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Biomedical subjects

J R Bierich

Publications and source records attributed to J R Bierich.

At least 37 records · Page 2Linked to original sources
PubMed1987

Clinical experience with authentic recombinant somatropin--German Collaborative Study.

A multicentre clinical trial with recombinant somatropin was initiated in West Germany in early 1986. Acceptance of patients to the study was determined according to criteria outlined in a detailed study protocol. To the present time, 41 patients with hGH deficiency not previously treated (naïve) and 28 patients previously treated with pituitary hGH have been admitted. Recombinant somatropin is given, 12 IU/m2/week s.c., divided into six doses. Height velocities during treatment rose dramatically for naïve patients from 3.5 cm/year (n = 40, before treatment), to 15.0 cm/year (n = 19, calculated at 3 months), and 13.3 cm/year (n = 8, calculated at 6 months). For previously treated patients, the increase in height velocity was from 5.8 cm/year (n = 20) to 9.2 cm/year (n = 19, after 3 months) and 8.6 cm/year (n = 9) at 6 months. Tolerance of recombinant somatropin was good, and no anti-hGH antibodies were detected in any of the patients.

Antibody Formation↗
PubMed1987

Multicentre clinical trial of authentic recombinant somatropin in growth hormone deficiency.

A German multicentre trial of recombinant somatropin was commenced in March 1986. A total of 77 patients with hGH deficiency were recruited, with heights at least 2.5 SD below the normal mean. Of these, 49 were previously untreated (naïve) and 28 had previously received pituitary hGH. Recombinant somatropin, 12 IU/m2/week was administered subcutaneously, divided into six doses. In the naïve group, the height velocity reached 14.9 cm/year in the first 3 months, and thereafter stabilized at 12 cm/year. In the previously treated patients, the growth rate was 10.7 cm/year in the first 3 months, and 8.5 cm/year at 9 and 12 months. There were no abnormal findings in tests of laboratory parameters. No anti-hGH antibodies were detected in any of the patients; seven patients had anti-ECP antibodies, but in six of these the antibodies were already present before treatment.

Body Height↗
PubMed1987

The effects of cyproterone acetate on statural growth in children with precocious puberty.

Forty-four patients (42 f, 2 m) with precocious puberty (31 idiopathic, 1 familial, 7 cerebral, 5 McCune-Albright) were treated with cyproterone acetate for periods of 1-8.75 years in different (P less than 0.05) daily dosages of 117 +/- 6.1 mg/m2 per day (mean +/- SEM, group A, N = 20) and 60.8 +/- 2.42 mg/m2 per day (group B, N = 24). Thirty-three girls had experienced menarche before therapy at a mean age of 4.89 +/- 0.42 years. Treatment was started at a chronologic age of 5.45 +/- 0.33 years in the girls and 5.74 +/- 1.34 years in the boys. At the time of evaluation, 31 of our patients had reached final height. With respect to the effects of treatment on statural growth, the Standard Deviation Scores were retrospectively determined for height, weight, and growth velocity. The initial Bayley-Pinneau height predictions were compared with final height and target height, and the skeletal maturation was studied. There were no significant differences between those parameters in the patients of group A and B or between treated and untreated subjects as far as final height and target height were concerned. It is concluded that cyproterone acetate administered orally at daily doses from 50-150 mg/m2 does not improve statural growth of patients with precocious puberty.

Body Height↗
PubMed1987

Growth hormone, somatomedin levels and growth regulation in Turner's syndrome.

In a total of 56 children and adolescents with Turner's syndrome (41 with karyotype 45,X) basal serum levels of somatomedin bioactivity, Sm-C/IGF-I (RIA), IGF II (RIA), GH response to arginine and GHRH (GRF(1-29)NH2), and spontaneous GH secretion during 5.5 h of deep sleep were determined in a cross-sectional manner. GH responses to GRF and arginine as well as IGF-II levels were found to be in the normal range. Levels of somatomedin bioactivity were higher than normal before a bone age of 10 years, in the low-normal range thereafter, and below normal in some patients. Levels of Sm-C/IGF-I were found normal before and low-normal after a bone age of ten years. There was a trend towards increasing Sm-C/IGF-I levels with age. In contrast to the normal pattern, spontaneous sleep-related GH secretion was declining with age and did not show the puberty-associated rise. These findings suggest a normally functioning growth hormone-somatomedin axis in Turner's syndrome with alterations of its functioning level occurring secondarily as a result of absent gonadal activation. In single patients abnormally low growth hormone and/or somatomedin secretion may be present.

Adolescent↗
PubMed1987

The polymorphic pattern of somatomedins during human development.

Human somatomedins (Sm) are heterogeneous on separation by chromatofocussing. Besides the 'classic' insulin-like growth factor I and II (IGF-I/Sm-C and IGF-II), a number of minor peaks emerge which can be classified as IGF-I/Sm-C-like or as IGF-II-like. The aim of the current study was to investigate whether or not polymorphism of somatomedins is present in individuals and whether or not the polymorphic pattern changes during development. Serum extracts from normal healthy children and adults were fractionated by chromatofocussing and the various somatomedin-like peptides were quantitated by specific radioimmunoassays for IGF-I/Sm-C or IGF-II. The results demonstrate 1) that heterogeneity of somatomedins is a common phenomenon existing in all individuals studied, and 2) that the polymorphic patterns of the IGF-I/Sm-C-family and of the IGF-II-family remain rather stable during development, although minor changes are evident.

Adolescent↗
PubMed1986

[Therapy of pituitary dwarfism with recombinant human growth hormone. A multicenter study].

During the period from 1982 to 1985, biosynthetic growth hormone (methionyl-hGH) was administered to 55 children with pituitary growth deficiency, 49 with idiopathic, six with other forms of the disorder. Preparations with a relatively high content of Escherichia coli polypeptides (ECP) were given to 32 children (group I), those with a markedly reduced ECP content to 12 (group II), while 11 children received almost ECP-free preparations (group III). The treatment achieved an intensive rise of growth acceleration in all three groups. At the same time, somatomedin C, biological somatomedin activity and alkaline phosphatase rose steeply, reaching a maximum after six months and remaining at high concentrations even thereafter. High antibody titres against ECP and hGH (with high binding capacity) were demonstrated in group I children, significantly lower titres with little binding capacity in those of group II, while most of those in group III had no measurable antibodies. Even in high concentrations the antibodies did not have any inhibiting effect on growth. No positive correlation between antibody titre and growth velocity was demonstrable. An exception was a boy with an allergy in group I, who had a maximal antibody titre and, at the same time, a high serum concentration of IgE. He had marked delay in growth which, however, quickly became normal on administration of extractive hGH.

Bacterial Proteins↗
PubMed1986

Testing with growth hormone-releasing factor (GRF(1-29)NH2) and somatomedin C measurements for the evaluation of growth hormone deficiency.

Growth hormone (GH) responses to GRF (1 microgram/kg BW i.v.) were investigated. Comparison between GRF(1-40) and GRF(1-29)NH2 in 11 young adult volunteers gave identical results. One hundred and thirty-one children and adolescents (45 with idiopathic GHD) were tested with GRF (1-29)NH2. The maximal GH levels (max GH) in response to GRF during the 120 min test period were found suitable to characterize the response. In cases without GHD no correlation to age, sex and pubertal development was observed. A maximal GH level of above 10 ng/ml was found to be normal. In 3 out of 86 children without GHD (one with Turner syndrome; two with simple obesity) max GH fell short of 10 ng/ml, while 11 of 45 cases with GHD exceeded this margin. In GHD, max GH was inversely correlated with age. There was no difference in max GH between groups with or without perinatal pathology as a presumed cause of GHD. GH levels to GRF were positively correlated with maximal GH level during sleep in GHD, but not correlated with responses seen to insulin or arginine. The value of GRF testing for the confirmation of GHD is discussed in the light of other GH stimulatory tests and basal somatomedin C measurements. It is suggested that the combination of testing with GRF and the determination of a basal SmC level offers a safe and convenient way to diagnose GHD in clinically suspected cases, though in some cases further diagnostic tests may be needed.

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↗
PubMed1986

Treatment of pituitary dwarfism with biosynthetic growth hormone.

Over 3 1/2 years, 54 previously untreated hypopituitary children were enrolled in three studies; 48 had idiopathic pituitary dwarfism. Three preparations of somatrem were used (SI, SII, Somatonorm). Growth velocities on all three preparations were similar, though SI and SII tended to produce slightly higher growth velocities. Serum somatomedin and alkaline phosphatase levels increased during treatment. Antibodies to Escherichia coli polypeptide (ECP) increased to a maximum Z score of about 0.7 with SI, but this was considerably lower with SII and below 0.1 with Somatonorm. Anti-hGH antibodies had the highest titre in children treated with SI and these antibodies also had quite high binding capacities. Anti-hGH antibody formation was negligible during Somatonorm treatment.

Antibody Formation↗
PubMed1986

Treatment by hGH of constitutional delay of growth and adolescence.

In constitutional delay of growth and adolescence (CDGA), all growth and maturation parameters are delayed by 2-4 years. Provocation tests of hGH secretion give normal values, but spontaneous (endogenous) secretion is low. This can be assessed by measuring night-time hGH secretion, when the differences between normal subjects and CDGA patients are highly significant. Replacement therapy with hGH produced growth spurts in all but one patient, improving their growth prognosis. A new series of 16 CDGA patients has now been treated with hGH for 1-3 years. Catch-up growth was seen during the first year, which decreased to normal growth velocity by the third year. This normal growth rate is still faster than the pretreatment velocity. Although hGH therapy may be effective in CDGA, it may only be justified in cases with psychological problems arising from their short stature.

Adolescent↗
PubMed1986

Isolation and partial characterization of six somatomedin-like peptides from human plasma Cohn fraction IV.

Six somatomedin-like peptides were purified from human plasma Cohn fraction IV by a six-step procedure which included ethanol precipitation, reversed-phase extraction, gel filtration, chromatofocusing and reversed-phase high pressure liquid chromatography (HPLC). Purification was monitored with a competitive protein binding assay using a crude preparations of somatomedin carrier protein. The peptides isolated were homogeneous by reversed-phase HPLC and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Their apparent isoelectric points determined by chromatofocusing were 9.2 (Sm I), (Sm II), 8.2 (Sm III), 6.7 (Sm IV), 6.3 (Sm V), and 6.15 (Sm VI). SDS-PAGE under reducing conditions revealed that they are composed of a single peptide chain with apparent molecular weights of 6800 for Sm I, II and IV and 6400 for Sm III, V, and VI. They were equally potent in the porcine costal cartilage in vitro bioassay. The basic peptides (Sm I-III) were significantly more active in radioimmunoassays for somatomedin C (SmC) and insulin-like growth factor I C-peptide (IGF-I (30 - 41], while only the slightly acidic peptides were active in a radioimmunoassay for insulin-like growth factor II C-peptide (IGF-II (33-40]. When receptor binding was tested with human placental cell membranes and Sm III as tracer, the basic peptides were significantly more potent than Sm IV-VI. With rat liver cell membranes and Sm V as tracer the slightly acidic peptides were more potent. These findings suggest 1) that human plasma may contain other somatomedin-like peptides besides the major components IGF-I/SmC and IGF-II, and 2) that the basic peptides are structurally related to IGF-I/SmC and the slightly acidic peptides are related to IGF-II.

Animals↗
PubMed1986

Effect on growth of patients with Turner's syndrome treated with low estrogen doses.

In 33 patients with Turner's syndrome growth during a one year period of treatment with low doses of estrogens was evaluated (group A: (N = 12) Presomen 5-9 micrograms/kg d; group B: (N = 9) Presomen 10-21 micrograms/kg d; group C: (N = 12) ethinylestradiol 45-155 ng/kg d) and compared to a group (N = 37) of untreated patients. The auxological evaluation was made using SDS derivations based on control data derived from 150 untreated patients. Based on chronological age (CA) SDS levels for height velocity and the increments in height at the end of treatment increased marginally. Compared to untreated patients no effect was seen when calculations were based on bone age (BA) due to an advancement in bone maturity. It is concluded that low doses of estrogens are not suitable to improve the height development in Turner's syndrome.

Age Determination by Skeleton↗
PubMed1985

[The Schwartz-Bartter syndrome].

Nine children with Schwartz-Bartter-syndrome are described. Seven suffered from severe diseases of the CNS, 2 developed the syndrome during treatment with vincristine, the damaging action of which on the CNS is known. The main symptoms of the syndrome are: hyponatremia with consecutive hypotonia of the extracellular space caused by excessive urinary sodium loss. The plasma volume is not diminished. Therapeutically administered NaCl appears in the urine which is hyperosmolar in spite of the hypoosmolarity of the plasma. The increased secretion of ADH which Schwartz et al. postulated to be the cause of the syndrome has been confirmed in recent years. The organism attempts to excrete the increased fluid volume which is retained by ADH, probably by means of a natriuretic hormone, so-called third factor. Enhanced activity of such a factor was assessed in one of our cases.

Brain Diseases↗
PubMed1985

[Growth in puberty].

During puberty growth velocity increases within 3 years from a prepubertal nadir to a maximum, in male to 9-10 cm/year, in female to 7-9 cm/year. This spurt is triggered by the androgenic steroids, in male mainly by testicular testosterone. In patients with anorchia the pubertal growth spurt is missing. The androgens have a dual effect. 1. As comes forth from observations in hypopituitary dwarfs being treated with constant replacement doses of hGH, these steroids potentiate the growth-stimulatory effect of hGH. In order to continue growing at all, these dwarfs need the additional medication of androgenic or anabolic steroids if they are hypogonadotrophic. 2. As demonstrated by our measurements of the nocturnal hGH secretion, androgenic steroids enhance the spontaneous production of hGH by a factor of 2-3. Biologically active androgens appear to be a conditio sine qua non for longitudinal growth after age 11-12. This is in concordance with the statement that adult male castrates are no giants as has often been claimed. The rather tall eunuchs in Istanbul were no Turks but as a rule Sudanese negroes who are racially much taller than Turks.

Adolescent↗
PubMed1984

Pseudopituitary dwarfism due to resistance to somatomedin: a new syndrome.

The case of an infant is described who at birth was already small and postnatally grew extremely slowly. At age 3 the girl's height was 65 cm, weight 5.6 kg, bone age 21 months. Basal plasma GH was 36-66 ng/ml, basal SM activity was rather high, being around 2.0 U/ml. RIA- and RRA-SM were also increased. Prolonged GH administration did not raise plasma SM. There was a tendency for hypoglycemic episodes in the presence of low insulin levels. Receptor studies with skin fibroblasts showed a diminution of the specific binding of SM-C by 50%. Apparently only the specific IGF-receptor is defective whereas the insulin receptor responds to the increased SM with hypoglycemia. The observation that the high plasma SM did not suppress the enhanced GH-secretion suggests that perhaps the hypothalamic IGF-receptor was also defective.

Child, Preschool↗