Sakda Patrapinyokul

Association of genetic polymorphisms in the RET-protooncogene and NRG1 with Hirschsprung disease in Thai patients.

Hirschsprung disease (HSCR) is a congenital developmental defect of the enteric nervous system known to be associated with the RET-protooncogene and other candidates. Recently, a genome-wide association study has added NRG1, a regulator of the development of the enteric ganglia precursors, as a new candidate gene. The aim of this study is to validate the association of the RET-protooncogene and the NRG1 in HSCR in Thai patients. The study used TaqMan single-nucleotide polymorphism (SNP) genotyping and PCR–restriction fragment length polymorphism for genotyping of 10 SNPs within the RET-protooncogene and four SNPs within the NRG1, in 68 Thai sporadic HSCR cases and 120 ethnic-matched controls. On univariate disease association analysis, 9 of 10 RET-protooncogene SNPs and all four NRG1 SNPs showed an association with HSCR. The rs2435357 (RET-protooncogene) and rs2439305 (NRG1) showed the strongest associations with the disease at P-values of 8.17E-09 (odds ratio (OR)=6.43, 95% confidence intervals (CI)=3.33–12.40) and 6.94E-03 (OR=3.28, 95% CI=1.28–8.38), respectively. The RET-protooncogene rs2435357 (TT genotype) in combination with the NRG1 rs2439305 (GG genotype) was strongly associated with an increased risk of HSCR with a P-value of 1.99E-04 (OR=20.34, 95% CI; 2.54–162.78) when compared with a single SNP of the RET-protooncogene or NRG1. Genetic variation of the RET-protooncogene and NRG1 is involved in the risk of HSCR development in the Thai population. Moreover, the study also detected a combined effect of SNPs by SNP–SNP interaction, which may help in predicting HSCR risk.

Massive gastrointestinal bleeding in infants with ascariasis

Although infestation with Ascaris lumbricoides causes various intestinal complications, massive gastrointestinal bleeding is rare. The authors report on 2 infants who presented with massive hematemesis. In the first patient, a gastroduodenoscopy was performed. Roundworms were found adhering to an oozing duodenal ulcer. Duodenal perforation occurred after extraction of the parasites. The second case was hematemesis together with peritonitis. Exploration found volvulus and a gangrenous segment of the distal ileum. Both infants previously passed roundworms with their stool. The authors conclude that the intestinal ascariasis can be a cause of massive gastrointestinal bleeding, especially in temperate and tropical countries.

Mutations and polymorphisms of Hirschsprung disease candidate genes in Thai patients

AbstractMutation and polymorphism data for Hirschsprung disease (HSCR) varies among ethnic groups. Single nucleotide polymorphisms (SNP) of RET proto-oncogene (RET) were recently shown to be associated with the disease, and with disease severity, in different populations. In this study, comprehensive analysis of RET, GDNF, EDNRB, ET-3, and SOX-10 genes among sporadic HSCR in Thailand was conducted by standard PCR-SSCP, RFLP, and sequencing methods. Of 41 patients, 30 cases had rectosigmoid disease (RSD) and 11 cases were assigned to the long-segment disease (LSD) group. Four missense mutations of RET, S100M, R231H, T278N, and G533S, were identified in three patients. One novel missense mutation, V111Q, was detected in EDNRB. For ET-3, two novel missense mutations, D166E and C173R, occurred concomitantly in a patient. The incidence of missense mutation was significantly higher in our female HSCR patient than in the male counterpart. Statistical analysis of the SNPs revealed a significant difference between allele distribution of RET L769L in patients in the LSD and RSD groups. The predominant genotype construct of RET A45A/L769L in our HSCR was GG/GG, which is obviously different from results from all previous studies. The GG/GG genotype construct was associated with RSD and with males. The study also detected a variant allele of RET S836S which has never been reported in Asian cohorts.

Renal abscess in healthy children: report of three cases

We report three cases of renal abscess in otherwise healthy boys. One had a history of blunt trauma and two of antecedent skin infection. All presented with flank pain and fever. Urine and blood cultures were sterile. The diagnosis was made using ultrasound and computerized axial tomography. The first patient had recurrent renal abscess, following surgery and a short course of antibiotics. Eventually all responded well to long-term antibiotics only.

Surgery in management of snake envenomation in children

BackgroundSnakebite is common in children especially in the developing countries. This study was undertaken to determine the role of surgery in the treatment of venomous snake bite in pediatric patients.MethodsThe clinical data of 58 pediatric patients aged 0–16 years who had been treated for venomous snakebite from January 1999 to December 2008 were analyzed.ResultsOf the 58 patients, 43 (74.6%) were male. Peak age incidence was around 2–3 years (28.8%). The majority of envenomations occurred in the summer and rainy seasons, especially in the latter, during flooding. The bites occurred during 6 pm to 12 pm in 27 patients (49.0%). The main bite site was the lower extremities in 49 patients (83.9%). The main species of the snake were Malayan pit viper (Calloselasma rhodostoma) in 28 patients (47.5%) and cobra (Ophiophagus hunnah or Naja spp.) in 21 patients (35.6%). Soft tissue necrosis occurred more in cobra bites (47.6%) than viper bites (3.6%). The most common organism identified in necrotic tissue was Morganella morgagnii. Four patients with cobra bite had respiratory failure that required ventilatory support. Compartment syndrome was suspected in 2 patients. Surgical intervention was necessary in 13 patients. Most procedures involved serial wound debridement, followed by skin grafting. One case needed a toe amputation because of necrosis. The average length of hospital stay in patients who needed surgical management was 18.8 days (range: 12.1–25.5 days). There were no mortalities.ConclusionsSurgery plays an important role in the management of snakebite patients, especially for those with cobra bite with tissue necrosis.

Infectious complications in infants with gastroschisis: an 11-year review from a referral hospital in southern Thailand

UNLABELLED MAIN PURPOSES: The study aimed to (1) examine the incidence of infectious complications (ICs) in our referral hospital in southern Thailand in infants with gastroschisis, with analysis of the impact of these complications on outcomes, and (2) identify associated factors to improve the practice at our institution for dealing with this condition. METHODS A retrospective review of consecutive gastroschisis cases at the major teaching and referral hospital in southern Thailand was conducted for an 11-year period (1996-2006). Cases referred after a primary operation at other hospitals were excluded. The study focused on postoperative nosocomial infections as identified by Centers for Disease Control and Prevention criteria. RESULTS Sixty-eight patients with gastroschisis were operated on. Twenty-seven patients (39.71%) underwent primary closure. Mortality was 4 of 68 patients (5.9%). Infectious complication occurred in 43 patients (63.2%). The complications significantly increased mechanical ventilation days (10.8 vs 3.8 days in noncomplicated cases), need for parenteral nutrition (25.3 vs 14.5 days), and postoperative stay (33.7 vs 21.1 days). Common ICs were wound infection (32.35%), isolated septicemia (19.1%), and pneumonia (13.24%). Univariate analysis identified an association between the occurrence of IC and birth order (multigravida), time from birth until arrival at our center (5 hours or more), hypoalbuminemia, hypoglycemia, type of operation (staged closure), use of central venous line, and prolonged use of ventilator. On multiple logistic regression, prolonged referral time, use of a central venous line, multigravida, and staged closure independently predicted the risk of IC. CONCLUSION Infectious complication was significantly related to outcome in gastroschisis cases and should not be overlooked. Our data suggest that prompt referral, limiting central line practice on a selective basis, and an attempt to reduce wound infection in cases that require a temporary silo may improve the overall outcomes.

Novel mutation of Endothelin-B receptor gene in Waardenburg–Hirschsprung disease

Homozygous mutations of EDNRB in human have been reported to result in Waardenburg–Hirschsprung disease (WS4), while mutated heterozygotes manifested isolated Hirschsprung disease in lower penetrance. We investigated a case of WS4 together with all members of her nuclear family for the alteration of the EDNRB gene by using PCR–SSCP and direct sequencing technique. The index patient, who was born to a family with no history of Hirschsprung disease, presented total colonic aganglionosis with small bowel extension, sensorineural hearing loss and generalized cutaneous pigmentary defects. Interestingly, both irides were normally black. The study detected a homozygous missense mutation at codon 196 in exon 2 (Ser196Asn), which has not been reported. Both parents and four in six siblings harbored heterozygous mutation without any clinical manifestation. Our findings were consistent with previous observations that full spectrum of WS4 occurred to the mutate homozygotes. Moreover, the non-penetrance of heterozygotes in our pedigree, which differs from other reports, demonstrates the high pleiotropic effect of EDNRB mutations in human.

Crucial role of rectoanal inhibitory reflex in emptying function after anoplasty in infants with anorectal malformations.

Constipation is a common problem after reconstructive surgery for anorectal malformations. The underlying pathophysiology of the constipation in these patients is unclear. The objective of this study was to compare manometric disturbance in infants with and without post-anoplasty constipation. Anorectal manometry studies were performed within 12 months of anoplasty, as a part of the follow-up protocol, in 24 infants aged less than 3 years who had anorectal malformations. The manometric profiles studied were mean resting anal pressure (ArP), mean resting rectal pressure (RrP), mean resting rectoanal pressure gradient (RRPG), peak squeeze pressure (PSP), and the presence of the rectoanal inhibitory reflex (RAIR). Eight of 24 infants (33%) experienced constipation during the examination period. There was no difference in pressure profiles between low and non-low anomalies. In the non-constipation group, RrP was 5.1 mmHg, ArP was 21.0 mmHg, RRPG was 16.0 mmHg, and PSP was 88.4 mmHg. In the constipation group, RrP was 7.3 mmHg (p = 0.37), ArP was 37.5 mmHg (p = 0.03), RRPG was 3.05 mmHg (p = 0.05), and PSP was 81.7 mmHg (p = 0.77). RAIR was present in 93.75% of cases without constipation and 12.5% of cases with constipation (p < 0.01). One patient who had clinical conversion from constipation to a good result also showed positive conversion of the RAIR. RAIR and anal resting tone play important roles in emptying function. As far as possible, these functions should be preserved during reconstruction.

Immunohistological evidence for Wnt-signaling activation in Peutz-Jeghers polyposis

ObjectiveMolecular pathogenesis of gastrointestinal polyposis in Peutz-Jegher’s syndrome (PJS) has been linked to the loss-of-function mutation of LKB1. Recent functional genetic studies have pointed out that LKB1 plays a physiological role in controlling the Wnt-signaling pathway and activation of the pathway as a consequence of LKB1 haploinsufficiency might be responsible for the development of harmatomatous polyps. This study aimed to look for immunohistochemical evidence of Wnt-signaling activation in PJS polyps.MethodBeta-catenin immunohistochemistry patterns were evaluated in gastrointestinal polyps from five cases of PJS. All patients were also evaluated for germline mutations of LKB1 and somatic mutations of beta-catenin in the polyps.ResultsFour of the five cases had germline mutations of LKB1, including two novel mutations, a one-base insertion at codon 53 and a large deletion encompassing exon 3 (codon 136–155). PJS polyps from all patients showed generalized membrane and cytoplasmic localizations of beta-catenin along the mucosal endothelium. Polyps from two cases with LKB1 mutations revealed moderate-intensity nuclear staining in approximately 20 and 70% of the polyps.ConclusionThe study offers additional evidence of Wnt-signaling activation in PJS polyp development at the tissue level, although the degree of up-regulation was not as high as has been found in Wnt-associated neoplasms.

Sutureless elastic ring silo for the gastroschisis.

Abstract Background: The definitive surgical management of gastroschisis is the return of the eviscerated abdominal content into the abdomen as soon as possible. Objectives: Assess the efficacy of using a sutureless elastic ring silo (SERS) for the management of gastroschisis. Methods: Neonates with gastroschisis were enrolled at Songklanagarind Hospital between January 2006 and December 2008. A primary repair (PR) was attempted in all cases. If this was not possible due to concerns about abdominal compartment syndrome, a stage abdominal closure with a silo pouch was fashioned: a traditional silo (TS) or SERS. When the bowel was completely reduced, a second-stage closure was performed in the operating room. Data collected included general demographic data, size of defect, associated anomalies, hospital course, mode of gastroschisis closure, duration of parenteral nutrition (PN) and ventilator, first feeding age, complications, and length of hospital stay (LOS). Results: Twenty-nine children with gastroschisis were treated (PR: 9, TS: 9, and SERS: 11). There were no differences (p >0.05) concerning gender, mode of delivery, APGAR scores, gestational age, birth weight, or defect size. A preformed silo was employed in 20 of 29 cases, TS in nine (31%), and SERS in 11 (38%) cases in an average operative time of 80.6 and 40 minutes, respectively, a significantly shorter operative time in the SERS (p =0.007). Overall, there were no differences (p >0.05) concerning duration of ventilator support (10.2 days), duration of PN (21.3 days), first feeding age (15 days), LOS (26.5 days), and complication. Conclusion: The use of a sutureless elastic ring silo with readily available inexpensive materials is simple, safe and efficacious in our setting.