Pamela Clark

Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids

Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys ( n = 16; n = 13) and girls ( n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination ( R 2) = 0.70, P < 0.001] and all boys ( R 2 = 0.60, P < 0.001) than the total fat mass (girls, R 2 = 0.52, P < 0.001; boys, R 2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin ( R 2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.Little is known about the influence of adiposity and hormone release on leptin levels in children and adolescents. We utilized criterion methods to examine the relationships among sex steroids, body composition (4 compartment), abdominal visceral and subcutaneous fat (magnetic resonance imagery), total subcutaneous fat (sum of 9 skinfolds), energy expenditure (doubly labeled water), aerobic fitness, and serum leptin levels in prepubertal and pubertal boys (n = 16; n = 13) and girls (n = 12; n = 15). The sum of skinfolds accounted for more variance in leptin levels of all girls [coefficient of determination (R2) = 0.70, P < 0.001] and all boys (R2 = 0.60, P < 0.001) than the total fat mass (girls, R2 = 0.52, P < 0.001; boys, R2 = 0.23, P < 0.001). Total energy expenditure, corrected for the influence of fat-free mass, correlated inversely with leptin (R2 = 0.18, P = 0.02). Gender differences in leptin disappeared when corrected for sex steroid levels or the combination of adiposity and energy expenditure. In multiple regression, the sum of skinfolds and free testosterone and estrogen levels accounted for 74% of the variance in leptin levels. We conclude that serum leptin levels are positively related to subcutaneous adiposity but negatively related to androgen levels. Energy expenditure may be negatively related to leptin levels by reduction of the adiposity, or a common genetic factor may influence both the activity and serum leptin levels.

GROWTH HORMONES AND SEX STEROID INTERACTIONS AT PUBERTY

Puberty is a period of dynamic changes mediated by GH and the gonadal steroid hormones. Although these substances exert important independent effects, their interaction is vital to normal pubertal growth and development. This is supported by observations of blunted growth and diminished levels of GH and IGF-1 during adolescence in individuals with panhypopituitarism in whom adequate replacement with both hormones had not been achieved. The independent roles of androgens and estrogens in mediating the rise in GH secretion at puberty have been studied in individuals with complete androgen insensitivity and through the administration of nonaromatizable androgens and the use of selective androgen- or estrogen-receptor blockade. The preponderance of evidence from studies of nonaromatizable (pure) androgens suggests that GH secretion is not enhanced as it is under the influence of testosterone. In addition, studies have shown increased GH secretion following androgen-receptor blockade and diminished GH release after estrogen-receptor blockade. Together these studies suggest a facilitory role of estrogen receptor-mediated processes on GH secretion and IGF-1 production. If androgens influence the GH/IGF-1 axis, it is most likely by an inhibitory mechanism. Observations of delayed skeletal maturation and deficient bone mineralization in individuals with estrogen receptor defects or mutations of the aromatase gene demonstrate the essential role of estrogen in promoting normal bone maturation, the accrual and maintenance of BMD, and control of the rate of bone turnover.

Rotational thromboelastometry-guided blood product management in major spine surgery

OBJECT Major spinal surgery in adult patients is often associated with significant intraoperative blood loss. Rotational thromboelastometry (ROTEM) is a functional viscoelastometric method for real-time hemostasis testing. In this study, the authors sought to characterize the coagulation abnormalities encountered in spine surgery and determine whether a ROTEM-guided, protocol-based approach to transfusion reduced blood loss and blood product use and cost. METHODS A hospital database was used to identify patients who had undergone adult deformity correction spine surgery with ROTEM-guided therapy. All patients who received ROTEM-guided therapy (ROTEM group) were matched with historical cohorts whose coagulation status had not been evaluated with ROTEM but who were treated using a conventional clinical and point-of-care laboratory approach to transfusion (Conventional group). Both groups were subdivided into 2 groups based on whether they had received intraoperative tranexamic acid (TXA), the only coagulation-modifying medication administered intraoperatively during the study period. In the ROTEM group, 26 patients received TXA (ROTEM-TXA group) and 24 did not (ROTEM-nonTXA group). Demographic, surgical, laboratory, and perioperative transfusion data were recorded. Data were analyzed by rank permutation test, adapted for the 1:2 ROTEM-to-Conventional matching structure, with p < 0.05 considered significant. RESULTS Comparison of the 2 groups in which TXA was used showed significantly less fresh-frozen plasma (FFP) use in the ROTEM-TXA group than in the Conventional-TXA group (median 0 units [range 0-4 units] vs 2.5 units [range 0-13 units], p < 0.0002) but significantly more cryoprecipitate use (median 1 unit [range 0-4 units] in the ROTEM-TXA group vs 0 units [range 0-2 units] in the Conventional-TXA group, p < 0.05), with a nonsignificant reduction in blood loss (median 2.6 L [range 0.9-5.4 L] in the ROTEM-TXA group vs 2.9 L [0.7-7.0 L] in the Conventional-TXA group, p = 0.21). In the 2 groups in which TXA was not used, the ROTEM-nonTXA group showed significantly less blood loss than the Conventional-nonTXA group (median 1 L [range 0.2-6.0 L] vs 1.5 L [range 1.0-4.5 L], p = 0.0005), with a trend toward less transfusion of packed red blood cells (pRBC) (median 0 units [range 0-4 units] vs 1 unit [range 0-9 units], p = 0.09]. Cryoprecipitate use was increased and FFP use decreased in response to ROTEM analysis identifying hypofibrinogenemia as a major contributor to ongoing coagulopathy. CONCLUSIONS In major spine surgery, ROTEM-guided transfusion allows for standardization of transfusion practices and early identification and treatment of hypofibrinogenemia. Hypofibrinogenemia is an important cause of the coagulopathy encountered during these procedures and aggressive management of this complication is associated with less intraoperative blood loss, reduced transfusion requirements, and decreased transfusion-related cost.

Factors affecting microbial contamination rate of cord blood collected for transplantation

BACKGROUND: Collection and processing of cord blood (CB) is associated with significant risk of microbial contamination and hence relevant standards mandate microbial screening of the final product. This study aimed to determine the contamination rate and associated risk factors during 14 years of banking at the Sydney Cord Blood Bank.

Assessment of the correlation of platelet morphology with in vivo recovery and survival

BACKGROUND:  There is continuing interest in the development of in vitro tests evaluating the in vivo function, recovery, and survival of platelets stored for transfusion. A recent forum concluded that no completely reliable test exists, although discoid morphology indicates a platelets good health. We evaluated a novel device, the NAPSAC (Noninvasive Assessment of Platelet Shape and Concentration), designed to determine noninvasively the proportion of discoid platelets in a stored concentrate, as well as platelet concentration.

Transfusion triggers for blood components.

Whereas there are general guidelines for acceptable transfusion therapy, optimal transfusion therapy has not been determined for most clinical settings. Recent research has focused on controlled studies of red cell transfusion in specific clinical settings. Better determinations of oxygen delivery and consumption are needed to guide clinicians in determining whether transfusion is justified for patients during the perioperative period, those with coronary artery disease, and those in intensive care units. For sickle cell disease, the role of transfusion for acute complications can be life saving; however, the role of chronic transfusion regimens awaits further research into efficacy. Finally, whereas criteria for the prophylactic transfusion of platelets in hematologic diseases are well described, relatively little information is available on the value of platelet transfusion where the absolute count is less than 100,000 but greater than 50,000. The value of fresh frozen plasma components, both standard and sterilized, also requires elucidation.

Effects of cryopreservation on microbial‐contaminated cord blood

Cord blood units (CBUs) are associated with significant risk of exposure to microbial contamination during collection and processing; however, the survival of bacteria within a CBU is poorly understood. This study aimed to determine whether contaminating organisms in CBU survive the cryopreservation, frozen storage, and subsequent thawing conditions before infusion.

Growth, Development, and Critical Disease

Normal growth and development is testimony to the overall good general health of a child or adolescent. What constitutes the range of normal varies with the age, gender, and genetic background of the individual. Deviation from a previously defined pattern of growth or failure to undergo adolescent development at the appropriate time or tempo can often be the first clue to an underlying disease process.

Reduction in Growth Velocity in Children and Adolescents with Asthma Treated with Inhaled Fluticasone

Reduction in Growth Velocity in Children and Adolescents with Asthma Treated with Inhaled Fluticasone

APPARENT ANDROGEN EXCESS IN A 4 YEAR-OLD MALE. 502

We describe a 4 year-old Afro-American male who presented with significant virilization, accelerated growth, and aggressive behavior of 1-2 years duration. Physical exam was remarkable for a height age of 6 years, skeletal age of 7.5 years, muscular body habitus, Tanner II pubic hair, and Tanner III genitalia, but prepubertal size testes. No source of exogenous androgen exposure was identified. Initial evaluation revealed prepubertal levels of gonadal and adrenal androgens (Table), normal ACTH-stimulated levels of adrenal steroids, undetectable levels of gonadotropins and β-hCG, and a negative routine urine steroid metabolite analysis. The child was admitted to the clinical research center for 24 h every 20 minute blood sampling to identify intermittent androgen secretion, a 24 h urine collection for detection of 39 unusual androgen metabolites by gas chromatography/mass spectometry, and a scrotal skin biopsy for qualitative and quantitative androgen receptor analysis. All were normal. Five months after initial evaluation the child underwent spontaneous resolution of symptoms. Growth slowed to an age-appropriate rate, skeletal maturation normalized, the pubic hair fell out, and the aggressive behavior ceased. We postulate a self-limited process of androgen production which apparently became quiescent during the course of our evaluation. The mechanism of such a process has not been previously described.