Boys with a simple delayed puberty reach their target height.

INTRODUCTION: Final height in boys with delayed puberty is thought to be below target height. This conclusion, however, is based on studies that included patients with genetic short stature. We therefore studied final height in a group of 33 untreated boys with delayed puberty with a target height >-1.5 SDS. METHODS: Standing height, sitting height, weight and arm span width were measured in each patient. Final height was predicted by the method of Greulich and Pyle using the tables of Bailey and Pinneau for retarded boys at their bone age (PAH1) and the tables of Bailey and Pinneau for average boys plus six months (PAH2). RESULTS: Mean final height (175.8 +/- 6.5 cm) was appropriate for the mean target height (174.7 +/- 4.5 cm). The prediction method of Bailey and Pinneau overestimated the final height by 1.4 cm and the modified prediction method slightly underestimated the final height (-0.15 cm). CONCLUSION: Boys with untreated delayed puberty reach a final height appropriate for their target height. Final height was best predicted by the method of Bailey and Pinneau using the tables for average boys at their bone age plus six months.

Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes.

The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.

Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index.

UNLABELLED: AIMS/HYPOTHESIS. We investigated whether the reported HLA-DQ/DR restricted male-to-female (M:F) excess in Type I (insulin-dependent) diabetes mellitus also exists in Belgian patients, is specific for immune-mediated diabetes, remains genotype-restricted after adjustment for age at diagnosis, and is associated with sex-dependent environmental factors. METHODS: Autoantibodies, HLA-DQ and 5'INS (5'insulin gene) polymorphisms were assessed in 2,532 diabetic patients (all phenotypes) diagnosed under 40 years of age. Autoantibodies and body mass index (expressed as a standard deviation score by comparison to age-matched and sex-matched control subjects; SDS-BMI) were measured in 1986 siblings or offspring of Type I diabetes patients (0-39 years). RESULTS: In patients aged 15-39 years at diagnosis, the male-to-female ratio was 1.5 or more regardless of their antibody status and significantly higher (p < 0.001) than that in the age-matched Belgian general population. There was no sex bias in patients under 15 years of age. Overall, the male-to-female ratio was significantly higher in patients without HLADQA1*0301-DQB1*0302 (p < or = 0.003) but stratification in age groups and multivariate analysis identified age as the major determinant of male-to-female ratio. The SDS-BMI increased (p < 0.01) in male antibodypositive relatives (n = 103) but not in female antibody-positive (n = 92) or in antibody-negative relatives (n = 1,791). This phenomenon tended to be restricted to male relatives who were positive only for glutamate decarboxylase antibodies (n = 44). CONCLUSIONS/INTERPRETATION: The male-to-female excess in Belgian diabetic patients diagnosed in early adulthood is not specific for immune-mediated Type I diabetes and not HLA-DQ or 5'INS restricted. Our data suggest that, similar to Type II (non-insulin-dependent) diabetes mellitus, the metabolic burden of obesity and insulin resistance could preferentially precipitate postpubertal clinical onset in male subjects with slowly progressive subclinical (immune-mediated) diabetes.

Gastric parietal cell antibodies are associated with glutamic acid decarboxylase-65 antibodies and the HLA DQA1*0501-DQB1*0301 haplotype in Type 1 diabetes mellitus. Belgian Diabetes Registry.

AIMS: To assess the prevalence of thyrogastric autoimmunity in relation to age, sex, beta-cell antibody status and HLA DQ haplotypes in Type 1 diabetes mellitus. METHODS: One hundred and seventy-one patients with Type 1 diabetes mellitus were studied (male/female 86/85; mean age 19 +/- 11 years; duration of diabetes 5 +/- 4 years). Islet cell antibodies (ICA) and parietal cell antibodies (PCA) were measured using indirect immunofluorescence; glutamic acid decarboxylase-65 antibodies (GADA) by radiobinding assay and thyroid peroxidase antibodies (TPO) with an immunoradiometric assay (IRMA). RESULTS: The majority of subjects (81.3%) showed one or more autoantibodies. The prevalence rates were: GADA 64.9%, ICA 46.2%, PCA 19.9% and TPO 19.3%. Patients with ICA+ > or = 3 years after diagnosis had a higher prevalence of GADA (P = 0.03, odds ratio (OR) 2.66) and thyrogastric antibodies (P = 0.05, OR 2.23) than subjects ICA- after 3 years. PCA+ patients were older (P = 0.04), had a higher prevalence of GADA (P = 0.005, OR 3.89) and TPO (P = 0.05, OR 2.50) than PCA- subjects. Logistic regression analysis showed that PCA status was determined by the HLA DQA1*0501-DQB1*0301 haplotype (beta = 2.94, P = 0.04) and GADA status (beta = 2.44, P = 0.041). CONCLUSIONS: Thyrogastric antibodies are highly prevalent in Type 1 diabetes mellitus, especially in patients with persisting ICA. Screening for gastric autoimmunity is particularly advised in patients who are positive for GADA and for the HLA DQA1*0501-DQB1*0301 haplotype.

Progressive deceleration in growth as an early sign of delayed puberty in boys.

OBJECTIVE: To describe the prepubertal growth pattern in boys with delayed puberty. METHODS: Growth curves for height and height velocity covering the age range 4-14 years were constructed on the basis of retrospectively obtained data in 85 boys with delayed puberty, who attained a normal final height. RESULTS: Between the age of 4 and 14 years the height in this cohort progressively deviated from the normal reference. At the age of 4 years, the height SDS was already significantly lower (median -0.8; p < 0.001) and progressively diminished during childhood, resulting in a median height SDS of -1.1 at the age of 12 years (p < 0.001). The median final height of this cohort (-0.4) was not different from their target height (-0.2). The degree of deceleration in growth during childhood was not determined by birth weight or birth height and did not influence final height. The decline of the height velocity with age in this group of boys with delayed puberty was significantly smaller (p < 0.001) than predicted by the model of Rikken and Wit. CONCLUSION: Late-maturing boys often show a prepubertal deceleration in growth that starts at an early age but that does not affect final height.

Does treatment of asthmatic children with inhaled corticosteroids affect their adult height?

In this retrospective study, adult height was assessed in young adult asthmatics who were treated with inhaled corticosteroids (ICs) during childhood (n = 42; 26 boys) and compared to those obtained in asthmatic patients who were never treated with ICs during childhood (n = 43; 23 boys). Standing height of all subjects and their parents was measured. Height data were analyzed using actual length and target height in centimeters, standard deviation scores (SDS), and difference between adult height of the patients and their target height (adult height minus target height). Mean adult height was the same in subjects who took ICs during childhood as compared to those who had never received ICs (boys: 179.3cm+/-6.8 vs. 180.4 cm+/-5.6; girls: 165.8 cm+/-7.5 vs. 167.7 cm+/-7.2). SDS of adult height was also not different between the two groups: in subjects who did not take ICs it was 0.89+/-1.00, while in those who took ICs it was 0.66+/-1.10 (P = 0.31). SDS of target height was also not different between the two groups: in subjects not taking ICs it was 0.95+/-0.86, while in those who took ICs it was 0.28+/-0.76 (P = 0.30). However, subjects who took ICs during childhood showed a statistically significant lower value of adult height minus target height than those who never took ICs (whole group: -0.003+/-5.9 vs. 2.54 +/-4.8, P = 0.03 ; boys: 0.004+/-5.8 vs. 3.09+/-4.5, P = 0.04 ; girls: -0.075+/-6.3 vs. 1.91+/-5.2, P = 0.31). Patients on ICs during childhood who had ever been hospitalized for asthma showed a lower value for adult height minus target height than those who took ICs but were never hospitalized (-3.08+/-7.8 vs. 1.06+/-4.8, P = 0.046). A logistic regression analysis predicting growth impairment showed that the best-fitting model was one that used only ICs as a dependent variable (crude odds ratio, 3.3; 95% CI, 1.3-8.4). Patients who were treated with ICs in combination with intranasal corticosteroids (treatment for rhinitis) tended to have a lower value of adult height minus target height than the other children, but the difference was not statistically significant (P = 0.07). We conclude that although adult height was the same in young adults who were treated with ICs during childhood compared to those who were not treated with ICs during childhood, there was a statistically significant difference between the two groups for adult height minus target height, suggesting mild growth retardation in patients who took ICs during childhood. These findings may be explained by the use of ICs, but it seems more likely that a difference in asthma severity between both groups was responsible for it.

Early, discontinuous, high dose growth hormone treatment to normalize height and weight of short children born small for gestational age: results over 6 years.

Most children born small for gestational age (SGA) normalize their size through spontaneous catch-up growth within the first 2 yr after birth. Some SGA children fail to do so and maintain an abnormally short stature throughout childhood. We have previously reported that high dose GH treatment (66 or 100 microg/kg x day s.c. over 2 yr; age at start, 2-8 yr; n = 38) induces pronounced catch-up growth in short children born SGA, thereby normalizing their height and weight in childhood. Here, we report on the further prepubertal growth course of these children over the first 4 yr after withdrawal of early, high dose GH treatment. Of the 38 treated children, none developed precocious puberty, and 22 remained prepubertal. Mean age of the latter at start of GH was 4.4 yr, height was -3.7 SD score, and height after adjustment for midparental height was -2.9 SD score. Height increased by an average of 2.5 SD during the 2 yr of GH treatment and decreased by 0.4 and 0.3 SD, respectively, during the first and second year after GH withdrawal. Subsequently, when stature was not extremely short at the start (mean adjusted height SD score, -2.7; n = 13), no further GH treatment was given, and the adjusted height was stabilized around -1.0 SD score; when stature was very short at the start (mean adjusted height, -3.3 SD score; n = 9), a second course of GH treatment (66 microg/kg x day s.c.) was initiated either 2 yr (n = 5) or 3 yr (n = 4) after initial GH withdrawal. This second course was associated with renewed catch-up growth and also resulted in a mean adjusted height of -1.0 SD score. In each subgroup, the pattern of the weight course paralleled that of the height course; GH treatment was well tolerated. In conclusion, early, discontinuous, high dose GH treatment appears to be a safe and efficient option to normalize prepubertal height and weight in the majority of short SGA children. It remains to be examined whether the normalized stature will be maintained during pubertal development, either with or without further GH treatment.

Epidemiology, clinical aspects, and biology of IDDM patients under age 40 years. Comparison of data from Antwerp with complete ascertainment with data from Belgium with 40% ascertainment. The Belgian Diabetes Registry.

OBJECTIVE: To compare the incidence rate of IDDM in the age-groups 0-14 and 15-39 years in Antwerp, Belgium, and to compare demographic, clinical, and biological data from Antwerp IDDM patients with 92% ascertainment with those from a larger Belgian patient group with 40% ascertainment. RESEARCH DESIGN AND METHODS: Incident cases of IDDM were reported by physicians of the Belgian Diabetes Registry and in Antwerp by several other sources. In Antwerp, completeness of ascertainment was calculated by the capture-recapture method. Demographic and clinical data were collected by questionnaire. Blood was sampled for HLA-DQ genotyping and, in new-inset patients, for autoantibodies. RESULTS: In Antwerp, the age- and sex-standardized IDDM incidence rates were similar in both age-groups (0-14 years: 11.8/100,000; 15-39 years: 8.9/100,000). The incidence rate decreased in girls above age 15 years (6.9/100,000; P = 0.003) but not in boys (11.0/100,000). Both in Antwerp and Belgium, IDDM was diagnosed more frequently in the 15-39 years age-group (60% of all cases) than under age 15 years, with a lower prevalence of acute symptoms, ketonuria, high-risk HLA-DQ genotype, and autoantibodies against insulin, islet cells, and IA-2, but with a higher prevalence of GAD65 autoantibodies. CONCLUSIONS: In Antwerp, the incidence rate of IDDM under age 15 years is intermediately high compared with the rates in other European regions. It is similar in the 15-39 years age-group, but with a marked male predominance. Demographic, clinical, and biological data show the same age-dependent heterogeneity as the data collected nationwide, with 40% ascertainment indicating the representativeness of the latter.

Detection of serum insulin-like growth factor binding proteins on western ligand blots by biotinylated IGF and enhanced chemiluminescence.

A novel procedure for the detection of IGF binding capacity of IGFBPs on Western ligand blots (WLB) was developed using biotinylated IGFs as probes. The biotinylated IGF-IGFBP complexes were visualized by streptavidin-horseradish peroxidase and enhanced chemiluminescence (ECL). The procedure was found to be faster and more efficient than the conventional method with iodinated IGFs. In normal human serum a predominant doublet at 38-42 kDa and five smaller bands at 35, 34, 30, 28 and 24 kDa were detected by both methods, whereas two additional bands at 26 and 16 kDa became visible with the ECL method. In pregnancy serum only one single faint band at 30 kDa could be detected by the iodinated method. In contrast, the ECL method revealed five other bands at 42, 34, 28, 26 and 16 kDa. Besides the 38-42 kDa doublet, the 30 and 16 kDa bands reacted strongly with anti-IGFBP-3 antibodies in Western immunoblotting (WIB) and therefore were related to IGFBP-3 fragments. The technical advantages of this ECL method include an extremely short exposure time to the radiographic film and a long stability of the probe. In addition, the ECL method is a non-radioactive method, making radioprotection and radioactive waste removal unnecessary.

High-dose growth hormone treatment of short children born small for gestational age.

The effect of GH administration was evaluated over 2 yr in 50 short, prepubertal, non-GH deficient children born small for gestational age, who had been randomly allocated to a group receiving no treatment or daily sc GH treatment at a dose of 0.2 or 0.3 IU/kg. At the start of the study, mean age was 5.2 yr, bone age was 4.0 yr, height SDS was -3.5, height velocity SDS was -0.8, weight SDS was -2.7, and body mass index SDS was -1.9. Catch-up growth was observed in none of the untreated and all of the treated children. The response to GH treatment included a near doubling of growth velocity and of weight gain and a mean height increment of more than 2 SDS. GH treatment was associated with a distinct acceleration of bone maturation. The differences between the growth responses evoked by the two GH doses were minor. The prepubertal GH-induced catch-up growth was associated with elevated serum concentrations of insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and osteocalcin, whereas insulin-like growth factor-II levels remained unaltered. GH treatment was well tolerated. In conclusion, high-dose GH administration over 2 yr is emerging as a potential therapy to increase the short stature that results from insufficient catch-up growth in young children born small for gestational age. The long-term impact of this approach remains to be delineated.

Low thyroxinaemia occurs in the majority of very preterm newborns.

UNLABELLED: Transient hypothyroxinaemia with normal thyroid stimulating hormone (TSH) levels is a well-known condition in preterm neonates and is generally assumed to be a harmless epiphenomenon of prematurity. This assumption is, however, based on studies that included very few neonates with a gestational age (GA) below 30 weeks. We therefore measured serum free thyroxine (FT4) and serum TSH on days 1 and 14 in 263 neonates with a GA between 26 and 41 weeks. In 13 infants (5%), transient hypothyroidism (low FT4 and TSH >20 mU/l on day 14) was found. In the remaining 250 patients FT4 on days 1 and 14 but not TSH correlated positively with GA. In neonates with a GA of 35-41 weeks, FT4 increased postnatally to levels within or above the normal adult range. In contrast, in the very preterm group (26-31 weeks) the already low FT4 levels declined to values significantly below the range observed in term neonates. A significant proportion of these neonates had FT4 levels within the hypothyroid range. There was no difference in thyroid function between neonates treated with povidone-iodine or chlorhexidine. CONCLUSION: Very preterm neonates have FT4 levels on day 14 that are much lower than is generally assumed while TSH remains in the normal range. We therefore propose to measure FT4 in all preterms with a GA below 33 weeks, during the 2nd week of life.

Longitudinal data on growth and final height in diabetic children.

The available data on growth in children with insulin-dependent diabetes mellitus are conflicting and are mainly derived from cross-sectional studies. In this longitudinal study, height, weight, skeletal age, and pubertal development were recorded until final height was attained in 46 children (22 girls and 24 boys) with onset of diabetes before the age of 10 y. At the onset of diabetes, height SD score (SDS) averaged 0.41 in girls and 0.56 in boys, which was normal when corrected for the secular trend. Prepubertal growth was unaffected in both sexes. Diabetic boys had a marked delay in onset of puberty (mean age at genitalia stage 2: 13.7 y) but attained a normal final height (final height SDS: 0.48 +/- 0.89). In girls final height was slightly reduced (height SDS 0.27 +/- 0.97) due to a suboptimal pubertal growth spurt. Mean pubertal height gain in girls was 16.6 cm and mean age at breast stage 2 was 11.6 y. Diabetic girls also tended to become obese during puberty. Skeletal maturation was normal at all ages. These data suggest that conventional therapy does not guarantee optimal growth, especially in girls.

[Growth inhibition using estrogens in constitutionally tall girls]. / Groeiremming met oestrogenen bij constitutioneel te lange meisjes.

Estrogen treatment in high doses is effective in reducing adult stature in constitutionally tall girls. In this study, growth data of 38 normal girls with a predicted final height beyond 178 cm, are reported. They were treated with ethinyloestradiol in a daily dose of 0.200 mg until the epiphyseal plates were practically fused. In addition, medroxyprogesterone acetate at a dose of 10 mg daily was given for 5 to 12 days every month. The reduction of final height occurred with decreased growth velocity and accelerated epiphyseal closure. The major factor affecting the response to treatment was skeletal age. The lower the skeletal age, the greater the difference between the predicted final height and the final height. This gain was directly related to the growth potential at start of therapy. The best time to start treatment might be the pre-menarche period at a bone age of 12 years. Serious side-effects were not reported, but treatment should be employed only when height prediction is excessive.

[Intracranial germinoma in children]. / Intracraniële germinomen bij kinderen.

Two cases of intracranial germinoma with different clinical expression, are described. The clinical symptomatology, the diagnosis and the treatment of this tumor are discussed. The symptoms depend on the localization of the tumor: in the suprasellar germinoma endocrinologic manifestations prevail while the symptoms in germinomas which are located in the pineal region, are mainly due to increased intracranial pressure. The diagnosis is suggested by the findings on CT-scan and MRI of the brain, but for the definitive diagnosis, pathologic examination of the tumor remains necessary. Blood HCG and alpha-fetoprotein are useful markers for follow-up; the value of angiotensin converting enzyme (ACE) as a marker, is still unclear. The ideal treatment of germinoma consists of surgical removal, postoperative chemotherapy and, afterwards, local radiotherapy. On the whole, the prognosis of this tumor is good.

Isolation of several fractions from human serum, inhibiting rabbit cartilage metabolism in vitro.

In contrast to the well characterized serum stimulators of cartilage metabolism, information is scarce on the nature of circulating inhibitors. Human serum was fractionated by molecular sieving chromatography on Sephadex G-200, G-75, G-50 and Biogel P-4 gels. Six fractions with molecular weights of 150, 45, 30, 16, 9 and 1.2 kD inhibited [35S]sulphate incorporation into rabbit cartilage segments. All fractions but the smallest one exhibited their inhibitory effect only in the serum-stimulated cartilage. The 1.2 kD fraction impaired [35S]sulphate and [3H]methyl-thymidine incorporation into the cartilage segments in both stimulated and basal conditions. A seventh inhibitory fraction corresponded to the serum salt peak.

Somatomedin inhibitors from human serum produce abnormalities in mouse embryos in culture.

Two human serum fractions, one from normal individuals (Mr 1,150-1,310 daltons) and the other (Mr 800-1,100 daltons) from patients suffering with uremia (renal failure, azotemia), were added to the medium used to grow embryos in whole-embryo culture (WEC) beginning at the 3-5 (day 9) or 18-21 (day 10) somite stage. Both of these fractions possessed somatomedin (insulin-like growth factor) inhibitory activity. Day 9 embryos exposed to either of the serum fractions for 24 hr exhibited incomplete rotation and neural tube closure defects and were smaller than control embryos (decreased total protein content). Developmental abnormalities induced in day 10 embryos following 24 hr in culture included a marked decrease in expansion of the brain regions, hypoplasia of the first two branchial arches, and decreased amounts of total protein compared to controls. The visceral yolk sacs (VYSs) of somatomedin inhibitor (SI)-exposed conceptuses were opaque, and those from day 10 conceptuses contained significantly more protein than controls. Morphologically, the VYS endoderm cells from SI-exposed embryos contained a much higher density of "vacuoles" than controls. These results mimic those produced by exposure of conceptuses to an SI of Mr800-1,100 obtained from the serum of diabetic rats and suggest that similar substances and mechanisms are involved.

Comparative study of the lipolytic potencies of pituitary-derived and biosynthetic human growth hormone in hypopituitary children.

Whether stimulation of lipolysis is an intrinsic property of the human growth hormone (hGH) molecule or is due to contaminants of pituitary origin is controversial. We compared the rises in plasma FFA levels 4 h after an im injection of 0.2 U/kg of either pituitary hGH (n = 5) or biosynthetic methionyl hGH (n = 32) to hypopituitary patients. In each patient, plasma FFA levels also were measured during a similar period of fasting alone, without hGH injection. Plasma FFA levels rose between 0800 and 1230 h in both subgroups of patients during fasting alone. Injection of either pituitary or biosynthetic methionyl hGH led to a greater increase in plasma FFA than that induced by fasting alone, and the percent increases over baseline plasma FFA levels induced by either pituitary or synthetic hGH were similar. Triceps skinfold thickness before and after 3 months of treatment with biosynthetic hGH in 20 patients diminished by a mean of 2.5 mm, a decrease similar to that reported with pituitary hGH. We conclude that the acute and chronic lipolytic effect of hGH in man is an intrinsic property of the hGH molecule.

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin).

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (+/- 1SD) was 0.85 +/- 0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between -0.74 and + 1.04 SDS (standard deviation score). These differences were inversely related (r = -0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.

A simplified 'sandwich' technique for in situ embedding and perpendicular sectioning of monolayer cultures of human skin fibroblasts.

In the processing of cell cultures, grown as a monolayer in tissue culture dishes for electron microscopy, the sectioning of the monolayer is an essential step. The monolayer can be sectioned either parallel or perpendicular to the plane of growth. Several methods for the perpendicular way of sectioning have already been described. We propose a simplified method in which the monolayer is sandwiched between two layers of resin, one of which is a prepolymerized block, the other being a layer of resin, applied at a second stage. Sectioning of this 'flat embedded' specimen yields thin sections perpendicular to the plane of growth of the monolayer without elaborate orientating procedures. The advantage of this procedure is that it can be done using only routine embedding techniques, avoiding special materials or complex manipulations. This sandwich technique provides an excellent mechanical fixation of the monolayer and protects it against external damage.