Double layer SiO2-TiO2 sol-gel thin films on glass for antireflection, antifogging, and UV recoverable self-cleaning.

Double layer thin films, mechanically stable and adhering to glass, were produced through the sol-gel process, using tetraethyl orthosilicate and titanium butoxide as precursors. The refractive index of the titania and silica-titania composite layers were typically 2.1 and 1.7, and their physical thicknesses were approximately 65 nm and 81 nm, respectively, as determined by ellipsometry. These optical constants allowed attainment of quarter-wave optical thicknesses at the center of the visible spectrum (550 nm) as designed, with an increase of 3.4% in transmittance. The nanometric surface roughness, measured by optical profilometry, was effective to decrease light scattering and water contact angles to below 10°. As novelty in dip-coated sol-gel films, superhydrophilicity for self-cleaning, antifogging, and antireflection in the mid-visible spectrum were simultaneously attained with durability of 9 weeks in the dark. Further application of UV light allowed regeneration of contact angles for self-cleaning.

Work-related respiratory symptoms in Champagne vineyard workers.

BACKGROUND: Vineyard workers (VW) are exposed to various respiratory allergens. The aims of the study were to determine the prevalence of work related respiratory symptoms (WRS) in Champagne VW in France and to analyze the relationships between symptoms, occupational exposure and sensitization profile. METHODS: VW of Reims area were prospectively recruited between 2007 and 2010. Demographic and occupational characteristics were recorded. Respiratory symptoms were scored for each month of the past year. Results of respiratory functional tests and skin prick tests for common respiratory allergens, grape moulds and vine pollen were recorded. RESULTS: 307 subjects were included. The prevalence of WRS was 11%. Compared to subjects with symptoms unrelated to work, subjects with WRS were more frequently sensitized to gramineae (34% vs 18%, p = 0.05), described ocular itching (74% vs 37%, p < 0.001) and seasonal symptoms (88% vs 69%, p = 0.03) mainly during lifting and trellising (57% vs 17%, p < 0.001). CONCLUSION: WRS are frequent in Champagne WV and are associated with a sensitization to gramineae and with activities performed close to vine in late spring.

Induction of invagination in insect epithelium: paradigm for embryonic invagination.

The proposal that adhesive disparities between inpocketing populations of cells and surrounding epithelia drive epithelial invagination was tested in grafting experiments with moth pupal wing epithelium. Evidence exists that a cellular adhesiveness gradient spans the proximodistal axis of the wing. Although pupal wing cells normally do not invaginate or evaginate, epithelial folding can be induced after exchange of grafts from opposite ends of the proximodistal axis. The hypothesis that cytoskeletal elements are the primary agents in epithelial invagination should be reevaluated.

Premature adrenarche--normal variant or forerunner of adult disease?

Adrenarche is the puberty of the adrenal gland. The descriptive term pubarche indicates the appearance of pubic hair, which may be accompanied by axillary hair. This process is considered premature if it occurs before age 8 yr in girls and 9 yr in boys. The chief hormonal product of adrenarche is dehydroepiandrosterone (DHEA) and its sulfated product DHEA-S. The well documented evolution of adrenarche in primates and man is incompatible with either a neutral or harmful role for DHEA and implies most likely a positive role for some aspect of young adult pubertal maturation and developmental maturation. Premature adrenarche has no adverse effects on the onset and progression of gonadarche in final height. Both extra- and intraadrenal factors regulate adrenal androgen secretion. Recent studies have shown that premature adrenarche in childhood may have consequences such as functional ovarian hyperandrogenism, polycystic ovarian syndrome, and insulin resistance in later life, sometimes already recognizable in childhood or adolescence. Premature adrenarche may thus be a forerunner of syndrome X in some children. The association of these endocrine-metabolic abnormalities with reduced fetal growth and their genetic basis remain to be elucidated.

[Systemic lupus erythematosus presenting as severe alveolar hypoventilation and the shrinking lung syndrome]. / Hypoventilation alvéolaire sévère révélant un shrinking lung syndrome lupique.

INTRODUCTION: The shrinking lung syndrome (SLS) is a rare complication of systemic lupus erythematosus. CASE REPORT: A 69-year-old man presented with exertional dyspnoea, muscle weakness, and weight loss of 15kg in 6months. Pulmonary function tests revealed a restrictive lung disorder, with a dramatic decrease in maximal inspiratory pressure (17% of theoretical value), and alveolar hypoventilation (pH 7.43; PaCO2 55mmHg). A thoracic CT-scan showed bilateral diaphragmatic elevation. The creatinine phophokinase level was increased at 280U/L. Progress was marked by a rapidly increasing respiratory acidosis (pH 7.24, PaCO2 109mmHg) requiring invasive ventilation. Auto-immune studies revealed positive anti-nuclear antibodies (1/800) and positive anti-native DNA antibody at 45U/L. Treatment with systemic corticosteroids led to an initial improvement but it was not possible to discontinue mechanical ventilation. The outcome was fatal. Autopsy did not reveal any other cause and a diagnosis of the SLS associated with lupus was confirmed. CONCLUSION: The interesting features of this case report consist of: 1) the presentation of the SLS as an alveolar hypoventilation with a fatal outcome, 2) the presentation of systemic lupus as SLS.

A decade of the Catalonian Arthroplasty Register (RACat): Variability, exhaustivity, and survival of prostheses between 2005 and 2014. / Una década del Registro de Artroplastias de Cataluña (RACat): exhaustividad, variabilidad y supervivencia de las prótesis entre 2005 y 2014.

BACKGROUND AND AIM: The Catalonian Arthroplasty Register (RACat) is a public health-based population register used to analyse and evaluate hip and knee replacements in Catalonia. The aim of this study is to present the outcomes after 10 years in operation (January 2005-December 2014). METHODOLOGY: Using the information from the RACat and the minimum basic data set at hospital discharge, an analysis was made of the quality and exhaustivity of the data, as well as a descriptive analysis of the patients, prostheses, and care process. Survival was also analysed by calculating the accumulated incidence of revisions (according to the cause of intervention in hip replacements and conservation or sacrifice of the posterior cruciate ligament in knee replacement). The relationship between revision risk and the fixation technique of the prosthesis is also analysed, using competitive risk models adjusted for gender, age, and comorbidities. RESULTS: The main reason for the primary hip and knee replacement surgery was arthrosis. The accumulated incidence of revisions at 10 years was 3.9% in hip replacements caused by arthrosis, and 2.3% in those caused by fracture. Conservation of the posterior cruciate ligament was achieved in 4.4% of knee replacements, with sacrifice in 5.1%. DISCUSSION: The RACat is consolidated as a tool for the evaluation of joint replacements, with great potential in the analysis of medium and long-term efficacy, the study of the variability in clinical practice, and post-marketing surveillance.

Insulin resistance in prepubertal African-American and Hispanic girls with premature adrenarche: a risk factor for polycystic ovary syndrome.

Recently, the modest hyperandrogenism of premature adrenarche has been linked to the more severe hyperandrogenism of polycystic ovary syndrome (PCOS). The presence of hyperandrogenism, obesity, acanthosis nigricans, hyperinsulinism and reduced insulin sensitivity in girls with premature adrenarche and in women with PCOS suggests that the two conditions might have a common mechanism. As the early appearance of pubic hair might be the first presentation of hyperandrogenism and insulin resistance, these girls should have continued.

[Eosinophilic pleuritic: An unusual complication of treatment with an angiotensin converting enzyme inhibitor]. / Pleurésie à éosinophiles: une complication rare d'un traitement par inhibiteur de l'enzyme de conversion de l'angiotensine.

BACKGROUND: Eosinophilic pleural effusions are defined by an eosinophil count ≥10% in pleural fluid and represent approximately 10% of exudative pleural effusions. OBSERVATION: We report the first case of eosinophilic pleural effusion occurring due to lisinopril treatment. Improvement after drug discontinuation and recurrence after reintroduction indicated that lisinopril was responsible for the effusion. CONCLUSION: The main causes of eosinophilic pleural effusions are infections including tuberculosis, and malignancies. Drug-induced eosinophilic pleural effusions have only rarely been described, mainly caused by cardiovascular or neuropsychiatric medicines.

Fasting glucose insulin ratio: a useful measure of insulin resistance in girls with premature adrenarche.

The purpose of this study was to determine whether the fasting glucose/insulin ratio is a useful screening test for insulin resistance in prepubertal girls with premature adrenarche. The glucose/insulin ratio was compared with the insulin sensitivity index calculated from the frequently sampled iv glucose tolerance test with tolbutamide using the minimal model computer program. Thirty-three prepubertal girls (22 Caribbean Hispanic and 11 African American; mean age, 6.8 yr; bone age, 8 yr) were studied. All underwent a 60-min ACTH stimulation test. The fasting glucose/insulin ratio was also compared with IGF-binding protein-1 and ACTH-stimulated androgen levels. Insulin sensitivity correlated significantly with the glucose/insulin ratio (0.76; P < 0.001), fasting insulin (0.75; P < 0.001), and IGF-binding protein-1 (0.59; P < 0.005). Stepwise regression analysis with the insulin sensitivity index as the dependent variable showed that the fasting glucose/insulin ratio was significantly predictive of the insulin sensitivity index (P < 0.002). When viewed as a screening test, setting a value of the fasting glucose/insulin ratio of less than 7 as abnormal and of less than 5.7 x 10(-4) min/microU.ml for the insulin sensitivity index as evidence of insulin resistance (normal prepubertal insulin sensitivity index, >5.7 x 10(-4) min/microU.ml), the sensitivity of the fasting glucose/insulin ratio was 87%, and the specificity was 89%. Furthermore, those girls with a low glucose/insulin ratio (<7) had higher body mass index, fasting insulin, free T, and ACTH-stimulated 17-hydroxypregnenolone and lower fasting IGF-binding protein-1 and SHBG than those girls with a glucose/insulin ratio greater than 7. The fasting glucose/insulin ratio is a useful screening test for insulin resistance in prepubertal Caribbean Hispanic and African American girls with premature adrenarche.

Decreased insulin sensitivity in prepubertal girls with premature adrenarche and acanthosis nigricans.

Benign premature adrenarche (PA) is the term used to refer to girls with the early development of pubic hair before the age of 8 yr and is characterized by mild hyperandrogenism. Hyperandrogenism in adult women is often not as benign and has been associated with insulin resistance, acanthosis nigricans (AN), and the polycystic ovary syndrome. We have seen a group of young girls with PA who have also been found to have AN. The purpose of this study was to determine whether there are any clinical and biochemical differences in those girls with PA with and without AN. Twelve girls with PA were divided into two groups at the time of evaluation: group I, those without AN (n = 5); and group II, those with AN (n = 7). Adrenal androgen levels were determined in all subjects by a 60-min ACTH stimulation test. Insulin sensitivity was measured by the frequently sampled iv glucose tolerance test with tolbutamide and was assessed using the modified minimal model. Mean chronological age, bone age, and weight for length index were similar in the two groups. The baseline and stimulated levels of adrenal androgens were also not significantly different between the two groups. The group I girls (without AN) had an insulin sensitivity index of 6.75 +/- 1.31, which was in the normal prepubertal range. This was significantly different from that in group II (with AN), who had an insulin sensitivity index of 3.69 +/- 1.29. Therefore, many girls with premature adrenarche can have AN and decreased insulin sensitivity. Whether these girls have a truly benign course or are at risk of ovarian dysfunction or carbohydrate intolerance needs to be assessed.

The effect of long-acting analog of luteinizing hormone-releasing hormone on growth hormone secretory dynamics in children with precocious puberty.

Long-acting preparations of LHRH (LHRHa), such as leuprolide acetate, have been shown to selectively and reversibly suppress the clinical and biochemical features of central precocious puberty (CPP). The withdrawal of gonadal sex steroids results in a decline of growth velocity and a decrease in the rate of bone age maturation, with resultant improvement in predicted adult stature. The purpose of this study was to define GH secretory dynamics in children treated with leuprolide acetate. Twelve-hour nocturnal GH studies were performed in five children (four girls and one boy) with CPP before and after 6 months of treatment with leuprolide acetate. Mean GH levels, GH secretory rate, and number of GH secretory episodes were determined. Secretory profiles were analyzed using the Cluster program. Growth velocity, somatomedin-C, and dehydroepiandrosterone sulfate were measured before and after 6 months of therapy. By 6 months of therapy, there was a significant decrease in mean growth velocity from 10.5 +/- 3.3 to 6.7 +/- 1.6 cm/yr. Somatomedin-C levels remained the same at 46.90 +/- 9.51 and 52.5 +/- 12.40 nmol/L. Levels of dehydroepiandrosterone sulfate remained unchanged at 118.6 +/- 71.4 and 139.0 +/- 61.3 mumol/L at 0 and 6 months of the study. By 6 months, there was a significant decrease in mean GH levels from 13.6 +/- 5.3 to 6.4 +/- 3.4 micrograms/L (P less than 0.05). Total GH levels decreased from 1367.9 +/- 687.3 to 447.0 +/- 186.5 ng/12 h. The number of GH secretory episodes remained the same at 5.4 +/- 1.5 and 4.8 +/- 1.0/12 h at 0 and 6 months of study. Therefore, the decrease in GH that occurs during the withdrawal of gonadal sex steroids with LHRHa in children with CPP is an amplitude-modulated phenomenon, as the number of secretory peaks remains unchanged.

Effects of growth hormone therapy on circadian osteocalcin rhythms in idiopathic short stature.

The effects of GH administration on the circadian osteocalcin (Oc) rhythm were determined in four prepubertal children with idiopathic short stature (height, less than 5th percentile; growth velocity, less than 50th percentile for age). Each child underwent 24-h sequential blood sampling on three occasions: immediately before the initiation of GH treatment, 6 months later, and at the end of 12 months of treatment. The growth rate increased more than 50% over baseline in three of the four children during at least one of the 6-month periods. Insulin-like growth factor-I levels increased during treatment in all of the children. Twenty-four-hour Oc levels increased on 7 of the 8 treatment days evaluated. When mean 24-h Oc patterns for each of the 3 study days were derived by averaging across individual subjects at each time point and then compared, we noted an upward shift in the entire pattern during treatment (t = 13.2 at P less than 0.001 and t = 5.9 at P less than 0.001 for 6 and 12 month comparisons vs. the pretreatment day, respectively). This was more easily appreciated after the data were smoothed using the method of running means. There was, in addition, a progressive improvement in the shape of the Oc pattern compared to a normative model derived from a study of healthy adult men. The correlation between the model and the pre-GH day was 0.46, that between the model and the 6 months of GH day was 0.77, and that between the model and the 12 months of GH day was 0.96. Cross-correlation analyses showed that the peak correlation between the 2 treatment days and the model occurred at zero lag. In contrast, the peak correlation between the pre-GH day and the model or the pre-GH day and either of the 2 treatment days occurred when the pre-GH series was lagged by 2-3 h. Thus, an additional finding is the synchronization of the Oc series that occurred during treatment. We conclude that GH treatment increases Oc concentrations in children with idiopathic short stature by affecting its circadian rhythm. This rise in Oc values may not necessarily reflect an increase in growth velocity.

The effect of luteinizing hormone-releasing hormone analog for central precocious puberty on growth hormone (GH) and GH-binding protein.

The pubertal growth spurt is characterized by a marked increase in the amplitude of GH secretory pulses. The high affinity GH-binding protein (GHBP) reportedly has an important role in enhancing the growth-promoting action of GH. Levels of GHBP are characteristic for an individual and increase only slightly as puberty progresses. It has been hypothesized that each individual adjusts GH production to a level appropriate for his GHBP environment. The withdrawal of gonadal steroids that occurs in children with central precocious puberty (CPP) treated with LH-releasing hormone agonist (LHRHa) therapy results in a decrease in growth velocity (GV) and GH secretion. This study was performed to determine the effect of treatment of CPP with the LHRHa leuprolide acetate for depot suspension on GH secretion and levels of GHBP. Six girls and one boy with CPP were studied before and 6 months after treatment was initiated. Within 6 months of initiation of therapy, there was a significant decline in GV, from 8.9 +/- 3.2 to 5.4 +/- 2.0 cm/yr (P < 0.05). Twelve-hour mean nocturnal GH levels decreased significantly from 8.6 +/- 3.5 to 5.1 +/- 2.3 micrograms/L (P < 0.05). This occurred via a decrease in the amplitude of GH pulses as the number of peaks remained 4.6 and 4.1/12 h. Individual levels of GHBP were variable and reflect the wide range of levels observed in normal children. Although GV and GH levels decreased substantially, mean GHBP levels remained unchanged at 139.9 +/- 46.0 and 152 +/- 39.8 pmol/L. In children with CPP, within 6 months of LHRHa therapy, the decrease in GV occurs via a decrease in nocturnal GH secretion as levels of GHBP remain unchanged. In children with CPP, the withdrawal of gonadal steroids may inhibit the child's ability to secrete the GH appropriate for his/her GH/GHBP milieu.

Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group.

In a multicenter study the metabolic effects of 5 yr of GH therapy in children with idiopathic short stature were evaluated. Patients received 0.3 mg/kg.week recombinant human GH. Of the 121 patients who entered the study, data for 62 were analyzed at the final 5 yr point. Routine laboratory determinations were available for all 62 subjects at the 5 yr point. Special laboratory determinations, such as postprandial glucose and insulin, were available for only a subset of patients. Mean insulin-like growth factor I levels rose to 283 +/- 101 micrograms/L, within the normal range using age-appropriate reference standards. T4, cholesterol, triglycerides, blood chemistries, and blood pressure showed no significant changes during the 5-yr period. Mean baseline and 2-h postprandial glucose levels remained unchanged. Both fasting and postprandial insulin levels rose substantively from low normal levels to the normal range (median, 4.9-43 mU/L). Mean hemoglobin A1c levels remained within the normal range throughout the study. In summary, careful monitoring has not revealed any currently discernible metabolic side-effects of clinical significance after GH therapy in this 5-yr study of children with idiopathic short stature.

The roles of insulin sensitivity, insulin-like growth factor I (IGF-I), and IGF-binding protein-1 and -3 in the hyperandrogenism of African-American and Caribbean Hispanic girls with premature adrenarche.

Recent reports indicate that girls with premature adrenarche are at risk of developing functional ovarian hyperandrogenism and polycystic ovarian syndrome (PCOS). As insulin and insulin-like growth factors (IGFs) have been implicated in the pathogenesis of PCOS, we hypothesize that they may also have a role in the hyperandrogenism of premature adrenarche. Thirty-five prepubertal girls (23 Caribbean Hispanics and 12 Black African-Americans) underwent a 60-min ACTH and LH-releasing hormone test. Insulin sensitivity (S(I)) was assessed using the frequently sampled i.v. glucose tolerance test with tolbutamide. Fasting levels of IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, sex hormone-binding globulin, and free testosterone (T) were also obtained. The mean age of the patients was 6.8 yr, and bone age was 8.0 yr. Twenty-five patients had a family history of noninsulin-dependent diabetes mellitus and 19 patients had acanthosis nigricans. The mean S(I) for the entire group was 6.78 +/- 5.21 x 10(-4) min/microU x mL (normal prepubertal S(I), 6.5 +/- 0.54 x 10(-4) min(-1) x microU(-1) x mL(-1)). However, 15 of the 35 girls had an S(I) that was more than 2 SD below the mean reported for normal prepubertal children. Of these 15 patients, 13 were obese, and 14 had acanthosis nigricans. For the entire group of girls, the mean ACTH-stimulated levels of 17-hydroxypregnenolone (17OHPreg), dehydroepiandrosterone (DHEA), androstenedione (AS), 17-hydroxyprogesterone (17OHP), and T and the ACTH-stimulated ratios of 17OHPreg/17OHP, 17OHPreg/DHEA, 17OHP/AS, and DHEA/AS did not differ from the levels reported for Tanner stage II-III pubertal girls. The girls were divided into two groups based on their S(I) (group I, S(I) >2 SD below the mean for age; group II, normal S(I)). The group I girls with a reduced S(I) had significantly higher ACTH-stimulated levels of 17OHPreg (group I, 760 +/- 87.84 ng/dL; group II, 428.9 +/- 46.28 ng/dL; P = 0.002), 17OHPreg/17OHP ratio (group I, 3.95 +/- 0.36; group II, 2.96 +/- 0.35; P = 0.05), 17OHPreg/DHEA (group I, 2.06 +/- 0.21; group II, 1.4 +/- 0.13; P = 0.01), and free T (group I, 1 +/- 0.23 ng/dL; group II, 0.49 +/- 0.19 ng/dL; P = 0.014). Levels of sex hormone-binding globulin were lower in the group I girls. Furthermore, for the entire group of girls, the S(I) correlated inversely with ACTH-stimulated levels of 17OHPreg, DHEA, and AS and the ACTH-stimulated ratio of 17OHPreg/17OHP. IGF-I correlated inversely with S(I) (r = -0.94; P < 0.001) and correlated directly with the ACTH-stimulated levels of 17OHPreg (r = 0.8; P < 0.001) and AS (r = 0.63; P < 0.05). IGF-I also correlated with the ACTH-stimulated ratios of 17OHPreg/17OHP (r = 0.61; P < 0.05), 17OHPreg/DHEA (r = 0.9; P < 0.001), 17OHP/AS (r = 0.79; P < 0.001), and DHEA/AS (r = 0.96; P < 0.001). IGFBP-1 correlated inversely with the ACTH-stimulated levels of 17OHPreg (r = -0.38; P < 0.05) and DHEA (r = -0.36; P < 0.05). To summarize, the ACTH-stimulated delta5-steroid levels were higher in prepubertal girls with premature adrenarche and reduced S(I). There was a significant inverse correlation among ACTH-stimulated hormone levels, S(I), and IGFBP-1, whereas IGF-I correlated directly with ACTH-stimulated androgens. These findings support the hypothesis that insulin and IGFs may have a role in the hyperandrogenism of premature adrenarche just as they do in PCOS. Hence, in certain girls with premature adrenarche, hyperandrogenism may be the first presentation of PCOS and/or insulin resistance.

Normative data for the steroidogenic response of mineralocorticoids and their precursors to adrenocorticotropin in a healthy pediatric population.

The responses of mineralocorticoids and their precursors 1 h after a 0.25-mg bolus of ACTH has not previously been established in infancy or childhood. We report the steroidogenic responses of pregnenolone, progesterone (Prog), deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone (18OHB), and aldosterone (A) measured 1 h after a 0.25-mg bolus of ACTH in 102 healthy children who were divided into 5 age groups: group 1 (< 1 yr; n = 22), group 2 (1-5 yr; n = 22), group 3 (6-12 yr; n = 15), group 4 (early to midpuberty; n = 21), and group 5 (late puberty; n = 22). Baseline pregnenolone levels were constant throughout childhood; however, there was a significant fall in the stimulated level after the first year of life (group 1 vs. 2, P < 0.0125). Baseline Prog levels rose significantly with the onset of puberty (group 3 vs. 4, P < 0.0125), but levels did not increase after ACTH stimulation during puberty. Both baseline and stimulated levels of Prog, DOC, and 18OHB were significantly higher in group 3 males than in group 3 females (P < 0.05). Stimulated levels of DOC and corticosterone were constant during childhood, the only exception being the fall in the stimulated level of both steroids with the onset of puberty in males (group 3 vs. 4, P < 0.0125). The baseline level of 18OHB also fell with the onset of puberty in males (P < 0.0125), but a similar fall was not seen in females or in the stimulated level of 18OHB in either sex. The stimulated aldosterone level was higher in group 1 males than in group 2 males (P < 0.0125); a similar difference was not observed in females. The differences that we observed confirm the importance of specific age- and sex-related reference data when patients with possible abnormalities of mineralocorticoid synthesis are evaluated.

Preservation of physiological growth hormone (GH) secretion in idiopathic short stature after recombinant GH therapy.

This study was undertaken to assess the recovery of spontaneous GH secretion 48 h after the cessation of GH therapy in children with idiopathic short stature treated with recombinant DNA-generated human GH (rhGH-M). Eleven prepubertal children with GH responses of 10.0 ng/mL or more after provocation were divided into therapeutic (n = 7) and control (n = 4) groups. GH was sampled every 20 min for 24 h in six treated and three control patients. One treated and one control patient had 12-h overnight studies because of their weight. The sampling studies were carried out before GH therapy was initiated and 48 h after rhGH was discontinued after 12 months of therapy. Three patients in the treated group also underwent a 24-h study at the 6 month time point. The treated group started treatment with rhGH (0.1 mg/kg), given three times a week. The results showed that pre- and posttreatment GH secretory profiles were comparable with respect to the number of peaks, mean concentrations, peak amplitude, and secretory rate. At the 6 month point, the mean GH and peak GH amplitude (n = 3) were greater than the means of the treatment group (n = 7) at the 0 and 12 month points, but the difference was not statistically significant. Somatomedin-C rose in the treated group from 0.42 +/- 0.1 to 1.25 +/- 0.3 U/mL (mean +/- SD; P less than 0.01). In the control group it rose from 0.56 +/- 0.1 to 1.16 +/- 0.8 U/mL (mean +/- SD; P greater than 0.05) because one patient entered puberty in the 12-month period of observation; his somatomedin-C level rose from 0.72 to 2.5 U/mL. We conclude that exogenous GH therapy does not interfere with the maintenance of endogenous pulsatile secretion of GH. These data show that exogenous GH therapy does not interfere with the maintenance of endogenous pulsatile secretion of GH and provide evidence for the resilience of the GH secretory system in the growing child.

Normative data for adrenal steroidogenesis in a healthy pediatric population: age- and sex-related changes after adrenocorticotropin stimulation.

The normal response to a single 0.25-mg dose of ACTH-(1-24) is not well established in infancy or childhood. We report the adrenal steroidogenic responses of 17-hydroxypregnenolone (17OH Preg), 17-hydroxyprogesterone (17OH Prog), 11-deoxycortisol, cortisol, deoxycorticosterone, dehydroepiandrosterone (DHEA), DHEA sulfate, androstenedione (A'dione), and testosterone in 102 healthy children who were divided into 5 groups: group 1 (less than 1 yr old; n = 22), group 2 (1-5 yr old; n = 22), group 3 (6-12 yr old; n = 15), group 4 (early-midpuberty; n = 21), and group 5 (late puberty; n = 22). Baseline and stimulated levels of 17OH Preg were significantly higher in group 1 infants than in group 2 children (P less than 0.01). Baseline levels of 17OH Prog increased in late puberty (P less than 0.01). Baseline and stimulated levels of DHEA rose in late puberty (group 5 vs. group 3, P less than 0.01). DHEA levels in late pubertal females were higher than those in their male counterparts (P less than 0.01). DHEA sulfate levels did not change after ACTH administration in any age group. Baseline and stimulated levels of A'dione rose significantly before the onset of puberty in female children (group 2 vs. group 3, P less than 0.01). The calculated ratio of 17OH Preg/17OH Prog in group 1 was significantly higher than that in other groups of children (P less than 0.01). The calculated, baseline DHEA/A'dione ratio was higher in group 1 than in older children (P less than 0.01). Stimulated ratios were higher in late pubertal females than in males (P less than 0.01). In both sexes baseline and stimulated ratios of 17OH Prog/deoxycorticosterone increased in puberty, such that late pubertal children had higher levels than prepubertal children (P less than 0.01). These data confirm the need for interpretation ACTH stimulation test data to be based upon age- and sex-specific norms.

Expression of lacunin, a large multidomain extracellular matrix protein, accompanies morphogenesis of epithelial monolayers in Manduca sexta.

Morphogenesis is a complex process operating at several levels of organization--organism, tissues, cells, and molecules. Complex interactions occur between and within these levels. Many of the molecules that mediate these interactions are predictably turning out to be large multidomain proteins. Here we describe one such novel protein associated with remodeling of epithelial monolayers in embryos and developing wings of the moth Manduca sexta. On the basis of its sequence and its expression pattern along lacunae of developing wings, we propose the name lacunin for this extracellular matrix protein that contains nine different types of domains, most of which are present in multiple copies. These include domains of various types: Kunitz proteinase inhibitors, thrombospondin type I, immunoglobulin-like, and several newly defined domains of unknown function (PAL, PLAC, and lagrin domains). This rich patchwork of distinct domains probably exerts multiple effects on a variety of cell behaviors associated with the complex phenomenon of epithelial morphogenesis.