Search PubMed⌕ Search

Biomedical subjects

M B Ranke

Publications and source records attributed to M B Ranke.

At least 181 records · Page 10Linked to original sources
PubMed1991

Left middle finger metacarpophalangeal growth in Turner syndrome. Normal values and changes after growth hormone treatment.

Tubular bone length of the left middle finger was determined by analysis of 259 hand radiographs of 118 patients with Turner syndrome (TS). Specific standards for TS children were developed and compared with those of normal children. The results show that in TS the growth pattern of the tubular bones of the left middle finger parallels statural growth and is not disproportional to height. In 14 patients with TS the length of the tubular finger bones was determined before and after a 1-year treatment with recombinant human growth hormone (rhGH) (mean dose 2.8 IU/m2 BSA/day). No disproportionate increment in the length of these bones compared to the respective height change was observed. The data suggest that over a short period of time the relatively high doses of growth hormone given in TS are unlikely to induce acromegaloid hand growth. The derived standards may serve to monitor hand growth in relation to height in TS during treatment in long-term trials with rhGH.

Adolescent↗
PubMed1991

Short-term changes in serum insulin-like growth factors (IGF) and IGF binding protein 3 after different modes of intravenous growth hormone (GH) exposure in GH-deficient patients.

Virtually all circulating insulin-like growth factors I and II (IGF-I and IGF-II) are bound to specific binding proteins (IGFBP), of which IGFBP-3 is the quantitatively most important. The mechanisms regulating the close coordination between serum levels of IGFs and IGFBP-3 is poorly understood. We therefore evaluated the temporal association of serum IGF-I, IGF-II, and IGFBP-3 measured by RIAs after well defined short-term GH exposure in GH-deficient patients. Six patients (mean +/- SE age: 20.5 +/- 1.1 yr) each underwent three GH study protocols in random order. Each study was preceded by 4 weeks without GH therapy. Two units of GH were administered iv as either: 1) two boluses, 2) eight boluses, or 3) a constant infusion. The duration of each study was 44 h including at least 16 h after termination of GH administration. Increments in serum IGF-I occurred 4-6 h after initiated GH exposure in all studies. In the two-bolus study the IGF-I increase was modest with mean +/- SE peak values of 12.4 +/- 2.1 nmol x L-1 after GH administration. In the eight bolus and constant infusion studies significantly higher IGF-I levels were generated: 17.0 +/- 2.2 nmol x L-1 (8 bolus) and 18.8 +/- 1.1 h nmol x L-1 (infusion). In contrast the time course change in serum IGF-II did not differ in the three studies, and it was characterised by a sluggish increase of approximately 30% evidenced after 16-20 h. The changes in IGFBP-3 were almost identical in the three studies. After a lag phase of approximately 18-20 h a gradual increase of approximately 40%, which had not ceased at the end of the study period, was observed. The molar ratio of serum IGF-I plus IGF-II:serum IGFBP-3 remained constant with values between 0.8-0.9 except in the constant infusion experiment, in which the ratio increased significantly with time reaching a mean peak value, which exceeded 1.0, after 24 h. Our data suggest that a pulsatile GH pattern is not superior to constant GH levels as regards generation of IGFs and IGFBP. The earlier increase in serum IGF-I compared to IGF-II and IGFBP-3 suggests that IGF-I may be the main regulator of IGFBP-3 production. Accordingly, the slow increase in serum IGF-II, which paralleled that of IGFBP-3, could indicate that serum IGF-II levels mainly depend on the concentration or binding site availability of IGFBP-3.

Adult↗
PubMed1991

Immunoreactive insulin-like growth factor binding protein-3 in the culture of human luteinized granulosa cells.

Granulosa cells from human preovulatory follicles were cultured under serum-free conditions to investigate the presence of immunoreactive insulin-like growth factor binding protein-3 (IGFBP-3). IGFBP-3 levels were measured by a radioimmunoassay developed against the acid-stable subunit of the protein. The antiserum had no cross-reactivity to the low molecular weight GH-independent IGFBP-1. Granulosa luteal cells exhibited a continuous release of IGFBP-3 into the culture medium during the whole time (6 days) of the incubation. A dose-dependent increase in IGFBP-3 was observed when the cells were treated by dibutyryl cAMP. Cycloheximide suppressed almost completely both the basal and the stimulated production of IGFBP-3. The smallest effective dose of dibutyryl cAMP enhancing the progesterone release was lower than that for IGFBP-3. The different time course of IGFBP-3 and progesterone secretion to dibutyryl cAMP treatment, as well as the failure of progesterone to elicit IGFBP-3 increase alone, do not support the participation of progesterone in the IGFBP-3 production of granulosa cells. It is concluded that 1. immunoreactive IGFBP-3 is produced by cultured granulosa luteal cells; 2. its synthesis is regulated by physiological intracellular mechanisms.

Bucladesine↗
PubMed1991

Approaches to the evaluation of growth and growth disorders in children after bone marrow transplantation (BMT).

Since impaired growth may occur as a long--term consequence in children treated with BMT this aspect of development needs particular attention for various reasons. Primarily, in each affected child parameters relevant for the evaluation of growth need to be documented regularly from the beginning in a prospective mode. In addition, treatment protocols should contain elements of a standardized follow-up for the documentation and evaluation of the endocrine, the nutritional and the emotional situation of the patient. This will eventually allow us to define--and hopefully avoid--adverse elements within complex treatment modalities--including BMT--for various malignant diseases. Thus it will be possible to develop a rational approach for the therapy of persistent adverse events following attempts of treatment primarily directed to ensure survival.

Bone Marrow Transplantation↗
PubMed1991

Growth response in prepubertal children with idiopathic growth hormone deficiency during the first two years of treatment with human growth hormone. Analysis of the Kabi Pharmacia International Growth Study.

From the large database of patients enrolled in the Kabi Pharmacia International Growth Study (KIGS), 289 prepubertal patients with idiopathic growth hormone deficiency (GHD), treated for 2 years with growth hormone (GH) substitution therapy, were selected. A multiple regression analysis was performed to determine both the auxological factors characterizing the patients at the beginning of the first and second years on GH therapy and the respective treatment modalities relevant to the magnitude of the growth response. It was observed that during the first year on GH therapy the magnitude of the growth response was negatively correlated with chronological age and height SDS, and positively correlated with target height SDS, GH dose (IU/kg/week) and frequency of GH injections. During the second year the growth response was negatively correlated with chronological age and the first-year GH dose (IU/kg/week), and positively correlated with height velocity during the first year, GH dose (second year), and injection frequency (second year). The data suggest that the forces of 'catch-up'--auxologically entrenched within the distance between target height SDS and height SDS--no longer prevail during the second year of GH therapy. The inverse influence of the first-year GH dose in the two yearly phases of growth suggests that optimizing GH treatment must be attempted by analysing growth in response to GH over longer periods of time and considering that the growth process is influenced by interactive factors.

Age Factors↗
PubMed1990

The Marfan syndrome--analysis of growth and cardiovascular manifestation.

Forty-eight children and adolescents (mean age 10.5 years, range 1.25-18 years) with clinical evidence of Marfan syndrome were studied. Height and weight percentiles were established. Cardiac dimensions and morphology were studied by M-mode and 2D-echocardiography. At diagnosis left atrial and left ventricular end-diastolic diameter and left ventricular posterior wall thickness were within normal limits except in a few adolescent patients. Interventricular septum was thickened in about 20% and aortic diameter increased in 56% of the patients. An additional 13% of patients developed aortic dilation during the study period. At diagnosis regression analysis revealed a significant (P less than 0.05) correlation of the aortic diameter, septal thickness and the posterior left ventricular wall thickness and body surface area. Follow up studies of 19 patients allowed documentation of the development of aortic root dilation.

Adolescent↗
PubMed1990

Growth-stimulating effects of recombinant human growth hormone in children with end-stage renal disease.

Because patients with uremia have evidence for growth hormone resistance, we investigated whether this resistance can be overcome by administration of recombinant human growth hormone in supraphysiologic doses in children with severe uremia. Nine stunted children with end-stage renal disease (median age 5.8 years, median bone age 2.7 years) were treated with recombinant human growth hormone, 4 IU/m2/day subcutaneously, for a period of 1 year. Median height velocity was increased from 4.4 cm/yr before therapy to 8.0 cm/yr during treatment. Negative values for height velocity standard deviation scores for chronologic age were improved from a median of -2.6 to +1.5 without advancing bone age more than chronologic age. The growth hormone-insulin-like growth factor I resistance may be explained in part by the increased serum concentration of the high molecular weight insulin-like growth factor binding protein despite normal insulin-like growth factor I serum concentration. Treatment with recombinant human growth hormone improved the ratio between the serum concentrations of insulin-like growth factor I and its binding protein, and normalized the somatomedin bioactivity in the growth cartilage bioassay.

Age Determination by Skeleton↗
PubMed1990

Growth response in prepubertal children with idiopathic growth hormone deficiency during the first year of treatment with human growth hormone. Analysis of the Kabi International Growth Study.

In order that children with growth hormone deficiency (GHD) reach the goal of normal adult stature, treatment modalities need to be optimized. From the large database of patients enrolled in the Kabi International Growth Study (KIGS), 257 prepubertal patients with idiopathic GHD undergoing their first year of growth hormone (GH) substitution therapy were selected. A multiple regression analysis was performed to determine both auxiological factors characterizing the patients and the factors related to the chosen treatment modalities which are of significance for the observed magnitude of the growth response. Due to the structure of the data, pretreatment height velocity and bone age-derived auxiological data were not considered. It was observed that the magnitude of the growth response was inversely correlated with chronological age and relative height (HT SDS) at the start of GH treatment but was positively correlated with mid-parental height. The growth response was also positively correlated with the GH dose (IU/kg/week) and the frequency of GH injections per week. A regression equation using these five parameters was derived, allowing the growth response of these patients to be predicted. The extension of this analytical approach in the future will allow the treatment of patients with GHD to be tailored to individual requirements.

Child↗
PubMed1990

Growth response in the first year of growth hormone treatment in prepubertal children with organic growth hormone deficiency: a comparison with idiopathic growth hormone deficiency. The Executive Scientific Committee of the Kabi International Growth Study.

Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first-year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted.

Adolescent↗
PubMed1990

Use of insulin-like growth factor-binding protein 3 for the evaluation of growth disorders.

A specific radioimmunoassay for insulin-like growth factor-binding protein 3 (IGFBP-3), developed against its binding subunit (IGFBP-3 beta), was used to investigate its diagnostic potential for the evaluation of growth disorders. Various factors were found to influence serum IGFBP-3. Most prominent was its considerable age dependence, showing low levels at birth and a peak at puberty. Its dependence on nutrition was obvious from a reduction by 16% after a 3-day fast. Low levels were observed in patients with impaired hepatic function due to biliary atresia, suggesting that the liver may be a major source. In end-stage renal failure, excessively high concentrations were found due to the accumulation of IGFBP-3-related low-molecular-weight forms, suggesting that the kidneys play an important role for clearance. The dependence of serum IGFBP-3 on GH was evident from a significant correlation with total spontaneous nocturnal GH secretion (n = 43; r = 0.62, p less than 0.001). Constant levels over 24 h and a slow response to GH in patients with GH deficiency indicate slow kinetics of variation. Therefore, serum IGFBP-3 appears to reflect the integrated GH secretion over days. In patients with GH deficiency, IGFBP-3 levels were below the 5th percentile of the normal range (133 of 137). In contrast, children with normal-variant short stature (136 of 142) had levels above this limit. Normal IGFBP-3 levels were also found in Turner syndrome and Silver-Russell syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
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

Circadian patterns of serum insulin-like growth factor (IGF) II and IGF binding protein 3 in growth hormone-deficient patients and age- and sex-matched normal subjects.

Knowledge of the circadian patterns of serum IGF-II and the large molecular weight IGF binding protein, IGFBP-3 might, apart from its physiological relevance, be of clinical interest, inasmuch as measurements of these parameters are being introduced into the evaluation of GH deficiency. We therefore evaluated the 24-h (08.00-08.00 h) patterns of serum IGF-II and IGFBP-3 in 8 GH-deficient patients who were studied during three periods when receiving 1. GH (2 IU) at 20.00 h; 2. GH (2 1U) at 08.00 h and 3. no GH. For comparison, 10 age- and sex-matched untreated healthy subjects were studied once under similar conditions. The serum IGF-II levels of the patients were relatively stable over the 24-h periods, yielding mean levels which were significantly lower during no GH: 553 +/- 78 (evening GH), 554 +/- 54 (morning GH), and 429 +/- 65 micrograms/l (no GH). The mean IGF-II level in the normal subjects was 635 +/- 29 micrograms/l, which was significantly higher than in either patient study. Similarly, stable 24-h levels of IGFBP-3 were recorded in all studies. The mean IGFBP-3 level of the patients was significantly lower when they received no GH, and the mean level in the healthy subjects was higher than in any of the patient studies: 1853 +/- 301 (no GH), 2755 +/- 317 (evening GH), 2904 +/- 269 (morning GH), and 3856 +/- 186 micrograms/l (healthy subjects). However, minute but significant changes over time, characterised by slight decrements at night, were observed for both parameters in several of the studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Unusual course of a Chlamydia pneumonia in an infant with IgG2/IgG4-deficiency.

An unusual case of Chlamydia trachomatis (C. trachomatis) pneumonia, complicated by the development of a pneumothorax, is reported in an IgG2/IgG4 deficient infant delivered by caesarean section. C. trachomatis was isolated initially from a throat smear and subsequently from pleural effusions. Serological examinations using the complement fixation test were negative in sera of both mother and child. However, using immunofluorescence the presence of an acute or recent infection was confirmed by IgM-antibodies in the serum of the infant and IgA-antibodies in the serum of the mother. At the age of 7 months the girl suffered from impetigo contagiosa which was partially resistant to antibiotic treatment. IgG-subclass deficiency was diagnosed after the onset of this disease and the girl was then treated by immunoglobulin transfusion.

Antibodies, Bacterial↗