-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to determine the effectiveness of laparoscopic cholecystectomy in children with biliary dyskinesia.
Reports of children with an abnormal cholecystokinin (CCK)-stimulated HIDA scan between January 2001 and July 2006 who underwent laparoscopic cholecystectomy were reviewed. Postoperatively, a 23-item Likert scale, symptom questionnaire was administered to parents.
Sixty-four children with chronic abdominal pain and no gallstones on ultrasound had an abnormal CCK-HIDA scan. Twenty-three children (median age, 14 years; 16 girls), with mean (SD) ejection fraction of 17% (8), underwent laparoscopic cholecystectomy and were further analyzed. Preoperatively, these children had right upper quadrant/epigastric pain (78%), nausea (52%), vomiting (43%), and generalized abdominal pain (22%) lasting for a median of 3 months (range, 1 month to 2.5 years). Median postoperative follow-up was 2.7 years. Sixteen (70%) parents completed the questionnaire. Of those who responded, 63% indicated that their children had no abdominal pain, 87% had no vomiting, and 69% had no nausea in the month preceding the questionnaire. Overall, 67% of parents indicated that their children's symptoms were completely relieved after cholecystectomy, whereas 7% indicated that the symptoms were not relieved.
Laparoscopic cholecystectomy is effective in providing both short-term and long-term improvement of symptoms in children with biliary dyskinesia.
Journal of Pediatric Surgery 07/2008; 43(6):1060-4. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of the study was to measure the effect of splenectomy on packed-cell transfusion requirement in children with sickle cell disease.
Thirty-seven sickle cell children who underwent splenectomies between January 2000 and May 2006 at a children's hospital were reviewed. Data were collected 6 months preoperatively to 12 months postsplenectomy. Paired t test, analysis of variance, and multivariable regression analyses were performed.
Of 37 children with median age 11 years (range, 2-18 years), 34 (21 males) had data that allowed analyses. Twenty-six had Hgb-SS, 5 had Hgb-SC, and 3 had Hgb S-Thal. Laparoscopic splenectomy was attempted in 36 and completed successfully in 34 (94% success). The number of units transfused decreased by 38% for 0 to 6 months and by 45% for 6 to 12 months postsplenectomy. Postoperatively, hematocrit levels increased and reticulocytes concurrently decreased with a reduction in transfusion clinic visits. The decrease in transfusion was not influenced by spleen weight, age, or hemoglobin type. Two children had acute chest syndrome (6%), and 1 had severe pneumonia (3%).
Laparoscopic splenectomy can be successfully completed in sickle cell children. Splenectomy significantly reduces the packed red cell transfusion requirement and frequency of clinic visits, in sickle cell children for at least 12 months postoperatively.
Journal of Pediatric Surgery 07/2008; 43(6):1052-6. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was conducted to determine the effect of age at diagnosis and length of ganglionated bowel resected on postoperative Hirschsprung-associated enterocolitis (HAEC).
Children who underwent endorectal pull-through (ERPT) between January 1993 and December 2004 were retrospectively reviewed. t Test, analysis of variance, Kaplan-Meier, and Cox's proportional hazards analyses were performed.
Fifty-two children with Hirschsprung disease (median age, 25 days; range, 2 days-16 years) were included. Nineteen (37%) had admissions for HAEC. Proportional hazards regression showed that HAEC admissions decreased by 30% with each doubling of age at diagnosis (P = .03) and increased 9-fold when postoperative stricture was present (P < .01), after controlling for type of ERPT, trisomy 21, transition zone level, and preoperative enterocolitis. Thirty-six children, with age at initial operation less than 6 months, were grouped based on length of ganglionated bowel excised (A [5 cm] and B [>5 cm]). No significant difference in the number of HAEC admissions during initial 2 years post-ERPT was seen between groups A (n = 18) and B (n = 18). The study had a power of 0.8 to detect a difference of 1 admission over 2 years.
Children diagnosed with Hirschsprung disease at younger ages are at a greater risk for postoperative enterocolitis. Excising a longer margin of ganglionated bowel (>5 cm) does not seem to be beneficial in decreasing HAEC admissions.
Journal of Pediatric Surgery 06/2008; 43(6):1115-23. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Laparoscopic and open pyloromyotomies are equally safe and effective, with the principal benefit of laparoscopy being better cosmesis. The goal of this study was to measure the perceived value of laparoscopic pyloromyotomy.
Four hundred sixteen subjects (177 college freshmen, 126 first-year medical students, and 101 parents) were asked to complete a questionnaire after photographs of mature pyloromyotomy (open and laparoscopic) scars were shown to them. To measure the perceived value, subjects' willingness to pay hypothetical additional out-of-pocket expenses for their preferred operation was assessed. Data were analyzed using Cochran-Mantel-Haenszel test, t test and multivariable regression.
Four hundred four surveys were complete. Overall, 74% preferred the appearance after laparoscopy. Eighty-eight percent would pay an additional out-of-pocket amount for their daughter and 85% for their son to have the cosmetic outcome after laparoscopy. Respondents were willing to pay more for their daughters (P < .0001) and sons (P < .0001) than themselves. As expected, income level (P < .0001) influenced the willingness to pay, whereas ethnicity, education, number of children, and sex did not.
The cosmetic benefit of laparoscopic pyloromyotomy was valued by a wide demographic with 85% being willing to pay additional expenses for their children to have smaller scars.
Journal of Pediatric Surgery 02/2008; 43(1):92-6; discussion 96. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The goal of this study was to estimate the 2-year cumulative thrombosis-free survival of basilic vein transposition (BVT) and brachiocephalic fistulae in children.
All children who underwent BVT or brachiocephalic fistula construction at a tertiary care children's hospital from June 2001 to July 2006 were reviewed. Kaplan-Meier analysis, log-rank test, and proportional hazards regression were done.
Sixteen children (7 girls) with inadequate forearm veins underwent creation of 18 fistulae (12 BVT, 6 brachiocephalic). Median age was 14 (9-19) years. Mean (+/-SE) operative times for BVT and brachiocephalic fistulae were 3.4 (+/- 0.6) hours and 1.9 (+/-0.4) hours, respectively. The overall 2-year cumulative survival rate was 74% (BVT, 66%; brachiocephalic fistula, 83%). Four fistulae failed (1 brachiocephalic, 3 BVT) and 14 fistulae were censored (5, patent fistula; 4, renal transplantation; 2, unrelated death; 1, elective conversion to peritoneal dialysis; 1, surgical ligation of fistula; 1, lost to follow-up). Of 18 fistulae, 6 underwent additional interventions (4, percutaneous angioplasty; 2, surgical thrombectomy). There were no significant differences in survival times based on fistula type, prior transplant status, age, or operative time.
Brachiocephalic and BVT fistulae create reliable hemodialysis access for children who have inadequate forearm veins to allow construction of more distal fistulae.
Journal of Pediatric Surgery 02/2008; 43(1):147-51. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a murine model of intestinal injury, we hypothesized that Toll-like receptor 2 (TLR2), a recognition molecule for commensal bacteria, plays an important role in the development of mucosal immunity and is protective against ischemia/reperfusion injury via the modulation of both innate and acquired immunity.
Interventional laboratory study.
Academic medical research center.
Four-week-old C57BL/6 wild-type (n = 12) and C57BL/6 TLR2-deficient mice (TLR2-/-) (n = 12).
Twenty-four mice underwent laparotomy only or laparotomy plus superior mesenteric artery occlusion (n = 6/group) for 60 mins, followed by 90 mins of recovery.
Mid-jejunal sections were taken for histopathology and messenger RNA expression (reverse transcriptase-polymerase chain reaction, normalized to 18s and laparotomy-only controls). Intestinal injury was scored from 0 (no injury) to 4 (transmural necrosis). Statistical analyses were performed using Mann-Whitney U test and Student's t-test (p < .05 significant). TLR2-/- mice had elevated intestinal injury scores (mean +/- SEM) after ischemia/reperfusion vs. wild-type (2.17 +/- 0.40 vs. 0.67 +/- 0.33, p < .05). Intestinal cytokine messenger RNA (mean fold change +/- SEM) of interferon-gamma (0.29 +/- 0.12 vs. 3313 +/- 1710), interleukin-4 (0.25 +/- 0.13 vs. 2.70 +/- 1.08), and interleukin-6 (250.63 +/- 69.60 vs. 320,300 +/- 215,964) in TLR2-/- was significantly decreased (p < .05) after ischemia/reperfusion vs. wild-type. Tumor necrosis factor-alpha messenger RNA levels were unchanged.
TLR2-/- mice have a dysregulated mucosal innate immune response and fail to mount a protective response after ischemia-reperfusion compared with wild-type mice. This murine model of intestinal injury may correlate with the early postnatal course of premature infants who may have decreased TLR2 expression and/or decreased luminal commensal bacteria secondary to antibiotic therapy, thus decreasing TLR2-mediated signaling.
Pediatric Critical Care Medicine 02/2008; 9(1):105-9. · 3.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to characterize the safety of laparoscopic pyloromyotomy and examine the effect of resident training on the occurrence of complications.
Five hundred consecutive infants who underwent laparoscopic pyloromyotomy between January 1997 and December 2005 were reviewed and analyzed.
Laparoscopic pyloromyotomy was successfully completed in 489 patients (97.8%). Four hundred seventeen patients were boys (83%). Intraoperative complication occurred in 8 (1.6%) patients (mucosal perforation, 7; serosal injury to the duodenum, 1). All were immediately recognized and uneventfully repaired. Six patients (1.2%) required revision pyloromyotomy for persistent or recurrent gastric outlet obstruction. There were 7 wound complications (1.4%) and no deaths. Pediatric surgery residents performed 81% of the operations, whereas 16% were done by general surgery residents (postgraduate years 3-4). There was a 5.4-fold increased risk of mucosal perforation or incomplete pyloromyotomy when a general surgery resident rather than a pediatric surgery resident performed the operation (95% confidence interval, 1.8-15.8; P = .003). These effects persisted even after controlling for weight, age, and attending experience.
The laparoscopic pyloromyotomy has an excellent success rate with low morbidity. The occurrence of complications is increased when the operation is performed by a general surgery resident, even when directly supervised by pediatric surgical faculty.
Journal of Pediatric Surgery 02/2008; 43(1):97-101. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Obesity is a common and rapidly growing health problem today. Obesity is characterized by the increase of body fat and an excess of total body fat and, in particular, visceral fat accumulation, is considered to be a risk factor for type 2 diabetes mellitus. To determine whether the malfunction of the mesenteric adipose tissue plays an important role in the diabetic related metabolic syndrome, in this study, lipolysis and gene expression in the subcutaneous, omental and mesenteric adipose tissue of the diabetic subjects were evaluated.
Lipolysis and real time PCR were utilized to determine adipocyte function.
Basal adipose tissue glycerol release is higher in diabetics than that of the non diabetics in all three fat depots. Isoproterenol (ISO) significantly increases glycerol release in subcutaneous, omental and mesenteric adipose tissues of non diabetic subjects but it stimulated glycerol release was significantly impaired in all three fat depots of the diabetic subjects. Gene expression studies indicate that leptin, Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), Fatty acid translocase (FAT/CD36) and 11beta-hydroysteroid dehydrogenase (HSD) gene expression were significantly up regulated in the mesenteric adipose tissue of the diabetic patients.
Human mesenteric adipose tissue in obese diabetic subjects has high basal glycerol release and impaired isoproterenol stimulated glycerol release. The obesity-related gene expressions in the mesenteric adipose tissue are up regulated, suggesting that the alterations of these genes in mesentery adipose depot may play a critical role in insulin resistance of type 2 diabetes and metabolic syndrome.
Cellular Physiology and Biochemistry 02/2008; 22(5-6):531-8. · 2.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The melanocortin-2 receptor (MC2R), also known as the adrenocorticotropic hormone (ACTH) receptor, plays an important role in regulating and maintaining adrenocortical function, specifically steroidogenesis. Mutations of the human MC2R (hMC2R) gene have also been identified in humans with familial glucocorticoid deficiency; however, the molecular basis responsible for hMC2R ligand binding and signaling remains unclear. In this study, both truncated ACTH peptides and site-directed mutagenesis studies were used to determine molecular mechanisms of hMC2R binding ACTH and signaling. Our results indicate that ACTH1-16 is the minimal peptide required for hMC2R binding and signaling. Mutations of common melanocortin receptor family amino acid residues E80 in transmembrane domain 2 (TM2), D107 in TM3, F178 in TM4, F235 and H238 in TM6, and F258 in TM7 significantly reduced ACTH-binding affinity and signaling. Furthermore, mutations of unique amino acids D104 and F108 in TM3 and F168 and F178 in TM4 significantly decreased ACTH binding and signaling. In conclusion, our results suggest that the residues in TM2, TM3, and TM6 of hMC2R share similar binding sites with other MCRs but the residues identified in TM4 and TM7 of hMC2R are unique and required for ACTH selectivity. Our study suggests that hMC2R may have a broad binding pocket in which both conserved and unique amino acid residues are required, which may be the reason why alpha-MSH was not able to bind hMC2R.
Biochemistry 11/2007; 46(40):11389-97. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Melanocortin 4 receptor (MC4R) plays an important role in the regulation of food intake and body weight. To determine the molecular basis of human MC4R (hMC4R) responsible for alpha-melanocortin-stimulating hormone (alpha-MSH) binding, in this study, we utilized both receptor domain exchange and site-directed mutagenesis studies to investigate the molecular determinants of hMC4R responsible for alpha-MSH binding and signaling. alpha-MSH is a potent agonist at hMC4R but not at hMC2R. Cassette substitutions of the second, third, fourth, fifth, and sixth transmembrane regions (TM) of the hMC4R with the homologous regions of hMC2R were performed and alpha-MSH binding and signaling were examined. Our results indicate that each chimeric receptor was expressed at the cell surface and the expression levels remain similar to that of the wild-type receptor. The cassette substitutions of the second, fourth, fifth, and sixth TMs of the hMC4R with homologous regions of the hMC2R did not significantly alter alpha-MSH binding affinity and potency except substitution of the TM3 of the hMC4R, suggesting that the conserved residues in TMs of the hMC4R are crucial for alpha-MSH binding and signaling. Further mutagenesis studies indicate that conserved residues Glu(100) in TM2, Asp(122), Asp(126) in TM3 and Trp(258), Phe(261), His(264) in TM6 are involved in alpha-MSH binding and signaling. In conclusion, our results suggest that the conserved residues in the TM2, TM3, and TM6 of the hMC4R are responsible for alpha-MSH binding and signaling.
Journal of Biological Chemistry 08/2007; 282(30):21712-9. · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Childhood morbid obesity is reaching epidemic proportions. Roux-en-Y gastric bypass (RYGB) results in many metabolic alterations, including changes in glucose and lipid metabolism, and changes in levels of the gastric hormone, ghrelin. As more children are undergoing RYGB, an animal model would be beneficial to further study RYGB and its subsequent metabolic effects. DIO Sprague Dawley rats underwent RYGB, sham jejunojejunostomy (SH), or no operation (HFC) after 6 weeks of high-fat diet. Non-obese rats fed standard chow (SC) were a final control group. Animals were post-operatively fed standard chow for 7 days before sacrifice. At sacrifice, venous blood and gastric mucosa was collected for metabolic parameters and ghrelin determination. RYGB rats weighed less than SH and HFC (361 +/- 8.8 vs. 437 +/- 9.3 and 443 +/- 6.2 g, P < 0.05). Compared to HFC, RYGB animals had decreased plasma glucose (292 +/- 23 vs. 141 +/- 10 mg/dL), cholesterol (80 +/- 12 vs. 45 +/- 5 mg/dL), triglycerides (138 +/- 37 vs. 52 +/- 7 mg/dL), HDL (43 +/- 5 vs. 20 +/- 3 mg/dL), and free fatty acids (0.72 +/- 0.14 vs. 0.23 +/- 0.02 mEq/L), all P < 0.05. Plasma ghrelin increased in RYGB rats compared to SC and HFC (116.22 +/- 32.27 vs. 31.60 +/- 2.66 and 31.75 +/- 0.75 pg/mL, P < 0.05). In a rat model of RYGB, we demonstrated improved metabolic parameters and increased plasma and gastric mRNA ghrelin levels. The rat model for RYBG appears to be a reasonable model for future study of the cellular and molecular regulatory pathways of obesity and its surgical treatment.
Pediatric Surgery International 07/2007; 23(7):653-7. · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Infants with short bowel syndrome (SBS) are at a high risk for infectious complications and liver failure. We hypothesized that SBS, independent of total parenteral nutrition, is a proinflammatory state that is magnified by sepsis.
Sprague-Dawley rats were divided into 2 groups: sham laparotomy (SH, n = 10) or 75% small bowel resection (n = 10). After 14 days, each group underwent a second sham laparotomy (SH/SH and SBS/SH) or cecal ligation and puncture, followed 16 hours later by cecal excision and peritoneal washout (SH/sepsis and SBS/sepsis). Animals were killed 56 hours later.
The SBS rats had higher serum levels of interleukin (IL) 6 vs SH (355 +/- 99 vs 104 +/- 71 pg/mL, P < .05). Liver injury scores were higher in SBS/sepsis compared with SBS/SH animals (3.7 +/- 0.7 vs 1.9 +/- 0.3, P < .05). Hepatic messenger RNA levels of IL-6 (12.8-fold change [FC]) and tumor necrosis factor alpha (5.65 FC) were elevated in SBS vs SH rats; and IL-6 (114 FC), tumor necrosis factor alpha (3.87 FC), and Toll-like receptor 4 (7.65 FC) were increased in SBS/sepsis compared with SH/sepsis animals.
Our results suggest that SBS, independent of total parenteral nutrition, is a proinflammatory state and that sepsis induces an exaggerated proinflammatory cytokine response that may play an important role in liver damage and may be mediated by Toll-like receptor 4.
Journal of Pediatric Surgery 06/2007; 42(6):992-7. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The initial nonoperative management of perforated appendicitis fails in 15% to 25% of children. These children have complications and increased hospitalization. The purpose of this study was to identify predictors of failure.
Children with perforated appendicitis treated with antibiotics and intent for nonoperative management over a 4-year period were reviewed. Seventy-five children were identified and included in the study. Failure was defined as undergoing appendectomy before the initially planned interval.
Nine (12%) of the patients required appendectomy sooner than initially planned. Age, presenting symptoms, physical examination findings, and white blood cell (WBC) count were similar in both success and failure groups. Absence of abscess and presence of appendicolith were both predictors of failure in a multivariate analysis, which included the presence of small bowel obstruction. The failed group had a longer median total length of stay (18 days [range, 4-67] vs 8 days [range, 4-31]; P = .002) and underwent 3 times as many computed tomography scans as successes (3 [range, 2-7] vs 1 [range, 0-5]; P < .001).
Lack of abscess and presence of an appendicolith predict failure of nonoperative management of perforated appendicitis in children even when the effect of small bowel obstruction is accounted for. Children with these characteristics may benefit from alternative management strategies.
Journal of Pediatric Surgery 06/2007; 42(6):934-8; discussion 938. · 1.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Gastrostomy tube placement is among the most common gastrointestinal procedures performed in children. The U-stitch laparoscopic technique allows primary button placement and the advantages of laparoscopy. The purpose of this study was to quantify the completion rate and the occurrence of complications in a large single-institution experience.
All laparoscopic gastrostomy procedures between April 2000 and May 2005 were reviewed. Complications that required operative treatment or hospital readmission were classified as early (<90 days) or late (> or =90 days).
Laparoscopic gastrostomies were created in 461 patients during the study period with primary buttons being placed in 444 (96%). No procedure-related deaths occurred. Early complications included: reoperation secondary to tube dislodgement in 7 patients (1.5%), herniation of omentum postoperatively in 3 patients (0.6%), and development of granulation tissue or everted gastric mucosa requiring excision in 13 patients (3.2%). Late complications occurred in 8 patients (1.7%), with three (0.7%) requiring revision of the gastrostomy due to local site problems. Five patients (1.1%) had intraperitoneal placement of tubes during attempted replacement after 90 days. Age, infancy, and neurological impairment were not associated with a higher rate of complications.
The U-stitch gastrostomy technique is safe and allows primary button placement in infants and children. Its complication rate compares favorably to other reported gastrostomy techniques.
Journal of Laparoendoscopic & Advanced Surgical Techniques 01/2007; 16(6):643-9. · 1.40 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Melanocortin-3 receptor (MC3R), primarily expressed in the hypothalamus, plays an important role in the regulation of energy homeostasis. MC3R-deficient (MC3R(-)(/)(-)) mice demonstrate increased fat mass, higher feeding efficiency, hyperleptinaemia, and mild hyperinsulinism. At least one specific mutation of MC3R has been identified to be associated with human obesity. Functional analysis of this altered MC3R (I183N) has indicated that the mutation completely abolishes agonist-mediated receptor activation. However, the specific molecular determinants of MC3R responsible for ligand binding and receptor signaling are currently unknown. The present study is to determine the structural aspects of MC3R responsible for ligand binding and receptor signaling. On the basis of our theoretical model for MC1R, using mutagenesis, we have examined 19 transmembrane domain amino acids selected for these potential roles in ligand binding and receptor signaling. Our results indicate that (i) substitutions of charged amino acid residues E131 in transmembrane domain 2 (TM2), D154 and D158 in TM3, and H298 in TM6 with alanine dramatically reduced NDP-MSH binding affinity and receptor signaling, (ii) substitutions of aromatic amino acids F295 and F296 in TM6 with alanine also significantly decreased NDP-MSH binding and receptor activity, (iii) substitutions of D121in TM2 and D332 in TM7 with alanine resulted in the complete loss of ligand binding, ligand induced receptor activation, and cell surface protein expression, and (iv) interestingly, substitution of L165 in TM3 with methionine or alanine switched antagonist SHU9119 into a receptor agonist. In conclusion: Our results suggest that TM3 and TM6 are important for NDP-MSH binding, while D121 in TM2 and D332 in TM7 are crucial for receptor activity and signaling. Importantly, L165 in TM3 is critical for agonist or antagonist selectivity. These results provide important information about the molecular determinants of hMC3R responsible for ligand binding and receptor signaling.
Biochemistry 02/2006; 45(4):1128-37. · 3.42 Impact Factor
