BALANCED (2q-; 14q+) TRANSLOCATION

A child presented at 6 years of age with virilization presumed due to maternal progesterone therapy during pregnancy. She was found to have a balanced translocation involving chromosomes 2 and 14.     

Renal Osteodystrophy in Children Treated with 1,25-Dihydroxy-Cholecalciferol [1,25-(OH)2D3]: Histologic Bone Studies

ABSTRACT. Eleven uremic children with osteodystrophy aged 3 to 17 years were studied during administration of l, 25-(OH)₂D, for periods up to 21 months. Nine children presented with pure hyperparathyroidism, one with osteomalacia and one with mixed bone disease. Bone biopsies were performed before initiation of therapy and after 6 to 21 months of treatment following double tetracycline labeling. Skeletal lesions were improved but not cured in 5 of 9 children with hyperparathyroidism. In three instances lesions remained unchanged and worsened in one. No significant change was observed in the child with osteomalacia. Moderate improvement was noted in the patient with mixed bone disease. The propensity to develop hypercalcemia was the major factor associated with treatment failure since it precluded administration of adequate amounts of medication. Therapy with l, 25-(OH)₂D₃ was associated with a spectacular improvement in growth velocity in two of six children under age twelve.     

The Value of the Sinusoidal tcPO2 Pattern in the Evaluation and Management of Cyanotic Congenital Heart Disease with Ductus Dependent Lesions

A characteristic sinusoidal tcPO₂ pattern was observed in 17(27%) of 62 patients with congenital heart disease manifested by cyanosis or heart failure during the neonatal period. All of these 17 patients were definitively diagnosed by cardiac catheterization, as having 8 PPA; 3 ToF; 2 TCA+VSD+PA; 2 asplenia with PA; 1 TGA+VSD+PS; and 1 TA (no TCA type). The transcutaneous oxygen pressure pattern of these patients showed a sinusoidal change with a cycle length of 6–20 min with the maximum pressure not exceeding 50 torr and the minimum pressure occasionally close to 0 torr. This sinusoidal tcPO₂ pattern was associated with various types of ductus-dependent congenital heart diseases and hence may be of diagnostic value. Transcutaneous oxygen pressure monitoring is also useful in evaluating the ductal response to PG. Other possible mechanisms underlying this phenomenon including biological oscillation should be considered.     

METABOLISM OF LITHOCHOLIC ACID-24–14C IN EXTRAHEPATIC BILIARY ATRESIA

Lithocholic acid-24-¹⁴C was given to 2 infants with extrahepatic biliary atresia. After oral administration about half of the amount of isotope was found to be adsorbed. After par- 9. Makino, I., Sjovall, J., Norman, A. & Strandvik, enteral administration about half of the amount of isotope was excreted in the urine for 3 days. Lithocholic acid was shown to be transformed to a small extent to more polar compounds. These metabolites were not cholic, chenodeoxycholic, α- or,β-muricholic, hyocholic, hyodeoxycholic or ursodeoxycholic acids. Most of the lithocholic acid was excreted as the sulphate esters of tauro- and glycolithocholic acid. No sulphate ester of lithocholic or free lithocholic acid was excreted.     

Concentrations of LTB4, LTC4, LTD4 and LTE4 in bronchiolitis due to respiratory syncytial virus

Fifty-five infants with bronchiolitis due to respiratory syncytial virus were evaluated for the presence of leukotriene B₄, C₄, D₄ and E₄ in nasopharyngeal secretions. An attempt was made to correlate concentrations of leukotrienes to arterial oxygen tension. Forty participants received conventional therapy consisting primarily of aerosolized albuterol and occasional aminophylline therapy. The other 15 individuals received ribavirin therapy in addition to conventional therapy, and leukotriene concentrations were compared among individuals in these groups. RSV infection was documented by standard methods, and leukotrienes were measured by reverse-phase high pressure liquid chromatography. The leukotriene detected most commonly was LTC₄ (up to 83% of subjects); LTD₄ and LTB₄ were present in approximately 30% of individuals. The mean partial pressure of oxygen was found to be lower in those individuals with detectable LTB₄ than in those without detectable LTB₄ (p < 0.025), and an overall inverse correlation of LTB₄ concentrations with initial pO₂ values was observed (r = 0.318, p < 0.05). The presence and quantity of other leukotrienes did not correlate with the severity of illness. During the first week of illness, the concentration of leukotrienes declined sharply in ribavirin recipients. Individuals receiving conventional therapy during the same time interval exhibited stable or increasing leukotriene concentrations. These observations suggest that LTB₄ may be important in the pathogenesis of bronchiolitis, and that ribavirin therapy may inhibit leukotriene release in the respiratory tract.     

A comparative study of growth hormone (GH) and GH-releasing hormone(1–29)-NH2 for stimulation of growth in children with GH deficiency

In this study, 60 patients with proven growth hormone deficiency (GHD) of hypothalamic origin were randomized into three equal groups, and received growth hormone-releasing hormone(1–29)-NH, (GHRH(1–29)-NH,), 30 or 60 μg/kg/day, or growth hormone (GH), 0.1 IU/kg/day, for 6 months. There were no significant differences in growth between the two groups given GHRH(1–29)-NH, but growth in the GH group was significantly better than in the other two groups ( p < 0.01). Mean height velocities at 6 months were 9.2, 9.3 and 14.6 cm/year for the three groups, respectively. Plasma GHRH concentrations increased steadily over the 6-month treatment period, with higher levels in the group on the higher dose. During GHRH(1–29)-NH₂ treatment, serum concentrations of insulin-like growth factor I rose initially, but then fell to values similar to those before treatment. No GH antibodies were detected, but all 20 patients on high-dose GHRH(1–29)-NH, and 19 of 20 patients on low-dose GHRH(1–29)-NH₂ developed GHRH antibodies. These had almost disappeared by 9 months after stopping treatment. There was no correlation between antibody titres and increase in height. No serious side-effects were seen, but three patients receiving GHRH(1–29)-NH, reported mild irritation at the injection site. These results from the continuous infusion of GHRH(1–29)-NH₂ over 6 months suggest that this treatment, or the related use of a depot preparation, is unlikely to be as effective as GH for the promotion of growth in GHD.     

Use of Continuous Subcutaneous Growth Hormone-Releasing Hormone (GHRH (1–29)NH2) Infusions to Augment Growth Hormone Secretion and to Promote Growth

Brain, C., Hindmarsh, P.C., Pringle, P.J. and Brook, C.G.D. (Endocrine Unit, the Middlesex Hospital, London, UK). Use of continuous subcutaneous growth hormone-releasing hormone (GHRH (1–29)NH₂) infusions to augment growth hormone secretion and to promote growth. Acta Paediatr Scand [Suppl] 349: 109, 1989.
It has previously been shown that an 8-day continuous subcutaneous infusion of GHRH (1–29)NH₂ in adult males augments growth hormone (GH) secretion with no evidence of desensitization of the response. The present report details the results of treatment with continuous subcutaneous infusions of CHRH (1–29)NH₂ in eight children aged 6–9 years with partial GH insufficiency. All the children showed augmentation of GH secretion and an increase in growth velocity after 3 and 6 months of therapy.     

Modification of 24-Hour Growth Hormone Secretion after Continuous Subcutaneous Infusion of Growth Hormone-Releasing Hormone (GHRH (1–29)NH2) in Short Children with Low 24-Hour Growth Hormone Secretion

Tauber, M.T., Pienkowski, C., Landier, F., Gunnarsson, R. and Rochiccioli, P. (Department of Paediatric Endocrinology, CHU Rangueil, Toulouse Cedex, and Kabi Laboratory, Paris, France and Kabi Peptide Hormones, Stockholm, Sweden). Modification of 24-hour growth hormone secretion after continuous subcutaneous infusion of growth hormone-releasing hormone (GHRH (1–29)NH₂) in short children with low 24-hour growth hormone secretion. Acta Paediatr Scand [Suppl] 349: 117, 1989.
Six short children with low 24-hour growth hormone (GH) secretion were treated with continuous subcutaneous infusion of GHRH (1–29)NH₂ for 3 weeks using a portable infusion pump. Restoration of pulsatile GH secretion was observed in all three children treated with 40 pg/kg/day of GHRH, but in only one of the three children treated with 20 pg/kg/day. All parameters of 24-hour GH secretion increased, but in five children the magnitude of the GH response was greater on day 1 than on day 21 of CHRH treatment. This decrease was not observed in the single child who responded to a low dose of GHRH (20 pg/kg/day); on the contrary, the response in this patient was greater after 21 days of GHRH treatment. Plasma levels of GHRH (1–29)NH₂ were significantly higher on day 21 than on day 1 of treatment, suggesting altered pharmacokinetics over time. The effect of GHRH treatment on growth could not be determined because of the short duration of the study, but the data obtained on 24-hour GH secretion and GHRH metabolism suggest that a long-acting analogue of GHRH could be useful for the treatment of GH deficient or insufficient children.     

REDUCED SERUM 1,25-(OH)2 VITAMIN D3 LEVELS IN PREDNISONE-TREATED ADOLESCENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract. The serum levels of 1,25-(OH)₂ vitamin D₃ were assayed in samples from 12 adolescent patients with SLE. Subnormal levels were observed in 7 of these 12 patients. Low levels of the metabolically active polar metabolite of vitamin D₃ may contribute to the development of osteopenia observed in this disease. The cumulative effects of the osteoporotic and anti vitamin D effects of long term steroid therapy in children with SLE may require the cautious administration of supplemental vitamin D.     

A New Method of Expired Gas Collection for the Measurement of Breath Hydrogen (H2) in Infants and Small Children

ABSTRACT. The measurement of hydrogen (H₂) in breath is becoming increasingly useful as a diagnostic and research tool, but there is still no satisfactory method of sampling expired air in infants and small children. We tested a modified open-flow hood method where the child's head is put in a perspex box and expired air is collected by sucking air from the box by means of an air pump. Comparison of this method with end-expiratory sampling by a modified Haldane-Priestly and nasopharyngeal catheter gave a correlation coefficient of 0.83 and 0.65, respectively, We conclude that expired air sampling in children with this method is a more satisfactory and as reliable a method as any available at present, and has the added advantage of being quantitative.     

Pharmacokinetics of growth hormone-releasing hormone(1–29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration

The growth hormone-releasing hormone analogue GHRH(1–29)-NH, was administered intravenously or intranasally to 30 healthy men aged 19–43 years. Intravenous injection of the lowest dose tested, 0.25 μg/kg body weight, elicited significant release of growth hormone (GH). Maximal release (mean GH peaks of about 90 mU/1) was obtained with a dose of 1–2 μg/kg. Although GHRH(1–29)-NH₂ was rapidly eliminated after intravenous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1–29)-NH₂ through the nasal mucosa was found to be low, and the bioavailability was only 3–5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1–29)-NH₂, with the maximal response obtained with about 50 μg/kg; this dose was approximately as potent as 1 μg/kg injected intravenously. The GH response after repeated intranasal administration of GHRH(1–29)-NH₂ was sustained; there was no suppression of GH secretion during the night following a day when GHRH(1–29)-NH₂ had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administration compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.     

THE EFFECT OF EXERCISE ON DIABETIC CONTROL AND HEMOGLOBIN A1 (HbA1) IN CHILDREN

Abstract. Dahl-Jørgensen, K., Meen, H. D., Hanssen, Kr. F. and Aagem, O. (Department of Paediatrics and Department of Internal Medicine, Aker Hospital and the Norwegian College of Physical Education and Sports, Oslo, Norway). Acta Paediatr Scand, Suppl. 283: 53, 1980.—14 children with juvenile diabetes mellitus (mean age 11 years, mean diabetes duration 5 years) were enrolled in a one-hour twice weekly supervised exercise program for 5 months. A group of 8 diabetic children of same age and diabetic duration served as control group. Maximum oxygen uptake was within normal range for all children. With this exercise program the maximum oxygen uptake of the training group did not change significantly compared with the control group. The physicians rating of degree of the metabolic control based on blood-glucose measurements and urinary glucose excretion did not change in any of the groups. The insulin dosage per kilo body weight remained unchanged in both groups. In the training group the HbA, values decreased during the exercise period from 15.1±2.2 (mean HbA₁%±1 S.D.) to 13.8±1.9 (2 p <0.001). In the control group the HbA₁ values did not change significantly (13.4± 1.9 to 12.9± 1.6; 2 p =0.20). In a co-study the effect of freezing and storage of hemolysates, resulting in increased levels of HbA₁, was demonstrated.     

Dose-related efficacy and safety of formoterol (Oxis®) Turbuhaler® compared with salmeterol Diskhaler® in children with asthma

To compare the dose‐related bronchodilator efficacy and tolerability of formoterol (Oxis^®) Turbuhaler^® with salmeterol Diskhaler^® and placebo in children with asthma. A single‐dose, randomized, double‐blind, incomplete crossover study of 68 children (7–17 years), with moderate‐to‐severe asthma, 82% receiving inhaled corticosteroids. Patients received four of six treatments [4.5, 9, 18, or 36 μg formoterol (6, 12, 24 or 48 μg metered doses), 50 μg salmeterol (metered dose) or placebo] at 12‐h visits, separated by ≥3 days. Forced expiratory volume in 1 s (FEV₁), pulse, blood pressure, electrocardiogram, adverse events and urine formoterol were assessed. The therapeutic ratio of formoterol vs. salmeterol was estimated from the efficacy and systemic effects results. All active treatments significantly improved FEV₁ compared with placebo. Formoterol 9–36 μg provided dose‐related increases over salmeterol in lung function: average 12‐h FEV₁ (increases of 4.9–8.7%, p < 0.001) and FEV₁ at 12 h post‐dose (7.0–12.2%, p < 0.001). The onset of effect of formoterol was also significantly faster than salmeterol for doses ≥9 μg. Salmeterol 50 μg was estimated to be equieffective to 3.3 μg formoterol for 12‐h average FEV₁ and the estimated equieffective dose for a variety of systemic effects was 7.8–13.5 μg formoterol. All treatments were well tolerated. Formoterol (Oxis) Turbuhaler 4.5–36 μg provided dose‐related improvements in bronchodilator efficacy in children with asthma. Formoterol ≥9 μg provided superior bronchodilator efficacy over 12 h compared with salmeterol Diskhaler 50 μg with no increase in systemic effects.