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Biomedical subjects

D P Drake

Publications and source records attributed to D P Drake.

At least 19 recordsLinked to original sources

Reduction in visceral slide is a good sign of underlying postoperative viscero-parietal adhesions in children.

BACKGROUND/PURPOSE: Viscera stuck to the anterior abdominal wall from previous surgery risk injury during laparoscopic surgery. A prospective study was conducted to determine if these adhesions are detectable on ultrasound scan by showing a reduction in the normal visceral slide. METHODS: Patients undergoing laparoscopic procedure after a previous laparotomy underwent preoperative real-time ultrasound scan to observe if viscera slides freely under the abdominal wall. A reduction in slide was considered a positive sign of underlying adhesions. These findings were correlated with the operative findings. RESULTS: Anterior abdominal wall scans were performed on 17 children. Reduced visceral slide was seen in 10. Viscero-parietal adhesions were found in 9 of 10 patients. Visceral slide was reduced in a very localized area in 6 patients, and, in these, a loop of bowel (n = 3), liver and bowel (n = 2), or liver (n = 1) was adherent. In 4, reduced visceral slide was seen over a wide area. Extensive adhesions were found in 3 of 4. One renal transplant patient with peritonitis had a false-positive ultrasound scan. At laparotomy there were no adhesions. The peritonitis is thought to have prevented an adequate examination. Seven patients had normal visceral slide. Of these, 4 had no adhesions, but 3 children had flimsy omental adhesions. The sensitivity and specificity of visceral slide in predicting adhesions were 75% and 80%, respectively. CONCLUSIONS: Reduction in visceral slide is a good sign of underlying postoperative viscero-parietal adhesions. Ultrasonographic mapping of the abdominal wall may be useful in selecting an adhesion-free site for trocar insertion in children with previous operations requiring laparoscopic procedures.

Abdominal Wall↗

Conservative management of pneumatosis intestinalis and pneumoperitoneum following bone-marrow transplantation.

Pneumatosis intestinalis (PI), with or without pneumoperitoneum (PP), may complicate allogenic bone-marrow transplantation (BMT). The aim of our study was to establish the incidence and outcome of this complication following BMT in children. A departmental database was used to identify children who underwent BMT in the 4-year period up to December 1999. The medical records of children who developed PI with or without PP were obtained for further study. All patients were managed without recourse to surgery. Conservative management included 7 days of intravenous antibiotics and 10 days of intestinal rest supported by parenteral nutrition. In the study period, 138 BMTs were carried out. Six children (4%) with a total of 7 episodes of PI/PP were identified, 1 boy and 5 girls with a median age of 8.5 years (range 0.8-11). Neutropenia was noted in 3 children at the time of presentation. Other risk factors identified included alternative BMT donors (5/6), steroid therapy (6/7), and graft-versus-host disease (5/6). Organisms were isolated from stool cultures sent at the time of diagnosis in 3 out of 7 instances. Diarrhoea was the predominant presenting symptom. All patients recovered from the acute episode, but 5 died at a mean of 12 months from the development of PI/PP (range 6-17 months). This mortality of 83% compares with a mortality of 33% (43 of 132) for the remainder of children who underwent BMT during the study period. Thus, while initial recovery can be anticipated, the medium-term mortality in this group of children is high.

Anti-Bacterial Agents↗

T cryptantigen activation is associated with advanced necrotizing enterocolitis.

BACKGROUND/PURPOSE: Thomsen-Friedenreich cryptantigen activation (TCA) exposes neonates with necrotizing enterocolitis NEC to the risk of hemolysis after transfusion of blood products. The authors aimed to determine the prevalence of TCA in neonates with NEC and to correlate TCA with severity of disease and outcome. METHODS: One hundred four neonates with NEC were tested for TCA on admission. Patients with TCA requiring transfusion were given packed red cells, low-titer anti-T fresh frozen plasma, and washed platelets to avoid hemolysis. RESULTS: Twenty-three infants had TCA, and 96% of these had stage III disease. The incidence of TCA was significantly higher in infants with stage III disease compared with those with stage II (30% v 4%; P <.01). A total of 91% of infants with TCA required laparotomy compared with 81% of those with no activation. At laparotomy, widespread disease was more common in the TCA group (71% v 55%). TCA did not significantly increase mortality rate (TCA, 39% v no TCA, 28%); this may reflect the transfusion policy of our unit. CONCLUSIONS: Twenty-two percent of neonates with NEC referred to our unit had TCA. There is an association between TCA and advanced NEC. Screening of neonates with advanced NEC for TCA is advised to identify those at risk of hematologic complications.

Antigens, Tumor-Associated, Carbohydrate↗

Glutamine and glutathione counteract the inhibitory effects of mediators of sepsis in neonatal hepatocytes.

BACKGROUND/PURPOSE: Surgical neonates are at risk of sepsis-associated liver dysfunction. Hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) are important mediators of sepsis, which impair neonatal hepatic metabolism. Glutamine has been shown to have beneficial effects on hepatocyte metabolism during neonatal sepsis. However, the molecular basis of these effects are unknown. The aim of this study was to test the hypotheses that (1) glutamine and its dipeptides counteract the inhibitory effect of septic mediators on neonatal hepatocyte oxygen consumption and (2) the effects of glutamine are specific and not shared by other amino acids. In addition, we wished to determine the metabolic pathways and mediators involved in the action of glutamine. METHODS: Hepatocytes were isolated from suckling rats, and O(2) consumption measured polarographically. Study A: the ability of 10 mmol/L glutamine to reverse the inhibitory effects of 1.5 mmol/L H(2)O(2) and 300 micromol/L S-Nitroso-N-acetylpenicillamine (SNAP; a nitric oxide donor) on O(2) consumption was examined. Study B: the ability of other amino acids and dipeptides of glutamine to reverse the effects of H(2)O(2) was examined. Study C: various concentrations of glutamine were tested for their ability to reverse the H(2)O(2) inhibition of O(2) consumption. Study D: the mechanism of action of glutamine was examined by incubating hepatocytes with either an inhibitor of entry into the Krebs cycle or an inhibitor of glutathione synthesis. Study E: the ability of glutathione to reverse the inhibitory effects of H(2)O(2) was examined. RESULTS: Study A: glutamine reversed the inhibition of hepatocyte O(2) consumption exerted by either H(2)O(2) or NO. Study B: glutamine dipeptides reversed the inhibition of hepatocyte O(2) consumption by H(2)O(2), but other amino acids did not. Study C: the counteracting effect of glutamine was proportional to the dose administered. Study D: blocking entry of glutamine into the Krebs cycle did not abolish the effects of glutamine, but blocking glutathione synthesis completely abolished the effect of glutamine. Study E: exogenous glutathione reversed the inhibitory effect of H(2)O(2) on hepatocyte O(2) consumption. CONCLUSIONS: This study found that glutamine and its dipeptides are unique in reversing the effects of septic mediators on neonatal rat liver oxidative metabolism. The effectiveness of glutamine appears to be mediated via glutathione synthesis. Addition of glutamine, glutamine dipeptides, or glutathione to total parenteral nutrition (TPN) may be beneficial in preventing liver damage in neonatal sepsis.

Animals↗

Colostomy for anorectal anomalies: high incidence of complications.

PURPOSE: The aim of this study was to characterize the type and incidence of complications related to colostomy formation in newborn infants with anorectal anomalies. METHODS: The authors reviewed a 5-year (1994 to 1999) experience of a single institution in the management of neonates with high and intermediate anorectal anomalies who required colostomy at birth. Patients with colostomy still in place have been excluded from the study to maximize the chances of detecting colostomy-related complications. RESULTS: There were 80 neonates with anorectal malformations, of whom, 49 (31 boys and 18 girls) were included in the study. The site of colostomy was sigmoid colon (n = 32), transverse colon (n = 7), and descending colon (n = 10). Thirty-nine colostomies were loop, and the remaining 7 were divided. The median birth weight was 2.96 kg (range, 1.46 to 3.88). The age at colostomy formation was 2 days (range, 1 to 210). Mechanical complications related to colostomy formation were observed in 16 infants (32%) with 3 infants having more than 1 mechanical complication. These included prolapse in 8 (50%), intestinal obstruction (adhesions, intussusception, and volvulus) in 7 (44%), and skin dehiscence in 3 (19%). One neonate had necrotizing enterocolitis (NEC) after colostomy formation. Urinary tract infection was observed after colostomy in 14 infants (29%). The incidence of urinary tract infection was not higher in infants who had loop colostomy (11 of 39, 28%) compared with infants who had divided colostomy (3 of 10, 30%). There were no differences in the incidence of colostomy-related complications and urinary tract infection between male and female infants. There were no deaths in this series. CONCLUSIONS: Formation of colostomy for anorectal anomalies should not be considered a minor procedure. In our experience the incidence of complications after colostomy formation is high. The incidence of urinary tract infections does not seem to be affected by the type of colostomy performed.

Age Factors↗

The clinical significance of thrombocytopenia in neonates with necrotizing enterocolitis.

PURPOSE: The aim of this study was to evaluate the clinical significance of low platelet count in the surgical management of neonates with necrotizing enterocolitis (NEC). METHODS: The clinical course of 58 consecutive neonates with advanced NEC (Bell's stages II or III) treated in the authors' hospital between 1995 and 1998 was reviewed. NEC in neonates who required operation was classified as isolated, multifocal, or pan-intestinal. Severe thrombocytopenia was defined as platelet count less than 100 x 10(9)/L. Rapid fall in platelet count was defined as fall greater than 150 x 10(9)/L within 24 hours to a level less than 100 x 10(9)/L. RESULTS: Median birth weight was 1,564 g (range, 550 to 4,270) and gestational age was 31 weeks (range 23 to 41). Twenty-two neonates (38%) were below 1,000 g. Age at the onset of the disease was 13 days (range, 1 to 62). NEC was treated medically in 7 neonates (12%). Indications for operation included pneumoperitoneum in 23 neonates (45%), clinical deterioration in 19 (37%), and intestinal obstruction in 9 (18%). The nadir platelet count (lowest level during the course of disease) was lower in patients with stage III disease than in patients with stage II disease (P <.05). The greater the extent of the disease, the lower the platelet count (P =.012). The nadir platelet count was lower in infants who died than in survivors (P <.05). None of the patients with platelet count greater than 100 x 10(9)/L died. In predicting intestinal gangrene, severe thrombocytopenia has a sensitivity of 69%, specificity of 60%, and positive predictive value of 89%; rapid fall in platelet count has a sensitivity of 32%, specificity of 89%, and positive predictive value of 92%. CONCLUSIONS: (1) A platelet count less than 100 x 10(9)/L or a rapid fall in platelet count represent poor prognostic factors. (2) Monitoring the platelet count during the course of NEC is useful; however, it cannot be used in isolation to predict the extent of the disease or survival rate.

Birth Weight↗

Colloid cyst in ectopic thyroid gland.

A five year old girl presented with a mid-line neck swelling. At operation, a multiloculated cyst was excised with a portion of hyoid bone and a suprahyoid gelatinous tract extending into the base of the tongue. Histology revealed a benign colloid cyst with associated thyroid tissue. Post-operative investigations indicated severe hypothyroidism. The cystic nature of the lesion was misleading at operation and pre-operative thyroid ultrasonography (US) is recommended for all patients with suspected thyroglossal tract cysts (TGC).

Child, Preschool↗

The management of oesophageal atresia in neonates with right-sided aortic arch.

BACKGROUND/PURPOSE: The management of oesophageal atresia (OA) in association with a right-sided aortic arch (RAA) is challenging. It is controversial whether right or left thoracotomy is the most appropriate surgical approach. The aim of this study was to determine the prevalence of RAA in patients with OA and the most appropriate surgical approach. METHODS: The case records of all the neonates with OA treated over an 18-year period (1980 through 1997) were reviewed. Patients with RAA were analysed with particular reference to the preoperative investigations, operative approach and findings, and postoperative complications. RESULTS: Of the 476 case notes reviewed, 12 (2.5%) had a RAA, and 5 of these infants had major cardiac anomalies. The diagnosis was not suspected on preoperative chest x-ray in any of these infants. In only 1 of the 5 neonates who had a preoperative echocardiogram was RAA suspected. A right thoracic approach was performed in the 11 infants in whom a RAA was not suspected. Immediate conversion to a left thoracotomy with primary anastomosis was carried out in 2 infants. In 2 further infants, fistula ligation alone was performed because of a long gap atresia. Anastomosis via the right thoracotomy was performed in 7 infants. There were 3 anastomotic leaks, 1 intractable stricture, and 1 recurrent fistula. Three patients (25%) had a double aortic arch, and, as a result, a left thoracotomy had to be abandoned in 2. There were 3 deaths, 2 as a result of major cardiac anomalies and 1 related to prematurity and sepsis. CONCLUSIONS: RAA occurs in 2.5% of infants with OA. Preoperative chest x-ray and echocardiogram are unreliable as diagnostic modalities. Anastomosis via a right thoracotomy is associated with a 42% leak rate. The presence of a double aortic arch can make the oesophageal anastomosis via a left thoracotomy as difficult as via a right thoracotomy.

Abnormalities, Multiple↗

Pelvic neuroblastoma: low mortality and high morbidity.

BACKGROUND/PURPOSE: Cervical, thoracic, and pelvic neuroblastomas are regarded as having a better outcome than abdominal primaries. The aim of the study was to analyze the results of treatment of pelvic neuroblastomas in our institution. METHODS: The authors reviewed the records of 284 patients with neuroblastoma treated in our hospital during the period 1983 through 1998 and identified 17 (6%) with pelvic tumors. The revised International Neuroblastoma Staging System was used. RESULTS: There were 6 patients with stage 1 disease, 8 with stage 2, 2 with stage 3, and 1 with stage 4 disease. Intraspinal extension of the tumor was present in 7 patients (41%). Except for one child with stage 4 disease, all patients underwent an attempt of tumor excision, and 6 had a complete resection. All 7 patients with intraspinal tumor survived. Permanent postoperative neurological complications occurred in 6 patients (35%). These included sciatic nerve palsy, urinary and fecal incontinence, neuropathic bladder, and leg weakness or nerve root injury L4-S1. Three of 17 patients died, but 1 fatality was unrelated to the tumor. The overall survival rate was 82% and was not influenced by the completeness of tumor resection. CONCLUSIONS: The survival of nonmetastatic pelvic neuroblastoma in our institution is good despite incomplete tumor resection. Intraspinal extension is not a negative prognostic factor. Considering the high incidence of permanent neurological damage after surgery and the generally favorable biological characteristics of these tumors, surgical treatment should not be overaggressive.

Antineoplastic Combined Chemotherapy Protocols↗

Investigation and treatment of thyroglossal cysts in children.

Thyroglossal cysts are the commonest midline neck masses in children. To evaluate current practice questionnaires were sent to all ear, nose and throat (ENT) and paediatric surgeons in the UK and 72% responded. The commonest investigation requested was an ultrasound scan (54%) and the commonest operation was a variant of Sistrunk's procedure (78%). Paediatric surgeons did fewer investigations than ENT surgeons and tended to excise more of the thyroglossal tract. Review of the published work suggests that ultrasound scanning and Sistrunk's procedure are the best management policy. The scan can avoid inadvertent excision of an ectopic thyroid gland. Extensive thyroglossal tract excisions give lower recurrence rates.

Child↗

Late death after extracorporeal membrane oxygenation for congenital diaphragmatic hernia.

PURPOSE: The aim of this study was to determine the long-term outcome of neonates who required extracorporeal membrane oxygenation (ECMO) for respiratory insufficiency associated with congenital diaphragmatic hernia (CDH). METHODS: All neonates born with CDH, who required ECMO (oxygenation index over 40 in the presence of maximal support) during a 6-year period, were reviewed. The median duration of follow-up for survivors was 14 months (range, 9 to 22 months). RESULTS: Of 72 neonates with CDH, 11 (15%) required ECMO. The median age at the start of ECMO was 2 days (range, 1 to 4); duration was 9 days (range, 4 to 17); post-ECMO ventilation was 27 days (range, 8 to 86); and stay in intensive care unit, 33 days (range, 8 to 133). Three patients survived and are not oxygen dependent. There were three early deaths at 9 to 16 days and five late deaths at a median of 6 months (range, 2 to 32 months) secondary to chronic lung disease (n = 3) and infection (n = 2). Four of the five patients with late deaths were oxygen dependent at discharge from hospital. Three of the late death patients and one survivor underwent a fundoplication for gastrooesophageal reflux. CONCLUSIONS: Neonates born with CDH and requiring ECMO had a significant late mortality. Follow-up for more than 1 year is indicated to assess the benefit of ECMO for this diagnosis. The authors report only three long-term survivors from 11 ECMO patients selected from a total of 72 neonates with CDH.

Extracorporeal Membrane Oxygenation↗

Surveillance of Barrett's esophagus in children.

PURPOSE: The aim of this study was to review the need for regular endoscopic biopsy of Barrett's esophagus in children. METHODS: This was a retrospective case-notes review of 38 children with Barrett's esophagus treated between January 1982 and August 1997. The mean age at diagnosis was 6.3 years (range, 1 to 15 years). All had gastroesophageal reflux at diagnosis. Two patients were treated medically, and 36 underwent antireflux surgery (32 Nissen fundoplication, four Thal procedures). At follow-up, for a mean of 43 months (range, 0 to 13 years), 25 underwent repeated endoscopy and biopsies, two underwent further surgery and biopsies, and four underwent endoscopy only. Seven have had follow-up at their referring hospital. RESULTS: In the 27 patients who underwent rebiopsy, there was continued evidence of Barrett's esophagus in 15. There was reversion to normal tissue in 10 patients, and mild esophagitis was present in two. There was no evidence of any dysplastic or malignant change in any patient. All cases that reverted to normal esophagus or mild esophagitis had previously undergone a Nissen fundoplication. CONCLUSIONS: Dysplastic degeneration and malignant change did not occur in any of the authors' patients. In addition, 12 patients with Barrett's esophagus reverted to normal. The authors therefore question whether regular endoscopic surveillance is necessary in children under 16 years of age.

Adolescent↗

Management and long-term follow-up of infants with total colonic aganglionosis.

BACKGROUND/PURPOSE: Although the survival rate for the infants with total colonic aganglionosis (TCA) has improved significantly, problems with the surgical management continue and the long-term consequences for growth and continence are poorly documented. The aim of this study was to review the experience in the management of 48 patients over a 17-year period (1980 to 1996). METHODS: The medical records of all patients were analyzed with particular emphasis on the number and type of surgical procedures, the attainment of anorectal continence, number of stools per day, and physical development. RESULTS: There were 30 boys and 18 girls. Three (6%) patients died: one of sepsis, one of associated major congenital cardiac anomaly, and one of Moebius syndrome and brain stem dysfunction. Forty-one patients (85%) went on to undergo a pull-through procedure: 38 Duhamel with 13 having Martin modification and three with Soave procedure. Inappropriate surgery (47 procedures) were carried out in 19 (40%) patients before the definitive diagnosis; only four of these infants were admitted primarily to our unit. Thirteen patients had a stoma in aganglionic intestine. An ileostomy was closed in six infants before the diagnosis was established, and six had a previous "negative" laparotomy. Long-term follow-up was possible in 27 patients, of whom 19 (70%) required a total of 39 additional procedures. Ten patients underwent a total of 16 anal dilatations and six underwent sphincterotomy. A permanent stoma was necessary in six patients (two with Down's syndrome). Two patients with Martin modification required resection of the side-to-side anastomosis for intractable diarrhea. The number of the stools per day decreased yearly. Fecal incontinence was common at the 5-year follow up (82%). However, at 10 and 15 years, the rate of incontinence decreased to 57% and 33%, respectively. The proportion of patients below the second percentile for body weight were 25% at 5 years, 20% at 10 years, and 63% at 15 years of age. The equivalent statistics for body height were 15%, 0%, and 23%, respectively. CONCLUSIONS: Patients with TCA tend to undergo multiple procedures. Anorectal function improves gradually over time. There are no advantages of the Martin modification. In the long-term follow-up over half of the patients are below the second percentile for weight and one quarter are below the second percentile for height. Careful long-term follow-up is necessary for the patients with TCA.

Colon↗

Meconium ileus secondary to cystic fibrosis. The East London experience.

Meconium ileus (MI) affects 15% of neonates with cystic fibrosis (CF). The authors reviewed the management and outcome of 51 neonates presenting to a single institution between 1976 and 1995 with MI secondary to CF. Clinical presentation included abdominal distension (96%), bilious vomiting (49%), and delayed passage of meconium (36%). A family history of CF was present in 4 cases (8%). Twenty-three neonates presented with MI and evidence of volvulus, atresia, or perforation (complicated MI). Of these, 16 underwent stoma formation, 1 appendicectomy, and 6 resection with primary anastomosis. Twenty-eight neonates presented with uncomplicated MI. Of these, 11 were managed non-operatively by Gastrografin enema (10) or enteral N-acetylcysteine (1). The remainder required stoma formation (15) or bowel resection with primary anastomosis (2). Early postoperative complications occurred in 2 neonates (4%). In this hospital the 1-year survival for this condition has increased from 49% (1953-1970) to 98% (1976-1995) irrespective of the surgical procedure performed or the presence of volvulus, atresia, or perforation. In our experience, bowel resection with primary anastomosis is as safe as stoma formation and is associated with a reduced length of initial hospital stay.

Anastomosis, Surgical↗

Disruption of local retinoid-mediated gene expression accompanies abnormal development in the mammalian olfactory pathway.

We have evaluated the role of retinoid signaling in the early development of the olfactory epithelium and olfactory bulb. When retinoid-mediated gene expression is blocked briefly in mouse embryos at midgestation with citral (a general alcohol dehydrogenase antagonist that is thought to interfere with retinoid synthesis), the spectrum of morphogenetic abnormalities includes disruption of olfactory pathway development. It is difficult, however, to assess the specificity of this pharmacological manipulation, insofar as it also compromises several other aspects of central nervous system development. In homozygous Pax6 mutant mice (small eye: Pax6(Sey-Neu)), there is a more discrete lesion to the olfactory pathway: The epithelium and bulb cannot be recognized at any time during development, whereas other forebrain subdivisions can still be recognized. This loss of the entire primary olfactory pathway is accompanied by a failure of retinoid-mediated gene expression limited to the frontonasal region and forebrain. Retinoid receptors are expressed in the forebrain of Pax6(Sey-Neu)/Pax6(Sey-Neu) embryos, and the mutant forebrain remains responsive to exogenous retinoic acid. However, in Pax6(Sey-Neu)/ Pax6(Sey-Neu) embryos, retinoic acid (RA) is not produced by the frontonasal mesenchyme, which normally provides local retinoid signals to the placode and forebrain. Together, these results suggest that local retinoid signaling is essential for the normal development of the mammalian olfactory pathway.

Acyclic Monoterpenes↗