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Biomedical subjects

J R Bierich

Publications and source records attributed to J R Bierich.

At least 19 recordsLinked to original sources
PubMed1992

Aetiology and pathogenesis of growth hormone deficiency.

Growth hormone deficiency (GHD) represents an aetiologically non-uniform disorder: it can have multiple causes. Three main groups can be differentiated: (1) GHD due to manifest organic alterations of the hypothalamo-hypophyseal system; (2) so-called idiopathic cases; and (3) genetically determined forms. The first group comprises the congenital malformations, affecting the midline structures of the brain more often than the pituitary itself, and the acquired lesions, mainly tumours, which are generally suprasellar rather than intrasellar. The large majority of the so-called idiopathic cases result from perinatal damage which affects the hypothalamus more often than the pituitary proper. Births in non-cephalic positions, in particular breech deliveries, play a significant role, but other difficult parturitions of prolonged duration also lead to such damage. With improved obstetric techniques, particularly the more frequent use of caesarean section, such lesions now occur far less frequently than 30 years ago. In the last 20 years, several genetically determined disorders associated with GHD have been described, four of them with isolated GHD, three with multiple deficiencies of pituitary hormones. Most cases are inherited by autosomal recessive transmission.

Congenital Abnormalities↗
PubMed1992

Constitutional delay of growth and adolescence.

Constitutional delay of growth and adolescence (CDGA) is characterized by simultaneous retardation of growth, skeletal maturation and sexual development. Primarily longitudinal growth is impaired. The late occurrence of puberty is a secondary phenomenon brought about by the retarded physical development. Plasma levels of sex hormones and gonadotrophin correlate with bone age, not with chronological age. The provocation tests for growth hormone (GH) show normal results. In contrast, the spontaneous secretion of GH, measured half-hourly through the night or over 24 hours, is markedly reduced. Plasma somatomedin C is diminished. According to these data, CDGA is not a genuine GH deficiency but represents a cybernetic disorder coinciding with a false threshold for GH. As shown by large series of investigations, the final height of the patients lies on average 1.85 SD below the mean of healthy adults, with large individual variations. The decision as to whether treatment by growth promoting hormones should be performed should be made with regard to the individual height prognosis. With GH in physiological doses growth velocity can be considerably increased. Bigger doses of the hormone appear to be necessary in order to enhance final height. Treatment by anabolics and testosterone increases height velocity only, not adult height.

Adolescent↗
PubMed1992

Constitutional delay of growth and adolescence. Results of short-term and long-term treatment with GH.

During recent years numerous reports on the favourable results of short-term trials with GH in patients with constitutional delay of growth and adolescence (CDGA) have been published, but it has been unclear whether such treatment affects final height. In the present study, the results of long-term therapy with GH in replacement doses have been evaluated in 15 patients who were treated with GH for several years (three years on average). At the start of treatment, 10 of the children were prepubertal and 5 were in puberty. All patients were followed up until final height was reached. Mean final height of the 13 male patients was 170.0 +/- 4.4 cm, i.e. -1.58 SDS. In the two female patients, final height was 150.0 cm (-3.5 SDS) and 164.0 cm (-0.8 SDS), respectively. Adult height of the patients lagged behind target height by 5.4 +/- 3.2 cm (mean +/- SD). Measured adult height corresponded to adult height as predicted prior to treatment. In conclusion, GH treatment of patients with CDGA did not increase final height.

Adolescent↗
PubMed1991

New observations on midline defects: coincidence of anophthalmos, microphthalmos and cryptophthalmos with hypothalamic disorders.

Four children with severe congenital eye anomalies are described of which three had related symptoms. Two had bilateral anophthalmia, the optic nerves not detectable by computed cranial tomography and magnetic resonance imaging, and the third child had bilateral microphthalmia and coloboma iridis. The fourth patient had bilateral cryptophthalmia as part of Fraser syndrome. All four patients were of small stature. In three of them growth hormone deficiency was demonstrated which was of hypothalamic origin as shown by growth hormone releasing hormone tests. In the fourth child hypogonadotropic hypogonadism and tertiary thyroid deficiency were diagnosed which responded well to thyroxine treatment. Pathogenetically the described disorders are due to congenital defects of midline structures as a common "developmental field".

Abnormalities, Multiple↗
PubMed1990

A specific radioimmunoassay for the growth hormone (GH)-dependent somatomedin-binding protein: its use for diagnosis of GH deficiency.

The acid-stable subunit of the GH-dependent large mol wt somatomedin-binding protein (SmBP) was isolated from human plasma Cohn fraction IV by a three-step procedure, and a specific RIA was developed which allowed measurement in unextracted serum. Although in normal human serum most of immunoreactive material was present as the large mol wt complex (150K), considerable amounts of smaller components were found by high performance liquid exclusion chromatography in the 60K, 42K, and 32K range. Normal serum levels were low at birth, rose sharply during the first weeks of life, and showed a moderate peak at puberty. To assess the diagnostic efficacy of SmBP for GH deficiency (GHD), patients previously diagnosed as GH-deficient by conventional criteria (n = 132) were compared to short statured children without GHD (n = 130). Taking the fifth centile as a limit of normality the majority of patients with GHD had subnormal levels, yielding high sensitivity of the test (0.97). In contrast, most of the non-GH-deficient children had SmBP levels within the normal range, resulting in high specificity (0.95) and, consequently, high accuracy (0.96). These results suggest that the large mol wt SmBP is an excellent screening parameter and is highly informative for GHD.

Adolescent↗
PubMed1990

[Natural science and humanitarian aspects of medicine].

In the 19th century the natural sciences took a rapid rise, connected with a mainly biological interpretation of all vital processes. To the physician fell the role of the analytical observer who--according to the findings obtained - made a precise diagnosis which in consequence led to the adequate therapy. Patient and disease were the objects of observation and treatment. In the twentieth of our century a radical change took place. R. von Weizsäcker and R. Siebeck established the "anthropologic medicine" resp. the "medicine of the person" where the doctor and the patient enter into a personal relationship. The significance of the patient's biography in the course of this disease was recognized. The "psychosomatic medicine" was developed. Our own time requires the reorientation to those values and principles and, moreover, and improved integration of the advanced medical technology.

Altruism↗
PubMed1989

Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I.

The insulin-like growth factors (IGF)-I and -II are bound to specific carrier proteins in the circulation. For investigation of their physiological role, the acid-stable subunit of the major binding protein (SmBP) was isolated from human plasma Cohn fraction IV. Its effect on the mitogenic activity of IGF-I was studied with baby hamster kidney fibroblasts (BHK-21) and human skin fibroblasts. While free IGF-I had no effect on thymidine incorporation into DNA with BHK-21 cells and only a moderate effect with human fibroblasts under standard conditions, DNA synthesis was significantly enhanced with both cell lines if IGF-I was complexed with SmBP before the experiment. The enhancement was optimal at an approximately equimolar ratio of both peptides. In contrast to experiments in which large concentrations of IGF-I were added at the beginning, repeated addition of small quantities of free IGF-I at hourly intervals clearly stimulated DNA synthesis in BHK-21 cells. Binding studies with radiolabeled SmBP revealed no evidence for direct interaction with either cell line. It is concluded that SmBP acts as a reservoir, releasing continuously low amounts of IGF-I and thereby creating a steady state situation of receptor occupancy, which appears to be a better mitogenic stimulus than temporary large concentrations of IGF-I.

Blood Proteins↗
PubMed1988

A specific radioimmunoassay for insulin-like growth factor II: the interference of IGF binding proteins can be blocked by excess IGF-I.

A specific antiserum for human IGF-II has been produced by immunizing rabbits against the synthetic peptide IGF-II(33-40). With this antiserum and IGF-II as tracer a radioimmunoassay for IGF-II has been developed. Cross-reactivity with IGF-I was 0.05% and half-maximal displacement occurred at 2.5 micrograms IGF-II per 1. It was demonstrated that residual IGF-binding protein (IGF-BP) in acid-ethanol extracts interferes with IGF-II measurements and may produce erroneously high values. This interference could be completely blocked by excess IGF-I (25 ng per tube). Utilizing this method IGF-II was measured in subjects at various developmental stages. In newborns, the mean serum level was 237 micrograms/l (N = 56) with a range of 132-430 micrograms/l (5- and 95-percentile, respectively). During the first year of life a considerable increase occurred. Thereafter IGF-II increased only slightly with age from 520 micrograms/l (range 368-735) to 647 micrograms/l (range 507-823) in adults. In patients with growth hormone deficiency (N = 57) IGF-II levels were significantly (P less than 0.001) lower than in controls (mean 261 micrograms/l, range 126-542). It is concluded 1) that residual IGF-binding proteins in acid-ethanol extracts may cause considerable error in IGF-II measurements, and 2) that this interference can be completely blocked by excess IGF-I, if highly specific antisera are used.

Adolescent↗
PubMed1988

Clinical relevance of serum measurements of insulin-like growth factors and somatomedin binding proteins.

With the presently available RIAs, serum levels of IGF-I, IGF-II and somatomedin binding protein can be determined specifically. Basal IGF-I and binding protein levels are low in GH deficiency, and normality of these parameters virtually excludes the condition. If, in a given clinical situation, auxological criteria and IGF-I (binding protein) levels suggest GH deficiency but the diagnosis is rejected by conventional stimulation tests, a further diagnostic work-up is needed, including measurements of spontaneously secreted GH. IGF measurements may serve as tools to disclose the unknown pathogenesis in growth disorders. Short-term responses of IGFs to exogenous GH may assist in defining the GH doses required to induce long-term growth.

Adolescent↗
PubMed1986

Treatment of growth hormone deficiency.

According to the results reported in the literature and from our own experience, the following recommendations for the treatment of children with GHD can be given: In order to start GH replacement therapy in early childhood the diagnosis of GHD should be made as early as possible. The growth hormone dose during prepubertal age should not fall short of 12 IU/m2 per week. During spontaneous or induced puberty, the dose needs to be increased, possibly by a factor of two. Daily subcutaneous injections appear most suitable. Treatment with growth hormone releasing factors in cases with hypothalamic GHD, although a promising alternative to the treatment with hGH (Thorner et al, 1985), must be considered experimental at this point. Thyroxine replacement at a daily dose of 75-100 micrograms/m2 should be given in cases of secondary hypothyroidism. Glucocorticoid replacement, if required, should be given at low doses (e.g. hydrocortisone 10 (to 15) mg/m2 per day in divided doses). In cases with additional gonadotropin deficiency, sex steroids (or anabolic steroids) should be given with frequent monitoring of bone maturity not before the age of 13 in girls or 15 years in boys. In boys depot testosterone starting at low doses (e.g. 50-100 mg/month i.m.) will induce a puberty-like increment in height velocity. Since the effect of oestrogens--even in low doses--on growth is uncertain, their administration before achievement of near-normal adult height should be avoided. With the advancement of diagnostic techniques and with the experience in treatment accumulated over the past 25 years, patients with GHD need no longer become dwarfs.

Body Height↗
PubMed1986

Recombinant human growth hormone.

All batches of Met-hGH examined stimulated statural growth to approximately the same extent. The growth rates measured partly exceeded the results obtained in previous studies with pituitary preparations in the same dosage. Under treatment with SI, i.e. the preparation with the highest amount of ECP, high antibody titres with high binding capacity against GH and ECP were found. With SII all antibody determinations showed much lower titres. With Somatonorm (SIII), in the large majority of cases no antibodies were detectable. The titres registered in a few children were low and the binding capacities were negligible. The biologically determined somatomedin activity was initially pathologically low. During treatment it rose to supraphysiological levels. Also the radioimmunologically assayed somatomedin and the alkaline phosphatase increased significantly. At the start of the first series, two patients showed allergic skin reactions which turned out to be caused by the insufficiently purified preparations. Therapy with extractive preparations was free of such side-effects and fully successful. Both of the patients were atopic. A third child who was also allergic developed after 6-9 months the highest antibody titres seen, combined with a high binding capacity. Also, with this boy, treatment was switched over to pit-hGH, with very good results. Two children with pituitary dwarfism already developed in utero high antibody titres against Met-hGH but not against ECP. For this response, neither the Somatonorm nor its impurities can be implicated. Rather, it is the reaction to GH generally, which the organism recognizes as a foreign protein and thus as an antigen. One of the patients stopped growing after nine months. Likewise, pituitary GH did not lead to any further improvement.

Alkaline Phosphatase↗
PubMed1979

[Alteration of TSH secretion in children with goitre after short-term treatment with potassium iodide (author's transl)].

300 microgram of potassium iodide daily were administered over a period of two weeks to 12 children with goitre. Basal TSH concentrations, maximal TSH increase after TRH and integrated TSH secretion after TRH were significantly decreased in this group whereas the increase of total thyroxine (T4-RIA) did not reach significance. It appears that in the development of iodine deficiency goitre in children a sensitive feed-back system is predominant. Early administration of iodine or even better general iodinated salt prophylaxis seem to be the pathogenetically correct approach in solving the common goitre problem.

Adolescent↗
PubMed1979

Long-term response to human growth hormone in 36 children with idiopathic growth hormone deficiency.

The results of long term treatment with human growth hormone (Crescormon, 12.4 IU/m2/week) in 36 patients with idiopathic growth hormone deficiency are given. Birth trauma--in particular assisted breech delivery (30%)--is the major aetiological cause. Twelve patients had isolated growth hormone deficiency (IGHD), 24 had multiple pituitary hormone deficiencies (MPHD) of which 19 were treated with additional thyroid hormones. The results were judged by the criteria of height velocity, total height gain and change of height prediction (TW2, age based). It is concluded that the growth hormone dose chosen in many cases is insufficient to maintain high growth rates after the first year of treatment, when "catch-up" no loner takes place. The tendency of patients supplemented with thyroid hormone to grow better--without additional bone-age advancement--calls for careful search for hypothyroidism and suggests the use of thyroxin in cases of doubt.

Body Height↗
PubMed1979

Alcohol embryo- and fetopathy. Neuropathology of 3 children and 3 fetuses.

Maternal chronic ethanol abuse during pregnancy causes malformations of the offspring. Three children (aged 6 months, 9 months, 4 1/2 years) and 3 fetuses (17th, 18th, and 20th gestational week) showed a wide spectrum of disorders ranging from severe dysraphic state, arhinencephaly, porencephaly, agenesis of corpus callosum, a range from hydranencephaly to microdysplasias (p.e. reduced gyration of dentate nucleus and inferior olives), and a range from gastrochisis or congenital heart defects to craniofacial dysmorphogenesis and palmar crease anomalies. The patterns of the cerebral malformations were not as uniform as the clinical phenotype of the alcohol embryopathy. The observations did not support the assumption that there exists a specific period for alcohol teratogenicity.

Abnormalities, Drug-Induced↗
PubMed1979

Alcohol embryopathy and diabetic fetopathy in the same newborn.

Both alcohol embryopathy and diabetic fetopathy were observed in the same female child. The mother was known to be alcoholic as well as diabetic. At birth the signs of diabetic fetopathy predominated: the child showed edematous subcutaneous fat, birth weight was 3650 g. The heart was enlarged. The patient's blood sugar levels ranged from 0 to 1.4 mMol/1 (0-25 mg/dl). Features of alcohol embryopathy were typical craniofacial dysmorphy, hypotonia of muscles and hyperexcitability. Later on the features of alcohol embryopathy predominated: the child became dystrophic with pronounced microcephaly, and the craniofacial dysmorphy clearly resembled other patients with alcohol embryopathy. This observation is in favour of the hypothesis, that alcohol induces cell hypoplasia in the embryo resulting in postnatal growth retardation. Maternal and consequently embryonic and fetal hyperglycemia induced cell hypertrophy in the embryo and fetus, which compensated the effect of alcohol on birth weight in our patient.

Abnormalities, Multiple↗