Search

Background Familial chylomicronemia syndrome (FCS) is caused by a genetic defect in triglyceride (TG) metabolism that leads to severe hypertriglyceridemia, which in turn is associated with multiple morbidities and may cause severe pancreatitis that is both recurrent and progressive. Management of hypertriglyceridemia in FCS is challenging, as both dietary and medical interventions are often ineffective. Therapeutic plasma exchange (TPE) has been shown to rapidly decrease circulating levels of chylomicrons and TGs in patients presenting with acute hypertriglyceridemic-associated pancreatitis. Conversely, limited evidence exists to suggest that prophylactic use of TPE is effective at preventing recurrence of acute pancreatitis. Case report Herein, we report our experience with the use of chronic, prophylactic TPE to reduce the incidence of recurrent acute pancreatitis in a patient with FCS.

Background Crepidiastrum denticulatum (CD) is a well-known, traditionally consumed vegetable in Korea, which was recently reported to contain bioactive compounds with detoxification and antioxidant properties. Ischemia-reperfusion injury (IRI) is a major problem after renal transplantation. Furthermore, inflammatory responses to IRI exacerbate the resultant renal injury. In the present study, we investigated whether CD extract exhibits renoprotective effects against IR-induced acute kidney injury in mice. Materials and methods Renal IRI was induced in male C57BL/6 mice by bilateral renal pedicle occlusion for 30 minutes followed by reperfusion for 48 hours. CD extract (75 mg/kg) was administered orally 5 days before IRI. Results Treatment with CD extract significantly decreased blood urea nitrogen and serum creatinine levels as well as kidney tubular injury. CD also prevented IRI-induced renal glutathione depletion and increased malondialdehyde levels. Western blotting and reverse transcriptase polymerase chain reaction indicated that CD extract significantly attenuates inducible nitric oxide synthase and toll-like receptor 2/4 protein levels 48 h after IRI. The expression of tumor necrosis factor-α and interleukin-1β was significantly decreased in the CD extract treatment group. Conclusion CD extract improved acute renal IRI through its antioxidant and anti-inflammatory effects. These findings suggest that CD extract is a potential therapeutic agent for acute ischemia-induced renal damage.

Objectives This study was designed to evaluate the usefulness of intra-operative frozen section for the evaluation of microscopic extrathyroidal extension (ETE) in papillary thyroid carcinoma (PTC). Design Retrospective cohort study. Setting Dong-A University Medical Center, Busan, Korea. Participants Three hundred and sixty-four patients who underwent thyroid surgery from January 2000 to December 2010 with PTC confined to one unilateral lobe as diagnosed using preoperative ultrasonography were enrolled. Main outcome measures The patients who had microscopic ETE on frozen section were classified into “group A,” and those who did not have microscopic ETE on frozen section were classified into “group B.” Clinicopathologic factors including age, gender, size of the tumour, extent of operation, ETE, multifocality, bilaterality, lymph node metastasis and recurrence were compared between the two groups. Results Of the 364 patients enrolled, ETE was confirmed in 100 patients (group A, 27.5%) on frozen biopsy. The nodule size in group A (0.94±0.87 cm) was larger than that in group B (0.86±0.79 cm) (P=.042). In group A, 15 patients (15%) showed multifocality and 11 patients (14.47%) showed bilaterality. In group B, 37 patients (14.02%) showed multifocality and seven patients (43.35%) showed bilaterality. They did not differ significantly between the two groups (P=.811, P=.182). There was a higher frequency of lymph node metastases in group A (52/86, 60.47%) than in group B (7/16, 43.75%, P=.214). Recurrence was observed in only two patients who had received thyroid lobectomy as the initial surgery in group A. Conclusions Intra-operative frozen biopsy can be a useful method for identifying the microscopic ETE. During the surgery, it can also help the surgeon to decide the optimal extent of surgery and the need for central compartment neck dissection in PTC patients.

Introduction: We report a pediatric case of primary hyperparathyroidism due to a parathyroid adenoma and Cushing’s disease due to a pituitary adenoma. Clinical Case: The patient presented at 13.5 years old for hypertension that was discovered during an exam for weight loss, headaches, and paresthesias. Evaluation was significant for elevated blood pressure (148/98 mmHg), obesity (BMI 96.5%), striae, and he was found to be midpubertal. Tests showed calcium levels 10.7 (RR 8.6-10.6 mg/dL), aldosterone 2.4 (RR 4.0-31.0), and 24 hour urine cortisol/creatinine 451 ug/g (prepubertal RR< 25, >18 yo

Background: Heterozygous loss of function mutations in GH1 are a cause of autosomal dominant isolated growth hormone deficiency (GHD) or IGHD type II. However, this condition is rare and a genotype/phenotype association is often based on single case or pedigree reports. Clinical Case: The male proband was born at 38 weeks following an uncomplicated pregnancy, birthweight 2585 gm (˗1.3SD), length 43 cm (˗2.7SD). At 20 months old: length ˗3.2SD, weight/length 16%. Peak growth hormone (GH) levels 4.42 ng/mL and 3.2 ng/mL following clonidine and arginine stimulation, respectively; cortrosyn-stimulated cortisol was 41.4 mcg/dL. Prolactin was 61.2 ng/mL (reference range 2.6 to 13.1 ng/mL); T4 and TSH levels were normal. Magnetic resonance imaging showed a flattened anterior pituitary gland, consistent with empty sella, with normal bright spot. He has had an intermittent and variable response to GH treatment due to noncompliance; recent recorded height was ˗3.6SD at 13.9 and he was early pubertal. Father had a history of childhood growth hormone treatment and is 151 cm tall, 2 paternal aunts did not receive treatment and are 145 cm tall, 3 children of these aunts are diagnosed with GHD. There is no maternal family history of GHD; mother is 155 cm. Proband testing revealed heterozygous GH1 c.291 + 34G>C (EGL Genetics), classified as a variant of unknown significance; father was also found to have this variant, mother was negative. Genetic testing for of additional family members is under consideration. Conclusion: Nine of 96 heterozygous GH1 variants are located in intron 3. Two have been classified as pathogenic and are predicted to cause exon skipping. Our proband’s variant cannot be considered a canonical splice site or in a mutational hot spot but has extremely low frequency in population databases. Functional studies clan clarify if our proband’s variant results in a 17.5 kDa GH isoform and dominant negative effect on full length GH production with potential detrimental effects on other anterior pituitary hormones. We present the second GHD pedigree with GH1 c.291 + 34G>C mutation. As in the previous report (1), no other hormone deficiencies are identified, despite the appearance of an empty sella for our proband. Reference: (1) Cho SY, Ki, CS, Park, HD, et al. Genetic investigation of patients with undetectable peaks of growth hormone after two provocation tests. Clin Endocrinol 2013; 78: 317-20.

Osteocalcin (OCN), a marker of osteoblast activity, has been implicated in the regulation of energy metabolism by the skeleton and thus may affect body fat measures. We examined the relationships of OCN to body fat measures and whether they vary according to markers of energy and vitamin D metabolism. Data was obtained from 58 obese adolescents aged 13–17.9 years (38 females, 8 black or African-American). We calculated total fat mass (FM) [dual X-ray absorptiometry (DXA)] and visceral adipose tissue (VAT) [computerized axial tomography (CT)]. Blood tests included leptin, OCN, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), thyroid function tests, and triglycerides. Markers of glucose metabolism were obtained from fasting and OGTT samples. Adolescents with 25(OH)D

It is possible to detect the presence of small field errors in a tokamak with an electron beam. This was demonstrated earlier on T-15 and TEXTOR. This paper discusses the concept, past experience on these tokamaks, calculations for the Korea Superconducting Tokamak Advanced Research (KSTAR) device, an electron beam source, measurement devices for these measurements, and some results. It is shown that small toroidally averaged field errors can be detected by this method. A low voltage electron beam (e-beam) gun and fluorescent screen were mounted in a vertical port and inserted into the vacuum vessel at the end of the KSTAR 2nd campaign plasma experiments. A camera with a narrow field of view was mounted in midplane port in a tube tangent to the field lines at R ∼ 1.3 m and photographed the beam striking the screen. The poloidal field (PF) currents were held constant during the camera exposure period. Many shots with various PF coils energized were made and the deflections of the e-beam were measured. The measurements were made with a camera integration time of 300 ms because of the low light intensity. The results show that there are large field errors that diminish as the PF currents are raised. There appears to be no significant up–down asymmetry for static fields. Measurements with a 7 PF coil scenario with a calculated field null located at e-beam radial position show much larger fields than calculated. KSTAR was constructed with Incoloy 908 conduit using cable-in-conduit conductors (CICC) in 10 of the 14 PF coils and all 16 of the toroidal field (TF) coils. Incoloy 908 has a relative magnetic permeability, μ, of about 10. The field errors appear to be largely due to Incoloy 908.

Objective: We report an unusual case of Prader-Willi Syndrome (PWS) presenting with clinical signs and symptoms suggestive of Angelman Syndrome (AS), without exclusive features of PWS.Methods: A deletion in the 15q11-13 region is associated with 2 distinctive genetic syndromes depending on the parent of origin: AS and PWS. AS is characterized by developmental delays, seizures, microcephaly, movement or balance disorders, speech disorders, and happy demeanor. PWS is characterized by hypotonia, hyperphagia, and developmental delays. An 11.5-year-old female was evaluated for developmental delay with cognitive disabilities, minimal speech, echolalia, and continuous hand motions. The patient had a pleasant but minimally interactive demeanor.Results: Chromosomal microarray analysis revealed a 5.02 Mb interstitial deletion of 15q11.2>q13.1 (base pairs 21,192,943 to 26,213,571), consistent with PWS or AS, and a 604 kb interstitial duplication of 16p11.2 (base pairs 29,530,197 to 30,134,432). Based on her presentation, AS was suspected; however, methylation analysis confirmed the diagnosis of PWS, with the presence of only the maternal copy of 15q11.2q13.1.Conclusion: Although variable phenotypic presentation of PWS has been reported, this case is particularly unusual in having only a few typical features of PWS while presenting as possible AS. We postulate that the 16p11.2 duplications, involving an autism susceptibility region, may have attenuated some features of PWS.Abbreviations: AS = Angelman Syndrome; ASD = Autism Spectrum Disorder; BMI = body mass index; CMA = chromosomal microarray; PWS = Prader-Willi Syndrome

Iron-overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron-overloaded subjects with Thal (n = 142; 54%M; age 25.8 +/- 8.1 years) and transfused sickle-cell disease (Tx-SCD; n = 199; 43%M, 24.9 +/- 13.2 years) to non-transfused SCD subjects (non-Tx-SCD; n = 64, 50%M, 25.3 +/- 11.3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0.001), hypogonadism (40% vs. 4%, P < 0.001), hypothyroidism (10% vs. 2%, P =

Although it is life saving, transfusion therapy has resulted in the majority of sickle cell anemia and thalassemia patients being at risk for hemosiderosis-induced organ damage. It is unknown whether the complications of iron overload are affected by the underlying disease. In order to address this problem, we compared the prevalence of organ dysfunction in both groups of patients receiving chronic transfusion therapy (beta thalassemia, N = 30; sickle cell anemia, N = 43). Both groups had similar quantitative liver iron. Thalassemia patients had greater cardiac disease (20% vs. 0%), growth failure (27% vs. 9%), and endocrine failure (37% vs. 0%). The strongest predictors of combined endocrine and cardiac disease in multivariate analysis were duration of chronic transfusion (P = 0.03) and diagnosis (P = 0.03). Quantitative liver iron concentration on a single liver biopsy was not predictive of cardiac or endocrine injury. Viral hepatitis is the strongest predictor of hepatocellular damage (P = 0.009), while the development of liver fibrosis is more closely related to liver iron concentration (P = 0.04). In conclusion, sickle cell anemia and thalassemia differ in the prevalence of organ injury. This difference is related to the duration of iron exposure and the specific hemoglobinopathy. A prospective study with a larger number of subjects is needed to confirm the relationships between specific diagnosis, liver iron concentration over time, and organ dysfunction.

We report a case of a girl with clinical features of Peters' Plus Syndrome (PPS) (association of anterior eye chamber defects; peculiar facies; cleft lip/palate; brachymelia; developmental delay; growth retardation) and documented growth hormone deficiency (height -3.5 SDS at chronological age 5 years 8 months; low growth factors; bone age delay; growth velocity 4.4 cm/year (

HANBIT is a magnetic mirror confinement device. Recently, after finishing the first campaign for the basic system development, it started the second campaign for high-temperature plasma confinement physics study in a mirror configuration. Here, we introduce briefly the HANBIT device and report initial physics experiment results on RF-plasma heating and confinement in the simple mirror configuration. It appears that the discharge characteristics of HANBIT are quite different from those in other mirror devices, and an explanation is presented to clarify the difference.

Prader-Willi Syndrome (PWS), first described in 1956, is a unique genetic condition with a prevalence of 1 in 10,000 - 25,000. Features include severe lifelong hypotonia, insatiable appetite, short stature, obsessive-compulsive behaviour, morbid obesity, hypogonadism, kyphosis, scoliosis and osteoporosis. Studies beginning in the 1970s demonstrated that PWS is associated with a deficiency in growth hormone. Growth hormone treatment in children with PWS improves linear growth and more importantly leads to an increased muscle mass, bone mineral density and physical performance. In mid-2000, growth hormone became the first pharmaceutical approved in the US and Europe for the treatment of childhood PWS. It is now considered an essential part of comprehensive care for this condition. Ongoing studies address issues of growth hormone dosage, long-term efficacy, effects on neonatal and childhood growth and development and effects in adults with PWS.

Introduction: The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. Methods: In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. Results: Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 ± 7 vs. 256 ± 30 ng/ml, p < 0.001; free IGF-I: 1.3 ± 0.3 vs. 3.5 ± 0.6 ng/ml, p < 0.01; IGF-II: 177 ± 28 vs. 618 ± 30 ng/ml, p < 0.001; IGFBP-3: 1,230 ± 136 vs. 3,665 ± 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 ± 40 vs. 90 ± 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 ± 296 vs. 1,303 ± 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). Conclusion: Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.

Standard weight-for-age and height-for-age charts have been used for many years to assess growth and body compositions of children, including curves specific to the Prader-Willi syndrome (PWS). However, a number of direct measures of body compositions have been developed in recent years. Dural-energy x-ray absorptiometry (DXA) provides a measure of bone mineral content and bone mineral density for the whole body and at specific bone regions (spine, hip, forearm). This technology now has been extended to include assessment of the body's lean tissue mass and body fat mass. An alternate technique, called bioelectrical impedance analysis (BIA), has gained wide use in recent years as an indirect measure of the fat-free mass. The older, underwater weighing method is giving way to the air-displacement plethysmographic technique for assessing body fatness. Total body potassium still remains the method of choice for a direct assessment of body cell mass, and body nitrogen is recognized as the best assay for body protein mass. Imaging techniques, such as a computer tomography and magnetic resonance imaging, continue to receive increasing attention for body composition assays, especially for the subcutaneous vs. visceral distribution of body fat. Although total body water and extracellular water can be measured by dilution techniques, these methods are slowly being replaced by the BIA assay. When these various techniques are used in combination, the patient's nutritional status can be obtained based on a comprehensive 5-level multicompartment model of the body composition. Each of these methods will be reviewed, and their specific strengths and limitations presented, relative to their application for assessing changes in body composition of the PWS patient.▪ The Endocrinologist 2000; 10: 57S-62S

Prader-Willi syndrome (PWS) is a disabling condition characterized by hypotonia, hyperphagia, obesity, short stature, delayed or absent puberty, and mental retardation. The syndrome complex was first described in 1956 by Dr. Andrea Prader and colleagues [1]. In the 1980s, a characteristic genetic defect was identified involving deletion of paternal alleles at chromosome 15q11-13 [2-6]. This occurs by deletion of alleles on the paternal copy of chromosome 15q, an absent paternal chromosome 15q with maternal disomy, or, rarely, by mutations of the imprinting center of chromosome 15q. The estimated population prevalence of PWS is 1 in 15,000 live births.

Short stature, decreased muscle mass (hypotonia), increased body fat, decreased bone mineral density and other somatic abnormalities are major causes of morbidity and social limitation in individuals with Prader-Willi syndrome. Detailed studies indicate that two major endocrine pathologies may account for many of these somatic abnormalities. A true deficiency of the growth hormone (GH)-insulin-like growth factor axis is a principal cause of the short stature and is probably a major contributor to the decreased muscle mass and osteopenia. Hypogonadotropic hypogonadism is the probable primary cause of osteopenia and osteoporosis. No other endocrine abnormalities have been specifically identified in Prader-Willi syndrome, although there may be increased risks of premature adrenarche and type 2 diabetes mellitus, both secondary to obesity. GH replacement therapy is effective in normalizing linear growth and also has positive effects on muscle mass and function, and on bone mineralization. Judicious gonadal steroid replacement may be effective in treating the osteopenia and preventing osteoporosis. GH and gonadal steroid replacement therapy should be considered for all patients with Prader-Willi syndrome.

Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

The activity of the hypothalamic-GH-insulin-like growth factor (IGF) network declines with age. It has recently been shown that increased cardiovascular mortality occurs in adults with GH deficiency. As hypercholesterolemia is common in GH-deficient adults, and because there is experimental evidence that GH may play a role in regulating plasma cholesterol, we decided to investigate the activity of the GH-IGF axis in an elderly population by measuring serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and to study their relationship with blood lipid levels. One hundred and thirty-two elderly subjects, 52 men and 80 women, were studied (age range, 60–91 yr). Men had significantly lower levels of IGFBP-3, high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) compared to the women, whereas IGF-I and IGF-II were only slightly lower. Using linear regression analysis, we observed an inverse relationship of age with IGF-I (r = −0.35; P < 0.001), IGF-II (r = 0.40; P < 0.001), IGFBP-3 (r = 0.52; P < 0.001), body mass index, and lipid levels. Univariate regression analysis showed a strong and positive correlation of both IGF-I and IGFBP-3 with HDL-C and ApoA1. Partial correlation analysis, after adjustment for age and body mass index, showed that IGFBP-3 and IGF-II were still significantly and positively related to HDL-C and ApoA1. Furthermore, a strong association was documented among IGF-I, IGF-II, and IGFBP-3. These data demonstrate that even in an elderly population, further aging is accompanied by a progressive decline in circulating IGF-I, IGF-II, and IGFBP-3, suggesting a continuing diminution of the GH-IGF axis throughout aging. Moreover, the strong correlation between HDL-C and an index of GH secretion, such as IGFBP-3, suggests that GH might play an important role in lipid metabolism in healthy elderly subjects.

We have studied molecular beam epitaxial growth of high-quality ZnSSe on GaAs substrates. From the results obtained by pyrometric oscillation behavior and X-ray rocking curve simulation, a new technique, called a three-step temperature correction method, is introduced. In this method, the temperature correction region is divided into T1 for compensating the heating effect by radiation, T2 for connecting the inverse gradient of temperature in T1 and T2, and T3 for compensating the temperature drop during ZnSxSe1 − x growth. Applying this method to ZnSxSe1 − x epitaxial layer growth on GaAs substrates, layers with better crystallinity are reproducibly grown as evaluated by the full-width at half-maximum of the double-crystal X-ray rocking curves, etch pit density, and photoluminescence. An etch pit density of ⩽ 5 × 103 cm−2 and photoluminescence broadening of about 1.8 meV at 4.2 K could be obtained for ZnSxSe1 − x with x = 0.06.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Children with chronic renal failure (CRF) have normal or high serum levels of GH, IGF-I, and IGF-II. Despite this, the serum of CRF patients has low IGF bioactivity, which may contribute to CRF growth failure. Recent studies suggest that excess IGF binding proteins (IGFBPs) in the approximately 35-kD fractions of CRF serum contribute to this low IGF bioactivity. This report characterizes a 29-kD form of IGFBP-3, IGFBP-3(29), which accumulates in the approximately 35-kD fractions of CRF serum and peritoneal dialysate. Deglycosylation and [125I]IGF ligand blot studies show that IGFBP-3(29) is a glycosylated IGFBP-3 fragment with low affinity for IGF peptides. Using an IGFBP-3 antibody column, IGFBP-3(29) was purified to homogeneity from the approximately 35-kD fractions of peritoneal dialysate from children with CRF. Compared with native IGFBP-3, pure IGFBP-3(29) has a 4-10-fold lower affinity for IGF-II and a 200-fold lower affinity for IGF-I. Consistent with the binding data, IGFBP-3(29) inhibited IGF-II-stimulated thymidine incorporation in chondrosarcoma cells, but was a less potent inhibitor than native IGFBP-3; also, native IGFBP-3 clearly inhibited IGF-I-stimulated thymidine incorporation in chondrosarcoma cells and potentiated IGF-I-stimulated aminoisobutyric acid uptake in bovine fibroblasts, but higher concentrations of IGFBP-3(29) had no effect on these IGF-I actions. Thus, the 29-kD IGFBP-3 form that accumulates in CRF serum and extravascular spaces is an IGFBP-3 fragment that may modulate IGF-II, but not IGF-I, effects on target tissues. Whether IGFBP-3(29) plays any role in the growth failure of children with CRF remains to be determined.

Modulation of growth factors by growth hormone in children with chronic renal failure. Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.05 mg/kg/day, and the studies were carried out at baseline and after 3 and 12 months. At baseline, serum insulin-like growth factor binding protein (IGFBP)-1 and -2 levels were, while IGFBP-3 levels were not, higher than those of children with normal renal function. In addition, height SDS at baseline correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0016), but did not correlate significantly with any other factor. After 12 months of study, the 30 children receiving rhGH showed: (i) greater increase in height (9.1 ± 2.8 vs. 5.5 ± 1.9 cm, P < 0.0001); (ii) increases in serum levels of IGF-I, IGF-II, free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in serum IGFBP-1 levels; and (iv) no significant difference in serum IGFBP-2 levels, when compared to the 14 control patients. The change in height SDS after 12 months of rhGH (+ 0.8) in the 30 treated children correlated significantly and positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF-II and free IGF-I levels measured during treatment. These observations suggest that, in children with growth failure associated with chronic renal failure: (i) IGFBP-2, and not IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth in part by increasing serum levels of IGF peptides; and (iii) linear growth is influenced by the balance between growth stimulating IGFs and growth inhibitory IGFBPs.

Background Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. Objective To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Design Multicenter, randomized, double-blind, placebo-controlled clinical trial. Setting The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Participants Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. Results After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Conclusion Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. Trial registration clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

Insulin is the principal regulator of hepatic insulin-like growth factor binding protein-1 (IGFBP-1) production, mediating the rapid decrease in plasma IGFBP-1 in response to nutritional intake. In this study, we defined IGFBP-1 regulation by insulin in upper and lower body obesity, conditions associated with insulin resistance and chronic hyperinsulinemia. Overnight postabsorptive IGFBP-1 levels in obese and nonobese women showed an inverse, nonlinear relationship with plasma insulin concentrations. Maximum suppression of IGFBP-1 was seen at 70-90 pmol/L plasma insulin. Both groups of obese women had mean fasting plasma insulin concentrations above this threshold level and, consequently, markedly suppressed IGFBP-1 levels. To assess the dynamics of insulin regulated IGFBP-1, 10 obese and 8 nonobese women were studied during sequential saline infusion (0-90 min), hyperinsulinemia (insulin infusion; 90-210 min) and hypoinsulinemia (somatostatin + GH infusion; 210-330 min). Insulin infusion rapidly decreased plasma IGFBP-1 levels in nonobese subjects (60% decrease in 2 h), but had little or no further suppressive effect in obese subjects. Complete insulin withdrawal resulted in a significant rise in plasma IGFBP-1 concentrations in all subjects, but the response was blunted in obese compared to nonobese groups. In contrast to plasma IGFBP-1, IGF-I concentrations did not vary during hyper- and hypoinsulinemic infusion periods and were not significantly different between groups. Basal GH levels were significantly higher in nonobese when compared to obese women, but did not change with infusions. In conclusion, low IGFBP-1 levels in obesity are related to elevated insulin levels which are, in turn, related to body fat distribution and insulin resistance. The chronically depressed levels of IGFBP-1 may promote IGF bioactivity as well as its feedback regulation of GH secretion, thus contributing to the metabolic and mitogenic consequences of obesity. In addition, our findings imply that hepatic insulin sensitivity in terms of IGFBP-1 production is preserved despite peripheral insulin resistance in obesity.

We examined the relationships between 4 glycated protein assays and home blood glucose monitoring (HBGM) in 26 children with poorly-controlled insulin-dependent diabetes mellitus (IDDM) during a period of improved management. At 2 week intervals for 6 visits (12 weeks in total), HBGM records were collected and a blood sample was obtained for measurement of glycated proteins and glucose. Assays included glycated hemoglobin (GHb) and glycated serum proteins (GP) by boronate affinity chromatography, hemoglobin A 1 C by PolyCAT A high performance liquid chromatography (HAC) and fructosamine (FA). All 4 glycated protein levels declined significantly over the 12 week period. Significant correlations between the glycated proteins and HBGM were observed over 2 week intervals. None of the 4 assays were affected by the glucose level in the sample. Changes in mean HBGM readings over 2 week intervals were correlated with both FA and GP with wide prediction intervals. Over cumulative 2 week intervals, which may more accurately reflect longitudinal trends, all 4 glycated proteins were correlated with mean HBGM readings. At each cumulative interval, GHb and GP showed the largest variation with MBG, while FA showed the least variation with MBG. Our data indicate that of the 4 assays tested, FA has limited clinical value as compared to other glycated protein assays, whereas assays based on boronate affinity chromatography (GHb and GP) provide the most useful clinical indicators of short-term changes in glycemic control. The clinical utility of a new HPLC method for determination of glycated hemoglobins is also demonstrated.

GH replacement in Prader-Willi syndrome (PWS) children has well-defined benefits and risks and is used extensively worldwide. Its use in PWS adults has been limited by documentation of benefits and risks, as determined by larger multisite studies.Our objective was to evaluate the effectiveness and safety of GH in GH-deficient genotype-positive PWS adults.We conducted a 12-month open-label multicenter trial with 6-month dose-optimization and 6-month stable treatment periods.The study was conducted at outpatient treatment facilities at four U.S. academic medical centers.Lean and obese PWS adults with diverse cognitive skills, behavioral traits, and living arrangements were recruited from clinical populations.Human recombinant GH (Genotropin) was initiated at 0.2 mg/d with monthly 0.2-mg increments to a maximum 1.0 mg/d, as tolerated.Lean body mass and percent fat were measured by dual-energy x-ray absorptiometry.Lean body mass increased from 42.65 +/- 2.25 (se) to 45.47 +/- 2.31 kg (Por = 0.0001), and percent fat decreased from 42.84 +/- 1.12 to 39.95 +/- 1.34% (P = 0.025) at a median final dose of 0.6 mg/d in 30 study subjects who completed 6-12 months of GH. Mean fasting glucose of 85.3 +/- 3.4 mg/dl, hemoglobin A1c of 5.5 +/- 0.2%, fasting insulin of 5.3 +/- 0.6 microU/ml, area under the curve for insulin of 60.4 +/- 7.5 microU/ml, and homeostasis model assessment of insulin resistance of 1.1 +/- 0.2 were normal at baseline in 38 study initiators, including five diabetics, and remained in normal range. Total T(3) increased 26.7% from 127.0 +/- 7.8 to 150.5 +/- 7.8 ng/dl (P = 0.021) with normalization in all subjects, including six (20%) with baseline T(3) values at least 2 sd below the mean. Mildly progressive ankle edema was the most serious treatment-emergent adverse event (five patients).This multicenter study demonstrates that GH improves body composition, normalizes T(3), and is well tolerated without glucose impairment in PWS genotype adults.

This paper describes the development of a high-performance single-phase line-interactive Dynamic voltage Restorer, which is composed of a full-bridge inverter and super- capacitors. The operational feasibility was verified through computer simulations with PSCAD/EMTDC software, and experimental works with 3 kVA prototype. The developed system can compensate the input voltage sag and interruption within 2 ms, in which the maximum allowable duration of voltage interruption is 2 seconds. It can be effectively used to compensate the voltage interruption in the sensitive load, such as computer, communication equipment, automation equipment, and medical equipment.

Isolated growth hormone deficiency (IGHD) represents conditions of GH deficiency that are not necessarily associated with other pituitary hormone deficiencies or with an organic lesion. Three sub-categories of IGHD have been clinically identified (IGHD types 1–3), and IGHD type 1 has been further separated into IGHD types 1a and b. However, this clinical sub-categorization of IGHD may need reconsideration due to the recent identification of molecular heterogeneity within each sub-type of IGHD. In a small number of children with IGHD, defects in the GH, GH-releasing hormone receptor (GHRH-R), and GH1 genes have been identified. In most cases, no cause for IGHD can be identified; however, the proportion of idiopathic IGHD cases may be decreasing due to identification of causative factors. The phenotype of IGHD is variable depending in part on the underlying genetic disorders in the affected individuals. Several studies have focused on the usefulness of MRI findings in patients with GHD but anatomic abnormalities of the pituitary gland are variable. We review current studies and the clinical, biochemical, and molecular features described for different groups of affected individuals with IGHD.

Pediatric pituitary diagnosis is complicated by the unique developmental characteristics, secretory patterns and regulation of each pituitary hormone system. Although dynamic test procedures have been described, validation of each procedure is limited and universally agreed diagnostic criteria are not available. Clinical acumen, experience and judgment continue to be primary elements of pituitary diagnosis.

Pituitary gigantism, a condition of endogenous growth hormone (GH) hypersecretion prior to epiphyseal closure, is a rare condition. In the adult condition of GH excess, acromegaly, the occurrence of type 2 diabetes mellitus (T2DM) and diabetic ketoacidosis (DKA) have been reported, with resolution following normalization of GH levels. We report the case of a 16-year-old male with pituitary gigantism due to a large invasive suprasellar adenoma who presented with T2DM and DKA. Despite surgical de-bulking, radiotherapy and medical treatment with cabergoline and pegvisomant, GH and insulin-like growth factor-I (IGF-I) levels remained elevated. However, the T2DM and recurrent DKA were successfully managed with metformin and low-dose glargine insulin, respectively. We review the pathophysiology of T2DM and DKA in growth hormone excess and available treatment options.

This work investigates NMOSFETs on thick biaxially strained silicon for digital logic applications. Strain and long channel mobility enhancement are shown to be maintained for strained films as thick as 300 nm, 15 times thicker than the equilibrium critical thickness, and misfit-dislocation induced off-current leakage is shown to be completely eliminated for tSi equiv 100 nm. Significant performance enhancement is achieved: short channel DC NMOS drive current is up to 18% higher than comparable unstrained silicon devices and thin strained silicon devices

Obesity or overweight is arguably the most obvious physical feature of PWS. Perhaps for this reason, more than 80% of the over 1,600 publications to date regarding PWS mention, discuss, and/or explore the topic of obesity. Despite this attention, the diagnosis, pathogenesis, optimal treatment, monitoring, and outcome of this condition in PWS remain undefi ned. In addition, the paradox of the underweight infant with PWS evolving into an overweight child and adult has led to considerable speculation regarding pathophysiology. In addition to the obvious physical feature of obesity/overweight and questions regarding optimal nutritional management, a variety of gastrointestinal (GI) disorders have been identifi ed in PWS, with frequencies similar to respiratory disorders. A description of the GI system and related disorders in PWS will start this chapter, followed by a discussion of obesity and related nutrition and medical issues. Finally, a discussion of analytical methods for body composition analysis and their application in PWS is presented (see Chapter 5 for a complete outline of Part II).

In the previous edition of this textbook, various lines of evidence for the occurrence of a defi ciency in the growth hormone (GH) axis were reviewed as one of several sections in a chapter entitled “Endocrine and Metabolic Aspects of Prader-Willi Syndrome.” At that time, it was suggested that GH therapy may have benefi cial effects on growth and body composition in individuals with PWS. Over the succeeding decade, a number of scientifi c investigations have provided defi nitive evidence in support of these suggestions. In 2000, biosynthetic GH became the fi rst and, to date, only medication to receive regulatory approval for treatment of children with PWS. In addition, it appears that GH may also have potential utility in adults with PWS. This chapter presents a comprehensive review of relevant physiology and pathophysiology of the GH system and GH treatment effi cacy and safety in PWS.

Diagnosis and Genetics.- Clinical Findings and Natural History of Prader-Willi Syndrome.- Diagnostic Criteria for Prader-Willi Syndrome.- Molecular Genetic Findings in Prader-Willi Syndrome.- Laboratory Testing for Prader-Willi Syndrome.- Medical Physiology and Treatment.- Medical Considerations in Prader-Willi Syndrome.- Gastrointestinal System, Obesity, and Body Composition.- Growth Hormone and Prader-Willi Syndrome.- Multidisciplinary Management.- Neurodevelopmental and Neuropsychological Aspects of Prader-Willi Syndrome.- Speech and Language Disorders Associated with Prader-Willi Syndrome.- Motor and Developmental Interventions.- Educational Considerations for Children with Prader-Willi Syndrome.- Tools for Psychological and Behavioral Management.- Educational and Social Issues for Adolescents with Prader-Willi Syndrome.- Transition from Adolescence to Young Adulthood: The Special Case of Prader-Willi Syndrome.- Vocational Training for People with Prader-Willi Syndrome.- Residential Care for Adults with Prader-Willi Syndrome.- Inpatient Crisis Intervention for Persons with Prader-Willi Syndrome.- Social Work Interventions: Advocacy and Support for Families.- A National Approach to Crisis Intervention and Advocacy.- Advocacy Issues: School Discipline and Expulsion.- Advocacy Issues: Sexuality.

This work proposes an algorithm that is developed for the video-oculograph method. It is used to detect a center of pupil for extraction of point of gaze in the eye image acquired by a charge coupled device camera and TV receiver card. The center of pupil could be detected accurately by applying the proposed algorithm in this study that removes noise effectively caused by eyelashes and image that is projected on pupil. In this study, we assume that the pupil is a perfect circle in the captured eye images.

How to construct an image source system for an arbitrarily shaped body is considered and its use in calculating the flow around a ship hull is demonstrated with the example of calculated wave pattern. Only the source strengths on the free surface, excluding the hull surface sources, play the role of unknowns by the use of this concept. The full nonlinear free surface boundary conditions are satisfied.

The KSTAR (Korea Superconducting Tokamak Advanced Research) project is the major effort of the Korean National Fusion Program to design, construct, and operate a steady-state-capable superconducting tokamak. The project is led by Korea Basic Science Institute and shared by national laboratories, universities, and industry along with international collaboration. It is in the conceptual design phase and aims for the first plasma by mid 2002. The key design features of KSTAR are: major radius 1.8 m, minor radius 0.5 m, toroidal field 3.5 T, plasma current 2 MA, and flexible plasma shaping (elongation 2.0; triangularity 0.8; double-null poloidal divertor). Both the toroidal and the poloidal field magnets are superconducting coils. The device is configured to be initially capable of 20 s pulse operation and then to be upgraded for operation up to 300 s with non-inductive current drive. The auxiliary heating and current drive system consists of neutral beam, ICRF, lower hybrid, and ECRF. Deuterium operation is planned with a full radiation shielding.

Postexercise facilitation (PEF) with clinical reflexes, H-reflex, and T-reflexes at the ankle and knee was systematically studied in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS). PEF was observed in ankle and knee deep tendon reflexes in five patients, in H-reflex in three patients, and in T-reflexes in six patients. When all reflex tests were combined, 7 (43.7%) of 16 patients showed PEF by at least one test. The authors conclude that the PEF of reflexes, the most helpful diagnostic clinical marker for LEMS, is not common.

The possible occurrence of increased non-enzymatic glycosylation of serum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP-3 and insulin-like growth factor-1 (IGF-I) were investigated. We measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled non-insulin-dependent diabetes (type 2) and from age-matched non-diabetic controls. Type 2 diabetic patients had significantly higher glycated serum protein (GlyP) levels. GlyP significantly correlated with age in the control (r = 0.315, P, Facultad de Ciencias Médicas