p-Cresyl sulfate and indoxyl sulfate in pediatric patients on chronic dialysis / 소아과

PURPOSE: Indoxyl sulfate and p-cresyl sulfate are important protein-bound uremic retention solutes whose levels can be partially reduced by renal replacement therapy. These solutes originate from intestinal bacterial protein fermentation and are associated with cardiovascular outcomes and chronic kidney disease progression. The aims of this study were to investigate the levels of indoxyl sulfate and p-cresyl sulfate as well as the effect of probiotics on reducing the levels of uremic toxins in pediatric patients on dialysis. METHODS: We enrolled 20 pediatric patients undergoing chronic dialysis; 16 patients completed the study. The patients underwent a 12-week regimen of VSL#3, a high-concentration probiotic preparation, and the serum levels of indoxyl sulfate and p-cresyl sulfate were measured before treatment and at 4, 8, and 12 weeks after the regimen by using fluorescence liquid chromatography. To assess the normal range of indoxyl sulfate and p-cresyl sulfate we enrolled the 16 children with normal glomerular filtration rate who had visited an outpatient clinic for asymptomatic microscopic hematuria that had been detected by a school screening in August 2011. RESULTS: The baseline serum levels of indoxyl sulfate and p-cresyl sulfate in the patients on chronic dialysis were significantly higher than those in the children with microscopic hematuria. The baseline serum levels of p-cresyl sulfate in the peritoneal dialysis group were significantly higher than those in the hemodialysis group. There were no significant changes in the levels of these uremic solutes after 12-week VSL#3 treatment in the patients on chronic dialysis. CONCLUSION: The levels of the uremic toxins p-cresyl sulfate and indoxyl sulfate are highly elevated in pediatric patients on dialysis, but there was no significant effect by probiotics on the reduction of uremic toxins in pediatric dialysis patients. Therefore, studies for other medical intervention to reduce uremic toxins are also necessary in pediatric patients on dialysis.

Continuous renal replacement therapy in neonates weighing less than 3 kg / 소아과

PURPOSE: Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for supporting critically ill pediatric patients. However, a few studies present have reported CRRT use and outcome in neonates weighing less than 3 kg. The aim of this study is to describe the clinical application, outcome, and complications of CRRT in small neonates. METHODS: A retrospective review was performed in 8 neonatal patients who underwent at least 24 hours of pumped venovenous CRRT at the Samsung Medical Center in Seoul, Korea, between March 2007 and July 2010. Data, including demographic characteristics, diagnosis, vital signs, medications, laboratory, and CRRT parameters were recorded. RESULTS: The data of 8 patients were analyzed. At the initiation of CRRT, the median age was 5 days (corrected age, 38(+2) weeks to 23 days), and the median body weight was 2.73 kg (range, 2.60 to 2.98 kg). Sixty-two patient-days of therapy were reviewed; the median time for CRRT in each patient was 7.8 days (range, 1 to 37 days). Adverse events included electrolyte disturbances, catheter-related complications, and CRRT-related hypotension. The mean circuit functional survival was 13.9+/-8.6 hours. Overall, 4 patients (50%) survived; the other 4 patients, who developed multiorgan dysfunction syndrome, died. CONCLUSION: The complications of CRRT in newborns are relatively high. However, the results of this study suggest that venovenous CRRT is feasible and effective in neonates weighing less than 3 kg under elaborate supportive care. Furthermore, for using potential benefit of CRRT in neonates, efforts are required for prolonging filter survival.

LIN28B polymorphisms are associated with central precocious puberty and early puberty in girls / 소아과

PURPOSE: Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. METHODS: Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. RESULTS: Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. CONCLUSION: The results of the present study showed that non-AC haplotypes of LIN28B had a significant association with PP in girls.

Changes in Glycogen and Glycosaminoglycan Levels in Hepatocytes of Iduronate-2-Sulfatase Knockout Mice before and after Recombinant Iduronate-2-Sulfatase Supplementation

PURPOSE: Mucopolysaccharidosis II (MPS II) is a lysosomal storage disorder caused by a deficiency of iduronate-2 sulfatase (IdS), which is involved in the degradation of glycosaminoglycan (GAG). In this study, the frequency of fasting hypoglycemia in patients with MPS II was investigated and changes in accumulation of glycogen and GAG in the hepatocytes of IdS-knockout (KO) mice were evaluated before and after recombinant IdS enzyme replacement therapy (ERT). MATERIALS AND METHODS: Plasma glucose levels were evaluated after an 8-hour fast in 50 patients with MPS II. The IdS-KO mice were divided into three groups (group 2; saline, group 3; 0.15 mg/kg of IdS, and group 4; 0.5 mg/kg of IdS); wild-type mice were included as controls (group 1). ERT was initiated intravenously at four weeks of age, and continued every week until 20 weeks of age. RESULTS: The mean glucose level after an 8-hour fast was 94.1 +/- 23.7 mg/dL in the patients with MPS II. Two (4%) out of 50 patients had fasting hypoglycemia. For the mice, GAG in the lysosomes nearly disappeared and glycogen particles in the cytoplasm were restored to the normal range in group 4. CONCLUSION: Glucose metabolism in patients with MPS II appeared to function well despite hepatocytic GAG accumulation and hypothetical glycogen depletion. A higher dose of IdS infusion in MPS II mice led to disappearance of lysosomal GAG and restoration of glycogen to the cytoplasm of hepatocytes.

Influence of VEGF Genetic Polymorphism on Peritoneal Solute Transport in Pediatric Dialysis Patients

PURPOSE: Genetic and clinical factors can influence the permeability of the peritoneal membrane. The peritoneal equilibration test (PET) is helpful in measuring peritoneal permeability in peritoneal dialysis (PD). We investigated the influence of genetic polymorphism of vascular endothelial growth factor (VEGF) on the PET parameters. METHODS: Pediatric patients who underwent PET within 12 months of initiating PD at Seoul National University Children's Hospital and Samsung Medical Center were selected. The patients with positive history of peritonitis before PET were excluded. The VEGF -2578C/A, -14978T/C, -1154G/A, -634G/C, and +936C/T single-nucleotide polymorphisms were genotyped. RESULTS: The mean 4-hour dialysate-to-plasma ratio for creatinine (D/P creatinine) and the mean 4-hour dialysate glucose to baseline dialysate glucose ratio (D/D0 glucose) were 0.56+/-0.13 and 0.43+/-0.11, respectively. The patients with haplotype CTGGC showed higher 4-hour D/P creatinine (0.67+/-0.12 vs 0.50+/-0.09, P=0.007) and lower 4-hour D/D0 glucose (0.35+/-0.12 vs 0.47+/-0.08, P=0.037) than those without haplotype CTGGC. CONCLUSION: The VEGF genetic polymorphism may influence the peritoneal solute transport.

Correlation between Hyperghrelinemia and Carotid Artery Intima-Media Thickness in Children with Prader-Willi Syndrome

PURPOSE: Prader-Willi syndrome (PWS) is a genetic disorder characterized by childhood-onset obesity and endocrine dysfunction that leads to cardiovascular disability. The objective of the study is to assess the relationship between carotid intima-media thickness (IMT) and atherosclerotic risk factors. MATERIALS AND METHODS: Twenty-seven PWS children and 24 normal controls were enrolled. Correlations of IMT with atherosclerotic risk factors were assessed. RESULTS: IMTs in the PWS group did not differ from those in the controls (p = 0.172), although total ghrelin levels were higher in the PWS children (p = 0.003). The multivariate analysis revealed positive correlations between total ghrelin levels (rho = 0.489, p = 0.046) and IMT in the PWS group and between body mass index-standard deviation score (BMI-SDS) (rho = 0.697, p = 0.005) and IMT in the controls. CONCLUSION: Considering the positive correlation of IMT with total ghrelin levels and the high level of ghrelin in PWS children, a further study is warranted to evaluate the role of elevated ghrelin on atherosclerosis for PWS.

Development of Korean Academy of Medical Sciences Guideline Rating the Physical Impairment; Kidney, Bladder, Urethra, Male and Female Reproductive Systems (Preliminary Report)

For the evaluation of the kidney impairment, serum creatinine concentrations or glomerular filtration rates are mainly used, and the conditions of solitary or transplanted kidney and chronic dialysis are also taken into the considerations. Some symptoms and signs of the chronic renal disability in spite of adequate treatment add one additional grade. For evaluating bladder and urethral impairment, the criteria include voiding symptoms and signs. The patients with urinary diversions have impairment grades depending on the alteration of upper urinary tract function. For penile impairment, the degrees are evaluated using the international index of erectile function, nocturnal penile tumescence and color doppler ultrasonography. For evaluating impairment of other male reproductive organs, functional and anatomical changes of these organs, analysis of the semen or hormones and the state of solitary testis are used as the criteria. For evaluating impairment of female reproductive organs, pregnancy potential, requirement of continuous treatment and the ability of sexual intercourse are used. Also, degree of impairment is modified according to the ages in evaluating female reproductive systems. We have tried to make this evaluation system objective, scientific, and convenient, but still find it leaving much to be desired.

Current Status of Children on Peritoneal Dialysis in Korea: A Cross-Sectional Multicenter Study

PURPOSE: Peritoneal dialysis (PD) is the major form of dialysis in use for infants and children with end-stage renal disease (ESRD). The aim of this study was to gain insight into the current status of children on PD in Korea. METHODS: In May 2008, questionnaires were sent to the pediatric nephrologists via e-mail. Four centers replied and those data were reviewed. RESULTS: A total of 103 patients were included in this study. Male to female ratio was 1.6:1. Mean age was 11.5+/-4.9 years (0-19 years). Primary renal diseases diagnosed were as follows: primary glomerular disease (34%), chronic pyelonephritis-reflux nephropathy (14.6%), systemic disease (9.7%), renal hypoplasia/dysplasia (8.7%), heredofamilial disease (6.8%), vascular disease (3.9%), drug-induced nephropathy (1.0%), and unknown (12.6%). PD modalities were as follows: CAPD (42.7%), CCPD (27.2%), NIPD (11.7%), and Hybrid (18.4%). Weekly total Kt/V was 2.1+/-0.7 (0.3- 4.1). Results of peritoneal equilibrium test were as follows: low 36.8%, low average 31.6%, high average 19.7%, and high 11.8%. Z-score for weight was -1.00+/-1.20 (-4.54~+2.50). Z-score for height was -1.55+/-1.65 (-9.42~+1.87). Growth hormone was administered in 24.3% of patients. Anti-hypertensive drugs were administered in 64.0% of patients. Laboratory findings were as follows: hemoglobin 10.5+/-1.4 g/dL, calcium 9.7+/-0.7 mg/dL, phosphorus 5.4+/-1.4 mg/dL, and parathyroid hormone 324.2+/-342.8 pg/mL. CONCLUSION: Primary glomerular disease was the most common cause of ESRD. CAPD was the most prevalent PD modality. Low and low average peritoneal transport type were common. Growth disturbance were noted in many patients. Some patients had hypertension even with anti- hypertensive drugs. Calcium-phosphorus levels were maintained adequately, but many patients had secondary hyperparathyroidism.

Comparative Study of the Effects of Different Growth Hormone Doses on Growth and Spatial Performance of Hypophysectomized Rats

This study was designed to examine the effects of recombinant human growth hormone replacement on somatic growth and cognitive function in hypophysectomized (HYPOX) female Sprague-Dawley rats. Rats (5 per group) were randomized by weight to 3 experimental groups: group 1, administered 200 microgram/kg of GH once daily for 9 days; group 2, administered 200 microgram/kg of GH twice daily; and group 3, administered saline daily. Somatic growth was evaluated by measurement of body weight daily and of the width of the proximal tibial growth plate of the HYPOX rats. Cognitive function was evaluated using the Morris water maze (MWM) test. The results indicated that GH replacement therapy in HYPOX rats promoted an increase in the body weight and the width of the tibial growth plate in a dose-dependent manner. On the third day of the MWM test, the escape latency in the GH-treated groups 1 and 2 was significantly shorter than that in the control rats (P<0.001 and P=0.032, respectively), suggesting that rhGH improved spatial memory acquisition in the MWM test. Therefore it is concluded that rhGH replacement therapy in HYPOX rats stimulates an increase in somatic growth in a dose-dependent manner and also has beneficial effects on cognitive functions.

Peritoneal Dialysis Associated Peritonitis and Empirical Antibiotics Therapy in Korean Children with Chronic Renal Failure

PURPOSE: This study aims to verify the effectiveness of initial empirical antibiotic choice recommended by the International Society for Peritoneal Dialysis(ISPD) guide among Korean children. METHODS: We have collected data on peritonitis from January 2001 to December 2007 in Samsung Medical Center. RESULTS: Of the 42 patients, 48 episodes of peritonitis had occurred in 21 patients. The rate of peritonitis was one episode over 35.3 patient-months. Mean dialysis duration before peritonitis was 18.06+/-15.81 months. Gram-positive organisms accounted for 58.3% of all episodes. Of the gram-positive organisms, the most common pathogen was Staphylococcus aureus(29.2 %), the next common pathogens were Coagulase negative staphylococcus(14.6%) and Streptococcus species(6.3%). 35.7% of gram-positive pathogens were resistant to 1st cephalosporin. However, in patients younger than 4 years old, 50% of gram-positive pathogens were resistant to 1st generation cephalosporin. 10 episodes of peritonitis were methicillin-resistant and were treated by vancomycin. Of the gram-negative organisms, E. coli was the most common (8.3%). 64.8% of all pathogens were sensitive to cephalothin or ceftazidime. CONCLUSION: The empirical therapy with 1st generation cephalosporin and ceftazidime can be also effective to peritoneal dialysis associated peritonitis in Korean children. However, in patients younger than 4 years old, glycopeptide should be considered as the first empirical therapy in Korean children.

Effects and adverse-effects of growth hormone therapy in children with Prader-Willi syndrome: A two year study / 소아과

PURPOSE: The objective of this study was to evaluate the effects and adverse side-effects of growth hormone (GH) therapy in children with Prader-Willi syndrome (PWS). METHODS: Forty-one patients who had been treated with GH for more than two years (24 boys and 17 girls, mean age 7.3+/-3.3 years during treatment initiation) were enrolled for this study. RESULTS: After 2 years of GH therapy, the height and weight standard deviation scores (SDS) increased significantly (- 1.19+/-1.37 vs. - 0.02+/-1.45, and 1.02+/-2.42 vs. 1.63+/-2.22, P<0.002); however the percentage body fat decreased (44.6+/-9.9% vs. 38.1+/-10.5%, P<0.001). Further, no change was observed in the thyroid and serum glucose levels, but the total cholesterol level decreased. GH therapy did not impact glucose control in the patients with diabetes. The most common adverse effects of GH therapy were the progression of scoliosis and adenoid hypertrophy. CONCLUSION: GH therapy improved the height SDS and body composition in patients with PWS. However, GH should be used with caution in patients with scoliosis and adenoid hypertrophy.

A Case of Adrenocortical Tumor in a 16-Month-Old Boy Presenting with Virilization / 대한소아내분비학회지

A 16-month-old boy had signs of virilization such as penile enlargement and pubic hair since 13 months of age. Hormone evaluation indicated increased levels of 17-OH-progesterone, dehydroepiandrosterone- sulfate (DHEA-S) and testosterone. Initially he was diagnosed as simple virilizing type of congenital adrenal hyperplasia and hydrocortisone was given to him. After 2 months, his penile enlargement continued and we did not find gene mutation for 21-hydroxylase deficiency. Adrenal magnetic resonance imaging revealed a 3.5x2.7x4.4 cm size of adrenal mass consistent with an adrenocortical tumor. The patient underwent surgical excision of the well-encapsulated tumor with normalization of his hormone levels. Childhood adrenocortical tumors are rare and are not well characterized. Surgery is the definitive treatment for adrenocortical tumors and prognosis is often poor. We report a case of adrenocortical tumor in a 16-month-old boy presenting with virilization with review of literature.

The Post-transplant Lymphoproliferative Disorder after Renal Transplantation / 대한이식학회지

Post-transplant lymphoproliferative disorder (PTLD) is a B cell proliferative disorder that is associated with Eptstein-Bar (EBV). This is a heterogeneous group of conditions characterized by EBV-driven proliferation of B-lymphocytes in the face of impaired T-cell immune surveillance. While new treatment modalities are being tried with variable success, regular EBV surveillance and carefully monitored reduction of immunosuppression remain the mainstay of treatment. This paper reviews the current knowledge of this increasingly common complications in renal transplant recipients.

The Effect of Growth Hormone and the Factors Influencing Growth in Pediatric Chronic Peritoneal Dialysis Patients

PURPOSE: Growth failure is a common problem in chronic renal failure(CRF). We studied the effect of growth hormone(GH) treatment and the factors influencing growth on chronic peritoneal dialysis patients. METHODS: Seventeen patients who were treated with peritoneal dialysis and GH for more than one year were enrolled. Factors influencing growth such as age, height at start of GH treatment, total Kt/Vurea, residual renal Kt/Vurea, hemoglobin, albumin, BUN, creatinine, total CO2, calcium, phosphate and iPTH during GH treatment were compared between the growth group(increase in height-standard deviation score(Ht-SDS) after one year of GH treatment, n=11) and poor growth group(no increase in Ht-SDS after one year of GH treatment, n=6). RESULTS: The mean age at the start of dialysis was 7.7+/-5.2 years and the mean age at the start of GH treatment was 8.5+/-4.8 years. In the growth group, Ht-SDS at start of GH treatment was smaller(-1.72+/-1.00 vs. -0.77+/-0.88, P=0.048) and residual renal Kt/Vurea was better (1.54+/-0.51 vs. 0.15+/-0.26, P=0.02) than the poor growth group. After three years of GH treatment, Ht-SDS of the growth group was better than the poor growth group. CONCLUSIONS: GH treatment in children with peritoneal dialysis was more effective on patients who had more severe growth retardation. The reservation of residual renal function was important for improvement of effect of GH treatment. And the growth response during the first year of GH treatment may be predicted as the indicator for long-term response.

Chronic Dialysis in Infants and Children Under 2 Years of Age

PURPOSE: Dialysis in children with chronic renal failure presents with many difficulies. The purpose of this study is to find an improved method in chronic dialysis in infants and children less than 2 years of age by analyzing the experience with 10 cases. METHODS: A retrospective review of the medical records of 10 patients(6 boys and 4 girls) was conducted. The patients had chronic renal failure and underwent chronic dialysis at Samsung medical center from March 1999 to February 2007. RESULTS: At initiation of dialysis, the median age was 3 months old(22 days-20 months), the median body weight was 3.75 kg(2.2-10.3 kg), and the median serum creatinine level was 4.3 mg/dL(2.0-11.4 mg/dL). The median duration of dialysis was 29.5 months(3-62 months). Dysplastic kidney disease was the most common underlying renal disease. Two patients were treated with hemodialysis, 4 patients with peritoneal dialysis, and 4 patients eventually switched dialysis modality. Nine of the 10 patients took erythropoietin and anti-hypertensive drugs. At the end of the follow up period, 1 patient received kidney transplantation, 2 patients died due to sepsis, and 5 patients were treated with peritoneal dialysis. Two patients were lost to follow up. The most common complication of dialysis was infection. Achieving vascular access and maintaining proper catheter function were the most important factors in treating patients with hemodialysis. The growth status of patients was aggravated after 6 month of dialysis but improved after 1 year of dialysis. Patients showed better growth on peritoneal dialysis than hemodialysis. CONCLUSION: Chronic dialysis can be performed successfully in infants and children under 2 years of age. Vascular access was the main limitation of hemodialysis, and infection was the common problem in both hemodialysis and peritoneal dialysis. To improve the patients survival rate and quality of life, major efforts should be directed toward the prevention of infection and preservation of catheter function.

Comparison of Early Complications after Peritoneal Dialysis Catheter Implantation by Laparoscopic Surgery and Conventional Surgery in Children

PURPOSE: To assess the early complication of laparoscopic peritoneal dialysis catheter implantation in children. METHODS: Medical record review was carried out on 21 laparoscopic and 16 conventional peritoneal dialysis catheter implantations which were performed in 31 children under 18 years of age between 2002 and 2006. All medical records were retrospectively analyzed. The patients were followed until 2 months after catheter placement. Patient characteristics and catheter-related complications, such as significant bleeding, leakage, obstruction, migration, insertion site infection and peritonitis during the first 60 days after implantation were recorded. RESULTS: After conventional operation, dialysate leakage occurred in 2 of 16 cases and all cases improved after conservative management. In 1 case, significant bleeding occurred and re-operation was performed. Three cases of obstruction due to migration were reported, 2 cases underwent reoperation and 1 case improved without intervention. After laparoscopic surgery, outflow obstruction occurred in 1 out of 21 cases, which was caused by adhesion after several reinsertions of the catheter and recurrent peritonitis. No migration was noted after laparoscopic surgery. There was no significant difference in the complication rate between the two groups. CONCLUSION: Laparoscopic peritoneal dialysis catheter placement is feasible in children of all age groups, with at least equivalent functional results compared to conventional surgery. The additional advantage of laparoscopic catheter insertion is the option to identify and eliminate anatomical risk factors, such as intra-abdominal adhesions, and to perform partial omentectomy without additional incisions.

Peptide YY, Cholecystokinin, Insulin and Ghrelin Response to Meal did not Change, but Mean Serum Levels of Insulin is Reduced in Children with Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Renal replacement therapy in children with acute renal failure / 소아과

Many dialysis modalities such as peritoneal dialysis (PD), hemodialysis (HD) and continuous hemofiltration or hemodialysis (CRRT) are available for the management of pediatric patients with acute renal failure (ARF). PD is a relatively simple, inexpensive modality and can be used in hemodynamically unstable patients. But, it may not be the optimal therapy for patients with severe volume overload or life threatening hyperkalemia. HD is the preferred modality for the treatment of severe volume overload, severe hyperkalemia, but it needs vascular access. Improvements in the HD equipment have allowed HD to be performend in small children. Recents technological improvements in CRRT therapies have enabled pediatric patients who are less stable to be treated. CRRT is becoming the preferred method of acute therapy in pediatric intensive care units. A sound knowledge of the underlying principles of dialysis and awareness of recent technological advancements in differnet dialysis modalities will hopefully result in improved management of children with ARF.

Ghrelin Levels in Gastric Mucosa before and after Eradication of Helicobacter pylori

BACKGROUND/AIMS: The relationship between Helicobacter pylori infection and ghrelin is controversial. We compared ghrelin levels in gastric mucosa and plasma between H. pylori-positive and -negative subjects, and between before and after H. pylori eradication. METHODS: We compared the ghrelin levels in the antrum, body, and fundus between H. pylori-positive and -negative subjects; in stomach tissues between before and after H. pylori eradication; and in plasma and tissue in 10-person cohorts between before and after H. pylori eradication therapy. Body mass index, age, and sex were controlled for when comparing ghrelin levels. RESULTS: Stomach ghrelin levels (in the antrum, body, and fundus) did not differ significantly between H. pylori-positive and -negative samples (p=0.095, 0.316, and 0.897, respectively), or between before and after H. pylori eradication (p=0.19, 0.178, and 0.513, respectively). In the ten-person cohort study, plasma ghrelin levels in the eight H. pylori-positive subjects were 2,260 pg/mL (range, 1,280-3,770 pg/mL) and 1,900 pg/mL (range, 1,350-5,200 pg/mL) before and after eradication therapy (p=0.871). Stomach ghrelin levels did not differ significantly in the eight H. pylori-positive subjects between before and after H. pylori eradication (p=0.732, 0.618, and 0.435 in the antrum, body, and fundus, respectively), or between six eradicated and two noneradicated subjects (p=0.071, 0.857, 0.429, and 0.857 in the antrum, body, fundus, and plasma, respectively). CONCLUSIONS: These results show that H. pylori infection has no effect on stomach ghrelin levels and that eradication therapy does not influence plasma or tissue ghrelin levels.

Marked Suppression of Ghrelin Concentration by Insulin in Prader-Willi Syndrome

The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS.