Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature

OBJECTIVE: To objectively define criteria for intracranial optic nerve (ON) size in ON hypoplasia (ONH) on magnetic resonance imaging (MRI) scans. STUDY DESIGN: Intracranial ON sizes from MRI were compared between 46 children with ONH diagnosed by ophthalmoscopy (group 1, isolated ONH, 8 children; and group 2, ONH associated with abnormalities of the hypothalamic-pituitary axis and septum pellucidum, 38 children) and children with multiple pituitary hormone deficiency (group 3, multiple pituitary hormone deficiency, 14 children), isolated growth hormone deficiency (group 4, isolated growth hormone deficiency, 15 children), and idiopathic short stature (group 5, idiopathic short stature, 10 children). Intracranial ON size was determined by the cross-sectional area, calculated as [pi x (1/2) height x (1/2) width]. RESULTS: Groups 1 and 2 had lower intracranial ON size than did groups 3, 4, and 5 (P < .001). No patients in groups 3 through 5 who had MRI after 12 months of age (when 95% adult size of ONs is attained) had ONs <2.9 mm 2 . Visual acuity correlated significantly with ON size (P < .01). CONCLUSIONS: Magnetic resonance imaging of the ONs with cross-sectional area <2.9 mm 2 in a short child more than 12 months of age, with or without hypothalamic-pituitary axis abnormalities, confirms the clinical diagnosis of ONH.     

A new locus for Seckel syndrome on chromosome 18p11.31-q11.2.

Seckel syndrome (MIM 210600) is a rare autosomal recessive disorder with a heterogeneous appearance. Key features are growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance. We have performed a genome-wide linkage scan in a consanguineous family of Iraqi descent. By homozygosity mapping a new locus for the syndrome was assigned to a approximately 30 cM interval between markers D18S78 and D18S866 with a maximum multipoint lod score of 3.1, corresponding to a trans-centromeric region on chromosome 18p11.31-q11.2. This second locus for Seckel syndrome demonstrates genetic heterogeneity and brings us a step further towards molecular genetic delineation of this heterogeneous condition.     

PGD15 Veterans'' Satisfaction with H2-Receptor Antagonist (H2RA) Drug Conversion

OBJECTIVES: To determine the relative cost-effectiveness of the inhaled corticosteroids beclomethasone dipropionate (BDP), budesonide (BUD), and fluticasone propionate (FP), for managing moderate to severe asthma in adults over a one-year time horizon from the perspective of the Ministry of Health (MOH) in Canada.
METHODS: A single-arm meta-analysis of randomized control trials containing at least one of FP, BUD, and BDP was performed in order to derive estimates of effectiveness and tolerance. A decision tree analysis was then used to model the cost-effectiveness analysis. Only direct medical costs were included in the analysis (i.e., inpatient care, emergency visits, physician services, nursing services, drugs, diagnostic tests). The time horizon of the study was 52 weeks, precluding discounting. All costs are presented in 1996 Canadian dollars (CDN$). The cost-effectiveness was the cost per additional symptom-free day ($/SFD).
RESULTS: 69 of 398 articles were included in the metaanalysis. The Monte Carlo base case analysis showed that FP and BUD resulted in an annual cost of $1,383 and $1,147 respectively (p > 0.01). FP produced 216 SFDs while BUD resulted in 214 SFDs, which were not significantly different at p = 0.01 (corrected for multiple comparisons). BDP cost $1,343/year and yielded 213 SFD/year (BDP was excluded from the final analysis, dominated by BUD). With no difference in effectiveness, a cost-minimization analysis showed that BUD was the cost-effective alternative, costing $236 CDN less than the FP strategy.
CONCLUSIONS: Of the inhaled corticosteroids available on the MOH Formulary in Canada, BUD is a costeffective alternative for the treatment of adults with moderate to severe asthma.     

New mutant and congenic mouse stocks expressing the murine leukemia virus-associated thymocyte surface antigen G(IX)

For several reasons the G(IX) antigen (1) has a prominent place in current work on murine leukemia virus (MuLV): In the prototype G(IX+) mouse strain 129, the G(IX) trait is mendelian, and is expressed selectively (though not exclusively) on thymocytes. Thus, expression of this cell surface component is under the control of cellular genes and is subject to the controls governing the differentiation of T lymphocytes (2). Although the 129 mouse produces no demonstrable leukemia virus such as that found in the AKR strain, it was soon realized that G(IX) antigen must in some way be related to MuLV, because productive infection with MuLV is frequently associated with appearance of G(IX) antigen on cells that are genotypically G(IX-), most notably on MuLV-infected rat cells, or cells that belong to other differentiation pathways (1). The basis of this connection between G(IX) and MuLV has recently become clear from the demonstration that G(IX) is one of MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) is one of the antigens present on gp69/71 (3,4), the major glycoprotein component of the MuLV envelope. Therefore, our working hypothesis is that the presence of G(IX) antigen always denotes the presence of gp69/71 (though not all variants of gp69/71 need necessarily carry G(IX)). Study of the circumstances under which G(IX) is expressed on the cell surface is thus potentially a powerful approach to understanding how the expression of C-type viral genomes is controlled. Such studies are greatly facilitated by the availability of mutant and congenic strains of inbred mice which differ from the nonmutant or partner strains only with respect to one or another manifestation of the viral genome. It is for this reason that we record here (Table I) some details of two G(IX) mutant and two G(IX) congenic stocks derived in our colonies at Memorial Sloan-Kettering Cancer Center (MSKCC). In addition, to these four strains, Table I includes data for the three relevant partner strains, and for strain AKR, for comparison. These eight strains all differ from one another with respect to one or more MuLV-related traits.     

The effect of 12 months' treatment with eicosapentaenoic acid in five children with cystic fibrosis

Abstract: Five children with cystic fibrosis (CF) and chronic suppurative lung disease had eicosapentaenoic acid (EPA) supplementation for 12 months. Outcome was measured by the change in frequency of admissions/bed days while taking EPA compared to the previous 2 years. Although no significant changes occurred, there is an indication that this treatment may benefit children who don't have end-stage disease. Further studies are indicated in the use of this neglected mode of treatment.     

Clinical impact of corticosteroid-induced adrenal suppression during treatment for acute lymphoblastic leukemia in children: a prospective observational study using the low-dose adrenocorticotropin test

OBJECTIVES: To investigate how frequently adrenal function fails to recover after corticosteroid therapy in children with acute lymphoblastic leukemia and to explore the clinical impact of slow adrenal recovery without steroid substitution. STUDY DESIGN: Low-dose (1 microg) adrenocorticotropic hormone tests were performed before and after steroid courses and during infectious episodes in 24 children. Test results were not available during the study. RESULTS: All 13 patients tested before treatment had normal adrenal responses. Adrenal suppression was found in 8 (47%) of 17 patients 5 days after discontinuation of a 5-week induction course of prednisolone and in 1 (20%) of 5 patients 7 days after a 3-week intensification course of dexamethasone, both courses being tapered over 9 days, as well as in all 13 patients tested 2 days after a 1-week prednisolone course. Clinically significant manifestations of adrenal suppression were noted in 3 (12%) patients. Of 204 scheduled tests, 131 were performed. CONCLUSIONS: High-dose glucocorticoid therapy may cause adrenal suppression lasting more than 1 week in children with acute lymphoblastic leukemia, even after tapering the dose. We suggest steroid replacement during stress episodes within 1 to 2 weeks after discontinuation and thereafter testing adrenal function selectively in accordance with symptoms.     

Residual β-Cell Function 3–6 Years After Onset of Type 1 Diabetes Reduces Risk of Severe Hypoglycemia in Children and Adolescents

OBJECTIVE

To determine the prevalence of residual β-cell function (RBF) in children after 3–6 years of type 1 diabetes, and to examine the association between RBF and incidence of severe hypoglycemia, glycemic control, and insulin requirements.

RESEARCH DESIGN AND METHODS

A total of 342 children (173 boys) 4.8–18.9 years of age with type 1 diabetes for 3–6 years were included. RBF was assessed by testing meal-stimulated C-peptide concentrations. Information regarding severe hypoglycemia within the past year, current HbA_1c, and daily insulin requirements was retrieved from the medical records and through patient interviews.

RESULTS

Ninety-two children (27%) had RBF >0.04 nmol/L. Patients with RBF <0.04 nmol/L were significantly more likely to have severe hypoglycemia than patients with RBF >0.04 nmol/L (odds ratio, 2.59; 95% CI, 1.10–7.08; P < 0.03). HbA_1c was significantly higher in patients with RBF <0.04 nmol/L compared with patients with RBF >0.04 nmol/L (mean, 8.49 ± 0.08% [69.3 ± 0.9 mmol/mol] vs. 7.92 ± 0.13% [63.1 ± 1.4 mmol/mol]; P < 0.01), and insulin requirements were significantly lower in patients with RBF >0.2 nmol/L (mean ± SE: 1.07 ± 0.02 vs. 0.93 ± 0.07 units/kg/day; P < 0.04).

CONCLUSIONS

We demonstrated considerable phenotypic diversity in RBF among children after 3–6 years of type 1 diabetes. Children with RBF are at lower risk for severe hypoglycemia, have better diabetes regulation, and have lower insulin requirements compared with children without RBF. There appears to be a lower limit for stimulated RBF of ∼0.04 nmol/L that confers a beneficial effect on hypoglycemia and metabolic control.Type 1 diabetes is the result of a selective immune-mediated destruction of the insulin-producing β-cells in the islets of Langerhans in the pancreas (1). Partial remission of type 1 diabetes often is seen in children and adolescents soon after initiating insulin treatment, and it is characterized by continuous and effective endogenous insulin secretion. After this period of remission of variable duration, the autoimmune cellular-mediated destruction of the β-cells continues and the endogenous insulin production declines gradually (2–4).The Diabetes Control and Complication Trial (DCCT) showed that a significant proportion of adults had sustained β-cell function several years after the onset of type 1 diabetes (5), and some type 1 diabetic patients even have detectable C-peptide after 50 years of diabetes (6). In adults, residual β-cell function (RBF) may have positive effects on diabetes regulation and complications. RBF may reduce the risk of hypoglycemia, improve metabolic control estimated by HbA_1c, lower exogenous insulin requirements, and lower the risk of long-term complications (5,7–13). Based on data from the DCCT adult population, it was reported that the incidence of severe hypoglycemia varied with differences in RBF (7). In the group with the highest RBF, the lowest incidence of hypoglycemia occurred (7). Yet, even those with “minimal” RBF, defined as stimulated C-peptide level of 0.04–0.2 nmol/L, showed lower incidence of severe hypoglycemia compared with the group with undetectable RBF (7).In children, the majority of studies of RBF have focused on the first year after clinical diagnosis (14–18). Data for RBF in children during later stages of type 1 diabetes and its effect on metabolic control and complications are scarce. In a population of 151 children with type 1 diabetes for 3 years, 23% had a stimulated C-peptide level of >0.06 nmol/L (19). Furthermore, in a case-control study, it was demonstrated that RBF was significantly higher in children without severe hypoglycemia compared with children with severe hypoglycemia (20).The increasing incidence of diabetes in children with reduced contribution of high-risk HLA haplotypes (21,22) may have changed the type 1 diabetes phenotype toward an increased number of children with detectable C-peptide years after diagnosis, which may have favorable effects on the incidence of severe hypoglycemia and glycemic control. Therefore, the aims of this study were to investigate the phenotypical characteristics regarding RBF among Danish children with type 1 diabetes for a duration of 3–6 years; to examine possible benefits of RBF on the incidence of severe hypoglycemia, glycemic control, and insulin requirements; and, finally, to evaluate the data to determine whether there is a lower limit of RBF at which RBF exerts beneficial effect on the incidence of severe hypoglycemia and metabolic control.