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Biomedical subjects

M B Ranke

Publications and source records attributed to M B Ranke.

At least 127 records · Page 7Linked to original sources
PubMed1997

Outcome in tall stature. Final height and psychological aspects in 220 patients with and without treatment.

UNLABELLED: In 135 women and 85 men who initially presented for tall stature, the outcome in treated (56 women and 33 men; cases) and untreated (controls) was investigated. At the time of height prediction, cases were significantly taller (P < or = 0.03) than the controls, they had higher target heights (P < 0.001) and adult height predictions (P < 0.001) (according to Bailey and Pinneau) compared to the controls. Bone age (according to Greulich and Pyle) and chronological age were well matched in both groups. Final height was measured after cessation of growth at a mean age above 21.5 years. The final height prediction according to Bailey and Pinneau (BP method) overestimated the final height in controls. The mean error of estimation was -0.14 cm (+/- 3.10) in women, and -1.86 cm (+/- 4.37) in men. Age at the time of prediction did not significantly correlate with the degree of the prediction error. Sex hormone therapy comprised a daily oral dose of 7.5 mg conjugated oestrogens in girls (plus 5 mg dydrogesterone for 10 days a month), while boys received 500 mg testosterone enantate, intramuscularly, every 2 weeks. Therapy was well tolerated. The mean corrected effect of height reducing therapy was 3.6 cm (range: 11.9 cm to -3.3 cm) in women and 4.4 cm (range: 14.2 cm to -5.2 cm) in men. Therapy was significantly more effective when started at an earlier chronological (P < 0.01) and bone age (P < 0.01). The residual mean growth, after therapy was stopped, was 1.8 (+/- 1.6) cm in women and 3.1 (+/- 2.3) cm in men. In men, post-treatment growth was inversely correlated to chronological age (P < 0.01) and bone age (P < 0.05) at the end of treatment, while these correlations were not significant in women. Both groups had a higher educational level than the normal population. Treated tall women reported teasing because of tallness more frequently than controls. In tall men, practical issues such as clothing size predominated. Maximum tolerated height in males was 200 cm and in females 180 cm, thus being nearly analogous to the actual professional criteria for treatment recommendation. A positive attitude to treatment was documented in over 90% of treated individuals. CONCLUSIONS: Our results show that the BP method gives acceptable adult height predictions in girls, but less accurate predictions in boys. The treatment with high doses of sex hormones was low effective in both sexes and showed a wide range of response. For success, treatment must be initiated in early puberty and terminated late. The answers to a questionnaire revealed no major psychological or social maladjustment of treated individuals compared to those untreated.

Adolescent↗
PubMed1997

Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology of uniparental disomy.

We report studies on the etiology of uniparental disomy (UPD) in Silver-Russell syndrome (SRS) patients. Thirty-seven SRS families were typed with short tandem repeat markers from chromosomes 2, 7, 9, 14, and 16. UPD for these chromosomes has either been described in association with growth retardation or has been observed in confined placental mosaicism, a mechanism that may result in UPD. Maternal UPD7 was detected in three SRS patients, accounting for approximately 10% of the tested SRS patients. These results agree with previously published studies. The allelic distribution in one of the three families indicates complete isodisomy, whereas allelic patterns in the other two families are consistent with partial and complete heterodisomy, respectively, suggesting that, in the latter cases, UPD originates from maternal meiosis, whereas in the first case, it seems to be of mitotic origin. STR typing for UPD of chromosomes 2, 9, 14, and 16 showed no abnormalities. Our results demonstrate the necessity of screening SRS patients for UPD7, although the effect of UPD7 cannot be correlated with the SRS phenotype as yet. An association between UPD for the other investigated chromosomes and SRS seems to be negligible.

Abnormalities, Multiple↗
PubMed1997

Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome.

Growth retardation resulting in short stature is a major concern for parents and due to its great variety of causes, a complex diagnostic challenge for clinicians. A major locus involved in linear growth has been implicated within the pseudoautosomal region (PAR1) of the human sex chromosomes. We have determined an interval of 170 kb of DNA within PAR1 which was deleted in 36 individuals with short stature and different rearrangements on Xp22 or Yp11.3. This deletion was not detected in any of the relatives with normal stature or in a further 30 individuals with rearrangements on Xp22 or Yp11.3 with normal height. We have isolated a homeobox-containing gene (SHOX) from this region, which has at least two alternatively spliced forms, encoding proteins with different patterns of expression. We also identified one functionally significant SHOX mutation by screening 91 individuals with idiopathic short stature. Our data suggest an involvement of SHOX in idiopathic growth retardation and in the short stature phenotype of Turner syndrome patients.

Adolescent↗
PubMed1997

Factors determining pubertal growth and final height in growth hormone treatment of idiopathic growth hormone deficiency. Analysis of 195 Patients of the Kabi Pharmacia International Growth Study.

A total of 195 children (117 males and 78 females) with idiopathic growth hormone deficiency (IGHD) treated with growth hormone (GH) for at least 1 year before puberty onset and who had completed treatment to adult height, were selected from the KIGS database for study of growth during puberty. Spontaneous and induced puberty started at 13.8 and 14.9 years in boys and at 12.9 and 13.7 years in girls, respectively. Duration of GH treatment and height gained prepubertally were greater when puberty was induced; prepubertal catch up growth (expressed as a percentage of the difference between target height and height at start of GH) was greater when puberty was induced in boys (59% induced vs. 45% spontaneous, p < 0.001), and in girls (72% induced vs. 53.9% spontaneous, p < 0.01). Final height was attained at 17.8 and 19.2 years in boys and at 16.0 and 17.0 years in girls following spontaneous and induced puberty, respectively. Final heights were greater after induced puberty compared with spontaneous puberty in boys (171.3 vs. 166.0 cm, p < 0.001) and in girls (157.0 vs. 155.0 cm, n.s.). Target height was also significantly greater in boys with spontaneous puberty (172.2 cm vs. induced = 174.2 cm) as compared to girls (spontaneous = 158 cm vs. induced = 160 cm). Duration of pubertal growth was longer in boys compared to girls (3.6 vs. 3.0 years, p < 0.001) and was negatively correlated with age, height, and distance from target height at onset of puberty, but was not correlated with the dose of GH. Catch-up growth during puberty (expressed as a percentage of the difference between target height and height at puberty onset) after induced and spontaneous puberty was 87.9% and 80.5% (not significant) in boys and 66.4% and 75.5% (not significant in girls. Total pubertal growth (TPG) (cm) was inversely correlated with prepubertal growth by simple linear regression. Multiple linear regression analysis indicated 5 independent predictors of TPG accounting for 78% of the variability, namely sex (boys grew more), distance of target height from height at onset of puberty (+), dose of GH at onset of puberty (+), age at onset of puberty (-), and age at end of growth (+).

Adolescent↗
PubMed1997

Functional role of insulin-like growth factor binding proteins.

Insulin-like growth factors (IGF-I, IGF-II) are important regulators of cell division and differentiation. In their free form, IGFs form a complex with specific binding proteins (IGFBPs), six of which have now been characterized. These IGFBPs differ in their ability to bind IGF-I and/or IGF-II, and, depending on their location and metabolic circumstances, they inhibit or augment IGF action to varying extents. New findings have changed our understanding of IGFBPs, which are now considered to be major regulators of IGF action and IGF transport proteins between compartments. Recently, the IGF-independent action of IGFBPs was discovered. Levels of IGFBP-3, for instance, are important indicators of states of altered growth hormone secretion and action, as well as being important during treatment with growth hormone or IGF-I. IGFBP-1 and -2 levels reflect changes related to nutrition, insulin secretion, foetal development and malignant state. The unravelling of the intricate interactions of IGFs, IGFBPs and their targets is bound to influence our understanding of the physiology and development of biological systems. Likewise, the possibility of regulating the IGFBP system is likely to open up new fields in the treatment of diseases in the future.

Animals↗
PubMed1997

Phenotype: genotype relationships in growth hormone insensitivity syndrome.

GH insensitivity syndrome (GHIS) is associated with many different mutations of the GH receptor (GHR) gene. We examined the phenotypic and biochemical features in 82 GHIS patients from 23 countries, each fulfilling diagnostic criteria of GHIS. There were 45 males and 37 females [mean age, 8.25 yr; mean height, -6.09 SD score, and mean insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3), -7.99 SD score]. Sixty-three were GH-binding protein (GHBP) negative; 19 were GHBP positive (> 10% binding). The mean height in GHBP-negative subjects was -6.5 SD score, and that in GHBP-positive patients was -4.9 SD score (P = < 0.001). Clinical and biochemical heterogeneity was demonstrated by the wide range of height (-2.2 to -10.4 SD score) and IGFBP-3 (-1.4 to -14.7 SD score) values, which were positively correlated (r2 = 0.45; P = < 0.001). This contrasted with the lack of correlation between mean parental height SD score and height SD score (r2 = 0.01). Fifteen different GH receptor gene mutations were identified in 27 patients. All had homozygous defects, except 1 who had a compound heterozygous defect. The mutations were 5 nonsense, 2 frame shift, 4 splice, 4 missense, and 1 compound heterozygote. There was no relationship between mutation type or exon of the GHR gene involved and height or IGFBP-3 SD score. In conclusion, GHIS is associated with wide variation in the severity of clinical and biochemical phenotypes. This variation cannot clearly be accounted for by defects in the GHR gene. Other genetic and/or environmental factors must, therefore, contribute to phenotype in GHIS.

Adolescent↗
PubMed1997

Incidence of IDDM in German children aged 0-14 years. A 6-year population-based study (1987-1993)

OBJECTIVE: Generally accepted data on the incidence of childhood diabetes in Germany have not been available up to now. To register the total number of newly diagnosed cases in Baden-Wuerttemberg (a federal state in southwest Germany), data on 1,160 children were retrospectively collected for the years 1987-1993. RESEARCH DESIGN AND METHODS: Hospital records were the primary data source. There were 32 hospital units in Baden-Wuerttemberg included in this study. A secondary independent data source was a questionnaire circulated among the patients' association, Deutscher Diabetiker Bund. Case definition was done according to criteria EURODIAB ACE, a collaborative European study set up to assess the incidence of childhood diabetes. The degree of ascertainment was 96.2%, using the capture-mark-recapture method. The study includes a population at risk, entailing 1.5 million children, corresponding to 12.3% of all German children. RESULTS: The incidence was found to be 11.6/100,000 (95% CI 10.9-12.2) for children aged 0-14 years. There was no significant difference between the incidence rates of boys and girls. Seasonal variation was observed, with cases increasing between November and February and incidence increasing with age. Peaks were found in early childhood (3-4 years of age) and prepuberty (10-12 years of age). There was marked geographical variation that did not correlate significantly with population density. CONCLUSIONS: For the first time, internationally comparable data on the incidence of diabetes in children up to 15 years of age are available for Germany. The yearly incidence of 11.6/100,000 proved to be much higher than assumed so far.

Age Factors↗
PubMed1996

Treatment of growth hormone insensitivity syndrome (GHIS) with insulin-like growth factor (IGF-I).

The newly available IGF-I therapy in GHIS is effective in promoting growth and may eventually prevent dwarfism in these patients. Nevertheless, this therapy is still in its experimental phase. The effects of subcutaneous IGF-I injection on various metabolic components are complex due to the intricate effects and regulation of the components of the IGF system in general and in particular in GHIS. More experience with IGF-I treatment is needed to exploit the full potential of this new therapeutic agent.

Adolescent↗
PubMed1996

Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS (Kabi International Growth Study), including the first report on final height.

The response to growth hormone (GH) therapy was studied in children born small for gestational age (SGA; n = 593) and in those with Silver-Russell syndrome (SRS; n = 127) using data from KIGS (Kabi International Growth Study). For the SGA patients, median birth weight was -2.6 SD scores (SDS), treatment was started at a median age of 9.2 years, at a time when median height was -2.8 SDS while median target height was -1.4 SDS. For the SRS patients, median birth weight was -3.1 SDS, treatment was started at a median age of 7.0 years, at a time when median height was -3.4 SDS with a median target height of -0.1 SDS. GH treatment increased height SDS in both SGA children and patients with SRS; in 16 SGA patients treated to (near) final height with GH (median dose, 0.7 IU/kg/week), height minus target height SDS was -2.0 at the start of treatment and -1.0 at final height. In conclusion, the results obtained in KIGS indicate that GH treatment of short children born SGA is effective in increasing final height above the predicted height and in achieving the target height.

Abnormalities, Multiple↗
PubMed1996

Spontaneous growth in idiopathic short stature. European Study Group.

Documenting the spontaneous growth pattern of children with idiopathic short stature (ISS) should be helpful in evaluating the effects of growth promoting treatments. Growth curves for children with ISS were constructed, based on 229 untreated children (145 boys and 84 girls) from nine European countries. The children were subdivided according to target range and onset of puberty, and the growth of these subgroups was evaluated from standard deviation scores (SDS). At birth, children with ISS were already shorter than normal (means; boys -0.8 SDS, girls -1.3 SDS). Height slowly decreased from -1.7 SDS at the age of 2 years to -2.7 SDS at the age of 16 years in boys and 13 years in girls. Final height was -1.5 SDS in boys and -1.6 SDS in girls (mean (SD): boys 164.8 (6.1) cm, girls 152.7 (5.3) cm)), which was 5-6 cm below their target height. The onset of puberty was delayed (boys 13.8 (1.3) years, girls 12.9 (1.1) years). Subclassification resulted in similar growth curves. These specific growth data may be more suitable for evaluating the effects of growth promoting treatments than population based references.

Adolescent↗
PubMed1996

Disease-specific standards in congenital syndromes.

A number of congenital diseases are associated with growth disorders. Over the past decade, efforts have been made to define disease-specific growth standards for these diseases. Such standards allow patients to be counselled, and it is useful to take the predicted growth of an individual into account before initiating any treatment regimen. In addition, knowledge of the growth pattern associated with a particular disorder may facilitate a greater understanding of the pathology of the disease, and deviations from the predicted pattern of growth may be indicative of additional disease processes. However, although growth standards are extremely useful, it is important to note that they are subject to a number of biases, which result from the way in which the study on which data used to calculate the standards was conducted. Until these biases are addressed, the standards that are currently available will not be entirely suitable for routine use.

Adolescent↗
PubMed1996

Insulin-like growth factor binding protein 2 is differentially expressed in leukaemic B- and T-cell lines.

Production of insulin-like growth factor binding protein (IGFBP)-2 and accumulation of IGFBP-2 mRNA was determined in six leukaemic T-, B- or promyelocytic cell lines. Cell growth was compared in serum free medium M-3 and in medium M-9 containing 5% FCS. In both media, high amounts of IGFBP-2 as measured by radioimmunoassay were detectable in culture supernatant of T-cell lines and promyelocytic HL-60 cells, whereas only small amounts of IGFBP-2 were secreted by the B-cell lines. Production of IGFBP-2 in M-9 was approximately 20-fold higher (up to 195 ng ml-1) than in M-3, partially reflecting higher proliferation. However, quantitative reverse transcriptase polymerase chain reaction analysis revealed that, independent of the culture medium 10(6) T-cells contained between 30 and 48 units IGFBP-2 mRNA relative to the glycerol aldehyde phosphate dehydrogenase control gene, but B-cells contained less than 1 unit. Since IGF-II is known to be a major regulator of IGFBP-2, its influence on IGFBP-2 expression has to be investigated.

Base Sequence↗
PubMed1995

Pelvic ultrasonography: early differentiation between isolated premature thelarche and central precocious puberty.

We examined 55 girls with isolated premature thelarche between the ages of 0.3 and 7.4 years (group A), 20 children with central precocious puberty between 2.1 and 7.7 years of age and 101 age-matched controls. The children with precocious puberty were divided according to distribution of pubic hair into group B (Tanner stages PH1, B2-3; n = 11), representing an early stage of the disorder, and group C (stages PH2-3, B3-4; n = 9), representing an advanced stage. Uterine and ovarian volumes were measured sonographically, peak serum levels of luteinizing hormone and follicle-stimulating hormone were determined after intravenous administration of luteinizing hormone-releasing hormone. The mean uterine and ovarian volumes were significantly greater in children with precocious puberty than in controls (group B: uterine volume: 3.8 +/- 2.0 ml vs 0.9 +/- 0.3 ml for controls, P < 0.001; ovarian volume: 2.2 +/- 1.3 ml vs 0.6 +/- 0.2 ml for controls, P < 0.01; group C: uterine volume: 8.0 +/- 4.4 ml vs 1.0 +/- 0.3 ml for controls, P < 0.01; ovarian volume; 2.6 +/- 1.3 ml vs 0.4 +/- 0.1 ml, P < 0.01). No significant differences were found between children with premature thelarche and the control group. As a diagnostic method for the early detection of central precocious puberty, ultrasound measurement of uterine volume had a sensitivity and specificity of 100% (cut-off value, 1.8 ml), while ultrasound determination of ovarian volume had a sensitivity of 82% and a specificity of 95% (cut-off value, 1.2 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1995

Growth and symptoms in Silver-Russell syndrome: review on the basis of 386 patients.

UNLABELLED: The spontaneous growth of 386 patients (163 girls and 223 boys) with Silver-Russell syndrome (SRS) was analysed in a mixed longitudinal and cross-sectional manner. One hundred and twenty patients were seen in the two centres between 1970 and 1993, additional definite cases were added from the literature. Mean (+/- SD) length of full-term babies with SRS at birth was 43.1 +/- 3.7 cm (n = 102) in both sexes. Mean weight at birth was 1940 +/- 353 g in boys and 1897 +/- 325 g in girls. During the first 3 years of life there was poor growth with a further loss in height. Between ages 4 and 10 years there was constant growth in parallel to the 3rd percentile with a mean height SDS of -4.3. The pubertal growth spurt was reduced in the whole group. Bone age development paralleled growth, retardation increased during the first years, remained constant during prepubertal time and caught up in early puberty. Mean adult height was 151.2 +/- 7.8 cm in males and 139.9 +/- 9.0 cm in females. Head circumference for age was in the lower normal range (mean SDS for 156 prepubertal boys -1.8; mean SDS for 97 prepubertal girls -2.2). CONCLUSION: Normative data on spontaneous growth of children with Silver-Russell syndrome are described, allowing a better counselling of patients as well as the judgement of the effects of growth promoting therapies.

Abnormalities, Multiple↗