A multicentre verification study of the QuantiFERON®-TB Gold Plus assay.

OBJECTIVES: The aim of this verification study was to compare the QuantiFERON®-TB Gold Plus (QFT-Plus) to the QuantiFERON®-TB Gold In Tube (QFT-GIT). The new QFT-Plus test contains an extra antigen tube which, according to the manufacturer additionally elicits a CD8+ T-cell response above the CD4+ T-cell response. We assessed the value of this tube in detecting recent latent tuberculosis infections. METHODS: Between May 2015 and December 2016, 1031 subjects underwent QFT-Plus and QFT-GIT test. Overall agreement between both tests and performance for different test indications and/or immune states was assessed. A difference of >0.6 IU/mL interferon-γ release between the two antigen tubes of the QFT-Plus assay was considered a true difference and used as estimation for CD8+ T-cell response. RESULTS: Analysis of the QuantiFERON tests resulted in an overall agreement between assays of 95%. Subjects considered to be recently exposed to tuberculosis had significantly more often a true difference in interferon-γ release compared to all other subjects (p = 0.029). CONCLUSION: Results of QFT-Plus are highly comparable to QFT-GIT. Although there is an indication that a true difference in interferon-γ release between the antigen tubes is associated with recent latent tuberculosis infection, the QFT-Plus could not be used to exclude recent exposure.

[Control of referral and duration of rehabilitation in federal insurance office provided rehabilitation]. / Steuerung der Einweisung und der Rehabilitationsdauer in der Rehabilitation der BfA.

Presented is a computer-based system for interactive assignment control, designed to cope with the increasing requirements in rehabilitation and health care concerning quality assurance, greater flexibility, as well as enhanced effectiveness and efficiency. Thanks to multi-factor control, medical, organizational and economic parameters can be taken into account selectively. In addition, an unbureaucratic approach to determining length of rehabilitation programme participation is described, which has been implemented successfully for the last three years.

Efficacy of a self-management program for childhood asthma--a prospective controlled study.

Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes. In order to evaluate two training programs for asthmatic children aged 7-14, 81 patients were randomly assigned to three groups. Group 1 consisted of 27 patients and their parents who participated in a five-day standardized family-oriented clinical asthma training program. They had monthly follow-up meetings with the training team for a period of six months. Group 2 (n = 29) had the same clinical training without follow-up interventions; a control group (n = 25) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group. Questionnaires regarding self-management aspects, coping and anxiety were filled out by patients, parents, family doctors and the training team prior to as well as twelve months after the training. The results indicate that Training group 1 benefitted most with respect to active asthma self-management, Training group 2 to some degree while the control group showed no significant effects. The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance. Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions.

[Outcome of structured asthma education in childhood and adolescence]. / Ergebnis einer strukturierten Asthmaschulung im Kindes-und Jugendalter.

From 1988 onwards inpatient asthma training courses have been conducted in Berlin and Osnabrück. A controlled study on asthma training was carried out from 1990 to 1992 at both centres with the support of the Robert Bosch Foundation. In the first intervention group a subsequent training course of 6 months' duration was conducted with the inclusion and participation of the relevant family doctors in addition to the main training course. Scrutiny of the result was done before (T1), directly after (T2) and 12 months subsequent to the training course (T3). Improvements are seen in somatic data or cost-relevant data (emergency referral to the hospital or family physician, inpatient hospital periods, referral because of mild obstruction, days of non-attendance in school due to illness, severity of asthma, incidence of symptoms, stress endurance in sports). There is also a marked improvement in the self-assessment ability of the children and in the management of asthma, as well as a decrease in the asthma-specific feeling of anxiety. Self-reliance and independence, as well as early intervention, are improved as seen by the parents, whereas on the other hand unfavourable factors such as arguments on the proper asthma therapy are diminished. Especially with regard to confidence in controls on the state of health or disease there are significant changes that are more marked in the group subjected to subsequent training than in the group without such additional training, compared with the control group. Structured asthma training exercises a strongly positive effect on the daily management of asthma bronchiale by the families on different planes of coping with the disease. These effects are enhanced by subsequent aftercare by the family physician. Intensive care in the asthma outpatient wards alone does not sufficiently modify the factors contributing to good coping with the disease.

[Long-term therapy of true precocious puberty in girls using Decapetyl-Depot, a superactive gonadoliberin agonist in depot microcapsulated form]. / Dlouhodobá lécba dívek s pubertas praecox vera prípravkem Decapeptyl-Depot, superaktivním agonistou gonadoliberinem ve forme retardovaných mikrotobolek.

Within the framework of an international prospective multicentre study 93 girls with gonadotropin-dependent precocious puberty were treated with Decapeptyl-Depot LHRH agonist (75 micrograms/kg, once a month by the i.m. route). This treatment led to prompt, immediate and long-term suppression of the pituitary-ovarian axis with subsequent regression of premature onset of secondary sex signs, to the arrest of premature menstruation, to normalization of the pathologically accelerated growth and inhibition of the accelerated bone maturation. This improved the mean expected growth during the first four years of treatment from 159 to 165 cm (p < or = 0.01). Concurrently in the majority complete normalization of the severely impaired mental condition of the affected girls due to the premature onset of puberty occurred (mean onset of puberty -4.5 years). Selective suppression of the pubertally increased gonadotropin secretion was even after prolonged treatment fully reversible after termination of treatment with a subsequent onset of normal puberty and cyclic ovarian activity. Undesirable side-effects and antibodies against Decapeptyl were not detected, the local tolerance of the injected microcapsules was satisfactory. GnRH agonists in depot form are becoming, due to their superior suppressive action incl. that on bone maturation, the drug of choice in long-term treatment of central precocious puberty as they are the first which mitigate or can prevent, if treatment is started in time, a final small stature which frequently is the greatest handicap for a life-time (frequently associated with adverse bodily disproportions).

[Growth, development and prediction of body height in children with central precocious puberty after 3 years of therapy with Decapeptyl-Depot, a slow-releasing GnRH agonist]. / Rust, vývoj a predikce telesné výsky detí centrální pubertas praecox po 3 letech lécby "slow-releasing" agonistou GnRH, prípravkem Decapeptyl-Depot.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.

[Comparison between complete and incomplete suppression of the hypophyseal-gonadal axis in girls with central precocious puberty: effect on growth and prospective final height]. / Vergleich zwischen kompletter und inkompletter Suppression der Hypophysen-Gonaden-Achse bei Mädchen mit zentraler Pubertas praecox: Einfluss auf Wachstum und prospektive Endlänge. Deutsch-Niederländische Decapeptyl-Depot-Studiengruppe.

BACKGROUND: Whether short-acting or slow-release gonadotropin-releasing hormone agonists have different effects on growth and bone maturation in children with central precocious puberty is still unknown. METHODS: In a meta-analysis, we studied 21 previously untreated girls with central precocious puberty treated with Buserelin and 22 previously untreated girls with central precocious puberty treated with Decapeptyl Depot. Duration of treatment was at least 18 months in both groups. RESULTS: At start of therapy, chronological age, bone age, height velocity and pubertal stage were well comparable between the groups. During the first 6 months of treatment, clinical and biochemical escapes from suppression were more frequent in the Buserelin group; height velocity and bone maturation (delta bone age/delta chronological age) remained significantly higher (p < 0.0001 and p < 0.01, resp.) in Buserelin than in Decapeptyl Depot patients. In contrast to the Decapeptyl Depot group, in the Buserelin patients height standard deviation score for bone age did not change and predicted adult height decreased. From 6 to 18 months of therapy, the development of height velocity, delta bone age/delta chronological age, standard deviation score for bone age and predicted adult height showed an almost parallel course in both groups. Height velocity and bone maturation tended to be faster in the Buserelin group. Mean predicted adult height rose significantly in the Decapeptyl Depot group, but not in the Buserelin-treated girls. CONCLUSIONS: A slow-release gonadotropin-releasing hormone agonist appears to be superior to short-acting drugs not only in terms of long-term tolerance but also for achieving the auxological objectives in central precocious puberty therapy. This is mainly due to their faster and more complete suppression of gonadotropins during the first 6 months of treatment.

Intranasal administration of growth hormone-releasing hormone(1-29)-NH2 in children with growth hormone deficiency: effects on growth hormone secretion and growth.

The growth-promoting potential of growth hormone-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2) in a new formulation for intranasal use was examined in a 6-month pilot study of eight short prepubertal children. The maximal plasma concentration of growth hormone (GH) was below 12 micrograms/l in two stimulation tests (arginine, insulin), but above 12 (24-90) micrograms/l after intravenous GHRH, 1 microgram/kg. GHRH, 50 micrograms/kg, was insufflated intranasally three times per day over 6 months. On day 1, GHRH insufflations were followed by distinct GHRH and GH plasma peaks, ranging from 1.2 to 5.4 micrograms/l and from 10 to 85 mIU/l, respectively. Peak amplitudes were variably reduced after 6 weeks in most patients, and further reduced at 6 months. GHRH antibodies (initially negative) were positive in three patients after 6 weeks. The mean knemometric growth rate rose from 0.24 to 0.48 mm/week after 6 weeks of treatment (p = 0.03) and then rapidly declined; the mean 6-month stadiometric height velocity did not increase. Local tolerance was good in one patient; most others reported sneezing immediately after insufflation, rhinorrhoea and mild mucosal burning. Treatment was discontinued in two patients after 6 and 12 weeks. It is concluded that intranasal GHRH, though non-invasive, is not suitable in its present form for use in children, because of decreasing absorption and effectiveness with concomitant development of antibodies and local reactions.

Comparison of complete and incomplete suppression of pituitary-gonadal activity in girls with central precocious puberty: influence on growth and predicted final height. The German-Dutch Precocious Puberty Study Group.

The question as to whether treatment with short-acting or with slow-release gonadotropin-releasing hormone (GnRH) agonists has different effects on growth and bone maturation when treating girls with central precocious puberty has not yet been studied. In a meta-analysis, we compared 21 naive girls with central precocious puberty who were treated with buserelin with 22 naive girls with central precocious puberty who received Decapeptyl in depot form. Treatment lasted for at least 18 months. At the start of therapy, chronological age, bone age, growth velocity and pubertal stage in the two groups were very similar. During the first 6 months of treatment, significantly more phases of incomplete suppression of pituitary-gonadal activity occurred in the buserelin group. As a result, growth velocity and bone maturation (delta bone age/delta chronological age) remained significantly higher than in the Decapeptyl Depot group (p < 0.0001 and p < 0.01, respectively). In contrast to the Decapeptyl Depot group, the height standard deviation score (SDS) for bone age in the buserelin group did not change significantly in the first 6 months of treatment, and the predicted adult height decreased. Between the 6th and 18th months of therapy, the development of growth rate, delta bone age/delta chronological age, height SDS for bone age and predicted adult height in both groups became almost identical. However, the rate of growth and bone maturation in the buserelin group remained faster than in the Decapeptyl group, though not significantly so. The mean predicted adult height had risen significantly after 18 months in the Decapeptyl Depot group but not in the group treated with buserelin.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.

Long-term results with a slow-release gonadotrophin-releasing hormone agonist in central precocious puberty. Dutch-German Precocious Puberty Study Group.

As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean +/- SD) increased from 158.9 +/- 6.8 to 164.9 +/- 6.6 cm in girls (n = 14, p less than 0.01), and from 174.4 +/- 18.5 to 184.3 +/- 17.1 cm in boys (n = 4, p less than 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 +/- 0.5 years, menses started 9.8 +/- 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 +/- 0.1 to 5.4 +/- 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2-3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth and pubertal development during and after treatment with a slow-release gonadotropin-releasing hormone agonist in central precocious puberty.

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Repetitive injections of growth hormone releasing hormone (GHRH1-44) to normal volunteers and patients with growth hormone deficiency.

The present study was designed to answer the following three questions: Is there any difference between the growth hormone (GH) response to i.v. injections of GHRH 1-44 by a slowly injecting hormone pump or to a s. s. or rapid i. v. injection by syringe? Do nocturnal injections of GHRH 1-44 i. v. elicit different GH levels than during daytime? Can repetitive administration of GHRH 1-44 in patient with GH deficiency induce a physiological GH pattern and thereby normalize the condition resulting from a hypothalamic defect? A rapid i. v. bolus injection of 50 micrograms GHRH 1-44 by syringe with an injection time of one second elicited in the same subject at the same time of the day a twofold greater response than a slowly injecting (60 seconds) hormone pump. In six male adult volunteers each GHRH i. v. bolus was followed by a GH secretory pulse. The GH response at night (area under the curve and peak plasma GH levels) was significantly greater than at daytime (P less than 0.05) and greater than the GH pulses measured during a spontaneous nocturnal profile (P less than 0.05). Out of six GH deficient young adult patients who had been receiving extractive GH until two years prior to the study, three responded much like the controls, the other three patients-those who lacked any spontaneous nocturnal GH peaks-had markedly lower GH levels after GHRH (P less than 0.05). However, there was a clear-cut GH release after GHRH injection in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist.

A total of 82 patients (74 girls, 8 boys) are presently participating in an international multicentre trial for treatment of central precocious puberty (CPP) with a slow release gonadotropin-releasing hormone (GnRH) agonist depot preparation: Decapeptyl-Depot (DD). Of these patients, 53 (3 boys) were previously untreated (group 1) and 29 (5 boys) have been treated before with either a short-acting GnRH analogue or cyproterone acetate (group 2). Fifty-one patients (44 girls, 7 boys) were treated with DD for 12 months or more. Basal plasma luteinizing hormone (LH) levels decreased in both groups after 1 year of therapy. The LH response to intravenous GnRH was reduced in both groups. Basal plasma follicle stimulating hormone (FSH) levels decreased in both groups. Stimulated FSH levels were reduced in both groups after 1 year of DD treatment. Plasma oestradiol levels in the girls decreased to prepubertal levels in both groups. In all patients the clinical signs of precocious gonadarche such as breast development and menstruations (girls) and an increased testis volume (boys), did not further progress and sometimes regressed in several patients. Growth velocity decreased in the girls of group 1 from 9.0 +/- 0.72 cm/year (mean +/- SEM) in the last half-year before treatment to 6.3 +/- 0.50 in the first half-year of treatment (P less than 0.01) and to 4.5 +/- 0.23 cm/year in the second half-year (P less than 0.01). After 12 months a stabilization of growth velocity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Reference ranges of lutropin and follitropin in the luliberin test in prepubertal and pubertal children using a monoclonal immunoradiometric assay.

Reference ranges of lutropin and follitropin in the luliberin test (60 micrograms/m2 body surface) were established for the various pubertal stages in a large sample of endocrinologically healthy children using a monoclonal immunoradiometric assay (LH and FSH MAIA Clone, Serono Diagnostika, Freiburg, FRG). Qualitatively, the results for lutropin were similar to those already reported from studies using polyclonal RIA's. Lutropin increased gradually throughout pubertal development. Quantitatively, however, the immunoradiometric assay system yielded considerably lower results than polyclonal RIA's. In contrast, follitropin showed a very good linear regression between monoclonal and polyclonal assays. Therefore the former reference ranges for follitropin are still applicable.

[The significance and characteristics of the LHRH test in diagnosing precocious puberty development in girls: the stimulated LH/FSH quotient differentiates between central precocious puberty and premature thelarche]. / Bedeutung und Charakteristika des LHRH-Testes in der Diagnostik der vorzeitigen Pubertätsentwicklung bei Mädchen: Der stimulierte LH/FSH-Quotient differenziert zwischen zentraler Pubertas praecox und prämaturer Thelarche.

LHRH tests (100 micrograms i.v.) were performed in 31 girls with central precocious puberty (PP); the girls were participating in an international multicentre trial for the treatment of PP with the LHRH agonist decapeptyl in microspheres, together with 18 girls with premature thelarche (PT). Assignment to these two groups was made after 6 months to 5 years of clinical follow-up. LH and FSH were determined centrally using a polyclonal RIA. Basal LH and FSH levels and stimulated LH levels were significantly higher in PP patients (p less than 0.001), but the stimulated FSH levels were not significantly different between the two groups. In the PP group, all stimulated LH levels were above the prepubertal range, whereas in the PT patients all stimulated LH levels were within the prepubertal reference limits. In PP and PT patients 52% and 56%, respectively, of the stimulated FSH levels were increased above the range for prepubertal girls. In 55% of the PP patients, stimulated LH levels were also above the reference range for the corresponding Tanner breast stage. In contrast, all stimulated LH levels of the PT group were within the reference limits for their breast stage. For FSH, 45% and 56% of the stimulated levels were above the normal ranges for the corresponding breast stages in the PP and PT groups, respectively. The LH-to-FSH ratio after LHRH stimulation was significantly higher in the PP than in the PT group (p less than 0.001). All but one of these ratios were above 1 in the PP patients and all ratios in the PT patients were below 1.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical value of the gonadotropic hormone releasing hormone (GHRH) test in the diagnosis of growth deficiency]. / Klinische Wertigkeit des GHRH-Tests in der Minderwuchsdiagnostik.

Many stimulation tests are available for the assessment of growth hormone release from the pituitary in clinical practice. Three of the most common tests are insulin-hypoglycaemia, arginine stimulation and spontaneous hGH nocturnal peaks and profiles. In this study we compared the Growth hormone releasing-hormone (GHRH)-test in a dose of 1 microgram/kg b.w. with these three other tests for evaluation of the somatotropic function of the pituitary. Each of these four tests was performed in 29 children with short stature due to growth failure of various etiologies and height-deficits (-SDS) of -3.0 +/- 0.5 SE. The peak plasma hGH levels of all patients after GHRH stimulation did not correlate with the respective peak values during insulin (r = 0.02) and arginine (r = 0.28) stimulation and with peak levels during the spontaneous nocturnal hGH profile (r = 0.18). The diagnostic value of the GHRH test alone is thus still questionable in establishing the diagnosis of a hypothalamic GHRH/GH defect, because some of these patients do not react to the first GHRH dose as one might expect, but only after a few days of repeated injections of GHRH (priming). The tolerance of intravenous injections of GHRH was excellent. The mean plasma GH response to GHRH was higher (p less than 0.05) in the group of children with constitutional short stature than in GH deficient patients, but there were overlaps in this group with normal volunteers and other groups of patients with growth failure.

Nine months' subcutaneous therapy with synthetic growth hormone releasing factor in children with short stature.

The growth promoting potential of GRF(1-29)NH2 was studied in nine boys with short stature over three periods of 3 months. Their short stature was due to partial hGH deficiency/hGH neurosecretory dysfunction and was diagnosed by arginine and insulin stimulation tests and hGH nocturnal profiles. Four patients (Group I) were given GRF, 3-4 micrograms/kg s.c. b.d. during the first period of 3 months, and after an interval of 1 month, the same dose once daily during the second treatment period of 3 months. Five patients (Group II) were given GRF, 3-4 micrograms/kg s.c., once daily during the first and b.d. during the second 3 months of therapy. After a second interval of 1 month without any GRF treatment, the third 3-month period for both groups consisted of one daily injection of GRF, 8-10 micrograms/kg s.c. at 19.00 hours. Total body height and lower leg length were measured by stadiometry and knemometry, respectively. GRF intravenous bolus tests were performed in each patient following fasting, before and at the end of the first and second 3-month periods. Serum IGF-1 and urinary hydroxyproline excretion were determined monthly. Stadiometric growth rate, determined over the whole study period of 11 months including the treatment-free intervals, increased from 4.92 cm/year to 5.97 cm/year (p greater than 0.05). Mean knemometric growth rates increased from 0.28 mm/week before therapy, to 0.35 mm/week during the one injection/day period at low dose, to 0.39 mm/week (p less than 0.05) during the b.d. period, and to 0.40 mm/week during the last 3 months of high-dose GRF given once daily.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous corticoids and lung development in the fetal rabbit.

Corticosteroid treatment of the fetus, which accelerates lung maturation, may mimic a modulating role of endogenous corticoids in normal development. To investigate this question, we determined the developmental pattern of plasma corticoids and their binding proteins in the rabbit, a commonly used species for studies of lung differentiation. The concentration of cortisol, the most potent glucocorticoid in the rabbit, was maximal at 23 days gestation (1.89 micrograms/dl), declining to 0.54 micrograms/dl at term (31 days). Levels of plasma corticosterone were always lower than those of cortisol. The adrenal content of corticoids, expressed per adrenal DNA or g BW, decreased during late gestation. Corticosteroid-binding globulin in fetal plasma decreased strikingly between day 23 (36 micrograms cortisol bound/dl) and day 31 (4.4 micrograms/dl; P less than 0.001), whereas maternal levels increased about 10-fold during this time. Free cortisol in the fetus increased between 21 and 23 days (0.041 micrograms/dl) and then decreased somewhat until after day 29 when there was an increase. To examine more directly the influence of endogenous glucocorticoids in the fetal lung, we assayed cortisol in extracts of purified lung nuclei as a reflection of receptor-cortisol complexes. The nuclear content of cortisol was constant between 23 and 30 days at levels (0.056-0.074 ng/mg DNA) comparable to those predicted from data for plasma free cortisol. Thus, in the rabbit, increases in plasma cortisol and nuclear receptor-cortisol complex are not temporally associated with the major events of lung development as in other species. We speculate that endogenous glucocorticoids may have a permissive or delayed influence on the lung during normal development in the rabbit.