Ulf Westgren

Daily subcutaneous administration of human growth hormone in growth hormone deficient children.

Sixteen children (10 boys, 6 girls) on treatment for some years with i.m. injections twice or thrice weekly of human growth hormone (hGH; Crescormon® KabiVitrum), participated in a prospective study. The weekly amount of hGH (8, 12, or 16 IU) was kept the same in each child, but divided into daily (7) s.c. injections at bedtime. The growth rate increased in all children during the first year on s.c. daily hGH (5.3 to 7.4 cm/year; 1.95 to 4.27 SDS). This increased growth rate did not persist during the second year on daily s.c. hGH, but an increased predicted final height was found. The plasma profile of hGH was followed: i.m. injected hGH gave mostly a high (200 mU/1) plasma level of some hours (wide intra‐ and inter‐patient variation), and s.c. injected hGH a lower max level of longer duration (wide inter patient variation). The daily s.c. regimen of hGH was extremely well accepted by the children and their parents and no GH‐antibodies or other adverse effects were found. We recommend daily s.c. injection of hGH as an alternative in the treatment of GH‐deficient children.

Lidocaine for treatment of severe seizures in newborn infants. I. Clinical effects and cerebral electrical activity monitoring

ABSTRACT. The anticonvulsive effect of lidocaine was evaluated in 46 newborn infants with severe, recurrent seizures. Before the lidocaine all infants were being given phenobarbital, and 22 infants were also treated with diazepam. Different dosages of lidocaine were tested. A loading dose of 2 mg/kg followed by i.v. infusion of 6 mg/kg/hour was the most effective dosage and had an immediate anticonvulsive effect in 18 of 25 infants; within 30 min the same effect was attained in another five of the infants, with an overall seizure control in 92% of the sample population. During the lidocaine treatment cerebral electrical activity was followed continuously with a cerebral function monitor (CFM), which also enabled evaluation of the treatment. No serious side effects on blood‐pressure, heart‐rate or cerebral electrical activity were registered. For newborn infants with severe recurrent seizures not responding to other drugs, lidocaine is an effective additional mode of treatment.

Growth hormone treatment of short children born small-for-gestational-age: the Nordic Multicentre Trial

The aims of this study were to evaluate the efficacy and safety of different doses of growth hormone (GH) treatment in prepubertal short children born small‐for‐gestational‐age (SGA). Forty‐eight children born SGA from Sweden, Finland, Denmark and Norway were randomly allocated to three groups: a control group of 12 children received no treatment for 2 y, one group was treated with GH at 0.1 IU/kg/d (n= 16), and one group was treated with GH at 0.2 IU/kg/d (n= 20). In total 42 children completed 2 y of follow‐up, and 24 children from the treated groups completed 3 y of treatment. Their mean (SD) age at the start of the study was 4.69 (1.61) y and their mean (SD) height was ‐3.16 (0.70) standard deviation scores (SDS). The children remained prepubertal during the course of the study. No catch‐up growth was observed in the untreated group, but a clear dose‐dependent growth response was found in the treated children. After the third year of treatment, the group receiving the higher dose of GH, achieved their target height. The major determinants of the growth response were the dose of GH used, the age at the start of treatment (the younger the child, the better the growth response) and the family‐corrected individual height deficit (the higher the deficit, the better the growth response). Concentration of insulin‐like growth factor‐I (IGF‐I) and IGF‐binding protein‐3 increased during treatment. An increase in insulin levels was found without negative effects on fasting glucose levels or glycosylated haemoglobin levels. GH treatment was well tolerated. In conclusion, short prepubertal children born SGA show a dose‐dependent growth response to GH therapy, and their target height SDS can be achieved within 3 y of treatment given GH at 0.2 IU/kg/d. However, the long‐term benefit of different regimens of GH treatment in children born SGA remains to be established.

Recurrent Pseudomonas bronchopneumonia and other symptoms as in cystic fibrosis in a child with type I pseudohypoaldosteronism

We report a child with multiple target organ pseudohypoaldosteronism type 1 with frequent recurrent pulmonary infections caused by Pseudomonas aeruginosa and Pasteurella multocida and high levels of chloride in sweat, urine and nasal secretion. Repetitive faecal chymotrypsin samples have all shown pathological values in spite of no other sign of exocrine pancreas dysfunction. The similarities with cystic fibrosis and the importance of the salt content in bronchial fluid are discussed.

Lidocaine for treatment of severe seizures in newborn infants. II. Blood concentrations of lidocaine and metabolites during intravenous infusion

The blood concentrations of lidocaine and its main active metabolites, methylethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in 24 newborn infants during anticonvulsive treatment with an iv infusion of lidocaine. After a bolus dose of 1.5–2.2 mg/kg and continuous infusion of lidocaine (4.7–6.3 mg/kg/h) there was accumulation of the drug and MEGX within 24 h. After termination of the iv infusion, both lidocaine and the metabolites were eliminated within 24–48 h. The anticonvulsive effectiveness–estimated by clinical observation and continuous amplitude integrated EEG monitoring (cerebral function monitor)–was immediate in 15 infants (nine term and six preterm). There was no correlation between blood concentrations of lidocaine and metabolites, and anticonvulsive effect (i. e. good, intermediate or no response). No differences in blood concentrations were found between full‐term and preterm babies, or between infants with or without birth asphyxia. In combination with a fast withdrawal of the drug, few adverse reactions were seen with the dosages used, even though blood concentrations were high. Routine measurements of lidocaine concentrations during anticonvulsive treatment in neonates seem to be of little clinical value. For evaluation of the anticonvulsive effect and for early detection of seizure activity during lidocaine withdrawal, continuous EEG monitoring is preferable.

Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty

Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin‐releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. Methods: Forty‐six girls with early or precocious puberty (age ± 9.5y) adopted from developing countries were randomized for treatment for 2–4 y with GnRH analogue, or with a combination of GH and GnRH analogue. Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue‐treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below –2 standard deviation scores (SDS).

Effect of growth hormone (GH) during puberty in GH-deficient children : preliminary results from an ongoing randomized trial with different dose regimens

Albertsson Wikland K, Alm F, Aronsson S, Gustafsson J, Hagenas L, Hager A, Ivarsson S, Kristrom B, Marcus C, Moe11 C, Nilsson KO, RitzCn M, Tuvemo T, Westgren U, Westphal 0, Aman J. Effect of growth hormone (GH) during puberty in GH‐deficient children: preliminary results from an ongoing randomized trial with different dose regimens. Acta Pxdiatr 1999; Suppl 428:80‐4. Stockholm. ISSN 0803‐5326

Growth Hormone Dose-Dependent Pubertal Growth: A Randomized Trial in Short Children with Low Growth Hormone Secretion

Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH⁶⁷) given as one (GH^67×1; n = 35) or two daily injections (GH^33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH^33×1; n = 40). Growth was assessed as height_SDSgain for prepubertal, pubertal and total periods, as well as AH_SDS versus the population and the midparental height. Results: Pubertal height_SDSgain was greater for patients receiving a high dose (GH⁶⁷, 0.73) than a low dose (GH^33×1, 0.41, p < 0.05). AH_SDS was greater on GH⁶⁷ (GH^67×1, -0.84; GH^33×2, -0.83) than GH³³ (-1.25, p < 0.05), and height_SDSgain was greater on GH⁶⁷ than GH³³ (2.04 and 1.56, respectively; p < 0.01). All groups reached their target height_SDS. Conclusion: Pubertal height_SDSgain and AH_SDS were dose dependent, with greater growth being observed for the GH⁶⁷ than the GH³³ randomization group; however, there were no differences between the once- and twice-daily GH⁶⁷ regimens.

Sympathetic innervation and noradrenaline content of normal human thyroid tissue from fetal, young, and elderly subjects

In man, as well as in the mouse, there is morphologic and functional evidence for a direct, stimulatory influence of the sympathetic nervous system on the secretion of thyroid hormone by noradrenaline (NA) released from interfollicular adrenergic nerve terminals. In mice and rats, an age-related reduction of the sympathetic innervation of the thyroid has recently been observed. In the present study, possible age-related variations of the sympathetic innervation and the concentration of NA in human thyroid tissue were examined. Interfollicular adrenergic nerve terminals were studied by fluorescence histochemistry, and the tissue concentration of NA was measured by fluorometry. In apparently normal thyroid tissue, obtained from fetuses, young (20–45), and elderly (>60) euthyroid people with thyroid cancer or hyperparathyroidism, the number of interfollicular adrenergic nerve terminals appeared to be reduced with increasing age, and the thyroid tissue concentration of NA was significantly lower in elderly than in young people. These findings may have functional importance.

Is Growth Hormone Secretion Related to Growth

Normal growth is dependent upon a delicate interplay of endocrine and metabolic factors. A crucial factor is the secretion of G H from the pituitary, although it should be borne in mind that a series of other hormones is also involved in growth, normal and pathological. This is amply illustrated by the fact that some children devoid of growth hormone, owing to surgical excision of craniopharyngiomas, continue to grow at normal rates ( I ) . Due to the abundant availability of biosynthetically derived GH, the relationship between GH secretion and growth has attracted increasing interest, The elucidation of this issue is difficult, however, as in all likelihood it is not only the quantity but also the pattern of GH secretion that are of importance (2). In this respect our knowledge has benefited from studies of the 24-hour G H profile. rather than of the G H response to provocative tests. which has been found to provide an inadequate picture of endogenous G H secretion. Postnatally the growth process is divided into three phases-infancy, childhood and puberty. Karlberg has recently elucidated the mathematical basis of these three different phases of growth (3). The pattern of growth varies from one phase to another. as does. presumably, the relative importance of the various growth regulatory systems. Thus, the question of whether growth is related to G H secretion must be considered separately for each ofthe three growth phases, as is previously discussed in the review by Brook et al(4).