M. van Leeuwen

The heritability of HbA1c and fasting blood glucose in different measurement settings.

In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.

The Next Generation of Burns Treatment: Intelligent Films and Matrix, Controlled Enzymatic Debridement, and Adult Stem Cells

We describe a novel technology based on nanoengineered multifunctional acellular biologic scaffolds combined with wound dressings and films of the same kind. This method allows selective delivery and release of shielded biomaterials and bioactive substances to a desired wound or damaged tissue while stimulating the selective anchoring and adhesion of endogenous circulating repairing cells, such as mesenchymal stem cells, to obtain a faster and more physiologic healing process. We also present a new controlled enzymatic debridement process for more effective burned tissue scarolysis. In light of our preliminary in vitro and in vivo data, we are convinced that these approaches can include the use of other kinds of adult stem cells, such as endometrial regenerative cells, to improve the vascularization of the constructs, with great potential in the entire tissue and organ regeneration field but especially for the treatment of severely burned patients, changing the way these lesions may be treated in the future.

Longitudinal Study of Hormonal and Physical Development in Young Twins

CONTEXT AND OBJECTIVE Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. DESIGN, SETTING, AND PARTICIPANTS One hundred twelve healthy 9-year-old twin pairs (n = 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n = 178). MAIN OUTCOME MEASURES Morning urinary LH, FSH, estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. RESULTS Over the 3-year interval, all hormone levels showed a 2- to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. CONCLUSIONS During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development.

Bone Mineral Density in Children and Adolescents With Prader-Willi Syndrome: A Longitudinal Study During Puberty and 9 Years of Growth Hormone Treatment

CONTEXT Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION The children received GH treatment, 1 mg/m(2)/day (≅ 0.035 mg/kg/d). MAIN OUTCOME MEASURES BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

Reply: High-dose-rate brachytherapy for the treatment of recalcitrant keloids: a unique effective treatment protocol.

Background: Keloids cause aesthetic disfigurement and physical complaints, mainly pain and pruritus. Treatment of these scars is difficult, with high recurrence rates forming the main issue. Surgical excision with adjuvant radiotherapy is considered the most efficacious treatment. At their institution, the authors have been treating keloids with a high-dose-rate brachytherapy procedure for over 10 years, using a protocol with the lowest total radiation dosage known in the literature. Methods: This prospective study included 43 patients of all Fitzpatrick skin types, with 67 keloids in total. After extralesional excision, a radiation scheme of 2 × 6 Gy was administered in two fractions: the first within 4 hours after surgery and the second within 24 hours. Scars were measured and recurrence was judged. Scar appearance was evaluated using the Patient and Observer Scar Assessment Scale. Results: The recurrence rate was 3.1 percent at a mean follow-up of 33.6 months. A significant average scar surface decrease of 56.7 percent was measured (p = 0.01). Complaints of pain and pruritus decreased by 82.9 and 87.2 percent, respectively. Patients were satisfied with the treatment in 88.6 percent of the cases and with the cosmetic result in 77.1 percent. Pigmentation problems were seen in 21.4 percent of the patients, mostly in Fitzpatrick type V and VI/African American individuals. Conclusions: The results of this prospective study show a good cosmetic outcome with a low recurrence rate. The unique radiation schedule proves the efficacy and safety of high-dose-rate brachytherapy and suggests the importance of immediate postoperative irradiation. In addition, only one outpatient treatment is required after surgery, enhancing patient convenience. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.