Leslie Plotnick

Long-term effects of budesonide or nedocromil in children with asthma

BACKGROUNDnAntiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use.nnnMETHODSnWe randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms.nnnRESULTSnThere was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups.nnnCONCLUSIONSnIn children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.

The childhood asthma management program (CAMP): Design, rationale, and methods

The Childhood Asthma Management Program (CAMP) is a multicenter, randomized, double-masked clinical trial designed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma: budesonide (a glucocorticoid used daily) and albuterol (a short-acting beta-agonist bronchodilator used as needed); nedocromil (a nonsteroid anti-inflammatory agent used daily) and albuterol; and placebo and albuterol. One thousand forty-one children (32% from ethnic minority groups), aged 5 to 12 years at screening, are currently participating. The primary outcome measure is lung growth as indicated by postbronchodilator forced expiratory volume in 1 second (FEV1) percent of predicted, observed over 5- to 6-year period. The trial also assesses differences between treatment groups with respect to airway responsiveness, morbidity, physical growth and development, and psychological growth and development. This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial.

Congenital micropenis: Long-term medical, surgical and psychosexual follow-up of individuals raised male or female

Objectives: to document long-term medical, surgical and psychosexual outcome of individuals with congenital micropenis (13 males, 5 females). Methods: Physical measurements from childhood were collected retrospectively from medical records and at adulthood by physical examination. An adult psychosexual assessment was conducted with a written questionnaire and oral discussion. Results: Adult penile length was below the normal mean in all men. Three women had vaginoplasty resulting in normal length. All men reported good or fair erections but 50% were dissatisfied with their genitalia. Dissatisfaction with body image resulted from having a small penis (66%), inadequate body hair (50%), gynecomastia (33%) and youthful appearance (33%). Ten men were heterosexual, 1 homosexual and 2 bisexual. Among women, 4 (80%) were dissatisfied with their genitalia. Three women reported average libido with orgasm and were also heterosexual. Two women had no sexual interest or experience. Finally, males were masculine and females feminine in their gender-role identity, and both groups were satisfied with their sex of rearing. Conclusions: Regarding choice of gender, male sex of rearing can result in satisfactory genito-sexual function. Female gender can also result in success, however it requires extensive feminizing surgery.

Age-related anti-thyroid antibodies and thyroid abnormalities in turner syndrome

ABSTRACT. One hundred pediatric patients with Turner syndrome were studied to determine the correlation between the presence of anti‐thyroid antibodies with age and karyotype, and the value of anti‐thyroid antibody titers as predictors of subsequent thyroid abnormalities. (54 patients = 45,X; 46 = other karyotypes.) The frequency of positive titers of anti‐thyroid antibodies increased linearly with cumulative age. Anti‐parietal cell and anti‐adrenocortical cell antibodies were not increased in these patients (1.3 and 2.6% respectively). The ability to use positive anti‐thyroid antibody titers to predict the development of thyroid abnormalities increased from age 10 years and became statistically significant at ages 13‐17 years for the whole group as well as 45,X patients. None of the patients had clinical symptoms of thyroid dysfunction although 22% developed thyroid abnormalities, which included elevated TSH, low T4, and/or goiter.

Oxandrolone therapy in patients with Turnersyndrome

Long-term, low-dosage androgen treatment of patients with Turner syndrome results in more rapid growth and significantly greater adult height than in control patients who receive only estrogen for pubertal development. Seventeen patients treated with oxandrolone for one year and ten treated for two years had significantly greater growth velocities during than before treatment. Mean adult height of 25 patients treated with oxandrolone, fluoxymesterone, or both was significantly taller than the height of adult patients with Turner syndrome treated with estrogen only. Excessive skeletal maturation was not generally observed.

Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15‐yr‐old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM

Mohamadi A, Clark LM, Lipkin PH, Mahone EM, Wodka EL, Plotnick LP. Medical and developmental impact of transition from subcutaneous insulin to oral glyburide in a 15‐yr‐old boy with neonatal diabetes mellitus and intermediate DEND syndrome: extending the age of KCNJ11 mutation testing in neonatal DM.

Studies of Insulin Binding in Children Using Human Erythrocytes in Small Amounts of Blood

We have demonstrated specific insulin binding by the erythrocytes (RBCs) of children. Complete binding studies were done using as little as 5 ml of blood. The receptors exhibited competition-inhibition curves and nonlinear Scatchard plots similar to those reported for insulin target tissues, such as the hepatocyte and the adipocyte. Compared with those from adults, the RBCs from children had significantly greater numbers of insulin receptors per cell (P < 0.05). The total insulin bound by the RBCs from both children and adults, however, was not different over the physiologic range of insulin concentrations. Cord blood RBCs showed greater numbers of receptors per cell than did those from either children or adults; however, the affinity for insulin was similar in both groups. The total amount of insulin bound by cord blood was significantly greater than that in either children (P < 0.01) or adults (P < 0.05) over the physiologic range of insulin concentrations. The method used to measure insulin binding by erythrocytes had relatively little intra- and interassay variability, and there was little diurnal variation in binding. Storage of heparinized blood at 4°C for 24-36h had no effect on insulin binding by the RBCs. We conclude that the measurement of insulin binding by RBCs from small volumes of blood may be particularly useful in the study of infants and children with disorders of carbohydrate metabolism to elucidate the role, if any, of abnormal receptor function in their condition.

Abnormalities of Thyroid Function and Glucose Control in Subjects with Rett Syndrome

We have identified subtle abnormalities of thyroid function and glucose control in patients with Rett syndrome. The mean serum total thyroxine (T4) concentration was significantly lower in a group of subjects with Rett syndrome (6.9 +/- 1.5 microgram/dl, n = 34; p < 0.001) than the adult reference range (8.5 +/- 1.75 microgram/dl, n = 200). This differences remained significant even for the 17 subjects not taking anticonvulsants (7.6 +/- 1.5 microgram/dl; p < 0.05 vs. adult reference). The difference was more marked when compared to age-adjusted normals, with 10 subjects having a serum total T4 concentration below normal for age including 3 of 17 of the subjects not taking anticonvulsants. This decrease in serum total T4 concentration was not due to changes in binding proteins as measured by 3,5,3-triiodothyronine resin uptake, and was associated with a decreased concentration of thyroid-stimulating hormone (1.7 +/- 1.6 mU/l, n = 23 vs. 2.5 +/- 1.0 mU/l, n = 200; p < 0.01). Oral glucose tolerance tests were performed in 10 of the subjects with Rett syndrome. They had a delay in the peak glucose and insulin concentrations. Glucose levels were elevated at 1 and 2 hours (p < 0.05), and insulin levels were elevated at 1, 2, and 3 hours (p < 0.05). Two subjects fulfilled criteria for impaired glucose tolerance.

Molecular Investigation of Two Male Subjects with Short Stature and a 45,X/46,X,Ring(Y) Karyotype

We studied 2 subjects with a 45,X/46,X,ring(Y) karyotype. Both of them were evaluated because of short stature and a subnormal rate of linear growth. One patient had additional features of the Ullrich-Turner syndrome. Both subjects had normal male external genitalia. Two copies of the pseudoautosomal gene, MIC2, were present in DNA of each individual. All sequences examined on the Y-specific portion of the short arm, including those for the sex-determining region Y (SRY) gene, were present. By contrast, portions of the long arm of the Y chromosome were missing from DNA of both subjects. In subject 1, deletion intervals 6 and 7 were missing. In subject 2, deletion interval 5, distal to 5B, was missing in addition to intervals 6 and 7. The most likely explanation for the ring formation in these subjects is a chromosomal break in the long arm and in the pseudoautosomal region of the short arm distal to MIC2 with subsequent ligation of the remaining sequences on the long arm and short arm. However, a complex rearrangement cannot be excluded.

Insulin pumps in children with diabetes

Insulin pump therapy or continuous subcutaneous insulin infusion is becoming more common. Nurses can expect to encounter a growing number of children who have insulin pumps and an increasing number of questions concerning the general application and efficacy of these pumps. Therefore it is important that pediatric nurse practitioners, school nurses, and pediatric nurses understand insulin pump therapy and its role in the overall treatment of children with diabetes. This article describes the advantages, disadvantages, and alternatives to insulin pump therapy. It also discusses staff expertise, patient selection criteria, and patient education as elements of successful insulin pump management.