease on a gluten free diet. In children with growth hormone deficiency mean (SD) height SD score increased from -4.3 (1.8) to -1.9 (1.4) and in patients with coeliac disease from -1.8 (0.9) to -0.1 (0.8). Height SD score after four years correlated positively with injection frequency and height SD score at start of treatment in children with growth hormone deficiency. All patients with coeliac disease reached a height above -2 SD scores after four years, while the height of 26% of children with growth hormone deficiency on daily injections and of 86% of children on 2 or 4 injections/week was still below -2 SD scores. In patients with growth hormone deficiency on daily injections with an initial height SD score between -2 and -4 catch-up was similar to that of patients with coeliac disease with a comparable initial height deficit. Growth hormone deficient children with an initial height SD score < -4 did not reach full catch-up growth within four years. In conclusion, catch-up growth in early treated children with growth hormone deficiency over four years is adequate provided that daily injections are given and the initial height SD score is not less than -4.

Age Factors↗
PubMed1995

Final height in a large cohort of Dutch patients with growth hormone deficiency treated with growth hormone. Dutch Growth Hormone Working Group.

Final height was evaluated in 203 patients with growth hormone (GH) deficiency, who had been treated with GH in childhood, and was related to other factors. Mean final height was 168.1 cm (men) and 154.7 cm (women), -2.07 and -2.20 SD of the population mean, respectively. Patients with GH deficiency due to cerebral tumour were taller than those with idiopathic GH deficiency, and patients with induced puberty were taller than those with spontaneous puberty. Target height (r = +0.37), birth length (r = 0.36), height SDS at the start of therapy (r = +0.51) and at the start of puberty (r = +0.58) were significantly correlated with final height. Multiple linear regression analysis revealed that after correction for height at the start of puberty, age at the start of puberty was also positively correlated with final height. Patients who were treated after 1983 (when treatment regimens were changed) were taller than patients who finished treatment before 1983. The results suggest the importance of preventing a large initial height deficit and attaining optimal height at the start of puberty.

Adolescent↗
PubMed1995

Treatment with two growth hormone regimens in girls with Turner syndrome: final height results. Dutch Growth Hormone Working Group.

In 1987 a multicentre trial of recombinant human growth hormone (GH) was started in girls with Turner syndrome. Fifty-four patients were randomly assigned to receive GH, 8 IU/m2 3 times/week (group 1), or 4 IU/m2 6 times/week (group 2). In addition, the 35 patients older than 12 years received ethinyloestradiol, 100 ng/kg body weight/day, and after 2 years GH therapy was increased to 6 IU/m2 6 times/week. Recombinant human GH treatment was stopped when the height increment during the previous 6 months of treatment was less than 0.5 cm. Treatment has so far been stopped in 48 patients: treatment was stopped early in 2 patients due to lack of motivation, 1 patient died suddenly and the treatment protocol was completed in 45 patients. The last height measurement obtained, which was considered as (near) final height, was 152.3 +/- 5.3 cm (mean +/- SD) in these patients, which is higher (p < 0.001) than the adult height of 147.0 +/- 6.3 cm reported in 63 untreated adult Dutch patients with Turner syndrome. No differences in outcome were found between the two dose regimens.

Body Height↗
PubMed1995

Immunologic studies in children with idiopathic short stature before and during growth hormone therapy. Dutch Growth Hormone Working Group.

In 34 children with idiopathic short stature (ISS) we studied parameters of humoral and cellular immunity before and during growth hormone (GH) therapy. The patients were treated with recombinant human GH 3.0 or 4.5 IU/m2 body surface/day, 6 times/week. Leucocyte and lymphocyte counts, percentages of neutrophils, eosinophils, basophils and monocytes were available up to 4 years of therapy (n = 34) and lymphocyte subsets and serum immunoglobulins during the first year of treatment (n = 16). Differences between the measurements at the start and during therapy were tested by a mixed model ANOVA to repeated measurements. Before the start of GH therapy all parameters of immunity were within the normal range in these children. During the first months of treatment the leucocyte and lymphocyte counts decreased and at 6 months were significantly lower than at the start (p = 0.003 and p = 0.006, respectively). Thereafter leucocyte numbers no longer differed from baseline. Lymphocytes were again lower at 36 months (p = 0.001). The percentages of neutrophils, eosinophils, basophils, monocytes and lymphocyte subsets did not change during therapy. Serum IgA concentrations showed a transient decrease at 3 and 6 months of GH therapy (p = 0.01 and p = 0.02). The observed changes were not related to GH dosage or height velocity. We conclude that GH treatment in children with ISS induced a small decrease in leucocyte and lymphocyte counts and serum IgA concentrations.

Adolescent↗
PubMed1995

Effect of gonadectomy on growth and GH responsiveness in dwarf rats.

Normal rats are sexually dimorphic in their growth and GH secretion. Gonadectomy (Gnx) changes the GH secretory pattern and this could explain differential growth rates in male and female rats. Gonadal steroids may also affect tissue growth directly, or by changing their responsiveness to GH. The effects of Gnx on growth, GH responsiveness, and hepatic GH receptors have now been studied in young (4-7 weeks old) GH-deficient dwarf rats in which the effects of steroid-induced alterations in residual endogenous GH secretion will be much less pronounced. Groups of intact and Gnx dwarf rats (n = 5-7) were infused with recombinant human GH (144 micrograms/day) either continuously or in a pulsatile pattern (every 3 h) for 7 days, whilst control groups received saline infusions. Gains in weight, length and tibial bone growth were measured. Female dwarf rats grew significantly more slowly than male dwarfs. Gnx in male dwarfs inhibited growth significantly, whereas ovariectomy had a lesser stimulatory effect in females. Hepatic lactogenic and somatogenic receptors were higher in females and ovariectomy lowered their values towards male levels. Pulsatile GH infusions were more effective than continuous infusions of the same daily GH dose, but when the different underlying growth rates (measured in saline-infused Gnx animals) were taken into account, the responsiveness to pulses of hGH was not different between males and females or between intact and Gnx animals. We have concluded that Gnx in dwarf rats does affect growth, but the effects are small in comparison with those seen in normal rats. Since pulsatile GH infusions stimulated growth more effectively than continuous GH, irrespective of the gonadal steroid status, and the responsiveness to exogenous GH was not changed by Gnx, the results imply that changes in the GH secretory pattern induced by gonadal steroids may have a larger impact on the growth rate than direct effects at the tissue level, at least in the rat.

Animals↗
PubMed1995

CALIPER: individualized-growth curves for the monitoring of children's growth.

Monitoring children's growth is a fundamental part of pediatric care. Deviation from the expected growth pattern can be an important sign of disease and often results in parental anxiety. Most preprinted growth curves are based on cross-sectional data derived from population-based studies of normal children. Since the age of the pubertal growth spurt varies substantially among the normal curves, these curves don't adequately reflect the expected growth pattern of an individual child. In addition, any preprinted growth curve based on the general population becomes less useful when the maturation of a child and the heights of it's parents differ substantially from the average. Established methods exist to adjust the general reference-growth curves for parental height. However, these methods generally are too time consuming to be used in clinic. Only heuristic methods are known to us to adjust the general-reference curves for maturation. We have developed the decision-support system CALIPER, that enables and standardizes the generation of individualized reference-growth curves. CALIPER consists of a graphical interface for data entry, a progress-report generator, and a module for the interactive, dynamic display of general-reference curves and individualized-reference curves. Preference settings such as ethnic background and gender determine the required population curves and individualization method. Individualization can be based on parental height and/or maturation. Maturation is based on an assessment of a child's bone age and/or pubertal stage. The bone age can be assessed by different methods. We have performed an evaluation of CALIPER's methodology by assessing the effect of individualization on the reference growth curves for 466 normally growing children. The individualized-reference curves reflect the growth pattern of children significantly better than the general-reference curves. CALIPER can be used on a case by case base as an aid in clinic (assessment of children's growth and communication with patient and parents) or as a tool to investigate current clinical questions concerning the relation of bone age, pubertal stage, and growth pattern for any part of the population. Besides providing for decision support by the interactive graphical representation of individualized-reference curves and growth data, CALIPER will be linked to a module that can provide automatic interpretation of the data (Kuilboer et al, SCAMC-93). CALIPER runs on a Macintosh, and requires 600K of memory. A color monitor is preferable, but not required. We will demonstrate several cases that will illustrate the clinical problem and CALIPER's potential.

Body Height↗
PubMed1994

The effect of oestrogen treatment on body proportions in constitutionally tall girls.

Body proportions were studied in 31 girls with constitutional tall stature during treatment with 200 micrograms ethinyl oestradiol per day continuously, combined with 5-10 mg medroxyprogesterone on the first 10 days of each month. Their mean (+/- SD) predicted adult height was 186.0 (+/- 4.0) cm. At the start of therapy, leg length (LL) standard deviation score (SDS) (3.8 +/- 0.7) was significantly greater than the sitting height (SH) SDS (2.3 +/- 1.1). During therapy, the mean sitting height increased by 2.9 cm, in contrast to an increment of only 0.8 cm for LL. The SDS of the ratio between SH and LL remained below zero. The expected gain without therapy, assuming a stable SDS position over time, was 5.4 cm for SH and 4.4 cm for LL, significantly more than the observed gains. In conclusion, tall girls have relatively long legs. Oestrogen therapy leads to an almost complete stop of leg growth, while the growth of the trunk is reduced to a lesser extent. This selective inhibition results in a trunk/leg ratio which is closer to, though still significantly different from that of normal girls.

Adolescent↗
PubMed1994

Catch-up growth in 60 children with celiac disease.

The growth pattern of 28 girls and 32 boys with celiac disease was analyzed up to the ages of 10 and 12 years, respectively. Fifty-four patients (90%) were diagnosed before 4 years of age and six patients (10%) between 5 and 9 years of age. At diagnosis, 18 of 60 patients (30%) had a height SD score below -2.0, and 45 of 59 patients (76%) had a weight-for-height below the median. The mean height SD score showed increasing growth retardation in the year before diagnosis, relatively quick catch-up growth in the year after diagnosis, and complete catch-up in 2-3 years. Mean weight-for-height showed a progressive decrease 12-18 months before diagnosis, increased to a maximum at the end of the first year of therapy, and returned to normal 15 months after dietary treatment. Independent of age at diagnosis, initial degree of wasting, diagnostic delay, and strictness of gluten-free diet, catch-up growth was complete in this group of patients who were diagnosed before 9 years of age.

Adolescent↗
PubMed1994

A mathematical model describing catch-up growth in celiac disease.

Celiac disease may lead to various degrees of growth retardation. In general, catch-up growth is completed in the first 2 years after the start of therapy. A mathematical model for catch-up growth in celiac disease can be useful as a reference to which the growth pattern observed during treatment of other conditions can be compared. In this study we performed a non-linear regression analysis on individual growth data of 16 celiac disease patients using a monomolecular growth function. The goodness of fit was significant in all cases (p < 0.05), which illustrates that this function adequately describes catch-up growth in individuals with celiac disease. From the individual models we have composed a cross-sectional curve and a longitudinal description of the pattern of catch-up growth for the entire population.

Celiac Disease↗
PubMed1994

Comparative effect of two doses of growth hormone for growth hormone deficiency. The Dutch Growth Hormone Working Group.

The comparative effect and safety of 2 IU compared with 4 IU/m2/day of recombinant human growth hormone (rhGH) was studied in 38 growth hormone deficient children regarding the impact of several factors on short term (one year) and long term (three year) growth response. In 21 newly diagnosed patients, three years of rhGH treatment resulted in a significant increase of height velocity SD score, height SD score, and predicted adult height SD score, irrespective of rhGH dose. In 17 transfer patients (previously treated with 12 IU rhGH/m2/week) 4 IU/m2/day resulted in a significantly higher height velocity SD score and height SD score for chronological age than 2 IU/m2/day, while more of them reached their target range or showed a substantial height SD score increment. Height SD score for bone age and predicted adult height SD score only increased significantly with 4 IU rhGH. After one year of rhGH treatment, new patients showed significant negative correlation between delta height SD score with age and baseline insulin-like growth factor I (IGF-I) SD score, and positive correlation with rhGH dose. After three years of treatment, delta height SD score for chronological age was significantly, negatively correlated with age and baseline 'corrected' height SD score (height SD score for chronological age minus target height SD score). There was no significant correlation with rhGH dose. Prolonged treatment with either dose had no adverse effect on IGF-I concentrations, carbohydrate or lipid metabolism. As early age and divergence between height SD score and target height SD score seem more important for growth response than rhGH dose, it is recommended that treatment starts early with 2 IU rhGH/m(2)/day and the dose is doubled if growth is insufficient after several years of treatment.

Body Height↗
PubMed1993

Body proportions in individuals with Turner syndrome. The Dutch Growth Hormone Working Group.

The body proportions in 191 individuals with Turner syndrome (TS) were investigated. At 3 years of age the mean sitting height in TS was normal, thereafter trunk growth was impaired, resulting in a standard deviation score (SDS) of -2.4 in the adult. From 3 to 12 years of age the mean SDS of leg length increased from -2.7 to -3.6; and then fell to -2.5. At 3 years of age the ratio of sitting height to leg length was 3.2 standard deviations (SD) above the normal mean. Thereafter the ratio slowly approached the normal percentiles. It was +0.6 SD in 15- to 18-year-old women. Thereafter it increased to 1.7 for adults with TS. Knemometric measurements in 32 individuals with TS and 32 controls revealed that in TS the upper legs were relatively shorter than the lower legs. We conclude that children with TS, and to a lesser extent adults, have a disproportionately short stature with relatively short legs whereas body proportions are almost normal in adolescents.

Adolescent↗
PubMed1993

Cosegregation of missense mutations of the luteinizing hormone receptor gene with familial male-limited precocious puberty.

Familial male-limited precocious puberty is a male-limited autosomal dominant condition. It is characterized by increased testosterone synthesis in the absence of testicular stimulation by luteinizing hormone (LH). We hypothesised that an abnormal configuration of the LH receptor might autonomously activate G protein coupling, and thereby cause the overproduction of testosterone in this condition. To test this hypothesis, we screened for mutations in a part of the LH receptor gene that is important for G protein binding. DNA sequence variation was detected in 2 out of 5 families with male-limited precocious puberty by the single strand conformation polymorphism technique. Direct sequencing demonstrated different single nucleotide substitutions in the sixth transmembrane region of the LH receptor gene. The mutations cosegregated with the disorder in both families (lod score 5.76 without recombination). Both mutations cause an amino acid substitution in the sixth transmembrane domain, close to the C-terminal portion of the third cytoplasmatic loop, a region which is important for the binding of G proteins. We conclude that familial male-limited precocious puberty cosegregates with missense mutations in the LH receptor gene. These findings support the hypothesis that increased activity of the LH receptor is the pathogenetic mechanism that causes the abnormal pubertal development in this condition.

Amino Acid Sequence↗
PubMed1993

Immunological findings in growth hormone-treated patients.

In vivo studies in experimental animals and in vitro studies using human lymphocytes have indicated that growth hormone (GH) is important for the development and function of the immune system. This is most clearly illustrated by the underdevelopment of the thymus in dwarf Snell mice, which is prevented by GH treatment. In contrast, in vivo studies in humans have generally shown only minor alterations of immune function in GH deficiency. GH administration to children with various growth disorders may lead to variable and subtle changes in some laboratory parameters of immune function, but no clinical symptoms associated with immune dysfunction have been reported.

Animals↗
PubMed1993

Results of long-term therapy with growth hormone in two dose regimens in Turner syndrome. Dutch Growth Hormone Working Group.

Girls with Turner syndrome were divided according to age (group A 6-12 years, and group B 12-19 years) and human growth hormone (GH) dose regimen (A1 and B1, three injections/week; A2 and B2, six injections/week). All groups responded to GH, 24 IU/m2/week, with an increase in height velocity, though in the older girls, the response was comparatively poor. Therefore, the dose regimens in groups B1 and B2 were increased to 36 IU/m2/week given as six injections in both groups. This change resulted in an increase in height velocity only in group B1. During the first 2 years only, the height velocity was greater in group A2 than group A1. The conclusion is that a regimen of six injections/week is more effective than one of three injections/week in terms of initial height gain and change in predicted adult height. In girls with Turner syndrome aged over 16 years, GH therapy has no significant effect.

Adolescent↗