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 < or =9.5 y) 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). CONCLUSION: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

Growth in rabbits during alternate-day cortisone injections: near normal growth on days without cortisone.

Longitudinal bone growth in rabbits during treatment with hydrocortisone was measured by means of Roentgen Stereophotogrammetric Analysis, RSA. This method allows accurate measurement of the distance between metallic markers inserted into long bones. Hydrocortisone was given in i.m. injections as single doses and as repeated doses, daily or every other day. Single injections of hydrocortisone resulted in three types of growth effect, depending on dosage. Low dosage (less than 4 mg/kg b.w.) produced no blunting of growth. Intermediate dosage (4-32 mg/kg b.w.) retarded growth during the first but not the second day after the injection. The effect of high dosage (64-128 mg/kg b.w.) lasted for two days. During daily treatment (4 and 16 mg/kg b.w.), growth decreased to a constant level. During alternate-day steroid injections with a double dose every other day, growth almost normalized during the steroid-free days. Average growth was significantly greater during alternate-day injections than during daily injections. It is concluded that alternate-day treatment has no unfavorable effect on growth so long as the interval between injections exceeds the duration of the growth effect of each single dose.

Tantalum markers in radiography. An assessment of tissue reactions.

The biocompatibility of two types of radiopaque tantalum markers was evaluated histologically. Reactions to pin markers (99.9% purity) and spherical markers (95.2% purity) were investigated after 3-6 weeks in rabbits and 5-48 weeks in children with abnormal growth. Both marker types were firmly attached to bone trabeculae; this was most pronounced in rabbit bone, and no adverse macroscopic reactions were observed. Microscopically, no reactions or only slight fibrosis of bone tissue were detected, while soft tissues only demonstrated a minor inflammatory reaction. Nevertheless, the need for careful preparation and execution of marker implantations is stressed, and particularly avoidance of the use of emery in sharpening of cannulae. The bioinertness of tantalum was reconfirmed as was its suitability for use as skeletal and soft tissue radiographic markers.

A roentgen stereophotogrammetric system. Construction, calibration and technical accuracy.

The principles for a system of roentgen stereophotogrammetric analysis for experimental and clinical applications are presented. Only the positions of implanted reference markers in the investigated object are measured. Tantalum balls, 0.5 or 0.8 mm in diameter, are used as reference markers. Standard roentgen equipment, permitting simultaneous exposure from two roentgen tubes, is employed. The calibration equipment, a glass calibration cage containing radiopaque markers, introduces a rectangular laboratory coordinate system in the roentgen investigation. The calibration of the calibration equipment itself and the obtained methodologic accuracy in determining distances, volumes and movement parameters is described for various film/screen and marker combinations.

Roentgen stereophotogrammetry for determination of daily longitudinal bone growth in the rabbit.

The spatial location of points in an object can be determined by roentgen stereophotogrammetry. A technique of high accuracy was applied in a determination of the daily skeletal growth of young rabbits. The tibia was labelled with tantalum markers on each side of the growth zones, and the increasing distance between these markers due to longitudinal bone growth was measured. Three different types of markers were tested, and the methodologic error was estimated. It varied between 30 and 43 micrometer for one growth interval, depending on the type of marker used. The method has clinical implications currently under investigation.

Roentgen stereophotogrammetry for determination of bone growth. Comparison with the tetracycline method.

Two different methods for determination of leg growth, the tetracycline method and roentgen stereophotogrammetry, were applied simultaneously in 41 young rabbits and compared 1 and 2, and 21 and 22 days after insertion of pins or balls of tantalum as markers. The tetracycline method gave slightly higher values than the other method, the difference varying between 77 and 6 micrometer/d on the first 2 days after marker insertion and between 32 and 1 micrometer/d after 3 weeks. When ball markers were used, agreement between the two methods was obtained 3 weeks after insertion. The difference between the methods used is due to that the two methods did not measure growth in precisely identical regions.

Bone growth in the rabbit after irradiation.

The effect on bone growth of two locally given, different, unfractionated radiation doses (0.1 and 24 Gy) was tested in a rabbit litter aged 57 days. The effects on growth were registered with roentgen stereophotogrammetric length measurements for 75 days after irradiation. Growth of the right irradiated tibia was compared with the growth of the left non-irradiated tibia. After 7 to 9 days, 24 Gy had caused a linear fall in growth to about 15 per cent. After a period of complete cessation, a slight growth was registered. 0.1 Gy had no significant growth retarding effect.

Effect of tantalum markers of longitudinal bone growth.

Small tantalum pins (0.50 x 1.5 mm and 0.32 x 1.2 mm), used as intraosseous radio-opaque markers, were investigated for their effect on growth in 62 young rabbits. The tetracycline growth method was used and a difference in daily growth rate between the marked right leg and the unmarked left leg indicated a slight growth stimulation. The growth rate was slightly stimulated (at most, 26 mum/day) on days 1 and 2 after insertion, only if the larger markers were used. No growth effects were detectable on days 12 and 21.

Essential amino acids in the treatment of advanced uremia: twenty-two months' experience in a 5-year-old girl.

The value of conservative treatment in a case of chronic advanced renal failure was investigated in a 5-year-old girl with congenital hypoplastic kidneys. Before treatment the patient was severely anorexic and her plasma urea nitrogen was 180 mg/100 ml. Protein restriction alone was fruitless. After a transitional period on total parenteral therapy the patient was put on a maintenance oral diet, where an energy-rich diet was supplemented with essential amino acids including histidine. Plasma urea nitrogen dropped and stayed at about 50 mg/100 ml during the whole treatment in spite of a rising plasma creatinine from 10 to 24 mg/100 ml. The general condition of the patient normalized as she went into an anabolic state with weight gain and growth in height. The nitrogen balance studied in two different periods was positive. An acute attack of pancreatitis, secondary to hyperparathyroidism, ended the patient's life after 22 months of treatment.

Manifest intestinal involvement during bone-marrow remission in a case of acute lymphoblastic leukaemia.

Massive leukaemic involvement of the intestine appeared in a 9-year-old girl with acute lymphoblastic leukaemia. The unusual feature in this case was that the gut involvement occurred during complete haematological remission. Surgical and subsequent radiological treatment completely eradicated the engagement and at autopsy 9 months later there were no signs of the intestinal involvement.

The Schultz--Dale reaction of the depolarized guinea-pig uterus.

1. The sensitized guinea-pig uterus contracted on addition of antigen (egg-albumin), even after it had been completely depolarized in an isotonic potassium sulphate solution.2. The contractile response of the depolarized preparation started at a later time after addition of the antigen, and had a smaller amplitude, than the Schultz-Dale contraction induced in the ordinary Ringer solution.3. A contracting substance was released from the depolarized uterus. The average histamine equivalent of this substance was 89% of the histamine concentration which reproduced the anaphylactic contraction and probably proportional to the mechanical response.4. The main component of the material released from the uterus in the ordinary Ringer was histamine. The material released from the depolarized uterus did not contain any demonstrable histamine activity.