Growth Pattern of Untreated Boys with Simple Virilizing Congenital Adrenal Hyperplasia Indicates Relative Androgen Insensitivity during the First Six Months of Life

Context: Mild forms of simple virilizing congenital adrenal hyperplasia (CAH) may be missed in newborn screening. In the pre-newborn-screening era, missed diagnosis of simple virilizing CAH was not infrequent in boys. Elevated adrenal androgens lead to accelerated growth and bone maturation. Traditional treatment of CA H consists of the suppression of ACTH through glucocorticoid replacement, in an attempt to reduce excessive androgen production. Objective: To retrospectively analyze early growth pattern and bone maturation in untreated boys with simple virilizing CAH. Patients: In the pre-newborn screening era, 13 boys had a late diagnosis of simple virilizing classical CAH. Diagnosis of 21-hydroxylase deficiency was confirmed by mutation analysis of the CYP21A2 gene in all patients. Growth data were retrospectively collected from standarized preventive medical checkups at the regular pediatrician until the time of diagnosis of CAH. Results: Length was 0.1 +/- 0.8 SDS (mean +/- SD) at birth, 0.2 +/- 1 SDS at 3 months, 0.2 +/- 0.9 SDS at 6 months, 0.7 +/- 1 SDS at 1 year, +1.1 +/- 0.9 SDS at 2 years and +1.8 +/- 1.2 SDS at 4 years. At diagnosis, mean chronological age was 4.4 +/- 1.6 years and height SDS was 2 +/- 1.7. Bone age was accelerated (9.4 +/- 4 years) at diagnosis. Signs that had led to diagnosis were pubic hair (n = 11), accelerated growth rate (n = 6) and birth of an affected sister (n = 3). Despite late start of hydrocortisone treatment, mean final height was 1 +/- 0.9 SDS. Seven of 18 patients had a final height within 1 SD of target height. Conclusion: Height velocity is not markedly increased in untreated boys with simple virilizing CAH in the first 6 months of life, indicating that infants are relatively androgen insensitive during that period. After the first 6 months of life, growth velocity increases significantly and elevated androgens lead to advanced skeletal maturation. This observation has implications for lower hydrocortisone doses to be used in CAH children during the first 6 months of life. In addition, staying alert for clinical symptoms and signs of simple virilizing CAH is still warranted, since mild forms may be missed in newborn screening. Copyright (C) 20105. Karger AG, Base

Growth Patterns in the First Three Years of Life in Children with Classical Congenital Adrenal Hyperplasia Diagnosed by Newborn Screening and Treated with Low Doses of Hydrocortisone

Background: Linear growth is the best clinical parameter for monitoring metabolic control in classical congenital adrenal hyperplasia (CAH). Objective: To analyze growth patterns in children with CAH diagnosed by newborn screening and treated with relatively low doses of hydrocortisone during the first year of life. Patients and Methods: 51 patients (27 females) were diagnosed with classical CAH by newborn screening. All patients were treated with relatively low doses of hydrocortisone (9-15 mg/m(2) body surface area). 47 patients were additionally treated with fludrocortisone. Results: At birth, height SDS (H-SDS) was 1.1 +/- 1 in girls and 0.9 +/- 1.5 in boys. After 3 months, H-SDS decreased to 0.4 +/- 0.9 in girls and to 0.1 +/- 1.3 in boys. Over the 3-year period, H-SDS further decreased to -0.4 +/- 1.8 in girls and to -0.8 +/- 1 in boys and approached the genetic height potential (target H-SDS of girls -0.5 +/- 0.3 and target H-SDS of boys -0.9 +/- 0.7). During the first 9 months of age, growth velocity was slightly decreased in girls (18.2 +/- 1.9 cm) and boys (17.3 +/- 1.6 cm) when compared to a healthy reference population (girls 19.0 +/- 3.9 cm and boys 18.7 +/- 4.7 cm). At the age of 3 years, bone age was appropriate for chronological age in both girls (2.7 +/- 0.5 years) and boys (2.9 +/- 0.5 years). Conclusion: Birth length is above average in children with classical CAH, which might be the result of untreated hyperandrogenism in utero. With relatively low doses of hydrocortisone treatment, growth velocity decreases slightly during the first 9 months and H-SDS then approaches the genetic height potential. Copyright (C) 2010 S. Karger AG, Base

Use of long-term microdialysis subcutaneous glucose monitoring in the management of neonatal diabetes - A first case report

In neonatal diabetes mellitus (NDM), a rare genetic disorder, insulin therapy is required but the management is difficult. Frequent blood glucose determinations are necessary in most cases. Microdialysis subcutaneous glucose monitoring (MSGM) is feasible in neonates and has been proposed to reduce painful blood sampling and blood loss. We have applied long-term MSGM to a small-fordate female newborn with transient NDM. We found a good correlation of subcutaneous and blood glucose concentration over a wide range of values. MSGM enabled a reduction in blood glucose determinations during optimization of intravenous insulin treatment and initiation of continuous subcutaneous insulin infusion. We conclude that long-term MSGM is feasible and may reduce painful blood sampling and blood loss in NDM. Furthermore, long-term MSGM may hold a potential for avoiding hypoglycemic episodes and earlier discharge. Copyright (C) 2006 S. Karger AG, Basel

A Special, Strict, Fat-Reduced, and Carbohydrate-Modified Diet Leads to Marked Weight Reduction even in Overweight Adolescents with Prader-Willi Syndrome (PWS)

Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. Previously, we reported that our special diet for PWS patients is effective in the long run, if started early at about 2 years of age. Our objective in this study was to investigate if our special diet is also effective in PWS adolescents who are already overweight. We provided a strict, fat-reduced, and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five adolescents (two female, three male) with PWS. Patients were prospectively followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index were recorded over that period. The special diet was started at a mean age of 16 years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m2 (range: 32.4-55.5 kg/m2), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for-Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased to 33 kg/m2 (range: 26.7-38 kg/m2), as well as BMI-SDS +2.7 (range: 1.7-3.4 SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special diet was still effective in reducing weight after 4–6 years, with a mean BMI of 30.5 kg/m2 (range: 24.6–34.5 kg/m2) and a mean BMI-SDS of +2.1 (range: 0.7–2.9). We conclude that in a period of 2–6 years, our strict, fat-reduced, and carbohydrate-modified diet, with 10 kcal/cm height, is effective even in adolescents with PWS who are already overweight

Sexual difference in bone geometry of adult patients with classical congenital adrenal hyperplasia: Data using peripheral quantitative computed tomography

BACKGROUND/AIMS Glucocorticoid treatment may influence bone and muscle development in patients with congenital adrenal hyperplasia (CAH). This study evaluated bone mineral density (BMD), bone geometry and muscle mass. METHODS 73 adult patients with classical CAH were followed. BMD, bone geometry and muscle mass were measured using peripheral quantitative computed tomography (pQCT). Glucocorticoid-equivalent doses throughout life were calculated and at the time pQCT androgen levels were measured. RESULTS In males the mean standard deviation (SD) score for trabecular BMD (-0.33 ± 0.71) was reduced, whereas mean cortical BMD (1.05 ± 1.11) was elevated. Mean total (0.86 ± 1.12) and medullary cross-sectional area (CSA; 1.12 ± 1.17) were significantly increased (p < 0.001). In all patients SD scores for cortical thickness (-0.65 ± 0.91) and muscle CSA (-0.83 ± 0.91) were reduced. Treatment duration was associated with lower trabecular BMD in males (r = -0.63, p < 0.001). Suppressed androgens and simple virilizing CAH had an adverse effect on the muscle CSA SD score (OR 0.58 and 0.46, respectively, p < 0.05). CONCLUSION There was a sexual difference with enlarged total and medullary CSA in females, whereas in males trabecular BMD was reduced and cortical BMD elevated. Cortical thickness and muscle CSA were reduced in all CAH patients with a possible long-term impact on bone development and stability. Monitoring of bone and muscle development might be warranted

Optical Fibre Sensors Using Graphene-Based Materials: A Review

Graphene and its derivatives have become the most explored materials since Novoselov and Geim (Nobel Prize winners for Physics in 2010) achieved its isolation in 2004. The exceptional properties of graphene have attracted the attention of the scientific community from different research fields, generating high impact not only in scientific journals, but also in general-interest newspapers. Optical fibre sensing is one of the many fields that can benefit from the use of these new materials, combining the amazing morphological, chemical, optical and electrical features of graphene with the advantages that optical fibre offers over other sensing strategies. In this document, a review of the current state of the art for optical fibre sensors based on graphene materials is presented

Post-translational derepression of invertase activity in source leaves via down-regulation of invertase inhibitor expression is part of the plant defense response

There is increasing evidence that pathogens do not only elicit direct defense responses, but also cause pronounced changes in primary carbohydrate metabolism. Cell-wall-bound invertases belong to the key regulators of carbohydrate partitioning and source-sink relations. Whereas studies have focused so far only on the transcriptional induction of invertase genes in response to pathogen infection, the role of post-translational regulation of invertase activity has been neglected and was the focus of the present study. Expression analyses revealed that the high mRNA level of one out of three proteinaceous invertase inhibitors in source leaves of Arabidopsis thaliana is strongly repressed upon infection by a virulent strain of Pseudomonas syringae pv. tomato DC3000. This repression is paralleled by a decrease in invertase inhibitor activity. The physiological role of this regulatory mechanism is revealed by the finding that in situ invertase activity was detectable only upon infection by P. syringae. In contrast, a high invertase activity could be measured in vitro in crude and cell wall extracts prepared from both infected and non-infected leaves. The discrepancy between the in situ and in vitro invertase activity of control leaves and the high in situ invertase activity in infected leaves can be explained by the pathogen-dependent repression of invertase inhibitor expression and a concomitant reduction in invertase inhibitor activity. The functional importance of the release of invertase from post-translational inhibition for the defense response was substantiated by the application of the competitive chemical invertase inhibitor acarbose. Post-translational inhibition of extracellular invertase activity by infiltration of acarbose in leaves was shown to increase the susceptibility to P. syringae. The impact of invertase inhibition on spatial and temporal dynamics of the repression of photosynthesis and promotion of bacterial growth during pathogen infection supports a role for extracellular invertase in plant defense. The acarbose-mediated increase in susceptibility was also detectable in sid2 and cpr6 mutants and resulted in slightly elevated levels of salicylic acid, demonstrating that the effect is independent of the salicylic acid-regulated defense pathway. These findings provide an explanation for high extractable invertase activity found in source leaves that is kept inhibited in situ by post-translational interaction between invertase and the invertase inhibitor proteins. Upon pathogen infection, the invertase activity is released by repression of invertase inhibitor expression, thus linking the local induction of sink strength to the plant defense response

Early changes in apoplast composition associated with defence and disease in interactions between Phaseolus vulgaris and the halo blight pathogen Pseudomonas syringae pv. phaseolicola

The apoplast is the arena in which endophytic pathogens such as Pseudomonas syringae grow and interact with plant cells. Using metabolomic and ion analysis techniques, this study shows how the composition of Phaseolus vulgaris leaf apoplastic fluid changes during the first six hours of compatible and incompatible interactions with two strains of Pseudomonas syringae pv. phaseolicola (Pph) that differ in the presence of the genomic island PPHGI-1. Leaf inoculation with the avirulent island-carrying strain Pph 1302A elicited effector-triggered immunity (ETI) and resulted in specific changes in apoplast composition, including increases in conductivity, pH, citrate, γ-aminobutyrate (GABA) and K+, that are linked to the onset of plant defence responses. Other apoplastic changes, including increases in Ca2+, Fe2/3+ Mg2+, sucrose, β-cyanoalanine and several amino acids, occurred to a relatively similar extent in interactions with both Pph 1302A and the virulent, island-less strain Pph RJ3. Metabolic footprinting experiments established that Pph preferentially metabolizes malate, glucose and glutamate, but excludes certain other abundant apoplastic metabolites, including citrate and GABA, until preferred metabolites are depleted. These results demonstrate that Pph is well-adapted to the leaf apoplast metabolic environment and that loss of PPHGI-1 enables Pph to avoid changes in apoplast composition linked to plant defences